Multivariate evoked response detection based on the spectral F-test.

PubMed

Rocha, Paulo Fábio F; Felix, Leonardo B; Miranda de Sá, Antonio Mauricio F L; Mendes, Eduardo M A M

2016-05-01

Objective response detection techniques, such as magnitude square coherence, component synchrony measure, and the spectral F-test, have been used to automate the detection of evoked responses. The performance of these detectors depends on both the signal-to-noise ratio (SNR) and the length of the electroencephalogram (EEG) signal. Recently, multivariate detectors were developed to increase the detection rate even in the case of a low signal-to-noise ratio or of short data records originated from EEG signals. In this context, an extension to the multivariate case of the spectral F-test detector is proposed. The performance of this technique is assessed using Monte Carlo. As an example, EEG data from 12 subjects during photic stimulation is used to demonstrate the usefulness of the proposed detector. The multivariate method showed detection rates consistently higher than those ones when only one signal was used. It is shown that the response detection in EEG signals with the multivariate technique was statistically significant if two or more EEG derivations were used. Copyright © 2016 Elsevier B.V. All rights reserved.

Radiation-induced functional connectivity alterations in nasopharyngeal carcinoma patients with radiotherapy

PubMed Central

Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun

2016-01-01

Abstract The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale. The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores. Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA. The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment. PMID:27442663

Short-term change detection for UAV video

NASA Astrophysics Data System (ADS)

Saur, Günter; Krüger, Wolfgang

2012-11-01

In the last years, there has been an increased use of unmanned aerial vehicles (UAV) for video reconnaissance and surveillance. An important application in this context is change detection in UAV video data. Here we address short-term change detection, in which the time between observations ranges from several minutes to a few hours. We distinguish this task from video motion detection (shorter time scale) and from long-term change detection, based on time series of still images taken between several days, weeks, or even years. Examples for relevant changes we are looking for are recently parked or moved vehicles. As a pre-requisite, a precise image-to-image registration is needed. Images are selected on the basis of the geo-coordinates of the sensor's footprint and with respect to a certain minimal overlap. The automatic imagebased fine-registration adjusts the image pair to a common geometry by using a robust matching approach to handle outliers. The change detection algorithm has to distinguish between relevant and non-relevant changes. Examples for non-relevant changes are stereo disparity at 3D structures of the scene, changed length of shadows, and compression or transmission artifacts. To detect changes in image pairs we analyzed image differencing, local image correlation, and a transformation-based approach (multivariate alteration detection). As input we used color and gradient magnitude images. To cope with local misalignment of image structures we extended the approaches by a local neighborhood search. The algorithms are applied to several examples covering both urban and rural scenes. The local neighborhood search in combination with intensity and gradient magnitude differencing clearly improved the results. Extended image differencing performed better than both the correlation based approach and the multivariate alternation detection. The algorithms are adapted to be used in semi-automatic workflows for the ABUL video exploitation system of Fraunhofer IOSB, see Heinze et. al. 2010.1 In a further step we plan to incorporate more information from the video sequences to the change detection input images, e.g., by image enhancement or by along-track stereo which are available in the ABUL system.

Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts.

PubMed

Kirschner, Gyöngyi; Balla, Bernadett; Horváth, Péter; Kövesdi, Andrea; Lakatos, Gergely; Takács, István; Nagy, Zsolt; Tóbiás, Bálint; Árvai, Kristóf; Kósa, János Pál; Lakatos, Péter

2016-09-01

Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.

{sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

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

Zhang, Ying; Lin, Lianjie; Xu, Yanbin

2013-04-19

Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected tomore » multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.« less

β-N-Methylamino-L-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling.

PubMed

Engskog, Mikael K R; Ersson, Lisa; Haglöf, Jakob; Arvidsson, Torbjörn; Pettersson, Curt; Brittebo, Eva

2017-05-01

β-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid that induces long-term cognitive deficits, as well as an increased neurodegeneration and intracellular fibril formation in the hippocampus of adult rodents following short-time neonatal exposure and in vervet monkey brain following long-term exposure. It has also been proposed to be involved in the etiology of neurodegenerative disease in humans. The aim of this study was to identify metabolic effects not related to excitotoxicity or oxidative stress in human neuroblastoma SH-SY5Y cells. The effects of BMAA (50, 250, 1000 µM) for 24 h on cells differentiated with retinoic acid were studied. Samples were analyzed using LC-MS and NMR spectroscopy to detect altered intracellular polar metabolites. The analysis performed, followed by multivariate pattern recognition techniques, revealed significant perturbations in protein biosynthesis, amino acid metabolism pathways and citrate cycle. Of specific interest were the BMAA-induced alterations in alanine, aspartate and glutamate metabolism and as well as alterations in various neurotransmitters/neuromodulators such as GABA and taurine. The results indicate that BMAA can interfere with metabolic pathways involved in neurotransmission in human neuroblastoma cells.

[Evaluation of diabetic microangiopathy using optical coherence tomography angiography].

PubMed

Czakó, Cecília; Sándor, Gábor László; Ecsedy, Mónika; Szepessy, Zsuzsanna; Borbándy, Ágnes; Resch, Miklós; Papp, András; Récsán, Zsuzsa; Horváth, Hajnalka; Nagy, Zoltán Zsolt; Kovács, Illés

2018-02-01

Optical coherence tomography angiography is a non-invasive imaging technique that is able to visualize the different retinal vascular layers using motion contrast to detect blood flow without intravenous dye injection. This method might help to assess microangiopathy in diabetic retinopathy during screening and follow-up. To quantify retinal microvasculature alterations in both eyes of diabetic patients in relation to systemic risk factors using optical coherence tomography angiography. Both eyes of 36 diabetic patients and 45 individuals without diabetes were examined. Duration of diabetes, insulin therapy, blood pressure, HbA 1c , dyslipidemia, axial length and the presence of diabetic retinopathy were recorded. Retinal vessel density was measured by optical coherence tomography angiography. The effect of risk factors on vessel density and between-eye asymmetry was assessed using multivariable regression analysis. Vessel density was significantly lower and between-eye difference was significantly higher in diabetic patients compared to controls (p<0.05). Both vessel density and between-eye asymmetry significantly correlated with diabetes duration (p<0.05) after controlling for the effect of risk factors. The between-eye asymmetry in vessel density was significantly higher in patients without clinically detectable diabetic retinopathy compared to control subjects (p<0.001). There is a decrease in retinal vessel density and an increase in between-eye asymmetry in patients with diabetes compared to healthy subjects. By using optical coherence tomography angiography, the detection of these microvascular alterations is possible before clinically detectable diabetic retinopathy and might serve as a useful tool in both screening and timing of treatment. Orv Hetil. 2018; 159(8): 320-326.

Hierarchical multivariate covariance analysis of metabolic connectivity

PubMed Central

Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J

2014-01-01

Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI). PMID:25294129

MicroRNA-34c-5p is related to recurrence in laryngeal squamous cell carcinoma.

PubMed

Re, Massimo; Çeka, Artan; Rubini, Corrado; Ferrante, Luigi; Zizzi, Antonio; Gioacchini, Federico M; Tulli, Michele; Spazzafumo, Liana; Sellari-Franceschini, Stefano; Procopio, Antonio D; Olivieri, Fabiola

2015-09-01

Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival. Retrospective cohort study. Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Hair sterol signatures coupled to multivariate data analysis reveal an increased 7β-hydroxycholesterol production in cognitive impairment.

PubMed

Son, Hyun-Hwa; Lee, Do-Yup; Seo, Hong Seog; Jeong, Jihyeon; Moon, Ju-Yeon; Lee, Jung-Eun; Chung, Bong Chul; Kim, Eosu; Choi, Man Ho

2016-01-01

Altered cholesterol metabolism could be associated with cognitive impairment. The quantitative profiling of 19 hair sterols was developed using gas chromatography-mass spectrometry coupled to multivariate data analysis. The limit of quantification of all sterols ranged from 5 to 20 ng/g, while the calibration linearity was higher than 0.98. The precision (% CV) and accuracy (% bias) ranged from 3.2% to 9.8% and from 83.2% to 119.4%, respectively. Among the sterols examined, 8 were quantitatively detected from two strands of 3-cm-long scalp hair samples of female participants, including mild cognitive impairment (MCI, n=15), Alzheimer's disease (AD, n=31), and healthy controls (HC, n=36). The cognitive impairment (MCI or AD) was correlated with a higher metabolic rate than that of HCs based on 7β-hydroxycholesterol (P<0.005). Significant negative correlations (r=-0.822) were detected between Mini-Mental State Examination (MMSE) scores and hair sample metabolic ratios of 7β-hydroxycholesterol to cholesterol, which is an accepted, sensitive, and specific tool for discriminating HCs from individuals with MCI or AD. In conclusion, improved diagnostic values can be obtained using hair sterol signatures coupled with MMSE scores. This method may prove useful for predictive diagnosis in population screening of cognitive impairment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Partial Least Squares Calibration Modeling Towards the Multivariate Limit of Detection for Enriched Isotopic Mixtures via Laser Ablation Molecular Isotopic Spectroscopy

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

Harris, Candace; Profeta, Luisa; Akpovo, Codjo

The psuedo univariate limit of detection was calculated to compare to the multivariate interval. ompared with results from the psuedounivariate LOD, the multivariate LOD includes other factors (i.e. signal uncertainties) and the reveals the significance in creating models that not only use the analyte’s emission line but also its entire molecular spectra.

Hot spots of multivariate extreme anomalies in Earth observations

NASA Astrophysics Data System (ADS)

Flach, M.; Sippel, S.; Bodesheim, P.; Brenning, A.; Denzler, J.; Gans, F.; Guanche, Y.; Reichstein, M.; Rodner, E.; Mahecha, M. D.

2016-12-01

Anomalies in Earth observations might indicate data quality issues, extremes or the change of underlying processes within a highly multivariate system. Thus, considering the multivariate constellation of variables for extreme detection yields crucial additional information over conventional univariate approaches. We highlight areas in which multivariate extreme anomalies are more likely to occur, i.e. hot spots of extremes in global atmospheric Earth observations that impact the Biosphere. In addition, we present the year of the most unusual multivariate extreme between 2001 and 2013 and show that these coincide with well known high impact extremes. Technically speaking, we account for multivariate extremes by using three sophisticated algorithms adapted from computer science applications. Namely an ensemble of the k-nearest neighbours mean distance, a kernel density estimation and an approach based on recurrences is used. However, the impact of atmosphere extremes on the Biosphere might largely depend on what is considered to be normal, i.e. the shape of the mean seasonal cycle and its inter-annual variability. We identify regions with similar mean seasonality by means of dimensionality reduction in order to estimate in each region both the `normal' variance and robust thresholds for detecting the extremes. In addition, we account for challenges like heteroscedasticity in Northern latitudes. Apart from hot spot areas, those anomalies in the atmosphere time series are of particular interest, which can only be detected by a multivariate approach but not by a simple univariate approach. Such an anomalous constellation of atmosphere variables is of interest if it impacts the Biosphere. The multivariate constellation of such an anomalous part of a time series is shown in one case study indicating that multivariate anomaly detection can provide novel insights into Earth observations.

Nuclear magnetic resonance (NMR) study of the effect of cisplatin on the metabolic profile of MG-63 osteosarcoma cells.

PubMed

Duarte, Iola F; Lamego, Ines; Marques, Joana; Marques, M Paula M; Blaise, Benjamin J; Gil, Ana M

2010-11-05

In the present study, (1)H HRMAS NMR spectroscopy was used to assess the changes in the intracellular metabolic profile of MG-63 human osteosarcoma (OS) cells induced by the chemotherapy agent cisplatin (CDDP) at different times of exposure. Multivariate analysis was applied to the cells spectra, enabling consistent variation patterns to be detected and drug-specific metabolic effects to be identified. Statistical recoupling of variables (SRV) analysis and spectral integration enabled the most relevant spectral changes to be evaluated, revealing significant time-dependent alterations in lipids, choline-containing compounds, some amino acids, polyalcohols, and nitrogenated bases. The metabolic relevance of these compounds in the response of MG-63 cells to CDDP treatment is discussed.

Discerning mild cognitive impairment and Alzheimer Disease from normal aging: morphologic characterization based on univariate and multivariate models.

PubMed

Liao, Weiqi; Long, Xiaojing; Jiang, Chunxiang; Diao, Yanjun; Liu, Xin; Zheng, Hairong; Zhang, Lijuan

2014-05-01

Differentiating mild cognitive impairment (MCI) and Alzheimer Disease (AD) from healthy aging remains challenging. This study aimed to explore the cerebral structural alterations of subjects with MCI or AD as compared to healthy elderly based on the individual and collective effects of cerebral morphologic indices using univariate and multivariate analyses. T1-weighted images (T1WIs) were retrieved from Alzheimer Disease Neuroimaging Initiative database for 116 subjects who were categorized into groups of healthy aging, MCI, and AD. Analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) were performed to explore the intergroup morphologic alterations indexed by surface area, curvature index, cortical thickness, and subjacent white matter volume with age and sex controlled as covariates, in 34 parcellated gyri regions of interest (ROIs) for both cerebral hemispheres based on the T1WI. Statistical parameters were mapped on the anatomic images to facilitate visual inspection. Global rather than region-specific structural alterations were revealed in groups of MCI and AD relative to healthy elderly using MANCOVA. ANCOVA revealed that the cortical thickness decreased more prominently in entorhinal, temporal, and cingulate cortices and was positively correlated with patients' cognitive performance in AD group but not in MCI. The temporal lobe features marked atrophy of white matter during the disease dynamics. Significant intercorrelations were observed among the morphologic indices with univariate analysis for given ROIs. Significant global structural alterations were identified in MCI and AD based on MANCOVA model with improved sensitivity. The intercorrelation among the morphologic indices may dampen the use of individual morphological parameter in featuring cerebral structural alterations. Decrease in cortical thickness is not reflective of the cognitive performance at the early stage of AD. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Identifying cognitive impairment in type 2 diabetes with functional connectivity: a multivariate pattern analysis of resting state fMRI data

NASA Astrophysics Data System (ADS)

Liu, Zhenyu; Cui, Xingwei; Tang, Zhenchao; Dong, Di; Zang, Yali; Tian, Jie

2017-03-01

Previous researches have shown that type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment. Early detection of brain abnormalities at the preclinical stage can be useful for developing preventive interventions to abate cognitive decline. We aimed to investigate the whole-brain resting-state functional connectivity (RSFC) patterns of T2DM patients between 90 regions of interest (ROIs) based on the RS-fMRI data, which can be used to test the feasibility of identifying T2DM patients with cognitive impairment from other T2DM patients. 74 patients were recruited in this study and multivariate pattern analysis was utilized to assess the prediction performance. Elastic net was firstly used to select the key features for prediction, and then a linear discrimination model was constructed. 23 RSFCs were selected and it achieved the performance with classification accuracy of 90.54% and areas under the receiver operating characteristic curve (AUC) of 0.944 using ten-fold cross-validation. The results provide strong evidence that functional interactions of brain regions undergo notable alterations between T2DM patients with cognitive impairment or not. By analyzing the RSFCs that were selected as key features, we found that most of them involved the frontal or temporal. We speculated that cognitive impairment in T2DM patients mainly impacted these two lobes. Overall, the present study indicated that RSFCs undergo notable alterations associated with the cognitive impairment in T2DM patients, and it is possible to predicted cognitive impairment early with RSFCs.

Evaluation of a Multivariate Syndromic Surveillance System for West Nile Virus.

PubMed

Faverjon, Céline; Andersson, M Gunnar; Decors, Anouk; Tapprest, Jackie; Tritz, Pierre; Sandoz, Alain; Kutasi, Orsolya; Sala, Carole; Leblond, Agnès

2016-06-01

Various methods are currently used for the early detection of West Nile virus (WNV) but their outputs are not quantitative and/or do not take into account all available information. Our study aimed to test a multivariate syndromic surveillance system to evaluate if the sensitivity and the specificity of detection of WNV could be improved. Weekly time series data on nervous syndromes in horses and mortality in both horses and wild birds were used. Baselines were fitted to the three time series and used to simulate 100 years of surveillance data. WNV outbreaks were simulated and inserted into the baselines based on historical data and expert opinion. Univariate and multivariate syndromic surveillance systems were tested to gauge how well they detected the outbreaks; detection was based on an empirical Bayesian approach. The systems' performances were compared using measures of sensitivity, specificity, and area under receiver operating characteristic curve (AUC). When data sources were considered separately (i.e., univariate systems), the best detection performance was obtained using the data set of nervous symptoms in horses compared to those of bird and horse mortality (AUCs equal to 0.80, 0.75, and 0.50, respectively). A multivariate outbreak detection system that used nervous symptoms in horses and bird mortality generated the best performance (AUC = 0.87). The proposed approach is suitable for performing multivariate syndromic surveillance of WNV outbreaks. This is particularly relevant, given that a multivariate surveillance system performed better than a univariate approach. Such a surveillance system could be especially useful in serving as an alert for the possibility of human viral infections. This approach can be also used for other diseases for which multiple sources of evidence are available.

Mapping the Critical Gestational Age at Birth that Alters Brain Development in Preterm-born Infants using Multi-Modal MRI

PubMed Central

Wu, Dan; Chang, Linda; Akazawa, Kentaro; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi

2017-01-01

Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model—the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the “critical” GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth. PMID:28111189

Mapping the critical gestational age at birth that alters brain development in preterm-born infants using multi-modal MRI.

PubMed

Wu, Dan; Chang, Linda; Akazawa, Kentaro; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi

2017-04-01

Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model-the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the "critical" GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Biomarker responses and contamination levels in crabs (Carcinus aestuarii) from the Lagoon of Venice: An integrated approach in biomonitoring estuarine environments.

PubMed

Ricciardi, Francesco; Matozzo, Valerio; Binelli, Andrea; Marin, Maria Gabriella

2010-03-01

An integrated biological-chemical approach is necessary to evaluate correctly the environmental status of bodies of water, as suggested by the EU Water Framework Directive. The shore crab Carcinus aestuarii, sampled in the Lagoon of Venice (NE Italy), was used as a biomonitor species, and the chemical concentrations of 42 organic pollutants (HCHs, PAHs, PCBs, DDTs, PBDEs), biological responses related to neurotoxicity (AChE inhibition), detoxification mechanisms (CYP450 induction) and endocrine alterations (vitellogenin-like protein induction) were measured at the same time. The responsiveness of biomarkers as predictors (or descriptors) of chemical contamination was evaluated by multivariate regression analysis, revealing good predictor potential for the selected biomarkers. Biomonitoring in the Lagoon of Venice revealed a predominance of DDT and PCB compounds, especially near industrial sites or large cities. Endocrine alterations, not always correlated with the presence of measured compounds, were also detected in many areas, suggesting exposure to compounds able to interfere with the crab endocrine system. Copyright 2009 Elsevier Ltd. All rights reserved.

Semi-automatic measuring of arteriovenous relation as a possible silent brain infarction risk index in hypertensive patients.

PubMed

Vázquez Dorrego, X M; Manresa Domínguez, J M; Heras Tebar, A; Forés, R; Girona Marcé, A; Alzamora Sas, M T; Delgado Martínez, P; Riba-Llena, I; Ugarte Anduaga, J; Beristain Iraola, A; Barandiaran Martirena, I; Ruiz Bilbao, S M; Torán Monserrat, P

2016-11-01

To evaluate the usefulness of a semiautomatic measuring system of arteriovenous relation (RAV) from retinographic images of hypertensive patients in assessing their cardiovascular risk and silent brain ischemia (ICS) detection. Semi-automatic measurement of arterial and venous width were performed with the aid of Imedos software and conventional fundus examination from the analysis of retinal images belonging to the 976 patients integrated in the cohort Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study (ISSYS), group of hypertensive patients. All patients have been subjected to a cranial magnetic resonance imaging (RMN) to assess the presence or absence of brain silent infarct. Retinal images of 768 patients were studied. Among the clinical findings observed, association with ICS was only detected in patients with microaneurysms (OR 2.50; 95% CI: 1.05-5.98) or altered RAV (<0.666) (OR: 4.22; 95% CI: 2.56-6.96). In multivariate logistic regression analysis adjusted by age and sex, only altered RAV continued demonstrating as a risk factor (OR: 3.70; 95% CI: 2.21-6.18). The results show that the semiautomatic analysis of the retinal vasculature from retinal images has the potential to be considered as an important vascular risk factor in hypertensive population. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

The distribution and mobility of uranium in glassy and zeolitized tuff, Keg Mountain area, Utah, U.S.A.

USGS Publications Warehouse

Zielinski, R.A.; Lindsey, D.A.; Rosholt, J.N.

1980-01-01

The distribution and mobility of uranium in a diagenetically altered, 8 Ma old tuff in the Keg Mountain area, Utah, are modelled in this study. The modelling represents an improvement over similar earlier studies in that it: (1) considers a large number of samples (76) collected with good geologic control and exhibiting a wide range of alteration; (2) includes radiometric data for Th, K and RaeU (radium equivalent uranium) as well as U; (3) considers mineralogic and trace-element data for the same samples; and (4) analyzes the mineral and chemical covariation by multivariate statistical methods. The variation of U in the tuff is controlled mainly by its primary abundance in glass and by the relative abundance of non-uraniferous detritus and uraniferous accessory minerals. Alteration of glass to zeolite, even though extensive, caused no large or systematic change in the bulk concentration of U in the tuff. Some redistribution of U during diagenesis is indicated by association of U with minor alteration products such as opal and hydrous Fe-Mn oxide minerals. Isotopic studies indicate that the zeolitized tuff has been open to migration of U decay products during the last 0.8 Ma. The tuff of Keg Mountain has not lost a statistically detectable fraction of its original U, even though it has a high (??? 9 ppm) trace U content and has been extensively altered to zeolite. Similar studies in a variety of geological environments are required in order to identify the particular combination of conditions most favorable for liberation and migration of U from tuffs. ?? 1980.

A Dynamic Intrusion Detection System Based on Multivariate Hotelling's T2 Statistics Approach for Network Environments

PubMed Central

Avalappampatty Sivasamy, Aneetha; Sundan, Bose

2015-01-01

The ever expanding communication requirements in today's world demand extensive and efficient network systems with equally efficient and reliable security features integrated for safe, confident, and secured communication and data transfer. Providing effective security protocols for any network environment, therefore, assumes paramount importance. Attempts are made continuously for designing more efficient and dynamic network intrusion detection models. In this work, an approach based on Hotelling's T2 method, a multivariate statistical analysis technique, has been employed for intrusion detection, especially in network environments. Components such as preprocessing, multivariate statistical analysis, and attack detection have been incorporated in developing the multivariate Hotelling's T2 statistical model and necessary profiles have been generated based on the T-square distance metrics. With a threshold range obtained using the central limit theorem, observed traffic profiles have been classified either as normal or attack types. Performance of the model, as evaluated through validation and testing using KDD Cup'99 dataset, has shown very high detection rates for all classes with low false alarm rates. Accuracy of the model presented in this work, in comparison with the existing models, has been found to be much better. PMID:26357668

A Dynamic Intrusion Detection System Based on Multivariate Hotelling's T2 Statistics Approach for Network Environments.

PubMed

Sivasamy, Aneetha Avalappampatty; Sundan, Bose

2015-01-01

The ever expanding communication requirements in today's world demand extensive and efficient network systems with equally efficient and reliable security features integrated for safe, confident, and secured communication and data transfer. Providing effective security protocols for any network environment, therefore, assumes paramount importance. Attempts are made continuously for designing more efficient and dynamic network intrusion detection models. In this work, an approach based on Hotelling's T(2) method, a multivariate statistical analysis technique, has been employed for intrusion detection, especially in network environments. Components such as preprocessing, multivariate statistical analysis, and attack detection have been incorporated in developing the multivariate Hotelling's T(2) statistical model and necessary profiles have been generated based on the T-square distance metrics. With a threshold range obtained using the central limit theorem, observed traffic profiles have been classified either as normal or attack types. Performance of the model, as evaluated through validation and testing using KDD Cup'99 dataset, has shown very high detection rates for all classes with low false alarm rates. Accuracy of the model presented in this work, in comparison with the existing models, has been found to be much better.

Robust multivariate nonparametric tests for detection of two-sample location shift in clinical trials

PubMed Central

Jiang, Xuejun; Guo, Xu; Zhang, Ning; Wang, Bo

2018-01-01

This article presents and investigates performance of a series of robust multivariate nonparametric tests for detection of location shift between two multivariate samples in randomized controlled trials. The tests are built upon robust estimators of distribution locations (medians, Hodges-Lehmann estimators, and an extended U statistic) with both unscaled and scaled versions. The nonparametric tests are robust to outliers and do not assume that the two samples are drawn from multivariate normal distributions. Bootstrap and permutation approaches are introduced for determining the p-values of the proposed test statistics. Simulation studies are conducted and numerical results are reported to examine performance of the proposed statistical tests. The numerical results demonstrate that the robust multivariate nonparametric tests constructed from the Hodges-Lehmann estimators are more efficient than those based on medians and the extended U statistic. The permutation approach can provide a more stringent control of Type I error and is generally more powerful than the bootstrap procedure. The proposed robust nonparametric tests are applied to detect multivariate distributional difference between the intervention and control groups in the Thai Healthy Choices study and examine the intervention effect of a four-session motivational interviewing-based intervention developed in the study to reduce risk behaviors among youth living with HIV. PMID:29672555

Multivariate Analysis and Machine Learning in Cerebral Palsy Research

PubMed Central

Zhang, Jing

2017-01-01

Cerebral palsy (CP), a common pediatric movement disorder, causes the most severe physical disability in children. Early diagnosis in high-risk infants is critical for early intervention and possible early recovery. In recent years, multivariate analytic and machine learning (ML) approaches have been increasingly used in CP research. This paper aims to identify such multivariate studies and provide an overview of this relatively young field. Studies reviewed in this paper have demonstrated that multivariate analytic methods are useful in identification of risk factors, detection of CP, movement assessment for CP prediction, and outcome assessment, and ML approaches have made it possible to automatically identify movement impairments in high-risk infants. In addition, outcome predictors for surgical treatments have been identified by multivariate outcome studies. To make the multivariate and ML approaches useful in clinical settings, further research with large samples is needed to verify and improve these multivariate methods in risk factor identification, CP detection, movement assessment, and outcome evaluation or prediction. As multivariate analysis, ML and data processing technologies advance in the era of Big Data of this century, it is expected that multivariate analysis and ML will play a bigger role in improving the diagnosis and treatment of CP to reduce mortality and morbidity rates, and enhance patient care for children with CP. PMID:29312134

Multivariate Analysis and Machine Learning in Cerebral Palsy Research.

PubMed

Zhang, Jing

2017-01-01

Cerebral palsy (CP), a common pediatric movement disorder, causes the most severe physical disability in children. Early diagnosis in high-risk infants is critical for early intervention and possible early recovery. In recent years, multivariate analytic and machine learning (ML) approaches have been increasingly used in CP research. This paper aims to identify such multivariate studies and provide an overview of this relatively young field. Studies reviewed in this paper have demonstrated that multivariate analytic methods are useful in identification of risk factors, detection of CP, movement assessment for CP prediction, and outcome assessment, and ML approaches have made it possible to automatically identify movement impairments in high-risk infants. In addition, outcome predictors for surgical treatments have been identified by multivariate outcome studies. To make the multivariate and ML approaches useful in clinical settings, further research with large samples is needed to verify and improve these multivariate methods in risk factor identification, CP detection, movement assessment, and outcome evaluation or prediction. As multivariate analysis, ML and data processing technologies advance in the era of Big Data of this century, it is expected that multivariate analysis and ML will play a bigger role in improving the diagnosis and treatment of CP to reduce mortality and morbidity rates, and enhance patient care for children with CP.

Overexpression of MutSα Complex Proteins Predicts Poor Prognosis in Oral Squamous Cell Carcinoma.

PubMed

Wagner, Vivian Petersen; Webber, Liana Preto; Salvadori, Gabriela; Meurer, Luise; Fonseca, Felipe Paiva; Castilho, Rogério Moraes; Squarize, Cristiane Helena; Vargas, Pablo Agustin; Martins, Manoela Domingues

2016-05-01

The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC).The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC.All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ± 15.21 and 31.46 ± 22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02).This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC.

Outlier Detection in Hyperspectral Imagery Using Closest Distance to Center with Ellipsoidal Multivariate Trimming

DTIC Science & Technology

2011-01-01

where r << P. The use of PCA for finding outliers in multivariate data is surveyed by Gnanadesikan and Kettenring16 and Rao.17 As alluded to earlier...1984. 16. Gnanadesikan R and Kettenring JR. Robust estimates, residu­ als, and outlier detection with multiresponse data. Biometrics 1972; 28: 81–124

Lysophosphatidylcholine and amide as metabolites for detecting alzheimer disease using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabonomics.

PubMed

Cui, Yu; Liu, Xiuqin; Wang, Maoqing; Liu, Liyan; Sun, Xiaohong; Ma, Lan; Xie, Wei; Wang, Chao; Tang, Sisi; Wang, Decai; Wu, Qunhong

2014-10-01

Alzheimer disease (AD) can be diagnosed by clinical and neuropsychologic tests and at autopsy, but there are no simple effective diagnostic methods for detecting biomarkers in patients at early stages of cognitive impairment. Early metabolic alterations that may facilitate AD diagnosis have not been thoroughly explored. We applied a nontargeted metabonomic approach using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry to analyze serum and urine samples from 46 patients with AD and 36 healthy controls. Metabolite profiles were processed using multivariate analysis to identify potential metabolites, which were further confirmed using tandem mass spectrometry. Ultrahigh-performance liquid chromatography mass spectrometry methods were additionally used to quantify potentially important biomarkers. Independent samples were then selected to validate the identified biomarkers. There was a clear separation between healthy controls and AD patients; AD patient samples had disordered amino acid and phospholipid metabolism and dysregulated palmitic amide. Receiver operator characteristic curve and quantification suggested that palmitic amide, lysophosphatidylcholine (LysoPC, 18:0), LysoPC(18:2), L-glutamine, and 5-L-glutamylglycine were the optimal metabolites. In addition, areas under the curve from the palmitic amide, LysoPC(18:2), and 5-L-glutamylglycine in the validation study were 0.714, 0.996, and 0.734, respectively. These data elucidate the metabolic alterations associated with AD and suggest new biomarkers for AD diagnosis, thereby permitting early intervention designed to prevent disease progression.

Synergistic Activation upon MET and ALK Coamplification Sustains Targeted Therapy in Sarcomatoid Carcinoma, a Deadly Subtype of Lung Cancer.

PubMed

Pelosi, Giuseppe; Gasparini, Patrizia; Conte, Davide; Fabbri, Alessandra; Perrone, Federica; Tamborini, Elena; Pupa, Serenella M; Ciravolo, Valentina; Caserini, Roberto; Rossi, Giulio; Cavazza, Alberto; Papotti, Mauro; Nakatani, Yukio; Maisonneuve, Patrick; Pastorino, Ugo; Sozzi, Gabriella

2016-05-01

Genetic alterations suitable for targeted therapy are poorly known issues in pulmonary sarcomatoid carcinoma (PSC), an uncommon and life-threatening family of non-small cell lung cancers. Ninety-eight PSCs were assessed for MNNG HOS Transforming gene (MET) and anaplastic lymphoma receptor tyrosine kinase gene (ALK) status by fluorescence in situ hybridization (FISH) and for relevant protein expression by immunohistochemical analysis, also taking advantage of phosphorylated (p-) antibodies. Moreover, levels of ALK and MET mRNA were also determined by real-time polymerase chain reaction and Western blot analysis for downstream activation pathways involving p-MET, p-protein kinase B, p-mitogen-activated protein kinase, p-SRC proto-oncogene tyrosine-protein kinase, and p-focal adhesion kinase (p-FAK). MET amplification was detected by FISH in 25 of 98 PSCs (25.6%) and ALK amplification (but not the relevant rearrangement) was found in 16 of 98 (16.3%), with all ALK-amplified tumors also showing MET amplification (p < 0.0001). Nine PSCs, however, showed MET amplification without any ALK gene alteration. ALK protein expression was always lacking, whereas MET and p-MET were confined to the relevant amplified tumors only. Increased levels of ALK and MET mRNA were detectable in tumors with no direct relationship between mRNA content, protein expression, or alterations detected by FISH. Western blot assays showed complete activation of downstream signal pathways up to p-SRC proto-oncogene tyrosine-protein kinase, and p-focal adhesion kinase recruitment in MET and ALK-coamplified tumors only, whereas isolated MET amplification, MET and ALK borderline amplification (5%-10% of tumor cells with ≥15 copies of the relevant gene), or negative tumors showing eusomy or chromosome polysomy were confined to p-mitogen-activated protein kinase, p-protein kinase B, and/or p-MET activation. Multivariate survival analysis pushed a higher percentage of MET altered cells or a higher value of MET copy gain per cell to marginally emerge for overall survival (p = 0.140) and disease-free survival (p = 0.060), respectively. ALK and MET seemed to act as synergistic, nonrandom coactivators of downstream signal when coamplified in a subset of patients with PSC, thus likely suggesting a combined mechanism of oncogene addiction. These alterations could be a suitable target for therapy based on specific inhibitors. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Using Statistical Process Control for detecting anomalies in multivariate spatiotemporal Earth Observations

NASA Astrophysics Data System (ADS)

Flach, Milan; Mahecha, Miguel; Gans, Fabian; Rodner, Erik; Bodesheim, Paul; Guanche-Garcia, Yanira; Brenning, Alexander; Denzler, Joachim; Reichstein, Markus

2016-04-01

The number of available Earth observations (EOs) is currently substantially increasing. Detecting anomalous patterns in these multivariate time series is an important step in identifying changes in the underlying dynamical system. Likewise, data quality issues might result in anomalous multivariate data constellations and have to be identified before corrupting subsequent analyses. In industrial application a common strategy is to monitor production chains with several sensors coupled to some statistical process control (SPC) algorithm. The basic idea is to raise an alarm when these sensor data depict some anomalous pattern according to the SPC, i.e. the production chain is considered 'out of control'. In fact, the industrial applications are conceptually similar to the on-line monitoring of EOs. However, algorithms used in the context of SPC or process monitoring are rarely considered for supervising multivariate spatio-temporal Earth observations. The objective of this study is to exploit the potential and transferability of SPC concepts to Earth system applications. We compare a range of different algorithms typically applied by SPC systems and evaluate their capability to detect e.g. known extreme events in land surface processes. Specifically two main issues are addressed: (1) identifying the most suitable combination of data pre-processing and detection algorithm for a specific type of event and (2) analyzing the limits of the individual approaches with respect to the magnitude, spatio-temporal size of the event as well as the data's signal to noise ratio. Extensive artificial data sets that represent the typical properties of Earth observations are used in this study. Our results show that the majority of the algorithms used can be considered for the detection of multivariate spatiotemporal events and directly transferred to real Earth observation data as currently assembled in different projects at the European scale, e.g. http://baci-h2020.eu/index.php/ and http://earthsystemdatacube.net/. Known anomalies such as the Russian heatwave are detected as well as anomalies which are not detectable with univariate methods.

Recent changes (1973-2014 versus 1903-1972) in the flow regime of the Lower Paraná River and current fluvial pollution warnings in its Delta Biosphere Reserve.

PubMed

Puig, Alba; Olguín Salinas, Héctor F; Borús, Juan A

2016-06-01

Alterations in flow regimes of large rivers may originate or increase risks to ecosystems and humans. The Paraná River basin (South America) undergoes human pressures (e.g., heavy damming in the upper basin, deforestation, and mixed pollution) that may affect the water quantity and quality of its terminal Delta (Argentina). In this study, after applying univariate and multivariate change-point detection and trend analyses to the daily data series of flows incoming to the Delta (Paraná-Santa Fe section), flow characteristics were compared by Indicators of Hydrologic Alteration (IHA) and Environmental Flow Components (EFC). Some flood characteristics were also compared from hydrometric levels in the middle Delta (San Pedro station). Chemical and microbiological water variables in the main rivers of the "Paraná Delta" Biosphere Reserve were examined during two extreme hydrologic years (October 2008 to July 2010) to detect potential risk factors in association with hydrologic conditions. In the Lower Paraná River, a historical period (1903-1972) and two more altered periods (1973-1999 wet period and 2000-2014 dry period) were identified. Flow duration curves evidenced different changes in both altered periods, reflecting the joint effect of climatic variability and human influence. The most evident alterations in the flow regime were the lack of record of the extreme-low-flow component, the attenuation of monthly flow seasonality, and the increase in the number of reversals (dry period) and in the variability of maximum and minimum flow dates. These alterations are consistent with the monthly and daily flow regulation by upstream dams evidenced by available data from the current dry period. In the middle Delta, the marked monthly seasonality in flood days decreased only in the wet period. The proportion between the number of flood days exceeding the evacuation level and that of those exceeding the warning level doubled in the wet period but decreased only slightly in the dry period. In the Delta Reserve rivers, concentrations of Escherichia coli, cadmium, lead, iron, manganese, and ammonium exceeded guideline levels under a severe drought and a dispersal of cyanobacteria appeared under a high-flow pulse in La Niña year. The ammonium concentration exceeded the level for human drink with the overbanking flood stage in El Niño year. These occasional detections pose a potential risk to the aquatic life and, especially, to the inhabitants of the Reserve. Flow duration curves, IHA, and EFC are useful tools to evaluate trends or changes of ecological and social relevance in flow regime characteristics.

Recent changes (1973-2014 versus 1903-1972) in the flow regime of the Lower Paraná River and current fluvial pollution warnings in its Delta Biosphere Reserve

NASA Astrophysics Data System (ADS)

Puig, Alba; Olguín Salinas, Héctor F.; Borús, Juan A.

2016-06-01

Alterations in flow regimes of large rivers may originate or increase risks to ecosystems and humans. The Paraná River basin (South America) undergoes human pressures (e.g., heavy damming in the upper basin, deforestation, and mixed pollution) that may affect the water quantity and quality of its terminal Delta (Argentina). In this study, after applying univariate and multivariate change-point detection and trend analyses to the daily data series of flows incoming to the Delta (Paraná-Santa Fe section), flow characteristics were compared by Indicators of Hydrologic Alteration (IHA) and Environmental Flow Components (EFC). Some flood characteristics were also compared from hydrometric levels in the middle Delta (San Pedro station). Chemical and microbiological water variables in the main rivers of the "Paraná Delta" Biosphere Reserve were examined during two extreme hydrologic years (October 2008 to July 2010) to detect potential risk factors in association with hydrologic conditions. In the Lower Paraná River, a historical period (1903-1972) and two more altered periods (1973-1999 wet period and 2000-2014 dry period) were identified. Flow duration curves evidenced different changes in both altered periods, reflecting the joint effect of climatic variability and human influence. The most evident alterations in the flow regime were the lack of record of the extreme-low-flow component, the attenuation of monthly flow seasonality, and the increase in the number of reversals (dry period) and in the variability of maximum and minimum flow dates. These alterations are consistent with the monthly and daily flow regulation by upstream dams evidenced by available data from the current dry period. In the middle Delta, the marked monthly seasonality in flood days decreased only in the wet period. The proportion between the number of flood days exceeding the evacuation level and that of those exceeding the warning level doubled in the wet period but decreased only slightly in the dry period. In the Delta Reserve rivers, concentrations of Escherichia coli, cadmium, lead, iron, manganese, and ammonium exceeded guideline levels under a severe drought and a dispersal of cyanobacteria appeared under a high-flow pulse in La Niña year. The ammonium concentration exceeded the level for human drink with the overbanking flood stage in El Niño year. These occasional detections pose a potential risk to the aquatic life and, especially, to the inhabitants of the Reserve. Flow duration curves, IHA, and EFC are useful tools to evaluate trends or changes of ecological and social relevance in flow regime characteristics.

Multivariate generalized multifactor dimensionality reduction to detect gene-gene interactions

PubMed Central

2013-01-01

Background Recently, one of the greatest challenges in genome-wide association studies is to detect gene-gene and/or gene-environment interactions for common complex human diseases. Ritchie et al. (2001) proposed multifactor dimensionality reduction (MDR) method for interaction analysis. MDR is a combinatorial approach to reduce multi-locus genotypes into high-risk and low-risk groups. Although MDR has been widely used for case-control studies with binary phenotypes, several extensions have been proposed. One of these methods, a generalized MDR (GMDR) proposed by Lou et al. (2007), allows adjusting for covariates and applying to both dichotomous and continuous phenotypes. GMDR uses the residual score of a generalized linear model of phenotypes to assign either high-risk or low-risk group, while MDR uses the ratio of cases to controls. Methods In this study, we propose multivariate GMDR, an extension of GMDR for multivariate phenotypes. Jointly analysing correlated multivariate phenotypes may have more power to detect susceptible genes and gene-gene interactions. We construct generalized estimating equations (GEE) with multivariate phenotypes to extend generalized linear models. Using the score vectors from GEE we discriminate high-risk from low-risk groups. We applied the multivariate GMDR method to the blood pressure data of the 7,546 subjects from the Korean Association Resource study: systolic blood pressure (SBP) and diastolic blood pressure (DBP). We compare the results of multivariate GMDR for SBP and DBP to the results from separate univariate GMDR for SBP and DBP, respectively. We also applied the multivariate GMDR method to the repeatedly measured hypertension status from 5,466 subjects and compared its result with those of univariate GMDR at each time point. Results Results from the univariate GMDR and multivariate GMDR in two-locus model with both blood pressures and hypertension phenotypes indicate best combinations of SNPs whose interaction has significant association with risk for high blood pressures or hypertension. Although the test balanced accuracy (BA) of multivariate analysis was not always greater than that of univariate analysis, the multivariate BAs were more stable with smaller standard deviations. Conclusions In this study, we have developed multivariate GMDR method using GEE approach. It is useful to use multivariate GMDR with correlated multiple phenotypes of interests. PMID:24565370

Multivariable bio-inspired photonic sensors for non-condensable gases

NASA Astrophysics Data System (ADS)

Potyrailo, Radislav A.; Karker, Nicholas; Carpenter, Michael A.; Minnick, Andrew

2018-02-01

Existing gas sensors often lose their measurement accuracy in practical field applications. To mitigate this significant problem, here, we report a demonstration of fabricated multivariable photonic sensors inspired by a known nanostructure of Morpho butterfly scales for detection of exemplary non-condensable gases such as H2, CO, and CO2. We fabricated bio-inspired nanostructures using conventional photolithography and chemical etching and detected individual gases that were difficult or unrealistic to detect using natural Morpho nanostructures. Such bio-inspired gas sensors are the critical step in the development of new sensors with improved accuracy for diverse operational scenarios. While this report is our initial demonstration of responses of fabricated multivariable sensors to individual gases in pristine laboratory conditions, it is a significant milestone in understanding the next steps toward field tests and practical applications of these sensors.

TATES: Efficient Multivariate Genotype-Phenotype Analysis for Genome-Wide Association Studies

PubMed Central

van der Sluis, Sophie; Posthuma, Danielle; Dolan, Conor V.

2013-01-01

To date, the genome-wide association study (GWAS) is the primary tool to identify genetic variants that cause phenotypic variation. As GWAS analyses are generally univariate in nature, multivariate phenotypic information is usually reduced to a single composite score. This practice often results in loss of statistical power to detect causal variants. Multivariate genotype–phenotype methods do exist but attain maximal power only in special circumstances. Here, we present a new multivariate method that we refer to as TATES (Trait-based Association Test that uses Extended Simes procedure), inspired by the GATES procedure proposed by Li et al (2011). For each component of a multivariate trait, TATES combines p-values obtained in standard univariate GWAS to acquire one trait-based p-value, while correcting for correlations between components. Extensive simulations, probing a wide variety of genotype–phenotype models, show that TATES's false positive rate is correct, and that TATES's statistical power to detect causal variants explaining 0.5% of the variance can be 2.5–9 times higher than the power of univariate tests based on composite scores and 1.5–2 times higher than the power of the standard MANOVA. Unlike other multivariate methods, TATES detects both genetic variants that are common to multiple phenotypes and genetic variants that are specific to a single phenotype, i.e. TATES provides a more complete view of the genetic architecture of complex traits. As the actual causal genotype–phenotype model is usually unknown and probably phenotypically and genetically complex, TATES, available as an open source program, constitutes a powerful new multivariate strategy that allows researchers to identify novel causal variants, while the complexity of traits is no longer a limiting factor. PMID:23359524

Integrated biomarker response in catfish Hypostomus ancistroides by multivariate analysis in the Pirapó River, southern Brazil.

PubMed

Ghisi, Nédia C; Oliveira, Elton C; Mendonça Mota, Thais F; Vanzetto, Guilherme V; Roque, Aliciane A; Godinho, Jayson P; Bettim, Franciele Lima; Silva de Assis, Helena Cristina da; Prioli, Alberto J

2016-10-01

Aquatic pollutants produce multiple consequences in organisms, populations, communities and ecosystems, affecting the function of organs, reproductive state, population size, species survival and even biodiversity. In order to monitor the health of aquatic organisms, biomarkers have been used as effective tools in environmental risk assessment. The aim of this study is to evaluate, through a multivariate and integrative analysis, the response of the native species Hypostomus ancistroides over a pollution gradient in the main water supply body of northwestern Paraná state (Brazil). The condition factor, micronucleus test and erythrocyte nuclear abnormalities (ENA), comet assay, measurement of the cerebral and muscular enzyme acetylcholinesterase (AChE), and histopathological analysis of liver and gill were evaluated in fishes from three sites of the Pirapó River during the dry and rainy seasons. The multivariate general result showed that the interaction between the seasons and the sites was significant: there are variations in the rates of alterations in the biological parameters, depending on the time of year researched at each site. In general, the best results were observed for the site nearest the spring, and alterations in the parameters at the intermediate and downstream sites. In sum, the results of this study showed the necessity of a multivariate analysis, evaluating several biological parameters, to obtain an integrated response to the effects of the environmental pollutants on the organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Achieving optimal SERS through enhanced experimental design

PubMed Central

Fisk, Heidi; Westley, Chloe; Turner, Nicholas J.

2016-01-01

One of the current limitations surrounding surface‐enhanced Raman scattering (SERS) is the perceived lack of reproducibility. SERS is indeed challenging, and for analyte detection, it is vital that the analyte interacts with the metal surface. However, as this is analyte dependent, there is not a single set of SERS conditions that are universal. This means that experimental optimisation for optimum SERS response is vital. Most researchers optimise one factor at a time, where a single parameter is altered first before going onto optimise the next. This is a very inefficient way of searching the experimental landscape. In this review, we explore the use of more powerful multivariate approaches to SERS experimental optimisation based on design of experiments and evolutionary computational methods. We particularly focus on colloidal‐based SERS rather than thin film preparations as a result of their popularity. © 2015 The Authors. Journal of Raman Spectroscopy published by John Wiley & Sons, Ltd. PMID:27587905

Comprehensive NMR analysis of compositional changes of black garlic during thermal processing.

PubMed

Liang, Tingfu; Wei, Feifei; Lu, Yi; Kodani, Yoshinori; Nakada, Mitsuhiko; Miyakawa, Takuya; Tanokura, Masaru

2015-01-21

Black garlic is a processed food product obtained by subjecting whole raw garlic to thermal processing that causes chemical reactions, such as the Maillard reaction, which change the composition of the garlic. In this paper, we report a nuclear magnetic resonance (NMR)-based comprehensive analysis of raw garlic and black garlic extracts to determine the compositional changes resulting from thermal processing. (1)H NMR spectra with a detailed signal assignment showed that 38 components were altered by thermal processing of raw garlic. For example, the contents of 11 l-amino acids increased during the first step of thermal processing over 5 days and then decreased. Multivariate data analysis revealed changes in the contents of fructose, glucose, acetic acid, formic acid, pyroglutamic acid, cycloalliin, and 5-(hydroxymethyl)furfural (5-HMF). Our results provide comprehensive information on changes in NMR-detectable components during thermal processing of whole garlic.

Achieving optimal SERS through enhanced experimental design.

PubMed

Fisk, Heidi; Westley, Chloe; Turner, Nicholas J; Goodacre, Royston

2016-01-01

One of the current limitations surrounding surface-enhanced Raman scattering (SERS) is the perceived lack of reproducibility. SERS is indeed challenging, and for analyte detection, it is vital that the analyte interacts with the metal surface. However, as this is analyte dependent, there is not a single set of SERS conditions that are universal. This means that experimental optimisation for optimum SERS response is vital. Most researchers optimise one factor at a time, where a single parameter is altered first before going onto optimise the next. This is a very inefficient way of searching the experimental landscape. In this review, we explore the use of more powerful multivariate approaches to SERS experimental optimisation based on design of experiments and evolutionary computational methods. We particularly focus on colloidal-based SERS rather than thin film preparations as a result of their popularity. © 2015 The Authors. Journal of Raman Spectroscopy published by John Wiley & Sons, Ltd.

Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection.

PubMed

Mwanza, Jean-Claude; Warren, Joshua L; Hochberg, Jessica T; Budenz, Donald L; Chang, Robert T; Ramulu, Pradeep Y

2015-01-01

To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. One hundred ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike's information criterion (AIC), and prediction confidence interval lengths. For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDx-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT×NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single-variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAP-FDT, and interaction GDx-TSNIT×NAP-FDT consistently provided better discriminating abilities for detecting early, moderate, and severe glaucoma than the best single-variable models. The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDx-TSNIT×NAP-FDT provides the best glaucoma prediction compared with all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared with using GDx or FDT alone.

Multivariate η-μ fading distribution with arbitrary correlation model

NASA Astrophysics Data System (ADS)

Ghareeb, Ibrahim; Atiani, Amani

2018-03-01

An extensive analysis for the multivariate ? distribution with arbitrary correlation is presented, where novel analytical expressions for the multivariate probability density function, cumulative distribution function and moment generating function (MGF) of arbitrarily correlated and not necessarily identically distributed ? power random variables are derived. Also, this paper provides exact-form expression for the MGF of the instantaneous signal-to-noise ratio at the combiner output in a diversity reception system with maximal-ratio combining and post-detection equal-gain combining operating in slow frequency nonselective arbitrarily correlated not necessarily identically distributed ?-fading channels. The average bit error probability of differentially detected quadrature phase shift keying signals with post-detection diversity reception system over arbitrarily correlated and not necessarily identical fading parameters ?-fading channels is determined by using the MGF-based approach. The effect of fading correlation between diversity branches, fading severity parameters and diversity level is studied.

Multivariate Bayesian modeling of known and unknown causes of events--an application to biosurveillance.

PubMed

Shen, Yanna; Cooper, Gregory F

2012-09-01

This paper investigates Bayesian modeling of known and unknown causes of events in the context of disease-outbreak detection. We introduce a multivariate Bayesian approach that models multiple evidential features of every person in the population. This approach models and detects (1) known diseases (e.g., influenza and anthrax) by using informative prior probabilities and (2) unknown diseases (e.g., a new, highly contagious respiratory virus that has never been seen before) by using relatively non-informative prior probabilities. We report the results of simulation experiments which support that this modeling method can improve the detection of new disease outbreaks in a population. A contribution of this paper is that it introduces a multivariate Bayesian approach for jointly modeling both known and unknown causes of events. Such modeling has general applicability in domains where the space of known causes is incomplete. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Impact of the ST101 clone on fatality among patients with colistin-resistant Klebsiella pneumoniae infection.

PubMed

Can, Fusun; Menekse, Sirin; Ispir, Pelin; Atac, Nazli; Albayrak, Ozgur; Demir, Tuana; Karaaslan, Doruk Can; Karahan, Salih Nafiz; Kapmaz, Mahir; Kurt Azap, Ozlem; Timurkaynak, Funda; Simsek Yavuz, Serap; Basaran, Seniha; Yoruk, Fugen; Azap, Alpay; Koculu, Safiye; Benzonana, Nur; Lack, Nathan A; Gönen, Mehmet; Ergonul, Onder

2018-05-01

We describe the molecular characteristics of colistin resistance and its impact on patient mortality. A prospective cohort study was performed in seven different Turkish hospitals. The genotype of each isolate was determined by MLST and repetitive extragenic palindromic PCR (rep-PCR). Alterations in mgrB were detected by sequencing. Upregulation of pmrCAB, phoQ and pmrK was quantified by RT-PCR. mcr-1 and the genes encoding OXA-48, NDM-1 and KPC were amplified by PCR. A total of 115 patients diagnosed with colistin-resistant K. pneumoniae (ColR-Kp) infection were included. Patients were predominantly males (55%) with a median age of 63 (IQR 46-74) and the 30 day mortality rate was 61%. ST101 was the most common ST and accounted for 68 (59%) of the ColR-Kp. The 30 day mortality rate in patients with these isolates was 72%. In ST101, 94% (64/68) of the isolates had an altered mgrB gene, whereas the alteration occurred in 40% (19/47) of non-ST101 isolates. The OXA-48 and NDM-1 carbapenemases were found in 93 (81%) and 22 (19%) of the total 115 isolates, respectively. In multivariate analysis for the prediction of 30 day mortality, ST101 (OR 3.4, CI 1.46-8.15, P = 0.005) and ICU stay (OR 7.4, CI 2.23-29.61, P = 0.002) were found to be significantly associated covariates. Besides ICU stay, ST101 was found to be a significant independent predictor of patient mortality among those infected with ColR-Kp. A significant association was detected between ST101 and OXA-48. ST101 may become a global threat in the dissemination of colistin resistance and the increased morbidity and mortality of K. pneumoniae infection.

Arterial alterations in severely obese children with obstructive sleep apnoea.

PubMed

Dubern, Beatrice; Aggoun, Yacine; Boulé, Michèle; Fauroux, Brigitte; Bonnet, Damien; Tounian, Patrick

2010-05-03

Obstructive sleep apnoea (OSA) in obese adults is associated with cardiovascular disease independently of obesity. Vascular alterations exist in children with obesity and may constitute the first stage in the development of adulthood cardiovascular disease. To investigate the relationship between OSA and early arterial alterations in obese children. Cross-sectional study of a prospective cohort. A total of 51 children with severe obesity managed at a teaching hospital outpatient clinic. Polysomnography was performed. We measured the intima-media thickness and incremental elastic modulus (Einc) to assess the mechanical characteristics of the common carotid artery. Arterial endothelial function was evaluated by measuring flow-mediated dilation and glyceryl trinitrate-mediated dilation (GTNMD) of the brachial artery. A total of 24 (47%) children had a desaturation index (DI) >10/h and 7 (14%) had a respiratory event index >10/h. DI >10/h was associated with significantly higher values of Einc (4.0 + or - 0.5 vs. 2.4 + or - 0.4 mm Hg(-1) x 10(3), p=0.003) and GTNMD (18.0 + or - 1.1 vs. 14.1 + or - 1.0 %, p=0.02) after adjustment for age, sex, body mass index, fasting insulin, and leptin. In the univariate analysis, GTNMD correlated positively with DI (r=0.14, p=0.02) after adjustment for age, sex, fasting insulin and leptin. By multivariate analysis with BMI as an additional independent variable, both GTNMD and Einc correlated significantly with DI (beta=0.4, p=0.02 and beta=0.27, p=0.04, respectively). OSA in children is associated with arterial alterations independently from obesity. The increased vasodilation in response to glyceryl trinitrate reflects pre-existing vasoconstriction probably induced by intermittent hypoxia. OSA should be detected early in children with severe obesity.

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy.

PubMed

Brufani, Claudia; Ciampalini, Paolo; Grossi, Armando; Fiori, Rossana; Fintini, Danilo; Tozzi, Alberto; Cappa, Marco; Barbetti, Fabrizio

2010-02-01

Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. The study group included 510 overweight/obese subjects (3-18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta-cell function was estimated by insulinogenic index. Fat mass was measured by dual-energy x-ray absorptiometry. Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA-IR and glucose-stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA-IR = 4.4 +/- 2.5 vs. 3.4 +/- 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.

A Cyber-Attack Detection Model Based on Multivariate Analyses

NASA Astrophysics Data System (ADS)

Sakai, Yuto; Rinsaka, Koichiro; Dohi, Tadashi

In the present paper, we propose a novel cyber-attack detection model based on two multivariate-analysis methods to the audit data observed on a host machine. The statistical techniques used here are the well-known Hayashi's quantification method IV and cluster analysis method. We quantify the observed qualitative audit event sequence via the quantification method IV, and collect similar audit event sequence in the same groups based on the cluster analysis. It is shown in simulation experiments that our model can improve the cyber-attack detection accuracy in some realistic cases where both normal and attack activities are intermingled.

A Hybrid Index for Characterizing Drought Based on a Nonparametric Kernel Estimator

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

Huang, Shengzhi; Huang, Qiang; Leng, Guoyong

This study develops a nonparametric multivariate drought index, namely, the Nonparametric Multivariate Standardized Drought Index (NMSDI), by considering the variations of both precipitation and streamflow. Building upon previous efforts in constructing Nonparametric Multivariate Drought Index, we use the nonparametric kernel estimator to derive the joint distribution of precipitation and streamflow, thus providing additional insights in drought index development. The proposed NMSDI are applied in the Wei River Basin (WRB), based on which the drought evolution characteristics are investigated. Results indicate: (1) generally, NMSDI captures the drought onset similar to Standardized Precipitation Index (SPI) and drought termination and persistence similar tomore » Standardized Streamflow Index (SSFI). The drought events identified by NMSDI match well with historical drought records in the WRB. The performances are also consistent with that by an existing Multivariate Standardized Drought Index (MSDI) at various timescales, confirming the validity of the newly constructed NMSDI in drought detections (2) An increasing risk of drought has been detected for the past decades, and will be persistent to a certain extent in future in most areas of the WRB; (3) the identified change points of annual NMSDI are mainly concentrated in the early 1970s and middle 1990s, coincident with extensive water use and soil reservation practices. This study highlights the nonparametric multivariable drought index, which can be used for drought detections and predictions efficiently and comprehensively.« less

On Restructurable Control System Theory

NASA Technical Reports Server (NTRS)

Athans, M.

1983-01-01

The state of stochastic system and control theory as it impacts restructurable control issues is addressed. The multivariable characteristics of the control problem are addressed. The failure detection/identification problem is discussed as a multi-hypothesis testing problem. Control strategy reconfiguration, static multivariable controls, static failure hypothesis testing, dynamic multivariable controls, fault-tolerant control theory, dynamic hypothesis testing, generalized likelihood ratio (GLR) methods, and adaptive control are discussed.

Ensembles of radial basis function networks for spectroscopic detection of cervical precancer

NASA Technical Reports Server (NTRS)

Tumer, K.; Ramanujam, N.; Ghosh, J.; Richards-Kortum, R.

1998-01-01

The mortality related to cervical cancer can be substantially reduced through early detection and treatment. However, current detection techniques, such as Pap smear and colposcopy, fail to achieve a concurrently high sensitivity and specificity. In vivo fluorescence spectroscopy is a technique which quickly, noninvasively and quantitatively probes the biochemical and morphological changes that occur in precancerous tissue. A multivariate statistical algorithm was used to extract clinically useful information from tissue spectra acquired from 361 cervical sites from 95 patients at 337-, 380-, and 460-nm excitation wavelengths. The multivariate statistical analysis was also employed to reduce the number of fluorescence excitation-emission wavelength pairs required to discriminate healthy tissue samples from precancerous tissue samples. The use of connectionist methods such as multilayered perceptrons, radial basis function (RBF) networks, and ensembles of such networks was investigated. RBF ensemble algorithms based on fluorescence spectra potentially provide automated and near real-time implementation of precancer detection in the hands of nonexperts. The results are more reliable, direct, and accurate than those achieved by either human experts or multivariate statistical algorithms.

Enteral tube feeding alters the oral indigenous microbiota in elderly adults.

PubMed

Takeshita, Toru; Yasui, Masaki; Tomioka, Mikiko; Nakano, Yoshio; Shimazaki, Yoshihiro; Yamashita, Yoshihisa

2011-10-01

Enteral tube feeding is widely used to maintain nutrition for elderly adults with eating difficulties, but its long-term use alters the environment of the oral ecosystem. This study characterized the tongue microbiota of tube-fed elderly adults by analyzing the 16S rRNA gene. The terminal restriction fragment length polymorphism (T-RFLP) profiles of 44 tube-fed subjects were compared with those of 54 subjects fed orally (average age, 86.4 ± 6.9 years). Bar-coded pyrosequencing data were also obtained for a subset of the subjects from each group (15 tube-fed subjects and 16 subjects fed orally). The T-RFLP profiles demonstrated that the microbiota of the tube-fed subjects was distinct from that of the subjects fed orally (permutational multivariate analysis of variance [perMANOVA], P < 0.001). The pyrosequencing data revealed that 22 bacterial genera, including Corynebacterium, Peptostreptococcus, and Fusobacterium, were significantly more predominant in tube-fed subjects, whereas the dominant genera in the subjects fed orally, such as Streptococcus and Veillonella, were present in much lower proportions. Opportunistic pathogens rarely detected in the normal oral microbiota, such as Corynebacterium striatum and Streptococcus agalactiae, were often found in high proportions in tube-fed subjects. The oral indigenous microbiota is disrupted by the use of enteral feeding, allowing health-threatening bacteria to thrive.

Proof of Principle for a Real-Time Pathogen Isolation Media Diagnostic: The Use of Laser-Induced Breakdown Spectroscopy to Discriminate Bacterial Pathogens and Antimicrobial-Resistant Staphylococcus aureus Strains Grown on Blood Agar

PubMed Central

Multari, Rosalie A.; Cremers, David A.; Bostian, Melissa L.; Dupre, Joanne M.

2013-01-01

Laser-Induced Breakdown Spectroscopy (LIBS) is a rapid, in situ, diagnostic technique in which light emissions from a laser plasma formed on the sample are used for analysis allowing automated analysis results to be available in seconds to minutes. This speed of analysis coupled with little or no sample preparation makes LIBS an attractive detection tool. In this study, it is demonstrated that LIBS can be utilized to discriminate both the bacterial species and strains of bacterial colonies grown on blood agar. A discrimination algorithm was created based on multivariate regression analysis of spectral data. The algorithm was deployed on a simulated LIBS instrument system to demonstrate discrimination capability using 6 species. Genetically altered Staphylococcus aureus strains grown on BA, including isogenic sets that differed only by the acquisition of mutations that increase fusidic acid or vancomycin resistance, were also discriminated. The algorithm successfully identified all thirteen cultures used in this study in a time period of 2 minutes. This work provides proof of principle for a LIBS instrumentation system that could be developed for the rapid discrimination of bacterial species and strains demonstrating relatively minor genomic alterations using data collected directly from pathogen isolation media. PMID:24109513

Potential use of MCR-ALS for the identification of coeliac-related biochemical changes in hyperspectral Raman maps from pediatric intestinal biopsies.

PubMed

Fornasaro, Stefano; Vicario, Annalisa; De Leo, Luigina; Bonifacio, Alois; Not, Tarcisio; Sergo, Valter

2018-05-14

Raman hyperspectral imaging is an emerging practice in biological and biomedical research for label free analysis of tissues and cells. Using this method, both spatial distribution and spectral information of analyzed samples can be obtained. The current study reports the first Raman microspectroscopic characterisation of colon tissues from patients with Coeliac Disease (CD). The aim was to assess if Raman imaging coupled with hyperspectral multivariate image analysis is capable of detecting the alterations in the biochemical composition of intestinal tissues associated with CD. The analytical approach was based on a multi-step methodology: duodenal biopsies from healthy and coeliac patients were measured and processed with Multivariate Curve Resolution Alternating Least Squares (MCR-ALS). Based on the distribution maps and the pure spectra of the image constituents obtained from MCR-ALS, interesting biochemical differences between healthy and coeliac patients has been derived. Noticeably, a reduced distribution of complex lipids in the pericryptic space, and a different distribution and abundance of proteins rich in beta-sheet structures was found in CD patients. The output of the MCR-ALS analysis was then used as a starting point for two clustering algorithms (k-means clustering and hierarchical clustering methods). Both methods converged with similar results providing precise segmentation over multiple Raman images of studied tissues.

Algebraic geometric methods for the stabilizability and reliability of multivariable and of multimode systems

NASA Technical Reports Server (NTRS)

Anderson, B. D. O.; Brockett, R. W.; Byrnes, C. I.; Ghosh, B. K.; Stevens, P. K.

1983-01-01

The extent to which feedback can alter the dynamic characteristics (e.g., instability, oscillations) of a control system, possibly operating in one or more modes (e.g., failure versus nonfailure of one or more components) is examined.

Clinical impact of altered T-cell homeostasis in treated HIV patients enrolled in a large observational cohort.

PubMed

Ndumbi, Patricia; Gillis, Jennifer; Raboud, Janet M; Cooper, Curtis; Hogg, Robert S; Montaner, Julio S G; Burchell, Ann N; Loutfy, Mona R; Machouf, Nima; Klein, Marina B; Tsoukas, Chris M

2013-11-28

We investigated the probability of transitioning in or out of the CD3⁺ T-cell homeostatic range during antiretroviral therapy, and we assessed the clinical impact of lost T-cell homeostasis (TCH) on AIDS-defining illnesses (ADIs) or death. Within the Canadian Observational Cohort (CANOC), we studied 4463 antiretroviral therapy (ART)-naive HIV-positive patients initiating combination ART (cART) between 2000 and 2010. CD3⁺ trajectories were estimated using a four state Markov model. CD3⁺ T-cel percentage states were classified as follows: very low (<50%), low (50-64%), normal (65-85%), and high (>85%). Covariates associated with transitioning between states were examined. The association between CD3⁺ T-cell percentage states and time to ADI/death from cART initiation was determined using Cox proportional hazards models. A total of 4463 patients were followed for a median of 3 years. Two thousand, five hundred and eight (56%) patients never transitioned from their baseline CD3⁺ T-cell percentage state; 85% of these had normal TCH. In multivariable analysis, individuals with time-updated low CD4⁺ cell count, time-updated detectable viral load, older age, and hepatitis C virus (HCV) coinfection were less likely to maintain TCH. In the multivariable proportional hazards model, both very low and high CD3⁺ T-cell percentages were associated with increased risk of ADI/death [adjusted hazard ratio=1.91 (95% confidence interval, CI: 1.27-2.89) and hazard ratio=1.49 (95% CI: 1.13-1.96), respectively]. Patients with very low or high CD3⁺ T-cell percentages are at risk for ADIs/death. To our knowledge, this is the first study linking altered TCH and morbidity/mortality in cART-treated HIV-positive patients.

Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection

PubMed Central

Mwanza, Jean-Claude; Warren, Joshua L.; Hochberg, Jessica T.; Budenz, Donald L.; Chang, Robert T.; Ramulu, Pradeep Y.

2014-01-01

Purpose To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. Methods One hundred and ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike’s information criterion (AIC), and prediction confidence interval lengths (PIL). Results For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDX-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT * NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAPFDT, and interaction GDx-TSNIT*NAP-FDT consistently provided better discriminating abilities for detecting early, moderate and severe glaucoma than the best single variable models. Conclusions The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDX-TSNIT * NAP-FDT provides the best glaucoma prediction compared to all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared to using GDx or FDT alone. PMID:24777046

Mining Recent Temporal Patterns for Event Detection in Multivariate Time Series Data

PubMed Central

Batal, Iyad; Fradkin, Dmitriy; Harrison, James; Moerchen, Fabian; Hauskrecht, Milos

2015-01-01

Improving the performance of classifiers using pattern mining techniques has been an active topic of data mining research. In this work we introduce the recent temporal pattern mining framework for finding predictive patterns for monitoring and event detection problems in complex multivariate time series data. This framework first converts time series into time-interval sequences of temporal abstractions. It then constructs more complex temporal patterns backwards in time using temporal operators. We apply our framework to health care data of 13,558 diabetic patients and show its benefits by efficiently finding useful patterns for detecting and diagnosing adverse medical conditions that are associated with diabetes. PMID:25937993

Two-sample tests and one-way MANOVA for multivariate biomarker data with nondetects.

PubMed

Thulin, M

2016-09-10

Testing whether the mean vector of a multivariate set of biomarkers differs between several populations is an increasingly common problem in medical research. Biomarker data is often left censored because some measurements fall below the laboratory's detection limit. We investigate how such censoring affects multivariate two-sample and one-way multivariate analysis of variance tests. Type I error rates, power and robustness to increasing censoring are studied, under both normality and non-normality. Parametric tests are found to perform better than non-parametric alternatives, indicating that the current recommendations for analysis of censored multivariate data may have to be revised. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Liquid chromatography with diode array detection and multivariate curve resolution for the selective and sensitive quantification of estrogens in natural waters.

PubMed

Pérez, Rocío L; Escandar, Graciela M

2014-07-04

Following the green analytical chemistry principles, an efficient strategy involving second-order data provided by liquid chromatography (LC) with diode array detection (DAD) was applied for the simultaneous determination of estriol, 17β-estradiol, 17α-ethinylestradiol and estrone in natural water samples. After a simple pre-concentration step, LC-DAD matrix data were rapidly obtained (in less than 5 min) with a chromatographic system operating isocratically. Applying a second-order calibration algorithm based on multivariate curve resolution with alternating least-squares (MCR-ALS), successful resolution was achieved in the presence of sample constituents that strongly coelute with the analytes. The flexibility of this multivariate model allowed the quantification of the four estrogens in tap, mineral, underground and river water samples. Limits of detection in the range between 3 and 13 ng L(-1), and relative prediction errors from 2 to 11% were achieved. Copyright © 2014 Elsevier B.V. All rights reserved.

A power analysis for multivariate tests of temporal trend in species composition.

PubMed

Irvine, Kathryn M; Dinger, Eric C; Sarr, Daniel

2011-10-01

Long-term monitoring programs emphasize power analysis as a tool to determine the sampling effort necessary to effectively document ecologically significant changes in ecosystems. Programs that monitor entire multispecies assemblages require a method for determining the power of multivariate statistical models to detect trend. We provide a method to simulate presence-absence species assemblage data that are consistent with increasing or decreasing directional change in species composition within multiple sites. This step is the foundation for using Monte Carlo methods to approximate the power of any multivariate method for detecting temporal trends. We focus on comparing the power of the Mantel test, permutational multivariate analysis of variance, and constrained analysis of principal coordinates. We find that the power of the various methods we investigate is sensitive to the number of species in the community, univariate species patterns, and the number of sites sampled over time. For increasing directional change scenarios, constrained analysis of principal coordinates was as or more powerful than permutational multivariate analysis of variance, the Mantel test was the least powerful. However, in our investigation of decreasing directional change, the Mantel test was typically as or more powerful than the other models.

Altered fingerprints: analysis and detection.

PubMed

Yoon, Soweon; Feng, Jianjiang; Jain, Anil K

2012-03-01

The widespread deployment of Automated Fingerprint Identification Systems (AFIS) in law enforcement and border control applications has heightened the need for ensuring that these systems are not compromised. While several issues related to fingerprint system security have been investigated, including the use of fake fingerprints for masquerading identity, the problem of fingerprint alteration or obfuscation has received very little attention. Fingerprint obfuscation refers to the deliberate alteration of the fingerprint pattern by an individual for the purpose of masking his identity. Several cases of fingerprint obfuscation have been reported in the press. Fingerprint image quality assessment software (e.g., NFIQ) cannot always detect altered fingerprints since the implicit image quality due to alteration may not change significantly. The main contributions of this paper are: 1) compiling case studies of incidents where individuals were found to have altered their fingerprints for circumventing AFIS, 2) investigating the impact of fingerprint alteration on the accuracy of a commercial fingerprint matcher, 3) classifying the alterations into three major categories and suggesting possible countermeasures, 4) developing a technique to automatically detect altered fingerprints based on analyzing orientation field and minutiae distribution, and 5) evaluating the proposed technique and the NFIQ algorithm on a large database of altered fingerprints provided by a law enforcement agency. Experimental results show the feasibility of the proposed approach in detecting altered fingerprints and highlight the need to further pursue this problem.

Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

PubMed

Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L

2017-02-01

Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC. © 2016 SETAC.

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation.

PubMed

Isobe, Kazutoshi; Hata, Yoshinobu; Tochigi, Naobumi; Kaburaki, Kyohei; Kobayashi, Hiroshi; Makino, Takashi; Otsuka, Hajime; Sato, Fumitomo; Ishida, Fumiaki; Kikuchi, Naoshi; Hirota, Nao; Sato, Keita; Sano, Go; Sugino, Keishi; Sakamoto, Susumu; Takai, Yujiro; Shibuya, Kazutoshi; Iyoda, Akira; Homma, Sakae

2014-04-01

Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non-small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations. We studied 70 patients with EGFR mutation-positive non-small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion. BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864-8.547; p < 0.001). Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

Chamber evaluation of a portable GC with tunable retention and microsensor-array detection for indoor air quality monitoring.

PubMed

Lu, Chia Jung; Jin, Chunguang; Zellers, Edward T

2006-02-01

The evaluation of a novel prototype instrument designed for on-site determinations of VOC mixtures found in indoor working environments is described. The instrument contains a miniature multi-stage preconcentrator, a dual-column separation module with pressure-tunable retention capabilities, and an integrated array of three polymer-coated surface acoustic wave sensors. It was challenged with dynamic test-atmospheres of a set of 15 common indoor air contaminants at parts-per-billion concentrations within a stainless-steel chamber under a range of conditions. Vapours were reliably identified at a known level of confidence by combining column retention times with sensor-array response patterns and applying a multivariate statistical test of pattern fidelity for the chromatographically resolved vapours. Estimates of vapour concentrations fell within 7% on average of those determined by EPA Method TO-17, and limits of detection ranged from 0.2 to 28 ppb at 25 degrees C for 1 L samples collected and analyzed in <12 min. No significant humidity effects were observed (0-90% RH). Increasing the chamber temperature from 25 to 30 degrees C reduced the retention times of the more volatile analytes which, in turn, demanded alterations in the scheduling of column-junction-point pressure (flow) modulations performed during the analysis. Reductions in sensor sensitivities with increasing temperature were predictable and similar among the sensors in the array such that most response patterns were not altered significantly. Short-term fluctuations in concentration were accurately tracked by the instrument. Results indicate that this type of instrument could provide routine, semi-autonomous, near-real-time, multi-vapour monitoring in support of efforts to assess air quality in office environments.

Drop coating deposition Raman spectroscopy of blood plasma for the detection of colorectal cancer

NASA Astrophysics Data System (ADS)

Li, Pengpeng; Chen, Changshui; Deng, Xiaoyuan; Mao, Hua; Jin, Shaoqin

2015-03-01

We have recently applied the technique of drop coating deposition Raman (DCDR) spectroscopy for colorectal cancer (CRC) detection using blood plasma. The aim of this study was to develop a more convenient and stable method based on blood plasma for noninvasive CRC detection. Significant differences are observed in DCDR spectra between healthy (n=105) and cancer (n=75) plasma from 15 CRC patients and 21 volunteers, particularly in the spectra that are related to proteins, nucleic acids, and β-carotene. The multivariate analysis principal components analysis and the linear discriminate analysis, together with leave-one-out, cross validation were used on DCDR spectra and yielded a sensitivity of 100% (75/75) and specificity of 98.1% (103/105) for detection of CRC. This study demonstrates that DCDR spectroscopy of blood plasma associated with multivariate statistical algorithms has the potential for the noninvasive detection of CRC.

Proteomic Signatures of the Zebrafish (Danio rerio) Embryo: Sensitivity and Specificity in Toxicity Assessment of Chemicals.

PubMed

Hanisch, Karen; Küster, Eberhard; Altenburger, Rolf; Gündel, Ulrike

2010-01-01

Studies using embryos of the zebrafish Danio rerio (DarT) instead of adult fish for characterising the (eco-) toxic potential of chemicals have been proposed as animal replacing methods. Effect analysis at the molecular level might enhance sensitivity, specificity, and predictive value of the embryonal studies. The present paper aimed to test the potential of toxicoproteomics with zebrafish eleutheroembryos for sensitive and specific toxicity assessment. 2-DE-based toxicoproteomics was performed applying low-dose (EC(10)) exposure for 48 h with three-model substances Rotenone, 4,6-dinitro-o-cresol (DNOC) and Diclofenac. By multivariate "pattern-only" PCA and univariate statistical analyses, alterations in the embryonal proteome were detectable in nonetheless visibly intact organisms and treatment with the three substances was distinguishable at the molecular level. Toxicoproteomics enabled the enhancement of sensitivity and specificity of the embryonal toxicity assay and bear the potency to identify protein markers serving as general stress markers and early diagnosis of toxic stress.

Proteomic Signatures of the Zebrafish (Danio rerio) Embryo: Sensitivity and Specificity in Toxicity Assessment of Chemicals

PubMed Central

Hanisch, Karen; Küster, Eberhard; Altenburger, Rolf; Gündel, Ulrike

2010-01-01

Studies using embryos of the zebrafish Danio rerio (DarT) instead of adult fish for characterising the (eco-) toxic potential of chemicals have been proposed as animal replacing methods. Effect analysis at the molecular level might enhance sensitivity, specificity, and predictive value of the embryonal studies. The present paper aimed to test the potential of toxicoproteomics with zebrafish eleutheroembryos for sensitive and specific toxicity assessment. 2-DE-based toxicoproteomics was performed applying low-dose (EC10) exposure for 48 h with three-model substances Rotenone, 4,6-dinitro-o-cresol (DNOC) and Diclofenac. By multivariate “pattern-only” PCA and univariate statistical analyses, alterations in the embryonal proteome were detectable in nonetheless visibly intact organisms and treatment with the three substances was distinguishable at the molecular level. Toxicoproteomics enabled the enhancement of sensitivity and specificity of the embryonal toxicity assay and bear the potency to identify protein markers serving as general stress markers and early diagnosis of toxic stress. PMID:22084678

Seagrass burial by dredged sediments: benthic community alteration, secondary production loss, biotic index reaction and recovery possibility.

PubMed

Tu Do, V; de Montaudouin, Xavier; Blanchet, Hugues; Lavesque, Nicolas

2012-11-01

In 2005, dredging activities in Arcachon Bay (France) led in burying 320,000 m(2) of Zostera noltii intertidal seagrass. Recovery by macrobenthos and seagrass was monitored. Six months after works, seagrass was absent and macrobenthos drastically different from surrounding vegetated stations. Rapidly and due to sediment dispersal, disposal area was divided into a sandflat with a specific benthic community which maintained its difference until the end of the survey (2010), and a mudflat where associated fauna became similar to those in adjacent seagrass. Macrobenthic community needs 3 years to recover while seagrass needs 5 years to recover in the station impacted by mud. The secondary production loss due to works was low. In this naturally carbon enriched system, univariate biotic indices did not perform well to detect seagrass destruction and recovery. Multivariate index MISS gave more relevant conclusions and a simplified version was tested with success, at this local scale. Copyright © 2012 Elsevier Ltd. All rights reserved.

Meal Detection in Patients With Type 1 Diabetes: A New Module for the Multivariable Adaptive Artificial Pancreas Control System.

PubMed

Turksoy, Kamuran; Samadi, Sediqeh; Feng, Jianyuan; Littlejohn, Elizabeth; Quinn, Laurie; Cinar, Ali

2016-01-01

A novel meal-detection algorithm is developed based on continuous glucose measurements. Bergman's minimal model is modified and used in an unscented Kalman filter for state estimations. The estimated rate of appearance of glucose is used for meal detection. Data from nine subjects are used to assess the performance of the algorithm. The results indicate that the proposed algorithm works successfully with high accuracy. The average change in glucose levels between the meals and the detection points is 16(±9.42) [mg/dl] for 61 successfully detected meals and snacks. The algorithm is developed as a new module of an integrated multivariable adaptive artificial pancreas control system. Meal detection with the proposed method is used to administer insulin boluses and prevent most of postprandial hyperglycemia without any manual meal announcements. A novel meal bolus calculation method is proposed and tested with the UVA/Padova simulator. The results indicate significant reduction in hyperglycemia.

An Efficient Pattern Mining Approach for Event Detection in Multivariate Temporal Data

PubMed Central

Batal, Iyad; Cooper, Gregory; Fradkin, Dmitriy; Harrison, James; Moerchen, Fabian; Hauskrecht, Milos

2015-01-01

This work proposes a pattern mining approach to learn event detection models from complex multivariate temporal data, such as electronic health records. We present Recent Temporal Pattern mining, a novel approach for efficiently finding predictive patterns for event detection problems. This approach first converts the time series data into time-interval sequences of temporal abstractions. It then constructs more complex time-interval patterns backward in time using temporal operators. We also present the Minimal Predictive Recent Temporal Patterns framework for selecting a small set of predictive and non-spurious patterns. We apply our methods for predicting adverse medical events in real-world clinical data. The results demonstrate the benefits of our methods in learning accurate event detection models, which is a key step for developing intelligent patient monitoring and decision support systems. PMID:26752800

Root Cause Analysis of Quality Defects Using HPLC-MS Fingerprint Knowledgebase for Batch-to-batch Quality Control of Herbal Drugs.

PubMed

Yan, Binjun; Fang, Zhonghua; Shen, Lijuan; Qu, Haibin

2015-01-01

The batch-to-batch quality consistency of herbal drugs has always been an important issue. To propose a methodology for batch-to-batch quality control based on HPLC-MS fingerprints and process knowledgebase. The extraction process of Compound E-jiao Oral Liquid was taken as a case study. After establishing the HPLC-MS fingerprint analysis method, the fingerprints of the extract solutions produced under normal and abnormal operation conditions were obtained. Multivariate statistical models were built for fault detection and a discriminant analysis model was built using the probabilistic discriminant partial-least-squares method for fault diagnosis. Based on multivariate statistical analysis, process knowledge was acquired and the cause-effect relationship between process deviations and quality defects was revealed. The quality defects were detected successfully by multivariate statistical control charts and the type of process deviations were diagnosed correctly by discriminant analysis. This work has demonstrated the benefits of combining HPLC-MS fingerprints, process knowledge and multivariate analysis for the quality control of herbal drugs. Copyright © 2015 John Wiley & Sons, Ltd.

Laser ablation molecular isotopic spectroscopy (LAMIS) towards the determination of multivariate LODs via PLS calibration model of 10B and 11B Boric acid mixtures

NASA Astrophysics Data System (ADS)

Harris, C. D.; Profeta, Luisa T. M.; Akpovo, Codjo A.; Johnson, Lewis; Stowe, Ashley C.

2017-05-01

A calibration model was created to illustrate the detection capabilities of laser ablation molecular isotopic spectroscopy (LAMIS) discrimination in isotopic analysis. The sample set contained boric acid pellets that varied in isotopic concentrations of 10B and 11B. Each sample set was interrogated with a Q-switched Nd:YAG ablation laser operating at 532 nm. A minimum of four band heads of the β system B2∑ -> Χ2∑transitions were identified and verified with previous literature on BO molecular emission lines. Isotopic shifts were observed in the spectra for each transition and used as the predictors in the calibration model. The spectra along with their respective 10/11B isotopic ratios were analyzed using Partial Least Squares Regression (PLSR). An IUPAC novel approach for determining a multivariate Limit of Detection (LOD) interval was used to predict the detection of the desired isotopic ratios. The predicted multivariate LOD is dependent on the variation of the instrumental signal and other composites in the calibration model space.

Microsatellite alterations as clonal markers for the detection of human cancer.

PubMed Central

Mao, L; Lee, D J; Tockman, M S; Erozan, Y S; Askin, F; Sidransky, D

1994-01-01

Microsatellite instability has been reported to be an important feature of tumors from hereditary nonpolyposis colorectal carcinoma (HNPCC) patients. The recent discovery of genetic instability in small cell lung carcinoma, a neoplasm not associated with HNPCC, led us to investigate the possible presence of microsatellite alterations in other tumor types. We examined 52 microsatellite repeat sequences in the DNA of normal and tumor pairs from 100 head and neck, bladder, and lung cancer patients by the polymerase chain reaction. Although alterations were rare in dinucleotide repeats, larger (tri- or tetranucleotide) repeats were found to be more prone to expansion or deletion. We screened 100 tumors with a panel of nine tri- and tetranucleotide repeat markers and identified 26 (26%) that displayed alterations in at least one locus. This observation prompted us to examine the possibility of using microsatellite alterations as markers to detect clonal tumor-derived cell populations in pathologic samples. The identical microsatellite alterations detected in the primary tumors were successfully identified in corresponding urine, sputum, and surgical margins from affected patients. This study demonstrates that appropriately selected microsatellite loci are commonly altered in many cancers and can serve as clonal markers for their detection. Images PMID:7937908

Enteral Tube Feeding Alters the Oral Indigenous Microbiota in Elderly Adults ▿ †

PubMed Central

Takeshita, Toru; Yasui, Masaki; Tomioka, Mikiko; Nakano, Yoshio; Shimazaki, Yoshihiro; Yamashita, Yoshihisa

2011-01-01

Enteral tube feeding is widely used to maintain nutrition for elderly adults with eating difficulties, but its long-term use alters the environment of the oral ecosystem. This study characterized the tongue microbiota of tube-fed elderly adults by analyzing the 16S rRNA gene. The terminal restriction fragment length polymorphism (T-RFLP) profiles of 44 tube-fed subjects were compared with those of 54 subjects fed orally (average age, 86.4 ± 6.9 years). Bar-coded pyrosequencing data were also obtained for a subset of the subjects from each group (15 tube-fed subjects and 16 subjects fed orally). The T-RFLP profiles demonstrated that the microbiota of the tube-fed subjects was distinct from that of the subjects fed orally (permutational multivariate analysis of variance [perMANOVA], P < 0.001). The pyrosequencing data revealed that 22 bacterial genera, including Corynebacterium, Peptostreptococcus, and Fusobacterium, were significantly more predominant in tube-fed subjects, whereas the dominant genera in the subjects fed orally, such as Streptococcus and Veillonella, were present in much lower proportions. Opportunistic pathogens rarely detected in the normal oral microbiota, such as Corynebacterium striatum and Streptococcus agalactiae, were often found in high proportions in tube-fed subjects. The oral indigenous microbiota is disrupted by the use of enteral feeding, allowing health-threatening bacteria to thrive. PMID:21821752

UPLC-QTOFMS-based metabolomic analysis of the serum of hypoxic preconditioning mice

PubMed Central

Liu, Jie; Zhang, Gang; Chen, Dewei; Chen, Jian; Yuan, Zhi-Bin; Zhang, Er-Long; Gao, Yi-Xing; Xu, Gang; Sun, Bing-Da; Liao, Wenting; Gao, Yu-Qi

2017-01-01

Hypoxic preconditioning (HPC) is well-known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC. PMID:28901489

Selective sensing of vapors of similar dielectric constants using peptide-capped gold nanoparticles on individual multivariable transducers.

PubMed

Nagraj, Nandini; Slocik, Joseph M; Phillips, David M; Kelley-Loughnane, Nancy; Naik, Rajesh R; Potyrailo, Radislav A

2013-08-07

Peptide-capped AYSSGAPPMPPF gold nanoparticles were demonstrated for highly selective chemical vapor sensing using individual multivariable inductor-capacitor-resistor (LCR) resonators. Their multivariable response was achieved by measuring their resonance impedance spectra followed by multivariate spectral analysis. Detection of model toxic vapors and chemical agent simulants, such as acetonitrile, dichloromethane and methyl salicylate, was performed. Dichloromethane (dielectric constant εr = 9.1) and methyl salicylate (εr = 9.0) were discriminated using a single sensor. These sensing materials coupled to multivariable transducers can provide numerous opportunities for tailoring the vapor response selectivity based on the diversity of the amino acid composition of the peptides, and by the modulation of the nature of peptide-nanoparticle interactions through designed combinations of hydrophobic and hydrophilic amino acids.

HYTESS 2: A Hypothetical Turbofan Engine Simplified Simulation with multivariable control and sensor analytical redundancy

NASA Technical Reports Server (NTRS)

Merrill, W. C.

1986-01-01

A hypothetical turbofan engine simplified simulation with a multivariable control and sensor failure detection, isolation, and accommodation logic (HYTESS II) is presented. The digital program, written in FORTRAN, is self-contained, efficient, realistic and easily used. Simulated engine dynamics were developed from linearized operating point models. However, essential nonlinear effects are retained. The simulation is representative of the hypothetical, low bypass ratio turbofan engine with an advanced control and failure detection logic. Included is a description of the engine dynamics, the control algorithm, and the sensor failure detection logic. Details of the simulation including block diagrams, variable descriptions, common block definitions, subroutine descriptions, and input requirements are given. Example simulation results are also presented.

Alterations of functional connectivities from early to middle adulthood: Clues from multivariate pattern analysis of resting-state fMRI data.

PubMed

Tian, Lixia; Ma, Lin; Wang, Linlin

2016-04-01

In contrast to extended research interests in the maturation and aging of human brain, alterations of brain structure and function from early to middle adulthood have been much less studied. The aim of the present study was to investigate the extent and pattern of the alterations of functional interactions between brain regions from early to middle adulthood. We carried out the study by multivariate pattern analysis of resting-state fMRI (RS-fMRI) data of 63 adults aged 18 to 45 years. Specifically, using elastic net, we performed brain age estimation and age-group classification (young adults aged 18-28 years vs. middle-aged adults aged 35-45 years) based on the resting-state functional connectivities (RSFCs) between 160 regions of interest (ROIs) evaluated on the RS-fMRI data of each subject. The results indicate that the estimated brain ages were significantly correlated with the chronological age (R=0.78, MAE=4.81), and a classification rate of 94.44% and area under the receiver operating characteristic curve (AUC) of 0.99 were obtained when classifying the young and middle-aged adults. These results provide strong evidence that functional interactions between brain regions undergo notable alterations from early to middle adulthood. By analyzing the RSFCs that contribute to brain age estimation/age-group classification, we found that a majority of the RSFCs were inter-network, and we speculate that inter-network RSFCs might mature late but age early as compared to intra-network ones. In addition, the strengthening/weakening of the RSFCs associated with the left/right hemispheric ROIs, the weakening of cortico-cerebellar RSFCs and the strengthening of the RSFCs between the default mode network and other networks contributed much to both brain age estimation and age-group classification. All these alterations might reflect that aging of brain function is already in progress in middle adulthood. Overall, the present study indicated that the RSFCs undergo notable alterations from early to middle adulthood and highlighted the necessity of careful considerations of possible influences of these alterations in related studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered blood glucose concentration is associated with risk of death among patients with community-acquired Gram-negative rod bacteremia.

PubMed

Peralta, Galo; Sánchez, M Blanca; Garrido, J Carlos; Ceballos, Begoña; Mateos, Fátima; De Benito, Inés; Roiz, M Pía

2010-06-22

Altered blood glucose concentration is commonly observed in patients with sepsis, even among those without hypoglycemic treatments or history of diabetes mellitus. These alterations in blood glucose are potentially detrimental, although the precise relationship with outcome in patients with bacteremia has not been yet determined. A retrospective cohort study design for analyzing patients with Gram negative rod bacteremia was employed, with the main outcome measure being in-hospital mortality. Patients were stratified in quintiles accordingly deviation of the blood glucose concentration from a central value with lowest mortality. Cox proportional-hazards regression model was used for determining the relationship of same day of bacteremia blood glucose and death. Of 869 patients identified 63 (7.4%) died. Same day of bacteremia blood glucose concentration had a U-shaped relationship with in-hospital mortality. The lowest mortality (2%) was detected in the range of blood glucose concentration from 150 to 160 mg/dL. Greater deviation of blood glucose concentration from the central value of this range (155 mg/dL, reference value) was directly associated with higher risk of death (p = 0.002, chi for trend). The low-risk group (quintile 1) had a mortality of 3.3%, intermediate-risk group (quintiles 2, 3 and 4) a mortality of 7.1%, and the high-risk group (quintile 5) a mortality of 12.05%. In a multivariable Cox regression model, the hazard ratio for death among patients in the intermediate-risk group as compared with that in the low risk group was 2.88 (95% confidence interval, 1.01 to 8.18; P = 0.048), and for the high risk group it was 4.26 (95% confidence interval, 1.41 to 12.94; P = 0.01). Same day of bacteremia blood glucose concentration is related with outcome of patients with Gram-negative rod bacteremia. Lowest mortality is detected in patients with blood glucose concentration in an interval of 150-160 mg/dL. Deviations from these values are associated with an increased risk of death.

Altered blood glucose concentration is associated with risk of death among patients with community-acquired Gram-negative rod bacteremia

PubMed Central

2010-01-01

Background Altered blood glucose concentration is commonly observed in patients with sepsis, even among those without hypoglycemic treatments or history of diabetes mellitus. These alterations in blood glucose are potentially detrimental, although the precise relationship with outcome in patients with bacteremia has not been yet determined. Methods A retrospective cohort study design for analyzing patients with Gram negative rod bacteremia was employed, with the main outcome measure being in-hospital mortality. Patients were stratified in quintiles accordingly deviation of the blood glucose concentration from a central value with lowest mortality. Cox proportional-hazards regression model was used for determining the relationship of same day of bacteremia blood glucose and death. Results Of 869 patients identified 63 (7.4%) died. Same day of bacteremia blood glucose concentration had a U-shaped relationship with in-hospital mortality. The lowest mortality (2%) was detected in the range of blood glucose concentration from 150 to 160 mg/dL. Greater deviation of blood glucose concentration from the central value of this range (155 mg/dL, reference value) was directly associated with higher risk of death (p = 0.002, chi for trend). The low-risk group (quintile 1) had a mortality of 3.3%, intermediate-risk group (quintiles 2, 3 and 4) a mortality of 7.1%, and the high-risk group (quintile 5) a mortality of 12.05%. In a multivariable Cox regression model, the hazard ratio for death among patients in the intermediate-risk group as compared with that in the low risk group was 2.88 (95% confidence interval, 1.01 to 8.18; P = 0.048), and for the high risk group it was 4.26 (95% confidence interval, 1.41 to 12.94; P = 0.01). Conclusions Same day of bacteremia blood glucose concentration is related with outcome of patients with Gram-negative rod bacteremia. Lowest mortality is detected in patients with blood glucose concentration in an interval of 150-160 mg/dL. Deviations from these values are associated with an increased risk of death. PMID:20569435

Esophageal cancer detection based on tissue surface-enhanced Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan

2013-01-01

The capability of using silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) spectroscopy combined with principal component analysis (PCA) and linear discriminate analysis (LDA) to differentiate esophageal cancer tissue from normal tissue was presented. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues. PCA-LDA multivariate analysis of the measured tissue SERS spectra achieved diagnostic sensitivity of 90.9% and specificity of 97.8%. This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection.

Fire frequency, agricultural history and the multivariate control of pine savanna understorey plant diversity

Treesearch

Joseph W. Veldman; Lars A. Brudvig; Ellen I. Damschen; John L. Orrock; W. Brett Mattingly; Joan L. Walker

2014-01-01

Question: Human-altered disturbance regimes and agricultural land uses are broadly associated with reduced plant species diversity in terrestrial ecosystems. In this study, we seek to understand how fire frequency and agricultural land-use history influence savanna understorey plant diversity through complex relationships (i.e. indirect effects) among multiple...

Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis

PubMed Central

Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh

2015-01-01

Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer. PMID:25797243

Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.

PubMed

Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

2015-03-30

Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.

Central sleep apnea detection from ECG-derived respiratory signals. Application of multivariate recurrence plot analysis.

PubMed

Maier, C; Dickhaus, H

2010-01-01

This study examines the suitability of recurrence plot analysis for the problem of central sleep apnea (CSA) detection and delineation from ECG-derived respiratory (EDR) signals. A parameter describing the average length of vertical line structures in recurrence plots is calculated at a time resolution of 1 s as 'instantaneous trapping time'. Threshold comparison of this parameter is used to detect ongoing CSA. In data from 26 patients (duration 208 h) we assessed sensitivity for detection of CSA and mixed apnea (MSA) events by comparing the results obtained from 8-channel Holter ECGs to the annotations (860 CSA, 480 MSA) of simultaneously registered polysomnograms. Multivariate combination of the EDR from different ECG leads improved the detection accuracy significantly. When all eight leads were considered, an average instantaneous vertical line length above 5 correctly identified 1126 of the 1340 events (sensitivity 84%) with a total number of 1881 positive detections. We conclude that recurrence plot analysis is a promising tool for detection and delineation of CSA epochs from EDR signals with high time resolution. Moreover, the approach is likewise applicable to directly measured respiratory signals.

Multivariate multiscale entropy of financial markets

NASA Astrophysics Data System (ADS)

Lu, Yunfan; Wang, Jun

2017-11-01

In current process of quantifying the dynamical properties of the complex phenomena in financial market system, the multivariate financial time series are widely concerned. In this work, considering the shortcomings and limitations of univariate multiscale entropy in analyzing the multivariate time series, the multivariate multiscale sample entropy (MMSE), which can evaluate the complexity in multiple data channels over different timescales, is applied to quantify the complexity of financial markets. Its effectiveness and advantages have been detected with numerical simulations with two well-known synthetic noise signals. For the first time, the complexity of four generated trivariate return series for each stock trading hour in China stock markets is quantified thanks to the interdisciplinary application of this method. We find that the complexity of trivariate return series in each hour show a significant decreasing trend with the stock trading time progressing. Further, the shuffled multivariate return series and the absolute multivariate return series are also analyzed. As another new attempt, quantifying the complexity of global stock markets (Asia, Europe and America) is carried out by analyzing the multivariate returns from them. Finally we utilize the multivariate multiscale entropy to assess the relative complexity of normalized multivariate return volatility series with different degrees.

ALK gene copy number gain and its clinical significance in hepatocellular carcinoma.

PubMed

Jia, Shou-Wei; Fu, Sha; Wang, Fang; Shao, Qiong; Huang, Hong-Bing; Shao, Jian-Yong

2014-01-07

To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients. A total of 213 cases of HCC were examined by fluorescent in situ hybridization using dual color break-apart ALK probes for the detection of chromosomal translocation and gene copy number gain. HCC tissue microarrays were constructed, and the correlation between the ALK status and clinicopathological variables was assessed by χ(2) test or Fisher's exact test. Survival analysis was estimated using the Kaplan-Meier approach with a Log-rank test. Univariate and multivariate analyses of clinical variables were performed using the Cox proportional hazards regression model. ALK gene translocation was not observed in any of the HCC cases included in the present study. ALK gene copy number gain (ALK/CNG) (≥ 4 copies/cell) was detected in 28 (13.15%) of the 213 HCC patients. The 3-year progression-free-survival (PFS) rate for ALK/CNG-positive HCC patients was significantly poorer than ALK/CNG-negative patients (27.3% vs 42.5%, P = 0.048), especially for patients with advanced stage III/IV (0% vs 33.5%, P = 0.007), and patients with grade III disease (24.8% vs 49.9%, P = 0.023). ALK/CNG-positive HCC patients had a significantly poorer prognosis than ALK/CNG-negative patients in the subgroup that was negative for serum hepatitis B virus DNA, with significantly different 3-year overall survival rates (18.2% vs 63.6%, P = 0.021) and PFS rates (18.2% vs 46.9%, P = 0.019). Multivariate Cox proportional hazards regression analysis suggested that ALK/CNG prevalence can predict death in HCC (HR = 1.596; 95%CI: 1.008-2.526, P = 0.046). ALK/CNG, but not translocation of ALK, is present in HCC and may be an unfavorable prognostic predictor.

ALK gene copy number gain and its clinical significance in hepatocellular carcinoma

PubMed Central

Jia, Shou-Wei; Fu, Sha; Wang, Fang; Shao, Qiong; Huang, Hong-Bing; Shao, Jian-Yong

2014-01-01

AIM: To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients. METHODS: A total of 213 cases of HCC were examined by fluorescent in situ hybridization using dual color break-apart ALK probes for the detection of chromosomal translocation and gene copy number gain. HCC tissue microarrays were constructed, and the correlation between the ALK status and clinicopathological variables was assessed by χ2 test or Fisher’s exact test. Survival analysis was estimated using the Kaplan-Meier approach with a Log-rank test. Univariate and multivariate analyses of clinical variables were performed using the Cox proportional hazards regression model. RESULTS: ALK gene translocation was not observed in any of the HCC cases included in the present study. ALK gene copy number gain (ALK/CNG) (≥ 4 copies/cell) was detected in 28 (13.15%) of the 213 HCC patients. The 3-year progression-free-survival (PFS) rate for ALK/CNG-positive HCC patients was significantly poorer than ALK/CNG-negative patients (27.3% vs 42.5%, P = 0.048), especially for patients with advanced stage III/IV (0% vs 33.5%, P = 0.007), and patients with grade III disease (24.8% vs 49.9%, P = 0.023). ALK/CNG-positive HCC patients had a significantly poorer prognosis than ALK/CNG-negative patients in the subgroup that was negative for serum hepatitis B virus DNA, with significantly different 3-year overall survival rates (18.2% vs 63.6%, P = 0.021) and PFS rates (18.2% vs 46.9%, P = 0.019). Multivariate Cox proportional hazards regression analysis suggested that ALK/CNG prevalence can predict death in HCC (HR = 1.596; 95%CI: 1.008-2.526, P = 0.046). CONCLUSION: ALK/CNG, but not translocation of ALK, is present in HCC and may be an unfavorable prognostic predictor. PMID:24415871

DNA methylation screening of primary prostate tumors identifies SRD5A2 and CYP11A1 as candidate markers for assessing risk of biochemical recurrence.

PubMed

Horning, Aaron M; Awe, Julius A; Wang, Chiou-Miin; Liu, Joseph; Lai, Zhao; Wang, Vickie Yao; Jadhav, Rohit R; Louie, Anna D; Lin, Chun-Lin; Kroczak, Tad; Chen, Yidong; Jin, Victor X; Abboud-Werner, Sherry L; Leach, Robin J; Hernandez, Javior; Thompson, Ian M; Saranchuk, Jeff; Drachenberg, Darrel; Chen, Chun-Liang; Mai, Sabine; Huang, Tim Hui-Ming

2015-11-01

Altered DNA methylation in CpG islands of gene promoters has been implicated in prostate cancer (PCa) progression and can be used to predict disease outcome. In this study, we determine whether methylation changes of androgen biosynthesis pathway (ABP)-related genes in patients' plasma cell-free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR). Methyl-binding domain capture sequencing (MBDCap-seq) was used to identify differentially methylated regions (DMRs) in primary tumors of patients who subsequently developed BCR or not, respectively. Methylation pyrosequencing of candidate loci was validated in cfDNA samples of 86 PCa patients taken at and/or post-radical prostatectomy (RP) using univariate and multivariate prediction analyses. Putative DMRs in 13 of 30 ABP-related genes were found between tumors of BCR (n = 12) versus no evidence of disease (NED) (n = 15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci-SRD5A2 and CYP11A1, which also correlated with their decreased expression, in tumors with subsequent BCR development. Their aberrant cfDNA methylation was also associated with detectable levels of PSA taken after patients' post-RP. Multivariate analysis of the change in cfDNA methylation at all of CpG sites measured along with patient's treatment history predicted if a patient will develop BCR with 77.5% overall accuracy. Overall, increased DNA methylation of SRD5A2 and CYP11A1 related to androgen biosynthesis functions may play a role in BCR after patients' RP. The correlation between aberrant cfDNA methylation and detectable PSA in post-RP further suggests their utility as predictive markers for PCa recurrence. . © 2015 Wiley Periodicals, Inc.

Detecting the impact of bank and channel modification on invertebrate communities in Mediterranean temporary streams (Sardinia, SW Italy).

PubMed

Buffagni, Andrea; Tenchini, Roberta; Cazzola, Marcello; Erba, Stefania; Balestrini, Raffaella; Belfiore, Carlo; Pagnotta, Romano

2016-09-15

We hypothesized that reach-scale, bank and channel modification would impact benthic communities in temporary rivers of Sardinia, when pollution and water abstraction are not relevant. A range of variables were considered, which include both artificial structures/alterations and natural features observed in a stream reach. Multivariate regression trees (MRT) were used to assess the effects of the explanatory variables on invertebrate assemblages and five groups, characterized by different habitat modification and/or features, were recognized. Four node variables determined the splits in the MRT analysis: channel reinforcement, tree-related bank and channel habitats, channel modification and bank modification. Continuity of trees in the river corridor diverged among MRT groups and significant differences among groups include presence of alders, extent of channel shading and substrate diversity. Also, the percentage of in-stream organic substrates, in particular CPOM/Xylal, showed highly significant differences among groups. For practical applications, thresholds for the extent of channel reinforcement (40%) and modification (10%) and for bank alteration (≈30%) were provided, that can be used to guide the implementation of restoration measures. In moderately altered river reaches, a significant extent of tree-related habitats (≈5%) can noticeably mitigate the effects of morphological alteration on aquatic invertebrates. The outcomes highlight the importance of riparian zone management as an opportune, achievable prospect in the restoration of Mediterranean temporary streams. The impact of bank and channel modification on ecological status (sensu WFD) was investigated and the tested benthic metrics, especially those based on abundance data, showed legible differences among MRT groups. Finally, bank and channel modification appears to be a potential threat for the conservation of a few Sardo-Corsican endemic species. The introduction of management criteria that openly use information on endemic species seems crucial to reduce the risk of improving overall ecological status while depleting biodiversity. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of livestock on a mosquito community (Diptera: Culicidae) in a Brazilian tropical dry forest.

PubMed

Santos, Cleandson Ferreira; Borges, Magno

2015-01-01

This study evaluated the effects of cattle removal on the Culicidae mosquito community structure in a tropical dry forest in Brazil. Culicidae were collected during dry and wet seasons in cattle presence and absence between August 2008 and October 2010 and assessed using multivariate statistical models. Cattle removal did not significantly alter Culicidae species richness and abundance. However, alterations were noted in Culicidae community composition. This is the first study to evaluate the impact of cattle removal on Culicidae community structure in Brazil and demonstrates the importance of assessing ecological parameters such as community species composition.

Association of Internalized and Social Network Level HIV Stigma With High-Risk Condomless Sex Among HIV-Positive African American Men.

PubMed

Wagner, Glenn J; Bogart, Laura M; Klein, David J; Green, Harold D; Mutchler, Matt G; McDavitt, Bryce; Hilliard, Charles

2016-08-01

We examined whether internalized HIV stigma and perceived HIV stigma from social network members (alters), including the most popular and most similar alter, predicted condomless intercourse with negative or unknown HIV status partners among 125 African American HIV-positive men. In a prospective, observational study, participants were administered surveys at baseline and months 6 and 12, with measures including sexual behavior, internalized HIV stigma, and an egocentric social network assessment that included several measures of perceived HIV stigma among alters. In longitudinal multivariable models comparing the relative predictive value of internalized stigma versus various measures of alter stigma, significant predictors of having had condomless intercourse included greater internalized HIV stigma (in all models), the perception that a popular (well-connected) alter or alter most like the participant agrees with an HIV stigma belief, and the interaction of network density with having any alter that agrees with a stigma belief. The interaction indicated that the protective effect of greater density (connectedness between alters) in terms of reduced risk behavior dissipated in the presence of perceived alter stigma. These findings call for interventions that help people living with HIV to cope with their diagnosis and reduce stigma, and inform the targets of social network-based and peer-driven HIV prevention interventions.

Association of Internalized and Social Network Level HIV Stigma With High-Risk Condomless Sex Among HIV-Positive African American Men

PubMed Central

Bogart, Laura M.; Klein, David J.; Green, Harold D.; Mutchler, Matt G.; McDavitt, Bryce; Hilliard, Charles

2016-01-01

We examined whether internalized HIV stigma and perceived HIV stigma from social network members (alters), including the most popular and most similar alter, predicted condomless intercourse with negative or unknown HIV status partners among 125 African American HIV-positive men. In a prospective, observational study, participants were administered surveys at baseline and months 6 and 12, with measures including sexual behavior, internalized HIV stigma, and an egocentric social network assessment that included several measures of perceived HIV stigma among alters. In longitudinal multivariable models comparing the relative predictive value of internalized stigma versus various measures of alter stigma, significant predictors of having had condomless intercourse included greater internalized HIV stigma (in all models), the perception that a popular (well-connected) alter or alter most like the participant agrees with an HIV stigma belief, and the interaction of network density with having any alter that agrees with a stigma belief. The interaction indicated that the protective effect of greater density (connectedness between alters) in terms of reduced risk behavior dissipated in the presence of perceived alter stigma. These findings call for interventions that help people living with HIV to cope with their diagnosis and reduce stigma, and inform the targets of social network-based and peer-driven HIV prevention interventions. PMID:26718361

Application of reflectance spectroscopies (FTIR-ATR & FT-NIR) coupled with multivariate methods for robust in vivo detection of begomovirus infection in papaya leaves

NASA Astrophysics Data System (ADS)

Haq, Quazi M. I.; Mabood, Fazal; Naureen, Zakira; Al-Harrasi, Ahmed; Gilani, Sayed A.; Hussain, Javid; Jabeen, Farah; Khan, Ajmal; Al-Sabari, Ruqaya S. M.; Al-khanbashi, Fatema H. S.; Al-Fahdi, Amira A. M.; Al-Zaabi, Ahoud K. A.; Al-Shuraiqi, Fatma A. M.; Al-Bahaisi, Iman M.

2018-06-01

Nucleic acid & serology based methods have revolutionized plant disease detection, however, they are not very reliable at asymptomatic stage, especially in case of pathogen with systemic infection, in addition, they need at least 1-2 days for sample harvesting, processing, and analysis. In this study, two reflectance spectroscopies i.e. Near Infrared reflectance spectroscopy (NIR) and Fourier-Transform-Infrared spectroscopy with Attenuated Total Reflection (FT-IR, ATR) coupled with multivariate exploratory methods like Principle Component Analysis (PCA) and Partial least square discriminant analysis (PLS-DA) have been deployed to detect begomovirus infection in papaya leaves. The application of those techniques demonstrates that they are very useful for robust in vivo detection of plant begomovirus infection. These methods are simple, sensitive, reproducible, precise, and do not require any lengthy samples preparation procedures.

Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation

PubMed Central

Yoshizato, Tetsuichi; Nannya, Yasuhito; Atsuta, Yoshiko; Shiozawa, Yusuke; Iijima-Yamashita, Yuka; Yoshida, Kenichi; Shiraishi, Yuichi; Suzuki, Hiromichi; Nagata, Yasunobu; Sato, Yusuke; Kakiuchi, Nobuyuki; Matsuo, Keitaro; Onizuka, Makoto; Kataoka, Keisuke; Chiba, Kenichi; Tanaka, Hiroko; Ueno, Hiroo; Nakagawa, Masahiro M.; Przychodzen, Bartlomiej; Haferlach, Claudia; Kern, Wolfgang; Aoki, Kosuke; Itonaga, Hidehiro; Kanda, Yoshinobu; Sekeres, Mikkael A.; Maciejewski, Jaroslaw P.; Haferlach, Torsten; Miyazaki, Yasushi; Horibe, Keizo; Sanada, Masashi; Miyano, Satoru; Makishima, Hideki

2017-01-01

Genetic alterations, including mutations and copy-number alterations, are central to the pathogenesis of myelodysplastic syndromes and related diseases (myelodysplasia), but their roles in allogeneic stem cell transplantation have not fully been studied in a large cohort of patients. We enrolled 797 patients who had been diagnosed with myelodysplasia at initial presentation and received transplantation via the Japan Marrow Donor Program. Targeted-capture sequencing was performed to identify mutations in 69 genes, together with copy-number alterations, whose effects on transplantation outcomes were investigated. We identified 1776 mutations and 927 abnormal copy segments among 617 patients (77.4%). In multivariate modeling using Cox proportional-hazards regression, genetic factors explained 30% of the total hazards for overall survival; clinical characteristics accounted for 70% of risk. TP53 and RAS-pathway mutations, together with complex karyotype (CK) as detected by conventional cytogenetics and/or sequencing-based analysis, negatively affected posttransplant survival independently of clinical factors. Regardless of disease subtype, TP53-mutated patients with CK were characterized by unique genetic features and associated with an extremely poor survival with frequent early relapse, whereas outcomes were substantially better in TP53-mutated patients without CK. By contrast, the effects of RAS-pathway mutations depended on disease subtype and were confined to myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). Our results suggest that TP53 and RAS-pathway mutations predicted a dismal prognosis, when associated with CK and MDS/MPNs, respectively. However, for patients with mutated TP53 or CK alone, long-term survival could be obtained with transplantation. Clinical sequencing provides vital information for accurate prognostication in transplantation. PMID:28223278

Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation.

PubMed

Yoshizato, Tetsuichi; Nannya, Yasuhito; Atsuta, Yoshiko; Shiozawa, Yusuke; Iijima-Yamashita, Yuka; Yoshida, Kenichi; Shiraishi, Yuichi; Suzuki, Hiromichi; Nagata, Yasunobu; Sato, Yusuke; Kakiuchi, Nobuyuki; Matsuo, Keitaro; Onizuka, Makoto; Kataoka, Keisuke; Chiba, Kenichi; Tanaka, Hiroko; Ueno, Hiroo; Nakagawa, Masahiro M; Przychodzen, Bartlomiej; Haferlach, Claudia; Kern, Wolfgang; Aoki, Kosuke; Itonaga, Hidehiro; Kanda, Yoshinobu; Sekeres, Mikkael A; Maciejewski, Jaroslaw P; Haferlach, Torsten; Miyazaki, Yasushi; Horibe, Keizo; Sanada, Masashi; Miyano, Satoru; Makishima, Hideki; Ogawa, Seishi

2017-04-27

Genetic alterations, including mutations and copy-number alterations, are central to the pathogenesis of myelodysplastic syndromes and related diseases (myelodysplasia), but their roles in allogeneic stem cell transplantation have not fully been studied in a large cohort of patients. We enrolled 797 patients who had been diagnosed with myelodysplasia at initial presentation and received transplantation via the Japan Marrow Donor Program. Targeted-capture sequencing was performed to identify mutations in 69 genes, together with copy-number alterations, whose effects on transplantation outcomes were investigated. We identified 1776 mutations and 927 abnormal copy segments among 617 patients (77.4%). In multivariate modeling using Cox proportional-hazards regression, genetic factors explained 30% of the total hazards for overall survival; clinical characteristics accounted for 70% of risk. TP53 and RAS-pathway mutations, together with complex karyotype (CK) as detected by conventional cytogenetics and/or sequencing-based analysis, negatively affected posttransplant survival independently of clinical factors. Regardless of disease subtype, TP53 -mutated patients with CK were characterized by unique genetic features and associated with an extremely poor survival with frequent early relapse, whereas outcomes were substantially better in TP53 -mutated patients without CK. By contrast, the effects of RAS-pathway mutations depended on disease subtype and were confined to myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). Our results suggest that TP53 and RAS-pathway mutations predicted a dismal prognosis, when associated with CK and MDS/MPNs, respectively. However, for patients with mutated TP53 or CK alone, long-term survival could be obtained with transplantation. Clinical sequencing provides vital information for accurate prognostication in transplantation. © 2017 by The American Society of Hematology.

Subtle metabolic alterations in adolescents with obesity and polycystic ovarian syndrome.

PubMed

Vital-Reyes, Víctor Saúl; Lopez-Alarcón, Mardia Guadalupe; Inda-Icaza, Patricia; Márquez-Maldonado, Concepción

2017-01-01

To evaluate the frequency of some subtle metabolic alterations in a group of adolescents with obesity and polycystic ovary syndrome (PCOS). A cross-sectional, comparative study was conducted in a group of adolescents with obesity, and characterized as with or without PCOS according with the Rotterdam Consensus. Medical history, anthropometry, gynecologic pelvic ultrasound (to evaluate ovarian volumes, number of antral follicles and endometrial width), as well as serum glucose, insulin, lipoproteins, interleukin-6, tumor necrosis factor alpha, total testosterone, dehydroepiandrosterone, sexual hormones binding globulin, leptin, adiponectin and insulin-like growth factor 1, the free-androgen index, free and available testosterone, and homeostatic model assessment index were calculated. For statistics, mean and standard deviation, or median and ranges were used for description as appropriate. Likewise, Student t-test or Mann-Whitney test were used for comparisons. From a sample of 180 adolescents, 47 attached to selection criteria. Mean age was 13.5 year and Z-score 2.5. Eighty percent of adolescents presented central distribution of body fat and 95% hyperinsulinemia. The more frequent dyslipidemias were hypertriglyceridemia in 57% and hypercholesterolemia in 12.8%; 25.5% of adolescents presented two out of three criteria for polycystic ovary syndrome (PCOS). Body mass index and insulin were correlated with free testosterone, but the multivariate analysis demonstrated that the magnitude of the association was significantly higher in SOP patients. The metabolic alterations detected in obese adolescents with SOP suggest that the clinical manifestations that accompany the syndrome characterize the PCOS as a metabolic disease, which carry important health risks at short, medium and long term. Therefore, they merit intervening actions to prevent, diagnose and provide timing treatment in order to limit the damage in the course of the natural history of PCOS. Copyright: © 2017 SecretarÍa de Salud

Skin autofluorescence and peripheral neuropathy four years later in type 1 diabetes.

PubMed

Rajaobelina, K; Farges, B; Nov, S; Maury, E; Cephise-Velayoudom, F L; Gin, H; Helmer, C; Rigalleau, V

2017-02-01

Advanced glycation end products (AGEs) are involved in diabetes complications. We aimed to investigate whether the accumulation of AGEs measured by skin autofluorescence (sAF) was associated with signs of diabetic peripheral neuropathy and to sensitivity, pain, motor and autonomic function 4 years later in patients with type 1 diabetes. At baseline, 188 patients (age 51 years, diabetes duration 22 years) underwent skin autofluorescence measurement using the AGE Reader. Four years later, signs of diabetic peripheral neuropathy were defined as the presence of neuropathic pain and/or feet sensory loss or foot ulceration. Neurological tests were systematically performed: vibration perception threshold by neuroesthesiometry, neuropathic pain by the Douleur Neuropathique en 4 Questions score, muscle strength by dynamometry and electrochemical skin conductance. Multivariate analyses were adjusted by age, sex, height, body mass index, tobacco, HbA 1c , diabetes duration, estimated glomerular filtration rate and albumin excretion rate. At the 4-year follow-up, 13.8% of patients had signs of diabetic peripheral neuropathy. The baseline sAF was higher in those with signs of diabetic peripheral neuropathy (2.5 ± 0.7 vs 2.1 ± 0.5 arbitrary units (AU), p < 0.0005). In the multivariate analysis, a 1 SD higher skin autofluorescence at baseline was associated with an increased risk of signs of neuropathy (OR = 2.68, p = 0.01). All of the neurological tests were significantly altered in the highest quartile of the baseline sAF (>2.4 AU) compared with the lowest quartiles after multivariate adjustment. This non-invasive measurement of skin autofluorescence may have a value for diabetic peripheral neuropathy in type 1 diabetes and a potential clinical utility for detection of diabetic peripheral neuropathy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Small Bowel Carcinomas in Coeliac or Crohn's Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium.

PubMed

Vanoli, Alessandro; Di Sabatino, Antonio; Furlan, Daniela; Klersy, Catherine; Grillo, Federica; Fiocca, Roberto; Mescoli, Claudia; Rugge, Massimo; Nesi, Gabriella; Fociani, Paolo; Sampietro, Gianluca; Ardizzone, Sandro; Luinetti, Ombretta; Calabrò, Antonio; Tonelli, Francesco; Volta, Umberto; Santini, Donatella; Caio, Giacomo; Giuffrida, Paolo; Elli, Luca; Ferrero, Stefano; Latella, Giovanni; Ciardi, Antonio; Caronna, Roberto; Solina, Gaspare; Rizzo, Aroldo; Ciacci, Carolina; D'Armiento, Francesco P; Salemme, Marianna; Villanacci, Vincenzo; Cannizzaro, Renato; Canzonieri, Vincenzo; Reggiani Bonetti, Luca; Biancone, Livia; Monteleone, Giovanni; Orlandi, Augusto; Santeusanio, Giuseppe; Macciomei, Maria C; D'Incà, Renata; Perfetti, Vittorio; Sandri, Giancarlo; Silano, Marco; Florena, Ada M; Giannone, Antonino G; Papi, Claudio; Coppola, Luigi; Usai, Paolo; Maccioni, Antonio; Astegiano, Marco; Migliora, Paola; Manca, Rachele; Martino, Michele; Trapani, Davide; Cerutti, Roberta; Alberizzi, Paola; Riboni, Roberta; Sessa, Fausto; Paulli, Marco; Solcia, Enrico; Corazza, Gino R

2017-08-01

An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancer-specific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI─which was the result of MLH1 promoter methylation in all but one cases─and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications. In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

[Abnormality of TOP2A expression and its gene copy number variations in neuroblastic tumors].

PubMed

Chen, J M; Zhou, C J; Ma, X L; Guan, D D; Yang, L Y; Yue, P; Gong, L P

2016-11-08

Objective: To detect TOP2A protein expression and gene copy number alterations, and to analyze related clinical and pathological implications in pediatric neuroblastic tumors (NT). Methods: Immunohistochemistry was used to detect TOP2A protein expression. Fluorescence in situ hybridization (FISH) was used to detect numerical aberrations of TOP2A. Results: TOP2A protein was expressed in 59.1%(52/88) of cases, which was associated with differentiation ( P =0.006), Ki-67 index ( P <0.01) and MKI ( P =0.001). Twenty-eight cases (35.0%, 28/88) showed TOP2A gene amplification, which was correlated with the age ( P <0.01), clinical stage ( P =0.028), high risk group ( P =0.001), Ki-67 index ( P =0.040) and differentiation ( P =0.014). Survival analysis showed that TOP2A expression was related to survival rate. Multivariate analyses showed that TOP2A expression was an independent predictor for poor prognosis ( P =0.010). Conclusions: More than half of the cases show TOP2A expression, which is more likely associated with NB, high Ki-67 index and high MKI. Cases with TOP2A expression have shorter survivals and poorer prognosis. TOP2A amplification is seen in 35% and likely occurs in patients older than 18 months and at advanced INSS stages (Ⅲ and Ⅳ). As a target of the anthracycline-based adjuvant drugs, TOP2A test can be used to select patient with NT for the therapy.

Extending Inferential Group Analysis in Type 2 Diabetic Patients with Multivariate GLM Implemented in SPM8.

PubMed

Ferreira, Fábio S; Pereira, João M S; Duarte, João V; Castelo-Branco, Miguel

2017-01-01

Although voxel based morphometry studies are still the standard for analyzing brain structure, their dependence on massive univariate inferential methods is a limiting factor. A better understanding of brain pathologies can be achieved by applying inferential multivariate methods, which allow the study of multiple dependent variables, e.g. different imaging modalities of the same subject. Given the widespread use of SPM software in the brain imaging community, the main aim of this work is the implementation of massive multivariate inferential analysis as a toolbox in this software package. applied to the use of T1 and T2 structural data from diabetic patients and controls. This implementation was compared with the traditional ANCOVA in SPM and a similar multivariate GLM toolbox (MRM). We implemented the new toolbox and tested it by investigating brain alterations on a cohort of twenty-eight type 2 diabetes patients and twenty-six matched healthy controls, using information from both T1 and T2 weighted structural MRI scans, both separately - using standard univariate VBM - and simultaneously, with multivariate analyses. Univariate VBM replicated predominantly bilateral changes in basal ganglia and insular regions in type 2 diabetes patients. On the other hand, multivariate analyses replicated key findings of univariate results, while also revealing the thalami as additional foci of pathology. While the presented algorithm must be further optimized, the proposed toolbox is the first implementation of multivariate statistics in SPM8 as a user-friendly toolbox, which shows great potential and is ready to be validated in other clinical cohorts and modalities.

Extending Inferential Group Analysis in Type 2 Diabetic Patients with Multivariate GLM Implemented in SPM8

PubMed Central

Ferreira, Fábio S.; Pereira, João M.S.; Duarte, João V.; Castelo-Branco, Miguel

2017-01-01

Background: Although voxel based morphometry studies are still the standard for analyzing brain structure, their dependence on massive univariate inferential methods is a limiting factor. A better understanding of brain pathologies can be achieved by applying inferential multivariate methods, which allow the study of multiple dependent variables, e.g. different imaging modalities of the same subject. Objective: Given the widespread use of SPM software in the brain imaging community, the main aim of this work is the implementation of massive multivariate inferential analysis as a toolbox in this software package. applied to the use of T1 and T2 structural data from diabetic patients and controls. This implementation was compared with the traditional ANCOVA in SPM and a similar multivariate GLM toolbox (MRM). Method: We implemented the new toolbox and tested it by investigating brain alterations on a cohort of twenty-eight type 2 diabetes patients and twenty-six matched healthy controls, using information from both T1 and T2 weighted structural MRI scans, both separately – using standard univariate VBM - and simultaneously, with multivariate analyses. Results: Univariate VBM replicated predominantly bilateral changes in basal ganglia and insular regions in type 2 diabetes patients. On the other hand, multivariate analyses replicated key findings of univariate results, while also revealing the thalami as additional foci of pathology. Conclusion: While the presented algorithm must be further optimized, the proposed toolbox is the first implementation of multivariate statistics in SPM8 as a user-friendly toolbox, which shows great potential and is ready to be validated in other clinical cohorts and modalities. PMID:28761571

Alteration mapping at Goldfield, Nevada, by cluster and discriminant analysis of LANDSAT digital data

NASA Technical Reports Server (NTRS)

Ballew, G.

1977-01-01

The ability of Landsat multispectral digital data to differentiate among 62 combinations of rock and alteration types at the Goldfield mining district of Western Nevada was investigated by using statistical techniques of cluster and discriminant analysis. Multivariate discriminant analysis was not effective in classifying each of the 62 groups, with classification results essentially the same whether data of four channels alone or combined with six ratios of channels were used. Bivariate plots of group means revealed a cluster of three groups including mill tailings, basalt and all other rock and alteration types. Automatic hierarchical clustering based on the fourth dimensional Mahalanobis distance between group means of 30 groups having five or more samples was performed. The results of the cluster analysis revealed hierarchies of mill tailings vs. natural materials, basalt vs. non-basalt, highly reflectant rocks vs. other rocks and exclusively unaltered rocks vs. predominantly altered rocks. The hierarchies were used to determine the order in which sets of multiple discriminant analyses were to be performed and the resulting discriminant functions were used to produce a map of geology and alteration which has an overall accuracy of 70 percent for discriminating exclusively altered rocks from predominantly altered rocks.

EEMD-based multiscale ICA method for slewing bearing fault detection and diagnosis

NASA Astrophysics Data System (ADS)

Žvokelj, Matej; Zupan, Samo; Prebil, Ivan

2016-05-01

A novel multivariate and multiscale statistical process monitoring method is proposed with the aim of detecting incipient failures in large slewing bearings, where subjective influence plays a minor role. The proposed method integrates the strengths of the Independent Component Analysis (ICA) multivariate monitoring approach with the benefits of Ensemble Empirical Mode Decomposition (EEMD), which adaptively decomposes signals into different time scales and can thus cope with multiscale system dynamics. The method, which was named EEMD-based multiscale ICA (EEMD-MSICA), not only enables bearing fault detection but also offers a mechanism of multivariate signal denoising and, in combination with the Envelope Analysis (EA), a diagnostic tool. The multiscale nature of the proposed approach makes the method convenient to cope with data which emanate from bearings in complex real-world rotating machinery and frequently represent the cumulative effect of many underlying phenomena occupying different regions in the time-frequency plane. The efficiency of the proposed method was tested on simulated as well as real vibration and Acoustic Emission (AE) signals obtained through conducting an accelerated run-to-failure lifetime experiment on a purpose-built laboratory slewing bearing test stand. The ability to detect and locate the early-stage rolling-sliding contact fatigue failure of the bearing indicates that AE and vibration signals carry sufficient information on the bearing condition and that the developed EEMD-MSICA method is able to effectively extract it, thereby representing a reliable bearing fault detection and diagnosis strategy.

Feature Sampling in Detection: Implications for the Measurement of Perceptual Independence

ERIC Educational Resources Information Center

Macho, Siegfried

2007-01-01

The article presents the feature sampling signal detection (FS-SDT) model, an extension of the multivariate signal detection (SDT) model. The FS-SDT model assumes that, because of attentional shifts, different subsets of features are sampled for different presentations of the same multidimensional stimulus. Contrary to the SDT model, the FS-SDT…

Identification of Differential Item Functioning in Multiple-Group Settings: A Multivariate Outlier Detection Approach

ERIC Educational Resources Information Center

Magis, David; De Boeck, Paul

2011-01-01

We focus on the identification of differential item functioning (DIF) when more than two groups of examinees are considered. We propose to consider items as elements of a multivariate space, where DIF items are outlying elements. Following this approach, the situation of multiple groups is a quite natural case. A robust statistics technique is…

Altered structural network architecture is predictive of the presence of psychotic symptoms in patients with 22q11.2 deletion syndrome.

PubMed

Padula, Maria C; Scariati, Elisa; Schaer, Marie; Sandini, Corrado; Ottet, Marie Christine; Schneider, Maude; Van De Ville, Dimitri; Eliez, Stephan

2017-01-01

22q11.2 deletion syndrome (22q11DS) represents a homogeneous model of schizophrenia particularly suitable for the search of neural biomarkers of psychosis. Impairments in structural connectivity related to the presence of psychotic symptoms have been reported in patients with 22q11DS. However, the relationships between connectivity changes in patients with different symptomatic profiles are still largely unknown and warrant further investigations. In this study, we used structural connectivity to discriminate patients with 22q11DS with ( N  = 31) and without ( N  = 31) attenuated positive psychotic symptoms. Different structural connectivity measures were used, including the number of streamlines connecting pairs of brain regions, graph theoretical measures, and diffusion measures. We used univariate group comparisons as well as predictive multivariate approaches. The univariate comparison of connectivity measures between patients with or without attenuated positive psychotic symptoms did not give significant results. However, the multivariate prediction revealed that altered structural network architecture discriminates patient subtypes (accuracy = 67.7%). Among the regions contributing to the classification we found the anterior cingulate cortex, which is known to be associated to the presence of psychotic symptoms in patients with 22q11DS. Furthermore, a significant discrimination (accuracy = 64%) was obtained with fractional anisotropy and radial diffusivity in the left inferior longitudinal fasciculus and the right cingulate gyrus. Our results point to alterations in structural network architecture and white matter microstructure in patients with 22q11DS with attenuated positive symptoms, mainly involving connections of the limbic system. These alterations may therefore represent a potential biomarker for an increased risk of psychosis that should be further tested in longitudinal studies.

Multivariate curve-resolution analysis of pesticides in water samples from liquid chromatographic-diode array data.

PubMed

Maggio, Rubén M; Damiani, Patricia C; Olivieri, Alejandro C

2011-01-30

Liquid chromatographic-diode array detection data recorded for aqueous mixtures of 11 pesticides show the combined presence of strongly coeluting peaks, distortions in the time dimension between experimental runs, and the presence of potential interferents not modeled by the calibration phase in certain test samples. Due to the complexity of these phenomena, data were processed by a second-order multivariate algorithm based on multivariate curve resolution and alternating least-squares, which allows one to successfully model both the spectral and retention time behavior for all sample constituents. This led to the accurate quantitation of all analytes in a set of validation samples: aldicarb sulfoxide, oxamyl, aldicarb sulfone, methomyl, 3-hydroxy-carbofuran, aldicarb, propoxur, carbofuran, carbaryl, 1-naphthol and methiocarb. Limits of detection in the range 0.1-2 μg mL(-1) were obtained. Additionally, the second-order advantage for several analytes was achieved in samples containing several uncalibrated interferences. The limits of detection for all analytes were decreased by solid phase pre-concentration to values compatible to those officially recommended, i.e., in the order of 5 ng mL(-1). Copyright © 2010 Elsevier B.V. All rights reserved.

Fast Detection of Copper Content in Rice by Laser-Induced Breakdown Spectroscopy with Uni- and Multivariate Analysis.

PubMed

Liu, Fei; Ye, Lanhan; Peng, Jiyu; Song, Kunlin; Shen, Tingting; Zhang, Chu; He, Yong

2018-02-27

Fast detection of heavy metals is very important for ensuring the quality and safety of crops. Laser-induced breakdown spectroscopy (LIBS), coupled with uni- and multivariate analysis, was applied for quantitative analysis of copper in three kinds of rice (Jiangsu rice, regular rice, and Simiao rice). For univariate analysis, three pre-processing methods were applied to reduce fluctuations, including background normalization, the internal standard method, and the standard normal variate (SNV). Linear regression models showed a strong correlation between spectral intensity and Cu content, with an R 2 more than 0.97. The limit of detection (LOD) was around 5 ppm, lower than the tolerance limit of copper in foods. For multivariate analysis, partial least squares regression (PLSR) showed its advantage in extracting effective information for prediction, and its sensitivity reached 1.95 ppm, while support vector machine regression (SVMR) performed better in both calibration and prediction sets, where R c 2 and R p 2 reached 0.9979 and 0.9879, respectively. This study showed that LIBS could be considered as a constructive tool for the quantification of copper contamination in rice.

Fast Detection of Copper Content in Rice by Laser-Induced Breakdown Spectroscopy with Uni- and Multivariate Analysis

PubMed Central

Ye, Lanhan; Song, Kunlin; Shen, Tingting

2018-01-01

Fast detection of heavy metals is very important for ensuring the quality and safety of crops. Laser-induced breakdown spectroscopy (LIBS), coupled with uni- and multivariate analysis, was applied for quantitative analysis of copper in three kinds of rice (Jiangsu rice, regular rice, and Simiao rice). For univariate analysis, three pre-processing methods were applied to reduce fluctuations, including background normalization, the internal standard method, and the standard normal variate (SNV). Linear regression models showed a strong correlation between spectral intensity and Cu content, with an R2 more than 0.97. The limit of detection (LOD) was around 5 ppm, lower than the tolerance limit of copper in foods. For multivariate analysis, partial least squares regression (PLSR) showed its advantage in extracting effective information for prediction, and its sensitivity reached 1.95 ppm, while support vector machine regression (SVMR) performed better in both calibration and prediction sets, where Rc2 and Rp2 reached 0.9979 and 0.9879, respectively. This study showed that LIBS could be considered as a constructive tool for the quantification of copper contamination in rice. PMID:29495445

Chromatography methods and chemometrics for determination of milk fat adulterants

NASA Astrophysics Data System (ADS)

Trbović, D.; Petronijević, R.; Đorđević, V.

2017-09-01

Milk and milk-based products are among the leading food categories according to reported cases of food adulteration. Although many authentication problems exist in all areas of the food industry, adequate control methods are required to evaluate the authenticity of milk and milk products in the dairy industry. Moreover, gas chromatography (GC) analysis of triacylglycerols (TAGs) or fatty acid (FA) profiles of milk fat (MF) in combination with multivariate statistical data processing have been used to detect adulterations of milk and dairy products with foreign fats. The adulteration of milk and butter is a major issue for the dairy industry. The major adulterants of MF are vegetable oils (soybean, sunflower, groundnut, coconut, palm and peanut oil) and animal fat (cow tallow and pork lard). Multivariate analysis enables adulterated MF to be distinguished from authentic MF, while taking into account many analytical factors. Various multivariate analysis methods have been proposed to quantitatively detect levels of adulterant non-MFs, with multiple linear regression (MLR) seemingly the most suitable. There is a need for increased use of chemometric data analyses to detect adulterated MF in foods and for their expanded use in routine quality assurance testing.

Alteration mapping at Goldfield, Nevada, by cluster and discriminant analysis of Landsat digital data. [mapping of hydrothermally altered volcanic rocks

NASA Technical Reports Server (NTRS)

Ballew, G.

1977-01-01

The ability of Landsat multispectral digital data to differentiate among 62 combinations of rock and alteration types at the Goldfield mining district of Western Nevada was investigated by using statistical techniques of cluster and discriminant analysis. Multivariate discriminant analysis was not effective in classifying each of the 62 groups, with classification results essentially the same whether data of four channels alone or combined with six ratios of channels were used. Bivariate plots of group means revealed a cluster of three groups including mill tailings, basalt and all other rock and alteration types. Automatic hierarchical clustering based on the fourth dimensional Mahalanobis distance between group means of 30 groups having five or more samples was performed using Johnson's HICLUS program. The results of the cluster analysis revealed hierarchies of mill tailings vs. natural materials, basalt vs. non-basalt, highly reflectant rocks vs. other rocks and exclusively unaltered rocks vs. predominantly altered rocks. The hierarchies were used to determine the order in which sets of multiple discriminant analyses were to be performed and the resulting discriminant functions were used to produce a map of geology and alteration which has an overall accuracy of 70 percent for discriminating exclusively altered rocks from predominantly altered rocks.

Digital image processing techniques for detecting surface alteration - An application on the Alaska Peninsula: A section in The United States Geological Survey in Alaska: Accomplishments during 1983

USGS Publications Warehouse

York, James; Wilson, Frederic H.; Gamble, Bruce M.

1985-01-01

The tectonic evolution of the Alaska Peninsula makes it a likely area for the discovery of significant mineral deposits. However, because of problems associated with remoteness and poor weather, little detailed mineral exploration work has been carried on there. This study focuses on using Landsat multispectral scanner data for the Port Moller, Stepovak Bay, and Simeon of Island Quadrangles to detect surface alteration, probably limonitic (iron oxide staining) and(or) argillic (secondary clay minerals) in character, that could be indicative of mineral deposits. The techniques used here are useful for mapping deposits that have exposed surface alteration of at least an hectare, the approximate spatial resolution of the Landsat data. Virtually cloud-free Landsat coverage was used, but to be detected, the alteration area must also be unobscured by vegetation. Not all mineral deposits will be associated with surface alteration, and not all areas of surface alteration will have valuable mineral deposits.

Multivariate analysis: A statistical approach for computations

NASA Astrophysics Data System (ADS)

Michu, Sachin; Kaushik, Vandana

2014-10-01

Multivariate analysis is a type of multivariate statistical approach commonly used in, automotive diagnosis, education evaluating clusters in finance etc and more recently in the health-related professions. The objective of the paper is to provide a detailed exploratory discussion about factor analysis (FA) in image retrieval method and correlation analysis (CA) of network traffic. Image retrieval methods aim to retrieve relevant images from a collected database, based on their content. The problem is made more difficult due to the high dimension of the variable space in which the images are represented. Multivariate correlation analysis proposes an anomaly detection and analysis method based on the correlation coefficient matrix. Anomaly behaviors in the network include the various attacks on the network like DDOs attacks and network scanning.

Apparatus and method for transient thermal infrared spectrometry of flowable enclosed materials

DOEpatents

McClelland, John F.; Jones, Roger W.

1993-03-02

A method and apparatus for enabling analysis of a flowable material enclosed in a transport system having an infrared transparent wall portion. A temperature differential is transiently generated between a thin surface layer portion of the material and a lower or deeper portion of the material sufficient to alter the thermal infrared emission spectrum of the material from the black-body thermal infrared emission spectrum of the material, and the altered thermal infrared emission spectrum is detected through the infrared transparent portion of the transport system while the altered thermal infrared emission spectrum is sufficiently free of self-absorption by the material of emitted infrared radiation. The detection is effected prior to the temperature differential propagating into the lower or deeper portion of the material to an extent such that the altered thermal infrared emission spectrum is no longer sufficiently free of self-absorption by the material of emitted infrared radiation. By such detection, the detected altered thermal infrared emission spectrum is indicative of characteristics relating to molecular composition of the material.

Lameness detection in dairy cattle: single predictor v. multivariate analysis of image-based posture processing and behaviour and performance sensing.

PubMed

Van Hertem, T; Bahr, C; Schlageter Tello, A; Viazzi, S; Steensels, M; Romanini, C E B; Lokhorst, C; Maltz, E; Halachmi, I; Berckmans, D

2016-09-01

The objective of this study was to evaluate if a multi-sensor system (milk, activity, body posture) was a better classifier for lameness than the single-sensor-based detection models. Between September 2013 and August 2014, 3629 cow observations were collected on a commercial dairy farm in Belgium. Human locomotion scoring was used as reference for the model development and evaluation. Cow behaviour and performance was measured with existing sensors that were already present at the farm. A prototype of three-dimensional-based video recording system was used to quantify automatically the back posture of a cow. For the single predictor comparisons, a receiver operating characteristics curve was made. For the multivariate detection models, logistic regression and generalized linear mixed models (GLMM) were developed. The best lameness classification model was obtained by the multi-sensor analysis (area under the receiver operating characteristics curve (AUC)=0.757±0.029), containing a combination of milk and milking variables, activity and gait and posture variables from videos. Second, the multivariate video-based system (AUC=0.732±0.011) performed better than the multivariate milk sensors (AUC=0.604±0.026) and the multivariate behaviour sensors (AUC=0.633±0.018). The video-based system performed better than the combined behaviour and performance-based detection model (AUC=0.669±0.028), indicating that it is worthwhile to consider a video-based lameness detection system, regardless the presence of other existing sensors in the farm. The results suggest that Θ2, the feature variable for the back curvature around the hip joints, with an AUC of 0.719 is the best single predictor variable for lameness detection based on locomotion scoring. In general, this study showed that the video-based back posture monitoring system is outperforming the behaviour and performance sensing techniques for locomotion scoring-based lameness detection. A GLMM with seven specific variables (walking speed, back posture measurement, daytime activity, milk yield, lactation stage, milk peak flow rate and milk peak conductivity) is the best combination of variables for lameness classification. The accuracy on four-level lameness classification was 60.3%. The accuracy improved to 79.8% for binary lameness classification. The binary GLMM obtained a sensitivity of 68.5% and a specificity of 87.6%, which both exceed the sensitivity (52.1%±4.7%) and specificity (83.2%±2.3%) of the multi-sensor logistic regression model. This shows that the repeated measures analysis in the GLMM, taking into account the individual history of the animal, outperforms the classification when thresholds based on herd level (a statistical population) are used.

Kernel canonical-correlation Granger causality for multiple time series

NASA Astrophysics Data System (ADS)

Wu, Guorong; Duan, Xujun; Liao, Wei; Gao, Qing; Chen, Huafu

2011-04-01

Canonical-correlation analysis as a multivariate statistical technique has been applied to multivariate Granger causality analysis to infer information flow in complex systems. It shows unique appeal and great superiority over the traditional vector autoregressive method, due to the simplified procedure that detects causal interaction between multiple time series, and the avoidance of potential model estimation problems. However, it is limited to the linear case. Here, we extend the framework of canonical correlation to include the estimation of multivariate nonlinear Granger causality for drawing inference about directed interaction. Its feasibility and effectiveness are verified on simulated data.

Multivariate image analysis of laser-induced photothermal imaging used for detection of caries tooth

NASA Astrophysics Data System (ADS)

El-Sherif, Ashraf F.; Abdel Aziz, Wessam M.; El-Sharkawy, Yasser H.

2010-08-01

Time-resolved photothermal imaging has been investigated to characterize tooth for the purpose of discriminating between normal and caries areas of the hard tissue using thermal camera. Ultrasonic thermoelastic waves were generated in hard tissue by the absorption of fiber-coupled Q-switched Nd:YAG laser pulses operating at 1064 nm in conjunction with a laser-induced photothermal technique used to detect the thermal radiation waves for diagnosis of human tooth. The concepts behind the use of photo-thermal techniques for off-line detection of caries tooth features were presented by our group in earlier work. This paper illustrates the application of multivariate image analysis (MIA) techniques to detect the presence of caries tooth. MIA is used to rapidly detect the presence and quantity of common caries tooth features as they scanned by the high resolution color (RGB) thermal cameras. Multivariate principal component analysis is used to decompose the acquired three-channel tooth images into a two dimensional principal components (PC) space. Masking score point clusters in the score space and highlighting corresponding pixels in the image space of the two dominant PCs enables isolation of caries defect pixels based on contrast and color information. The technique provides a qualitative result that can be used for early stage caries tooth detection. The proposed technique can potentially be used on-line or real-time resolved to prescreen the existence of caries through vision based systems like real-time thermal camera. Experimental results on the large number of extracted teeth as well as one of the thermal image panoramas of the human teeth voltanteer are investigated and presented.

Changes in chemical composition of bone matrix in ovariectomized (OVX) rats detected by Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Iimura, Tadahiro; Saitou, Takashi; Imamura, Takeshi

2015-02-01

Osteoporosis is a major bone disease that connotes the risk of fragility fractures resulting from alterations to bone quantity and/or quality to mechanical competence. Bone strength arises from both bone quantity and quality. Assessment of bone quality and bone quantity is important for prediction of fracture risk. In spite of the two factors contribute to maintain the bone strength, only one factor, bone mineral density is used to determine the bone strength in the current diagnosis of osteoporosis. On the other hand, there is no practical method to measure chemical composition of bone tissue including hydroxyapatite and collagen non-invasively. Raman spectroscopy is a powerful technique to analyze chemical composition and material properties of bone matrix non-invasively. Here we demonstrated Raman spectroscopic analysis of the bone matrix in osteoporosis model rat. Ovariectomized (OVX) rat was made and the decalcified sections of tibias were analyzed by a Raman microscope. In the results, Raman bands of typical collagen appeared in the obtained spectra. Although the typical mineral bands at 960 cm-1 (Phosphate) was absent due to decalcified processing, we found that Raman peak intensities of amide I and C-C stretching bands were significantly different between OVX and sham-operated specimens. These differences on the Raman spectra were statistically compared by multivariate analyses, principal component analysis (PCA) and liner discrimination analysis (LDA). Our analyses suggest that amide I and C-C stretching bands can be related to stability of bone matrix which reflects bone quality.

Gene Methylation and Cytological Atypia in Random Fine Needle Aspirates for Assessment of Breast Cancer Risk

PubMed Central

Hafeez, Sidra; Bujanda, Zoila Lopez; Chatterton, Robert T.; Jacobs, Lisa K.; Khouri, Nagi F.; Ivancic, David; Kenney, Kara; Shehata, Christina; Jeter, Stacie C.; Wolfman, Judith A.; Zalles, Carola M.; Huang, Peng

2016-01-01

Methods to determine individualized breast cancer risk lack sufficient sensitivity to select women most likely to benefit from preventive strategies. Alterations in DNA methylation occur early in breast cancer. We hypothesized that cancer-specific methylation markers could enhance breast cancer risk assessment. We evaluated 380 women without a history of breast cancer. We determined their menopausal status or menstrual cycle phase, risk of developing breast cancer (Gail model), and breast density, and obtained random fine needle aspiration (rFNA) samples for assessment of cytopathology and cumulative methylation index (CMI). Eight methylated gene markers were identified through whole genome methylation analysis and included novel and previously established breast cancer detection genes. We performed correlative and multivariate linear regression analyses to evaluate DNA methylation of a gene panel as a function of clinical factors associated with breast cancer risk. CMI and individual gene methylation were independent of age, menopausal status or menstrual phase, lifetime Gail risk score, and breast density. CMI and individual gene methylation for the eight genes increased significantly (p<0.001) with increasing cytological atypia. The findings were verified with multivariate analyses correcting for age, log (Gail), log (percent density), rFNA cell number and BMI. Our results demonstrate a significant association between cytological atypia and high CMI, which does not vary with menstrual phase or menopause and is independent of Gail risk and mammographic density. Thus CMI is an excellent candidate breast cancer risk biomarker, warranting larger prospective studies to establish its utility for cancer risk assessment. PMID:27261491

A Novel Approach to Detect Accelerated Aged and Surface-Mediated Degradation in Explosives by UPLC-ESI-MS.

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

Beppler, Christina L

2015-12-01

A new approach was created for studying energetic material degradation. This approach involved detecting and tentatively identifying non-volatile chemical species by liquid chromatography-mass spectrometry (LC-MS) with multivariate statistical data analysis that form as the CL-20 energetic material thermally degraded. Multivariate data analysis showed clear separation and clustering of samples based on sample group: either pristine or aged material. Further analysis showed counter-clockwise trends in the principal components analysis (PCA), a type of multivariate data analysis, Scores plots. These trends may indicate that there was a discrete shift in the chemical markers as the went from pristine to aged material, andmore » then again when the aged CL-20 mixed with a potentially incompatible material was thermally aged for 4, 6, or 9 months. This new approach to studying energetic material degradation should provide greater knowledge of potential degradation markers in these materials.« less

Prevalence of plasmid-mediated qnr determinants and gyrase alteration in Klebsiella pneumoniae isolated from a university teaching hospital in Malaysia.

PubMed

Saiful Anuar, A S; Mohd Yusof, M Y; Tay, S T

2013-07-01

The ciprofloxacin resistance of Klebsiella (K.) pneumoniae is mediated primarily through alterations in type II topoisomerase (gyrA) gene and plasmid-mediated quinolone resistance-conferring genes (qnr). This study aimed to define the prevalence of plasmid-mediated quinolone resistance-conferring genes (qnr) and type II topoisomerase (gyrA) alterations of a population of ciprofloxacin-resistant (n = 21), intermediate (n = 8), and sensitive (n = 18) K. pneumoniae isolates obtained from a teaching hospital at Kuala Lumpur, Malaysia. A multiplex PCR assay was performed for simultaneous detection of qnrA, qnrB and qnrS. Sequence analysis of the amplified gyrA and gyrB regions of the isolates were performed. The findings in this study revealed the emergence of a high prevalence (48.9%) of qnr determinants in our isolates. Four variants of plasmid-mediated qnr determinants (qnrB1, qnrB6, qnrB10 and qnrS1) were detected from 11 (52.4%) ciprofloxacin-resistant, 5 (62.5%) intermediate and 7 (38.9%) sensitive isolates. gyrA alterations were detected from 18 (85.7%) ciprofloxacin-resistant isolates. Single gyrA alterations, Ser83→Tyr, Ser83→Ile, and Asp87→Gly, and double alterations, Ser83→Phe plus Asp87→Ala and Ser83→Tyr plus Asp87→Asn were detected. While ciprofloxacin resistance was significantly associated with gyrA alteration (Ser83, p = 0.003; Asp87, p = 0.005; double alteration, p = 0.016), no significant association of ciprofloxacin resistance was noted with the presence of qnr determinants (p = 0.283). The findings in this study demonstrate the emergence of qnr determinants and gyrA alterations contributed to the development and spread of fluoroquinolone resistance in the Malaysian isolates.

Staphylococcus aureus Redirects Central Metabolism to Increase Iron Availability

PubMed Central

Pishchany, Gleb; Whitwell, Corbin W; Torres, Victor J; Skaar, Eric P

2006-01-01

Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment) or genetic (Δfur) alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB), a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus. PMID:16933993

Factors associated with the prevalence of anterior open bite among preschool children: A population-based study in Brazil

PubMed Central

Machado, Daniella Borges; Brizon, Valéria Silva Cândido; Ambrosano, Gláucia Maria Bovi; Madureira, Davidson Fróis; Gomes, Viviane Elisângela; de Oliveira, Ana Cristina Borges

2014-01-01

INTRODUCTION: The aim of this study was to identify factors associated with the prevalence of anterior open bite among five-year-old Brazilian children. METHODS: A cross-sectional study was undertaken using data from the National Survey of Oral Health (SB Brazil 2010). The outcome variable was anterior open bite classified as present or absent. The independent variables were classified by individual, sociodemographic and clinical factors. Data were analyzed through bivariate and multivariate analysis using SPSS statistical software (version 18.0) with a 95% level of significance. RESULTS: The prevalence of anterior open bite was 12.1%. Multivariate analysis showed that preschool children living in Southern Brazil had an increased chance of 1.8 more times of having anterior open bite (CI 95%: 1.16 - 3.02). Children identified with alterations in overjet had 14.6 times greater chances of having anterior open bite (CI 95%: 8.98 - 24.03). CONCLUSION: There was a significant association between anterior open bite and the region of Brazil where the children lived, the presence of altered overjet and the prevalence of posterior crossbite. PMID:25715723

Genetic alteration profiling of patients with resected squamous cell lung carcinomas

PubMed Central

Zhang, Ningning; Lin, Dongmei; Wu, Di; Zhu, Xinxin; Song, Wenya; Shi, Yuankai

2016-01-01

In this study, we analyzed the genetic profiles of squamous cell lung carcinoma (SqCLC) to identify potential therapeutic targets. Approximately 2,800 COSMIC mutations from 50 genes were determined by next-generation sequencing. Amplification/deletion of SOX2, CDKN2A, PTEN, FGFR1, EGFR, CCND1, HER2 and PDGFRA were detected by FISH and expression of VEGFR2, PD-L1 and PTEN were examined by IHC. One hundred and fifty-seven samples of SqCLC were collected. Somatic mutations was identified in 73.9% of cases, with TP53 (56.1%), CDKN2A (8.9%), PIK3CA (8.9%), KRAS (4.5%) and EGFR (3.2%). Gene copy number alterations were identified in 75.8% of cases, including SOX2 amplification (31.2%), CDKN2A deletion (21.7%), PTEN deletion (16.6%), FGFR1 amplification (15.9%), EGFR amplification (14.0%), CCND1 amplification (14.0%), HER2 amplification (9.6%) and PDGFRA amplification (7.6%). Positive expression of VEGFR2 and PD-L1 and loss of PTEN expression were observed in 80.5%, 47.2%, and 42.7% of cases, respectively. Multivariate analysis showed that positive expression of PD-L1 was an independent favorable prognostic factor for DFS (HR = 0.610; P = 0.044). In conclusion, nearly all (93.6%) SqCLC cases harbored at least one potential druggable target. The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of SqCLC. PMID:27145277

Toward high value sensing: monolayer-protected metal nanoparticles in multivariable gas and vapor sensors.

PubMed

Potyrailo, Radislav A

2017-08-29

For detection of gases and vapors in complex backgrounds, "classic" analytical instruments are an unavoidable alternative to existing sensors. Recently a new generation of sensors, known as multivariable sensors, emerged with a fundamentally different perspective for sensing to eliminate limitations of existing sensors. In multivariable sensors, a sensing material is designed to have diverse responses to different gases and vapors and is coupled to a multivariable transducer that provides independent outputs to recognize these diverse responses. Data analytics tools provide rejection of interferences and multi-analyte quantitation. This review critically analyses advances of multivariable sensors based on ligand-functionalized metal nanoparticles also known as monolayer-protected nanoparticles (MPNs). These MPN sensing materials distinctively stand out from other sensing materials for multivariable sensors due to their diversity of gas- and vapor-response mechanisms as provided by organic and biological ligands, applicability of these sensing materials for broad classes of gas-phase compounds such as condensable vapors and non-condensable gases, and for several principles of signal transduction in multivariable sensors that result in non-resonant and resonant electrical sensors as well as material- and structure-based photonic sensors. Such features should allow MPN multivariable sensors to be an attractive high value addition to existing analytical instrumentation.

Multivariate normative comparisons using an aggregated database

PubMed Central

Murre, Jaap M. J.; Huizenga, Hilde M.

2017-01-01

In multivariate normative comparisons, a patient’s profile of test scores is compared to those in a normative sample. Recently, it has been shown that these multivariate normative comparisons enhance the sensitivity of neuropsychological assessment. However, multivariate normative comparisons require multivariate normative data, which are often unavailable. In this paper, we show how a multivariate normative database can be constructed by combining healthy control group data from published neuropsychological studies. We show that three issues should be addressed to construct a multivariate normative database. First, the database may have a multilevel structure, with participants nested within studies. Second, not all tests are administered in every study, so many data may be missing. Third, a patient should be compared to controls of similar age, gender and educational background rather than to the entire normative sample. To address these issues, we propose a multilevel approach for multivariate normative comparisons that accounts for missing data and includes covariates for age, gender and educational background. Simulations show that this approach controls the number of false positives and has high sensitivity to detect genuine deviations from the norm. An empirical example is provided. Implications for other domains than neuropsychology are also discussed. To facilitate broader adoption of these methods, we provide code implementing the entire analysis in the open source software package R. PMID:28267796

Multivariate analysis of ultrasound-recorded dorsal strain sequences: Investigation of dynamic neck extensions in women with chronic whiplash associated disorders.

PubMed

Peolsson, Anneli; Peterson, Gunnel; Trygg, Johan; Nilsson, David

2016-08-03

Whiplash Associated Disorders (WAD) refers to the multifaceted and chronic burden that is common after a whiplash injury. Tools to assist in the diagnosis of WAD and an increased understanding of neck muscle behaviour are needed. We examined the multilayer dorsal neck muscle behaviour in nine women with chronic WAD versus healthy controls during the entire sequence of a dynamic low-loaded neck extension exercise, which was recorded using real-time ultrasound movies with high frame rates. Principal component analysis and orthogonal partial least squares were used to analyse mechanical muscle strain (deformation in elongation and shortening). The WAD group showed more shortening during the neck extension phase in the trapezius muscle and during both the neck extension and the return to neutral phase in the multifidus muscle. For the first time, a novel non-invasive method is presented that is capable of detecting altered dorsal muscle strain in women with WAD during an entire exercise sequence. This method may be a breakthrough for the future diagnosis and treatment of WAD.

Multivariate analysis of ultrasound-recorded dorsal strain sequences: Investigation of dynamic neck extensions in women with chronic whiplash associated disorders

PubMed Central

Peolsson, Anneli; Peterson, Gunnel; Trygg, Johan; Nilsson, David

2016-01-01

Whiplash Associated Disorders (WAD) refers to the multifaceted and chronic burden that is common after a whiplash injury. Tools to assist in the diagnosis of WAD and an increased understanding of neck muscle behaviour are needed. We examined the multilayer dorsal neck muscle behaviour in nine women with chronic WAD versus healthy controls during the entire sequence of a dynamic low-loaded neck extension exercise, which was recorded using real-time ultrasound movies with high frame rates. Principal component analysis and orthogonal partial least squares were used to analyse mechanical muscle strain (deformation in elongation and shortening). The WAD group showed more shortening during the neck extension phase in the trapezius muscle and during both the neck extension and the return to neutral phase in the multifidus muscle. For the first time, a novel non-invasive method is presented that is capable of detecting altered dorsal muscle strain in women with WAD during an entire exercise sequence. This method may be a breakthrough for the future diagnosis and treatment of WAD. PMID:27484361

Multivariate analysis of ultrasound-recorded dorsal strain sequences: Investigation of dynamic neck extensions in women with chronic whiplash associated disorders

NASA Astrophysics Data System (ADS)

Peolsson, Anneli; Peterson, Gunnel; Trygg, Johan; Nilsson, David

2016-08-01

Whiplash Associated Disorders (WAD) refers to the multifaceted and chronic burden that is common after a whiplash injury. Tools to assist in the diagnosis of WAD and an increased understanding of neck muscle behaviour are needed. We examined the multilayer dorsal neck muscle behaviour in nine women with chronic WAD versus healthy controls during the entire sequence of a dynamic low-loaded neck extension exercise, which was recorded using real-time ultrasound movies with high frame rates. Principal component analysis and orthogonal partial least squares were used to analyse mechanical muscle strain (deformation in elongation and shortening). The WAD group showed more shortening during the neck extension phase in the trapezius muscle and during both the neck extension and the return to neutral phase in the multifidus muscle. For the first time, a novel non-invasive method is presented that is capable of detecting altered dorsal muscle strain in women with WAD during an entire exercise sequence. This method may be a breakthrough for the future diagnosis and treatment of WAD.

Preliminary report on the use of LANDSAT-1 (ERTS-1) reflectance data in locating alteration zones associated with uranium mineralization near Cameron, Arizona

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

Spirakis, C.S.; Condit, C.D.

1975-01-01

LANDSAT-1 (ERTS-1) multispectral reflectance data were used to enhance the detection of alteration around uranium deposits near Cameron, Ariz. The technique involved stretching and ratioing computer-enhanced data from which electronic noise and atmospheric haze had been removed. Using present techniques, the work proves that LANDSAT-1 data are useful in detecting alteration around uranium deposits, but the method may still be improved. Bluish-gray mudstone in the target area could not be differentiated from the altered zones on the ratioed images. Further experiments involving combinations of ratioed and nonratioed data will be required to uniquely define the altered zones.

Concomitant ALK translocation and EGFR mutation in lung cancer: a comparison of direct sequencing and sensitive assays and the impact on responsiveness to tyrosine kinase inhibitor.

PubMed

Won, J K; Keam, B; Koh, J; Cho, H J; Jeon, Y K; Kim, T M; Lee, S H; Lee, D S; Kim, D W; Chung, D H

2015-02-01

Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation are considered mutually exclusive in nonsmall-cell lung cancer (NSCLC). However, sporadic cases having concomitant EGFR and ALK alterations have been reported. The present study aimed to assess the prevalence of NSCLCs with concomitant EGFR and ALK alterations using mutation detection methods with different sensitivity and to propose an effective diagnostic and therapeutic strategy. A total of 1458 cases of lung cancer were screened for EGFR and ALK alterations by direct sequencing and flourescence in situ hybridization (FISH), respectively. For the 91 patients identified as having an ALK translocation, peptide nucleic acid (PNA)-clamping real-time PCR, targeted next-generation sequencing (NGS), and mutant-enriched NGS assays were carried out to detect EGFR mutation. EGFR mutations and ALK translocations were observed in 42.4% (612/1445) and 6.3% (91/1445) of NSCLCs by direct sequencing and FISH, respectively. Concomitant EGFR and ALK alterations were detected in four cases, which accounted for 4.4% (4/91) of ALK-translocated NSCLCs. Additional analyses for EGFR using PNA real-time PCR and ultra-deep sequencing by NGS, mutant-enriched NGS increased the detection rate of concomitant EGFR and ALK alterations to 8.8% (8/91), 12.1% (11/91), and 15.4% (14/91) of ALK-translocated NSCLCs, respectively. Of the 14 patients, 3 who were treated with gefitinib showed poor response to gefitinib with stable disease in one and progressive disease in two patients. However, eight patients who received ALK inhibitor (crizotinib or ceritinib) showed good response, with response rate of 87.5% (7/8 with partial response) and durable progression-free survival. A portion of NSCLC patients have concomitant EGFR and ALK alterations and the frequency of co-alteration detection increases when sensitive detection methods for EGFR mutation are applied. ALK inhibitors appear to be effective for patients with co-alterations. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effect of UV-A and UV-B irradiation on the metabolic profile of aqueous humor in rabbits analyzed by 1H NMR spectroscopy.

PubMed

Tessem, May-Britt; Bathen, Tone F; Cejková, Jitka; Midelfart, Anna

2005-03-01

This study was conducted to investigate metabolic changes in aqueous humor from rabbit eyes exposed to either UV-A or -B radiation, by using (1)H nuclear magnetic resonance (NMR) spectroscopy and unsupervised pattern recognition methods. Both eyes of adult albino rabbits were irradiated with UV-A (366 nm, 0.589 J/cm(2)) or UV-B (312 nm, 1.667 J/cm(2)) radiation for 8 minutes, once a day for 5 days. Three days after the last irradiation, samples of aqueous humor were aspirated, and the metabolic profiles analyzed with (1)H NMR spectroscopy. The metabolic concentrations in the exposed and control materials were statistically analyzed and compared, with multivariate methods and one-way ANOVA. UV-B radiation caused statistically significant alterations of betaine, glucose, ascorbate, valine, isoleucine, and formate in the rabbit aqueous humor. By using principal component analysis, the UV-B-irradiated samples were clearly separated from the UV-A-irradiated samples and the control group. No significant metabolic changes were detected in UV-A-irradiated samples. This study demonstrates the potential of using unsupervised pattern recognition methods to extract valuable metabolic information from complex (1)H NMR spectra. UV-B irradiation of rabbit eyes led to significant metabolic changes in the aqueous humor detected 3 days after the last exposure.

Impact of innate and environmental factors on wheezing persistence during childhood.

PubMed

Just, Jocelyne; Belfar, Samira; Wanin, Stéphanie; Pribil, Céline; Grimfeld, Alain; Duru, Gérard

2010-05-01

Persistent asthma in adults starts often early in childhood and is associated with alterations in respiratory function that occur early in life. The aim of this study was to evaluate the importance of innate and environmental factors associated with occurrence of asthma during childhood in a population of recurrent wheezing infants followed prospectively. A cohort of infants less than 30 months old with recurrent wheezing was established in order to assess severity of respiratory symptoms and to look for the presence of atopy and environmental risk factors. At the age of 6 years, they were reevaluated with respect to remission or persistence of wheezing over the previous 12-month period. Data were available for 219 subjects aged 15 +/- 5 months. In 27% of the infants with recurrent wheeze, wheezing persisted until the age of 6 years. In multivariate analysis, stepwise logit analysis showed that the risk factors for persistent wheezing are eosinophilia >or=470/mm(3), allergenic sensitization, and a father with asthma. Environmental factors present during the first year of life that protect from persistence of wheezing are ( 1 ) breastfeeding for longer than 3 months, ( 2 ) pets at home, and ( 3 ) >or=3 siblings. The detection rate for persistent wheezing in this model is 72%. The persistence score showed good specificity 91% but low sensitivity 35%. This study confirms the role of atopic host factors on wheezing persistence during childhood and detected protective environmental factors.

Fourier Transform Infrared Imaging analysis of dental pulp inflammatory diseases.

PubMed

Giorgini, E; Sabbatini, S; Conti, C; Rubini, C; Rocchetti, R; Fioroni, M; Memè, L; Orilisi, G

2017-05-01

Fourier Transform Infrared microspectroscopy let characterize the macromolecular composition and distribution of tissues and cells, by studying the interaction between infrared radiation and matter. Therefore, we hypothesize to exploit this analytical tool in the analysis of inflamed pulps, to detect the different biochemical features related to various degrees of inflammation. IR maps of 13 irreversible and 12 hyperplastic pulpitis, together with 10 normal pulps, were acquired, compared with histological findings and submitted to multivariate (HCA, PCA, SIMCA) and statistical (one-way ANOVA) analysis. The fit of convoluted bands let calculate meaningful band area ratios (means ± s.d., P < 0.05). The infrared imaging analysis pin-pointed higher amounts of water and lower quantities of type I collagen in all inflamed pulps. Specific vibrational markers were defined for irreversible pulpitis (Lipids/Total Biomass, PhII/Total Biomass, CH 2 /CH 3 , and Ty/AII) and hyperplastic ones (OH/Total Biomass, Collagen/Total Biomass, and CH 3 Collagen/Total Biomass). The study confirmed that FTIR microspectroscopy let discriminate tissues' biological features. The infrared imaging analysis evidenced, in inflamed pulps, alterations in tissues' structure and composition. Changes in lipid metabolism, increasing amounts of tyrosine, and the occurrence of phosphorylative processes were highlighted in irreversible pulpitis, while high amounts of water and low quantities of type I collagen were detected in hyperplastic samples. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A micro-Raman spectroscopic investigation of leukemic U-937 cells in aged cultures

NASA Astrophysics Data System (ADS)

Fazio, Enza; Trusso, Sebastiano; Franco, Domenico; Nicolò, Marco Sebastiano; Allegra, Alessandro; Neri, Fortunato; Musolino, Caterina; Guglielmino, Salvatore P. P.

2016-04-01

Recently it has been shown that micro-Raman spectroscopy combined with multivariate analysis is able to discriminate among different types of tissues and tumoral cells by the detection of significant alterations and/or reorganizations of complex biological molecules, such as nucleic acids, lipids and proteins. Moreover, its use, being in principle a non-invasive technique, appears an interesting clinical tool for the evaluation of the therapeutical effects and of the disease progression. In this work we analyzed molecular changes in aged cultures of leukemia model U937 cells with respect to fresh cultures of the same cell line. In fact, structural variations of individual neoplastic cells on aging may lead to a heterogeneous data set, therefore falsifying confidence intervals, increasing error levels of analysis and consequently limiting the use of Raman spectroscopy analysis. We found that the observed morphological changes of U937 cells corresponded to well defined modifications of the Raman contributions in selected spectral regions, where markers of specific functional groups, useful to characterize the cell state, are present. A detailed subcellular analysis showed a change in cellular organization as a function of time, and correlated to a significant increase of apoptosis levels. Besides the aforementioned study, Raman spectra were used as input for principal component analysis (PCA) in order to detect and classify spectral changes among U937 cells.

Preoperative chemoradiotherapy alters the expression and prognostic significance of adhesion molecules in Barrett's-associated adenocarcinoma.

PubMed

Turner, J R; Torres, C M; Wang, H H; Shahsafaei, A; Richards, W G; Sugarbaker, D; Odze, R D

2000-03-01

A variety of prognostic markers have been related to decreased patient survival in patients with epithelial malignancies. These include expression of the homotypic adhesion molecule E-cadherin (ECAD) and the hyaluronic acid receptor CD44. Expression of ECAD and CD44 was evaluated in Barrett's-associated adenocarcinoma (BAd) from 67 patients. Expression was determined by immunoperoxidase staining and graded semiquantitatively based on the proportion of positively stained cells. These data were then correlated with clinical and pathological parameters, including the presence or absence of chemoradiotherapy (chemrad) and patient survival. There were 56 men and 11 women (mean age, 62 years). Thirty-nine (58%) patients received preoperative chemrad. ECAD expression was detected in all (100%) tumors. The ECAD staining grade did not correlate with other pathological features of the tumors. However, ECAD staining was significantly increased in BAd of patients who received chemrad (P = .003), in comparison with those who did not, and in individual patients when prechemrad biopsies and postchemrad resection specimens were compared (P = .04). In terms of prognosis, increased ECAD expression was associated with shortened patient survival only in BAd patients who had received chemrad (univariate analysis of chemrad patients with stage I and II BAd, P = .02). ECAD expression was not significantly associated with survival in BAd patients who did not receive chemrad. CD44 expression was detected in 88% of cases. CD44 expression did not correlate with any of the pathological features of the tumors or with chemrad status. Increased expression of CD44 was significantly associated with shortened patient survival in chemrad patients only (univariate analysis P = .03, multivariate analysis P = .04), although a strong trend was observed when all patients were analyzed regardless of chemrad status (P = .07). The results of this study indicate that chemrad alters the expression of ECAD in BAd. Thus, the prognostic utility of ECAD expression must be evaluated in the context of chemrad status. CD44 also may be a valuable prognostic marker in BAd.

Organochlorines and metals induce changes in the mitochondria-rich cells of fish gills: an integrative field study involving chemical, biochemical and morphological analyses.

PubMed

Fernandes, M N; Paulino, M G; Sakuragui, M M; Ramos, C A; Pereira, C D S; Sadauskas-Henrique, H

2013-01-15

Through integrating chemical, biochemical and morphological analyses, this study investigated the effects of multiple pollutants on the gill mitochondria-rich cells (MRCs) in two fish species, Astyanax fasciatus and Pimelodus maculatus, collected from five sites (FU10, FU20, FU30, FU40 and FU50) in the Furnas Hydroelectric Power Station reservoir. Water analyses revealed aluminum, iron and zinc as well as organochlorine (aldrin/dieldrin, endosulfan, heptachlor/heptachlor epoxide and metolachlor) contamination at all of the sites, with the exception of FU10. Copper, chrome, iron and zinc were detected in the gills of both species, and aldrin/dieldrin, endosulfan and heptachlor/heptachlor epoxide were detected in the gills of fish from all of the sites, with the exception of FU10. Fish collected at FU20, FU30 and FU50 exhibited numerous alterations in the surface architecture of their pavement cells and MRCs. The surface MRC density and MRC fractional area were lower in fish from FU20, FU30, FU40 and FU50 than in those from the reference site (FU10) in the winter, and some variability between the sites was observed in the summer. The organochlorine contamination at FU20 and FU50 was associated with variable changes in the MRCs and inhibition of Na(+)/K(+)-ATPase (NKA) activity, especially in P. maculatus. At FU30, the alterations in the MRCs were associated with the contaminants present, especially metals. A multivariate analysis demonstrated a positive association between the biological responses of both species and environmental contamination, indicating that under realistic conditions, a mixture of organochlorines and metals affected the MRCs by inhibiting NKA activity and inducing morphological changes, which may cause an ionic imbalance. Copyright © 2012 Elsevier B.V. All rights reserved.

Localization of genes involved in the metabolic syndrome using multivariate linkage analysis.

PubMed

Olswold, Curtis; de Andrade, Mariza

2003-12-31

There are no well accepted criteria for the diagnosis of the metabolic syndrome. However, the metabolic syndrome is identified clinically by the presence of three or more of these five variables: larger waist circumference, higher triglyceride levels, lower HDL-cholesterol concentrations, hypertension, and impaired fasting glucose. We use sets of two or three variables, which are available in the Framingham Heart Study data set, to localize genes responsible for this syndrome using multivariate quantitative linkage analysis. This analysis demonstrates the applicability of using multivariate linkage analysis and how its use increases the power to detect linkage when genes are involved in the same disease mechanism.

Trend Detection and Bivariate Frequency Analysis for Nonstrationary Rainfall Data

NASA Astrophysics Data System (ADS)

Joo, K.; Kim, H.; Shin, J. Y.; Heo, J. H.

2017-12-01

Multivariate frequency analysis has been developing for hydro-meteorological data such as rainfall, flood, and drought. Particularly, the copula has been used as a useful tool for multivariate probability model which has no limitation on deciding marginal distributions. The time-series rainfall data can be characterized to rainfall event by inter-event time definition (IETD) and each rainfall event has a rainfall depth and rainfall duration. In addition, nonstationarity in rainfall event has been studied recently due to climate change and trend detection of rainfall event is important to determine the data has nonstationarity or not. With the rainfall depth and duration of a rainfall event, trend detection and nonstationary bivariate frequency analysis has performed in this study. 62 stations from Korea Meteorological Association (KMA) over 30 years of hourly recorded data used in this study and the suitability of nonstationary copula for rainfall event has examined by the goodness-of-fit test.

Detecting seasonal and cyclical trends in agricultural runoff water quality-hypothesis tests and block bootstrap power analysis.

PubMed

Uddameri, Venkatesh; Singaraju, Sreeram; Hernandez, E Annette

2018-02-21

Seasonal and cyclic trends in nutrient concentrations at four agricultural drainage ditches were assessed using a dataset generated from a multivariate, multiscale, multiyear water quality monitoring effort in the agriculturally dominant Lower Rio Grande Valley (LRGV) River Watershed in South Texas. An innovative bootstrap sampling-based power analysis procedure was developed to evaluate the ability of Mann-Whitney and Noether tests to discern trends and to guide future monitoring efforts. The Mann-Whitney U test was able to detect significant changes between summer and winter nutrient concentrations at sites with lower depths and unimpeded flows. Pollutant dilution, non-agricultural loadings, and in-channel flow structures (weirs) masked the effects of seasonality. The detection of cyclical trends using the Noether test was highest in the presence of vegetation mainly for total phosphorus and oxidized nitrogen (nitrite + nitrate) compared to dissolved phosphorus and reduced nitrogen (total Kjeldahl nitrogen-TKN). Prospective power analysis indicated that while increased monitoring can lead to higher statistical power, the effect size (i.e., the total number of trend sequences within a time-series) had a greater influence on the Noether test. Both Mann-Whitney and Noether tests provide complementary information on seasonal and cyclic behavior of pollutant concentrations and are affected by different processes. The results from these statistical tests when evaluated in the context of flow, vegetation, and in-channel hydraulic alterations can help guide future data collection and monitoring efforts. The study highlights the need for long-term monitoring of agricultural drainage ditches to properly discern seasonal and cyclical trends.

Apparatus and method for transient thermal infrared spectrometry

DOEpatents

McClelland, John F.; Jones, Roger W.

1991-12-03

A method and apparatus for enabling analysis of a material (16, 42) by applying a cooling medium (20, 54) to cool a thin surface layer portion of the material and to transiently generate a temperature differential between the thin surface layer portion and the lower portion of the material sufficient to alter the thermal infrared emission spectrum of the material from the black-body thermal infrared emission spectrum of the material. The altered thermal infrared emission spectrum of the material is detected by a spectrometer/detector (28, 50) while the altered thermal infrared emission spectrum is sufficiently free of self-absorption by the material of the emitted infrared radiation. The detection is effected prior to the temperature differential propagating into the lower portion of the material to an extent such that the altered thermal infrared emission spectrum is no longer sufficiently free of self-absorption by the material of emitted infrared radiation, so that the detected altered thermal infrared emission spectrum is indicative of the characteristics relating to the molecular composition of the material.

Methods, media, and systems for detecting attack on a digital processing device

DOEpatents

Stolfo, Salvatore J.; Li, Wei-Jen; Keromylis, Angelos D.; Androulaki, Elli

2014-07-22

Methods, media, and systems for detecting attack are provided. In some embodiments, the methods include: comparing at least part of a document to a static detection model; determining whether attacking code is included in the document based on the comparison of the document to the static detection model; executing at least part of the document; determining whether attacking code is included in the document based on the execution of the at least part of the document; and if attacking code is determined to be included in the document based on at least one of the comparison of the document to the static detection model and the execution of the at least part of the document, reporting the presence of an attack. In some embodiments, the methods include: selecting a data segment in at least one portion of an electronic document; determining whether the arbitrarily selected data segment can be altered without causing the electronic document to result in an error when processed by a corresponding program; in response to determining that the arbitrarily selected data segment can be altered, arbitrarily altering the data segment in the at least one portion of the electronic document to produce an altered electronic document; and determining whether the corresponding program produces an error state when the altered electronic document is processed by the corresponding program.

Methods, media, and systems for detecting attack on a digital processing device

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

Stolfo, Salvatore J.; Li, Wei-Jen; Keromytis, Angelos D.

Methods, media, and systems for detecting attack are provided. In some embodiments, the methods include: comparing at least part of a document to a static detection model; determining whether attacking code is included in the document based on the comparison of the document to the static detection model; executing at least part of the document; determining whether attacking code is included in the document based on the execution of the at least part of the document; and if attacking code is determined to be included in the document based on at least one of the comparison of the document tomore » the static detection model and the execution of the at least part of the document, reporting the presence of an attack. In some embodiments, the methods include: selecting a data segment in at least one portion of an electronic document; determining whether the arbitrarily selected data segment can be altered without causing the electronic document to result in an error when processed by a corresponding program; in response to determining that the arbitrarily selected data segment can be altered, arbitrarily altering the data segment in the at least one portion of the electronic document to produce an altered electronic document; and determining whether the corresponding program produces an error state when the altered electronic document is processed by the corresponding program.« less

Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

DTIC Science & Technology

2016-12-01

Award Number: W81XWH-11-1-0744 TITLE: Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated...Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non- Neoplastic Prostate Tissue 5b. GRANT NUMBER 10623678 5c...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this project was to develop molecular models to

A comparison of hyperspectral reflectance and fluorescence imaging techniques for detection of contaminants on leafy greens

USDA-ARS?s Scientific Manuscript database

Ensuring the supply of safe, contaminant free fresh fruit and vegetables is of importance to consumers, suppliers and governments worldwide. In this study, three hyperspectral imaging (HSI) configurations coupled with two multivariate image analysis techniques are compared for detection of fecal con...

Detecting Outliers in Factor Analysis Using the Forward Search Algorithm

ERIC Educational Resources Information Center

Mavridis, Dimitris; Moustaki, Irini

2008-01-01

In this article we extend and implement the forward search algorithm for identifying atypical subjects/observations in factor analysis models. The forward search has been mainly developed for detecting aberrant observations in regression models (Atkinson, 1994) and in multivariate methods such as cluster and discriminant analysis (Atkinson, Riani,…

ORIENTATION REQUIREMENT TO DETECT MAGNETIC FIELD-INDUCTED ALTERATION OF GAP JUNCTION COMMUNICATION IN EPITHELIAL CELLS

EPA Science Inventory

ORIENTATION REQUIREMENT TO DETECT MAGNETIC FIELD-INDUCED ALTERATION OF GAP JUNCTION COMMUNICATION IN EPITHELIAL CELLS.
OBJECTIVE: We have shown that functional gap junction communication as measured by Lucifer yellow dye transfer (DT) in Clone-9 rat liver epithelial cells, c...

Serotonin and aggressive motivation in crustaceans: altering the decision to retreat.

PubMed

Huber, R; Smith, K; Delago, A; Isaksson, K; Kravitz, E A

1997-05-27

In crustaceans, as in most animal species, the amine serotonin has been suggested to serve important roles in aggression. Here we show that injection of serotonin into the hemolymph of subordinate, freely moving animals results in a renewed willingness of these animals to engage the dominants in further agonistic encounters. By multivariate statistical analysis, we demonstrate that this reversal results principally from a reduction in the likelihood of retreat and an increase in the duration of fighting. Serotonin infusion does not alter other aspects of fighting behavior, including which animal initiates an encounter, how quickly fighting escalates, or which animal eventually retreats. Preliminary studies suggest that serotonin uptake plays an important role in this behavioral reversal.

Lithologic discrimination and alteration mapping from AVIRIS Data, Socorro, New Mexico

NASA Technical Reports Server (NTRS)

Beratan, K. K.; Delillo, N.; Jacobson, A.; Blom, R.; Chapin, C. E.

1993-01-01

Geologic maps are, by their very nature, interpretive documents. In contrasts, images prepared from AVIRIS data can be used as uninterpreted, and thus unbiased, geologic maps. We are having significant success applying AVIRIS data in this non-quantitative manner to geologic problems. Much of our success has come from the power of the Linked Windows Interactive Data System. LinkWinds is a visual data analysis and exploration system under development at JPL which is designed to rapidly and interactively investigate large multivariate data sets. In this paper, we present information on the analysis technique, and preliminary results from research on potassium metasomatism, a distinctive and structurally significant type of alteration associated with crustal extension.

[Algorithm of toxigenic genetically altered Vibrio cholerae El Tor biovar strain identification].

PubMed

Smirnova, N I; Agafonov, D A; Zadnova, S P; Cherkasov, A V; Kutyrev, V V

2014-01-01

Development of an algorithm of genetically altered Vibrio cholerae biovar El Tor strai identification that ensures determination of serogroup, serovar and biovar of the studied isolate based on pheno- and genotypic properties, detection of genetically altered cholera El Tor causative agents, their differentiation by epidemic potential as well as evaluation of variability of key pathogenicity genes. Complex analysis of 28 natural V. cholerae strains was carried out by using traditional microbiological methods, PCR and fragmentary sequencing. An algorithm of toxigenic genetically altered V. cholerae biovar El Tor strain identification was developed that includes 4 stages: determination of serogroup, serovar and biovar based on phenotypic properties, confirmation of serogroup and biovar based on molecular-genetic properties determination of strains as genetically altered, differentiation of genetically altered strains by their epidemic potential and detection of ctxB and tcpA key pathogenicity gene polymorphism. The algorithm is based on the use of traditional microbiological methods, PCR and sequencing of gene fragments. The use of the developed algorithm will increase the effectiveness of detection of genetically altered variants of the cholera El Tor causative agent, their differentiation by epidemic potential and will ensure establishment of polymorphism of genes that code key pathogenicity factors for determination of origins of the strains and possible routes of introduction of the infection.

Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.

PubMed

Park, Ju Yeon; Lee, Sang-Hak; Shin, Min-Jeong; Hwang, Geum-Sook

2015-01-01

Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.

Untangling Magmatic Processes and Hydrothermal Alteration of in situ Superfast Spreading Ocean Crust at ODP/IODP Site 1256 with Fuzzy c-means Cluster Analysis of Rock Magnetic Properties

NASA Astrophysics Data System (ADS)

Dekkers, M. J.; Heslop, D.; Herrero-Bervera, E.; Acton, G.; Krasa, D.

2014-12-01

Ocean Drilling Program (ODP)/Integrated ODP (IODP) Hole 1256D (6.44.1' N, 91.56.1' W) on the Cocos Plate occurs in 15.2 Ma oceanic crust generated by superfast seafloor spreading. Presently, it is the only drill hole that has sampled all three oceanic crust layers in a tectonically undisturbed setting. Here we interpret down-hole trends in several rock-magnetic parameters with fuzzy c-means cluster analysis, a multivariate statistical technique. The parameters include the magnetization ratio, the coercivity ratio, the coercive force, the low-field susceptibility, and the Curie temperature. By their combined, multivariate, analysis the effects of magmatic and hydrothermal processes can be evaluated. The optimal number of clusters - a key point in the analysis because there is no a priori information on this - was determined through a combination of approaches: by calculation of several cluster validity indices, by testing for coherent cluster distributions on non-linear-map plots, and importantly by testing for stability of the cluster solution from all possible starting points. Here, we consider a solution robust if the cluster allocation is independent of the starting configuration. The five-cluster solution appeared to be robust. Three clusters are distinguished in the extrusive segment of the Hole that express increasing hydrothermal alteration of the lavas. The sheeted dike and gabbro portions are characterized by two clusters, both with higher coercivities than in lava samples. Extensive alteration, however, can obliterate magnetic property differences between lavas, dikes, and gabbros. The imprint of thermochemical alteration on the iron-titanium oxides is only partially related to the porosity of the rocks. All clusters display rock magnetic characteristics in line with a stable NRM. This implies that the entire sampled sequence of ocean crust can contribute to marine magnetic anomalies. Determination of the absolute paleointensity with thermal techniques is not straightforward because of the propensity of oxyexsolution during laboratory heating and/or the presence of intergrowths. The upper part of the extrusive sequence, the granoblastic portion of the dikes, and moderately altered gabbros may contain a comparatively uncontaminated thermoremanent magnetization.

Family-Based Rare Variant Association Analysis: A Fast and Efficient Method of Multivariate Phenotype Association Analysis.

PubMed

Wang, Longfei; Lee, Sungyoung; Gim, Jungsoo; Qiao, Dandi; Cho, Michael; Elston, Robert C; Silverman, Edwin K; Won, Sungho

2016-09-01

Family-based designs have been repeatedly shown to be powerful in detecting the significant rare variants associated with human diseases. Furthermore, human diseases are often defined by the outcomes of multiple phenotypes, and thus we expect multivariate family-based analyses may be very efficient in detecting associations with rare variants. However, few statistical methods implementing this strategy have been developed for family-based designs. In this report, we describe one such implementation: the multivariate family-based rare variant association tool (mFARVAT). mFARVAT is a quasi-likelihood-based score test for rare variant association analysis with multiple phenotypes, and tests both homogeneous and heterogeneous effects of each variant on multiple phenotypes. Simulation results show that the proposed method is generally robust and efficient for various disease models, and we identify some promising candidate genes associated with chronic obstructive pulmonary disease. The software of mFARVAT is freely available at http://healthstat.snu.ac.kr/software/mfarvat/, implemented in C++ and supported on Linux and MS Windows. © 2016 WILEY PERIODICALS, INC.

Setting up a probe based, closed tube real-time PCR assay for focused detection of variable sequence alterations.

PubMed

Becságh, Péter; Szakács, Orsolya

2014-10-01

During diagnostic workflow when detecting sequence alterations, sometimes it is important to design an algorithm that includes screening and direct tests in combination. Normally the use of direct test, which is mainly sequencing, is limited. There is an increased need for effective screening tests, with "closed tube" during the whole process and therefore decreasing the risk of PCR product contamination. The aim of this study was to design such a closed tube, detection probe based screening assay to detect different kind of sequence alterations in the exon 11 of the human c-kit gene region. Inside this region there are variable possible deletions and single nucleotide changes. During assay setup, more probe chemistry formats were screened and tested. After some optimization steps the taqman probe format was selected.

On the Power of Multivariate Latent Growth Curve Models to Detect Correlated Change

ERIC Educational Resources Information Center

Hertzog, Christopher; Lindenberger, Ulman; Ghisletta, Paolo; Oertzen, Timo von

2006-01-01

We evaluated the statistical power of single-indicator latent growth curve models (LGCMs) to detect correlated change between two variables (covariance of slopes) as a function of sample size, number of longitudinal measurement occasions, and reliability (measurement error variance). Power approximations following the method of Satorra and Saris…

Rapid and early detection of salmonella serotypes with hyperspectral microscope and multivariate data analysis

USDA-ARS?s Scientific Manuscript database

This study was designed to evaluate hyperspectral microscope images for early and rapid detection of Salmonella serotypes: S. Enteritidis, S. Heidelberg, S. Infantis, S. Kentucky, and S. Typhimurium at incubation times of 6, 8, 10, 12, and 24 hours. Images were collected by an acousto-optical tunab...

Multidimensional Approach to Detecting Creative Potential in Managers

ERIC Educational Resources Information Center

Caroff, Xavier; Lubart, Todd

2012-01-01

Creativity is increasingly recognized as a key component to success in the workplace. This article explores the detection of creative potential in managers. In a first part, creative potential is defined and a multivariate approach concerning the psychological resources for creativity is presented. Then, in a second part, an application of this…

Detecting spatial regimes in ecosystems

USGS Publications Warehouse

Sundstrom, Shana M.; Eason, Tarsha; Nelson, R. John; Angeler, David G.; Barichievy, Chris; Garmestani, Ahjond S.; Graham, Nicholas A.J.; Granholm, Dean; Gunderson, Lance; Knutson, Melinda; Nash, Kirsty L.; Spanbauer, Trisha; Stow, Craig A.; Allen, Craig R.

2017-01-01

Research on early warning indicators has generally focused on assessing temporal transitions with limited application of these methods to detecting spatial regimes. Traditional spatial boundary detection procedures that result in ecoregion maps are typically based on ecological potential (i.e. potential vegetation), and often fail to account for ongoing changes due to stressors such as land use change and climate change and their effects on plant and animal communities. We use Fisher information, an information theory-based method, on both terrestrial and aquatic animal data (U.S. Breeding Bird Survey and marine zooplankton) to identify ecological boundaries, and compare our results to traditional early warning indicators, conventional ecoregion maps and multivariate analyses such as nMDS and cluster analysis. We successfully detected spatial regimes and transitions in both terrestrial and aquatic systems using Fisher information. Furthermore, Fisher information provided explicit spatial information about community change that is absent from other multivariate approaches. Our results suggest that defining spatial regimes based on animal communities may better reflect ecological reality than do traditional ecoregion maps, especially in our current era of rapid and unpredictable ecological change.

Testing for the Presence of Correlation Changes in a Multivariate Time Series: A Permutation Based Approach.

PubMed

Cabrieto, Jedelyn; Tuerlinckx, Francis; Kuppens, Peter; Hunyadi, Borbála; Ceulemans, Eva

2018-01-15

Detecting abrupt correlation changes in multivariate time series is crucial in many application fields such as signal processing, functional neuroimaging, climate studies, and financial analysis. To detect such changes, several promising correlation change tests exist, but they may suffer from severe loss of power when there is actually more than one change point underlying the data. To deal with this drawback, we propose a permutation based significance test for Kernel Change Point (KCP) detection on the running correlations. Given a requested number of change points K, KCP divides the time series into K + 1 phases by minimizing the within-phase variance. The new permutation test looks at how the average within-phase variance decreases when K increases and compares this to the results for permuted data. The results of an extensive simulation study and applications to several real data sets show that, depending on the setting, the new test performs either at par or better than the state-of-the art significance tests for detecting the presence of correlation changes, implying that its use can be generally recommended.

Detection and discrimination of microorganisms on various substrates with quantum cascade laser spectroscopy

NASA Astrophysics Data System (ADS)

Padilla-Jiménez, Amira C.; Ortiz-Rivera, William; Rios-Velazquez, Carlos; Vazquez-Ayala, Iris; Hernández-Rivera, Samuel P.

2014-06-01

Investigations focusing on devising rapid and accurate methods for developing signatures for microorganisms that could be used as biological warfare agents' detection, identification, and discrimination have recently increased significantly. Quantum cascade laser (QCL)-based spectroscopic systems have revolutionized many areas of defense and security including this area of research. In this contribution, infrared spectroscopy detection based on QCL was used to obtain the mid-infrared (MIR) spectral signatures of Bacillus thuringiensis, Escherichia coli, and Staphylococcus epidermidis. These bacteria were used as microorganisms that simulate biothreats (biosimulants) very truthfully. The experiments were conducted in reflection mode with biosimulants deposited on various substrates including cardboard, glass, travel bags, wood, and stainless steel. Chemometrics multivariate statistical routines, such as principal component analysis regression and partial least squares coupled to discriminant analysis, were used to analyze the MIR spectra. Overall, the investigated infrared vibrational techniques were useful for detecting target microorganisms on the studied substrates, and the multivariate data analysis techniques proved to be very efficient for classifying the bacteria and discriminating them in the presence of highly IR-interfering media.

Multivariate Feature Selection of Image Descriptors Data for Breast Cancer with Computer-Assisted Diagnosis

PubMed Central

Galván-Tejada, Carlos E.; Zanella-Calzada, Laura A.; Galván-Tejada, Jorge I.; Celaya-Padilla, José M.; Gamboa-Rosales, Hamurabi; Garza-Veloz, Idalia; Martinez-Fierro, Margarita L.

2017-01-01

Breast cancer is an important global health problem, and the most common type of cancer among women. Late diagnosis significantly decreases the survival rate of the patient; however, using mammography for early detection has been demonstrated to be a very important tool increasing the survival rate. The purpose of this paper is to obtain a multivariate model to classify benign and malignant tumor lesions using a computer-assisted diagnosis with a genetic algorithm in training and test datasets from mammography image features. A multivariate search was conducted to obtain predictive models with different approaches, in order to compare and validate results. The multivariate models were constructed using: Random Forest, Nearest centroid, and K-Nearest Neighbor (K-NN) strategies as cost function in a genetic algorithm applied to the features in the BCDR public databases. Results suggest that the two texture descriptor features obtained in the multivariate model have a similar or better prediction capability to classify the data outcome compared with the multivariate model composed of all the features, according to their fitness value. This model can help to reduce the workload of radiologists and present a second opinion in the classification of tumor lesions. PMID:28216571

Multivariate Feature Selection of Image Descriptors Data for Breast Cancer with Computer-Assisted Diagnosis.

PubMed

Galván-Tejada, Carlos E; Zanella-Calzada, Laura A; Galván-Tejada, Jorge I; Celaya-Padilla, José M; Gamboa-Rosales, Hamurabi; Garza-Veloz, Idalia; Martinez-Fierro, Margarita L

2017-02-14

Breast cancer is an important global health problem, and the most common type of cancer among women. Late diagnosis significantly decreases the survival rate of the patient; however, using mammography for early detection has been demonstrated to be a very important tool increasing the survival rate. The purpose of this paper is to obtain a multivariate model to classify benign and malignant tumor lesions using a computer-assisted diagnosis with a genetic algorithm in training and test datasets from mammography image features. A multivariate search was conducted to obtain predictive models with different approaches, in order to compare and validate results. The multivariate models were constructed using: Random Forest, Nearest centroid, and K-Nearest Neighbor (K-NN) strategies as cost function in a genetic algorithm applied to the features in the BCDR public databases. Results suggest that the two texture descriptor features obtained in the multivariate model have a similar or better prediction capability to classify the data outcome compared with the multivariate model composed of all the features, according to their fitness value. This model can help to reduce the workload of radiologists and present a second opinion in the classification of tumor lesions.

Visualizing frequent patterns in large multivariate time series

NASA Astrophysics Data System (ADS)

Hao, M.; Marwah, M.; Janetzko, H.; Sharma, R.; Keim, D. A.; Dayal, U.; Patnaik, D.; Ramakrishnan, N.

2011-01-01

The detection of previously unknown, frequently occurring patterns in time series, often called motifs, has been recognized as an important task. However, it is difficult to discover and visualize these motifs as their numbers increase, especially in large multivariate time series. To find frequent motifs, we use several temporal data mining and event encoding techniques to cluster and convert a multivariate time series to a sequence of events. Then we quantify the efficiency of the discovered motifs by linking them with a performance metric. To visualize frequent patterns in a large time series with potentially hundreds of nested motifs on a single display, we introduce three novel visual analytics methods: (1) motif layout, using colored rectangles for visualizing the occurrences and hierarchical relationships of motifs in a multivariate time series, (2) motif distortion, for enlarging or shrinking motifs as appropriate for easy analysis and (3) motif merging, to combine a number of identical adjacent motif instances without cluttering the display. Analysts can interactively optimize the degree of distortion and merging to get the best possible view. A specific motif (e.g., the most efficient or least efficient motif) can be quickly detected from a large time series for further investigation. We have applied these methods to two real-world data sets: data center cooling and oil well production. The results provide important new insights into the recurring patterns.

Multivariate Tensor-based Morphometry on Surfaces: Application to Mapping Ventricular Abnormalities in HIV/AIDS

PubMed Central

Wang, Yalin; Zhang, Jie; Gutman, Boris; Chan, Tony F.; Becker, James T.; Aizenstein, Howard J.; Lopez, Oscar L.; Tamburo, Robert J.; Toga, Arthur W.; Thompson, Paul M.

2010-01-01

Here we developed a new method, called multivariate tensor-based surface morphometry (TBM), and applied it to study lateral ventricular surface differences associated with HIV/AIDS. Using concepts from differential geometry and the theory of differential forms, we created mathematical structures known as holomorphic one-forms, to obtain an efficient and accurate conformal parameterization of the lateral ventricular surfaces in the brain. The new meshing approach also provides a natural way to register anatomical surfaces across subjects, and improves on prior methods as it handles surfaces that branch and join at complex 3D junctions. To analyze anatomical differences, we computed new statistics from the Riemannian surface metrics - these retain multivariate information on local surface geometry. We applied this framework to analyze lateral ventricular surface morphometry in 3D MRI data from 11 subjects with HIV/AIDS and 8 healthy controls. Our method detected a 3D profile of surface abnormalities even in this small sample. Multivariate statistics on the local tensors gave better effect sizes for detecting group differences, relative to other TBM-based methods including analysis of the Jacobian determinant, the largest and smallest eigenvalues of the surface metric, and the pair of eigenvalues of the Jacobian matrix. The resulting analysis pipeline may improve the power of surface-based morphometry studies of the brain. PMID:19900560

Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study

PubMed Central

Le Strat, Yann

2017-01-01

The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F1-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances. PMID:28715489

Multivariate thermo-hygrometric characterisation of the archaeological site of Plaza de l'Almoina (Valencia, Spain) for preventive conservation.

PubMed

Fernández-Navajas, Angel; Merello, Paloma; Beltrán, Pedro; García-Diego, Fernando-Juan

2013-07-29

Preventive conservation requires monitoring and control of the parameters involved in the deterioration process, mainly temperature and relative humidity. It is important to characterise an archaeological site prior to carrying out comparative studies in the future for preventive conservation, either by regular studies to verify whether the conditions are constant, or occasional ones when the boundary conditions are altered. There are numerous covered archaeological sites, but few preventive conservation works that give special attention to the type of cover installed. In particular, there is no background of microclimatic studies in sites that are in the ground and, as in the Plaza de l'Almoina (Valencia, Spain), are buried and partially covered by a transparent roof. A large effect of the transparent cover was found by the sensors located below this area, with substantial increases in temperature and a decrease in the relative humidity during the day. Surrounding zones also have values above the recommended temperature values. On the other hand, the influence of a buried water drainage line near the site is notable, causing an increase in relative humidity levels in the surrounding areas. Multivariate statistical analyses enabled us to characterise the microclimate of the archaeological site, allowing future testing to determine whether the conservation conditions have been altered.

Multivariate Thermo-Hygrometric Characterisation of the Archaeological Site of Plaza de l’Almoina (Valencia, Spain) for Preventive Conservation

PubMed Central

Fernández-Navajas, Ángel; Merello, Paloma; Beltrán, Pedro; García-Diego, Fernando-Juan

2013-01-01

Preventive conservation requires monitoring and control of the parameters involved in the deterioration process, mainly temperature and relative humidity. It is important to characterise an archaeological site prior to carrying out comparative studies in the future for preventive conservation, either by regular studies to verify whether the conditions are constant, or occasional ones when the boundary conditions are altered. There are numerous covered archaeological sites, but few preventive conservation works that give special attention to the type of cover installed. In particular, there is no background of microclimatic studies in sites that are in the ground and, as in the Plaza de l’Almoina (Valencia, Spain), are buried and partially covered by a transparent roof. A large effect of the transparent cover was found by the sensors located below this area, with substantial increases in temperature and a decrease in the relative humidity during the day. Surrounding zones also have values above the recommended temperature values. On the other hand, the influence of a buried water drainage line near the site is notable, causing an increase in relative humidity levels in the surrounding areas. Multivariate statistical analyses enabled us to characterise the microclimate of the archaeological site, allowing future testing to determine whether the conservation conditions have been altered. PMID:23899937

Multivariate Modeling of Proteins Related to Trapezius Myalgia, a Comparative Study of Female Cleaners with or without Pain

PubMed Central

Hadrevi, Jenny; Ghafouri, Bijar; Larsson, Britt; Gerdle, Björn; Hellström, Fredrik

2013-01-01

The prevalence of chronic trapezius myalgia is high in women with high exposure to awkward working positions, repetitive movements and movements with high precision demands. The mechanisms behind chronic trapezius myalgia are not fully understood. The purpose of this study was to explore the differences in protein content between healthy and myalgic trapezius muscle using proteomics. Muscle biopsies from 12 female cleaners with work-related trapezius myalgia and 12 pain free female cleaners were obtained from the descending part of the trapezius. Proteins were separated with two-dimensional differential gel electrophoresis (2D-DIGE) and selected proteins were identified with mass spectrometry. In order to discriminate the two groups, quantified proteins were fitted to a multivariate analysis: partial least square discriminate analysis. The model separated 28 unique proteins which were related to glycolysis, the tricaboxylic acid cycle, to the contractile apparatus, the cytoskeleton and to acute response proteins. The results suggest altered metabolism, a higher abundance of proteins related to inflammation in myalgic cleaners compared to healthy, and a possible alteration of the contractile apparatus. This explorative proteomic screening of proteins related to chronic pain in the trapezius muscle provides new important aspects of the pathophysiology behind chronic trapezius myalgia. PMID:24023854

Multivariate modeling of proteins related to trapezius myalgia, a comparative study of female cleaners with or without pain.

PubMed

Hadrevi, Jenny; Ghafouri, Bijar; Larsson, Britt; Gerdle, Björn; Hellström, Fredrik

2013-01-01

The prevalence of chronic trapezius myalgia is high in women with high exposure to awkward working positions, repetitive movements and movements with high precision demands. The mechanisms behind chronic trapezius myalgia are not fully understood. The purpose of this study was to explore the differences in protein content between healthy and myalgic trapezius muscle using proteomics. Muscle biopsies from 12 female cleaners with work-related trapezius myalgia and 12 pain free female cleaners were obtained from the descending part of the trapezius. Proteins were separated with two-dimensional differential gel electrophoresis (2D-DIGE) and selected proteins were identified with mass spectrometry. In order to discriminate the two groups, quantified proteins were fitted to a multivariate analysis: partial least square discriminate analysis. The model separated 28 unique proteins which were related to glycolysis, the tricaboxylic acid cycle, to the contractile apparatus, the cytoskeleton and to acute response proteins. The results suggest altered metabolism, a higher abundance of proteins related to inflammation in myalgic cleaners compared to healthy, and a possible alteration of the contractile apparatus. This explorative proteomic screening of proteins related to chronic pain in the trapezius muscle provides new important aspects of the pathophysiology behind chronic trapezius myalgia.

Ultrasound detection of prostatic calculi as a parameter to predict the appearance of hematospermia after a prostate biopsy.

PubMed

Dell'Atti, Lucio

2017-01-01

We evaluated the correlation between prostate calculi and hematospermia in patients undergoing prostate biopsy, and its impact on sexual activity of patients. A single-center prospective randomized study of 212 patients referred for transrectal ultrasound-guided prostate biopsy (TRUSBx) was performed. All patients were divided into two groups: Group A (GA), 106 patients with moderate/marked presence of prostatic calculi visualized by TRUS; Group B (GB), 106 patients with absence/scarce of prostatic calcifications. Patients were handed questionnaires to obtain a validated data on the duration and impact of hematospermia on sexual activity. The anxiety scores were recorded using a visual analogue scale. No significant difference was noted between the two groups when comparing age, preoperative PSA level, prostate volume, and biopsy number, except for digital rectal examination (DRE) findings. Post-biopsy results of patients included in GA revealed that the complication of hematospermia was present in 65.1%, while in GB was present in 39.7% (p<0.001). On multivariate analysis for identifying significant preoperative predictors of hematospermia, which included variables of age, PSA, prostate volume, and prostate cancer were not shown to be significant predictors of hematospermia, except DRE and prostate calculi (p<0.001). The mean anxiety score was 3.7±2.8 in GA and 2.3±1.9 in GB, respectively (p<0.001). Prostatic calculi are an independent predictive factor of severe hematospermia after TRUSBx on the basis of multivariate analysis, but don't affect the positive rate of prostate cancer. Patients should be adequately counselled before TRUSBx to avoid undue anxiety and alterations in sexual activity. Copyright® by the International Brazilian Journal of Urology.

Gene Methylation and Cytological Atypia in Random Fine-Needle Aspirates for Assessment of Breast Cancer Risk.

PubMed

Stearns, Vered; Fackler, Mary Jo; Hafeez, Sidra; Bujanda, Zoila Lopez; Chatterton, Robert T; Jacobs, Lisa K; Khouri, Nagi F; Ivancic, David; Kenney, Kara; Shehata, Christina; Jeter, Stacie C; Wolfman, Judith A; Zalles, Carola M; Huang, Peng; Khan, Seema A; Sukumar, Saraswati

2016-08-01

Methods to determine individualized breast cancer risk lack sufficient sensitivity to select women most likely to benefit from preventive strategies. Alterations in DNA methylation occur early in breast cancer. We hypothesized that cancer-specific methylation markers could enhance breast cancer risk assessment. We evaluated 380 women without a history of breast cancer. We determined their menopausal status or menstrual cycle phase, risk of developing breast cancer (Gail model), and breast density and obtained random fine-needle aspiration (rFNA) samples for assessment of cytopathology and cumulative methylation index (CMI). Eight methylated gene markers were identified through whole-genome methylation analysis and included novel and previously established breast cancer detection genes. We performed correlative and multivariate linear regression analyses to evaluate DNA methylation of a gene panel as a function of clinical factors associated with breast cancer risk. CMI and individual gene methylation were independent of age, menopausal status or menstrual phase, lifetime Gail risk score, and breast density. CMI and individual gene methylation for the eight genes increased significantly (P < 0.001) with increasing cytological atypia. The findings were verified with multivariate analyses correcting for age, log (Gail), log (percent density), rFNA cell number, and body mass index. Our results demonstrate a significant association between cytological atypia and high CMI, which does not vary with menstrual phase or menopause and is independent of Gail risk and mammographic density. Thus, CMI is an excellent candidate breast cancer risk biomarker, warranting larger prospective studies to establish its utility for cancer risk assessment. Cancer Prev Res; 9(8); 673-82. ©2016 AACR. ©2016 American Association for Cancer Research.

Adherence to secondary antibiotic prophylaxis for patients with rheumatic heart disease diagnosed through screening in Fiji.

PubMed

Engelman, Daniel; Mataika, Reapi L; Kado, Joseph H; Ah Kee, Maureen; Donath, Susan; Parks, Tom; Steer, Andrew C

2016-12-01

Echocardiographic screening for rheumatic heart disease (RHD) can detect subclinical cases; however, adequate adherence to secondary antibiotic prophylaxis (SAP) is required to alter disease outcomes. We aimed to investigate the adherence to SAP among young people with RHD diagnosed through echocardiographic screening in Fiji and to investigate factors associated with adherence. Patients diagnosed with RHD through echocardiographic screening in Fiji from 2006 to 2014 were included. Dates of benzathine penicillin G injections were collected from 76 health clinics nationally from December 2011 to December 2014. Adherence was measured using the proportion of days covered (PDC). Multivariate logistic regression analysis was used to identify characteristics associated with any adherence (≥1 injection received) and adequate adherence (PDC ≥0.80). Of 494 patients, 268 (54%) were female and the median age was 14 years. Overall, 203 (41%) had no injections recorded and just 33 (7%) had adequate adherence. Multivariate logistic regression showed increasing age (OR 0.93 per year, 95% CI 0.87-0.99) and time since diagnosis ≥1.5 years (OR 0.53, 95% CI 0.37-0.79) to be inversely associated with any adherence. Non-iTaukei ethnicity (OR 2.58, 95%CI 1.04-6.33) and urban residence (OR 3.36, 95% CI 1.54-7.36) were associated with adequate adherence, whereas time since diagnosis ≥1.5 years (OR 0.38, 95%CI 0.17-0.83) was inversely associated with adequate adherence. Adherence to SAP after screening in Fiji is currently inadequate for individual patient protection or population disease control. Secondary prevention should be strengthened before further screening can be justified. © 2016 John Wiley & Sons Ltd.

Expression Levels and Clinical Significance of miR-21-5p, miR-let-7a, and miR-34c-5p in Laryngeal Squamous Cell Carcinoma

PubMed Central

Gioacchini, Federico M.; Çeka, Artan; Rubini, Corrado; Ferrante, Luigi; Procopio, Antonio D.; Olivieri, Fabiola

2017-01-01

Objective Altered microRNAs (miRNAs) expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). The aim of this study was to determine the role and clinical value of three LSCC-related miRs, such as miR-21-5p, miR-let-7a, and miR-34c-5p in a homogeneous cohort of patients with primary LSCC treated by primary surgery. Methods Expression levels of miR-21-5p, miR-let-7a, and miR-34c-5p were detected in 43 pairs of LSCC and adjacent normal tissues by reverse-transcription quantitative PCR. Overall survival and disease-free survival were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results miR-21-5p is significantly upregulated, while miR-let-7a is significantly downregulated in LSCC tumor tissues compared with the corresponding adjacent normal tissues. The downregulation of miR-34c-5p expression significantly correlated with a shorter disease-free survival and, in the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. Conclusions miR-21-5p, miR-let-7a, and miR-34c-5p seem to play a critical role in LSCC carcinogenesis and might have a diagnostic and prognostic clinical value. The miR-let-7a levels could have a predictive role for lymph node metastases and miR-34c-5p might be a promising biomarker of patient outcome. PMID:29082244

External Influences on Modeled and Observed Cloud Trends

NASA Technical Reports Server (NTRS)

Marvel, Kate; Zelinka, Mark; Klein, Stephen A.; Bonfils, Celine; Caldwell, Peter; Doutriaux, Charles; Santer, Benjamin D.; Taylor, Karl E.

2015-01-01

Understanding the cloud response to external forcing is a major challenge for climate science. This crucial goal is complicated by intermodel differences in simulating present and future cloud cover and by observational uncertainty. This is the first formal detection and attribution study of cloud changes over the satellite era. Presented herein are CMIP5 (Coupled Model Intercomparison Project - Phase 5) model-derived fingerprints of externally forced changes to three cloud properties: the latitudes at which the zonally averaged total cloud fraction (CLT) is maximized or minimized, the zonal average CLT at these latitudes, and the height of high clouds at these latitudes. By considering simultaneous changes in all three properties, the authors define a coherent multivariate fingerprint of cloud response to external forcing and use models from phase 5 of CMIP (CMIP5) to calculate the average time to detect these changes. It is found that given perfect satellite cloud observations beginning in 1983, the models indicate that a detectable multivariate signal should have already emerged. A search is then made for signals of external forcing in two observational datasets: ISCCP (International Satellite Cloud Climatology Project) and PATMOS-x (Advanced Very High Resolution Radiometer (AVHRR) Pathfinder Atmospheres - Extended). The datasets are both found to show a poleward migration of the zonal CLT pattern that is incompatible with forced CMIP5 models. Nevertheless, a detectable multivariate signal is predicted by models over the PATMOS-x time period and is indeed present in the dataset. Despite persistent observational uncertainties, these results present a strong case for continued efforts to improve these existing satellite observations, in addition to planning for new missions.

BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations

PubMed Central

Carranza, Hernán; Vargas, Carlos; Otero, Jorge; Corrales-Rodriguez, Luis; Martín, Claudio; Reguart, Noemí; Archila, Pilar; Rodríguez, July; Cuello, Mauricio; Ortíz, Carlos; Franco, Sandra; Rolfo, Christian; Rosell, Rafael

2016-01-01

Background Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations. Results BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM-del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006). Methods We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM-del. Conclusions The incidence of BIM-del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation. PMID:27926478

Assessment of biomarkers for contaminants of emerging concern on aquatic organisms downstream of a municipal wastewater discharge.

PubMed

Jasinska, Edyta J; Goss, Greg G; Gillis, Patricia L; Van Der Kraak, Glen J; Matsumoto, Jacqueline; de Souza Machado, Anderson A; Giacomin, Marina; Moon, Thomas W; Massarsky, Andrey; Gagné, Francois; Servos, Mark R; Wilson, Joanna; Sultana, Tamanna; Metcalfe, Chris D

2015-10-15

Contaminants of emerging concern (CECs), including pharmaceuticals, personal care products and estrogens, are detected in wastewater treatment plant (WWTP) discharges. However, analytical monitoring of wastewater and surface water does not indicate whether CECs are affecting the organisms downstream. In this study, fathead minnows (Pimephales promelas) and freshwater mussels Pyganodon grandis Say, 1829 (synonym: Anodonta grandis Say, 1829) were caged for 4 weeks in the North Saskatchewan River, upstream and downstream of the discharge from the WWTP that serves the Edmonton, AB, Canada. Passive samplers deployed indicated that concentrations of pharmaceuticals, personal care products, an estrogen (estrone) and an androgen (androstenedione) were elevated at sites downstream of the WWTP discharge. Several biomarkers of exposure were significantly altered in the tissues of caged fathead minnows and freshwater mussels relative to the upstream reference sites. Biomarkers altered in fish included induction of CYP3A metabolism, an increase in vitellogenin (Vtg) gene expression in male minnows, elevated ratios of oxidized to total glutathione (i.e. GSSG/TGSH), and an increase in the activity of antioxidant enzymes (i.e. glutathione reductase, glutathione-S-transferase). In mussels, there were no significant changes in biomarkers of oxidative stress and the levels of Vtg-like proteins were reduced, not elevated, indicating a generalized stress response. Immune function was altered in mussels, as indicated by elevated lysosomal activity per hemocyte in P. grandis caged closest to the wastewater discharge. This immune response may be due to exposure to bacterial pathogens in the wastewater. Multivariate analysis indicated a response to the CECs Carbamazepine (CBZ) and Trimethoprim (TPM). Overall, these data indicate that there is a 1 km zone of impact for aquatic organisms downstream of WWTP discharge. However, multiple stressors in municipal wastewater make measurement and interpretation of impact of CECs difficult since water temperature, conductivity and bacteria are also inducing biomarker responses in both fish and mussels. Copyright © 2015 Elsevier B.V. All rights reserved.

Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease.

PubMed

Sartini, Alessandro; Gitto, Stefano; Bianchini, Marcello; Verga, Maria Chiara; Di Girolamo, Maria; Bertani, Angela; Del Buono, Mariagrazia; Schepis, Filippo; Lei, Barbara; De Maria, Nicola; Villa, Erica

2018-01-24

Non-alcoholic fatty liver disease (NAFLD) can be detected in up to 33.6% of inflammatory bowel disease (IBD) patients, often in absence of metabolic risk factors. Nevertheless, most of previous studies on such issue were conducted within the IBD population only. The primary aim of this study was to compare clinical and metabolic features of NAFLD in patients with and without IBD (w/o IBD) and to identify specific NAFLD phenotypes within the IBD population. Among 223 NAFLD patients, 78 patients with IBD were younger compared to 145 without (w/o) IBD, were less likely to have altered liver enzymes, had lower mean body weight, smaller waist circumference and lower body mass index (BMI); at the same time, MetS was more prevalent among patients w/o IBD (56.6 vs. 23.1%, p < 0.001). Within IBD population, patients with severe IBD showed more often severe steatosis (S3) at ultrasound (US) (32.1 vs. 16.6%, p = 0.01), compared to mild-to-moderate disease. Independent risk factors for S3 US steatosis in IBD patients at the multivariate logistic regression analysis were: more than 1 IBD relapse per year during disease history (OR 17.3, 95% CI 3.6-84), surgery for IBD (OR 15.1, 95% CI 3.1-73.7) and more extensive intestinal involvement (OR 19.4, 95% CI 3.4-110.9); the ongoing anti-Tumor Necrosis Factor alpha (antiTNFα) therapy was the only independent factor which protect toward the presence of altered liver enzymes (OR 0.15, 95% CI 0-0.8, p = 0.02). In conclusion, NAFLD in IBD patients is different from that in patients w/o IBD, who seem to develop different NAFLD phenotypes according to intestinal disease clinical course. More severe IBD seem to predict the presence of more severe steatosis. Therapy with antiTNFα antibodies could prevent alteration of liver enzymes in such population.

BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations.

PubMed

Cardona, Andrés F; Rojas, Leonardo; Wills, Beatriz; Arrieta, Oscar; Carranza, Hernán; Vargas, Carlos; Otero, Jorge; Corrales-Rodriguez, Luis; Martín, Claudio; Reguart, Noemí; Archila, Pilar; Rodríguez, July; Cuello, Mauricio; Ortíz, Carlos; Franco, Sandra; Rolfo, Christian; Rosell, Rafael; on behalf of the CLICaP

2016-09-19

Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations. BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM-del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006). We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM-del. The incidence of BIM-del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation.

Comparing the impact of ultrafine particles from petrodiesel and biodiesel combustion to bacterial metabolism by targeted HPLC-MS/MS metabolic profiling.

PubMed

Zhong, Fanyi; Xu, Mengyang; Schelli, Katie; Rutowski, Joshua; Holmén, Britt A; Zhu, Jiangjiang

2017-08-01

Alterations of gut bacterial metabolism play an important role in their host metabolism, and can result in diseases such as obesity and diabetes. While many factors were discovered influencing the gut bacterial metabolism, exposure to ultrafine particles (UFPs) from engine combustions were recently proposed to be a potential risk factor for the perturbation of gut bacterial metabolism, and consequentially to obesity and diabetes development. This study focused on evaluation of how UFPs from diesel engine combustions impact gut bacterial metabolism. We hypothesize that UFPs from different type of diesel (petrodiesel vs. biodiesel) will both impact bacterial metabolism, and the degree of impact is also diesel type-dependent. Targeted metabolic profiling of 221 metabolites were applied to three model gut bacteria in vitro, Streptococcus salivarius, Lactobacillus acidophilus and Lactobacillus fermentum. UFPs from two types of fuels, petrodiesel (B0) and a biodiesel blend (B20: 20% soy biodiesel/80% B0 by volume), were exposed to the bacteria and their metabolic changes were compared. For each bacterial strain, metabolites with significantly changed abundance were observed in both perturbations, and all three strains have increased number of altered metabolites detected from B20 UFPs perturbation in comparison to B0 UFPs. Multivariate statistical analysis further confirmed that the metabolic profiles were clearly different between testing groups. Metabolic pathway analyses also demonstrated several important metabolic pathways, including pathways involves amino acids biosynthesis and sugar metabolism, were significantly impacted by UFPs exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

[New topics regarding equations for GFR estimation based on serum creatinine and cystatin C].

PubMed

Horio, Masaru

2014-02-01

Japanese GFR equations and CKD-EPI equations based on standardized serum creatinine and standardized cystatin C are recommended in recent Japanese CKD guides and KDIGO guidelines for CKD management, respectively. CKD-EPIcreat overestimates GFR in Japanese subjects, probably due to the difference in muscle mass between Japanese and Caucasians. Unlike CKD-EPIcreat, CKD-EPIcys performs well in Japanese subjects, indicating the advantages of using cystatin C as a GFR marker. KDIGO guidelines suggest measuring eGFRcys in adults with eGFRcreat of 45-59 ml/min/1.73 m2 who do not have markers of kidney damage if confirmation of CKD is required. Creatinine is excreted by glomerular filtration, but also secreted by the tubules. Alteration of the tubular secretion of creatinine may influence the performance of GFR equations based on serum creatinine. Multivariate analysis showed that GFR and serum albumin levels were independent parameters affecting the fractional excretion of creatinine (FE-Cr). Alteration of FE-Cr according to the serum albumin levels may be one of the reasons for the bias of GFR equations based on serum creatinine. Low GFR is a risk factor for all-cause and cardiovascular mortality in a general population. However, the relationship between eGFR and the hazard risk of events is different depending on whether cystatin C or creatinine is used to calculate eGFR. The association between eGFRcys and the hazard risk is much stronger compared with eGFRcreat. Cystatin C may be a useful alternative to creatinine for detecting a high risk of complications in a general population and subjects with CKD.

Exploring the effect of Vitamin E in Cancer Chemotherapy- A Biochemical and Biophysical Insight.

PubMed

Bhori, Mustansir; Singh, Kanchanlata; Marar, Thankamani; MuraliKrishna, C

2018-05-16

Many oncologists contend that patient undergoing chemotherapy must avoid antioxidant supplementation as it may interfere with the activity of the drug. In the present investigation, we have explored the influence of vitamin E, a well known antioxidant on Camptothecin (CPT), a potent anti-cancer drug induced cell apoptosis and death of cervical cancer cells. HeLa cells were treated with different concentrations of CPT in presence and absence of 100μm vitamin E. Treated cells were subjected to cytotoxicity studies, catalase assay, DNA fragmentation assay, clonogenic assay and flow cytometry based apoptosis detection. Also, Raman spectroscopy a label free technique which provides global information in conjunction with multivariate tools like PCA, PCLDA and FDA, was investigated to explore vitamin E supplementation induced alterations. Our data based on biochemical and biophysical experimental analysis reveals that CPT causes DNA damage along with protein and lipid alteration culminating in cell death. Importantly, Raman spectroscopic analysis could uniquely differentiate the cluster of control and vitamin E control from CPT and CPT+Vit E treated cells. We conclusively prove that presence of vitamin E at 100μM concentration shows promising antioxidant activity and displays no modulatory role on CPT induced effect, thereby causing no possible hindrance with the efficacy of the drug. Vitamin E may prove beneficial to alleviate chemotherapy associated side effects in patients during clinical settings which may open the doors further for subsequent exploration in in vivo pre clinical studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS

EPA Science Inventory

ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS

Stoker, Tammy E.1; Laws, Susan C.1; Ferrell, Janet M.1; Cooper, Ralph L.1.

Endocrinology Branch, RTD, NHEERL, ORD, U.S. EPA, RTP, NC, 27711.

The...

Multivariate estimation of the limit of detection by orthogonal partial least squares in temperature-modulated MOX sensors.

PubMed

Burgués, Javier; Marco, Santiago

2018-08-17

Metal oxide semiconductor (MOX) sensors are usually temperature-modulated and calibrated with multivariate models such as partial least squares (PLS) to increase the inherent low selectivity of this technology. The multivariate sensor response patterns exhibit heteroscedastic and correlated noise, which suggests that maximum likelihood methods should outperform PLS. One contribution of this paper is the comparison between PLS and maximum likelihood principal components regression (MLPCR) in MOX sensors. PLS is often criticized by the lack of interpretability when the model complexity increases beyond the chemical rank of the problem. This happens in MOX sensors due to cross-sensitivities to interferences, such as temperature or humidity and non-linearity. Additionally, the estimation of fundamental figures of merit, such as the limit of detection (LOD), is still not standardized in multivariate models. Orthogonalization methods, such as orthogonal projection to latent structures (O-PLS), have been successfully applied in other fields to reduce the complexity of PLS models. In this work, we propose a LOD estimation method based on applying the well-accepted univariate LOD formulas to the scores of the first component of an orthogonal PLS model. The resulting LOD is compared to the multivariate LOD range derived from error-propagation. The methodology is applied to data extracted from temperature-modulated MOX sensors (FIS SB-500-12 and Figaro TGS 3870-A04), aiming at the detection of low concentrations of carbon monoxide in the presence of uncontrolled humidity (chemical noise). We found that PLS models were simpler and more accurate than MLPCR models. Average LOD values of 0.79 ppm (FIS) and 1.06 ppm (Figaro) were found using the approach described in this paper. These values were contained within the LOD ranges obtained with the error-propagation approach. The mean LOD increased to 1.13 ppm (FIS) and 1.59 ppm (Figaro) when considering validation samples collected two weeks after calibration, which represents a 43% and 46% degradation, respectively. The orthogonal score-plot was a very convenient tool to visualize MOX sensor data and to validate the LOD estimates. Copyright © 2018 Elsevier B.V. All rights reserved.

Enzymatic electrochemical detection coupled to multivariate calibration for the determination of phenolic compounds in environmental samples.

PubMed

Hernandez, Silvia R; Kergaravat, Silvina V; Pividori, Maria Isabel

2013-03-15

An approach based on the electrochemical detection of the horseradish peroxidase enzymatic reaction by means of square wave voltammetry was developed for the determination of phenolic compounds in environmental samples. First, a systematic optimization procedure of three factors involved in the enzymatic reaction was carried out using response surface methodology through a central composite design. Second, the enzymatic electrochemical detection coupled with a multivariate calibration method based in the partial least-squares technique was optimized for the determination of a mixture of five phenolic compounds, i.e. phenol, p-aminophenol, p-chlorophenol, hydroquinone and pyrocatechol. The calibration and validation sets were built and assessed. In the calibration model, the LODs for phenolic compounds oscillated from 0.6 to 1.4 × 10(-6) mol L(-1). Recoveries for prediction samples were higher than 85%. These compounds were analyzed simultaneously in spiked samples and in water samples collected close to tanneries and landfills. Published by Elsevier B.V.

Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis

NASA Astrophysics Data System (ADS)

Chen, Po-Hsiung; Shimada, Rintaro; Yabumoto, Sohshi; Okajima, Hajime; Ando, Masahiro; Chang, Chiou-Tzu; Lee, Li-Tzu; Wong, Yong-Kie; Chiou, Arthur; Hamaguchi, Hiro-O.

2016-01-01

We have developed an automatic and objective method for detecting human oral squamous cell carcinoma (OSCC) tissues with Raman microspectroscopy. We measure 196 independent Raman spectra from 196 different points of one oral tissue sample and globally analyze these spectra using a Multivariate Curve Resolution (MCR) analysis. Discrimination of OSCC tissues is automatically and objectively made by spectral matching comparison of the MCR decomposed Raman spectra and the standard Raman spectrum of keratin, a well-established molecular marker of OSCC. We use a total of 24 tissue samples, 10 OSCC and 10 normal tissues from the same 10 patients, 3 OSCC and 1 normal tissues from different patients. Following the newly developed protocol presented here, we have been able to detect OSCC tissues with 77 to 92% sensitivity (depending on how to define positivity) and 100% specificity. The present approach lends itself to a reliable clinical diagnosis of OSCC substantiated by the “molecular fingerprint” of keratin.

Enhancing Multimedia Imbalanced Concept Detection Using VIMP in Random Forests.

PubMed

Sadiq, Saad; Yan, Yilin; Shyu, Mei-Ling; Chen, Shu-Ching; Ishwaran, Hemant

2016-07-01

Recent developments in social media and cloud storage lead to an exponential growth in the amount of multimedia data, which increases the complexity of managing, storing, indexing, and retrieving information from such big data. Many current content-based concept detection approaches lag from successfully bridging the semantic gap. To solve this problem, a multi-stage random forest framework is proposed to generate predictor variables based on multivariate regressions using variable importance (VIMP). By fine tuning the forests and significantly reducing the predictor variables, the concept detection scores are evaluated when the concept of interest is rare and imbalanced, i.e., having little collaboration with other high level concepts. Using classical multivariate statistics, estimating the value of one coordinate using other coordinates standardizes the covariates and it depends upon the variance of the correlations instead of the mean. Thus, conditional dependence on the data being normally distributed is eliminated. Experimental results demonstrate that the proposed framework outperforms those approaches in the comparison in terms of the Mean Average Precision (MAP) values.

Potential of non-invasive esophagus cancer detection based on urine surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Huang, Shaohua; Wang, Lan; Chen, Weisheng; Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Li, Buhong; Chen, Rong

2014-11-01

Non-invasive esophagus cancer detection based on urine surface-enhanced Raman spectroscopy (SERS) analysis was presented. Urine SERS spectra were measured on esophagus cancer patients (n = 56) and healthy volunteers (n = 36) for control analysis. Tentative assignments of the urine SERS spectra indicated some interesting esophagus cancer-specific biomolecular changes, including a decrease in the relative content of urea and an increase in the percentage of uric acid in the urine of esophagus cancer patients compared to that of healthy subjects. Principal component analysis (PCA) combined with linear discriminant analysis (LDA) was employed to analyze and differentiate the SERS spectra between normal and esophagus cancer urine. The diagnostic algorithms utilizing a multivariate analysis method achieved a diagnostic sensitivity of 89.3% and specificity of 83.3% for separating esophagus cancer samples from normal urine samples. These results from the explorative work suggested that silver nano particle-based urine SERS analysis coupled with PCA-LDA multivariate analysis has potential for non-invasive detection of esophagus cancer.

Power and sample size for multivariate logistic modeling of unmatched case-control studies.

PubMed

Gail, Mitchell H; Haneuse, Sebastien

2017-01-01

Sample size calculations are needed to design and assess the feasibility of case-control studies. Although such calculations are readily available for simple case-control designs and univariate analyses, there is limited theory and software for multivariate unconditional logistic analysis of case-control data. Here we outline the theory needed to detect scalar exposure effects or scalar interactions while controlling for other covariates in logistic regression. Both analytical and simulation methods are presented, together with links to the corresponding software.

Association between socioeconomic status and altered appearance distress, body image, and quality of life among breast cancer patients.

PubMed

Chang, Oliver; Choi, Eun-Kyung; Kim, Im-Ryung; Nam, Seok-Jin; Lee, Jeong Eon; Lee, Se Kyung; Im, Young-Hyuck; Park, Yeon Hee; Cho, Juhee

2014-01-01

Breast cancer patients experience a variety of altered appearance--such as loss or disfigurement of breasts, discolored skin, and hair loss--which result in psychological distress that affect their quality of life. This study aims to evaluate the impact of socioeconomic status on the altered appearance distress, body image, and quality of life among Korean breast cancer patients. A cross-sectional survey was conducted at advocacy events held at 16 different hospitals in Korea. Subjects were eligible to participate if they were 18 years of age or older, had a histologically confirmed diagnosis of breast cancer, had no evidence of recurrence or metastasis, and had no psychological problems at the time of the survey. Employment status, marital status, education, and income were assessed for patient socioeconomic status. Altered appearance distress was measured using the NCI's cancer treatment side effects scale; body image and quality of life were measured by the EORTC QLC-C30 and BR23. Means and standard deviations of each outcome were compared by socioeconomic status and multivariate linear regression models for evaluating the association between socioeconomic status and altered appearance distress, body image, and quality of life. A total of 126 breast cancer patients participated in the study; the mean age of participants was 47.7 (SD=8.4). Of the total, 83.2% were married, 85.6% received more than high school education, 35.2% were employed, and 41% had more than $3000 in monthly household income. About 46% had mastectomy, and over 30% were receiving either chemotherapy or radiation therapy at the time of the survey. With fully adjusted models, the employed patients had significantly higher altered appearance distress (1.80 vs 1.48; p<0.05) and poorer body image (36.63 vs 51.69; p<0.05) compared to the patients who were unemployed. Higher education (10.58, standard error (SE)=7.63) and family income (12.88, SE=5.08) was positively associated with better body image after adjusting for age, disease stage at diagnosis, current treatment status, and breast surgery type. Similarly, patients who were married and who had higher education had better quality of life were statistically significant in the multivariate models. Socioeconomic status is significantly associated with altered appearance distress, body image, and quality of life in Korean women with breast cancer. Patients who suffer from altered appearance distress or lower body image are much more likely to experience psychosocial, physical, and functional problems than women who do not, therefore health care providers should be aware of the changes and distresses that these breast cancer patients go through and provide specific information and psychosocial support to socioeconomically more vulnerable patients.

A non-targeted UHPLC-UV methid with classical and multi-variate data analysis to detect adulteration of skim milk powder with foreign proteins

USDA-ARS?s Scientific Manuscript database

Ultra-High performance liquid chromatography (UHPLC) with single wavelength (215 nm) detection was used to obtain chromatographic profiles of authentic skim milk powder (SMP) and synthetic mixtures of SMP with variable amounts of soy (SPI), pea (PPI), brown rice (BRP), and hydrolyzed wheat protein (...

Contamination Event Detection with Multivariate Time-Series Data in Agricultural Water Monitoring †

PubMed Central

Mao, Yingchi; Qi, Hai; Ping, Ping; Li, Xiaofang

2017-01-01

Time series data of multiple water quality parameters are obtained from the water sensor networks deployed in the agricultural water supply network. The accurate and efficient detection and warning of contamination events to prevent pollution from spreading is one of the most important issues when pollution occurs. In order to comprehensively reduce the event detection deviation, a spatial–temporal-based event detection approach with multivariate time-series data for water quality monitoring (M-STED) was proposed. The M-STED approach includes three parts. The first part is that M-STED adopts a Rule K algorithm to select backbone nodes as the nodes in the CDS, and forward the sensed data of multiple water parameters. The second part is to determine the state of each backbone node with back propagation neural network models and the sequential Bayesian analysis in the current timestamp. The third part is to establish a spatial model with Bayesian networks to estimate the state of the backbones in the next timestamp and trace the “outlier” node to its neighborhoods to detect a contamination event. The experimental results indicate that the average detection rate is more than 80% with M-STED and the false detection rate is lower than 9%, respectively. The M-STED approach can improve the rate of detection by about 40% and reduce the false alarm rate by about 45%, compared with the event detection with a single water parameter algorithm, S-STED. Moreover, the proposed M-STED can exhibit better performance in terms of detection delay and scalability. PMID:29207535

Automatic Detection and Estimation of Unannounced Meals for Multivariable Artificial Pancreas System.

PubMed

Samadi, Sediqeh; Rashid, Mudassir; Turksoy, Kamuran; Feng, Jianyuan; Hajizadeh, Iman; Hobbs, Nicole; Lazaro, Caterina; Sevil, Mert; Littlejohn, Elizabeth; Cinar, Ali

2018-03-01

Automatically attenuating the postprandial rise in the blood glucose concentration without manual meal announcement is a significant challenge for artificial pancreas (AP) systems. In this study, a meal module is proposed to detect the consumption of a meal and to estimate the amount of carbohydrate (CHO) intake. The meals are detected based on qualitative variables describing variation of continuous glucose monitoring (CGM) readings. The CHO content of the meals/snacks is estimated by a fuzzy system using CGM and subcutaneous insulin delivery data. The meal bolus amount is computed according to the patient's insulin to CHO ratio. Integration of the meal module into a multivariable AP system allows revision of estimated CHO based on knowledge about physical activity, sleep, and the risk of hypoglycemia before the final decision for a meal bolus is made. The algorithm is evaluated by using 117 meals/snacks in retrospective data from 11 subjects with type 1 diabetes. Sensitivity, defined as the percentage of correctly detected meals and snacks, is 93.5% for meals and 68.0% for snacks. The percentage of false positives, defined as the proportion of false detections relative to the total number of detected meals and snacks, is 20.8%. Integration of a meal detection module in an AP system is a further step toward an automated AP without manual entries. Detection of a consumed meal/snack and infusion of insulin boluses using an estimate of CHO enables the AP system to automatically prevent postprandial hyperglycemia.

Multiple biomarkers in molecular oncology. I. Molecular diagnostics applications in cervical cancer detection.

PubMed

Malinowski, Douglas P

2007-03-01

The screening for cervical carcinoma and its malignant precursors (cervical neoplasia) currently employs morphology-based detection methods (Papanicolaou [Pap] smear) in addition to the detection of high-risk human papillomavirus. The combination of the Pap smear with human papillomavirus testing has achieved significant improvements in sensitivity for the detection of cervical disease. Diagnosis of cervical neoplasia is dependent upon histology assessment of cervical biopsy specimens. Attempts to improve the specificity of cervical disease screening have focused on the investigation of molecular biomarkers for adjunctive use in combination with the Pap smear. Active research into the genomic and proteomic alterations that occur during human papillomavirus-induced neoplastic transformation have begun to characterize some of the basic mechanisms inherent to the disease process of cervical cancer development. This research continues to demonstrate the complexity of multiple genomic and proteomic alterations that accumulate during the tumorigenesis process. Despite this diversity, basic patterns of uncontrolled signal transduction, cell cycle deregulation, activation of DNA replication and altered extracellular matrix interactions are beginning to emerge as common features inherent to cervical cancer development. Some of these gene or protein expression alterations have been investigated as potential biomarkers for screening and diagnostics applications. The contribution of multiple gene alterations in the development of cervical cancer suggests that the application of multiple biomarker panels has the potential to develop clinically useful molecular diagnostics. In this review, the application of biomarkers for the improvement of sensitivity and specificity of the detection of cervical neoplasia within cytology specimens will be discussed.

Broad Detection of Alterations Predicted to Confer Lack of Benefit From EGFR Antibodies or Sensitivity to Targeted Therapy in Advanced Colorectal Cancer.

PubMed

Rankin, Andrew; Klempner, Samuel J; Erlich, Rachel; Sun, James X; Grothey, Axel; Fakih, Marwan; George, Thomas J; Lee, Jeeyun; Ross, Jeffrey S; Stephens, Philip J; Miller, Vincent A; Ali, Siraj M; Schrock, Alexa B

2016-09-28

A KRAS mutation represented the first genomic biomarker to predict lack of benefit from anti-epidermal growth factor receptor (EGFR) antibody therapy in advanced colorectal cancer (CRC). Expanded RAS testing has further refined the treatment approach, but understanding of genomic alterations underlying primary and acquired resistance is limited and further study is needed. We prospectively analyzed 4,422 clinical samples from patients with advanced CRC, using hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians. Comparison with prior molecular testing results, when available, was performed to assess concordance. We identified a RAS/RAF pathway mutation or amplification in 62% of cases, including samples harboring KRAS mutations outside of the codon 12/13 hotspot region in 6.4% of cases. Among cases with KRAS non-codon 12/13 alterations for which prior test results were available, 79 of 90 (88%) were not identified by focused testing. Of 1,644 RAS/RAF wild-type cases analyzed by CGP, 31% harbored a genomic alteration (GA) associated with resistance to anti-EGFR therapy in advanced CRC including mutations in PIK3CA, PTEN, EGFR, and ERBB2. We also identified other targetable GA, including novel kinase fusions, receptor tyrosine kinase amplification, activating point mutations, as well as microsatellite instability. Extended genomic profiling reliably detects alterations associated with lack of benefit to anti-EGFR therapy in advanced CRC, while simultaneously identifying alterations potentially important in guiding treatment. The use of CGP during the course of clinical care allows for the refined selection of appropriate targeted therapies and clinical trials, increasing the chance of clinical benefit and avoiding therapeutic futility. Comprehensive genomic profiling (CGP) detects diverse genomic alterations associated with lack of benefit to anti-epidermal growth factor receptor therapy in advanced colorectal cancer (CRC), as well as targetable alterations in many other genes. This includes detection of a broad spectrum of activating KRAS alterations frequently missed by focused molecular hotspot testing, as well as other RAS/RAF pathway alterations, mutations shown to disrupt antibody binding, RTK activating point mutations, amplifications, and rearrangements, and activating alterations in downstream effectors including PI3K and MEK1. The use of CGP in clinical practice is critical to guide appropriate selection of targeted therapies for patients with advanced CRC. ©AlphaMed Press.

[Computed tomography as a tool to detect potential brain-dead donors].

PubMed

Revuelto-Rey, Jaume; Aldabó-Pallás, Teresa; Egea-Guerrero, Juan José; Vilches-Arenas, Ángel; Lara, Enrique Javier; Gordillo-Escobar, Elena

2015-06-22

To assess the ability of urgent head computed tomography (CT) scan screening to detect patients who can evolve to brain death (BD). Patients who underwent urgent head CT scan and meet the following criteria: midline shift greater than 5mm and/or decrease or absence of basal cisterns. A follow-up for 28 days of each patient was made. Epidemiological data (sex, age, cause of brain injury), clinical data (level of consciousness, severity index in the CT) and patient outcomes (death, BD, discharge or transfer) were recorded. This was a prospective observational study. One hundred and sixty-six patients were selected for study, with mean age 60.08 (SD 21.8) years. A percentage of 49.4 were men and the rest women. In the follow-up, 20,5% (n=34) had BD. In univariate analysis, intracerebral hemorrhage, Glasgow Coma Scale score less than 8 and alteration of basal cisterns were statistically significant in predicting BD (P<.05). Multivariate analysis showed that patients with compression of basal cisterns were 20 (95% confidence interval [95% CI] 2.61 to 153.78; P=.004] times more likely to progress to brain death, while the absence there of 62.6 (95% CI 13.1 to 738.8; P<.001] times more. Our work shows that data as easy to interpret as compression/absence of basal cisterns can be a powerful tool for screening patients at risk for progression to BD. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

p53 predictive value for pT1-2 N0 disease at radical cystectomy.

PubMed

Shariat, Shahrokh F; Lotan, Yair; Karakiewicz, Pierre I; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J; Nielsen, Matthew E; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C; Karam, Jose A; Heukamp, Lukas C; Netto, George; Lerner, Seth P; Sagalowsky, Arthur I; Cote, Richard J

2009-09-01

Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

The Potential Impact of Changes in Fertility on Infant, Child, and Maternal Mortality. World Bank Staff Working Papers No. 698 and Population and Development Series No. 23.

ERIC Educational Resources Information Center

Trussell, James; Pebley, Anne R.

The relationship between changes in the timing and quantity of fertility, such as those that might result from an effective family planning program in developing countries, and changes in child and maternal mortality is examined. Results from five multivariate studies estimate the changes in mortality that might occur from altering maternal age,…

Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets

PubMed Central

Santagata, Sandro; Cahill, Daniel P.; Taylor-Weiner, Amaro; Jones, Robert T.; Van Allen, Eliezer M.; Lawrence, Michael S.; Horowitz, Peleg M.; Cibulskis, Kristian; Ligon, Keith L.; Tabernero, Josep; Seoane, Joan; Martinez-Saez, Elena; Curry, William T.; Dunn, Ian F.; Paek, Sun Ha; Park, Sung-Hye; McKenna, Aaron; Chevalier, Aaron; Rosenberg, Mara; Barker, Frederick G.; Gill, Corey M.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Hoang, Mai P.; Choueiri, Toni K.; Signoretti, Sabina; Sougnez, Carrie; Rabin, Michael S.; Lin, Nancy U.; Winer, Eric P.; Stemmer-Rachamimov, Anat; Meyerson, Matthew; Garraway, Levi; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Batchelor, Tracy T.; Baselga, Jose; Louis, David N.

2016-01-01

Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. PMID:26410082

Probability of detecting atrazine/desethyl-atrazine and elevated concentrations of nitrate in ground water in Colorado

USGS Publications Warehouse

Rupert, Michael G.

2003-01-01

Draft Federal regulations may require that each State develop a State Pesticide Management Plan for the herbicides atrazine, alachlor, metolachlor, and simazine. Maps were developed that the State of Colorado could use to predict the probability of detecting atrazine and desethyl-atrazine (a breakdown product of atrazine) in ground water in Colorado. These maps can be incorporated into the State Pesticide Management Plan and can help provide a sound hydrogeologic basis for atrazine management in Colorado. Maps showing the probability of detecting elevated nitrite plus nitrate as nitrogen (nitrate) concentrations in ground water in Colorado also were developed because nitrate is a contaminant of concern in many areas of Colorado. Maps showing the probability of detecting atrazine and(or) desethyl-atrazine (atrazine/DEA) at or greater than concentrations of 0.1 microgram per liter and nitrate concentrations in ground water greater than 5 milligrams per liter were developed as follows: (1) Ground-water quality data were overlaid with anthropogenic and hydrogeologic data using a geographic information system to produce a data set in which each well had corresponding data on atrazine use, fertilizer use, geology, hydrogeomorphic regions, land cover, precipitation, soils, and well construction. These data then were downloaded to a statistical software package for analysis by logistic regression. (2) Relations were observed between ground-water quality and the percentage of land-cover categories within circular regions (buffers) around wells. Several buffer sizes were evaluated; the buffer size that provided the strongest relation was selected for use in the logistic regression models. (3) Relations between concentrations of atrazine/DEA and nitrate in ground water and atrazine use, fertilizer use, geology, hydrogeomorphic regions, land cover, precipitation, soils, and well-construction data were evaluated, and several preliminary multivariate models with various combinations of independent variables were constructed. (4) The multivariate models that best predicted the presence of atrazine/DEA and elevated concentrations of nitrate in ground water were selected. (5) The accuracy of the multivariate models was confirmed by validating the models with an independent set of ground-water quality data. (6) The multivariate models were entered into a geographic information system and the probability maps were constructed.

Carbapenemase-producing Enterobacteriaceae: Risk factors for infection and impact of resistance on outcomes

PubMed Central

Mariappan, Shanthi; Sekar, Uma; Kamalanathan, Arunagiri

2017-01-01

Background: Carbapenemase-producing Enterobacteriaceae (CPE) have increased in recent years leading to limitations of treatment options. The present study was undertaken to detect CPE, risk factors for acquiring them and their impact on clinical outcomes. Methods: This retrospective observational study included 111 clinically significant Enterobacteriaceae resistant to cephalosporins subclass III and exhibiting a positive modified Hodge test. Screening for carbapenemase production was done by phenotypic methods, and polymerase chain reaction was performed to detect genes encoding them. Retrospectively, the medical records of the patients were perused to assess risk factors for infections with CPE and their impact. The data collected were duration of hospital stay, Intensive Care Unit (ICU) stay, use of invasive devices, mechanical ventilation, the presence of comorbidities, and antimicrobial therapy. The outcome was followed up. Univariate and multivariate analysis of the data were performed using SPSS software. Results: Carbapenemase-encoding genes were detected in 67 isolates. The genes detected were New Delhi metallo-β-lactamase, Verona integron-encoded metallo-β-lactamase, and oxacillinase-181.Although univariate analysis identified risk factors associated with acquiring CPE infections as ICU stay (P = 0.021), mechanical ventilation (P = 0.013), indwelling device (P = 0.011), diabetes mellitus (P = 0.036), usage of multiple antimicrobial agents (P = 0.007), administration of carbapenems (P = 0.042), presence of focal infection or sepsis (P = 0.013), and surgical interventions (P = 0.016), multivariate analysis revealed that all these factors were insignificant. Mortality rate was 56.7% in patients with CPE infections. By both univariate and multivariate analysis of impact of the variables on mortality in these patients, the significant factors were mechanical ventilation (odds ratio [OR]: 0.141, 95% confidence interval [CI]: 0.024–0.812) and presence of indwelling invasive device (OR: 8.034; 95% CI: 2.060–31.335). Conclusion: In this study, no specific factor was identified as an independent risk for acquisition of CPE infection. However, as it is evident by multivariate analysis, there is an increased risk of mortality in patients with CPE infections when they are ventilated and are supported by indwelling devices. PMID:28251105

Untangling the effects of tinnitus and hypersensitivity to sound (hyperacusis) in the gap detection test.

PubMed

Salloum, R H; Sandridge, S; Patton, D J; Stillitano, G; Dawson, G; Niforatos, J; Santiago, L; Kaltenbach, J A

2016-01-01

In recent years, there has been increasing use of the gap detection reflex test to demonstrate induction of tinnitus in animals. Animals with tinnitus show weakened gap detection ability for background noise that matches the pitch of the tinnitus. The usual explanation is that the tinnitus 'fills in the gap'. It has recently been shown, however, that tinnitus is commonly associated with hyperacusis-like enhancements of the acoustic startle response, a change which might potentially alter responses in the gap detection test. We hypothesized that such enhancements could lead to an apparent reduction of gap suppression, resembling that caused by tinnitus, by altering responses to the startle stimulus or the background noise. To test this hypothesis, we compared gap detection abilities in 3 subsets of noise-exposed animals with those in unexposed controls. The results showed that exposed animals demonstrated altered gap detection abilities, but these alterations were sometimes explained as consequences of hyper-responsiveness to either the startle stimulus or to the background noise. Two of the three subsets of animals studied, however, displayed weakened gap detection abilities that could not be explained by enhanced responses to these stimuli or by reduced sound sensitivity or a reduction of temporal processing speed, consistent with the induction of tinnitus. These results demonstrate that not only hearing loss but also changes in sensitivity to background noise or to startle stimuli are potential confounds that, when present, can underlie changes in gap detection irrespective of tinnitus. We discuss how such confounds can be recognized and how they can be avoided. Copyright © 2015 Elsevier B.V. All rights reserved.

Late diagenetic indicators of buried oil and gas: II, Direct detection experiment at Cement and Garza oil fields, Oklahoma and Texas, using enhanced LANDSAT I and II images

USGS Publications Warehouse

Donovan, Terrence J.; Termain, Patricia A.; Henry, Mitchell E.

1979-01-01

The Cement oil field, Oklahoma, was a test site for an experiment designed to evaluate LANDSAT's capability to detect an alteration zone in surface rocks caused by hydrocarbon microseepage. Loss of iron and impregnation of sandstone by carbonate cements and replacement of gypsum by calcite are the major alteration phenomena at Cement. The bedrock alterations are partially masked by unaltered overlying beds, thick soils, and dense natural and cultivated vegetation. Interpreters biased by detailed ground truth were able to map the alteration zone subjectively using a magnified, filtered, and sinusoidally stretched LANDSAT composite image; other interpreters, unbiased by ground truth data, could not duplicate that interpretation. Similar techniques were applied at a secondary test site (Garza oil field, Texas), where similar alterations in surface rocks occur. Enhanced LANDSAT images resolved the alteration zone to a biased interpreter and some individual altered outcrops could be mapped using higher resolution SKYLAB color and conventional black and white aerial photographs suggesting repeat experiments with LANDSAT C and D.

Video processing of remote sensor data applied to uranium exploration in Wyoming. [Roll-front U deposits

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

Levinson, R.A.; Marrs, R.W.; Crockell, F.

1979-06-30

LANDSAT satellite imagery and aerial photography can be used to map areas of altered sandstone associated with roll-front uranium deposits. Image data must be enhanced so that alteration spectral contrasts can be seen, and video image processing is a fast, low-cost, and efficient tool. For LANDSAT data, the 7/4 ratio produces the best enhancement of altered sandstone. The 6/4 ratio is most effective for color infrared aerial photography. Geochemical and mineralogical associations occur in unaltered, altered, and ore roll-front zones. Samples from Pumpkin Buttes show that iron is the primary coloring agent which makes alteration visually detectable. Eh and pHmore » changes associated with passage of a roll front cause oxidation of magnetite and pyrite to hematite, goethite, and limonite in the host sandstone, thereby producing the alteration. Statistical analysis show that the detectability of geochemical and color zonation in host sands is weakened by soil-forming processes. Alteration can only be mapped in areas of thin soil cover and moderate to sparse vegetative cover.« less

Multivariate two-part statistics for analysis of correlated mass spectrometry data from multiple biological specimens.

PubMed

Taylor, Sandra L; Ruhaak, L Renee; Weiss, Robert H; Kelly, Karen; Kim, Kyoungmi

2017-01-01

High through-put mass spectrometry (MS) is now being used to profile small molecular compounds across multiple biological sample types from the same subjects with the goal of leveraging information across biospecimens. Multivariate statistical methods that combine information from all biospecimens could be more powerful than the usual univariate analyses. However, missing values are common in MS data and imputation can impact between-biospecimen correlation and multivariate analysis results. We propose two multivariate two-part statistics that accommodate missing values and combine data from all biospecimens to identify differentially regulated compounds. Statistical significance is determined using a multivariate permutation null distribution. Relative to univariate tests, the multivariate procedures detected more significant compounds in three biological datasets. In a simulation study, we showed that multi-biospecimen testing procedures were more powerful than single-biospecimen methods when compounds are differentially regulated in multiple biospecimens but univariate methods can be more powerful if compounds are differentially regulated in only one biospecimen. We provide R functions to implement and illustrate our method as supplementary information CONTACT: sltaylor@ucdavis.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Serum-based diagnostic prediction of oral submucous fibrosis using FTIR spectrometry

NASA Astrophysics Data System (ADS)

Rai, Vertika; Mukherjee, Rashmi; Routray, Aurobinda; Ghosh, Ananta Kumar; Roy, Seema; Ghosh, Barnali Paul; Mandal, Puspendu Bikash; Bose, Surajit; Chakraborty, Chandan

2018-01-01

Oral submucous fibrosis (OSF) is found to have the highest malignant potentiality among all other pre-cancerous lesions. However, its detection prior to tissue biopsy can be challenging in clinics. Moreover, biopsy examination is invasive and painful. Hence, there is an urgent need of new technology that facilitates accurate diagnostic prediction of OSF prior to biopsy. Here, we used FTIR spectroscopy coupled with chemometric techniques to distinguish the serum metabolic signatures of OSF patients (n = 30) and healthy controls (n = 30). Serum biochemical analyses have been performed to further support the FTIR findings. Absorbance intensities of 45 infrared wavenumbers differed significantly between OSF and normal serum FTIR spectra representing alterations in carbohydrates, proteins, lipids and nucleic acids. Nineteen prominent significant wavenumbers (P ≤ 0.001) at 1020, 1025, 1035, 1039, 1045, 1078, 1055, 1100, 1117, 1122, 1151, 1169, 1243, 1313, 1398, 1453, 1544, 1650 and 1725 cm- 1 provided excellent segregation of OSF spectra from normal using multivariate statistical techniques. These findings provided essential information on the metabolic features of blood serum of OSF patients and established that FTIR spectroscopy coupled with chemometric analysis can be potentially useful in the rapid and accurate preoperative screening/diagnosis of OSF.

Multivariate Associations Among Behavioral, Clinical, and Multimodal Imaging Phenotypes in Patients With Psychosis.

PubMed

Moser, Dominik A; Doucet, Gaelle E; Lee, Won Hee; Rasgon, Alexander; Krinsky, Hannah; Leibu, Evan; Ing, Alex; Schumann, Gunter; Rasgon, Natalie; Frangou, Sophia

2018-04-01

Alterations in multiple neuroimaging phenotypes have been reported in psychotic disorders. However, neuroimaging measures can be influenced by factors that are not directly related to psychosis and may confound the interpretation of case-control differences. Therefore, a detailed characterization of the contribution of these factors to neuroimaging phenotypes in psychosis is warranted. To quantify the association between neuroimaging measures and behavioral, health, and demographic variables in psychosis using an integrated multivariate approach. This imaging study was conducted at a university research hospital from June 26, 2014, to March 9, 2017. High-resolution multimodal magnetic resonance imaging data were obtained from 100 patients with schizophrenia, 40 patients with bipolar disorder, and 50 healthy volunteers; computed were cortical thickness, subcortical volumes, white matter fractional anisotropy, task-related brain activation (during working memory and emotional recognition), and resting-state functional connectivity. Ascertained in all participants were nonimaging measures pertaining to clinical features, cognition, substance use, psychological trauma, physical activity, and body mass index. The association between imaging and nonimaging measures was modeled using sparse canonical correlation analysis with robust reliability testing. Multivariate patterns of the association between nonimaging and neuroimaging measures in patients with psychosis and healthy volunteers. The analyses were performed in 92 patients with schizophrenia (23 female [25.0%]; mean [SD] age, 27.0 [7.6] years), 37 patients with bipolar disorder (12 female [32.4%]; mean [SD] age, 27.5 [8.1] years), and 48 healthy volunteers (20 female [41.7%]; mean [SD] age, 29.8 [8.5] years). The imaging and nonimaging data sets showed significant covariation (r = 0.63, P < .001), which was independent of diagnosis. Among the nonimaging variables examined, age (r = -0.53), IQ (r = 0.36), and body mass index (r = -0.25) were associated with multiple imaging phenotypes; cannabis use (r = 0.23) and other substance use (r = 0.33) were associated with subcortical volumes, and alcohol use was associated with white matter integrity (r = -0.15). Within the multivariate models, positive symptoms retained associations with the global neuroimaging (r = -0.13), the cortical thickness (r = -0.22), and the task-related activation variates (r = -0.18); negative symptoms were mostly associated with measures of subcortical volume (r = 0.23), and depression/anxiety was associated with measures of white matter integrity (r = 0.12). Multivariate analyses provide a more accurate characterization of the association between brain alterations and psychosis because they enable the modeling of other key factors that influence neuroimaging phenotypes.

Multivariate objective response detectors (MORD): statistical tools for multichannel EEG analysis during rhythmic stimulation.

PubMed

Felix, Leonardo Bonato; Miranda de Sá, Antonio Mauricio Ferreira Leite; Infantosi, Antonio Fernando Catelli; Yehia, Hani Camille

2007-03-01

The presence of cerebral evoked responses can be tested by using objective response detectors. They are statistical tests that provide a threshold above which responses can be assumed to have occurred. The detection power depends on the signal-to-noise ratio (SNR) of the response and the amount of data available. However, the correlation within the background noise could also affect the power of such detectors. For a fixed SNR, the detection can only be improved at the expense of using a longer stretch of signal. This can constitute a limitation, for instance, in monitored surgeries. Alternatively, multivariate objective response detection (MORD) could be used. This work applies two MORD techniques (multiple coherence and multiple component synchrony measure) to EEG data collected during intermittent photic stimulation. They were evaluated throughout Monte Carlo simulations, which also allowed verifying that correlation in the background reduces the detection rate. Considering the N EEG derivations as close as possible to the primary visual cortex, if N = 4, 6 or 8, multiple coherence leads to a statistically significant higher detection rate in comparison with multiple component synchrony measure. With the former, the best performance was obtained with six signals (O1, O2, T5, T6, P3 and P4).

Successive Projections Algorithm-Multivariable Linear Regression Classifier for the Detection of Contaminants on Chicken Carcasses in Hyperspectral Images

NASA Astrophysics Data System (ADS)

Wu, W.; Chen, G. Y.; Kang, R.; Xia, J. C.; Huang, Y. P.; Chen, K. J.

2017-07-01

During slaughtering and further processing, chicken carcasses are inevitably contaminated by microbial pathogen contaminants. Due to food safety concerns, many countries implement a zero-tolerance policy that forbids the placement of visibly contaminated carcasses in ice-water chiller tanks during processing. Manual detection of contaminants is labor consuming and imprecise. Here, a successive projections algorithm (SPA)-multivariable linear regression (MLR) classifier based on an optimal performance threshold was developed for automatic detection of contaminants on chicken carcasses. Hyperspectral images were obtained using a hyperspectral imaging system. A regression model of the classifier was established by MLR based on twelve characteristic wavelengths (505, 537, 561, 562, 564, 575, 604, 627, 656, 665, 670, and 689 nm) selected by SPA , and the optimal threshold T = 1 was obtained from the receiver operating characteristic (ROC) analysis. The SPA-MLR classifier provided the best detection results when compared with the SPA-partial least squares (PLS) regression classifier and the SPA-least squares supported vector machine (LS-SVM) classifier. The true positive rate (TPR) of 100% and the false positive rate (FPR) of 0.392% indicate that the SPA-MLR classifier can utilize spatial and spectral information to effectively detect contaminants on chicken carcasses.

Advances in industrial biopharmaceutical batch process monitoring: Machine-learning methods for small data problems.

PubMed

Tulsyan, Aditya; Garvin, Christopher; Ündey, Cenk

2018-04-06

Biopharmaceutical manufacturing comprises of multiple distinct processing steps that require effective and efficient monitoring of many variables simultaneously in real-time. The state-of-the-art real-time multivariate statistical batch process monitoring (BPM) platforms have been in use in recent years to ensure comprehensive monitoring is in place as a complementary tool for continued process verification to detect weak signals. This article addresses a longstanding, industry-wide problem in BPM, referred to as the "Low-N" problem, wherein a product has a limited production history. The current best industrial practice to address the Low-N problem is to switch from a multivariate to a univariate BPM, until sufficient product history is available to build and deploy a multivariate BPM platform. Every batch run without a robust multivariate BPM platform poses risk of not detecting potential weak signals developing in the process that might have an impact on process and product performance. In this article, we propose an approach to solve the Low-N problem by generating an arbitrarily large number of in silico batches through a combination of hardware exploitation and machine-learning methods. To the best of authors' knowledge, this is the first article to provide a solution to the Low-N problem in biopharmaceutical manufacturing using machine-learning methods. Several industrial case studies from bulk drug substance manufacturing are presented to demonstrate the efficacy of the proposed approach for BPM under various Low-N scenarios. © 2018 Wiley Periodicals, Inc.

A Multivariate Granger Causality Concept towards Full Brain Functional Connectivity.

PubMed

Schmidt, Christoph; Pester, Britta; Schmid-Hertel, Nicole; Witte, Herbert; Wismüller, Axel; Leistritz, Lutz

2016-01-01

Detecting changes of spatially high-resolution functional connectivity patterns in the brain is crucial for improving the fundamental understanding of brain function in both health and disease, yet still poses one of the biggest challenges in computational neuroscience. Currently, classical multivariate Granger Causality analyses of directed interactions between single process components in coupled systems are commonly restricted to spatially low- dimensional data, which requires a pre-selection or aggregation of time series as a preprocessing step. In this paper we propose a new fully multivariate Granger Causality approach with embedded dimension reduction that makes it possible to obtain a representation of functional connectivity for spatially high-dimensional data. The resulting functional connectivity networks may consist of several thousand vertices and thus contain more detailed information compared to connectivity networks obtained from approaches based on particular regions of interest. Our large scale Granger Causality approach is applied to synthetic and resting state fMRI data with a focus on how well network community structure, which represents a functional segmentation of the network, is preserved. It is demonstrated that a number of different community detection algorithms, which utilize a variety of algorithmic strategies and exploit topological features differently, reveal meaningful information on the underlying network module structure.

ARID1B alterations identify aggressive tumors in neuroblastoma.

PubMed

Lee, Soo Hyun; Kim, Jung-Sun; Zheng, Siyuan; Huse, Jason T; Bae, Joon Seol; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kyung, Sungkyu; Park, Woong-Yang; Sung, Ki W

2017-07-11

Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without (p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis.

A Diagnostic Calculator for Detecting Glaucoma on the Basis of Retinal Nerve Fiber Layer, Optic Disc, and Retinal Ganglion Cell Analysis by Optical Coherence Tomography.

PubMed

Larrosa, José Manuel; Moreno-Montañés, Javier; Martinez-de-la-Casa, José María; Polo, Vicente; Velázquez-Villoria, Álvaro; Berrozpe, Clara; García-Granero, Marta

2015-10-01

The purpose of this study was to develop and validate a multivariate predictive model to detect glaucoma by using a combination of retinal nerve fiber layer (RNFL), retinal ganglion cell-inner plexiform (GCIPL), and optic disc parameters measured using spectral-domain optical coherence tomography (OCT). Five hundred eyes from 500 participants and 187 eyes of another 187 participants were included in the study and validation groups, respectively. Patients with glaucoma were classified in five groups based on visual field damage. Sensitivity and specificity of all glaucoma OCT parameters were analyzed. Receiver operating characteristic curves (ROC) and areas under the ROC (AUC) were compared. Three predictive multivariate models (quantitative, qualitative, and combined) that used a combination of the best OCT parameters were constructed. A diagnostic calculator was created using the combined multivariate model. The best AUC parameters were: inferior RNFL, average RNFL, vertical cup/disc ratio, minimal GCIPL, and inferior-temporal GCIPL. Comparisons among the parameters did not show that the GCIPL parameters were better than those of the RNFL in early and advanced glaucoma. The highest AUC was in the combined predictive model (0.937; 95% confidence interval, 0.911-0.957) and was significantly (P = 0.0001) higher than the other isolated parameters considered in early and advanced glaucoma. The validation group displayed similar results to those of the study group. Best GCIPL, RNFL, and optic disc parameters showed a similar ability to detect glaucoma. The combined predictive formula improved the glaucoma detection compared to the best isolated parameters evaluated. The diagnostic calculator obtained good classification from participants in both the study and validation groups.

Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

PubMed

Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

2017-09-01

Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

Mapping advanced argillic alteration zones with ASTER and Hyperion data in the Andes Mountains of Peru

NASA Astrophysics Data System (ADS)

Ramos, Yuddy; Goïta, Kalifa; Péloquin, Stéphane

2016-04-01

This study evaluates Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and Hyperion hyperspectral sensor datasets to detect advanced argillic minerals. The spectral signatures of some alteration clay minerals, such as dickite and alunite, have similar absorption features; thus separating them using multispectral satellite images is a complex challenge. However, Hyperion with its fine spectral bands has potential for good separability of features. The Spectral Angle Mapper algorithm was used in this study to map three advanced argillic alteration minerals (alunite, kaolinite, and dickite) in a known alteration zone in the Peruvian Andes. The results from ASTER and Hyperion were analyzed, compared, and validated using a Portable Infrared Mineral Analyzer field spectrometer. The alterations corresponding to kaolinite and alunite were detected with both ASTER and Hyperion (80% to 84% accuracy). However, the dickite mineral was identified only with Hyperion (82% accuracy).

Protein alterations in women with chronic widespread pain--An explorative proteomic study of the trapezius muscle.

PubMed

Olausson, Patrik; Gerdle, Björn; Ghafouri, Nazdar; Sjöström, Dick; Blixt, Emelie; Ghafouri, Bijar

2015-07-07

Chronic widespread pain (CWP) has a high prevalence in the population and is associated with prominent negative individual and societal consequences. There is no clear consensus concerning the etiology behind CWP although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Here, we use proteomics to study protein changes in trapezius muscle from 18 female patients diagnosed with CWP compared to 19 healthy female subjects. The 2-dimensional gel electrophoresis (2-DE) in combination with multivariate statistical analyses revealed 17 proteins to be differently expressed between the two groups. Proteins were identified by mass spectrometry. Many of the proteins are important enzymes in metabolic pathways like the glycolysis and gluconeogenesis. Other proteins are associated with muscle damage, muscle recovery, stress and inflammation. The altered expressed levels of these proteins suggest abnormalities and metabolic changes in the myalgic trapezius muscle in CWP. Taken together, this study gives further support that peripheral factors may be of importance in maintaining CWP.

Protein alterations in women with chronic widespread pain – An explorative proteomic study of the trapezius muscle

PubMed Central

Olausson, Patrik; Gerdle, Björn; Ghafouri, Nazdar; Sjöström, Dick; Blixt, Emelie; Ghafouri, Bijar

2015-01-01

Chronic widespread pain (CWP) has a high prevalence in the population and is associated with prominent negative individual and societal consequences. There is no clear consensus concerning the etiology behind CWP although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Here, we use proteomics to study protein changes in trapezius muscle from 18 female patients diagnosed with CWP compared to 19 healthy female subjects. The 2-dimensional gel electrophoresis (2-DE) in combination with multivariate statistical analyses revealed 17 proteins to be differently expressed between the two groups. Proteins were identified by mass spectrometry. Many of the proteins are important enzymes in metabolic pathways like the glycolysis and gluconeogenesis. Other proteins are associated with muscle damage, muscle recovery, stress and inflammation. The altered expressed levels of these proteins suggest abnormalities and metabolic changes in the myalgic trapezius muscle in CWP. Taken together, this study gives further support that peripheral factors may be of importance in maintaining CWP. PMID:26150212

Data-driven modeling of background and mine-related acidity and metals in river basins

USGS Publications Warehouse

Friedel, Michael J

2013-01-01

A novel application of self-organizing map (SOM) and multivariate statistical techniques is used to model the nonlinear interaction among basin mineral-resources, mining activity, and surface-water quality. First, the SOM is trained using sparse measurements from 228 sample sites in the Animas River Basin, Colorado. The model performance is validated by comparing stochastic predictions of basin-alteration assemblages and mining activity at 104 independent sites. The SOM correctly predicts (>98%) the predominant type of basin hydrothermal alteration and presence (or absence) of mining activity. Second, application of the Davies–Bouldin criteria to k-means clustering of SOM neurons identified ten unique environmental groups. Median statistics of these groups define a nonlinear water-quality response along the spatiotemporal hydrothermal alteration-mining gradient. These results reveal that it is possible to differentiate among the continuum between inputs of background and mine-related acidity and metals, and it provides a basis for future research and empirical model development.

Detecting spatial regimes in ecosystems | Science Inventory ...

EPA Pesticide Factsheets

Research on early warning indicators has generally focused on assessing temporal transitions with limited application of these methods to detecting spatial regimes. Traditional spatial boundary detection procedures that result in ecoregion maps are typically based on ecological potential (i.e. potential vegetation), and often fail to account for ongoing changes due to stressors such as land use change and climate change and their effects on plant and animal communities. We use Fisher information, an information theory based method, on both terrestrial and aquatic animal data (US Breeding Bird Survey and marine zooplankton) to identify ecological boundaries, and compare our results to traditional early warning indicators, conventional ecoregion maps, and multivariate analysis such as nMDS (non-metric Multidimensional Scaling) and cluster analysis. We successfully detect spatial regimes and transitions in both terrestrial and aquatic systems using Fisher information. Furthermore, Fisher information provided explicit spatial information about community change that is absent from other multivariate approaches. Our results suggest that defining spatial regimes based on animal communities may better reflect ecological reality than do traditional ecoregion maps, especially in our current era of rapid and unpredictable ecological change. Use an information theory based method to identify ecological boundaries and compare our results to traditional early warning

Ellipsoids for anomaly detection in remote sensing imagery

NASA Astrophysics Data System (ADS)

Grosklos, Guenchik; Theiler, James

2015-05-01

For many target and anomaly detection algorithms, a key step is the estimation of a centroid (relatively easy) and a covariance matrix (somewhat harder) that characterize the background clutter. For a background that can be modeled as a multivariate Gaussian, the centroid and covariance lead to an explicit probability density function that can be used in likelihood ratio tests for optimal detection statistics. But ellipsoidal contours can characterize a much larger class of multivariate density function, and the ellipsoids that characterize the outer periphery of the distribution are most appropriate for detection in the low false alarm rate regime. Traditionally the sample mean and sample covariance are used to estimate ellipsoid location and shape, but these quantities are confounded both by large lever-arm outliers and non-Gaussian distributions within the ellipsoid of interest. This paper compares a variety of centroid and covariance estimation schemes with the aim of characterizing the periphery of the background distribution. In particular, we will consider a robust variant of the Khachiyan algorithm for minimum-volume enclosing ellipsoid. The performance of these different approaches is evaluated on multispectral and hyperspectral remote sensing imagery using coverage plots of ellipsoid volume versus false alarm rate.

Advantages of Data Fusion: First Multivariate Curve Resolution Analysis of Fused Liquid Chromatographic Second-Order Data with Dual Diode Array-Fluorescent Detection.

PubMed

Pellegrino Vidal, Rocío B; Ibañez, Gabriela A; Escandar, Graciela M

2017-03-07

For the first time, liquid chromatography-diode array detection (LC-DAD) and liquid-chromatography fluorescence detection (LC-FLD) second-order data, collected in a single chromatographic run, were fused and chemometrically processed for the quantitation of coeluting analytes. Two different experimental mixtures composed of fluorescent and nonfluorescent endocrine disruptors were analyzed. Adequate pretreatment of the matrices before their fusion was crucial to attain reliable results. Multivariate curve resolution-alternating least-squares (MCR-ALS) was applied to LC-DAD, LC-FLD, and fused LC-DAD-FLD data. Although different degrees of improvement are observed when comparing the fused matrix results in relation to those obtained using a single detector, clear benefits of data fusion are demonstrated through: (1) the obtained limits of detection in the ranges 2.1-24 ng mL -1 and 0.9-6.3 ng mL -1 for the two evaluated systems and (2) the low relative prediction errors, below 7% in all cases, indicating good recoveries and precision. The feasibility of fusing data and its advantages in the analysis of real samples was successfully assessed through the study of spiked tap, underground, and river water samples.

LSST Astroinformatics And Astrostatistics: Data-oriented Astronomical Research

NASA Astrophysics Data System (ADS)

Borne, Kirk D.; Stassun, K.; Brunner, R. J.; Djorgovski, S. G.; Graham, M.; Hakkila, J.; Mahabal, A.; Paegert, M.; Pesenson, M.; Ptak, A.; Scargle, J.; Informatics, LSST; Statistics Team

2011-01-01

The LSST Informatics and Statistics Science Collaboration (ISSC) focuses on research and scientific discovery challenges posed by the very large and complex data collection that LSST will generate. Application areas include astroinformatics, machine learning, data mining, astrostatistics, visualization, scientific data semantics, time series analysis, and advanced signal processing. Research problems to be addressed with these methodologies include transient event characterization and classification, rare class discovery, correlation mining, outlier/anomaly/surprise detection, improved estimators (e.g., for photometric redshift or early onset supernova classification), exploration of highly dimensional (multivariate) data catalogs, and more. We present sample science results from these data-oriented approaches to large-data astronomical research. We present results from LSST ISSC team members, including the EB (Eclipsing Binary) Factory, the environmental variations in the fundamental plane of elliptical galaxies, and outlier detection in multivariate catalogs.

Integration of multivariate empirical mode decomposition and independent component analysis for fetal ECG separation from abdominal signals.

PubMed

Thanaraj, Palani; Roshini, Mable; Balasubramanian, Parvathavarthini

2016-11-14

The fetal electrocardiogram (FECG) signals are essential to monitor the health condition of the baby. Fetal heart rate (FHR) is commonly used for diagnosing certain abnormalities in the formation of the heart. Usually, non-invasive abdominal electrocardiogram (AbECG) signals are obtained by placing surface electrodes in the abdomen region of the pregnant woman. AbECG signals are often not suitable for the direct analysis of fetal heart activity. Moreover, the strength and magnitude of the FECG signals are low compared to the maternal electrocardiogram (MECG) signals. The MECG signals are often superimposed with the FECG signals that make the monitoring of FECG signals a difficult task. Primary goal of the paper is to separate the fetal electrocardiogram (FECG) signals from the unwanted maternal electrocardiogram (MECG) signals. A multivariate signal processing procedure is proposed here that combines the Multivariate Empirical Mode Decomposition (MEMD) and Independent Component Analysis (ICA). The proposed method is evaluated with clinical abdominal signals taken from three pregnant women (N= 3) recorded during the 38-41 weeks of the gestation period. The number of fetal R-wave detected (NEFQRS), the number of unwanted maternal peaks (NMQRS), the number of undetected fetal R-wave (NUFQRS) and the FHR detection accuracy quantifies the performance of our method. Clinical investigation with three test subjects shows an overall detection accuracy of 92.8%. Comparative analysis with benchmark signal processing method such as ICA suggests the noteworthy performance of our method.

Novel high-resolution computed tomography-based radiomic classifier for screen-identified pulmonary nodules in the National Lung Screening Trial.

PubMed

Peikert, Tobias; Duan, Fenghai; Rajagopalan, Srinivasan; Karwoski, Ronald A; Clay, Ryan; Robb, Richard A; Qin, Ziling; Sicks, JoRean; Bartholmai, Brian J; Maldonado, Fabien

2018-01-01

Optimization of the clinical management of screen-detected lung nodules is needed to avoid unnecessary diagnostic interventions. Herein we demonstrate the potential value of a novel radiomics-based approach for the classification of screen-detected indeterminate nodules. Independent quantitative variables assessing various radiologic nodule features such as sphericity, flatness, elongation, spiculation, lobulation and curvature were developed from the NLST dataset using 726 indeterminate nodules (all ≥ 7 mm, benign, n = 318 and malignant, n = 408). Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) method for variable selection and regularization in order to enhance the prediction accuracy and interpretability of the multivariate model. The bootstrapping method was then applied for the internal validation and the optimism-corrected AUC was reported for the final model. Eight of the originally considered 57 quantitative radiologic features were selected by LASSO multivariate modeling. These 8 features include variables capturing Location: vertical location (Offset carina centroid z), Size: volume estimate (Minimum enclosing brick), Shape: flatness, Density: texture analysis (Score Indicative of Lesion/Lung Aggression/Abnormality (SILA) texture), and surface characteristics: surface complexity (Maximum shape index and Average shape index), and estimates of surface curvature (Average positive mean curvature and Minimum mean curvature), all with P<0.01. The optimism-corrected AUC for these 8 features is 0.939. Our novel radiomic LDCT-based approach for indeterminate screen-detected nodule characterization appears extremely promising however independent external validation is needed.

Long-Term Impacts on Macroinvertebrates Downstream of Reclaimed Mountaintop Mining Valley Fills in Central Appalachia

NASA Astrophysics Data System (ADS)

Pond, Gregory J.; Passmore, Margaret E.; Pointon, Nancy D.; Felbinger, John K.; Walker, Craig A.; Krock, Kelly J. G.; Fulton, Jennifer B.; Nash, Whitney L.

2014-10-01

Recent studies have documented adverse effects to biological communities downstream of mountaintop coal mining and valley fills (VF), but few data exist on the longevity of these impacts. We sampled 15 headwater streams with VFs reclaimed 11-33 years prior to 2011 and sampled seven local reference sites that had no VFs. We collected chemical, habitat, and benthic macroinvertebrate data in April 2011; additional chemical samples were collected in September 2011. To assess ecological condition, we compared VF and reference abiotic and biotic data using: (1) ordination to detect multivariate differences, (2) benthic indices (a multimetric index and an observed/expected predictive model) calibrated to state reference conditions to detect impairment, and (3) correlation and regression analysis to detect relationships between biotic and abiotic data. Although VF sites had good instream habitat, nearly 90 % of these streams exhibited biological impairment. VF sites with higher index scores were co-located near unaffected tributaries; we suggest that these tributaries were sources of sensitive taxa as drifting colonists. There were clear losses of expected taxa across most VF sites and two functional feeding groups (% scrapers and %shredders) were significantly altered. Percent VF and forested area were related to biological quality but varied more than individual ions and specific conductance. Within the subset of VF sites, other descriptors (e.g., VF age, site distance from VF, the presence of impoundments, % forest) had no detectable relationships with biological condition. Although these VFs were constructed pursuant to permits and regulatory programs that have as their stated goals that (1) mined land be reclaimed and restored to its original use or a use of higher value, and (2) mining does not cause or contribute to violations of water quality standards, we found sustained ecological damage in headwaters streams draining VFs long after reclamation was completed.

Using the epigenetic field defect to detect prostate cancer in biopsy negative patients.

PubMed

Truong, Matthew; Yang, Bing; Livermore, Andrew; Wagner, Jennifer; Weeratunga, Puspha; Huang, Wei; Dhir, Rajiv; Nelson, Joel; Lin, Daniel W; Jarrard, David F

2013-06-01

We determined whether a novel combination of field defect DNA methylation markers could predict the presence of prostate cancer using histologically normal transrectal ultrasound guided biopsy cores. Methylation was assessed using quantitative Pyrosequencing® in a training set consisting of 65 nontumor and tumor associated prostate tissues from University of Wisconsin. A multiplex model was generated using multivariate logistic regression and externally validated in blinded fashion in a set of 47 nontumor and tumor associated biopsy specimens from University of Washington. We observed robust methylation differences in all genes at all CpGs assayed (p <0.0001). Regression models incorporating individual genes (EVX1, CAV1 and FGF1) and a gene combination (EVX1 and FGF1) discriminated nontumor from tumor associated tissues in the original training set (AUC 0.796-0.898, p <0.001). On external validation uniplex models incorporating EVX1, CAV1 or FGF1 discriminated tumor from nontumor associated biopsy negative specimens (AUC 0.702, 0.696 and 0.658, respectively, p <0.05). A multiplex model (EVX1 and FGF1) identified patients with prostate cancer (AUC 0.774, p = 0.001) and had a negative predictive value of 0.909. Comparison between 2 separate cores in patients in this validation set revealed similar methylation defects, indicating detection of a widespread field defect. A widespread epigenetic field defect can be used to detect prostate cancer in patients with histologically negative biopsies. To our knowledge this assay is unique, in that it detects alterations in nontumor cells. With further validation this marker combination (EVX1 and FGF1) has the potential to decrease the need for repeat prostate biopsies, a procedure associated with cost and complications. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multivariate longitudinal data analysis with censored and intermittent missing responses.

PubMed

Lin, Tsung-I; Lachos, Victor H; Wang, Wan-Lun

2018-05-08

The multivariate linear mixed model (MLMM) has emerged as an important analytical tool for longitudinal data with multiple outcomes. However, the analysis of multivariate longitudinal data could be complicated by the presence of censored measurements because of a detection limit of the assay in combination with unavoidable missing values arising when subjects miss some of their scheduled visits intermittently. This paper presents a generalization of the MLMM approach, called the MLMM-CM, for a joint analysis of the multivariate longitudinal data with censored and intermittent missing responses. A computationally feasible expectation maximization-based procedure is developed to carry out maximum likelihood estimation within the MLMM-CM framework. Moreover, the asymptotic standard errors of fixed effects are explicitly obtained via the information-based method. We illustrate our methodology by using simulated data and a case study from an AIDS clinical trial. Experimental results reveal that the proposed method is able to provide more satisfactory performance as compared with the traditional MLMM approach. Copyright © 2018 John Wiley & Sons, Ltd.

Increased levels of N(ε)- Carboxy methyl lysine (N(ε)-CML) are associated with topographic alterations in retinal pigment epithelium: A preliminary study.

PubMed

Mishra, Nibha; Saxena, Sandeep; Ruia, Surabhi; Prasad, Senthamizh; Singh, Vinita; Khanna, Vinay; Staffa, Robert; Gaspar, Ludovit; Kruzliak, Peter

2016-07-01

To evaluate the association of serum levels of N(ε)- Carboxy methyl lysine (N(ε)-CML), an advanced glycation end product with topographic alterations in retinal pigment epithelium (RPE) in diabetic retinopathy on spectral domain optical coherence tomography (SD-OCT). Consecutive cases of type 2 diabetes mellitus with no retinopathy (n=20); non-proliferative diabetic retinopathy (n=20); proliferative diabetic retinopathy (n=20) and healthy controls (n=20) between the ages of 40 and 65years were included. RPE alterations were graded on segmentation map of SD-OCT: grade 0, No RPE alterations; grade 1, RPE alterations in up to two quadrants and grade 2, RPE alterations in more than two quadrants. Serum level of N(ε)-CML and glycated hemoglobin (HbA1c) was analyzed using the standard protocol. Statistical analysis was done. Significant increase in N(ε)-CML was observed with increased severity of diabetic retinopathy (F=34.1; p<0.0001). Fisher exact test revealed significant increase in grades of RPE alterations with increased severity of diabetic retinopathy (p<0.001). Univariate ordinal regression analysis was done to calculate the risk of progression in grades of RPE alteration with individual changes in variables like duration of diabetes (odds ratio=1.37; p=0.001), HbA1c (odds ratio=1.37; p=0.002) and Nε-CML (odds ratio=1.37; p<0.0001). Multivariate ordinal regression analysis for predicting progression in grades of RPE alteration revealed Nε-CML to be an independent predictor of increase in grades of RPE alteration (adjusted odds ratio=1.07; p<0.01) when duration of diabetes and HbA1c were held constant. Increase in serum levels of N(ε)- Carboxy methyl lysine is significantly associated with topographic alterations in RPE. Grades of RPE alteration increase significantly with increased severity of diabetic retinopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of the high-resolution satellite images for detection of fractures related to the ore deposits

NASA Astrophysics Data System (ADS)

Cruz-Mondaca, M.; Soto-Pinto, C. A.; Arellano-Baeza, A. A.

2012-12-01

The Aster and GeoEye satellite high-resolution images were used to detect the structures related to the fracturing of the upper crust in the North of Chile. In particular, lineament analysis has been applied to detect the presence of epithermal fluids of low sulfurization associated with the Paleozoic ore deposits. These results have been compared with the location of the minerals altered by the presence of geothermal fluids detected using the spectral libraries. Later, the presence of fractures has been corroborated during recognition of fractures in situ and the geochemical analysis of samples of minerals altered by the presence of fluids. It was shown that the results obtained are relevant for the gold vein detection.

Feasibility Study on the Use of On-line Multivariate Statistical Process Control for Safeguards Applications in Natural Uranium Conversion Plants

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

Ladd-Lively, Jennifer L

2014-01-01

The objective of this work was to determine the feasibility of using on-line multivariate statistical process control (MSPC) for safeguards applications in natural uranium conversion plants. Multivariate statistical process control is commonly used throughout industry for the detection of faults. For safeguards applications in uranium conversion plants, faults could include the diversion of intermediate products such as uranium dioxide, uranium tetrafluoride, and uranium hexafluoride. This study was limited to a 100 metric ton of uranium (MTU) per year natural uranium conversion plant (NUCP) using the wet solvent extraction method for the purification of uranium ore concentrate. A key component inmore » the multivariate statistical methodology is the Principal Component Analysis (PCA) approach for the analysis of data, development of the base case model, and evaluation of future operations. The PCA approach was implemented through the use of singular value decomposition of the data matrix where the data matrix represents normal operation of the plant. Component mole balances were used to model each of the process units in the NUCP. However, this approach could be applied to any data set. The monitoring framework developed in this research could be used to determine whether or not a diversion of material has occurred at an NUCP as part of an International Atomic Energy Agency (IAEA) safeguards system. This approach can be used to identify the key monitoring locations, as well as locations where monitoring is unimportant. Detection limits at the key monitoring locations can also be established using this technique. Several faulty scenarios were developed to test the monitoring framework after the base case or normal operating conditions of the PCA model were established. In all of the scenarios, the monitoring framework was able to detect the fault. Overall this study was successful at meeting the stated objective.« less

Rapid Assessment of Genotoxicity by Flow Cytometric Detection of Cell Cycle Alterations.

PubMed

Bihari, Nevenka

2017-01-01

Flow cytometry is a convenient method for the determination of genotoxic effects of environmental pollution and can reveal genotoxic compounds in unknown environmental mixtures. It is especially suitable for the analyses of large numbers of samples during monitoring programs. The speed of detection is one of the advantages of this technique which permits the acquisition of 10 4 -10 5 cells per sample in 5 min. This method can rapidly detect cell cycle alterations resulting from DNA damage. The outcome of such an analysis is a diagram of DNA content across the cell cycle which indicates cell proliferation, G 2 arrests, G 1 delays, apoptosis, and ploidy.Here, we present the flow cytometric procedure for rapid assessment of genotoxicity via detection of cell cycle alterations. The described protocol simplifies the analysis of genotoxic effects in marine environments and is suitable for monitoring purposes. It uses marine mussel cells in the analysis and can be adapted to investigations on a broad range of marine invertebrates.

Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects on thyroid endpoints.

PubMed

Stoker, T E; Ferrell, J M; Laws, S C; Cooper, R L; Buckalew, A

2006-11-10

The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and lubricants. Over the past 50 years, potassium perchlorate has been used to treat hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by competitively inhibiting iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats based on a pilot study of oral dosing. Doses of 125-500 mg/kg perchlorate decreased T4 in a dose-dependent manner. TSH was significantly increased in a dose-responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of iodide). This study also found that perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.

Early Detection of NSCLC Using Stromal Markers in Peripheral Blood

DTIC Science & Technology

2017-11-01

transcriptionally altered and the alteration is tumor dependent . The specific transcriptomic signature of circulating myeloid cells may provide us unique...signature, which may be useful for early lung cancer diagnosis. The specific aims are: Aim 1. To identify a NSCLC- dependent transcriptomic signature in...circulating myeloid cells are transcriptionally altered and the alteration is tumor dependent . The specific transcriptomic signature of circulating

Sleep Characteristics, Mental Health, and Diabetes Risk: A Prospective Study of U.S. Military Service Members in the Millennium Cohort Study

DTIC Science & Technology

2013-10-01

on body weight regulation through hormonal alterations (e.g., leptin, ghrelin , insulin) that may affect appetite regulation, and sleep- mediated...sleep duration for trou- ble sleeping in multivariable modeling yielded nearly identical results, with significantly higher risk seen with ,6 h of sleep...Riddle, Colonel (Retired) (U.S. Air Force, Bio - medical Science Corps); Margaret Ryan (Naval Hospital Camp Pendleton, Camp Pendleton, CA); and Timothy

A multivariate pattern analysis study of the HIV-related white matter anatomical structural connections alterations

NASA Astrophysics Data System (ADS)

Tang, Zhenchao; Liu, Zhenyu; Li, Ruili; Cui, Xinwei; Li, Hongjun; Dong, Enqing; Tian, Jie

2017-03-01

It's widely known that HIV infection would cause white matter integrity impairments. Nevertheless, it is still unclear that how the white matter anatomical structural connections are affected by HIV infection. In the current study, we employed a multivariate pattern analysis to explore the HIV-related white matter connections alterations. Forty antiretroviraltherapy- naïve HIV patients and thirty healthy controls were enrolled. Firstly, an Automatic Anatomical Label (AAL) atlas based white matter structural network, a 90 × 90 FA-weighted matrix, was constructed for each subject. Then, the white matter connections deprived from the structural network were entered into a lasso-logistic regression model to perform HIV-control group classification. Using leave one out cross validation, a classification accuracy (ACC) of 90% (P=0.002) and areas under the receiver operating characteristic curve (AUC) of 0.96 was obtained by the classification model. This result indicated that the white matter anatomical structural connections contributed greatly to HIV-control group classification, providing solid evidence that the white matter connections were affected by HIV infection. Specially, 11 white matter connections were selected in the classification model, mainly crossing the regions of frontal lobe, Cingulum, Hippocampus, and Thalamus, which were reported to be damaged in previous HIV studies. This might suggest that the white matter connections adjacent to the HIV-related impaired regions were prone to be damaged.

Late diagenetic indicators of buried oil and gas. 2: Direct detection experiment at Cement and Garza fields, Oklahoma and Texas, using enhanced LANDSAT 1 and 2 images

NASA Technical Reports Server (NTRS)

Donovan, T. J.; Termain, P. A.; Henry, M. E. (Principal Investigator)

1979-01-01

The author has identified the following significant results. The Cement oil field, Oklahoma, was a test site for an experiment designed to evaluate LANDSAT's capability to detect an alteration zone in surface rocks caused by hydrocarbon microseepage. Loss of iron and impregnation of sandstone by carbonate cements and replacement of gypsum by calcite were the major alteration phenomena at Cement. The bedrock alterations were partially masked by unaltered overlying beds, thick soils, and dense natural and cultivated vegetation. Interpreters, biased by detailed ground truth, were able to map the alteration zone subjectively using a magnified, filtered, and sinusoidally stretched LANDSAT composite image; other interpreters, unbiased by ground truth data, could not duplicate that interpretation.

LANDSAT detection of hydrothermal alteration in the Nogal Canyon Cauldron, New Mexico

NASA Technical Reports Server (NTRS)

Vincent, R. K.; Rouse, G.

1977-01-01

In 1974 a circular-shaped iron oxide anomaly was observed in an image of a LANDSAT frame centered near Truth or Consequences, New Mexico. Field examination of the anomaly has shown that it coincides with a zone of hydrothermal alteration on the northern edge of the Nogal Canyon Cauldron. The altered area contains clay minerals ranging in colors from white to vivid red, the latter presumably resulting from hematite staining. In situ gas measurements showed no evidence of active hydrogen sulfide seepage. Preliminary geochemical analyses of grab samples have detected no significant amounts of mineralization. Whereas this area does not at present appear to be economically important, it provides an example of how LANDSAT can be utilized in reconnaissance mapping for cauldrons, calderas, and other volcanic features which display hydrothermal alteration.

Multivariate-$t$ nonlinear mixed models with application to censored multi-outcome AIDS studies.

PubMed

Lin, Tsung-I; Wang, Wan-Lun

2017-10-01

In multivariate longitudinal HIV/AIDS studies, multi-outcome repeated measures on each patient over time may contain outliers, and the viral loads are often subject to a upper or lower limit of detection depending on the quantification assays. In this article, we consider an extension of the multivariate nonlinear mixed-effects model by adopting a joint multivariate-$t$ distribution for random effects and within-subject errors and taking the censoring information of multiple responses into account. The proposed model is called the multivariate-$t$ nonlinear mixed-effects model with censored responses (MtNLMMC), allowing for analyzing multi-outcome longitudinal data exhibiting nonlinear growth patterns with censorship and fat-tailed behavior. Utilizing the Taylor-series linearization method, a pseudo-data version of expectation conditional maximization either (ECME) algorithm is developed for iteratively carrying out maximum likelihood estimation. We illustrate our techniques with two data examples from HIV/AIDS studies. Experimental results signify that the MtNLMMC performs favorably compared to its Gaussian analogue and some existing approaches. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prefrontal gray matter volume mediates genetic risks for obesity.

PubMed

Opel, N; Redlich, R; Kaehler, C; Grotegerd, D; Dohm, K; Heindel, W; Kugel, H; Thalamuthu, A; Koutsouleris, N; Arolt, V; Teuber, A; Wersching, H; Baune, B T; Berger, K; Dannlowski, U

2017-05-01

Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.

CHESS (CgHExpreSS): a comprehensive analysis tool for the analysis of genomic alterations and their effects on the expression profile of the genome.

PubMed

Lee, Mikyung; Kim, Yangseok

2009-12-16

Genomic alterations frequently occur in many cancer patients and play important mechanistic roles in the pathogenesis of cancer. Furthermore, they can modify the expression level of genes due to altered copy number in the corresponding region of the chromosome. An accumulating body of evidence supports the possibility that strong genome-wide correlation exists between DNA content and gene expression. Therefore, more comprehensive analysis is needed to quantify the relationship between genomic alteration and gene expression. A well-designed bioinformatics tool is essential to perform this kind of integrative analysis. A few programs have already been introduced for integrative analysis. However, there are many limitations in their performance of comprehensive integrated analysis using published software because of limitations in implemented algorithms and visualization modules. To address this issue, we have implemented the Java-based program CHESS to allow integrative analysis of two experimental data sets: genomic alteration and genome-wide expression profile. CHESS is composed of a genomic alteration analysis module and an integrative analysis module. The genomic alteration analysis module detects genomic alteration by applying a threshold based method or SW-ARRAY algorithm and investigates whether the detected alteration is phenotype specific or not. On the other hand, the integrative analysis module measures the genomic alteration's influence on gene expression. It is divided into two separate parts. The first part calculates overall correlation between comparative genomic hybridization ratio and gene expression level by applying following three statistical methods: simple linear regression, Spearman rank correlation and Pearson's correlation. In the second part, CHESS detects the genes that are differentially expressed according to the genomic alteration pattern with three alternative statistical approaches: Student's t-test, Fisher's exact test and Chi square test. By successive operations of two modules, users can clarify how gene expression levels are affected by the phenotype specific genomic alterations. As CHESS was developed in both Java application and web environments, it can be run on a web browser or a local machine. It also supports all experimental platforms if a properly formatted text file is provided to include the chromosomal position of probes and their gene identifiers. CHESS is a user-friendly tool for investigating disease specific genomic alterations and quantitative relationships between those genomic alterations and genome-wide gene expression profiling.

Detection of HPV-DNA, p53 alterations, and methylation in penile squamous cell carcinoma in Japanese men.

PubMed

Yanagawa, Naoki; Osakabe, Mitsumasa; Hayashi, Masahiro; Tamura, Gen; Motoyama, Teiichi

2008-08-01

Penile carcinoma is a rare disease, accordingly there are few studies on molecular changes, and these results also vary greatly. A total of 26 penile squamous cell carcinomas in Japanese men were studied with respect to HPV, p53 alterations, and methylation of gene promoter region. HPV-DNA was detected in three of 26 patients (11.5%). Overexpression of p53 was observed in 13 of 26 patients (50%), and p53 gene mutations were detected in four of 26 patients (15.4%). The frequency of methylation was as follows: DAPK, 26.9% (7/26); FHIT, 88.4% (23/26); MGMT, 19.2% (5/26); p14, 3.8% (1/26); p16, 23.1% (6/26); RAR-beta, 23.1% (6/26); RASSF1A, 11.5% (3/26); and RUNX3, 42.3% (11/26). As for correlation between HPV and p53 alterations, and methylation status, mutations of the p53 gene were detected only in HPV-negative patients, and methylation was more frequently found in HPV-negative than in HPV-positive patients. The present results suggest that the majority of penile squamous cell carcinomas in Japanese men are unrelated to HPV, and gene alterations accumulate more frequently in HPV-unrelated penile carcinomas.

Methodological challenges to multivariate syndromic surveillance: a case study using Swiss animal health data.

PubMed

Vial, Flavie; Wei, Wei; Held, Leonhard

2016-12-20

In an era of ubiquitous electronic collection of animal health data, multivariate surveillance systems (which concurrently monitor several data streams) should have a greater probability of detecting disease events than univariate systems. However, despite their limitations, univariate aberration detection algorithms are used in most active syndromic surveillance (SyS) systems because of their ease of application and interpretation. On the other hand, a stochastic modelling-based approach to multivariate surveillance offers more flexibility, allowing for the retention of historical outbreaks, for overdispersion and for non-stationarity. While such methods are not new, they are yet to be applied to animal health surveillance data. We applied an example of such stochastic model, Held and colleagues' two-component model, to two multivariate animal health datasets from Switzerland. In our first application, multivariate time series of the number of laboratories test requests were derived from Swiss animal diagnostic laboratories. We compare the performance of the two-component model to parallel monitoring using an improved Farrington algorithm and found both methods yield a satisfactorily low false alarm rate. However, the calibration test of the two-component model on the one-step ahead predictions proved satisfactory, making such an approach suitable for outbreak prediction. In our second application, the two-component model was applied to the multivariate time series of the number of cattle abortions and the number of test requests for bovine viral diarrhea (a disease that often results in abortions). We found that there is a two days lagged effect from the number of abortions to the number of test requests. We further compared the joint modelling and univariate modelling of the number of laboratory test requests time series. The joint modelling approach showed evidence of superiority in terms of forecasting abilities. Stochastic modelling approaches offer the potential to address more realistic surveillance scenarios through, for example, the inclusion of times series specific parameters, or of covariates known to have an impact on syndrome counts. Nevertheless, many methodological challenges to multivariate surveillance of animal SyS data still remain. Deciding on the amount of corroboration among data streams that is required to escalate into an alert is not a trivial task given the sparse data on the events under consideration (e.g. disease outbreaks).

Multivariate selection and intersexual genetic constraints in a wild bird population.

PubMed

Poissant, J; Morrissey, M B; Gosler, A G; Slate, J; Sheldon, B C

2016-10-01

When selection differs between the sexes for traits that are genetically correlated between the sexes, there is potential for the effect of selection in one sex to be altered by indirect selection in the other sex, a situation commonly referred to as intralocus sexual conflict (ISC). While potentially common, ISC has rarely been studied in wild populations. Here, we studied ISC over a set of morphological traits (wing length, tarsus length, bill depth and bill length) in a wild population of great tits (Parus major) from Wytham Woods, UK. Specifically, we quantified the microevolutionary impacts of ISC by combining intra- and intersex additive genetic (co)variances and sex-specific selection estimates in a multivariate framework. Large genetic correlations between homologous male and female traits combined with evidence for sex-specific multivariate survival selection suggested that ISC could play an appreciable role in the evolution of this population. Together, multivariate sex-specific selection and additive genetic (co)variance for the traits considered accounted for additive genetic variance in fitness that was uncorrelated between the sexes (cross-sex genetic correlation = -0.003, 95% CI = -0.83, 0.83). Gender load, defined as the reduction in a population's rate of adaptation due to sex-specific effects, was estimated at 50% (95% CI = 13%, 86%). This study provides novel insights into the evolution of sexual dimorphism in wild populations and illustrates how quantitative genetics and selection analyses can be combined in a multivariate framework to quantify the microevolutionary impacts of ISC. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Nicotinic cholinergic receptors in esophagus: Early alteration during carcinogenesis and prognostic value

PubMed Central

Chianello Nicolau, Marina; Pinto, Luis Felipe Ribeiro; Nicolau-Neto, Pedro; de Pinho, Paulo Roberto Alves; Rossini, Ana; de Almeida Simão, Tatiana; Soares Lima, Sheila Coelho

2016-01-01

AIM To compare expression of nicotinic cholinergic receptors (CHRNs) in healthy and squamous cell carcinoma-affected esophagus and determine the prognostic value. METHODS We performed RT-qPCR to measure the expression of CHRNs in 44 esophageal samples from healthy individuals and in matched normal surrounding mucosa, and in tumors from 28 patients diagnosed with esophageal squamous cell carcinoma (ESCC). Next, we performed correlation analysis for the detected expression of these receptors with the habits and clinico-pathological characteristics of all study participants. In order to investigate the possible correlations between the expression of the different CHRN subunits in both healthy esophagus and tissues from ESCC patients, correlation matrices were generated. Subsequently, we evaluated whether the detected alterations in expression of the various CHRNs could precede histopathological modifications during the esophageal carcinogenic processes by using receiver operating characteristic curve analysis. Finally, we evaluated the impact of CHRNA5 and CHRNA7 expression on overall survival by using multivariate analysis. RESULTS CHRNA3, CHRNA5, CHRNA7 and CHRNB4, but not CHRNA1, CHRNA4, CHRNA9 or CHRNA10, were found to be expressed in normal (healthy) esophageal mucosa. In ESCC, CHRNA5 and CHRNA7 were overexpressed as compared with patient-matched surrounding non-tumor mucosa (ESCC-adjacent mucosa; P < 0.0001 and P = 0.0091, respectively). Positive correlations were observed between CHRNA3 and CHRNB4 expression in all samples analyzed. Additionally, CHRNB4 was found to be differentially expressed in the healthy esophagus and the normal-appearing ESCC-adjacent mucosa, allowing for distinguishment between these tissues with a sensitivity of 75.86% and a specificity of 78.95% (P = 0.0002). Finally, CHRNA5 expression was identified as an independent prognostic factor in ESCC; patients with high CHRNA5 expression showed an increased overall survival, in comparison with those with low expression. The corresponding age- and tumor stage-adjusted hazard ratio was 0.2684 (95%CI: 0.075-0.97, P = 0.0448). CONCLUSION Expression of CHRNs is homogeneous along healthy esophagus and deregulated in ESCC, suggesting a pathogenic role for these receptors in ESCC development and progression. PMID:27610024

Nicotinic cholinergic receptors in esophagus: Early alteration during carcinogenesis and prognostic value.

PubMed

Chianello Nicolau, Marina; Pinto, Luis Felipe Ribeiro; Nicolau-Neto, Pedro; de Pinho, Paulo Roberto Alves; Rossini, Ana; de Almeida Simão, Tatiana; Soares Lima, Sheila Coelho

2016-08-21

To compare expression of nicotinic cholinergic receptors (CHRNs) in healthy and squamous cell carcinoma-affected esophagus and determine the prognostic value. We performed RT-qPCR to measure the expression of CHRNs in 44 esophageal samples from healthy individuals and in matched normal surrounding mucosa, and in tumors from 28 patients diagnosed with esophageal squamous cell carcinoma (ESCC). Next, we performed correlation analysis for the detected expression of these receptors with the habits and clinico-pathological characteristics of all study participants. In order to investigate the possible correlations between the expression of the different CHRN subunits in both healthy esophagus and tissues from ESCC patients, correlation matrices were generated. Subsequently, we evaluated whether the detected alterations in expression of the various CHRNs could precede histopathological modifications during the esophageal carcinogenic processes by using receiver operating characteristic curve analysis. Finally, we evaluated the impact of CHRNA5 and CHRNA7 expression on overall survival by using multivariate analysis. CHRNA3, CHRNA5, CHRNA7 and CHRNB4, but not CHRNA1, CHRNA4, CHRNA9 or CHRNA10, were found to be expressed in normal (healthy) esophageal mucosa. In ESCC, CHRNA5 and CHRNA7 were overexpressed as compared with patient-matched surrounding non-tumor mucosa (ESCC-adjacent mucosa; P < 0.0001 and P = 0.0091, respectively). Positive correlations were observed between CHRNA3 and CHRNB4 expression in all samples analyzed. Additionally, CHRNB4 was found to be differentially expressed in the healthy esophagus and the normal-appearing ESCC-adjacent mucosa, allowing for distinguishment between these tissues with a sensitivity of 75.86% and a specificity of 78.95% (P = 0.0002). Finally, CHRNA5 expression was identified as an independent prognostic factor in ESCC; patients with high CHRNA5 expression showed an increased overall survival, in comparison with those with low expression. The corresponding age- and tumor stage-adjusted hazard ratio was 0.2684 (95%CI: 0.075-0.97, P = 0.0448). Expression of CHRNs is homogeneous along healthy esophagus and deregulated in ESCC, suggesting a pathogenic role for these receptors in ESCC development and progression.

Observational difference between gamma and X-ray properties of optically dark and bright GRBs

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

Balazs, L. G.; Horvath, I.; Bagoly, Zs.

2008-05-22

Using the discriminant analysis of the multivariate statistical analysis we compared the distribution of the physical quantities of the optically dark and bright GRBs, detected by the BAT and XRT on board of the Swift Satellite. We found that the GRBs having detected optical transients (OT) have systematically higher peak fluxes and lower HI column densities than those without OT.

Sensor failure and multivariable control for airbreathing propulsion systems. Ph.D. Thesis - Dec. 1979 Final Report

NASA Technical Reports Server (NTRS)

Behbehani, K.

1980-01-01

A new sensor/actuator failure analysis technique for turbofan jet engines was developed. Three phases of failure analysis, namely detection, isolation, and accommodation are considered. Failure detection and isolation techniques are developed by utilizing the concept of Generalized Likelihood Ratio (GLR) tests. These techniques are applicable to both time varying and time invariant systems. Three GLR detectors are developed for: (1) hard-over sensor failure; (2) hard-over actuator failure; and (3) brief disturbances in the actuators. The probability distribution of the GLR detectors and the detectability of sensor/actuator failures are established. Failure type is determined by the maximum of the GLR detectors. Failure accommodation is accomplished by extending the Multivariable Nyquest Array (MNA) control design techniques to nonsquare system designs. The performance and effectiveness of the failure analysis technique are studied by applying the technique to a turbofan jet engine, namely the Quiet Clean Short Haul Experimental Engine (QCSEE). Single and multiple sensor/actuator failures in the QCSEE are simulated and analyzed and the effects of model degradation are studied.

Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats

PubMed Central

Marfà, Santiago; Morales-Ruiz, Manuel; Oró, Denise; Ribera, Jordi; Fernández-Varo, Guillermo; Jiménez, Wladimiro

2016-01-01

ABSTRACT At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1) were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis. PMID:27230648

The brown seaweed Sargassum cymosum: changes in metabolism and cellular organization after long-term exposure to cadmium.

PubMed

Costa, Giulia B; Simioni, Carmen; Pereira, Débora T; Ramlov, Fernanda; Maraschin, Marcelo; Chow, Fungyi; Horta, Paulo A; Bouzon, Zenilda L; Schmidt, Éder C

2017-03-01

Sargassum cymosum was exposed to cadmium (Cd) to determine any physiological and ultrastructural effects. To accomplish this, S. cymosum samples were cultivated under photosynthetic active radiation (PAR) and Cd (0, 0.1, 0.2, 0.4 and 0.8 mg L -1 ) during 7 and 14 days in laboratory-controlled conditions (0 mg L -1 Cd at both exposure times as control). Seaweeds had high retention capacity (over 90 %) for both exposure times. Growth rates showed significant increases by 14 days, especially for 0.1 and 0.4 mg L -1 Cd. Photosynthetic parameters were unaffected by Cd treatments. Chlorophyll contents were present in higher concentrations for all Cd treatments compared to respective control. Carotenoid profile showed significant differences in total composition and proportion of fucoxanthin and β-carotene, and no lutein was detected at 14 days. Phenolic and flavonoid compounds showed major accumulation at 14 days. Transmission electron microscopy (TEM) analyses presented major alterations in Cd-treated samples, when compared with respective control, in particular disorganization of cell wall fibrils. When compared to respective control samples, multivariate analyses showed disparate and complex interactions among metabolites in Cd-exposed seaweeds, giving evidence of physiological defence response. Thus, it can be concluded that Cd is a stressor for S. cymosum, resulting in physiological and structural alterations related to defence mechanisms against oxidative stress and toxicological effects resulting from long-term metal exposure. However, in the present paper, some observed changes also appear to result from acclimation mechanisms under lower concentration of Cd relative to the tolerance of S. cymosum to experimental conditions.

metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis.

PubMed

Cichonska, Anna; Rousu, Juho; Marttinen, Pekka; Kangas, Antti J; Soininen, Pasi; Lehtimäki, Terho; Raitakari, Olli T; Järvelin, Marjo-Riitta; Salomaa, Veikko; Ala-Korpela, Mika; Ripatti, Samuli; Pirinen, Matti

2016-07-01

A dominant approach to genetic association studies is to perform univariate tests between genotype-phenotype pairs. However, analyzing related traits together increases statistical power, and certain complex associations become detectable only when several variants are tested jointly. Currently, modest sample sizes of individual cohorts, and restricted availability of individual-level genotype-phenotype data across the cohorts limit conducting multivariate tests. We introduce metaCCA, a computational framework for summary statistics-based analysis of a single or multiple studies that allows multivariate representation of both genotype and phenotype. It extends the statistical technique of canonical correlation analysis to the setting where original individual-level records are not available, and employs a covariance shrinkage algorithm to achieve robustness.Multivariate meta-analysis of two Finnish studies of nuclear magnetic resonance metabolomics by metaCCA, using standard univariate output from the program SNPTEST, shows an excellent agreement with the pooled individual-level analysis of original data. Motivated by strong multivariate signals in the lipid genes tested, we envision that multivariate association testing using metaCCA has a great potential to provide novel insights from already published summary statistics from high-throughput phenotyping technologies. Code is available at https://github.com/aalto-ics-kepaco anna.cichonska@helsinki.fi or matti.pirinen@helsinki.fi Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Finding structure in data using multivariate tree boosting

PubMed Central

Miller, Patrick J.; Lubke, Gitta H.; McArtor, Daniel B.; Bergeman, C. S.

2016-01-01

Technology and collaboration enable dramatic increases in the size of psychological and psychiatric data collections, but finding structure in these large data sets with many collected variables is challenging. Decision tree ensembles such as random forests (Strobl, Malley, & Tutz, 2009) are a useful tool for finding structure, but are difficult to interpret with multiple outcome variables which are often of interest in psychology. To find and interpret structure in data sets with multiple outcomes and many predictors (possibly exceeding the sample size), we introduce a multivariate extension to a decision tree ensemble method called gradient boosted regression trees (Friedman, 2001). Our extension, multivariate tree boosting, is a method for nonparametric regression that is useful for identifying important predictors, detecting predictors with nonlinear effects and interactions without specification of such effects, and for identifying predictors that cause two or more outcome variables to covary. We provide the R package ‘mvtboost’ to estimate, tune, and interpret the resulting model, which extends the implementation of univariate boosting in the R package ‘gbm’ (Ridgeway et al., 2015) to continuous, multivariate outcomes. To illustrate the approach, we analyze predictors of psychological well-being (Ryff & Keyes, 1995). Simulations verify that our approach identifies predictors with nonlinear effects and achieves high prediction accuracy, exceeding or matching the performance of (penalized) multivariate multiple regression and multivariate decision trees over a wide range of conditions. PMID:27918183

metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis

PubMed Central

Cichonska, Anna; Rousu, Juho; Marttinen, Pekka; Kangas, Antti J.; Soininen, Pasi; Lehtimäki, Terho; Raitakari, Olli T.; Järvelin, Marjo-Riitta; Salomaa, Veikko; Ala-Korpela, Mika; Ripatti, Samuli; Pirinen, Matti

2016-01-01

Motivation: A dominant approach to genetic association studies is to perform univariate tests between genotype-phenotype pairs. However, analyzing related traits together increases statistical power, and certain complex associations become detectable only when several variants are tested jointly. Currently, modest sample sizes of individual cohorts, and restricted availability of individual-level genotype-phenotype data across the cohorts limit conducting multivariate tests. Results: We introduce metaCCA, a computational framework for summary statistics-based analysis of a single or multiple studies that allows multivariate representation of both genotype and phenotype. It extends the statistical technique of canonical correlation analysis to the setting where original individual-level records are not available, and employs a covariance shrinkage algorithm to achieve robustness. Multivariate meta-analysis of two Finnish studies of nuclear magnetic resonance metabolomics by metaCCA, using standard univariate output from the program SNPTEST, shows an excellent agreement with the pooled individual-level analysis of original data. Motivated by strong multivariate signals in the lipid genes tested, we envision that multivariate association testing using metaCCA has a great potential to provide novel insights from already published summary statistics from high-throughput phenotyping technologies. Availability and implementation: Code is available at https://github.com/aalto-ics-kepaco Contacts: anna.cichonska@helsinki.fi or matti.pirinen@helsinki.fi Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153689

Detecting a currency’s dominance using multivariate time series analysis

NASA Astrophysics Data System (ADS)

Syahidah Yusoff, Nur; Sharif, Shamshuritawati

2017-09-01

A currency exchange rate is the price of one country’s currency in terms of another country’s currency. There are four different prices; opening, closing, highest, and lowest can be achieved from daily trading activities. In the past, a lot of studies have been carried out by using closing price only. However, those four prices are interrelated to each other. Thus, the multivariate time series can provide more information than univariate time series. Therefore, the enthusiasm of this paper is to compare the results of two different approaches, which are mean vector and Escoufier’s RV coefficient in constructing similarity matrices of 20 world currencies. Consequently, both matrices are used to substitute the correlation matrix required by network topology. With the help of degree centrality measure, we can detect the currency’s dominance for both networks. The pros and cons for both approaches will be presented at the end of this paper.

Near Infrared Spectroscopy Detection and Quantification of Herbal Medicines Adulterated with Sibutramine.

PubMed

da Silva, Neirivaldo Cavalcante; Honorato, Ricardo Saldanha; Pimentel, Maria Fernanda; Garrigues, Salvador; Cervera, Maria Luisa; de la Guardia, Miguel

2015-09-01

There is an increasing demand for herbal medicines in weight loss treatment. Some synthetic chemicals, such as sibutramine (SB), have been detected as adulterants in herbal formulations. In this study, two strategies using near infrared (NIR) spectroscopy have been developed to evaluate potential adulteration of herbal medicines with SB: a qualitative screening approach and a quantitative methodology based on multivariate calibration. Samples were composed by products commercialized as herbal medicines, as well as by laboratory adulterated samples. Spectra were obtained in the range of 14,000-4000 per cm. Using PLS-DA, a correct classification of 100% was achieved for the external validation set. In the quantitative approach, the root mean squares error of prediction (RMSEP), for both PLS and MLR models, was 0.2% w/w. The results prove the potential of NIR spectroscopy and multivariate calibration in quantifying sibutramine in adulterated herbal medicines samples. © 2015 American Academy of Forensic Sciences.

Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

PubMed

Loeb, Stacy; Shin, Sanghyuk S; Broyles, Dennis L; Wei, John T; Sanda, Martin; Klee, George; Partin, Alan W; Sokoll, Lori; Chan, Daniel W; Bangma, Chris H; van Schaik, Ron H N; Slawin, Kevin M; Marks, Leonard S; Catalona, William J

2017-07-01

To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Hepatocellular Carcinoma Screening Associated with Early Tumor Detection and Improved Survival Among Patients with Cirrhosis in the US.

PubMed

Singal, Amit G; Mittal, Sahil; Yerokun, Olutola A; Ahn, Chul; Marrero, Jorge A; Yopp, Adam C; Parikh, Neehar D; Scaglione, Steve J

2017-09-01

Professional societies recommend hepatocellular carcinoma screening in patients with cirrhosis, but high-quality data evaluating its effectiveness to improve early tumor detection and survival in "real world" clinical practice are needed. We aim to characterize the association between hepatocellular carcinoma screening and early tumor detection, curative treatment, and overall survival among patients with cirrhosis. We performed a retrospective cohort study of patients diagnosed with hepatocellular carcinoma between June 2012 and May 2013 at 4 health systems in the US. Patients were categorized in the screening group if hepatocellular carcinoma was detected by imaging performed for screening purposes. Generalized linear models and multivariate Cox regression with frailty adjustment were used to compare early detection, curative treatment, and survival between screen-detected and non-screen-detected patients. Among 374 hepatocellular carcinoma patients, 42% (n = 157) were detected by screening. Screen-detected patients had a significantly higher proportion of early tumors (Barcelona Clinic Liver Cancer stage A 63.1% vs 36.4%, P <.001) and were more likely to undergo curative treatment (31% vs 13%, P = .02). Hepatocellular carcinoma screening was significantly associated with improved survival in multivariate analysis (hazards ratio 0.41; 95% confidence interval, 0.26-0.65) after adjusting for patient demographics, Child-Pugh class, and performance status. Median survival of screen-detected patients was 14.6 months, compared with 6.0 months for non-screen-detected patients, with the difference remaining significant after adjusting for lead-time bias (hazards ratio 0.59, 95% confidence interval, 0.37-0.93). Hepatocellular carcinoma screening is associated with increased early tumor detection and improved survival; however, a minority of hepatocellular carcinoma patients are detected by screening. Interventions to increase screening use in patients with cirrhosis may help curb hepatocellular carcinoma mortality rates. Copyright © 2017 Elsevier Inc. All rights reserved.

Rapid discrimination between buffalo and cow milk and detection of adulteration of buffalo milk with cow milk using synchronous fluorescence spectroscopy in combination with multivariate methods.

PubMed

Durakli Velioglu, Serap; Ercioglu, Elif; Boyaci, Ismail Hakki

2017-05-01

This research paper describes the potential of synchronous fluorescence (SF) spectroscopy for authentication of buffalo milk, a favourable raw material in the production of some premium dairy products. Buffalo milk is subjected to fraudulent activities like many other high priced foodstuffs. The current methods widely used for the detection of adulteration of buffalo milk have various disadvantages making them unattractive for routine analysis. Thus, the aim of the present study was to assess the potential of SF spectroscopy in combination with multivariate methods for rapid discrimination between buffalo and cow milk and detection of the adulteration of buffalo milk with cow milk. SF spectra of cow and buffalo milk samples were recorded between 400-550 nm excitation range with Δλ of 10-100 nm, in steps of 10 nm. The data obtained for ∆λ = 10 nm were utilised to classify the samples using principal component analysis (PCA), and detect the adulteration level of buffalo milk with cow milk using partial least square (PLS) methods. Successful discrimination of samples and detection of adulteration of buffalo milk with limit of detection value (LOD) of 6% are achieved with the models having root mean square error of calibration (RMSEC) and the root mean square error of cross-validation (RMSECV) and root mean square error of prediction (RMSEP) values of 2, 7, and 4%, respectively. The results reveal the potential of SF spectroscopy for rapid authentication of buffalo milk.

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.

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

Southern Analysis of Genomic Alterations in Gamma-Ray-Induced Aprt- Hamster Cell Mutants

PubMed Central

Grosovsky, Andrew J.; Drobetsky, Elliot A.; deJong, Pieter J.; Glickman, Barry W.

1986-01-01

The role of genomic alterations in mutagenesis induced by ionizing radiation has been the subject of considerable speculation. By Southern blotting analysis we show here that 9 of 55 (approximately 1/6) gamma-ray-induced mutants at the adenine phosphoribosyl transferase (aprt) locus of Chinese hamster ovary (CHO) cells have a detectable genomic rearrangement. These fall into two classes: intragenic deletions and chromosomal rearrangements. In contrast, no major genomic alterations were detected among 67 spontaneous mutants, although two restriction site loss events were observed. Three gamma-ray-induced mutants were found to be intragenic deletions; all may have identical break-points. The remaining six gamma-ray-induced mutants demonstrating a genomic alteration appear to be the result of chromosomal rearrangements, possibly translocation or inversion events. None of the remaining gamma-ray-induced mutants showed any observable alteration in blotting pattern indicating a substantial role for point mutation in gamma-ray-induced mutagenesis at the aprt locus. PMID:3013724

Influence assessment in censored mixed-effects models using the multivariate Student’s-t distribution

PubMed Central

Matos, Larissa A.; Bandyopadhyay, Dipankar; Castro, Luis M.; Lachos, Victor H.

2015-01-01

In biomedical studies on HIV RNA dynamics, viral loads generate repeated measures that are often subjected to upper and lower detection limits, and hence these responses are either left- or right-censored. Linear and non-linear mixed-effects censored (LMEC/NLMEC) models are routinely used to analyse these longitudinal data, with normality assumptions for the random effects and residual errors. However, the derived inference may not be robust when these underlying normality assumptions are questionable, especially the presence of outliers and thick-tails. Motivated by this, Matos et al. (2013b) recently proposed an exact EM-type algorithm for LMEC/NLMEC models using a multivariate Student’s-t distribution, with closed-form expressions at the E-step. In this paper, we develop influence diagnostics for LMEC/NLMEC models using the multivariate Student’s-t density, based on the conditional expectation of the complete data log-likelihood. This partially eliminates the complexity associated with the approach of Cook (1977, 1986) for censored mixed-effects models. The new methodology is illustrated via an application to a longitudinal HIV dataset. In addition, a simulation study explores the accuracy of the proposed measures in detecting possible influential observations for heavy-tailed censored data under different perturbation and censoring schemes. PMID:26190871

FGWAS: Functional genome wide association analysis.

PubMed

Huang, Chao; Thompson, Paul; Wang, Yalin; Yu, Yang; Zhang, Jingwen; Kong, Dehan; Colen, Rivka R; Knickmeyer, Rebecca C; Zhu, Hongtu

2017-10-01

Functional phenotypes (e.g., subcortical surface representation), which commonly arise in imaging genetic studies, have been used to detect putative genes for complexly inherited neuropsychiatric and neurodegenerative disorders. However, existing statistical methods largely ignore the functional features (e.g., functional smoothness and correlation). The aim of this paper is to develop a functional genome-wide association analysis (FGWAS) framework to efficiently carry out whole-genome analyses of functional phenotypes. FGWAS consists of three components: a multivariate varying coefficient model, a global sure independence screening procedure, and a test procedure. Compared with the standard multivariate regression model, the multivariate varying coefficient model explicitly models the functional features of functional phenotypes through the integration of smooth coefficient functions and functional principal component analysis. Statistically, compared with existing methods for genome-wide association studies (GWAS), FGWAS can substantially boost the detection power for discovering important genetic variants influencing brain structure and function. Simulation studies show that FGWAS outperforms existing GWAS methods for searching sparse signals in an extremely large search space, while controlling for the family-wise error rate. We have successfully applied FGWAS to large-scale analysis of data from the Alzheimer's Disease Neuroimaging Initiative for 708 subjects, 30,000 vertices on the left and right hippocampal surfaces, and 501,584 SNPs. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-Gaussian and Multivariate Noise Models for Signal Detection.

DTIC Science & Technology

1982-09-01

follow, some of the basic results of asymptotic "theory are presented. both to make the notation clear. and to give some i ~ background for the...densities are considered within a detection framework. The discussions include specific examples and also some general methods of density generation ...densities generated by a memoryless, nonlinear transformation of a correlated, Gaussian source is discussed in some detail. A member of this class has the

Biomarker evidence of tobacco smoke exposure in children participating in lead screening.

PubMed

Joseph, Anne; Spector, Logan; Wickham, Katherine; Janis, Gregory; Winickoff, Jonathan; Lindgren, Bruce; Murphy, Sharon

2013-12-01

We assessed tobacco smoke exposure (TSE), defined according to detection of cotinine, in dried blood spots collected from children for lead screening. Dried blood spots collected from a national sample of 1541 Black and White children and submitted to a commercial laboratory for lead analysis were analyzed for cotinine. We used an anonymous administrative data set including information on children's characteristics to conduct univariate and multivariate analyses. Cotinine was detected in 61% of dried blood spots; 17% of samples had cotinine levels above 3 nanograms per gram. Median cotinine levels were significantly higher among Black than White children (0.66 ng/g vs 0.30 ng/g) and among Medicaid recipients (0.94 ng/g vs < 0.3 ng/g). In multivariate analyses, significant increases in cotinine levels were associated with Black (vs White) race, older age, Medicaid coverage, higher state smoking rate, and higher average winter temperature. Detectable cotinine levels were significantly associated with higher lead levels. TSE is highly prevalent among children undergoing lead screening, and exposure levels are greater among Black children and children on Medicaid. TSE may contribute to lead exposure. Concurrent lead screening and biological screening for TSE may be a feasible approach to increasing childhood TSE detection.

Prevalence of the Fibromyalgia Phenotype in Spine Pain Patients Presenting to a Tertiary Care Pain Clinic and the Potential Treatment Implications

PubMed Central

Brummett, Chad M.; Goesling, Jenna; Tsodikov, Alex; Meraj, Taha S.; Wasserman, Ronald A.; Clauw, Daniel J.; Hassett, Afton L.

2014-01-01

Objective Injections for spinal pain have high failure rates, emphasizing the importance of patient selection. It is possible that detecting the presence of a fibromyalgia-like phenotype could aid in prediction, because in these individuals a peripheral injection would not address pain due to alterations in central neurotransmission. We hypothesized that spine pain patients meeting survey criteria for fibromyalgia would be phenotypically distinct from those who do not meet criteria. Methods 548 patients with a primary spine pain diagnosis were studied. All patients completed validated self-report questionnaires, including the Brief Pain Inventory, PainDETECT, Hospital Anxiety and Depression Scale, measures of physical function, and the American College of Rheumatology survey criteria for fibromyalgia. Results 42% met survey criteria for fibromyalgia (FM+). When compared with criteria negative patients, FM+ patients were more likely to be younger, unemployed, receiving compensation, have greater pain intensity, pain interference and neuropathic pain descriptors, as well as higher levels of depression and anxiety, and lower level of physical function (p < 0.0001 for each comparison). Gender, neuropathic pain, pain interference, physical function, and anxiety were independently predictive of fibromyalgia status in a multivariate analysis (p < 0.01, all variables). ROC analysis showed the strength of association of 0.81 as measured by the cross-validated C-statistic. Conclusion Using the survey criteria for fibromyalgia, we demonstrated profound phenotypic differences in a spine pain population. Although centralized pain cannot be confirmed with a survey alone, the pathophysiology of fibromyalgia may help explain a portion of the variability of responses to spine interventions. PMID:24022710

l-DOPA Decarboxylase (DDC) Expression Status as a Novel Molecular Tumor Marker for Diagnostic and Prognostic Purposes in Laryngeal Cancer.

PubMed

Patsis, Christos; Glyka, Vasiliki; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

2012-08-01

l-DOPA decarboxylase (DDC) plays an essential role in the enzymatic synthesis of dopamine and alterations in its gene expression have been reported in several malignancies. Our objective was to analyze DDC messenger RNA (mRNA) and protein expression in laryngeal tissues and to evaluate the clinical implication of this molecule in laryngeal cancer. In this study, total RNA was isolated from 157 tissue samples surgically removed from 100 laryngeal cancer patients. A highly sensitive real-time polymerase chain reaction methodology based on SYBR Green I fluorescent dye was developed for the quantification of DDC mRNA levels. In addition, Western blot analysis was performed for the detection of DDC protein. DDC mRNA expression was revealed to be significantly downregulated in primary laryngeal cancer samples compared with their nonmalignant counterparts (P = .001). A significant negative association was also disclosed between DDC mRNA levels and TNM staging (P = .034). Univariate analysis showed that patients bearing DDC-positive tumors had a significantly decreased risk of death (hazard ratio = 0.23, P = .012) and local recurrence (hazard ratio = 0.32, P =.006), whereas DDC expression retained its favorable prognostic significance in the multivariate analysis. Kaplan-Meier curves further demonstrated that DDC-positive patients experienced longer overall and disease-free survival periods (P = .006 and P = .004, respectively). Moreover, DDC protein was detected in both neoplastic and noncancerous tissues. Therefore, our results suggest that DDC expression status could qualify as a promising biomarker for the future clinical management of laryngeal cancer patients.

l-DOPA Decarboxylase (DDC) Expression Status as a Novel Molecular Tumor Marker for Diagnostic and Prognostic Purposes in Laryngeal Cancer1

PubMed Central

Patsis, Christos; Glyka, Vasiliki; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

2012-01-01

l-DOPA decarboxylase (DDC) plays an essential role in the enzymatic synthesis of dopamine and alterations in its gene expression have been reported in several malignancies. Our objective was to analyze DDC messenger RNA (mRNA) and protein expression in laryngeal tissues and to evaluate the clinical implication of this molecule in laryngeal cancer. In this study, total RNA was isolated from 157 tissue samples surgically removed from 100 laryngeal cancer patients. A highly sensitive real-time polymerase chain reaction methodology based on SYBR Green I fluorescent dye was developed for the quantification of DDC mRNA levels. In addition, Western blot analysis was performed for the detection of DDC protein. DDC mRNA expression was revealed to be significantly downregulated in primary laryngeal cancer samples compared with their nonmalignant counterparts (P = .001). A significant negative association was also disclosed between DDC mRNA levels and TNM staging (P = .034). Univariate analysis showed that patients bearing DDC-positive tumors had a significantly decreased risk of death (hazard ratio = 0.23, P = .012) and local recurrence (hazard ratio = 0.32, P =.006), whereas DDC expression retained its favorable prognostic significance in the multivariate analysis. Kaplan-Meier curves further demonstrated that DDC-positive patients experienced longer overall and disease-free survival periods (P = .006 and P = .004, respectively). Moreover, DDC protein was detected in both neoplastic and noncancerous tissues. Therefore, our results suggest that DDC expression status could qualify as a promising biomarker for the future clinical management of laryngeal cancer patients. PMID:22937181

Neurochemical abnormalities in premanifest and early spinocerebellar ataxias.

PubMed

Joers, James M; Deelchand, Dinesh K; Lyu, Tianmeng; Emir, Uzay E; Hutter, Diane; Gomez, Christopher M; Bushara, Khalaf O; Eberly, Lynn E; Öz, Gülin

2018-04-01

To investigate whether early neurochemical abnormalities are detectable by high-field magnetic resonance spectroscopy (MRS) in individuals with spinocerebellar ataxias (SCAs) 1, 2, 3, and 6, including patients without manifestation of ataxia. A cohort of 100 subjects (N = 18-21 in each SCA group, including premanifest mutation carriers; mean score on the Scale for the Assessment and Rating of Ataxia [SARA] <10 for all genotypes, and 22 matched controls) was scanned at 7 Tesla to obtain neurochemical profiles of the cerebellum and brainstem. A novel multivariate approach (distance-weighted discrimination) was used to combine regional profiles into an "MRS score." MRS scores robustly distinguished individuals with SCA from controls, with misclassification rates of 0% (SCA2), 2% (SCA3), 5% (SCA1), and 17% (SCA6). Premanifest mutation carriers with estimated disease onset within 10 years had MRS scores in the range of early-manifest SCA subjects. Levels of neuronal and glial markers significantly correlated with SARA and an Activities of Daily Living score in subjects with SCA. Regional neurochemical alterations were different between SCAs at comparable disease severity, with SCA2 displaying the most extensive neurochemical abnormalities, followed by SCA1, SCA3, and SCA6. Neurochemical abnormalities are detectable in individuals before manifest disease, which may allow premanifest enrollment in future SCA trials. Correlations with ataxia and quality-of-life scores show that neurochemical levels can serve as clinically meaningful endpoints in trials. Ranking of SCA types by degree of neurochemical abnormalities indicates that the neurochemistry may reflect synaptic function or density. Ann Neurol 2018;83:816-829. © 2018 American Neurological Association.

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

PubMed

Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study.

PubMed

Conway, Kathleen; Edmiston, Sharon N; Parrish, Eloise; Bryant, Christopher; Tse, Chiu-Kit; Swift-Scanlan, Theresa; McCullough, Lauren E; Kuan, Pei Fen

2017-06-01

Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation contributes to breast cancer development and may provide a mechanistic link between smoking and gene expression changes leading to cancer development or progression. Using a cancer-focused array, we examined methylation at 933 CpGs in 517 invasive breast tumors in the Carolina Breast Cancer Study to determine whether methylation patterns differ by exposure to tobacco smoke. Multivariable generalized linear regression models were used to compare tumor methylation profiles between smokers and never smokers, overall, or stratified on hormone receptor (HR) status. Modest differences in CpG methylation were detected at p < 0.05 in breast tumors from current or ever smokers compared with never smokers. In stratified analyses, HR- tumors from smokers exhibited primarily hypomethylation compared with tumors from never smokers; hypomethylation was similarly detected within the more homogeneous basal-like subtype. Most current smoking-associated CpG loci exhibited methylation levels in former smokers that were intermediate between those in current and never smokers and exhibited progressive changes in methylation with increasing duration of smoking. Among former smokers, restoration of methylation toward baseline (never smoking) levels was observed with increasing time since quitting. Moreover, smoking-related hypermethylation was stronger in HR+ breast tumors from blacks than in whites. Our results suggest that breast tumor methylation patterns differ with tobacco smoke exposure; however, additional studies are needed to confirm these findings.

Proteomics Analysis of Molecular Risk Factors in the Ocular Hypertensive Human Retina

PubMed Central

Yang, Xiangjun; Hondur, Gözde; Li, Ming; Cai, Jian; Klein, Jon B.; Kuehn, Markus H.; Tezel, Gülgün

2015-01-01

Purpose To better understand ocular hypertension–induced early molecular alterations that may determine the initiation of neurodegeneration in human glaucoma, this study analyzed retinal proteomic alterations in the ocular hypertensive human retina. Methods Retina samples were obtained from six human donors with ocular hypertension (without glaucomatous injury) and six age- and sex-matched normotensive controls. Retinal proteins were analyzed by two-dimensional LC-MS/MS (liquid chromatography and linear ion trap mass spectrometry) using oxygen isotope labeling for relative quantification of protein expression. Proteomics data were validated by Western blot and immunohistochemical analyses of selected proteins. Results Out of over 2000 retinal proteins quantified, hundreds exhibited over 2-fold increased or decreased expression in ocular hypertensive samples relative to normotensive controls. Bioinformatics linked the proteomics datasets to various pathways important for maintenance of cellular homeostasis in the ocular hypertensive retina. Upregulated proteins included various heat shock proteins, ubiquitin proteasome pathway components, antioxidants, and DNA repair enzymes, while many proteins involved in mitochondrial oxidative phosphorylation exhibited downregulation in the ocular hypertensive retina. Despite the altered protein expression reflecting intrinsic adaptive/protective responses against mitochondrial energy failure, oxidative stress, and unfolded proteins, no alterations suggestive of an ongoing cell death process or neuroinflammation were detectable. Conclusions This study provides information about ocular hypertension–related molecular risk factors for glaucoma development. Molecular alterations detected in the ocular hypertensive human retina as opposed to previously detected alterations in human donor retinas with clinically manifest glaucoma suggest that proteome alterations determine the individual threshold to tolerate the ocular hypertension–induced tissue stress or convert to glaucomatous neurodegeneration when intrinsic adaptive/protective responses are overwhelmed. PMID:26348630

Satellite detection of vegetative damage and alteration caused by pollutants emitted by a zinc smelter

NASA Technical Reports Server (NTRS)

Mcmurtry, G. J.; Petersen, G. W. (Principal Investigator); Fritz, E. L.; Pennypacker, S. P.

1974-01-01

The author has identified the following significant results. Field observations and data collected by low flying aircraft were used to verify the accuracy of maps produced from the satellite data. Although areas of vegetation as small as six acres can accurately be detected, a white pine stand that was severely damaged by sulfur dioxide could not be differentiated from a healthy white pine stand because spectral differences were not large enough. When winter data were used to eliminate interference from herbaceous and deciduous vegetation, the damage was still undetectable. The analysis was able to produce a character map that accurately delineated areas of vegetative alteration due to high zinc levels accumulating in the soil. The map depicted a distinct gradient of less damage and alteration as the distance from the smelter increased. Although the satellite data will probably not be useful for detecting small acreages of damaged vegetation, it is concluded that the data may be very useful as an inventory tool to detect and delineate large vegetative areas possessing differing spectral signatures.

Multichannel perimetric alterations in systemic lupus erythematosus treated with hydroxychloroquine.

PubMed

Piñero, David P; Monllor, Begoña; Camps, Vicente J; de Fez, Dolores

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. We report the first case of SLE in which visual alterations were evaluated with multichannel perimetry. Some achromatic and color vision alterations may be present in SLE, especially when treated with hydroxychloroquine. The sensitivity losses detected in the chromatic channels in the central zone of the visual field were consistent with the results of the FM 100 Hue color test. Likewise, the multichannel perimetry detected sensitivity losses in the parafoveal area for both chromatic channels, especially for the blue-yellow. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Texture analysis of pulmonary parenchymateous changes related to pulmonary thromboembolism in dogs - a novel approach using quantitative methods.

PubMed

Marschner, C B; Kokla, M; Amigo, J M; Rozanski, E A; Wiinberg, B; McEvoy, F J

2017-07-11

Diagnosis of pulmonary thromboembolism (PTE) in dogs relies on computed tomography pulmonary angiography (CTPA), but detailed interpretation of CTPA images is demanding for the radiologist and only large vessels may be evaluated. New approaches for better detection of smaller thrombi include dual energy computed tomography (DECT) as well as computer assisted diagnosis (CAD) techniques. The purpose of this study was to investigate the performance of quantitative texture analysis for detecting dogs with PTE using grey-level co-occurrence matrices (GLCM) and multivariate statistical classification analyses. CT images from healthy (n = 6) and diseased (n = 29) dogs with and without PTE confirmed on CTPA were segmented so that only tissue with CT numbers between -1024 and -250 Houndsfield Units (HU) was preserved. GLCM analysis and subsequent multivariate classification analyses were performed on texture parameters extracted from these images. Leave-one-dog-out cross validation and receiver operator characteristic (ROC) showed that the models generated from the texture analysis were able to predict healthy dogs with optimal levels of performance. Partial Least Square Discriminant Analysis (PLS-DA) obtained a sensitivity of 94% and a specificity of 96%, while Support Vector Machines (SVM) yielded a sensitivity of 99% and a specificity of 100%. The models, however, performed worse in classifying the type of disease in the diseased dog group: In diseased dogs with PTE sensitivities were 30% (PLS-DA) and 38% (SVM), and specificities were 80% (PLS-DA) and 89% (SVM). In diseased dogs without PTE the sensitivities of the models were 59% (PLS-DA) and 79% (SVM) and specificities were 79% (PLS-DA) and 82% (SVM). The results indicate that texture analysis of CTPA images using GLCM is an effective tool for distinguishing healthy from abnormal lung. Furthermore the texture of pulmonary parenchyma in dogs with PTE is altered, when compared to the texture of pulmonary parenchyma of healthy dogs. The models' poorer performance in classifying dogs within the diseased group, may be related to the low number of dogs compared to texture variables, a lack of balanced number of dogs within each group or a real lack of difference in the texture features among the diseased dogs.

Improving the detection of evoked responses to periodic stimulation by using bivariate local spectral F-test - Application to EEG during photic stimulation.

PubMed

Felix, Leonardo Bonato; Rocha, Paulo Fábio; Mendes, Eduardo Mazoni Andrade Marçal; Miranda de Sá, Antonio Mauricio Ferreira Leite

2017-10-01

The spectral local F-test has been applied for detecting evoked responses to rhythmic stimulation that are embedded in the ongoing electroencephalogram (EEG). Based on the sampling distribution of a flat spectrum at the neighbourhood of the stimulation frequency, spectral peaks in an EEG signal that are due to the stimulation may be readily assessed. Nevertheless, the performance of the technique is strongly affected by both the signal-to-noise ratio (SNR) of the responses and the number of data segments used in the estimation. The present work aims at both deriving and evaluating a multivariate extension of local F-test by including the EEG collected at a second distinct derivation. The detection rate with this multivariate detector was found to be greater than that using a single channel in case of equal SNR in both signals. Monte Carlo simulation results showed that the probability of detection with this new detector saturates for signal-to-noise ratios above 12 dB and indicated a greater detection rate in practical situations, even when smaller SNR-values are found in the added signal (e.g. 5 dB for 16 neighbouring frequencies used in the estimation). The technique was next applied to the EEG from 12 subjects during intermittent, photic stimulation leading to superior performance in comparison with the univariate local F-test. Since a higher detection rate with the proposed technique is achieved without the need of increasing the number of data segments, it allows evoked responses to be detected faster, once the same detection rate may be accomplished with less segments. This might be useful in clinical practice. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Application of advanced control techniques to aircraft propulsion systems

NASA Technical Reports Server (NTRS)

Lehtinen, B.

1984-01-01

Two programs are described which involve the application of advanced control techniques to the design of engine control algorithms. Multivariable control theory is used in the F100 MVCS (multivariable control synthesis) program to design controls which coordinate the control inputs for improved engine performance. A systematic method for handling a complex control design task is given. Methods of analytical redundancy are aimed at increasing the control system reliability. The F100 DIA (detection, isolation, and accommodation) program, which investigates the uses of software to replace or augment hardware redundancy for certain critical engine sensor, is described.

Detection of fibrin generation alterations in dogs with haemangiosarcoma using resonance thrombography.

PubMed

Mischke, R; Wohlsein, P; Schoon, H-A

2005-01-01

The objective of the study was to examine the alterations of fibrin generation in dogs with haemangiosarcoma using resonance thrombography. The second objective was to evaluate the sensitivity of this method for the detection of hypofibrinogenaemia and/or increased fibrin(ogen) degradation product (FDP) concentration. Resonance thrombogram (RTG) measurements with two different instruments were performed in 30 unselected dogs with haemangiosarcoma, 14 of which had decreased fibrinogen and 28 of which had an increased FDP concentration (p<0.0001). The RTG-reaction time was less sensitive than the fibrin formation time (RTG-f) and fibrin amplitude (RTG-F). The RTG-f and RTG-F indicated reliably a decrease in fibrinogen concentration (sensitivity: 0.93). The sensitivity of detection of increased FDP levels was considerably higher than that of thrombin time. However, false-negative results were found even at FDP concentrations > or =120 mg/l, especially in cases with high fibrinogen level. Both machines showed similar sensitivity. The results of this study indicate that canine haemangiosarcoma is frequently associated with severe alterations of fibrin generation due to low fibrinogen and high FDP levels leading to distinct RTG abnormalities. The global test RTG reacts sensitively to a decreased fibrinogen level whereas its accuracy to detect FDP concentrations occurring under pathophysiological conditions is limited. A significant alteration of fibrin generation induced by FDPs may not occur until the serum FDP concentration exceeds 60 mg/l.

Applying the multivariate time-rescaling theorem to neural population models

PubMed Central

Gerhard, Felipe; Haslinger, Robert; Pipa, Gordon

2011-01-01

Statistical models of neural activity are integral to modern neuroscience. Recently, interest has grown in modeling the spiking activity of populations of simultaneously recorded neurons to study the effects of correlations and functional connectivity on neural information processing. However any statistical model must be validated by an appropriate goodness-of-fit test. Kolmogorov-Smirnov tests based upon the time-rescaling theorem have proven to be useful for evaluating point-process-based statistical models of single-neuron spike trains. Here we discuss the extension of the time-rescaling theorem to the multivariate (neural population) case. We show that even in the presence of strong correlations between spike trains, models which neglect couplings between neurons can be erroneously passed by the univariate time-rescaling test. We present the multivariate version of the time-rescaling theorem, and provide a practical step-by-step procedure for applying it towards testing the sufficiency of neural population models. Using several simple analytically tractable models and also more complex simulated and real data sets, we demonstrate that important features of the population activity can only be detected using the multivariate extension of the test. PMID:21395436

Use of Multivariate Linkage Analysis for Dissection of a Complex Cognitive Trait

PubMed Central

Marlow, Angela J.; Fisher, Simon E.; Francks, Clyde; MacPhie, I. Laurence; Cherny, Stacey S.; Richardson, Alex J.; Talcott, Joel B.; Stein, John F.; Monaco, Anthony P.; Cardon, Lon R.

2003-01-01

Replication of linkage results for complex traits has been exceedingly difficult, owing in part to the inability to measure the precise underlying phenotype, small sample sizes, genetic heterogeneity, and statistical methods employed in analysis. Often, in any particular study, multiple correlated traits have been collected, yet these have been analyzed independently or, at most, in bivariate analyses. Theoretical arguments suggest that full multivariate analysis of all available traits should offer more power to detect linkage; however, this has not yet been evaluated on a genomewide scale. Here, we conduct multivariate genomewide analyses of quantitative-trait loci that influence reading- and language-related measures in families affected with developmental dyslexia. The results of these analyses are substantially clearer than those of previous univariate analyses of the same data set, helping to resolve a number of key issues. These outcomes highlight the relevance of multivariate analysis for complex disorders for dissection of linkage results in correlated traits. The approach employed here may aid positional cloning of susceptibility genes in a wide spectrum of complex traits. PMID:12587094

Identification of Reliable Components in Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS): a Data-Driven Approach across Metabolic Processes.

PubMed

Motegi, Hiromi; Tsuboi, Yuuri; Saga, Ayako; Kagami, Tomoko; Inoue, Maki; Toki, Hideaki; Minowa, Osamu; Noda, Tetsuo; Kikuchi, Jun

2015-11-04

There is an increasing need to use multivariate statistical methods for understanding biological functions, identifying the mechanisms of diseases, and exploring biomarkers. In addition to classical analyses such as hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis, various multivariate strategies, including independent component analysis, non-negative matrix factorization, and multivariate curve resolution, have recently been proposed. However, determining the number of components is problematic. Despite the proposal of several different methods, no satisfactory approach has yet been reported. To resolve this problem, we implemented a new idea: classifying a component as "reliable" or "unreliable" based on the reproducibility of its appearance, regardless of the number of components in the calculation. Using the clustering method for classification, we applied this idea to multivariate curve resolution-alternating least squares (MCR-ALS). Comparisons between conventional and modified methods applied to proton nuclear magnetic resonance ((1)H-NMR) spectral datasets derived from known standard mixtures and biological mixtures (urine and feces of mice) revealed that more plausible results are obtained by the modified method. In particular, clusters containing little information were detected with reliability. This strategy, named "cluster-aided MCR-ALS," will facilitate the attainment of more reliable results in the metabolomics datasets.

Simple Sugars to Complex Disease—Mucin-Type O-Glycans in Cancer

PubMed Central

Kudelka, Matthew R.; Ju, Tongzhong; Heimburg-Molinaro, Jamie; Cummings, Richard D.

2017-01-01

Mucin-type O-glycans are a class of glycans initiated with N-acetylgalactosamine (GalNAc) α-linked primarily to Ser/Thr residues within glycoproteins and often extended or branched by sugars or saccharides. Most secretory and membrane-bound proteins receive this modification, which is important in regulating many biological processes. Alterations in mucin-type O-glycans have been described across tumor types and include expression of relatively small-sized, truncated O-glycans and altered terminal structures, both of which are associated with patient prognosis. New discoveries in the identity and expression of tumor-associated O-glycans are providing new avenues for tumor detection and treatment. This chapter describes mucin-type O-glycan biosynthesis, altered mucin-type O-glycans in primary tumors, including mechanisms for structural changes and contributions to the tumor phenotype, and clinical approaches to detect and target altered O-glycans for cancer treatment and management. PMID:25727146

Alterations in ATR in nasal NK/T-cell lymphoma and chronic active Epstein-Barr virus infection.

PubMed

Liu, Angen; Takakuwa, Tetsuya; Luo, Wen-Juan; Fujita, Shigeki; Aozasa, Katsuyuki

2006-07-01

Nasal natural killer (NK)/T-cell lymphoma (NKTCL) and chronic active Epstein-Barr virus infection (CAEBV) are relatively frequent, especially in Asia, and are poor in prognosis. Both diseases are proliferative diseases of NK/T cells that show highly complicated karyotypes, suggesting the involvement of chromosomal instability. ATR is an important gene for DNA damage response and chromosomal stability. To evaluate the role of ATR gene alterations in the pathogenesis of NKTCL and CAEBV, the whole coding region of the ATR gene was examined in cell lines derived from NKTCL and CAEBV, as well as tumor samples from patients. ATR alterations were detected in two of eight NKTCL and in one of three CAEBV lines. Most aberrant transcripts observed were deletions resulting from aberrant splicing. ATR alterations were also detected in four of 10 NKTCL clinical samples. Both NKTCL and CAEBV cell lines with ATR alterations showed a delay or abrogation in repair of ionizing radiation-induced DNA double-strand breaks and ultraviolet-induced DNA single-strand breaks, and both exhibited a defect in p53 accumulation. These findings show that alterations in the ATR gene result in an abnormal response to DNA double-strand break and single-strand break repair, suggesting a role for ATR gene alterations in NKTCL lymphomagenesis.

28 CFR 36.407 - Temporary suspension of certain detectable warning requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... detectable warning requirements. 36.407 Section 36.407 Judicial Administration DEPARTMENT OF JUSTICE... and Alterations § 36.407 Temporary suspension of certain detectable warning requirements. The detectable warning requirements contained in sections 4.7.7, 4.29.5, and 4.29.6 of appendix A to this part...

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

Anderson, Marshall

Lung cancer is one of the leading causes of death in the United States and in Western Europe. The incidence of lung cancer in developing countries is rising as their cigarette smoking habits increase. The objectives of this proposed research are to analyze genetic alterations associated with the development and progression on non-small cell lung carcinoma (MSCLC). Endpoints that may be realized from this proposed research are: (1) detection of early genetic and/or cellular alterations which ultimately could lead to diagnostic modalities for the early detection of lung cancer; and (2) detection of novel tumor suppressor genes on chromosome 9p.more » This proposal will analyze both tumor specimens and sputum samples.« less

MULTIVARIATE RECEPTOR MODELING BY N-DIMENSIONAL EDGE DETECTION. (R826238)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Rapid detection of bacterial pathogens using flourescence spectroscopy and chemometrics

USDA-ARS?s Scientific Manuscript database

This work presents the development of a method for rapid bacterial identification based on the fluorescence spectroscopy combined with multivariate analysis. Fluorescence spectra of pure three different genera of bacteria (Escherichia coli, Salmonella, and Campylobacter) were collected from 200...

Characterization of System Status Signals for Multivariate Time Series Discretization Based on Frequency and Amplitude Variation

PubMed Central

2018-01-01

Many fault detection methods have been proposed for monitoring the health of various industrial systems. Characterizing the monitored signals is a prerequisite for selecting an appropriate detection method. However, fault detection methods tend to be decided with user’s subjective knowledge or their familiarity with the method, rather than following a predefined selection rule. This study investigates the performance sensitivity of two detection methods, with respect to status signal characteristics of given systems: abrupt variance, characteristic indicator, discernable frequency, and discernable index. Relation between key characteristics indicators from four different real-world systems and the performance of two fault detection methods using pattern recognition are evaluated. PMID:29316731

Review: Behavioral signs of estrus and the potential of fully automated systems for detection of estrus in dairy cattle.

PubMed

Reith, S; Hoy, S

2018-02-01

Efficient detection of estrus is a permanent challenge for successful reproductive performance in dairy cattle. In this context, comprehensive knowledge of estrus-related behaviors is fundamental to achieve optimal estrus detection rates. This review was designed to identify the characteristics of behavioral estrus as a necessary basis for developing strategies and technologies to improve the reproductive management on dairy farms. The focus is on secondary symptoms of estrus (mounting, activity, aggressive and agonistic behaviors) which seem more indicative than standing behavior. The consequences of management, housing conditions and cow- and environmental-related factors impacting expression and detection of estrus as well as their relative importance are described in order to increase efficiency and accuracy of estrus detection. As traditional estrus detection via visual observation is time-consuming and ineffective, there has been a considerable advancement of detection aids during the last 10 years. By now, a number of fully automated technologies including pressure sensing systems, activity meters, video cameras, recordings of vocalization as well as measurements of body temperature and milk progesterone concentration are available. These systems differ in many aspects regarding sustainability and efficiency as keys to their adoption for farm use. As being most practical for estrus detection a high priority - according to the current research - is given to the detection based on sensor-supported activity monitoring, especially accelerometer systems. Due to differences in individual intensity and duration of estrus multivariate analysis can support herd managers in determining the onset of estrus. Actually, there is increasing interest in investigating the potential of combining data of activity monitoring and information of several other methods, which may lead to the best results concerning sensitivity and specificity of detection. Future improvements will likely require more multivariate detection by data and systems already existing on farms.

Prevalence of c.2268dup and detection of two novel alterations, c.670_672del and c.1186C>T, in the TPO gene in a cohort of Malaysian–Chinese with thyroid dyshormonogenesis

PubMed Central

Lee, Ching Chin; Harun, Fatimah; Jalaludin, Muhammad Yazid; Heh, Choon Han; Othman, Rozana; Junit, Sarni Mat

2015-01-01

Objectives The c.2268dup mutation in the thyroid peroxidase (TPO) gene is the most common TPO alteration reported in Taiwanese patients with thyroid dyshormonogenesis. The ancestors of these patients are believed to originate from the southern province of China. Our previous study showed that this mutation leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in a Malaysian–Chinese family with goitrous hypothyroidism. The aim of our study was to provide further data on the incidence of the c.2268dup mutation in a cohort of Malaysian–Chinese and its possible phenotypic effects. Setting Cohort study. Participants Twelve biologically unrelated Malaysian–Chinese patients with congenital hypothyroidism were recruited in this study. All patients showed high thyrotropin and low free thyroxine levels at the time of diagnosis with proven presence of a thyroid gland. Primary outcome measure Screening of the c.2268dup mutation in the TPO gene in all patients was carried out using a PCR–direct DNA sequencing method. Secondary outcome measure Further screening for mutations in other exonic regions of the TPO gene was carried out if the patient was a carrier of the c.2268dup mutation. Results The c.2268dup mutation was detected in 4 of the 12 patients. Apart from the c.2268dup and a previously documented mutation (c.2647C>T), two novel TPO alterations, c.670_672del and c.1186C>T, were also detected in our patients. In silico analyses predicted that the novel alterations affect the structure/function of the TPO protein. Conclusions The c.2268dup mutation was detected in approximately one-third of the Malaysian–Chinese patients with thyroid dyshormonogenesis. The detection of the novel c.670_672del and c.1186C>T alterations expand the mutation spectrum of TPO associated with thyroid dyshormonogenesis. PMID:25564141

Correlation of thermocouple data with voiding function after prostate cryoablation.

PubMed

Levy, David A

2010-02-01

To identify possible correlations of thermocouple recorded data with altered postoperative voiding function after prostate cryosurgery. A retrospective analysis of the records of 58 patients treated with prostate cryoablation from October 2005 through April 2009 was conducted. Multivariate analysis of patient age, presenting prostate-specific antigen level, Gleason score, clinical T stage, prostate volume, maximum low temperature thermocouple recordings, history of radiation and or hormonal therapy, were studied as possible correlative factors for altered postoperative voiding function. Of 58 patients, 22 (37.9%) manifested postcryoablation urgency and frequency (n = 13) requiring medical therapy or retention (n = 9). On multivariate analysis, age (P = .037) and an external sphincter temperature < or = 23 degrees C (P = .012) were associated with voiding frequency, urgency, or retention (odds ratio = 6.26, 95% CI: 1.62-24.16), whereas anterior rectal wall temperature (Denon) was weakly associated (P = .079). Thermocouple data provide an objective means of assessing cryosurgical outcomes. This is the first report of a correlation of such data to post-treatment voiding function. A total of 37.9% of patients experienced urgency and/or frequency or urinary retention after cryoablation of the prostate for localized disease. Older age and external sphincter temperature < or = 23 degrees C were statistically significant predictors of these events. The data suggest that limiting the degree of freezing at the external sphincter may decrease procedure related morbidity. Further study is warranted to better delineate temperature-related data on treatment outcomes. 2010 Elsevier Inc. All rights reserved.

The association of longitudinal trend of fasting plasma glucose with retinal microvasculature in people without established diabetes.

PubMed

Hu, Yin; Niu, Yong; Wang, Dandan; Wang, Ying; Holden, Brien A; He, Mingguang

2015-01-22

Structural changes of retinal vasculature, such as altered retinal vascular calibers, are considered as early signs of systemic vascular damage. We examined the associations of 5-year mean level, longitudinal trend, and fluctuation in fasting plasma glucose (FPG) with retinal vascular caliber in people without established diabetes. A prospective study was conducted in a cohort of Chinese people age ≥40 years in Guangzhou, southern China. The FPG was measured at baseline in 2008 and annually until 2012. In 2012, retinal vascular caliber was assessed using standard fundus photographs and validated software. A total of 3645 baseline nondiabetic participants with baseline and follow-up data on FPG for 3 or more visits was included for statistical analysis. The associations of retinal vascular caliber with 5-year mean FPG level, longitudinal FPG trend (slope of linear regression-FPG), and fluctuation (standard deviation and root mean square error of FPG) were analyzed using multivariable linear regression analyses. Multivariate regression models adjusted for baseline FPG and other potential confounders showed that a 10% annual increase in FPG was associated independently with a 2.65-μm narrowing in retinal arterioles (P = 0.008) and a 3.47-μm widening in venules (P = 0. 0.004). Associations with mean FPG level and fluctuation were not statistically significant. Annual rising trend in FPG, but not its mean level or fluctuation, is associated with altered retinal vasculature in nondiabetic people. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

The Relationship between Oxygen Saturation and Color Alteration of a Compromised Skin Flap: Experimental Study on the Rabbit.

PubMed

Prasetyono, Theddeus O H; Adianto, Senja

2013-09-01

The aim of this study was to collect important data on the time of oxygen saturation change in relation to skin flap color alteration using non-invasive pulse oximetry to evaluate its ability to provide continuous monitoring of skin flap perfusion. An experimental study on the monitoring of blood perfusion of 20 tube-island groin flaps of 10 male New Zealand rabbits was performed using pulse oximetry. The animals were randomly assigned to one of two groups representing a blockage of either arterial or venous blood flow. The oxygen saturation change and clinical color alteration were monitored from the beginning of vessel clamping until the saturation became undetectable. The result was analyzed by the t-test using SSPS ver. 10.0. The mean times from the vessel clamping until the saturation became undetectable were 20.19±2.13 seconds and 74.91±10.57 seconds for the artery and vein clamping groups, respectively. The mean time of the clinical alteration from the beginning of vein clamping was 34.5±11.72 minutes, while the alteration in flaps with artery clamping could not be detected until 2.5 hours after clamping. The use of neonate-type reusable flex sensor-pulse oximetry is objective and effective in early detection of arterial and vein blockage. It provides real-time data on vessel occlusion, which in turn will allow for early salvaging. The detection periods of both arterial occlusion and venous congestion are much earlier than the color alteration one may encounter clinically.

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.

Selected sperm traits are simultaneously altered after scrotal heat stress and play specific roles in in vitro fertilization and embryonic development.

PubMed

Lucio, Aline C; Alves, Benner G; Alves, Kele A; Martins, Muller C; Braga, Lucas S; Miglio, Luisa; Alves, Bruna G; Silva, Thiago H; Jacomini, José O; Beletti, Marcelo E

2016-09-01

Improvements in the estimation of male fertility indicators require advances in laboratory tests for sperm assessment. The aims of the present work were (1) to apply a multivariate analysis to examine sperm set of alterations and interactions and (2) to evaluate the importance of sperm parameters on the outcome of standard IVF and embryonic development. Bulls (n = 3) were subjected to scrotal insulation, and ejaculates were collected before (preinsulation = Day 0) and through 56 days (Days 7, 14, 21, 28, 35, 42, 49, and 56) of the experimental period. Sperm head morphometry and chromatin variables were assessed by a computational image analysis, and IVF was performed. Scrotal heat stress induced alterations in all evaluated sperm head features, as well as cleavage and blastocyst rates. A principal component analysis revealed three main components (factors) that represented almost 89% of the cumulative variance. In addition, an association of factor scores with cleavage (factor 1) and blastocyst (factor 3) rates was observed. In conclusion, several sperm traits were simultaneously altered as a result of a thermal insult. These sperm traits likely play specific roles in IVF and embryonic development. Copyright © 2016 Elsevier Inc. All rights reserved.

The relationship of quantitative nuclear morphology to molecular genetic alterations in the adenoma-carcinoma sequence of the large bowel.

PubMed Central

Mulder, J. W.; Offerhaus, G. J.; de Feyter, E. P.; Floyd, J. J.; Kern, S. E.; Vogelstein, B.; Hamilton, S. R.

1992-01-01

The relationship of abnormal nuclear morphology to molecular genetic alterations that are important in colorectal tumorigenesis is unknown. Therefore, Feulgen-stained isolated nuclei from 22 adenomas and 42 carcinomas that had been analyzed for ras gene mutations and allelic deletions on chromosomes 5q, 18q, and 17p were characterized by computerized image analysis. Both nuclear area and the nuclear shape factor representing irregularity correlated with adenoma-carcinoma progression (r = 0.57 and r = 0.52, P < 0.0001), whereas standard nuclear texture, a parameter of chromatin homogeneity, was inversely correlated with progression (r = -0.80, P < 0.0001). The nuclear parameters were strongly interrelated (P < 0.0005). In multivariate analysis, the nuclear parameters were predominantly associated with adenoma-carcinoma progression (P < or = 0.0001) and were not influenced significantly by the individual molecular genetic alterations. Nuclear texture, however, was inversely correlated with fractional allelic loss, a global measure of genetic changes, in carcinomas (r = -0.39, P = 0.011). The findings indicate that nuclear morphology in colorectal neoplasms is strongly related to tumor progression. Nuclear morphology and biologic behavior appear to be influenced by accumulated alterations in cancer-associated genes. Images Figure 1 PMID:1357973

Integrated Multivariate Health Monitoring System for Helicopters Main Rotor Drives: Development and Validation with In-Service Data

DTIC Science & Technology

2014-10-02

potential advantages of using multi- variate classification/discrimination/ anomaly detection meth- ods on real world accelerometric condition monitoring ...case of false anomaly reports. A possible explanation of this phenomenon could be given 8 ANNUAL CONFERENCE OF THE PROGNOSTICS AND HEALTH MANAGEMENT...of those helicopters. 1. Anomaly detection by means of a self-learning Shewhart control chart. A problem highlighted by the experts of Agusta- Westland

Diffuse-light absorption spectroscopy by fiber optics for detecting and quantifying the adulteration of extra virgin olive oil

NASA Astrophysics Data System (ADS)

Mignani, A. G.; Ciaccheri, L.; Ottevaere, H.; Thienpont, H.; Conte, L.; Marega, M.; Cichelli, A.; Attilio, C.; Cimato, A.

2010-09-01

A fiber optic setup for diffuse-light absorption spectroscopy in the wide 400-1700 nm spectral range is experimented for detecting and quantifying the adulteration of extra virgin olive oil caused by lower-grade olive oils. Absorption measurements provide spectral fingerprints of authentic and adulterated oils. A multivariate processing of spectroscopic data is applied for discriminating the type of adulterant and for predicting its fraction.

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

PubMed

Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

2017-01-01

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A global × global test for testing associations between two large sets of variables.

PubMed

Chaturvedi, Nimisha; de Menezes, Renée X; Goeman, Jelle J

2017-01-01

In high-dimensional omics studies where multiple molecular profiles are obtained for each set of patients, there is often interest in identifying complex multivariate associations, for example, copy number regulated expression levels in a certain pathway or in a genomic region. To detect such associations, we present a novel approach to test for association between two sets of variables. Our approach generalizes the global test, which tests for association between a group of covariates and a single univariate response, to allow high-dimensional multivariate response. We apply the method to several simulated datasets as well as two publicly available datasets, where we compare the performance of multivariate global test (G2) with univariate global test. The method is implemented in R and will be available as a part of the globaltest package in R. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organic metal neutron detector

DOEpatents

Butler, M.A.; Ginley, D.S.

1984-11-21

A device for detection of neutrons comprises: as an active neutron sensing element, a conductive organic polymer having an electrical conductivity and a cross-section for said neutrons whereby a detectable change in said conductivity is caused by impingement of said neutrons on the conductive organic polymer which is responsive to a property of said polymer which is altered by impingement of said neutrons on the polymer; and means for associating a change in said alterable property with the presence of neutrons at the location of said device.

Application of two tests of multivariate discordancy to fisheries data sets

USGS Publications Warehouse

Stapanian, M.A.; Kocovsky, P.M.; Garner, F.C.

2008-01-01

The generalized (Mahalanobis) distance and multivariate kurtosis are two powerful tests of multivariate discordancies (outliers). Unlike the generalized distance test, the multivariate kurtosis test has not been applied as a test of discordancy to fisheries data heretofore. We applied both tests, along with published algorithms for identifying suspected causal variable(s) of discordant observations, to two fisheries data sets from Lake Erie: total length, mass, and age from 1,234 burbot, Lota lota; and 22 combinations of unique subsets of 10 morphometrics taken from 119 yellow perch, Perca flavescens. For the burbot data set, the generalized distance test identified six discordant observations and the multivariate kurtosis test identified 24 discordant observations. In contrast with the multivariate tests, the univariate generalized distance test identified no discordancies when applied separately to each variable. Removing discordancies had a substantial effect on length-versus-mass regression equations. For 500-mm burbot, the percent difference in estimated mass after removing discordancies in our study was greater than the percent difference in masses estimated for burbot of the same length in lakes that differed substantially in productivity. The number of discordant yellow perch detected ranged from 0 to 2 with the multivariate generalized distance test and from 6 to 11 with the multivariate kurtosis test. With the kurtosis test, 108 yellow perch (90.7%) were identified as discordant in zero to two combinations, and five (4.2%) were identified as discordant in either all or 21 of the 22 combinations. The relationship among the variables included in each combination determined which variables were identified as causal. The generalized distance test identified between zero and six discordancies when applied separately to each variable. Removing the discordancies found in at least one-half of the combinations (k=5) had a marked effect on a principal components analysis. In particular, the percent of the total variation explained by second and third principal components, which explain shape, increased by 52 and 44% respectively when the discordancies were removed. Multivariate applications of the tests have numerous ecological advantages over univariate applications, including improved management of fish stocks and interpretation of multivariate morphometric data. ?? 2007 Springer Science+Business Media B.V.

Prenatal Sonographic Predictors of Neonatal Coarctation of the Aorta.

PubMed

Anuwutnavin, Sanitra; Satou, Gary; Chang, Ruey-Kang; DeVore, Greggory R; Abuel, Ashley; Sklansky, Mark

2016-11-01

To identify practical prenatal sonographic markers for the postnatal diagnosis of coarctation of the aorta. We reviewed the fetal echocardiograms and postnatal outcomes of fetal cases of suspected coarctation of the aorta seen at a single institution between 2010 and 2014. True- and false-positive cases were compared. Logistic regression analysis was used to determine echocardiographic predictors of coarctation of the aorta. Optimal cutoffs for these markers and a multivariable threshold scoring system were derived to discriminate fetuses with coarctation of the aorta from those without coarctation of the aorta. Among 35 patients with prenatal suspicion of coarctation of the aorta, the diagnosis was confirmed postnatally in 9 neonates (25.7% true-positive rate). Significant predictors identified from multivariate analysis were as follows: Z score for the ascending aorta diameter of -2 or less (P = < .001), Z score for the mitral valve annulus of -2 or less (P= .033), Zscore for the transverse aortic arch diameter of -2 or less (P= .028), and abnormal aortic valve morphologic features (P= .026). Among all variables studied, the ascending aortic Z score had the highest sensitivity (78%) and specificity (92%) for detection of coarctation of the aorta. A multivariable threshold scoring system identified fetuses with coarctation of the aorta with still greater sensitivity (89%) and only mildly decreased specificity (88%). The finding of a diminutive ascending aorta represents a powerful and practical prenatal predictor of neonatal coarctation of the aorta. A multivariable scoring system, including dimensions of the ascending and transverse aortas, mitral valve annulus, and morphologic features of the aortic valve, provides excellent sensitivity and specificity. The use of these practical sonographic markers may improve prenatal detection of coarctation of the aorta. © 2016 by the American Institute of Ultrasound in Medicine.

Measurement bias detection with Kronecker product restricted models for multivariate longitudinal data: an illustration with health-related quality of life data from thirteen measurement occasions

PubMed Central

Verdam, Mathilde G. E.; Oort, Frans J.

2014-01-01

Highlights Application of Kronecker product to construct parsimonious structural equation models for multivariate longitudinal data. A method for the investigation of measurement bias with Kronecker product restricted models. Application of these methods to health-related quality of life data from bone metastasis patients, collected at 13 consecutive measurement occasions. The use of curves to facilitate substantive interpretation of apparent measurement bias. Assessment of change in common factor means, after accounting for apparent measurement bias. Longitudinal measurement invariance is usually investigated with a longitudinal factor model (LFM). However, with multiple measurement occasions, the number of parameters to be estimated increases with a multiple of the number of measurement occasions. To guard against too low ratios of numbers of subjects and numbers of parameters, we can use Kronecker product restrictions to model the multivariate longitudinal structure of the data. These restrictions can be imposed on all parameter matrices, including measurement invariance restrictions on factor loadings and intercepts. The resulting models are parsimonious and have attractive interpretation, but require different methods for the investigation of measurement bias. Specifically, additional parameter matrices are introduced to accommodate possible violations of measurement invariance. These additional matrices consist of measurement bias parameters that are either fixed at zero or free to be estimated. In cases of measurement bias, it is also possible to model the bias over time, e.g., with linear or non-linear curves. Measurement bias detection with Kronecker product restricted models will be illustrated with multivariate longitudinal data from 682 bone metastasis patients whose health-related quality of life (HRQL) was measured at 13 consecutive weeks. PMID:25295016

Measurement bias detection with Kronecker product restricted models for multivariate longitudinal data: an illustration with health-related quality of life data from thirteen measurement occasions.

PubMed

Verdam, Mathilde G E; Oort, Frans J

2014-01-01

Application of Kronecker product to construct parsimonious structural equation models for multivariate longitudinal data.A method for the investigation of measurement bias with Kronecker product restricted models.Application of these methods to health-related quality of life data from bone metastasis patients, collected at 13 consecutive measurement occasions.The use of curves to facilitate substantive interpretation of apparent measurement bias.Assessment of change in common factor means, after accounting for apparent measurement bias.Longitudinal measurement invariance is usually investigated with a longitudinal factor model (LFM). However, with multiple measurement occasions, the number of parameters to be estimated increases with a multiple of the number of measurement occasions. To guard against too low ratios of numbers of subjects and numbers of parameters, we can use Kronecker product restrictions to model the multivariate longitudinal structure of the data. These restrictions can be imposed on all parameter matrices, including measurement invariance restrictions on factor loadings and intercepts. The resulting models are parsimonious and have attractive interpretation, but require different methods for the investigation of measurement bias. Specifically, additional parameter matrices are introduced to accommodate possible violations of measurement invariance. These additional matrices consist of measurement bias parameters that are either fixed at zero or free to be estimated. In cases of measurement bias, it is also possible to model the bias over time, e.g., with linear or non-linear curves. Measurement bias detection with Kronecker product restricted models will be illustrated with multivariate longitudinal data from 682 bone metastasis patients whose health-related quality of life (HRQL) was measured at 13 consecutive weeks.

Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD.

PubMed

Yang, Mingxing; Kohler, Maxie; Heyder, Tina; Forsslund, Helena; Garberg, Hilde K; Karimi, Reza; Grunewald, Johan; Berven, Frode S; Magnus Sköld, C; Wheelock, Åsa M

2018-03-08

Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV 1 /FVC as well as the percentage of CD8 + T-cells and CD8 + CD69 + T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV 1 /FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. ClinicalTrials.gov identifier NCT02627872 ; Retrospectively registered on December 9, 2015.

Clinical and radiological features of invasive Klebsiella pneumoniae liver abscess syndrome.

PubMed

Shin, Sung Ui; Park, Chang Min; Lee, Youkyung; Kim, Eui-Chong; Kim, Soo Jin; Goo, Jin Mo

2013-06-01

Recently, a striking new clinical manifestation of Klebsiella pneumoniae (KP) infection referred to as invasive KP liver abscess syndrome (IKPLAS), defined by liver abscess with contemporaneous metastatic KP infections at other body sites has been documented. Until now, however, there have been relatively few reports regarding its radiologic features. To describe the clinical and radiological features of IKPLAS patients, and to compare them with those with KP liver abscess without metastatic infections to ascertain possible predictors of IKPLAS. From January 2008 to May 2010, 35 patients (26 men and 9 women; mean age, 59.4 years) with both liver abscess and metastatic KP infections were diagnosed with IKPLAS. Their clinical and radiological features were retrospectively evaluated and compared with those of 25 contemporaneous non-metastatic patients to investigate predictive factors for metastatic infections. The rate of intensive care unit admissions and overall mortality was 34.3% and 17.1% in IKPLAS patients, and was significantly higher than those of the non-metastatic group (8% and 0%, respectively). As for metastatic infections, the lung was the most common site and multiple nodules or masses (n = 9) were the most common manifestations. Univariate analysis revealed that liver abscess ≤5.8 cm, bilobar involvement of abscess and altered mentality were significantly related with IKPLAS. At multivariate analysis, liver abscess ≤5.8 cm was proven to be a significant independent predictor of IKPLAS (OR, 3.6; P = 0.038). In addition, altered mentality was present solely in IKPLAS (25.7% vs. 0%) although its P value (P = 0.052) did not reach a statistical significance at multivariate analysis. IKPLAS has significantly worse prognosis than non-metastatic KP abscess patients. In patients with KP liver abscess, liver abscess ≤5.8 cm can be used as an independent predictor of IKPLAS and altered mentality as a very specific feature in diagnosing IKPLAS. © 2013 The Foundation Acta Radiologica.

Urine Metabolomics Analysis for Biomarker Discovery and Detection of Jaundice Syndrome in Patients With Liver Disease*

PubMed Central

Wang, Xijun; Zhang, Aihua; Han, Ying; Wang, Ping; Sun, Hui; Song, Gaochen; Dong, Tianwei; Yuan, Ye; Yuan, Xiaoxia; Zhang, Miao; Xie, Ning; Zhang, He; Dong, Hui; Dong, Wei

2012-01-01

Metabolomics is a powerful new technology that allows for the assessment of global metabolic profiles in easily accessible biofluids and biomarker discovery in order to distinguish between diseased and nondiseased status information. Deciphering the molecular networks that distinguish diseases may lead to the identification of critical biomarkers for disease aggressiveness. However, current diagnostic methods cannot predict typical Jaundice syndrome (JS) in patients with liver disease and little is known about the global metabolomic alterations that characterize JS progression. Emerging metabolomics provides a powerful platform for discovering novel biomarkers and biochemical pathways to improve diagnostic, prognostication, and therapy. Therefore, the aim of this study is to find the potential biomarkers from JS disease by using a nontarget metabolomics method, and test their usefulness in human JS diagnosis. Multivariate data analysis methods were utilized to identify the potential biomarkers. Interestingly, 44 marker metabolites contributing to the complete separation of JS from matched healthy controls were identified. Metabolic pathways (Impact-value≥0.10) including alanine, aspartate, and glutamate metabolism and synthesis and degradation of ketone bodies were found to be disturbed in JS patients. This study demonstrates the possibilities of metabolomics as a diagnostic tool in diseases and provides new insight into pathophysiologic mechanisms. PMID:22505723

Upregulation of long noncoding RNA HOXA-AS3 promotes tumor progression and predicts poor prognosis in glioma

PubMed Central

Wu, Fan; Zhang, Chuanbao; Cai, Jinquan; Yang, Fan; Liang, Tingyu; Yan, Xiaoyan; Wang, Haoyuan; Wang, Wen; Chen, Jing; Jiang, Tao

2017-01-01

Long noncoding RNAs (lncRNAs) have recently emerged as new potentially promising therapeutic targets in many cancers. However, their prognostic value and biological functions associated with glioma remain to be elucidated. Here, High-throughput RNAseq was performed to detect the expression profiles of lncRNAs in 325 human glioma tissues. It was shown that a novel lncRNA HOXA-AS3 was one of the most significantly upregulated lncRNAs in glioma tissues. Quantitative PCR further verified the increased expression of HOXA-AS3 in patient samples and glioma cell lines. Uni and Multivariate Cox regression analysis revealed that HOXA-AS3 was an independent prognostic factor in glioma patients. Gene set enrichment analysis indicated that the gene sets correlated with HOXA-AS3 expression were involved in cell cycle progression and E2F targets. Functionally, HOXA-AS3 silencing resulted in proliferation arrest by altering cell cycle progression and promoting cell apoptosis, and impaired cell migration in glioma cells. Furthermore, the growth-inhibiting effect of HOXA-AS3 knockdown was also demonstrated in Xenograft mouse model. Our results highlight the important role of HOXA-AS3 in glioma progression, and indicate that HOXA-AS3 may be served as a valuable prognostic biomarker for glioma. PMID:28881797

In-shoe loading in rearfoot and non-rearfoot strikers during running using minimalist footwear.

PubMed

Kernozek, T W; Meardon, S; Vannatta, C N

2014-12-01

Recent trends promote a "barefoot" running style to reduce injury. "Minimalist" shoes are designed to mimic the barefoot running with some foot protection. However, it is unknown how "minimalist" shoes alter plantar loading. Our purpose was to compare plantar loads between rearfoot strikers and non-rearfoot strikers after 4 weeks of running in minimalist footwear. 30 females were provided Vibram(®) Bikila shoes and instructed to gradually transition to running in these shoes. Plantar loading was measured using an in-shoe pressure sensor after the 4 weeks. Multivariate analysis was performed to detect differences in loading between rearfoot and non-rearfoot strikers in different plantar regions. Differences in plantar loading occurred between foot strike patterns running in minimalist footwear. Pressure and force variables were greater in the metatarsals and lower in the heel region in non-rearfoot strikers. Peak pressure for the whole foot was greater in non-rearfoot strikers while no difference was observed in maximum force or contact time for the whole foot between strike types. Allowing time for accommodation and adaptation to different stresses on the foot may be warranted when using minimalist footwear depending on foot strike pattern of the -runner. © Georg Thieme Verlag KG Stuttgart · New York.

Predictors of future anabolic androgenic steroid use.

PubMed

Wichstrøm, Lars

2006-09-01

To prospectively study the stability of anabolic androgenic steroid (AAS) use and predictors of AAS use, and to investigate whether AAS use alters the risk of later emotional and behavioral problems. Survey of a national sample of Norwegian high school students (age 15-19) in 1994 followed up in 1999 (N = 2924). Measures of frequent alcohol intoxication (50+ times per 12 months), cannabis use (12 months), hard drug use (12 months), being offered cannabis, eating problems, conduct problems, sexual debut before age 15, BMI, involvement in power sports, perceived physical appearance, and satisfaction with body parts were obtained. Life-time prevalence of AAS use were 1.9 and 0.8% in the follow-up period. Multivariate logistic regression revealed that future AAS use was predicted by young age, male gender, previous AAS use, involvement in power sports, and frequent alcohol intoxication. AAS use did not predict future emotional or behavioral problems other than reducing the risk of future frequent alcohol intoxication. Frequent alcohol intoxication and involvement in power sports appear to predict future AAS use. At the population level there was little stability in individual AAS use from adolescence to early adulthood. No detrimental effects of AAS use could be detected in this study, but low statistical power limits this conclusion.

Multivariate analysis of progressive thermal desorption coupled gas chromatography-mass spectrometry.

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

Van Benthem, Mark Hilary; Mowry, Curtis Dale; Kotula, Paul Gabriel

Thermal decomposition of poly dimethyl siloxane compounds, Sylgard{reg_sign} 184 and 186, were examined using thermal desorption coupled gas chromatography-mass spectrometry (TD/GC-MS) and multivariate analysis. This work describes a method of producing multiway data using a stepped thermal desorption. The technique involves sequentially heating a sample of the material of interest with subsequent analysis in a commercial GC/MS system. The decomposition chromatograms were analyzed using multivariate analysis tools including principal component analysis (PCA), factor rotation employing the varimax criterion, and multivariate curve resolution. The results of the analysis show seven components related to offgassing of various fractions of siloxanes that varymore » as a function of temperature. Thermal desorption coupled with gas chromatography-mass spectrometry (TD/GC-MS) is a powerful analytical technique for analyzing chemical mixtures. It has great potential in numerous analytic areas including materials analysis, sports medicine, in the detection of designer drugs; and biological research for metabolomics. Data analysis is complicated, far from automated and can result in high false positive or false negative rates. We have demonstrated a step-wise TD/GC-MS technique that removes more volatile compounds from a sample before extracting the less volatile compounds. This creates an additional dimension of separation before the GC column, while simultaneously generating three-way data. Sandia's proven multivariate analysis methods, when applied to these data, have several advantages over current commercial options. It also has demonstrated potential for success in finding and enabling identification of trace compounds. Several challenges remain, however, including understanding the sources of noise in the data, outlier detection, improving the data pretreatment and analysis methods, developing a software tool for ease of use by the chemist, and demonstrating our belief that this multivariate analysis will enable superior differentiation capabilities. In addition, noise and system artifacts challenge the analysis of GC-MS data collected on lower cost equipment, ubiquitous in commercial laboratories. This research has the potential to affect many areas of analytical chemistry including materials analysis, medical testing, and environmental surveillance. It could also provide a method to measure adsorption parameters for chemical interactions on various surfaces by measuring desorption as a function of temperature for mixtures. We have presented results of a novel method for examining offgas products of a common PDMS material. Our method involves utilizing a stepped TD/GC-MS data acquisition scheme that may be almost totally automated, coupled with multivariate analysis schemes. This method of data generation and analysis can be applied to a number of materials aging and thermal degradation studies.« less

The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours.

PubMed

Varley, J M; Armour, J; Swallow, J E; Jeffreys, A J; Ponder, B A; T'Ang, A; Fung, Y K; Brammar, W J; Walker, R A

1989-06-01

We have analysed the organisation of the retinoblastoma (RB1) gene in 77 primary breast carcinomas, in metastatic tissue derived from 16 of those primary tumours, and in a variety of benign breast lesions. Expression of RB1 was also assessed in most samples by immunohistochemical detection of the RB1 protein in tissue sections. Structural abnormalities to RB1 were detected in DNA from 15/77 (19%) of primary breast carcinomas examined. Where DNA was available from metastatic tissue derived from such primary tumours, the same aberration could be detected. No alterations were seen in benign breast lesions. 16/56 (29%) of tumours examined for expression by immunohistochemical methods showed a proportion of tumour cells to be completely negative for the RB1 protein. All tumours in which a structural alteration to RB1 was detected had a proportion of negative cells, except for one case where all cells were positive. Several primary tumour samples were identified where there was no detectable structural change to the gene, but there was loss of expression in some tumour cells. The data presented here demonstrate that changes to the RB1 gene leading to loss of expression of both alleles are frequent in primary human breast tumours.

Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates.

PubMed

Parrella, P; Xiao, Y; Fliss, M; Sanchez-Cespedes, M; Mazzarelli, P; Rinaldi, M; Nicol, T; Gabrielson, E; Cuomo, C; Cohen, D; Pandit, S; Spencer, M; Rabitti, C; Fazio, V M; Sidransky, D

2001-10-15

To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.

PubMed

Brooks, James D; Wei, Wei; Hawley, Sarah; Auman, Heidi; Newcomb, Lisa; Boyer, Hilary; Fazli, Ladan; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Feng, Ziding; McKenney, Jesse K

2015-01-01

Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39%) were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤ 3+4=7) and improved recurrence free survival (RFS). On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS) or overall survival (OS). High-level SPINK1 protein expression (33/1067 cases; 3%) was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28%) cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate cancer.

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients

PubMed Central

Brooks, James D.; Wei, Wei; Hawley, Sarah; Auman, Heidi; Newcomb, Lisa; Boyer, Hilary; Fazli, Ladan; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A.; Carroll, Peter R.; Gleave, Martin; Lance, Raymond; Lin, Daniel W.; Nelson, Peter S.; Thompson, Ian M.; True, Lawrence D.; Feng, Ziding; McKenney, Jesse K.

2015-01-01

Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39%) were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤3+4=7) and improved recurrence free survival (RFS). On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS) or overall survival (OS). High-level SPINK1 protein expression (33/1067 cases; 3%) was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28%) cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate cancer. PMID:26172920

Evaluation of direct and indirect ethanol biomarkers using a likelihood ratio approach to identify chronic alcohol abusers for forensic purposes.

PubMed

Alladio, Eugenio; Martyna, Agnieszka; Salomone, Alberto; Pirro, Valentina; Vincenti, Marco; Zadora, Grzegorz

2017-02-01

The detection of direct ethanol metabolites, such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs), in scalp hair is considered the optimal strategy to effectively recognize chronic alcohol misuses by means of specific cut-offs suggested by the Society of Hair Testing. However, several factors (e.g. hair treatments) may alter the correlation between alcohol intake and biomarkers concentrations, possibly introducing bias in the interpretative process and conclusions. 125 subjects with various drinking habits were subjected to blood and hair sampling to determine indirect (e.g. CDT) and direct alcohol biomarkers. The overall data were investigated using several multivariate statistical methods. A likelihood ratio (LR) approach was used for the first time to provide predictive models for the diagnosis of alcohol abuse, based on different combinations of direct and indirect alcohol biomarkers. LR strategies provide a more robust outcome than the plain comparison with cut-off values, where tiny changes in the analytical results can lead to dramatic divergence in the way they are interpreted. An LR model combining EtG and FAEEs hair concentrations proved to discriminate non-chronic from chronic consumers with ideal correct classification rates, whereas the contribution of indirect biomarkers proved to be negligible. Optimal results were observed using a novel approach that associates LR methods with multivariate statistics. In particular, the combination of LR approach with either Principal Component Analysis (PCA) or Linear Discriminant Analysis (LDA) proved successful in discriminating chronic from non-chronic alcohol drinkers. These LR models were subsequently tested on an independent dataset of 43 individuals, which confirmed their high efficiency. These models proved to be less prone to bias than EtG and FAEEs independently considered. In conclusion, LR models may represent an efficient strategy to sustain the diagnosis of chronic alcohol consumption and provide a suitable gradation to support the judgment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Spectral imaging of chemical compounds using multivariate optically enhanced filters integrated with InGaAs VGA cameras

NASA Astrophysics Data System (ADS)

Priore, Ryan J.; Jacksen, Niels

2016-05-01

Infrared hyperspectral imagers (HSI) have been fielded for the detection of hazardous chemical and biological compounds, tag detection (friend versus foe detection) and other defense critical sensing missions over the last two decades. Low Size/Weight/Power/Cost (SWaPc) methods of identification of chemical compounds spectroscopy has been a long term goal for hand held applications. We describe a new HSI concept for low cost / high performance InGaAs SWIR camera chemical identification for military, security, industrial and commercial end user applications. Multivariate Optical Elements (MOEs) are thin-film devices that encode a broadband, spectroscopic pattern allowing a simple broadband detector to generate a highly sensitive and specific detection for a target analyte. MOEs can be matched 1:1 to a discrete analyte or class prediction. Additionally, MOE filter sets are capable of sensing an orthogonal projection of the original sparse spectroscopic space enabling a small set of MOEs to discriminate a multitude of target analytes. This paper identifies algorithms and broadband optical filter designs that have been demonstrated to identify chemical compounds using high performance InGaAs VGA detectors. It shows how some of the initial models have been reduced to simple spectral designs and tested to produce positive identification of such chemicals. We also are developing pixilated MOE compressed detection sensors for the detection of a multitude of chemical targets in challenging backgrounds/environments for both commercial and defense/security applications. This MOE based, real-time HSI sensor will exhibit superior sensitivity and specificity as compared to currently fielded HSI systems.

Multivariate optical element platform for compressed detection of fluorescence markers

NASA Astrophysics Data System (ADS)

Priore, Ryan J.; Swanstrom, Joseph A.

2014-05-01

The success of a commercial fluorescent diagnostic assay is dependent on the selection of a fluorescent biomarker; due to the broad nature of fluorescence biomarker emission profiles, only a small number of fluorescence biomarkers may be discriminated from each other as a function of excitation source. Multivariate Optical Elements (MOEs) are thin-film devices that encode a broad band, spectroscopic pattern allowing a simple broadband detector to generate a highly sensitive and specific detection for a target analyte. MOEs have historically been matched 1:1 to a discrete analyte or class prediction; however, MOE filter sets are capable of sensing projections of the original sparse spectroscopic space enabling a small set of MOEs to discriminate a multitude of target analytes. This optical regression can offer real-time measurements with relatively high signal-to-noise ratios that realize the advantages of multiplexed detection and pattern recognition in a simple optical instrument. The specificity advantage of MOE-based sensors allows fluorescent biomarkers that were once incapable of discrimination from one another via optical band pass filters to be employed in a common assay panel. A simplified MOE-based sensor may ultimately reduce the requirement for highly trained operators as well as move certain life science applications like disease prognostication from the laboratory to the point of care. This presentation will summarize the design and fabrication of compressed detection MOE filter sets for detecting multiple fluorescent biomarkers simultaneously with strong spectroscopic interference as well as comparing the detection performance of the MOE sensor with traditional optical band pass filter methodologies.

Fiber-optic Fourier transform infrared (FO-FTIR) spectroscopy for detecting endotoxin contamination in ophthalmic viscosurgical devices (OVDS) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hassan, Moinuddin; Ilev, Ilko

2016-03-01

Ophthalmic Viscosurgical Devices (OVDs) in clinical setting are a major health risk factor for potential endotoxin contamination in the eye, due to their extensive applications in cataract surgery for space creation, stabilization and protection of intraocular tissue and intraocular lens (IOL) during implantation. Endotoxin contamination of OVDs is implicated in toxic anterior syndrome (TASS), a severe complication of cataract surgery that leads to intraocular damage and even blindness. Current standard methods for endotoxin contamination detection utilize rabbit assay or Limulus amoebocyte lysate (LAL) assays. These endotoxin detection strategies are extremely difficult for gel-like type devices such as OVDs. To overcome the endotoxin detection limitations in OVDs, we have developed an alternative optical detection methodology for label-free and real-time sensing of bacterial endotoxin in OVDs, based on fiber-optic Fourier transform infrared (FO-FTIR) transmission spectrometry in the mid-IR spectral range from 2.5 micron to 12 micron. Endotoxin contaminated OVD test samples were prepared by serial dilutions of endotoxins on OVDs. The major results of this study revealed two salient spectral peak shifts (in the regions 2925 to 2890 cm^-1 and 1125 to 1100 cm^-1), which are associated with endotoxin in OVDs. In addition, FO-FTIR experimental results processed using a multivariate analysis confirmed the observed specific peak shifts associated with endotoxin contamination in OVDs. Thus, employing the FO-FTIR sensing methodology integrated with a multivariate analysis could potentially be used as an alternative endotoxin detection technique in OVD.

Chemotaxonomy of Hawaiian Anthurium cultivars based on multivariate analysis of phenolic metabolites

USDA-ARS?s Scientific Manuscript database

Thirty-six anthurium spathes, sampled from species and commercial cultivars, were extracted and profiled using liquid-chromatography-mass spectrometry (LC-MS). 315 compounds, including anthocyanins, flavonoid glycosides, and flavanols, were detected from these extracts and used in chemotaxonomic ana...

Application of the ELOHA Framework to Regulated Rivers in the Upper Tennessee River Basin: A Case Study

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

McManamay, Ryan A; Orth, Dr. Donald J; Dolloff, Dr. Charles A

2013-01-01

In order for habitat restoration in regulated rivers to be effective at large scales, broadly applicable frameworks are needed that provide measurable objectives and contexts for management. The Ecological Limits of Hydrologic Alteration (ELOHA) framework was created as a template to assess hydrologic alterations, develop relationships between altered streamflow and ecology, and establish environmental flow standards. We tested the utility of ELOHA in informing flow restoration applications for fish and riparian communities in regulated rivers in the Upper Tennessee River Basin (UTRB). We followed the steps of ELOHA to generate flow alteration-ecological response relationships and then determined whether those relationshipsmore » could predict fish and riparian responses to flow restoration in the Cheoah River, a regulated system within the UTRB. Although ELOHA provided a robust template to construct hydrologic information and predict hydrology for ungaged locations, our results do not support the assertion that over-generalized univariate relationships between flow and ecology can produce results sufficient to guide management in regulated rivers. After constructing multivariate models, we successfully developed predictive relationships between flow alterations and fish/riparian responses. In accordance with model predictions, riparian encroachment displayed consistent decreases with increases in flow magnitude in the Cheoah River; however, fish richness did not increase as predicted four years post- restoration. Our results suggest that altered temperature and substrate and the current disturbance regime may have reduced opportunities for fish species colonization. Our case study highlights the need for interdisciplinary science in defining environmental flows for regulated rivers and the need for adaptive management approaches once flows are restored.« less

High-performance liquid chromatography with fast-scanning fluorescence detection and multivariate curve resolution for the efficient determination of galantamine and its main metabolites in serum.

PubMed

Culzoni, María J; Aucelio, Ricardo Q; Escandar, Graciela M

2012-08-31

Based on green analytical chemistry principles, an efficient approach was applied for the simultaneous determination of galantamine, a widely used cholinesterase inhibitor for the treatment of Alzheimer's disease, and its major metabolites in serum samples. After a simple serum deproteinization step, second-order data were rapidly obtained (less than 6 min) with a chromatographic system operating in the isocratic regime using ammonium acetate/acetonitrile (94:6) as mobile phase. Detection was made with a fast-scanning spectrofluorimeter, which allowed the efficient collection of data to obtain matrices of fluorescence intensity as a function of retention time and emission wavelength. Successful resolution was achieved in the presence of matrix interferences in serum samples using multivariate curve resolution-alternating least-squares (MCR-ALS). The developed approach allows the quantification of the analytes at levels found in treated patients, without the need of applying either preconcentration or extraction steps. Limits of detection in the range between 8 and 11 ng mL(-1), relative prediction errors from 7 to 12% and coefficients of variation from 4 to 7% were achieved. Copyright © 2012 Elsevier B.V. All rights reserved.

Regression analysis for LED color detection of visual-MIMO system

NASA Astrophysics Data System (ADS)

Banik, Partha Pratim; Saha, Rappy; Kim, Ki-Doo

2018-04-01

Color detection from a light emitting diode (LED) array using a smartphone camera is very difficult in a visual multiple-input multiple-output (visual-MIMO) system. In this paper, we propose a method to determine the LED color using a smartphone camera by applying regression analysis. We employ a multivariate regression model to identify the LED color. After taking a picture of an LED array, we select the LED array region, and detect the LED using an image processing algorithm. We then apply the k-means clustering algorithm to determine the number of potential colors for feature extraction of each LED. Finally, we apply the multivariate regression model to predict the color of the transmitted LEDs. In this paper, we show our results for three types of environmental light condition: room environmental light, low environmental light (560 lux), and strong environmental light (2450 lux). We compare the results of our proposed algorithm from the analysis of training and test R-Square (%) values, percentage of closeness of transmitted and predicted colors, and we also mention about the number of distorted test data points from the analysis of distortion bar graph in CIE1931 color space.

Different approaches in the molecular analysis of the SHOX gene dysfunctions.

PubMed

Stuppia, L; Gatta, V; Antonucci, I; Giuliani, R; Palka, G

2010-06-01

Deficit of the short stature homeobox containing gene (SHOX) accounts for 2.15% of cases of idiopathic short stature (ISS) and 50-100% of cases of Leri-Weill dyschondrosteosis (LWD). It has been demonstrated that patients with SHOX deficit show a good response to treatment with GH. Thus, the early identification of SHOX alterations is a crucial point in order to choose the best treatment for ISS and LWD patients. In this study, we analyze the most commonly used molecular techniques for the detection of SHOX gene alterations. multiple ligation-dependent probe amplification analysis appears to represent the gold standard for the detection of deletion involving the SHOX gene or the enhancer region, being able to show both alterations in a single assay.

Toward the development of Raman spectroscopy as a nonperturbative online monitoring tool for gasoline adulteration.

PubMed

Tan, Khay M; Barman, Ishan; Dingari, Narahara C; Singh, Gajendra P; Chia, Tet F; Tok, Wee L

2013-02-05

There is a critical need for a real-time, nonperturbative probe for monitoring the adulteration of automotive gasoline. Running on adulterated fuel leads to a substantive increase in air pollution, because of increased tailpipe emissions of harmful pollutants, as well as a reduction in engine performance. Consequently, both classification of the gasoline type and quantification of the adulteration content are of great significance for quality control. Gasoline adulteration detection is currently carried out in the laboratory with gas chromatography, which is time-consuming and costly. Here, we propose the application of Raman spectroscopic measurements for on-site rapid detection of gasoline adulteration. In this proof-of-principle report, we demonstrate the effectiveness of Raman spectra, in conjunction with multivariate analysis methods, in classifying the base oil types and simultaneously detecting the adulteration content in a wide range of commercial gasoline mixtures, both in their native states and spiked with different adulterants. In particular, we show that Raman spectra acquired with an inexpensive noncooled detector provides adequate specificity to clearly discriminate between the gasoline samples and simultaneously characterize the specific adulterant content with a limit of detection below 5%. Our promising results in this study illustrate, for the first time, the capability and the potential of Raman spectroscopy, together with multivariate analysis, as a low-cost, powerful tool for on-site rapid detection of gasoline adulteration and opens substantive avenues for applications in related fields of quality control in the oil industry.

Algorithms Based on CWT and Classifiers to Control Cardiac Alterations and Stress Using an ECG and a SCR

PubMed Central

Villarejo, María Viqueira; Zapirain, Begoña García; Zorrilla, Amaia Méndez

2013-01-01

This paper presents the results of using a commercial pulsimeter as an electrocardiogram (ECG) for wireless detection of cardiac alterations and stress levels for home control. For these purposes, signal processing techniques (Continuous Wavelet Transform (CWT) and J48) have been used, respectively. The designed algorithm analyses the ECG signal and is able to detect the heart rate (99.42%), arrhythmia (93.48%) and extrasystoles (99.29%). The detection of stress level is complemented with Skin Conductance Response (SCR), whose success is 94.02%. The heart rate variability does not show added value to the stress detection in this case. With this pulsimeter, it is possible to prevent and detect anomalies for a non-intrusive way associated to a telemedicine system. It is also possible to use it during physical activity due to the fact the CWT minimizes the motion artifacts. PMID:23666135

Algorithms based on CWT and classifiers to control cardiac alterations and stress using an ECG and a SCR.

PubMed

Villarejo, María Viqueira; Zapirain, Begoña García; Zorrilla, Amaia Méndez

2013-05-10

This paper presents the results of using a commercial pulsimeter as an electrocardiogram (ECG) for wireless detection of cardiac alterations and stress levels for home control. For these purposes, signal processing techniques (Continuous Wavelet Transform (CWT) and J48) have been used, respectively. The designed algorithm analyses the ECG signal and is able to detect the heart rate (99.42%), arrhythmia (93.48%) and extrasystoles (99.29%). The detection of stress level is complemented with Skin Conductance Response (SCR), whose success is 94.02%. The heart rate variability does not show added value to the stress detection in this case. With this pulsimeter, it is possible to prevent and detect anomalies for a non-intrusive way associated to a telemedicine system. It is also possible to use it during physical activity due to the fact the CWT minimizes the motion artifacts.

Investigation of the Sensitivity of Transmission Raman Spectroscopy for Polymorph Detection in Pharmaceutical Tablets.

PubMed

Feng, Hanzhou; Bondi, Robert W; Anderson, Carl A; Drennen, James K; Igne, Benoît

2017-08-01

Polymorph detection is critical for ensuring pharmaceutical product quality in drug substances exhibiting polymorphism. Conventional analytical techniques such as X-ray powder diffraction and solid-state nuclear magnetic resonance are utilized primarily for characterizing the presence and identity of specific polymorphs in a sample. These techniques have encountered challenges in analyzing the constitution of polymorphs in the presence of other components commonly found in pharmaceutical dosage forms. Laborious sample preparation procedures are usually required to achieve satisfactory data interpretability. There is a need for alternative techniques capable of probing pharmaceutical dosage forms rapidly and nondestructively, which is dictated by the practical requirements of applications such as quality monitoring on production lines or when quantifying product shelf lifetime. The sensitivity of transmission Raman spectroscopy for detecting polymorphs in final tablet cores was investigated in this work. Carbamazepine was chosen as a model drug, polymorph form III is the commercial form, whereas form I is an undesired polymorph that requires effective detection. The concentration of form I in a direct compression tablet formulation containing 20% w/w of carbamazepine, 74.00% w/w of fillers (mannitol and microcrystalline cellulose), and 6% w/w of croscarmellose sodium, silicon dioxide, and magnesium stearate was estimated using transmission Raman spectroscopy. Quantitative models were generated and optimized using multivariate regression and data preprocessing. Prediction uncertainty was estimated for each validation sample by accounting for all the main variables contributing to the prediction. Multivariate detection limits were calculated based on statistical hypothesis testing. The transmission Raman spectroscopic model had an absolute prediction error of 0.241% w/w for the independent validation set. The method detection limit was estimated at 1.31% w/w. The results demonstrated that transmission Raman spectroscopy is a sensitive tool for polymorphs detection in pharmaceutical tablets.

COPS: A Sensitive and Accurate Tool for Detecting Somatic Copy Number Alterations Using Short-Read Sequence Data from Paired Samples

PubMed Central

Krishnan, Neeraja M.; Gaur, Prakhar; Chaudhary, Rakshit; Rao, Arjun A.; Panda, Binay

2012-01-01

Copy Number Alterations (CNAs) such as deletions and duplications; compose a larger percentage of genetic variations than single nucleotide polymorphisms or other structural variations in cancer genomes that undergo major chromosomal re-arrangements. It is, therefore, imperative to identify cancer-specific somatic copy number alterations (SCNAs), with respect to matched normal tissue, in order to understand their association with the disease. We have devised an accurate, sensitive, and easy-to-use tool, COPS, COpy number using Paired Samples, for detecting SCNAs. We rigorously tested the performance of COPS using short sequence simulated reads at various sizes and coverage of SCNAs, read depths, read lengths and also with real tumor:normal paired samples. We found COPS to perform better in comparison to other known SCNA detection tools for all evaluated parameters, namely, sensitivity (detection of true positives), specificity (detection of false positives) and size accuracy. COPS performed well for sequencing reads of all lengths when used with most upstream read alignment tools. Additionally, by incorporating a downstream boundary segmentation detection tool, the accuracy of SCNA boundaries was further improved. Here, we report an accurate, sensitive and easy to use tool in detecting cancer-specific SCNAs using short-read sequence data. In addition to cancer, COPS can be used for any disease as long as sequence reads from both disease and normal samples from the same individual are available. An added boundary segmentation detection module makes COPS detected SCNA boundaries more specific for the samples studied. COPS is available at ftp://115.119.160.213 with username “cops” and password “cops”. PMID:23110103

Geology, mineralization, and hydrothermal alteration and relationships to acidic and metal-bearing surface waters in the Palmetto Gulch area, southwestern Colorado

USGS Publications Warehouse

Bove, Dana J.; Kurtz, Jeffrey P.; Wright, Winfield G.

2002-01-01

The Palmetto Gulch area is affected by low pH and metal-bearing drainage from abandoned mines, and perhaps, from natural weathering around vein zones. To investigate these anthropogenic and potential natural sources of acidity and metals, we mapped the geology, veins, and hydrothermally altered areas; conducted mine dump leachate studies; and collected reconnaissance water quality data. Several small abandoned mines are present in the Palmetto Gulch area that produced small amounts of relatively high-grade silver ore from fault-controlled polymetallic vein deposits. These veins are hosted in lavas, breccias, and related volcaniclastic sediments that ponded within the 28 Ma San Juan-Uncompahgre caldera complex. These rock units generally have conformable contacts and have shallow dips to the northwest. Lava flows of pyroxene andesite, which host the Roy-Pray mine, are massive near their base and typically grade upward into tightly jointed rock with 2-15 cm joint spacing. In general, most hydrothermally altered rock within the Palmetto Gulch area is restricted to envelopes surrounding the mineralized veins and faults. Composite zones of vein-related alteration vary from about 50 to 80 m wide along the high ridgelines and narrow to less than 10 to 15 m beneath an elevation of about 5,462 m. Where unaffected by surficial oxidation, these altered zones contain as much as 7 to 10 volume percent finely-disseminated pyrite. The majority of rocks in the area were affected by regional and vein-related propylitic alteration. These greenish-colored rocks have alteration products consisting of chlorite, illite, and calcite; and feldspars are typically weakly altered. Most of these rocks have detectable amounts of calcite, while as much as 11 percent by weight was detected in samples collected during this study. The Palmetto Gulch area is affected by low pH and metal-bearing drainage from abandoned mines, and perhaps, from natural weathering around vein zones. To investigate these anthropogenic and potential natural sources of acidity and metals, we mapped the geology, veins, and hydrothermally altered areas; conducted mine dump leachate studies; and collected reconnaissance water quality data. Several small abandoned mines are present in the Palmetto Gulch area that produced small amounts of relatively high-grade silver ore from fault-controlled polymetallic vein deposits. These veins are hosted in lavas, breccias, and related volcaniclastic sediments that ponded within the 28 Ma San Juan-Uncompahgre caldera complex. These rock units generally have conformable contacts and have shallow dips to the northwest. Lava flows of pyroxene andesite, which host the Roy-Pray mine, are massive near their base and typically grade upward into tightly jointed rock with 2-15 cm joint spacing. In general, most hydrothermally altered rock within the Palmetto Gulch area is restricted to envelopes surrounding the mineralized veins and faults. Composite zones of vein-related alteration vary from about 50 to 80 m wide along the high ridgelines and narrow to less than 10 to 15 m beneath an elevation of about 5,462 m. Where unaffected by surficial oxidation, these altered zones contain as much as 7 to 10 volume percent finely-disseminated pyrite. The majority of rocks in the area were affected by regional and vein-related propylitic alteration. These greenish-colored rocks have alteration products consisting of chlorite, illite, and calcite; and feldspars are typically weakly altered. Most of these rocks have detectable amounts of calcite, while as much as 11 percent by weight was detected in samples collected during this study.

Experimental Alteration of Basalt to Support Interpretation of Remote Sensing and In Situ Meausrements from Mars

NASA Technical Reports Server (NTRS)

Bell, M. S.

2014-01-01

Major occurrences of hydrous alteration minerals on Mars have been found in Noachian impact craters formed in basaltic targets and detected using visible/near infrared (VNIR) spectroscopy. Until recently phyllosilicates were detected only in craters in the southern hemisphere [1, 2]. However, it has been reported that at least nine craters in the northern plains apparently excavated thick layers of lava and sediment to expose phyllosilicates [3] as well. The MER (Mars Exploration Rovers) rovers previously reported results of in situ measurement indicating the presence of alteration minerals on Mars [4,5] and it was recently reported that the Mars Curiosity rover has detected alteration phases in situ at Yellowknife Bay in Gale crater as well [6,7]. An important discovery for Mars geochronology is that the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument on Curiosity detected phyllosilicates indicating that phyllosilicate formation on Mars extended beyond the Noachian Epoch [8]. These discoveries indicate that Mars was globally altered by water in the past but does not constrain formation conditions for alteration phase occurrences, which have important implications for the evolution of the surface and the biological potential on Mars. Understanding the alteration assemblages produced by a range of conditions is vital for the interpretation of phyllosilicate spectral signatures as well as in situ measurements and to decipher the environment and evolution of early Mars. The martian surface has been intensely altered by meteorite impacts whose effects include brecciation and melting of target materials as well as the initiation of hydrothermal circulation in a hydrous target [9,10,11,12]. Impact effects may facilitate aqueous alteration of a basaltic target because the rate of silicate dissolution is a function of the degree of crystallinity, surface area, and temperature. The resultant alteration mineralogies from shocked basaltic target material are a function of the original mineral assemblage in the parent rocks, the chemistry of fluids that interacted with the rocks, and physico-chemical conditions (pH, temperatures, and pressure) during the time of mineral formation. Understanding the alteration assemblages produced by a range of conditions is vital for the interpretation of phyllosilicate spectral signatures and to decipher the environment and evolution of early Mars, and especially for identifying habitable niches in which life could be initiated and sustained. No experimentally controlled and well characterized analog materials that simulate martian shock metamorphism and alteration conditions currently exist for calibrating either remote sensing or in situ measurements of Mars. A series of experiments was initiated to assess the effects of systematic changes in the physico-chemical conditions on Mars analog materials thereby providing samples to ground-truth Mars remote sensing observations from CRISM (Compact Reconnaissance Imaging Spectrometer for Mars) and in situ measurements from Opportunity's Mössbauer and Curiosity's CHEMIN (Chemistry and Mineralogy X-Ray Diffraction/XRay Fluorescence) instruments. Results of initial experimental runs as analysed by SEM-EDS (Secondary Electron Microscopy -Energy Dispersive Spectroscopy) and X-ray Diffraction (XRD) analysis are reported here and lay the foundation for comparison with shocked and altered samples that will be characterized in the next phase of this work.

Integrated Multivariate Analysis with Nondetects for the Development of Human Sewage Source-Tracking Tools Using Bacteriophages of Enterococcus faecalis.

PubMed

Wangkahad, Bencharong; Mongkolsuk, Skorn; Sirikanchana, Kwanrawee

2017-02-21

We developed sewage-specific microbial source tracking (MST) tools using enterococci bacteriophages and evaluated their performance with univariate and multivariate analyses involving data below detection limits. Newly isolated Enterococci faecalis bacterial strains AIM06 (DSM100702) and SR14 (DSM100701) demonstrated 100% specificity and 90% sensitivity to human sewage without detecting 68 animal manure pooled samples of cats, chickens, cows, dogs, ducks, pigs, and pigeons. AIM06 and SR14 bacteriophages were present in human sewage at 2-4 orders of magnitude. A principal component analysis confirmed the importance of both phages as main water quality parameters. The phages presented only in the polluted water, as classified by a cluster analysis, and at median concentrations of 1.71 × 10 2 and 4.27 × 10 2 PFU/100 mL, respectively, higher than nonhost specific RYC2056 phages and sewage-specific KS148 phages (p < 0.05). Interestingly, AIM06 and SR14 phages exhibited significant correlations with each other and with total coliforms, E. coli, enterococci, and biochemical oxygen demand (Kendall's tau = 0.348 to 0.605, p < 0.05), a result supporting their roles as water quality indicators. This research demonstrates the multiregional applicability of enterococci hosts in MST application and highlights the significance of multivariate analysis with nondetects in evaluating the performance of new MST host strains.

Clinical and laboratory factors associated with mortality in dengue.

PubMed

Saroch, Atul; Arya, Vivek; Sinha, Nitin; Taneja, R S; Sahai, Pooja; Mahajan, R K

2017-04-01

Dengue is endemic in more than 100 countries, giving rise to an increased number of deaths in the last five years in the South-East Asian region. We report our findings from a retrospective study of adults admitted with confirmed dengue at our institution. We studied the clinical and laboratory parameters associated with mortality in these patients. Of the 172 hospitalised patients studied, 156 (90.69 %) recovered while 16 (9.3%) died. Univariate analysis showed altered sensorium on presentation, lower haemoglobin and haematocrit levels, higher serum creatinine, higher serum transaminase and lower serum albumin levels to be significantly associated with mortality in dengue. Further, using stepwise multivariate logistic regression, altered sensorium ( P = 0.006) and hypoalbuminemia ( P = 0.013) were identified as independent predictors of mortality in dengue. Identification of these parameters early in the course of disease should prompt intensification of treatment in dengue cases.

Multivariate pattern recognition for diagnosis and prognosis in clinical neuroimaging: state of the art, current challenges and future trends.

PubMed

Haller, Sven; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon; Van De Ville, Dimitri

2014-05-01

Many diseases are associated with systematic modifications in brain morphometry and function. These alterations may be subtle, in particular at early stages of the disease progress, and thus not evident by visual inspection alone. Group-level statistical comparisons have dominated neuroimaging studies for many years, proving fascinating insight into brain regions involved in various diseases. However, such group-level results do not warrant diagnostic value for individual patients. Recently, pattern recognition approaches have led to a fundamental shift in paradigm, bringing multivariate analysis and predictive results, notably for the early diagnosis of individual patients. We review the state-of-the-art fundamentals of pattern recognition including feature selection, cross-validation and classification techniques, as well as limitations including inter-individual variation in normal brain anatomy and neurocognitive reserve. We conclude with the discussion of future trends including multi-modal pattern recognition, multi-center approaches with data-sharing and cloud-computing.

A Forward Glimpse into Inverse Problems through a Geology Example

ERIC Educational Resources Information Center

Winkel, Brian J.

2012-01-01

This paper describes a forward approach to an inverse problem related to detecting the nature of geological substrata which makes use of optimization techniques in a multivariable calculus setting. The true nature of the related inverse problem is highlighted. (Contains 2 figures.)

Multiple imputation for multivariate data with missing and below-threshold measurements: time-series concentrations of pollutants in the Arctic.

PubMed

Hopke, P K; Liu, C; Rubin, D B

2001-03-01

Many chemical and environmental data sets are complicated by the existence of fully missing values or censored values known to lie below detection thresholds. For example, week-long samples of airborne particulate matter were obtained at Alert, NWT, Canada, between 1980 and 1991, where some of the concentrations of 24 particulate constituents were coarsened in the sense of being either fully missing or below detection limits. To facilitate scientific analysis, it is appealing to create complete data by filling in missing values so that standard complete-data methods can be applied. We briefly review commonly used strategies for handling missing values and focus on the multiple-imputation approach, which generally leads to valid inferences when faced with missing data. Three statistical models are developed for multiply imputing the missing values of airborne particulate matter. We expect that these models are useful for creating multiple imputations in a variety of incomplete multivariate time series data sets.

Detecting synchronization clusters in multivariate time series via coarse-graining of Markov chains.

PubMed

Allefeld, Carsten; Bialonski, Stephan

2007-12-01

Synchronization cluster analysis is an approach to the detection of underlying structures in data sets of multivariate time series, starting from a matrix R of bivariate synchronization indices. A previous method utilized the eigenvectors of R for cluster identification, analogous to several recent attempts at group identification using eigenvectors of the correlation matrix. All of these approaches assumed a one-to-one correspondence of dominant eigenvectors and clusters, which has however been shown to be wrong in important cases. We clarify the usefulness of eigenvalue decomposition for synchronization cluster analysis by translating the problem into the language of stochastic processes, and derive an enhanced clustering method harnessing recent insights from the coarse-graining of finite-state Markov processes. We illustrate the operation of our method using a simulated system of coupled Lorenz oscillators, and we demonstrate its superior performance over the previous approach. Finally we investigate the question of robustness of the algorithm against small sample size, which is important with regard to field applications.

Determination of enantiomeric composition of ibuprofen in pharmaceutical formulations by partial least-squares regression of strongly overlapped chromatographic profiles.

PubMed

Grisales, Jaiver Osorio; Arancibia, Juan A; Castells, Cecilia B; Olivieri, Alejandro C

2012-12-01

In this report, we demonstrate how chiral liquid chromatography combined with multivariate chemometric techniques, specifically unfolded-partial least-squares regression (U-PLS), provides a powerful analytical methodology. Using U-PLS, strongly overlapped enantiomer profiles in a sample could be successfully processed and enantiomeric purity could be accurately determined without requiring baseline enantioresolution between peaks. The samples were partially enantioseparated with a permethyl-β-cyclodextrin chiral column under reversed-phase conditions. Signals detected with a diode-array detector within a wavelength range from 198 to 241 nm were recorded, and the data were processed by a second-order multivariate algorithm to decrease detection limits. The R-(-)-enantiomer of ibuprofen in tablet formulation samples could be determined at the level of 0.5 mg L⁻¹ in the presence of 99.9% of the S-(+)-enantiomorph with relative prediction error within ±3%. Copyright © 2012 Elsevier B.V. All rights reserved.

Geology of central Libya Montes, Mars: Aqueous alteration history from mineralogical and morphological mapping

NASA Astrophysics Data System (ADS)

Tirsch, D.; Bishop, J. L.; Voigt, J. R. C.; Tornabene, L. L.; Erkeling, G.; Jaumann, R.

2018-11-01

We analyze the emplacement chronology and aqueous alteration history of distinctive mineral assemblages and related geomorphic units near Hashir and Bradbury impact craters located within the Libya Montes, which are part of the southern rim of the Isidis Basin on Mars. We derive our results from a spectro-morphological mapping project that combines spectral detections from CRISM near-infrared imagery with geomorphology and topography from HRSC, CTX, and HiRISE imagery. Through this combination of data sets, we were able to use the morphology associated with specific mineral detections to extrapolate the possible extent of the units hosting these compositions. We characterize multiple units consistent with formation through volcanic, impact, hydrothermal, lacustrine and evaporative processes. Altered pyroxene-bearing basement rocks are unconformably overlain by an olivine-rich unit, which is in turn covered by a pyroxene-bearing capping unit. Aqueously altered outcrops identified here include nontronite, saponite, beidellite, opal, and dolomite. The diversity of mineral assemblages suggests that the nature of aqueous alteration at Libya Montes varied in space and time. This mineralogy together with geologic features shows a transition from Noachian aged impact-induced hydrothermal alteration and the alteration of Noachian bedrock by neutral to slightly basic waters via Hesperian aged volcanic emplacements and evaporative processes in lacustrine environments followed by Amazonian resurfacing in the form of aeolian erosion.

The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer

PubMed Central

2013-01-01

Background We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples. Methods Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)–mass spectrometry (MS). Results High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers. Conclusions These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer. PMID:23409863

Progress in the detection of neoplastic progress and cancer by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Bakker Schut, Tom C.; Stone, Nicholas; Kendall, Catherine A.; Barr, Hugh; Bruining, Hajo A.; Puppels, Gerwin J.

2000-05-01

Early detection of cancer is important because of the improved survival rates when the cancer is treated early. We study the application of NIR Raman spectroscopy for detection of dysplasia because this technique is sensitive to the small changes in molecular invasive in vivo detection using fiber-optic probes. The result of an in vitro study to detect neoplastic progress of esophageal Barrett's esophageal tissue will be presented. Using multivariate statistics, we developed three different linear discriminant analysis classification models to predict tissue type on the basis of the measured spectrum. Spectra of normal, metaplastic and dysplasia tissue could be discriminated with an accuracy of up to 88 percent. Therefore Raman spectroscopy seems to be a very suitable technique to detect dysplasia in Barrett's esophageal tissue.

Principal component directed partial least squares analysis for combining nuclear magnetic resonance and mass spectrometry data in metabolomics: application to the detection of breast cancer.

PubMed

Gu, Haiwei; Pan, Zhengzheng; Xi, Bowei; Asiago, Vincent; Musselman, Brian; Raftery, Daniel

2011-02-07

Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) are the two most commonly used analytical tools in metabolomics, and their complementary nature makes the combination particularly attractive. A combined analytical approach can improve the potential for providing reliable methods to detect metabolic profile alterations in biofluids or tissues caused by disease, toxicity, etc. In this paper, (1)H NMR spectroscopy and direct analysis in real time (DART)-MS were used for the metabolomics analysis of serum samples from breast cancer patients and healthy controls. Principal component analysis (PCA) of the NMR data showed that the first principal component (PC1) scores could be used to separate cancer from normal samples. However, no such obvious clustering could be observed in the PCA score plot of DART-MS data, even though DART-MS can provide a rich and informative metabolic profile. Using a modified multivariate statistical approach, the DART-MS data were then reevaluated by orthogonal signal correction (OSC) pretreated partial least squares (PLS), in which the Y matrix in the regression was set to the PC1 score values from the NMR data analysis. This approach, and a similar one using the first latent variable from PLS-DA of the NMR data resulted in a significant improvement of the separation between the disease samples and normals, and a metabolic profile related to breast cancer could be extracted from DART-MS. The new approach allows the disease classification to be expressed on a continuum as opposed to a binary scale and thus better represents the disease and healthy classifications. An improved metabolic profile obtained by combining MS and NMR by this approach may be useful to achieve more accurate disease detection and gain more insight regarding disease mechanisms and biology. Copyright © 2010 Elsevier B.V. All rights reserved.

Detection of systemic inflammation in severely impaired chronic pain patients, and effects of a CBT-ACT-based multi-modal pain rehabilitation program.

PubMed

Hysing, E-B; Smith, L; Thulin, M; Karlsten, R; Gordh, T

2017-12-29

Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear signs of increased inflammatory activity were detected in the pain patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43 of the 92 inflammatory biomarkers. The expression of 8 biomarkers were 4 times higher in patients compared to controls. Three biomarkers, CXCL5, SIRT2, AXIN1 were more than 8 times higher. The conventional marker for inflammation, CRP, did not differ. Of the 28 patients available for follow up one year after the intervention, all showed lower levels of the inflammatory biomarker initially raised. Conclusions The results indicate that CPP suffer from a low grade of chronic systemic inflammation, not detectable by CRP analysis. This may have implications for the general pain hypersensitivity, and other symptoms, often described in this group of patients. We conclude that inflammatory plasma proteins may be measureable molecular markers to distinguishes CPP from pain free controls, and that a CBT-ACT pain rehab program seem to decrease this inflammatory activity.

The clinical performance evaluation of novel protein chips for eleven biomarkers detection and the diagnostic model study.

PubMed

Luo, Yuan; Zhu, Xu; Zhang, Pengjun; Shen, Qian; Wang, Zi; Wen, Xinyu; Wang, Ling; Gao, Jing; Dong, Jin; Yang, Caie; Wu, Tangming; Zhu, Zheng; Tian, Yaping

2015-01-01

We aimed to develop and validate two novel protein chips, which are based on microarray chemiluminescence immunoassay and can simultaneously detected 11 biomarkers, and then to evaluate their clinical diagnostic value by comparing with the traditional methods. Protein chips were evaluated for limit of detection, specificity, common interferences, linearity, precision and accuracy. 11 biomarkers were simultaneously detected by traditional methods and protein chips in 3683 samples, which included 1723 cancer patients, 1798 benign diseases patients and 162 healthy controls. After assay validation, protein chips demonstrated high sensitivity, high specificity, good linearity, low imprecision and were free of common interferences. Compared with the traditional methods, protein chips have good correlation in the detection of all the 13 kinds of biomarkers (r≥0.935, P<0.001). For specific cancer detection, there were no statistically significant differences between the traditional method and novel protein chips, except that male protein chip showed significantly better diagnostic value on NSE detection (P=0.004) but significantly worse value on pro-GRP detection (P=0.012), female chip showed significantly better diagnostic value on pro-GRP detection (P=0.005). Furthermore, both male and female multivariate diagnostic models had significantly better diagnostic value than single detection of PGI, PG II, pro-GRP, NSE and CA125 (P<0.05). In addition, male models had significantly better diagnostic value than single CA199 and free-PSA (P<0.05), while female models observed significantly better diagnostic value than single CA724 and β-HCG (P<0.05). For total disease or cancer detection, the AUC of multivariate logistic regression for the male and female disease detection was 0.981 (95% CI: 0.975-0.987) and 0.836 (95% CI: 0.798-0.874), respectively. While, that for total cancer detection was 0.691 (95% CI: 0.666-0.717) and 0.753 (95% CI: 0.731-0.775), respectively. The new designed protein chips are simple, multiplex and reliable clinical assays and the multi-parameter diagnostic models based on them could significantly improve their clinical performance.

The clinical performance evaluation of novel protein chips for eleven biomarkers detection and the diagnostic model study

PubMed Central

Luo, Yuan; Zhu, Xu; Zhang, Pengjun; Shen, Qian; Wang, Zi; Wen, Xinyu; Wang, Ling; Gao, Jing; Dong, Jin; Yang, Caie; Wu, Tangming; Zhu, Zheng; Tian, Yaping

2015-01-01

We aimed to develop and validate two novel protein chips, which are based on microarray chemiluminescence immunoassay and can simultaneously detected 11 biomarkers, and then to evaluate their clinical diagnostic value by comparing with the traditional methods. Protein chips were evaluated for limit of detection, specificity, common interferences, linearity, precision and accuracy. 11 biomarkers were simultaneously detected by traditional methods and protein chips in 3683 samples, which included 1723 cancer patients, 1798 benign diseases patients and 162 healthy controls. After assay validation, protein chips demonstrated high sensitivity, high specificity, good linearity, low imprecision and were free of common interferences. Compared with the traditional methods, protein chips have good correlation in the detection of all the 13 kinds of biomarkers (r≥0.935, P<0.001). For specific cancer detection, there were no statistically significant differences between the traditional method and novel protein chips, except that male protein chip showed significantly better diagnostic value on NSE detection (P=0.004) but significantly worse value on pro-GRP detection (P=0.012), female chip showed significantly better diagnostic value on pro-GRP detection (P=0.005). Furthermore, both male and female multivariate diagnostic models had significantly better diagnostic value than single detection of PGI, PG II, pro-GRP, NSE and CA125 (P<0.05). In addition, male models had significantly better diagnostic value than single CA199 and free-PSA (P<0.05), while female models observed significantly better diagnostic value than single CA724 and β-HCG (P<0.05). For total disease or cancer detection, the AUC of multivariate logistic regression for the male and female disease detection was 0.981 (95% CI: 0.975-0.987) and 0.836 (95% CI: 0.798-0.874), respectively. While, that for total cancer detection was 0.691 (95% CI: 0.666-0.717) and 0.753 (95% CI: 0.731-0.775), respectively. The new designed protein chips are simple, multiplex and reliable clinical assays and the multi-parameter diagnostic models based on them could significantly improve their clinical performance. PMID:26884957

investigating the use of geophysical techniques to detect hydrocarbon seeps

NASA Astrophysics Data System (ADS)

Somwe, Vincent Tambwe

In the Cement oil field, seeps occur in the Hydrocarbon Induced Diagenetic Aureole (HIDA).This 14 square km diagenetic alteration region is mainly characterized by the: (1) secondary carbonate minerals deposition that tends to form ridges throughout the oil field; (2) disseminated pyrite in the vicinity of the fault zones; (3) uranium occurrence and the change in color pattern from red to bleached red sandstone. Generally the HIDA of the Cement oil field is subdivided into four zones: (1) carbonate cemented sandstone zone (zone 1), (2) altered sandstone zone (zone 2), (3) sulfide zone (zone 3) and (4) unaltered sandstone zone (zone 4). This study investigated the use of geophysical techniques to detect alteration zones over the Cement oil field. Magnetic and electromagnetic data were acquired at 5 m interval using the geometric G858 magnetometer and the Geonics EM-31 respectively. Both total magnetic intensity and bulk conductivity were found to decrease across boundaries between unaltered and altered sandstones. Boundaries between sulfide and carbonate zones, which in most cases were located in fault zones, were found to be characterized by higher magnetic and bulk conductivity readings. The contrast between the background and the highest positive peak was found to be in the range of 0.5-10% for total magnetic intensity and 258-450% for bulk conductivity respectively; suggesting that the detection of hydrocarbon seeps would be more effective with EM techniques. The study suggests that geophysical techniques can be used to delineate contact between the different alteration zones especially where metallic minerals such as pyrite are precipitated. The occurrence of carbonate cemented sandstone in the Cement oil field can be used as a pathfinder for hydrocarbon reservoir. The change in color in the altered sandstone zone can still be useful in the hydrocarbon exploration.

Short-term Natural History of High-Risk Human Papillomavirus Infection in Mid-Adult Women Sampled Monthly (Short title: Short-term HPV Natural History in Mid-Adult Women)

PubMed Central

Fu, Tsung-chieh (Jane); Xi, Long Fu; Hulbert, Ayaka; Hughes, James P.; Feng, Qinghua; Schwartz, Stephen M.; Hawes, Stephen E.; Koutsky, Laura A.; Winer, Rachel L.

2015-01-01

Characterizing short-term HPV detection patterns and viral load may inform HPV natural history in mid-adult women. From 2011–2012, we recruited women aged 30–50 years. Women submitted monthly self-collected vaginal samples for high-risk HPV DNA testing for 6 months. Positive samples were tested for type-specific HPV DNA load by real-time PCR. HPV type-adjusted linear and Poisson regression assessed factors associated with 1) viral load at initial HPV detection and 2) repeat type-specific HPV detection. One-hundred thirty-nine women (36% of 387 women with ≥4 samples) contributed 243 type-specific HR HPV infections during the study; 54% of infections were prevalent and 46% were incident. Incident (versus prevalent) detection and past pregnancy were associated with lower viral load, whereas current smoking was associated with higher viral load. In multivariate analysis, current smoking was associated with a 40% (95%CI:5%–87%) increase in the proportion of samples that were repeatedly positive for the same HPV type, whereas incident (versus prevalent) detection status and past pregnancy were each associated with a reduction in the proportion of samples repeatedly positive (55%,95%CI:38%–67% and 26%,95%CI:10%–39%, respectively). In a separate multivariate model, each log10 increase in viral load was associated with a 10% (95%CI:4%–16%) increase in the proportion of samples repeatedly positive. Factors associated with repeat HPV detection were similar to those observed in longer-term studies, suggesting that short-term repeat detection may relate to long-term persistence. The negative associations between incident HPV detection and both viral load and repeat detection suggest that reactivation or intermittent persistence was more common than new acquisition. PMID:25976733

Quantitative susceptibility mapping as a biomarker for evaluating white matter alterations in Parkinson's disease.

PubMed

Guan, Xiaojun; Huang, Peiyu; Zeng, Qiaoling; Liu, Chunlei; Wei, Hongjiang; Xuan, Min; Gu, Quanquan; Xu, Xiaojun; Wang, Nian; Yu, Xinfeng; Luo, Xiao; Zhang, Minming

2018-02-07

Myelinated white matter showing diamagnetic susceptibility is important for information transfer in the brain. In Parkinson's disease (PD), the white matter is also suffering degenerative alterations. Quantitative susceptibility mapping (QSM) is a novel technique for noninvasive assessment of regional white matter ultrastructure, and provides different information of white matter in addition to standard diffusion tensor imaging (DTI). In this study, we used QSM to detect spatial white matter alterations in PD patients (n = 65) and age- and sex-matched normal controls (n = 46). Voxel-wise tract-based spatial statistics were performed to analyze QSM and DTI data. QSM showed extensive white matter involvement-including regions adjacent to the frontal, parietal, and temporal lobes-in PD patients, which was more widespread than that observed using DTI. Both QSM and DTI showed similar alterations in the left inferior longitudinal fasciculus and right cerebellar hemisphere. Further, alterations in the white matter were correlated with motor impairment and global disease severity in PD patients. We suggest that QSM may provide a novel approach for detecting white matter alterations and underlying network disruptions in PD. Further, the combination of QSM and DTI would provide a more complete evaluation of the diseased brain by analyzing different biological tissue properties.

MGAS: a powerful tool for multivariate gene-based genome-wide association analysis.

PubMed

Van der Sluis, Sophie; Dolan, Conor V; Li, Jiang; Song, Youqiang; Sham, Pak; Posthuma, Danielle; Li, Miao-Xin

2015-04-01

Standard genome-wide association studies, testing the association between one phenotype and a large number of single nucleotide polymorphisms (SNPs), are limited in two ways: (i) traits are often multivariate, and analysis of composite scores entails loss in statistical power and (ii) gene-based analyses may be preferred, e.g. to decrease the multiple testing problem. Here we present a new method, multivariate gene-based association test by extended Simes procedure (MGAS), that allows gene-based testing of multivariate phenotypes in unrelated individuals. Through extensive simulation, we show that under most trait-generating genotype-phenotype models MGAS has superior statistical power to detect associated genes compared with gene-based analyses of univariate phenotypic composite scores (i.e. GATES, multiple regression), and multivariate analysis of variance (MANOVA). Re-analysis of metabolic data revealed 32 False Discovery Rate controlled genome-wide significant genes, and 12 regions harboring multiple genes; of these 44 regions, 30 were not reported in the original analysis. MGAS allows researchers to conduct their multivariate gene-based analyses efficiently, and without the loss of power that is often associated with an incorrectly specified genotype-phenotype models. MGAS is freely available in KGG v3.0 (http://statgenpro.psychiatry.hku.hk/limx/kgg/download.php). Access to the metabolic dataset can be requested at dbGaP (https://dbgap.ncbi.nlm.nih.gov/). The R-simulation code is available from http://ctglab.nl/people/sophie_van_der_sluis. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

In vitro detection of androgenic and estrogenic activity in complex environmental effluent samples: Lessions learned

EPA Science Inventory

Fish living in ecosystems contaminated with effluents from human or domestic animal wastes display reproductive alterations suggesting hormone disruption. Recent research with effluent from cattle feeding operations in the US have associated morphological alterations in fish col...

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.

Assessing Principal Component Regression Prediction of Neurochemicals Detected with Fast-Scan Cyclic Voltammetry

PubMed Central

2011-01-01

Principal component regression is a multivariate data analysis approach routinely used to predict neurochemical concentrations from in vivo fast-scan cyclic voltammetry measurements. This mathematical procedure can rapidly be employed with present day computer programming languages. Here, we evaluate several methods that can be used to evaluate and improve multivariate concentration determination. The cyclic voltammetric representation of the calculated regression vector is shown to be a valuable tool in determining whether the calculated multivariate model is chemically appropriate. The use of Cook’s distance successfully identified outliers contained within in vivo fast-scan cyclic voltammetry training sets. This work also presents the first direct interpretation of a residual color plot and demonstrated the effect of peak shifts on predicted dopamine concentrations. Finally, separate analyses of smaller increments of a single continuous measurement could not be concatenated without substantial error in the predicted neurochemical concentrations due to electrode drift. Taken together, these tools allow for the construction of more robust multivariate calibration models and provide the first approach to assess the predictive ability of a procedure that is inherently impossible to validate because of the lack of in vivo standards. PMID:21966586

Assessing principal component regression prediction of neurochemicals detected with fast-scan cyclic voltammetry.

PubMed

Keithley, Richard B; Wightman, R Mark

2011-06-07

Principal component regression is a multivariate data analysis approach routinely used to predict neurochemical concentrations from in vivo fast-scan cyclic voltammetry measurements. This mathematical procedure can rapidly be employed with present day computer programming languages. Here, we evaluate several methods that can be used to evaluate and improve multivariate concentration determination. The cyclic voltammetric representation of the calculated regression vector is shown to be a valuable tool in determining whether the calculated multivariate model is chemically appropriate. The use of Cook's distance successfully identified outliers contained within in vivo fast-scan cyclic voltammetry training sets. This work also presents the first direct interpretation of a residual color plot and demonstrated the effect of peak shifts on predicted dopamine concentrations. Finally, separate analyses of smaller increments of a single continuous measurement could not be concatenated without substantial error in the predicted neurochemical concentrations due to electrode drift. Taken together, these tools allow for the construction of more robust multivariate calibration models and provide the first approach to assess the predictive ability of a procedure that is inherently impossible to validate because of the lack of in vivo standards.

Splicing-factor alterations in cancers

PubMed Central

Anczuków, Olga; Krainer, Adrian R.

2016-01-01

Tumor-associated alterations in RNA splicing result either from mutations in splicing-regulatory elements or changes in components of the splicing machinery. This review summarizes our current understanding of the role of splicing-factor alterations in human cancers. We describe splicing-factor alterations detected in human tumors and the resulting changes in splicing, highlighting cell-type-specific similarities and differences. We review the mechanisms of splicing-factor regulation in normal and cancer cells. Finally, we summarize recent efforts to develop novel cancer therapies, based on targeting either the oncogenic splicing events or their upstream splicing regulators. PMID:27530828

Study on optimization method of test conditions for fatigue crack detection using lock-in vibrothermography

NASA Astrophysics Data System (ADS)

Min, Qing-xu; Zhu, Jun-zhen; Feng, Fu-zhou; Xu, Chao; Sun, Ji-wei

2017-06-01

In this paper, the lock-in vibrothermography (LVT) is utilized for defect detection. Specifically, for a metal plate with an artificial fatigue crack, the temperature rise of the defective area is used for analyzing the influence of different test conditions, i.e. engagement force, excitation intensity, and modulated frequency. The multivariate nonlinear and logistic regression models are employed to estimate the POD (probability of detection) and POA (probability of alarm) of fatigue crack, respectively. The resulting optimal selection of test conditions is presented. The study aims to provide an optimized selection method of the test conditions in the vibrothermography system with the enhanced detection ability.

Magnetic Resonance Spectroscopy (MRS) of Prostatic Fluids for Early Detection of Prostate Cancer

DTIC Science & Technology

2005-10-01

measured using external 1H-NMRS coils, increasing the practicality of the metabonomic approach. In conclusion, the absolute concentrations of the...Lindon, J.C., and Holmes, E. “ Metabonomics ”: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate

The added value of percentage of free to total prostate-specific antigen, PCA3, and a kallikrein panel to the ERSPC risk calculator for prostate cancer in prescreened men.

PubMed

Vedder, Moniek M; de Bekker-Grob, Esther W; Lilja, Hans G; Vickers, Andrew J; van Leenders, Geert J L H; Steyerberg, Ewout W; Roobol, Monique J

2014-12-01

Prostate-specific antigen (PSA) testing has limited accuracy for the early detection of prostate cancer (PCa). To assess the value added by percentage of free to total PSA (%fPSA), prostate cancer antigen 3 (PCA3), and a kallikrein panel (4k-panel) to the European Randomised Study of Screening for Prostate Cancer (ERSPC) multivariable prediction models: risk calculator (RC) 4, including transrectal ultrasound, and RC 4 plus digital rectal examination (4+DRE) for prescreened men. Participants were invited for rescreening between October 2007 and February 2009 within the Dutch part of the ERSPC study. Biopsies were taken in men with a PSA level ≥3.0 ng/ml or a PCA3 score ≥10. Additional analyses of the 4k-panel were done on serum samples. Outcome was defined as PCa detectable by sextant biopsy. Receiver operating characteristic curve and decision curve analyses were performed to compare the predictive capabilities of %fPSA, PCA3, 4k-panel, the ERSPC RCs, and their combinations in logistic regression models. PCa was detected in 119 of 708 men. The %fPSA did not perform better univariately or added to the RCs compared with the RCs alone. In 202 men with an elevated PSA, the 4k-panel discriminated better than PCA3 when modelled univariately (area under the curve [AUC]: 0.78 vs. 0.62; p=0.01). The multivariable models with PCA3 or the 4k-panel were equivalent (AUC: 0.80 for RC 4+DRE). In the total population, PCA3 discriminated better than the 4k-panel (univariate AUC: 0.63 vs. 0.56; p=0.05). There was no statistically significant difference between the multivariable model with PCA3 (AUC: 0.73) versus the model with the 4k-panel (AUC: 0.71; p=0.18). The multivariable model with PCA3 performed better than the reference model (0.73 vs. 0.70; p=0.02). Decision curves confirmed these patterns, although numbers were small. Both PCA3 and, to a lesser extent, a 4k-panel have added value to the DRE-based ERSPC RC in detecting PCa in prescreened men. We studied the added value of novel biomarkers to previously developed risk prediction models for prostate cancer. We found that inclusion of these biomarkers resulted in an increase in predictive ability. Copyright © 2014. Published by Elsevier B.V.

Race-specific molecular alterations correlate with differential outcomes for black and white endometrioid endometrial cancer patients.

PubMed

Bateman, Nicholas W; Dubil, Elizabeth A; Wang, Guisong; Hood, Brian L; Oliver, Julie M; Litzi, Tracy A; Gist, Glenn D; Mitchell, David A; Blanton, Brian; Phippen, Neil T; Tian, Chunqiao; Zahn, Christopher M; Cohn, David E; Havrilesky, Laura J; Berchuck, Andrew; Shriver, Craig D; Darcy, Kathleen M; Hamilton, Chad A; Conrads, Thomas P; Maxwell, G Larry

2017-10-15

The objective of this study was to identify molecular alterations associated with disease outcomes for white and black patients with endometrioid endometrial cancer (EEC). EEC samples from black (n = 17) and white patients (n = 13) were analyzed by proteomics (liquid chromatography-tandem mass spectrometry) and transcriptomics (RNA-seq). Coordinate alterations were validated with RNA-seq data from black (n = 49) and white patients (n = 216). Concordantly altered candidates were further tested for associations with race-specific progression-free survival (PFS) in black (n = 64) or white patients (n = 267) via univariate and multivariate Cox regression modeling and log-rank testing. Discovery analyses revealed significantly altered candidate proteins and transcripts between black and white patients, suggesting modulation of tumor cell viability in black patients and cell death signaling in black and white patients. Eighty-nine candidates were validated as altered between these patient cohorts, and a subset significantly correlated with differential PFS. White-specific PFS candidates included serpin family A member 4 (SERPINA4; hazard ratio [HR], 0.89; Wald P value = .02), integrin subunit α3 (ITGA3; HR, 0.76; P = .03), and Bet1 Golgi vesicular membrane trafficking protein like (BET1L; HR, 0.48; P = .04). Black-specific PFS candidates included family with sequence similarity 228 member B (FAM228B; HR, 0.13; P = .001) and HEAT repeat containing 6 (HEATR6; HR, 4.94; P = .047). Several candidates were also associated with overall survival (SERPINA4 and ITGA3) as well as PFS independent of disease stage, grade and myometrial invasion (SERPINA4, BET1L and FAM228B). This study has identified and validated molecular alterations in tumors from black and white EEC patients, including candidates significantly associated with altered disease outcomes within these patient cohorts. Cancer 2017;123:4004-12. © 2017 American Cancer Society. © 2017 American Cancer Society.

Detecting the global and regional effects of sulphate aerosol geoengineering

NASA Astrophysics Data System (ADS)

Lo, Eunice; Charlton-Perez, Andrew; Highwood, Ellie

2017-04-01

Climate warming is unequivocal. In addition to carbon dioxide emission mitigation, some geoengineering ideas have been proposed to reduce future surface temperature rise. One of these proposals involves injecting sulphate aerosols into the stratosphere to increase the planet's albedo. Monitoring the effectiveness of sulphate aerosol injection (SAI) would require us to be able to distinguish and detect its cooling effect from the climate system's internal variability and other externally forced temperature changes. This research uses optimal fingerprinting techniques together with simulations from the GeoMIP data base to estimate the number of years of observations that would be needed to detect SAI's cooling signal in near-surface air temperature, should 5 Tg of sulphur dioxide be injected into the stratosphere per year on top of RCP4.5 from 2020-2070. The first part of the research compares the application of two detection methods that have different null hypotheses to SAI detection in global mean near-surface temperature. The first method assumes climate noise to be dominated by unforced climate variability and attempts to detect the SAI cooling signal and greenhouse gas driven warming signal in the "observations" simultaneously against this noise. The second method considers greenhouse gas driven warming to be a non-stationary background climate and attempts to detect the net cooling effect of SAI against this background. Results from this part of the research show that the conventional multi-variate detection method that has been extensively used to attribute climate warming to anthropogenic sources could also be applied for geoengineering detection. The second part of the research investigates detection of geoengineering effects on the regional scale. The globe is divided into various sub-continental scale regions and the cooling effect of SAI is looked for in the temperature time series in each of these regions using total least squares multi-variate detection. Results show that surface temperature observations would be most useful for SAI detection in the Northern Hemisphere mid-latitudes, especially in East Asia. This can be used to indicate the optimal observational network for monitoring the effectiveness of SAI in the future, should that be needed.

Functional analysis of a large set of BRCA2 exon 7 variants highlights the predictive value of hexamer scores in detecting alterations of exonic splicing regulatory elements.

PubMed

Di Giacomo, Daniela; Gaildrat, Pascaline; Abuli, Anna; Abdat, Julie; Frébourg, Thierry; Tosi, Mario; Martins, Alexandra

2013-11-01

Exonic variants can alter pre-mRNA splicing either by changing splice sites or by modifying splicing regulatory elements. Often these effects are difficult to predict and are only detected by performing RNA analyses. Here, we analyzed, in a minigene assay, 26 variants identified in the exon 7 of BRCA2, a cancer predisposition gene. Our results revealed eight new exon skipping mutations in this exon: one directly altering the 5' splice site and seven affecting potential regulatory elements. This brings the number of splicing regulatory mutations detected in BRCA2 exon 7 to a total of 11, a remarkably high number considering the total number of variants reported in this exon (n = 36), all tested in our minigene assay. We then exploited this large set of splicing data to test the predictive value of splicing regulator hexamers' scores recently established by Ke et al. (). Comparisons of hexamer-based predictions with our experimental data revealed high sensitivity in detecting variants that increased exon skipping, an important feature for prescreening variants before RNA analysis. In conclusion, hexamer scores represent a promising tool for predicting the biological consequences of exonic variants and may have important applications for the interpretation of variants detected by high-throughput sequencing. © 2013 WILEY PERIODICALS, INC.

Sparse representation and Bayesian detection of genome copy number alterations from microarray data.

PubMed

Pique-Regi, Roger; Monso-Varona, Jordi; Ortega, Antonio; Seeger, Robert C; Triche, Timothy J; Asgharzadeh, Shahab

2008-02-01

Genomic instability in cancer leads to abnormal genome copy number alterations (CNA) that are associated with the development and behavior of tumors. Advances in microarray technology have allowed for greater resolution in detection of DNA copy number changes (amplifications or deletions) across the genome. However, the increase in number of measured signals and accompanying noise from the array probes present a challenge in accurate and fast identification of breakpoints that define CNA. This article proposes a novel detection technique that exploits the use of piece wise constant (PWC) vectors to represent genome copy number and sparse Bayesian learning (SBL) to detect CNA breakpoints. First, a compact linear algebra representation for the genome copy number is developed from normalized probe intensities. Second, SBL is applied and optimized to infer locations where copy number changes occur. Third, a backward elimination (BE) procedure is used to rank the inferred breakpoints; and a cut-off point can be efficiently adjusted in this procedure to control for the false discovery rate (FDR). The performance of our algorithm is evaluated using simulated and real genome datasets and compared to other existing techniques. Our approach achieves the highest accuracy and lowest FDR while improving computational speed by several orders of magnitude. The proposed algorithm has been developed into a free standing software application (GADA, Genome Alteration Detection Algorithm). http://biron.usc.edu/~piquereg/GADA

BCORL1 is an independent prognostic marker and contributes to cell migration and invasion in human hepatocellular carcinoma.

PubMed

Yin, Guozhi; Liu, Zhikui; Wang, Yufeng; Dou, Changwei; Li, Chao; Yang, Wei; Yao, Yingmin; Liu, Qingguang; Tu, Kangsheng

2016-02-15

The deregulation of E-cadherin has been considered as a leading cause of hepatocellular carcinoma (HCC) metastasis. BCL6 corepressor-like 1 (BCORL1) is a transcriptional corepressor and contributes to the repression of E-cadherin. However, the clinical significance of BCORL1 and its role in the metastasis of HCC remain unknown. Differentially expressed BCORL1 between HCC and matched tumor-adjacent tissues, HCC cell lines and normal hepatic cell line were detected by Western blot. The expression of BCORL1 was altered by siRNAs or lentivirus-mediated vectors. Transwell assays were performed to determine HCC cell invasion and migration. Increased expression of BCORL1 protein was detected in HCC specimens and cell lines. Clinical association analysis showed that BCORL1 protein was expressed at significant higher levels in HCC patients with multiple tumor nodes, venous infiltration and advanced TNM tumor stage. Survival analysis indicated that high expression of BCORL1 protein conferred shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients. Multivariate Cox regression analysis disclosed that BCORL1 expression was an independent prognostic marker for predicting survival of HCC patients. Our in vitro studies demonstrated that BCORL1 prominently promoted HCC cell migration and invasion. Otherwise, an inverse correlation between BCORL1 and E-cadherin expression was observed in HCC tissues. BCORL1 inversely regulated E-cadherin abundance and subsequently facilitated epithelial-mesenchymal transition (EMT) in HCC cells. Notably, the effect of BCORL1 knockdown on HCC cells was abrogated by E-cadherin silencing. BCORL1 may be a novel prognostic factor and promotes cell migration and invasion through E-cadherin repression-induced EMT in HCC.

Changes in metabolic markers in insulin-producing β-cells during hypoxia-induced cell death as studied by NMR metabolomics.

PubMed

Tian, Lianji; Kim, Hoe Suk; Kim, Heyonjin; Jin, Xing; Jung, Hye Seung; Park, Kyong Soo; Cho, Kyoung Won; Park, Sunghyouk; Moon, Woo Kyung

2013-08-02

This study was designed to investigate changes in the metabolites in the intracellular fluid of the pancreatic β-cell line INS-1 to identify potential early and late biomarkers for predicting hypoxia-induced cell death. INS-1 cells were incubated under normoxic conditions (95% air, 5% CO₂) or hypoxic conditions (1% O₂, 5% CO₂, 95% N₂) for 2, 4, 6, 12, or 24 h. The biological changes indicating the process of cell death were analyzed using the MTT assay, flow cytometry, Western blotting, and immunostaining. Changes in the metabolic profiles from cell lysates were identified using ¹H nuclear magnetic resonance (¹H NMR) spectroscopy, and the spectra were analyzed by the multivariate model Orthogonal Projections to Latent Structure-Discriminant Analysis. Cell viability decreased approximately 40% after 12-24 h of hypoxia, coincident with a high level of cleaved caspase-3. A high level of HIF-1α was detected in the 12-24 h hypoxic conditions. The metabolite profiles were altered according to the degree of exposure to hypoxia. A spectral analysis showed significant differences in creatine-containing compounds at the early stage (2-6 h) and taurine-containing compounds at the late stage (12-24 h), with the detection of HIF-1α and cleaved caspase-3 in cells exposed to hypoxia compared to normoxia. Glycerophosphocholine decreased during the early stage hypoxia. The change in taurine- and creatine-containing compounds and choline species could be involved in the β-cell death process as inhibitors or activators of cell death. Our results imply that assessment by ¹H NMR spectroscopy would be a useful tool to predict the cell death process and to identify molecules regulating hypoxia-induced cell death mechanisms.

Increased fibroblast density in actinic cheilitis: association with tryptase-positive mast cells, actinic elastosis and epithelial p53 and COX-2 expression.

PubMed

Rojas, Isolde G; Boza, Yadira V; Spencer, Maria Loreto; Flores, Maritza; Martínez, Alejandra

2012-01-01

Actinic cheilitis (AC) is characterized by epithelial and connective tissue alterations caused by ultraviolet sunlight overexposure known as photodamage. Fibroblasts have been linked to photodamage and tumor progression during skin carcinogenesis; however, their role in early lip carcinogenesis remains unknown. The aim of this study was to assess the density of fibroblasts in AC and normal lip (NL) samples and determine their association with markers of lip photodamage. Fibroblasts, mast cells, p53, COX-2, and elastin were detected in NL (n = 20) and AC (n = 28) biopsies using immunohistochemistry/histochemistry. Mast cell and fibroblast density and epithelial p53 and COX-2 expression scores were then obtained. Elastosis was scored 1-4 according to elastin fiber density and tortuosity. Fibroblasts, mast cells, p53, COX-2, and elastosis were increased in AC as compared to NL (P < 0.001). Multivariate analysis showed an association between fibroblast and mast cell density at the papillary and reticular areas of AC and NL (P < 0.05). Papillary fibroblast density was also associated with epithelial p53 and COX-2 expression (P < 0.05). Increased fibroblast density, both papillary and reticular, was found in the high elastosis group (scores 3-4) as compared to the low elastosis group (scores 1-2) (P < 0.01). Increased reticular mast cell density was detected only in the high elastosis group (P < 0.01). Fibroblasts are increased in AC, and they are associated with mast cell density, epithelial p53 and COX-2 expression, and actinic elastosis. Therefore, fibroblasts may contribute to lip photodamage and could be considered useful markers of early lip carcinogenesis. © 2011 John Wiley & Sons A/S.

Von Willebrand factor antigen predicts response to double dose of aspirin and clopidogrel by PFA-100 in patients undergoing primary angioplasty for ST elevation myocardial infarction.

PubMed

Gianetti, Jacopo; Parri, Maria Serena; Della Pina, Francesca; Marchi, Federica; Koni, Endrin; De Caterina, Alberto; Maffei, Stefano; Berti, Sergio

2013-01-01

Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P < 0.001). Delta of CEPI-CT (T1 - T0) was significantly related to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

Evaluation of a national data set for insights into sources, composition, and concentrations of per- and polyfluoroalkyl substances (PFASs) in U.S. drinking water.

PubMed

Guelfo, Jennifer L; Adamson, David T

2018-05-01

The United States Environmental Protection Agency (USEPA) completed nationwide screening of six perfluoroalkyl substances in U.S. drinking water from 2013 to 2015 under the Third Unregulated Contaminant Monitoring Rule (UCMR3). UCMR3 efforts yielded a dataset of 36,139 samples containing analytical results from >5000 public water systems (PWSs). This study used UCMR3 data to investigate three aspects of per- and polyfluoroalkyl substances (PFASs) in drinking water: the occurrence of PFAS and co-contaminant mixtures, trends in PFAS detections relative to PWS characteristics and potential release types, and temporal trends in PFAS occurrence. This was achieved through bivariate and multivariate analyses including categorical analysis, concentration ratios, and hierarchical cluster analysis. Approximately 50% of samples with PFAS detections contained ≥2 PFASs, and 72% of detections occurred in groundwater. Large PWSs (>10,000 customers) were 5.6 times more likely than small PWSs (≤10,000 customers) to exhibit PFAS detections; however, when detected, median total PFAS concentrations were higher in small PWSs (0.12 μg/L) than in large (0.053 μg/L). Bivariate and multivariate analyses of PFAS composition suggested PWSs reflect impacts due to firefighting foam use and WWTP effluent as compared to other source types for which data were available. Mann-Kendall analysis of quarterly total PFAS detection rates indicated an increasing trend over time (p = 0.03). UCMR3 data provide a foundation for tiered design of targeted sampling and analysis plans to address remaining knowledge gaps in the sources, composition, and concentrations of PFASs in U.S. drinking water. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Relationship between alcohol dependence and new detected hypertension in adult residents of Xuzhou city].

PubMed

Dong, Zongmei; Lou, Pei'an; Zhang, Pan; Chen, Peipei; Qiao, Cheng; Li, Ting

2015-12-01

To observe the relationship between alcohol dependence and new detected hypertension in adult residents of Xuzhou city. Participants were sampled by stratified multi-stage randomly cluster sampling method from February 2013 to June 2013 among permanent residents aged 18 and more in Xuzhou city. The alcohol dependence was defined with Michigan Alcoholism Screening Test (MAST). Other information was obtained by questionnaire. Spearman correlation analysis and multivariate logistic regression analysis were performed to identify the relationship between alcohol dependence and new detected hypertension. The alcohol dependence rate was 11.56% on the whole cohort (n=36 157), and 22.02%(3 854/17 501) for male and 1.74%(324/18 656) for female(P<0.01). The new detected hypertension rate was 9.46%(3 422/36 157) in the whole cohort. The new detected hypertension rate increased in proportion with the severity of alcohol dependence (P<0.01). Spearman correlation analysis showed that alcohol dependence was positively correlated with systemic blood pressure(r=0.071, P<0.01) and diastolic blood pressure (r=0.077, P<0.01). After adjusting for gender, age, marital status, body mass index, smoking status, physical activity level, educational level, income level and region, multivariate logistic regression analysis showed that alcohol dependence was an independent risk factor for hypertension (low alcohol dependence: OR=1.44, 95%CI 1.14-1.81, P<0.01; light alcohol dependence: OR=1.35, 95%CI 1.11-1.64, P<0.01; medium alcohol dependence: OR=1.83, 95%CI 1.40-2.41, P<0.01). The alcohol dependence is an independent risk factor for new detected hypertension in adult residents of Xuzhou city. Intensive hypertension prevention and treatment strategies should be performed on this population based on our results.

Socioeconomic Drought in a Changing Climate: Modeling and Management

NASA Astrophysics Data System (ADS)

AghaKouchak, Amir; Mehran, Ali; Mazdiyasni, Omid

2016-04-01

Drought is typically defined based on meteorological, hydrological and land surface conditions. However, in many parts of the world, anthropogenic changes and water management practices have significantly altered local water availability. Socioeconomic drought refers to conditions whereby the available water supply cannot satisfy the human and environmental water needs. Surface water reservoirs provide resilience against local climate variability (e.g., droughts), and play a major role in regional water management. This presentation focuses on a framework for describing socioeconomic drought based on both water supply and demand information. We present a multivariate approach as a measure of socioeconomic drought, termed Multivariate Standardized Reliability and Resilience Index (MSRRI; Mehran et al., 2015). This model links the information on inflow and surface reservoir storage to water demand. MSRRI integrates a "top-down" and a "bottom-up" approach for describing socioeconomic drought. The "top-down" component describes processes that cannot be simply controlled or altered by local decision-makers and managers (e.g., precipitation, climate variability, climate change), whereas the "bottom-up" component focuses on the local resilience, and societal capacity to respond to droughts. The two components (termed, Inflow-Demand Reliability (IDR) indicator and Water Storage Resilience (WSR) indicator) are integrated using a nonparametric multivariate approach. We use this framework to assess the socioeconomic drought during the Australian Millennium Drought (1998-2010) and the 2011-2014 California Droughts. MSRRI provides additional information on socioeconomic drought onset, development and termination based on local resilience and human demand that cannot be obtained from the commonly used drought indicators. We show that MSRRI can be used for water management scenario analysis (e.g., local water availability based on different human water demands scenarios). Finally, we provide examples of using the proposed modeling framework for analyzing water availability in a changing climate considering local conditions. Reference: Mehran A., Mazdiyasni O., AghaKouchak A., 2015, A Hybrid Framework for Assessing Socioeconomic Drought: Linking Climate Variability, Local Resilience, and Demand, Journal of Geophysical Research, 120 (15), 7520-7533, doi: 10.1002/2015JD023147

Human EEG responses to controlled alterations of the Earth's magnetic field.

PubMed

Sastre, Antonio; Graham, Charles; Cook, Mary R; Gerkovich, Mary M; Gailey, Paul

2002-09-01

Examine the effects of controlled changes in the Earth's magnetic field on electroencephalogram (EEG) and subjective report. Fifty volunteers were exposed double-blind to changes in field magnitude, angle of inclination, and angle of deviation. Volunteers were also exposed to magnetic field conditions found near the North and South Pole. EEG recorded over temporal and occipital sites was compared across 4s baseline, field exposure, and no-change control trials. No EEG spectral differences as a function of gender or recording site were found. Geomagnetic field alterations had no effect on total energy (0.5-42 Hz), energy within traditional EEG analysis bands, or on the 95% spectral edge. Most volunteers reported no sensations; others reported non-specific symptoms unrelated to type of field change. Three hypothesized field detection mechanisms were not supported: (1) mechanical reception through torque exerted on the ferromagnetic material magnetite; (2) movement-induced induction of an electric field in the body; and (3) enhanced sensitivity due to alterations in the rates of chemical reactions involving electron spin states. Humans have little ability to detect brief alterations in the geomagnetic field, even if these alteration are of a large magnitude.

Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

PubMed Central

Schrock, Alexa B.; Anderson, Peter M.; Morris, John C.; Heilmann, Andreas M.; Holmes, Oliver; Wang, Kai; Johnson, Adrienne; Waguespack, Steven G.; Ou, Sai‐Hong Ignatius; Khan, Saad; Fung, Kar‐Ming; Stephens, Philip J.; Erlich, Rachel L.; Miller, Vincent A.; Ross, Jeffrey S.; Ali, Siraj M.

2017-01-01

Background. Thyroid carcinoma, which is rare in pediatric patients (age 0–18 years) but more common in adolescent and young adult (AYA) patients (age 15–39 years), carries the potential for morbidity and mortality. Methods. Hybrid‐capture‐based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results. GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety‐three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of these MTC patients with novel alterations in RET experienced clinical benefit from vandetanib treatment. Conclusion. CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy. Implications for Practice. The detection of diverse clinically relevant genomic alterations in the majority of pediatric, adolescent, and young adult patients with thyroid carcinoma in this study suggests that comprehensive genomic profiling may be beneficial for young patients with papillary, anaplastic, or medullary thyroid carcinoma, particularly for advanced or refractory cases for which clinical trials involving molecularly targeted therapies may be appropriate. PMID:28209747

A multivariate analysis of age-related differences in functional networks supporting conflict resolution.

PubMed

Salami, Alireza; Rieckmann, Anna; Fischer, Håkan; Bäckman, Lars

2014-02-01

Functional neuroimaging studies demonstrate age-related differences in recruitment of a large-scale attentional network during interference resolution, especially within dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). These alterations in functional responses have been frequently observed despite equivalent task performance, suggesting age-related reallocation of neural resources, although direct evidence for a facilitating effect in aging is sparse. We used the multi-source interference task and multivariate partial-least-squares to investigate age-related differences in the neuronal signature of conflict resolution, and their behavioral implications in younger and older adults. There were interference-related increases in activity, involving fronto-parietal and basal ganglia networks that generalized across age. In addition an age-by-task interaction was observed within a distributed network, including DLPFC and ACC, with greater activity during interference in the old. Next, we combined brain-behavior and functional connectivity analyses to investigate whether compensatory brain changes were present in older adults, using DLPFC and ACC as regions of interest (i.e. seed regions). This analysis revealed two networks differentially related to performance across age groups. A structural analysis revealed age-related gray-matter losses in regions facilitating performance in the young, suggesting that functional reorganization may partly reflect structural alterations in aging. Collectively, these findings suggest that age-related structural changes contribute to reductions in the efficient recruitment of a youth-like interference network, which cascades into instantiation of a different network facilitating conflict resolution in elderly people. © 2013. Published by Elsevier Inc. All rights reserved.

Prevalence of c.2268dup and detection of two novel alterations, c.670_672del and c.1186C>T, in the TPO gene in a cohort of Malaysian-Chinese with thyroid dyshormonogenesis.

PubMed

Lee, Ching Chin; Harun, Fatimah; Jalaludin, Muhammad Yazid; Heh, Choon Han; Othman, Rozana; Junit, Sarni Mat

2015-01-05

The c.2268dup mutation in the thyroid peroxidase (TPO) gene is the most common TPO alteration reported in Taiwanese patients with thyroid dyshormonogenesis. The ancestors of these patients are believed to originate from the southern province of China. Our previous study showed that this mutation leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in a Malaysian-Chinese family with goitrous hypothyroidism. The aim of our study was to provide further data on the incidence of the c.2268dup mutation in a cohort of Malaysian-Chinese and its possible phenotypic effects. Cohort study. Twelve biologically unrelated Malaysian-Chinese patients with congenital hypothyroidism were recruited in this study. All patients showed high thyrotropin and low free thyroxine levels at the time of diagnosis with proven presence of a thyroid gland. Screening of the c.2268dup mutation in the TPO gene in all patients was carried out using a PCR-direct DNA sequencing method. Further screening for mutations in other exonic regions of the TPO gene was carried out if the patient was a carrier of the c.2268dup mutation. The c.2268dup mutation was detected in 4 of the 12 patients. Apart from the c.2268dup and a previously documented mutation (c.2647C>T), two novel TPO alterations, c.670_672del and c.1186C>T, were also detected in our patients. In silico analyses predicted that the novel alterations affect the structure/function of the TPO protein. The c.2268dup mutation was detected in approximately one-third of the Malaysian-Chinese patients with thyroid dyshormonogenesis. The detection of the novel c.670_672del and c.1186C>T alterations expand the mutation spectrum of TPO associated with thyroid dyshormonogenesis. 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.

Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer.

PubMed

Sanguedolce, Francesca; Cormio, Antonella; Massenio, Paolo; Pedicillo, Maria C; Cagiano, Simona; Fortunato, Francesca; Calò, Beppe; Di Fino, Giuseppe; Carrieri, Giuseppe; Bufo, Pantaleo; Cormio, Luigi

2018-04-01

The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

The correlations between alteration of p16 gene and clinicopathological factors and prognosis in squamous cell carcinomas of the buccal mucosa.

PubMed

Dong, Yuying; Wang, Jie; Dong, Fusheng; Wang, Xu; Zhang, Yinghuai

2012-07-01

To evaluate relationships between the alteration of p16 gene and the clinical status and prognosis of the patients with squamous cell carcinoma of the buccal mucosa. Thirty buccal cancers were included in the analysis. Deletion analysis was performed by PCR. Point mutation analysis was used by PCR-SSCP and direct sequencing. Methylation-specific PCR methods were adopted for the evaluation of p16 methylation. The correlation between alteration of p16 gene and clinicopathological factors buccal cancer was evaluated by Fisher's exact test. Kaplan-Meier and Cox regression were used to investigate the relationship between p16 alteration and survival time. The frequency of p16 alteration was 63.3% in buccal carcinomas. P16 deletion was associated significantly with tumor size (P = 0.01). P16 point mutation was associated significantly with differentiation (P = 0.006). P16 methylation was associated significantly with nodes metastasis (P = 0.027). The overall survival rate of 30 buccal carcinomas was 53.3%. The Log-rank test (P = 0.021) and univariate Cox regression analysis (P = 0.030) revealed that p16 methylation was significantly associated with the overall survival rate. Multivariate analysis showed that p16 deletion, p16 mutation, and p16 methylation were not statistically significant. The alterations of p16 gene may play a major role in malignancy and development and metastases of buccal carcinoma and may be an excellent marker of aggressive clinical behavior. P16 methylation has a prognostic value in buccal carcinoma but not an independent prognosis factor. P16 point mutation and p16 deletion have not prognostic significance in buccal carcinoma. © 2012 John Wiley & Sons A/S.

Chemical Sensor Systems and Associated Algorithms for Fire Detection: A Review.

PubMed

Fonollosa, Jordi; Solórzano, Ana; Marco, Santiago

2018-02-11

Indoor fire detection using gas chemical sensing has been a subject of investigation since the early nineties. This approach leverages the fact that, for certain types of fire, chemical volatiles appear before smoke particles do. Hence, systems based on chemical sensing can provide faster fire alarm responses than conventional smoke-based fire detectors. Moreover, since it is known that most casualties in fires are produced from toxic emissions rather than actual burns, gas-based fire detection could provide an additional level of safety to building occupants. In this line, since the 2000s, electrochemical cells for carbon monoxide sensing have been incorporated into fire detectors. Even systems relying exclusively on gas sensors have been explored as fire detectors. However, gas sensors respond to a large variety of volatiles beyond combustion products. As a result, chemical-based fire detectors require multivariate data processing techniques to ensure high sensitivity to fires and false alarm immunity. In this paper, we the survey toxic emissions produced in fires and defined standards for fire detection systems. We also review the state of the art of chemical sensor systems for fire detection and the associated signal and data processing algorithms. We also examine the experimental protocols used for the validation of the different approaches, as the complexity of the test measurements also impacts on reported sensitivity and specificity measures. All in all, further research and extensive test under different fire and nuisance scenarios are still required before gas-based fire detectors penetrate largely into the market. Nevertheless, the use of dynamic features and multivariate models that exploit sensor correlations seems imperative.

Chemical Sensor Systems and Associated Algorithms for Fire Detection: A Review

PubMed Central

Fonollosa, Jordi

2018-01-01

Indoor fire detection using gas chemical sensing has been a subject of investigation since the early nineties. This approach leverages the fact that, for certain types of fire, chemical volatiles appear before smoke particles do. Hence, systems based on chemical sensing can provide faster fire alarm responses than conventional smoke-based fire detectors. Moreover, since it is known that most casualties in fires are produced from toxic emissions rather than actual burns, gas-based fire detection could provide an additional level of safety to building occupants. In this line, since the 2000s, electrochemical cells for carbon monoxide sensing have been incorporated into fire detectors. Even systems relying exclusively on gas sensors have been explored as fire detectors. However, gas sensors respond to a large variety of volatiles beyond combustion products. As a result, chemical-based fire detectors require multivariate data processing techniques to ensure high sensitivity to fires and false alarm immunity. In this paper, we the survey toxic emissions produced in fires and defined standards for fire detection systems. We also review the state of the art of chemical sensor systems for fire detection and the associated signal and data processing algorithms. We also examine the experimental protocols used for the validation of the different approaches, as the complexity of the test measurements also impacts on reported sensitivity and specificity measures. All in all, further research and extensive test under different fire and nuisance scenarios are still required before gas-based fire detectors penetrate largely into the market. Nevertheless, the use of dynamic features and multivariate models that exploit sensor correlations seems imperative. PMID:29439490

Breast Cancer Knowledge, Behaviors, and Preferences in Malawi: Implications for Early Detection Interventions From a Discrete Choice Experiment.

PubMed

Kohler, Racquel E; Gopal, Satish; Lee, Clara N; Weiner, Bryan J; Reeve, Bryce B; Wheeler, Stephanie B

2017-10-01

Breast cancer is the most common female cancer in Africa and leading cause of death resulting from cancer; however, many countries lack early detection services. In Malawi, women are frequently diagnosed with large tumors after long symptomatic periods. Little is known about local cancer knowledge. We administered a cross-sectional survey with a discrete choice experiment to a random sample in urban and rural areas of Lilongwe district. Bivariable and multivariable analyses determined factors associated with knowledge. Preference utilities for early detection interventions were estimated using a hierarchical Bayesian model in Sawtooth software. Of 213 women recruited, fewer than half were aware of breast cancer. In multivariable analysis, electricity at home and knowing someone with cancer increased the odds of awareness. Women were more knowledgeable about symptoms than treatment or risk factors; more than 60% erroneously believed local misconceptions. Seventeen percent were aware of breast self-examination, and 20% were aware of clinical breast examination (CBE); few reported either behavior. Common barriers included not knowing where to access CBE and transportation difficulties. Discrete choice experiment results indicated the detection strategy (breast health awareness, CBE, or both) was the most important attribute of an intervention, followed by the encounter setting and travel time. Addressing misconceptions in health messages and engaging survivors to promote early detection may help improve breast cancer knowledge in Malawi. Program designs accounting for women's preferences should provide breast health education and CBEs in convenient settings to address transportation barriers, particularly for women with low socioeconomic position.

Breast Cancer Knowledge, Behaviors, and Preferences in Malawi: Implications for Early Detection Interventions From a Discrete Choice Experiment

PubMed Central

Gopal, Satish; Lee, Clara N.; Weiner, Bryan J.; Reeve, Bryce B.; Wheeler, Stephanie B.

2017-01-01

Purpose Breast cancer is the most common female cancer in Africa and leading cause of death resulting from cancer; however, many countries lack early detection services. In Malawi, women are frequently diagnosed with large tumors after long symptomatic periods. Little is known about local cancer knowledge. Methods We administered a cross-sectional survey with a discrete choice experiment to a random sample in urban and rural areas of Lilongwe district. Bivariable and multivariable analyses determined factors associated with knowledge. Preference utilities for early detection interventions were estimated using a hierarchical Bayesian model in Sawtooth software. Results Of 213 women recruited, fewer than half were aware of breast cancer. In multivariable analysis, electricity at home and knowing someone with cancer increased the odds of awareness. Women were more knowledgeable about symptoms than treatment or risk factors; more than 60% erroneously believed local misconceptions. Seventeen percent were aware of breast self-examination, and 20% were aware of clinical breast examination (CBE); few reported either behavior. Common barriers included not knowing where to access CBE and transportation difficulties. Discrete choice experiment results indicated the detection strategy (breast health awareness, CBE, or both) was the most important attribute of an intervention, followed by the encounter setting and travel time. Conclusion Addressing misconceptions in health messages and engaging survivors to promote early detection may help improve breast cancer knowledge in Malawi. Program designs accounting for women’s preferences should provide breast health education and CBEs in convenient settings to address transportation barriers, particularly for women with low socioeconomic position. PMID:29094086

Anatomical distribution and detection rate of colorectal neoplasms according to age in the colonoscopic screening of a Korean population.

PubMed

Lee, Suk-Young; Song, Wan Hee; Oh, Sang Cheul; Min, Byung-Wook; Lee, Sun Il

2018-01-01

Because data as a basis for the determination of proper age and modality for screening of colorectal neoplasms is lacking, we evaluated detection rates and anatomical distribution of colorectal neoplasms according to age in healthy individuals who underwent total colonoscopy for health checkup. A total of 16,100 cases that had received the colonoscopic examination from January to December in 2014 were analyzed. The total number of individuals who received total colonoscopy were divided by the number of individuals harboring colorectal adenoma to calculate the detection rate of colorectal adenoma. Individuals ≤50 years old were classified as young-age group and aged >50 were old-age group. Differences in anatomical locations of colorectal neoplasms were analyzed in the 2 age groups by chi-square test. Risk factors for colorectal adenoma in each age group were analyzed using univariate and multivariate logistic regression analyses. Detection rates of colorectal adenoma were 13.7% in all cases and 12.8% for those in their 40's. The main anatomical location of colorectal adenoma was proximal colon in both age groups (P < 0.001). Hyperplastic polyp was mainly distributed to the distal colon in both age groups (P < 0.001). Distal colon was the major site for colorectal cancer in the old-age group (P = 0.001). Proximal location of neoplasms was a risk factor for colorectal adenoma in both age groups with multivariate analysis. These data could be the bases for earlier initiation of screening for colorectal neoplasms with total colonoscopy to detect clinically significant colorectal polyps.

Detection of Problem Gambler Subgroups Using Recursive Partitioning

ERIC Educational Resources Information Center

Markham, Francis; Young, Martin; Doran, Bruce

2013-01-01

The multivariate socio-demographic risk factors for problem gambling have been well documented. While this body of research is valuable in determining risk factors aggregated across various populations, the majority of studies tend not to specifically identify particular subgroups of problem gamblers based on the interaction between variables. The…

A Study of Item Bias for Attitudinal Measurement Using Maximum Likelihood Factor Analysis.

ERIC Educational Resources Information Center

Mayberry, Paul W.

A technique for detecting item bias that is responsive to attitudinal measurement considerations is a maximum likelihood factor analysis procedure comparing multivariate factor structures across various subpopulations, often referred to as SIFASP. The SIFASP technique allows for factorial model comparisons in the testing of various hypotheses…

FINGERPRINT ANALYSIS OF CONTAMINANT DATA: A FORENSIC TOOL FOR EVALUATING ENVIRONMENTAL CONTAMINATION

EPA Science Inventory

Several studies have been conducted on behalf of the U .S. Environmental Protection Agency (EPA) to identify detection monitoring parameters for specific industries.1,2,3,4,5 One outcome of these studies was the evolution of an empirical multi-variant contaminant fingerprinting p...

Gut microbiota and its implications in small bowel transplantation.

PubMed

Wang, Chenyang; Li, Qiurong; Li, Jieshou

2018-06-01

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

Assessment of trace elements levels in patients with Type 2 diabetes using multivariate statistical analysis.

PubMed

Badran, M; Morsy, R; Soliman, H; Elnimr, T

2016-01-01

The trace elements metabolism has been reported to possess specific roles in the pathogenesis and progress of diabetes mellitus. Due to the continuous increase in the population of patients with Type 2 diabetes (T2D), this study aims to assess the levels and inter-relationships of fast blood glucose (FBG) and serum trace elements in Type 2 diabetic patients. This study was conducted on 40 Egyptian Type 2 diabetic patients and 36 healthy volunteers (Hospital of Tanta University, Tanta, Egypt). The blood serum was digested and then used to determine the levels of 24 trace elements using an inductive coupled plasma mass spectroscopy (ICP-MS). Multivariate statistical analysis depended on correlation coefficient, cluster analysis (CA) and principal component analysis (PCA), were used to analysis the data. The results exhibited significant changes in FBG and eight of trace elements, Zn, Cu, Se, Fe, Mn, Cr, Mg, and As, levels in the blood serum of Type 2 diabetic patients relative to those of healthy controls. The statistical analyses using multivariate statistical techniques were obvious in the reduction of the experimental variables, and grouping the trace elements in patients into three clusters. The application of PCA revealed a distinct difference in associations of trace elements and their clustering patterns in control and patients group in particular for Mg, Fe, Cu, and Zn that appeared to be the most crucial factors which related with Type 2 diabetes. Therefore, on the basis of this study, the contributors of trace elements content in Type 2 diabetic patients can be determine and specify with correlation relationship and multivariate statistical analysis, which confirm that the alteration of some essential trace metals may play a role in the development of diabetes mellitus. Copyright © 2015 Elsevier GmbH. All rights reserved.

Discordance Between Preoperative and Postoperative Bladder Cancer Location: Implications for Partial-Bladder Radiation

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

Goldsmith, Benjamin; Tucker, Kai; Conway, Robert Greg

2013-03-01

Purpose: There is strong interest in partial-bladder radiation whether as a boost or definitive therapy to limit long-term toxicity. It is unclear that a standard preoperative examination can accurately identify all sites of disease within the bladder. The purpose of this study was to determine the correlation between preoperative localization of bladder tumors with postoperative findings to facilitate partial-bladder radiation techniques when appropriate. Methods and Materials: We examined patients with clinically staged T1-T4 invasive transitional cell carcinoma (TCC) or TCC with variant histology with no history of radiation or partial cystectomy undergoing radical cystectomy. Patients were scored as “under-detected” ifmore » a bladder site was involved with invasive disease (≥T1) at the time of cystectomy, but not identified preoperatively. Patients were additionally scored as “widely under-detected” if they had postoperative lesions that were not identified preoperatively in a given site, nor in any adjacent site. Rates of under-detected and widely under-detected lesions, as well as univariate and multivariate association between clinical variables and under-detection, were evaluated using logistic regression. Results: Among 222 patients, 96% (213/222) had at least 1 area of discordance. Fifty-eight percent of patients were under-detected in at least 1 location, whereas 12% were widely under-detected. Among 24 patients with a single site of disease on preoperative evaluation, 21/24 (88%) had at least 1 under-detected lesion and 14/24 (58%) were widely under-detected. On multivariate analysis, only solitary site of preoperative disease was associated with increased levels of under-detection of invasive disease (OR = 4.161, 95% CI, 1.368-12.657). Conclusion: Our study shows a stark discordance between preoperative and postoperative localization of bladder tumors. From a clinical perspective, incomplete localization of all sites of disease within the bladder may lead to marginal misses when a partial-bladder technique is used.« less

Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis.

PubMed

de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

2015-01-01

In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8-91.5) and from detectable PSA was 18 months (IQR 11-32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery.

Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis

PubMed Central

de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

2015-01-01

Introduction: In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. Methods: We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. Results: The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8–91.5) and from detectable PSA was 18 months (IQR 11–32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. Conclusion: The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery. PMID:25624961

Discriminative Power of Arterial Spin Labeling Magnetic Resonance Imaging and 18F-Fluorodeoxyglucose Positron Emission Tomography Changes for Amyloid-β-Positive Subjects in the Alzheimer's Disease Continuum.

PubMed

Tosun, Duygu; Schuff, Norbert; Jagust, William; Weiner, Michael W

2016-01-01

Recent studies have demonstrated that arterial spin labeling magnetic resonance imaging (ASL-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) identify similar regional abnormalities and have comparable diagnostic accuracy in Alzheimer's disease (AD). The agreement between these modalities in the AD continuum, which is an important concept for early detection and disease monitoring, is yet unclear. We aimed to assess the ability of the cerebral blood flow (CBF) measures from ASL-MRI and cerebral metabolic rate for glucose (CMRgl) measures from FDG-PET to distinguish amyloid-β-positive (Aβ+) subjects in the AD continuum from healthy controls. The study included asymptomatic, cognitively normal (CN) controls and patients with early mild cognitive impairment (MCI), late MCI, and AD, all with significant levels of cortical Aβ based on their florbetapir PET scans to restrict the study to patients truly in the AD continuum. The discrimination power of each modality was based on the whole-brain patterns of CBF and CMRgl changes identified by partial least squares logistic regression, a multivariate analysis technique. While CBF changes in the posterior inferior aspects of the brain and a pattern of CMRgl changes in the superior aspects of the brain including frontal and parietal regions best discriminated the Aβ+ subjects in the early disease stages from the Aβ- CN subjects, there was a greater agreement in the whole-brain patterns of CBF and CMRgl changes that best discriminated the Aβ+ subjects from the Aβ- CN subjects in the later disease stages. Despite the differences in the whole-brain patterns of CBF and CMRgl changes, the discriminative powers of both modalities were similar with statistically nonsignificant performance differences in sensitivity and specificity. The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Aβ+ subjects across the AD continuum compared with Aβ- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum. © 2015 S. Karger AG, Basel.

Functional Testing of SLC26A4 Variants—Clinical and Molecular Analysis of a Cohort with Enlarged Vestibular Aqueduct from Austria

PubMed Central

Bernardinelli, Emanuele; Nofziger, Charity; Patsch, Wolfgang; Rasp, Gerd; Paulmichl, Markus; Dossena, Silvia

2018-01-01

The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration of the vestibular aqueduct underwent Sanger sequencing of SLC26A4 and GJB2, coding for connexin 26. The pathogenicity of sequence alterations detected was assessed by determining ion transport and molecular features of the corresponding SLC26A4 protein variants. In this group, four uncharacterized sequence alterations within the SLC26A4 coding region were found. Three of these lead to protein variants with abnormal functional and molecular features, while one should be considered with no pathogenic potential. Pathogenic SLC26A4 sequence alterations were only found in 12% of patients. SLC26A4 sequence alterations commonly found in other Caucasian populations were not detected. This survey represents the first study on the prevalence and spectrum of SLC26A4 sequence alterations in an Austrian cohort and further suggests that genetic testing should always be integrated with functional characterization and determination of the molecular features of protein variants in order to unequivocally identify or exclude a causal link between genotype and phenotype. PMID:29320412

The Use of Purified Rat Leydig Cells Complements the H295R Screen to Detect Chemical Induced Alterations in Testosterone Production

EPA Science Inventory

Exposure to endocrine disrupting contaminants can compromise testosterone production and lead to abnormal male reproductive development and altered spermatogenesis. In vitro high throughput screening (HTS) assays are needed to evaluate risk to testosterone production, yet the mai...

The Use of Purified Rat Leydig Cells Complements the H295R Screen to Detect Chemical-Induced Alterations in Testosterone Production

EPA Science Inventory

Exposure to endocrine disrupting contaminants can compromise testosterone production and lead to abnormal male reproductive development and altered spermatogenesis. In vitro high throughput screening (HTS) assays are needed to evaluate risk to testosterone production, yet the mai...

Application of a multivariate analysis method for non-target screening detection of persistent transformation products during the cork boiling wastewater treatment.

PubMed

Ponce-Robles, L; Oller, I; Agüera, A; Trinidad-Lozano, M J; Yuste, F J; Malato, S; Perez-Estrada, L A

2018-08-15

Cork boiling wastewater is a very complex mixture of naturally occurring compounds leached and partially oxidized during the boiling cycles. The effluent generated is recalcitrant and could cause a significant environmental impact. Moreover, if this untreated industrial wastewater enters a municipal wastewater treatment plant it could hamper or reduce the efficiency of most activated sludge degradation processes. Despite the efforts to treat the cork boiling wastewater for reusing purposes, is still not well-known how safe these compounds (original compounds and oxidation by-products) will be. The purpose of this work was to apply an HPLC-high resolution mass spectrometry method and subsequent non-target screening using a multivariate analysis method (PCA), to explore relationships between samples (treatments) and spectral features (masses or compounds) that could indicate changes in formation, degradation or polarity, during coagulation/flocculation (C/F) and photo-Fenton (PhF). Although, most of the signal intensities were reduced after the treatment line, 16 and 4 new peaks were detected to be formed after C/F and PhF processes respectively. The use of this non-target approach showed to be an effective strategy to explore, classify and detect transformation products during the treatment of an unknown complex mixture. Copyright © 2018 Elsevier B.V. All rights reserved.

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes

NASA Astrophysics Data System (ADS)

Wang, Qi; Grozdanic, Sinisa D.; Harper, Matthew M.; Hamouche, Nicolas; Kecova, Helga; Lazic, Tatjana; Yu, Chenxu

2011-10-01

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.

Multivariate Classification of Structural MRI Data Detects Chronic Low Back Pain

PubMed Central

Ung, Hoameng; Brown, Justin E.; Johnson, Kevin A.; Younger, Jarred; Hush, Julia; Mackey, Sean

2014-01-01

Chronic low back pain (cLBP) has a tremendous personal and socioeconomic impact, yet the underlying pathology remains a mystery in the majority of cases. An objective measure of this condition, that augments self-report of pain, could have profound implications for diagnostic characterization and therapeutic development. Contemporary research indicates that cLBP is associated with abnormal brain structure and function. Multivariate analyses have shown potential to detect a number of neurological diseases based on structural neuroimaging. Therefore, we aimed to empirically evaluate such an approach in the detection of cLBP, with a goal to also explore the relevant neuroanatomy. We extracted brain gray matter (GM) density from magnetic resonance imaging scans of 47 patients with cLBP and 47 healthy controls. cLBP was classified with an accuracy of 76% by support vector machine analysis. Primary drivers of the classification included areas of the somatosensory, motor, and prefrontal cortices—all areas implicated in the pain experience. Differences in areas of the temporal lobe, including bordering the amygdala, medial orbital gyrus, cerebellum, and visual cortex, were also useful for the classification. Our findings suggest that cLBP is characterized by a pattern of GM changes that can have discriminative power and reflect relevant pathological brain morphology. PMID:23246778

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes.

PubMed

Wang, Qi; Grozdanic, Sinisa D; Harper, Matthew M; Hamouche, Nicolas; Kecova, Helga; Lazic, Tatjana; Yu, Chenxu

2011-10-01

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.

Exploring laser-induced breakdown spectroscopy for nuclear materials analysis and in-situ applications

NASA Astrophysics Data System (ADS)

Martin, Madhavi Z.; Allman, Steve; Brice, Deanne J.; Martin, Rodger C.; Andre, Nicolas O.

2012-08-01

Laser-induced breakdown spectroscopy (LIBS) has been used to determine the limits of detection of strontium (Sr) and cesium (Cs), common nuclear fission products. Additionally, detection limits were determined for cerium (Ce), often used as a surrogate for radioactive plutonium in laboratory studies. Results were obtained using a laboratory instrument with a Nd:YAG laser at fundamental wavelength of 1064 nm, frequency doubled to 532 nm with energy of 50 mJ/pulse. The data was compared for different concentrations of Sr and Ce dispersed in a CaCO3 (white) and carbon (black) matrix. We have addressed the sampling errors, limits of detection, reproducibility, and accuracy of measurements as they relate to multivariate analysis in pellets that were doped with the different elements at various concentrations. These results demonstrate that LIBS technique is inherently well suited for in situ analysis of nuclear materials in hot cells. Three key advantages are evident: (1) small samples (mg) can be evaluated; (2) nuclear materials can be analyzed with minimal sample preparation; and (3) samples can be remotely analyzed very rapidly (ms-seconds). Our studies also show that the methods can be made quantitative. Very robust multivariate models have been used to provide quantitative measurement and statistical evaluation of complex materials derived from our previous research on wood and soil samples.

A new test of multivariate nonlinear causality

PubMed Central

Bai, Zhidong; Jiang, Dandan; Lv, Zhihui; Wong, Wing-Keung; Zheng, Shurong

2018-01-01

The multivariate nonlinear Granger causality developed by Bai et al. (2010) (Mathematics and Computers in simulation. 2010; 81: 5-17) plays an important role in detecting the dynamic interrelationships between two groups of variables. Following the idea of Hiemstra-Jones (HJ) test proposed by Hiemstra and Jones (1994) (Journal of Finance. 1994; 49(5): 1639-1664), they attempt to establish a central limit theorem (CLT) of their test statistic by applying the asymptotical property of multivariate U-statistic. However, Bai et al. (2016) (2016; arXiv: 1701.03992) revisit the HJ test and find that the test statistic given by HJ is NOT a function of U-statistics which implies that the CLT neither proposed by Hiemstra and Jones (1994) nor the one extended by Bai et al. (2010) is valid for statistical inference. In this paper, we re-estimate the probabilities and reestablish the CLT of the new test statistic. Numerical simulation shows that our new estimates are consistent and our new test performs decent size and power. PMID:29304085

A new test of multivariate nonlinear causality.

PubMed

Bai, Zhidong; Hui, Yongchang; Jiang, Dandan; Lv, Zhihui; Wong, Wing-Keung; Zheng, Shurong

2018-01-01

The multivariate nonlinear Granger causality developed by Bai et al. (2010) (Mathematics and Computers in simulation. 2010; 81: 5-17) plays an important role in detecting the dynamic interrelationships between two groups of variables. Following the idea of Hiemstra-Jones (HJ) test proposed by Hiemstra and Jones (1994) (Journal of Finance. 1994; 49(5): 1639-1664), they attempt to establish a central limit theorem (CLT) of their test statistic by applying the asymptotical property of multivariate U-statistic. However, Bai et al. (2016) (2016; arXiv: 1701.03992) revisit the HJ test and find that the test statistic given by HJ is NOT a function of U-statistics which implies that the CLT neither proposed by Hiemstra and Jones (1994) nor the one extended by Bai et al. (2010) is valid for statistical inference. In this paper, we re-estimate the probabilities and reestablish the CLT of the new test statistic. Numerical simulation shows that our new estimates are consistent and our new test performs decent size and power.

Determination of rice syrup adulterant concentration in honey using three-dimensional fluorescence spectra and multivariate calibrations

NASA Astrophysics Data System (ADS)

Chen, Quansheng; Qi, Shuai; Li, Huanhuan; Han, Xiaoyan; Ouyang, Qin; Zhao, Jiewen

2014-10-01

To rapidly and efficiently detect the presence of adulterants in honey, three-dimensional fluorescence spectroscopy (3DFS) technique was employed with the help of multivariate calibration. The data of 3D fluorescence spectra were compressed using characteristic extraction and the principal component analysis (PCA). Then, partial least squares (PLS) and back propagation neural network (BP-ANN) algorithms were used for modeling. The model was optimized by cross validation, and its performance was evaluated according to root mean square error of prediction (RMSEP) and correlation coefficient (R) in prediction set. The results showed that BP-ANN model was superior to PLS models, and the optimum prediction results of the mixed group (sunflower ± longan ± buckwheat ± rape) model were achieved as follow: RMSEP = 0.0235 and R = 0.9787 in the prediction set. The study demonstrated that the 3D fluorescence spectroscopy technique combined with multivariate calibration has high potential in rapid, nondestructive, and accurate quantitative analysis of honey adulteration.

Multivariate fault isolation of batch processes via variable selection in partial least squares discriminant analysis.

PubMed

Yan, Zhengbing; Kuang, Te-Hui; Yao, Yuan

2017-09-01

In recent years, multivariate statistical monitoring of batch processes has become a popular research topic, wherein multivariate fault isolation is an important step aiming at the identification of the faulty variables contributing most to the detected process abnormality. Although contribution plots have been commonly used in statistical fault isolation, such methods suffer from the smearing effect between correlated variables. In particular, in batch process monitoring, the high autocorrelations and cross-correlations that exist in variable trajectories make the smearing effect unavoidable. To address such a problem, a variable selection-based fault isolation method is proposed in this research, which transforms the fault isolation problem into a variable selection problem in partial least squares discriminant analysis and solves it by calculating a sparse partial least squares model. As different from the traditional methods, the proposed method emphasizes the relative importance of each process variable. Such information may help process engineers in conducting root-cause diagnosis. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Multivariate approach to matrimonial mobility in Catalonia.

PubMed

Calafell, F; Hernández, M

1993-10-01

Matrimonial mobility in Catalonia was studied using 1986 census data. Comarca (a geographic division) of birth was used as the population unit, and a measure of affinity (a statistical distance) between comarques in spouse geographic origin was defined. This distance was analyzed with multivariate methods drawn from numerical taxonomy to detect any discontinuities in matrimonial mobility and gene flow between comarques. Results show a three-level pattern of gene flow in Catalonia: (1) a strong endogamy within comarques; (2) a 100-km matrimonial circle around every comarca; and (3) the capital, Barcelona, which attracts migrants from all over Catalonia. The regionalization in matrimonial mobility follows the geographically clear-cut groups of comarques almost exactly.

Application of curve resolution algorithms in the study of drug photodegradation kinetics -- the example of moclobemide.

PubMed

Skibiński, Robert; Komsta, Łukasz

2012-01-01

The photodegradation of moclobemide was studied in methanolic media. Ultra-HPLC (UHPLC)/MS/MS analysis proved decomposition to 4-chlorobenzamide as a major degradation product and small amounts of Ro 16-3177 (4-chloro-N-[2-[(2-hydroxyethyl)amino] ethyl]benzamide) and 2-[(4-chlorobenzylidene)amino]-N-[2-ethoxyethenyl]ethenamine. The methanolic solution was investigated spectrophotometrically in the UV region, registering the spectra during 30 min of degradation. Using reference spectra and a multivariate chemometric method (multivariate curve resolution-alternating least squares), the spectra were resolved and concentration profiles were obtained. The obtained results were in good agreement with a quantitative approach, with UHPLC-diode array detection as the reference method.

Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

PubMed

Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

2009-08-01

To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

Nanoribbon field-effect transistors as direct and label-free sensors of enzyme-substrate interactions

NASA Astrophysics Data System (ADS)

Mu, Luye; Droujinine, Ilia; Rajan, Nitin; Sawtelle, Sonya; Reed, Mark

2015-03-01

The ability to measure enzyme-substrate interactions is essential in areas such as diagnostics, treatment, and biochemical screens. Many enzymatic reactions alter the pH of its environment, suggesting of a simple and direct method for detection. We show the ability of Al2O3-coated Si nanoribbon field-effect transistor biosensors to sensitively measure various aspects of enzyme-substrate interactions through measuring the pH. Urea in phosphate buffered saline (PBS) and penicillinase in PBS and urine were measured to limits of <200 μM and 0.02 units/mL, respectively. We also show the ability to extract accurate kinetics from the interaction of acetylcholine and its esterase. Prior work on FET sensors has been limited by the use of surface functionalization, which not only alters enzyme-substrate affinity, but also makes enzyme activity quantification difficult. Our method involves direct detection of reactions in solution without requiring alteration to the reactants, allowing us to obtain repeatable results and sensitive limits of detection. This method is a simple, inexpensive, and effective platform for detection of enzymatic reactions, and can be readily generalized to many unrelated classes of reactants. This work was supported in part by U.S. Army Research Office and Air Force Research Laboratory.

Molecular alterations and biomarkers in colorectal cancer

PubMed Central

Grady, William M.; Pritchard, Colin C.

2013-01-01

The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

Age-Specific Prevalence of and Risk Factors for Anal Human Papillomavirus (HPV) among Men Who Have Sex with Women and Men Who Have Sex with Men: The HPV in Men (HIM) Study

PubMed Central

Carvalho da Silva, Roberto J.; Baggio, Maria Luiza; Lu, Beibei; Smith, Danélle; Abrahamsen, Martha; Papenfuss, Mary; Villa, Luisa L.; Lazcano-Ponce, Eduardo; Giuliano, Anna R.

2011-01-01

Background. An increasing incidence of anal cancer among men suggests a need to better understand anal canal human papillomavirus (HPV) infection among human immunodeficiency virus–negative men. Methods. Genotyping for HPV was conducted on cells from the anal canal among men who have sex with women (MSW) and men who have sex with men (MSM), aged 18–70 years, from Brazil, Mexico, and the United States. Factors associated with anal HPV infection were assessed using multivariable logistic regression. Results. The prevalence of any HPV type and oncogenic HPV types did not differ by city. Anal canal HPV prevalence was 12.2% among 1305 MSW and 47.2% among 176 MSM. Among MSW, reporting a lifetime number of ≥10 female sex partners, a primary sexual relationship <1 year in duration, and a prior hepatitis B diagnosis were independently associated with detection of any anal HPV in multivariable analysis. Among MSM, a younger age, reporting ≥2 male anal sex partners in the past 3 months, and never using a condom for anal sex in the past 6 months were independently associated with detection of any anal HPV in multivariable analysis. Conclusions. Number of sex partners was associated with anal HPV infection in both MSW and MSM. Anal HPV infection in men may be mediated by age, duration of sexual relationship, and condom use. PMID:21148496

Simultaneous quantification of the boar-taint compounds skatole and androstenone by surface-enhanced Raman scattering (SERS) and multivariate data analysis.

PubMed

Sørensen, Klavs M; Westley, Chloe; Goodacre, Royston; Engelsen, Søren Balling

2015-10-01

This study investigates the feasibility of using surface-enhanced Raman scattering (SERS) for the quantification of absolute levels of the boar-taint compounds skatole and androstenone in porcine fat. By investigation of different types of nanoparticles, pH and aggregating agents, an optimized environment that promotes SERS of the analytes was developed and tested with different multivariate spectral pre-processing techniques, and this was combined with variable selection on a series of analytical standards. The resulting method exhibited prediction errors (root mean square error of cross validation, RMSECV) of 2.4 × 10(-6) M skatole and 1.2 × 10(-7) M androstenone, with a limit of detection corresponding to approximately 2.1 × 10(-11) M for skatole and approximately 1.8 × 10(-10) for androstenone. The method was subsequently tested on porcine fat extract, leading to prediction errors (RMSECV) of 0.17 μg/g for skatole and 1.5 μg/g for androstenone. It is clear that this optimized SERS method, when combined with multivariate analysis, shows great potential for optimization into an on-line application, which will be the first of its kind, and opens up possibilities for simultaneous detection of other meat-quality metabolites or pathogen markers. Graphical abstract Artistic rendering of a laser-illuminated gold colloid sphere with skatole and androstenone adsorbed on the surface.

Center for Infrastructure Assurance and Security - Attack and Defense Exercises

DTIC Science & Technology

2010-06-01

conclusion of the research funding under this program. 4.1. Steganography Detection Tools Steganography is the art of hiding information in a cover image ...Some of the more common methods are altering the LSB (least significant bit) of the pixels of the image , altering the palette of an RGB image , or...altering parts of the image in the transform domain. Algorithms that embed information in the transform domain are usually more robust to common

Gravitational Wave Detection of Compact Binaries Through Multivariate Analysis

NASA Astrophysics Data System (ADS)

Atallah, Dany Victor; Dorrington, Iain; Sutton, Patrick

2017-01-01

The first detection of gravitational waves (GW), GW150914, as produced by a binary black hole merger, has ushered in the era of GW astronomy. The detection technique used to find GW150914 considered only a fraction of the information available describing the candidate event: mainly the detector signal to noise ratios and chi-squared values. In hopes of greatly increasing detection rates, we want to take advantage of all the information available about candidate events. We employ a technique called Multivariate Analysis (MVA) to improve LIGO sensitivity to GW signals. MVA techniques are efficient ways to scan high dimensional data spaces for signal/noise classification. Our goal is to use MVA to classify compact-object binary coalescence (CBC) events composed of any combination of black holes and neutron stars. CBC waveforms are modeled through numerical relativity. Templates of the modeled waveforms are used to search for CBCs and quantify candidate events. Different MVA pipelines are under investigation to look for CBC signals and un-modelled signals, with promising results. One such MVA pipeline used for the un-modelled search can theoretically analyze far more data than the MVA pipelines currently explored for CBCs, potentially making a more powerful classifier. In principle, this extra information could improve the sensitivity to GW signals. We will present the results from our efforts to adapt an MVA pipeline used in the un-modelled search to classify candidate events from the CBC search.

Endpoint in plasma etch process using new modified w-multivariate charts and windowed regression

NASA Astrophysics Data System (ADS)

Zakour, Sihem Ben; Taleb, Hassen

2017-09-01

Endpoint detection is very important undertaking on the side of getting a good understanding and figuring out if a plasma etching process is done in the right way, especially if the etched area is very small (0.1%). It truly is a crucial part of supplying repeatable effects in every single wafer. When the film being etched has been completely cleared, the endpoint is reached. To ensure the desired device performance on the produced integrated circuit, the high optical emission spectroscopy (OES) sensor is employed. The huge number of gathered wavelengths (profiles) is then analyzed and pre-processed using a new proposed simple algorithm named Spectra peak selection (SPS) to select the important wavelengths, then we employ wavelet analysis (WA) to enhance the performance of detection by suppressing noise and redundant information. The selected and treated OES wavelengths are then used in modified multivariate control charts (MEWMA and Hotelling) for three statistics (mean, SD and CV) and windowed polynomial regression for mean. The employ of three aforementioned statistics is motivated by controlling mean shift, variance shift and their ratio (CV) if both mean and SD are not stable. The control charts show their performance in detecting endpoint especially W-mean Hotelling chart and the worst result is given by CV statistic. As the best detection of endpoint is given by the W-Hotelling mean statistic, this statistic will be used to construct a windowed wavelet Hotelling polynomial regression. This latter can only identify the window containing endpoint phenomenon.

Classification of the medicinal plants of the genus Atractylodes using high-performance liquid chromatography with diode array and tandem mass spectrometry detection combined with multivariate statistical analysis.

PubMed

Cho, Hyun-Deok; Kim, Unyong; Suh, Joon Hyuk; Eom, Han Young; Kim, Junghyun; Lee, Seul Gi; Choi, Yong Seok; Han, Sang Beom

2016-04-01

Analytical methods using high-performance liquid chromatography with diode array and tandem mass spectrometry detection were developed for the discrimination of the rhizomes of four Atractylodes medicinal plants: A. japonica, A. macrocephala, A. chinensis, and A. lancea. A quantitative study was performed, selecting five bioactive components, including atractylenolide I, II, III, eudesma-4(14),7(11)-dien-8-one and atractylodin, on twenty-six Atractylodes samples of various origins. Sample extraction was optimized to sonication with 80% methanol for 40 min at room temperature. High-performance liquid chromatography with diode array detection was established using a C18 column with a water/acetonitrile gradient system at a flow rate of 1.0 mL/min, and the detection wavelength was set at 236 nm. Liquid chromatography with tandem mass spectrometry was applied to certify the reliability of the quantitative results. The developed methods were validated by ensuring specificity, linearity, limit of quantification, accuracy, precision, recovery, robustness, and stability. Results showed that cangzhu contained higher amounts of atractylenolide I and atractylodin than baizhu, and especially atractylodin contents showed the greatest variation between baizhu and cangzhu. Multivariate statistical analysis, such as principal component analysis and hierarchical cluster analysis, were also employed for further classification of the Atractylodes plants. The established method was suitable for quality control of the Atractylodes plants. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Correlation Between Extravasation and Alterations of Cerebrovascular Laminin and β-Dystroglycan Immunoreactivity Following Cryogenic Lesions in Rats.

PubMed

Kálmán, Mihály; Tóth, László; Szöllosi, Dávid; Oszwald, Erzsébet; Mahalek, Judit; Sadeghian, Sam

2017-11-01

The blood-brain barrier becomes "leaky" following lesions. Former studies revealed that following lesions the immunoreactivity of cerebrovascular laminin becomes detectable whereas that of β-dystroglycan disappears. These alterations may be indicators of glio-vascular decoupling that may result in the impairment of the blood-brain-barrier. This study investigates correlation between the post-lesion extravasation and the above-mentioned immunohistochemical alterations. Following cryogenic lesions, the survival periods lasted 5, 10, 30 minutes, 1 or 12 hours, or 1 day. Some brains were fixed immediately post-lesion. Immunofluorescent reactions were performed in floating sections. The extravasation was detected with immunostaining for plasma fibronectin and rat immunoglobulins. When the survival period was 30 minutes or longer, the area of extravasation corresponded to the area of altered laminin and β-dystroglycan immunoreactivities. Following immediate fixation some laminin immunoreactivity was already detected. The extravasation seemed to precede this early appearance of laminin immunoreactivity. The β-dystroglycan immunoreactivity disappeared later. When the extravasation spread into the corpus callosum, vascular laminin immunoreactivity appeared but the β-dystroglycan immunoreactivity persisted. It seems that extravasation separates the glial and vascular basal laminae, which results in the appearance of laminin immunoreactivity. The disappearance of β-dystroglycan immunoreactivity is neither a condition nor an inevitable consequence of the 2 other phenomena. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Stability of medicines after repackaging into multicompartment compliance aids: eight criteria for detection of visual alteration.

PubMed

Albert, Valerie; Lanz, Michael; Imanidis, Georgios; Hersberger, Kurt E; Arnet, Isabelle

2017-01-01

Multicompartment compliance aids (MCA) are widely used by patients. They support the management of medication and reduce unintentional nonadherence. MCA are filled with medicines unpacked from their original packaging. Swiss pharmacists currently provide MCA for 1-2 weeks, although little and controversial information exists on the stability of repackaged medicines. We aimed to validate the usefulness of a simple screening method capable of detecting visual stability problems with repackaged medicines. We selected eight criteria for solid formulations from The International Pharmacopoeia : (1) rough surface, (2) chipping, (3) cracking, (4) capping, (5) mottling, (6) discoloration, (7) swelling, and (8) crushing. A selection of 24 critical medicines was repackaged in three different MCA (Pharmis ® , SureMed™, and self-produced blister) and stored at room temperature for 4 weeks. Pharmis ® was additionally stored at accelerated conditions. Appearance was scored weekly. Six alterations (rough surface, cracking, mottling, discoloration, swelling, and crushing) were observed at accelerated conditions. No alteration was observed at room temperature, except for the chipping of tablets that had been stuck to cold seal glue. The eight criteria can detect alterations of the appearance of oral solid medicines repackaged in MCA. In the absence of specific guidelines, they can serve as a simple screening method in community pharmacies for identifying medicines unsuitable for repackaging.

Multivariate pattern dependence

PubMed Central

Saxe, Rebecca

2017-01-01

When we perform a cognitive task, multiple brain regions are engaged. Understanding how these regions interact is a fundamental step to uncover the neural bases of behavior. Most research on the interactions between brain regions has focused on the univariate responses in the regions. However, fine grained patterns of response encode important information, as shown by multivariate pattern analysis. In the present article, we introduce and apply multivariate pattern dependence (MVPD): a technique to study the statistical dependence between brain regions in humans in terms of the multivariate relations between their patterns of responses. MVPD characterizes the responses in each brain region as trajectories in region-specific multidimensional spaces, and models the multivariate relationship between these trajectories. We applied MVPD to the posterior superior temporal sulcus (pSTS) and to the fusiform face area (FFA), using a searchlight approach to reveal interactions between these seed regions and the rest of the brain. Across two different experiments, MVPD identified significant statistical dependence not detected by standard functional connectivity. Additionally, MVPD outperformed univariate connectivity in its ability to explain independent variance in the responses of individual voxels. In the end, MVPD uncovered different connectivity profiles associated with different representational subspaces of FFA: the first principal component of FFA shows differential connectivity with occipital and parietal regions implicated in the processing of low-level properties of faces, while the second and third components show differential connectivity with anterior temporal regions implicated in the processing of invariant representations of face identity. PMID:29155809

A novel SERRS sandwich-hybridization assay to detect specific DNA target.

PubMed

Feuillie, Cécile; Merheb, Maxime Mohamad; Gillet, Benjamin; Montagnac, Gilles; Daniel, Isabelle; Hänni, Catherine

2011-01-01

In this study, we have applied Surface Enhanced Resonance Raman Scattering (SERRS) technology to the specific detection of DNA. We present an innovative SERRS sandwich-hybridization assay that allows specific DNA detection without any enzymatic amplification, such as is the case with Polymerase Chain Reaction (PCR). In some substrates, such as ancient or processed remains, enzymatic amplification fails due to DNA alteration (degradation, chemical modification) or to the presence of inhibitors. Consequently, the development of a non-enzymatic method, allowing specific DNA detection, could avoid long, expensive and inconclusive amplification trials. Here, we report the proof of concept of a SERRS sandwich-hybridization assay that leads to the detection of a specific chamois DNA. This SERRS assay reveals its potential as a non-enzymatic alternative technology to DNA amplification methods (particularly the PCR method) with several applications for species detection. As the amount and type of damage highly depend on the preservation conditions, the present SERRS assay would enlarge the range of samples suitable for DNA analysis and ultimately would provide exciting new opportunities for the investigation of ancient DNA in the fields of evolutionary biology and molecular ecology, and of altered DNA in food frauds detection and forensics.

A Novel SERRS Sandwich-Hybridization Assay to Detect Specific DNA Target

PubMed Central

Gillet, Benjamin; Montagnac, Gilles; Daniel, Isabelle; Hänni, Catherine

2011-01-01

In this study, we have applied Surface Enhanced Resonance Raman Scattering (SERRS) technology to the specific detection of DNA. We present an innovative SERRS sandwich-hybridization assay that allows specific DNA detection without any enzymatic amplification, such as is the case with Polymerase Chain Reaction (PCR). In some substrates, such as ancient or processed remains, enzymatic amplification fails due to DNA alteration (degradation, chemical modification) or to the presence of inhibitors. Consequently, the development of a non-enzymatic method, allowing specific DNA detection, could avoid long, expensive and inconclusive amplification trials. Here, we report the proof of concept of a SERRS sandwich-hybridization assay that leads to the detection of a specific chamois DNA. This SERRS assay reveals its potential as a non-enzymatic alternative technology to DNA amplification methods (particularly the PCR method) with several applications for species detection. As the amount and type of damage highly depend on the preservation conditions, the present SERRS assay would enlarge the range of samples suitable for DNA analysis and ultimately would provide exciting new opportunities for the investigation of ancient DNA in the fields of evolutionary biology and molecular ecology, and of altered DNA in food frauds detection and forensics. PMID:21655320

Designing a risk-based surveillance program for Mycobacterium avium ssp. paratuberculosis in Norwegian dairy herds using multivariate statistical process control analysis.

PubMed

Whist, A C; Liland, K H; Jonsson, M E; Sæbø, S; Sviland, S; Østerås, O; Norström, M; Hopp, P

2014-11-01

Surveillance programs for animal diseases are critical to early disease detection and risk estimation and to documenting a population's disease status at a given time. The aim of this study was to describe a risk-based surveillance program for detecting Mycobacterium avium ssp. paratuberculosis (MAP) infection in Norwegian dairy cattle. The included risk factors for detecting MAP were purchase of cattle, combined cattle and goat farming, and location of the cattle farm in counties containing goats with MAP. The risk indicators included production data [culling of animals >3 yr of age, carcass conformation of animals >3 yr of age, milk production decrease in older lactating cows (lactations 3, 4, and 5)], and clinical data (diarrhea, enteritis, or both, in animals >3 yr of age). Except for combined cattle and goat farming and cattle farm location, all data were collected at the cow level and summarized at the herd level. Predefined risk factors and risk indicators were extracted from different national databases and combined in a multivariate statistical process control to obtain a risk assessment for each herd. The ordinary Hotelling's T(2) statistic was applied as a multivariate, standardized measure of difference between the current observed state and the average state of the risk factors for a given herd. To make the analysis more robust and adapt it to the slowly developing nature of MAP, monthly risk calculations were based on data accumulated during a 24-mo period. Monitoring of these variables was performed to identify outliers that may indicate deviance in one or more of the underlying processes. The highest-ranked herds were scattered all over Norway and clustered in high-density dairy cattle farm areas. The resulting rankings of herds are being used in the national surveillance program for MAP in 2014 to increase the sensitivity of the ongoing surveillance program in which 5 fecal samples for bacteriological examination are collected from 25 dairy herds. The use of multivariate statistical process control for selection of herds will be beneficial when a diagnostic test suitable for mass screening is available and validated on the Norwegian cattle population, thus making it possible to increase the number of sampled herds. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Satellite image collection optimization

NASA Astrophysics Data System (ADS)

Martin, William

2002-09-01

Imaging satellite systems represent a high capital cost. Optimizing the collection of images is critical for both satisfying customer orders and building a sustainable satellite operations business. We describe the functions of an operational, multivariable, time dynamic optimization system that maximizes the daily collection of satellite images. A graphical user interface allows the operator to quickly see the results of what if adjustments to an image collection plan. Used for both long range planning and daily collection scheduling of Space Imaging's IKONOS satellite, the satellite control and tasking (SCT) software allows collection commands to be altered up to 10 min before upload to the satellite.

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.

Tuning the properties of conjugated polyelectrolytes and application in a biosensor platform

DOEpatents

Chen, Liaohai

2004-05-18

The present invention provides a method of detecting a biological agent including contacting a sample with a sensor including a polymer system capable of having an alterable measurable property from the group of luminescence, anisotropy, redox potential and uv/vis absorption, the polymer system including an ionic conjugated polymer and an electronically inert polyelectrolyte having a biological agent recognition element bound thereto, the electronically inert polyelectrolyte adapted for undergoing a conformational structural change upon exposure to a biological agent having affinity for binding to the recognition element bound to the electronically inert polyelectrolyte, and, detecting the detectable change in the alterable measurable property. A chemical moiety being the reaction product of (i) a polyelectrolyte monomer and (ii) a biological agent recognition element-substituted polyelectrolyte monomer is also provided.

Assessment of flow regime alterations over a spectrum of temporal scales using wavelet-based approaches

NASA Astrophysics Data System (ADS)

Wu, Fu-Chun; Chang, Ching-Fu; Shiau, Jenq-Tzong

2015-05-01

The full range of natural flow regime is essential for sustaining the riverine ecosystems and biodiversity, yet there are still limited tools available for assessment of flow regime alterations over a spectrum of temporal scales. Wavelet analysis has proven useful for detecting hydrologic alterations at multiple scales via the wavelet power spectrum (WPS) series. The existing approach based on the global WPS (GWPS) ratio tends to be dominated by the rare high-power flows so that alterations of the more frequent low-power flows are often underrepresented. We devise a new approach based on individual deviations between WPS (DWPS) that are root-mean-squared to yield the global DWPS (GDWPS). We test these two approaches on the three reaches of the Feitsui Reservoir system (Taiwan) that are subjected to different classes of anthropogenic interventions. The GDWPS reveal unique features that are not detected with the GWPS ratios. We also segregate the effects of individual subflow components on the overall flow regime alterations using the subflow GDWPS. The results show that the daily hydropeaking waves below the reservoir not only intensified the flow oscillations at daily scale but most significantly eliminated subweekly flow variability. Alterations of flow regime were most severe below the diversion weir, where the residual hydropeaking resulted in a maximum impact at daily scale while the postdiversion null flows led to large hydrologic alterations over submonthly scales. The smallest impacts below the confluence reveal that the hydrologic alterations at scales longer than 2 days were substantially mitigated with the joining of the unregulated tributary flows, whereas the daily-scale hydrologic alteration was retained because of the hydropeaking inherited from the reservoir releases. The proposed DWPS approach unravels for the first time the details of flow regime alterations at these intermediate scales that are overridden by the low-frequency high-power flows when the long-term averaged GWPS are used.

Obese asthmatic patients have decreased surfactant protein A levels: Mechanisms and implications.

PubMed

Lugogo, Njira; Francisco, Dave; Addison, Kenneth J; Manne, Akarsh; Pederson, William; Ingram, Jennifer L; Green, Cynthia L; Suratt, Benjamin T; Lee, James J; Sunday, Mary E; Kraft, Monica; Ledford, Julie G

2018-03-01

Eosinophils are prominent in some patients with asthma and are increased in the submucosa in a subgroup of obese patients with asthma (OAs). Surfactant protein A (SP-A) modulates host responses to infectious and environmental insults. We sought to determine whether SP-A levels are altered in OAs compared with a control group and to determine the implications of these alterations in SP-A levels in asthmatic patients. Bronchoalveolar lavage fluid from 23 lean, 12 overweight, and 20 obese subjects were examined for SP-A. Mouse tracheal epithelial cells grown at an air-liquid interface were used for mechanistic studies. SP-A -/- mice were challenged in allergen models, and exogenous SP-A therapy was given after the last challenge. Eosinophils were visualized and quantitated in lung parenchyma by means of immunostaining. Significantly less SP-A (P = .002) was detected in samples from OAs compared with those from control subjects. A univariable regression model found SP-A levels were significantly negatively correlated with body mass index (r = -0.33, P = .014), whereas multivariable modeling demonstrated that the correlation depended both on asthma status (P = .017) and the interaction of asthma and body mass index (P = .008). Addition of exogenous TNF-α to mouse tracheal epithelial cells was sufficient to attenuate SP-A and eotaxin secretion. Allergen-challenged SP-A -/- mice that received SP-A therapy had significantly less tissue eosinophilia compared with mice receiving vehicle. SP-A functions as an important mediator in resolving tissue and lavage fluid eosinophilia in allergic mouse models. Decreased levels of SP-A in OAs, which could be due to increased local TNF-α levels, might lead to impaired eosinophil resolution and could contribute to the eosinophilic asthma phenotype. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Left Ventricular Geometry and Blood Pressure as Predictors of Adverse Progression of Fabry Cardiomyopathy.

PubMed

Krämer, Johannes; Bijnens, Bart; Störk, Stefan; Ritter, Christian O; Liu, Dan; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

2015-01-01

In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated. In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed. Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05). LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy.

Left Ventricular Geometry and Blood Pressure as Predictors of Adverse Progression of Fabry Cardiomyopathy

PubMed Central

Krämer, Johannes; Bijnens, Bart; Störk, Stefan; Ritter, Christian O.; Liu, Dan; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

2015-01-01

Background In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated. Methods In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed. Results Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05). Conclusions LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy. PMID:26600044

Hyperspectral fluorescence imaging using violet LEDs as excitation sources for fecal matter contaminate identification on spinach leaves

USDA-ARS?s Scientific Manuscript database

Food safety in the production of fresh produce for human consumption is a worldwide issue and needs to be addressed to decrease foodborne illnesses and resulting costs. Hyperspectral fluorescence imaging coupled with multivariate image analysis techniques for detection of fecal contaminates on spina...

Evaluation of statistical protocols for quality control of ecosystem carbon dioxide fluxes

Treesearch

Jorge F. Perez-Quezada; Nicanor Z. Saliendra; William E. Emmerich; Emilio A. Laca

2007-01-01

The process of quality control of micrometeorological and carbon dioxide (CO2) flux data can be subjective and may lack repeatability, which would undermine the results of many studies. Multivariate statistical methods and time series analysis were used together and independently to detect and replace outliers in CO2 flux...

A multivariate analysis of genetic constraints to life history evolution in a wild population of red deer.

PubMed

Walling, Craig A; Morrissey, Michael B; Foerster, Katharina; Clutton-Brock, Tim H; Pemberton, Josephine M; Kruuk, Loeske E B

2014-12-01

Evolutionary theory predicts that genetic constraints should be widespread, but empirical support for their existence is surprisingly rare. Commonly applied univariate and bivariate approaches to detecting genetic constraints can underestimate their prevalence, with important aspects potentially tractable only within a multivariate framework. However, multivariate genetic analyses of data from natural populations are challenging because of modest sample sizes, incomplete pedigrees, and missing data. Here we present results from a study of a comprehensive set of life history traits (juvenile survival, age at first breeding, annual fecundity, and longevity) for both males and females in a wild, pedigreed, population of red deer (Cervus elaphus). We use factor analytic modeling of the genetic variance-covariance matrix ( G: ) to reduce the dimensionality of the problem and take a multivariate approach to estimating genetic constraints. We consider a range of metrics designed to assess the effect of G: on the deflection of a predicted response to selection away from the direction of fastest adaptation and on the evolvability of the traits. We found limited support for genetic constraint through genetic covariances between traits, both within sex and between sexes. We discuss these results with respect to other recent findings and to the problems of estimating these parameters for natural populations. Copyright © 2014 Walling et al.

A Multivariate Analysis of Genetic Constraints to Life History Evolution in a Wild Population of Red Deer

PubMed Central

Walling, Craig A.; Morrissey, Michael B.; Foerster, Katharina; Clutton-Brock, Tim H.; Pemberton, Josephine M.; Kruuk, Loeske E. B.

2014-01-01

Evolutionary theory predicts that genetic constraints should be widespread, but empirical support for their existence is surprisingly rare. Commonly applied univariate and bivariate approaches to detecting genetic constraints can underestimate their prevalence, with important aspects potentially tractable only within a multivariate framework. However, multivariate genetic analyses of data from natural populations are challenging because of modest sample sizes, incomplete pedigrees, and missing data. Here we present results from a study of a comprehensive set of life history traits (juvenile survival, age at first breeding, annual fecundity, and longevity) for both males and females in a wild, pedigreed, population of red deer (Cervus elaphus). We use factor analytic modeling of the genetic variance–covariance matrix (G) to reduce the dimensionality of the problem and take a multivariate approach to estimating genetic constraints. We consider a range of metrics designed to assess the effect of G on the deflection of a predicted response to selection away from the direction of fastest adaptation and on the evolvability of the traits. We found limited support for genetic constraint through genetic covariances between traits, both within sex and between sexes. We discuss these results with respect to other recent findings and to the problems of estimating these parameters for natural populations. PMID:25278555

Total anthocyanin content determination in intact açaí (Euterpe oleracea Mart.) and palmitero-juçara (Euterpe edulis Mart.) fruit using near infrared spectroscopy (NIR) and multivariate calibration.

PubMed

Inácio, Maria Raquel Cavalcanti; de Lima, Kássio Michell Gomes; Lopes, Valquiria Garcia; Pessoa, José Dalton Cruz; de Almeida Teixeira, Gustavo Henrique

2013-02-15

The aim of this study was to evaluate near-infrared reflectance spectroscopy (NIR), and multivariate calibration potential as a rapid method to determinate anthocyanin content in intact fruit (açaí and palmitero-juçara). Several multivariate calibration techniques, including partial least squares (PLS), interval partial least squares, genetic algorithm, successive projections algorithm, and net analyte signal were compared and validated by establishing figures of merit. Suitable results were obtained with the PLS model (four latent variables and 5-point smoothing) with a detection limit of 6.2 g kg(-1), limit of quantification of 20.7 g kg(-1), accuracy estimated as root mean square error of prediction of 4.8 g kg(-1), mean selectivity of 0.79 g kg(-1), sensitivity of 5.04×10(-3) g kg(-1), precision of 27.8 g kg(-1), and signal-to-noise ratio of 1.04×10(-3) g kg(-1). These results suggest NIR spectroscopy and multivariate calibration can be effectively used to determine anthocyanin content in intact açaí and palmitero-juçara fruit. Copyright © 2012 Elsevier Ltd. All rights reserved.

Towards better process understanding: chemometrics and multivariate measurements in manufacturing of solid dosage forms.

PubMed

Matero, Sanni; van Den Berg, Frans; Poutiainen, Sami; Rantanen, Jukka; Pajander, Jari

2013-05-01

The manufacturing of tablets involves many unit operations that possess multivariate and complex characteristics. The interactions between the material characteristics and process related variation are presently not comprehensively analyzed due to univariate detection methods. As a consequence, current best practice to control a typical process is to not allow process-related factors to vary i.e. lock the production parameters. The problem related to the lack of sufficient process understanding is still there: the variation within process and material properties is an intrinsic feature and cannot be compensated for with constant process parameters. Instead, a more comprehensive approach based on the use of multivariate tools for investigating processes should be applied. In the pharmaceutical field these methods are referred to as Process Analytical Technology (PAT) tools that aim to achieve a thorough understanding and control over the production process. PAT includes the frames for measurement as well as data analyzes and controlling for in-depth understanding, leading to more consistent and safer drug products with less batch rejections. In the optimal situation, by applying these techniques, destructive end-product testing could be avoided. In this paper the most prominent multivariate data analysis measuring tools within tablet manufacturing and basic research on operations are reviewed. Copyright © 2013 Wiley Periodicals, Inc.

Describing the complexity of systems: multivariable "set complexity" and the information basis of systems biology.

PubMed

Galas, David J; Sakhanenko, Nikita A; Skupin, Alexander; Ignac, Tomasz

2014-02-01

Context dependence is central to the description of complexity. Keying on the pairwise definition of "set complexity," we use an information theory approach to formulate general measures of systems complexity. We examine the properties of multivariable dependency starting with the concept of interaction information. We then present a new measure for unbiased detection of multivariable dependency, "differential interaction information." This quantity for two variables reduces to the pairwise "set complexity" previously proposed as a context-dependent measure of information in biological systems. We generalize it here to an arbitrary number of variables. Critical limiting properties of the "differential interaction information" are key to the generalization. This measure extends previous ideas about biological information and provides a more sophisticated basis for the study of complexity. The properties of "differential interaction information" also suggest new approaches to data analysis. Given a data set of system measurements, differential interaction information can provide a measure of collective dependence, which can be represented in hypergraphs describing complex system interaction patterns. We investigate this kind of analysis using simulated data sets. The conjoining of a generalized set complexity measure, multivariable dependency analysis, and hypergraphs is our central result. While our focus is on complex biological systems, our results are applicable to any complex system.

Buried landmine detection using multivariate normal clustering

NASA Astrophysics Data System (ADS)

Duston, Brian M.

2001-10-01

A Bayesian classification algorithm is presented for discriminating buried land mines from buried and surface clutter in Ground Penetrating Radar (GPR) signals. This algorithm is based on multivariate normal (MVN) clustering, where feature vectors are used to identify populations (clusters) of mines and clutter objects. The features are extracted from two-dimensional images created from ground penetrating radar scans. MVN clustering is used to determine the number of clusters in the data and to create probability density models for target and clutter populations, producing the MVN clustering classifier (MVNCC). The Bayesian Information Criteria (BIC) is used to evaluate each model to determine the number of clusters in the data. An extension of the MVNCC allows the model to adapt to local clutter distributions by treating each of the MVN cluster components as a Poisson process and adaptively estimating the intensity parameters. The algorithm is developed using data collected by the Mine Hunter/Killer Close-In Detector (MH/K CID) at prepared mine lanes. The Mine Hunter/Killer is a prototype mine detecting and neutralizing vehicle developed for the U.S. Army to clear roads of anti-tank mines.

Multivariate statistical analysis strategy for multiple misfire detection in internal combustion engines

NASA Astrophysics Data System (ADS)

Hu, Chongqing; Li, Aihua; Zhao, Xingyang

2011-02-01

This paper proposes a multivariate statistical analysis approach to processing the instantaneous engine speed signal for the purpose of locating multiple misfire events in internal combustion engines. The state of each cylinder is described with a characteristic vector extracted from the instantaneous engine speed signal following a three-step procedure. These characteristic vectors are considered as the values of various procedure parameters of an engine cycle. Therefore, determination of occurrence of misfire events and identification of misfiring cylinders can be accomplished by a principal component analysis (PCA) based pattern recognition methodology. The proposed algorithm can be implemented easily in practice because the threshold can be defined adaptively without the information of operating conditions. Besides, the effect of torsional vibration on the engine speed waveform is interpreted as the presence of super powerful cylinder, which is also isolated by the algorithm. The misfiring cylinder and the super powerful cylinder are often adjacent in the firing sequence, thus missing detections and false alarms can be avoided effectively by checking the relationship between the cylinders.

Multivariate curve resolution-assisted determination of pseudoephedrine and methamphetamine by HPLC-DAD in water samples.

PubMed

Vosough, Maryam; Mohamedian, Hadi; Salemi, Amir; Baheri, Tahmineh

2015-02-01

In the present study, a simple strategy based on solid-phase extraction (SPE) with a cation exchange sorbent (Finisterre SCX) followed by fast high-performance liquid chromatography (HPLC) with diode array detection coupled with chemometrics tools has been proposed for the determination of methamphetamine and pseudoephedrine in ground water and river water. At first, the HPLC and SPE conditions were optimized and the analytical performance of the method was determined. In the case of ground water, determination of analytes was successfully performed through univariate calibration curves. For river water sample, multivariate curve resolution and alternating least squares was implemented and the second-order advantage was achieved in samples containing uncalibrated interferences and uncorrected background signals. The calibration curves showed good linearity (r(2) > 0.994).The limits of detection for pseudoephedrine and methamphetamine were 0.06 and 0.08 μg/L and the average recovery values were 104.7 and 102.3% in river water, respectively. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Surface Enhanced Raman Spectroscopy (SERS) and multivariate analysis as a screening tool for detecting Sudan I dye in culinary spices

NASA Astrophysics Data System (ADS)

Di Anibal, Carolina V.; Marsal, Lluís F.; Callao, M. Pilar; Ruisánchez, Itziar

2012-02-01

Raman spectroscopy combined with multivariate analysis was evaluated as a tool for detecting Sudan I dye in culinary spices. Three Raman modalities were studied: normal Raman, FT-Raman and SERS. The results show that SERS is the most appropriate modality capable of providing a proper Raman signal when a complex matrix is analyzed. To get rid of the spectral noise and background, Savitzky-Golay smoothing with polynomial baseline correction and wavelet transform were applied. Finally, to check whether unadulterated samples can be differentiated from samples adulterated with Sudan I dye, an exploratory analysis such as principal component analysis (PCA) was applied to raw data and data processed with the two mentioned strategies. The results obtained by PCA show that Raman spectra need to be properly treated if useful information is to be obtained and both spectra treatments are appropriate for processing the Raman signal. The proposed methodology shows that SERS combined with appropriate spectra treatment can be used as a practical screening tool to distinguish samples suspicious to be adulterated with Sudan I dye.

Dyes assay for measuring physicochemical parameters.

PubMed

Moczko, Ewa; Meglinski, Igor V; Bessant, Conrad; Piletsky, Sergey A

2009-03-15

A combination of selective fluorescent dyes has been developed for simultaneous quantitative measurements of several physicochemical parameters. The operating principle of the assay is similar to electronic nose and tongue systems, which combine nonspecific or semispecific elements for the determination of diverse analytes and chemometric techniques for multivariate data analysis. The analytical capability of the proposed mixture is engendered by changes in fluorescence signal in response to changes in environment such as pH, temperature, ionic strength, and presence of oxygen. The signal is detected by a three-dimensional spectrofluorimeter, and the acquired data are processed using an artificial neural network (ANN) for multivariate calibration. The fluorescence spectrum of a solution of selected dyes allows discreet reading of emission maxima of all dyes composing the mixture. The variations in peaks intensities caused by environmental changes provide distinctive fluorescence patterns which can be handled in the same way as the signals collected from nose/tongue electrochemical or piezoelectric devices. This optical system opens possibilities for rapid, inexpensive, real-time detection of a multitude of physicochemical parameters and analytes of complex samples.

Using Boosting Decision Trees in Gravitational Wave Searches triggered by Gamma-ray Bursts

NASA Astrophysics Data System (ADS)

Zuraw, Sarah; LIGO Collaboration

2015-04-01

The search for gravitational wave bursts requires the ability to distinguish weak signals from background detector noise. Gravitational wave bursts are characterized by their transient nature, making them particularly difficult to detect as they are similar to non-Gaussian noise fluctuations in the detector. The Boosted Decision Tree method is a powerful machine learning algorithm which uses Multivariate Analysis techniques to explore high-dimensional data sets in order to distinguish between gravitational wave signal and background detector noise. It does so by training with known noise events and simulated gravitational wave events. The method is tested using waveform models and compared with the performance of the standard gravitational wave burst search pipeline for Gamma-ray Bursts. It is shown that the method is able to effectively distinguish between signal and background events under a variety of conditions and over multiple Gamma-ray Burst events. This example demonstrates the usefulness and robustness of the Boosted Decision Tree and Multivariate Analysis techniques as a detection method for gravitational wave bursts. LIGO, UMass, PREP, NEGAP.

Altered plasma lipidome profile of dairy cows with fatty liver disease.

PubMed

Gerspach, C; Imhasly, S; Gubler, M; Naegeli, H; Ruetten, M; Laczko, E

2017-02-01

Fatty liver disease is a common health problem of dairy cows occurring during the transition from pregnancy to lactation. It is a direct response to fat mobilization due to negative energy balance. Accumulation of lipids in the liver occurs if the uptake of non-esterified fatty acids by the liver exceeds the capacity of lipid oxidation or secretion by the liver. Currently, the diagnosis of fatty liver disease requires confirmation through biopsies to determine the hepatic lipid content. In view of this lack of a practical diagnostic tool, we compared the plasma lipidome of diseased dairy cows using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Multivariate data analysis yielded 20 m/z values that were able to distinguish between dairy cows with no hepatic lipidosis and those exhibiting different stages of the disease. Based on the chromatography retention time and m/z ratios, we identified phosphatidylcholines with reduced plasma abundances in cows with fatty liver disease. The abundances of different bile acids tended to be increased. In addition, we detected two metabolites related to inflammation, resolvin E1 and palmitoyl-ethanolamine (PEA), which need to be further investigated in cattle. These results indicate that the measurement of specific representatives of phosphatidylcholines in plasma may provide a novel diagnostic biomarker of fatty liver disease in dairy cows. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum metabolite profiles are altered by erlotinib treatment and the integrin α1-null genotype, but not by post traumatic osteoarthritis

PubMed Central

Mickiewicz, Beata; Shin, Sung Y.; Pozzi, Ambra; Vogel, Hans J.; Clark, Andrea L.

2016-01-01

The risk of developing post traumatic osteoarthritis (PTOA) following joint injury is high. Furthering our understanding of the molecular mechanisms underlying PTOA and/or identifying novel biomarkers for early detection may help improve treatment outcomes. Increased expression of integrin α1β1 and inhibition of epidermal growth factor receptor (EGFR) signaling protect the knee from spontaneous OA, however the impact of the integrin α1β1/EGFR axis on PTOA is currently unknown. We sought to determine metabolic changes in serum samples collected from wild type and integrin α1-null mice that underwent surgery to destabilize the medial meniscus and were treated with the EGFR inhibitor erlotinib. Following 1H nuclear magnetic resonance spectroscopy we generated multivariate statistical models that distinguished between the metabolic profiles of erlotinib- versus vehicle-treated mice, and the integrin α1-null versus wild type mouse genotype. Our results show the sex dependent effects of erlotinib treatment and highlight glutamine as a metabolite that counteracts this treatment. Furthermore, we identified a set of metabolites associated with increased reactive oxygen species production, susceptibility to OA and regulation of TRP channels in α1-null mice. Our study indicates that systemic pharmacological and genetic factors have a greater effect on serum metabolic profiles than site specific factors such as surgery. PMID:26784366

Plantar loading changes with alterations in foot strike patterns during a single session in habitual rear foot strike female runners.

PubMed

Kernozek, Thomas W; Vannatta, Charles N; Gheidi, Naghmeh; Kraus, Sydnie; Aminaka, Naoko

2016-03-01

Characterize plantar loading parameters when habitually rear foot strike (RFS) runners change their pattern to a non-rear foot strike (NRFS). Experimental. University biomechanics laboratory. Twenty three healthy female runners (Age: 22.17 ± 1.64 yrs; Height: 168.91 ± 5.46 cm; Mass: 64.29 ± 7.11 kg). Plantar loading was measured using an in-sole pressure sensor while running down a 20-m runway restricted to a range of 3.52-3.89 m/s under two conditions, using the runner's typical RFS, and an adapted NRFS pattern. Repeated measures multivariate analysis of variance was performed to detect differences in loading between these two conditions. Force and pressure variables were greater in the forefoot and phalanx in NRFS and greater in the heel and mid foot in RFS pattern, but the total force imposed upon the whole foot and contact time remained similar between conditions. Total peak pressure was higher and contact area was lower during NRFS running. The primary finding of this investigation is that there are distinctly different plantar loads when changing from a RFS to NRFS during running. So, during a transition from RFS to a NRFS pattern; a period of acclimation should be considered to allow for adaptations to these novel loads incurred on plantar regions of the foot. Copyright © 2015 Elsevier Ltd. All rights reserved.

Saturated fatty acids as possible important metabolites for epithelial ovarian cancer based on the free and esterified fatty acid profiles determined by GC-MS analysis.

PubMed

Yin, Rui; Yang, Tongshu; Su, Hui; Ying, Li; Liu, Liyan; Sun, Changhao

2016-09-26

The aims were to investigate the serum free fatty acid (FFA) and esterified fatty acid (EFA) profiles and to identify biomarkers that can be used to identify patients with epithelial ovarian cancer (EOC) based on the metabolomics approach. We applied a targeted gas chromatography-mass spectrometry metabolomics approach to serum samples from 40 EOC patients and 35 healthy controls for achieving the FFA and EFA profiles. These metabolite profiles were processed using multivariate analysis to obtain potential biomarkers. And then, some independent samples were chosen to validate these potential biomarkers. There were higher saturated fatty acids and lower unsaturated fatty acids in EOC patients when compared with the healthy controls. EFA (C16:0), EFA (C18:0) and FFA (C16:0) were identified as potential biomarkers that distinguished EOC from the healthy controls. The areas under the curve from the EFA (C16:0), EFA (C18:0) and FFA (C16:0) in validated study were 0.745, 0.701, 0.682, respectively. Our study provides useful information to bridge the gaps in our understanding to the fatty acids metabolic alterations associated with EOC, and this study has demonstrated saturated fatty acid biomarkers might be helpful for the detection and characterization of EOC patients.

An Integrated Strategy to Qualitatively Differentiate Components of Raw and Processed Viticis Fructus Based on NIR, HPLC and UPLC-MS Analysis.

PubMed

Diao, Jiayin; Xu, Can; Zheng, Huiting; He, Siyi; Wang, Shumei

2018-06-21

Viticis Fructus is a traditional Chinese herbal drug processed by various methods to achieve different clinical purposes. Thermal treatment potentially alters chemical composition, which may impact on effectiveness and toxicity. In order to interpret the constituent discrepancies of raw versus processed (stir-fried) Viticis Fructus, a multivariate detection method (NIR, HPLC, and UPLC-MS) based on metabonomics and chemometrics was developed. Firstly, synergy interval partial least squares and partial least squares-discriminant analysis were employed to screen the distinctive wavebands (4319 - 5459 cm -1 ) based on preprocessed near-infrared spectra. Then, HPLC with principal component analysis was performed to characterize the distinction. Subsequently, a total of 49 compounds were identified by UPLC-MS, among which 42 compounds were eventually characterized as having a significant change during processing via the semiquantitative volcano plot analysis. Moreover, based on the partial least squares-discriminant analysis, 16 compounds were chosen as characteristic markers that could be in close correlation with the discriminatory near-infrared wavebands. Together, all of these characterization techniques effectively discriminated raw and processed products of Viticis Fructus. In general, our work provides an integrated way of classifying Viticis Fructus, and a strategy to explore discriminatory chemical markers for other traditional Chinese herbs, thus ensuring safety and efficacy for consumers. Georg Thieme Verlag KG Stuttgart · New York.

Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis.

PubMed

Chen, Rui; Han, Su; Liu, Xuefeng; Wang, Kunpeng; Zhou, Yong; Yang, Chundong; Zhang, Xi

2018-05-15

Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA. Copyright © 2018 Elsevier B.V. All rights reserved.

Soil-borne microbial functional structure across different land uses.

PubMed

Kuramae, Eiko E; Zhou, Jizhong Z; Kowalchuk, George A; van Veen, Johannes A

2014-01-01

Land use change alters the structure and composition of microbial communities. However, the links between environmental factors and microbial functions are not well understood. Here we interrogated the functional structure of soil microbial communities across different land uses. In a multivariate regression tree analysis of soil physicochemical properties and genes detected by functional microarrays, the main factor that explained the different microbial community functional structures was C : N ratio. C : N ratio showed a significant positive correlation with clay and soil pH. Fields with low C : N ratio had an overrepresentation of genes for carbon degradation, carbon fixation, metal reductase, and organic remediation categories, while fields with high C : N ratio had an overrepresentation of genes encoding dissimilatory sulfate reductase, methane oxidation, nitrification, and nitrogen fixation. The most abundant genes related to carbon degradation comprised bacterial and fungal cellulases; bacterial and fungal chitinases; fungal laccases; and bacterial, fungal, and oomycete polygalacturonases. The high number of genes related to organic remediation was probably driven by high phosphate content, while the high number of genes for nitrification was probably explained by high total nitrogen content. The functional gene diversity found in different soils did not group the sites accordingly to land management. Rather, the soil factors, C : N ratio, phosphate, and total N, were the main factors driving the differences in functional genes across the fields examined.

Which adherence measure - self-report, clinician recorded or pharmacy refill - is best able to predict detectable viral load in a public ART programme without routine plasma viral load monitoring?

PubMed

Mekuria, Legese A; Prins, Jan M; Yalew, Alemayehu W; Sprangers, Mirjam A G; Nieuwkerk, Pythia T

2016-07-01

Combination antiretroviral therapy (cART) suppresses viral replication to an undetectable level if a sufficiently high level of adherence is achieved. We investigated which adherence measurement best distinguishes between patients with and without detectable viral load in a public ART programme without routine plasma viral load monitoring. We randomly selected 870 patients who started cART between May 2009 and April 2012 in 10 healthcare facilities in Addis Ababa, Ethiopia. Six hundred and sixty-four (76.3%) patients who were retained in HIV care and were receiving cART for at least 6 months were included and 642 had their plasma HIV-1 RNA concentration measured. Patients' adherence to cART was assessed according to self-report, clinician recorded and pharmacy refill measures. Multivariate logistic regression model was fitted to identify the predictors of detectable viremia. Model accuracy was evaluated by computing the area under the receiver operating characteristic (ROC) curve. A total of 9.2% and 5.5% of the 642 patients had a detectable viral load of ≥40 and ≥400 RNA copies/ml, respectively. In the multivariate analyses, younger age, lower CD4 cell count at cART initiation, being illiterate and widowed, and each of the adherence measures were significantly and independently predictive of having ≥400 RNA copies/ml. The ROC curve showed that these variables altogether had a likelihood of more than 80% to distinguish patients with a plasma viral load of ≥400 RNA copies/ml from those without. Adherence to cART was remarkably high. Self-report, clinician recorded and pharmacy refill non-adherence were all significantly predictive of detectable viremia. The choice for one of these methods to detect non-adherence and predict a detectable viral load can therefore be based on what is most practical in a particular setting. © 2016 John Wiley & Sons Ltd.

Sensitivity of Helicobacter pylori detection by Giemsa staining is poor in comparison with immunohistochemistry and fluorescent in situ hybridization and strongly depends on inflammatory activity.

PubMed

Kocsmár, Éva; Szirtes, Ildikó; Kramer, Zsófia; Szijártó, Attila; Bene, László; Buzás, György Miklós; Kenessey, István; Bronsert, Peter; Csanadi, Agnes; Lutz, Lisa; Werner, Martin; Wellner, Ulrich Friedrich; Kiss, András; Schaff, Zsuzsa; Lotz, Gábor

2017-08-01

Conventional stainings (including H&E and special stains like Giemsa) are the most widely applied histopathologic detection methods of Helicobacter pylori (HP). We aimed to compare the diagnostic performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and relate results to histologic alterations in order to find such histopathologic subgroups in which these methods underperform. All cases were categorized regarding presence or absence of chronic gastritis, inflammatory activity, and mucosal structural alterations. Giemsa revealed 687 cases (23.7%), IHC 795 cases (27.5%), and FISH 788 cases (27.2%) as being HP positive. Giemsa showed significantly lower overall sensitivity (83.3%) compared to IHC (98.8%) and FISH (98.0%). Moreover, the sensitivity of Giemsa dramatically dropped to 33.6% in the nonactive cases. We found that sensitivity of Giemsa strongly depends on HP density and, accordingly, on the presence of activity. Structural alterations (intestinal metaplasia, atrophy, etc.) had only no or weak effect on sensitivity of the three stainings. Both IHC and FISH proved to be equally reliable HP detecting techniques whose diagnostic performance is minimally influenced by mucosal inflammatory and structural alterations contrary to conventional stainings. We highly recommend immunohistochemistry for clinically susceptible, nonactive chronic gastritis cases, if the conventional stain-based HP detection is negative. Moreover, we recommend to use IHC more widely as basic HP stain. Helicobacter pylori FISH technique is primarily recommended to determine bacterial clarithromycin resistance. Furthermore, it is another accurate diagnostic tool for HP. © 2017 John Wiley & Sons Ltd.

Diagnosis and classification of hematologic malignancies on the basis of genetics

PubMed Central

2017-01-01

Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia. Among patients with MDS, detection of mutations in SF3B1 define a subgroup of patients with the ring sideroblast form of MDS and a favorable prognosis. For patients with MPNs, detection of the BCR-ABL1 fusion delineates chronic myeloid leukemia from classic BCR-ABL1− MPNs, which are largely defined by mutations in JAK2, CALR, or MPL. In the B-cell lymphomas, detection of characteristic rearrangements involving MYC in Burkitt lymphoma, BCL2 in follicular lymphoma, and MYC/BCL2/BCL6 in high-grade B-cell lymphomas are essential for diagnosis. In T-cell lymphomas, anaplastic large-cell lymphoma is defined by mutually exclusive rearrangements of ALK, DUSP22/IRF4, and TP63. Genetic alterations affecting TP53 and the mutational status of the immunoglobulin heavy-chain variable region are important in clinical management of chronic lymphocytic leukemia. Additionally, detection of BRAFV600E mutations is helpful in the diagnosis of classical hairy cell leukemia and a number of histiocytic neoplasms. Numerous additional examples provided here demonstrate how clinical evaluation of genomic alterations have refined classification of myeloid neoplasms and major forms of lymphomas arising from B, T, or natural killer cells. PMID:28600336

Detection of target staphylococcal enterotoxin B antigen in orange juice and popular carbonated beverages using antibody-dependent antigen-capture assays.

PubMed

Principato, MaryAnn; Njoroge, Joyce M; Perlloni, Andrei; O' Donnell, Michael; Boyle, Thomas; Jones, Robert L

2010-10-01

There is a critical need for qualitative and quantitative methodologies that provide the rapid and accurate detection of food contaminants in complex food matrices. However, the sensitivity of the assay can be affected when antigen-capture is applied to certain foods or beverages that are extremely acidic. This study was undertaken to assess the effects of orange juice and popular carbonated soft drink upon the fidelity of antibody-based antigen-capture assays and to develop simple approaches that could rescue assay performance without the introduction of additional or extensive extraction procedures. We examined the effects of orange juice and a variety of popular carbonated soft drink beverages upon a quantitative Interleukin-2 (IL-2) enzyme-linked immunosorbent assay (ELISA) assay system and a lateral flow device (LFD) adapted for the detection of staphylococcal enterotoxin B (SEB) in foods. Alterations in the performance and sensitivity of the assay were directly attributable to the food matrix, and alterations in pH were especially critical. The results demonstrate that approaches such as an alteration of pH and the use of milk as a blocking agent, either singly or in combination, will partially rescue ELISA performance. The same approaches permit lateral flow to efficiently detect antigen. Practical Application: The authors present ways to rescue an ELISA assay compromised by acidity in beverages and show that either the alteration of pH, or the use of milk as a blocking agent are not always capable of restoring the assay to its intended efficiency. However, the same methods, when employed with lateral flow technology, are rapid and extremely successful.

Memory blindness: Altered memory reports lead to distortion in eyewitness memory.

PubMed

Cochran, Kevin J; Greenspan, Rachel L; Bogart, Daniel F; Loftus, Elizabeth F

2016-07-01

Choice blindness refers to the finding that people can often be misled about their own self-reported choices. However, little research has investigated the more long-term effects of choice blindness. We examined whether people would detect alterations to their own memory reports, and whether such alterations could influence participants' memories. Participants viewed slideshows depicting crimes, and then either reported their memories for episodic details of the event (Exp. 1) or identified a suspect from a lineup (Exp. 2). Then we exposed participants to manipulated versions of their memory reports, and later tested their memories a second time. The results indicated that the majority of participants failed to detect the misinformation, and that exposing witnesses to misleading versions of their own memory reports caused their memories to change to be consistent with those reports. These experiments have implications for eyewitness memory.

Acidification and γ-aminobutyric acid independently alter kairomone-induced behaviour

PubMed Central

Cohen, Jonathan H.

2016-01-01

Exposure to high pCO2 or low pH alters sensation and behaviour in many marine animals. We show that crab larvae lose their ability to detect and/or process predator kairomones after exposure to low pH over a time scale relevant to diel pH cycles in coastal environments. Previous work suggests that acidification affects sensation and behaviour through altered neural function, specifically the action of γ-aminobutyric acid (GABA), because a GABA antagonist, gabazine, restores the original behaviour. Here, however, gabazine resulted in a loss of kairomone detection/processing, regardless of pH. Our results also suggest that GABAergic signalling is necessary for kairomone identification in these larvae. Hence, the mechanism for the observed pH effect varies from the original GABA hypothesis. Furthermore, we suggest that this pH effect is adaptive under diel-cycling pH. PMID:27703697

Molecular genetic heterogeneity in undifferentiated endometrial carcinomas.

PubMed

Rosa-Rosa, Juan M; Leskelä, Susanna; Cristóbal-Lana, Eva; Santón, Almudena; López-García, Ma Ángeles; Muñoz, Gloria; Pérez-Mies, Belen; Biscuola, Michele; Prat, Jaime; Esther, Oliva E; Soslow, Robert A; Matias-Guiu, Xavier; Palacios, Jose

2016-11-01

Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole-exome sequencing of the endometrioid and undifferentiated components, as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group, whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumors. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumors, which may have prognostic value.

Molecular genetic heterogeneity in undifferentiated endometrial carcinomas

PubMed Central

Rosa-Rosa, J.M.; Leskelä, S.; Cristóbal-Lana, E.; Santón, A.; López-García, M.A.; Muñoz, G.; Pérez-Mies, B.; Biscuola, M; Prat, J.; Oliva, E.; Soslow, R.A.; Matias-Guiu, X.; Palacios, J.

2017-01-01

Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumours, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole exome sequencing of the endometrioid and undifferentiated components as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: a) hypermutated tumours with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); c) high copy number alterations (copy-number high) tumours group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%) ; and d) low copy number alterations (copy-number low) tumours with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumours. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumours, which may have prognostic value. PMID:27491810

Síndrome metabólico y otros factores asociados a gonartrosis.

PubMed

Charles-Lozoya, Sergio; Treviño-Báez, Joaquín Darío; Ramos-Rivera, Jesús Alejandro; Rangel-Flores, Jesús María; Tamez-Montes, Juan Carlos; Brizuela-Ventura, Jesús Miguel

2017-01-01

To evaluate whether an association exists between gonarthrosis and metabolic syndrome X (MS) as well as other potential risk factors. Comparative cross-sectional study of 310 patients evaluated by pathology of knee grouped in patients with gonarthrosis and without it. Sociodemographic, anthropometric and laboratory data was obtained. Gonarthrosis was defined as a ≥ 2 score in Kellgren-Lawrence radiological scale, and MS was assessed using the International Diabetes Federation criteria. Odds ratio and logistic regression were used for bivariate and multivariate analysis respectively. The prevalence of MS in patients who had gonarthrosis was 79.9%, statistically higher than in patients without gonarthrosis (p = 0.001). Other factors that had a statistically higher frequency in this group included diabetes mellitus (p = 0.02) and hypertension (p = 0.02). Multivariate analysis revealed MS had an association with a higher prevalence of gonarthrosis (p = 0.003), while high density lipoproteins (p = 0.02) was associated with a lower prevalence. MS and its related alterations are associated to gonarthrosis; their adequate control could prevent patients from developing the disease. Copyright: © 2017 SecretarÍa de Salud

AMBI indices and multivariate approach to assess the ecological health of Vellar-Coleroon estuarine system undergoing various human activities.

PubMed

Sigamani, Sivaraj; Perumal, Murugesan; Arumugam, Silambarasan; Preetha Mini Jose, H M; Veeraiyan, Bharathidasan

2015-11-15

Estuaries receive a considerable amount of pollutants from various sources. Presently an attempt has been made to assess whether the aquaculture discharges and dredging activities alter the ecological conditions of Vellar-Coleroon estuarine complex. The European Water Framework Directive (WFD) established a framework for the protection of marine waters. In this commission, a variety of indices were used, among them, AMBI (AZTI Marine Biotic Index) indices along with multivariate statistical approach is unique, to assess the ecological status by using macrobenthic communities. Keeping this in view, stations VE-1 and VE-4 in Vellar; CE-6 and CE-7 in Coleroon estuaries showed moderately disturbed with the AMBI values ranging between 3.45 and 3.72. The above said stations were situated near the shrimp farm discharge point and sites of dredging activities. The present study proves that various statistical and biotic indices have great potential in assessing the nature of the ecosystem undergoing various human pressures. Copyright © 2015 Elsevier Ltd. All rights reserved.

The use of time-series data in the assessment of macrobenthic community change after the cessation of sewage-sludge disposal in Liverpool Bay (UK).

PubMed

Whomersley, P; Schratzberger, M; Huxham, M; Bates, H; Rees, H

2007-01-01

Sewage sludge was disposed of in Liverpool Bay for over 100 years. Annual amounts increased from 0.5 million tonnes per annum in 1900 to approximately 2 million tonnes per annum by 1995. Macrofauna and a suite of environmental variables were collected at a station adjacent to, and a reference station distant from, the disposal site over 13 years, spanning a pre- (1990-1998) and post- (1999-2003) cessation period. Univariate and multivariate analyses of the time-series data showed significant community differences between reference and disposal site stations and multivariate analyses revealed station-specific community development post-disposal. Temporal variability of communities collected at the disposal station post-cessation was higher than during years of disposal, when temporally stable dominance patterns of disturbance-tolerant species had established. Alterations of community structure post-disturbance reflected successional changes possibly driven by facilitation. Subtle faunistic changes at the Liverpool Bay disposal site indicate that the near-field effects of the disposal of sewage sludge were small and therefore could be considered environmentally acceptable.

The deferred embryo transfer strategy improves cumulative pregnancy rates in endometriosis-related infertility: A retrospective matched cohort study

PubMed Central

Maignien, Chloé; Gayet, Vanessa; Pocate-Cheriet, Khaled; Marcellin, Louis; Chapron, Charles

2018-01-01

Background Controlled ovarian stimulation in assisted reproduction technology (ART) may alters endometrial receptivity by an advancement of endometrial development. Recently, technical improvements in vitrification make deferred frozen-thawed embryo transfer (Def-ET) a feasible alternative to fresh embryo transfer (ET). In endometriosis-related infertility the eutopic endometrium is abnormal and its functional alterations are seen as likely to alter the quality of endometrial receptivity. One question in the endometriosis ART-management is to know whether Def-ET could restore optimal receptivity in endometriosis-affected women leading to increase in pregnancy rates. Objective To compare cumulative ART-outcomes between fresh versus Def-ET in endometriosis-infertile women. Materials and methods This matched cohort study compared def-ET strategy to fresh ET strategy between 01/10/2012 and 31/12/2014. One hundred and thirty-five endometriosis-affected women with a scheduled def-ET cycle and 424 endometriosis-affected women with a scheduled fresh ET cycle were eligible for matching. Matching criteria were: age, number of prior ART cycles, and endometriosis phenotype. Statistical analyses were conducted using univariable and multivariable logistic regression models. Results 135 in the fresh ET group and 135 in the def-ET group were included in the analysis. The cumulative clinical pregnancy rate was significantly increased in the def-ET group compared to the fresh ET group [58 (43%) vs. 40 (29.6%), p = 0.047]. The cumulative ongoing pregnancy rate was 34.8% (n = 47) and 17.8% (n = 24) respectively in the Def-ET and the fresh-ET groups (p = 0.005). After multivariable conditional logistic regression analysis, Def-ET was associated with a significant increase in the cumulative ongoing pregnancy rate as compared to fresh ET (OR = 1.76, CI95% 1.06–2.92, p = 0.028). Conclusion Def-ET in endometriosis-affected women was associated with significantly higher cumulative ongoing pregnancy rates. Our preliminary results suggest that Def-ET for endometriosis-affected women is an attractive option that could increase their ART success rates. Future studies, with a randomized design, should be conducted to further confirm those results. PMID:29630610

Risk factors for bowel dysfunction after sphincter-preserving rectal cancer surgery: a prospective study using the Memorial Sloan Kettering Cancer Center bowel function instrument.

PubMed

Ihn, Myong Hoon; Kang, Sung-Bum; Kim, Duck-Woo; Oh, Heung-Kwon; Lee, Soo Young; Hong, Sa Min

2014-08-01

Until recently, no studies have prospectively evaluated bowel function after sphincter-preserving surgery for rectal cancer with the use of a validated bowel function scoring system. The aim of this study was to investigate possible risk factors for altered bowel function after sphincter-preserving surgery. This was a prospective study. The study was conducted between January 2006 and May 2012 at the authors' institution. Patients who underwent sphincter-preserving rectal cancer surgery were recruited. Bowel function was assessed 1 day before (baseline) and at 1 year after sphincter-preserving surgery or temporary ileostomy takedown with the use of the Memorial Sloan Kettering Cancer Center questionnaire. Multivariable analysis was performed to identify the factors associated with altered bowel function after surgery. Overall, 266 patients were eligible for the analysis. The tumor was located in the upper, middle, and lower rectum in 68 (25.5%), 113 (42.5%), and 85 (32.0%) patients. Intersphincteric resection and temporary ileostomy were performed in 18 (6.8%) and 129 (48.5%) patients. The mean Memorial Sloan Kettering Cancer Center score was 64.5 ± 7.6 at 1 year after sphincter-preserving surgery or temporary ileostomy takedown. The Memorial Sloan Kettering Cancer Center score decreased in 163/266 patients (61.3%) between baseline and 1 year after surgery. Tumor location (p = 0.01), operative method (p = 0.03), anastomotic type (p = 0.01), and temporary ileostomy (p = 0.01) were associated with altered bowel function after sphincter-preserving surgery in univariate analyses. In multivariable analysis, only tumor location was independently associated with impaired bowel function after sphincter-preserving rectal cancer surgery. This study was limited by its nonrandomized design and the lack of measurement before preoperative chemoradiotherapy. We suggest that preoperative counseling should be implemented to inform patients of the risk of bowel dysfunction, especially in patients with lower rectal cancer, although this study cannot exclude the effect of chemoradiotherapy owing to the limitation of study.

Signatures of Subacute Potentially Catastrophic Illness in the ICU: Model Development and Validation.

PubMed

Moss, Travis J; Lake, Douglas E; Calland, J Forrest; Enfield, Kyle B; Delos, John B; Fairchild, Karen D; Moorman, J Randall

2016-09-01

Patients in ICUs are susceptible to subacute potentially catastrophic illnesses such as respiratory failure, sepsis, and hemorrhage that present as severe derangements of vital signs. More subtle physiologic signatures may be present before clinical deterioration, when treatment might be more effective. We performed multivariate statistical analyses of bedside physiologic monitoring data to identify such early subclinical signatures of incipient life-threatening illness. We report a study of model development and validation of a retrospective observational cohort using resampling (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis type 1b internal validation) and a study of model validation using separate data (type 2b internal/external validation). University of Virginia Health System (Charlottesville), a tertiary-care, academic medical center. Critically ill patients consecutively admitted between January 2009 and June 2015 to either the neonatal, surgical/trauma/burn, or medical ICUs with available physiologic monitoring data. None. We analyzed 146 patient-years of vital sign and electrocardiography waveform time series from the bedside monitors of 9,232 ICU admissions. Calculations from 30-minute windows of the physiologic monitoring data were made every 15 minutes. Clinicians identified 1,206 episodes of respiratory failure leading to urgent unplanned intubation, sepsis, or hemorrhage leading to multi-unit transfusions from systematic individual chart reviews. Multivariate models to predict events up to 24 hours prior had internally validated C-statistics of 0.61-0.88. In adults, physiologic signatures of respiratory failure and hemorrhage were distinct from each other but externally consistent across ICUs. Sepsis, on the other hand, demonstrated less distinct and inconsistent signatures. Physiologic signatures of all neonatal illnesses were similar. Subacute potentially catastrophic illnesses in three diverse ICU populations have physiologic signatures that are detectable in the hours preceding clinical detection and intervention. Detection of such signatures can draw attention to patients at highest risk, potentially enabling earlier intervention and better outcomes.

The impact of colorectal screening program on the detection of right-sided colorectal cancer. A 5-year cohort study in the Mantua District.

PubMed

Asteria, Corrado R; Pucciarelli, Salvatore; Gerard, Leonardo; Mantovani, Nicola; Pagani, Mauro; Boccia, Luigi; Ricci, Paolo; Troiano, Luigi; Lucchini, Giuseppe; Pulica, Coriolano

2015-12-01

High rates of advanced colorectal cancer (CRC) are still diagnosed in the right side of the colon. This study aimed to investigate whether screening programs increase CRC detection and whether tumor location is associated with survival outcome. Patients affected by CRC, aged from 50 to 69 years and operated on from 2005 to 2009 were reviewed. Other than patient-, disease-, and treatment-related factors, detection mode and tumor location were recorded. Overall (OS) and disease-free survival (DFS) were investigated, using univariate and multivariate analyses. Mean age of 386 patients included was 62.0 years, 59 % were males. CRC was detected by screening in 17 % of cases, and diagnosis was made from symptoms in 67 % and emergency surgery for 16 %. Screen-detected CRCs were located in the left colon (59 %), then in rectum (25 %) and in proximal colon (16 %) (p = 0.02). Most of CRC patients urgently operated on had cancer located in proximal colon (45 %), then in the left colon (36 %) and in rectum (18 %) (p = 0.001). Right-sided CRC demonstrated higher pTNM stage (p = 0.001), adequate harvest count nodes (p = 0.0001), metastatic nodes (p = 0.02), and poor differentiation grading (p = 0.0001). With multivariate analysis, poor differentiation grade was independently associated with both worse OS (HR 3.6, p = 0.05) and worse DFS (HR 8.1, p = 0.0001), while distant recurrence was associated with worse OS (HR 20.1, p = 0.0001). Low rates of right-sided CRC are diagnosed following screening program. Proximal CRC demonstrates aggressive behavior without impact on outcome. These findings prompt concern about population awareness for CRC screening.

Manipulation Detection and Preference Alterations in a Choice Blindness Paradigm

PubMed Central

Taya, Fumihiko; Gupta, Swati; Farber, Ilya; Mullette-Gillman, O'Dhaniel A.

2014-01-01

Objectives It is commonly believed that individuals make choices based upon their preferences and have access to the reasons for their choices. Recent studies in several areas suggest that this is not always the case. In choice blindness paradigms, two-alternative forced-choice in which chosen-options are later replaced by the unselected option, individuals often fail to notice replacement of their chosen option, confabulate explanations for why they chose the unselected option, and even show increased preferences for the unselected-but-replaced options immediately after choice (seconds). Although choice blindness has been replicated across a variety of domains, there are numerous outstanding questions. Firstly, we sought to investigate how individual- or trial-factors modulated detection of the manipulations. Secondly, we examined the nature and temporal duration (minutes vs. days) of the preference alterations induced by these manipulations. Methods Participants performed a computerized choice blindness task, selecting the more attractive face between presented pairs of female faces, and providing a typewritten explanation for their choice on half of the trials. Chosen-face cue manipulations were produced on a subset of trials by presenting the unselected face during the choice explanation as if it had been selected. Following all choice trials, participants rated the attractiveness of each face individually, and rated the similarity of each face pair. After approximately two weeks, participants re-rated the attractiveness of each individual face online. Results Participants detected manipulations on only a small proportion of trials, with detections by fewer than half of participants. Detection rates increased with the number of prior detections, and detection rates subsequent to first detection were modulated by the choice certainty. We show clear short-term modulation of preferences in both manipulated and non-manipulated explanation trials compared to choice-only trials (with opposite directions of effect). Preferences were altered in the direction that subjects were led to believe they selected. PMID:25247886

Linking Deforestation to Malaria in the Amazon: Characterization of the Breeding Habitat of the Principal Malaria Vector, Anopheles darlingi

PubMed Central

Vittor, Amy Y.; Pan, William; Gilman, Robert H.; Tielsch, James; Glass, Gregory; Shields, Tim; Sánchez-Lozano, Wagner; Pinedo, Viviana V.; Salas-Cobos, Erit; Flores, Silvia; Patz, Jonathan A.

2009-01-01

This study examined the larval breeding habitat of a major South American malaria vector, Anopheles darlingi, in areas with varying degrees of ecologic alteration in the Peruvian Amazon. Water bodies were repeatedly sampled across 112 km of transects along the Iquitos-Nauta road in ecologically varied areas. Field data and satellite imagery were used to determine the landscape composition surrounding each site. Seventeen species of Anopheles larvae were collected. Anopheles darlingi larvae were present in 87 of 844 sites (10.3%). Sites with A. darlingi larvae had an average of 24.1% forest cover, compared with 41.0% for sites without A. darlingi (P < 0.0001). Multivariate analysis identified seasonality, algae, water body size, presence of human populations, and the amount of forest and secondary growth as significant determinants of A. darlingi presence. We conclude that deforestation and associated ecologic alterations are conducive to A. darlingi larval presence, and thereby increase malaria risk. PMID:19556558

Population-level coordination of pigment response in individual cyanobacterial cells under altered nitrogen levels

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

Murton, Jaclyn; Nagarajan, Aparna; Nguyen, Amelia Y.

Cyanobacterial phycobilisome (PBS) pigment-protein complexes harvest light and transfer the energy to reaction centers. Previous ensemble studies have shown that cyanobacteria respond to changes in nutrient availability by modifying the structure of PBS complexes, but this process has not been visualized for individual pigments at the single-cell level due to spectral overlap. We characterized the response of four key photosynthetic pigments to nitrogen depletion and repletion at the subcellular level in individual, live Synechocystis sp. PCC 6803 cells using hyperspectral confocal fluorescence microscopy and multivariate image analysis. Our results revealed that PBS degradation and re-synthesis comprise a rapid response tomore » nitrogen fluctuations, with coordinated populations of cells undergoing pigment modifications. Chlorophyll fluorescence originating from photosystem I and II decreased during nitrogen starvation, but no alteration in subcellular chlorophyll localization was found. Lastly, we observed differential rod and core pigment responses to nitrogen deprivation, suggesting that PBS complexes undergo a stepwise degradation process.« less

Benthic foraminifera as indicators of habitat change in anthropogenically impacted coastal wetlands of the Ebro Delta (NE Iberian Peninsula).

PubMed

Benito, Xavier; Trobajo, Rosa; Ibáñez, Carles; Cearreta, Alejandro; Brunet, Manola

2015-12-15

Present-day habitats of the Ebro Delta, NE Iberian Peninsula, have been ecologically altered as a consequence of intensive human impacts in the last two centuries (especially rice farming). Benthic foraminiferal palaeoassemblages and sediment characteristics of five short cores were used to reconstruct past wetland habitats, through application of multivariate DCA and CONISS techniques, and dissimilarity coefficients (SCD). The timing of environmental changes was compared to known natural and anthropogenic events in order to identify their possible relationships. In deltaic wetlands under altered hydrological conditions, we found a decrease in species diversity and calcareous-dominated assemblages, and a significant positive correlation between microfaunal changes and organic matter content. Modern analogues supported palaeoenvironmental interpretation of the recent evolution of the Delta wetlands. This research provides the first recent reconstruction of change in the Ebro Delta wetlands, and also illustrates the importance of benthic foraminifera for biomonitoring present and future conditions in Mediterranean deltas. Copyright © 2015 Elsevier Ltd. All rights reserved.

Deoxygenation alters bacterial diversity and community composition in the ocean's largest oxygen minimum zone.

PubMed

Beman, J Michael; Carolan, Molly T

2013-01-01

Oceanic oxygen minimum zones (OMZs) have a central role in biogeochemical cycles and are expanding as a consequence of climate change, yet how deoxygenation will affect the microbial communities that control these cycles is unclear. Here we sample across dissolved oxygen gradients in the oceans' largest OMZ and show that bacterial richness displays a unimodal pattern with decreasing dissolved oxygen, reaching maximum values on the edge of the OMZ and decreasing within it. Rare groups on the OMZ margin are abundant at lower dissolved oxygen concentrations, including sulphur-cycling Chromatiales, for which 16S rRNA was amplified from extracted RNA. Microbial species distribution models accurately replicate community patterns based on multivariate environmental data, demonstrate likely changes in distributions and diversity in the eastern tropical North Pacific Ocean, and highlight the sensitivity of key bacterial groups to deoxygenation. Through these mechanisms, OMZ expansion may alter microbial composition, competition, diversity and function, all of which have implications for biogeochemical cycling in OMZs.

Deoxygenation alters bacterial diversity and community composition in the ocean’s largest oxygen minimum zone

NASA Astrophysics Data System (ADS)

Beman, J. Michael; Carolan, Molly T.

2013-10-01

Oceanic oxygen minimum zones (OMZs) have a central role in biogeochemical cycles and are expanding as a consequence of climate change, yet how deoxygenation will affect the microbial communities that control these cycles is unclear. Here we sample across dissolved oxygen gradients in the oceans’ largest OMZ and show that bacterial richness displays a unimodal pattern with decreasing dissolved oxygen, reaching maximum values on the edge of the OMZ and decreasing within it. Rare groups on the OMZ margin are abundant at lower dissolved oxygen concentrations, including sulphur-cycling Chromatiales, for which 16S rRNA was amplified from extracted RNA. Microbial species distribution models accurately replicate community patterns based on multivariate environmental data, demonstrate likely changes in distributions and diversity in the eastern tropical North Pacific Ocean, and highlight the sensitivity of key bacterial groups to deoxygenation. Through these mechanisms, OMZ expansion may alter microbial composition, competition, diversity and function, all of which have implications for biogeochemical cycling in OMZs.

Population-level coordination of pigment response in individual cyanobacterial cells under altered nitrogen levels

DOE PAGES

Murton, Jaclyn; Nagarajan, Aparna; Nguyen, Amelia Y.; ...

2017-07-21

Cyanobacterial phycobilisome (PBS) pigment-protein complexes harvest light and transfer the energy to reaction centers. Previous ensemble studies have shown that cyanobacteria respond to changes in nutrient availability by modifying the structure of PBS complexes, but this process has not been visualized for individual pigments at the single-cell level due to spectral overlap. We characterized the response of four key photosynthetic pigments to nitrogen depletion and repletion at the subcellular level in individual, live Synechocystis sp. PCC 6803 cells using hyperspectral confocal fluorescence microscopy and multivariate image analysis. Our results revealed that PBS degradation and re-synthesis comprise a rapid response tomore » nitrogen fluctuations, with coordinated populations of cells undergoing pigment modifications. Chlorophyll fluorescence originating from photosystem I and II decreased during nitrogen starvation, but no alteration in subcellular chlorophyll localization was found. Lastly, we observed differential rod and core pigment responses to nitrogen deprivation, suggesting that PBS complexes undergo a stepwise degradation process.« less

Social Network Characteristics Moderate the Association Between Stigmatizing Attributions About HIV and Non-adherence Among Black Americans Living with HIV: a Longitudinal Assessment.

PubMed

Bogart, Laura M; Wagner, Glenn J; Green, Harold D; Mutchler, Matt G; Klein, David J; McDavitt, Bryce

2015-12-01

Stigma may contribute to HIV-related disparities among HIV-positive Black Americans. We examined whether social network characteristics moderate stigma's effects. At baseline and 6 months post-baseline, 147 HIV-positive Black Americans on antiretroviral treatment completed egocentric social network assessments, from which we derived a structural social support capacity measure (i.e., ability to leverage support from the network, represented by the average interaction frequency between the participant and each alter). Stigma was operationalized with an indicator of whether any social network member had expressed stigmatizing attributions of blame or responsibility about HIV. Daily medication adherence was monitored electronically. In a multivariate regression, baseline stigma was significantly related to decreased adherence over time. The association between stigma and non-adherence was attenuated among participants who increased the frequency of their interactions with alters over time. Well-connected social networks have the potential to buffer the effects of stigma.

Simultaneous Detection of Both Single Nucleotide Variations and Copy Number Alterations by Next-Generation Sequencing in Gorlin Syndrome

PubMed Central

Morita, Kei-ichi; Naruto, Takuya; Tanimoto, Kousuke; Yasukawa, Chisato; Oikawa, Yu; Masuda, Kiyoshi; Imoto, Issei; Inazawa, Johji; Omura, Ken; Harada, Hiroyuki

2015-01-01

Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions. PMID:26544948

Simultaneous Detection of Both Single Nucleotide Variations and Copy Number Alterations by Next-Generation Sequencing in Gorlin Syndrome.

PubMed

Morita, Kei-ichi; Naruto, Takuya; Tanimoto, Kousuke; Yasukawa, Chisato; Oikawa, Yu; Masuda, Kiyoshi; Imoto, Issei; Inazawa, Johji; Omura, Ken; Harada, Hiroyuki

2015-01-01

Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions.

Treatment effect of methylphenidate on intrinsic functional brain network in medication-naïve ADHD children: A multivariate analysis.

PubMed

Yoo, Jae Hyun; Kim, Dohyun; Choi, Jeewook; Jeong, Bumseok

2018-04-01

Methylphenidate is a first-line therapeutic option for treating attention-deficit/hyperactivity disorder (ADHD); however, elicited changes on resting-state functional networks (RSFNs) are not well understood. This study investigated the treatment effect of methylphenidate using a variety of RSFN analyses and explored the collaborative influences of treatment-relevant RSFN changes in children with ADHD. Resting-state functional magnetic resonance imaging was acquired from 20 medication-naïve ADHD children before methylphenidate treatment and twelve weeks later. Changes in large-scale functional connectivity were defined using independent component analysis with dual regression and graph theoretical analysis. The amplitude of low frequency fluctuation (ALFF) was measured to investigate local spontaneous activity alteration. Finally, significant findings were recruited to random forest regression to identify the feature subset that best explains symptom improvement. After twelve weeks of methylphenidate administration, large-scale connectivity was increased between the left fronto-parietal RSFN and the left insula cortex and the right fronto-parietal and the brainstem, while the clustering coefficient (CC) of the global network and nodes, the left fronto-parietal, cerebellum, and occipital pole-visual network, were decreased. ALFF was increased in the bilateral superior parietal cortex and decreased in the right inferior fronto-temporal area. The subset of the local and large-scale RSFN changes, including widespread ALFF changes, the CC of the global network and the cerebellum, could explain the 27.1% variance of the ADHD Rating Scale and 13.72% of the Conner's Parent Rating Scale. Our multivariate approach suggests that the neural mechanism of methylphenidate treatment could be associated with alteration of spontaneous activity in the superior parietal cortex or widespread brain regions as well as functional segregation of the large-scale intrinsic functional network.

Symptoms associated with adverse dengue fever prognoses at the time of reporting in the 2015 dengue outbreak in Taiwan.

PubMed

Yeh, Chun-Yin; Chen, Po-Lin; Chuang, Kun-Ta; Shu, Yu-Chen; Chien, Yu-Wen; Perng, Guey Chuen; Ko, Wen-Chien; Ko, Nai-Ying

2017-12-01

Tainan experienced the most severe dengue epidemic in Taiwan in 2015. This study investigates the association between the signs and symptoms at the time of reporting with the adverse dengue prognoses. A descriptive study was conducted using secondary data from the Dengue Disease Reporting System in Tainan, Taiwan, between January 1 and December 31, 2015. A multivariate stepwise logistic regression was used to identify the risk factors for the adverse prognoses: ICU admissions and mortality. There were 22,777 laboratory-confirmed reported cases (mean age 45.6 ± 21.2 years), of which 3.7% were admitted to intensive care units (ICU), and 0.8% were fatal. The most common symptoms were fever (92.8%), myalgia (26.6%), and headache (22.4%). The prevalence of respiratory distress, altered consciousness, shock, bleeding, and thrombocytopenia increased with age. The multivariate analysis indicated that being in 65-89 years old age group [Adjusted Odds Ratio (aOR):4.95], or the 90 years old and above age group (aOR: 9.06), and presenting with shock (aOR: 8.90) and respiratory distress (aOR: 5.31) were significantly associated with the risk of ICU admission. While old age (aOR: 1.11), respiratory distress (aOR: 9.66), altered consciousness (aOR: 7.06), and thrombocytopenia (aOR: 2.55) were significantly associated with the risk of mortality. Dengue patients older than 65 and those with severe and non-specific signs and symptoms at the time of reporting were at a higher risk of ICU admission and mortality. First-line healthcare providers need to be aware of the varied presentations between the different age groups to allow early diagnosis and in-time management, which would prevent ICU admissions and fatalities in dengue patients.

Relationships between nesting populations of wading birds and habitat features along the Atlantic Coast

USGS Publications Warehouse

Erwin, R.M.; Spendelow, J.A.; Geissler, P.H.; Williams, B.K.; Whitman, William R.; Meredith, William H.

1987-01-01

Using previously published atlas data for 122 mixed-species wading bird colonies on islands along the Atlantic coast (Maine to Florida, 1976-77), we examined relationships between population sizes of 11 species of egrets, herons, ibises, and wood storks (Mycteria americana) and nine habitat variables. On nautical charts, we measured four island characteristics (area, length, width, shape), three isolation factors (distances to nearest island, mainland, and a water barrier),, and two variables related to potential feeding habitat within 5 km of the center of the colony (wetland area and land-water interface, i.e., the linear distance between the marsh/upland and all water bodies within the same 5-km radius). One univariable and five multivariable .procedures were used to determine which habitat features were best related to population size .(all species combined). Multicollinearity problems among the variables limited interpretation for most procedures. Both univariable and the multivariable procedures indicated that land-water interface was the most important of the nine variables, but for all models, less than 10% of the total variance was explained (rz is less than 0.10). The size of the colony was not related to the amount of wetland area (within 5-km).per se. Colony data showed better 'structure' when examined on the basis of geographic and disturbance gradients. Population sizes of colonies near man-altered habitats were compared with those surrounded by relatively natural habitats in three geographic zones: north, middle, and south. Significant differences were found in colony size among the three zones (south largest) and between disturbance types. Surprisingly, in all three zones, colonies near man-altered areas were larger on average than those near more natural habitats in this region. A possible reason for this difference is suggested.

KRAS driven expression signature has prognostic power superior to mutation status in non-small cell lung cancer.

PubMed

Nagy, Ádám; Pongor, Lőrinc Sándor; Szabó, András; Santarpia, Mariacarmela; Győrffy, Balázs

2017-02-15

KRAS is the most frequently mutated oncogene in non-small cell lung cancer (NSCLC). However, the prognostic role of KRAS mutation status in NSCLC still remains controversial. We hypothesize that the expression changes of genes affected by KRAS mutation status will have the most prominent effect and could be used as a prognostic signature in lung cancer. We divided NSCLC patients with mutation and RNA-seq data into KRAS mutated and wild type groups. Mann-Whitney test was used to identify genes showing altered expression between these cohorts. Mean expression of the top five genes was designated as a "transcriptomic fingerprint" of the mutation. We evaluated the effect of this signature on clinical outcome in 2,437 NSCLC patients using univariate and multivariate Cox regression analysis. Mutation of KRAS was most common in adenocarcinoma. Mutation status and KRAS expression were not correlated to prognosis. The transcriptomic fingerprint of KRAS include FOXRED2, KRAS, TOP1, PEX3 and ABL2. The KRAS signature had a high prognostic power. Similar results were achieved when using the second and third set of strongest genes. Moreover, all cutoff values delivered significant prognostic power (p < 0.01). The KRAS signature also remained significant (p < 0.01) in a multivariate analysis including age, gender, smoking history and tumor stage. We generated a "surrogate signature" of KRAS mutation status in NSCLC patients by computationally linking genotype and gene expression. We show that secondary effects of a mutation can have a higher prognostic relevance than the primary genetic alteration itself. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin–lysoPA axis in COPD

PubMed Central

Naz, Shama; Kolmert, Johan; Yang, Mingxing; Reinke, Stacey N.; Kamleh, Muhammad Anas; Snowden, Stuart; Heyder, Tina; Levänen, Bettina; Erle, David J.; Sköld, C. Magnus; Wheelock, Åsa M.; Wheelock, Craig E.

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD. Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform. Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung. These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence. PMID:28642310

Comparison of Arterial Oxygenation Following Head-Down and Head-Up Laparoscopic Surgery.

PubMed

Imani, Farsad; Shirani Amniyeh, Fatemeh; Bastan Hagh, Ehsan; Khajavi, Mohammad Reza; Samimi, Saghar; Yousefshahi, Fardin

2017-12-01

Regarding the role of gas entry in abdomen and cardiorespiratory effects, the ability of anesthesiologists would be challenged in laparoscopic surgeries. Considering few studies in this area and the relevance of the subject, this study was performed to compare the arterial oxygen alterations before operation in comparison with after surgery between laparoscopic cholecystectomy and ovarian cystectomy. In this prospective cohort, 70 consecutive women aged from 20 to 60 years who were candidate for laparoscopic cholecystectomy (n = 35) and ovarian cystectomy (n = 35) with reverse (20 degrees) and direct (30 degrees) Trendelenburg positions, respectively, with ASA class I or II were enrolled. After intubation and before operation, for the first time, the arterial blood gas from radial artery in supine position was obtained for laboratory assessment. Then, the second blood sample was collected from radial artery in supine position and sent to the lab to be assessed with the same device after 30 minutes from surgery termination. The measured variables from arterial blood gas were arterial partial pressure of oxygen (PaO 2 ) and Oxygen saturation (SpO 2 ) alterations. Total PaO 2 was higher in the first measurement. The higher values of PaO 2 in cholecystectomy (upward) than in ovarian cystectomy (downward) were not significant in univariate (P = 0.060) and multivariate analysis (P = 0.654). Furthermore, higher values of SpO 2 in cholecystectomy (upward) than in ovarian cystectomy (downward) were not significant in univariate (P = 0.412) and multivariate analysis (P = 0.984). In general, based on the results of this study, the values of PaO 2 in cholecystectomy (upward) were not significantly higher than the values in cystectomy (downward) in laparoscopic surgeries when measured 30 minutes after surgery.

Comparison of Arterial Oxygenation Following Head-Down and Head-Up Laparoscopic Surgery

PubMed Central

Imani, Farsad; Shirani Amniyeh, Fatemeh; Bastan Hagh, Ehsan; Khajavi, Mohammad Reza; Samimi, Saghar; Yousefshahi, Fardin

2017-01-01

Background Regarding the role of gas entry in abdomen and cardiorespiratory effects, the ability of anesthesiologists would be challenged in laparoscopic surgeries. Considering few studies in this area and the relevance of the subject, this study was performed to compare the arterial oxygen alterations before operation in comparison with after surgery between laparoscopic cholecystectomy and ovarian cystectomy. Methods In this prospective cohort, 70 consecutive women aged from 20 to 60 years who were candidate for laparoscopic cholecystectomy (n = 35) and ovarian cystectomy (n = 35) with reverse (20 degrees) and direct (30 degrees) Trendelenburg positions, respectively, with ASA class I or II were enrolled. After intubation and before operation, for the first time, the arterial blood gas from radial artery in supine position was obtained for laboratory assessment. Then, the second blood sample was collected from radial artery in supine position and sent to the lab to be assessed with the same device after 30 minutes from surgery termination. The measured variables from arterial blood gas were arterial partial pressure of oxygen (PaO2) and Oxygen saturation (SpO2) alterations. Results Total PaO2 was higher in the first measurement. The higher values of PaO2 in cholecystectomy (upward) than in ovarian cystectomy (downward) were not significant in univariate (P = 0.060) and multivariate analysis (P = 0.654). Furthermore, higher values of SpO2 in cholecystectomy (upward) than in ovarian cystectomy (downward) were not significant in univariate (P = 0.412) and multivariate analysis (P = 0.984). Conclusions In general, based on the results of this study, the values of PaO2 in cholecystectomy (upward) were not significantly higher than the values in cystectomy (downward) in laparoscopic surgeries when measured 30 minutes after surgery. PMID:29696125

Congenital Hypothyroidism with Neurological and Respiratory Alterations: A Case Detected Using a Variable Diagnostic Threshold for TSH

PubMed Central

Barreiro, Jesús; Castro-Feijoo, Lidia; Colón, Cristóbal; Cabanas, Paloma; Heredia, Claudia; Castaño, Luis Antonio; Gómez-Lado, Carmen; Couce, M.Luz; Pombo, Manuel

2011-01-01

We report a case of congenital hypothyroidism (CH) with neurological and respiratory alterations due to a heterozygotic c.374-1G > A mutation of TITF1/NKX2-1. The hypothyroidism was detected using a neonatal screening protocol in which the thyroid stimulating hormone (TSH) threshold is re-set each day on the basis of within-day variability and between-day variation. In this case, the threshold on the day of the initial analysis was 8.2 mIU/L, and the measured TSH level in heel-prick blood was 8.3 mIU/L. Conflict of interest:None declared. PMID:22155464

Opportunity, Geologic and Structural Context of Aqueous Alteration in Noachian Outcrops, Marathon Valley and Rim and Endeavour Crater

NASA Technical Reports Server (NTRS)

Crumpler, L. S.; Arvidson, R. E.; Mittlefehldt, D. W.; Jolliff, B. L.; Farrand, W. H.; Fox, V.; Golombek, M. P.

2016-01-01

In its 12th year of exploration and 1600 sols since arrival at the rim of the 22 km-diameter Noachian Endeavour impact crater, Mars Exploration Rover Opportunity traversed from the summit of the western rim segment "Cape Tribulation" to "Marathon Valley", a shallow trough dissecting the rim and the site of strong orbital detection of smectites. In situ analysis of the exposures within Marathon Valley is establishing some of the geologic and geochemical controls on the aqueous alteration responsible for smectite detection known to occur in crater rims throughout Noachian terrains of Mars.

Alterations in regional homogeneity of baseline brain activity in pediatric temporal lobe epilepsy.

PubMed

Mankinen, Katariina; Long, Xiang-Yu; Paakki, Jyri-Johan; Harila, Marika; Rytky, Seppo; Tervonen, Osmo; Nikkinen, Juha; Starck, Tuomo; Remes, Jukka; Rantala, Heikki; Zang, Yu-Feng; Kiviniemi, Vesa

2011-02-10

Recent findings on intracortical EEG measurements show that the synchrony of localized neuronal networks is altered in epileptogenesis, leading to generalized seizure activity via connector hubs in the neuronal networks. Regional homogeneity (ReHo) analysis of blood oxygen level-dependent (BOLD) signals has demonstrated localized signal synchrony and disease-related alterations in a number of instances. We wanted to find out whether the ReHo of resting-state activity can be used to detect regional signal synchrony alterations in children with non-lesional temporal lobe epilepsy (TLE). Twenty-one TLE patients were compared with age and gender-matched healthy controls. Significantly increased ReHo was discovered in the posterior cingulate gyrus and the right medial temporal lobe of the patients, and they also had significantly decreased ReHo in the cerebellum compared with the healthy controls. However, the alterations in ReHo differed between the patients with normal and abnormal interictal EEGs, the latter showing significantly increased ReHo in the right fusiform gyrus and significantly decreased ReHo in the right medial frontal gyrus relative to the controls, while those with normal EEGs had significantly increased ReHo in the right inferior temporal gyrus and the left posterior cingulate gyrus. We conclude that altered BOLD signal synchrony can be detected in the cerebral and cerebellar cortices of children with TLE even in the absence of interictal EEG abnormalities. Copyright © 2010 Elsevier B.V. All rights reserved.

Consumption of fermented milk product with probiotic modulates brain activity.

PubMed

Tillisch, Kirsten; Labus, Jennifer; Kilpatrick, Lisa; Jiang, Zhiguo; Stains, Jean; Ebrat, Bahar; Guyonnet, Denis; Legrain-Raspaud, Sophie; Trotin, Beatrice; Naliboff, Bruce; Mayer, Emeran A

2013-06-01

Changes in gut microbiota have been reported to alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes in rodents. However, alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans. We investigated whether consumption of a fermented milk product with probiotic (FMPP) for 4 weeks by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks. Healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to groups given FMPP (n = 12), a nonfermented milk product (n = 11, controls), or no intervention (n = 13) twice daily for 4 weeks. The FMPP contained Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis. Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed. FMPP intake was associated with reduced task-related response of a distributed functional network (49% cross-block covariance; P = .004) containing affective, viscerosensory, and somatosensory cortices. Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was associated with changes in midbrain connectivity, which could explain the observed differences in activity during the task. Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.