Factor complexity of crash occurrence: An empirical demonstration using boosted regression trees.

PubMed

Chung, Yi-Shih

2013-12-01

Factor complexity is a characteristic of traffic crashes. This paper proposes a novel method, namely boosted regression trees (BRT), to investigate the complex and nonlinear relationships in high-variance traffic crash data. The Taiwanese 2004-2005 single-vehicle motorcycle crash data are used to demonstrate the utility of BRT. Traditional logistic regression and classification and regression tree (CART) models are also used to compare their estimation results and external validities. Both the in-sample cross-validation and out-of-sample validation results show that an increase in tree complexity provides improved, although declining, classification performance, indicating a limited factor complexity of single-vehicle motorcycle crashes. The effects of crucial variables including geographical, time, and sociodemographic factors explain some fatal crashes. Relatively unique fatal crashes are better approximated by interactive terms, especially combinations of behavioral factors. BRT models generally provide improved transferability than conventional logistic regression and CART models. This study also discusses the implications of the results for devising safety policies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Using Classification and Regression Trees (CART) and random forests to analyze attrition: Results from two simulations.

PubMed

Hayes, Timothy; Usami, Satoshi; Jacobucci, Ross; McArdle, John J

2015-12-01

In this article, we describe a recent development in the analysis of attrition: using classification and regression trees (CART) and random forest methods to generate inverse sampling weights. These flexible machine learning techniques have the potential to capture complex nonlinear, interactive selection models, yet to our knowledge, their performance in the missing data analysis context has never been evaluated. To assess the potential benefits of these methods, we compare their performance with commonly employed multiple imputation and complete case techniques in 2 simulations. These initial results suggest that weights computed from pruned CART analyses performed well in terms of both bias and efficiency when compared with other methods. We discuss the implications of these findings for applied researchers. (c) 2015 APA, all rights reserved).

Using Classification and Regression Trees (CART) and Random Forests to Analyze Attrition: Results From Two Simulations

PubMed Central

Hayes, Timothy; Usami, Satoshi; Jacobucci, Ross; McArdle, John J.

2016-01-01

In this article, we describe a recent development in the analysis of attrition: using classification and regression trees (CART) and random forest methods to generate inverse sampling weights. These flexible machine learning techniques have the potential to capture complex nonlinear, interactive selection models, yet to our knowledge, their performance in the missing data analysis context has never been evaluated. To assess the potential benefits of these methods, we compare their performance with commonly employed multiple imputation and complete case techniques in 2 simulations. These initial results suggest that weights computed from pruned CART analyses performed well in terms of both bias and efficiency when compared with other methods. We discuss the implications of these findings for applied researchers. PMID:26389526

Personalized Risk Prediction in Clinical Oncology Research: Applications and Practical Issues Using Survival Trees and Random Forests.

PubMed

Hu, Chen; Steingrimsson, Jon Arni

2018-01-01

A crucial component of making individualized treatment decisions is to accurately predict each patient's disease risk. In clinical oncology, disease risks are often measured through time-to-event data, such as overall survival and progression/recurrence-free survival, and are often subject to censoring. Risk prediction models based on recursive partitioning methods are becoming increasingly popular largely due to their ability to handle nonlinear relationships, higher-order interactions, and/or high-dimensional covariates. The most popular recursive partitioning methods are versions of the Classification and Regression Tree (CART) algorithm, which builds a simple interpretable tree structured model. With the aim of increasing prediction accuracy, the random forest algorithm averages multiple CART trees, creating a flexible risk prediction model. Risk prediction models used in clinical oncology commonly use both traditional demographic and tumor pathological factors as well as high-dimensional genetic markers and treatment parameters from multimodality treatments. In this article, we describe the most commonly used extensions of the CART and random forest algorithms to right-censored outcomes. We focus on how they differ from the methods for noncensored outcomes, and how the different splitting rules and methods for cost-complexity pruning impact these algorithms. We demonstrate these algorithms by analyzing a randomized Phase III clinical trial of breast cancer. We also conduct Monte Carlo simulations to compare the prediction accuracy of survival forests with more commonly used regression models under various scenarios. These simulation studies aim to evaluate how sensitive the prediction accuracy is to the underlying model specifications, the choice of tuning parameters, and the degrees of missing covariates.

Stratification of the severity of critically ill patients with classification trees

PubMed Central

2009-01-01

Background Development of three classification trees (CT) based on the CART (Classification and Regression Trees), CHAID (Chi-Square Automatic Interaction Detection) and C4.5 methodologies for the calculation of probability of hospital mortality; the comparison of the results with the APACHE II, SAPS II and MPM II-24 scores, and with a model based on multiple logistic regression (LR). Methods Retrospective study of 2864 patients. Random partition (70:30) into a Development Set (DS) n = 1808 and Validation Set (VS) n = 808. Their properties of discrimination are compared with the ROC curve (AUC CI 95%), Percent of correct classification (PCC CI 95%); and the calibration with the Calibration Curve and the Standardized Mortality Ratio (SMR CI 95%). Results CTs are produced with a different selection of variables and decision rules: CART (5 variables and 8 decision rules), CHAID (7 variables and 15 rules) and C4.5 (6 variables and 10 rules). The common variables were: inotropic therapy, Glasgow, age, (A-a)O2 gradient and antecedent of chronic illness. In VS: all the models achieved acceptable discrimination with AUC above 0.7. CT: CART (0.75(0.71-0.81)), CHAID (0.76(0.72-0.79)) and C4.5 (0.76(0.73-0.80)). PCC: CART (72(69-75)), CHAID (72(69-75)) and C4.5 (76(73-79)). Calibration (SMR) better in the CT: CART (1.04(0.95-1.31)), CHAID (1.06(0.97-1.15) and C4.5 (1.08(0.98-1.16)). Conclusion With different methodologies of CTs, trees are generated with different selection of variables and decision rules. The CTs are easy to interpret, and they stratify the risk of hospital mortality. The CTs should be taken into account for the classification of the prognosis of critically ill patients. PMID:20003229

[Predicting very early rebleeding after acute variceal bleeding based in classification and regression tree analysis (CRTA).].

PubMed

Altamirano, J; Augustin, S; Muntaner, L; Zapata, L; González-Angulo, A; Martínez, B; Flores-Arroyo, A; Camargo, L; Genescá, J

2010-01-01

Variceal bleeding (VB) is the main cause of death among cirrhotic patients. About 30-50% of early rebleeding is encountered few days after the acute episode of VB. It is necessary to stratify patients with high risk of very early rebleeding (VER) for more aggressive therapies. However, there are few and incompletely understood prognostic models for this purpose. To determine the risk factors associated with VER after an acute VB. Assessment and comparison of a novel prognostic model generated by Classification and Regression Tree Analysis (CART) with classic-used models (MELD and Child-Pugh [CP]). Sixty consecutive cirrhotic patients with acute variceal bleeding. CART analysis, MELD and Child-Pugh scores were performed at admission. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the models. Very early rebleeding rate was 13%. Variables associated with VER were: serum albumin (p = 0.027), creatinine (p = 0.021) and transfused blood units in the first 24 hrs (p = 0.05). The area under the ROC for MELD, CHILD-Pugh and CART were 0.46, 0.50 and 0.82, respectively. The value of cut analyzed by CART for the significant variables were: 1) Albumin 2.85 mg/dL, 2) Packed red cells 2 units and 3) Creatinine 1.65 mg/dL the ABC-ROC. Serum albumin, creatinine and number of transfused blood units were associated with VER. A simple CART algorithm combining these variables allows an accurate predictive assessment of VER after acute variceal bleeding. Key words: cirrhosis, variceal bleeding, esophageal varices, prognosis, portal hypertension.

Evaluation of alternative model selection criteria in the analysis of unimodal response curves using CART

USGS Publications Warehouse

Ribic, C.A.; Miller, T.W.

1998-01-01

We investigated CART performance with a unimodal response curve for one continuous response and four continuous explanatory variables, where two variables were important (ie directly related to the response) and the other two were not. We explored performance under three relationship strengths and two explanatory variable conditions: equal importance and one variable four times as important as the other. We compared CART variable selection performance using three tree-selection rules ('minimum risk', 'minimum risk complexity', 'one standard error') to stepwise polynomial ordinary least squares (OLS) under four sample size conditions. The one-standard-error and minimum-risk-complexity methods performed about as well as stepwise OLS with large sample sizes when the relationship was strong. With weaker relationships, equally important explanatory variables and larger sample sizes, the one-standard-error and minimum-risk-complexity rules performed better than stepwise OLS. With weaker relationships and explanatory variables of unequal importance, tree-structured methods did not perform as well as stepwise OLS. Comparing performance within tree-structured methods, with a strong relationship and equally important explanatory variables, the one-standard-error-rule was more likely to choose the correct model than were the other tree-selection rules 1) with weaker relationships and equally important explanatory variables; and 2) under all relationship strengths when explanatory variables were of unequal importance and sample sizes were lower.

Using CART to Identify Thresholds and Hierarchies in the Determinants of Funding Decisions.

PubMed

Schilling, Chris; Mortimer, Duncan; Dalziel, Kim

2017-02-01

There is much interest in understanding decision-making processes that determine funding outcomes for health interventions. We use classification and regression trees (CART) to identify cost-effectiveness thresholds and hierarchies in the determinants of funding decisions. The hierarchical structure of CART is suited to analyzing complex conditional and nonlinear relationships. Our analysis uncovered hierarchies where interventions were grouped according to their type and objective. Cost-effectiveness thresholds varied markedly depending on which group the intervention belonged to: lifestyle-type interventions with a prevention objective had an incremental cost-effectiveness threshold of $2356, suggesting that such interventions need to be close to cost saving or dominant to be funded. For lifestyle-type interventions with a treatment objective, the threshold was much higher at $37,024. Lower down the tree, intervention attributes such as the level of patient contribution and the eligibility for government reimbursement influenced the likelihood of funding within groups of similar interventions. Comparison between our CART models and previously published results demonstrated concurrence with standard regression techniques while providing additional insights regarding the role of the funding environment and the structure of decision-maker preferences.

[RS estimation of inventory parameters and carbon storage of moso bamboo forest based on synergistic use of object-based image analysis and decision tree].

PubMed

Du, Hua Qiang; Sun, Xiao Yan; Han, Ning; Mao, Fang Jie

2017-10-01

By synergistically using the object-based image analysis (OBIA) and the classification and regression tree (CART) methods, the distribution information, the indexes (including diameter at breast, tree height, and crown closure), and the aboveground carbon storage (AGC) of moso bamboo forest in Shanchuan Town, Anji County, Zhejiang Province were investigated. The results showed that the moso bamboo forest could be accurately delineated by integrating the multi-scale ima ge segmentation in OBIA technique and CART, which connected the image objects at various scales, with a pretty good producer's accuracy of 89.1%. The investigation of indexes estimated by regression tree model that was constructed based on the features extracted from the image objects reached normal or better accuracy, in which the crown closure model archived the best estimating accuracy of 67.9%. The estimating accuracy of diameter at breast and tree height was relatively low, which was consistent with conclusion that estimating diameter at breast and tree height using optical remote sensing could not achieve satisfactory results. Estimation of AGC reached relatively high accuracy, and accuracy of the region of high value achieved above 80%.

Beating the Odds: Trees to Success in Different Countries

ERIC Educational Resources Information Center

Finch, W. Holmes; Marchant, Gregory J.

2017-01-01

A recursive partitioning model approach in the form of classification and regression trees (CART) was used with 2012 PISA data for five countries (Canada, Finland, Germany, Singapore-China, and the Unites States). The objective of the study was to determine demographic and educational variables that differentiated between low SES student that were…

BAYESIAN METHODS FOR REGIONAL-SCALE EUTROPHICATION MODELS. (R830887)

EPA Science Inventory

We demonstrate a Bayesian classification and regression tree (CART) approach to link multiple environmental stressors to biological responses and quantify uncertainty in model predictions. Such an approach can: (1) report prediction uncertainty, (2) be consistent with the amou...

Comparison of stream invertebrate response models for bioassessment metric

USGS Publications Warehouse

Waite, Ian R.; Kennen, Jonathan G.; May, Jason T.; Brown, Larry R.; Cuffney, Thomas F.; Jones, Kimberly A.; Orlando, James L.

2012-01-01

We aggregated invertebrate data from various sources to assemble data for modeling in two ecoregions in Oregon and one in California. Our goal was to compare the performance of models developed using multiple linear regression (MLR) techniques with models developed using three relatively new techniques: classification and regression trees (CART), random forest (RF), and boosted regression trees (BRT). We used tolerance of taxa based on richness (RICHTOL) and ratio of observed to expected taxa (O/E) as response variables and land use/land cover as explanatory variables. Responses were generally linear; therefore, there was little improvement to the MLR models when compared to models using CART and RF. In general, the four modeling techniques (MLR, CART, RF, and BRT) consistently selected the same primary explanatory variables for each region. However, results from the BRT models showed significant improvement over the MLR models for each region; increases in R2 from 0.09 to 0.20. The O/E metric that was derived from models specifically calibrated for Oregon consistently had lower R2 values than RICHTOL for the two regions tested. Modeled O/E R2 values were between 0.06 and 0.10 lower for each of the four modeling methods applied in the Willamette Valley and were between 0.19 and 0.36 points lower for the Blue Mountains. As a result, BRT models may indeed represent a good alternative to MLR for modeling species distribution relative to environmental variables.

Modeling flash floods in ungauged mountain catchments of China: A decision tree learning approach for parameter regionalization

NASA Astrophysics Data System (ADS)

Ragettli, S.; Zhou, J.; Wang, H.; Liu, C.; Guo, L.

2017-12-01

Flash floods in small mountain catchments are one of the most frequent causes of loss of life and property from natural hazards in China. Hydrological models can be a useful tool for the anticipation of these events and the issuing of timely warnings. One of the main challenges of setting up such a system is finding appropriate model parameter values for ungauged catchments. Previous studies have shown that the transfer of parameter sets from hydrologically similar gauged catchments is one of the best performing regionalization methods. However, a remaining key issue is the identification of suitable descriptors of similarity. In this study, we use decision tree learning to explore parameter set transferability in the full space of catchment descriptors. For this purpose, a semi-distributed rainfall-runoff model is set up for 35 catchments in ten Chinese provinces. Hourly runoff data from in total 858 storm events are used to calibrate the model and to evaluate the performance of parameter set transfers between catchments. We then present a novel technique that uses the splitting rules of classification and regression trees (CART) for finding suitable donor catchments for ungauged target catchments. The ability of the model to detect flood events in assumed ungauged catchments is evaluated in series of leave-one-out tests. We show that CART analysis increases the probability of detection of 10-year flood events in comparison to a conventional measure of physiographic-climatic similarity by up to 20%. Decision tree learning can outperform other regionalization approaches because it generates rules that optimally consider spatial proximity and physical similarity. Spatial proximity can be used as a selection criteria but is skipped in the case where no similar gauged catchments are in the vicinity. We conclude that the CART regionalization concept is particularly suitable for implementation in sparsely gauged and topographically complex environments where a proximity-based regionalization concept is not applicable.

Weighing risk factors associated with bee colony collapse disorder by classification and regression tree analysis.

PubMed

VanEngelsdorp, Dennis; Speybroeck, Niko; Evans, Jay D; Nguyen, Bach Kim; Mullin, Chris; Frazier, Maryann; Frazier, Jim; Cox-Foster, Diana; Chen, Yanping; Tarpy, David R; Haubruge, Eric; Pettis, Jeffrey S; Saegerman, Claude

2010-10-01

Colony collapse disorder (CCD), a syndrome whose defining trait is the rapid loss of adult worker honey bees, Apis mellifera L., is thought to be responsible for a minority of the large overwintering losses experienced by U.S. beekeepers since the winter 2006-2007. Using the same data set developed to perform a monofactorial analysis (PloS ONE 4: e6481, 2009), we conducted a classification and regression tree (CART) analysis in an attempt to better understand the relative importance and interrelations among different risk variables in explaining CCD. Fifty-five exploratory variables were used to construct two CART models: one model with and one model without a cost of misclassifying a CCD-diagnosed colony as a non-CCD colony. The resulting model tree that permitted for misclassification had a sensitivity and specificity of 85 and 74%, respectively. Although factors measuring colony stress (e.g., adult bee physiological measures, such as fluctuating asymmetry or mass of head) were important discriminating values, six of the 19 variables having the greatest discriminatory value were pesticide levels in different hive matrices. Notably, coumaphos levels in brood (a miticide commonly used by beekeepers) had the highest discriminatory value and were highest in control (healthy) colonies. Our CART analysis provides evidence that CCD is probably the result of several factors acting in concert, making afflicted colonies more susceptible to disease. This analysis highlights several areas that warrant further attention, including the effect of sublethal pesticide exposure on pathogen prevalence and the role of variability in bee tolerance to pesticides on colony survivorship.

Comparing Methodologies for Developing an Early Warning System: Classification and Regression Tree Model versus Logistic Regression. REL 2015-077

ERIC Educational Resources Information Center

Koon, Sharon; Petscher, Yaacov

2015-01-01

The purpose of this report was to explicate the use of logistic regression and classification and regression tree (CART) analysis in the development of early warning systems. It was motivated by state education leaders' interest in maintaining high classification accuracy while simultaneously improving practitioner understanding of the rules by…

Establishing Decision Trees for Predicting Successful Postpyloric Nasoenteric Tube Placement in Critically Ill Patients.

PubMed

Chen, Weisheng; Sun, Cheng; Wei, Ru; Zhang, Yanlin; Ye, Heng; Chi, Ruibin; Zhang, Yichen; Hu, Bei; Lv, Bo; Chen, Lifang; Zhang, Xiunong; Lan, Huilan; Chen, Chunbo

2016-08-31

Despite the use of prokinetic agents, the overall success rate for postpyloric placement via a self-propelled spiral nasoenteric tube is quite low. This retrospective study was conducted in the intensive care units of 11 university hospitals from 2006 to 2016 among adult patients who underwent self-propelled spiral nasoenteric tube insertion. Success was defined as postpyloric nasoenteric tube placement confirmed by abdominal x-ray scan 24 hours after tube insertion. Chi-square automatic interaction detection (CHAID), simple classification and regression trees (SimpleCart), and J48 methodologies were used to develop decision tree models, and multiple logistic regression (LR) methodology was used to develop an LR model for predicting successful postpyloric nasoenteric tube placement. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of these models. Successful postpyloric nasoenteric tube placement was confirmed in 427 of 939 patients enrolled. For predicting successful postpyloric nasoenteric tube placement, the performance of the 3 decision trees was similar in terms of the AUCs: 0.715 for the CHAID model, 0.682 for the SimpleCart model, and 0.671 for the J48 model. The AUC of the LR model was 0.729, which outperformed the J48 model. Both the CHAID and LR models achieved an acceptable discrimination for predicting successful postpyloric nasoenteric tube placement and were useful for intensivists in the setting of self-propelled spiral nasoenteric tube insertion. © 2016 American Society for Parenteral and Enteral Nutrition.

Establishing Decision Trees for Predicting Successful Postpyloric Nasoenteric Tube Placement in Critically Ill Patients.

PubMed

Chen, Weisheng; Sun, Cheng; Wei, Ru; Zhang, Yanlin; Ye, Heng; Chi, Ruibin; Zhang, Yichen; Hu, Bei; Lv, Bo; Chen, Lifang; Zhang, Xiunong; Lan, Huilan; Chen, Chunbo

2018-01-01

Despite the use of prokinetic agents, the overall success rate for postpyloric placement via a self-propelled spiral nasoenteric tube is quite low. This retrospective study was conducted in the intensive care units of 11 university hospitals from 2006 to 2016 among adult patients who underwent self-propelled spiral nasoenteric tube insertion. Success was defined as postpyloric nasoenteric tube placement confirmed by abdominal x-ray scan 24 hours after tube insertion. Chi-square automatic interaction detection (CHAID), simple classification and regression trees (SimpleCart), and J48 methodologies were used to develop decision tree models, and multiple logistic regression (LR) methodology was used to develop an LR model for predicting successful postpyloric nasoenteric tube placement. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of these models. Successful postpyloric nasoenteric tube placement was confirmed in 427 of 939 patients enrolled. For predicting successful postpyloric nasoenteric tube placement, the performance of the 3 decision trees was similar in terms of the AUCs: 0.715 for the CHAID model, 0.682 for the SimpleCart model, and 0.671 for the J48 model. The AUC of the LR model was 0.729, which outperformed the J48 model. Both the CHAID and LR models achieved an acceptable discrimination for predicting successful postpyloric nasoenteric tube placement and were useful for intensivists in the setting of self-propelled spiral nasoenteric tube insertion. © 2016 American Society for Parenteral and Enteral Nutrition.

Risk factors for amendment in type, duration and setting of prescribed outpatient parenteral antimicrobial therapy (OPAT) for adult patients with cellulitis: a retrospective cohort study and CART analysis.

PubMed

Quirke, Michael; Curran, Emma May; O'Kelly, Patrick; Moran, Ruth; Daly, Eimear; Aylward, Seamus; McElvaney, Gerry; Wakai, Abel

2018-01-01

To measure the percentage rate and risk factors for amendment in the type, duration and setting of outpatient parenteral antimicrobial therapy ( OPAT) for the treatment of cellulitis. A retrospective cohort study of adult patients receiving OPAT for cellulitis was performed. Treatment amendment (TA) was defined as hospital admission or change in antibiotic therapy in order to achieve clinical response. Multivariable logistic regression (MVLR) and classification and regression tree (CART) analysis were performed. There were 307 patients enrolled. TA occurred in 36 patients (11.7%). Significant risk factors for TA on MVLR were increased age, increased Numerical Pain Scale Score (NPSS) and immunocompromise. The median OPAT duration was 7 days. Increased age, heart rate and C reactive protein were associated with treatment prolongation. CART analysis selected age <64.5 years, female gender and NPSS <2.5 in the final model, generating a low-sensitivity (27.8%), high-specificity (97.1%) decision tree. Increased age, NPSS and immunocompromise were associated with OPAT amendment. These identified risk factors can be used to support an evidence-based approach to patient selection for OPAT in cellulitis. The CART algorithm has good specificity but lacks sensitivity and is shown to be inferior in this study to logistic regression modelling. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Classification and regression tree (CART) model to predict pulmonary tuberculosis in hospitalized patients.

PubMed

Aguiar, Fabio S; Almeida, Luciana L; Ruffino-Netto, Antonio; Kritski, Afranio Lineu; Mello, Fernanda Cq; Werneck, Guilherme L

2012-08-07

Tuberculosis (TB) remains a public health issue worldwide. The lack of specific clinical symptoms to diagnose TB makes the correct decision to admit patients to respiratory isolation a difficult task for the clinician. Isolation of patients without the disease is common and increases health costs. Decision models for the diagnosis of TB in patients attending hospitals can increase the quality of care and decrease costs, without the risk of hospital transmission. We present a predictive model for predicting pulmonary TB in hospitalized patients in a high prevalence area in order to contribute to a more rational use of isolation rooms without increasing the risk of transmission. Cross sectional study of patients admitted to CFFH from March 2003 to December 2004. A classification and regression tree (CART) model was generated and validated. The area under the ROC curve (AUC), sensitivity, specificity, positive and negative predictive values were used to evaluate the performance of model. Validation of the model was performed with a different sample of patients admitted to the same hospital from January to December 2005. We studied 290 patients admitted with clinical suspicion of TB. Diagnosis was confirmed in 26.5% of them. Pulmonary TB was present in 83.7% of the patients with TB (62.3% with positive sputum smear) and HIV/AIDS was present in 56.9% of patients. The validated CART model showed sensitivity, specificity, positive predictive value and negative predictive value of 60.00%, 76.16%, 33.33%, and 90.55%, respectively. The AUC was 79.70%. The CART model developed for these hospitalized patients with clinical suspicion of TB had fair to good predictive performance for pulmonary TB. The most important variable for prediction of TB diagnosis was chest radiograph results. Prospective validation is still necessary, but our model offer an alternative for decision making in whether to isolate patients with clinical suspicion of TB in tertiary health facilities in countries with limited resources.

CADDIS Volume 4. Data Analysis: Basic Analyses

EPA Pesticide Factsheets

Use of statistical tests to determine if an observation is outside the normal range of expected values. Details of CART, regression analysis, use of quantile regression analysis, CART in causal analysis, simplifying or pruning resulting trees.

Study and Ranking of Determinants of Taenia solium Infections by Classification Tree Models

PubMed Central

Mwape, Kabemba E.; Phiri, Isaac K.; Praet, Nicolas; Dorny, Pierre; Muma, John B.; Zulu, Gideon; Speybroeck, Niko; Gabriël, Sarah

2015-01-01

Taenia solium taeniasis/cysticercosis is an important public health problem occurring mainly in developing countries. This work aimed to study the determinants of human T. solium infections in the Eastern province of Zambia and rank them in order of importance. A household (HH)-level questionnaire was administered to 680 HHs from 53 villages in two rural districts and the taeniasis and cysticercosis status determined. A classification tree model (CART) was used to define the relative importance and interactions between different predictor variables in their effect on taeniasis and cysticercosis. The Katete study area had a significantly higher taeniasis and cysticercosis prevalence than the Petauke area. The CART analysis for Katete showed that the most important determinant for cysticercosis infections was the number of HH inhabitants (6 to 10) and for taeniasis was the number of HH inhabitants > 6. The most important determinant in Petauke for cysticercosis was the age of head of household > 32 years and for taeniasis it was age < 55 years. The CART analysis showed that the most important determinant for both taeniasis and cysticercosis infections was the number of HH inhabitants (6 to 10) in Katete district and age in Petauke. The results suggest that control measures should target HHs with a high number of inhabitants and older individuals. PMID:25404073

Inside the black box: starting to uncover the underlying decision rules used in one-by-one expert assessment of occupational exposure in case-control studies

PubMed Central

Wheeler, David C.; Burstyn, Igor; Vermeulen, Roel; Yu, Kai; Shortreed, Susan M.; Pronk, Anjoeka; Stewart, Patricia A.; Colt, Joanne S.; Baris, Dalsu; Karagas, Margaret R.; Schwenn, Molly; Johnson, Alison; Silverman, Debra T.; Friesen, Melissa C.

2014-01-01

Objectives Evaluating occupational exposures in population-based case-control studies often requires exposure assessors to review each study participants' reported occupational information job-by-job to derive exposure estimates. Although such assessments likely have underlying decision rules, they usually lack transparency, are time-consuming and have uncertain reliability and validity. We aimed to identify the underlying rules to enable documentation, review, and future use of these expert-based exposure decisions. Methods Classification and regression trees (CART, predictions from a single tree) and random forests (predictions from many trees) were used to identify the underlying rules from the questionnaire responses and an expert's exposure assignments for occupational diesel exhaust exposure for several metrics: binary exposure probability and ordinal exposure probability, intensity, and frequency. Data were split into training (n=10,488 jobs), testing (n=2,247), and validation (n=2,248) data sets. Results The CART and random forest models' predictions agreed with 92–94% of the expert's binary probability assignments. For ordinal probability, intensity, and frequency metrics, the two models extracted decision rules more successfully for unexposed and highly exposed jobs (86–90% and 57–85%, respectively) than for low or medium exposed jobs (7–71%). Conclusions CART and random forest models extracted decision rules and accurately predicted an expert's exposure decisions for the majority of jobs and identified questionnaire response patterns that would require further expert review if the rules were applied to other jobs in the same or different study. This approach makes the exposure assessment process in case-control studies more transparent and creates a mechanism to efficiently replicate exposure decisions in future studies. PMID:23155187

CART DIAGNOSIS OF WATERSHED IMPAIRMENT IN THE MID-ATLANTIC REGION

EPA Science Inventory

Many factors ( stressors ) can lead to increased concentrations of nutrients and sediments, and these factors change across watersheds. Classification and Regression Tree (CART) is a statistical approach that can be used to "diagnose" which factors are important stressors on a pe...

Decision tree methods: applications for classification and prediction.

PubMed

Song, Yan-Yan; Lu, Ying

2015-04-25

Decision tree methodology is a commonly used data mining method for establishing classification systems based on multiple covariates or for developing prediction algorithms for a target variable. This method classifies a population into branch-like segments that construct an inverted tree with a root node, internal nodes, and leaf nodes. The algorithm is non-parametric and can efficiently deal with large, complicated datasets without imposing a complicated parametric structure. When the sample size is large enough, study data can be divided into training and validation datasets. Using the training dataset to build a decision tree model and a validation dataset to decide on the appropriate tree size needed to achieve the optimal final model. This paper introduces frequently used algorithms used to develop decision trees (including CART, C4.5, CHAID, and QUEST) and describes the SPSS and SAS programs that can be used to visualize tree structure.

Study and ranking of determinants of Taenia solium infections by classification tree models.

PubMed

Mwape, Kabemba E; Phiri, Isaac K; Praet, Nicolas; Dorny, Pierre; Muma, John B; Zulu, Gideon; Speybroeck, Niko; Gabriël, Sarah

2015-01-01

Taenia solium taeniasis/cysticercosis is an important public health problem occurring mainly in developing countries. This work aimed to study the determinants of human T. solium infections in the Eastern province of Zambia and rank them in order of importance. A household (HH)-level questionnaire was administered to 680 HHs from 53 villages in two rural districts and the taeniasis and cysticercosis status determined. A classification tree model (CART) was used to define the relative importance and interactions between different predictor variables in their effect on taeniasis and cysticercosis. The Katete study area had a significantly higher taeniasis and cysticercosis prevalence than the Petauke area. The CART analysis for Katete showed that the most important determinant for cysticercosis infections was the number of HH inhabitants (6 to 10) and for taeniasis was the number of HH inhabitants > 6. The most important determinant in Petauke for cysticercosis was the age of head of household > 32 years and for taeniasis it was age < 55 years. The CART analysis showed that the most important determinant for both taeniasis and cysticercosis infections was the number of HH inhabitants (6 to 10) in Katete district and age in Petauke. The results suggest that control measures should target HHs with a high number of inhabitants and older individuals. © The American Society of Tropical Medicine and Hygiene.

A novel dendrochronological approach reveals drivers of carbon sequestration in tree species of riparian forests across spatiotemporal scales.

PubMed

Rieger, Isaak; Kowarik, Ingo; Cherubini, Paolo; Cierjacks, Arne

2017-01-01

Aboveground carbon (C) sequestration in trees is important in global C dynamics, but reliable techniques for its modeling in highly productive and heterogeneous ecosystems are limited. We applied an extended dendrochronological approach to disentangle the functioning of drivers from the atmosphere (temperature, precipitation), the lithosphere (sedimentation rate), the hydrosphere (groundwater table, river water level fluctuation), the biosphere (tree characteristics), and the anthroposphere (dike construction). Carbon sequestration in aboveground biomass of riparian Quercus robur L. and Fraxinus excelsior L. was modeled (1) over time using boosted regression tree analysis (BRT) on cross-datable trees characterized by equal annual growth ring patterns and (2) across space using a subsequent classification and regression tree analysis (CART) on cross-datable and not cross-datable trees. While C sequestration of cross-datable Q. robur responded to precipitation and temperature, cross-datable F. excelsior also responded to a low Danube river water level. However, CART revealed that C sequestration over time is governed by tree height and parameters that vary over space (magnitude of fluctuation in the groundwater table, vertical distance to mean river water level, and longitudinal distance to upstream end of the study area). Thus, a uniform response to climatic drivers of aboveground C sequestration in Q. robur was only detectable in trees of an intermediate height class and in taller trees (>21.8m) on sites where the groundwater table fluctuated little (≤0.9m). The detection of climatic drivers and the river water level in F. excelsior depended on sites at lower altitudes above the mean river water level (≤2.7m) and along a less dynamic downstream section of the study area. Our approach indicates unexploited opportunities of understanding the interplay of different environmental drivers in aboveground C sequestration. Results may support species-specific and locally adapted forest management plans to increase carbon dioxide sequestration from the atmosphere in trees. Copyright © 2016 Elsevier B.V. All rights reserved.

Propensity score estimation: neural networks, support vector machines, decision trees (CART), and meta-classifiers as alternatives to logistic regression.

PubMed

Westreich, Daniel; Lessler, Justin; Funk, Michele Jonsson

2010-08-01

Propensity scores for the analysis of observational data are typically estimated using logistic regression. Our objective in this review was to assess machine learning alternatives to logistic regression, which may accomplish the same goals but with fewer assumptions or greater accuracy. We identified alternative methods for propensity score estimation and/or classification from the public health, biostatistics, discrete mathematics, and computer science literature, and evaluated these algorithms for applicability to the problem of propensity score estimation, potential advantages over logistic regression, and ease of use. We identified four techniques as alternatives to logistic regression: neural networks, support vector machines, decision trees (classification and regression trees [CART]), and meta-classifiers (in particular, boosting). Although the assumptions of logistic regression are well understood, those assumptions are frequently ignored. All four alternatives have advantages and disadvantages compared with logistic regression. Boosting (meta-classifiers) and, to a lesser extent, decision trees (particularly CART), appear to be most promising for use in the context of propensity score analysis, but extensive simulation studies are needed to establish their utility in practice. Copyright (c) 2010 Elsevier Inc. All rights reserved.

An application in identifying high-risk populations in alternative tobacco product use utilizing logistic regression and CART: a heuristic comparison.

PubMed

Lei, Yang; Nollen, Nikki; Ahluwahlia, Jasjit S; Yu, Qing; Mayo, Matthew S

2015-04-09

Other forms of tobacco use are increasing in prevalence, yet most tobacco control efforts are aimed at cigarettes. In light of this, it is important to identify individuals who are using both cigarettes and alternative tobacco products (ATPs). Most previous studies have used regression models. We conducted a traditional logistic regression model and a classification and regression tree (CART) model to illustrate and discuss the added advantages of using CART in the setting of identifying high-risk subgroups of ATP users among cigarettes smokers. The data were collected from an online cross-sectional survey administered by Survey Sampling International between July 5, 2012 and August 15, 2012. Eligible participants self-identified as current smokers, African American, White, or Latino (of any race), were English-speaking, and were at least 25 years old. The study sample included 2,376 participants and was divided into independent training and validation samples for a hold out validation. Logistic regression and CART models were used to examine the important predictors of cigarettes + ATP users. The logistic regression model identified nine important factors: gender, age, race, nicotine dependence, buying cigarettes or borrowing, whether the price of cigarettes influences the brand purchased, whether the participants set limits on cigarettes per day, alcohol use scores, and discrimination frequencies. The C-index of the logistic regression model was 0.74, indicating good discriminatory capability. The model performed well in the validation cohort also with good discrimination (c-index = 0.73) and excellent calibration (R-square = 0.96 in the calibration regression). The parsimonious CART model identified gender, age, alcohol use score, race, and discrimination frequencies to be the most important factors. It also revealed interesting partial interactions. The c-index is 0.70 for the training sample and 0.69 for the validation sample. The misclassification rate was 0.342 for the training sample and 0.346 for the validation sample. The CART model was easier to interpret and discovered target populations that possess clinical significance. This study suggests that the non-parametric CART model is parsimonious, potentially easier to interpret, and provides additional information in identifying the subgroups at high risk of ATP use among cigarette smokers.

Classification and regression tree (CART) analysis of endometrial carcinoma: Seeing the forest for the trees.

PubMed

Barlin, Joyce N; Zhou, Qin; St Clair, Caryn M; Iasonos, Alexia; Soslow, Robert A; Alektiar, Kaled M; Hensley, Martee L; Leitao, Mario M; Barakat, Richard R; Abu-Rustum, Nadeem R

2013-09-01

The objectives of the study are to evaluate which clinicopathologic factors influenced overall survival (OS) in endometrial carcinoma and to determine if the surgical effort to assess para-aortic (PA) lymph nodes (LNs) at initial staging surgery impacts OS. All patients diagnosed with endometrial cancer from 1/1993-12/2011 who had LNs excised were included. PALN assessment was defined by the identification of one or more PALNs on final pathology. A multivariate analysis was performed to assess the effect of PALNs on OS. A form of recursive partitioning called classification and regression tree (CART) analysis was implemented. Variables included: age, stage, tumor subtype, grade, myometrial invasion, total LNs removed, evaluation of PALNs, and adjuvant chemotherapy. The cohort included 1920 patients, with a median age of 62 years. The median number of LNs removed was 16 (range, 1-99). The removal of PALNs was not associated with OS (P=0.450). Using the CART hierarchically, stage I vs. stages II-IV and grades 1-2 vs. grade 3 emerged as predictors of OS. If the tree was allowed to grow, further branching was based on age and myometrial invasion. Total number of LNs removed and assessment of PALNs as defined in this study were not predictive of OS. This innovative CART analysis emphasized the importance of proper stage assignment and a binary grading system in impacting OS. Notably, the total number of LNs removed and specific evaluation of PALNs as defined in this study were not important predictors of OS. Copyright © 2013 Elsevier Inc. All rights reserved.

Tree Classification Software

NASA Technical Reports Server (NTRS)

Buntine, Wray

1993-01-01

This paper introduces the IND Tree Package to prospective users. IND does supervised learning using classification trees. This learning task is a basic tool used in the development of diagnosis, monitoring and expert systems. The IND Tree Package was developed as part of a NASA project to semi-automate the development of data analysis and modelling algorithms using artificial intelligence techniques. The IND Tree Package integrates features from CART and C4 with newer Bayesian and minimum encoding methods for growing classification trees and graphs. The IND Tree Package also provides an experimental control suite on top. The newer features give improved probability estimates often required in diagnostic and screening tasks. The package comes with a manual, Unix 'man' entries, and a guide to tree methods and research. The IND Tree Package is implemented in C under Unix and was beta-tested at university and commercial research laboratories in the United States.

Nonparametric Subgroup Identification by PRIM and CART: A Simulation and Application Study

PubMed Central

2017-01-01

Two nonparametric methods for the identification of subgroups with outstanding outcome values are described and compared to each other in a simulation study and an application to clinical data. The Patient Rule Induction Method (PRIM) searches for box-shaped areas in the given data which exceed a minimal size and average outcome. This is achieved via a combination of iterative peeling and pasting steps, where small fractions of the data are removed or added to the current box. As an alternative, Classification and Regression Trees (CART) prediction models perform sequential binary splits of the data to produce subsets which can be interpreted as subgroups of heterogeneous outcome. PRIM and CART were compared in a simulation study to investigate their strengths and weaknesses under various data settings, taking different performance measures into account. PRIM was shown to be superior in rather complex settings such as those with few observations, a smaller signal-to-noise ratio, and more than one subgroup. CART showed the best performance in simpler situations. A practical application of the two methods was illustrated using a clinical data set. For this application, both methods produced similar results but the higher amount of user involvement of PRIM became apparent. PRIM can be flexibly tuned by the user, whereas CART, although simpler to implement, is rather static. PMID:28611849

Nonparametric Subgroup Identification by PRIM and CART: A Simulation and Application Study.

PubMed

Ott, Armin; Hapfelmeier, Alexander

2017-01-01

Two nonparametric methods for the identification of subgroups with outstanding outcome values are described and compared to each other in a simulation study and an application to clinical data. The Patient Rule Induction Method (PRIM) searches for box-shaped areas in the given data which exceed a minimal size and average outcome. This is achieved via a combination of iterative peeling and pasting steps, where small fractions of the data are removed or added to the current box. As an alternative, Classification and Regression Trees (CART) prediction models perform sequential binary splits of the data to produce subsets which can be interpreted as subgroups of heterogeneous outcome. PRIM and CART were compared in a simulation study to investigate their strengths and weaknesses under various data settings, taking different performance measures into account. PRIM was shown to be superior in rather complex settings such as those with few observations, a smaller signal-to-noise ratio, and more than one subgroup. CART showed the best performance in simpler situations. A practical application of the two methods was illustrated using a clinical data set. For this application, both methods produced similar results but the higher amount of user involvement of PRIM became apparent. PRIM can be flexibly tuned by the user, whereas CART, although simpler to implement, is rather static.

Combinations of techniques that effectively change health behavior: evidence from Meta-CART analysis.

PubMed

Dusseldorp, Elise; van Genugten, Lenneke; van Buuren, Stef; Verheijden, Marieke W; van Empelen, Pepijn

2014-12-01

Many health-promoting interventions combine multiple behavior change techniques (BCTs) to maximize effectiveness. Although, in theory, BCTs can amplify each other, the available meta-analyses have not been able to identify specific combinations of techniques that provide synergistic effects. This study overcomes some of the shortcomings in the current methodology by applying classification and regression trees (CART) to meta-analytic data in a special way, referred to as Meta-CART. The aim was to identify particular combinations of BCTs that explain intervention success. A reanalysis of data from Michie, Abraham, Whittington, McAteer, and Gupta (2009) was performed. These data included effect sizes from 122 interventions targeted at physical activity and healthy eating, and the coding of the interventions into 26 BCTs. A CART analysis was performed using the BCTs as predictors and treatment success (i.e., effect size) as outcome. A subgroup meta-analysis using a mixed effects model was performed to compare the treatment effect in the subgroups found by CART. Meta-CART identified the following most effective combinations: Provide information about behavior-health link with Prompt intention formation (mean effect size ḡ = 0.46), and Provide information about behavior-health link with Provide information on consequences and Use of follow-up prompts (ḡ = 0.44). Least effective interventions were those using Provide feedback on performance without using Provide instruction (ḡ = 0.05). Specific combinations of BCTs increase the likelihood of achieving change in health behavior, whereas other combinations decrease this likelihood. Meta-CART successfully identified these combinations and thus provides a viable methodology in the context of meta-analysis.

CART (Classification and Regression Trees) Program: The Implementation of the CART Program and Its Application to Estimating Attrition Rates.

DTIC Science & Technology

1985-12-01

consists of the node t and all descendants of t in T. (3) Definition 3. Pruning a branch Tt from a tree T con- sists of deleting from T all...The default is 1.0 so that actually, this keyword did not need to appear in the above file. (5) DELETE . This keyword does not appear in our example, but...when it is used associated with some variable names, it indicates that we want to delete these vari- ables from the regression. If this keyword is

A hybrid PCA-CART-MARS-based prognostic approach of the remaining useful life for aircraft engines.

PubMed

Sánchez Lasheras, Fernando; García Nieto, Paulino José; de Cos Juez, Francisco Javier; Mayo Bayón, Ricardo; González Suárez, Victor Manuel

2015-03-23

Prognostics is an engineering discipline that predicts the future health of a system. In this research work, a data-driven approach for prognostics is proposed. Indeed, the present paper describes a data-driven hybrid model for the successful prediction of the remaining useful life of aircraft engines. The approach combines the multivariate adaptive regression splines (MARS) technique with the principal component analysis (PCA), dendrograms and classification and regression trees (CARTs). Elements extracted from sensor signals are used to train this hybrid model, representing different levels of health for aircraft engines. In this way, this hybrid algorithm is used to predict the trends of these elements. Based on this fitting, one can determine the future health state of a system and estimate its remaining useful life (RUL) with accuracy. To evaluate the proposed approach, a test was carried out using aircraft engine signals collected from physical sensors (temperature, pressure, speed, fuel flow, etc.). Simulation results show that the PCA-CART-MARS-based approach can forecast faults long before they occur and can predict the RUL. The proposed hybrid model presents as its main advantage the fact that it does not require information about the previous operation states of the input variables of the engine. The performance of this model was compared with those obtained by other benchmark models (multivariate linear regression and artificial neural networks) also applied in recent years for the modeling of remaining useful life. Therefore, the PCA-CART-MARS-based approach is very promising in the field of prognostics of the RUL for aircraft engines.

A Hybrid PCA-CART-MARS-Based Prognostic Approach of the Remaining Useful Life for Aircraft Engines

PubMed Central

Lasheras, Fernando Sánchez; Nieto, Paulino José García; de Cos Juez, Francisco Javier; Bayón, Ricardo Mayo; Suárez, Victor Manuel González

2015-01-01

Prognostics is an engineering discipline that predicts the future health of a system. In this research work, a data-driven approach for prognostics is proposed. Indeed, the present paper describes a data-driven hybrid model for the successful prediction of the remaining useful life of aircraft engines. The approach combines the multivariate adaptive regression splines (MARS) technique with the principal component analysis (PCA), dendrograms and classification and regression trees (CARTs). Elements extracted from sensor signals are used to train this hybrid model, representing different levels of health for aircraft engines. In this way, this hybrid algorithm is used to predict the trends of these elements. Based on this fitting, one can determine the future health state of a system and estimate its remaining useful life (RUL) with accuracy. To evaluate the proposed approach, a test was carried out using aircraft engine signals collected from physical sensors (temperature, pressure, speed, fuel flow, etc.). Simulation results show that the PCA-CART-MARS-based approach can forecast faults long before they occur and can predict the RUL. The proposed hybrid model presents as its main advantage the fact that it does not require information about the previous operation states of the input variables of the engine. The performance of this model was compared with those obtained by other benchmark models (multivariate linear regression and artificial neural networks) also applied in recent years for the modeling of remaining useful life. Therefore, the PCA-CART-MARS-based approach is very promising in the field of prognostics of the RUL for aircraft engines. PMID:25806876

In silico prediction of toxicity of phenols to Tetrahymena pyriformis by using genetic algorithm and decision tree-based modeling approach.

PubMed

Abbasitabar, Fatemeh; Zare-Shahabadi, Vahid

2017-04-01

Risk assessment of chemicals is an important issue in environmental protection; however, there is a huge lack of experimental data for a large number of end-points. The experimental determination of toxicity of chemicals involves high costs and time-consuming process. In silico tools such as quantitative structure-toxicity relationship (QSTR) models, which are constructed on the basis of computational molecular descriptors, can predict missing data for toxic end-points for existing or even not yet synthesized chemicals. Phenol derivatives are known to be aquatic pollutants. With this background, we aimed to develop an accurate and reliable QSTR model for the prediction of toxicity of 206 phenols to Tetrahymena pyriformis. A multiple linear regression (MLR)-based QSTR was obtained using a powerful descriptor selection tool named Memorized_ACO algorithm. Statistical parameters of the model were 0.72 and 0.68 for R training 2 and R test 2 , respectively. To develop a high-quality QSTR model, classification and regression tree (CART) was employed. Two approaches were considered: (1) phenols were classified into different modes of action using CART and (2) the phenols in the training set were partitioned to several subsets by a tree in such a manner that in each subset, a high-quality MLR could be developed. For the first approach, the statistical parameters of the resultant QSTR model were improved to 0.83 and 0.75 for R training 2 and R test 2 , respectively. Genetic algorithm was employed in the second approach to obtain an optimal tree, and it was shown that the final QSTR model provided excellent prediction accuracy for the training and test sets (R training 2 and R test 2 were 0.91 and 0.93, respectively). The mean absolute error for the test set was computed as 0.1615. Copyright © 2016 Elsevier Ltd. All rights reserved.

Importance of physical and hydraulic characteristics to unionid mussels: A retrospective analysis in a reach of large river

USGS Publications Warehouse

Zigler, S.J.; Newton, T.J.; Steuer, J.J.; Bartsch, M.R.; Sauer, J.S.

2008-01-01

Interest in understanding physical and hydraulic factors that might drive distribution and abundance of freshwater mussels has been increasing due to their decline throughout North America. We assessed whether the spatial distribution of unionid mussels could be predicted from physical and hydraulic variables in a reach of the Upper Mississippi River. Classification and regression tree (CART) models were constructed using mussel data compiled from various sources and explanatory variables derived from GIS coverages. Prediction success of CART models for presence-absence of mussels ranged from 71 to 76% across three gears (brail, sled-dredge, and dive-quadrat) and 51% of the deviance in abundance. Models were largely driven by shear stress and substrate stability variables, but interactions with simple physical variables, especially slope, were also important. Geospatial models, which were based on tree model results, predicted few mussels in poorly connected backwater areas (e.g., floodplain lakes) and the navigation channel, whereas main channel border areas with high geomorphic complexity (e.g., river bends, islands, side channel entrances) and small side channels were typically favorable to mussels. Moreover, bootstrap aggregation of discharge-specific regression tree models of dive-quadrat data indicated that variables measured at low discharge were about 25% more predictive (PMSE = 14.8) than variables measured at median discharge (PMSE = 20.4) with high discharge (PMSE = 17.1) variables intermediate. This result suggests that episodic events such as droughts and floods were important in structuring mussel distributions. Although the substantial mussel and ancillary data in our study reach is unusual, our approach to develop exploratory statistical and geospatial models should be useful even when data are more limited. ?? 2007 Springer Science+Business Media B.V.

Industrial and occupational ergonomics in the petrochemical process industry: a regression trees approach.

PubMed

Bevilacqua, M; Ciarapica, F E; Giacchetta, G

2008-07-01

This work is an attempt to apply classification tree methods to data regarding accidents in a medium-sized refinery, so as to identify the important relationships between the variables, which can be considered as decision-making rules when adopting any measures for improvement. The results obtained using the CART (Classification And Regression Trees) method proved to be the most precise and, in general, they are encouraging concerning the use of tree diagrams as preliminary explorative techniques for the assessment of the ergonomic, management and operational parameters which influence high accident risk situations. The Occupational Injury analysis carried out in this paper was planned as a dynamic process and can be repeated systematically. The CART technique, which considers a very wide set of objective and predictive variables, shows new cause-effect correlations in occupational safety which had never been previously described, highlighting possible injury risk groups and supporting decision-making in these areas. The use of classification trees must not, however, be seen as an attempt to supplant other techniques, but as a complementary method which can be integrated into traditional types of analysis.

PRIM versus CART in subgroup discovery: when patience is harmful.

PubMed

Abu-Hanna, Ameen; Nannings, Barry; Dongelmans, Dave; Hasman, Arie

2010-10-01

We systematically compare the established algorithms CART (Classification and Regression Trees) and PRIM (Patient Rule Induction Method) in a subgroup discovery task on a large real-world high-dimensional clinical database. Contrary to current conjectures, PRIM's performance was generally inferior to CART's. PRIM often considered "peeling of" a large chunk of data at a value of a relevant discrete ordinal variable unattractive, ultimately missing an important subgroup. This finding has considerable significance in clinical medicine where ordinal scores are ubiquitous. PRIM's utility in clinical databases would increase when global information about (ordinal) variables is better put to use and when the search algorithm keeps track of alternative solutions.

Application of data mining techniques to explore predictors of upper urinary tract damage in patients with neurogenic bladder.

PubMed

Fang, H; Lu, B; Wang, X; Zheng, L; Sun, K; Cai, W

2017-08-17

This study proposed a decision tree model to screen upper urinary tract damage (UUTD) for patients with neurogenic bladder (NGB). Thirty-four NGB patients with UUTD were recruited in the case group, while 78 without UUTD were included in the control group. A decision tree method, classification and regression tree (CART), was then applied to develop the model in which UUTD was used as a dependent variable and history of urinary tract infections, bladder management, conservative treatment, and urodynamic findings were used as independent variables. The urethra function factor was found to be the primary screening information of patients and treated as the root node of the tree; Pabd max (maximum abdominal pressure, >14 cmH2O), Pves max (maximum intravesical pressure, ≤89 cmH2O), and gender (female) were also variables associated with UUTD. The accuracy of the proposed model was 84.8%, and the area under curve was 0.901 (95%CI=0.844-0.958), suggesting that the decision tree model might provide a new and convenient way to screen UUTD for NGB patients in both undeveloped and developing areas.

Regression trees modeling and forecasting of PM10 air pollution in urban areas

NASA Astrophysics Data System (ADS)

Stoimenova, M.; Voynikova, D.; Ivanov, A.; Gocheva-Ilieva, S.; Iliev, I.

2017-10-01

Fine particulate matter (PM10) air pollution is a serious problem affecting the health of the population in many Bulgarian cities. As an example, the object of this study is the pollution with PM10 of the town of Pleven, Northern Bulgaria. The measured concentrations of this air pollutant for this city consistently exceeded the permissible limits set by European and national legislation. Based on data for the last 6 years (2011-2016), the analysis shows that this applies both to the daily limit of 50 micrograms per cubic meter and the allowable number of daily concentration exceedances to 35 per year. Also, the average annual concentration of PM10 exceeded the prescribed norm of no more than 40 micrograms per cubic meter. The aim of this work is to build high performance mathematical models for effective prediction and forecasting the level of PM10 pollution. The study was conducted with the powerful flexible data mining technique Classification and Regression Trees (CART). The values of PM10 were fitted with respect to meteorological data such as maximum and minimum air temperature, relative humidity, wind speed and direction and others, as well as with time and autoregressive variables. As a result the obtained CART models demonstrate high predictive ability and fit the actual data with up to 80%. The best models were applied for forecasting the level pollution for 3 to 7 days ahead. An interpretation of the modeling results is presented.

Effect of symptom-based risk stratification on the costs of managing patients with chronic rhinosinusitis symptoms.

PubMed

Tan, Bruce K; Lu, Guanning; Kwasny, Mary J; Hsueh, Wayne D; Shintani-Smith, Stephanie; Conley, David B; Chandra, Rakesh K; Kern, Robert C; Leung, Randy

2013-11-01

Current symptom criteria poorly predict a diagnosis of chronic rhinosinusitis (CRS) resulting in excessive treatment of patients with presumed CRS. The objective of this study was analyze the positive predictive value of individual symptoms, or symptoms in combination, in patients with CRS symptoms and examine the costs of the subsequent diagnostic algorithm using a decision tree-based cost analysis. We analyzed previously collected patient-reported symptoms from a cross-sectional study of patients who had received a computed tomography (CT) scan of their sinuses at a tertiary care otolaryngology clinic for evaluation of CRS symptoms to calculate the positive predictive value of individual symptoms. Classification and regression tree (CART) analysis then optimized combinations of symptoms and thresholds to identify CRS patients. The calculated positive predictive values were applied to a previously developed decision tree that compared an upfront CT (uCT) algorithm against an empiric medical therapy (EMT) algorithm with further analysis that considered the availability of point of care (POC) imaging. The positive predictive value of individual symptoms ranged from 0.21 for patients reporting forehead pain and to 0.69 for patients reporting hyposmia. The CART model constructed a dichotomous model based on forehead pain, maxillary pain, hyposmia, nasal discharge, and facial pain (C-statistic 0.83). If POC CT were available, median costs ($64-$415) favored using the upfront CT for all individual symptoms. If POC CT was unavailable, median costs favored uCT for most symptoms except intercanthal pain (-$15), hyposmia (-$100), and discolored nasal discharge (-$24), although these symptoms became equivocal on cost sensitivity analysis. The three-tiered CART model could subcategorize patients into tiers where uCT was always favorable (median costs: $332-$504) and others for which EMT was always favorable (median costs -$121 to -$275). The uCT algorithm was always more costly if the nasal endoscopy was positive. Among patients with classic CRS symptoms, the frequency of individual symptoms varied the likelihood of a CRS diagnosis marginally. Only hyposmia, the absence of facial pain, and discolored discharge sufficiently increased the likelihood of diagnosis to potentially make EMT less costly. The development of an evidence-based, multisymptom-based risk stratification model could substantially affect the management costs of the subsequent diagnostic algorithm. © 2013 ARS-AAOA, LLC.

New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients.

PubMed

Kohrt, Holbrook E; Olshen, Richard A; Bermas, Honnie R; Goodson, William H; Wood, Douglas J; Henry, Solomon; Rouse, Robert V; Bailey, Lisa; Philben, Vicki J; Dirbas, Frederick M; Dunn, Jocelyn J; Johnson, Denise L; Wapnir, Irene L; Carlson, Robert W; Stockdale, Frank E; Hansen, Nora M; Jeffrey, Stefanie S

2008-03-04

Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model. We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University. 285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic invasion and size of SLN metastasis, and the product of tumor size and square of SLN metastasis size. We present a new model developed from a community-based SLN database that uses only three rather than eight variables to achieve higher accuracy than the Nomogram for predicting NSLN status in two different datasets.

Introduction in IND and recursive partitioning

NASA Technical Reports Server (NTRS)

Buntine, Wray; Caruana, Rich

1991-01-01

This manual describes the IND package for learning tree classifiers from data. The package is an integrated C and C shell re-implementation of tree learning routines such as CART, C4, and various MDL and Bayesian variations. The package includes routines for experiment control, interactive operation, and analysis of tree building. The manual introduces the system and its many options, gives a basic review of tree learning, contains a guide to the literature and a glossary, and lists the manual pages for the routines and instructions on installation.

Chronic subdural hematoma: Surgical management and outcome in 986 cases: A classification and regression tree approach

PubMed Central

Rovlias, Aristedis; Theodoropoulos, Spyridon; Papoutsakis, Dimitrios

2015-01-01

Background: Chronic subdural hematoma (CSDH) is one of the most common clinical entities in daily neurosurgical practice which carries a most favorable prognosis. However, because of the advanced age and medical problems of patients, surgical therapy is frequently associated with various complications. This study evaluated the clinical features, radiological findings, and neurological outcome in a large series of patients with CSDH. Methods: A classification and regression tree (CART) technique was employed in the analysis of data from 986 patients who were operated at Asclepeion General Hospital of Athens from January 1986 to December 2011. Burr holes evacuation with closed system drainage has been the operative technique of first choice at our institution for 29 consecutive years. A total of 27 prognostic factors were examined to predict the outcome at 3-month postoperatively. Results: Our results indicated that neurological status on admission was the best predictor of outcome. With regard to the other data, age, brain atrophy, thickness and density of hematoma, subdural accumulation of air, and antiplatelet and anticoagulant therapy were found to correlate significantly with prognosis. The overall cross-validated predictive accuracy of CART model was 85.34%, with a cross-validated relative error of 0.326. Conclusions: Methodologically, CART technique is quite different from the more commonly used methods, with the primary benefit of illustrating the important prognostic variables as related to outcome. Since, the ideal therapy for the treatment of CSDH is still under debate, this technique may prove useful in developing new therapeutic strategies and approaches for patients with CSDH. PMID:26257985

Combining logistic regression with classification and regression tree to predict quality of care in a home health nursing data set.

PubMed

Guo, Huey-Ming; Shyu, Yea-Ing Lotus; Chang, Her-Kun

2006-01-01

In this article, the authors provide an overview of a research method to predict quality of care in home health nursing data set. The results of this study can be visualized through classification an regression tree (CART) graphs. The analysis was more effective, and the results were more informative since the home health nursing dataset was analyzed with a combination of the logistic regression and CART, these two techniques complete each other. And the results more informative that more patients' characters were related to quality of care in home care. The results contributed to home health nurse predict patient outcome in case management. Improved prediction is needed for interventions to be appropriately targeted for improved patient outcome and quality of care.

Using the PDD Behavior Inventory as a Level 2 Screener: A Classification and Regression Trees Analysis

ERIC Educational Resources Information Center

Cohen, Ira L.; Liu, Xudong; Hudson, Melissa; Gillis, Jennifer; Cavalari, Rachel N. S.; Romanczyk, Raymond G.; Karmel, Bernard Z.; Gardner, Judith M.

2016-01-01

In order to improve discrimination accuracy between Autism Spectrum Disorder (ASD) and similar neurodevelopmental disorders, a data mining procedure, Classification and Regression Trees (CART), was used on a large multi-site sample of PDD Behavior Inventory (PDDBI) forms on children with and without ASD. Discrimination accuracy exceeded 80%,…

Predicting assemblages and species richness of endemic fish in the upper Yangtze River.

PubMed

He, Yongfeng; Wang, Jianwei; Lek-Ang, Sithan; Lek, Sovan

2010-09-01

The present work describes the ability of two modeling methods, Classification and Regression Tree (CART) and Random Forest (RF), to predict endemic fish assemblages and species richness in the upper Yangtze River, and then to identify the determinant environmental factors contributing to the models. The models included 24 predictor variables and 2 response variables (fish assemblage and species richness) for a total of 46 site units. The predictive quality of the modeling approaches was judged with a leave-one-out validation procedure. There was an average success of 60.9% and 71.7% to assign each site unit to the correct assemblage of fish, and 73% and 84% to explain the variance in species richness, by using CART and RF models, respectively. RF proved to be better than CART in terms of accuracy and efficiency in ecological applications. In any case, the mixed models including both land cover and river characteristic variables were more powerful than either individual one in explaining the endemic fish distribution pattern in the upper Yangtze River. For instance, altitude, slope, length, discharge, runoff, farmland and alpine and sub-alpine meadow played important roles in driving the observed endemic fish assemblage structure, while farmland, slope grassland, discharge, runoff, altitude and drainage area in explaining the observed patterns of endemic species richness. Therefore, the various effects of human activity on natural aquatic ecosystems, in particular, the flow modification of the river and the land use changes may have a considerable effect on the endemic fish distribution patterns on a regional scale. Copyright 2010 Elsevier B.V. All rights reserved.

Introduction to IND and recursive partitioning, version 1.0

NASA Technical Reports Server (NTRS)

Buntine, Wray; Caruana, Rich

1991-01-01

This manual describes the IND package for learning tree classifiers from data. The package is an integrated C and C shell re-implementation of tree learning routines such as CART, C4, and various MDL and Bayesian variations. The package includes routines for experiment control, interactive operation, and analysis of tree building. The manual introduces the system and its many options, gives a basic review of tree learning, contains a guide to the literature and a glossary, lists the manual pages for the routines, and instructions on installation.

Learning classification trees

NASA Technical Reports Server (NTRS)

Buntine, Wray

1991-01-01

Algorithms for learning classification trees have had successes in artificial intelligence and statistics over many years. How a tree learning algorithm can be derived from Bayesian decision theory is outlined. This introduces Bayesian techniques for splitting, smoothing, and tree averaging. The splitting rule turns out to be similar to Quinlan's information gain splitting rule, while smoothing and averaging replace pruning. Comparative experiments with reimplementations of a minimum encoding approach, Quinlan's C4 and Breiman et al. Cart show the full Bayesian algorithm is consistently as good, or more accurate than these other approaches though at a computational price.

Prediction of strontium bromide laser efficiency using cluster and decision tree analysis

NASA Astrophysics Data System (ADS)

Iliev, Iliycho; Gocheva-Ilieva, Snezhana; Kulin, Chavdar

2018-01-01

Subject of investigation is a new high-powered strontium bromide (SrBr2) vapor laser emitting in multiline region of wavelengths. The laser is an alternative to the atom strontium lasers and electron free lasers, especially at the line 6.45 μm which line is used in surgery for medical processing of biological tissues and bones with minimal damage. In this paper the experimental data from measurements of operational and output characteristics of the laser are statistically processed by means of cluster analysis and tree-based regression techniques. The aim is to extract the more important relationships and dependences from the available data which influence the increase of the overall laser efficiency. There are constructed and analyzed a set of cluster models. It is shown by using different cluster methods that the seven investigated operational characteristics (laser tube diameter, length, supplied electrical power, and others) and laser efficiency are combined in 2 clusters. By the built regression tree models using Classification and Regression Trees (CART) technique there are obtained dependences to predict the values of efficiency, and especially the maximum efficiency with over 95% accuracy.

Improving the prediction of going concern of Taiwanese listed companies using a hybrid of LASSO with data mining techniques.

PubMed

Goo, Yeung-Ja James; Chi, Der-Jang; Shen, Zong-De

2016-01-01

The purpose of this study is to establish rigorous and reliable going concern doubt (GCD) prediction models. This study first uses the least absolute shrinkage and selection operator (LASSO) to select variables and then applies data mining techniques to establish prediction models, such as neural network (NN), classification and regression tree (CART), and support vector machine (SVM). The samples of this study include 48 GCD listed companies and 124 NGCD (non-GCD) listed companies from 2002 to 2013 in the TEJ database. We conduct fivefold cross validation in order to identify the prediction accuracy. According to the empirical results, the prediction accuracy of the LASSO-NN model is 88.96 % (Type I error rate is 12.22 %; Type II error rate is 7.50 %), the prediction accuracy of the LASSO-CART model is 88.75 % (Type I error rate is 13.61 %; Type II error rate is 14.17 %), and the prediction accuracy of the LASSO-SVM model is 89.79 % (Type I error rate is 10.00 %; Type II error rate is 15.83 %).

A Recursive Partitioning Method for the Prediction of Preference Rankings Based Upon Kemeny Distances.

PubMed

D'Ambrosio, Antonio; Heiser, Willem J

2016-09-01

Preference rankings usually depend on the characteristics of both the individuals judging a set of objects and the objects being judged. This topic has been handled in the literature with log-linear representations of the generalized Bradley-Terry model and, recently, with distance-based tree models for rankings. A limitation of these approaches is that they only work with full rankings or with a pre-specified pattern governing the presence of ties, and/or they are based on quite strict distributional assumptions. To overcome these limitations, we propose a new prediction tree method for ranking data that is totally distribution-free. It combines Kemeny's axiomatic approach to define a unique distance between rankings with the CART approach to find a stable prediction tree. Furthermore, our method is not limited by any particular design of the pattern of ties. The method is evaluated in an extensive full-factorial Monte Carlo study with a new simulation design.

Assessing College Student Interest in Math and/or Computer Science in a Cross-National Sample Using Classification and Regression Trees

ERIC Educational Resources Information Center

Kitsantas, Anastasia; Kitsantas, Panagiota; Kitsantas, Thomas

2012-01-01

The purpose of this exploratory study was to assess the relative importance of a number of variables in predicting students' interest in math and/or computer science. Classification and regression trees (CART) were employed in the analysis of survey data collected from 276 college students enrolled in two U.S. and Greek universities. The results…

Diagnostic classification scheme in Iranian breast cancer patients using a decision tree.

PubMed

Malehi, Amal Saki

2014-01-01

The objective of this study was to determine a diagnostic classification scheme using a decision tree based model. The study was conducted as a retrospective case-control study in Imam Khomeini hospital in Tehran during 2001 to 2009. Data, including demographic and clinical-pathological characteristics, were uniformly collected from 624 females, 312 of them were referred with positive diagnosis of breast cancer (cases) and 312 healthy women (controls). The decision tree was implemented to develop a diagnostic classification scheme using CART 6.0 Software. The AUC (area under curve), was measured as the overall performance of diagnostic classification of the decision tree. Five variables as main risk factors of breast cancer and six subgroups as high risk were identified. The results indicated that increasing age, low age at menarche, single and divorced statues, irregular menarche pattern and family history of breast cancer are the important diagnostic factors in Iranian breast cancer patients. The sensitivity and specificity of the analysis were 66% and 86.9% respectively. The high AUC (0.82) also showed an excellent classification and diagnostic performance of the model. Decision tree based model appears to be suitable for identifying risk factors and high or low risk subgroups. It can also assists clinicians in making a decision, since it can identify underlying prognostic relationships and understanding the model is very explicit.

Heterogeneous models for an early discrimination between sepsis and non-infective SIRS in medical ward patients: a pilot study.

PubMed

Mearelli, Filippo; Fiotti, Nicola; Altamura, Nicola; Zanetti, Michela; Fernandes, Giovanni; Burekovic, Ismet; Occhipinti, Alessandro; Orso, Daniele; Giansante, Carlo; Casarsa, Chiara; Biolo, Gianni

2014-10-01

The objective of the study was to determine the accuracy of phospholipase A2 group II (PLA2-II), interferon-gamma-inducible protein 10 (IP-10), angiopoietin-2 (Ang-2), and procalcitonin (PCT) plasma levels in early ruling in/out of sepsis among systemic inflammatory response syndrome (SIRS) patients. Biomarker levels were determined in 80 SIRS patients during the first 4 h of admission to the medical ward. The final diagnosis of sepsis or non-infective SIRS was issued according to good clinical practice. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for sepsis diagnosis were assessed. The optimal biomarker combinations with clinical variables were investigated by logistic regression and decision tree (CART). PLA2-II, IP-10 and PCT, but not Ang-2, were significantly higher in septic (n = 60) than in non-infective SIRS (n = 20) patients (P ≤ 0.001, 0.027, and 0.002, respectively). PLA2-II PPV and NPV were 88 and 86%, respectively. The corresponding figures were 100 and 31% for IP-10, and 93 and 35% for PCT. Binary logistic regression model had 100% PPV and NPV, while manual and software-generated CART reached an overall accuracy of 95 and 98%, respectively, both with 100% NPV. PLA2-II and IP-10 associated with clinical variables in regression or decision tree heterogeneous models may be valuable biomarkers for sepsis diagnosis in SIRS patients admitted to medical ward (MW). Further studies are needed to introduce them into clinical practice.

Utility of salivary biomarkers for demonstrating acute myocardial infarction.

PubMed

Miller, C S; Foley, J D; Floriano, P N; Christodoulides, N; Ebersole, J L; Campbell, C L; Bailey, A L; Rose, B G; Kinane, D F; Novak, M J; McDevitt, J T; Ding, X; Kryscio, R J

2014-07-01

The comparative utility of serum and saliva as diagnostic fluids for identifying biomarkers of acute myocardial infarction (AMI) was investigated. The goal was to determine if salivary biomarkers could facilitate a screening diagnosis of AMI, especially in cases of non-ST elevation MI (NSTEMI), since these cases are not readily identified by electrocardiogram (ECG). Serum and unstimulated whole saliva (UWS) collected from 92 AMI patients within 48 hours of chest pain onset and 105 asymptomatic healthy control individuals were assayed for 13 proteins relevant to cardiovascular disease, by Beadlyte technology (Luminex(®)) and enzyme immunoassays. Data were analyzed with concentration cut-points, ECG findings, logistic regression (LR) (adjusted for matching for age, gender, race, smoking, number of teeth, and oral health status), and classification and regression tree (CART) analysis. A sensitivity analysis was conducted by repetition of the CART analysis in 58 cases and 58 controls, each matched by age and gender. Serum biomarkers demonstrated AMI sensitivity and specificity superior to that of saliva, as determined by LR and CART. The predominant discriminators in serum by LR were troponin I (TnI), B-type natriuretic peptide (BNP), and creatine kinase-MB (CK-MB), and TnI and BNP by CART. In saliva, LR identified C-reactive protein (CRP) as the biomarker most predictive of AMI. A combination of smoking tobacco, UWS CRP, CK-MB, sCD40 ligand, gender, and number of teeth identified AMI in the CART decision trees. When ECG findings, salivary biomarkers, and confounders were included, AMI was predicted with 80.0% sensitivity and 100% specificity. These analyses support the potential utility of salivary biomarker measurements used with ECG for the identification of AMI. Thus, saliva-based tests may provide additional diagnostic screening information in the clinical course for patients suspected of having an AMI. © International & American Associations for Dental Research.

Ranking malaria risk factors to guide malaria control efforts in African highlands.

PubMed

Protopopoff, Natacha; Van Bortel, Wim; Speybroeck, Niko; Van Geertruyden, Jean-Pierre; Baza, Dismas; D'Alessandro, Umberto; Coosemans, Marc

2009-11-25

Malaria is re-emerging in most of the African highlands exposing the non immune population to deadly epidemics. A better understanding of the factors impacting transmission in the highlands is crucial to improve well targeted malaria control strategies. A conceptual model of potential malaria risk factors in the highlands was built based on the available literature. Furthermore, the relative importance of these factors on malaria can be estimated through "classification and regression trees", an unexploited statistical method in the malaria field. This CART method was used to analyse the malaria risk factors in the Burundi highlands. The results showed that Anopheles density was the best predictor for high malaria prevalence. Then lower rainfall, no vector control, higher minimum temperature and houses near breeding sites were associated by order of importance to higher Anopheles density. In Burundi highlands monitoring Anopheles densities when rainfall is low may be able to predict epidemics. The conceptual model combined with the CART analysis is a decision support tool that could provide an important contribution toward the prevention and control of malaria by identifying major risk factors.

Preclinical Models in Chimeric Antigen Receptor-Engineered T-Cell Therapy.

PubMed

Siegler, Elizabeth Louise; Wang, Pin

2018-05-01

Cancer immunotherapy has enormous potential in inducing long-term remission in cancer patients, and chimeric antigen receptor (CAR)-engineered T cells have been largely successful in treating hematological malignancies in the clinic. CAR-T therapy has not been as effective in treating solid tumors, in part due to the immunosuppressive tumor microenvironment. Additionally, CAR-T therapy can cause dangerous side effects, including off-tumor toxicity, cytokine release syndrome, and neurotoxicity. Animal models of CAR-T therapy often fail to predict such adverse events and frequently overestimate the efficacy of the treatment. Nearly all preclinical CAR-T studies have been performed in mice, including syngeneic, xenograft, transgenic, and humanized mouse models. Recently, a few studies have used primate models to mimic clinical side effects better. To date, no single model perfectly recapitulates the human immune system and tumor microenvironment, and some models have revealed CAR-T limitations that were contradicted or missed entirely in other models. Careful model selection based on the primary goals of the study is a crucial step in evaluating CAR-T treatment. Advancements are being made in preclinical models, with the ultimate objective of providing safer, more effective CAR-T therapy to patients.

Using CART to segment road images

NASA Astrophysics Data System (ADS)

Davies, Bob; Lienhart, Rainer

2006-01-01

The 2005 DARPA Grand Challenge is a 132 mile race through the desert with autonomous robotic vehicles. Lasers mounted on the car roof provide a map of the road up to 20 meters ahead of the car but the car needs to see further in order to go fast enough to win the race. Computer vision can extend that map of the road ahead but desert road is notoriously similar to the surrounding desert. The CART algorithm (Classification and Regression Trees) provided a machine learning boost to find road while at the same time measuring when that road could not be distinguished from surrounding desert.

Method of Grassland Information Extraction Based on Multi-Level Segmentation and Cart Model

NASA Astrophysics Data System (ADS)

Qiao, Y.; Chen, T.; He, J.; Wen, Q.; Liu, F.; Wang, Z.

2018-04-01

It is difficult to extract grassland accurately by traditional classification methods, such as supervised method based on pixels or objects. This paper proposed a new method combing the multi-level segmentation with CART (classification and regression tree) model. The multi-level segmentation which combined the multi-resolution segmentation and the spectral difference segmentation could avoid the over and insufficient segmentation seen in the single segmentation mode. The CART model was established based on the spectral characteristics and texture feature which were excavated from training sample data. Xilinhaote City in Inner Mongolia Autonomous Region was chosen as the typical study area and the proposed method was verified by using visual interpretation results as approximate truth value. Meanwhile, the comparison with the nearest neighbor supervised classification method was obtained. The experimental results showed that the total precision of classification and the Kappa coefficient of the proposed method was 95 % and 0.9, respectively. However, the total precision of classification and the Kappa coefficient of the nearest neighbor supervised classification method was 80 % and 0.56, respectively. The result suggested that the accuracy of classification proposed in this paper was higher than the nearest neighbor supervised classification method. The experiment certificated that the proposed method was an effective extraction method of grassland information, which could enhance the boundary of grassland classification and avoid the restriction of grassland distribution scale. This method was also applicable to the extraction of grassland information in other regions with complicated spatial features, which could avoid the interference of woodland, arable land and water body effectively.

Potential habitat distribution for the freshwater diatom Didymosphenia geminata in the continental US

USGS Publications Warehouse

Kumar, S.; Spaulding, S.A.; Stohlgren, T.J.; Hermann, K.A.; Schmidt, T.S.; Bahls, L.L.

2009-01-01

The diatom Didymosphenia geminata is a single-celled alga found in lakes, streams, and rivers. Nuisance blooms of D geminata affect the diversity, abundance, and productivity of other aquatic organisms. Because D geminata can be transported by humans on waders and other gear, accurate spatial prediction of habitat suitability is urgently needed for early detection and rapid response, as well as for evaluation of monitoring and control programs. We compared four modeling methods to predict D geminata's habitat distribution; two methods use presence-absence data (logistic regression and classification and regression tree [CART]), and two involve presence data (maximum entropy model [Maxent] and genetic algorithm for rule-set production [GARP]). Using these methods, we evaluated spatially explicit, bioclimatic and environmental variables as predictors of diatom distribution. The Maxent model provided the most accurate predictions, followed by logistic regression, CART, and GARP. The most suitable habitats were predicted to occur in the western US, in relatively cool sites, and at high elevations with a high base-flow index. The results provide insights into the factors that affect the distribution of D geminata and a spatial basis for the prediction of nuisance blooms. ?? The Ecological Society of America.

Data mining: Potential applications in research on nutrition and health.

PubMed

Batterham, Marijka; Neale, Elizabeth; Martin, Allison; Tapsell, Linda

2017-02-01

Data mining enables further insights from nutrition-related research, but caution is required. The aim of this analysis was to demonstrate and compare the utility of data mining methods in classifying a categorical outcome derived from a nutrition-related intervention. Baseline data (23 variables, 8 categorical) on participants (n = 295) in an intervention trial were used to classify participants in terms of meeting the criteria of achieving 10 000 steps per day. Results from classification and regression trees (CARTs), random forests, adaptive boosting, logistic regression, support vector machines and neural networks were compared using area under the curve (AUC) and error assessments. The CART produced the best model when considering the AUC (0.703), overall error (18%) and within class error (28%). Logistic regression also performed reasonably well compared to the other models (AUC 0.675, overall error 23%, within class error 36%). All the methods gave different rankings of variables' importance. CART found that body fat, quality of life using the SF-12 Physical Component Summary (PCS) and the cholesterol: HDL ratio were the most important predictors of meeting the 10 000 steps criteria, while logistic regression showed the SF-12PCS, glucose levels and level of education to be the most significant predictors (P ≤ 0.01). Differing outcomes suggest caution is required with a single data mining method, particularly in a dataset with nonlinear relationships and outliers and when exploring relationships that were not the primary outcomes of the research. © 2017 Dietitians Association of Australia.

Exploring the social determinants of mental health service use using intersectionality theory and CART analysis.

PubMed

Cairney, John; Veldhuizen, Scott; Vigod, Simone; Streiner, David L; Wade, Terrance J; Kurdyak, Paul

2014-02-01

Fewer than half of individuals with a mental disorder seek formal care in a given year. Much research has been conducted on the factors that influence service use in this population, but the methods generally used cannot easily identify the complex interactions that are thought to exist. In this paper, we examine predictors of subsequent service use among respondents to a population health survey who met criteria for a past-year mood, anxiety or substance-related disorder. To determine service use, we use an administrative database including all physician consultations in the period of interest. To identify predictors, we use classification tree (CART) analysis, a data mining technique with the ability to identify unsuspected interactions. We compare results to those from logistic regression models. We identify 1213 individuals with past-year disorder. In the year after the survey, 24% (n=312) of these had a mental health-related physician consultation. Logistic regression revealed that age, sex and marital status predicted service use. CART analysis yielded a set of rules based on age, sex, marital status and income adequacy, with marital status playing a role among men and by income adequacy important among women. CART analysis proved moderately effective overall, with agreement of 60%, sensitivity of 82% and specificity of 53%. Results highlight the potential of data-mining techniques to uncover complex interactions, and offer support to the view that the intersection of multiple statuses influence health and behaviour in ways that are difficult to identify with conventional statistics. The disadvantages of these methods are also discussed.

A Comparative Assessment of the Influences of Human Impacts on Soil Cd Concentrations Based on Stepwise Linear Regression, Classification and Regression Tree, and Random Forest Models

PubMed Central

Qiu, Lefeng; Wang, Kai; Long, Wenli; Wang, Ke; Hu, Wei; Amable, Gabriel S.

2016-01-01

Soil cadmium (Cd) contamination has attracted a great deal of attention because of its detrimental effects on animals and humans. This study aimed to develop and compare the performances of stepwise linear regression (SLR), classification and regression tree (CART) and random forest (RF) models in the prediction and mapping of the spatial distribution of soil Cd and to identify likely sources of Cd accumulation in Fuyang County, eastern China. Soil Cd data from 276 topsoil (0–20 cm) samples were collected and randomly divided into calibration (222 samples) and validation datasets (54 samples). Auxiliary data, including detailed land use information, soil organic matter, soil pH, and topographic data, were incorporated into the models to simulate the soil Cd concentrations and further identify the main factors influencing soil Cd variation. The predictive models for soil Cd concentration exhibited acceptable overall accuracies (72.22% for SLR, 70.37% for CART, and 75.93% for RF). The SLR model exhibited the largest predicted deviation, with a mean error (ME) of 0.074 mg/kg, a mean absolute error (MAE) of 0.160 mg/kg, and a root mean squared error (RMSE) of 0.274 mg/kg, and the RF model produced the results closest to the observed values, with an ME of 0.002 mg/kg, an MAE of 0.132 mg/kg, and an RMSE of 0.198 mg/kg. The RF model also exhibited the greatest R2 value (0.772). The CART model predictions closely followed, with ME, MAE, RMSE, and R2 values of 0.013 mg/kg, 0.154 mg/kg, 0.230 mg/kg and 0.644, respectively. The three prediction maps generally exhibited similar and realistic spatial patterns of soil Cd contamination. The heavily Cd-affected areas were primarily located in the alluvial valley plain of the Fuchun River and its tributaries because of the dramatic industrialization and urbanization processes that have occurred there. The most important variable for explaining high levels of soil Cd accumulation was the presence of metal smelting industries. The good performance of the RF model was attributable to its ability to handle the non-linear and hierarchical relationships between soil Cd and environmental variables. These results confirm that the RF approach is promising for the prediction and spatial distribution mapping of soil Cd at the regional scale. PMID:26964095

A Comparative Assessment of the Influences of Human Impacts on Soil Cd Concentrations Based on Stepwise Linear Regression, Classification and Regression Tree, and Random Forest Models.

PubMed

Qiu, Lefeng; Wang, Kai; Long, Wenli; Wang, Ke; Hu, Wei; Amable, Gabriel S

2016-01-01

Soil cadmium (Cd) contamination has attracted a great deal of attention because of its detrimental effects on animals and humans. This study aimed to develop and compare the performances of stepwise linear regression (SLR), classification and regression tree (CART) and random forest (RF) models in the prediction and mapping of the spatial distribution of soil Cd and to identify likely sources of Cd accumulation in Fuyang County, eastern China. Soil Cd data from 276 topsoil (0-20 cm) samples were collected and randomly divided into calibration (222 samples) and validation datasets (54 samples). Auxiliary data, including detailed land use information, soil organic matter, soil pH, and topographic data, were incorporated into the models to simulate the soil Cd concentrations and further identify the main factors influencing soil Cd variation. The predictive models for soil Cd concentration exhibited acceptable overall accuracies (72.22% for SLR, 70.37% for CART, and 75.93% for RF). The SLR model exhibited the largest predicted deviation, with a mean error (ME) of 0.074 mg/kg, a mean absolute error (MAE) of 0.160 mg/kg, and a root mean squared error (RMSE) of 0.274 mg/kg, and the RF model produced the results closest to the observed values, with an ME of 0.002 mg/kg, an MAE of 0.132 mg/kg, and an RMSE of 0.198 mg/kg. The RF model also exhibited the greatest R2 value (0.772). The CART model predictions closely followed, with ME, MAE, RMSE, and R2 values of 0.013 mg/kg, 0.154 mg/kg, 0.230 mg/kg and 0.644, respectively. The three prediction maps generally exhibited similar and realistic spatial patterns of soil Cd contamination. The heavily Cd-affected areas were primarily located in the alluvial valley plain of the Fuchun River and its tributaries because of the dramatic industrialization and urbanization processes that have occurred there. The most important variable for explaining high levels of soil Cd accumulation was the presence of metal smelting industries. The good performance of the RF model was attributable to its ability to handle the non-linear and hierarchical relationships between soil Cd and environmental variables. These results confirm that the RF approach is promising for the prediction and spatial distribution mapping of soil Cd at the regional scale.

Combined use of two supervised learning algorithms to model sea turtle behaviours from tri-axial acceleration data.

PubMed

Jeantet, L; Dell'Amico, F; Forin-Wiart, M-A; Coutant, M; Bonola, M; Etienne, D; Gresser, J; Regis, S; Lecerf, N; Lefebvre, F; de Thoisy, B; Le Maho, Y; Brucker, M; Châtelain, N; Laesser, R; Crenner, F; Handrich, Y; Wilson, R; Chevallier, D

2018-05-23

Accelerometers are becoming ever more important sensors in animal-attached technology, providing data that allow determination of body posture and movement and thereby helping to elucidate behaviour in animals that are difficult to observe. We sought to validate the identification of sea turtle behaviours from accelerometer signals by deploying tags on the carapace of a juvenile loggerhead ( Caretta caretta ), an adult hawksbill ( Eretmochelys imbricata ) and an adult green turtle ( Chelonia mydas ) at Aquarium La Rochelle, France. We recorded tri-axial acceleration at 50 Hz for each species for a full day while two fixed cameras recorded their behaviours. We identified behaviours from the acceleration data using two different supervised learning algorithms, Random Forest and Classification And Regression Tree (CART), treating the data from the adult animals as separate from the juvenile data. We achieved a global accuracy of 81.30% for the adult hawksbill and green turtle CART model and 71.63% for the juvenile loggerhead, identifying 10 and 12 different behaviours, respectively. Equivalent figures were 86.96% for the adult hawksbill and green turtle Random Forest model and 79.49% for the juvenile loggerhead, for the same behaviours. The use of Random Forest combined with CART algorithms allowed us to understand the decision rules implicated in behaviour discrimination, and thus remove or group together some 'confused' or under--represented behaviours in order to get the most accurate models. This study is the first to validate accelerometer data to identify turtle behaviours and the approach can now be tested on other captive sea turtle species. © 2018. Published by The Company of Biologists Ltd.

Modeling ready biodegradability of fragrance materials.

PubMed

Ceriani, Lidia; Papa, Ester; Kovarich, Simona; Boethling, Robert; Gramatica, Paola

2015-06-01

In the present study, quantitative structure activity relationships were developed for predicting ready biodegradability of approximately 200 heterogeneous fragrance materials. Two classification methods, classification and regression tree (CART) and k-nearest neighbors (kNN), were applied to perform the modeling. The models were validated with multiple external prediction sets, and the structural applicability domain was verified by the leverage approach. The best models had good sensitivity (internal ≥80%; external ≥68%), specificity (internal ≥80%; external 73%), and overall accuracy (≥75%). Results from the comparison with BIOWIN global models, based on group contribution method, show that specific models developed in the present study perform better in prediction than BIOWIN6, in particular for the correct classification of not readily biodegradable fragrance materials. © 2015 SETAC.

Modified TAROT for cross-selling personal financial products

NASA Astrophysics Data System (ADS)

Tee, Ya-Mei; LEE, Lai-Soon; LEE, Chew-Ging; SEOW, Hsin-Vonn

2014-09-01

The Top Application characteristics Remainder Offer characteristics Tree (TAROT) was first introduced in 2007. This is a modified Classification and Regression Trees (CART) used to help decide which question(s) to ask potential applicants to customise an offer of a personal financial product so that it would have a high probability of take up. In this piece of work the authors are presenting, they have further modified the TAROT to cross TAROT, using its properties and modeling steps to deal with the issue of cross-selling. Since the bank already has ready customers, it would be ideal to cross-sell the financial products seeing that one can ask one (or more) further question(s) based on the initial offer to identify and customise another financial product to offer.

Cervical cancer survival prediction using hybrid of SMOTE, CART and smooth support vector machine

NASA Astrophysics Data System (ADS)

Purnami, S. W.; Khasanah, P. M.; Sumartini, S. H.; Chosuvivatwong, V.; Sriplung, H.

2016-04-01

According to the WHO, every two minutes there is one patient who died from cervical cancer. The high mortality rate is due to the lack of awareness of women for early detection. There are several factors that supposedly influence the survival of cervical cancer patients, including age, anemia status, stage, type of treatment, complications and secondary disease. This study wants to classify/predict cervical cancer survival based on those factors. Various classifications methods: classification and regression tree (CART), smooth support vector machine (SSVM), three order spline SSVM (TSSVM) were used. Since the data of cervical cancer are imbalanced, synthetic minority oversampling technique (SMOTE) is used for handling imbalanced dataset. Performances of these methods are evaluated using accuracy, sensitivity and specificity. Results of this study show that balancing data using SMOTE as preprocessing can improve performance of classification. The SMOTE-SSVM method provided better result than SMOTE-TSSVM and SMOTE-CART.

[A strategy for assessing environmental influence on airway allergy using a regression binary tree-based method].

PubMed

Yoshioka, Fumi; Azuma, Emiko; Nakajima, Takae; Hashimoto, Masafumi; Toyoshima, Kyoichiro; Komachi, Yoshio

2004-08-01

To clarify the living environment factors that increase the risk of allergic sensitization to house dust mites, we applied a regression binary tree-based method (CART, Classification & Regression Trees) to an epidemiological study on airway allergy. The utility of the tree map in personal sanitary guidance for preventing allergic sensitization was examined with respect to feasibility and validity. A questionnaire was given to 386 healthy adult women, asking them about their individual living environments. Also, blood samples were collected to measure Dermatophagoides pteronyssinus (Dp)-specific IgE, the presence/absence of Dp-sensitization being expressed as positive/negative. The questionnaire consisted of nine items on (1) home ventilation by keeping windows open, (2) personal or family smoking habits, (3) use of air conditioners in hot weather, (4) type of flooring (tatami/wooden/carpet) in the living room, (5) visible mold proliferation in the kitchen, (6) type of housing (concrete/wooden), (7) residential area (heavy or light traffic area) (8) heating system (use of unventilated combustion appliances), and (9) frequency of cleaning (every day or less often). There also were queries on the past history of airway allergic diseases, such as bronchial asthma and allergic rhinitis. CART and a multivariate logistic regression analysis (MLRA) were performed. The subjects were first classified into two groups, with and without a history of airway allergic diseases (Groups WPH and WOPH). In each group, the involvement of living environment factors in Dp-sensitization was examined using CART and MLRA. In the MLRA study, individual living environment factors showed promotional or suppressive effects on Dp-sensitization with differences between the two groups. With respect to the CART results, the two groups were first split by the factor that had the most significant odds ratio for MLRA. In Group WPH, which had a Dp-sensitization risk of 19.5%, the first split was by the factor of visible mold proliferation in the kitchen into the factor-present group with a risk value of 45.5% and the factor-absent group with 13.5%. The mold proliferation group was split with reference to frequent cleaning, and the risk rose to 75% in the factor-absent group and to 100% when family smoking habits were reported. Group WOPH (the risk: 10.8%) was first split into two groups according to the use of air conditioners in hot weather for more than 6 hours a day or less, which showed risk values of 16.7% and 6.9%, respectively. The risk of the group that intensively used air conditioners fell to 8.3% with tatami as flooring in the living room, and, if others, rose to 20.8%. The risk of the factor-lacking group fell to 4.0% without wooden flooring. CART analysis enables us to express complex relationships between living environment factors and Dp-sensitization simply by a binary regression tree, pointing to preventive strategies that can be flexibly changed according to the individual living environments of the subjects.

Predicting the probability of mortality of gastric cancer patients using decision tree.

PubMed

Mohammadzadeh, F; Noorkojuri, H; Pourhoseingholi, M A; Saadat, S; Baghestani, A R

2015-06-01

Gastric cancer is the fourth most common cancer worldwide. This reason motivated us to investigate and introduce gastric cancer risk factors utilizing statistical methods. The aim of this study was to identify the most important factors influencing the mortality of patients who suffer from gastric cancer disease and to introduce a classification approach according to decision tree model for predicting the probability of mortality from this disease. Data on 216 patients with gastric cancer, who were registered in Taleghani hospital in Tehran,Iran, were analyzed. At first, patients were divided into two groups: the dead and alive. Then, to fit decision tree model to our data, we randomly selected 20% of dataset to the test sample and remaining dataset considered as the training sample. Finally, the validity of the model examined with sensitivity, specificity, diagnosis accuracy and the area under the receiver operating characteristic curve. The CART version 6.0 and SPSS version 19.0 softwares were used for the analysis of the data. Diabetes, ethnicity, tobacco, tumor size, surgery, pathologic stage, age at diagnosis, exposure to chemical weapons and alcohol consumption were determined as effective factors on mortality of gastric cancer. The sensitivity, specificity and accuracy of decision tree were 0.72, 0.75 and 0.74 respectively. The indices of sensitivity, specificity and accuracy represented that the decision tree model has acceptable accuracy to prediction the probability of mortality in gastric cancer patients. So a simple decision tree consisted of factors affecting on mortality of gastric cancer may help clinicians as a reliable and practical tool to predict the probability of mortality in these patients.

Making `Internal Thermal Energy' Visible

NASA Astrophysics Data System (ADS)

Zou, Xueli

2004-09-01

In a 1992 paper published in this journal, Uri Ganiel described a pair of model carts used to demonstrate elastic and inelastic collisions. The wooden carts had low-friction wheels and a steel-strip bumper on one end. On one of the carts, a number of brass washers were rigidly mounted in vertical stacks to a wooden framework. The other cart was similar except that the washers were tied to rubber bands that were stretched horizontally and diagonally across the framework. When the first cart was rolled into a wall it bounced off with only a small reduction in speed ("elastic" collision). The second cart, on the other hand, was found to come nearly to a complete stop upon colliding with the wall ("inelastic" collision). Following the instructions given in Ganiel's paper, I built a pair of carts and demonstrated them to introductory-level physics students at a large public university. It was interesting to find that many students were distracted by the different-looking structures of the two model carts.2 They thought the different distributions of washers between the carts resulted in the rubber-band cart bouncing back a significantly shorter distance than the rigid-rod one after they both collided with a wall at the same initial speed. Apparently, the students had difficulties in understanding the collisions and used surface features to reason about them. To avoid this superficial distraction and to help students visualize easily "where the kinetic energy goes in an inelastic collision," I modified the rigid-rod cart to have washers fixed on hollow aluminum rods mounted at four different levels horizontally and diagonally (see Fig. 1). The new pair of the model carts look very similar to each other: They have the same bumpers, same wheels, same distributions of washers, and same masses.

Proposed Clinical Decision Rules to Diagnose Acute Rhinosinusitis Among Adults in Primary Care.

PubMed

Ebell, Mark H; Hansen, Jens Georg

2017-07-01

To reduce inappropriate antibiotic prescribing, we sought to develop a clinical decision rule for the diagnosis of acute rhinosinusitis and acute bacterial rhinosinusitis. Multivariate analysis and classification and regression tree (CART) analysis were used to develop clinical decision rules for the diagnosis of acute rhinosinusitis, defined using 3 different reference standards (purulent antral puncture fluid or abnormal finding on a computed tomographic (CT) scan; for acute bacterial rhinosinusitis, we used a positive bacterial culture of antral fluid). Signs, symptoms, C-reactive protein (CRP), and reference standard tests were prospectively recorded in 175 Danish patients aged 18 to 65 years seeking care for suspected acute rhinosinusitis. For each reference standard, we developed 2 clinical decision rules: a point score based on a logistic regression model and an algorithm based on a CART model. We identified low-, moderate-, and high-risk groups for acute rhinosinusitis or acute bacterial rhinosinusitis for each clinical decision rule. The point scores each had between 5 and 6 predictors, and an area under the receiver operating characteristic curve (AUROCC) between 0.721 and 0.767. For positive bacterial culture as the reference standard, low-, moderate-, and high-risk groups had a 16%, 49%, and 73% likelihood of acute bacterial rhinosinusitis, respectively. CART models had an AUROCC ranging from 0.783 to 0.827. For positive bacterial culture as the reference standard, low-, moderate-, and high-risk groups had a likelihood of acute bacterial rhinosinusitis of 6%, 31%, and 59% respectively. We have developed a series of clinical decision rules integrating signs, symptoms, and CRP to diagnose acute rhinosinusitis and acute bacterial rhinosinusitis with good accuracy. They now require prospective validation and an assessment of their effect on clinical and process outcomes. © 2017 Annals of Family Medicine, Inc.

HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

PubMed

Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

2016-10-15

While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In this study, we isolated and sequenced HIV from postmortem tissues from three HIV(+) cART(+) individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve, and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV expansion, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Topographic influences on vegetation mosaics and tree diversity in the Chihuahuan Desert Borderlands.

PubMed

Poulos, Helen M; Camp, Ann E

2010-04-01

The abundance and distribution of species reflect how the niche requirements of species and the dynamics of populations interact with spatial and temporal variation in the environment. This study investigated the influence of geographical variation in environmental site conditions on tree dominance and diversity patterns in three topographically dissected mountain ranges in west Texas, USA, and northern Mexico. We measured tree abundance and basal area using a systematic sampling design across the forested areas of three mountain ranges and related these data to a suite of environmental parameters derived from field and digital elevation model data. We employed cluster analysis, classification and regression trees (CART), and rarefaction to identify (1) the dominant forest cover types across the three study sites and (2) environmental influences on tree distribution and diversity patterns. Elevation, topographic position, and incident solar radiation were the major influences on tree dominance and diversity. Mesic valley bottoms hosted high-diversity vegetation types, while hotter and drier mid-slopes and ridgetops supported lower tree diversity. Valley bottoms and other topographic positions shared few species, indicating high species turnover at the landscape scale. Mountain ranges with high topographic complexity also had higher species richness, suggesting that geographical variability in environmental conditions was a major influence on tree diversity. This study stressed the importance of landscape- and regional-scale topographic variability as a key factor controlling vegetation pattern and diversity in southwestern North America.

Pesticides in Urban Multiunit Dwellings: Hazard IdentificationUsing Classification and Regression Tree (CART) Analysis

EPA Science Inventory

Many units in public housing or other low-income urban dwellings may have elevated pesticide residues, given recurring infestation, but it would be logistically and economically infeasible to sample a large number of units to identify highly exposed households to design interven...

Differential Diagnosis of Erythmato-Squamous Diseases Using Classification and Regression Tree.

PubMed

Maghooli, Keivan; Langarizadeh, Mostafa; Shahmoradi, Leila; Habibi-Koolaee, Mahdi; Jebraeily, Mohamad; Bouraghi, Hamid

2016-10-01

Differential diagnosis of Erythmato-Squamous Diseases (ESD) is a major challenge in the field of dermatology. The ESD diseases are placed into six different classes. Data mining is the process for detection of hidden patterns. In the case of ESD, data mining help us to predict the diseases. Different algorithms were developed for this purpose. we aimed to use the Classification and Regression Tree (CART) to predict differential diagnosis of ESD. we used the Cross Industry Standard Process for Data Mining (CRISP-DM) methodology. For this purpose, the dermatology data set from machine learning repository, UCI was obtained. The Clementine 12.0 software from IBM Company was used for modelling. In order to evaluation of the model we calculate the accuracy, sensitivity and specificity of the model. The proposed model had an accuracy of 94.84% (. 24.42) in order to correct prediction of the ESD disease. Results indicated that using of this classifier could be useful. But, it would be strongly recommended that the combination of machine learning methods could be more useful in terms of prediction of ESD.

75 FR 4769 - Hand Trucks and Certain Parts Thereof From The People's Republic of China: Notice of Decision of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

...''), requested the Department to determine whether two of the welding carts that it imported, models 93851 and... Ruling for Central Purchasing, LLC's Two Models of Welding Carts,'' dated February 15, 2006 (``Final... reevaluated its position and determined that both models of welding carts were subject to the Order. The trial...

HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer

PubMed Central

Rose, Rebecca; Lamers, Susanna L.; Nolan, David J.; Maidji, Ekaterina; Faria, N. R.; Pybus, Oliver G.; Dollar, James J.; Maruniak, Samuel A.; McAvoy, Andrew C.; Salemi, Marco; Stoddart, Cheryl A.; Singer, Elyse J.

2016-01-01

ABSTRACT While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV+ cART-treated (cART+) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART+ and cART-naive (cART−) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA+ cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. IMPORTANCE Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In this study, we isolated and sequenced HIV from postmortem tissues from three HIV+ cART+ individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve, and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV expansion, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies. PMID:27466425

Rolling Friction on a Wheeled Laboratory Cart

ERIC Educational Resources Information Center

Mungan, Carl E.

2012-01-01

A simple model is developed that predicts the coefficient of rolling friction for an undriven laboratory cart on a track that is approximately independent of the mass loaded onto the cart and of the angle of inclination of the track. The model includes both deformation of the wheels/track and frictional torque at the axles/bearings. The concept of…

Demographic and financial characteristics of school districts with low and high à la Carte sales in rural Kansas Public Schools.

PubMed

Nollen, Nicole L; Kimminau, Kim S; Nazir, Niaman

2011-06-01

Reducing à la carte items in schools-foods and beverages sold outside the reimbursable meals program-can have important implications for childhood obesity. However, schools are reluctant to reduce à la carte offerings because of the impact these changes could have on revenue. Some foodservice programs operate with limited à la carte sales, but little is known about these programs. This secondary data analysis compared rural and urban/suburban school districts with low and high à la carte sales. Foodservice financial records (2007-2008) were obtained from the Kansas State Department of Education for all public K-12 school districts (n=302). χ² and t tests were used to examine the independent association of variables to à la carte sales. A multivariate model was then constructed of the factors most strongly associated with low à la carte sales. In rural districts with low à la carte sales, lunch prices and participation were higher, lunch costs and à la carte quality were lower, and fewer free/reduced price lunches were served compared to rural districts with high à la carte sales. Lunch price (odds ratio=1.2; 95% confidence interval, 1.1 to 1.4) and free/reduced price lunch participation (odds ratio=3.0; 95% confidence interval, 1.0 to 9.8) remained in the multivariate model predicting low à la carte sales. No differences were found between urban/suburban districts with low and high à la carte sales. Findings highlight important factors to maintaining low à la carte sales. Schools should consider raising lunch prices and increasing meal participation rates as two potential strategies for reducing the sale of à la carte items without compromising foodservice revenue. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

Prediction of Potential Hit Song and Musical Genre Using Artificial Neural Networks

NASA Astrophysics Data System (ADS)

Monterola, Christopher; Abundo, Cheryl; Tugaff, Jeric; Venturina, Lorcel Ericka

Accurately quantifying the goodness of music based on the seemingly subjective taste of the public is a multi-million industry. Recording companies can make sound decisions on which songs or artists to prioritize if accurate forecasting is achieved. We extract 56 single-valued musical features (e.g. pitch and tempo) from 380 Original Pilipino Music (OPM) songs (190 are hit songs) released from 2004 to 2006. Based on an effect size criterion which measures a variable's discriminating power, the 20 highest ranked features are fed to a classifier tasked to predict hit songs. We show that regardless of musical genre, a trained feed-forward neural network (NN) can predict potential hit songs with an average accuracy of ΦNN = 81%. The accuracy is about +20% higher than those of standard classifiers such as linear discriminant analysis (LDA, ΦLDA = 61%) and classification and regression trees (CART, ΦCART = 57%). Both LDA and CART are above the proportional chance criterion (PCC, ΦPCC = 50%) but are slightly below the suggested acceptable classifier requirement of 1.25*ΦPCC = 63%. Utilizing a similar procedure, we demonstrate that different genres (ballad, alternative rock or rock) of OPM songs can be automatically classified with near perfect accuracy using LDA or NN but only around 77% using CART.

Assessing the Effectiveness of Statistical Classification Techniques in Predicting Future Employment of Participants in the Temporary Assistance for Needy Families Program

ERIC Educational Resources Information Center

Montoya, Isaac D.

2008-01-01

Three classification techniques (Chi-square Automatic Interaction Detection [CHAID], Classification and Regression Tree [CART], and discriminant analysis) were tested to determine their accuracy in predicting Temporary Assistance for Needy Families program recipients' future employment. Technique evaluation was based on proportion of correctly…

Student Self-Reported Learning Outcomes of Field Trips: The Pedagogical Impact

ERIC Educational Resources Information Center

Alon, Nirit Lavie; Tal, Tali

2015-01-01

In this study, we used the classification and regression trees (CART) method to draw relationships between student self-reported learning outcomes in 26 field trips to natural environments and various characteristics of the field trip that include variables associated with preparation and pedagogy. We wished to examine the extent to which the…

Assessing wildfire risks at multiple spatial scales

Treesearch

Justin Fitch

2008-01-01

In continuation of the efforts to advance wildfire science and develop tools for wildland fire managers, a spatial wildfire risk assessment was carried out using Classification and Regression Tree analysis (CART) and Geographic Information Systems (GIS). The analysis was performed at two scales. The small-scale assessment covered the entire state of New Mexico, while...

Study on Ecological Risk Assessment of Guangxi Coastal Zone Based on 3s Technology

NASA Astrophysics Data System (ADS)

Zhong, Z.; Luo, H.; Ling, Z. Y.; Huang, Y.; Ning, W. Y.; Tang, Y. B.; Shao, G. Z.

2018-05-01

This paper takes Guangxi coastal zone as the study area, following the standards of land use type, divides the coastal zone of ecological landscape into seven kinds of natural wetland landscape types such as woodland, farmland, grassland, water, urban land and wetlands. Using TM data of 2000-2015 such 15 years, with the CART decision tree algorithm, for analysis the characteristic of types of landscape's remote sensing image and build decision tree rules of landscape classification to extract information classification. Analyzing of the evolution process of the landscape pattern in Guangxi coastal zone in nearly 15 years, we may understand the distribution characteristics and change rules. Combined with the natural disaster data, we use of landscape index and the related risk interference degree and construct ecological risk evaluation model in Guangxi coastal zone for ecological risk assessment results of Guangxi coastal zone.

Propensity score estimation: machine learning and classification methods as alternatives to logistic regression

PubMed Central

Westreich, Daniel; Lessler, Justin; Funk, Michele Jonsson

2010-01-01

Summary Objective Propensity scores for the analysis of observational data are typically estimated using logistic regression. Our objective in this Review was to assess machine learning alternatives to logistic regression which may accomplish the same goals but with fewer assumptions or greater accuracy. Study Design and Setting We identified alternative methods for propensity score estimation and/or classification from the public health, biostatistics, discrete mathematics, and computer science literature, and evaluated these algorithms for applicability to the problem of propensity score estimation, potential advantages over logistic regression, and ease of use. Results We identified four techniques as alternatives to logistic regression: neural networks, support vector machines, decision trees (CART), and meta-classifiers (in particular, boosting). Conclusion While the assumptions of logistic regression are well understood, those assumptions are frequently ignored. All four alternatives have advantages and disadvantages compared with logistic regression. Boosting (meta-classifiers) and to a lesser extent decision trees (particularly CART) appear to be most promising for use in the context of propensity score analysis, but extensive simulation studies are needed to establish their utility in practice. PMID:20630332

Field Research Validation Sites | Wind | NREL

Science.gov Websites

, independent pitch control of the Controls Advanced Research Turbine (CART) blades Variable-speed or constant CART2 600-kW Turbine Model: Westinghouse Blades: 2 Hub height: 36.6 m Rotor diameter: 42.6 m Extensively instrumented CART3 600-kW Turbine Model: Westinghouse Blades: 3 Hub height: 36.6 m Rotor diameter: 42.6 m

Building community resilience to disasters through a community-based intervention: CART applications.

PubMed

Pfefferbaum, Rose L; Pfefferbaum, Betty; Van Horn, Richard L; Neas, Barbara R; Houston, J Brian

2013-01-01

The Communities Advancing Resilience Toolkit (CART)* is a community-driven, publicly available, theory-based, and evidence-informed community intervention designed to build community resilience to disasters and other adversities. Based on principles of participatory action research, CART applications contribute to community resilience by encouraging and supporting community participation and cooperation, communication, self-awareness, and critical reflection. The primary value of CART lies in its ability to stimulate analysis, collaboration, skill building, resource sharing, and purposeful action. In addition to generating community assessment data, CART can be used as a vehicle for delivering other interventions and creating sustainable capacity within communities. Two models for CART implementation are described.

Bounding species distribution models

USGS Publications Warehouse

Stohlgren, T.J.; Jarnevich, C.S.; Esaias, W.E.; Morisette, J.T.

2011-01-01

Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used. ?? 2011 Current Zoology.

Bounding Species Distribution Models

NASA Technical Reports Server (NTRS)

Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

2011-01-01

Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

Improving Odometric Accuracy for an Autonomous Electric Cart.

PubMed

Toledo, Jonay; Piñeiro, Jose D; Arnay, Rafael; Acosta, Daniel; Acosta, Leopoldo

2018-01-12

In this paper, a study of the odometric system for the autonomous cart Verdino, which is an electric vehicle based on a golf cart, is presented. A mathematical model of the odometric system is derived from cart movement equations, and is used to compute the vehicle position and orientation. The inputs of the system are the odometry encoders, and the model uses the wheels diameter and distance between wheels as parameters. With this model, a least square minimization is made in order to get the nominal best parameters. This model is updated, including a real time wheel diameter measurement improving the accuracy of the results. A neural network model is used in order to learn the odometric model from data. Tests are made using this neural network in several configurations and the results are compared to the mathematical model, showing that the neural network can outperform the first proposed model.

[Prediction of histological liver damage in asymptomatic alcoholic patients by means of clinical and laboratory data].

PubMed

Iturriaga, H; Hirsch, S; Bunout, D; Díaz, M; Kelly, M; Silva, G; de la Maza, M P; Petermann, M; Ugarte, G

1993-04-01

Looking for a noninvasive method to predict liver histologic alterations in alcoholic patients without clinical signs of liver failure, we studied 187 chronic alcoholics recently abstinent, divided in 2 series. In the model series (n = 94) several clinical variables and results of common laboratory tests were confronted to the findings of liver biopsies. These were classified in 3 groups: 1. Normal liver; 2. Moderate alterations; 3. Marked alterations, including alcoholic hepatitis and cirrhosis. Multivariate methods used were logistic regression analysis and a classification and regression tree (CART). Both methods entered gamma-glutamyltransferase (GGT), aspartate-aminotransferase (AST), weight and age as significant and independent variables. Univariate analysis with GGT and AST at different cutoffs were also performed. To predict the presence of any kind of damage (Groups 2 and 3), CART and AST > 30 IU showed the higher sensitivity, specificity and correct prediction, both in the model and validation series. For prediction of marked liver damage, a score based on logistic regression and GGT > 110 IU had the higher efficiencies. It is concluded that GGT and AST are good markers of alcoholic liver damage and that, using sample cutoffs, histologic diagnosis can be correctly predicted in 80% of recently abstinent asymptomatic alcoholics.

Analyzing injury severity factors at highway railway grade crossing accidents involving vulnerable road users: A comparative study.

PubMed

Ghomi, Haniyeh; Bagheri, Morteza; Fu, Liping; Miranda-Moreno, Luis F

2016-11-16

The main objective of this study is to identify the main factors associated with injury severity of vulnerable road users (VRUs) involved in accidents at highway railroad grade crossings (HRGCs) using data mining techniques. This article applies an ordered probit model, association rules, and classification and regression tree (CART) algorithms to the U.S. Federal Railroad Administration's (FRA) HRGC accident database for the period 2007-2013 to identify VRU injury severity factors at HRGCs. The results show that train speed is a key factor influencing injury severity. Further analysis illustrated that the presence of illumination does not reduce the severity of accidents for high-speed trains. In addition, there is a greater propensity toward fatal accidents for elderly road users compared to younger individuals. Interestingly, at night, injury accidents involving female road users are more severe compared to those involving males. The ordered probit model was the primary technique, and CART and association rules act as the supporter and identifier of interactions between variables. All 3 algorithms' results consistently show that the most influential accident factors are train speed, VRU age, and gender. The findings of this research could be applied for identifying high-risk hotspots and developing cost-effective countermeasures targeting VRUs at HRGCs.

Hypothalamic CART is a new anorectic peptide regulated by leptin.

PubMed

Kristensen, P; Judge, M E; Thim, L; Ribel, U; Christjansen, K N; Wulff, B S; Clausen, J T; Jensen, P B; Madsen, O D; Vrang, N; Larsen, P J; Hastrup, S

1998-05-07

The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.

A decision tree to assess short-term mortality after an emergency department visit for an exacerbation of COPD: a cohort study.

PubMed

Esteban, Cristóbal; Arostegui, Inmaculada; Garcia-Gutierrez, Susana; Gonzalez, Nerea; Lafuente, Iratxe; Bare, Marisa; Fernandez de Larrea, Nerea; Rivas, Francisco; Quintana, José M

2015-12-22

Creating an easy-to-use instrument to identify predictors of short-term (30/60-day) mortality after an exacerbation of chronic obstructive pulmonary disease (eCOPD) could help clinicians choose specific measures of medical care to decrease mortality in these patients. The objective of this study was to develop and validate a classification and regression tree (CART) to predict short term mortality among patients evaluated in an emergency department (ED) for an eCOPD. We conducted a prospective cohort study including participants from 16 hospitals in Spain. COPD patients with an exacerbation attending the emergency department (ED) of any of the hospitals between June 2008 and September 2010 were recruited. Patients were randomly divided into derivation (50%) and validation samples (50%). A CART based on a recursive partitioning algorithm was created in the derivation sample and applied to the validation sample. Two thousand four hundred eighty-seven patients, 1252 patients in the derivation sample and 1235 in the validation sample, were enrolled in the study. Based on the results of the univariate analysis, five variables (baseline dyspnea, cardiac disease, the presence of paradoxical breathing or use of accessory inspiratory muscles, age, and Glasgow Coma Scale score) were used to build the CART. Mortality rates 30 days after discharge ranged from 0% to 55% in the five CART classes. The lowest mortality rate was for the branch composed of low baseline dyspnea and lack of cardiac disease. The highest mortality rate was in the branch with the highest baseline dyspnea level, use of accessory inspiratory muscles or paradoxical breathing upon ED arrival, and Glasgow score <15. The area under the receiver-operating curve (AUC) in the derivation sample was 0.835 (95% CI: 0.783, 0.888) and 0.794 (95% CI: 0.723, 0.865) in the validation sample. CART was improved to predict 60-days mortality risk by adding the Charlson Comorbidity Index, reaching an AUC in the derivation sample of 0.817 (95% CI: 0.776, 0.859) and 0.770 (95% CI: 0.716, 0.823) in the validation sample. We identified several easy-to-determine variables that allow clinicians to classify eCOPD patients by short term mortality risk, which can provide useful information for establishing appropriate clinical care. NCT02434536.

Multivariate Linear Regression and CART Regression Analysis of TBM Performance at Abu Hamour Phase-I Tunnel

NASA Astrophysics Data System (ADS)

Jakubowski, J.; Stypulkowski, J. B.; Bernardeau, F. G.

2017-12-01

The first phase of the Abu Hamour drainage and storm tunnel was completed in early 2017. The 9.5 km long, 3.7 m diameter tunnel was excavated with two Earth Pressure Balance (EPB) Tunnel Boring Machines from Herrenknecht. TBM operation processes were monitored and recorded by Data Acquisition and Evaluation System. The authors coupled collected TBM drive data with available information on rock mass properties, cleansed, completed with secondary variables and aggregated by weeks and shifts. Correlations and descriptive statistics charts were examined. Multivariate Linear Regression and CART regression tree models linking TBM penetration rate (PR), penetration per revolution (PPR) and field penetration index (FPI) with TBM operational and geotechnical characteristics were performed for the conditions of the weak/soft rock of Doha. Both regression methods are interpretable and the data were screened with different computational approaches allowing enriched insight. The primary goal of the analysis was to investigate empirical relations between multiple explanatory and responding variables, to search for best subsets of explanatory variables and to evaluate the strength of linear and non-linear relations. For each of the penetration indices, a predictive model coupling both regression methods was built and validated. The resultant models appeared to be stronger than constituent ones and indicated an opportunity for more accurate and robust TBM performance predictions.

Identifying changes in dissolved organic matter content and characteristics by fluorescence spectroscopy coupled with self-organizing map and classification and regression tree analysis during wastewater treatment.

PubMed

Yu, Huibin; Song, Yonghui; Liu, Ruixia; Pan, Hongwei; Xiang, Liancheng; Qian, Feng

2014-10-01

The stabilization of latent tracers of dissolved organic matter (DOM) of wastewater was analyzed by three-dimensional excitation-emission matrix (EEM) fluorescence spectroscopy coupled with self-organizing map and classification and regression tree analysis (CART) in wastewater treatment performance. DOM of water samples collected from primary sedimentation, anaerobic, anoxic, oxic and secondary sedimentation tanks in a large-scale wastewater treatment plant contained four fluorescence components: tryptophan-like (C1), tyrosine-like (C2), microbial humic-like (C3) and fulvic-like (C4) materials extracted by self-organizing map. These components showed good positive linear correlations with dissolved organic carbon of DOM. C1 and C2 were representative components in the wastewater, and they were removed to a higher extent than those of C3 and C4 in the treatment process. C2 was a latent parameter determined by CART to differentiate water samples of oxic and secondary sedimentation tanks from the successive treatment units, indirectly proving that most of tyrosine-like material was degraded by anaerobic microorganisms. C1 was an accurate parameter to comprehensively separate the samples of the five treatment units from each other, indirectly indicating that tryptophan-like material was decomposed by anaerobic and aerobic bacteria. EEM fluorescence spectroscopy in combination with self-organizing map and CART analysis can be a nondestructive effective method for characterizing structural component of DOM fractions and monitoring organic matter removal in wastewater treatment process. Copyright © 2014 Elsevier Ltd. All rights reserved.

Level 2 Screening with the PDD Behavior Inventory: Subgroup Profiles and Implications for Differential Diagnosis

ERIC Educational Resources Information Center

Cohen, Ira L.; Liu, Xudong; Hudson, Melissa; Gillis, Jennifer; Cavalari, Rachel N. S.; Romanczyk, Raymond G.; Karmel, Bernard Z.; Gardner, Judith M.

2017-01-01

The PDD Behavior Inventory (PDDBI) has recently been shown, in a large multisite study, to discriminate well between autism spectrum disorder (ASD) and other groups when its scores were examined using a machine learning tool, Classification and Regression Trees (CART). Discrimination was good for toddlers, preschoolers, and school-age children;…

Subpopulations of Older Foster Youths With Differential Risk of Diagnosis for Alcohol Abuse or Dependence*

PubMed Central

Keller, Thomas E.; Blakeslee, Jennifer E.; Lemon, Stephenie C.; Courtney, Mark E.

2010-01-01

Objective: Distinctive combinations of factors are likely to be associated with serious alcohol problems among adolescents about to emancipate from the foster care system and face the difficult transition to independent adulthood. This study identifies particular subpopulations of older foster youths that differ markedly in the probability of a lifetime diagnosis for alcohol abuse or dependence. Method: Classification and regression tree (CART) analysis was applied to a large, representative sample (N = 732) of individuals, 17 years of age or older, placed in the child welfare system for more than 1 year. CART evaluated two exploratory sets of variables for optimal splits into groups distinguished from each other on the criterion of lifetime alcohol-use disorder diagnosis. Results: Each classification tree yielded four terminal groups with different rates of lifetime alcohol-use disorder diagnosis. Notable groups in the first tree included one characterized by high levels of both delinquency and violence exposure (53% diagnosed) and another that featured lower delinquency but an independent-living placement (21% diagnosed). Notable groups in the second tree included African American adolescents (only 8% diagnosed), White adolescents not close to caregivers (40% diagnosed), and White adolescents closer to caregivers but with a history of psychological abuse (36% diagnosed). Conclusions: Analyses incorporating variables that could be comorbid with or symptomatic of alcohol problems, such as delinquency, yielded classifications potentially useful for assessment and service planning. Analyses without such variables identified other factors, such as quality of caregiving relationships and maltreatment, associated with serious alcohol problems, suggesting opportunities for prevention or intervention. PMID:20946738

A combined M5P tree and hazard-based duration model for predicting urban freeway traffic accident durations.

PubMed

Lin, Lei; Wang, Qian; Sadek, Adel W

2016-06-01

The duration of freeway traffic accidents duration is an important factor, which affects traffic congestion, environmental pollution, and secondary accidents. Among previous studies, the M5P algorithm has been shown to be an effective tool for predicting incident duration. M5P builds a tree-based model, like the traditional classification and regression tree (CART) method, but with multiple linear regression models as its leaves. The problem with M5P for accident duration prediction, however, is that whereas linear regression assumes that the conditional distribution of accident durations is normally distributed, the distribution for a "time-to-an-event" is almost certainly nonsymmetrical. A hazard-based duration model (HBDM) is a better choice for this kind of a "time-to-event" modeling scenario, and given this, HBDMs have been previously applied to analyze and predict traffic accidents duration. Previous research, however, has not yet applied HBDMs for accident duration prediction, in association with clustering or classification of the dataset to minimize data heterogeneity. The current paper proposes a novel approach for accident duration prediction, which improves on the original M5P tree algorithm through the construction of a M5P-HBDM model, in which the leaves of the M5P tree model are HBDMs instead of linear regression models. Such a model offers the advantage of minimizing data heterogeneity through dataset classification, and avoids the need for the incorrect assumption of normality for traffic accident durations. The proposed model was then tested on two freeway accident datasets. For each dataset, the first 500 records were used to train the following three models: (1) an M5P tree; (2) a HBDM; and (3) the proposed M5P-HBDM, and the remainder of data were used for testing. The results show that the proposed M5P-HBDM managed to identify more significant and meaningful variables than either M5P or HBDMs. Moreover, the M5P-HBDM had the lowest overall mean absolute percentage error (MAPE). Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential Diagnosis of Erythmato-Squamous Diseases Using Classification and Regression Tree

PubMed Central

Maghooli, Keivan; Langarizadeh, Mostafa; Shahmoradi, Leila; Habibi-koolaee, Mahdi; Jebraeily, Mohamad; Bouraghi, Hamid

2016-01-01

Introduction: Differential diagnosis of Erythmato-Squamous Diseases (ESD) is a major challenge in the field of dermatology. The ESD diseases are placed into six different classes. Data mining is the process for detection of hidden patterns. In the case of ESD, data mining help us to predict the diseases. Different algorithms were developed for this purpose. Objective: we aimed to use the Classification and Regression Tree (CART) to predict differential diagnosis of ESD. Methods: we used the Cross Industry Standard Process for Data Mining (CRISP-DM) methodology. For this purpose, the dermatology data set from machine learning repository, UCI was obtained. The Clementine 12.0 software from IBM Company was used for modelling. In order to evaluation of the model we calculate the accuracy, sensitivity and specificity of the model. Results: The proposed model had an accuracy of 94.84% ( Standard Deviation: 24.42) in order to correct prediction of the ESD disease. Conclusions: Results indicated that using of this classifier could be useful. But, it would be strongly recommended that the combination of machine learning methods could be more useful in terms of prediction of ESD. PMID:28077889

The Accuracy of the VISA-P Questionnaire, Single-Leg Decline Squat, and Tendon Pain History to Identify Patellar Tendon Abnormalities in Adult Athletes.

PubMed

Mendonça, Luciana de Michelis; Ocarino, Juliana Melo; Bittencourt, Natália Franco Netto; Fernandes, Ludmila Maria Oliveira; Verhagen, Evert; Fonseca, Sérgio Teixeira

2016-08-01

Study Design Cross-sectional clinical assessment. Background Patellar tendinopathy is not always accompanied by patellar tendon abnormalities (PTAs). Thus, clinical screening tools to help identify patients with patellar tendon pain who have PTAs could enhance clinical decision making and patient prognosis. Objectives To test the diagnostic accuracy of the Victorian Institute of Sport Assessment-Patella (VISA-P) questionnaire, a single-leg decline squat (SLDS), tendon pain history, age, and years of sports participation to identify athletes with symptomatic patellar tendons who have PTAs confirmed on imaging. Methods Data provided by ultrasound examination, the VISA-P questionnaire, the SLDS, tendon pain history, age, and years of sport participation were collected in 43 athletes. A classification and regression tree (CART) model was developed to verify variables associated with PTA occurrence. Likelihood ratios (LRs) were computed for positive and negative tests. Results The SLDS, VISA-P questionnaire, and tendon pain history were associated with PTA occurrence. Athletes with negative results on all 3 tests (CART model) had a lower likelihood of having PTAs (negative LR = 0.3; 95% confidence interval [CI]: 0.2, 0.5). The isolated use of the SLDS or tendon pain history (positive LR = 4.2; 95% CI: 2.3, 7.14 and 4.5; 95% CI: 1.8, 11.1, respectively) had similar influence on probability of PTA presence compared to the CART model (positive LR = 4.1; 95% CI: 2.5, 6.3). Conclusion Although the objective was to investigate a clinical test to identify PTAs, the combined use of the tests had greater accuracy to identify individuals without PTAs. Level of Evidence Diagnosis, level 3b. J Orthop Sports Phys Ther 2016;46(8):673-680. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6192.

Barriers and facilitators to antiretroviral therapy adherence among Peruvian adolescents living with HIV: A qualitative study

PubMed Central

Wong, Milagros; Muñoz, Maribel; Valle, Emiliano; Leon, Segundo R.; Díaz Perez, Dayana; Kolevic, Lenka; Franke, Molly

2018-01-01

AIDS deaths among adolescents are increasing globally. This qualitative study investigated the barriers and facilitators to cART adherence among Peruvian adolescents living with HIV. Guided by a social ecological model, we analyzed transcripts from 24 psychosocial support groups for HIV-positive adolescents aged 13–17 years and 15 individual, in-depth interviews with cART providers and caregivers to identify the barriers and facilitators to cART adherence at the individual, family/caregiver and hospital levels. Most barriers and facilitators to cART adherence clustered at the individual and family/caregiver levels, centering on support provided to adolescents; history of declining health due to suboptimal cART adherence; side effects from antiretroviral drugs; and cART misinformation. Interventions to support adolescent HIV cART adherence should begin at the individual and family/caregiver levels and include an educational component. No adolescent living with HIV should die from AIDS in an era of accessible cART. PMID:29447226

Discrimination of rectal cancer through human serum using surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Yang, Tianyue; Li, Siqi; Zhang, Su; Jin, Lili

2015-05-01

In this paper, surface-enhanced Raman spectroscopy (SERS) was used to detect the changes in blood serum components that accompany rectal cancer. The differences in serum SERS data between rectal cancer patients and healthy controls were examined. Postoperative rectal cancer patients also participated in the comparison to monitor the effects of cancer treatments. The results show that there are significant variations at certain wavenumbers which indicates alteration of corresponding biological substances. Principal component analysis (PCA) and parameters of intensity ratios were used on the original SERS spectra for the extraction of featured variables. These featured variables then underwent linear discriminant analysis (LDA) and classification and regression tree (CART) for the discrimination analysis. Accuracies of 93.5 and 92.4 % were obtained for PCA-LDA and parameter-CART, respectively.

On the detection of pornographic digital images

NASA Astrophysics Data System (ADS)

Schettini, Raimondo; Brambilla, Carla; Cusano, Claudio; Ciocca, Gianluigi

2003-06-01

The paper addresses the problem of distinguishing between pornographic and non-pornographic photographs, for the design of semantic filters for the web. Both, decision forests of trees built according to CART (Classification And Regression Trees) methodology and Support Vectors Machines (SVM), have been used to perform the classification. The photographs are described by a set of low-level features, features that can be automatically computed simply on gray-level and color representation of the image. The database used in our experiments contained 1500 photographs, 750 of which labeled as pornographic on the basis of the independent judgement of several viewers.

Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia

PubMed Central

Kenderian, Saad S.; Shen, Feng; Ruella, Marco; Shestova, Olga; Kozlowski, Miroslaw; Li, Yong; Schrank-Hacker, April; Morrissette, Jennifer J. D.; Carroll, Martin; June, Carl H.; Grupp, Stephan A.; Gill, Saar

2017-01-01

We and others previously reported potent antileukemia efficacy of CD123-redirected chimeric antigen receptor (CAR) T cells in preclinical human acute myeloid leukemia (AML) models at the cost of severe hematologic toxicity. This observation raises concern for potential myeloablation in patients with AML treated with CD123-redirected CAR T cells and mandates novel approaches for toxicity mitigation. We hypothesized that CAR T-cell depletion with optimal timing after AML eradication would preserve leukemia remission and allow subsequent hematopoietic stem cell transplantation. To test this hypothesis, we compared 3 CAR T-cell termination strategies: (1) transiently active anti-CD123 messenger RNA–electroporated CART (RNA-CART123); (2) T-cell ablation with alemtuzumab after treatment with lentivirally transduced anti–CD123-4-1BB-CD3ζ T cells (CART123); and (3) T-cell ablation with rituximab after treatment with CD20-coexpressing CART123 (CART123-CD20). All approaches led to rapid leukemia elimination in murine xenograft models of human AML. Subsequent antibody-mediated depletion of CART123 or CART123-CD20 did not impair leukemia remission. Time-course studies demonstrated that durable leukemia remission required CAR T-cell persistence for 4 weeks prior to ablation. Upon CAR T-cell termination, we further demonstrated successful hematopoietic engraftment with a normal human donor to model allogeneic stem cell rescue. Results from these studies will facilitate development of T-cell depletion strategies to augment the feasibility of CAR T-cell therapy for patients with AML. PMID:28246194

Fire frequency in the Interior Columbia River Basin: Building regional models from fire history data

USGS Publications Warehouse

McKenzie, D.; Peterson, D.L.; Agee, James K.

2000-01-01

Fire frequency affects vegetation composition and successional pathways; thus it is essential to understand fire regimes in order to manage natural resources at broad spatial scales. Fire history data are lacking for many regions for which fire management decisions are being made, so models are needed to estimate past fire frequency where local data are not yet available. We developed multiple regression models and tree-based (classification and regression tree, or CART) models to predict fire return intervals across the interior Columbia River basin at 1-km resolution, using georeferenced fire history, potential vegetation, cover type, and precipitation databases. The models combined semiqualitative methods and rigorous statistics. The fire history data are of uneven quality; some estimates are based on only one tree, and many are not cross-dated. Therefore, we weighted the models based on data quality and performed a sensitivity analysis of the effects on the models of estimation errors that are due to lack of cross-dating. The regression models predict fire return intervals from 1 to 375 yr for forested areas, whereas the tree-based models predict a range of 8 to 150 yr. Both types of models predict latitudinal and elevational gradients of increasing fire return intervals. Examination of regional-scale output suggests that, although the tree-based models explain more of the variation in the original data, the regression models are less likely to produce extrapolation errors. Thus, the models serve complementary purposes in elucidating the relationships among fire frequency, the predictor variables, and spatial scale. The models can provide local managers with quantitative information and provide data to initialize coarse-scale fire-effects models, although predictions for individual sites should be treated with caution because of the varying quality and uneven spatial coverage of the fire history database. The models also demonstrate the integration of qualitative and quantitative methods when requisite data for fully quantitative models are unavailable. They can be tested by comparing new, independent fire history reconstructions against their predictions and can be continually updated, as better fire history data become available.

Effect of combination antiretroviral therapy on Chinese rhesus macaques of simian immunodeficiency virus infection.

PubMed

Ling, Binhua; Rogers, Linda; Johnson, Ann-Marie; Piatak, Michael; Lifson, Jeffrey; Veazey, Ronald S

2013-11-01

Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (<30 vRNA copies/ml plasma) with cART in such models. As ease of viral suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to <30 copies/ml upon initiation of cART. Cell-associated SIV DNA levels in lymphocytes from the gut were also significantly reduced. Jejunal and colonic CCR5(+)CD4(+) mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to <30 vRNA copies/ml in SIVmac239-infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.

Interactions between large-scale modes of climate and their relationship with Australian climate and hydrology

NASA Astrophysics Data System (ADS)

Whan, K. R.; Lindesay, J. A.; Timbal, B.; Raupach, M. R.; Williams, E.

2010-12-01

Australia’s natural environment is adapted to low rainfall availability and high variability but human systems are less able to adapt to variability in the hydrological cycle. Understanding the mechanisms underlying drought persistence and severity is vital to contextualising future climate change. Multiple external forcings mean the mechanisms of drought occurrence in south-eastern Australian are complex. The key influences on SEA climate are El Niño-Southern Oscillation (ENSO), the Indian Ocean Dipole (IOD), the Southern Annular Mode (SAM) and the sub-tropical ridge (STR); each of these large-scale climate modes (LSCM) has been studied widely. The need for research into the interactions among the modes has been noted [1], although to date this has received limited attention. Relationships between LSCM and hydrometeorological variability are nonlinear, making linearity assumptions underlying usual statistical techniques (e.g. correlation, principle components analysis) questionable. In the current research a statistical technique that can deal with nonlinear interactions is applied to a new dataset enabling a full examination of the Australian water balance. The Australian Water Availability Project (AWAP) dataset models the Australian water balance on a fine grid [2]. Hydrological parameters (e.g. soil moisture, evaporation, runoff) are modelled from meteorological data, allowing the complete Australian water balance (climate and hydrology) to be examined and the mechanisms of drought to be studied holistically. Classification and regression trees (CART) are a powerful regression-based technique that is capable of accounting for nonlinear effects. Although it has limited previous application in climate research [3] this methodology is particularly informative in cases with multiple predictors and nonlinear relationships such as climate variability. Statistical relationships between variables are the basis for the decision rules in CART that are used to split the data into increasingly homogeneous groups. CART is applied to the AWAP dataset to identify the hydroclimatic regimes associated with various combinations of LSCM and the importance of each mode in producing the regime. Analysis of the LSCM is conducted on a range of hydroclimatic variables to assess the relative and combined influences of these LSCM on the Australian water balance. This gives information about interactions between LSCM that are vital for specific hydroclimatic states (e.g. drought) and about which combinations of LSCM result in specific regimes. The dominant LSCM in different seasons and the relationships among the climate drivers have been identified. 1. Ummenhofer, C., et al., What causes southeast Australia's worst droughts? Geophysical Research Letters, 2009. 36: p. L04706. 2. Raupach, M., et al., Australian Water Availability Project (AWAP). CSIRO Marine and Atmospheric Research Component: Final Report for Phase 3. 2008. 3. Burrows, W., et al., CART Decision-Tree Statistical Analysis and Prediction of Summer Season Maximum Surface Ozone for the Vancouver, Montreal and Atlantic Regions of Canada. Journal of Applied Meteorology, 1995. 34: p. 1848-1862.

Patient casemix classification for medicare psychiatric prospective payment.

PubMed

Drozd, Edward M; Cromwell, Jerry; Gage, Barbara; Maier, Jan; Greenwald, Leslie M; Goldman, Howard H

2006-04-01

For a proposed Medicare prospective payment system for inpatient psychiatric facility treatment, the authors developed a casemix classification to capture differences in patients' real daily resource use. Primary data on patient characteristics and daily time spent in various activities were collected in a survey of 696 patients from 40 inpatient psychiatric facilities. Survey data were combined with Medicare claims data to estimate intensity-adjusted daily cost. Classification and Regression Trees (CART) analysis of average daily routine and ancillary costs yielded several hierarchical classification groupings. Regression analysis was used to control for facility and day-of-stay effects in order to compare hierarchical models with models based on the recently proposed payment system of the Centers for Medicare & Medicaid Services. CART analysis identified a small set of patient characteristics strongly associated with higher daily costs, including age, psychiatric diagnosis, deficits in daily living activities, and detox or ECT use. A parsimonious, 16-group, fully interactive model that used five major DSM-IV categories and stratified by age, illness severity, deficits in daily living activities, dangerousness, and use of ECT explained 40% (out of a possible 76%) of daily cost variation not attributable to idiosyncratic daily changes within patients. A noninteractive model based on diagnosis-related groups, age, and medical comorbidity had explanatory power of only 32%. A regression model with 16 casemix groups restricted to using "appropriate" payment variables (i.e., those with clinical face validity and low administrative burden that are easily validated and provide proper care incentives) produced more efficient and equitable payments than did a noninteractive system based on diagnosis-related groups.

Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies

PubMed Central

Barrett, David M.; Shestova, Olga; Hofmann, Ted J.; Perazzelli, Jessica; Klichinsky, Michael; Aikawa, Vania; Nazimuddin, Farzana; Kozlowski, Miroslaw; Scholler, John; Lacey, Simon F.; Melenhorst, Jan J.; Morrissette, Jennifer J.D.; Christian, David A.; Hunter, Christopher A.; Kalos, Michael; Porter, David L.; June, Carl H.; Grupp, Stephan A.

2016-01-01

Potent CD19-directed immunotherapies, such as chimeric antigen receptor T cells (CART) and blinatumomab, have drastically changed the outcome of patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). However, CD19-negative relapses have emerged as a major problem that is observed in approximately 30% of treated patients. Developing approaches to preventing and treating antigen-loss escapes would therefore represent a vertical advance in the field. Here, we found that in primary patient samples, the IL-3 receptor α chain CD123 was highly expressed on leukemia-initiating cells and CD19-negative blasts in bulk B-ALL at baseline and at relapse after CART19 administration. Using intravital imaging in an antigen-loss CD19-negative relapse xenograft model, we determined that CART123, but not CART19, recognized leukemic blasts, established protracted synapses, and eradicated CD19-negative leukemia, leading to prolonged survival. Furthermore, combining CART19 and CART123 prevented antigen-loss relapses in xenograft models. Finally, we devised a dual CAR-expressing construct that combined CD19- and CD123-mediated T cell activation and demonstrated that it provides superior in vivo activity against B-ALL compared with single-expressing CART or pooled combination CART. In conclusion, these findings indicate that targeting CD19 and CD123 on leukemic blasts represents an effective strategy for treating and preventing antigen-loss relapses occurring after CD19-directed therapies PMID:27571406

The Impact of a Community-Based Intervention Including a Monthly Food Ration on Food Insecurity Among HIV-Positive Adults During the First Year of Antiretroviral Therapy.

PubMed

Rothman, Jessica; Kayigamba, Felix; Hills, Victoria; Gupta, Neil; Machara, Faustin; Niyigena, Peter; Franke, Molly F

2018-01-01

The objective of this study was to examine how food insecurity changed among HIV-positive adults during the first 12 months of combination antiretroviral therapy (cART) and whether any change differed according to the receipt of food support, which was provided in the context of a comprehensive community-based intervention. We conducted secondary data analyses of data from a prospective cohort study of the effectiveness of a community-based cART delivery model when added to clinic-based cART delivery in Rwanda. We included patients from four health centers that implemented a clinic-based cART delivery model alone and five health centers that additionally implemented the intervention, which included 10 months of food support. We compared food insecurity at 3, 6, and 12 months, relative to baseline, and stratified by receipt of the intervention. Relative to baseline, median food insecurity score decreased after 3, 6, and 12 months (p value <0.0001 for all) for patients receiving a food ration through the community-based model for cART delivery. Among patients receiving care under the clinic-based cART model, food insecurity scores remained unchanged at 3 and 12 months and were significantly higher after 6 months. In adjusted analyses, participants enrolled in the community-based intervention with a food ration had a lower risk of severe food insecurity and a lower risk of moderate or severe food insecurity after 12 months. A comprehensive community-based HIV program including a food ration likely contributes to an alleviation of food insecurity among adults newly initiating cART.

Climate, CO2, and the history of North American grasses since the Last Glacial Maximum

PubMed Central

Cotton, Jennifer M.; Cerling, Thure E.; Hoppe, Kathryn A.; Mosier, Thomas M.; Still, Christopher J.

2016-01-01

The spread of C4 grasses in the late Neogene is one of the most important ecological transitions of the Cenozoic, but the primary driver of this global expansion is widely debated. We use the stable carbon isotopic composition (δ13C) of bison and mammoth tissues as a proxy for the relative abundance of C3 and C4 vegetation in their grazing habitat to determine climatic and atmospheric CO2 controls on C4 grass distributions from the Last Glacial Maximum (LGM) to the present. We predict the spatial variability of grass δ13C in North America using a mean of three different methods of classification and regression tree (CART) machine learning techniques and nine climatic variables. We show that growing season precipitation and temperature are the strongest predictors of all single climate variables. We apply this CART analysis to high-resolution gridded climate data and Coupled Model Intercomparison Project (CMIP5) mean paleoclimate model outputs to produce predictive isotope landscape models (“isoscapes”) for the current, mid-Holocene, and LGM average δ13C of grass-dominated areas across North America. From the LGM to the present, C4 grass abundances substantially increased in the Great Plains despite concurrent increases in atmospheric CO2. These results suggest that changes in growing season precipitation rather than atmospheric CO2 were critically important in the Neogene expansion of C4 grasses. PMID:27051865

Can Predictive Modeling Identify Head and Neck Oncology Patients at Risk for Readmission?

PubMed

Manning, Amy M; Casper, Keith A; Peter, Kay St; Wilson, Keith M; Mark, Jonathan R; Collar, Ryan M

2018-05-01

Objective Unplanned readmission within 30 days is a contributor to health care costs in the United States. The use of predictive modeling during hospitalization to identify patients at risk for readmission offers a novel approach to quality improvement and cost reduction. Study Design Two-phase study including retrospective analysis of prospectively collected data followed by prospective longitudinal study. Setting Tertiary academic medical center. Subjects and Methods Prospectively collected data for patients undergoing surgical treatment for head and neck cancer from January 2013 to January 2015 were used to build predictive models for readmission within 30 days of discharge using logistic regression, classification and regression tree (CART) analysis, and random forests. One model (logistic regression) was then placed prospectively into the discharge workflow from March 2016 to May 2016 to determine the model's ability to predict which patients would be readmitted within 30 days. Results In total, 174 admissions had descriptive data. Thirty-two were excluded due to incomplete data. Logistic regression, CART, and random forest predictive models were constructed using the remaining 142 admissions. When applied to 106 consecutive prospective head and neck oncology patients at the time of discharge, the logistic regression model predicted readmissions with a specificity of 94%, a sensitivity of 47%, a negative predictive value of 90%, and a positive predictive value of 62% (odds ratio, 14.9; 95% confidence interval, 4.02-55.45). Conclusion Prospectively collected head and neck cancer databases can be used to develop predictive models that can accurately predict which patients will be readmitted. This offers valuable support for quality improvement initiatives and readmission-related cost reduction in head and neck cancer care.

Quantitative Evaluation of CART-Containing Cells in Urinary Bladder of Rats with Renovascular Hypertension

PubMed Central

Janiuk, I.; Kasacka, I.

2015-01-01

Recent biological advances make it possible to discover new peptides associated with hypertension. The cocaine- and amphetamine-regulated transcript (CART) is a known factor in appetite and feeding behaviour. Various lines of evidence suggest that this peptide participates not only in control of feeding behaviour but also in the regulation of the cardiovascular and sympathetic systems and blood pressure. The role of CART in blood pressure regulation led us to undertake a study aimed at analysing quantitative changes in CART-containing cells in urinary bladders (UB) of rats with renovascular hypertension. We used the Goldblatt model of arterial hypertension (two-kidney, one clip) to evaluate quantitative changes. This model provides researchers with a commonly used tool to analyse the renin-angiotensin system of blood pressure control and, eventually, to develop drugs for the treatment of chronic hypertension. The study was performed on sections of urinary bladders of rats after 3-, 14-, 28-, 42 and 91 days from hypertension induction. Immunohistochemical identification of CART cells was performed on paraffin for the UBs of all the study animals. CART was detected in the endocrine cells, especially numerous in the submucosa and muscularis layers, with a few found in the transitional epithelium and only occasionally in serosa. Hypertension significantly increased the number of CART-positive cells in the rat UBs. After 3 and 42 days following the procedure, statistically significantly higher numbers of CART-positive cells were identified in comparison with the control animals. The differences between the hypertensive rats and the control animals concerned not only the number density of CART-immunoreactive cells but also their localization. After a 6-week period, each of the rats subjected to the renal artery clipping procedure developed stable hypertension. CART appeared in numerous transitional epithelium cells. As this study provides novel findings, the question appears about the type of connection between hypertension and the functioning and activity of CART in the urinary tract (UT). The study gives rise to the assumption that high blood pressure can be a factor that intensifies CART secretion. In conclusion, the endocrine system of the urinary tract is modified by renovascular hypertension. This may affect the production of hormones and biologically active substances and contribute to the development of possible hypertension complications. In order to fully comprehend the role of the CART peptide in blood pressure regulation, further analyses are necessary. PMID:26150151

Quantitative evaluation of CART-containing cells in urinary bladder of rats with renovascular hypertension.

PubMed

Janiuk, I; Kasacka, I

2015-04-13

Recent biological advances make it possible to discover new peptides associated with hypertension. The cocaine- and amphetamine-regulated transcript (CART) is a known factor in appetite and feeding behaviour. Various lines of evidence suggest that this peptide participates not only in control of feeding behaviour but also in the regulation of the cardiovascular and sympathetic systems and blood pressure. The role of CART in blood pressure regulation led us to undertake a study aimed at analysing quantitative changes in CART-containing cells in urinary bladders (UB) of rats with renovascular hypertension. We used the Goldblatt model of arterial hypertension (two-kidney, one clip) to evaluate quantitative changes. This model provides researchers with a commonly used tool to analyse the renin-angiotensin system of blood pressure control and, eventually, to develop drugs for the treatment of chronic hypertension. The study was performed on sections of urinary bladders of rats after 3-, 14-, 28-, 42 and 91 days from hypertension induction. Immunohistochemical identification of CART cells was performed on paraffin for the UBs of all the study animals. CART was detected in the endocrine cells, especially numerous in the submucosa and muscularis layers, with a few found in the transitional epithelium and only occasionally in serosa. Hypertension significantly increased the number of CART-positive cells in the rat UBs. After 3 and 42 days following the procedure, statistically significantly higher numbers of CART-positive cells were identified in comparison with the control animals. The differences between the hypertensive rats and the control animals concerned not only the number density of CART-immunoreactive cells but also their localization. After a 6-week period, each of the rats subjected to the renal artery clipping procedure developed stable hypertension. CART appeared in numerous transitional epithelium cells. As this study provides novel findings, the question appears about the type of connection between hypertension and the functioning and activity of CART in the urinary tract (UT). The study gives rise to the assumption that high blood pressure can be a factor that intensifies CART secretion. In conclusion, the endocrine system of the urinary tract is modified by renovascular hypertension. This may affect the production of hormones and biologically active substances and contribute to the development of possible hypertension complications. In order to fully comprehend the role of the CART peptide in blood pressure regulation, further analyses are necessary.

Improving medical diagnosis reliability using Boosted C5.0 decision tree empowered by Particle Swarm Optimization.

PubMed

Pashaei, Elnaz; Ozen, Mustafa; Aydin, Nizamettin

2015-08-01

Improving accuracy of supervised classification algorithms in biomedical applications is one of active area of research. In this study, we improve the performance of Particle Swarm Optimization (PSO) combined with C4.5 decision tree (PSO+C4.5) classifier by applying Boosted C5.0 decision tree as the fitness function. To evaluate the effectiveness of our proposed method, it is implemented on 1 microarray dataset and 5 different medical data sets obtained from UCI machine learning databases. Moreover, the results of PSO + Boosted C5.0 implementation are compared to eight well-known benchmark classification methods (PSO+C4.5, support vector machine under the kernel of Radial Basis Function, Classification And Regression Tree (CART), C4.5 decision tree, C5.0 decision tree, Boosted C5.0 decision tree, Naive Bayes and Weighted K-Nearest neighbor). Repeated five-fold cross-validation method was used to justify the performance of classifiers. Experimental results show that our proposed method not only improve the performance of PSO+C4.5 but also obtains higher classification accuracy compared to the other classification methods.

Modeling the surface evapotranspiration over the southern Great Plains

NASA Technical Reports Server (NTRS)

Liljegren, J. C.; Doran, J. C.; Hubbe, J. M.; Shaw, W. J.; Zhong, S.; Collatz, G. J.; Cook, D. R.; Hart, R. L.

1996-01-01

We have developed a method to apply the Simple Biosphere Model of Sellers et al to calculate the surface fluxes of sensible heat and water vapor at high spatial resolution over the domain of the US DOE's Cloud and Radiation Testbed (CART) in Kansas and Oklahoma. The CART, which is within the GCIP area of interest for the Mississippi River Basin, is an extensively instrumented facility operated as part of the DOE's Atmospheric Radiation Measurement (ARM) program. Flux values calculated with our method will be used to provide lower boundary conditions for numerical models to study the atmosphere over the CART domain.

Chimeric Antigen Receptor-Modified T Cells for Solid Tumors: Challenges and Prospects

PubMed Central

Guo, Yelei; Wang, Yao; Han, Weidong

2016-01-01

Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART-) cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. The few published clinical studies of CART cells in solid tumors have addressed safety and feasibility, but the clinical outcome data are limited. Although antitumor effects were confirmed in vitro and in animal models, CART-cell-based therapy still faces several challenges when directed towards solid tumors, and it has been difficult to achieve the desired outcomes in clinical practice. Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. In this review, the status quo of CART cells and their clinical applications for solid tumors will be summarized first. Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and their future clinical applications. These interventions will make treatment with CART cells an effective and routine therapy for solid tumors. PMID:26998495

Long-term survival in HIV positive patients with up to 15 Years of antiretroviral therapy.

PubMed

McManus, Hamish; O'Connor, Catherine C; Boyd, Mark; Broom, Jennifer; Russell, Darren; Watson, Kerrie; Roth, Norman; Read, Phillip J; Petoumenos, Kathy; Law, Matthew G

2012-01-01

Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0-4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2-10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5-2.9) for CD4 = 350-499 cells/µl; and 1.5 (95% CI: 1.1-2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy

PubMed Central

McManus, Hamish; O'Connor, Catherine C.; Boyd, Mark; Broom, Jennifer; Russell, Darren; Watson, Kerrie; Roth, Norman; Read, Phillip J.; Petoumenos, Kathy; Law, Matthew G.

2012-01-01

Background Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. Methods Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. Results The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4 = 350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. Conclusion Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population. PMID:23144991

Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway.

PubMed

Wang, Y; Qiu, B; Liu, J; Zhu, Wei-Guo; Zhu, S

2014-09-26

Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide that plays neuroprotective roles in cerebral ischemia and reperfusion (I/R) injury in animal models or oxygen and glucose deprivation (OGD) in cultured neurons. Recent data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain. However, little is known about the effects of post-treatment with CART during the neuronal recovery after OGD and reoxygenation in cultured primary cortical neurons. The present study was to investigate the role of CART treated after OGD injury in neurons. Primary mouse cortical neurons were subjected to OGD and then treated with CART. Our data show that post-treatment with CART reduced the neuronal apoptosis caused by OGD injury. In addition, CART repaired OGD-impaired cortical neurons by increasing the expression of growth-associated protein 43 (GAP43), which promotes neurite outgrowth. This effect depends on pleiotrophin (PTN) as siRNA-mediated PTN knockdown totally abolished the increase in CART-stimulated GAP43 protein levels. In summary, our findings demonstrate that CART repairs the neuronal injury after OGD by facilitating neurite outgrowth through PTN-dependent pathway. The role for CART in neurite outgrowth makes it a new potential therapeutic agent for the treatment of neurodegenerative diseases. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Geospatial analysis of lake and landscape interactions within the Toolik Lake region, North Slope of Alaska

NASA Astrophysics Data System (ADS)

Pathak, Prasad A.

The Arctic region of Alaska is experiencing severe impacts of climate change. The Arctic lakes ecosystems are bound to undergo alterations in its trophic structure and other chemical properties. However, landscape factors controlling the lake influxes were not studied till date. This research has examined the currently existing lake landscape interactions using Remote Sensing and GIS technology. The statistical modeling was carried out using Regression and CART methods. Remote sensing data was applied to derive the required landscape indices. Remote sensing in the Arctic Alaska faces many challenges including persistent cloud cover, low sun angle and limited snow free period. Tundra vegetation types are interspersed and intricate to classify unlike managed forest stands. Therefore, historical studies have remained underachieved with respect thematic accuracies. However, looking at vegetation communities at watershed level and the implementation of expert classification system achieved the accuracies up to 90%. The research has highlighted the probable role of interactions between vegetation root zones, nutrient availability within active zone, as well as importance of permafrost thawing. Multiple regression analyses and Classification Trees were developed to understand relationships between landscape factors with various chemical parameters as well as chlorophyll readings. Spatial properties of Shrubs and Riparian complexes such as complexity of individual patches at watershed level and within proximity of water channels were influential on Chlorophyll production of lakes. Till-age had significant impact on Total Nitrogen contents. Moreover, relatively young tills exhibited significantly positive correlation with concentration of various ions and conductivity of lakes. Similarly, density of patches of Heath complexes was found to be important with respect to Total Phosphorus contents in lakes. All the regression models developed in this study were significant at 95% confidence level. However, the classification trees could not achieve high predictabilities due to limited number of lakes sampled. Keywords: Landscape factors, Lake primary productivity, Arctic, Climate change, Regression, CART

Schistosoma mansoni reinfection: Analysis of risk factors by classification and regression tree (CART) modeling

PubMed Central

Oliveira-Prado, Roberta; Matoso, Leonardo Ferreira; Veloso, Bráulio M.; Andrade, Gisele; Kloos, Helmut; Bethony, Jeffrey M.; Assunção, Renato M.; Correa-Oliveira, Rodrigo

2017-01-01

Praziquantel (PZQ) is an effective chemotherapy for schistosomiasis mansoni and a mainstay for its control and potential elimination. However, it does not prevent against reinfection, which can occur rapidly in areas with active transmission. A guide to ranking the risk factors for Schistosoma mansoni reinfection would greatly contribute to prioritizing resources and focusing prevention and control measures to prevent rapid reinfection. The objective of the current study was to explore the relationship among the socioeconomic, demographic, and epidemiological factors that can influence reinfection by S. mansoni one year after successful treatment with PZQ in school-aged children in Northeastern Minas Gerais state Brazil. Parasitological, socioeconomic, demographic, and water contact information were surveyed in 506 S. mansoni-infected individuals, aged 6 to 15 years, resident in these endemic areas. Eligible individuals were treated with PZQ until they were determined to be negative by the absence of S. mansoni eggs in the feces on two consecutive days of Kato-Katz fecal thick smear. These individuals were surveyed again 12 months from the date of successful treatment with PZQ. A classification and regression tree modeling (CART) was then used to explore the relationship between socioeconomic, demographic, and epidemiological variables and their reinfection status. The most important risk factor identified for S. mansoni reinfection was their “heavy” infection at baseline. Additional analyses, excluding heavy infection status, showed that lower socioeconomic status and a lower level of education of the household head were also most important risk factors for S. mansoni reinfection. Our results provide an important contribution toward the control and possible elimination of schistosomiasis by identifying three major risk factors that can be used for targeted treatment and monitoring of reinfection. We suggest that control measures that target heavily infected children in the most economically disadvantaged households would be most beneficial to maintain the success of mass chemotherapy campaigns. PMID:28813451

Assessing coastal plain wetland composition using advanced spaceborne thermal emission and reflection radiometer imagery

NASA Astrophysics Data System (ADS)

Pantaleoni, Eva

Establishing wetland gains and losses, delineating wetland boundaries, and determining their vegetative composition are major challenges that can be improved through remote sensing studies. We used the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) to separate wetlands from uplands in a study of 870 locations on the Virginia Coastal Plain. We used the first five bands from each of two ASTER scenes (6 March 2005 and 16 October 2005), covering the visible to the short-wave infrared region (0.52-2.185mum). We included GIS data layers for soil survey, topography, and presence or absence of water in a logistic regression model that predicted the location of over 78% of the wetlands. While this was slightly less accurate (78% vs. 86%) than current National Wetland Inventory (NWI) aerial photo interpretation procedures of locating wetlands, satellite imagery analysis holds great promise for speeding wetland mapping, lowering costs, and improving update frequency. To estimate wetland vegetation composition classes, we generated a classification and regression tree (CART) model and a multinomial logistic regression (logit) model, and compared their accuracy in separating woody wetlands, emergent wetlands and open water. The overall accuracy of the CART model was 73.3%, while for the logit model was 76.7%. The CART producer's accuracy of the emergent wetlands was higher than the accuracy from the multinomial logit (57.1% vs. 40.7%). However, we obtained the opposite result for the woody wetland category (68.7% vs. 52.6%). A McNemar test between the two models and NWI maps showed that their accuracies were not statistically different. We conducted a subpixel analysis of the ASTER images to estimate canopy cover of forested wetlands. We used top-of-atmosphere reflectance from the visible and near infrared bands, Delta Normalized Difference Vegetation Index, and a tasseled cap brightness, greenness, and wetness in linear regression model with canopy cover as the dependent variable. The model achieved an adjusted-R 2 of 0.69 (RMSE = 2.7%) for canopy cover less than 16%, and an adjusted-R 2 of 0.04 (RMSE = 19.8%) for higher canopy cover values. Taken together, these findings suggest that satellite remote sensing, in concert with other spatial data, has strong potential for mapping both wetland presence and type.

Systematization method for distinguishing plastic groups by using NIR spectroscopy.

PubMed

Kaihara, Mikio; Satoh, Minami; Satoh, Minoru

2007-07-01

A systematic classification method for polymers is not yet available in case of using near infrared spectra (NIR). That is why we have been searching for a systematic method. Because raw NIR spectra usually have few obvious peaks, NIR spectra have been pretreated by 2nd derivation for taking well modulated spectra. After the pretreatment, we applied classification and regression trees (CART) to the discrimination between the spectra and the species of polymers. As a result, we obtained a relatively simple classification tree. Judging from the obtained splitting conditions and the classified polymers, we concluded that obtained knowledge on the chemical function groups estimated by the important wavelength regions is not always applicable to this classification tree. However, we clarified the splitting rules for polymer species from the NIR spectral point of view.

A screening system for smear-negative pulmonary tuberculosis using artificial neural networks.

PubMed

de O Souza Filho, João B; de Seixas, José Manoel; Galliez, Rafael; de Bragança Pereira, Basilio; de Q Mello, Fernanda C; Dos Santos, Alcione Miranda; Kritski, Afranio Lineu

2016-08-01

Molecular tests show low sensitivity for smear-negative pulmonary tuberculosis (PTB). A screening and risk assessment system for smear-negative PTB using artificial neural networks (ANNs) based on patient signs and symptoms is proposed. The prognostic and risk assessment models exploit a multilayer perceptron (MLP) and inspired adaptive resonance theory (iART) network. Model development considered data from 136 patients with suspected smear-negative PTB in a general hospital. MLP showed higher sensitivity (100%, 95% confidence interval (CI) 78-100%) than the other techniques, such as support vector machine (SVM) linear (86%; 95% CI 60-96%), multivariate logistic regression (MLR) (79%; 95% CI 53-93%), and classification and regression tree (CART) (71%; 95% CI 45-88%). MLR showed a slightly higher specificity (85%; 95% CI 59-96%) than MLP (80%; 95% CI 54-93%), SVM linear (75%, 95% CI 49-90%), and CART (65%; 95% CI 39-84%). In terms of the area under the receiver operating characteristic curve (AUC), the MLP model exhibited a higher value (0.918, 95% CI 0.824-1.000) than the SVM linear (0.796, 95% CI 0.651-0.970) and MLR (0.782, 95% CI 0.663-0.960) models. The significant signs and symptoms identified in risk groups are coherent with clinical practice. In settings with a high prevalence of smear-negative PTB, the system can be useful for screening and also to aid clinical practice in expediting complementary tests for higher risk patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

One-Dimensional Collision Carts Computer Model and Its Design Ideas for Productive Experiential Learning

ERIC Educational Resources Information Center

Wee, Loo Kang

2012-01-01

We develop an Easy Java Simulation (EJS) model for students to experience the physics of idealized one-dimensional collision carts. The physics model is described and simulated by both continuous dynamics and discrete transition during collision. In designing the simulations, we discuss briefly three pedagogical considerations namely (1) a…

Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis.

PubMed

Chammartin, Frédérique; Zürcher, Kathrin; Keiser, Olivia; Weigel, Ralf; Chu, Kathryn; Kiragga, Agnes N; Ardura-Garcia, Cristina; Anderegg, Nanina; Laurent, Christian; Cornell, Morna; Tweya, Hannock; Haas, Andreas D; Rice, Brian D; Geng, Elvin H; Fox, Matthew P; Hargreaves, James R; Egger, Matthias

2018-06-08

Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/μL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

Predicting fecal indicator organism contamination in Oregon coastal streams.

PubMed

Pettus, Paul; Foster, Eugene; Pan, Yangdong

2015-12-01

In this study, we used publicly available GIS layers and statistical tree-based modeling (CART and Random Forest) to predict pathogen indicator counts at a regional scale using 88 spatially explicit landscape predictors and 6657 samples from non-estuarine streams in the Oregon Coast Range. A total of 532 frequently sampled sites were parsed down to 93 pathogen sampling sites to control for spatial and temporal biases. This model's 56.5% explanation of variance, was comparable to other regional models, while still including a large number of variables. Analysis showed the most important predictors on bacteria counts to be: forest and natural riparian zones, cattle related activities, and urban land uses. This research confirmed linkages to anthropogenic activities, with the research prediction mapping showing increased bacteria counts in agricultural and urban land use areas and lower counts with more natural riparian conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling ozone episodes in the Baltimore-Washington region

NASA Technical Reports Server (NTRS)

Ryan, William F.

1994-01-01

Surface ozone (O3) concentrations in excess of the National Ambient Air Quality Standard (NAAQS) continue to occur in metropolitan areas in the United States despite efforts to control emissions of O3 precursors. Future O3 control strategies will be based on results from modeling efforts that have just begun in many areas. Two initial questions that arise are model sensitivity to domain-specific conditions and the selection of episodes for model evaluation and control strategy development. For the Baltimore-Washington region (B-W), the presence of the Chesapeake Bay introduces a number of issues relevant to model sensitivity. In this paper, the specific questions of the determination of model volume (mixing height) for the Urban Airshed Model (UAM) is discussed and various alternative methods compared. For the latter question, several analytic approaches, Cluster Analysis and classification and Regression Tree (CART) analysis are undertaken to determine meteorological conditions associated with severe O3 events in the B-W domain.

Interactions among genetic variants in apoptosis pathway genes, reflux symptoms, body mass index, and smoking indicate two distinct etiologic patterns of esophageal adenocarcinoma.

PubMed

Zhai, Rihong; Chen, Feng; Liu, Geoffrey; Su, Li; Kulke, Matthew H; Asomaning, Kofi; Lin, Xihong; Heist, Rebecca S; Nishioka, Norman S; Sheu, Chau-Chyun; Wain, John C; Christiani, David C

2010-05-10

Apoptosis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with esophageal adenocarcinoma (EA) development. However, how multiple factors jointly affect EA risk remains unclear. In total, 305 patients with EA and 339 age- and sex-matched controls were studied. High-order interactions among reflux, BMI, smoking, and functional polymorphisms in five apoptotic genes (FAS, FASL, IL1B, TP53BP, and BAT3) were investigated by entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional logistic regression (LR) models. In LR analysis, reflux, BMI, and smoking were significantly associated with EA risk, with reflux as the strongest individual factor. No individual single nucleotide polymorphism was associated with EA susceptibility. However, there was a two-way interaction between IL1B + 3954C>T and reflux (P = .008). In both CART and MDR analyses, reflux was also the strongest individual factor for EA risk. In individuals with reflux symptoms, CART analysis indicated that strongest interaction was among variant genotypes of IL1B + 3954C>T and BAT3S625P, higher BMI, and smoking (odds ratio [OR], 5.76; 95% CI, 2.48 to 13.38), a finding independently found using MDR analysis. In contrast, for participants without reflux symptoms, the strongest interaction was found between higher BMI and smoking (OR, 3.27; 95% CI, 1.88 to 5.68), also echoed by entropy-based MDR analysis. Although a history of reflux is an important risk for EA, multifactor interactions also play important roles in EA risk. Gene-environment interaction patterns differ between patients with and without reflux symptoms.

Protein-coding genes combined with long noncoding RNA as a novel transcriptome molecular staging model to predict the survival of patients with esophageal squamous cell carcinoma.

PubMed

Guo, Jin-Cheng; Wu, Yang; Chen, Yang; Pan, Feng; Wu, Zhi-Yong; Zhang, Jia-Sheng; Wu, Jian-Yi; Xu, Xiu-E; Zhao, Jian-Mei; Li, En-Min; Zhao, Yi; Xu, Li-Yan

2018-04-09

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal carcinoma in China. This study was to develop a staging model to predict outcomes of patients with ESCC. Using Cox regression analysis, principal component analysis (PCA), partitioning clustering, Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, and classification and regression tree (CART) analysis, we mined the Gene Expression Omnibus database to determine the expression profiles of genes in 179 patients with ESCC from GSE63624 and GSE63622 dataset. Univariate cox regression analysis of the GSE63624 dataset revealed that 2404 protein-coding genes (PCGs) and 635 long non-coding RNAs (lncRNAs) were associated with the survival of patients with ESCC. PCA categorized these PCGs and lncRNAs into three principal components (PCs), which were used to cluster the patients into three groups. ROC analysis demonstrated that the predictive ability of PCG-lncRNA PCs when applied to new patients was better than that of the tumor-node-metastasis staging (area under ROC curve [AUC]: 0.69 vs. 0.65, P < 0.05). Accordingly, we constructed a molecular disaggregated model comprising one lncRNA and two PCGs, which we designated as the LSB staging model using CART analysis in the GSE63624 dataset. This LSB staging model classified the GSE63622 dataset of patients into three different groups, and its effectiveness was validated by analysis of another cohort of 105 patients. The LSB staging model has clinical significance for the prognosis prediction of patients with ESCC and may serve as a three-gene staging microarray.

IND - THE IND DECISION TREE PACKAGE

NASA Technical Reports Server (NTRS)

Buntine, W.

1994-01-01

A common approach to supervised classification and prediction in artificial intelligence and statistical pattern recognition is the use of decision trees. A tree is "grown" from data using a recursive partitioning algorithm to create a tree which has good prediction of classes on new data. Standard algorithms are CART (by Breiman Friedman, Olshen and Stone) and ID3 and its successor C4 (by Quinlan). As well as reimplementing parts of these algorithms and offering experimental control suites, IND also introduces Bayesian and MML methods and more sophisticated search in growing trees. These produce more accurate class probability estimates that are important in applications like diagnosis. IND is applicable to most data sets consisting of independent instances, each described by a fixed length vector of attribute values. An attribute value may be a number, one of a set of attribute specific symbols, or it may be omitted. One of the attributes is delegated the "target" and IND grows trees to predict the target. Prediction can then be done on new data or the decision tree printed out for inspection. IND provides a range of features and styles with convenience for the casual user as well as fine-tuning for the advanced user or those interested in research. IND can be operated in a CART-like mode (but without regression trees, surrogate splits or multivariate splits), and in a mode like the early version of C4. Advanced features allow more extensive search, interactive control and display of tree growing, and Bayesian and MML algorithms for tree pruning and smoothing. These often produce more accurate class probability estimates at the leaves. IND also comes with a comprehensive experimental control suite. IND consists of four basic kinds of routines: data manipulation routines, tree generation routines, tree testing routines, and tree display routines. The data manipulation routines are used to partition a single large data set into smaller training and test sets. The generation routines are used to build classifiers. The test routines are used to evaluate classifiers and to classify data using a classifier. And the display routines are used to display classifiers in various formats. IND is written in C-language for Sun4 series computers. It consists of several programs with controlling shell scripts. Extensive UNIX man entries are included. IND is designed to be used on any UNIX system, although it has only been thoroughly tested on SUN platforms. The standard distribution medium for IND is a .25 inch streaming magnetic tape cartridge in UNIX tar format. An electronic copy of the documentation in PostScript format is included on the distribution medium. IND was developed in 1992.

Experiments to Determine Whether Recursive Partitioning (CART) or an Artificial Neural Network Overcomes Theoretical Limitations of Cox Proportional Hazards Regression

NASA Technical Reports Server (NTRS)

Kattan, Michael W.; Hess, Kenneth R.; Kattan, Michael W.

1998-01-01

New computationally intensive tools for medical survival analyses include recursive partitioning (also called CART) and artificial neural networks. A challenge that remains is to better understand the behavior of these techniques in effort to know when they will be effective tools. Theoretically they may overcome limitations of the traditional multivariable survival technique, the Cox proportional hazards regression model. Experiments were designed to test whether the new tools would, in practice, overcome these limitations. Two datasets in which theory suggests CART and the neural network should outperform the Cox model were selected. The first was a published leukemia dataset manipulated to have a strong interaction that CART should detect. The second was a published cirrhosis dataset with pronounced nonlinear effects that a neural network should fit. Repeated sampling of 50 training and testing subsets was applied to each technique. The concordance index C was calculated as a measure of predictive accuracy by each technique on the testing dataset. In the interaction dataset, CART outperformed Cox (P less than 0.05) with a C improvement of 0.1 (95% Cl, 0.08 to 0.12). In the nonlinear dataset, the neural network outperformed the Cox model (P less than 0.05), but by a very slight amount (0.015). As predicted by theory, CART and the neural network were able to overcome limitations of the Cox model. Experiments like these are important to increase our understanding of when one of these new techniques will outperform the standard Cox model. Further research is necessary to predict which technique will do best a priori and to assess the magnitude of superiority.

Computer aided diagnosis system for the Alzheimer's disease based on partial least squares and random forest SPECT image classification.

PubMed

Ramírez, J; Górriz, J M; Segovia, F; Chaves, R; Salas-Gonzalez, D; López, M; Alvarez, I; Padilla, P

2010-03-19

This letter shows a computer aided diagnosis (CAD) technique for the early detection of the Alzheimer's disease (AD) by means of single photon emission computed tomography (SPECT) image classification. The proposed method is based on partial least squares (PLS) regression model and a random forest (RF) predictor. The challenge of the curse of dimensionality is addressed by reducing the large dimensionality of the input data by downscaling the SPECT images and extracting score features using PLS. A RF predictor then forms an ensemble of classification and regression tree (CART)-like classifiers being its output determined by a majority vote of the trees in the forest. A baseline principal component analysis (PCA) system is also developed for reference. The experimental results show that the combined PLS-RF system yields a generalization error that converges to a limit when increasing the number of trees in the forest. Thus, the generalization error is reduced when using PLS and depends on the strength of the individual trees in the forest and the correlation between them. Moreover, PLS feature extraction is found to be more effective for extracting discriminative information from the data than PCA yielding peak sensitivity, specificity and accuracy values of 100%, 92.7%, and 96.9%, respectively. Moreover, the proposed CAD system outperformed several other recently developed AD CAD systems. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

EAST Multicenter Trial on Targeted Temperature Management for Hanging-Induced Cardiac Arrest.

PubMed

Hsu, Cindy H; Haac, Bryce E; Drake, Mack; Bernard, Andrew C; Aiolfi, Alberto; Inaba, Kenji; Hinson, Holly E; Agarwal, Chinar; Galante, Joseph; Tibbits, Emily M; Johnson, Nicholas J; Carlbom, David; Mirhoseini, Mina F; Patel, Mayur B; OʼBosky, Karen R; Chan, Christian; Udekwu, Pascal O; Farrell, Megan; Wild, Jeffrey L; Young, Katelyn A; Cullinane, Daniel C; Gojmerac, Deborah J; Weissman, Alexandra; Callaway, Clifton; Perman, Sarah M; Guerrero, Mariana; Aisiku, Imoigele P; Seethala, Raghu R; Co, Ivan N; Madhok, Debbie Y; Darger, Bryan; Kim, Dennis Y; Spence, Lara; Scalea, Thomas M; Stein, Deborah M

2018-04-19

We sought to determine the outcome of suicidal hanging and the impact of targeted temperature management (TTM) on hanging-induced cardiac arrest (CA) through an Eastern Association for the Surgery of Trauma (EAST) multicenter retrospective study. We analyzed hanging patient data and TTM variables from January 1992 to December 2015. Cerebral performance category (CPC) score of 1 or 2 was considered good neurologic outcome, while CPC of 3 or 4 was considered poor outcome. Classification and Regression Trees (CART) recursive partitioning was used to develop multivariate predictive models for survival and neurological outcome. Total of 692 hanging patients from 17 centers were analyzed for this study. Their overall survival rate was 77%, and the CA survival rate was 28.6%. The CA patients had significantly higher severity of illness and worse outcome than the non-CA patients. Of the 175 CA patients who survived to hospital admission, 81 patients (46.3%) received post-cardiac arrest TTM. The unadjusted survival of TTM CA patients (24.7% vs 39.4%, p<0.05) and good neurologic outcome (19.8% vs 37.2%, p<0.05) were worse than non-TTM CA patients. However, when subgroup analyses were performed between those with admission GCS of 3-8, the differences between TTM and non-TTM CA survival (23.8% vs 30.0%, p=0.37) and good neurologic outcome (18.8% vs 28.7%, p=0.14) were not significant. TTM implementation and post-cardiac arrest management varied between the participating centers. CART models identified variables predictive of favorable and poor outcome for hanging and TTM patients with excellent accuracy. CA hanging patients had worse outcome than non-CA patients. TTM CA patients had worse unadjusted survival and neurologic outcome than non-TTM patients. These findings may be explained by their higher severity of illness, variable TTM implementation, and differences in post-cardiac arrest management. Future prospective studies are necessary to ascertain the effect of TTM on hanging outcome and to validate our CART models. Therapeutic study, level III; prognostic study, level III.

Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

NASA Astrophysics Data System (ADS)

Xu, Yun; Zhang, Wenri; Klaus, Judith; Young, Jennifer; Koerner, Ines; Sheldahl, Laird C.; Hurn, Patricia D.; Martínez-Murillo, Francisco; Alkayed, Nabil J.

2006-09-01

Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.v. administration of a rat CART peptide is protective against ischemic brain injury in vivo. We further demonstrated binding of cAMP response element (CRE)-binding protein to a CART promoter CRE site in ischemic brain and rapid activation by CART of ERK in primary cultured cortical neurons. The findings suggest that CART is an important player in estrogen-mediated neuroprotection and a potential therapeutic agent for stroke and other neurodegenerative diseases. ischemia | stroke | estrogen

Psychometric properties of the Belgian coach version of the coach-athlete relationship questionnaire (CART-Q).

PubMed

Balduck, A-L; Jowett, S

2010-10-01

The study examined the psychometric properties of the Belgian coach version of the Coach-Athlete Relationship Questionnaire (CART-Q). The questionnaire includes three dimensions (Closeness, Commitment, and Complementarity) in a model that intends to measure the quality of the coach-athlete relationship. Belgian coaches (n=144) of athletes who performed at various competition levels in such sports as football, basketball, and volleyball responded to the CART-Q and to the Leadership Scale for Sport (LSS). A confirmatory factor analysis proved to be slightly more satisfactory for a three-order factor model, compared with a hierarchical first-order factor model. The three factors showed acceptable internal consistency scores. Moreover, functional associations between the three factors and coach leadership behaviors were found offering support to the instrument's concurrent validity. The findings support previous validation studies and verify the psychometric properties of the CART-Q applied to Belgian coaches of team sports. © 2009 John Wiley & Sons A/S.

Magnitude of virologic blips is associated with a higher risk for virologic rebound in HIV-infected individuals: a recurrent events analysis.

PubMed

Grennan, J Troy; Loutfy, Mona R; Su, DeSheng; Harrigan, P Richard; Cooper, Curtis; Klein, Marina; Machouf, Nima; Montaner, Julio S G; Rourke, Sean; Tsoukas, Christos; Hogg, Bob; Raboud, Janet

2012-04-15

The importance of human immunodeficiency virus (HIV) blip magnitude on virologic rebound has been raised in clinical guidelines relating to viral load assays. Antiretroviral-naive individuals initiating combination antiretroviral therapy (cART) after 1 January 2000 and achieving virologic suppression were studied. Negative binomial models were used to identify blip correlates. Recurrent event models were used to determine the association between blips and rebound by incorporating multiple periods of virologic suppression per individual. 3550 participants (82% male; median age, 40 years) were included. In a multivariable negative binomial regression model, the Amplicor assay was associated with a lower blip rate than branched DNA (rate ratio, 0.69; P < .01), controlling for age, sex, region, baseline HIV-1 RNA and CD4 count, AIDS-defining illnesses, year of cART initiation, cART type, and HIV-1 RNA testing frequency. In a multivariable recurrent event model controlling for age, sex, intravenous drug use, cART start year, cART type, assay type, and HIV-1 RNA testing frequency, blips of 500-999 copies/mL were associated with virologic rebound (hazard ratio, 2.70; P = .002), whereas blips of 50-499 were not. HIV-1 RNA assay was an important determinant of blip rates and should be considered in clinical guidelines. Blips ≥500 copies/mL were associated with increased rebound risk.

Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

PubMed

Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

2017-07-01

Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation. Copyright © 2017 American Society for Microbiology.

Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia

PubMed Central

Peterson, Christopher W.; Kiem, Hans-Peter

2017-01-01

ABSTRACT Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the “Berlin patient” remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation. PMID:28404854

Modern modelling techniques are data hungry: a simulation study for predicting dichotomous endpoints.

PubMed

van der Ploeg, Tjeerd; Austin, Peter C; Steyerberg, Ewout W

2014-12-22

Modern modelling techniques may potentially provide more accurate predictions of binary outcomes than classical techniques. We aimed to study the predictive performance of different modelling techniques in relation to the effective sample size ("data hungriness"). We performed simulation studies based on three clinical cohorts: 1282 patients with head and neck cancer (with 46.9% 5 year survival), 1731 patients with traumatic brain injury (22.3% 6 month mortality) and 3181 patients with minor head injury (7.6% with CT scan abnormalities). We compared three relatively modern modelling techniques: support vector machines (SVM), neural nets (NN), and random forests (RF) and two classical techniques: logistic regression (LR) and classification and regression trees (CART). We created three large artificial databases with 20 fold, 10 fold and 6 fold replication of subjects, where we generated dichotomous outcomes according to different underlying models. We applied each modelling technique to increasingly larger development parts (100 repetitions). The area under the ROC-curve (AUC) indicated the performance of each model in the development part and in an independent validation part. Data hungriness was defined by plateauing of AUC and small optimism (difference between the mean apparent AUC and the mean validated AUC <0.01). We found that a stable AUC was reached by LR at approximately 20 to 50 events per variable, followed by CART, SVM, NN and RF models. Optimism decreased with increasing sample sizes and the same ranking of techniques. The RF, SVM and NN models showed instability and a high optimism even with >200 events per variable. Modern modelling techniques such as SVM, NN and RF may need over 10 times as many events per variable to achieve a stable AUC and a small optimism than classical modelling techniques such as LR. This implies that such modern techniques should only be used in medical prediction problems if very large data sets are available.

Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-cell Engager.

PubMed

Wing, Anna; Fajardo, Carlos Alberto; Posey, Avery D; Shaw, Carolyn; Da, Tong; Young, Regina M; Alemany, Ramon; June, Carl H; Guedan, Sonia

2018-05-01

T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors. We report that CART cells targeting the folate receptor alpha (FR-α) successfully infiltrated preestablished xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. We demonstrated that OAd-BiTE-mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells redirected CART cells toward EGFR in the absence of FR-α, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells. The combinatorial approach improved antitumor efficacy and prolonged survival in mouse models of cancer when compared with the monotherapies, and this was the result of an increased BiTE-mediated T-cell activation in tumors. Overall, these results demonstrated that the combination of a BiTE-expressing oncolytic virus with adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as monotherapies in solid tumors and encourage its further evaluation in human trials. Cancer Immunol Res; 6(5); 605-16. ©2018 AACR . ©2018 American Association for Cancer Research.

Spatial partitioning of environmental correlates of avian biodiversity in the conterminous United States

USGS Publications Warehouse

O'Connor, R.J.; Jones, M.T.; White, D.; Hunsaker, C.; Loveland, Tom; Jones, Bruce; Preston, E.

1996-01-01

Classification and regression tree (CART) analysis was used to create hierarchically organized models of the distribution of bird species richness across the conterminous United States. Species richness data were taken from the Breeding Bird Survey and were related to climatic and land use data. We used a systematic spatial grid of approximately 12,500 hexagons, each approximately 640 square kilometres in area. Within each hexagon land use was characterized by the Loveland et al. land cover classification based on Advanced Very High Resolution Radiometer (AVHRR) data from NOAA polar orbiting meteorological satellites. These data were aggregated to yield fourteen land classes equivalent to an Anderson level II coverage; urban areas were added from the Digital Chart of the World. Each hexagon was characterized by climate data and landscape pattern metrics calculated from the land cover. A CART model then related the variation in species richness across the 1162 hexagons for which bird species richness data were available to the independent variables, yielding an R2-type goodness of fit metric of 47.5% deviance explained. The resulting model recognized eleven groups of hexagons, with species richness within each group determined by unique sequences of hierarchically constrained independent variables. Within the hierarchy, climate data accounted for more variability in the bird data, followed by land cover proportion, and then pattern metrics. The model was then used to predict species richness in all 12,500 hexagons of the conterminous United States yielding a map of the distribution of these eleven classes of bird species richness as determined by the environmental correlates. The potential for using this technique to interface biogeographic theory with the hierarchy theory of ecology is discussed. ?? 1996 Blackwell Science Ltd.

Acid rain, air pollution, and tree growth in southeastern New York

USGS Publications Warehouse

Puckett, L.J.

1982-01-01

Whether dendroecological analyses could be used to detect changes in the relationship of tree growth to climate that might have resulted from chronic exposure to components of the acid rain-air pollution complex was determined. Tree-ring indices of white pine (Pinus strobus L.), eastern hemlock (Tsuga canadensis (L.) Cart.), pitch pine (Pinus rigida Mill.), and chestnut oak (Quercus prinus L.) were regressed against orthogonally transformed values of temperature and precipitation in order to derive a response-function relationship. Results of the regression analyses for three time periods, 1901–1920, 1926–1945, and 1954–1973 suggest that the relationship of tree growth to climate has been altered. Statistical tests of the temperature and precipitation data suggest that this change was nonclimatic. Temporally, the shift in growth response appears to correspond with the suspected increase in acid rain and air pollution in the Shawangunk Mountain area of southeastern New York in the early 1950's. This change could be the result of physiological stress induced by components of the acid rain-air pollution complex, causing climatic conditions to be more limiting to tree growth.

Association between prescription cost sharing and adherence to initial combination antiretroviral therapy in commercially insured antiretroviral-naïve patients with HIV.

PubMed

Johnston, Stephen S; Juday, Timothy; Seekins, Daniel; Espindle, Derek; Chu, Bong-Chul

2012-03-01

In treatment of human immunodeficiency virus (HIV), high levels of adherence to combination antiretroviral therapy (cART) are required to prevent failure of virologic suppression, development of drug resistance, and permanent loss of therapeutic options. No published research has assessed the association between cART prescription cost sharing and adherence to cART. To analyze the association between cART prescription cost sharing and adherence to initial cART in commercially insured antiretroviral (ARV)-naïve patients with HIV. This retrospective observational cohort study used 2002-2008 data from a large U.S. claims database of more than 56 million commercially insured individuals. Study subjects were patients aged 18 years or older who initiated cART during the period January 1, 2003, to December 31, 2007, had no ARV claims during the 6-month period prior to the initiation date, and had at least 1 ICD-9-CM diagnosis code for HIV infection (042, 795.71, V08) from 12 months before to 12 months after cART initiation. A minimum 12-month period of continuous enrollment after cART initiation was used to construct a patient-quarter repeated measures panel dataset in which each quarter of data that a patient contributed represented an observation. The evaluation period extended from cART initiation until the occurrence of 1 of the following events: addition of an ARV that was not part of the initial cART regimen, 30-day gap in possession of an ARV within the initiated cART regimen, hospitalization of 30 or more days, loss to follow-up due to study end (December 31, 2008), or disenrollment. The study's outcome was quarterly adherence to cART, defined as the number of days within the quarter that a patient possessed all components of the initial cART regimen. Each patient's cART cost-sharing amount was calculated per 30-day supply of the entire cART regimen. Adherence was dichotomized for analysis at the clinically meaningful thresholds of 95% and 78%. The dichotomized adherence outcomes were separately modeled using population-averaged generalized estimating equations (GEEs) with time-varying and time-constant covariates and an exchangeable working correlation structure. Independent variables included cost-sharing amount; sequential quarter number after cART initiation; interaction between cost-sharing amount and sequential quarter number (to capture any changes in the association of cost sharing with adherence that may occur over time after initiation of cART); and patient demographic, clinical, and insurance characteristics. For each sequential quarter after cART initiation, the GEE models were used to generate average predicted probabilities of adherence reaching each threshold (95% and 78%) at cost-sharing levels of $25, $75, and $144, which represented the 25th, 75th, and 90th percentiles of the cost-sharing distribution, respectively. The study sample included 19,199 patient-quarters and 3,731 patients: mean age 41.1 years; 83.2% male; mean (SD) duration of post-index period 5.1 (4.2) quarters; mean (SD) daily cART pill count 3.2 (2.2); mean (median) cost sharing per 30-day supply of the entire cART regimen $67 ($40). In the unadjusted analyses of patient-quarters, mean adherence ranged from 97.2% for cost-sharing levels within the 0-20th percentiles (from $0 to $20 per 30-day cART supply) to 94.0% for cost-sharing levels exceeding the 80th percentile (from $84 to $3,832 per 30-day cART supply). In the adjusted analyses for the second quarter (25th percentile of follow-up duration, n = 3,117 cases still under observation) at the cost-sharing levels of $25, $75, and $144, the predicted probabilities of at least 95% adherence were 0.782, 0.770, and 0.752, respectively, and the predicted probabilities of at least 78% adherence were 0.936, 0.931, and 0.924, respectively. The differences in the predicted probabilities of adherence grew over time. By the seventh quarter (the 75th percentile of follow-up duration, n = 1,096 cases still under observation), the predicted probabilities were 0.773, 0.746, and 0.707 for 95% adherence and 0.933, 0.922, and 0.904 for 78% adherence at cost-sharing levels of $25, $75, and $144, respectively. Increasing cART prescription cost sharing was associated with modestly decreased probability of maintaining clinically meaningful levels of cART adherence.

Predicting membrane protein types using various decision tree classifiers based on various modes of general PseAAC for imbalanced datasets.

PubMed

Sankari, E Siva; Manimegalai, D

2017-12-21

Predicting membrane protein types is an important and challenging research area in bioinformatics and proteomics. Traditional biophysical methods are used to classify membrane protein types. Due to large exploration of uncharacterized protein sequences in databases, traditional methods are very time consuming, expensive and susceptible to errors. Hence, it is highly desirable to develop a robust, reliable, and efficient method to predict membrane protein types. Imbalanced datasets and large datasets are often handled well by decision tree classifiers. Since imbalanced datasets are taken, the performance of various decision tree classifiers such as Decision Tree (DT), Classification And Regression Tree (CART), C4.5, Random tree, REP (Reduced Error Pruning) tree, ensemble methods such as Adaboost, RUS (Random Under Sampling) boost, Rotation forest and Random forest are analysed. Among the various decision tree classifiers Random forest performs well in less time with good accuracy of 96.35%. Another inference is RUS boost decision tree classifier is able to classify one or two samples in the class with very less samples while the other classifiers such as DT, Adaboost, Rotation forest and Random forest are not sensitive for the classes with fewer samples. Also the performance of decision tree classifiers is compared with SVM (Support Vector Machine) and Naive Bayes classifier. Copyright © 2017 Elsevier Ltd. All rights reserved.

Substance use and adherence among people living with HIV/AIDS receiving cART in Latin America

PubMed Central

De Boni, Raquel B.; Shepherd, Bryan E.; Grinsztejn, Beatriz; Cesar, Carina; Cortés, Claudia; Padgett, Denis; Gotuzzo, Eduardo; Belaunzarán-Zamudio, Pablo F.; Rebeiro, Peter F.; Duda, Stephany N.; McGowan, Catherine C.

2016-01-01

This cross-sectional study describes substance use prevalence and its association with cART adherence among 3343 individuals receiving care at HIV clinics in Argentina, Brazil, Chile, Honduras, Mexico, and Peru. A rapid screening tool evaluated self-reported 7-day recall of alcohol, marijuana, cocaine, heroin, and methamphetamine use, and missed cART doses. Overall, 29.3% individuals reported having ≥ 1 alcoholic drinks, 5.0% reported any illicit drug use and 17.0% reported missed cART doses. In the logistic regression model, compared to no substance use, alcohol use (adjusted odds ratio (AOR)=2.46, 95% confidence interval (CI): 1.99–3.05), illicit drug use (AOR=3.57, 95% CI: 2.02–6.30), and using both alcohol and illicit drugs (AOR=4.98, 95% CI: 3.19–7.79) were associated with missed cART doses. The associations between substance use and likelihood of missing cART doses point to the need of targeting alcohol and illicit drug use to improve adherence among people living with HIV in Latin America. PMID:27091028

Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database

PubMed Central

2010-01-01

Background The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Methods Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. Results A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. Conclusions After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain. PMID:21182796

Energy behavior of an electromechanical system with internal impacts and uncertainties

NASA Astrophysics Data System (ADS)

Lima, Roberta; Sampaio, Rubens

2016-07-01

This paper analyzes the maximal energy stored in an elastic barrier due to the impacts of a pendulum fitted within a vibro-impact electromechanical system considering the existence of epistemic uncertainties in the system parameters. The vibro-impact electromechanical system is composed of two subsystems. The first subsystem is the electromechanical system composed by a motor, cart and pendulum, and the second is an elastic barrier. The first will be called striker system. The pendulum is fitted within the cart. Its suspension point is fixed in the cart, so that it may exist a relative motion between cart and pendulum. The influence of the DC motor in the dynamic behavior of the pendulum is considered. The coupling between the motor and the cart is made by a scotch yoke mechanism, so that the motor rotational motion is transformed in horizontal cart motion over a rail. The pendulum is modeled as a mathematical pendulum (bar without mass and particle of mass mp at the end). A flexible barrier, placed inside the cart, constrains the pendulum motion. Due to the relative motion between the cart and the pendulum, impacts may occur between these two elements. The objective of the paper is to analyze the energy stored in the barrier due to impacts as a function of some parameters of the electromechanical system from a deterministic and from a stochastic viewpoint. The system is designed as an aid in drilling. The impacts damage or fracture the rock and facilitate the conventional drilling.

Investigating the management performance of disinfection analysis of water distribution networks using data mining approaches.

PubMed

Zounemat-Kermani, Mohammad; Ramezani-Charmahineh, Abdollah; Adamowski, Jan; Kisi, Ozgur

2018-06-13

Chlorination, the basic treatment utilized for drinking water sources, is widely used for water disinfection and pathogen elimination in water distribution networks. Thereafter, the proper prediction of chlorine consumption is of great importance in water distribution network performance. In this respect, data mining techniques-which have the ability to discover the relationship between dependent variable(s) and independent variables-can be considered as alternative approaches in comparison to conventional methods (e.g., numerical methods). This study examines the applicability of three key methods, based on the data mining approach, for predicting chlorine levels in four water distribution networks. ANNs (artificial neural networks, including the multi-layer perceptron neural network, MLPNN, and radial basis function neural network, RBFNN), SVM (support vector machine), and CART (classification and regression tree) methods were used to estimate the concentration of residual chlorine in distribution networks for three villages in Kerman Province, Iran. Produced water (flow), chlorine consumption, and residual chlorine were collected daily for 3 years. An assessment of the studied models using several statistical criteria (NSC, RMSE, R 2 , and SEP) indicated that, in general, MLPNN has the greatest capability for predicting chlorine levels followed by CART, SVM, and RBF-ANN. Weaker performance of the data-driven methods in the water distribution networks, in some cases, could be attributed to improper chlorination management rather than the methods' capability.

Serum eotaxin-1 is increased in extremely-low-birth-weight infants with bronchopulmonary dysplasia or death.

PubMed

Kandasamy, Jegen; Roane, Claire; Szalai, Alexander; Ambalavanan, Namasivayam

2015-11-01

Early systemic inflammation in extremely-low-birth-weight (ELBW) infants is associated with an increased risk of bronchopulmonary dysplasia (BPD). Our objective was to identify circulating biomarkers and develop prediction models for BPD/death soon after birth. Blood samples from postnatal day 1 were analyzed for C-reactive protein (CRP) by enzyme-linked immunosorbent assay and for 39 cytokines/chemokines by a multiplex assay in 152 ELBW infants. The primary outcome was physiologic BPD or death by 36 wk. CRP, cytokines, and clinical variables available at ≤24 h were used for forward stepwise regression and Classification and Regression Tree (CART) analysis to identify predictors of BPD/death. Overall, 24% developed BPD and 35% died or developed BPD. Regression analysis identified birth weight and eotaxin (CCL11) as the two most significant variables. CART identified FiO2 at 24 h (11% BPD/death if FiO2 ≤28%, 49% if >28%) and eotaxin in infants with FiO2 > 28% (29% BPD/death if eotaxin was ≤84 pg/ml; 65% if >84) as variables most associated with outcome. Eotaxin measured on the day of birth is useful for identifying ELBW infants at risk of BPD/death. Further investigation is required to determine if eotaxin is involved in lung injury and pathogenesis of BPD.

Why choose Random Forest to predict rare species distribution with few samples in large undersampled areas? Three Asian crane species models provide supporting evidence.

PubMed

Mi, Chunrong; Huettmann, Falk; Guo, Yumin; Han, Xuesong; Wen, Lijia

2017-01-01

Species distribution models (SDMs) have become an essential tool in ecology, biogeography, evolution and, more recently, in conservation biology. How to generalize species distributions in large undersampled areas, especially with few samples, is a fundamental issue of SDMs. In order to explore this issue, we used the best available presence records for the Hooded Crane ( Grus monacha , n  = 33), White-naped Crane ( Grus vipio , n  = 40), and Black-necked Crane ( Grus nigricollis , n  = 75) in China as three case studies, employing four powerful and commonly used machine learning algorithms to map the breeding distributions of the three species: TreeNet (Stochastic Gradient Boosting, Boosted Regression Tree Model), Random Forest, CART (Classification and Regression Tree) and Maxent (Maximum Entropy Models). In addition, we developed an ensemble forecast by averaging predicted probability of the above four models results. Commonly used model performance metrics (Area under ROC (AUC) and true skill statistic (TSS)) were employed to evaluate model accuracy. The latest satellite tracking data and compiled literature data were used as two independent testing datasets to confront model predictions. We found Random Forest demonstrated the best performance for the most assessment method, provided a better model fit to the testing data, and achieved better species range maps for each crane species in undersampled areas. Random Forest has been generally available for more than 20 years and has been known to perform extremely well in ecological predictions. However, while increasingly on the rise, its potential is still widely underused in conservation, (spatial) ecological applications and for inference. Our results show that it informs ecological and biogeographical theories as well as being suitable for conservation applications, specifically when the study area is undersampled. This method helps to save model-selection time and effort, and allows robust and rapid assessments and decisions for efficient conservation.

Why choose Random Forest to predict rare species distribution with few samples in large undersampled areas? Three Asian crane species models provide supporting evidence

PubMed Central

Mi, Chunrong; Huettmann, Falk; Han, Xuesong; Wen, Lijia

2017-01-01

Species distribution models (SDMs) have become an essential tool in ecology, biogeography, evolution and, more recently, in conservation biology. How to generalize species distributions in large undersampled areas, especially with few samples, is a fundamental issue of SDMs. In order to explore this issue, we used the best available presence records for the Hooded Crane (Grus monacha, n = 33), White-naped Crane (Grus vipio, n = 40), and Black-necked Crane (Grus nigricollis, n = 75) in China as three case studies, employing four powerful and commonly used machine learning algorithms to map the breeding distributions of the three species: TreeNet (Stochastic Gradient Boosting, Boosted Regression Tree Model), Random Forest, CART (Classification and Regression Tree) and Maxent (Maximum Entropy Models). In addition, we developed an ensemble forecast by averaging predicted probability of the above four models results. Commonly used model performance metrics (Area under ROC (AUC) and true skill statistic (TSS)) were employed to evaluate model accuracy. The latest satellite tracking data and compiled literature data were used as two independent testing datasets to confront model predictions. We found Random Forest demonstrated the best performance for the most assessment method, provided a better model fit to the testing data, and achieved better species range maps for each crane species in undersampled areas. Random Forest has been generally available for more than 20 years and has been known to perform extremely well in ecological predictions. However, while increasingly on the rise, its potential is still widely underused in conservation, (spatial) ecological applications and for inference. Our results show that it informs ecological and biogeographical theories as well as being suitable for conservation applications, specifically when the study area is undersampled. This method helps to save model-selection time and effort, and allows robust and rapid assessments and decisions for efficient conservation. PMID:28097060

Characterizing the Intersection of Co-Occurring Risk Factors for Illicit Drug Abuse and Dependence in a U.S. Nationally Representative Sample

PubMed Central

Kurti, Allison N.; Keith, Diana R.; Noble, Alyssa; Priest, Jeff S.; Sprague, Brian; Higgins, Stephen T.

2016-01-01

Few studies have attempted to characterize how co-occurring risk factors for substance use disorders intersect. A recent study examined this question regarding cigarette smoking and demonstrated that co-occurring risk factors generally act independently. The present study examines whether that same pattern of independent intersection of risk factors extends to illicit drug abuse/dependence using a U.S. nationally representative sample (National Survey on Drug Use and Health, 2011–2013). Logistic regression and classification and regression tree (CART) modeling were used to examine risk of past-year drug abuse/dependence associated with a well-established set of risk factors for substance use (age, gender, race/ethnicity, education, poverty, smoking status, alcohol abuse/dependence, mental illness). Each of these risk factors was associated with significant increases in the odds of drug abuse/dependence in univariate logistic regressions. Each remained significant in a multivariate model examining all eight risk factors simultaneously. CART modeling of these 8 risk factors identified subpopulation risk profiles wherein drug abuse/dependence prevalence varied from < 1% to > 80% corresponding to differing combinations of risk factors present. Alcohol abuse/dependence and cigarette smoking had the strongest associations with drug abuse/dependence risk. These results demonstrate that co-occurring risk factors for illicit drug/abuse dependence generally intersect in the same independent manner as risk factors for cigarette smoking, underscoring further fundamental commonalities across these different types of substance use disorders. These results also underscore the fundamental importance of differences in the presence of co-occurring risk factors when considering the often strikingly different prevalence rates of illicit drug abuse/dependence in U.S. population subgroups. PMID:27687534

Co-occurring risk factors for current cigarette smoking in a U.S. nationally representative sample

PubMed Central

Higgins, Stephen T.; Kurti, Allison N.; Redner, Ryan; White, Thomas J.; Keith, Diana R.; Gaalema, Diann E.; Sprague, Brian L.; Stanton, Cassandra A.; Roberts, Megan E.; Doogan, Nathan J.; Priest, Jeff S.

2016-01-01

Introduction Relatively little has been reported characterizing cumulative risk associated with co-occurring risk factors for cigarette smoking. The purpose of the present study was to address that knowledge gap in a U.S. nationally representative sample. Methods Data were obtained from 114,426 adults (≥ 18 years) in the U.S. National Survey on Drug Use and Health (years 2011–13). Multiple logistic regression and classification and regression tree (CART) modeling were used to examine risk of current smoking associated with eight co-occurring risk factors (age, gender, race/ethnicity, educational attainment, poverty, drug abuse/dependence, alcohol abuse/dependence, mental illness). Results Each of these eight risk factors was independently associated with significant increases in the odds of smoking when concurrently present in a multiple logistic regression model. Effects of risk-factor combinations were typically summative. Exceptions to that pattern were in the direction of less-than-summative effects when one of the combined risk factors was associated with generally high or low rates of smoking (e.g., drug abuse/dependence, age ≥65). CART modeling identified subpopulation risk profiles wherein smoking prevalence varied from a low of 11% to a high of 74% depending on particular risk factor combinations. Being a college graduate was the strongest independent predictor of smoking status, classifying 30% of the adult population. Conclusions These results offer strong evidence that the effects associated with common risk factors for cigarette smoking are independent, cumulative, and generally summative. The results also offer potentially useful insights into national population risk profiles around which U.S. tobacco policies can be developed or refined. PMID:26902875

Association of genetic variations in the serotonin and dopamine systems with aggressive behavior in the Chinese adolescent population: Single- and multiple-risk genetic variants.

PubMed

Chang, Hongjuan; Yan, Qiuge; Tang, Lina; Huang, Juan; Ma, Yuqiao; Ye, Xiaozhou; Wu, Chunxia; Wu, Linguo; Yu, Yizhen

2018-01-01

Genetic predisposition is an important factor leading to aggressive behavior. However, the relationship between genetic polymorphisms and aggressive behavior has not been elucidated. We identified candidate genes located in the dopaminergic and serotonin system (DRD3, DRD4, and FEV) that had been previously reported to be associated with aggressive behavior. We investigated 14 tag single-nucleotide polymorphisms (SNPs) using a multi-analytic strategy combining logistic regression (LR) and classification and regression tree (CART) to explore higher-order interactions between these SNPs and aggressive behavior in 318 patients and 558 controls. Both LR and CART analyses suggested that the rs16859448 polymorphism is the strongest individual factor associated with aggressive behavior risk. In CART analysis, individuals carrying the combined genotypes of rs16859448TT/GT-rs11246228CT/TT-rs3773679TT had the highest risk, while rs16859448GG-rs2134655CT had the lowest risk (OR = 5.25, 95% CI: 2.53-10.86). This study adds to the growing evidence on the association of single- and multiple-risk variants in DRD3, DRD4, and FEV with aggressive behavior in Chinese adolescents. However, the aggressive behavior scale used to diagnose aggression in this study did not account for comorbid conditions; therefore, further studies are needed to confirm our observations. Copyright © 2017 Elsevier B.V. All rights reserved.

[Nevirapine related hepatotoxicity: the prevalence and risk factors in a cohort of ART naive Han Chinese with AIDS].

PubMed

Gao, Shi-cheng; Gui, Xi-en; Deng, Li-ping; Zhang, Yong-xi; Yan, Ya-jun; Rong, Yu-ping; Liang, Ke; Yang, Rong-rong

2010-09-01

To investigate the incidence of hepatotoxicity in acquired immunodeficiency syndrome (AIDS) patients on combined anti-retroviral therapy (cART) containing nevirapine (NVP) and to assess the risk factors and its impact on cART. 330 AIDS patients from March 2003 to June 2008 at local county were enrolled and a retrospective study using Kaplan-meier survival and Multivariate logistic regression modeling was conducted. 267 out of 330 patients received NVP based cART and 63 cases received EFV-based cART. The deference of prevalences of hepatotoxicity between the two groups is statistically significant (Chi2 = 6.691, P = 0.01). 133 out of 267 (49.8%) patients on NVP based cART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time, amounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV co-infection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+ T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: Chi2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz. NVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.

The distribution of ticks (Acari: Ixodidae) of domestic livestock in Portugal.

PubMed

Estrada-Peña, Agustín; Santos-Silva, Maria Margarida

2005-01-01

This paper introduces the first countrywide faunistic study of the tick parasites on ruminants in Portugal. The aim of this study was to map accurately the distribution of the ticks Dermacentor marginatus, Rhipicephalus (Boophilus) annulatus, R. bursa, Hyalomma m. marginatum, H. lusitanicum and Ixodes ricinus in Portugal. Additional information about the abiotic preferences of these species has been obtained through the use of abiotic (temperature- and vegetation-derived) variables have been recorded from remotely sensed information at a nominal resolution of 1.1 km(2). A further aim was the development of predictive models of distribution using Classification and Regression Trees (CART) methodologies. Four species (R. annulatus, R. bursa, D. marginatus and H. m. marginatum) are mostly restricted to south-eastern parts of the country, under hot and dry climate conditions of Mediterranean type. H. lusitanicum has been collected almost only in the southern half of Portugal. I. ricinus has a very patchy distribution and is mainly associated with vegetation of Quercus spp., found in southern zones of the country, but it is present also in the more humid western part. A variable number of abiotic variables, mainly temperature derived, are able to describe the preferences of the tick species. It is remarkable that variables derived from maximum values of the Normalized Derived Vegetation Index (yearly or summer-derived) only apply to discriminate areas where I. ricinus has been collected. CART models are able to map the distribution of these ticks with accuracy ranging within 75.3 and 96.4% of actual positive sites.

Characterization of the Two CART Genes (CART1 and CART2) in Chickens (Gallus gallus)

PubMed Central

Huang, Long; Li, Juan; Wang, Yajun

2015-01-01

Cocaine- and amphetamine-regulated transcript (CART) peptide is implicated in the control of avian energy balance, however, the structure and expression of CART gene(s) remains largely unknown in birds. Here, we cloned and characterized two CART genes (named cCART1 and cCART2) in chickens. The cloned cCART1 is predicted to generate two bioactive peptides, cCART1(42-89) and cCART1(49-89), which share high amino acid sequence identity (94-98%) with their mammalian counterparts, while the novel cCART2 may produce a bioactive peptide cCART2(51-91) with 59% identity to cCART1. Interestingly, quantitative RT-PCR revealed that cCART1 is predominantly expressed in the anterior pituitary and less abundantly in the hypothalamus. In accordance with this finding, cCART1 peptide was easily detected in the anterior pituitary by Western blot, and its secretion from chick pituitaries incubated in vitro was enhanced by ionomycin and forskolin treatment, indicating that cCART1 is a novel peptide hormone produced by the anterior pituitary. Moreover, cCART1 mRNA expression in both the pituitary and hypothalamus is down-regulated by 48-h fasting, suggesting its expression is affected by energy status. Unlike cCART1, cCART2 is only weakly expressed in most tissues examined by RT-PCR, implying a less significant role of cCART2 in chickens. As in chickens, 2 or more CART genes, likely generated by gene and genome duplication event(s), were also identified in other non-mammalian vertebrate species including coelacanth. Collectively, the identification and characterization of CART genes in birds helps to uncover the roles of CART peptide(s) in vertebrates and provides clues to the evolutionary history of vertebrate CART genes. PMID:25992897

Simulation and Mixed Integer Linear Programming Models for Analysis of Semi-Automated Mail Processing

DTIC Science & Technology

1989-12-01

Sincere appreciation is deserved by Geraldo Veiga , Department of Industrial Engineering and Operations Research, at the University of California, Berkeley...Convergence 124 Veiga , University of California, Berkeley, must be credited with applying the MINOS code to our GMF-A problems). MINOS is a FORTRAN...placed in cart ACT,O,,TS23; and if the cart is full, an ACT,O,LSN8l3CARr.GE.LSMBl3FULL,TS24; entity is sent to TS24 to ACr,O,,TT fl ; empty the cart

Robust Control Algorithm for a Two Cart System and an Inverted Pendulum

NASA Technical Reports Server (NTRS)

Wilson, Chris L.; Capo-Lugo, Pedro

2011-01-01

The Rectilinear Control System can be used to simulate a launch vehicle during liftoff. Several control schemes have been developed that can control different dynamic models of the rectilinear plant. A robust control algorithm was developed that can control a pendulum to maintain an inverted position. A fluid slosh tank will be attached to the pendulum in order to test robustness in the presence of unknown slosh characteristics. The rectilinear plant consists of a DC motor and three carts mounted in series. Each cart s weight can be adjusted with brass masses and the carts can be coupled with springs. The pendulum is mounted on the first cart and an adjustable air damper can be attached to the third cart if desired. Each cart and the pendulum have a quadrature encoder to determine position. Full state feedback was implemented in order to develop the control algorithm along with a state estimator to determine the velocity states of the system. A MATLAB program was used to convert the state space matrices from continuous time to discrete time. This program also used a desired phase margin and damping ratio to determine the feedback gain matrix that would be used in the LabVIEW program. This experiment will allow engineers to gain a better understanding of liquid propellant slosh dynamics, therefore enabling them to develop more robust control algorithms for launch vehicle systems

Decoding intentions from movement kinematics

PubMed Central

Cavallo, Andrea; Koul, Atesh; Ansuini, Caterina; Capozzi, Francesca; Becchio, Cristina

2016-01-01

How do we understand the intentions of other people? There has been a longstanding controversy over whether it is possible to understand others’ intentions by simply observing their movements. Here, we show that indeed movement kinematics can form the basis for intention detection. By combining kinematics and psychophysical methods with classification and regression tree (CART) modeling, we found that observers utilized a subset of discriminant kinematic features over the total kinematic pattern in order to detect intention from observation of simple motor acts. Intention discriminability covaried with movement kinematics on a trial-by-trial basis, and was directly related to the expression of discriminative features in the observed movements. These findings demonstrate a definable and measurable relationship between the specific features of observed movements and the ability to discriminate intention, providing quantitative evidence of the significance of movement kinematics for anticipating others’ intentional actions. PMID:27845434

Identifying the critical success factors in the coverage of low vision services using the classification analysis and regression tree methodology.

PubMed

Chiang, Peggy Pei-Chia; Xie, Jing; Keeffe, Jill Elizabeth

2011-04-25

To identify the critical success factors (CSF) associated with coverage of low vision services. Data were collected from a survey distributed to Vision 2020 contacts, government, and non-government organizations (NGOs) in 195 countries. The Classification and Regression Tree Analysis (CART) was used to identify the critical success factors of low vision service coverage. Independent variables were sourced from the survey: policies, epidemiology, provision of services, equipment and infrastructure, barriers to services, human resources, and monitoring and evaluation. Socioeconomic and demographic independent variables: health expenditure, population statistics, development status, and human resources in general, were sourced from the World Health Organization (WHO), World Bank, and the United Nations (UN). The findings identified that having >50% of children obtaining devices when prescribed (χ(2) = 44; P < 0.000), multidisciplinary care (χ(2) = 14.54; P = 0.002), >3 rehabilitation workers per 10 million of population (χ(2) = 4.50; P = 0.034), higher percentage of population urbanized (χ(2) = 14.54; P = 0.002), a level of private investment (χ(2) = 14.55; P = 0.015), and being fully funded by government (χ(2) = 6.02; P = 0.014), are critical success factors associated with coverage of low vision services. This study identified the most important predictors for countries with better low vision coverage. The CART is a useful and suitable methodology in survey research and is a novel way to simplify a complex global public health issue in eye care.

CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

PubMed

Wright, Stephen T; Carr, Andrew; Woolley, Ian; Giles, Michelle; Hoy, Jennifer; Cooper, David A; Law, Matthew G

2011-09-01

To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death.

Evaluation of leaf wetness duration models for operational use in strawberry disease-warning systems in four US states.

PubMed

Montone, Verona O; Fraisse, Clyde W; Peres, Natalia A; Sentelhas, Paulo C; Gleason, Mark; Ellis, Michael; Schnabel, Guido

2016-11-01

Leaf wetness duration (LWD) plays a key role in disease development and is often used as an input in disease-warning systems. LWD is often estimated using mathematical models, since measurement by sensors is rarely available and/or reliable. A strawberry disease-warning system called "Strawberry Advisory System" (SAS) is used by growers in Florida, USA, in deciding when to spray their strawberry fields to control anthracnose and Botrytis fruit rot. Currently, SAS is implemented at six locations, where reliable LWD sensors are deployed. A robust LWD model would facilitate SAS expansion from Florida to other regions where reliable LW sensors are not available. The objective of this study was to evaluate the use of mathematical models to estimate LWD and time of spray recommendations in comparison to on site LWD measurements. Specific objectives were to (i) compare model estimated and observed LWD and resulting differences in timing and number of fungicide spray recommendations, (ii) evaluate the effects of weather station sensors precision on LWD models performance, and (iii) compare LWD models performance across four states in the USA. The LWD models evaluated were the classification and regression tree (CART), dew point depression (DPD), number of hours with relative humidity equal or greater than 90 % (NHRH ≥90 %), and Penman-Monteith (P-M). P-M model was expected to have the lowest errors, since it is a physically based and thus portable model. Indeed, the P-M model estimated LWD most accurately (MAE <2 h) at a weather station with high precision sensors but was the least accurate when lower precision sensors of relative humidity and estimated net radiation (based on solar radiation and temperature) were used (MAE = 3.7 h). The CART model was the most robust for estimating LWD and for advising growers on fungicide-spray timing for anthracnose and Botrytis fruit rot control and is therefore the model we recommend for expanding the strawberry disease warning beyond Florida, to other locations where weather stations may be deployed with lower precision sensors, and net radiation observations are not available.

Evaluation of leaf wetness duration models for operational use in strawberry disease-warning systems in four US states

NASA Astrophysics Data System (ADS)

Montone, Verona O.; Fraisse, Clyde W.; Peres, Natalia A.; Sentelhas, Paulo C.; Gleason, Mark; Ellis, Michael; Schnabel, Guido

2016-11-01

Leaf wetness duration (LWD) plays a key role in disease development and is often used as an input in disease-warning systems. LWD is often estimated using mathematical models, since measurement by sensors is rarely available and/or reliable. A strawberry disease-warning system called "Strawberry Advisory System" (SAS) is used by growers in Florida, USA, in deciding when to spray their strawberry fields to control anthracnose and Botrytis fruit rot. Currently, SAS is implemented at six locations, where reliable LWD sensors are deployed. A robust LWD model would facilitate SAS expansion from Florida to other regions where reliable LW sensors are not available. The objective of this study was to evaluate the use of mathematical models to estimate LWD and time of spray recommendations in comparison to on site LWD measurements. Specific objectives were to (i) compare model estimated and observed LWD and resulting differences in timing and number of fungicide spray recommendations, (ii) evaluate the effects of weather station sensors precision on LWD models performance, and (iii) compare LWD models performance across four states in the USA. The LWD models evaluated were the classification and regression tree (CART), dew point depression (DPD), number of hours with relative humidity equal or greater than 90 % (NHRH ≥90 %), and Penman-Monteith (P-M). P-M model was expected to have the lowest errors, since it is a physically based and thus portable model. Indeed, the P-M model estimated LWD most accurately (MAE <2 h) at a weather station with high precision sensors but was the least accurate when lower precision sensors of relative humidity and estimated net radiation (based on solar radiation and temperature) were used (MAE = 3.7 h). The CART model was the most robust for estimating LWD and for advising growers on fungicide-spray timing for anthracnose and Botrytis fruit rot control and is therefore the model we recommend for expanding the strawberry disease warning beyond Florida, to other locations where weather stations may be deployed with lower precision sensors, and net radiation observations are not available.

Quantification of CD4 Responses to Combined Antiretroviral Therapy Over 5 Years Among HIV-Infected Children in Kinshasa, Democratic Republic of Congo

PubMed Central

Edmonds, Andrew; Yotebieng, Marcel; Lusiama, Jean; Matumona, Yori; Kitetele, Faustin; Nku, David; Napravnik, Sonia; Cole, Stephen R.; Van Rie, Annelies; Behets, Frieda

2017-01-01

Background The long-term effects of combined antiretroviral therapy (cART) on CD4 percentage in HIV-infected children are incompletely understood, with evidence from resource-deprived areas particularly scarce even though most children with HIV live in such settings. We sought to describe this relationship. Methods Observational longitudinal data from cART-naive children enrolled between December 2004 and May 2010 into an HIV care and treatment program in Kinshasa, Democratic Republic of Congo were analyzed. To estimate the effect of cART on CD4 percentage while accounting for time-dependent confounders affected by prior exposure to cART, a marginal structural linear mean model was used. Results Seven hundred ninety children were active for 2090 person-years and a median of 31 months; 619 (78%) initiated cART. At baseline, 405 children (51%) were in HIV clinical stage 3 or 4; 528 (67%) had advanced or severe immunodeficiency. Compared with no cART, the estimated absolute rise in CD4 percentage was 6.8% [95% confidence interval (CI), 4.7% to 8.9%] after 6 months of cART, 8.6% (95% CI, 7.0% to 10.2%) after 12 months, and 20.5% (95% CI, 16.1% to 24.9%) after 60 months. cART-mediated CD4 percentage gains were slowest but greatest among children with baseline CD4 percentage <15. The cumulative incidence of recovery to “not significant” World Health Organization age-specific immunodeficiency was lower if cART was started when immunodeficiency was severe rather than mild or advanced. Conclusions cART increased CD4 percentages among HIV-infected children in a resource-deprived setting, as previously noted among children in the United States. More gradual and protracted recovery in children with lower baseline CD4 percentages supports earlier initiation of pediatric cART. PMID:22732464

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

PubMed

Balagopal, Ashwin; Asmuth, David M; Yang, Wei-Teng; Campbell, Thomas B; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R; Lalloo, Umesh G; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B; Semba, Richard D; Thomas, David L; Bollinger, Robert C; Gupta, Amita

2015-10-01

Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatment-naive adults who initiated cART; CD4 T-cell count <300 cells/mm; 9 countries) was conducted. A subcohort of 30 participants per country was randomly selected; additional cases were added from the main cohort. Cases [n = 236 (random subcohort 36; main cohort 200)] had clinical progression (incident WHO stage 3/4 event or death) within 96 weeks after cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4 T-cell count was 167 cells per cubic millimeter. In multivariate analysis, highest quartile C-reactive protein concentration [adjusted hazard ratio (aHR), 2.53; 95% confidence interval (CI): 1.02 to 6.28] and CD4 T-cell activation (aHR, 5.18; 95% CI: 1.09 to 24.47) were associated with primary outcomes, compared with lowest quartiles. sCD14 had a trend toward association with clinical failure (aHR, 2.24; 95% CI: 0.96 to 5.21). Measuring C-reactive protein and CD4 T-cell activation may identify patients with CD4 T-cell counts <300 cells per cubic millimeter at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.

Pre-cART Elevation of CRP and CD4+ T-cell Immune Activation Associated with HIV Clinical Progression in a Multinational Case-Cohort Study

PubMed Central

Balagopal, Ashwin; Asmuth, David M.; Yang, Wei-Teng; Campbell, Thomas B.; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R.; Lalloo, Umesh G.; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B.; Semba, Richard D.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita

2015-01-01

Background Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. Methods A case-cohort study (n=470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) clinical trial (1571 HIV treatment-naïve adults who initiated cART; CD4+ T cell count <300 cells/mm3; nine countries) was conducted. A subcohort of 30 participants/country was randomly selected; additional cases were added from the main cohort. Cases (n=236 [random subcohort–36; main cohort–200]) had clinical progression (incident WHO Stage 3/4 event or death) within 96 weeks following cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Results Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4+ T-cell count was 167 cells/mm3. In multivariate analysis, highest quartile CRP concentration (adjusted hazards ratio [aHR] 2.53, 95%CI 1.02-6.28) and CD4+ T-cell activation (aHR 5.18, 95CI 1.09-24.47) were associated with primary outcomes, compared to lowest quartiles. sCD14 had a trend towards association with clinical failure (aHR 2.24, 95%CI 0.96–5.21). Conclusions Measuring CRP and CD4+ T-cell activation may identify patients with CD4+ T cell counts < 300 cells/mm3 at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART. PMID:26017661

Impact of drug stock-outs on death and retention to care among HIV-infected patients on combination antiretroviral therapy in Abidjan, Côte d'Ivoire.

PubMed

Pasquet, Armelle; Messou, Eugène; Gabillard, Delphine; Minga, Albert; Depoulosky, Ayeby; Deuffic-Burban, Sylvie; Losina, Elena; Freedberg, Kenneth A; Danel, Christine; Anglaret, Xavier; Yazdanpanah, Yazdan

2010-10-15

To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Côte d'Ivoire. We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25-6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46-3.16). cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs.

Damped Mechanical Oscillator: Experiment and Detailed Energy Analysis

NASA Astrophysics Data System (ADS)

Corridoni, Tommaso; D'Anna, Michele; Fuchs, Hans

2014-02-01

The damped oscillator is discussed in every high school textbook or introductory physics course, and a large number of papers are devoted to it in physics didactics journals. Papers typically focus on kinematic and dynamic aspects and less often on energy. Among the latter, some are devoted to the peculiar decreasing behavior of energy characterized by ripples, which can easily be demonstrated by using a dynamic modeling approach.8 In this note we consider an oscillator consisting of a cart running on a horizontal track, two springs, and a damping device created with magnets and a metal plate attached to the cart (Fig. 1). Using sensors and data-acquisition software,9 we measure kinematic quantities and three forces: those of the springs on the cart and, separately, the force between magnets and the plate. A detailed analysis of the energy exchanges between the cart and the interacting parts is obtained. In particular, we show that only the energy exchanges with the magnets are affected by dissipative processes while over a suitable time interval the net energy exchanged between cart and springs equals zero.

Purification and characterisation of a new hypothalamic satiety peptide, cocaine and amphetamine regulated transcript (CART), produced in yeast.

PubMed

Thim, L; Nielsen, P F; Judge, M E; Andersen, A S; Diers, I; Egel-Mitani, M; Hastrup, S

1998-05-29

Cocaine and amphetamine regulated transcript (CART) is a newly discovered hypothalamic peptide with a potent appetite suppressing activity following intracerebroventricular administration. When the mature rat CART sequence encoding CART(1-102) was inserted in the yeast expression plasmid three CART peptides could be purified from the fermentation broth reflecting processing at dibasic sequences. None of these corresponded to the naturally occurring CART(55-102). In order to obtain CART(55-102) the precursor Glu-Glu-Ile-Asp-CART(55-102) has been produced and CART(55-102) was generated by digestion of the precursor with dipeptidylaminopeptidase-1. All four generated CART peptides have been characterised by N-terminal amino acid sequencing and mass spectrometry. The CART peptides contain six cysteine residues and using the yeast expressed CART(62-102) the disulphide bond configuration was found to be I-III, II-V and IV-VI. When the four CART peptides were intracerebroventricularly injected in fasted mice (0.1 to 2.0 microg) they all produced a dose dependent inhibition of food intake.

A Simple Algorithm to Predict Falls in Primary Care Patients Aged 65 to 74 Years: The International Mobility in Aging Study.

PubMed

Gomez, Fernando; Wu, Yan Yan; Auais, Mohammad; Vafaei, Afshin; Zunzunegui, Maria-Victoria

2017-09-01

Primary care practitioners need simple algorithms to identify older adults at higher risks of falling. Classification and regression tree (CaRT) analyses are useful tools for identification of clinical predictors of falls. Prospective cohort. Community-dwelling older adults at 5 diverse sites: Tirana (Albania), Natal (Brazil), Manizales (Colombia), Kingston (Ontario, Canada), and Saint-Hyacinthe (Quebec, Canada). In 2012, 2002 participants aged 65-74 years from 5 international sites were assessed in the International Mobility in Aging Study. In 2014 follow-up, 86% of the participants (n = 1718) were reassessed. These risk factors for the occurrence of falls in 2014 were selected based on relevant literature and were entered into the CaRT as measured at baseline in 2012: age, sex, body mass index, multimorbidity, cognitive deficit, depression, number of falls in the past 12 months, fear of falling (FoF) categories, and timed chair-rises, balance, and gait. The 1-year prevalence of falls in 2014 was 26.9%. CaRT procedure identified 3 subgroups based on reported number of falls in 2012 (none, 1, ≥2). The 2014 prevalence of falls in these 3 subgroups was 20%, 30%, and 50%, respectively. The "no fall" subgroup was split using FoF: 30% of the high FoF category (score >27) vs 20% of low and moderate FoF categories (scores: 16-27) experienced a fall in 2014. Those with multiple falls were split by their speed in the chair-rise test: 56% of the slow category (>16.7 seconds) and the fast category (<11.2 seconds) had falls vs 28% in the intermediate group (between 11.2 and 16.7 seconds). No additional variables entered into the decision tree. Three simple indicators: FoF, number of previous falls, and time of chair rise could identify those with more than 50% probability of falling. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Modelling the cost-effectiveness of HIV care shows a clear benefit when transmission risk is considered in the calculations - A message for Central and Eastern Europe.

PubMed

Kowalska, Justyna D; Wójcik, Grzegorz; Rutkowski, Jakub; Ankiersztejn-Bartczak, Magdalena; Siewaszewicz, Ewa

2017-01-01

HIV epidemic remains a major global health issue. Data from cost-effectiveness analyses base on CD4+ count and morbidity in patients with symptomatic and asymptomatic HIV infection. The approach adopted in these analyses includes many other factors, previously not investigated. Additionally, we evaluate the impact of sexual HIV transmission due to delayed cART on the cost-effectiveness of care. A lifetime Markov model (1-month cycle) was developed to estimate the cost per quality adjusted life years (QALY) for a 1- and 3-year delay in starting cART (as compared to starting immediately at linkage to care) lifetime costs, clinical outcomes and cost-effectiveness. Patients were categorized into having asymptomatic HIV, AIDS, Hodgkin's Lymphoma, and non-AIDS defining condition. Mortality rates and utility values were obtained from published literature. The number of new infected persons was estimated on the basis of sexual orientation, the number of sexual partners per year, the number of sex acts per month, frequency of condom use and use of cART. For the input Test and Keep in Care (TAK) project cohort data were used. Costs of care, cART and potential life-years lost were based on estimated total costs and the difference in expected QALY gained between an HIV-positive and an average person in Polish population. Costs were based on real expenditures of the Ministry of Health, National Health Fund, available studies and experts' opinion. Costs and effects were discounted at rates of 5% and 3.5%, respectively. Input data were available for 141 patients form TAK cohort. The estimated number of new HIV infections in low, medium and high risk transmission groups were 0.28, 0.61, 2.07 with 1 and 0.82, 1.80, 6.11 with a 3-year delay, respectively. This reflected QALY loss due to cART delay of 0.52, 1.13, 3.84 and 2.02, 4.43, 15.03 for a 1- and 3-year delay, respectively. If additional costs of treatment and potential life-years lost due to new HIV infections were not taken into account, initiating cART immediately at linkage to care was not cost-saving irrespective of cART delay. Otherwise, when additional costs and QALY lost due to new HIV infections were included, immediate cART initiation was cost-saving regardless of the chosen scenarios. If new HIV infections are not taken into account, then starting cART immediately does not dominate comparing to delaying cART. When taking into account HIV transmission in cost-effectiveness analysis, immediate initiation of HIV treatment is a profitable decision from the public payer's perspective.

Modelling the cost-effectiveness of HIV care shows a clear benefit when transmission risk is considered in the calculations – A message for Central and Eastern Europe

PubMed Central

Wójcik, Grzegorz; Rutkowski, Jakub; Ankiersztejn-Bartczak, Magdalena; Siewaszewicz, Ewa

2017-01-01

Background HIV epidemic remains a major global health issue. Data from cost-effectiveness analyses base on CD4+ count and morbidity in patients with symptomatic and asymptomatic HIV infection. The approach adopted in these analyses includes many other factors, previously not investigated. Additionally, we evaluate the impact of sexual HIV transmission due to delayed cART on the cost-effectiveness of care. Methods A lifetime Markov model (1-month cycle) was developed to estimate the cost per quality adjusted life years (QALY) for a 1- and 3-year delay in starting cART (as compared to starting immediately at linkage to care) lifetime costs, clinical outcomes and cost-effectiveness. Patients were categorized into having asymptomatic HIV, AIDS, Hodgkin’s Lymphoma, and non-AIDS defining condition. Mortality rates and utility values were obtained from published literature. The number of new infected persons was estimated on the basis of sexual orientation, the number of sexual partners per year, the number of sex acts per month, frequency of condom use and use of cART. For the input Test and Keep in Care (TAK) project cohort data were used. Costs of care, cART and potential life-years lost were based on estimated total costs and the difference in expected QALY gained between an HIV-positive and an average person in Polish population. Costs were based on real expenditures of the Ministry of Health, National Health Fund, available studies and experts’ opinion. Costs and effects were discounted at rates of 5% and 3.5%, respectively. Results Input data were available for 141 patients form TAK cohort. The estimated number of new HIV infections in low, medium and high risk transmission groups were 0.28, 0.61, 2.07 with 1 and 0.82, 1.80, 6.11 with a 3-year delay, respectively. This reflected QALY loss due to cART delay of 0.52, 1.13, 3.84 and 2.02, 4.43, 15.03 for a 1- and 3-year delay, respectively. If additional costs of treatment and potential life-years lost due to new HIV infections were not taken into account, initiating cART immediately at linkage to care was not cost-saving irrespective of cART delay. Otherwise, when additional costs and QALY lost due to new HIV infections were included, immediate cART initiation was cost-saving regardless of the chosen scenarios. Conclusions If new HIV infections are not taken into account, then starting cART immediately does not dominate comparing to delaying cART. When taking into account HIV transmission in cost–effectiveness analysis, immediate initiation of HIV treatment is a profitable decision from the public payer’s perspective. PMID:29131849

Expression of Cocaine and Amphetamine Regulated Transcript (CART) in the Porcine Intramural Neurons of Stomach in the Course of Experimentally Induced Diabetes Mellitus.

PubMed

Bulc, Michał; Gonkowski, Sławomir; Całka, Jarosław

2015-11-01

In the present study, the effect of streptozotocin-induced diabetes on the cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) enteric nervous structures was investigated within the porcine stomach. To induce diabetes, the pigs were administered intravenously streptozotocin at a dose of 150 mg/kg of body weight. A significant decrease of the number of CART-LI perikarya was observed in the myenteric plexus of the gastric antrum, corpus, and pylorus in the experimental group. In contrast, submucous plexus was devoid of CART-positive neuronal cells both in control and experimental animals. In the control group, the highest densities of CART-LI nerve fibers were observed in the circular muscle layer of antrum and slightly less nerve fibers were present in the muscle layer of corpus and pylorus. In turn, submucous layer of all studied stomach regions revealed relatively smaller number of CART-positive nerve fibers. Diabetes caused statistically significant decrease in the expression of CART-LI nerve fibers only in the antrum circular muscle layer. Also, no changes in the CART-like immunoreactivity in the intraganglionic nerve fibers were observed. The obtained results suggest that acute hyperglycemia produced significant reduction of the CART expression in enteric perikarya throughout entire stomach as well as decrease of density the CART-LI fibers in circular muscle layer of the antrum. Additionally, we suggest that CART might be involved in the regulation of stomach function especially in the gastric motility.

Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients

PubMed Central

Hsieh, Yi-Chen; Jeng, Jiann-Shing; Lin, Huey-Juan; Hu, Chaur-Jong; Yu, Chia-Chen; Lien, Li-Ming; Peng, Giia-Sheun; Chen, Chin-I; Tang, Sung-Chun; Chi, Nai-Fang; Tseng, Hung-Pin; Chern, Chang-Ming; Hsieh, Fang-I; Bai, Chyi-Huey; Chen, Yi-Rhu; Chiou, Hung-Yi; Jeng, Jiann-Shing; Tang, Sung-Chun; Yeh, Shin-Joe; Tsai, Li-Kai; Kong, Shin; Lien, Li-Ming; Chiu, Hou-Chang; Chen, Wei-Hung; Bai, Chyi-Huey; Huang, Tzu-Hsuan; Chi-Ieong, Lau; Wu, Ya-Ying; Yuan, Rey-Yue; Hu, Chaur-Jong; Sheu, Jau- Jiuan; Yu, Jia-Ming; Ho, Chun-Sum; Chen, Chin-I; Sung, Jia-Ying; Weng, Hsing-Yu; Han, Yu-Hsuan; Huang, Chun-Ping; Chung, Wen-Ting; Ke, Der-Shin; Lin, Huey-Juan; Chang, Chia-Yu; Yeh, Poh-Shiow; Lin, Kao-Chang; Cheng, Tain-Junn; Chou, Chih-Ho; Yang, Chun-Ming; Peng, Giia-Sheun; Lin, Jiann-Chyun; Hsu, Yaw-Don; Denq, Jong-Chyou; Lee, Jiunn-Tay; Hsu, Chang-Hung; Lin, Chun-Chieh; Yen, Che-Hung; Cheng, Chun-An; Sung, Yueh-Feng; Chen, Yuan-Liang; Lien, Ming-Tung; Chou, Chung-Hsing; Liu, Chia-Chen; Yang, Fu-Chi; Wu, Yi-Chung; Tso, An-Chen; Lai, Yu- Hua; Chiang, Chun-I; Tsai, Chia-Kuang; Liu, Meng-Ta; Lin, Ying-Che; Hsu, Yu-Chuan; Chen, Chih-Hung; Sung, Pi-Shan; Chern, Chang-Ming; Hu, Han-Hwa; Wong, Wen-Jang; Luk, Yun-On; Hsu, Li-Chi; Chung, Chih-Ping; Tseng, Hung-Pin; Liu, Chin-Hsiung; Lin, Chun-Liang; Lin, Hung-Chih; Hu, Chaur-Jong

2012-01-01

Background Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1). Methods A case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454−397 T/C and c.454−351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models. Results COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174). Conclusions Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects. PMID:23112845

Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients.

PubMed

Chen, Jinyun; Pande, Mala; Huang, Yu-Jing; Wei, Chongjuan; Amos, Christopher I; Talseth-Palmer, Bente A; Meldrum, Cliff J; Chen, Wei V; Gorlov, Ivan P; Lynch, Patrick M; Scott, Rodney J; Frazier, Marsha L

2013-02-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle-related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle-related genes and 31 DNA repair-related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan-Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P < 5 × 10(-4)). Furthermore, risk modeling using CART analysis defined combinations of genotypes for these SNPs with which subjects could be classified into low-risk, moderate-risk and high-risk groups that had median ages of colorectal cancer onset of 63, 50 and 42 years, respectively. The age-associated risk of colorectal cancer in the high-risk group was more than four times the risk in the low-risk group (hazard ratio = 4.67, 95% CI = 3.16-6.92). The additional genetic markers identified may help in refining risk groups for more tailored screening and follow-up of non-Hispanic white patients with Lynch syndrome.

Cell cycle–related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients

PubMed Central

Chen, Jinyun; Pande, Mala

2013-01-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle–related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle–related genes and 31 DNA repair–related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan–Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P < 5×10–4). Furthermore, risk modeling using CART analysis defined combinations of genotypes for these SNPs with which subjects could be classified into low-risk, moderate-risk and high-risk groups that had median ages of colorectal cancer onset of 63, 50 and 42 years, respectively. The age-associated risk of colorectal cancer in the high-risk group was more than four times the risk in the low-risk group (hazard ratio = 4.67, 95% CI = 3.16–6.92). The additional genetic markers identified may help in refining risk groups for more tailored screening and follow-up of non-Hispanic white patients with Lynch syndrome. PMID:23125224

Determining β-lactam exposure threshold to suppress resistance development in Gram-negative bacteria.

PubMed

Tam, Vincent H; Chang, Kai-Tai; Zhou, Jian; Ledesma, Kimberly R; Phe, Kady; Gao, Song; Van Bambeke, Françoise; Sánchez-Díaz, Ana María; Zamorano, Laura; Oliver, Antonio; Cantón, Rafael

2017-05-01

β-Lactams are commonly used for nosocomial infections and resistance to these agents among Gram-negative bacteria is increasing rapidly. Optimized dosing is expected to reduce the likelihood of resistance development during antimicrobial therapy, but the target for clinical dose adjustment is not well established. We examined the likelihood that various dosing exposures would suppress resistance development in an in vitro hollow-fibre infection model. Two strains of Klebsiella pneumoniae and two strains of Pseudomonas aeruginosa (baseline inocula of ∼10 8  cfu/mL) were examined. Various dosing exposures of cefepime, ceftazidime and meropenem were simulated in the hollow-fibre infection model. Serial samples were obtained to ascertain the pharmacokinetic simulations and viable bacterial burden for up to 120 h. Drug concentrations were determined by a validated LC-MS/MS assay and the simulated exposures were expressed as C min /MIC ratios. Resistance development was detected by quantitative culture on drug-supplemented media plates (at 3× the corresponding baseline MIC). The C min /MIC breakpoint threshold to prevent bacterial regrowth was identified by classification and regression tree (CART) analysis. For all strains, the bacterial burden declined initially with the simulated exposures, but regrowth was observed in 9 out of 31 experiments. CART analysis revealed that a C min /MIC ratio ≥3.8 was significantly associated with regrowth prevention (100% versus 44%, P  = 0.001). The development of β-lactam resistance during therapy could be suppressed by an optimized dosing exposure. Validation of the proposed target in a well-designed clinical study is warranted. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A New Take on Exploding Carts

ERIC Educational Resources Information Center

Broder, Darren; Burleigh, James; Christian, Matthew; Mowry, Shawn; Hassel, George E.

2017-01-01

The Exploding Carts is a popular introductory physics activity in which a one-dimensional explosion is simulated utilizing two dynamics carts that are pushed apart by a spring-loaded plunger released from one of the carts. Traditional treatments of the Exploding Carts usually involve multiple trials where the mass of one or both of the carts is…

Rapid Erosion Modeling in a Western Kenya Watershed using Visible Near Infrared Reflectance, Classification Tree Analysis and 137Cesium.

PubMed

deGraffenried, Jeff B; Shepherd, Keith D

2009-12-15

Human induced soil erosion has severe economic and environmental impacts throughout the world. It is more severe in the tropics than elsewhere and results in diminished food production and security. Kenya has limited arable land and 30 percent of the country experiences severe to very severe human induced soil degradation. The purpose of this research was to test visible near infrared diffuse reflectance spectroscopy (VNIR) as a tool for rapid assessment and benchmarking of soil condition and erosion severity class. The study was conducted in the Saiwa River watershed in the northern Rift Valley Province of western Kenya, a tropical highland area. Soil 137 Cs concentration was measured to validate spectrally derived erosion classes and establish the background levels for difference land use types. Results indicate VNIR could be used to accurately evaluate a large and diverse soil data set and predict soil erosion characteristics. Soil condition was spectrally assessed and modeled. Analysis of mean raw spectra indicated significant reflectance differences between soil erosion classes. The largest differences occurred between 1,350 and 1,950 nm with the largest separation occurring at 1,920 nm. Classification and Regression Tree (CART) analysis indicated that the spectral model had practical predictive success (72%) with Receiver Operating Characteristic (ROC) of 0.74. The change in 137 Cs concentrations supported the premise that VNIR is an effective tool for rapid screening of soil erosion condition.

Active-passive vibration absorber of beam-cart-seesaw system with piezoelectric transducers

NASA Astrophysics Data System (ADS)

Lin, J.; Huang, C. J.; Chang, Julian; Wang, S.-W.

2010-09-01

In contrast with fully controllable systems, a super articulated mechanical system (SAMS) is a controlled underactuated mechanical system in which the dimensions of the configuration space exceed the dimensions of the control input space. The objectives of the research are to develop a novel SAMS model which is called beam-cart-seesaw system, and renovate a novel approach for achieving a high performance active-passive piezoelectric vibration absorber for such system. The system consists of two mobile carts, which are coupled via rack and pinion mechanics to two parallel tracks mounted on pneumatic rodless cylinders. One cart carries an elastic beam, and the other cart acts as a counterbalance. One adjustable counterweight mass is also installed underneath the seesaw to serve as a passive damping mechanism to absorb impact and shock energy. The motion and control of a Bernoulli-Euler beam subjected to the modified cart/seesaw system are analyzed first. Moreover, gray relational grade is utilized to investigate the sensitivity of tuning the active proportional-integral-derivative (PID) controller to achieve desired vibration suppression performance. Consequently, it is shown that the active-passive vibration absorber can not only provide passive damping, but can also enhance the active action authority. The proposed software/hardware platform can also be profitable for the standardization of laboratory equipment, as well as for the development of entertainment tools.

Trends in detectable viral load by calendar year in the Australian HIV observational database.

PubMed

Law, Matthew G; Woolley, Ian; Templeton, David J; Roth, Norm; Chuah, John; Mulhall, Brian; Canavan, Peter; McManus, Hamish; Cooper, David A; Petoumenos, Kathy

2011-02-23

Recent papers have suggested that expanded combination antiretroviral treatment (cART) through lower viral load may be a strategy to reduce HIV transmission at a population level. We assessed calendar trends in detectable viral load in patients recruited to the Australian HIV Observational Database who were receiving cART. Patients were included in analyses if they had started cART (defined as three or more antiretrovirals) and had at least one viral load assessment after 1 January 1997. We analyzed detectable viral load (>400 copies/ml) in the first and second six months of each calendar year while receiving cART. Repeated measures logistic regression methods were used to account for within and between patient variability. Rates of detectable viral load were predicted allowing for patients lost to follow up. Analyses were based on 2439 patients and 31,339 viral load assessments between 1 January 1997 and 31 March 2009. Observed detectable viral load in patients receiving cART declined to 5.3% in the first half of 2009. Predicted detectable viral load based on multivariate models, allowing for patient loss to follow up, also declined over time, but at higher levels, to 13.8% in 2009. Predicted detectable viral load in Australian HIV Observational Database patients receiving cART declined over calendar time, albeit at higher levels than observed. However, over this period, HIV diagnoses and estimated HIV incidence increased in Australia.

QSRR modeling for diverse drugs using different feature selection methods coupled with linear and nonlinear regressions.

PubMed

Goodarzi, Mohammad; Jensen, Richard; Vander Heyden, Yvan

2012-12-01

A Quantitative Structure-Retention Relationship (QSRR) is proposed to estimate the chromatographic retention of 83 diverse drugs on a Unisphere poly butadiene (PBD) column, using isocratic elutions at pH 11.7. Previous work has generated QSRR models for them using Classification And Regression Trees (CART). In this work, Ant Colony Optimization is used as a feature selection method to find the best molecular descriptors from a large pool. In addition, several other selection methods have been applied, such as Genetic Algorithms, Stepwise Regression and the Relief method, not only to evaluate Ant Colony Optimization as a feature selection method but also to investigate its ability to find the important descriptors in QSRR. Multiple Linear Regression (MLR) and Support Vector Machines (SVMs) were applied as linear and nonlinear regression methods, respectively, giving excellent correlation between the experimental, i.e. extrapolated to a mobile phase consisting of pure water, and predicted logarithms of the retention factors of the drugs (logk(w)). The overall best model was the SVM one built using descriptors selected by ACO. Copyright © 2012 Elsevier B.V. All rights reserved.

Fruit Carts: A Domain and Corpus for Research in Dialogue Systems and Psycholinguistics.

PubMed

Aist, Gregory; Campana, Ellen; Allen, James; Swift, Mary; Tanenhaus, Michael K

2012-09-01

We describe a novel domain, Fruit Carts, aimed at eliciting human language production for the twin purposes of (a) dialogue system research and development and (b) psycholinguistic research. Fruit Carts contains five tasks: choosing a cart, placing it on a map, painting the cart, rotating the cart, and filling the cart with fruit. Fruit Carts has been used for research in psycholinguistics and in dialogue systems. Based on these experiences, we discuss how well the Fruit Carts domain meets four desired features: unscripted, context-constrained, controllable difficulty, and separability into semi-independent subdialogues. We describe the domain in sufficient detail to allow others to replicate it; researchers interested in using the corpora themselves are encouraged to contact the authors directly.

Distribution of cocaine and amphetamine regulated transcript in ureters and urinary bladder of hypertensive rats.

PubMed

Janiuk, I; Kasacka, I

2013-01-01

Cocaine and amphetamine regulated transcript (CART), a neuropeptide of the central and peripheral nervous system plays an essential role in maintaining body homeostasis by regulating body temperature, orexia, digestive motility and blood pressure. Very few studies describe the relationship of hyperten¬sion with CART. Therefore, the present research was undertaken to identify, locate and determine the number of CART-immunopositive neuroendocrine cells (NE) and structures in the urinary bladder and ureter of rats with experimentally induced nephrogenic hypertension. The experiments were conducted on 20 Wistar rats in which hypertension was experimentally induced by applying a clamp on the left renal artery based on the two kidney, one clip experimental model (2K1C). After 6 weeks, fragments of the ureters and urinary bladder were sampled from rats with permanent hypertension. Immunohisto¬chemical analyses revealed a salient effect of renovascular hypertension on the neuroendocrine system of rat ureters and urinary bladder. Differences in the number of neuroendocrine cells and in the density of CART-positive structures were identified between the hypertensive and normotensive (control) rats. Hypertension greatly increased the number of NE cells and the density of CART- immunoreactive (IR) structures in the analysed urinary system organs.

The Communities Advancing Resilience Toolkit (CART): development of a survey instrument to assess community resilience.

PubMed

Pfefferbaum, Rose L; Neas, Barbara R; Pfefferbaum, Betty; Norris, Fran H; Van Horn, Richard L

2013-01-01

While building community resilience to disasters is becoming an important strategy in emergency management, this is a new field of research with few available instruments for assessing community resilience. This article describes the development of the Communities Advancing Resilience Toolkit (CART) survey instrument. CART is a community intervention designed to enhance community resilience to disasters, in part, by engaging communities in measuring it. The survey instrument, originally based on community capacity and related literature and on key informant input, was refined through a series of four field tests. Community organizations worked with researchers in a participatory action process that provided access to samples and helped to guide the research. Exploratory factor analysis performed after each field test led to the identification of four interrelated constructs (also called domains) which represent the foundation for CART Connection and Caring, Resources, Transformative Potential, and Disaster Management. This model was confirmed using confirmatory factor analysis on two community samples. The CART survey can provide data for organizations and communities interested in assessing a community's resilience to disasters. Baseline data, preferably collected pre disaster can be compared to data collected post disaster and/or post intervention.

Automated parking garage system model

NASA Technical Reports Server (NTRS)

Collins, E. R., Jr.

1975-01-01

A one-twenty-fifth scale model of the key components of an automated parking garage system is described. The design of the model required transferring a vehicle from an entry level, vertically (+Z, -Z), to a storage location at any one of four storage positions (+X, -X, +Y, +Y, -Y) on the storage levels. There are three primary subsystems: (1) a screw jack to provide the vertical motion of the elevator, (2) a cam-driven track-switching device to provide X to Y motion, and (3) a transfer cart to provide horizontal travel and a small amount to vertical motion for transfer to the storage location. Motive power is provided by dc permanent magnet gear motors, one each for the elevator and track switching device and two for the transfer cart drive system (one driving the cart horizontally and the other providing the vertical transfer). The control system, through the use of a microprocessor, provides complete automation through a feedback system which utilizes sensing devices.

One-dimensional collision carts computer model and its design ideas for productive experiential learning

NASA Astrophysics Data System (ADS)

Wee, Loo Kang

2012-05-01

We develop an Easy Java Simulation (EJS) model for students to experience the physics of idealized one-dimensional collision carts. The physics model is described and simulated by both continuous dynamics and discrete transition during collision. In designing the simulations, we discuss briefly three pedagogical considerations namely (1) a consistent simulation world view with a pen and paper representation, (2) a data table, scientific graphs and symbolic mathematical representations for ease of data collection and multiple representational visualizations and (3) a game for simple concept testing that can further support learning. We also suggest using a physical world setup augmented by simulation by highlighting three advantages of real collision carts equipment such as a tacit 3D experience, random errors in measurement and the conceptual significance of conservation of momentum applied to just before and after collision. General feedback from the students has been relatively positive, and we hope teachers will find the simulation useful in their own classes.

Gender-specific increase of bone mass by CART peptide treatment is ovary-dependent.

PubMed

Gerrits, Han; Bakker, Nicole Ec; van de Ven-de Laat, Cindy Jm; Bourgondien, Freek Gm; Peddemors, Carolien; Litjens, Ralph Hgm; Kok, Han J; Vogel, Gerard Mt; Krajnc-Franken, Magda Am; Gossen, Jan A

2011-12-01

Cocaine- and amphetamine-regulated transcript (CART) has emerged as a neurotransmitter and hormone that has been implicated in many processes including food intake, maintenance of body weight, and reward, but also in the regulation of bone mass. CART-deficient mice are characterized by an osteoporotic phenotype, whereas female transgenic mice overexpressing CART display an increase in bone mass. Here we describe experiments that show that peripheral subcutaneous sustained release of different CART peptide isoforms for a period up to 60 days increased bone mass by 80% in intact mice. CART peptides increased trabecular bone mass, but not cortical bone mass, and the increase was caused by reduced osteoclast activity in combination with normal osteoblast activity. The observed effect on bone was gender-specific, because male mice did not respond to treatment with CART peptides. In addition, male transgenic CART overexpressing mice did not display increased bone mass. Ovariectomy (OVX) completely abolished the increase of bone mass by CART peptides, both in CART peptide-treated wild-type mice and in CART transgenic mice. The effect of CART peptide treatment on trabecular bone was not mediated by 17β-estradiol (E(2)) because supplementation of OVX mice with E(2) could not rescue the effect of CART peptides on bone. Together, these results indicate that sustained release of CART peptides increases bone mass in a gender-specific way via a yet unknown mechanism that requires the presence of the ovary. Copyright © 2011 American Society for Bone and Mineral Research.

Quad-polarized synthetic aperture radar and multispectral data classification using classification and regression tree and support vector machine-based data fusion system

NASA Astrophysics Data System (ADS)

Bigdeli, Behnaz; Pahlavani, Parham

2017-01-01

Interpretation of synthetic aperture radar (SAR) data processing is difficult because the geometry and spectral range of SAR are different from optical imagery. Consequently, SAR imaging can be a complementary data to multispectral (MS) optical remote sensing techniques because it does not depend on solar illumination and weather conditions. This study presents a multisensor fusion of SAR and MS data based on the use of classification and regression tree (CART) and support vector machine (SVM) through a decision fusion system. First, different feature extraction strategies were applied on SAR and MS data to produce more spectral and textural information. To overcome the redundancy and correlation between features, an intrinsic dimension estimation method based on noise-whitened Harsanyi, Farrand, and Chang determines the proper dimension of the features. Then, principal component analysis and independent component analysis were utilized on stacked feature space of two data. Afterward, SVM and CART classified each reduced feature space. Finally, a fusion strategy was utilized to fuse the classification results. To show the effectiveness of the proposed methodology, single classification on each data was compared to the obtained results. A coregistered Radarsat-2 and WorldView-2 data set from San Francisco, USA, was available to examine the effectiveness of the proposed method. The results show that combinations of SAR data with optical sensor based on the proposed methodology improve the classification results for most of the classes. The proposed fusion method provided approximately 93.24% and 95.44% for two different areas of the data.

Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia

PubMed Central

2016-01-01

Background. The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)–infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. Methods. We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged <16 years at cART initiation from 1996 onward. We used Cox models to calculate hazard ratios (HRs), adjusted for region and origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation. Results. We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55–133), 11 in southern Africa (95% CI, 4–35), and 81 (95% CI, 26–252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0–50) and in Asia (95% CI, 0–27). KS risk was lower in girls than in boys (adjusted HR [aHR], 0.3; 95% CI, .1–.9) and increased with age (10–15 vs 0–4 years; aHR, 3.4; 95% CI, 1.2–10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8–7.3) at cART initiation. Conclusions. HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk. PMID:27578823

Advantages of Chinese medicine for patients with acquired immunodeficiency syndrome in rural central China.

PubMed

Xu, Qian-Lei; Guo, Hui-Jun; Jin, Yan-Tao; Wang, Jian; Jiang, Zi-Qiang; Li, Zheng-Wei; Chen, Xiu-Min; Liu, Ying; Xu, Li-Ran

2017-09-08

To analyze the effect of Chinese medicine (CM) on mortality and quality of life (QOL) of acquired immunodeficiency syndrome (AIDS) patients treated with combined antiretroviral therapy (cART). A random sample of AIDS patients enrolled in the National Chinese Medicine Treatment Trial Program (NCMTP) that met the inclusion criteria was included in this study. NCMTP patients were included as the CM+cART group, and those not in the NCMTP were included as the cART group. Survival from September 2004 to September 2012 was analyzed by retrospective cohort study. QOL was analyzed by cross-sectional study. The retrospective cohort study included 528 AIDS patients, 322 in the CM+cART group and 206 in the cART group. After 8 years, the mortality in the CM+cART group was 3.3/100 person-years, which was lower than the cART group of 5.3/100 person-years (P <0.05). The hazard ratio (HR) for mortality in the cART group was 1.6 times that of the CM+cART group by Cox proportional hazard model analysis. After controlling for gender, age, marital status, education, and CD4 T-cell count, the HR was 1.9 times higher in the cART group compared with the CM+cART group (P <0.05). The cross-sectional study investigated 275 AIDS patients. The mean scores of all QOL domains except spirituality/personal beliefs were higher in the CM+cART group than in the cART group (P <0.05). For AIDS patients, CM could help to prolong life, decrease mortality, and improve QOL. However, there were limitations in the study, so prospective studies should be carried out to confirm our primary results.

GIS, geostatistics, metadata banking, and tree-based models for data analysis and mapping in environmental monitoring and epidemiology.

PubMed

Schröder, Winfried

2006-05-01

By the example of environmental monitoring, some applications of geographic information systems (GIS), geostatistics, metadata banking, and Classification and Regression Trees (CART) are presented. These tools are recommended for mapping statistically estimated hot spots of vectors and pathogens. GIS were introduced as tools for spatially modelling the real world. The modelling can be done by mapping objects according to the spatial information content of data. Additionally, this can be supported by geostatistical and multivariate statistical modelling. This is demonstrated by the example of modelling marine habitats of benthic communities and of terrestrial ecoregions. Such ecoregionalisations may be used to predict phenomena based on the statistical relation between measurements of an interesting phenomenon such as, e.g., the incidence of medically relevant species and correlated characteristics of the ecoregions. The combination of meteorological data and data on plant phenology can enhance the spatial resolution of the information on climate change. To this end, meteorological and phenological data have to be correlated. To enable this, both data sets which are from disparate monitoring networks have to be spatially connected by means of geostatistical estimation. This is demonstrated by the example of transformation of site-specific data on plant phenology into surface data. The analysis allows for spatial comparison of the phenology during the two periods 1961-1990 and 1991-2002 covering whole Germany. The changes in both plant phenology and air temperature were proved to be statistically significant. Thus, they can be combined by GIS overlay technique to enhance the spatial resolution of the information on the climate change and use them for the prediction of vector incidences at the regional scale. The localisation of such risk hot spots can be done by geometrically merging surface data on promoting factors. This is demonstrated by the example of the transfer of heavy metals through soils. The predicted hot spots of heavy metal transfer can be validated empirically by measurement data which can be inquired by a metadata base linked with a geographic information system. A corresponding strategy for the detection of vector hot spots in medical epidemiology is recommended. Data on incidences and habitats of the Anophelinae in the marsh regions of Lower Saxony (Germany) were used to calculate a habitat model by CART, which together with climate data and data on ecoregions can be further used for the prediction of habitats of medically relevant vector species. In the future, this approach should be supported by an internet-based information system consisting of three components: metadata questionnaire, metadata base, and GIS to link metadata, surface data, and measurement data on incidences and habitats of medically relevant species and related data on climate, phenology, and ecoregional characteristic conditions.

Effect of changing from first- to second-line antiretroviral therapy on renal function: a retrospective study based on data from a single health facility in Namibia.

PubMed

Kalemeera, Francis; Mbango, Christofina; Mubita, Mwangana; Naikaku, Esther; Gaida, Razia; Godman, Brian

2016-08-01

Tenofovir disoproxil fumarate (TDF) and lopinavir/ritonavir (LPV/r) can cause renal impairment with this combination co-administered during second-line combination antiretroviral therapy (cART) potentially associated with greater risk of nephrotoxicity. As a result, the aim of this study is to assess effects of second-line cART on renal function. Retrospective longitudinal study in patients receiving cART. 71 patients received TDF, zidovudine or stavudine, each combined with 3TC/NVP or 3TC/EFV. Before second-line cART, 46.5% had abnormal kidney function. First-line cART had no relationship with calculated creatinine clearance (CrCl). During second-line cART, more males than females had abnormal renal function and more females experienced increases in CrCl. Calculated CrCl during second-line cART related strongly with CrCl during first-line cART. Time spent on cART had a weak relationship with CrCl. Patients on first-line cART for several years without renal impairment may experience new onset impairment during second line cART. Patients with pre-existing renal impairment just before switching to second-line cART may experience a further decline.

Immunological quality and performance of tumor vessel-targeting CAR-T cells prepared by mRNA-EP for clinical research

PubMed Central

Inoo, Kanako; Inagaki, Ryo; Fujiwara, Kento; Sasawatari, Shigemi; Kamigaki, Takashi; Nakagawa, Shinsaku; Okada, Naoki

2016-01-01

We previously reported that tumor vessel-redirected T cells, which were genetically engineered with chimeric antigen receptor (CAR) specific for vascular endothelial growth factor receptor 2 (VEGFR2), demonstrated significant antitumor effects in various murine solid tumor models. In the present study, we prepared anti-VEGFR2 CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP) and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6–12 hours after mRNA-EP. Triple transfer of murine anti-VEGFR2 CAR-T cells into B16BL6 tumor-bearing mice demonstrated an antitumor effect comparable to that for the single transfer of CAR-T cells engineered with retroviral vector. The mRNA-EP did not cause any damage or defects to human T-cell characteristics, as determined by viability, growth, and phenotypic parameters. Additionally, two kinds of human anti-VEGFR2 CAR-T cells, which expressed different CAR construction, differentiated to effector phase with cytokine secretion and cytotoxic activity in antigen-specific manner. These results indicate that our anti-VEGFR2 CAR-T cells prepared by mRNA-EP have the potential in terms of quality and performance to offer the prospect of safety and efficacy in clinical research as cellular medicine. PMID:27909701

Cocaine-and Amphetamine Regulated Transcript (CART) Peptide Is Expressed in Precursor Cells and Somatotropes of the Mouse Pituitary Gland

PubMed Central

Mortensen, Amanda H.

2016-01-01

Cocaine-and Amphetamine Regulated Transcript (CART) peptide is expressed in the brain, endocrine and neuroendocrine systems and secreted into the serum. It is thought to play a role in regulation of hypothalamic pituitary functions. Here we report a spatial and temporal analysis of Cart expression in the pituitaries of adult and developing normal and mutant mice with hypopituitarism. We found that Prop1 is not necessary for initiation of Cart expression in the fetal pituitary at e14.5, but it is required indirectly for maintenance of Cart expression in the postnatal anterior pituitary gland. Pou1f1 deficiency has no effect on Cart expression before or after birth. There is no 1:1 correspondence between CART and any particular cell type. In neonates, CART is detected primarily in non-proliferating, POU1F1-positive cells. CART is also found in some cells that express TSH and GH suggesting a correspondence with committed progenitors of the POU1F1 lineage. In summary, we have characterized the normal temporal and cell specific expression of CART in mouse development and demonstrate that postnatal CART expression in the pituitary gland requires PROP1. PMID:27685990

Design and Evaluation of a Stand-Up Motorized Prone Cart

PubMed Central

Harrow, Jeffrey J; Malassigné, Pascal; Nelson, Audrey L; Jensen, Robert P; Amato, Margaret; Palacios, Polly L

2007-01-01

Background/Objective: Prone carts are used for mobility by individuals with spinal cord injury in whom seated mobility (wheelchair) is contraindicated due to ischial or sacral pressure ulcers. Currently available prone carts are uncomfortable, subjecting the user to neck and shoulder strain, and make social interaction and performing activities of daily living difficult. A better design of prone carts is needed. In addition, standing devices have shown some medical benefits. The objective was to design and evaluate an improved prone cart that facilitates standing. Design: Engineering development project with user feedback through questionnaire. Users selected by convenience sampling. Methods: A marketing survey was performed of nurse managers of spinal cord injury units. Then 2 prototype carts were designed and built. These carts are able to tilt up to 45° and have a joystick-controlled motor for propulsion and other design features, including a workspace storage shelf and rearview mirrors. The carts were evaluated by both patients and caregivers at 2 Veteran's Administration hospitals. Outcome Measures: Questionnaire of subjects, both patients and caregivers, who used the cart. Findings: Both patients and caregivers liked the carts and the ability to assume a nonhorizontal body angle. The major complaint about the cart was that it seemed too long when it came to making turns. Conclusion: This prone cart design is an improvement over the standard, flat variety. However, further design changes will be necessary. This study provided valuable information that will be useful in the next-generation prone cart design project. PMID:17385270

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.

Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA) on SIV-infected Chinese rhesus macaques.

PubMed

Ling, Binhua; Piatak, Michael; Rogers, Linda; Johnson, Ann-Marie; Russell-Lodrigue, Kasi; Hazuda, Daria J; Lifson, Jeffrey D; Veazey, Ronald S

2014-01-01

Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART)-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM) treated with intensive combination antiretroviral therapy (cART) and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA). SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations. Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters. The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

Calibration of the maximum carboxylation velocity (vcmax) for the Caatinga for use in dynamic global vegetation models (DGVMs)

NASA Astrophysics Data System (ADS)

Rezende, L. C.; Arenque, B.; von Randow, C.; Moura, M. S.; Aidar, S. D.; Buckeridge, M. S.; Menezes, R.; Souza, L. S.; Ometto, J. P.

2013-12-01

The Caatinga biome in the semi-arid region of northeastern Brazil is extremely important due to its biodiversity and endemism. This biome, which is under high anthropogenic influences, presents high levels of environmental degradation, land use being among the main causes of such degradation. The simulations of land cover and the vegetation dynamic under different climate scenarios are important features for prediction of environmental risks and determination of sustainable pathways for the planet in the future. Modeling of the vegetation can be performed by use of dynamic global vegetation models (DGVMs). The DGVMs simulate the surface processes (e.g. transfer of energy, water, CO2 and momentum); plant physiology (e.g. photosynthesis, stomatal conductance) phenology; gross and net primary productivity, respiration, plant species classified by functional traits; competition for light, water and nutrients, soil characteristics and processes (e.g. nutrients, heterotrophic respiration). Currently, most of the parameters used in DGVMs are static pre-defined values, and the lack of observational information to aid choosing the most adequate values for these parameters is particularly critical for the semi-arid regions in the world. Through historical meteorological data and measurements of carbon assimilation we aim to calibrate the maximum carboxylation velocity (Vcmax), for the native species Poincianella microphylla, abundant in the Caatinga region. The field data (collected at Lat: 90 2' S, Lon: 40019' W) displayed two contrasting meteorological conditions, with precipitations of 16 mm and 104 mm prior to the sampling campaigns (April 9-13, 2012 and February 4-8, 2013; respectively). Calibration (obtaining values of Vcmax more suitable for vegetation of Caatinga) has been performed through an algorithm of pattern recognition: Classification And Regression Tree (CART) and calculation of the vapor pressure deficit (VPD), which was used as attribute for discrimination of data. CART can be utilized for classification or regression, being used in the context of this work for non-linear regression. Our results show that CART algorithm correctly classified data according to the two contrasting periods (i.e. correctly distinguished assimilation data measured during drier or rainy periods), and suggest average Vcmax values of 14.2 μmol CO2 m-2 s-1 for the drier period and of 102.5 μmol CO2 m-2 s-1 for the rainy period. Comparing the values obtained in this work with values obtained through a traditional parameter optimization technique, it is possible to gauge pros and cons of such a combination of field measurements and machine learning technique.

Land use and land cover change in the Greater Yellowstone Ecosystem: 1975-1995

USGS Publications Warehouse

Parmenter, A.W.; Hansen, A.; Kennedy, R.E.; Cohen, W.; Langner, U.; Lawrence, R.; Maxwell, B.; Gallant, Alisa; Aspinall, R.

2003-01-01

Shifts in the demographic and economic character of the Greater Yellowstone Ecosystem (GYE) are driving patterns of land cover and land use change in the region. Such changes may have important consequences for ecosystem functioning. The objective of this paper is to quantify the trajectories and rates of change in land cover and use across the GYE for the period 1975-1995 using satellite imagery. Spectral and geographic variables were used as inputs to classification tree regression analysis (CART) to find "rules" which defined land use and land cover classes on the landscape. The resulting CART functions were used to map land cover and land use across seven Landsat TM scenes for 1995. We then used a thresholding technique to identify locations that differed in spectral properties between the 1995 and 1985 time periods. These "changed" locations were classified using CART functions derived from spectral and geographic data from 1985. This was similarly done for the year 1975 based on Landsat MSS data. Differences between the 1975, 1985, and 1995 maps were considered change in land cover and use. We calibrated and tested the accuracy of our models using data acquired through manual interpretation of aerial photos. Elevation and vegetative indices derived from the remotely sensed satellite imagery explained the most variance in the land use and land cover classes (-i.e., defined the "rules" most often). Overall accuracies from our study were good, ranging from 94% at the coarsest level of detail to 74% at the finest. The largest changes over the study period were the increases in burned, urban, and mixed conifer-herbaceous classes and decreases in woody deciduous, mixed woody deciduous-herbaceous, and conifer habitats. These changes have important implications for ecological function and biodiversity. The expansion of mixed conifer classes may increase fuel loads and enhance risk to the growing number of rural homes. The reduction of woody deciduous cover types is likely reducing population sizes for the numerous plant and animal species that specialize on this habitat type. Some of these species are also negatively influenced by the increase of rural homes in and near woody deciduous habitats.

Multiparameter comparative analysis reveals differential impacts of various cytokines on CART cell phenotype and function ex vivo and in vivo

PubMed Central

Xu, Xiao-Jun; Song, De-Gang; Poussin, Mathilde; Ye, Qunrui; Sharma, Prannda; Rodríguez-García, Alba; Tang, Yong-Min; Powell, Daniel J.

2016-01-01

Exogenous cytokines are widely applied to enhance the anti-tumor ability of immune cells. However, systematic comparative studies of their effects on chimeric antigen receptor (CAR)-engineered T (CART) cells are lacking. In this study, CART cells targeting folate receptor-alpha were generated and expanded ex vivo in the presence of different cytokines (IL-2, IL-7, IL-15, IL-18, and IL-21), and their expansion, phenotype and cytotoxic capacity were evaluated, in vitro and in vivo. Moreover, the effect of the administration of these cytokines along with CART cells in vivo was also studied. IL-2, IL-7, and IL-15 favored the ex vivo expansion of CART cells compared to other cytokines or no cytokine treatment. IL-7 induced the highest proportion of memory stem cell-like CART cells in the final product, and IL-21 supported the expansion of CART cells with a younger phenotype, while IL-2 induced more differentiated CART cells. IL-2 and IL-15-exposed CART cells secreted more proinflammatory cytokines and presented stronger tumor-lysis ability in vitro. However, when tested in vivo, CART cells exposed to IL-2 ex vivo showed the least anti-tumor effect. In contrast, the administration of IL-15 and IL-21 in combination with CART cells in vivo increased their tumor killing capacity. According to our results, IL-7 and IL-15 show promise to promote ex vivo expansion of CART cells, while IL-15 and IL-21 seem better suited for in vivo administration after CART cell infusion. Collectively, these results may have a profound impact on the efficacy of CART cells in both hematologic and solid cancers. PMID:27409425

The hypothalamic satiety peptide CART is expressed in anorectic and non-anorectic pancreatic islet tumors and in the normal islet of Langerhans.

PubMed

Jensen, P B; Kristensen, P; Clausen, J T; Judge, M E; Hastrup, S; Thim, L; Wulff, B S; Foged, C; Jensen, J; Holst, J J; Madsen, O D

1999-03-26

The hypothalamic satiety peptide CART (cocaine and amphetamine regulated transcript) is expressed at high levels in anorectic rat glucagonomas but not in hypoglycemic insulinomas. However, a non-anorectic metastasis derived from the glucagonoma retained high CART expression levels and produced circulating CART levels comparable to that of the anorectic tumors. Moreover, distinct glucagonoma lines derived by stable HES-1 transfection of the insulinoma caused severe anorexia but retained low circulating levels of CART comparable to that of insulinoma bearing or control rats. Islet tumor associated anorexia and circulating CART levels are thus not correlated, and in line with this peripheral administration of CART (5-50 mg/kg) produced no effect on feeding behavior. In the rat two alternatively spliced forms of CART mRNA exist and quantitative PCR revealed expression of both forms in the hypothalamus, in the different islet tumors, and in the islets of Langerhans. Immunocytochemistry as well as in situ hybridization localized CART expression to the somatostatin producing islet D cell. A potential endocrine/paracrine role of islet CART remains to be clarified.

P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain.

PubMed

Iioka, Takashi; Furukawa, Keizo; Yamaguchi, Akira; Shindo, Hiroyuki; Yamashita, Shunichi; Tsukazaki, Tomoo

2003-08-01

The paired-like homeoprotein, Cart1, is involved in skeletal development. We describe here that the general coactivator p300/CBP controls the transcription activity of Cart1 through acetylation of a lysine residue that is highly conserved in other homeoproteins. Acetylation of this residue increases the interaction between p300/CBP and Cart1 and enhances its transcriptional activation. Cart1 encodes a paired-like homeoprotein expressed selectively in chondrocyte lineage during embryonic development. Although its target gene remains unknown, gene disruption studies have revealed that Cart1 plays an important role for craniofacial bone formation as well as limb development by cooperating with another homeoprotein, Alx4. In this report, we study the functional involvement of p300/CBP, coactivators with intrinsic histone acetyltransferase (HAT) activity, in the transcriptional control of Cart1. To study the transcription activity of Cart1, a reporter construct containing a putative Cart1 binding site was transiently transfected with the expression vectors of each protein. The interaction between p300/CBP and Cart1 was investigated by glutathione S-transferase (GST) pull-down, yeast two-hybrid, and immunoprecipitation assays. In vitro acetylation assay was performed with the recombinant p300-HAT domain and Cart1 in the presence of acetyl-CoA. p300 and CBP stimulate Cart1-dependent transcription activity, and this transactivation is inhibited by E1A and Tax, oncoproteins that suppress the activity of p300/CBP. Cart1 binds to p300 in vivo and in vitro, and this requires the homeodomain of Cart 1 and N-terminal 139 amino acids of p300. Confocal microscopy analysis shows that Cart1 recruits overexpressed and endogenous p300 to a Cart1-specific subnuclear compartment. Cart1 is acetylated in vivo and sodium butyrate and trichostatin A, histone deacetylase inhibitors, markedly enhance the transcription activity of Cart1. Deletion and mutagenesis analysis identifies the 131st lysine that locates immediately adjacent to the homeodomain as a target of p300-HAT, and a point mutation to this residue attenuates the binding affinity to p300 as well as p300-dependent transcription activity. Together, these results indicate that p300/CBP acts as a cotransactivator to Cart1 through a direct interaction and specific lysine acetylation. In addition, because 131st lysine is highly conserved in other types of homeoprotein, this lysine may be a common target for HAT of p300/CBP for these proteins.

Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit.

PubMed

Larsen, P J; Seier, V; Fink-Jensen, A; Holst, J J; Warberg, J; Vrang, N

2003-03-01

Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalamic neuroendocrine neurones. Adult male rats received a systemic injection of the neuronal tracer Fluorogold (FG) 2 days before fixation, and subsequent double- and triple-labelling immunoflourescence analysis demonstrated that neuroendocrine CART-containing neurones were present in the anteroventral periventricular, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro-opiomelanocortin in the ventrolateral part, but completely absent from neuroendocrine neurones of the dorsomedial part. To assess the possible role of CART as a hypothalamic-releasing factor, immunoreactive CART was measured in blood samples from the long portal vessels connecting the median eminence with the anterior pituitary gland. Adult male rats were anaesthetized and the infundibular stalk exposed via a transpharyngeal approach. The long portal vessels were transected and blood collected in 30-min periods (one prestimulatory and three poststimulatory periods). Compared to systemic venous plasma samples, baseline concentrations of immunoreactive CART were elevated in portal plasma. Exposure to sodium nitroprusside hypotension triggered a two-fold elevation of portal CART42-89 immunoreactivity throughout the 90-min stimulation period. In contrast, the concentration of portal plasma CART immunoreactivity dropped in the vehicle infused rats. The current study provides further evidence that CART is a neuroendocrine-releasing factor with a possible impact on anterior pituitary function during states of haemodynamic stress.

Atmospheric Radiation Measurement Program Facilities Newsletter - September 1999

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

Holdridge, D. J., ed

The Atmospheric Radiation Measurement Program September 1999 Facilities Newsletter discusses the several Intensive Observation Periods (IOPs) that the ARM SGP CART site will host in the near future. Two projects of note are the International Pyrgeometer Intercomparison and the Fall Single Column Model (SCM)/Nocturnal Boundary Layer (NBL) IOP. Both projects will bring many US and international scientists to the SGP CART site to participate in atmospheric research.

King’s College Hospital criteria for non-acetaminophen induced acute liver failure in an international cohort of children

PubMed Central

Sundaram, Vinay; Shneider, Benjamin L.; Dhawan, Anil; Ng, Vicky L.; Im, Kyungah; Belle, Steven; Squires, Robert H.

2012-01-01

Objective To validate King’s College Hospital criteria (KCHC) in children with non-acetaminophen (APAP) induced pediatric acute liver failure (PALF) and to determine whether re-optimizing the KCHC would improve predictive accuracy. Study design We utilized the PALF study group database. Primary outcomes were survival without liver transplantation (LT) versus death at 21 days following enrollment. Classification and Regression Tree (CART) analysis was used to determine if modification of KCHC parameters would improve classification of death versus survival. Results Among 163 patients who met KCHC, 54 patients (33.1%) died within 21 days. Sensitivity of KCHC in this cohort was significantly lower than in the original study (61% vs 91%, p=0.002), and specificity did not differ significantly. The positive predictive value (PPV) and negative predictive value (NPV) of KCHC for this cohort was 33% and 88% respectively. CART analysis yielded the following optimized parameters to predict death: grade 2–4 encephalopathy, international normalized ratio >4.02 and total bilirubin >2.02 mg/dL. These parameters did not improve PPV, but NPV was significantly better (88% vs. 92%, p<0.0001). Conclusions KCHC does not reliably predict death in PALF. With a PPV of 33%, twice as many participants who met KCHC recovered spontaneously than died, indicating that using KCHC may cause over utilization of LT. Re-optimized cutpoints for KCHC parameters improved NPV, but not PPV. Parameters beyond the KCHC should be evaluated to create a predictive model for PALF. PMID:22906509

Identification of immune correlates of protection in Shigella infection by application of machine learning.

PubMed

Arevalillo, Jorge M; Sztein, Marcelo B; Kotloff, Karen L; Levine, Myron M; Simon, Jakub K

2017-10-01

Immunologic correlates of protection are important in vaccine development because they give insight into mechanisms of protection, assist in the identification of promising vaccine candidates, and serve as endpoints in bridging clinical vaccine studies. Our goal is the development of a methodology to identify immunologic correlates of protection using the Shigella challenge as a model. The proposed methodology utilizes the Random Forests (RF) machine learning algorithm as well as Classification and Regression Trees (CART) to detect immune markers that predict protection, identify interactions between variables, and define optimal cutoffs. Logistic regression modeling is applied to estimate the probability of protection and the confidence interval (CI) for such a probability is computed by bootstrapping the logistic regression models. The results demonstrate that the combination of Classification and Regression Trees and Random Forests complements the standard logistic regression and uncovers subtle immune interactions. Specific levels of immunoglobulin IgG antibody in blood on the day of challenge predicted protection in 75% (95% CI 67-86). Of those subjects that did not have blood IgG at or above a defined threshold, 100% were protected if they had IgA antibody secreting cells above a defined threshold. Comparison with the results obtained by applying only logistic regression modeling with standard Akaike Information Criterion for model selection shows the usefulness of the proposed method. Given the complexity of the immune system, the use of machine learning methods may enhance traditional statistical approaches. When applied together, they offer a novel way to quantify important immune correlates of protection that may help the development of vaccines. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients.

PubMed

Hoffmann, Jean-Marc; Schubert, Maria-Luisa; Wang, Lei; Hückelhoven, Angela; Sellner, Leopold; Stock, Sophia; Schmitt, Anita; Kleist, Christian; Gern, Ulrike; Loskog, Angelica; Wuchter, Patrick; Hofmann, Susanne; Ho, Anthony D; Müller-Tidow, Carsten; Dreger, Peter; Schmitt, Michael

2017-01-01

Therapy with chimeric antigen receptor T (CART) cells for hematological malignancies has shown promising results. Effectiveness of CART cells may depend on the ratio of naive (T N ) vs. effector (T E ) T cells, T N cells being responsible for an enduring antitumor activity through maturation. Therefore, we investigated factors influencing the T N /T E ratio of CART cells. CART cells were generated upon transduction of peripheral blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation retroviral vector under two different stimulating culture conditions: anti-CD3/anti-CD28 antibodies adding either interleukin (IL)-7/IL-15 or IL-2. CART cells were maintained in culture for 20 days. We evaluated 24 healthy donors (HDs) and 11 patients with chronic lymphocytic leukemia (CLL) for the composition of cell subsets and produced CART cells. Phenotype and functionality were tested using flow cytometry and chromium release assays. IL-7/IL-15 preferentially induced differentiation into T N , stem cell memory (T SCM : naive CD27+ CD95+), CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory (T EM ), CD56+ and CD4+ T regulatory (T Reg ) CART cells. The net amplification of different CART subpopulations derived from HDs and untreated CLL patients was compared. Particularly the expansion of CD4+ CART N cells differed significantly between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+ CART N cells of untreated CLL patients expanded less than 10-fold. Expression of exhaustion marker programmed cell death 1 on CART N cells on day 10 of culture was significantly higher in patient samples compared to HD samples. As the percentage of malignant B cells was expectedly higher within patient samples, an excessive amount of B cells during culture could account for the reduced expansion potential of CART N cells in untreated CLL patients. Final T N /T E ratio stayed <0.3 despite stimulation condition for patients, whereas this ratio was >2 in samples from HDs stimulated with IL-7/IL-15, thus demonstrating efficient CART N expansion. Untreated CLL patients might constitute a challenge for long-lasting CART effects in vivo since only a low number of T N among the CART product could be generated. Depletion of malignant B cells before starting CART production might be considered to increase the T N /T E ratio within the CART product.

CART PEPTIDE IN THE NUCLEUS ACCUMBENS REGULATES PSYCHOSTIMULANTS: CORRELATIONS BETWEEN PSYCHOSTIMULANT AND CART PEPTIDE EFFECTS

PubMed Central

JOB, MARTIN O.; KUHAR, MICHAEL J.

2017-01-01

In this study, we reexamined the effect of CART peptide on psychostimulant (PS)-induced locomotor activity (LMA) in individual rats. The Methods utilized were as previously published. The PS-induced LMA was defined as the distance traveled after PS administration (intraperitoneal), and the CART peptide effect was defined as the change in the PS-induced activity after bilateral intra-NAc administration of CART peptide. The experiments included both male and female Sprague-Dawley rats, and varying the CART peptide dose and the PS dose. While the average effect of CART peptide was to inhibit PS-induced LMA, the effect of CART peptide on individual PS treated animals was not always inhibitory and sometimes even produced an increase or no change in PS-induced LMA. Upon further analysis, we observed a linear correlation, reported for the first time, between the magnitude of PS-induced LMA and the CART peptide effect. Because CART peptide inhibits PS-induced LMA when it is large, and increases PS-induced LMA when it is small, the peptide can be considered a homeostatic regulator of dopamine (DA)-induced LMA, which supports our earlier homeostatic hypothesis. PMID:28215744

New Splitting Criteria for Decision Trees in Stationary Data Streams.

PubMed

Jaworski, Maciej; Duda, Piotr; Rutkowski, Leszek; Jaworski, Maciej; Duda, Piotr; Rutkowski, Leszek; Rutkowski, Leszek; Duda, Piotr; Jaworski, Maciej

2018-06-01

The most popular tools for stream data mining are based on decision trees. In previous 15 years, all designed methods, headed by the very fast decision tree algorithm, relayed on Hoeffding's inequality and hundreds of researchers followed this scheme. Recently, we have demonstrated that although the Hoeffding decision trees are an effective tool for dealing with stream data, they are a purely heuristic procedure; for example, classical decision trees such as ID3 or CART cannot be adopted to data stream mining using Hoeffding's inequality. Therefore, there is an urgent need to develop new algorithms, which are both mathematically justified and characterized by good performance. In this paper, we address this problem by developing a family of new splitting criteria for classification in stationary data streams and investigating their probabilistic properties. The new criteria, derived using appropriate statistical tools, are based on the misclassification error and the Gini index impurity measures. The general division of splitting criteria into two types is proposed. Attributes chosen based on type- splitting criteria guarantee, with high probability, the highest expected value of split measure. Type- criteria ensure that the chosen attribute is the same, with high probability, as it would be chosen based on the whole infinite data stream. Moreover, in this paper, two hybrid splitting criteria are proposed, which are the combinations of single criteria based on the misclassification error and Gini index.

A data mining approach to predict in situ chlorinated ethene detoxification potential

NASA Astrophysics Data System (ADS)

Lee, J.; Im, J.; Kim, U.; Loeffler, F. E.

2015-12-01

Despite major advances in physicochemical remediation technologies, in situ biostimulation and bioaugmentation treatment aimed at stimulating Dehalococcoides mccartyi (Dhc) reductive dechlorination activity remains a cornerstone approach to remedy sites impacted with chlorinated ethenes. In practice, selecting the best remedial strategy is challenging due to uncertainties associated with the microbiology (e.g., presence and activity of Dhc) and geochemical factors influencing Dhc activity. Extensive groundwater datasets collected over decades of monitoring exist, but have not been systematically analyzed. In the present study, geochemical and microbial data sets collected from 35 wells at 5 contaminated sites were used to develop a predictive empirical model using a machine learning algorithm (i) to rank the relative importance of parameters that affect in situ reductive dechlorination potential, and (ii) to provide recommendations for selecting the optimal remediation strategy at a specific site. Classification and regression tree (CART) analysis was applied, and a representative classification tree model was developed that allowed short-term prediction of dechlorination potential. Indirect indicators for low dissolved oxygen (e.g., low NO3-and NO2-, high Fe2+ and CH4) were the most influential factors for predicting dechlorination potential, followed by total organic carbon content (TOC) and Dhc cell abundance. These findings indicate that machine learning-based data mining techniques applied to groundwater monitoring data can lead to the development of predictive groundwater remediation models. A major need for improving the predictive capabilities of the data mining approach is a curated, up-to-date and comprehensive collection of groundwater monitoring data.

D Semantic Labeling of ALS Data Based on Domain Adaption by Transferring and Fusing Random Forest Models

NASA Astrophysics Data System (ADS)

Wu, J.; Yao, W.; Zhang, J.; Li, Y.

2018-04-01

Labeling 3D point cloud data with traditional supervised learning methods requires considerable labelled samples, the collection of which is cost and time expensive. This work focuses on adopting domain adaption concept to transfer existing trained random forest classifiers (based on source domain) to new data scenes (target domain), which aims at reducing the dependence of accurate 3D semantic labeling in point clouds on training samples from the new data scene. Firstly, two random forest classifiers were firstly trained with existing samples previously collected for other data. They were different from each other by using two different decision tree construction algorithms: C4.5 with information gain ratio and CART with Gini index. Secondly, four random forest classifiers adapted to the target domain are derived through transferring each tree in the source random forest models with two types of operations: structure expansion and reduction-SER and structure transfer-STRUT. Finally, points in target domain are labelled by fusing the four newly derived random forest classifiers using weights of evidence based fusion model. To validate our method, experimental analysis was conducted using 3 datasets: one is used as the source domain data (Vaihingen data for 3D Semantic Labelling); another two are used as the target domain data from two cities in China (Jinmen city and Dunhuang city). Overall accuracies of 85.5 % and 83.3 % for 3D labelling were achieved for Jinmen city and Dunhuang city data respectively, with only 1/3 newly labelled samples compared to the cases without domain adaption.

Machine learning techniques applied to the determination of road suitability for the transportation of dangerous substances.

PubMed

Matías, J M; Taboada, J; Ordóñez, C; Nieto, P G

2007-08-17

This article describes a methodology to model the degree of remedial action required to make short stretches of a roadway suitable for dangerous goods transport (DGT), particularly pollutant substances, using different variables associated with the characteristics of each segment. Thirty-one factors determining the impact of an accident on a particular stretch of road were identified and subdivided into two major groups: accident probability factors and accident severity factors. Given the number of factors determining the state of a particular road segment, the only viable statistical methods for implementing the model were machine learning techniques, such as multilayer perceptron networks (MLPs), classification trees (CARTs) and support vector machines (SVMs). The results produced by these techniques on a test sample were more favourable than those produced by traditional discriminant analysis, irrespective of whether dimensionality reduction techniques were applied. The best results were obtained using SVMs specifically adapted to ordinal data. This technique takes advantage of the ordinal information contained in the data without penalising the computational load. Furthermore, the technique permits the estimation of the utility function that is latent in expert knowledge.

Voice based gender classification using machine learning

NASA Astrophysics Data System (ADS)

Raahul, A.; Sapthagiri, R.; Pankaj, K.; Vijayarajan, V.

2017-11-01

Gender identification is one of the major problem speech analysis today. Tracing the gender from acoustic data i.e., pitch, median, frequency etc. Machine learning gives promising results for classification problem in all the research domains. There are several performance metrics to evaluate algorithms of an area. Our Comparative model algorithm for evaluating 5 different machine learning algorithms based on eight different metrics in gender classification from acoustic data. Agenda is to identify gender, with five different algorithms: Linear Discriminant Analysis (LDA), K-Nearest Neighbour (KNN), Classification and Regression Trees (CART), Random Forest (RF), and Support Vector Machine (SVM) on basis of eight different metrics. The main parameter in evaluating any algorithms is its performance. Misclassification rate must be less in classification problems, which says that the accuracy rate must be high. Location and gender of the person have become very crucial in economic markets in the form of AdSense. Here with this comparative model algorithm, we are trying to assess the different ML algorithms and find the best fit for gender classification of acoustic data.

Regional differences in rates of HIV-1 viral load monitoring in Canada: Insights and implications for antiretroviral care in high income countries.

PubMed

Raboud, Janet M; Loutfy, Mona R; Su, DeSheng; Bayoumi, Ahmed M; Klein, Marina B; Cooper, Curtis; Machouf, Nima; Rourke, Sean; Walmsley, Sharon; Rachlis, Anita; Harrigan, P Richard; Smieja, Marek; Tsoukas, Christos; Montaner, Julio S G; Hogg, Robert S

2010-02-25

Viral load (VL) monitoring is an essential component of the care of HIV positive individuals. Rates of VL monitoring have been shown to vary by HIV risk factor and clinical characteristics. The objective of this study was to determine whether there are differences among regions in Canada in the rates of VL testing of HIV-positive individuals on combination antiretroviral therapy (cART), where the testing is available without financial barriers under the coverage of provincial health insurance programs. The Canadian Observational Cohort (CANOC) is a collaboration of nine Canadian cohorts of HIV-positive individuals who initiated cART after January 1, 2000. The study included participants with at least one year of follow-up. Generalized Estimating Equation (GEE) regression models were used to determine the effect of geographic region on (1) the occurrence of an interval of 9 months or more between two consecutive recorded VL tests and (2) the number of days between VL tests, after adjusting for demographic and clinical covariates. Overall and regional annual rates of VL testing were also reported. 3,648 individuals were included in the analysis with a median follow-up of 42.9 months and a median of 15 VL tests. In multivariable GEE logistic regression models, gaps in VL testing >9 months were more likely in Quebec (Odds Ratio (OR) = 1.72, p < 0.0001) and Ontario (OR = 1.78, p < 0.0001) than in British Columbia and among injection drug users (OR = 1.68, p < 0.0001) and were less likely among older individuals (OR = 0.77 per 10 years, p < 0.0001), among men having sex with men (OR = 0.62, p < 0.0001), within the first year of cART (OR = 0.15, p < 0.0001), among individuals on cART at the time of the blood draw (OR = 0.34, p < 0.0001) and among individuals with VL < 50 copies/ml at the previous visit (OR = 0.56, p < .0001). Significant variation in rates of VL testing and the probability of a significant gap in testing were related to geographic region, HIV risk factor, age, year of cART initiation, type of cART regimen, being in the first year of cART, AIDS-defining illness and whether or not the previous VL was below the limit of detection.

Predictors of success of external cephalic version and cephalic presentation at birth among 1253 women with non-cephalic presentation using logistic regression and classification tree analyses.

PubMed

Hutton, Eileen K; Simioni, Julia C; Thabane, Lehana

2017-08-01

Among women with a fetus with a non-cephalic presentation, external cephalic version (ECV) has been shown to reduce the rate of breech presentation at birth and cesarean birth. Compared with ECV at term, beginning ECV prior to 37 weeks' gestation decreases the number of infants in a non-cephalic presentation at birth. The purpose of this secondary analysis was to investigate factors associated with a successful ECV procedure and to present this in a clinically useful format. Data were collected as part of the Early ECV Pilot and Early ECV2 Trials, which randomized 1776 women with a fetus in breech presentation to either early ECV (34-36 weeks' gestation) or delayed ECV (at or after 37 weeks). The outcome of interest was successful ECV, defined as the fetus being in a cephalic presentation immediately following the procedure, as well as at the time of birth. The importance of several factors in predicting successful ECV was investigated using two statistical methods: logistic regression and classification and regression tree (CART) analyses. Among nulliparas, non-engagement of the presenting part and an easily palpable fetal head were independently associated with success. Among multiparas, non-engagement of the presenting part, gestation less than 37 weeks and an easily palpable fetal head were found to be independent predictors of success. These findings were consistent with results of the CART analyses. Regardless of parity, descent of the presenting part was the most discriminating factor in predicting successful ECV and cephalic presentation at birth. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Socio-economic and lifestyle parameters associated with diet quality of children and adolescents using classification and regression tree analysis: the DIATROFI study.

PubMed

Yannakoulia, Mary; Lykou, Anastasia; Kastorini, Christina Maria; Saranti Papasaranti, Eirini; Petralias, Athanassios; Veloudaki, Afroditi; Linos, Athena

2016-02-01

To explore factors affecting children's and adolescents' diet quality, in the framework of a food aid and promotion of healthy nutrition programme implemented in areas of low socio-economic status of Greece, during the current financial crisis. From a total of 162 schools participating in the programme during 2012-2013, we gathered 15 897 questionnaires recording sociodemographic characteristics, lifestyle parameters and dietary habits of children and their families. As a measure of socio-economic status, the Family Affluence Scale (FAS) was used; whereas for the assessment of diet quality, the KIDMED score was computed. Associations between KIDMED and FAS, physical activity and socio-economic parameters were examined using regression and classification-regression tree analysis (CART). The higher the FAS score, the greater the percentage of children and adolescents who reported to consume, on a daily basis, fruits and vegetables, dairy products and breakfast (P<0·001). Results from CART showed that children and adolescents in the medium or high FAS groups had higher KIDMED score, compared with those in the low FAS group. For those in the low FAS group, KIDMED score is expected to increase by 12·4 % when they spend more than 0·25 h/week in sports activities. The respective threshold for the medium and high FAS groups is 1·75 h/week, while education of the mother and father affected KIDMED score significantly as well. Diet quality is strongly influenced by socio-economic parameters in children and adolescents living in economically disadvantaged areas of Greece, so that lower family affluence is associated with worse diet quality.

Shape classification of wear particles by image boundary analysis using machine learning algorithms

NASA Astrophysics Data System (ADS)

Yuan, Wei; Chin, K. S.; Hua, Meng; Dong, Guangneng; Wang, Chunhui

2016-05-01

The shape features of wear particles generated from wear track usually contain plenty of information about the wear states of a machinery operational condition. Techniques to quickly identify types of wear particles quickly to respond to the machine operation and prolong the machine's life appear to be lacking and are yet to be established. To bridge rapid off-line feature recognition with on-line wear mode identification, this paper presents a new radial concave deviation (RCD) method that mainly involves the use of the particle boundary signal to analyze wear particle features. Signal output from the RCDs subsequently facilitates the determination of several other feature parameters, typically relevant to the shape and size of the wear particle. Debris feature and type are identified through the use of various classification methods, such as linear discriminant analysis, quadratic discriminant analysis, naïve Bayesian method, and classification and regression tree method (CART). The average errors of the training and test via ten-fold cross validation suggest CART is a highly suitable approach for classifying and analyzing particle features. Furthermore, the results of the wear debris analysis enable the maintenance team to diagnose faults appropriately.

Beluga whale (Delphinapterus leucas) vocalizations and call classification from the eastern Beaufort Sea population.

PubMed

Garland, Ellen C; Castellote, Manuel; Berchok, Catherine L

2015-06-01

Beluga whales, Delphinapterus leucas, have a graded call system; call types exist on a continuum making classification challenging. A description of vocalizations from the eastern Beaufort Sea beluga population during its spring migration are presented here, using both a non-parametric classification tree analysis (CART), and a Random Forest analysis. Twelve frequency and duration measurements were made on 1019 calls recorded over 14 days off Icy Cape, Alaska, resulting in 34 identifiable call types with 83% agreement in classification for both CART and Random Forest analyses. This high level of agreement in classification, with an initial subjective classification of calls into 36 categories, demonstrates that the methods applied here provide a quantitative analysis of a graded call dataset. Further, as calls cannot be attributed to individuals using single sensor passive acoustic monitoring efforts, these methods provide a comprehensive analysis of data where the influence of pseudo-replication of calls from individuals is unknown. This study is the first to describe the vocal repertoire of a beluga population using a robust and repeatable methodology. A baseline eastern Beaufort Sea beluga population repertoire is presented here, against which the call repertoire of other seasonally sympatric Alaskan beluga populations can be compared.

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.

PubMed

Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G; Henry, Keith; Jain, Mamta K; Palfreeman, Adrian; Mugyenyi, Peter; Domingo, Pere; Hoffmann, Christian; Read, Tim R H; Pujari, Sanjay; Meulbroek, Michael; Johnson, Margaret; Wilkin, Timothy; Mitsuyasu, Ronald

2016-12-15

 In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.  There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.  Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Life expectancy in HIV-positive persons in Switzerland: matched comparison with general population

PubMed Central

Gueler, Aysel; Moser, André; Calmy, Alexandra; Günthard, Huldrych F.; Bernasconi, Enos; Furrer, Hansjakob; Fux, Christoph A.; Battegay, Manuel; Cavassini, Matthias; Vernazza, Pietro; Zwahlen, Marcel; Egger, Matthias

2017-01-01

Objectives: To estimate life expectancy over 25 years in HIV-positive people and to compare their life expectancy with recent estimates for the general population, by education. Methods: Patients aged 20 years or older enrolled in the Swiss HIV Cohort Study 1988–2013 were eligible. Patients alive in 2001 were matched to up to 100 Swiss residents, by sex, year of birth, and education. Life expectancy at age 20 was estimated for monotherapy (1988–1991), dual therapy (1992–1995), early combination antiretroviral therapy (cART, 1996–1998), later cART (1999–2005) and recent cART (2006–2013) eras. Parametric survival regression was used to model life expectancy. Results: In all, 16 532 HIV-positive patients and 927 583 residents were included. Life expectancy at age 20 of HIV-positive individuals increased from 11.8 years [95% confidence interval (CI) 11.2–12.5] in the monotherapy era to 54.9 years (95% CI 51.2–59.6) in the most recent cART era. Differences in life expectancy across educational levels emerged with cART. In the most recent cART period, life expectancy at age 20 years was 52.7 years (95% CI 46.4–60.1) with compulsory education, compared to 60.0 years (95% CI 53.4–67.8) with higher education. Estimates for the general population were 61.5 and 65.6 years, respectively. Male sex, smoking, injection drug use, and low CD4+ cell counts at enrolment were also independently associated with mortality. Conclusion: In Switzerland, educational inequalities in life expectancy were larger among HIV-infected persons than in the general population. Highly educated HIV-positive people have an estimated life expectancy similar to Swiss residents with compulsory education. Earlier start of cART and effective smoking-cessation programs could improve HIV-positive life expectancy further and reduce inequalities. PMID:27831953

Mortality in Children with Human Immunodeficiency Virus Initiating Treatment: A Six-Cohort Study in Latin America.

PubMed

Luque, Marco T; Jenkins, Cathy A; Shepherd, Bryan E; Padgett, Denis; Rouzier, Vanessa; Succi, Regina Célia M; Machado, Daisy M; McGowan, Catherine C; Vermund, Sten H; Pinto, Jorge A

2017-03-01

To assess the risks of and factors associated with mortality, loss to follow-up, and changing regimens after children with HIV infected perinatally initiate combination antiretroviral therapy (cART) in Latin America and the Caribbean. This 1997-2013 retrospective cohort study included 1174 antiretroviral therapy-naïve, perinatally infected children who started cART age when they were younger than 18 years of age (median 4.7 years; IQR 1.7-8.8) at 1 of 6 cohorts from Argentina, Brazil, Haiti, and Honduras, within the Caribbean, Central and South America Network for HIV Epidemiology. Median follow-up was 5.6 years (IQR 2.3-9.3). Study outcomes were all-cause mortality, loss to follow-up, and major changes in cART. We used Cox proportional hazards models stratified by site to examine the association between predictors and times to death or changing regimens. Only 52% started cART at younger than 5 years of age; 19% began a protease inhibitor. At cART initiation, median CD4 count was 472 cells/mm 3 (IQR 201-902); median CD4% was 16% (IQR 10-23). Probability of death was high in the first year of cART: 0.06 (95% CI 0.04-0.07). Five years after cART initiation, the cumulative mortality incidence was 0.12 (95% CI 0.10-0.14). Cumulative incidences for loss to follow-up and regimen change after 5 years were 0.16 (95% 0.14-0.18) and 0.30 (95% 0.26-0.34), respectively. Younger children had the greatest risk of mortality, whereas older children had the greatest risk of being lost to follow-up or changing regimens. Innovative clinical and community approaches are needed for quality improvement in the pediatric care of HIV in the Americas. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of CART3D to Complex Propulsion-Airframe Integration with Vehicle Sketch Pad

NASA Technical Reports Server (NTRS)

Hahn, Andrew S.

2012-01-01

Vehicle Sketch Pad (VSP) is an easy-to-use modeler used to generate aircraft geometries for use in conceptual design and analysis. It has been used in the past to generate metageometries for aerodynamic analyses ranging from handbook methods to Navier-Stokes computational fluid dynamics (CFD). As desirable as it is to bring high order analyses, such as CFD, into the conceptual design process, this has been difficult and time consuming in practice due to the manual nature of both surface and volume grid generation. Over the last couple of years, VSP has had a major upgrade of its surface triangulation and export capability. This has enhanced its ability to work with Cart3D, an inviscid, three dimensional fluid flow toolset. The combination of VSP and Cart3D allows performing inviscid CFD on complex geometries with relatively high productivity. This paper will illustrate the use of VSP with Cart3D through an example case of a complex propulsion-airframe integration (PAI) of an over-wing nacelle (OWN) airliner configuration.

Hand and goods judgment algorithm based on depth information

NASA Astrophysics Data System (ADS)

Li, Mingzhu; Zhang, Jinsong; Yan, Dan; Wang, Qin; Zhang, Ruiqi; Han, Jing

2016-03-01

A tablet computer with a depth camera and a color camera is loaded on a traditional shopping cart. The inside information of the shopping cart is obtained by two cameras. In the shopping cart monitoring field, it is very important for us to determine whether the customer with goods in or out of the shopping cart. This paper establishes a basic framework for judging empty hand, it includes the hand extraction process based on the depth information, process of skin color model building based on WPCA (Weighted Principal Component Analysis), an algorithm for judging handheld products based on motion and skin color information, statistical process. Through this framework, the first step can ensure the integrity of the hand information, and effectively avoids the influence of sleeve and other debris, the second step can accurately extract skin color and eliminate the similar color interference, light has little effect on its results, it has the advantages of fast computation speed and high efficiency, and the third step has the advantage of greatly reducing the noise interference and improving the accuracy.

Cocaine- and amphetamine-regulated transcript and calcium binding proteins immunoreactivity in the subicular complex of the guinea pig.

PubMed

Wasilewska, Barbara; Najdzion, Janusz; Równiak, Maciej; Bogus-Nowakowska, Krystyna; Hermanowicz, Beata; Kolenkiewicz, Małgorzata; Żakowski, Witold; Robak, Anna

2016-03-01

In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S. In the PrS and PaS, single CART-IR perikarya were dispersed, however with a tendency to be found only in superficial layers. CART-IR fibers were observed throughout the entire guinea pig subicular neuropil. Double-labeling immunofluorescence showed that CART-IR perikarya, as well as fibers, did not stain positively for any of the three CaBPs. CART-IR fibers were only located near the CB-, CR-, PV-IR perikarya, whereas CART-IR fibers occasionally intersected fibers containing one of the three CaBPs. The distribution pattern of CART was more similar to that of CB and CR than to that of PV. In the PrS, the CART, CB and CR immunoreactivity showed a laminar distribution pattern. In the case of the PV, this distribution pattern in the PrS was much less prominent than that of CART, CB and CR. We conclude that a heterogeneous distribution of the CART and CaBPs in the guinea pig SC is in keeping with findings from other mammals, however species specific differences have been observed. Copyright © 2015 Elsevier GmbH. All rights reserved.

L4-L5 compression and anterior/posterior joint shear forces in cabin attendants during the initial push/pull actions of airplane meal carts.

PubMed

Sandfeld, Jesper; Rosgaard, Christian; Jensen, Bente Rona

2014-07-01

The aim of the present study was to assess the acute low back load of cabin attendants during cart handling and to identify working situations which present the highest strain on the worker. In a setup, 17 cabin attendants (ten females and seven males) pushed, pulled and turned a 20 kg standard meal cart (L: 0.5m × W: 0.3 m × H: 0.92 m) loaded with extra 20 kg and 40 kg, respectively on two different surfaces (carpet and linoleum) and at three floor inclinations (-2°, 0° and +2°). Two force transducers were mounted as handles. Two-dimensional movement analysis was performed and a 4D WATBAK modelling tool was used to calculate the acute L4-L5 load. No working situations created loads greater than the accepted values for single exertions, however compression and anterior/posterior shear forces during pulling and turning were much higher when compared with pushing. There were significant effects of handling the cart on different floor types, at the varying inclinations and with different cart weights. Additionally, when external forces were reduced, the cabin attendants did not decrease push/pull force proportionally and thus the L4-L5 load did not decrease as much as expected. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Mother-to-child transmission of HIV and its predictors among HIV-exposed infants at Bamenda Regional Hospital, Cameroon.

PubMed

Fondoh, Victor N; Mom, Njong A

2017-01-01

Mother-to-child transmission (MTCT) of HIV, has been a major global public health burden. Despite the use of antiretroviral prophylaxis by HIV-positive pregnant women and their infants, safe obstetric practice and safe infant feeding habits in the prevention of MTCT of HIV, the prevalence of HIV among HIV-exposed infants is still high in Cameroon. Our objectives were to determine the prevalence, assess the predictors and determine the effect of combination antiretroviral therapy (cART) on MTCT of HIV at the regional hospital in Bamenda, Cameroon. This was a retrospective study. Secondary data from 877 HIV-exposed infants aged ≤ 72 weeks were extracted from the records between January 2008 and December 2014. The predictors and effect of cART on MTCT of HIV were analysed using a multivariable logistic regression model and risk analysis, respectively. Out of 877 HIV-exposed infants, 62 were positive for HIV, giving a prevalence of 7.1%. Maternal antiretroviral intervention and infant age group were statistically significant predictors of MTCT of HIV. HIV-positive mothers who were on cART were 2.49 times less likely to transmit HIV than those who were not on cART. In order to reduce the prevalence of HIV among HIV-exposed infants, maternal antiretroviral intervention should be targeted and the use of cART by HIV-positive pregnant women should be encouraged.

CATIA V5 Virtual Environment Support for Constellation Ground Operations

NASA Technical Reports Server (NTRS)

Kelley, Andrew

2009-01-01

This summer internship primarily involved using CATIA V5 modeling software to design and model parts to support ground operations for the Constellation program. I learned several new CATIA features, including the Imagine and Shape workbench and the Tubing Design workbench, and presented brief workbench lessons to my co-workers. Most modeling tasks involved visualizing design options for Launch Pad 39B operations, including Mobile Launcher Platform (MLP) access and internal access to the Ares I rocket. Other ground support equipment, including a hydrazine servicing cart, a mobile fuel vapor scrubber, a hypergolic propellant tank cart, and a SCAPE (Self Contained Atmospheric Protective Ensemble) suit, was created to aid in the visualization of pad operations.

Temperature dependence of the control of energy homeostasis requires CART signaling.

PubMed

Lau, Jackie; Shi, Yan-Chuan; Herzog, Herbert

2016-10-01

Cocaine- and amphetamine-regulated transcript (CART) is a key neuropeptide with predominant expression in the hypothalamus central to the regulation of diverse biological processes, including food intake and energy expenditure. While there is considerable information on CART's role in the control of feeding, little is known about its thermoregulatory potential. Here we show the consequences of lack of CART signaling on major parameters of energy homeostasis in CART -/- mice under standard ambient housing (RT, 22°C), which is considered a mild cold exposure for mice, and thermoneutral conditions (TN, 30°C). WT mice kept at RT showed an increase in food intake, energy expenditure, BAT UCP-1 expression, and physical activity compared with TN condition, reflecting the augmented energy demand for thermogenesis at RT. On the molecular level, RT housing led to upregulated mRNA expression of TH, CRH, and TRH at the PVN, while NPY, AgRP and CART mRNA levels in the Arc were downregulated. CART -/- mice displayed elevated adiposity and diminished lean mass across both RT and TN. At RT, CART -/- mice showed unchanged food consumption yet greater body weight gain. In addition, an increase in energy expenditure and heightened BAT thermogenesis marked by UCP-1 protein expression was observed in the CART -/- mice. In contrast, TN-housed CART -/- mice exhibited lower weight gain than WT mice accompanied with pronounced reduction in basal feeding. These findings were correlated with reduced BAT temperature, but unchanged energy expenditure and UCP-1 levels. Interestingly, the respiratory exchange ratio for CART -/- mice, which shifted from lower at RT to higher at TN with respect to WT controls, indicates a transition of relative fuel source preference from fat to carbohydrate in the absence of CART signaling. Taken together, these results demonstrate that CART is a critical regulator of energy expenditure, energy partitioning and utilization dependent on the thermal environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cart Regulates Food Intake in Channel Catfish

USDA-ARS?s Scientific Manuscript database

Cocaine-and Amphetamine-Regulated Transcript (CART) is a potent hypothalamic anorectic peptide in mammals and fish. We hypothesized that increased food intake is associated with changes in expression of CART mRNA within the brain of channel catfish. Objectives were to clone the CART gene, examine ...

Mercury Shopping Cart Interface

NASA Technical Reports Server (NTRS)

Pfister, Robin; McMahon, Joe

2006-01-01

Mercury Shopping Cart Interface (MSCI) is a reusable component of the Power User Interface 5.0 (PUI) program described in another article. MSCI is a means of encapsulating the logic and information needed to describe an orderable item consistent with Mercury Shopping Cart service protocol. Designed to be used with Web-browser software, MSCI generates Hypertext Markup Language (HTML) pages on which ordering information can be entered. MSCI comprises two types of Practical Extraction and Report Language (PERL) modules: template modules and shopping-cart logic modules. Template modules generate HTML pages for entering the required ordering details and enable submission of the order via a Hypertext Transfer Protocol (HTTP) post. Shopping cart modules encapsulate the logic and data needed to describe an individual orderable item to the Mercury Shopping Cart service. These modules evaluate information entered by the user to determine whether it is sufficient for the Shopping Cart service to process the order. Once an order has been passed from MSCI to a deployed Mercury Shopping Cart server, there is no further interaction with the user.

Control of an Omni-directional Power-assisted Cart

NASA Astrophysics Data System (ADS)

Maeda, Hiroshi; Fujiwara, Shigeki; Kitano, Hitoshi; Yamashita, Hideki; Fukunaga, Hideo

This paper describes an easy-to-operate, omni-directional cart. This cart includes power assist technology that acts for both the longitudinal and rotational motions of the cart. Two objectives are set for this development. The first objective is to overcome the difficulty of shifting the cart laterally. Therefore, the equation for calculating the cart turning speed is modified so that the moment, which is driven by the operating force in the right/left direction, is offset. As a result, it becomes possible to stabilize the balance between the operating force in the right/left direction and the operating moment, and improve the operating performance. The second objective is to overcome the other difficulty whereby, during the one-hand pull-operation, the cart tended to run off course to the right/left. To solve this problem, we add a positional control in the right/left direction. As a result, we reduce the lateral deviation of the cart, and improve the operating performance.

Prediction of Mortality in Patients with Isolated Traumatic Subarachnoid Hemorrhage Using a Decision Tree Classifier: A Retrospective Analysis Based on a Trauma Registry System.

PubMed

Rau, Cheng-Shyuan; Wu, Shao-Chun; Chien, Peng-Chen; Kuo, Pao-Jen; Chen, Yi-Chun; Hsieh, Hsiao-Yun; Hsieh, Ching-Hua

2017-11-22

Background: In contrast to patients with traumatic subarachnoid hemorrhage (tSAH) in the presence of other types of intracranial hemorrhage, the prognosis of patients with isolated tSAH is good. The incidence of mortality in these patients ranges from 0-2.5%. However, few data or predictive models are available for the identification of patients with a high mortality risk. In this study, we aimed to construct a model for mortality prediction using a decision tree (DT) algorithm, along with data obtained from a population-based trauma registry, in a Level 1 trauma center. Methods: Five hundred and forty-five patients with isolated tSAH, including 533 patients who survived and 12 who died, between January 2009 and December 2016, were allocated to training ( n = 377) or test ( n = 168) sets. Using the data on demographics and injury characteristics, as well as laboratory data of the patients, classification and regression tree (CART) analysis was performed based on the Gini impurity index, using the rpart function in the rpart package in R. Results: In this established DT model, three nodes (head Abbreviated Injury Scale (AIS) score ≤4, creatinine (Cr) <1.4 mg/dL, and age <76 years) were identified as important determinative variables in the prediction of mortality. Of the patients with isolated tSAH, 60% of those with a head AIS >4 died, as did the 57% of those with an AIS score ≤4, but Cr ≥1.4 and age ≥76 years. All patients who did not meet the above-mentioned criteria survived. With all the variables in the model, the DT achieved an accuracy of 97.9% (sensitivity of 90.9% and specificity of 98.1%) and 97.7% (sensitivity of 100% and specificity of 97.7%), for the training set and test set, respectively. Conclusions: The study established a DT model with three nodes (head AIS score ≤4, Cr <1.4, and age <76 years) to predict fatal outcomes in patients with isolated tSAH. The proposed decision-making algorithm may help identify patients with a high risk of mortality.

Effect of Suberoylanilide Hydroxamic Acid (SAHA) Administration on the Residual Virus Pool in a Model of Combination Antiretroviral Therapy-Mediated Suppression in SIVmac239-Infected Indian Rhesus Macaques

PubMed Central

Del Prete, Gregory Q.; Shoemaker, Rebecca; Oswald, Kelli; Lara, Abigail; Trubey, Charles M.; Fast, Randy; Schneider, Douglas K.; Kiser, Rebecca; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Freemire, Brandi; Keele, Brandon F.; Estes, Jacob D.; Quiñones, Octavio A.; Smedley, Jeremy; Macallister, Rhonda; Sanchez, Rosa I.; Wai, John S.; Tan, Christopher M.; Alvord, W. Gregory; Hazuda, Daria J.; Piatak, Michael

2014-01-01

Nonhuman primate models are needed for evaluations of proposed strategies targeting residual virus that persists in HIV-1-infected individuals receiving suppressive combination antiretroviral therapy (cART). However, relevant nonhuman primate (NHP) models of cART-mediated suppression have proven challenging to develop. We used a novel three-class, six-drug cART regimen to achieve durable 4.0- to 5.5-log reductions in plasma viremia levels and declines in cell-associated viral RNA and DNA in blood and tissues of simian immunodeficiency virus SIVmac239-infected Indian-origin rhesus macaques, then evaluated the impact of treatment with the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA; Vorinostat) on the residual virus pool. Ex vivo SAHA treatment of CD4+ T cells obtained from cART-suppressed animals increased histone acetylation and viral RNA levels in culture supernatants. cART-suppressed animals each received 84 total doses of oral SAHA. We observed SAHA dose-dependent increases in acetylated histones with evidence for sustained modulation as well as refractoriness following prolonged administration. In vivo virologic activity was demonstrated based on the ratio of viral RNA to viral DNA in peripheral blood mononuclear cells, a presumptive measure of viral transcription, which significantly increased in SAHA-treated animals. However, residual virus was readily detected at the end of treatment, suggesting that SAHA alone may be insufficient for viral eradication in the setting of suppressive cART. The effects observed were similar to emerging data for repeat-dose SAHA treatment of HIV-infected individuals on cART, demonstrating the feasibility, utility, and relevance of NHP models of cART-mediated suppression for in vivo assessments of AIDS virus functional cure/eradication approaches. PMID:25182644

Modeling potential habitats for alien species Dreissena polymorpha in continental USA

USGS Publications Warehouse

Mingyang, Li; Yunwei, Ju; Kumar, Sunil; Stohlgren, Thomas J.

2008-01-01

The effective measure to minimize the damage of invasive species is to block the potential invasive species to enter into suitable areas. 1864 occurrence points with GPS coordinates and 34 environmental variables from Daymet datasets were gathered, and 4 modeling methods, i.e., Logistic Regression (LR), Classification and Regression Trees (CART), Genetic Algorithm for Rule-Set Prediction (GARP), and maximum entropy method (Maxent), were introduced to generate potential geographic distributions for invasive species Dreissena polymorpha in Continental USA. Then 3 statistical criteria of the area under the Receiver Operating Characteristic curve (AUC), Pearson correlation (COR) and Kappa value were calculated to evaluate the performance of the models, followed by analyses on major contribution variables. Results showed that in terms of the 3 statistical criteria, the prediction results of the 4 ecological niche models were either excellent or outstanding, in which Maxent outperformed the others in 3 aspects of predicting current distribution habitats, selecting major contribution factors, and quantifying the influence of environmental variables on habitats. Distance to water, elevation, frequency of precipitation and solar radiation were 4 environmental forcing factors. The method suggested in the paper can have some reference meaning for modeling habitats of alien species in China and provide a direction to prevent Mytilopsis sallei on the Chinese coast line.

[Association of the cocaine and amphetamine-regulated transcript gene with type 2 diabetes mellitus].

PubMed

Fu, Mao; Cheng, Hua; Chen, Lihong; Wu, Bin; Cai, Mengyin; Xie, Ding; Fu, Zuzhi

2002-12-01

To investigate whether genetic variation in cocaine and amphetamine-regulated transcript (CART) gene might contribute to the genesis of type 2 diabetes. Screening for mutations in the entire coding region for the CART gene were performed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in 180 normoglycemic control subjects and 221 patients with type 2 diabetes. (1) Adenine deletion was identified at position 1,457 nucleotide located at untranslation area of exon 3. In normal weight control, the frequencies of CART-A + and CART-A-alleles were 83.6% and 16.4% respectively. The frequencies of CART-A + A +, A + A-, A-A- genotype were 68.9%, 29.4% and 1.7% respectively. (2) In diabetic patients, the frequencies of CART-A + and A-alleles were 84.6% and 15.4% respectively; the frequencies of CART-A + A +, A + A-, A-A- genotype were 71.9%, 25.3% and 2.7% respectively. The frequency of A deletion of the CART gene in diabetic patients did not differ significantly from normoglycemic control subjects. (3) Diabetic patients with the A deletion had increased total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Polymorphism was found in the 3'-untranslated region (Delta A1457) of CART in Chinese. A deletion in CART is not associated with type 2 diabetes, but may contribute to dyslipidemia.

Age, sex, and nutritional status modify the CD4+ T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy.

PubMed

Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

2015-06-01

Baseline age and combination antiretroviral therapy (cART) were examined as determinants of CD4+ T-cell recovery during 6 months of tuberculosis (TB) therapy with/without cART. It was determined whether this association was modified by patient sex and nutritional status. This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+ T-cell counts were measured using flow cytometry. Age was defined as ≤24, 25-29, 30-34, and 35-39 vs. ≥40 years. Nutritional status was defined as normal (>18.5kg/m(2)) vs. underweight (≤18.5kg/m(2)) using the body mass index (BMI). Multivariate random effects linear mixed models were fitted to estimate differences in CD4+ T-cell recovery in relation to specified determinants. cART was associated with a monthly rise of 15.7 cells/μl (p<0.001). Overall, age was not associated with CD4+ T-cell recovery during TB therapy (p = 0.655). However, among patients on cART, the age-associated CD4+ T-cell recovery rate varied by sex and nutritional status, such that age <40 vs. ≥40 years predicted superior absolute CD4+ T-cell recovery among females (p=0.006) and among patients with a BMI ≥18.5kg/m(2) (p<0.001). TB-infected HIV-positive patients aged ≥40 years have a slower rate of immune restoration given cART, particularly if BMI is >18.5kg/m(2) or they are female. These patients may benefit from increased monitoring and nutritional support during cART. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Age, Sex & Nutritional Status Modify CD4+T-Cell Recovery Rate in HIV/Tuberculosis Co-infected Patients on cART

PubMed Central

Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

2015-01-01

Background We examined baseline age and combination antiretroviral therapy (cART) as determinants of CD4+T-cell recovery during six months of tuberculosis (TB) therapy with/without cART. We determined whether this association was modified by patient sex and nutritional status. Methods This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+T-cell count was measured using flow cytometry. Age was defined as ≤24, 25–29, 30–34, 35–39 vs. ≥ 40 years. Nutritional status was defined as normal (>18.5kg/m2) vs. underweight (≤18.5kg/m2) using body mass index (BMI). Multivariate random-effects linear mixed models were fitted to estimate differences in CD4+T-cell recovery in relation to specified determinants. Results cART was associated with a monthly rise of 15.7 cells/μL (p<0.001). Overall, age was not associated with CD4+T-cell recovery during TB therapy (p=0.655). However, among patients on cART, age-associated CD4+T-cell recovery rate varied by sex and nutritional status such that age <40 vs. ≥ 40 years predicted superior absolute CD4+T-cell recovery among females (p=0.006) and among patients with BMI≥18.5kg/m2 (p<0.001). Conclusions TB infected HIV-positive patients ≥ 40 years have a slower rate of immune restoration given cART-particularly if BMI>18.5kg/m2 or female. They may benefit from increased monitoring and nutritional support during cART. PMID:25910854

Simulation at the point of care: reduced-cost, in situ training via a mobile cart.

PubMed

Weinstock, Peter H; Kappus, Liana J; Garden, Alexander; Burns, Jeffrey P

2009-03-01

The rapid growth of simulation in health care has challenged traditional paradigms of hospital-based education and training. Simulation addresses patient safety through deliberative practice of high-risk low-frequency events within a safe, structured environment. Despite its inherent appeal, widespread adoption of simulation is prohibited by high cost, limited space, interruptions to clinical duties, and the inability to replicate important nuances of clinical environments. We therefore sought to develop a reduced-cost low-space mobile cart to provide realistic simulation experiences to a range of providers within the clinical environment and to serve as a model for transportable, cost-effective, widespread simulation-based training of bona-fide workplace teams. Descriptive study. A tertiary care pediatric teaching hospital. A self-contained mobile simulation cart was constructed at a cost of $8054 (mannequin not included). The cart is compatible with any mannequin and contains all equipment needed to produce a high quality simulation experience equivalent to that of our on-site center--including didactics and debriefing with videotaped recordings complete with vital sign overlay. Over a 3-year period the cart delivered 57 courses to 425 participants from five pediatric departments. All individuals were trained among their native teams and within their own clinical environment. By bringing all pedagogical elements to the actual clinical environment, a mobile cart can provide simulation to hospital teams that might not otherwise benefit from the educational tool. By reducing the setup cost and the need for dedicated space, the mobile approach provides a mechanism to increase the number of institutions capable of harnessing the power of simulation-based education internationally.

Ageing and long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience.

PubMed

Wright, S T; Petoumenos, K; Boyd, M; Carr, A; Downing, S; O'Connor, C C; Grotowski, M; Law, M G

2013-04-01

The aim of this study was to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell count changes following the completion of 5 years of cART using linear mixed models. A total of 37 916 CD4 measurements were observed for 892 patients over a combined total of 9753 patient-years. Older patients (> 50 years old) at cART initiation had estimated mean (95% confidence interval) changes in CD4 counts by year-5 CD4 count strata (< 500, 500-750 and > 750 cells/μL) of 14 (7 to 21), 3 (-5 to 11) and -6 (-17 to 4) cells/μL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. Our results suggest that duration of cART and increasing age do not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients, indicating that the level of immune recovery achieved during the first 5 years of treatment is sustained through long-term cART. © 2012 British HIV Association.

Ageing & long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience

PubMed Central

WRIGHT, ST; PETOUMENOS, K; BOYD, M; CARR, A; DOWNING, S; O’CONNOR, CC; GROTOWSKI, M; LAW, MG

2012-01-01

Background The aim of this analysis is to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. Methods Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell counts changes following the completion of 5 years of cART using linear mixed models. Results A total of 37,916 CD4 measurements were observed for 892 patients over a combined total of 9,753 patient years. Older patients (>50 years) at cART initiation had estimated mean(95% confidence interval) change in CD4 counts by Year-5 CD4 count strata (<500, 501–750 and >750 cells/μL) of 14(7 to 21), 3(−5 to 11) and −6(−17 to 4) cells/μL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. Conclusions Our results suggest that duration of cART and increasing age does not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients. Indicating that level of immune recovery achieved during the first 5 years of treatment are sustained through long-term cART. PMID:23036045

The nucleus accumbens 5-HTR₄-CART pathway ties anorexia to hyperactivity.

PubMed

Jean, A; Laurent, L; Bockaert, J; Charnay, Y; Dusticier, N; Nieoullon, A; Barrot, M; Neve, R; Compan, V

2012-12-11

In mental diseases, the brain does not systematically adjust motor activity to feeding. Probably, the most outlined example is the association between hyperactivity and anorexia in Anorexia nervosa. The neural underpinnings of this 'paradox', however, are poorly elucidated. Although anorexia and hyperactivity prevail over self-preservation, both symptoms rarely exist independently, suggesting commonalities in neural pathways, most likely in the reward system. We previously discovered an addictive molecular facet of anorexia, involving production, in the nucleus accumbens (NAc), of the same transcripts stimulated in response to cocaine and amphetamine (CART) upon stimulation of the 5-HT(4) receptors (5-HTR(4)) or MDMA (ecstasy). Here, we tested whether this pathway predisposes not only to anorexia but also to hyperactivity. Following food restriction, mice are expected to overeat. However, selecting hyperactive and addiction-related animal models, we observed that mice lacking 5-HTR(1B) self-imposed food restriction after deprivation and still displayed anorexia and hyperactivity after ecstasy. Decryption of the mechanisms showed a gain-of-function of 5-HTR(4) in the absence of 5-HTR(1B), associated with CART surplus in the NAc and not in other brain areas. NAc-5-HTR(4) overexpression upregulated NAc-CART, provoked anorexia and hyperactivity. NAc-5-HTR(4) knockdown or blockade reduced ecstasy-induced hyperactivity. Finally, NAc-CART knockdown suppressed hyperactivity upon stimulation of the NAc-5-HTR(4). Additionally, inactivating NAc-5-HTR(4) suppressed ecstasy's preference, strengthening the rewarding facet of anorexia. In conclusion, the NAc-5-HTR(4)/CART pathway establishes a 'tight-junction' between anorexia and hyperactivity, suggesting the existence of a primary functional unit susceptible to limit overeating associated with resting following homeostasis rules.

Analysis of contemporary HIV/AIDS health care costs in Germany

PubMed Central

Treskova, Marina; Kuhlmann, Alexander; Bogner, Johannes; Hower, Martin; Heiken, Hans; Stellbrink, Hans-Jürgen; Mahlich, Jörg; von der Schulenburg, Johann-Matthias Graf; Stoll, Matthias

2016-01-01

Abstract To analyze contemporary costs of HIV health care and the cost distribution across lines of combination antiretroviral therapy (cART). To identify variations in expenditures with patient characteristics and to identify main cost determinants. To compute cost ratios between patients with varying characteristics. Empirical data on costs are collected in Germany within a 2-year prospective observational noninterventional multicenter study. The database contains information for 1154 HIV-infected patients from 8 medical centers. Means and standard deviations of the total costs are estimated for each cost fraction and across cART lines and regimens. The costs are regressed against various patient characteristics using a generalized linear model. Relative costs are calculated using the resultant coefficients. The average annual total costs (SD) per patient are €22,231.03 (8786.13) with a maximum of €83,970. cART medication is the major cost fraction (83.8%) with a mean of €18,688.62 (5289.48). The major cost-driving factors are cART regimen, CD4-T cell count, cART drug resistance, and concomitant diseases. Viral load, pathology tests, and demographics have no significant impact. Standard non-nucleoside reverse transcriptase inhibitor-based regimens induce 28% lower total costs compared with standard PI/r regimens. Resistance to 3 or more antiretroviral classes induces a significant increase in costs. HIV treatment in Germany continues to be expensive. Majority of costs are attributable to cART. Main cost determinants are CD4-T cells count, comorbidity, genotypic antiviral resistance, and therapy regimen. Combinations of characteristics associated with higher expenditures enhance the increasing effect on the costs and induce high cost cases. PMID:27367993

The nucleus accumbens 5-HTR4-CART pathway ties anorexia to hyperactivity

PubMed Central

Jean, A; Laurent, L; Bockaert, J; Charnay, Y; Dusticier, N; Nieoullon, A; Barrot, M; Neve, R; Compan, V

2012-01-01

In mental diseases, the brain does not systematically adjust motor activity to feeding. Probably, the most outlined example is the association between hyperactivity and anorexia in Anorexia nervosa. The neural underpinnings of this ‘paradox', however, are poorly elucidated. Although anorexia and hyperactivity prevail over self-preservation, both symptoms rarely exist independently, suggesting commonalities in neural pathways, most likely in the reward system. We previously discovered an addictive molecular facet of anorexia, involving production, in the nucleus accumbens (NAc), of the same transcripts stimulated in response to cocaine and amphetamine (CART) upon stimulation of the 5-HT4 receptors (5-HTR4) or MDMA (ecstasy). Here, we tested whether this pathway predisposes not only to anorexia but also to hyperactivity. Following food restriction, mice are expected to overeat. However, selecting hyperactive and addiction-related animal models, we observed that mice lacking 5-HTR1B self-imposed food restriction after deprivation and still displayed anorexia and hyperactivity after ecstasy. Decryption of the mechanisms showed a gain-of-function of 5-HTR4 in the absence of 5-HTR1B, associated with CART surplus in the NAc and not in other brain areas. NAc-5-HTR4 overexpression upregulated NAc-CART, provoked anorexia and hyperactivity. NAc-5-HTR4 knockdown or blockade reduced ecstasy-induced hyperactivity. Finally, NAc-CART knockdown suppressed hyperactivity upon stimulation of the NAc-5-HTR4. Additionally, inactivating NAc-5-HTR4 suppressed ecstasy's preference, strengthening the rewarding facet of anorexia. In conclusion, the NAc-5-HTR4/CART pathway establishes a ‘tight-junction' between anorexia and hyperactivity, suggesting the existence of a primary functional unit susceptible to limit overeating associated with resting following homeostasis rules. PMID:23233022

CAR-T cells and allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia.

PubMed

Liu, Jun; Zhang, Xi; Zhong, Jiang F; Zhang, Cheng

2017-10-01

Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL. In this review, we first discuss the different types of CAR-T cells. We then discuss the treatment of relapsed/refractory ALL using only CAR-T cells. Finally, we discuss the use of CAR-T cells, followed by allo-HSCT, for the treatment of relapsed/refractory ALL.

Cart'Eaux: an automatic mapping procedure for wastewater networks using machine learning and data mining

NASA Astrophysics Data System (ADS)

Bailly, J. S.; Delenne, C.; Chahinian, N.; Bringay, S.; Commandré, B.; Chaumont, M.; Derras, M.; Deruelle, L.; Roche, M.; Rodriguez, F.; Subsol, G.; Teisseire, M.

2017-12-01

In France, local government institutions must establish a detailed description of wastewater networks. The information should be available, but it remains fragmented (different formats held by different stakeholders) and incomplete. In the "Cart'Eaux" project, a multidisciplinary team, including an industrial partner, develops a global methodology using Machine Learning and Data Mining approaches applied to various types of large data to recover information in the aim of mapping urban sewage systems for hydraulic modelling. Deep-learning is first applied using a Convolution Neural Network to localize manhole covers on 5 cm resolution aerial RGB images. The detected manhole covers are then automatically connected using a tree-shaped graph constrained by industry rules. Based on a Delaunay triangulation, connections are chosen to minimize a cost function depending on pipe length, slope and possible intersection with roads or buildings. A stochastic version of this algorithm is currently being developed to account for positional uncertainty and detection errors, and generate sets of probable networks. As more information is required for hydraulic modeling (slopes, diameters, materials, etc.), text data mining is used to extract network characteristics from data posted on the Web or available through governmental or specific databases. Using an appropriate list of keywords, the web is scoured for documents which are saved in text format. The thematic entities are identified and linked to the surrounding spatial and temporal entities. The methodology is developed and tested on two towns in southern France. The primary results are encouraging: 54% of manhole covers are detected with few false detections, enabling the reconstruction of probable networks. The data mining results are still being investigated. It is clear at this stage that getting numerical values on specific pipes will be challenging. Thus, when no information is found, decision rules will be used to assign admissible numerical values to enable the final hydraulic modelling. Consequently, sensitivity analysis of the hydraulic model will be performed to take into account the uncertainty associated with each piece of information. Project funded by the European Regional Development Fund and the Occitanie Region.

Using individual patient anatomy to predict protocol compliance for prostate intensity-modulated radiotherapy

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

Caine, Hannah; Whalley, Deborah; Kneebone, Andrew

If a prostate intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) plan has protocol violations, it is often a challenge knowing whether this is due to unfavorable anatomy or suboptimal planning. This study aimed to create a model to predict protocol violations based on patient anatomical variables and their potential relationship to target and organ at risk (OAR) end points in the setting of definitive, dose-escalated IMRT/VMAT prostate planning. Radiotherapy plans from 200 consecutive patients treated with definitive radiation for prostate cancer using IMRT or VMAT were analyzed. The first 100 patient plans (hypothesis-generating cohort) were examined to identifymore » anatomical variables that predict for dosimetric outcome, in particular OAR end points. Variables that scored significance were further assessed for their ability to predict protocol violations using a Classification and Regression Tree (CART) analysis. These results were then validated in a second group of 100 patients (validation cohort). In the initial analysis of the hypothesis-generating cohort, percentage of rectum overlap in the planning target volume (PTV) (%OR) and percentage of bladder overlap in the PTV (%OB) were highlighted as significant predictors of rectal and bladder dosimetry. Lymph node treatment was also significant for bladder outcomes. For the validation cohort, CART analysis showed that %OR of < 6%, 6% to 9% and > 9% predicted a 13%, 63%, and 100% rate of rectal protocol violations respectively. For the bladder, %OB of < 9% vs > 9% is associated with 13% vs 88% rate of bladder constraint violations when lymph nodes were not treated. If nodal irradiation was delivered, plans with a %OB of < 9% had a 59% risk of violations. Percentage of rectum and bladder within the PTV can be used to identify individual plan potential to achieve dose-volume histogram (DVH) constraints. A model based on these factors could be used to reduce planning time, improve work flow, and strengthen plan quality and consistency.« less

Is atmospheric pollution exposure during pregnancy associated with individual and contextual characteristics? A nationwide study in France.

PubMed

Ouidir, Marion; Lepeule, Johanna; Siroux, Valérie; Malherbe, Laure; Meleux, Frederik; Rivière, Emmanuel; Launay, Ludivine; Zaros, Cécile; Cheminat, Marie; Charles, Marie-Aline; Slama, Rémy

2017-10-01

Exposure to atmospheric pollutants is a danger for the health of pregnant mother and children. Our objective was to identify individual (socioeconomic and behavioural) and contextual factors associated with atmospheric pollution pregnancy exposure at the nationwide level. Among 14 921 women from the French nationwide ELFE (French Longitudinal Study of Children) mother-child cohort recruited in 2011, outdoor exposure levels of PM 2.5 , PM 10 (particulate matter <2.5 µm and <10 µm in diameter) and NO 2 (nitrogen dioxide) were estimated at the pregnancy home address from a dispersion model with 1 km resolution. We used classification and regression trees (CART) and linear regression to characterise the association of atmospheric pollutants with individual (maternal age, body mass index, parity, education level, relationship status, smoking status) and contextual (European Deprivation Index, urbanisation level) factors. Patterns of associations were globally similar across pollutants. For the CART approach, the highest tertile of exposure included mainly women not in a relationship living in urban and socially deprived areas, with lower education level. Linear regression models identified different determinants of atmospheric pollutants exposure according to the residential urbanisation level. In urban areas, atmospheric pollutants exposure increased with social deprivation, while in rural areas a U-shaped relationship was observed. We highlighted social inequalities in atmospheric pollutants exposure according to contextual characteristics such as urbanisation level and social deprivation and also according to individual characteristics such as education, being in a relationship and smoking status. In French urban areas, pregnant women from the most deprived neighbourhoods were those most exposed to health-threatening atmospheric pollutants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Practical application of cure mixture model for long-term censored survivor data from a withdrawal clinical trial of patients with major depressive disorder.

PubMed

Arano, Ichiro; Sugimoto, Tomoyuki; Hamasaki, Toshimitsu; Ohno, Yuko

2010-04-23

Survival analysis methods such as the Kaplan-Meier method, log-rank test, and Cox proportional hazards regression (Cox regression) are commonly used to analyze data from randomized withdrawal studies in patients with major depressive disorder. However, unfortunately, such common methods may be inappropriate when a long-term censored relapse-free time appears in data as the methods assume that if complete follow-up were possible for all individuals, each would eventually experience the event of interest. In this paper, to analyse data including such a long-term censored relapse-free time, we discuss a semi-parametric cure regression (Cox cure regression), which combines a logistic formulation for the probability of occurrence of an event with a Cox proportional hazards specification for the time of occurrence of the event. In specifying the treatment's effect on disease-free survival, we consider the fraction of long-term survivors and the risks associated with a relapse of the disease. In addition, we develop a tree-based method for the time to event data to identify groups of patients with differing prognoses (cure survival CART). Although analysis methods typically adapt the log-rank statistic for recursive partitioning procedures, the method applied here used a likelihood ratio (LR) test statistic from a fitting of cure survival regression assuming exponential and Weibull distributions for the latency time of relapse. The method is illustrated using data from a sertraline randomized withdrawal study in patients with major depressive disorder. We concluded that Cox cure regression reveals facts on who may be cured, and how the treatment and other factors effect on the cured incidence and on the relapse time of uncured patients, and that cure survival CART output provides easily understandable and interpretable information, useful both in identifying groups of patients with differing prognoses and in utilizing Cox cure regression models leading to meaningful interpretations.

A prognostic classifier for patients with colorectal cancer liver metastasis, based on AURKA, PTGS2 and MMP9.

PubMed

Goos, Jeroen A C M; Coupé, Veerle M H; van de Wiel, Mark A; Diosdado, Begoña; Delis-Van Diemen, Pien M; Hiemstra, Annemieke C; de Cuba, Erienne M V; Beliën, Jeroen A M; Menke-van der Houven van Oordt, C Willemien; Geldof, Albert A; Meijer, Gerrit A; Hoekstra, Otto S; Fijneman, Remond J A

2016-01-12

Prognosis of patients with colorectal cancer liver metastasis (CRCLM) is estimated based on clinicopathological models. Stratifying patients based on tumor biology may have additional value. Tissue micro-arrays (TMAs), containing resected CRCLM and corresponding primary tumors from a multi-institutional cohort of 507 patients, were immunohistochemically stained for 18 candidate biomarkers. Cross-validated hazard rate ratios (HRRs) for overall survival (OS) and the proportion of HRRs with opposite effect (P(HRR < 1) or P(HRR > 1)) were calculated. A classifier was constructed by classification and regression tree (CART) analysis and its prognostic value determined by permutation analysis. Correlations between protein expression in primary tumor-CRCLM pairs were calculated. Based on their putative prognostic value, EGFR (P(HRR < 1) = .02), AURKA (P(HRR < 1) = .02), VEGFA (P(HRR < 1) = .02), PTGS2 (P(HRR < 1) = .01), SLC2A1 (P(HRR > 1) < 01), HIF1α (P(HRR > 1) = .06), KCNQ1 (P(HRR > 1) = .09), CEA (P (HRR > 1) = .05) and MMP9 (P(HRR < 1) = .07) were included in the CART analysis (n = 201). The resulting classifier was based on AURKA, PTGS2 and MMP9 expression and was associated with OS (HRR 2.79, p < .001), also after multivariate analysis (HRR 3.57, p < .001). The prognostic value of the biomarker-based classifier was superior to the clinicopathological model (p = .001). Prognostic value was highest for colon cancer patients (HRR 5.71, p < .001) and patients not treated with systemic therapy (HRR 3.48, p < .01). Classification based on protein expression in primary tumors could be based on AURKA expression only (HRR 2.59, p = .04). A classifier was generated for patients with CRCLM with improved prognostic value compared to the standard clinicopathological prognostic parameters, which may aid selection of patients who may benefit from adjuvant systemic therapy.

Neurologic examination at 24–48 hours predicts functional outcomes in basilar artery occlusion stroke

PubMed Central

Rangaraju, Srikant; Jovin, Tudor G.; Frankel, Michael; Schonewille, Wouter J.; Algra, Ale; Kappelle, L. Jaap; Nogueira, Raul G.

2016-01-01

Background and Purpose Accurate long-term outcome prognostication in basilar artery occlusion (BAO) strokes may guide clinical management in the subacute stage. We determine the prognostic value of the follow-up neurologic examination using the NIH stroke scale (NIHSS) and identify 24–48 hours NIHSS risk categories in BAO patients. Methods Participants of an observational registry of radiologically-confirmed acute BAO (BASICS) with prospectively collected 24–48 hours NIHSS and 1-month modified Rankin Scale (mRS) scores were included. Uni- and multivariable modeling were performed to identify independent predictors of poor outcome. Predictive powers of baseline and 24–48 hour NIHSS for poor outcome (mRS 4–6) and 1-month mortality were determined by Receiver Operating Characteristic analyses. Classification and regression tree (CART) analysis was performed to identify risk groups. Results 376 of 619 BASICS participants were included of whom 65.4% had poor outcome. In multivariable analyses, 24–48 hours NIHSS (OR=1.28 [1.21–1.35]), history of minor stroke (OR=2.64 [1.04–6.74], time to treatment >6 hours (OR=3.07 [1.35–6.99]) and age (OR 1.02 [0.99–1.04] were retained in the final model as predictors of poor outcome. Prognostic power of 24–48 hours NIHSS was higher than baseline NIHSS for 1-month poor outcome (AUC 0.92 vs. 0.75) and mortality (AUC 0.85 vs. 0.72). CART analysis identified five 24–48 hour NIHSS risk categories with poor outcome rates of 9.4% (NIHSS 0–4), 36% (NIHSS 5–11), 84.3% (NIHSS 12–22), 96.1% (NIHSS 23–27) and 100% (NIHSS≥28). Conclusion 24–48 hour NIHSS accurately predicts 1-month poor outcome and mortality and represents a clinically valuable prognostic tool for the care of BAO patients. PMID:27586683

Artificial Intelligence and Amikacin Exposures Predictive of Outcomes in Multidrug-Resistant Tuberculosis Patients.

PubMed

Modongo, Chawangwa; Pasipanodya, Jotam G; Magazi, Beki T; Srivastava, Shashikant; Zetola, Nicola M; Williams, Scott M; Sirugo, Giorgio; Gumbo, Tawanda

2016-10-01

Aminoglycosides such as amikacin continue to be part of the backbone of treatment of multidrug-resistant tuberculosis (MDR-TB). We measured amikacin concentrations in 28 MDR-TB patients in Botswana receiving amikacin therapy together with oral levofloxacin, ethionamide, cycloserine, and pyrazinamide and calculated areas under the concentration-time curves from 0 to 24 h (AUC0-24). The patients were followed monthly for sputum culture conversion based on liquid cultures. The median duration of amikacin therapy was 184 (range, 28 to 866) days, at a median dose of 17.30 (range 11.11 to 19.23) mg/kg. Only 11 (39%) patients had sputum culture conversion during treatment; the rest failed. We utilized classification and regression tree analyses (CART) to examine all potential predictors of failure, including clinical and demographic features, comorbidities, and amikacin peak concentrations (Cmax), AUC0-24, and trough concentrations. The primary node for failure had two competing variables, Cmax of <67 mg/liter and AUC0-24 of <568.30 mg · h/L; weight of >41 kg was a secondary node with a score of 35% relative to the primary node. The area under the receiver operating characteristic curve for the CART model was an R(2) = 0.90 on posttest. In patients weighing >41 kg, sputum conversion was 3/3 (100%) in those with an amikacin Cmax of ≥67 mg/liter versus 3/15 (20%) in those with a Cmax of <67 mg/liter (relative risk [RR] = 5.00; 95% confidence interval [CI], 1.82 to 13.76). In all patients who had both amikacin Cmax and AUC0-24 below the threshold, 7/7 (100%) failed, compared to 7/15 (47%) of those who had these parameters above threshold (RR = 2.14; 95% CI, 1.25 to 43.68). These amikacin dose-schedule patterns and exposures are virtually the same as those identified in the hollow-fiber system model. Copyright © 2016 Modongo et al.

Evaluation of Nigerian hospital meal carts

NASA Astrophysics Data System (ADS)

Ayodeji, Sesan P.; Adeyeri, Michael K.; Omoniyi, Olaoluwa

2015-09-01

Hospital meal carts are used to deliver meals, drugs and some other materials to patients in the hospital environment. These carts which are moved manually by operators, the health workers, mostly do not comply with ergonomics guidelines and physical requirements of the equipment users in terms of anthropometry data of the region thus increasing the risk of musculoskeletal disorder among the meal cart users. This study carried out ergonomic evaluation of the available meal carts in some western Nigeria hospitals. A well-structured questionnaire has two major segments: Operational survey and biomechanical survey, which were administered to the health workers using hospital meal carts in some hospitals in southwestern Nigeria, and physical assessment, which was undertaken to collect data for the ergonomic evaluation. The responses from the questionnaires show that some areas on the existing hospital meal carts are of concern to the users which need to be improved upon.

A good walk spoiled: on the disappearance of golf as an active sport in America.

PubMed

Puterbaugh, James S

2011-07-01

During the past 60 years, there has been a major transition in the way golf is played in America. Its potential as exercise largely has been negated by the increase in motorized golf cart usage to approximately two of every three rounds played in this country. Accidents in golf carts have increased rapidly, which, by making the sport more dangerous, will likely bring future regulations. Consequently, playing golf has gradually become more of a public health threat than a benefit. The motorized cart also has resulted in an almost doubling of the size of golf courses, which now occupy a large amount of the built environment designated for activity. These changes are a major loss to society, portend future problems, and call for the sport to reevaluate its current model.

Cutpoints for Low Appendicular Lean Mass That Identify Older Adults With Clinically Significant Weakness

PubMed Central

Peters, Katherine W.; Shardell, Michelle D.; McLean, Robert R.; Dam, Thuy-Tien L.; Kenny, Anne M.; Fragala, Maren S.; Harris, Tamara B.; Kiel, Douglas P.; Guralnik, Jack M.; Ferrucci, Luigi; Kritchevsky, Stephen B.; Vassileva, Maria T.; Studenski, Stephanie A.; Alley, Dawn E.

2014-01-01

Background. Low lean mass is potentially clinically important in older persons, but criteria have not been empirically validated. As part of the FNIH (Foundation for the National Institutes of Health) Sarcopenia Project, this analysis sought to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that discriminate the presence or absence of weakness (defined in a previous report in the series as grip strength <26kg in men and <16kg in women). Methods. In pooled cross-sectional data stratified by sex (7,582 men and 3,688 women), classification and regression tree (CART) analysis was used to derive cutpoints for appendicular lean body mass (ALM) that best discriminated the presence or absence of weakness. Mixed-effects logistic regression was used to quantify the strength of the association between lean mass category and weakness. Results. In primary analyses, CART models identified cutpoints for low lean mass (ALM <19.75kg in men and <15.02kg in women). Sensitivity analyses using ALM divided by body mass index (BMI: ALMBMI) identified a secondary definition (ALMBMI <0.789 in men and ALMBMI <0.512 in women). As expected, after accounting for study and age, low lean mass (compared with higher lean mass) was associated with weakness by both the primary (men, odds ratio [OR]: 6.9 [95% CI: 5.4, 8.9]; women, OR: 3.6 [95% CI: 2.9, 4.3]) and secondary definitions (men, OR: 4.3 [95% CI: 3.4, 5.5]; women, OR: 2.2 [95% CI: 1.8, 2.8]). Conclusions. ALM cutpoints derived from a large, diverse sample of older adults identified lean mass thresholds below which older adults had a higher likelihood of weakness. PMID:24737559

Predictors of pharmacological treatment outcomes with atomoxetine or methylphenidate in patients with attention-deficit/hyperactivity disorder from China, Egypt, Lebanon, Russian Federation, Taiwan, and United Arab Emirates.

PubMed

Treuer, T; Feng, Q; Desaiah, D; Altin, M; Wu, S; El-Shafei, A; Serebryakova, E; Gado, M; Faries, D

2014-09-01

The reduced availability of data from non-Western countries limits our ability to understand attention-deficit/hyperactivity disorder (ADHD) treatment outcomes, specifically, adherence and persistence of ADHD in children and adolescents. This analysis assessed predictors of treatment outcomes in a non-Western cohort of patients with ADHD treated with atomoxetine or methylphenidate. Data from a 12-month, prospective, observational study in outpatients aged 6-17 years treated with atomoxetine (N = 234) or methylphenidate (N = 221) were analysed post hoc to determine potential predictors of treatment outcomes. Participating countries included the Russian Federation, China, Taiwan, Egypt, United Arab Emirates and Lebanon. Factors associated with remission were analysed with stepwise multiple logistic regression and classification and regression trees (CART). Cox proportional hazards models with propensity score adjustment assessed differences in atomoxetine persistence among initial-dose cohorts. In patients treated with atomoxetine who had available dosing information (N = 134), Cox proportional hazards revealed lower (< 0.5 mg/kg) initial dose was significantly associated with shorter medication persistence (p < 0.01). multiple logistic regression analysis revealed greater rates of remission for atomoxetine-treated patients were associated with age (older), country (United Arab Emirates) and gender (female) (all p < 0.05). CART analysis confirmed older age and lack of specific phobias were associated with greater remission rates. For methylphenidate, greater baseline weight (highly correlated with the age factor found for atomoxetine) and prior atomoxetine use were associated with greater remission rates. These findings may help clinicians assess factors upon initiation of ADHD treatment to improve course prediction, proper dosing and treatment adherence and persistence. Observational study, therefore no registration. © 2014 John Wiley & Sons Ltd.

Different responses of weather factors on hand, foot and mouth disease in three different climate areas of Gansu, China.

PubMed

Gou, Faxiang; Liu, Xinfeng; He, Jian; Liu, Dongpeng; Cheng, Yao; Liu, Haixia; Yang, Xiaoting; Wei, Kongfu; Zheng, Yunhe; Jiang, Xiaojuan; Meng, Lei; Hu, Wenbiao

2018-01-08

To determine the linear and non-linear interacting relationships between weather factors and hand, foot and mouth disease (HFMD) in children in Gansu, China, and gain further traction as an early warning signal based on weather variability for HFMD transmission. Weekly HFMD cases aged less than 15 and meteorological information from 2010 to 2014 in Jiuquan, Lanzhou and Tianshu, Gansu, China were collected. Generalized linear regression models (GLM) with Poisson link and classification and regression trees (CART) were employed to determine the combined and interactive relationship of weather factors and HFMD in both linear and non-linear ways. GLM suggested an increase in weekly HFMD of 5.9% [95% confidence interval (CI): 5.4%, 6.5%] in Tianshui, 2.8% [2.5%, 3.1%] in Lanzhou and 1.8% [1.4%, 2.2%] in Jiuquan in association with a 1 °C increase in average temperature, respectively. And 1% increase of relative humidity could increase weekly HFMD of 2.47% [2.23%, 2.71%] in Lanzhou and 1.11% [0.72%, 1.51%] in Tianshui. CART revealed that average temperature and relative humidity were the first two important determinants, and their threshold values for average temperature deceased from 20 °C of Jiuquan to 16 °C in Tianshui; and for relative humidity, threshold values increased from 38% of Jiuquan to 65% of Tianshui. Average temperature was the primary weather factor in three areas, more sensitive in southeast Tianshui, compared with northwest Jiuquan; Relative humidity's effect on HFMD showed a non-linear interacting relationship with average temperature.

Radiocarbon Dating of an Olive Tree Cross-Section: New Insights on Growth Patterns and Implications for Age Estimation of Olive Trees.

PubMed

Ehrlich, Yael; Regev, Lior; Kerem, Zohar; Boaretto, Elisabetta

2017-01-01

The age of living massive olive trees is often assumed to be between hundreds and even thousands of years. These estimations are usually based on the girth of the trunk and an extrapolation based on a theoretical annual growth rate. It is difficult to objectively verify these claims, as a monumental tree may not be cut down for analysis of its cross-section. In addition, the inner and oldest part of the trunk in olive trees usually rots, precluding the possibility of carting out radiocarbon analysis of material from the first years of life of the tree. In this work we present a cross-section of an olive tree, previously estimated to be hundreds of years old, which was cut down post-mortem in 2013. The cross-section was radiocarbon dated at numerous points following the natural growth pattern, which was made possible to observe by viewing the entire cross-section. Annual growth rate values were calculated and compared between different radii. The cross-section also revealed a nearly independent segment of growth, which would clearly offset any estimations based solely on girth calculations. Multiple piths were identified, indicating the beginning of branching within the trunk. Different radii were found to have comparable growth rates, resulting in similar estimates dating the piths to the 19th century. The estimated age of the piths represent a terminus ante quem for the age of the tree, as these are piths of separate branches. However, the tree is likely not many years older than the dated piths, and certainly not centuries older. The oldest radiocarbon-datable material in this cross-section was less than 200 years old, which is in agreement with most other radiocarbon dates of internal wood from living olive trees, rarely older than 300 years.

Cable-Dispensing Cart

NASA Technical Reports Server (NTRS)

Bredberg, Alan S.

2003-01-01

A versatile cable-dispensing cart can support as many as a few dozen reels of cable, wire, and/or rope. The cart can be adjusted to accommodate reels of various diameters and widths, and can be expanded, contracted, or otherwise reconfigured by use of easily installable and removable parts that can be carried onboard. Among these parts are dispensing rods and a cable guide that enables dispensing of cables without affecting the direction of pull. Individual reels can be mounted on or removed from the cart without affecting the other reels: this feature facilitates the replacement or reuse of partially depleted reels, thereby helping to reduce waste. Multiple cables, wires, or ropes can be dispensed simultaneously. For maneuverability, the cart is mounted on three wheels. Once it has been positioned, the cart is supported by rubber mounts for stability and for prevention of sliding or rolling during dispensing operations. The stability and safety of the cart are enhanced by a low-center-of-gravity design. The cart can readily be disassembled into smaller units for storage or shipping, then reassembled in the desired configuration at a job site.

Shoulder joint loading and posture during medicine cart pushing task.

PubMed

Xu, Xu; Lin, Jia-Hua; Boyer, Jon

2013-01-01

Excessive physical loads and awkward shoulder postures during pushing and pulling are risk factors for shoulder pain. Pushing a medicine cart is a major component of a work shift for nurses and medical assistants in hospitals and other health care facilities. A laboratory experiment was conducted to examine the effects of common factors (e.g., lane congestion, cart load stability, floor surface friction) on shoulder joint moment and shoulder elevation angle of participants during cart pushing. Participants pushed a medicine cart on straight tracks and turning around right-angle corners. Peak shoulder joint moments reached 25.1 Nm, 20.3 Nm, and 26.8 Nm for initial, transition, and turning phases of the pushing tasks, indicating that shoulder joint loading while pushing a medical cart is comparable to levels previously reported from heavy manual activities encountered in industry (e.g., garbage collection). Also, except for user experience, all other main study factors, including congestion level, cart load stability, location of transition strip, shoulder tendency, surface friction, and handedness, significantly influenced shoulder joint moment and shoulder elevation angle. The findings provide a better understanding of shoulder exposures associated with medicine cart operations and may be helpful in designing and optimizing the physical environment where medicine carts are used.

Survival of HIV-1 vertically infected children

PubMed Central

Davies, Mary-Ann; Gibb, Diana; Turkova, Anna

2017-01-01

Purpose of review It is 20 years since the start of the combination antiretroviral therapy (cART) era and >10 years since cART scale-up began in resource-limited settings. We examined survival of vertically HIV-infected infants and children in the cART era. Recent findings Good survival has been achieved on cART in all settings with up to ten-fold mortality reductions compared to before cART availability. Although mortality risk remains high in the first few months after cART initiation in young children with severe disease, it drops rapidly thereafter even for those who started with advanced disease, and longer term mortality risk is low. However, suboptimal retention on cART in routine programs threatens good survival outcomes and even on treatment children continue to experience high comorbidity risk; infections remain the major cause of death. Interventions to address infection risk include co-trimoxazole prophylaxis, isoniazid preventive therapy, routine childhood and influenza immunization and improving maternal survival. Summary Pediatric survival has improved substantially with cART and HIV-infected children are aging into adulthood. It is important to ensure access to diagnosis and early cART, good program retention and optimal co-morbidity prophylaxis and treatment to achieve the best possible long-term survival and health outcomes for vertically infected children. PMID:27716730

Combination antiretroviral therapy and cancer risk.

PubMed

Borges, Álvaro H

2017-01-01

To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer risk. The relationship between cART exposure and cancer risk is complex and nuanced. It is an intriguing fact that, whether initiated during severe immunosuppression or not, cART reduces risk of Kaposi sarcoma and NHL. Further research should identify mediators of the benefit of immediate cART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.

Myeloid Conditioning with c-kit-Targeted CAR-T Cells Enables Donor Stem Cell Engraftment.

PubMed

Arai, Yasuyuki; Choi, Uimook; Corsino, Cristina I; Koontz, Sherry M; Tajima, Masaki; Sweeney, Colin L; Black, Mary A; Feldman, Steven A; Dinauer, Mary C; Malech, Harry L

2018-05-02

We report a novel approach to bone marrow (BM) conditioning using c-kit-targeted chimeric antigen receptor T (c-kit CAR-T) cells in mice. Previous reports using anti-c-kit or anti-CD45 antibody linked to a toxin such as saporin have been promising. We developed a distinctly different approach using c-kit CAR-T cells. Initial studies demonstrated in vitro killing of hematopoietic stem cells by c-kit CAR-T cells but poor expansion in vivo and poor migration of CAR-T cells into BM. Pre-treatment of recipient mice with low-dose cyclophosphamide (125 mg/kg) together with CXCR4 transduction in the CAR-T cells enhanced trafficking to and expansion in BM (<1%-13.1%). This resulted in significant depletion of the BM c-kit + population (9.0%-0.1%). Because congenic Thy1.1 CAR-T cells were used in the Thy1.2-recipient mice, anti-Thy1.1 antibody could be used to deplete CAR-T cells in vivo before donor BM transplant. This achieved 20%-40% multilineage engraftment. We applied this conditioning to achieve an average of 28% correction of chronic granulomatous disease mice by wild-type BM transplant. Our findings provide a proof of concept that c-kit CAR-T cells can achieve effective BM conditioning without chemo-/radiotherapy. Our work also demonstrates that co-expression of a trafficking receptor can enhance targeting of CAR-T cells to a designated tissue. Published by Elsevier Inc.

Evaluation of the Placement of Mobile Fruit and Vegetable Vendors to Alleviate Food Deserts in New York City

PubMed Central

Cromley, Ellen K.; Fox, Ashley M.; Horowitz, Carol R.

2014-01-01

Introduction In 2008, the New York City (NYC) health department licensed special mobile produce vendors (Green Carts) to increase access to fruits and vegetables in neighborhoods with the lowest reported fruit and vegetable consumption and the highest obesity rates. Because economic incentives may push vendors to locate in more trafficked, less produce-deprived areas, we examined characteristics of areas with and without Green Carts to explore whether Carts are positioned to reach the intended populations. Methods Using ArcGIS software, we mapped known NYC Green Cart locations noted through 2013 and generated a list of potential (candidate) sites where Carts could have located. We compared the food environment (via categorizing “healthy” or “unhealthy” food stores using federal classification codes corroborated by online storefront images) and other factors that might explain Cart location (eg, demographic, business, neighborhood characteristics) near actual and candidate sites descriptively and inferentially. Results Seven percent of Green Carts (n = 265) were in food deserts (no healthy stores within one-quarter mile) compared with 36% of candidate sites (n = 644, P < .001). Most Carts (78%) were near 2 or more healthy stores. Green Carts had nearly 60 times the odds of locating near subway stops (P < .001), were closer to large employers (odds ratio [OR], 6.4; P < .001), other food stores (OR, 14.1; P < .001), and in more populous tracts (OR, 2.9, P <.01) compared with candidate sites. Conclusion Green Carts were rarely in food deserts and usually had multiple healthy stores nearby, suggesting that Carts may not be serving the neediest neighborhoods. Exploration of Carts’ benefits in non–food desert areas is needed, but incentivizing vendors to locate in still-deprived places may increase program impact. PMID:25211506

Distribution of cocaine- and amphetamine-regulated transcript in the hippocampal formation of the guinea pig and domestic pig.

PubMed

Kolenkiewicz, M; Robak, A; Równiak, M; Bogus-Nowakowska, K; Całka, J; Majewski, M

2009-02-01

This study provides a detailed description concerning the distribution of cocaineand amphetamine-regulated transcript (CART) subunits - CART(61-102) and rhCART(28-116) - in the hippocampal formation (HF) of the guinea pig and domestic pig, focussing on the dentate gyrus (DG) and hippocampus proper (HP). Although in both studied species CART-immunoreactive (CART-IR) neuronal somata and processes were present generally in the same layers, some species-specific differences were still found. In the granular layer (GL) of both species, the ovalshaped neurons and some thick varicose fibres were encountered. In the guinea pig there was an immunoreactive "band of dots", probably representing crosssectioned terminals within the DG molecular layer (MOL), whereas in the domestic pig, some varicose fibres were detected, thus suggesting a different orientation of, at least, some nerve terminals. Furthermore, some CART-positive cells and fibres were observed in the hilus (HL) of the guinea pig, whereas in the analogical part of the domestic pig only nerve terminals were labelled. In both species, in the pyramidal layer (PL) of the hippocampus proper, CART-IR triangular somata were observed in the CA3 sector, as well as some positive processes in MOL; however, a few immunoreactive perikarya were found only in the CA1 sector of the guinea pig. As regards the localization patterns of two isoforms of CART in the guinea pig, both peptide fragments were present simultaneously in each of the labelled neurons or fibres, whereas in the domestic pig three types of fibres may be distinguished within the area of the DG. In the hilus and MOL of the dentate gyrus, there were fibres expressing both isoforms of CART in their whole length (fibres of the first type). Fibres of the second type (in GL) coexpressed both peptides only on their short segments, and the last ones (in MOL) expressed solely rhCART(28-116). These results indicate that the distribution of the two CART isoforms are specifically related, thus the relationship between the two CART isoforms may imply different metabolic profiles of CART-expressing neurons.

Preconception use of cART by HIV-positive pregnant women increases the risk of infants being born small for gestational age.

PubMed

Snijdewind, Ingrid J M; Smit, Colette; Godfried, Mieke H; Bakker, Rachel; Nellen, Jeannine F J B; Jaddoe, Vincent W V; van Leeuwen, Elisabeth; Reiss, Peter; Steegers, Eric A P; van der Ende, Marchina E

2018-01-01

The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands. We included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015. Multivariate logistic regression analysis for single and multiple pregnancies was used to evaluate predictors of small for gestational age (SGA, birth weight <10th percentile for gestational age), low birth weight and preterm delivery. A total of 1392 children born to 1022 mothers were included. Of these, 331 (23.8%) children were SGA. Women starting cART before conception had an increased risk of having a SGA infant compared to women starting cART after conception (OR 1.35, 95% CI 1.03-1.77, p = 0.03). The risk for SGA was highest in women who started a protease inhibitor-(PI) based regimen prior to pregnancy, compared with women who initiated PI-based cART during pregnancy. While the association of preterm delivery and preconception cART was significant in univariate analysis, on multivariate analysis only a non-significant trend was observed (OR 1.39, 95% CI 0.94-1.92, p = 0.06) in women who had started cART before compared to after conception. In multivariate analysis, the risk of low birth weight (OR 1.34, 95% CI 0.94-1.92, p = 0.11) was not significantly increased in women who had started cART prior to conception compared to after conception. In our cohort of pregnant HIV-positive women, the use of cART prior to conception, most notably a PI-based regimen, was associated with intrauterine growth restriction resulting in SGA. Data showed a non-significant trend in the risk of PTD associated with preconception use of cART compared to its use after conception. More studies are needed with regard to the mechanisms taking place in the placenta during fetal growth in pregnant HIV-positive women using cART. It will only be with this knowledge that we can begin to understand the potential impact of HIV and cART on the fetus, in order to be able to determine the optimal individualised drug regimen for HIV-infected women of childbearing age.

Preconception use of cART by HIV-positive pregnant women increases the risk of infants being born small for gestational age

PubMed Central

Smit, Colette; Godfried, Mieke H.; Bakker, Rachel; Nellen, Jeannine F. J. B.; Jaddoe, Vincent W. V.; van Leeuwen, Elisabeth; Reiss, Peter; Steegers, Eric A. P.; van der Ende, Marchina E.

2018-01-01

Background The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands. Materials and methods We included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015. Multivariate logistic regression analysis for single and multiple pregnancies was used to evaluate predictors of small for gestational age (SGA, birth weight <10th percentile for gestational age), low birth weight and preterm delivery. Results A total of 1392 children born to 1022 mothers were included. Of these, 331 (23.8%) children were SGA. Women starting cART before conception had an increased risk of having a SGA infant compared to women starting cART after conception (OR 1.35, 95% CI 1.03−1.77, p = 0.03). The risk for SGA was highest in women who started a protease inhibitor-(PI) based regimen prior to pregnancy, compared with women who initiated PI-based cART during pregnancy. While the association of preterm delivery and preconception cART was significant in univariate analysis, on multivariate analysis only a non-significant trend was observed (OR 1.39, 95% CI 0.94−1.92, p = 0.06) in women who had started cART before compared to after conception. In multivariate analysis, the risk of low birth weight (OR 1.34, 95% CI 0.94−1.92, p = 0.11) was not significantly increased in women who had started cART prior to conception compared to after conception. Conclusion In our cohort of pregnant HIV-positive women, the use of cART prior to conception, most notably a PI-based regimen, was associated with intrauterine growth restriction resulting in SGA. Data showed a non-significant trend in the risk of PTD associated with preconception use of cART compared to its use after conception. More studies are needed with regard to the mechanisms taking place in the placenta during fetal growth in pregnant HIV-positive women using cART. It will only be with this knowledge that we can begin to understand the potential impact of HIV and cART on the fetus, in order to be able to determine the optimal individualised drug regimen for HIV-infected women of childbearing age. PMID:29351561

Service Cart For Engines

NASA Technical Reports Server (NTRS)

Ng, Gim Shek

1995-01-01

Cart supports rear-mounted air-cooled engine from Volkswagen or Porsche automobile. One person removes, repairs, tests, and reinstalls engine of car, van, or home-built airplane. Consists of framework of wood, steel, and aluminum components supported by four wheels. Engine lifted from vehicle by hydraulic jack and gently lowered onto waiting cart. Jack removed from under engine. Rear of vehicle raised just enough that engine can be rolled out from under it. Cart easily supports 200-lb engine. Also used to hold transmission. With removable sheet-metal top, cart used as portable seat.

Calibration of the maximum carboxylation velocity (Vcmax) using data mining techniques and ecophysiological data from the Brazilian semiarid region, for use in Dynamic Global Vegetation Models.

PubMed

Rezende, L F C; Arenque-Musa, B C; Moura, M S B; Aidar, S T; Von Randow, C; Menezes, R S C; Ometto, J P B H

2016-06-01

The semiarid region of northeastern Brazil, the Caatinga, is extremely important due to its biodiversity and endemism. Measurements of plant physiology are crucial to the calibration of Dynamic Global Vegetation Models (DGVMs) that are currently used to simulate the responses of vegetation in face of global changes. In a field work realized in an area of preserved Caatinga forest located in Petrolina, Pernambuco, measurements of carbon assimilation (in response to light and CO2) were performed on 11 individuals of Poincianella microphylla, a native species that is abundant in this region. These data were used to calibrate the maximum carboxylation velocity (Vcmax) used in the INLAND model. The calibration techniques used were Multiple Linear Regression (MLR), and data mining techniques as the Classification And Regression Tree (CART) and K-MEANS. The results were compared to the UNCALIBRATED model. It was found that simulated Gross Primary Productivity (GPP) reached 72% of observed GPP when using the calibrated Vcmax values, whereas the UNCALIBRATED approach accounted for 42% of observed GPP. Thus, this work shows the benefits of calibrating DGVMs using field ecophysiological measurements, especially in areas where field data is scarce or non-existent, such as in the Caatinga.

Mother-to-child transmission of HIV and its predictors among HIV-exposed infants at Bamenda Regional Hospital, Cameroon

PubMed Central

Mom, Njong A.

2017-01-01

Background Mother-to-child transmission (MTCT) of HIV, has been a major global public health burden. Despite the use of antiretroviral prophylaxis by HIV-positive pregnant women and their infants, safe obstetric practice and safe infant feeding habits in the prevention of MTCT of HIV, the prevalence of HIV among HIV-exposed infants is still high in Cameroon. Objective Our objectives were to determine the prevalence, assess the predictors and determine the effect of combination antiretroviral therapy (cART) on MTCT of HIV at the regional hospital in Bamenda, Cameroon. Methods This was a retrospective study. Secondary data from 877 HIV-exposed infants aged ≤ 72 weeks were extracted from the records between January 2008 and December 2014. The predictors and effect of cART on MTCT of HIV were analysed using a multivariable logistic regression model and risk analysis, respectively. Results Out of 877 HIV-exposed infants, 62 were positive for HIV, giving a prevalence of 7.1%. Maternal antiretroviral intervention and infant age group were statistically significant predictors of MTCT of HIV. HIV-positive mothers who were on cART were 2.49 times less likely to transmit HIV than those who were not on cART. Conclusion In order to reduce the prevalence of HIV among HIV-exposed infants, maternal antiretroviral intervention should be targeted and the use of cART by HIV-positive pregnant women should be encouraged. PMID:29435421

Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies

PubMed Central

Rodgers, David T.; Mazagova, Magdalena; Hampton, Eric N.; Cao, Yu; Ramadoss, Nitya S.; Hardy, Ian R.; Schulman, Andrew; Du, Juanjuan; Wang, Feng; Singer, Oded; Ma, Jennifer; Nunez, Vanessa; Shen, Jiayin; Woods, Ashley K.; Wright, Timothy M.; Schultz, Peter G.; Kim, Chan Hyuk; Young, Travis S.

2016-01-01

Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive results in clinical trials for B-cell malignancies. However, safety concerns related to the inability to control CAR-T cells once infused into the patient remain a significant challenge. Here we report the engineering of recombinant antibody-based bifunctional switches that consist of a tumor antigen-specific Fab molecule engrafted with a peptide neo-epitope, which is bound exclusively by a peptide-specific switchable CAR-T cell (sCAR-T). The switch redirects the activity of the bio-orthogonal sCAR-T cells through the selective formation of immunological synapses, in which the sCAR-T cell, switch, and target cell interact in a structurally defined and temporally controlled manner. Optimized switches specific for CD19 controlled the activity, tissue-homing, cytokine release, and phenotype of sCAR-T cells in a dose-titratable manner in a Nalm-6 xenograft rodent model of B-cell leukemia. The sCAR–T-cell dosing regimen could be tuned to provide efficacy comparable to the corresponding conventional CART-19, but with lower cytokine levels, thereby offering a method of mitigating cytokine release syndrome in clinical translation. Furthermore, we demonstrate that this methodology is readily adaptable to targeting CD20 on cancer cells using the same sCAR-T cell, suggesting that this approach may be broadly applicable to heterogeneous and resistant tumor populations, as well as other liquid and solid tumor antigens. PMID:26759369

Reprogramming T-cells for adoptive immunotherapy of ovarian cancer.

PubMed

Genta, Sofia; Ghisoni, Eleonora; Giannone, Gaia; Mittica, Gloria; Valabrega, Giorgio

2018-04-01

Epithelial ovarian cancer (EOC) is the most common cause of death among gynecological malignancies. Despite surgical and pharmacological efforts to improve patients' outcome, persistent and recurrent EOC remains an un-eradicable disease. Chimeric associated antigens (CAR) T cells are T lymphocytes expressing an engineered T cell receptor that activate the immune response after an MHC unrestricted recognition of specific antigens, including tumor associated antigens (TAAs). CART cells have been shown to be effective in the treatment of hematologic tumors even if frequently associated with potentially severe toxicity and high production costs. Areas covered: In this review, we will focus on preclinical and clinical studies evaluating CART activity in EOC in order to identify possible difficulties and advantages of their use in this particular setting. Expert Opinion: The pattern of diffusion within the peritoneal cavity, the tumor microenvironment and the high rate of TAAs make EOC a particularly interesting model for CART cells use. Data from preclinical studies indicate a potential activity of CARTs in EOC, but robust clinical data are still awaited. Further studies are needed to determine the best methods of administration and the most effective CAR type to treat EOC patients.

Low speed vehicle passenger ejection restraint effectiveness.

PubMed

Seluga, Kristopher J; Ojalvo, Irving U; Obert, Richard M

2005-07-01

Current golf carts and LSV's (Low Speed Vehicles) produce a significant number of passenger ejections during sharp turns. These LSV's do not typically possess seatbelts, but do provide outboard bench seat hip restraints that also serve as handholds. However, many current restraint designs appear incapable of preventing passenger ejections due to their low height and inefficient handhold position. Alternative handhold and hip restraint designs may improve passenger safety. Accordingly, this paper examines minimum size requirements for hip restraints to prevent passenger ejection during sharp turns and evaluates the effectiveness of a handhold mounted at the center of the bench seat. In this study, a simulation of a turning cart supplies the dynamic input to a biomechanical model of an adult male seated in a golf cart. Various restraint combinations are considered, both with and without the central handhold, to determine the likelihood of passenger ejection. It is shown that only the largest restraint geometries prevent passenger ejection. Adequate hip restraints should be much larger than current designs and a central handhold should be provided. In this way, golf cart and LSV manufacturers could reduce passenger ejections and improve fleet safety by incorporating recommendations provided herein.

A soil map of a large watershed in China: applying digital soil mapping in a data sparse region

NASA Astrophysics Data System (ADS)

Barthold, F.; Blank, B.; Wiesmeier, M.; Breuer, L.; Frede, H.-G.

2009-04-01

Prediction of soil classes in data sparse regions is a major research challenge. With the advent of machine learning the possibilities to spatially predict soil classes have increased tremendously and given birth to new possibilities in soil mapping. Digital soil mapping is a research field that has been established during the last decades and has been accepted widely. We now need to develop tools to reduce the uncertainty in soil predictions. This is especially challenging in data sparse regions. One approach to do this is to implement soil taxonomic distance as a classification error criterion in classification and regression trees (CART) as suggested by Minasny et al. (Geoderma 142 (2007) 285-293). This approach assumes that the classification error should be larger between soils that are more dissimilar, i.e. differ in a larger number of soil properties, and smaller between more similar soils. Our study area is the Xilin River Basin, which is located in central Inner Mongolia in China. It is characterized by semi arid climate conditions and is representative for the natural occurring steppe ecosystem. The study area comprises 3600 km2. We applied a random, stratified sampling design after McKenzie and Ryan (Geoderma 89 (1999) 67-94) with landuse and topography as stratifying variables. We defined 10 sampling classes, from each class 14 replicates were randomly drawn and sampled. The dataset was split into 100 soil profiles for training and 40 soil profiles for validation. We then applied classification and regression trees (CART) to quantify the relationships between soil classes and environmental covariates. The classification tree explained 75.5% of the variance with land use and geology as most important predictor variables. Among the 8 soil classes that we predicted, the Kastanozems cover most of the area. They are predominantly found in steppe areas. However, even some of the soils at sand dune sites, which were thought to show only little soil formation, can be classified as Kastanozems. Besides the Kastanozems, Regosols are most common at the sand dune sites as well as at sites that are defined as bare soil which are characterized by little or no vegetation. Gleysols are mostly found at sites in the vicinity of the Xilin river, which are connected to the groundwater. They can also be found in small valleys or depressions where sub-surface waters from neighboring areas collect. The richest soils are found in mountain meadow areas. Pedogenetic conditions here are most favorable and lead to the formation of Chernozems with deep humic Ah horizons. Other soil types that occur in the study area are Arenosols, Calcisols, Cambisol and Phaeozems. In addition, soil taxonomic distance is implemented into the decision tree procedure as a measure of classification error. The results of incorporating taxonomic distance as a loss function in the decision tree will be compared with the standard application of the decision tree.

Effect of desipramine and citalopram treatment on forced swimming test-induced changes in cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in mice.

PubMed

Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Kim, Jin Wook; Kim, Jeong Min; Shin, Kyung Ho

2014-05-01

Recent study demonstrates antidepressant-like effect of cocaine- and amphetamine-regulated transcript (CART) in the forced swimming test (FST), but less is known about whether antidepressant treatments alter levels of CART immunoreactivity (CART-IR) in the FST. To explore this possibility, we assessed the treatment effects of desipramine and citalopram, which inhibit the reuptake of norepinephrine and serotonin into the presynaptic terminals, respectively, on changes in levels of CART-IR before and after the test swim in mouse brain. Levels of CART-IR in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), and hypothalamic paraventricular nucleus (PVN) were significantly increased before the test swim by desipramine and citalopram treatments. This increase in CART-IR in the AcbSh, dBNST, and PVN before the test swim remained elevated by desipramine treatment after the test swim, but this increase in these brain areas returned to near control levels after test swim by citalopram treatment. Citalopram, but not desipramine, treatment increased levels of CART-IR in the central nucleus of the amygdala (CeA) and the locus ceruleus (LC) before the test swim, and this increase was returned to control levels after the test swim in the CeA, but not in the LC. These results suggest common and distinct regulation of CART by desipramine and citalopram treatments in the FST and raise the possibility that CART in the AcbSh, dBNST, and CeA may be involved in antidepressant-like effect in the FST.

The Impact of Verbal Prompts on Child Safety-Belt Use in Shopping Carts

ERIC Educational Resources Information Center

Barker, Mae R.; Bailey, Jon S.; Lee, Natalie

2004-01-01

Each year thousands of children are injured by falling from shopping carts. Buckling children into the seats of shopping carts could prevent many of these injuries. A combined reversal and multiple baseline across settings design was used to evaluate the impact of verbal prompts on shopping cart safety-belt use in two stores. Safety-belt use…

Art on a Cart: A National Mixed Methods Investigation of Elementary Art Teacher Experiences and Perceptions

ERIC Educational Resources Information Center

Lung, Heidi K.

2013-01-01

This study investigated the practice of elementary art teachers who utilize carts for the delivery of art lessons; to understand how the art on a cart practice influences art educators' approaches to curriculum development and instruction; and to identify challenges, benefits, and best practices. The practice of art on a cart is defined as the…

When to Initiate Combined Antiretroviral Therapy to Reduce Mortality and AIDS-Defining Illness in HIV-Infected Persons in Developed Countries

PubMed Central

2012-01-01

Background Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 109 cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. Objective To identify the optimal CD4 cell count at which cART should be initiated. Design Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 109 cells/L. Setting HIV clinics in Europe and the Veterans Health Administration system in the United States. Patients 20 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 109 cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 109 cells/L and were included in the analysis. Measurements Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. Results Compared with initiating cART at the CD4 cell count threshold of 0.500 × 109 cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations CD4 cell count at cART initiation was not randomized. Residual confounding may exist. Conclusion Initiation of cART at a threshold CD4 count of 0.500 × 109 cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 ×109 cells/L. Primary Funding Source National Institutes of Health. PMID:21502648

When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study.

PubMed

Cain, Lauren E; Logan, Roger; Robins, James M; Sterne, Jonathan A C; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; van Sighem, Ard; de Wolf, Frank; Bucher, Heiner C; von Wyl, Viktor; Esteve, Anna; Casabona, Jordi; del Amo, Julia; Moreno, Santiago; Seng, Remonie; Meyer, Laurence; Perez-Hoyos, Santiago; Muga, Roberto; Lodi, Sara; Lanoy, Emilie; Costagliola, Dominique; Hernan, Miguel A

2011-04-19

Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. To identify the optimal CD4 cell count at which cART should be initiated. Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. HIV clinics in Europe and the Veterans Health Administration system in the United States. 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. CD4 cell count at cART initiation was not randomized. Residual confounding may exist. Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.

Effect of gender and calendar year on time to and duration of virologic suppression among antiretroviral-naïve HIV-infected individuals initiating combination antiretroviral therapy.

PubMed

Raboud, Janet; Blitz, Sandra; Walmsley, Sharon; Thompson, Courtney; Rourke, Sean B; Loutfy, Mona R

2010-01-01

To determine the effects of gender and calendar year on time to and duration of virologic suppression among HIV-infected antiretroviral-naïve individuals initiating combination antiretroviral therapy (cART). Ontario Cohort Study antiretroviral-naïve participants who initiated cART after December 31, 1998, and who had ≥2 follow-up viral loads were included. Multivariable Cox proportional hazard models were used to estimate the effects of gender and calendar year on times to virologic suppression and rebound. Of the 840 patients, 81% were male (median age 40 years; interquartile range [IQR], 34-46). Time to virologic suppression was shorter among women (hazard ratio [HR]=1.27, P=.01) and in more recent calendar time periods (2002-2004: HR, 1.04, P=.67; 2005-2006: HR, 1.22, P=.06; 2007-2008: HR, 1.36, P=.004) compared to 1999-2001 after adjusting for age and type of cART regimens. Women had shorter times to virologic rebound (HR, 1.57; P<.01) after adjusting for age, injection drug use, and type of cART regimen. However, 14/18 (78%) women suspected to be taking cART only for prevention of mother-to-child transmission of HIV experienced virologic rebound compared to 28% of women who required cART for their own health, suggesting that the increased rate of virologic rebound was due to women stopping ART at the termination of a pregnancy if they did not need it for their own health. Rates of rebound did not differ by calendar year period. Time to virologic suppression has steadily decreased over time while duration of suppression remained stable. Time to virologic suppression was shorter for women than for men, whereas durability of virologic suppression was slightly longer for men than women. However, gender differences in virologic rebound were likely due to women discontinuing cART at the end of the pregnancy if it was not needed for their own health.

Cocaine-and-Amphetamine-Regulated-Transcript (CART) peptide attenuates dopamine- and cocaine-mediated locomotor activity in both male and female rats: lack of sex differences

PubMed Central

Job, Martin O.; Perry, JoAnna; Shen, Li L.; Kuhar, Michael J.

2014-01-01

Cocaine-and-Amphetamine Regulated Transcript peptide (CART peptide) is known for having an inhibitory effect on dopamine (DA)- and cocaine-mediated actions and is postulated to be a homeostatic, regulatory factor in the nucleus accumbens (NAc). Some sex differences in cocaine-mediated LMA and in the expression and function of CART peptide have been reported. However, it is not known if the inhibitory effect of CART peptide on cocaine-mediated locomotor activity (LMA) is sexually dimorphic. In this study, the effect of CART 55-102 on LMA due to intra-NAc DA and i.p. cocaine were determined in male and female Sprague-Dawley rats. The results show that CART 55-102 blunted or reduced both the DA- and cocaine-induced LMA in both males and females. In conclusion, CART peptide is effective in blunting DA- and cocaine-mediated LMA in both males and females. PMID:24630272

Chimeric antigen receptor T cells: a novel therapy for solid tumors.

PubMed

Yu, Shengnan; Li, Anping; Liu, Qian; Li, Tengfei; Yuan, Xun; Han, Xinwei; Wu, Kongming

2017-03-29

The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.

A multi-state model examining patterns of transitioning among states of engagement in care in HIV-positive individuals initiating combination antiretroviral therapy

PubMed Central

Gillis, Jennifer; Loutfy, Mona; Bayoumi, Ahmed M; Antoniou, Tony; Burchell, Ann N; Walmsley, Sharon; Cooper, Curtis; Klein, Marina B.; Machouf, Nima; Montaner, Julio SG; Rourke, Sean B.; Tsoukas, Christos; Hogg, Robert; Raboud, Janet

2016-01-01

Background Common measures of engagement in care fail to acknowledge that infrequent follow-up may occur either intentionally among patients with sustained virologic suppression or unintentionally among patients with poor clinical outcomes. Methods Five states of HIV care were defined within the Canadian Observational Cohort (CANOC) Collaboration following combination antiretroviral therapy (cART) initiation: (1) guidelines HIV care (suppressed viral load (VL) and CD4 >200 cells/mm3, no gaps in cART >3 months, no gaps in CD4 or VL measurement >6 months), (2) successful care with decreased frequency of follow-up (as above except no gaps in CD4 or VL measurement >12 months), (3) suboptimal care (unsuppressed VL, CD4<200 cells/mm3 on 2 consecutive visits, ≥1 gap in cART >3 months, or ≥1 gap in CD4 or VL measurement >12 months), (4) loss to follow-up (no contact for 18 months), and (5) death. Multi-state models were used to determine factors associated with transitioning among states. Results 7810 participants were included. Younger age, female gender, Indigenous ethnicity and people who have injected drugs (PWID) were associated with increased likelihoods of transitioning from guidelines to suboptimal care and decreased likelihoods of transitioning from suboptimal to guidelines care. One-fifth of individuals in successful, decreased follow-up after cART initiation (mean sojourn time 0.72 years) were in suboptimal care in subsequent years. Conclusions Using routinely collected data, we have developed a flexible framework that characterizes patient transitions among states of HIV clinical care. We have demonstrated that multi-state models provide a useful approach to supplement ‘cascade of care’ work. PMID:27851713

Effect of HIV type 1 subtype on virological and immunological response to combination antiretroviral therapy: evidence for a more rapid viral suppression for subtype A than subtype B-infected Greek individuals.

PubMed

Paraskevis, Dimirios; Touloumi, Giota; Bakoyannis, Giorgos; Paparizos, Vassilios; Lazanas, Marios; Gargalianos, Panagiotis; Chryssos, Georgios; Antoniadou, Anastasia; Psichogiou, Mina; Panos, Georgios; Katsarou, Olga; Sambatakou, Helen; Kordossis, Theodoros; Hatzakis, Angelos

2013-03-01

Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA <500 copies/ml) and time to failure (>500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B.

Spending at mobile fruit and vegetable carts and using SNAP benefits to pay, Bronx, New York, 2013 and 2014.

PubMed

Breck, Andrew; Kiszko, Kamila M; Abrams, Courtney; Elbel, Brian

2015-06-04

This study examines purchases at fruit and vegetable carts and evaluates the potential benefits of expanding the availability of electronic benefit transfer machines at Green Carts. Customers at 4 Green Carts in the Bronx, New York, were surveyed in 3 waves from June 2013 through July 2014. Customers who used Supplemental Nutrition Assistance Program benefits spent on average $3.86 more than customers who paid with cash. This finding suggests that there may be benefits to increasing the availability of electronic benefit transfer machines at Green Carts.

Demographic and clinical predictors of mortality from highly pathogenic avian influenza A (H5N1) virus infection: CART analysis of international cases.

PubMed

Patel, Rita B; Mathur, Maya B; Gould, Michael; Uyeki, Timothy M; Bhattacharya, Jay; Xiao, Yang; Khazeni, Nayer

2014-01-01

Human infections with highly pathogenic avian influenza (HPAI) A (H5N1) viruses have occurred in 15 countries, with high mortality to date. Determining risk factors for morbidity and mortality from HPAI H5N1 can inform preventive and therapeutic interventions. We included all cases of human HPAI H5N1 reported in World Health Organization Global Alert and Response updates and those identified through a systematic search of multiple databases (PubMed, Scopus, and Google Scholar), including articles in all languages. We abstracted predefined clinical and demographic predictors and mortality and used bivariate logistic regression analyses to examine the relationship of each candidate predictor with mortality. We developed and pruned a decision tree using nonparametric Classification and Regression Tree methods to create risk strata for mortality. We identified 617 human cases of HPAI H5N1 occurring between December 1997 and April 2013. The median age of subjects was 18 years (interquartile range 6-29 years) and 54% were female. HPAI H5N1 case-fatality proportion was 59%. The final decision tree for mortality included age, country, per capita government health expenditure, and delay from symptom onset to hospitalization, with an area under the receiver operator characteristic (ROC) curve of 0.81 (95% CI: 0.76-0.86). A model defined by four clinical and demographic predictors successfully estimated the probability of mortality from HPAI H5N1 illness. These parameters highlight the importance of early diagnosis and treatment and may enable early, targeted pharmaceutical therapy and supportive care for symptomatic patients with HPAI H5N1 virus infection.

A simple algorithm for the identification of clinical COPD phenotypes.

PubMed

Burgel, Pierre-Régis; Paillasseur, Jean-Louis; Janssens, Wim; Piquet, Jacques; Ter Riet, Gerben; Garcia-Aymerich, Judith; Cosio, Borja; Bakke, Per; Puhan, Milo A; Langhammer, Arnulf; Alfageme, Inmaculada; Almagro, Pere; Ancochea, Julio; Celli, Bartolome R; Casanova, Ciro; de-Torres, Juan P; Decramer, Marc; Echazarreta, Andrés; Esteban, Cristobal; Gomez Punter, Rosa Mar; Han, MeiLan K; Johannessen, Ane; Kaiser, Bernhard; Lamprecht, Bernd; Lange, Peter; Leivseth, Linda; Marin, Jose M; Martin, Francis; Martinez-Camblor, Pablo; Miravitlles, Marc; Oga, Toru; Sofia Ramírez, Ana; Sin, Don D; Sobradillo, Patricia; Soler-Cataluña, Juan J; Turner, Alice M; Verdu Rivera, Francisco Javier; Soriano, Joan B; Roche, Nicolas

2017-11-01

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses.Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative.Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV 1 , dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV 1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years).A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes. Copyright ©ERS 2017.

Depression is the predominant factor contributing to morale as measured by the Philadelphia Geriatric Morale Scale in elderly Chinese aged 70 years and over.

PubMed

Woo, J; Ho, S C; Wong, E M C

2005-11-01

To examine factors contributing to the total Philadelphia Geriatric Morale Scale (PGMS) and its two subscales: reconciled ageing and unstrained affect. The PGMS was administered to 759 community-living subjects aged 70 years and over. Information regarding socioeconomic status, health conditions, sensory impairment, physical symptoms, social support, activities of daily living as measured by the Barthel Index, life satisfaction, and the Geriatric Depression Score, was collected. Associations between these factors and PGMS and its subscale were examined using univariate analysis (Mann-Whitney; Kruskal-Wallis tests), and multivariate analysis using the classification and regression tree (CART) method. Gender, old age, physical, socioeconomic and social factors were significantly associated with PGMS. There was a strong correlation with GDS (r = 0.77, p < 0.001). In the CART analysis, for both subscales and the total score, GDS was the predominant factor contributing to the score. Other factors include self perception of health, enough expenses, overall satisfaction with life, gender, and constipation. The PGMS and GDS are closely related. In addition to the GDS, health perception, life satisfaction, and adequate finance were factors contributing to quality of life in elderly Hong Kong Chinese. Copyright (c) 2005 John Wiley & Sons, Ltd.

A feature alignment score for online cone-beam CT-based image-guided radiotherapy for prostate cancer.

PubMed

Hargrave, Catriona; Deegan, Timothy; Poulsen, Michael; Bednarz, Tomasz; Harden, Fiona; Mengersen, Kerrie

2018-05-17

To develop a method for scoring online cone-beam CT (CBCT)-to-planning CT image feature alignment to inform prostate image-guided radiotherapy (IGRT) decision-making. The feasibility of incorporating volume variation metric thresholds predictive of delivering planned dose into weighted functions, was investigated. Radiation therapists and radiation oncologists participated in workshops where they reviewed prostate CBCT-IGRT case examples and completed a paper-based survey of image feature matching practices. For 36 prostate cancer patients, one daily CBCT was retrospectively contoured then registered with their plan to simulate delivered dose if (a) no online setup corrections and (b) online image alignment and setup corrections, were performed. Survey results were used to select variables for inclusion in classification and regression tree (CART) and boosted regression trees (BRT) modeling of volume variation metric thresholds predictive of delivering planned dose to the prostate, proximal seminal vesicles (PSV), bladder, and rectum. Weighted functions incorporating the CART and BRT results were used to calculate a score of individual tumor and organ at risk image feature alignment (FAS TV _ OAR ). Scaled and weighted FAS TV _ OAR were then used to calculate a score of overall treatment compliance (FAS global ) for a given CBCT-planning CT registration. The FAS TV _ OAR were assessed for sensitivity, specificity, and predictive power. FAS global thresholds indicative of high, medium, or low overall treatment plan compliance were determined using coefficients from multiple linear regression analysis. Thirty-two participants completed the prostate CBCT-IGRT survey. While responses demonstrated consensus of practice for preferential ranking of planning CT and CBCT match features in the presence of deformation and rotation, variation existed in the specified thresholds for observed volume differences requiring patient repositioning or repeat bladder and bowel preparation. The CART and BRT modeling indicated that for a given registration, a Dice similarity coefficient >0.80 and >0.60 for the prostate and PSV, respectively, and a maximum Hausdorff distance <8.0 mm for both structures were predictive of delivered dose ± 5% of planned dose. A normalized volume difference <1.0 and a CBCT anterior rectum wall >1.0 mm anterior to the planning CT anterior rectum wall were predictive of delivered dose >5% of planned rectum dose. A normalized volume difference <0.88, and a CBCT bladder wall >13.5 mm inferior and >5.0 mm posterior to the planning CT bladder were predictive of delivered dose >5% of planned bladder dose. A FAS TV _ OAR >0 is indicative of delivery of planned dose. For calculated FAS TV _ OAR for the prostate, PSV, bladder, and rectum using test data, sensitivity was 0.56, 0.75, 0.89, and 1.00, respectively; specificity 0.90, 0.94, 0.59, and 1.00, respectively; positive predictive power 0.90, 0.86, 0.53, and 1.00, respectively; and negative predictive power 0.56, 0.89, 0.91, and 1.00, respectively. Thresholds for the calculated FAS global of were low <60, medium 60-80, and high >80, with a 27% misclassification rate for the test data. A FAS global incorporating nested FAS TV _ OAR and volume variation metric thresholds predictive of treatment plan compliance was developed, offering an alternative to pretreatment dose calculations to assess treatment delivery accuracy. © 2018 American Association of Physicists in Medicine.

Demonstration of the Berkeley UXO Discrimination at Live Sites

DTIC Science & Technology

2010-02-01

BUD then occupied each of the 11 points and acquired a stationary measurement. The cart was equipped with a two-component tiltmeter and three...component magnetometer. Both devices were calibrated before the survey. The tiltmeters readings were used to compute the cart pitch (positive pitch...cart front down = negative tiltmeter change), and roll (positive=cart rightside down - positive tiltmeter change). The magnetometer values were used to

Italian translation and cross-cultural comparison with the Childhood Attachment and Relational Trauma Screen (CARTS).

PubMed

Simonelli, A; Sacchi, C; Cantoni, L; Brown, M; Frewen, P

2017-01-01

Background : The Childhood Attachment and Relational Trauma Screen (CARTS) is a computer-administered survey designed to assess retrospectively the socio-ecological context in which instances of child abuse may have occurred. To date, studies supporting the validity of the CARTS have only been undertaken in English-speaking North American populations. Validation projects in other countries and cross-cultural comparisons are therefore warranted. Objective : Develop and preliminarily evaluate the psychometric properties of an Italian version of the CARTS on college students and compare such observations to data acquired from Canadian students. Method : Seventy-nine undergraduate students from the University of Padua (Italy) completed an Italian translation of the CARTS as well as measures of childhood experiences, mental health and attachment, responses to which were compared to those obtained in 288 Canadian students who completed the CARTS in English. Results : Internal consistency and convergent validity with the Childhood Trauma Questionnaire and Parental Bonding Instrument were found to be acceptable for the Italian translation. Within the Italian sample, correlation analyses suggested that CARTS Mother ratings referring to attachment and abuse were associated with romantic attachment, whereas CARTS Father ratings were significantly correlated to PTSD symptoms and other symptoms of psychopathology-distress. Significant differences between Italian and Canadian students across the relationship types for the CARTS abuse and attachment scales were found, indicating that Italian students rated their mothers and fathers as simultaneously less abusive, but also less as a source of secure attachment. Conclusions : The results of this preliminary study seem to suggest convergent validity of the Italian CARTS and the association between childhood attachment-related experiences and romantic attachment. Cultural variations were identified between Canadian and Italian students in both attachment and abuse scales. Future studies to investigate cross-cultural variations in the relational context of childhood abuse and in order to boost Italian CARTS psychometric features are warranted.

Italian translation and cross-cultural comparison with the Childhood Attachment and Relational Trauma Screen (CARTS)

PubMed Central

Simonelli, A.; Sacchi, C.; Cantoni, L.; Brown, M.; Frewen, P.

2017-01-01

ABSTRACT Background: The Childhood Attachment and Relational Trauma Screen (CARTS) is a computer-administered survey designed to assess retrospectively the socio-ecological context in which instances of child abuse may have occurred. To date, studies supporting the validity of the CARTS have only been undertaken in English-speaking North American populations. Validation projects in other countries and cross-cultural comparisons are therefore warranted. Objective: Develop and preliminarily evaluate the psychometric properties of an Italian version of the CARTS on college students and compare such observations to data acquired from Canadian students. Method: Seventy-nine undergraduate students from the University of Padua (Italy) completed an Italian translation of the CARTS as well as measures of childhood experiences, mental health and attachment, responses to which were compared to those obtained in 288 Canadian students who completed the CARTS in English. Results: Internal consistency and convergent validity with the Childhood Trauma Questionnaire and Parental Bonding Instrument were found to be acceptable for the Italian translation. Within the Italian sample, correlation analyses suggested that CARTS Mother ratings referring to attachment and abuse were associated with romantic attachment, whereas CARTS Father ratings were significantly correlated to PTSD symptoms and other symptoms of psychopathology-distress. Significant differences between Italian and Canadian students across the relationship types for the CARTS abuse and attachment scales were found, indicating that Italian students rated their mothers and fathers as simultaneously less abusive, but also less as a source of secure attachment. Conclusions: The results of this preliminary study seem to suggest convergent validity of the Italian CARTS and the association between childhood attachment-related experiences and romantic attachment. Cultural variations were identified between Canadian and Italian students in both attachment and abuse scales. Future studies to investigate cross-cultural variations in the relational context of childhood abuse and in order to boost Italian CARTS psychometric features are warranted. PMID:29163857

CD19 targeted CAR-T therapy versus chemotherapy in re-induction treatment of refractory/relapsed acute lymphoblastic leukemia: results of a case-controlled study.

PubMed

Wei, Guoqing; Hu, Yongxian; Pu, Chengfei; Yu, Jian; Luo, Yi; Shi, Jimin; Cui, Qu; Wu, Wenjun; Wang, Jinping; Xiao, Lei; Wu, Zhao; Huang, He

2018-05-01

Chimeric antigen receptor modified T cells against CD19 (CART19s) have potent anti-leukemia activities in patients with refractory/relapsed acute lymphoblastic leukemia (R/R ALL). This study was designed to investigate the correlation between safety/efficacy and therapeutic modalities including chemotherapy and CART19 therapy. Total 23 and 69 patients were enrolled in the CART19 group and in the chemotherapy group, respectively. The safety and efficacy profiles of 66 and 22 patients in the 2 groups were evaluated. The complete remission (CR) rate was higher in the CART19 group than that in the chemotherapy group (90.9 vs 37.9%, P = 0.000). For patients relapsed after allo-HSCT and chemotherapy, CR rates were 100% (8/8) vs 48.0% (12/25) (P = 0.009) and 85.7% (12/14) vs 31.7% (13/41) (P = 0.000), respectively. Moreover, a higher percentage in the CART19 group had results below the threshold for minimal residual disease (100 vs 7.58%, P = 0.000). In survival analysis, the overall survival rate at 12 months was higher in the CART19 group than that in the chemotherapy group (60.9 vs 10.1%, P = 0.000). For post-transplant patients achieving CR, 25.0% (2/8) and 75.0% (9/12) complicated with GVHD (P = 0.04) in the CART19 group and chemotherapy group, respectively. For all CR patients, the median duration of absolute neutrophil count less than 500/μL and platelet count less than 20,000/μL were longer in the CART19 group than in the chemotherapy group (p = 0.0047 and 0.0003, respectively). Our data demonstrated that patients with CART19s therapy acquired higher rates of remission and longer survival, confirming the encouraging application of CART19 therapy in R/R ALL.

Stop waiting and start creating: service learning with an outpatient bone marrow transplant unit art cart program.

PubMed

Fletcher, Tina; Bayer, Christina; Beyer, Emily; Gonzales, Jessica; Ralston, Ashley; Yount, Phyllis

2013-01-01

This paper examines how master of occupational therapy students, their occupational therapy instructor, and a community-based licensed clinical social worker collaborated in a service learning art cart program on an outpatient bone marrow transplant unit. As they progressed through the phases of Kolb's model of service learning, occupational therapy students, their occupational therapy instructor, and the licensed clinical social worker were all able to meet mutual goals of serving a unique patient population, increasing knowledge of best practices, and building and fostering university/community relationships.

Cocaine- and amphetamine-regulated transcript peptide (CART) in the telencephalon of the catfish, Clarias gariepinus: distribution and response to fasting, 2-deoxy-D-glucose, glucose, insulin, and leptin treatments.

PubMed

Subhedar, Nishikant; Barsagade, Vikas G; Singru, Praful S; Thim, Lars; Clausen, Jes Thorn

2011-05-01

The cocaine- and amphetamine-regulated transcript peptide (CART)-containing system in the forebrain of Clarias gariepinus was studied with immunocytochemistry. While the immunoreactivity was prominently seen in the neurons of the entopeduncular nucleus (EN) located in the ventral telencephalon, CART-immunoreactive fibers were widely distributed in the dorsal and ventral telencephalon. In view of the established role of CART in energy metabolism, we investigated the response of the CART immunoreactive system to positive and negative nutritional conditions. Neurons of the EN and fibers in the different areas of the telencephalon showed significant reduction in CART immunoreactivity following 48 hours food deprivation, or 2 hours following intracranial administration of 2-deoxy-D-glucose (2DG, 100 ng/g body weight, a metabolic antagonist of glucose). However, intracranial injection of glucose (100 ng/g body weight) resulted in a distinct increase in CART immunoreactivity in these components. In mammals, insulin and leptin have been recognized as adiposity agents that convey peripheral energy status-related information to brain. Intracranial administration of insulin (3 mU/fish) and leptin (10 ng/g body weight) significantly increased CART immunoreactivity in the EN neurons and in the fiber network within 2 hours. Superfusion of the EN-containing tissue fragments in the medium enriched in glucose, insulin, or leptin evoked a significant increase in CART immunoreactivity in the EN neurons, but 2DG reduced the immunoreactivity. We suggest that CART-containing neurons of the EN, and fibers in the telencephalon, may process the energy status-related information and contribute to satiety. Copyright © 2011 Wiley-Liss, Inc.

Evaluation of CART peptide level in rat plasma and CSF: Possible role as a biomarker in opioid addiction.

PubMed

Bakhtazad, Atefeh; Vousooghi, Nasim; Garmabi, Behzad; Zarrindast, Mohammad Reza

2016-10-01

It has been shown previously that cocaine- and amphetamine-regulated transcript (CART) peptide has a modulatory role and homeostatic regulatory effect in motivation to and reward of the drugs of abuse specially psychostimulants. Recent data also showed that in addition to psychostimulants, CART is critically involved in the different stages of opioid addiction. Here we have evaluated the fluctuations in the level of CART peptide in plasma and CSF in different phases of opioid addiction to find out whether CART can serve as a suitable marker in opioid addiction studies. Male rats were randomly distributed in groups of control, acute low-dose (10mg/kg) morphine, acute high-dose morphine (80mg/kg), chronic escalating doses of morphine, withdrawal syndrome precipitated by administration of naloxone (1mg/kg), and abstinent after long-term drug-free maintenance of addicted animals. The level of CART peptide in CSF and plasma samples was measured by enzyme immunoassay. CART peptide concentration in the CSF and plasma was significantly elevated in acute high-dose morphine and withdrawal state animals and down-regulated in addicted rats. In abstinent group, CART peptide level was up-regulated in plasma but not in CSF samples. As the observed results are in agreement with data regarding the CART mRNA and protein expression in the brain reward pathway in opioid addiction phases, it may be suggested that evaluation of CART peptide level in CSF or plasma could be a suitable marker which reflects the rises and falls of the peptide concentration in brain in the development of opioid addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

New analogs of the CART peptide with anorexigenic potency: the importance of individual disulfide bridges.

PubMed

Blechová, Miroslava; Nagelová, Veronika; Záková, Lenka; Demianová, Zuzana; Zelezná, Blanka; Maletínská, Lenka

2013-01-01

The CART (cocaine- and amphetamine-regulated transcript) peptide is an anorexigenic neuropeptide that acts in the hypothalamus. The receptor and the mechanism of action of this peptide are still unknown. In our previous study, we showed that the CART peptide binds specifically to PC12 rat pheochromocytoma cells in both the native and differentiated into neuronal phenotype. Two biologically active forms, CART(55-102) and CART(61-102), with equal biological activity, contain three disulfide bridges. To clarify the importance of each of these disulfide bridges in maintaining the biological activity of CART(61-102), an Ala scan at particular S-S bridges forming cysteines was performed, and analogs with only one or two disulfide bridges were synthesized. In this study, a stabilized CART(61-102) analog with norleucine instead of methionine at position 67 was also prepared and was found to bind to PC12 cells with an anorexigenic potency similar to that of CART(61-102). The binding study revealed that out of all analogs tested, [Ala(68,86)]CART(61-102), which contains two disulfide bridges (positions 74-94 and 88-101), preserved a high affinity to both native PC12 cells and those that had been differentiated into neurons. In food intake and behavioral tests with mice after intracerebroventricular administration, this analog showed strong and long-lasting anorexigenic potency. Therefore, the disulfide bridge between cysteines 68 and 86 in CART(61-102) can be omitted without a loss of biological activity, but the preservation of two other disulfide bridges and the full-length peptide are essential for biological activity. Copyright © 2012 Elsevier Inc. All rights reserved.

Actual use of and satisfaction associated with rollators and "shopping carts" among frail elderly Japanese people using day-service facilities.

PubMed

Kitajima, Eiji; Moriuchi, Takefumi; Iso, Naoki; Sagari, Akira; Kikuchi, Yasuyuki; Higashi, Toshio

2017-07-01

Purpose This study aimed at clarifying the actual use of and satisfaction with rollators and "shopping carts" (wheeled walkers with storage) among frail elderly people, who were certified by a long-term care insurance system as users of facilities that provide day-service nursing care and rehabilitation. Methods We identified 1247 frail elderly people who used day-service facilities, and evaluated their actual use of, and satisfaction with, rollators and shopping carts. Results Forty-four (3.5%) individuals used rollators, and 53 (4.3%) used shopping carts. The shopping cart group contained more individuals who were certified as care level 1 (26.4%), than the rollator group (20.5%), and 52.8% of the shopping cart group was certified as care levels 1-3. The scores for "repairs and services" and "follow-up" from the Quebec User Evaluation of Satisfaction with assistive Technology second version (QUEST 2.0) survey were significantly higher in the rollator group than in the shopping cart group. Conclusions The QUEST 2.0 scores revealed that shopping cart users exhibit insufficient "repairs and services" and "follow-up" scores. As frail elderly people with poor care status accounted for >50% of the shopping cart group, these individuals urgently need walking aids that are tailored to their care status. Implications for Rehabilitation We conclude that walking aid fitting must be tailored to each persons care status, and suggest that a system should be established to allow occupational or physical therapists to provide this fitting Moreover, our analysis of the QUEST2.0 service scores revealed that repairs, services, and follow-up are insufficient to meet the needs of shopping cart users.

Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

PubMed

Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

2015-04-01

Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Case-mix groups for VA hospital-based home care.

PubMed

Smith, M E; Baker, C R; Branch, L G; Walls, R C; Grimes, R M; Karklins, J M; Kashner, M; Burrage, R; Parks, A; Rogers, P

1992-01-01

The purpose of this study is to group hospital-based home care (HBHC) patients homogeneously by their characteristics with respect to cost of care to develop alternative case mix methods for management and reimbursement (allocation) purposes. Six Veterans Affairs (VA) HBHC programs in Fiscal Year (FY) 1986 that maximized patient, program, and regional variation were selected, all of which agreed to participate. All HBHC patients active in each program on October 1, 1987, in addition to all new admissions through September 30, 1988 (FY88), comprised the sample of 874 unique patients. Statistical methods include the use of classification and regression trees (CART software: Statistical Software; Lafayette, CA), analysis of variance, and multiple linear regression techniques. The resulting algorithm is a three-factor model that explains 20% of the cost variance (R2 = 20%, with a cross validation R2 of 12%). Similar classifications such as the RUG-II, which is utilized for VA nursing home and intermediate care, the VA outpatient resource allocation model, and the RUG-HHC, utilized in some states for reimbursing home health care in the private sector, explained less of the cost variance and, therefore, are less adequate for VA home care resource allocation.

Relationships of Biomass with Environmental Factors in the Grassland Area of Hulunbuir, China

PubMed Central

Liu, Miao; Liu, Guohua; Gong, Li; Wang, Dongbo; Sun, Jian

2014-01-01

Many studies have focused on the relationship between vegetation biomass and environmental factors in grassland. However, several questions remain to be answered, especially with regards to the spatial pattern of vegetation biomass. Thus, the distributed mechanism will be explored in the present study. Here, plant biomass was measured at 23 sites along a transect survey during the peak growing season in 2006. The data were analyzed with a classification and regression tree (CART) model. The structural equation modeling (SEM) was conducted to explicitly evaluate the both direct and indirect effects of these critical environmental elements on vegetation biomass. The results demonstrated that mean annual temperature (MAT) affected aboveground biomass (AGB) scored at −0.811 (P<0.05). The direct effect of MAT on belowground biomass (BGB) was −0.490 (P<0.05). The results were determined by SEM. Our results indicate that AGB and BGB in semi-arid ecosystems is strongly affected by precipitation and temperature. Future work shall attempt to take into account the integrated effects of precipitation and temperature. Meanwhile, partitioning the influences of environmental variations and vegetation types are helpful in illuminating the internal mechanism of biomass distribution. PMID:25032808

Relationships of biomass with environmental factors in the grassland area of Hulunbuir, China.

PubMed

Liu, Miao; Liu, Guohua; Gong, Li; Wang, Dongbo; Sun, Jian

2014-01-01

Many studies have focused on the relationship between vegetation biomass and environmental factors in grassland. However, several questions remain to be answered, especially with regards to the spatial pattern of vegetation biomass. Thus, the distributed mechanism will be explored in the present study. Here, plant biomass was measured at 23 sites along a transect survey during the peak growing season in 2006. The data were analyzed with a classification and regression tree (CART) model. The structural equation modeling (SEM) was conducted to explicitly evaluate the both direct and indirect effects of these critical environmental elements on vegetation biomass. The results demonstrated that mean annual temperature (MAT) affected aboveground biomass (AGB) scored at -0.811 (P<0.05). The direct effect of MAT on belowground biomass (BGB) was -0.490 (P<0.05). The results were determined by SEM. Our results indicate that AGB and BGB in semi-arid ecosystems is strongly affected by precipitation and temperature. Future work shall attempt to take into account the integrated effects of precipitation and temperature. Meanwhile, partitioning the influences of environmental variations and vegetation types are helpful in illuminating the internal mechanism of biomass distribution.

Learning and Tuning of Fuzzy Rules

NASA Technical Reports Server (NTRS)

Berenji, Hamid R.

1997-01-01

In this chapter, we review some of the current techniques for learning and tuning fuzzy rules. For clarity, we refer to the process of generating rules from data as the learning problem and distinguish it from tuning an already existing set of fuzzy rules. For learning, we touch on unsupervised learning techniques such as fuzzy c-means, fuzzy decision tree systems, fuzzy genetic algorithms, and linear fuzzy rules generation methods. For tuning, we discuss Jang's ANFIS architecture, Berenji-Khedkar's GARIC architecture and its extensions in GARIC-Q. We show that the hybrid techniques capable of learning and tuning fuzzy rules, such as CART-ANFIS, RNN-FLCS, and GARIC-RB, are desirable in development of a number of future intelligent systems.

Fan Cart: The Next Generation

NASA Astrophysics Data System (ADS)

Lamore, Brian

2016-10-01

For years the fan cart has provided physics students with an excellent resource for exploring fundamental mechanics concepts such as acceleration, Newton's laws, impulse, momentum, work-energy, and energy conversions. The Physics Teacher has even seen some excellent do-it-yourself (DIY) fan carts and activities. If you are interested in developing the `E' portion of your and your students' STEM (science, technology, engineering, and math) skills, one way to accomplish this is to revisit the DIY fan cart. In this article I share a design of a new edition of the DIY fan cart and some ideas for incorporating the engineering design process into your high school curriculum.

Elimination of Mother-To-Child Transmission of HIV Infection: The Drug Resource Enhancement against AIDS and Malnutrition Model

PubMed Central

Liotta, Giuseppe; Marazzi, Maria Cristina; Mothibi, Khethimipilo E.; Zimba, Ines; Amangoua, Evelyne E.; Bonje, Esther K.; Bossiky, Bernard N. B.; Robinson, Precious A.; Scarcella, Paola; Musokotwane, Kebby; Palombi, Leonardo; Germano, Paola; Narciso, Pasquale; de Luca, Andrea; Alumando, Elard; Mamary, Sangare H.; Magid, Nurja A.; Guidotti, Giovanni; Mancinelli, Sandro; Orlando, Stefano; Peroni, Marco; Buonomo, Ersilia; Nielsen-Saines, Karin

2015-01-01

The Drug Resource Enhancement against AIDS and Malnutrition Program (DREAM) gathered professionals in the field of Elimination of HIV-Mother-To-Child Transmission (EMTCT) in Maputo in 2013 to discuss obstacles and solutions for the elimination of HIV vertical transmission in sub-Saharan Africa. During this workshop, the benefits of administrating combined antiretroviral therapy (cART) to HIV positive women from pregnancy throughout breastfeeding were reviewed. cART is capable of reducing vertical transmission to less than 5% at 24 months of age, as well as maternal mortality and infant mortality in both HIV infected and exposed populations to levels similar to those of uninfected individuals. The challenge for programs targeting eMTCT in developing countries is retention in care and treatment adherence. Both are intrinsically related to the model of care. The drop-out from eMTCT programs before cART initiation ranges from 33%–88% while retention rates at 18–24 months are less than 50%. Comprehensive strategies including peer-to-peer education, social support and laboratory monitoring can reduce refusals to less than 5% and attain retention rates approaching 90%. Several components of the model of care for reduction of HIV-1 MTCT are feasible and implementable in scale-up strategies. A review of this model of care for HIV eMTCT is provided. PMID:26506365

Failure to achieve immunological recovery in HIV-infected patients with clinical and virological success after 10 years of combined ART: role of treatment course.

PubMed

Raffi, François; Le Moing, Vincent; Assuied, Alex; Habak, Sofiane; Spire, Bruno; Cazanave, Charles; Billaud, Eric; Dellamonica, Pierre; Ferry, Tristan; Fagard, Catherine; Leport, Catherine

2017-01-01

We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART). In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART. Failure of CD4 response (CD4 >500/mm 3 ) was associated with age ≥40 years at baseline (P < 0.001), CD4 cell counts ≤500/mm 3 at month 4 (P = 0.016) or month 12 (P < 0.001) and ≥3 months of cART interruption (P = 0.016). Factors associated with failure to achieve complete immunological response (CD4 >500/mm 3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P < 0.001) or month 12 (P < 0.001), ≥3 months of cumulative cART interruption (P = 0.011), ≥3 antiretroviral regimens (P = 0.009) and ≤4 treatment lines (P = 0.015). Baseline CD4 and CD4:CD8 ratio were not predictors of the 10 year immunological outcomes. In this therapeutic cohort of patients starting first-generation PI-containing cART in 1997-99, poor initial immunological response had a negative impact on 10 year CD4 and CD4 plus CD4:CD8 ratio response, despite prolonged virological success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia.

PubMed

Wang, Jinghua; Chen, Siyu; Xiao, Wei; Li, Wende; Wang, Liang; Yang, Shuo; Wang, Weida; Xu, Liping; Liao, Shuangye; Liu, Wenjian; Wang, Yang; Liu, Nawei; Zhang, Jianeng; Xia, Xiaojun; Kang, Tiebang; Chen, Gong; Cai, Xiuyu; Yang, Han; Zhang, Xing; Lu, Yue; Zhou, Penghui

2018-01-10

Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment. We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific single-chain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-ζ signaling domain. We further investigate the function of CLL-1 CAR-T cells. The CLL-1 CAR-T cells specifically lysed CLL-1 + cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1 + myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression. CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML.

Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease.

PubMed

Garvey, L; Winston, A; Walsh, J; Post, F; Porter, K; Gazzard, B; Fisher, M; Leen, C; Pillay, D; Hill, T; Johnson, M; Gilson, R; Anderson, J; Easterbrook, P; Bansi, L; Orkin, C; Ainsworth, J; Palfreeman, A; Gompels, M; Phillips, A N; Sabin, C A

2011-02-22

The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death. Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.

Emergency-Evacuation Cart

NASA Technical Reports Server (NTRS)

Fedor, Otto H.; Owens, Lester J.

1988-01-01

Proposed cart designed to remove injured worker from vicinity of hazardous chemical spill. Self-propelled cart enables rescuer to move victim of industrial accident quickly away from toxic, flammable, explosive, corrosive, carcinogenic, asphyxiating, or extremely cold liquids. Intended for use where too dangerous for ambulances and other vehicles to approach accident site. Constructed of high-strength tubing, rides on bicycle wheels with balloon tires. Rescuer steers cart with handle at rear. Estimated mass of fully equipped vehicle is 650 lb.

Influence of the Biosphere on Precipitation: July 1995 Studies with the ARM-CART Data

NASA Technical Reports Server (NTRS)

Sud, Y. C.; Mocko, D. M.; Walker, G. K.; Koster, Randal D.

2000-01-01

Ensemble sets of simulation experiments were conducted with a single column model (SCM) using the Goddard GEOS II GCM physics containing a recent version of the Cumulus Scheme (McRAS) and a biosphere based land-fluxes scheme (SSiB). The study used the 18 July to 5 August 1995 ARM-CART (Atmospheric Radiation Measurement-Cloud Atmospheric Radiation Test-bed) data, which was collected at the ARM-CART site in the mid-western United States and analyzed for single column modeling (SCM) studies. The new findings affirm the earlier findings that the vegetation, which increases the solar energy absorption at the surface together with soil and soil-moisture dependent processes, which modulate the surface, fluxes (particularly evapotranspiration) together help to increase the local rainfall. In addition, the results also show that for the particular study period roughly 50% of the increased evaporation over the ARM-CART site would be converted into rainfall with the Column, while the remainder would be advected out to the large-scale. Notwithstanding the limitations of only one-way interaction (i.e., the large-scale influencing the regional physics and not vice versa), the current SCM simulations show a very robust relationship. The evaporation-precipitation relationship turns out to be independent of the soil types, and soil moisture; however, it is weakly dependent on the vegetation cover because of its surface-albedo effect. Clearly, these inferences are prone to weaknesses of the SCM physics, the assumptions of the large-scale being unaffected by gridscale (SCM-scale) changes in moist processes, and other limitations of the evaluation procedures.

Intermittent Feedback-Control Strategy for Stabilizing Inverted Pendulum on Manually Controlled Cart as Analogy to Human Stick Balancing

PubMed Central

Yoshikawa, Naoya; Suzuki, Yasuyuki; Kiyono, Ken; Nomura, Taishin

2016-01-01

The stabilization of an inverted pendulum on a manually controlled cart (cart-inverted-pendulum; CIP) in an upright position, which is analogous to balancing a stick on a fingertip, is considered in order to investigate how the human central nervous system (CNS) stabilizes unstable dynamics due to mechanical instability and time delays in neural feedback control. We explore the possibility that a type of intermittent time-delayed feedback control, which has been proposed for human postural control during quiet standing, is also a promising strategy for the CIP task and stick balancing on a fingertip. Such a strategy hypothesizes that the CNS exploits transient contracting dynamics along a stable manifold of a saddle-type unstable upright equilibrium of the inverted pendulum in the absence of control by inactivating neural feedback control intermittently for compensating delay-induced instability. To this end, the motions of a CIP stabilized by human subjects were experimentally acquired, and computational models of the system were employed to characterize the experimental behaviors. We first confirmed fat-tailed non-Gaussian temporal fluctuation in the acceleration distribution of the pendulum, as well as the power-law distributions of corrective cart movements for skilled subjects, which was previously reported for stick balancing. We then showed that the experimental behaviors could be better described by the models with an intermittent delayed feedback controller than by those with the conventional continuous delayed feedback controller, suggesting that the human CNS stabilizes the upright posture of the pendulum by utilizing the intermittent delayed feedback-control strategy. PMID:27148031

Intermittent Feedback-Control Strategy for Stabilizing Inverted Pendulum on Manually Controlled Cart as Analogy to Human Stick Balancing.

PubMed

Yoshikawa, Naoya; Suzuki, Yasuyuki; Kiyono, Ken; Nomura, Taishin

2016-01-01

The stabilization of an inverted pendulum on a manually controlled cart (cart-inverted-pendulum; CIP) in an upright position, which is analogous to balancing a stick on a fingertip, is considered in order to investigate how the human central nervous system (CNS) stabilizes unstable dynamics due to mechanical instability and time delays in neural feedback control. We explore the possibility that a type of intermittent time-delayed feedback control, which has been proposed for human postural control during quiet standing, is also a promising strategy for the CIP task and stick balancing on a fingertip. Such a strategy hypothesizes that the CNS exploits transient contracting dynamics along a stable manifold of a saddle-type unstable upright equilibrium of the inverted pendulum in the absence of control by inactivating neural feedback control intermittently for compensating delay-induced instability. To this end, the motions of a CIP stabilized by human subjects were experimentally acquired, and computational models of the system were employed to characterize the experimental behaviors. We first confirmed fat-tailed non-Gaussian temporal fluctuation in the acceleration distribution of the pendulum, as well as the power-law distributions of corrective cart movements for skilled subjects, which was previously reported for stick balancing. We then showed that the experimental behaviors could be better described by the models with an intermittent delayed feedback controller than by those with the conventional continuous delayed feedback controller, suggesting that the human CNS stabilizes the upright posture of the pendulum by utilizing the intermittent delayed feedback-control strategy.

Etiologies of pediatric craniofacial injuries: a comparison of injuries involving all-terrain vehicles and golf carts.

PubMed

White, Lauren C; McKinnon, Brian J; Hughes, C Anthony

2013-03-01

To determine incidence and etiologies of craniofacial injuries in the pediatric population through comparison of injuries caused by all-terrain vehicles and golf cart trauma. Case series with chart review. Level 1 trauma center. Retrospective review of pediatric traumas at a tertiary academic medical center from 2003 to 2012 identified 196 patients whose injuries resulted from accidents involving either all-terrain vehicles or golf carts. Data was collected and variables such as age, gender, driver vs. passenger, location of accident, Glasgow coma scale, Injury severity scale, Abbreviated injury scale, and presence or absence of helmet use were examined. 196 pediatric patients were identified: 68 patients had injuries resulting from golf cart accidents, and 128 patients from ATV accidents. 66.4% of ATV-related traumas were male, compared to 52.9% of golf cart-related traumas. Ages of injured patients were similar between the two modalities with average age of ATV traumas 10.8 (±4.0) years and golf cart traumas 10.0 (±4.6) years. Caucasians were most commonly involved in both ATV (79.7%) and golf cart traumas (85.3%). 58.6% of all ATV related trauma and 69.1% of all golf cart trauma resulted in craniofacial injuries. The most common craniofacial injury was a closed head injury with brief loss of consciousness, occurring in 46.1% of the ATV traumas and 54.4% of the golf cart traumas. Temporal bone fractures were the second most common type of craniofacial injury, occurring in 5.5% of ATV accidents and 7.4% of the golf cart traumas. Length of hospital stay and, cases requiring surgery and severity scores were similar between both populations. Intensive care admissions and injury severity scores approached but not reach statistical significance (0.096 and 0.083, respectively). The only statistically significant differences between the two modalities were helmet use (P=0.00018%) and days requiring ventilator assistance (P=0.025). ATVs and golf carts are often exempt from the safety features and regulations required of motor vehicles, and ATV and golf cart accidents represent a significant portion of pediatric traumas. This study found that ATV and golf cart accidents contribute significantly to craniofacial trauma requiring hospitalization, with resultant morbidity and mortality. Further investigation of these injuries and their prevention in the pediatric population is needed before efforts to promote effective safety regulations for such vehicles in the future can be addressed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

PubMed

Hege, Kristen M; Bergsland, Emily K; Fisher, George A; Nemunaitis, John J; Warren, Robert S; McArthur, James G; Lin, Andy A; Schlom, Jeffrey; June, Carl H; Sherwin, Stephen A

2017-01-01

T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 10 10 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72. Fourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111 Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed. These findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity.

Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis

PubMed Central

Chi, Zhixia; Du, Shou-Hui; Chen, Can; Tay, Johan C.K.; Toh, Han Chong; Connolly, John E.; Xu, Xue Hu; Wang, Shu

2017-01-01

The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells. A single intraperitoneal injection of the CART cells eradicated established ovarian xenografts and resulted in significantly prolonged animal survival. Since EpCAM is also expressed on normal epithelium, anti-EpCAM CART cells were generated by mRNA electroporation that display a controlled cytolytic activity with a limited CAR expression duration. Multiple repeated infusions of these RNA CAR-modified T cells delayed disease progression in immunodeficient mice bearing well-established peritoneal ovarian and colorectal xenografts. Thus, our study demonstrates the effectiveness of using anti-EpCAM CAR-expressing T cells for local treatment of PC in mice. The possibility of using this approach for clinical treatment of EpCAM-positive gastrointestinal and gynecological malignancies warrants further validation. PMID:28088790

CART in the brain of vertebrates: circuits, functions and evolution.

PubMed

Subhedar, Nishikant K; Nakhate, Kartik T; Upadhya, Manoj A; Kokare, Dadasaheb M

2014-04-01

Cocaine- and amphetamine-regulated transcript peptide (CART) with its wide distribution in the brain of mammals has been the focus of considerable research in recent years. Last two decades have witnessed a steady rise in the information on the genes that encode this neuropeptide and regulation of its transcription and translation. CART is highly enriched in the hypothalamic nuclei and its relevance to energy homeostasis and neuroendocrine control has been understood in great details. However, the occurrence of this peptide in a range of diverse circuitries for sensory, motor, vegetative, limbic and higher cortical areas has been confounding. Evidence that CART peptide may have role in addiction, pain, reward, learning and memory, cognition, sleep, reproduction and development, modulation of behavior and regulation of autonomic nervous system are accumulating, but an integration has been missing. A steady stream of papers has been pointing at the therapeutic potentials of CART. The current review is an attempt at piecing together the fragments of available information, and seeks meaning out of the CART elements in their anatomical niche. We try to put together the CART containing neuronal circuitries that have been conclusively demonstrated as well as those which have been proposed, but need confirmation. With a view to finding out the evolutionary antecedents, we visit the CART systems in sub-mammalian vertebrates and seek the answer why the system is shaped the way it is. We enquire into the conservation of the CART system and appreciate its functional diversity across the phyla. Copyright © 2014 Elsevier Inc. All rights reserved.

Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response.

PubMed

Xue, Qiong; Bettini, Emily; Paczkowski, Patrick; Ng, Colin; Kaiser, Alaina; McConnell, Timothy; Kodrasi, Olja; Quigley, Máire F; Heath, James; Fan, Rong; Mackay, Sean; Dudley, Mark E; Kassim, Sadik H; Zhou, Jing

2017-11-21

It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods. We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors. Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high dimensional data requires new visualization methods to further define precise polyfunctional response differences in these products. The presented biomarker capture and analysis system provides a more sensitive and comprehensive functional assessment of CAR-T pre-infusion products and may provide insights into the safety and efficacy of CAR-T cell therapy.

The PASCO Wireless Smart Cart: A Game Changer in the Undergraduate Physics Laboratory

NASA Astrophysics Data System (ADS)

Shakur, Asif; Connor, Rainor

2018-03-01

With the introduction of the Wireless Smart Cart by PASCO scientific in April 2016, we expect a paradigm shift in undergraduate physics laboratory instruction. We have evaluated the feasibility of using the smart cart by carrying out experiments that are usually performed using traditional PASCO equipment. The simplicity, convenience, and cost-saving achieved by replacing a plethora of traditional laboratory sensors, wires, and equipment clutter with the smart cart are reported here.

Wide-field Diffuse Amacrine Cells in the Monkey Retina Contain Immunoreactive Cocaine- and Amphetamine-Regulated Transcript (CART)

PubMed Central

Liu, Weiley S.; Davis, Elizabeth P.; Lee, Stephen J.; Tseng, Luke; Chuang, Alice Z.; Whitaker, Christopher M.; Massey, Stephen C.; Sherman, Michael B.; Marshak, David W.

2016-01-01

The goals of this study were to localize the neuropeptide Cocaine- and Amphetamine-Regulated Transcript (CART) in primate retinas and to describe the morphology, neurotransmitter content and synaptic connections of the neurons that contain it. Using in situ hybridization, light and electron microscopic immunolabeling, CART was localized to GABAergic amacrine cells in baboon retinas. The CART-positive cells had thin, varicose dendrites that gradually descended through the inner plexiform layer and ramified extensively in the innermost stratum. They resembled two types of wide-field diffuse amacrine cells that had been described previously in macaque retinas using the Golgi method and also A17, serotonin-accumulating and waterfall cells of other mammals. The CART-positive cells received synapses from rod bipolar cell axons and made synapses onto the axons in a reciprocal configuration. The CART-positive cells also received synapses from other amacrine cells. Some of these were located on their primary dendrites, and the presynaptic cells there included dopaminergic amacrine cells. Although some CART-positive somas were localized in the ganglion cell layer, they did not contain the ganglion cell marker RNA binding protein with multiple splicing (RBPMS). Based on these results and electrophysiological studies in other mammals, the CART-positive amacrine cells would be expected to play a major role in the primary rod pathway of primates, providing feedback inhibition to rod bipolar cells. PMID:27568514

Professor: A motorized field-based phenotyping cart

USDA-ARS?s Scientific Manuscript database

An easy-to-customize, low-cost, low disturbance, motorized proximal sensing cart for field-based high-throughput phenotyping is described. General dimensions, motor specifications, and a remote operation application are given. The cart, named Professor, supports mounting multiple proximal sensors an...

Vitamin D supplementation as a potential cause of U-shaped associations between vitamin D levels and negative health outcomes: a decision tree analysis for risk of frailty.

PubMed

Kojima, Gotaro; Iliffe, Steve; Tanabe, Marianne

2017-10-16

A recent controversy in vitamin D research is a "U-shaped association", with elevated disease risks at both high and low 25-hydroxyvitamin D (25 (OH) D) levels. This is a cross-sectional study of 238 male nursing home veterans in Hawaii. Classification and regression tree (CART) analysis identified groups based on 25 (OH) D and vitamin D supplementation for frailty risk. Characteristics were examined and compared across the groups using logistic regression and receiver operating characteristic (ROC) curve analyses. CART analysis identified three distinct groups: vitamin D supplement users (n = 86), non-users with low vitamin D (n = 55), and non-users with high vitamin D (n = 97). Supplement users were the most frail, but had high mean 25 (OH) D of 26.6 ng/mL, which was compatible with 27.1 ng/mL in non-users with high vitamin D, while mean 25 (OH) D of non-users with low vitamin D was 11.7 ng/mL. Supplement users and non-users with low vitamin D were significantly more likely to be frail (odds ratio (OR) = 9.90, 95% CI = 2.18-44.86, p = 0.003; OR = 4.28, 95% CI = 1.44-12.68, p = 0.009, respectively), compared with non-users with low vitamin D. ROC curve analysis showed the three groups significantly predicted frailty (area under the curve = 0.73), with sensitivity of 64.4% and specificity of 76.7%, while 25 (OH) D did not predict frailty. In these nursing home veterans, vitamin D supplement users were the most frail but with high 25 (OH) D. This can potentially be a cause of U-shaped associations between vitamin D levels and negative health outcomes.

Methylation of L1RE1, RARB, and RASSF1 function as possible biomarkers for the differential diagnosis of lung cancer.

PubMed

Walter, R F H; Rozynek, P; Casjens, S; Werner, R; Mairinger, F D; Speel, E J M; Zur Hausen, A; Meier, S; Wohlschlaeger, J; Theegarten, D; Behrens, T; Schmid, K W; Brüning, T; Johnen, G

2018-01-01

Lung cancer is the major cause of cancer-related deaths worldwide. Differential diagnosis can be difficult, especially when only small samples are available. Epigenetic changes are frequently tissue-specific events in carcinogenesis and hence may serve as diagnostic biomarkers. 138 representative formalin-fixed, paraffin-embedded (FFPE) tissues (116 lung cancer cases and 22 benign controls) were used for targeted DNA methylation analysis via pyrosequencing of ten literature-derived methylation markers (APC, CDH1, CDKN2A, EFEMP1, FHIT, L1RE1, MGMT, PTEN, RARB, and RASSF1). Methylation levels were analyzed with the Classification and Regression Tree Algorithm (CART), Conditional Interference Trees (ctree) and ROC. Validation was performed with additional 27 lung cancer cases and 38 benign controls. TCGA data for 282 lung cancer cases was included in the analysis. CART and ctree analysis identified the combination of L1RE1 and RARB as well as L1RE1 and RASSF1 as independent methylation markers with high discriminative power between tumor and benign tissue (for each combination, 91% specificity and 100% sensitivity). L1RE1 methylation associated significantly with tumor type and grade (p<0.001) with highest methylation in the control group. The opposite was found for RARB (p<0.001). RASSF1 methylation increased with tumor type and grade (p<0.001) with strongest methylation in neuroendocrine tumors (NET). Hypomethylation of L1RE1 is frequent in tumors compared to benign controls and associates with higher grade, whereas increasing methylation of RARB is an independent marker for tumors and higher grade. RASSF1 hypermethylation was frequent in tumors and most prominent in NET making it an auxiliary marker for separation of NSCLC and NET. L1RE1 in combination with either RARB or RASSF1 could function as biomarkers for separating lung cancer and non-cancerous tissue and could be useful for samples of limited size such as biopsies.

Very Low Food Security in US Households Is Predicted by Complex Patterns of Health, Economics, and Service Participation.

PubMed

Choi, Seul Ki; Fram, Maryah S; Frongillo, Edward A

2017-10-01

Background: Very low food security (VLFS) happens at the intersection of nuanced and complex patterns of risk characteristics across multiple domains. Little is known about the idiosyncratic situations that lead households to experience VLFS. Objective: We used classification and regression tree (CART) analysis, which can handle complex combinations of predictors, to identify patterns of characteristics that distinguish VLFS households in the United States from other households. Methods: Data came from 3 surveys, the 2011-2014 National Health Interview Survey (NHIS), the 2005-2012 NHANES, and the 2002-2012 Current Population Survey (CPS), with sample participants aged ≥18 y and households with income <300% of the federal poverty line. Survey participants were stratified into households with children, adult-only households, and older-adult households (NHIS, CPS) or individuals aged 18-64 y and individuals aged ≥65 y (NHANES). Household food security was measured with the use of the 10-item US Adult Food Security Scale. Variables from multiple domains, including sociodemographic characteristics, health, health care, and participation in social welfare and food assistance programs, were considered as predictors. The 3 data sources were analyzed separately with the use of CART analysis. Results: Household experiences of VLFS were associated with different predictors for different types of households and often occurred at the intersection of multiple characteristics spanning unmet medical needs, poor health, disability, limitation, depressive symptoms, low income, and food assistance program participation. These predictors built complex trees with various combinations in different types of households. Conclusions: This study showed that multiple characteristics across multiple domains distinguished VLFS households. Flexible and nonlinear methods focusing on a wide range of risk characteristics should be used to identify VLFS households and to inform policies and programs that can address VLFS households' various needs. © 2017 American Society for Nutrition.

Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in the brain of the CCK-1 receptor deficient obese OLETF rat

PubMed Central

Abraham, Hajnalka; Covasa, Mihai; Hajnal, Andras

2013-01-01

Cocaine- and amphetamine regulated transcript (CART) peptide is expressed in brain areas involved in homeostatic regulation and reward. CART has been shown to reduce food intake but the underlying mechanisms and the relevance of this effect to obesity yet remain unknown. Therefore, we used immunohistochemistry to investigate expression of CART peptide in various brain regions of the obese Otsuka Long Evans Tokushima Fatty (OLETF) rats lacking the CCK-1 receptor. Analysis revealed that whereas the distribution of CART peptide-immunoreactive neurons and axonal networks was identical in OLETF rats and lean controls, intensity of CART immunoreactivity was significantly reduced in the rostral part of the nucleus accumbens (p<0.01), the basolateral complex of the amygdala (p<0.05), and the rostro-medial nucleus of solitary tract (p<0.001) of the OLETF rats. These areas are involved in reward and integration of taste and viscerosensory information and have been previously associated with altered functions in this strain. The findings suggest that in addition to previously described deficits in peripheral satiety signals and augmented orexigenic regulation, the anorectic effect of CART peptide may also be diminished in OLETF rats. PMID:19533109

Cocaine- and amphetamine-regulated transcript peptide increases mitochondrial respiratory chain complex II activity and protects against oxygen-glucose deprivation in neurons.

PubMed

Sha, Dujuan; Wang, Luna; Zhang, Jun; Qian, Lai; Li, Qiming; Li, Jin; Qian, Jian; Gu, Shuangshuang; Han, Ling; Xu, Peng; Xu, Yun

2014-09-25

The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55-102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. The above-mentioned effects of CART55-102 were most significant at 0.4nM. These results indicated that CART55-102 suppressed neurotoxicity and enhanced neuronal survival after oxygen-glucose deprivation. CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55-102 as an antioxidant drug. Copyright © 2014 Elsevier B.V. All rights reserved.

GDF15(MIC1) H6D Polymorphism Does Not Influence Cardiovascular Disease in a Latin American Population with Rheumatoid Arthritis

PubMed Central

Amaya-Amaya, Jenny; Rojas-Villarraga, Adriana; Molano-Gonzalez, Nicolas; Montoya-Sánchez, Laura; Nath, Swapan K.; Anaya, Juan-Manuel

2015-01-01

Objective. Rheumatoid arthritis (RA) is the most common autoimmune arthropathy worldwide. The increased prevalence of cardiovascular disease (CVD) in RA is not fully explained by classic risk factors. The aim of this study was to determine the influence of rs1058587 SNP within GDF15(MIC1) gene on the risk of CVD in a Colombian RA population. Methods. This was a cross-sectional analytical study in which 310 consecutive Colombian patients with RA and 228 age- and sex-matched controls were included and assessed for variables associated with CVD. The mixed cluster methodology based on multivariate descriptive methods such as principal components analysis and multiple correspondence analyses and regression tree (CART) predictive model were performed. Results. Of the 310 patients, 87.4% were women and CVD was reported in 69.5%. Significant differences concerning GDF15 polymorphism were not observed between patients and controls. Mean arterial pressure, current smoking, and some clusters were significantly associated with CVD. Conclusion. GDF15 (rs1058587) does not influence the development of CVD in the population studied. PMID:26090487

21 CFR 868.6175 - Cardiopulmonary emergency cart.

Code of Federal Regulations, 2011 CFR

2011-04-01

... cardiopulmonary resuscitation. (b) Classification. Class I (general controls). The device is exempt from the... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary emergency cart. 868.6175 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6175 Cardiopulmonary emergency cart...

21 CFR 868.6175 - Cardiopulmonary emergency cart.

Code of Federal Regulations, 2010 CFR

2010-04-01

... cardiopulmonary resuscitation. (b) Classification. Class I (general controls). The device is exempt from the... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary emergency cart. 868.6175 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6175 Cardiopulmonary emergency cart...

21 CFR 868.6175 - Cardiopulmonary emergency cart.

Code of Federal Regulations, 2014 CFR

2014-04-01

... cardiopulmonary resuscitation. (b) Classification. Class I (general controls). The device is exempt from the... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary emergency cart. 868.6175 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6175 Cardiopulmonary emergency cart...

21 CFR 868.6175 - Cardiopulmonary emergency cart.

Code of Federal Regulations, 2012 CFR

2012-04-01

... cardiopulmonary resuscitation. (b) Classification. Class I (general controls). The device is exempt from the... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary emergency cart. 868.6175 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6175 Cardiopulmonary emergency cart...

21 CFR 868.6175 - Cardiopulmonary emergency cart.

Code of Federal Regulations, 2013 CFR

2013-04-01

... cardiopulmonary resuscitation. (b) Classification. Class I (general controls). The device is exempt from the... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary emergency cart. 868.6175 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6175 Cardiopulmonary emergency cart...

Naturally Inspired Firefly Controller For Stabilization Of Double Inverted Pendulum

NASA Astrophysics Data System (ADS)

Srikanth, Kavirayani; Nagesh, Gundavarapu

2015-12-01

A double inverted pendulum plant as an established model that is analyzed as part of this work was tested under the influence of time delay, where the controller was fine tuned using a firefly algorithm taking into considering the fitness function of variation of the cart position and to minimize the cart position displacement and still stabilize it effectively. The naturally inspired algorithm which imitates the fireflies definitely is an energy efficient method owing to the inherent logic of the way the fireflies respond collectively and has shown that critical time delays makes the system healthy.

Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

PubMed Central

Lodi, Sara; Phillips, Andrew; Fidler, Sarah; Hawkins, David; Gilson, Richard; McLean, Ken; Fisher, Martin; Post, Frank; Johnson, Anne M.; Walker-Nthenda, Louise; Dunn, David; Porter, Kholoud

2013-01-01

Background The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation. Methods Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion). Results Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm3 and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively. Conclusion Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance. PMID:24086588

Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment

PubMed Central

Cooper, Jason D.; Tomasik, Jakub; Bahn, Sabine; Aerts, Joeri L.; Osterhaus, Albert D. M. E.; Gruters, Rob A.; Andeweg, Arno C.

2018-01-01

Objectives To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level. Design An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vaccination was evaluated at the plasma protein level during the period preceding cART interruption, during analytical therapy interruption and at viral reactivation. Healthy controls and post-exposure prophylactically treated healthy individuals were included as controls. Methods Plasma marker (‘analyte’) levels including cytokines, chemokines, growth factors, and hormones were measured in trial participants and control plasma samples using a multiplex immunoassay. Analyte levels were analysed using principle component analysis, cluster analysis and limma. Blood neutrophil counts were analysed using linear regression. Results Plasma analyte levels of HIV-infected individuals are markedly different from those of healthy controls and HIV-negative individuals receiving post-exposure prophylaxis. Viral reactivation following cART interruption also affects multiple analytes, but cART interruption itself only has only a minor effect. We find that Thyroxine-Binding Globulin (TBG) levels and late-stage neutrophil numbers correlate with the time off cART after DC vaccination. Furthermore, analysis shows that cART alters several regulators of blood glucose levels, including C-peptide, chromogranin-A and leptin. HIV reactivation is associated with the upregulation of CXCR3 ligands. Conclusions Chronic HIV infection leads to a change in multiple plasma analyte levels, as does virus reactivation after cART interruption. Furthermore, we find evidence for the involvement of TBG and neutrophils in the response to DC-vaccination in the setting of HIV-infection. PMID:29389978

Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma.

PubMed

Feng, Kai-Chao; Guo, Ye-Lei; Liu, Yang; Dai, Han-Ren; Wang, Yao; Lv, Hai-Yan; Huang, Jian-Hua; Yang, Qing-Ming; Han, Wei-Dong

2017-01-05

Cholangiocarcinoma (CCA) is one of the most fatal malignant tumors with increasing incidence, mortality, and insensitivity to traditional chemo-radiotherapy and targeted therapy. Chimeric antigen receptor-modified T cell (CART) immunotherapy represents a novel strategy for the management of many malignancies. However, the potential of CART therapy in treating advanced unresectable/metastatic CCA is uncharted so far. In this case, a 52-year-old female who was diagnosed as advanced unresectable/metastatic CCA and resistant to the following chemotherapy and radiotherapy was treated with CART cocktail immunotherapy, which was composed of successive infusions of CART cells targeting epidermal growth factor receptor (EGFR) and CD133, respectively. The patient finally achieved an 8.5-month partial response (PR) from the CART-EGFR therapy and a 4.5-month-lasting PR from the CART133 treatment. The CART-EGFR cells induced acute infusion-related toxicities such as mild chills, fever, fatigue, vomiting and muscle soreness, and a 9-day duration of delayed lower fever, accompanied by escalation of IL-6 and C reactive protein (CRP), acute increase of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase, and grade 2 lichen striatus-like skin pathological changes. The CART133 cells induced an intermittent upper abdominal dull pain, chills, fever, and rapidly deteriorative grade 3 systemic subcutaneous hemorrhages and congestive rashes together with serum cytokine release, which needed emergent medical intervention including intravenous methylprednisolone. This case suggests that CART cocktail immunotherapy may be feasible for the treatment of CCA as well as other solid malignancies; however, the toxicities, especially the epidermal/endothelial damages, require a further investigation. ClinicalTrials.gov NCT01869166 and NCT02541370 .

An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells.

PubMed

Zhang, Yajing; Zhang, Wenying; Dai, Hanren; Wang, Yao; Shi, Fengxia; Wang, Chunmeng; Guo, Yelei; Liu, Yang; Chen, Meixia; Feng, Kaichao; Zhang, Yan; Liu, Chuanjie; Yang, Qingming; Li, Suxia; Han, Weidong

2016-04-01

Anti-CD19 chimeric antigen receptor-modified T (CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune- cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines (mainly interleukin 6 and C-reactive protein) were identified in two patients (Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission.

Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment.

PubMed

van den Ham, Henk-Jan; Cooper, Jason D; Tomasik, Jakub; Bahn, Sabine; Aerts, Joeri L; Osterhaus, Albert D M E; Gruters, Rob A; Andeweg, Arno C

2018-01-01

To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level. An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vaccination was evaluated at the plasma protein level during the period preceding cART interruption, during analytical therapy interruption and at viral reactivation. Healthy controls and post-exposure prophylactically treated healthy individuals were included as controls. Plasma marker ('analyte') levels including cytokines, chemokines, growth factors, and hormones were measured in trial participants and control plasma samples using a multiplex immunoassay. Analyte levels were analysed using principle component analysis, cluster analysis and limma. Blood neutrophil counts were analysed using linear regression. Plasma analyte levels of HIV-infected individuals are markedly different from those of healthy controls and HIV-negative individuals receiving post-exposure prophylaxis. Viral reactivation following cART interruption also affects multiple analytes, but cART interruption itself only has only a minor effect. We find that Thyroxine-Binding Globulin (TBG) levels and late-stage neutrophil numbers correlate with the time off cART after DC vaccination. Furthermore, analysis shows that cART alters several regulators of blood glucose levels, including C-peptide, chromogranin-A and leptin. HIV reactivation is associated with the upregulation of CXCR3 ligands. Chronic HIV infection leads to a change in multiple plasma analyte levels, as does virus reactivation after cART interruption. Furthermore, we find evidence for the involvement of TBG and neutrophils in the response to DC-vaccination in the setting of HIV-infection.

Comparison of a hybrid medication distribution system to simulated decentralized distribution models.

PubMed

Gray, John P; Ludwig, Brad; Temple, Jack; Melby, Michael; Rough, Steve

2013-08-01

The results of a study to estimate the human resource and cost implications of changing the medication distribution model at a large medical center are presented. A two-part study was conducted to evaluate alternatives to the hospital's existing hybrid distribution model (64% of doses dispensed via cart fill and 36% via automated dispensing cabinets [ADCs]). An assessment of nurse, pharmacist, and pharmacy technician workloads within the hybrid system was performed through direct observation, with time standards calculated for each dispensing task; similar time studies were conducted at a comparator hospital with a decentralized medication distribution system involving greater use of ADCs. The time study data were then used in simulation modeling of alternative distribution scenarios: one involving no use of cart fill, one involving no use of ADCs, and one heavily dependent on ADC dispensing (89% via ADC and 11% via cart fill). Simulation of the base-case and alternative scenarios indicated that as the modeled percentage of doses dispensed from ADCs rose, the calculated pharmacy technician labor requirements decreased, with a proportionately greater increase in the nursing staff workload. Given that nurses are a higher-cost resource than pharmacy technicians, the projected human resource opportunity cost of transitioning from the hybrid system to a decentralized system similar to the comparator facility's was estimated at $229,691 per annum. Based on the simulation results, it was decided that a transition from the existing hybrid medication distribution system to a more ADC-dependent model would result in an unfavorable shift in staff skill mix and corresponding human resource costs at the medical center.

STS-37 crewmembers move CETA electrical cart along rail in JSC's WETF pool

NASA Image and Video Library

1989-12-06

STS-37 Atlantis, Orbiter Vehicle (OV) 104, Mission Specialist (MS) Jerry L. Ross generates electrical power using hand pedals to move crew and equipment translation aid (CETA) cart along a rail during underwater session in JSC's Weightless Environment Training Facility (WETF) Bldg 29. Wearing an extravehicular mobility unit (EMU), Ross operates CETA electrical cart as MS Jerome Apt holds onto the back of the cart. The two crewmembers are practicing a extravehicular activity (EVA) spacewalk they will perform in OV-104's payload bay during STS-37. CETA is a type of railroad hand cart planned as a spacewalker's transportation system along the truss of Space Station Freedom (SSF). SCUBA divers monitor astronauts' underwater activity.

Strategies from a nationwide health information technology implementation: the VA CART story.

PubMed

Box, Tamára L; McDonell, Mary; Helfrich, Christian D; Jesse, Robert L; Fihn, Stephan D; Rumsfeld, John S

2010-01-01

The VA Cardiovascular Assessment, Reporting, and Tracking (CART) system is a customized electronic medical record system which provides standardized report generation for cardiac catheterization procedures, serves as a national data repository, and is the centerpiece of a national quality improvement program. Like many health information technology projects, CART implementation did not proceed without some barriers and resistance. We describe the nationwide implementation of CART at the 77 VA hospitals which perform cardiac catheterizations in three phases: (1) strategic collaborations; (2) installation; and (3) adoption. Throughout implementation, success required a careful balance of technical, clinical, and organizational factors. We offer strategies developed through CART implementation which are broadly applicable to technology projects aimed at improving the quality, reliability, and efficiency of health care.

Environmental assessment for the Atmospheric Radiation Measurement (ARM) Program: Southern Great Plains Cloud and Radiation Testbed (CART) site

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

Policastro, A.J.; Pfingston, J.M.; Maloney, D.M.

The Atmospheric Radiation Measurement (ARM) Program is aimed at supplying improved predictive capability of climate change, particularly the prediction of cloud-climate feedback. The objective will be achieved by measuring the atmospheric radiation and physical and meteorological quantities that control solar radiation in the earth`s atmosphere and using this information to test global climate and related models. The proposed action is to construct and operate a Cloud and Radiation Testbed (CART) research site in the southern Great Plains as part of the Department of Energy`s Atmospheric Radiation Measurement Program whose objective is to develop an improved predictive capability of global climatemore » change. The purpose of this CART research site in southern Kansas and northern Oklahoma would be to collect meteorological and other scientific information to better characterize the processes controlling radiation transfer on a global scale. Impacts which could result from this facility are described.« less

Advanced multiphysics coupling for LWR fuel performance analysis

DOE PAGES

Hales, J. D.; Tonks, M. R.; Gleicher, F. N.; ...

2015-10-01

Even the most basic nuclear fuel analysis is a multiphysics undertaking, as a credible simulation must consider at a minimum coupled heat conduction and mechanical deformation. The need for more realistic fuel modeling under a variety of conditions invariably leads to a desire to include coupling between a more complete set of the physical phenomena influencing fuel behavior, including neutronics, thermal hydraulics, and mechanisms occurring at lower length scales. This paper covers current efforts toward coupled multiphysics LWR fuel modeling in three main areas. The first area covered in this paper concerns thermomechanical coupling. The interaction of these two physics,more » particularly related to the feedback effect associated with heat transfer and mechanical contact at the fuel/clad gap, provides numerous computational challenges. An outline is provided of an effective approach used to manage the nonlinearities associated with an evolving gap in BISON, a nuclear fuel performance application. A second type of multiphysics coupling described here is that of coupling neutronics with thermomechanical LWR fuel performance. DeCART, a high-fidelity core analysis program based on the method of characteristics, has been coupled to BISON. DeCART provides sub-pin level resolution of the multigroup neutron flux, with resonance treatment, during a depletion or a fast transient simulation. Two-way coupling between these codes was achieved by mapping fission rate density and fast neutron flux fields from DeCART to BISON and the temperature field from BISON to DeCART while employing a Picard iterative algorithm. Finally, the need for multiscale coupling is considered. Fission gas production and evolution significantly impact fuel performance by causing swelling, a reduction in the thermal conductivity, and fission gas release. The mechanisms involved occur at the atomistic and grain scale and are therefore not the domain of a fuel performance code. However, it is possible to use lower length scale models such as those used in the mesoscale MARMOT code to compute average properties, e.g. swelling or thermal conductivity. These may then be used by an engineering-scale model. Examples of this type of multiscale, multiphysics modeling are shown.« less

Risk of Progressive Multifocal Leukoencephalopathy in the Combination Antiretroviral Therapy Era in the French Hospital Database on Human Immunodeficiency Virus (ANRS-C4).

PubMed

Melliez, Hugues; Mary-Krause, Murielle; Bocket, Laurence; Guiguet, Marguerite; Abgrall, Sophie; De Truchis, Pierre; Katlama, Christine; Martin-Blondel, Guillaume; Henn, Aurelia; Revest, Matthieu; Robineau, Olivier; Khuong-Josses, Marie-Aude; Canestri, Anna; De Castro, Nathalie; Joly, Véronique; Mokhtari, Saadia; Risso, Karine; Gasnault, Jacques; Costagliola, Dominique

2018-04-04

Risk factors for progressive multifocal leukoencephalopathy (PML) in individuals with human immunodeficiency virus (HIV) infection are poorly documented in the era of combination antiretroviral therapy (cART). We studied HIV-1-infected individuals aged ≥15 years who had no history of PML and were prospectively followed up between 1997 and 2011 in the French Hospital Database on HIV (FHDH-ANRS CO4) cohort. Cox models were used to calculate adjusted hazard ratios (HRs), focusing on sub-Saharan origin, suggested to be protective, and recent cART initiation, potentially associated with an increased risk of PML. PML developed in 555 individuals, in 57 during the first 6 months of cART. From 1997-2000 to 2009-2011, the incidence fell from 1.15 (95% confidence interval [CI], .98-1.31) to 0.49 (.37-.61) per 1000 person-years. Sub-Saharan African origin had no clear influence (HR, 0.80; 95% CI, .58-1.11). Compared with men who have sex with men, injection drug users (IDUs) were at higher risk (HR, 1.80 [95% CI, 1.32-2.45] for male and 1.68 [1.13-2.48] for female IDUs). When IDUs were excluded, hepatitis C virus seropositivity was associated with an increased risk (HR, 1.40; 95% CI, 1.02-1.93). Compared with no cART initiation, initiation <6 months previously was associated with PML onset (HR, 4.91; 95% CI, 2.42-9.95). Recent cART initiation is associated with an increased risk of PML, as are injection drug use and hepatitis C virus seropositivity. Sub-Saharan African origin had no protective effect.

Effects of cryopreservation on chimeric antigen receptor T cell functions.

PubMed

Xu, Hao; Cao, Wenyue; Huang, Liang; Xiao, Min; Cao, Yang; Zhao, Lei; Wang, Na; Zhou, Jianfeng

2018-06-14

Chimeric antigen receptor T (CART) cell therapy has emerged as a potentially curative "drug" for cancer treatment. Cryopreservation of CART cells is necessary for their clinical application. Systematic studies on the effects of cryopreservation on the antitumor function of CART cells are lacking. Therefore, we compared the phenotypes and functions of CART cells that were cryopreserved during ex vivo expansion with those of freshly isolated populations. T cells expressing an anti-B-cell-maturation-antigen (BCMA) chimeric antigen receptor (CAR) were expanded in vitro for 10 days and then cryopreserved. After one month, the cells were resuscitated, and their transduction rates, apoptosis rates and cell subsets were examined via flow cytometry. The results indicated no significant changes in transduction rates or cell subsets, and the survival rate of the resuscitated cells was approximately 90% Furthermore, similar tumoricidal effects and degranulation functions of the resuscitated cells compared with normally cultured cells were verified by calcein release and CD107a assays. A NOD/SCID mouse model was used to estimate the differences in the in vivo antitumor effects of the cryopreserved and normally cultured T cells, but no significant differences were observed. Following co-culture with several target cell types, the cytokines released by the cryopreserved and normally cultured T cells were measured via enzyme-linked immunosorbent assays (ELISAs). The results revealed that the release of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was significantly decreased. These data demonstrated that with the exception of a decrease in cytokine release, the cryopreserved CART cells retained their antitumor functions. Copyright © 2018. Published by Elsevier Inc.

Antiretroviral therapy CNS penetration and HIV-1–associated CNS disease

PubMed Central

Winston, A.; Walsh, J.; Post, F.; Porter, K.; Gazzard, B.; Fisher, M.; Leen, C.; Pillay, D.; Hill, T.; Johnson, M.; Gilson, R.; Anderson, J.; Easterbrook, P.; Bansi, L.; Orkin, C.; Ainsworth, J.; Palfreeman, A.; Gompels, M.; Phillips, A.N.; Sabin, C.A.

2011-01-01

Objective: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5–8) in 1996–1997 to 9 (8–10) in 2000–2001 and subsequently declined to 6 (7–8) in 2006–2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤4, and less frequently in those with scores ≥10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤4 were independently associated with increased risk of death. Conclusion: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. PMID:21339496

Antiretroviral Regimens and CD4/CD8 Ratio Normalization in HIV-Infected Patients during the Initial Year of Treatment: A Cohort Study

PubMed Central

De Salvador-Guillouët, F.; Sakarovitch, C.; Durant, J.; Risso, K.; Demonchy, E.; Roger, P. M.; Fontas, E.

2015-01-01

Background As CD4/CD8 ratio inversion has been associated with non-AIDS morbidity and mortality, predictors of ratio normalization after cART need to be studied. Here, we aimed to investigate the association of antiretroviral regimens with CD4/CD8 ratio normalization within an observational cohort. Methods We selected, from a French cohort at the Nice University Hospital, HIV-1 positive treatment-naive patients who initiated cART between 2000 and 2011 with a CD4/CD8 ratio <1. Association between cART and ratio normalization (>1) in the first year was assessed using multivariate logistic regression models. Specific association with INSTI-containing regimens was examined. Results 567 patients were included in the analyses; the median CD4/CD8 ratio was 0.36. Respectively, 52.9%, 29.6% and 10.4% initiated a PI-based, NNRTI-based or NRTI-based cART regimens. About 8% of the population started an INSTI-containing regimen. 62 (10.9%) patients achieved a CD4/CD8 ratio ≥1 (N group). cART regimen was not associated with normalization when coded as PI-, NNRTI- or NRTI-based regimen. However, when considering INSTI-containing regimens alone, there was a strong association with normalization [OR, 7.67 (2.54–23.2)]. Conclusions Our findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year in naïve patients. Should it be confirmed in a larger population, it would be another argument for their use as first-line regimen as it is recommended in the recent update of the “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents”. PMID:26485149

Poor Linkage to Care Despite Significant Improvement in Access to Early cART in Central Poland - Data from Test and Keep in Care (TAK) Project.

PubMed

Kowalska, Justyna D; Shepherd, Leah; Ankiersztejn-Bartczak, Magdalena; Cybula, Aneta; Czeszko-Paprocka, Hanna; Firląg-Burkacka, Ewa; Mocroft, Amanda; Horban, Andrzej

2016-01-01

The main objective of the TAK project is investigating barriers in accessing HIV care after HIV-diagnosis at the CBVCTs of central Poland. Here we describe factors associated with and changes over time in linkage to care and access to cART. Data collected in 2010-2013 in CBVCTs were linked with HIV clinics records using unique identifiers. Individuals were followed from the day of CBVCTs visit until first clinical visit or 4/06/2014. Cox-proportional hazard models were used to identify factors associated with being linked to care and starting cART. In total 232 persons were diagnosed HIV-positive and 144 (62.1% 95%CI: 55.5-68.3) persons were linked to care. There was no change over time in linkage to care (p = 0.48), while time to starting cART decreased (p = 0.02). Multivariate factors associated with a lower rate of linkage to care were hetero/bisexual sexual orientation, lower education, not having an HIV-positive partner and not using condoms in a stable relationship. Multivariate factors associated with starting cART were lower education, recent year of linked to care, and first HIV RNA and CD4 cell count. Benefits of linkage to care, measured by access to early treatment, steadily improved in recent years. However at least 1 in 3 persons aware of their HIV status in central Poland remained outside professional healthcare. Persons at higher risk of remaining outside care, thus target population for future interventions, are bi/heterosexuals and those with lower levels of education.

Impact of HIV drug resistance on virologic and immunologic failure and mortality in a cohort of patients on antiretroviral therapy in China

PubMed Central

Liao, Lingjie; Xing, Hui; Su, Bin; Wang, Zhe; Ruan, Yuhua; Wang, Xia; Liu, Zhendong; Lu, Yanan; Yang, Shimei; Zhao, Quanbi; Vermund, Sten H.; Chen, Ray Y.; Shao, Yiming

2013-01-01

Objectives: To study the dynamics of HIV drug resistance (HIVDR) and its association with virologic and immunologic failure as well as mortality among patients on combination antiretroviral therapy (cART) in China. Design: We recruited 365 patients on cART in two rural Chinese counties in 2003–2004 and followed them every 6 months until May 2010. Methods: Virologic failure, HIVDR, immunologic failure and death were documented. We used Kaplan–Meier and the proportional hazards models to identify the timing of the events, and risk factors for mortality. Results: At the end of study, patients had been followed for 1974.3 person-years, a median of 6.1 years. HIVDR mutations were found in 235 (64.4%) patients and 75 died (20.5%, 3.8/100 person-years). Median time from cART to detection of virologic failure was 17.5 months, to HIVDR 36.6 months and to immunologic failure 55.2 months (≈18-month median interval between each adverse milestone). Being male, having a baseline CD4+ cell count of less than 50 cells/μl and HIVDR were associated with higher mortality. Patients who developed HIVDR in the first year of treatment had higher mortality than those developing HIVDR later (adjusted hazard ratio 1.90, 95% confidence interval 1.01–3.48). Conclusion: HIVDR was common and was associated with higher mortality among Chinese patients on cART, particular when HIVDR was detected early in therapy. Our study reinforces the importance of improving patient adherence to cART in order to delay the emergence of HIVDR and obviate the need to switch to costly second-line drug regimens too early. PMID:23803794

AZ-101 Mixer Pump Demonstration Data Acquisition System and Gamma Cart Data Acquisition Control System Software Configuration Management Plan

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

WHITE, D.A.

1999-12-29

This Software Configuration Management Plan (SCMP) provides the instructions for change control of the AZ1101 Mixer Pump Demonstration Data Acquisition System (DAS) and the Sludge Mobilization Cart (Gamma Cart) Data Acquisition and Control System (DACS).

The Ballistic Cart on an Incline Revisited.

ERIC Educational Resources Information Center

Serway, Raymond A.; And Others

1995-01-01

Presents the theory behind the mechanics demonstration that involves projecting a ball vertically upward from a ballistic cart moving along an inclined plane. The measured overshoot is believed to be due, in part, to the presence of rolling friction and the inertial properties of the cart wheels. (JRH)

Fan Cart: The Next Generation

ERIC Educational Resources Information Center

Lamore, Brian

2016-01-01

For years the fan cart has provided physics students with an excellent resource for exploring fundamental mechanics concepts such as acceleration, Newton's laws, impulse, momentum, work-energy, and energy conversions. "The Physics Teacher" has even seen some excellent do-it-yourself (DIY) fan carts and activities. If you are interested…

Field responses of Prunus serotina and Asclepias syriaca to ozone around southern Lake Michigan.

PubMed

Bennett, J P; Jepsen, E A; Roth, J A

2006-07-01

Higher ozone concentrations east of southern Lake Michigan compared to west of the lake were used to test hypotheses about injury and growth effects on two plant species. We measured approximately 1000 black cherry trees and over 3000 milkweed stems from 1999 to 2001 for this purpose. Black cherry branch elongation and milkweed growth and pod formation were significantly higher west of Lake Michigan while ozone injury was greater east of Lake Michigan. Using classification and regression tree (CART) analyses we determined that departures from normal precipitation, soil nitrogen and ozone exposure/peak hourly concentrations were the most important variables affecting cherry branch elongation, and milkweed stem height and pod formation. The effects of ozone were not consistently comparable with the effects of soil nutrients, weather, insect or disease injury, and depended on species. Ozone SUM06 exposures greater than 13 ppm-h decreased cherry branch elongation 18%; peak 1-h exposures greater than 93 ppb reduced milkweed stem height 13%; and peak 1-h concentrations greater than 98 ppb reduced pod formation 11% in milkweed.

Increased mortality among Indigenous persons in a multisite cohort of people living with HIV in Canada.

PubMed

Benoit, Anita C; Younger, Jaime; Beaver, Kerrigan; Jackson, Randy; Loutfy, Mona; Masching, Renée; Nobis, Tony; Nowgesic, Earl; O'Brien-Teengs, Doe; Whitebird, Wanda; Zoccole, Art; Hull, Mark; Jaworsky, Denise; Benson, Elizabeth; Rachlis, Anita; Rourke, Sean B; Burchell, Ann N; Cooper, Curtis; Hogg, Robert S; Klein, Marina B; Machouf, Nima; Montaner, Julio S G; Tsoukas, Chris; Raboud, Janet

2017-06-16

Compare all-cause mortality between Indigenous participants and participants of other ethnicities living with HIV initiating combination antiretroviral therapy (cART) in an interprovincial multi-site cohort. The Canadian Observational Cohort is a collaboration of 8 cohorts of treatment-naïve persons with HIV initiating cART after January 1, 2000. Participants were followed from the cART initiation date until death or last viral load (VL) test date on or before December 31, 2012. Cox proportional hazard models were used to estimate the effect of ethnicity on time until death after adjusting for age, gender, injection drug use, being a man who has sex with men, hepatitis C, province of origin, baseline VL and CD4 count, year of cART initiation and class of antiretroviral medication. The study sample consisted of 7080 participants (497 Indigenous, 2471 Caucasian, 787 African/Caribbean/Black (ACB), 629 other, and 2696 unknown ethnicity). Most Indigenous persons were from British Columbia (BC) (83%), with smaller numbers from Ontario (13%) and Québec (4%). During the study period, 714 (10%) participants died. The five-year survival probability was lower for Indigenous persons (0.77) than for Caucasian (0.94), ACB (0.98), other ethnicities (0.96) and unknown ethnicities (0.85) (p < 0.0001). In an adjusted proportional hazard model for which missing data were imputed, Indigenous persons were more likely to die than Caucasian participants (hazard ratio = 2.69, p < 0.0001). The mortality rate for Indigenous persons was higher than for other ethnicities and is largely reflective of the BC population. Addressing treatment challenges and identifying HIV- and non-HIV-related causes for mortality among Indigenous persons is required to optimize their clinical management.

Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection

PubMed Central

Hulgan, Todd; Samuels, David C.; Bush, William; Ellis, Ronald J.; Letendre, Scott L.; Heaton, Robert K.; Franklin, Donald R.; Straub, Peter; Murdock, Deborah G.; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin B.; Marra, Christina M.; McArthur, Justin C.; McCutchan, J. Allen; Morgello, Susan; Simpson, David M.; Grant, Igor; Kallianpur, Asha R.

2015-01-01

Background. Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Methods. CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir. Results. Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm3, 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P < .001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = −0.34; P = .008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval, .04, .63; P = .009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry. Conclusions. In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons. PMID:26129753

Engineer pedals STS-37 CETA electrical cart along track in JSC MAIL Bldg 9A

NASA Technical Reports Server (NTRS)

1990-01-01

McDonnell Douglas engineer Gary Peters operates crew and equipment translation aid (CETA) electrical hand pedal cart in JSC's Mockup and Integration Laboratory (MAIL) Bldg 9A. Peters, wearing extravehicular mobility unit (EMU) boots and positioned in portable foot restraint (PFR), is suspended above CETA cart and track via harness to simulate weightlessness. The electrical cart is moved by electricity generated from turning hand pedals. CETA will be tested in orbit in the payload bay of Atlantis, Orbiter Vehicle (OV) 104, during STS-37.

Apparatus and method for servicing an elongated suspended pump motor in an electric power plant with limited access

DOEpatents

Chavez, Rossemary V.; Ekeroth, Douglas E.; Johnson, F. Thomas; Matusz, John M.

1994-01-01

Elongated coolant pumps suspended under steam generators within containment in a power plant with limited access space, are removed and replaced by an elongated maintenance cart with an elongated opening along one side in which the motor is received. Rollers support the cart for conveying the elongated motor in an upright position out from under the steam generator and onto an elevator. The elevator is lowered to transfer support of the cart and motor through trunnions to saddles straddling the elevator for rotation of the cart to a generally horizontal position. The elevator then raises the horizontally disposed cart carrying the motor to a higher floor where it is rolled off the elevator and out through the auxiliary equipment hatch.

Apparatus and method for servicing an elongated suspended pump motor in an electric power plant with limited access

DOEpatents

Chavez, R.V.; Ekeroth, D.E.; Johnson, F.T.; Matusz, J.M.

1994-04-26

Elongated coolant pumps suspended under steam generators within containment in a power plant with limited access space, are removed and replaced by an elongated maintenance cart with an elongated opening along one side in which the motor is received. Rollers support the cart for conveying the elongated motor in an upright position out from under the steam generator and onto an elevator. The elevator is lowered to transfer support of the cart and motor through trunnions to saddles straddling the elevator for rotation of the cart to a generally horizontal position. The elevator then raises the horizontally disposed cart carrying the motor to a higher floor where it is rolled off the elevator and out through the auxiliary equipment hatch. 14 figures.

Nursing perception of the impact of medication carts on patient safety and ergonomics in a teaching health care center.

PubMed

Rochais, Élise; Atkinson, Suzanne; Bussières, Jean-François

2013-04-01

In our Quebec (Canada) University Hospital Center, 68 medication carts have been implemented as part of a nationally funded project on drug distribution technologies. There are limited data published about the impact of medication carts in point-of-care units. Our main objective was to assess nursing staff's perception and satisfaction of medication carts on patient safety and ergonomics. Quantitative and qualitative cross-sectional study. Data were gathered from a printed questionnaire administered to nurses and an organized focus group composed of nurses and pharmacists. A total of 195 nurses completed the questionnaire. Eighty percent of the nurses agreed that medication carts made health care staff's work easier and 64% agreed that it helped to reduce medication incidents/accidents. Only 27% and 43% agreed that carts' location reduces the risk of patients' interruptions and colleagues' interruptions, respectively. A total of 17 suggestions were extracted from the focus group (n = 7 nurses; n = 3 pharmacist) and will be implemented in the next year. This descriptive study confirms the positive perception and satisfaction of nurses exposed to medication carts. However, interruptions are a major concern and source of dissatisfaction. The focus group has revealed many issues which will be improved.

Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in high-income countries.

PubMed

del Amo, Julia; Moreno, Santiago; Bucher, Heiner C; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Lodi, Sara; van Sighem, Ard; de Wolf, Wolf; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; Miró, José M; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Toulomi, Giota; Gargalianos, Panagiotis; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A

2012-05-01

The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries. The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting. Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL. Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.

Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study.

PubMed

Van der Watt, Johan J; Wilkinson, Katalin A; Wilkinson, Robert J; Heckmann, Jeannine M

2014-02-10

In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study. One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays. Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002). The initiation of cART in previously treatment naïve individuals was associated with a cytokine 'burst' between 2- and 4 weeks compared with pre-cART levels. Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of "pain-associated" cytokine and soluble receptors shortly after cART initiation.

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review].

PubMed

Zuo, Yingxi; Wang, Jingbo; Lu, Aidong; Jia, Yueping; Wu, Jun; Dong, Lujia; Chang, Lungji; Zhang, Leping

2016-02-01

To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL). A relapsed B-ALL child after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was treated with CAR-T, and the related literatures were reviewed. An 11-year-old girl with TEL-AML1 fusion gene positive BALL who suffered a bone marrow relapse 28 months after remission from conventional chemotherapy. During the second remission, the patient received haploidentical allo-HSCT. She relapsed with detectable TEL-AML1 fusion gene even after chemotherapy and donor leukocyte infusions. She received an experimental donor-derived fourth generation CD19 CAR-T therapy. After infusion of 1 × 10(6)/kg CAR-T cells, she experienced only mild or moderate cytokine-release syndrome and the minimal residual disease turned negative. Then three maintenance of CAR-T cell infusions [(0.83-1.65)×10(6)/kg] was administered, and the disease-free survival had lasted for 10 months. However, the TEL-AML1 copies in her blood still increased and she died with leukemia relapse after additional CAR-T cell infusion. Treatment of relapsed B-ALL with the fourth generation CAR-T cells directed against CD19 was effective and safe. CAR-T therapy is a novel therapeutic approach that could be useful for patients with relapsed and refractory B-ALL who have failed all other treatment options.

Antiretroviral therapy modifies the genetic effect of known type 2 diabetes-associated risk variants in HIV-infected women.

PubMed

Frasco, Melissa A; Karim, Roksana; Van Den Berg, David; Watanabe, Richard M; Anastos, Kathryn; Cohen, Mardge; Gange, Stephen J; Gustafson, Deborah R; Liu, Chenglong; Tien, Phyllis C; Mack, Wendy J; Pearce, Celeste L

2014-07-31

Type 2 diabetes mellitus incidence is increased in HIV-infected persons. We examined the associations of diabetes mellitus with known diabetes mellitus-risk alleles from the general population in the context of HIV infection, and explored effect modification by combination antiretroviral therapy (cART). The Women's Interagency HIV Study is a prospective cohort of HIV-infected women. Seventeen European-derived diabetes mellitus-risk polymorphisms were genotyped in the eligible participants of the Women's Interagency HIV Study. Analyses were run separately for non-African Americans (Whites, Hispanics, Asians, and other; n = 378, 49 with incident diabetes mellitus) and African Americans (n = 591, 49 with incident diabetes mellitus). Cox proportional-hazards models were fit to estimate hazard ratios for diabetes mellitus overall and within strata of cART. In non-African Americans, heterogeneity across cART regimen was observed for nine of the 14 polymorphisms (phet < 0.05). One polymorphism was statistically significantly inversely associated with diabetes mellitus risk among women taking two nucleotide reverse transcriptase inhibitors (NRTIs) + non-nucleotide reverse transcriptase inhibitor (NNRTI). Five polymorphisms were statistically significantly associated with diabetes mellitus among women treated with at least two NRTIs + at least one protease inhibitor and one polymorphism was associated with diabetes mellitus among those treated with at least three NRTIs ± NNRTI. The hazard ratio per risk allele for IGF2BP2 rs1470579 was 2.67 (95% confidence interval 1.67-4.31) for women taking cART with at least two NRTIs + at least one protease inhibitor and 2.45 (95% confidence interval 1.08-5.53) in women taking at least three NRTIs ± NNRTI (phet = 2.50 × 10⁻³). No such associations were observed in the African Americans. Genetic susceptibility to diabetes mellitus, based on the variants studied, is substantially elevated among HIV-infected women using cART containing three or more NRTI/protease inhibitor components. A personalized medicine approach to cART selection may be indicated for HIV-infected persons carrying these diabetes mellitus-risk variants.

The PASCO Wireless Smart Cart: A Game Changer in the Undergraduate Physics Laboratory

ERIC Educational Resources Information Center

Shakur, Asif; Connor, Rainor

2018-01-01

With the introduction of the Wireless Smart Cart by PASCO scientific in April 2016, we expect a paradigm shift in undergraduate physics laboratory instruction. We have evaluated the feasibility of using the smart cart by carrying out experiments that are usually performed using traditional PASCO equipment. The simplicity, convenience, and…

CART (Communication Access Realtime Translation). PEPNet Tipsheet

ERIC Educational Resources Information Center

Larson, Judy, Comp.

1999-01-01

Communication Access Realtime Translation--(CART)--is the instant translation of the spoken word into English text performed by a CART reporter using a stenotype machine, notebook computer and realtime software. The text is then displayed on a computer monitor or other display device for the student who is deaf or hard of hearing to read. This…

Classification of Dust Days by Satellite Remotely Sensed Aerosol Products

NASA Technical Reports Server (NTRS)

Sorek-Hammer, M.; Cohen, A.; Levy, Robert C.; Ziv, B.; Broday, D. M.

2013-01-01

Considerable progress in satellite remote sensing (SRS) of dust particles has been seen in the last decade. From an environmental health perspective, such an event detection, after linking it to ground particulate matter (PM) concentrations, can proxy acute exposure to respirable particles of certain properties (i.e. size, composition, and toxicity). Being affected considerably by atmospheric dust, previous studies in the Eastern Mediterranean, and in Israel in particular, have focused on mechanistic and synoptic prediction, classification, and characterization of dust events. In particular, a scheme for identifying dust days (DD) in Israel based on ground PM10 (particulate matter of size smaller than 10 nm) measurements has been suggested, which has been validated by compositional analysis. This scheme requires information regarding ground PM10 levels, which is naturally limited in places with sparse ground-monitoring coverage. In such cases, SRS may be an efficient and cost-effective alternative to ground measurements. This work demonstrates a new model for identifying DD and non-DD (NDD) over Israel based on an integration of aerosol products from different satellite platforms (Moderate Resolution Imaging Spectroradiometer (MODIS) and Ozone Monitoring Instrument (OMI)). Analysis of ground-monitoring data from 2007 to 2008 in southern Israel revealed 67 DD, with more than 88 percent occurring during winter and spring. A Classification and Regression Tree (CART) model that was applied to a database containing ground monitoring (the dependent variable) and SRS aerosol product (the independent variables) records revealed an optimal set of binary variables for the identification of DD. These variables are combinations of the following primary variables: the calendar month, ground-level relative humidity (RH), the aerosol optical depth (AOD) from MODIS, and the aerosol absorbing index (AAI) from OMI. A logistic regression that uses these variables, coded as binary variables, demonstrated 93.2 percent correct classifications of DD and NDD. Evaluation of the combined CART-logistic regression scheme in an adjacent geographical region (Gush Dan) demonstrated good results. Using SRS aerosol products for DD and NDD, identification may enable us to distinguish between health, ecological, and environmental effects that result from exposure to these distinct particle populations.

A Novel approach for monitoring cyanobacterial blooms using an ensemble based system from MODIS imagery downscaled to 250 metres spatial resolution

NASA Astrophysics Data System (ADS)

El Alem, A.; Chokmani, K.; Laurion, I.; El-Adlouni, S. E.

2014-12-01

In reason of inland freshwaters sensitivity to Harmful algae blooms (HAB) development and the limits coverage of standards monitoring programs, remote sensing data have become increasingly used for monitoring HAB extension. Usually, HAB monitoring using remote sensing data is based on empirical and semi-empirical models. Development of such models requires a great number of continuous in situ measurements to reach an acceptable accuracy. However, Ministries and water management organizations often use two thresholds, established by the World Health Organization, to determine water quality. Consequently, the available data are ordinal «semi-qualitative» and they are mostly unexploited. Use of such databases with remote sensing data and statistical classification algorithms can produce hazard management maps linked to the presence of cyanobacteria. Unlike standard classification algorithms, which are generally unstable, classifiers based on ensemble systems are more general and stable. In the present study, an ensemble based classifier was developed and compared to a standard classification method called CART (Classification and Regression Tree) in a context of HAB monitoring in freshwaters using MODIS images downscaled to 250 spatial resolution and ordinal in situ data. Calibration and validation data on cyanobacteria densities were collected by the Ministère du Développement durable, de l'Environnement et de la Lutte contre les changements climatiques on 22 waters bodies between 2000 and 2010. These data comprise three density classes: waters poorly (< 20,000 cells mL-1), moderately (20,000 - 100,000 cells mL-1), and highly (> 100,000 cells mL-1) loaded in cyanobacteria. Results were very interesting and highlighted that inland waters exhibit different spectral response allowing them to be classified into the three above classes for water quality monitoring. On the other, even if the accuracy (Kappa-index = 0.86) of the proposed approach is relatively lower than that of the CART algorithm (Kappa-index = 0.87), but its robustness is higher with a standard-deviation of 0.05 versus 0.06, specifically when applied on MODIS images. A new accurate, robust, and quick approach is thus proposed for a daily near real-time monitoring of HAB in southern Quebec freshwaters.

Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis.

PubMed

Bezemer, Daniela; Cori, Anne; Ratmann, Oliver; van Sighem, Ard; Hermanides, Hillegonda S; Dutilh, Bas E; Gras, Luuk; Rodrigues Faria, Nuno; van den Hengel, Rob; Duits, Ashley J; Reiss, Peter; de Wolf, Frank; Fraser, Christophe

2015-11-01

The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.

Cell-Free and Concentrated Ascites Reinfusion Therapy for Decompensated Liver Cirrhosis.

PubMed

Kozaki, Koichi; IInuma, Masahiro; Takagi, Tomoyuki; Fukuda, Takanori; Sanpei, Takaya; Terunuma, Yusuke; Yatabe, Yoshiharu; Akano, Kazuhiro

2016-08-01

Cell-free and concentrated ascites reinfusion therapy (CART) is expected to improve symptoms associated with refractory ascites of the decompensated liver cirrhosis patients. The aim of this study was to evaluate the safety and efficacy of the CART system performed on the decompensated liver cirrhosis patients. In this retrospective observational study, we evaluated 24 CART processes performed on 11 patients with decompensated liver cirrhosis. We evaluated the effectiveness and adverse events during CART procedures. The amounts of collected and concentrated ascites were 4491.7 ± 2222.8 mL (mean ± SD), respectively, and the concentration ratio was 22.4 ± 15.3 times, respectively. The amount of collected protein in ascites was 2.3 ± 0.5 g/dL, and concentration ratio of protein was 8.2 ± 9.4 times. Serum protein level was not significantly different between before and after CART sessions. Thus, CART allowed for the reduction of doses of albumin preparations (Alb) to be administered. CART has been reported to cause two adverse reactions: elevation of body temperature and decrease in blood pressure. In our study, decreased blood pressure was not observed even in patients with > 5 L of ascites drained. Although a transient elevation in body temperature was seen in only one patient, this febrile patient immediately returned to normal body temperature with the use of NSAIDs. In patients with refractory ascites of decompensated liver cirrhosis in whom complete cure cannot be expected, CART improves their QOL and, in terms of medical economy, allows for the reduction of doses of Alb. CART can be effectively applied as a palliative procedure for refractory ascites of decompensated liver cirrhosis patients. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Assessing the HIV Care Continuum in Latin America: progress in clinical retention, cART use and viral suppression

PubMed Central

Rebeiro, Peter F; Cesar, Carina; Shepherd, Bryan E; De Boni, Raquel B; Cortés, Claudia P; Rodriguez, Fernanda; Belaunzarán-Zamudio, Pablo; Pape, Jean W; Padgett, Denis; Hoces, Daniel; McGowan, Catherine C; Cahn, Pedro

2016-01-01

Introduction We assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART) use and viral suppression (VS). Methods Adults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV-1 RNA <200 copies/mL at last measurement annually. cART and VS denominators were subjects with at least one visit annually. Multivariable modified Poisson regression was used to assess temporal trends and examine associations between age, sex, HIV transmission mode, cohort, calendar year and time in care. Results Among 18,799 individuals in retention analyses, 14,380 in cART analyses and 13,330 in VS analyses, differences existed between those meeting indicator definitions versus those not by most characteristics. Retention, cART and VS significantly improved from 2003 to 2012 (63 to 77%, 74 to 91% and 53 to 82%, respectively; p<0.05, each). Female sex (risk ratio (RR)=0.97 vs. males) and injection drug use as HIV transmission mode (RR=0.83 vs. male sexual contact with males (MSM)) were significantly associated with lower retention, but unrelated with cART or VS. MSM (RR=0.96) significantly decreased the probability of cART compared with heterosexual transmission. Conclusions HIV Care Continuum outcomes improved over time in Latin America, though disparities for vulnerable groups remain. Efforts must be made to increase retention, cART and VS, while engaging in additional research to sustain progress in these settings. PMID:27065108

Innovative Varied-Fidelity Simulation Mobile Teaching Cart and Education Project.

PubMed

Harding, Andrew D; Cullinane Whalen, Kathryn; Silverman, Bradley S

2015-09-01

The use of a varied-fidelity simulation mobile teaching cart is a teaching tool that offers unique advantages in the acute care setting. The cart is used to demonstrate the use of patient monitoring devices, and there are a variety of software tools available with the monitoring technology to ensure that the outputs, including electrocardiographic waves, are analyzed appropriately by nursing staff using this varied-fidelity simulation mobile teaching cart. Bringing varied-fidelity simulation to the nurses' work area is a unique application setting. Copyright © 2015 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

Les traces matérielles de la Carte du Ciel. Le cas des observatoires d'Alger et de Bordeaux.

NASA Astrophysics Data System (ADS)

Le Guet Tully, F.; Davoigneau, J.; Lamy, J.; de La Noë, J.; Rousseau, J.-M.; Sadsaoud, H.

2008-06-01

Le chapitre évoque les traces matérielles de la Carte du ciel subsistant dans les observatoires d'Alger et de Bordeaux. Les auteurs examinent d'abord l'opération d'inventaire du patrimoine astronomique entreprise à partir du milieu des années 1990. Ils examinent ensuite les éléments concrets constituant aujourd'hui le patrimoine de la Carte du Ciel : lunettes, abris, accessoires, laboratoires, réseaux, plaques de verre, registres, machines à mesurer les clichés, et cartes.

Perceptions regarding barriers and facilitators to combination antiretroviral therapy adherence among people living with HIV/AIDS in Gujarat, India: A qualitative study

PubMed Central

Patel, Sangita; Baxi, Rajendra K.; Patel, Shilpa N.; Golin, Carol E; Mehta, Mansi; Bakshi, Harsh; Shingrapure, Kalpita; Modi, Ekta; Coonor, Priyanka; Mehta, Kedar

2012-01-01

Objectives: To know the perceptions regarding barriers and facilitators to cART adherence among people living with HIV/AIDS Materials and Methods: To adapt U.S. based SAFETALK “prevention with positives” intervention to be culturally relevant in Gujarat, India in assisting PLWHA, a formative study was conducted. We conducted 30 in-depth interviews with PLWHA in the local language, assessing the experiences, perceived barriers, and facilitators to combination antiretroviral therapy (cART) among PLWHA in Gujarat. PLWHA were selected from the Voluntary Counseling and Testing Centre (VCTC) in Gujarat. To triangulate interview findings, we conducted two focus group discussions (FGDs) with medical and non-medical providers, respectively. Results: Travel and commuting to clinic, fear of possible physical reactions, high cost of ART from private practitioners, CD4 count being in normal limits and resistance to medication acted as barriers to cART adherence. Initiation of cART was facilitated by family members′ suggestion, advice of treating doctors and counselors, appropriate counseling before starting cART, belief that cART would aid in living a better and longer life and due to lowering of the CD4 count. Interpretation and Conclusions: Our study suggests that several issues need to be considered when providing cART. Further research is needed to study interactions between patients and their health care providers. PMID:23188935

Quantifying sub-pixel urban impervious surface through fusion of optical and inSAR imagery

USGS Publications Warehouse

Yang, L.; Jiang, L.; Lin, H.; Liao, M.

2009-01-01

In this study, we explored the potential to improve urban impervious surface modeling and mapping with the synergistic use of optical and Interferometric Synthetic Aperture Radar (InSAR) imagery. We used a Classification and Regression Tree (CART)-based approach to test the feasibility and accuracy of quantifying Impervious Surface Percentage (ISP) using four spectral bands of SPOT 5 high-resolution geometric (HRG) imagery and three parameters derived from the European Remote Sensing (ERS)-2 Single Look Complex (SLC) SAR image pair. Validated by an independent ISP reference dataset derived from the 33 cm-resolution digital aerial photographs, results show that the addition of InSAR data reduced the ISP modeling error rate from 15.5% to 12.9% and increased the correlation coefficient from 0.71 to 0.77. Spatially, the improvement is especially noted in areas of vacant land and bare ground, which were incorrectly mapped as urban impervious surfaces when using the optical remote sensing data. In addition, the accuracy of ISP prediction using InSAR images alone is only marginally less than that obtained by using SPOT imagery. The finding indicates the potential of using InSAR data for frequent monitoring of urban settings located in cloud-prone areas.

Extricating Sex and Gender in Air Pollution Research: A Community-Based Study on Cardinal Symptoms of Exposure

PubMed Central

Oiamo, Tor H.; Luginaah, Isaac N.

2013-01-01

This study investigated sex and gender differences in cardinal symptoms of exposure to a mixture of ambient pollutants. A cross sectional population-based study design was utilized in Sarnia, ON, Canada. Stratified random sampling in census tracts of residents aged 18 and over recruited 804 respondents. Respondents completed a community health survey of chronic disease, general health, and socioeconomic indicators. Residential concentrations of NO2, SO2, benzene, toluene, ethylbenzene and o/m/p-xylene were estimated by land use regression on data collected through environmental monitoring. Classification and Regression Tree (CART) analysis was used to identify variables that interacted with sex and cardinal symptoms of exposure, and a series of logistic regression models were built to predict the reporting of five or more cardinal symptoms (5+ CS). Without controlling for confounders, higher pollution ranks increased the odds ratio (OR) of reporting 5+ CS by 28% (p < 0.01; Confidence Interval (CI): 1.07–1.54). Females were 1.52 (p < 0.05; CI: 1.03–2.26) times more likely more likely to report 5+ CS after controlling for income, age and chronic diseases. The CART analysis showed that allergies and occupational exposure classified the sample into the most homogenous groups of males and females. The likelihood of reporting 5+ CS among females was higher after stratifying the sample based on occupational exposure. However, stratifying by allergic disease resulted in no significant sex difference in symptom reporting. The results confirmed previous research that found pre-existing health conditions to increase susceptibility to ambient air pollution, but additionally indicated that stronger effects on females is partly due to autoimmune disorders. Furthermore, gender differences in occupational exposure confound the effect size of exposure in studies based on residential levels of air pollution. PMID:23975108

Schoolchildren's Consumption of Competitive Foods and Beverages, Excluding a la Carte

ERIC Educational Resources Information Center

Kakarala, Madhuri; Keast, Debra R.; Hoerr, Sharon

2010-01-01

Background: Competitive foods/beverages are those in school vending machines, school stores, snack bars, special sales, and items sold a la carte in the school cafeteria that compete with United States Department of Agriculture (USDA) meal program offerings. Grouping a la carte items with less nutritious items allowed in less regulated venues may…

Automatic State Space Aggregation Using a Density Based Technique

DTIC Science & Technology

2012-05-01

learner: the position of the cart X , the velocity of the cart X ′, the angle each beam makes with the cart, θ1 and θ2, and the angular velocities of the...ulation of 100 neural networks per generation, with a maximum of 200 generations of learning. Neuroevolution is provided by Another NEAT Java Implementation

Clinical Predictors of Immune Reconstitution following Combination Antiretroviral Therapy in Patients from the Australian HIV Observational Database

PubMed Central

Rajasuriar, Reena; Gouillou, Maelenn; Spelman, Tim; Read, Tim; Hoy, Jennifer; Law, Matthew; Cameron, Paul U.; Petoumenos, Kathy; Lewin, Sharon R.

2011-01-01

Background A small but significant number of patients do not achieve CD4 T-cell counts >500cells/µl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART. Methods Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count <500cells/µl, HIV RNA<500copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts >500cells/µl and >200cells/µl. Results 501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32–47) years and 236 (130–350) cells/µl, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3–10) years. Most patients (80%) achieved CD4 T-cell counts >500cells/µl, but in 8%, this took >5 years. Among the patients who failed to reach a CD4 T-cell count >500cells/µl, 16% received cART for >10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count >500cells/µl was associated with higher baseline CD4 T-cell counts (p<0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts >200cells/µl included higher baseline CD4 T-cell count (p<0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p<0.001). Conclusion The time taken to achieve a CD4 T-cell count >500cells/µl despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen) is associated with more rapid recovery of a CD4 T-cell count >500cells/µl. PMID:21674057

Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

PubMed Central

Mussini, Cristina; Lorenzini, Patrizia; Puoti, Massimo; Lichtner, Miriam; Lapadula, Giuseppe; Di Giambenedetto, Simona; Antinori, Andrea; Madeddu, Giordano; Cozzi-Lepri, Alessandro; d’Arminio Monforte, Antonella; De Luca, Andrea

2015-01-01

Objective To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design Retrospective analysis of a prospective cohort study. Setting Italian HIV care centers participating to the ICONA Foundation cohort. Participants Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45–3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6–3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45–3.25: HR 3.55, 95% CI 1.09–11.58; FIB-4>3.25: HR 4.25, 1.21–14.92) and time-updated FIB-4 (FIB-4 1.45–3.25: HR 3.40, 1.02–11.40; FIB-4>3.25: HR 21.24, 6.75–66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART. PMID:26640953

Maternal Combination Antiretroviral Therapy is Associated with Improved Retention of HIV-Exposed Infants in Kinshasa, Democratic Republic of Congo

PubMed Central

FEINSTEIN, Lydia; EDMONDS, Andrew; OKITOLONDA, Vitus; COLE, Stephen R; VAN RIE, Annelies; CHI, Benjamin H; NDJIBU, Papy; LUSIAMA, Jean; CHALACHALA, Jean Lambert; BEHETS, Frieda

2015-01-01

Background Programs to prevent mother-to-child HIV transmission (PMTCT) are plagued by loss to follow-up (LTFU) of HIV-exposed infants. We assessed if providing combination antiretroviral therapy (cART) to HIV-infected mothers was associated with reduced LTFU of their HIV-exposed infants in Kinshasa, DR Congo. Methods We constructed a cohort of mother-infant pairs using routinely collected clinical data. Maternal cART eligibility was based on national guidelines in effect at the time. Infants were considered LTFU following three failed tracking attempts after a missed visit or if more than six months passed since they were last seen in clinic. Statistical methods accounted for competing risks (e.g. death). Results 1318 infants enrolled at a median age of 2.6 weeks (interquartile range [IQR]: 2.1-6.9), at which point 24% of mothers were receiving cART. Overall, 5% of infants never returned to care following enrollment and 18% were LTFU by 18 months. The 18-month cumulative incidence of LTFU was 8% among infants whose mothers initiated cART by infant enrollment and 20% among infants whose mothers were not yet on cART. Adjusted for baseline factors, infants whose mothers were not on cART were over twice as likely to be LTFU, with a subdistribution hazard ratio of 2.75 (95% confidence limit: 1.81, 4.16). The association remained strong regardless of maternal CD4 count at infant enrollment. Conclusion Increasing access to cART for pregnant women could improve retention of HIV-exposed infants, thereby increasing the clinical and population-level impacts of PMTCT interventions and access to early cART for HIV-infected infants. PMID:25886922

CD4+ cell count recovery in naïve patients initiating cART, who achieved and maintained plasma HIV-RNA suppression.

PubMed

Costagliola, Dominique; Lacombe, Jean-Marc; Ghosn, Jade; Delaugerre, Constance; Pialoux, Gilles; Cuzin, Lise; Launay, Odile; Ménard, Amélie; de Truchis, Pierre; Mary-Krause, Murielle; Weiss, Laurence; Delfraissy, Jean-François

2014-01-01

A key objective of combined antiretroviral therapy (cART) is to reach and maintain high CD4 cell counts to provide long-term protection against AIDS-defining opportunistic infections and malignancies, as well as other comorbidities. However, a high proportion of patients present late for care. Our objective was to assess CD4 cell count recovery up to seven years in naïve patients initiating cART with at least three drugs in usual clinical care. From the French Hospital Database on HIV, we selected naïve individuals initiating cART from 2000 with at least two years of follow-up. Participants were further required to have achieved viral load suppression by six months after initiating cART and were censored in case of virological failure. We calculated the proportion of patients (Kaplan-Meier estimates) who achieved CD4 recovery to >500/mm(3) according to baseline CD4 cell count. A total of 15,025 patients were analyzed with a median follow-up on ART of 65.5 months (IQR: 42.3-96.0). At cART initiation, the median age was 38.6 years (IQR: 32.2-46.0), 9734 (64.8%) were men, median CD4 cell count was 239 (IQR: 130-336) and 2668 (17.8%) had a prior AIDS event. RESULTS are presented in the Table 1. This study shows that CD4 cell counts continue to increase seven years after cART initiation, whatever the baseline CD4 cell count. Failing to achieve CD4 recovery with continuous viral load suppression is rare for naïve patients initiating cART in routine clinical practice, but takes substantially longer in patients who initiate antiretroviral therapy at low CD4 cell counts.

Ejection of a rear facing, golf cart passenger.

PubMed

Schau, Kyle; Masory, Oren

2013-10-01

The following report details the findings of a series of experiments and simulations performed on a commercially available, shuttle style golf cart during several maneuvers involving rapid accelerations of the vehicle. It is determined that the current set of passive restraints on these types of golf carts are not adequate in preventing ejection of a rear facing passenger during rapid accelerations in the forward and lateral directions. Experimental data and simulations show that a hip restraint must be a minimum of 13 in. above the seat in order to secure a rear facing passenger during sharp turns, compared to the current restraint height of 5 in. Furthermore, it is determined that a restraint directly in front of the rear facing passenger is necessary to prevent ejection. In addressing these issues, golf cart manufacturers could greatly reduce the likelihood of injury due to ejection of a rear facing, golf cart passenger. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse

PubMed Central

Kenderian, Saad S.; Porter, David L.; Gill, Saar

2016-01-01

Hematopoietic cell transplantation (HCT) remains an important and potentially curative option in most hematological malignancies. As a form of immunotherapy, allogeneic HCT offers the potential for durable remissions but is limited by transplant related morbidity and mortality due to organ toxicity, infection and graft versus host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematological malignancies. Clinical trials will now need to address the relative roles of CART cells and HCT in the context of transplant-eligible patients. In this review we summarize the state of the art of the development of CART cell therapy for leukemia, lymphoma and myeloma and discuss our perspective of how CART cell therapy can be applied in the context of HCT. PMID:27638367

The Communities Advancing Resilience Toolkit (CART): an intervention to build community resilience to disasters.

PubMed

Pfefferbaum, Rose L; Pfefferbaum, Betty; Van Horn, Richard L; Klomp, Richard W; Norris, Fran H; Reissman, Dori B

2013-01-01

Community resilience has emerged as a construct to support and foster healthy individual, family, and community adaptation to mass casualty incidents. The Communities Advancing Resilience Toolkit (CART) is a publicly available theory-based and evidence-informed community intervention designed to enhance community resilience by bringing stakeholders together to address community issues in a process that includes assessment, feedback, planning, and action. Tools include a field-tested community resilience survey and other assessment and analytical instruments. The CART process encourages public engagement in problem solving and the development and use of local assets to address community needs. CART recognizes 4 interrelated domains that contribute to community resilience: connection and caring, resources, transformative potential, and disaster management. The primary value of CART is its contribution to community participation, communication, self-awareness, cooperation, and critical reflection and its ability to stimulate analysis, collaboration, skill building, resource sharing, and purposeful action.

Diagnosis of colorectal cancer by near-infrared optical fiber spectroscopy and random forest

NASA Astrophysics Data System (ADS)

Chen, Hui; Lin, Zan; Wu, Hegang; Wang, Li; Wu, Tong; Tan, Chao

2015-01-01

Near-infrared (NIR) spectroscopy has such advantages as being noninvasive, fast, relatively inexpensive, and no risk of ionizing radiation. Differences in the NIR signals can reflect many physiological changes, which are in turn associated with such factors as vascularization, cellularity, oxygen consumption, or remodeling. NIR spectral differences between colorectal cancer and healthy tissues were investigated. A Fourier transform NIR spectroscopy instrument equipped with a fiber-optic probe was used to mimic in situ clinical measurements. A total of 186 spectra were collected and then underwent the preprocessing of standard normalize variate (SNV) for removing unwanted background variances. All the specimen and spots used for spectral collection were confirmed staining and examination by an experienced pathologist so as to ensure the representative of the pathology. Principal component analysis (PCA) was used to uncover the possible clustering. Several methods including random forest (RF), partial least squares-discriminant analysis (PLSDA), K-nearest neighbor and classification and regression tree (CART) were used to extract spectral features and to construct the diagnostic models. By comparison, it reveals that, even if no obvious difference of misclassified ratio (MCR) was observed between these models, RF is preferable since it is quicker, more convenient and insensitive to over-fitting. The results indicate that NIR spectroscopy coupled with RF model can serve as a potential tool for discriminating the colorectal cancer tissues from normal ones.

Data mining for rapid prediction of facility fit and debottlenecking of biomanufacturing facilities.

PubMed

Yang, Yang; Farid, Suzanne S; Thornhill, Nina F

2014-06-10

Higher titre processes can pose facility fit challenges in legacy biopharmaceutical purification suites with capacities originally matched to lower titre processes. Bottlenecks caused by mismatches in equipment sizes, combined with process fluctuations upon scale-up, can result in discarding expensive product. This paper describes a data mining decisional tool for rapid prediction of facility fit issues and debottlenecking of biomanufacturing facilities exposed to batch-to-batch variability and higher titres. The predictive tool comprised advanced multivariate analysis techniques to interrogate Monte Carlo stochastic simulation datasets that mimicked batch fluctuations in cell culture titres, step yields and chromatography eluate volumes. A decision tree classification method, CART (classification and regression tree) was introduced to explore the impact of these process fluctuations on product mass loss and reveal the root causes of bottlenecks. The resulting pictorial decision tree determined a series of if-then rules for the critical combinations of factors that lead to different mass loss levels. Three different debottlenecking strategies were investigated involving changes to equipment sizes, using higher capacity chromatography resins and elution buffer optimisation. The analysis compared the impact of each strategy on mass output, direct cost of goods per gram and processing time, as well as consideration of extra capital investment and space requirements. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

The Retarding Force on a Fan-Cart Reversing Direction

ERIC Educational Resources Information Center

Aurora, Tarlok S.; Brunner, Bernard J.

2011-01-01

In introductory physics, students learn that an object tossed upward has a constant downward acceleration while going up, at the highest point and while falling down. To demonstrate this concept, a self-propelled fan cart system is used on a frictionless track. A quick push is given to the fan cart and it is allowed to move away on a track under…

Treatment of solid tumors with chimeric antigen receptor-engineered T cells: current status and future prospects.

PubMed

Di, Shengmeng; Li, Zonghai

2016-04-01

Chimeric antigen receptors (CARs) are artificial recombinant receptors that generally combine the antigen-recognition domain of a monoclonal antibody with T cell activation domains. Recent years have seen great success in clinical trials employing CD19-specific CAR-T cell therapy for B cell leukemia. Nevertheless, solid tumors remain a major challenge for CAR-T cell therapy. This review summarizes the preclinical and clinical studies on the treatment of solid tumors with CAR-T cells. The major hurdles for the success of CAR-T and the novel strategies to address these hurdles have also been described and discussed.

[Consensus Statement by GeSIDA/National AIDS Plan Secretariat on antiretroviral treatment in adults infected by the human immunodeficiency virus (Updated January 2013)].

PubMed

2013-11-01

This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the GeSIDA/National AIDS Plan Secretariat (Grupo de Estudio de Sida and the Secretaría del Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations and the evidence which support them are based on a modification of the criteria of Infectious Diseases Society of America. cART is recommended in patients with symptoms of HIV infection, in pregnant women, in serodiscordant couples with high risk of transmission, in hepatitisB co-infection requiring treatment, and in HIV nephropathy. cART is recommended in asymptomatic patients if CD4 is <500cells/μl. If CD4 are >500cells/μl cART should be considered in the case of chronic hepatitisC, cirrhosis, high cardiovascular risk, plasma viral load >100.000 copies/ml, proportion of CD4 cells <14%, neurocognitive deficits, and in people aged >55years. The objective of cART is to achieve an undetectable viral load. The first cART should include 2 reverse transcriptase inhibitors (RTI) nucleoside analogs and a third drug (a non-analog RTI, a ritonavir boosted protease inhibitor, or an integrase inhibitor). The panel has consensually selected some drug combinations, for the first cART and specific criteria for cART in acute HIV infection, in tuberculosis and other HIV related opportunistic infections, for the women and in pregnancy, in hepatitisB or C co-infection, in HIV-2 infection, and in post-exposure prophylaxis. These new guidelines update previous recommendations related to first cART (when to begin and what drugs should be used), how to monitor, and what to do in case of viral failure or adverse drug reactions. cART specific criteria in comorbid patients and special situations are similarly updated. Copyright © 2013 Elsevier España, S.L. All rights reserved.

A Car Transportation System in Cooperation by Multiple Mobile Robots for Each Wheel: iCART II

NASA Astrophysics Data System (ADS)

Kashiwazaki, Koshi; Yonezawa, Naoaki; Kosuge, Kazuhiro; Sugahara, Yusuke; Hirata, Yasuhisa; Endo, Mitsuru; Kanbayashi, Takashi; Shinozuka, Hiroyuki; Suzuki, Koki; Ono, Yuki

The authors proposed a car transportation system, iCART (intelligent Cooperative Autonomous Robot Transporters), for automation of mechanical parking systems by two mobile robots. However, it was difficult to downsize the mobile robot because the length of it requires at least the wheelbase of a car. This paper proposes a new car transportation system, iCART II (iCART - type II), based on “a-robot-for-a-wheel” concept. A prototype system, MRWheel (a Mobile Robot for a Wheel), is designed and downsized less than half the conventional robot. First, a method for lifting up a wheel by MRWheel is described. In general, it is very difficult for mobile robots such as MRWheel to move to desired positions without motion errors caused by slipping, etc. Therefore, we propose a follower's motion error estimation algorithm based on the internal force applied to each follower by extending a conventional leader-follower type decentralized control algorithm for cooperative object transportation. The proposed algorithm enables followers to estimate their motion errors and enables the robots to transport a car to a desired position. In addition, we analyze and prove the stability and convergence of the resultant system with the proposed algorithm. In order to extract only the internal force from the force applied to each robot, we also propose a model-based external force compensation method. Finally, proposed methods are applied to the car transportation system, the experimental results confirm their validity.

HIV Protease Inhibitor Use During Pregnancy Is Associated With Decreased Progesterone Levels, Suggesting a Potential Mechanism Contributing to Fetal Growth Restriction

PubMed Central

Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R.; Yudin, Mark H.; Murphy, Kellie E.; Walmsley, Sharon L.; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

2015-01-01

Background. Protease inhibitor (PI)–based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. PMID:25030058

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

PubMed

Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R; Yudin, Mark H; Murphy, Kellie E; Walmsley, Sharon L; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

2015-01-01

Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy

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

Kusabuka, Hotaka; Fujiwara, Kento; Tokunaga, Yusuke

Adoptive immunotherapy using chimeric antigen receptor-expressing T (CAR-T) cells has attracted attention as an efficacious strategy for cancer treatment. To prove the efficacy and safety of CAR-T cell therapy, the elucidation of immunological mechanisms underlying it in mice is required. Although a retroviral vector (Rv) is mainly used for the introduction of CAR to murine T cells, gene transduction efficiency is generally less than 50%. The low transduction efficiency causes poor precision in the functional analysis of CAR-T cells. We attempted to improve the Rv gene transduction protocol to more efficiently generate functional CAR-T cells by optimizing the period ofmore » pre-cultivation and antibody stimulation. In the improved protocol, gene transduction efficiency to murine T cells was more than 90%. In addition, almost all of the prepared murine T cells expressed CAR after puromycin selection. These CAR-T cells had antigen-specific cytotoxic activity and secreted multiple cytokines by antigen stimulation. We believe that our optimized gene transduction protocol for murine T cells contributes to the advancement of T cell biology and development of immunotherapy using genetically engineered T cells. - Highlights: • We established highly efficient gene transduction protocols for murine T cells. • CD8{sup +} CAR-T cells had antigen-specific cytotoxic activity. • CD4{sup +} CAR-T cells secreted multiple cytokines by antigen stimulation. • This finding can contribute to the development of T-cell biology and immunotherapy.« less

Executive summary of the Consensus Document of GeSIDA and Spanish Secretariat for the National Plan on AIDS on combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2013).

PubMed

2013-11-01

In the present update of the guidelines, a starting combination antiretroviral treatment (cART) is recommended in symptomatic patients, in pregnant women, in serodiscordant couples with a high risk of transmission, in patients co-infected with hepatitis B virus requiring treatment, and in patients with HIV-related nephropathy. Guidelines on cART are included in the event of a concurrent diagnosis of HIV infection with an AIDS-defining event. In asymptomatic naïve patients, cART is recommended if the CD4(+) lymphocyte count is <500cells/μL; if the CD4(+) lymphocyte count is >500cells/μL, cART can be delayed, although it may be considered in patients with liver cirrhosis, chronic infection due to hepatitis C virus, high cardiovascular risk, plasma viral load (PVL) >10(5)copies/mL, CD4(+) lymphocyte percentage <14%, cognitive impairment, and age >55 years. cART in naïve patients requires a combination of 3 drugs, and its aim is to achieve undetectable PVL. Treatment adherence plays a key role in sustaining a favorable response. cART can, and should be, changed if virological failure occurs, in order to return to undetectable PVL. Approaches to cART in acute HIV infection, in women, in pregnancy, in tuberculosis, and post-exposure prophylaxis are also examined. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Classification of US hydropower dams by their modes of operation

DOE PAGES

McManamay, Ryan A.; Oigbokie, II, Clement O.; Kao, Shih -Chieh; ...

2016-02-19

A key challenge to understanding ecohydrologic responses to dam regulation is the absence of a universally transferable classification framework for how dams operate. In the present paper, we develop a classification system to organize the modes of operation (MOPs) for U.S. hydropower dams and powerplants. To determine the full diversity of MOPs, we mined federal documents, open-access data repositories, and internet sources. W then used CART classification trees to predict MOPs based on physical characteristics, regulation, and project generation. Finally, we evaluated how much variation MOPs explained in sub-daily discharge patterns for stream gages downstream of hydropower dams. After reviewingmore » information for 721 dams and 597 power plants, we developed a 2-tier hierarchical classification based on 1) the storage and control of flows to powerplants, and 2) the presence of a diversion around the natural stream bed. This resulted in nine tier-1 MOPs representing a continuum of operations from strictly peaking, to reregulating, to run-of-river, and two tier-2 MOPs, representing diversion and integral dam-powerhouse configurations. Although MOPs differed in physical characteristics and energy production, classification trees had low accuracies (<62%), which suggested accurate evaluations of MOPs may require individual attention. MOPs and dam storage explained 20% of the variation in downstream subdaily flow characteristics and showed consistent alterations in subdaily flow patterns from reference streams. Lastly, this standardized classification scheme is important for future research including estimating reservoir operations for large-scale hydrologic models and evaluating project economics, environmental impacts, and mitigation.« less

Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations.

PubMed

Yang, Yang; Velayudhan, Ajoy; Thornhill, Nina F; Farid, Suzanne S

2017-09-01

The need for high-concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high-concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high-concentration mAb formulation conditions in terms of their ease of manufacture. This is illustrated by analyzing published high-throughput biophysical screening data that explores the influence of different formulation conditions (pH, ions, and excipients) on the solution viscosity and product thermostability. A decision tree classification method, CART (Classification and Regression Tree) is used to identify the critical formulation conditions that influence the viscosity and thermostability. In this work, three different multi-criteria data analysis frameworks were investigated to derive manufacturability indices from analysis of the stress maps and the process conditions experienced in the final UF/DF step. Polynomial regression techniques were used to transform the experimental data into a set of stress maps that show viscosity and thermostability as functions of the formulation conditions. A mathematical filtrate flux model was used to capture the time profiles of protein concentration and flux decay behavior during UF/DF. Multi-criteria decision-making analysis was used to identify the optimal formulation conditions that minimize the potential for both viscosity and aggregation issues during UF/DF. Biotechnol. Bioeng. 2017;114: 2043-2056. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc.

Multi‐criteria manufacturability indices for ranking high‐concentration monoclonal antibody formulations

PubMed Central

Velayudhan, Ajoy; Thornhill, Nina F.

2017-01-01

ABSTRACT The need for high‐concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high‐concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high‐concentration mAb formulation conditions in terms of their ease of manufacture. This is illustrated by analyzing published high‐throughput biophysical screening data that explores the influence of different formulation conditions (pH, ions, and excipients) on the solution viscosity and product thermostability. A decision tree classification method, CART (Classification and Regression Tree) is used to identify the critical formulation conditions that influence the viscosity and thermostability. In this work, three different multi‐criteria data analysis frameworks were investigated to derive manufacturability indices from analysis of the stress maps and the process conditions experienced in the final UF/DF step. Polynomial regression techniques were used to transform the experimental data into a set of stress maps that show viscosity and thermostability as functions of the formulation conditions. A mathematical filtrate flux model was used to capture the time profiles of protein concentration and flux decay behavior during UF/DF. Multi‐criteria decision‐making analysis was used to identify the optimal formulation conditions that minimize the potential for both viscosity and aggregation issues during UF/DF. Biotechnol. Bioeng. 2017;114: 2043–2056. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc. PMID:28464235

Classification of US hydropower dams by their modes of operation

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

McManamay, Ryan A.; Oigbokie, II, Clement O.; Kao, Shih -Chieh

A key challenge to understanding ecohydrologic responses to dam regulation is the absence of a universally transferable classification framework for how dams operate. In the present paper, we develop a classification system to organize the modes of operation (MOPs) for U.S. hydropower dams and powerplants. To determine the full diversity of MOPs, we mined federal documents, open-access data repositories, and internet sources. W then used CART classification trees to predict MOPs based on physical characteristics, regulation, and project generation. Finally, we evaluated how much variation MOPs explained in sub-daily discharge patterns for stream gages downstream of hydropower dams. After reviewingmore » information for 721 dams and 597 power plants, we developed a 2-tier hierarchical classification based on 1) the storage and control of flows to powerplants, and 2) the presence of a diversion around the natural stream bed. This resulted in nine tier-1 MOPs representing a continuum of operations from strictly peaking, to reregulating, to run-of-river, and two tier-2 MOPs, representing diversion and integral dam-powerhouse configurations. Although MOPs differed in physical characteristics and energy production, classification trees had low accuracies (<62%), which suggested accurate evaluations of MOPs may require individual attention. MOPs and dam storage explained 20% of the variation in downstream subdaily flow characteristics and showed consistent alterations in subdaily flow patterns from reference streams. Lastly, this standardized classification scheme is important for future research including estimating reservoir operations for large-scale hydrologic models and evaluating project economics, environmental impacts, and mitigation.« less

Impact of Portion-Size Control for School a la Carte Items: Changes in Kilocalories and Macronutrients Purchased by Middle School Students

USDA-ARS?s Scientific Manuscript database

We assessed the impact of a pilot middle school a la carte intervention on food and beverage purchases, kilocalories, fat, carbohydrate, and protein sold per student, and nutrient density of the foods sold. A la carte sales were obtained from six middle schools in three states for 1 baseline week an...

The HIV-Brazil Cohort Study: Design, Methods and Participant Characteristics

PubMed Central

Grangeiro, Alexandre; Escuder, Maria Mercedes; Cassanote, Alex Jones Flores; Souza, Rosa Alencar; Kalichman, Artur O.; Veloso, Valdiléa; Ikeda, Maria Letícia Rodrigues; Barcellos, Nêmora Tregnago; Brites, Carlos; Tupinanbás, Unai; Lucena, Noaldo O.; da Silva, Carlos Lima; Lacerda, Heloisa Ramos; Grinsztejn, Beatriz; Castilho, Euclides Ayres

2014-01-01

Background The HIV-Brazil Cohort Study was established to analyze the effectiveness of combination antiretroviral therapy (cART) and the impact of this treatment on morbidity, quality of life (QOL) and mortality. The study design, patients’ profiles and characteristics of cART initiation between 2003 and 2010 were described. Methodology/Principal Findings Since 2003, the HIV-Brazil Cohort has been following HIV-infected adults receiving cART at 26 public health care facilities, using routine clinical care data and self-reported QOL questionnaires. When not otherwise available, data are obtained from national information systems. The main outcomes of interest are diseases related or unrelated to HIV; suppression of viral replication; adverse events; virological, clinical and immunological failures; changes in the cART; and mortality. For the 5,061 patients who started cART between 2003 and 2010, the median follow-up time was 4.1 years (IQR 2.2–5.9 years) with an 83.4% retention rate. Patient profiles were characterized by a predominance of men (male/female ratio 1.7∶1), with a mean age of 36.9 years (SD 9.9 years); 55.2% had been infected with HIV via heterosexual contact. The majority of patients (53.4%) initiated cART with a CD4+ T-cell count ≤200 cells/mm3. The medications most often used in the various treatment regimens were efavirenz (59.7%) and lopinavir/ritonavir (18.2%). The proportion of individuals achieving viral suppression within the first 12 months of cART use was 77.4% (95% CI 76.1–78.6). Nearly half (45.4%) of the patients presented HIV-related clinical manifestations after starting cART, and the AIDS mortality rate was 13.9 per 1,000 person-years. Conclusions/Significance Results from cART use in the daily practice of health services remain relatively unknown in low- and middle-income countries, and studies with the characteristics of the HIV-Brazil Cohort contribute to minimizing these shortcomings, given its scope and patient profile, which is similar to that of the AIDS epidemic in the country. PMID:24789106

Predictors of unstructured antiretroviral treatment interruption and resumption among HIV-positive individuals in Canada.

PubMed

Samji, H; Taha, T E; Moore, D; Burchell, A N; Cescon, A; Cooper, C; Raboud, J M; Klein, M B; Loutfy, M R; Machouf, N; Tsoukas, C M; Montaner, J S G; Hogg, R S

2015-02-01

Sustained optimal use of combination antiretroviral therapy (cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption (TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort (CANOC) collaboration. cART-naïve individuals ≥ 18 years of age who initiated cART between 2000 and 2011 were included in the study. We defined TIs as ≥ 90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. A total of 7633 participants were eligible for inclusion in the study, of whom 1860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women [adjusted hazard ratio (aHR) 1.59; 95% confidence interval (CI) 1.33-1.92], younger individuals (aHR 1.27; 95% CI 1.15-1.37 per decade increase), earlier treatment initiators (CD4 count ≥ 350 vs. <200 cells/μL: aHR 1.46; 95% CI 1.17-1.81), Aboriginal participants (aHR 1.67; 95% CI 1.27-2.20), injecting drug users (aHR 1.43; 95% CI 1.09-1.89) and users of zidovudine vs. tenofovir in the initial cART regimen (aHR 2.47; 95% CI 1.92-3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count <200 cells/μL at cART initiation. Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART. © 2014 British HIV Association.

Technical Performance and Clinical Effectiveness of Drop Type With Adjustable Concentrator-Cell Free and Concentrated Ascites Reinfusion Therapy.

PubMed

Yamada, Yosuke; Harada, Makoto; Yamaguchi, Akinori; Kobayashi, Yasuko; Chino, Takashi; Minowa, Takashi; Kosuge, Takashi; Tsukada, Wataru; Hashimoto, Koji; Kamijo, Yuji

2017-12-01

Cell-free and concentrated ascites reinfusion therapy (CART) is a very useful treatment method for refractory ascites but is difficult for many hospitals to employ due to its need for specialized equipment. We have therefore developed drop-type with adjustable concentrator CART (DC-CART) that uses a drop-type filtration mechanism and requires only a simple pump and pressure monitor for its concentration process. Easy adjustment of ascites concentration is possible through a recirculation loop, and filter membrane washing is aided by DC-CART's external pressure-type filtration to enable the processing of any quality or quantity of ascites. Moreover, the absence of a roller pump before filtration avoids inflammatory substance release from compressed cells. A total of 268 sessions of DC-CART using ascites from 98 patients were performed with good clinical results at our hospitals between January 2012 and June 2016. This report presents the detailed methods of DC-CART and summarizes its clinical effectiveness using patient ascites and blood data obtained from 59 sessions between March 2015 and February 2016. This novel technique successfully processed refractory ascites in numerous diseases with no serious adverse events. DC-CART could concentrate large amounts of ascites (from median weight: 4900 g [max: 20 200 g] to median weight: 695 g; median concentration ratio: 7.4), and a high amount of protein (median weight: 73 g [max: 294 g]) could be reinfused. Serum albumin levels were significantly increased (P = 0.010) and kidney function and systemic hemodynamics were well maintained in treated subjects. Additional concentration of ascites and adjustment of ascites volume were easily performed by recirculation (from median weight: 615 g to median weight: 360 g; median concentration ratio: 1.5). Time was needed during DC-CART for filter membrane cleaning, especially for viscous ascites. Overall, DC-CART represents a safe and useful treatment method for various forms of refractory ascites that can be performed at a wide range of health care institutions. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Liver macrophage-associated inflammation correlates with SIV burden and is substantially reduced following cART

PubMed Central

Green, Richard R.; Brown, Rachel R.; Wood, Matthew P.; Hensley-McBain, Tiffany; Chang, Jean; Miller, Andrew D.; Lifson, Jeffrey D.; Mavigner, Maud; Gale, Michael; Silvestri, Guido; Chahroudi, Ann; Klatt, Nichole R.

2018-01-01

Liver disease is a leading contributor to morbidity and mortality during HIV infection, despite the use of combination antiretroviral therapy (cART). The precise mechanisms of liver disease during HIV infection are poorly understood partially due to the difficulty in obtaining human liver samples as well as the presence of confounding factors (e.g. hepatitis co-infection, alcohol use). Utilizing the simian immunodeficiency virus (SIV) macaque model, a controlled study was conducted to evaluate the factors associated with liver inflammation and the impact of cART. We observed an increase in hepatic macrophages during untreated SIV infection that was associated with a number of inflammatory and fibrosis mediators (TNFα, CCL3, TGFβ). Moreover, an upregulation in the macrophage chemoattractant factor CCL2 was detected in the livers of SIV-infected macaques that coincided with an increase in the number of activated CD16+ monocyte/macrophages and T cells expressing the cognate receptor CCR2. Expression of Mac387 on monocyte/macrophages further indicated that these cells recently migrated to the liver. The hepatic macrophage and T cell levels strongly correlated with liver SIV DNA levels, and were not associated with the levels of 16S bacterial DNA. Utilizing in situ hybridization, SIV-infected cells were found primarily within portal triads, and were identified as T cells. Microarray analysis identified a strong antiviral transcriptomic signature in the liver during SIV infection. In contrast, macaques treated with cART exhibited lower levels of liver macrophages and had a substantial, but not complete, reduction in their inflammatory profile. In addition, residual SIV DNA and bacteria 16S DNA were detected in the livers during cART, implicating the liver as a site on-going immune activation during antiretroviral therapy. These findings provide mechanistic insights regarding how SIV infection promotes liver inflammation through macrophage recruitment, with implications for in HIV-infected individuals. PMID:29466439

Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor-Based Combination Antiretroviral Therapy.

PubMed

Papp, Eszter; Balogun, Kayode; Banko, Nicole; Mohammadi, Hakimeh; Loutfy, Mona; Yudin, Mark H; Shah, Rajiv; MacGillivray, Jay; Murphy, Kellie E; Walmsley, Sharon L; Silverman, Michael; Serghides, Lena

2016-05-15

It has been reported that pregnant women receiving protease inhibitor (PI)-based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level. We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)-infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism. HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P= .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00-4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66-1.26 AU;P= .002). Prolactin, a key regulator of 20α-HSD, was lower (P= .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART-induced decreases in progesterone levels. Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor–Based Combination Antiretroviral Therapy

PubMed Central

Papp, Eszter; Balogun, Kayode; Banko, Nicole; Mohammadi, Hakimeh; Loutfy, Mona; Yudin, Mark H.; Shah, Rajiv; MacGillivray, Jay; Murphy, Kellie E.; Walmsley, Sharon L.; Silverman, Michael; Serghides, Lena

2016-01-01

Background. It has been reported that pregnant women receiving protease inhibitor (PI)–based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level. Methods. We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)–infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism. Results. HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P = .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00–4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66–1.26 AU; P = .002). Prolactin, a key regulator of 20α-HSD, was lower (P = .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART–induced decreases in progesterone levels. Conclusions. Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women. PMID:26740274

Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.

PubMed

Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni

2017-09-01

CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [ 3 H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal levels of DOPET. At the same concentration, 0.1μM, CART (55-102) peptide did not have any effect on the release of noradrenaline. In the presence of CART (55-102) peptide, 0.1μM, the effect of cocaine, 30μM, on the basal dopamine release was inhibited and the effect on the basal DOPAC release substantially increased. To our knowledge, our findings are the first to show direct neurochemical evidence that CART (55-102) peptide plays a neuromodulatory role on the dopaminergic reward system by decreasing dopamine in the mouse nucleus accumbens and by attenuating cocaine-induced effects on dopamine release. Copyright © 2017 Elsevier Inc. All rights reserved.

STS-37 crewmembers test CETA hand cart during training session in JSC's WETF

NASA Technical Reports Server (NTRS)

1989-01-01

STS-37 Atlantis, Orbiter Vehicle (OV) 104, Mission Specialist (MS) Jerry L. Ross and MS Jerome Apt test crew and equipment translation aid (CETA) manual hand over hand cart during underwater session in JSC's Weightless Environment Training Facility (WETF) Bldg 29. Wearing an extravehicular mobility unit (EMU), Ross pulls the CETA manual cart along the rail while Apt holds onto the back of the cart. The test will determine how difficult it is to maneuver cargo in such a manner when it is done in space on STS-37. The goal is to find the best method for astronauts to move around the exterior of Space Station Freedom (SSF).

Object Transportation by Two Mobile Robots with Hand Carts

PubMed Central

Hara, Tatsunori

2014-01-01

This paper proposes a methodology by which two small mobile robots can grasp, lift, and transport large objects using hand carts. The specific problems involve generating robot actions and determining the hand cart positions to achieve the stable loading of objects onto the carts. These problems are solved using nonlinear optimization, and we propose an algorithm for generating robot actions. The proposed method was verified through simulations and experiments using actual devices in a real environment. The proposed method could reduce the number of robots required to transport large objects with 50–60%. In addition, we demonstrated the efficacy of this task in real environments where errors occur in robot sensing and movement. PMID:27433499

Object Transportation by Two Mobile Robots with Hand Carts.

PubMed

Sakuyama, Takuya; Figueroa Heredia, Jorge David; Ogata, Taiki; Hara, Tatsunori; Ota, Jun

2014-01-01

This paper proposes a methodology by which two small mobile robots can grasp, lift, and transport large objects using hand carts. The specific problems involve generating robot actions and determining the hand cart positions to achieve the stable loading of objects onto the carts. These problems are solved using nonlinear optimization, and we propose an algorithm for generating robot actions. The proposed method was verified through simulations and experiments using actual devices in a real environment. The proposed method could reduce the number of robots required to transport large objects with 50-60%. In addition, we demonstrated the efficacy of this task in real environments where errors occur in robot sensing and movement.

Neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and cholecystokinin (CCK) in winter skate (Raja ocellata): cDNA cloning, tissue distribution and mRNA expression responses to fasting.

PubMed

MacDonald, Erin; Volkoff, Hélène

2009-04-01

cDNAs encoding for neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and cholecystokinin (CCK) were cloned in an elasmobranch fish, the winter skate. mRNA tissue distribution was examined for the three peptides as well as the effects of two weeks of fasting on their expression. Skate NPY, CART and CCK sequences display similarities with sequences for teleost fish but in general the degree of identity is relatively low (50%). All three peptides are present in brain and in several peripheral tissues, including gut and gonads. Within the brain, the three peptides are expressed in the hypothalamus, telencephalon, optic tectum and cerebellum. Two weeks of fasting induced an increase in telencephalon NPY and an increase in CCK in the gut but had no effects on hypothalamic NPY, CART and CCK, or on telencephalon CART. Our results provide basis for further investigation into the regulation of feeding in winter skate.

Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse.

PubMed

Kenderian, Saad S; Porter, David L; Gill, Saar

2017-02-01

Hematopoietic cell transplantation (HCT) remains an important and potentially curative option for most hematologic malignancies. As a form of immunotherapy, allogeneic HCT (allo-HCT) offers the potential for durable remissions but is limited by transplantation- related morbidity and mortality owing to organ toxicity, infection, and graft-versus-host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematologic malignancies as well. Clinical trials are now needed to address the relative roles of CART cells and HCT in the context of transplantation-eligible patients. In this review, we summarize the state of the art of the development of CART cell therapy for leukemia, lymphoma, and myeloma and discuss our perspective of how CART cell therapy can be applied in the context of HCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Pretreatment CD4 Cell Slope and Progression to AIDS or Death in HIV-Infected Patients Initiating Antiretroviral Therapy—The CASCADE Collaboration: A Collaboration of 23 Cohort Studies

PubMed Central

Wolbers, Marcel; Babiker, Abdel; Sabin, Caroline; Young, Jim; Dorrucci, Maria; Chêne, Geneviève; Mussini, Cristina; Porter, Kholoud; Bucher, Heiner C.

2010-01-01

Background CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the decision on when to initiate cART. Methods and Findings We carried out survival analyses of patients from the 23 cohorts of the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) collaboration with a known date of HIV seroconversion and with at least two CD4 measurements prior to initiating cART. For each patient, a pre-cART CD4 slope was estimated using a linear mixed effects model. Our primary outcome was time from initiating cART to a first new AIDS event or death. We included 2,820 treatment-naïve patients initiating cART with a median (interquartile range) pre-cART CD4 cell decline of 61 (46–81) cells/µl per year; 255 patients subsequently experienced a new AIDS event or death and 125 patients died. In an analysis adjusted for established risk factors, the hazard ratio for AIDS or death was 1.01 (95% confidence interval 0.97–1.04) for each 10 cells/µl per year reduction in pre-cART CD4 cell decline. There was also no association between pre-cART CD4 cell slope and survival. Alternative estimates of CD4 cell slope gave similar results. In 1,731 AIDS-free patients with >350 CD4 cells/µl from the pre-cART era, the rate of CD4 cell decline was also not significantly associated with progression to AIDS or death (hazard ratio 0.99, 95% confidence interval 0.94–1.03, for each 10 cells/µl per year reduction in CD4 cell decline). Conclusions The CD4 cell slope does not improve the prediction of clinical outcome in patients with a CD4 cell count above 350 cells/µl. Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate cART in asymptomatic patients. Please see later in the article for the Editors' Summary PMID:20186270

Second Servings and a La Carte Sales to Elementary Children in the National School Lunch Program and Potential Implications for Childhood Obesity

ERIC Educational Resources Information Center

Wilder, Amanda J.

2012-01-01

The sale of second servings and/or a la carte purchases made by elementary students participating in the National School Lunch Program (NSLP) was investigated in this mixed methods case study. The percentage of elementary students in one school district who purchase second servings and/or a la carte items, in addition to the regularly purchased…

Towards an HIV cure based on targeted killing of infected cells: different approaches against acute versus chronic infection.

PubMed

Dey, Barna; Berger, Edward A

2015-05-01

Current regimens of combination antiretroviral therapy (cART) offer effective control of HIV infection, with maintenance of immune health and near-normal life expectancy. What will it take to progress beyond the status quo, whereby infectious virus can be eradicated (a 'sterilizing cure') or fully controlled without the need for ongoing cART (a 'functional cure')? On the basis of therapeutic advances in the cancer field, we propose that targeted cytotoxic therapy to kill HIV-infected cells represents a logical complement to cART for achieving an HIV cure. This concept is based on the fact that cART effectively blocks replication of the virus, but does not eliminate cells that are already infected; targeted cytotoxic therapy would contribute precisely this missing component. We suggest that different modalities are suited for curing primary acute versus established chronic infection. For acute infection, relatively short-acting potent agents such as recombinant immunotoxins might prove sufficient for HIV eradication, whereas for chronic infection, a long-lasting (lifelong?) modality is required to maintain full virus control, as might be achieved with genetically modified autologous T cells. We present perspectives for complementing cART with targeted cytotoxic therapy, whereby HIV infection is either eradicated or fully controlled, thereby eliminating the need for lifelong cART.

Synergistic use of optical and InSAR data for urban impervious surface mapping: A case study in Hong Kong

USGS Publications Warehouse

Jiang, L.; Liao, M.; Lin, H.; Yang, L.

2009-01-01

A wide range of urban ecosystem studies, including urban hydrology, urban climate, land use planning and watershed resource management, require accurate and up‐to‐date geospatial data of urban impervious surfaces. In this study, the potential of the synergistic use of optical and InSAR data in urban impervious surface mapping at the sub‐pixel level was investigated. A case study in Hong Kong was conducted for this purpose by applying a classification and regression tree (CART) algorithm to SPOT 5 multispectral imagery and ERS‐2 SAR data. Validated by reference data derived from high‐resolution colour‐infrared (CIR) aerial photographs, our results show that the addition of InSAR feature information can improve the estimation of impervious surface percentage (ISP) in comparison with using SPOT imagery alone. The improvement is especially notable in separating urban impervious surface from the vacant land/bare ground, which has been a difficult task in ISP modelling with optical remote sensing data. In addition, the results demonstrate the potential to map urban impervious surface by using InSAR data alone. This allows frequent monitoring of world's cities located in cloud‐prone and rainy areas.

Predicting Occurrence of Spine Surgery Complications Using "Big Data" Modeling of an Administrative Claims Database.

PubMed

Ratliff, John K; Balise, Ray; Veeravagu, Anand; Cole, Tyler S; Cheng, Ivan; Olshen, Richard A; Tian, Lu

2016-05-18

Postoperative metrics are increasingly important in determining standards of quality for physicians and hospitals. Although complications following spinal surgery have been described, procedural and patient variables have yet to be incorporated into a predictive model of adverse-event occurrence. We sought to develop a predictive model of complication occurrence after spine surgery. We used longitudinal prospective data from a national claims database and developed a predictive model incorporating complication type and frequency of occurrence following spine surgery procedures. We structured our model to assess the impact of features such as preoperative diagnosis, patient comorbidities, location in the spine, anterior versus posterior approach, whether fusion had been performed, whether instrumentation had been used, number of levels, and use of bone morphogenetic protein (BMP). We assessed a variety of adverse events. Prediction models were built using logistic regression with additive main effects and logistic regression with main effects as well as all 2 and 3-factor interactions. Least absolute shrinkage and selection operator (LASSO) regularization was used to select features. Competing approaches included boosted additive trees and the classification and regression trees (CART) algorithm. The final prediction performance was evaluated by estimating the area under a receiver operating characteristic curve (AUC) as predictions were applied to independent validation data and compared with the Charlson comorbidity score. The model was developed from 279,135 records of patients with a minimum duration of follow-up of 30 days. Preliminary assessment showed an adverse-event rate of 13.95%, well within norms reported in the literature. We used the first 80% of the records for training (to predict adverse events) and the remaining 20% of the records for validation. There was remarkable similarity among methods, with an AUC of 0.70 for predicting the occurrence of adverse events. The AUC using the Charlson comorbidity score was 0.61. The described model was more accurate than Charlson scoring (p < 0.01). We present a modeling effort based on administrative claims data that predicts the occurrence of complications after spine surgery. We believe that the development of a predictive modeling tool illustrating the risk of complication occurrence after spine surgery will aid in patient counseling and improve the accuracy of risk modeling strategies. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Pediatric head and neck injuries due to golf cart trauma.

PubMed

Miller, Brandon; Yelverton, Eden; Monico, Jesus; Replogle, William; Jordan, J Randall

2016-09-01

Golf carts are increasingly used off the golf course and are often viewed as innocuous modes of transportation. However, research has shown they can cause significant injuries, particularly to children. Analyze golf cart related head and neck injuries in children and adults from a national database. The National Electronic Injury Surveillance System (NEISS) was queried for golf cart injuries. The NEISS tracks consumer product related injuries from a sampling of approximately 100 emergency departments across the United States. Age, general diagnosis (concussion, fracture, laceration), body-part injured, disposition (hospitalized, discharged), location injury occurred, and mechanism of injury were analyzed. Over an 11-year period, a total of 3433 total patients were identified. There were 1471 children (16 years old or younger), which compromised 42.9% of the cohort. Children were injured at home or on the road 44.7% of the time compared to only 16.6% of adults (p < 0.003). Children injured their head or neck 42.6% of the time compared to 28.6% of adults (p < 0.0001). Adults who were hit by a car while riding a golf cart or were ejected from the golf cart 44.6% of the time compared to 61.7% of children (p < 0.0001). There were 3.9% of children with a face, head, or neck fracture compared to only 2.4% of adults (p = 0.01). Children are more vulnerable to golf cart related injuries, specifically to the head and neck. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation.

PubMed

Jose, S; Quinn, K; Dunn, D; Cox, A; Sabin, C; Fidler, S

2016-05-01

No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL. We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL. © 2015 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Incidence of golf cart-related injury in the United States.

PubMed

McGwin, Gerald; Zoghby, Jonathan T; Griffin, Russell; Rue, Loring W

2008-06-01

Golf carts have become a popular mode of transportation off of the links because of their small size, low maintenance, and ease of use. Case reports suggest severe, debilitating injuries as a consequence of golf cart incidents. To date, there has been no national population-based study of golf cart- related injuries. The National Electronic Injury Surveillance System identified individuals who visited participating emergency departments from January 1, 2002 to December 31, 2005 for injuries sustained as a result of golf carts. An estimated 48,255 (95% confidence interval, 35,342-61,108) golf cart-related injuries occurred in the U.S. between 2002 and 2005; the injury rate was 4.14 of 100,000 population. The highest injury rates were observed in 10 to 19 year olds and those aged 80 and older. Male patients had a higher injury rate than female patients, and whites had a higher rate than blacks or Asians. Contusions/abrasions were the most common diagnosis for the hip and lower extremity region; fractures were the most common diagnosis for shoulder and upper extremity region; and intracranial injuries, including concussions, subdural hematomas, and hemorrhage, were the most common diagnosis for head and neck region. The two most common geographic settings of injuries were sports fields such as golf courses (45.0%) and places of residence (16.0%). The popularity of golf carts as a means of transportation calls for mandatory safety standards to be met along with implementation of available safety courses for children who will potentially be operating these vehicles.

Feasibility of Routinely Offering Early Combined Antiretroviral Therapy to HIV-infected Infants in a Resource-limited Country: The ANRS-PediaCAM Study in Cameroon.

PubMed

Tejiokem, Mathurin Cyrille; Warszawski, Josiane; Ateba Ndongo, Francis; Tetang Ndiang, Suzie; Ndongo, Jean Audrey; Owona, Félicité; Ngoupo, Paul Alain; Tchendjou, Patrice; Kfutwah, Anfumbom; Penda, Ida Calixte; Faye, Albert

2015-10-01

Early diagnosis of HIV is increasingly available for infants in resource-limited settings. We assessed the timing of events until combined antiretroviral therapy (cART) initiation in infants diagnosed before 7 months of age in Cameroon. The ANRS-PediaCAM cohort included HIV-infected infants followed from birth associated with prevention of mother-to-child transmission activities (group 1) or diagnosed for any other reason before 7 months of age (group 2). All infants were offered free cART early after diagnosis. Frequency and factors associated with no or delayed cART initiation, were studied using univariable and multivariable logistic regressions. Between 2007 and 2011, 210 HIV-infected infants (group 1: 69; group 2: 141) were included. Fewer group 1 (14.3%) than group 2 (59.1%) infants were symptomatic (World Health Organization stage 3 or 4). Overall, 5.7% (n = 12) died before receiving any cART. Of the remaining 198 infants, 3.0% (n = 6) were not treated. The median age at initiating cART was 4.1 months [interquartile range (IQR): 3.2-5.6]. The median time until cART initiation after HIV testing was 6.2 weeks (IQR: 4.4-9.4) in group 1 and 5.1 weeks (IQR: 2.9-9.4) in group 2. No or delayed cART, observed for 37.9% (75 of 198) of the infants, was associated with clinical site [adjusted odds ratio (aOR): 4.8; 95% confidence interval: (2.1-11.2)], late diagnosis [aOR: 2.0 (0.9-4.1)], and delayed pretherapeutic biological assessment [aOR: 3.7 (1.4-10.0)]. Although most children included were treated before age 7 months, the initiation of therapy was delayed for more than 1 in 3. The period around HIV diagnosis is critical and should be better managed to reduce delays before cART initiation.

CETA truck and EVA restraint system

NASA Technical Reports Server (NTRS)

Beals, David C.; Merson, Wayne R.

1991-01-01

The Crew Equipment Translation Aid (CETA) experiment is an extravehicular activity (EVA) Space Transportation System (STS) based flight experiment which will explore various modes of transporting astronauts and light equipment for Space Station Freedom (SSF). The basic elements of CETA are: (1) two 25 foot long sections of monorail, which will be EVA assembled in the STS cargo bay to become a single 50 ft. rail called the track; (2) a wheeled baseplate called the truck which rolls along the track and can accept three cart concepts; and (3) the three carts which are designated manual, electric, and mechanical. The three carts serve as the astronaut restraint and locomotive interfaces with the track. The manual cart is powered by the astronaut grasping the track's handrail and pulling himself along. The electric cart is operated by an astronaut turning a generator which powers the electric motor and drives the cart. The mechanical cart is driven by a Bendix type transmission and is similar in concept to a man-propelled railroad cart. During launch and landing, the truck is attached to the deployable track by means of EVA removable restraint bolts and held in position by a system of retractable shims. These shims are positioned on the exterior of the rail for launch and landing and rotate out of the way for the duration of the experiment. The shims are held in position by strips of Velcro nap, which rub against the sides of the shim and exert a tailored force. The amount of force required to rotate the shims was a major EVA concern, along with operational repeatability and extreme temperature effects. The restraint system was tested in a thermal-vac and vibration environment and was shown to meet all of the initial design requirements. Using design inputs from the astronauts who will perform the EVA, CETA evolved through an iterative design process and represented a cooperative effort.

A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma.

PubMed

O'Rourke, Donald M; Nasrallah, MacLean P; Desai, Arati; Melenhorst, Jan J; Mansfield, Keith; Morrissette, Jennifer J D; Martinez-Lage, Maria; Brem, Steven; Maloney, Eileen; Shen, Angela; Isaacs, Randi; Mohan, Suyash; Plesa, Gabriela; Lacey, Simon F; Navenot, Jean-Marc; Zheng, Zhaohui; Levine, Bruce L; Okada, Hideho; June, Carl H; Brogdon, Jennifer L; Maus, Marcela V

2017-07-19

We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up. All patients demonstrated detectable transient expansion of CART-EGFRvIII cells in peripheral blood. Seven patients had post-CART-EGFRvIII surgical intervention, which allowed for tissue-specific analysis of CART-EGFRvIII trafficking to the tumor, phenotyping of tumor-infiltrating T cells and the tumor microenvironment in situ, and analysis of post-therapy EGFRvIII target antigen expression. Imaging findings after CART immunotherapy were complex to interpret, further reinforcing the need for pathologic sampling in infused patients. We found trafficking of CART-EGFRvIII cells to regions of active GBM, with antigen decrease in five of these seven patients. In situ evaluation of the tumor environment demonstrated increased and robust expression of inhibitory molecules and infiltration by regulatory T cells after CART-EGFRvIII infusion, compared to pre-CART-EGFRvIII infusion tumor specimens. Our initial experience with CAR T cells in recurrent GBM suggests that although intravenous infusion results in on-target activity in the brain, overcoming the adaptive changes in the local tumor microenvironment and addressing the antigen heterogeneity may improve the efficacy of EGFRvIII-directed strategies in GBM. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Methylation of L1RE1, RARB, and RASSF1 function as possible biomarkers for the differential diagnosis of lung cancer

PubMed Central

Casjens, S.; Werner, R.; Mairinger, F. D.; Speel, E. J. M.; Zur Hausen, A.; Meier, S.; Wohlschlaeger, J.; Theegarten, D.; Behrens, T.; Schmid, K. W.; Brüning, T.; Johnen, G.

2018-01-01

Background Lung cancer is the major cause of cancer-related deaths worldwide. Differential diagnosis can be difficult, especially when only small samples are available. Epigenetic changes are frequently tissue-specific events in carcinogenesis and hence may serve as diagnostic biomarkers. Material and methods 138 representative formalin-fixed, paraffin-embedded (FFPE) tissues (116 lung cancer cases and 22 benign controls) were used for targeted DNA methylation analysis via pyrosequencing of ten literature-derived methylation markers (APC, CDH1, CDKN2A, EFEMP1, FHIT, L1RE1, MGMT, PTEN, RARB, and RASSF1). Methylation levels were analyzed with the Classification and Regression Tree Algorithm (CART), Conditional Interference Trees (ctree) and ROC. Validation was performed with additional 27 lung cancer cases and 38 benign controls. TCGA data for 282 lung cancer cases was included in the analysis. Results CART and ctree analysis identified the combination of L1RE1 and RARB as well as L1RE1 and RASSF1 as independent methylation markers with high discriminative power between tumor and benign tissue (for each combination, 91% specificity and 100% sensitivity). L1RE1 methylation associated significantly with tumor type and grade (p<0.001) with highest methylation in the control group. The opposite was found for RARB (p<0.001). RASSF1 methylation increased with tumor type and grade (p<0.001) with strongest methylation in neuroendocrine tumors (NET). Conclusion Hypomethylation of L1RE1 is frequent in tumors compared to benign controls and associates with higher grade, whereas increasing methylation of RARB is an independent marker for tumors and higher grade. RASSF1 hypermethylation was frequent in tumors and most prominent in NET making it an auxiliary marker for separation of NSCLC and NET. L1RE1 in combination with either RARB or RASSF1 could function as biomarkers for separating lung cancer and non-cancerous tissue and could be useful for samples of limited size such as biopsies. PMID:29851970

[Study on sensitivity of climatic factors on influenza A (H1N1) based on classification and regression tree and wavelet analysis].

PubMed

Xiao, Hong; Lin, Xiao-ling; Dai, Xiang-yu; Gao, Li-dong; Chen, Bi-yun; Zhang, Xi-xing; Zhu, Pei-juan; Tian, Huai-yu

2012-05-01

To analyze the periodicity of pandemic influenza A (H1N1) in Changsha in year 2009 and its correlation with sensitive climatic factors. The information of 5439 cases of influenza A (H1N1) and synchronous meteorological data during the period between May 22th and December 31st in year 2009 (223 days in total) in Changsha city were collected. The classification and regression tree (CART) was employed to screen the sensitive climatic factors on influenza A (H1N1); meanwhile, cross wavelet transform and wavelet coherence analysis were applied to assess and compare the periodicity of the pandemic disease and its association with the time-lag phase features of the sensitive climatic factors. The results of CART indicated that the daily minimum temperature and daily absolute humidity were the sensitive climatic factors for the popularity of influenza A (H1N1) in Changsha. The peak of the incidence of influenza A (H1N1) was in the period between October and December (Median (M) = 44.00 cases per day), simultaneously the daily minimum temperature (M = 13°C) and daily absolute humidity (M = 6.69 g/m(3)) were relatively low. The results of wavelet analysis demonstrated that a period of 16 days was found in the epidemic threshold in Changsha, while the daily minimum temperature and daily absolute humidity were the relatively sensitive climatic factors. The number of daily reported patients was statistically relevant to the daily minimum temperature and daily absolute humidity. The frequency domain was mostly in the period of (16 ± 2) days. In the initial stage of the disease (from August 9th and September 8th), a 6-day lag was found between the incidence and the daily minimum temperature. In the peak period of the disease, the daily minimum temperature and daily absolute humidity were negatively relevant to the incidence of the disease. In the pandemic period, the incidence of influenza A (H1N1) showed periodic features; and the sensitive climatic factors did have a "driving effect" on the incidence of influenza A (H1N1).

A Nocturnal Boundary Layer Simulation over the ARM-CART Site

NASA Astrophysics Data System (ADS)

Werth, D.; Leclerc, M.; Duarte, H.; Fischer, M.; Kurzeja, R.; Parker, M.

2008-12-01

The nocturnal boundary layer (NBL) is characterized by strong inversions and weak turbulent motions. It is during this time that low-level jets (LLJs) often form as the winds aloft reach speeds approaching 15-25m/s at levels below 1000m. During the daytime, turbulent mixing quickly damps such organized motion, but at night the surface cooling establishes an inversion which reduces turbulence and allows jets to form uninhibited. A field project over the ARM-CART site during a period of several nights in September, 2007 was conducted to explore the jet evolution. Data was collected from a tower and analyzed for turbulent behavior. With data limited to a single location, however, the full range of NBL behavior is difficult to determine. The Regional Atmospheric Modeling System (RAMS) is therefore used to simulate the ARM-CART NBL field experiment and validated against the data collected from the site. This model was run at high resolution, and is ideal for calculating the interactions among the various motions within the boundary layer and their influence on the surface. The model can provide information throughout the NBL - with a larger domain, a simulation of the NBL can provide information over a large range of locations and heights. In particular, we are interested in the way that the simulated NBL eddies are affected by their height and proximity to the LLJ, and how this compares to the tower results. The eddy sizes that exist in the model are limited by its grid spacing, but a series of smaller, finer nests allow us to study eddy motion at the relevant scales for short periods.

Tuberculous Pericarditis is Multibacillary and Bacterial Burden Drives High Mortality

PubMed Central

Pasipanodya, Jotam G.; Mubanga, Mwenya; Ntsekhe, Mpiko; Pandie, Shaheen; Magazi, Beki T.; Gumedze, Freedom; Myer, Landon; Gumbo, Tawanda; Mayosi, Bongani M.

2015-01-01

Background Tuberculous pericarditis is considered to be a paucibacillary process; the large pericardial fluid accumulation is attributed to an inflammatory response to tuberculoproteins. Mortality rates are high. We investigated the role of clinical and microbial factors predictive of tuberculous pericarditis mortality using the artificial intelligence algorithm termed classification and regression tree (CART) analysis. Methods Patients were prospectively enrolled and followed in the Investigation of the Management of Pericarditis (IMPI) registry. Clinical and laboratory data of 70 patients with confirmed tuberculous pericarditis, including time-to-positive (TTP) cultures from pericardial fluid, were extracted and analyzed for mortality outcomes using CART. TTP was translated to log10 colony forming units (CFUs) per mL, and compared to that obtained from sputum in some of our patients. Findings Seventy patients with proven tuberculous pericarditis were enrolled. The median patient age was 35 (range: 20–71) years. The median, follow up was for 11.97 (range: 0·03–74.73) months. The median TTP for pericardial fluid cultures was 22 (range: 4–58) days or 3.91(range: 0·5–8·96) log10CFU/mL, which overlapped with the range of 3.24–7.42 log10CFU/mL encountered in sputum, a multi-bacillary disease. The overall mortality rate was 1.43 per 100 person-months. CART identified follow-up duration of 5·23 months on directly observed therapy, a CD4 + count of ≤ 199.5/mL, and TTP ≤ 14 days (bacillary load ≥ 5.53 log10 CFU/mL) as predictive of mortality. TTP interacted with follow-up duration in a non-linear fashion. Interpretation Patients with culture confirmed tuberculous pericarditis have a high bacillary burden, and this bacterial burden drives mortality. Thus proven tuberculosis pericarditis is not a paucibacillary disease. Moreover, the severe immunosuppression suggests limited inflammation. There is a need for the design of a highly bactericidal regimen for this condition. PMID:26870789

The Rain-Powered Cart

DTIC Science & Technology

2016-08-05

publication 11 July 2016 Published 5 August 2016 Abstract A frictionless cart in the shape of a right triangle (with the vertical side forward) is...elastically impacted by vertically falling raindrops. The speed of the cart as a function of time can be analytically deduced as an exercise in the use...horizontal surface under the impulse of raindrops (or hail) falling vertically at terminal speed u that bounce elastically [4, 5] off the cart’s two

Weight as predictors of clinical progression and treatment failure: results from the TREAT Asia Pediatric HIV Observational Database.

PubMed

Kariminia, Azar; Durier, Nicolas; Jourdain, Gonzague; Saghayam, Suneeta; Do, Chau V; Nguyen, Lam Van; Hansudewechakul, Rawiwan; Lumbiganon, Pagakrong; Chokephaibulkit, Kulkanya; Truong, Khanh Huu; Sirisanthana, Virat; Ung, Vibol; Vonthanak, Saphonn; Ananworanich, Jintanat; Nik Yusoff, Nik Khairulddin; Kurniati, Nia; Azahar Razali, Kamarul; Fong, Moy Siew; Nallusamy, Revathy; Wati, Dewi Kumara

2014-09-01

To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART). We used Cox regression to analyze data of a cohort of Asian children. A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score < -3 was associated with mortality (P < 0.001) independent of CD4% and < -2 was associated with immunological failure (P ≤ 0.03) independent of age at cART. Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings.

The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals.

PubMed

Ray, Maile; Logan, Roger; Sterne, Jonathan A C; Hernández-Díaz, Sonia; Robins, James M; Sabin, Caroline; Bansi, Loveleen; van Sighem, Ard; de Wolf, Frank; Costagliola, Dominique; Lanoy, Emilie; Bucher, Heiner C; von Wyl, Viktor; Esteve, Anna; Casbona, Jordi; del Amo, Julia; Moreno, Santiago; Justice, Amy; Goulet, Joseph; Lodi, Sara; Phillips, Andrew; Seng, Rémonie; Meyer, Laurence; Pérez-Hoyos, Santiago; García de Olalla, Patricia; Hernán, Miguel A

2010-01-02

To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication. A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication. Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001). We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.

Antiretroviral treatment-based cost saving interventions may offset expenses for new patients and earlier treatment start.

PubMed

Angeletti, C; Pezzotti, P; Antinori, A; Mammone, A; Navarra, A; Orchi, N; Lorenzini, P; Mecozzi, A; Ammassari, A; Murachelli, S; Ippolito, G; Girardi, E

2014-03-01

Combination antiretroviral therapy (cART) has become the main driver of total costs of caring for persons living with HIV (PLHIV). The present study estimated the short/medium-term cost trends in response to the recent evolution of national guidelines and regional therapeutic protocols for cART in Italy. We developed a deterministic mathematical model that was calibrated using epidemic data for Lazio, a region located in central Italy with about six million inhabitants. In the Base Case Scenario, the estimated number of PLHIV in the Lazio region increased over the period 2012-2016 from 14 414 to 17 179. Over the same period, the average projected annual cost for treating the HIV-infected population was €147.0 million. An earlier cART initiation resulted in a rise of 2.3% in the average estimated annual cost, whereas an increase from 27% to 50% in the proportion of naïve subjects starting cART with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen resulted in a reduction of 0.3%. Simplification strategies based on NNRTIs co-formulated in a single tablet regimen and protease inhibitor/ritonavir-boosted monotherapy produced an overall reduction in average annual costs of 1.5%. A further average saving of 3.3% resulted from the introduction of generic antiretroviral drugs. In the medium term, cost saving interventions could finance the increase in costs resulting from the inertial growth in the number of patients requiring treatment and from the earlier treatment initiation recommended in recent guidelines. © 2013 British HIV Association.

Data systems for science integration within the Atmospheric Radiation Measurement Program

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

Gracio, D.K.; Hatfield, L.D.; Yates, K.R.

The Atmospheric Radiation Measurement (ARM) Program was developed by the US Department of Energy to support the goals and mission of the US Global Change Research Program. The purpose of the ARM program is to improve the predictive capabilities of General Circulation Models (GCMs) in their treatment of clouds and radiative transfer effects. Three experimental testbeds were designed for the deployment of instruments to collect atmospheric data used to drive the GCMs. Each site, known as a Cloud and Radiation Testbed (CART), consists of a highly available, redundant data system for the collection of data from a variety of instrumentation.more » The first CART site was deployed in April 1992 in the Southern Great Plains (SGP), Lamont, Oklahoma, with the other two sites to follow in early 1996 in the Tropical Western Pacific (TWP) and in 1997 on the North Slope of Alaska (NSA). Approximately 1.5 GB of data are transferred per day via the Internet from the CART sites, and external data sources to the ARM Experiment Center (EC) at Pacific Northwest Laboratory in Richland, Washington. The Experimental Center is central to the ARM data path and provides for the collection, processing, analysis and delivery of ARM data. Data from the CART sites from a variety of instrumentation, observational systems and from external data sources are transferred to the Experiment Center. The EC processes these data streams on a continuous basis to provide derived data products to the ARM Science Team in near real-time while maintaining a three-month running archive of data.« less

[GESIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2015)].

PubMed

2015-10-01

This consensus document is an update of combined antiretroviral therapy (cART) guidelines and recommendations for HIV-1 infected adult patients. To formulate these recommendations, a panel composed of members of the AIDS Study Group and the AIDS National Plan (GeSIDA/Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, and cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations, and the evidence that supports them, are based on modified criteria of the Infectious Diseases Society of America. In this update, cART is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and level of the recommendation depends on the CD4+T-lymphocyte count, the presence of opportunistic diseases or comorbid conditions, age, and prevention of transmission of HIV. The objective of cART is to achieve an undetectable plasma viral load. Initial cART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors, and a third drug from a different family. Three out of the ten recommended regimes are regarded as preferential (all of them with an integrase inhibitor as the third drug), and the other seven (based on a non-nucleoside reverse transcriptase inhibitor, a ritonavir-boosted protease inhibitor, or an integrase inhibitor) as alternatives. This update presents the causes and criteria for switching cART in patients with undetectable plasma viral load, and in cases of virological failure where rescue cART should comprise 3 (or at least 2) drugs that are fully active against the virus. An update is also provided for the specific criteria for cART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). These new guidelines update previous recommendations related to cART (when to begin and what drugs should be used), how to monitor and what to do in case of viral failure or drug adverse reactions. cART specific criteria in comorbid patients and special situations are equally updated. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Deploying a Proximal Sensing Cart to Identify Drought-Adaptive Traits in Upland Cotton for High-Throughput Phenotyping

PubMed Central

Thompson, Alison L.; Thorp, Kelly R.; Conley, Matthew; Andrade-Sanchez, Pedro; Heun, John T.; Dyer, John M.; White, Jeffery W.

2018-01-01

Field-based high-throughput phenotyping is an emerging approach to quantify difficult, time-sensitive plant traits in relevant growing conditions. Proximal sensing carts represent an alternative platform to more costly high-clearance tractors for phenotyping dynamic traits in the field. A proximal sensing cart and specifically a deployment protocol, were developed to phenotype traits related to drought tolerance in the field. The cart-sensor package included an infrared thermometer, ultrasonic transducer, multi-spectral reflectance sensor, weather station, and RGB cameras. The cart deployment protocol was evaluated on 35 upland cotton (Gossypium hirsutum L.) entries grown in 2017 at Maricopa, AZ, United States. Experimental plots were grown under well-watered and water-limited conditions using a (0,1) alpha lattice design and evaluated in June and July. Total collection time of the 0.87 hectare field averaged 2 h and 27 min and produced 50.7 MB and 45.7 GB of data from the sensors and RGB cameras, respectively. Canopy temperature, crop water stress index (CWSI), canopy height, normalized difference vegetative index (NDVI), and leaf area index (LAI) differed among entries and showed an interaction with the water regime (p < 0.05). Broad-sense heritability (H2) estimates ranged from 0.097 to 0.574 across all phenotypes and collections. Canopy cover estimated from RGB images increased with counts of established plants (r = 0.747, p = 0.033). Based on the cart-derived phenotypes, three entries were found to have improved drought-adaptive traits compared to a local adapted cultivar. These results indicate that the deployment protocol developed for the cart and sensor package can measure multiple traits rapidly and accurately to characterize complex plant traits under drought conditions. PMID:29868041

Crypto-Giardia antigen rapid test versus conventional modified Ziehl-Neelsen acid fast staining method for diagnosis of cryptosporidiosis.

PubMed

Zaglool, Dina Abdulla Muhammad; Mohamed, Amr; Khodari, Yousif Abdul Wahid; Farooq, Mian Usman

2013-03-01

To evaluate the validity of Crypto-Giardia antigen rapid test (CA-RT) in comparison with the conventional modified Ziehl-Neelsen acid fast (MZN-AF) staining method for the diagnosis of cryptosporidiosis. Fifteen preserved stool samples from previously confirmed infections were used as positive controls and 40 stool samples from healthy people were used as negative control. A total of 85 stool samples were collected from suspected patients with cryptosporidiosis over 6 months during the period from January till June, 2011. The study was conducted in the department of parasitology, central laboratory, Alnoor Specialist Hospital, Makkah, Saudi Arabia. All samples were subjected to CA-RT and conventional MZN-AF staining method. Validation parameters including sensitivity (SN), specificity (SP), accuracy index (AI), positive predictive value (PPV), and negative predictive value (NPV) were evaluated for both tests. Out of 15 positive controls, CA-RT detected 13 (86.7%) while MZN-AF detected 11(73.3%) positive cases. However, CA-RT detected no positive case in 40 normal controls but MZN-AF detected 2(5%) as positive cases. Based on the results, the SN, SP, AI, PPV and NPV were high in CA-RT than MZN-AF staining method, ie., 86.7%vs. 73.3%, 100%vs. 95%, 96.4%vs. 89.1%, 100%vs. 84.6% and 95.2%vs. 90.5%, respectively. Out of a total of 85 suspected specimens, CA-RT detected 7(8.2%) but MZN-AF detected 6(7.1%) cases as positive. CA-RT immunoassay is more valid and reliable than MZN-AF staining method. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Community action research track: Community-based participatory research and service-learning experiences for medical students.

PubMed

Gimpel, Nora; Kindratt, Tiffany; Dawson, Alvin; Pagels, Patti

2018-04-01

Community-based participatory research (CBPR) and service-learning are unique experiential approaches designed to train medical students how to provide individualized patient care from a population perspective. Medical schools in the US are required to provide support for service-learning and community projects. Despite this requirement, few medical schools offer structured service-learning. We developed the Community Action Research Track (CART) to integrate population medicine, health promotion/disease prevention and the social determinants of health into the medical school curriculum through CBPR and service-learning experiences. This article provides an overview of CART and reports the program impact based on students' participation, preliminary evaluations and accomplishments. CART is an optional 4‑year service-learning experience for medical students interested in community health. The curriculum includes a coordinated longitudinal program of electives, community service-learning and lecture-based instruction. From 2009-2015, 146 CART students participated. Interests in public health (93%), community service (73%), primary care (73%), CBPR (60%) and community medicine (60%) were the top reasons for enrolment. Significant improvements in mean knowledge were found when measuring the principles of CBPR, levels of prevention, determining health literacy and patient communication strategies (all p's < 0.05). Most students (73%) were satisfied with CART. Projects were disseminated by at least 65 posters and four oral presentations at local, national and international professional meetings. Six manuscripts were published in peer-reviewed journals. CART is an innovative curriculum for training future physicians to be community-responsive physicians. CART can be replicated by other medical schools interested in offering a longitudinal CBPR and service-learning track in an urban metropolitan setting.

Cocaine- and Amphetamine-Regulated Transcript (CART) Expression is Differentially Regulated in the Hypothalamic Para ventricular Nucleus of Lactating Rats Exposed to Suckling or Cold Stimulation

PubMed Central

Sánchez, Edith; Fekete, Csaba; Lechan, Ronald M.; Joseph-Bravo, Patricia

2007-01-01

Neural stimuli, such as suckling or cold exposure, increase TRH mRNA in the paraventricular nucleus (PVN) of the rat hypothalamus, yet only suckling induces prolactin secretion. As TRH co-localizes with cocaine-and amphetamine-regulated transcript (CART) in hypophysiotropic neurons of the PVN, and CART inhibits TRH-induced prolactin release but not TRH-induced TSH release in adenohypophyseal cell cultures, we raised the possibility that differential regulation of CART gene expression in the PVN may explain the differences in prolactin secretion following each of the two stimuli. Primiparous female rats were mated and handled daily during the pre- and postpartum periods. After delivery, the litter was adjusted to 8 pups and at mid-lactation, dams were separated from their pups for 8 hours and exposed to either 1h of cold or 30 min of suckling. Long term effects of suckling were studied by separating pups from their mothers for 24h, followed by a 12h period of continuous suckling. Serum TSH levels increased in response to cold exposure, while prolactin levels were increased by suckling and diminished by cold exposure. CART mRNA levels increased in rostral and mid parts of the medial parvocellular PVN following cold exposure but not after suckling stimulation. These data demonstrate a differential regulation of CART gene expression in hypophysiotropic neurons in response to stimuli that increase TRH mRNA levels, and suggest that CART activation in the PVN may contribute to the decrease in PRL release when the thyroid axis is activated by cold exposure. Section: Regulatory systems PMID:17174283

Summer Research Program (1992). Graduate Student Research Programs Reports. Armstrong Laboratory. Volume 7

DTIC Science & Technology

1992-12-28

vehicle rolled over a switch which caused hydraulic cylinders to actuate. These cylinders pushed the truck from the cart, and the cart decelerated. The... hydraulic cylinders on the cart began to push the vehicle. So, to determine the exact time that the 30 cylinders began to move, plots were 25 - studied...attempts because of its dependence on well understood hydraulic principles and because of the wealth of understanding about the various constituent

Non-viral RNA chimeric antigen receptor modified T cells in patients with Hodgkin lymphoma.

PubMed

Svoboda, Jakub; Rheingold, Susan R; Gill, Saar I; Grupp, Stephan A; Lacey, Simon F; Kulikovskaya, Irina; Suhoski, Megan M; Melenhorst, J Joseph; Loudon, Brandon; Mato, Anthony R; Nasta, Sunita Dwivedy; Landsburg, Daniel J; Youngman, Matthew R; Levine, Bruce L; Porter, David L; June, Carl H; Schuster, Stephen J

2018-06-20

Chimeric antigen receptor (CAR) modified T cells are being investigated in many settings including classical Hodgkin lymphoma (cHL). The unique biology of cHL, characterized by scant Hodgkin and Reed-Sternberg (HRS) cells within an immunosuppressive tumor microenvironment (TME), may pose challenges for cellular therapies directly targeting antigens expressed on HRS. We hypothesized that eradicating CD19 positive (+) B cells within the TME and the putative circulating CD19+ HRS clonotypic cells using anti-CD19 directed CAR modified T cells (CART19) may indirectly affect HRS cells, which do not express CD19. Here we describe our pilot trial using CART19 in patients with relapsed and refractory cHL. To limit potential toxicities, we used non-viral RNA CART19 cells which are expected to express CAR protein only a few days, as opposed to CART19 generated by viral vector transduction, which expand in vivo and retain CAR expression. All 5 enrolled patients underwent successful manufacturing of non-viral RNA CART19 and 4 were infused with protocol specified cell dose. There were no severe toxicities. Responses were seen, but these were transient. To our knowledge, this is the first CART19 clinical trial to use non-viral RNA gene delivery. This trial was registered at www.clinicaltrials.gov as NCT02277522 (adult) and NCT02624258 (pediatric). Copyright © 2018 American Society of Hematology.

Genetic Regulation of Hypothalamic Cocaine and Amphetamine-Regulated Transcript (CART) in BxD Inbred Mice

PubMed Central

Hawks, Brian W.; Li, Wei; Garlow, Steven J.

2009-01-01

Cocaine-Amphetamine Regulated Transcript (CART) peptides are implicated in a wide range of behaviors including in the reinforcing properties of psychostimulants, feeding and energy balance and stress and anxiety responses. We conducted a complex trait analysis to examine natural variation in the regulation of CART transcript abundance (CARTta) in the hypothalamus. CART transcript abundance was measured in total hypothalamic RNA from 26 BxD recombinant inbred (RI) mouse strains and in the C57BL/6 (B6) and DBA/2J (D2) progenitor strains. The strain distribution pattern for CARTta was continuous across the RI panel, which is consistent with this being a quantitative trait. Marker regression and interval mapping revealed significant quantitative trait loci (QTL) on mouse chromosome 4 (around 58.2cM) and chromosome 11 (between 20–36cM) that influence CARTta and account for 31% of the between strain variance in this phenotype. There are numerous candidate genes and QTL in these chromosomal regions that may indicate shared genetic regulation between CART expression and other neurobiological processes referable to known actions of this neuropeptide. PMID:18199428

Computer assisted analysis of auroral images obtained from high altitude polar satellites

NASA Technical Reports Server (NTRS)

Samadani, Ramin; Flynn, Michael

1993-01-01

Automatic techniques that allow the extraction of physically significant parameters from auroral images were developed. This allows the processing of a much larger number of images than is currently possible with manual techniques. Our techniques were applied to diverse auroral image datasets. These results were made available to geophysicists at NASA and at universities in the form of a software system that performs the analysis. After some feedback from users, an upgraded system was transferred to NASA and to two universities. The feasibility of user-trained search and retrieval of large amounts of data using our automatically derived parameter indices was demonstrated. Techniques based on classification and regression trees (CART) were developed and applied to broaden the types of images to which the automated search and retrieval may be applied. Our techniques were tested with DE-1 auroral images.

Glove Changing Habits in Mobile Food Vendors in New York City.

PubMed

Basch, Corey H; Guerra, Laura A; MacDonald, Zerlina; Marte, Myladys; Basch, Charles E

2015-08-01

The aim of this study was to determine how often mobile food cart vendors in New York City (NYC) changed gloves after exchanging money, which is required by the current NYC health code as one of various measures to prevent foodborne illness. A total of 100 carts (10 carts in 10 zones) throughout Manhattan were observed. In the majority (56.9%, n = 1,026) of the 1,804 money exchanges, food cart vendors did not change their gloves. Not changing gloves after exchanging money was widespread regardless of food type served (46.6% for breakfast to 63.7% for lunch), and across all 10 zones. Not changing gloves after touching money may result in indirect transmission of agents of disease and pose health risks for consumers.

Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T

PubMed Central

Yoon, Dok Hyun; Osborn, Mark J.; Tolar, Jakub; Kim, Chong Jai

2018-01-01

Chimeric antigen receptor (CAR) T cell therapy represents the first U.S. Food and Drug Administration approved gene therapy and these engineered cells function with unprecedented efficacy in the treatment of refractory CD19 positive hematologic malignancies. CAR translation to solid tumors is also being actively investigated; however, efficacy to date has been variable due to tumor-evolved mechanisms that inhibit local immune cell activity. To bolster the potency of CAR-T cells, modulation of the immunosuppressive tumor microenvironment with immune-checkpoint blockade is a promising strategy. The impact of this approach on hematological malignancies is in its infancy, and in this review we discuss CAR-T cells and their synergy with immune-checkpoint blockade. PMID:29364163

Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities

PubMed Central

Xia, An-Liang; Wang, Xiao-Chen; Lu, Yi-Jun; Lu, Xiao-Jie; Sun, Beicheng

2017-01-01

Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have been shown to have unprecedented efficacy in B cell malignancies, most notably in B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate using anti-CD19 CAR-T cells. However, CAR T-cell therapy for solid tumors currently is faced with numerous challenges such as physical barriers, the immunosuppressive tumor microenvironment and the specificity and safety. The clinical results in solid tumors have been much less encouraging, with multiple cases of toxicity and a lack of therapeutic response. In this review, we will discuss the current stats and challenges of CAR-T cell therapy for solid tumors, and propose possibl e solutions and future perspectives. PMID:29163850

NeoCart, an autologous cartilage tissue implant, compared with microfracture for treatment of distal femoral cartilage lesions: an FDA phase-II prospective, randomized clinical trial after two years.

PubMed

Crawford, Dennis C; DeBerardino, Thomas M; Williams, Riley J

2012-06-06

Despite introduction of autologous chondrocyte therapy for repair of hyaline articular cartilage injury in 1994, microfracture remains a primary standard of care. NeoCart, an autologous cartilage tissue implant, was compared with microfracture in a multisite prospective, randomized trial of a tissue-engineered bioimplant for treating articular cartilage injuries in the knee. Thirty patients were randomized at a ratio of two to one (two were treated with an autologous cartilage tissue implant [NeoCart] for each patient treated with microfracture) at the time of arthroscopic confirmation of an International Cartilage Repair Society (ICRS) grade-III lesion(s). Microfracture or cartilage biopsy was performed. NeoCart, produced by seeding a type-I collagen matrix scaffold with autogenous chondrocytes and bioreactor treatment, was implanted six weeks following arthroscopic cartilage biopsy. Standard evaluations were performed with validated clinical outcomes measures. Three, six, twelve, and twenty-four-month data are reported. The mean duration of follow-up (and standard deviation) was 26 ± 2 months. There were twenty-one patients in the NeoCart group and nine in the microfracture group. The mean age (40 ± 9 years), body mass index (BMI) (28 ± 4 kg/m2), duration between the first symptoms and treatment (3 ± 5 years), and lesion size (287 ± 138 mm2 in the NeoCart group and 252 ± 135 mm2 in the microfracture group) were similar between the groups. Adverse event rates per procedure did not differ between the treatment arms. The scores on the Short Form-36 (SF-36), Knee Injury and Osteoarthritis Outcome Score (KOOS) activities of daily living (ADL) scale, and International Knee Documentation Committee (IKDC) form improved from baseline (p < 0.05) to two years postoperatively in both treatment groups. In the NeoCart group, improvement, compared with baseline, was significant (p < 0.05) for all measures at six, twelve, and twenty-four months. Improvement in the NeoCart group was significantly greater (p < 0.05) than that in the microfracture group for the KOOS pain score at six, twelve, and twenty-four months; the KOOS symptom score at six months; the IKDC, KOOS sports, and visual analog scale (VAS) pain scores at twelve and twenty-four months; and the KOOS quality of life (QOL) score at twenty-four months. Analysis of covariance (ANCOVA) at one year indicated that the change in the KOOS pain (p = 0.016) and IKDC (p = 0.028) scores from pretreatment levels favored the NeoCart group. Significantly more NeoCart-treated patients (p = 0.0125) had responded to therapy (were therapeutic responders) at six months (43% versus 25% in the microfracture group) and twelve months (76% versus 22% in the microfracture group). This trend continued, as the proportion of NeoCart-treated patients (fifteen of nineteen) who were therapeutic responders at twenty-four months was greater than the proportion of microfracture-treated participants (four of nine) who were therapeutic responders at that time. This randomized study suggests that the safety of autologous cartilage tissue implantation, with use of the NeoCart technique, is similar to that of microfracture surgery and is associated with greater clinical efficacy at two years after treatment.

State of the cart.

PubMed

Bernstein, C; Weiss, S; Lorenzini, B

1994-03-15

Food on wheels: it's here, there and everywhere. But while some operations rev up cart expansion plans, others have shifted into low gear. Here's an update on that '90s phenomenon: mobile merchandising.

Subgroup identification of early preterm birth (ePTB): informing a future prospective enrichment clinical trial design.

PubMed

Zhang, Chuanwu; Garrard, Lili; Keighley, John; Carlson, Susan; Gajewski, Byron

2017-01-10

Despite the widely recognized association between the severity of early preterm birth (ePTB) and its related severe diseases, little is known about the potential risk factors of ePTB and the sub-population with high risk of ePTB. Moreover, motivated by a future confirmatory clinical trial to identify whether supplementing pregnant women with docosahexaenoic acid (DHA) has a different effect on the risk subgroup population or not in terms of ePTB prevalence, this study aims to identify potential risk subgroups and risk factors for ePTB, defined as babies born less than 34 weeks of gestation. The analysis data (N = 3,994,872) were obtained from CDC and NCHS' 2014 Natality public data file. The sample was split into independent training and validation cohorts for model generation and model assessment, respectively. Logistic regression and CART models were used to examine potential ePTB risk predictors and their interactions, including mothers' age, nativity, race, Hispanic origin, marital status, education, pre-pregnancy smoking status, pre-pregnancy BMI, pre-pregnancy diabetes status, pre-pregnancy hypertension status, previous preterm birth status, infertility treatment usage status, fertility enhancing drug usage status, and delivery payment source. Both logistic regression models with either 14 or 10 ePTB risk factors produced the same C-index (0.646) based on the training cohort. The C-index of the logistic regression model based on 10 predictors was 0.645 for the validation cohort. Both C-indexes indicated a good discrimination and acceptable model fit. The CART model identified preterm birth history and race as the most important risk factors, and revealed that the subgroup with a preterm birth history and a race designation as Black had the highest risk for ePTB. The c-index and misclassification rate were 0.579 and 0.034 for the training cohort, and 0.578 and 0.034 for the validation cohort, respectively. This study revealed 14 maternal characteristic variables that reliably identified risk for ePTB through either logistic regression model and/or a CART model. Moreover, both models efficiently identify risk subgroups for further enrichment clinical trial design.

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis.

PubMed

Grigor, Emma J M; Fergusson, Dean A; Haggar, Fatima; Kekre, Natasha; Atkins, Harold; Shorr, Risa; Holt, Robert A; Hutton, Brian; Ramsay, Tim; Seftel, Matthew; Jonker, Derek; Daugaard, Mads; Thavorn, Kednapa; Presseau, Justin; Lalu, Manoj M

2017-12-29

Patients with relapsed or refractory malignancies have a poor prognosis. Immunotherapy with chimeric antigen receptor T (CAR-T) cells redirects a patient's immune cells against the tumour antigen. CAR-T cell therapy has demonstrated promise in treating patients with several haematological malignancies, including acute B-cell lymphoblastic leukaemia and B-cell lymphomas. CAR-T cell therapy for patients with other solid tumours is also being tested. Safety is an important consideration in CAR-T cell therapy given the potential for serious adverse events, including death. Previous reviews on CAR-T cell therapy have been limited in scope and methodology. Herein, we present a protocol for a systematic review to identify CAR-T cell interventional studies and examine the safety and efficacy of this therapy in patients with haematology malignancies and solid tumours. We will search MEDLINE, including In-Process and Epub Ahead of Print, EMBASE and the Cochrane Central Register of Controlled Trials from 1946 to 22 February 2017. Studies will be screened by title, abstract and full text independently and in duplicate. Studies that report administering CAR-T cells of any chimeric antigen receptor construct targeting antigens in patients with haematological malignancies and solid tumours will be eligible for inclusion. Outcomes to be extracted will include complete response rate (primary outcome), overall response rate, overall survival, relapse and adverse events. A meta-analysis will be performed to synthesise the prevalence of outcomes reported as proportions with 95% CIs. The potential for bias within included studies will be assessed using a modified Institute of Health Economics tool. Heterogeneity of effect sizes will be determined using the Cochrane I 2 statistic. The review findings will be submitted for peer-reviewed journal publication and presented at relevant conferences and scientific meetings to promote knowledge transfer. CRD42017075331. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The use of decision tree induction and artificial neural networks for recognizing the geochemical distribution patterns of LREE in the Choghart deposit, Central Iran

NASA Astrophysics Data System (ADS)

Zaremotlagh, S.; Hezarkhani, A.

2017-04-01

Some evidences of rare earth elements (REE) concentrations are found in iron oxide-apatite (IOA) deposits which are located in Central Iranian microcontinent. There are many unsolved problems about the origin and metallogenesis of IOA deposits in this district. Although it is considered that felsic magmatism and mineralization were simultaneous in the district, interaction of multi-stage hydrothermal-magmatic processes within the Early Cambrian volcano-sedimentary sequence probably caused some epigenetic mineralizations. Secondary geological processes (e.g., multi-stage mineralization, alteration, and weathering) have affected on variations of major elements and possible redistribution of REE in IOA deposits. Hence, the geochemical behaviors and distribution patterns of REE are expected to be complicated in different zones of these deposits. The aim of this paper is recognizing LREE distribution patterns based on whole-rock chemical compositions and automatic discovery of their geochemical rules. For this purpose, the pattern recognition techniques including decision tree and neural network were applied on a high-dimensional geochemical dataset from Choghart IOA deposit. Because some data features were irrelevant or redundant in recognizing the distribution patterns of each LREE, a greedy attribute subset selection technique was employed to select the best subset of predictors used in classification tasks. The decision trees (CART algorithm) were pruned optimally to more accurately categorize independent test data than unpruned ones. The most effective classification rules were extracted from the pruned tree to describe the meaningful relationships between the predictors and different concentrations of LREE. A feed-forward artificial neural network was also applied to reliably predict the influence of various rock compositions on the spatial distribution patterns of LREE with a better performance than the decision tree induction. The findings of this study could be effectively used to visualize the LREE distribution patterns as geochemical maps.

Modelling, Simulation, Animation, and Real-Time Control (Mosart) for a Class of Electromechanical Systems: A System-Theoretic Approach

ERIC Educational Resources Information Center

Rodriguez, Armando A.; Metzger, Richard P.; Cifdaloz, Oguzhan; Dhirasakdanon, Thanate; Welfert, Bruno

2004-01-01

This paper describes an interactive modelling, simulation, animation, and real-time control (MoSART) environment for a class of 'cart-pendulum' electromechanical systems that may be used to enhance learning within differential equations and linear algebra classes. The environment is useful for conveying fundamental mathematical/systems concepts…

Teachers' Pets II--Circling Carts

ERIC Educational Resources Information Center

Gardner, Robert

1975-01-01

Describes a demonstration which illustrates that a body moving with constant speed can be accelerating. The students ride in a circle on a cart made with plywood and roller skates and equipped with bubble accelerometers. (MLH)

Chimeric Antigen Receptor-Redirected T cells return to the bench

PubMed Central

Geldres, Claudia; Savoldo, Barbara; Dotti, Gianpietro

2016-01-01

While the clinical progress of chimeric antigen receptor T cell (CAR-T) immunotherapy has garnered attention to the field, our understanding of the biology of these chimeric molecules is still emerging. Our aim within this review is to bring to light the mechanistic understanding of these multi-modular receptors and how these individual components confer particular properties to CAR-Ts. In addition, we will discuss extrinsic factors that can be manipulated to influence CAR-T performance such as choice of cellular population, culturing conditions and additional modifications that enhance their activity particularly in solid tumors. Finally, we will also consider the emerging toxicity associated with CAR-Ts. By breaking apart the CAR and examining the role of each piece, we can build a better functioning cellular vehicle for optimized treatment of cancer patients. PMID:26797495

Predicted coreceptor usage at end-stage HIV disease in tissues derived from subjects on antiretroviral therapy with an undetectable plasma viral load.

PubMed

Lamers, S L; Fogel, G B; Liu, E S; Nolan, D J; Salemi, M; Barbier, A E; Rose, R; Singer, E J; McGrath, M S

2017-07-01

HIV cure research is increasingly focused on anatomical tissues as sites for residual HIV replication during combined antiretroviral therapy (cART). Tissue-based HIV could contribute to low-level immune activation and viral rebound over the course of infection and could also influence the development of diseases, such as atherosclerosis, neurological disorders and cancers. cART-treated subjects have a decreased and irregular presence of HIV among tissues, which has resulted in a paucity of actual evidence concerning how or if HIV persists, replicates and evolves in various anatomical sites during therapy. In this study, we pooled 1806 HIV envelope V3 loop sequences from twenty-six tissue types (seventy-one total tissues) of six pre-cART subjects, four subjects with an unknown cART history who died with profound AIDS, and five subjects who died while on cART with an undetectable plasma viral load. A computational approach was used to assess sequences for their ability to utilize specific cellular coreceptors (R5, R5 and X4, or X4). We found that autopsied tissues obtained from virally suppressed cART+ subjects harbored both integrated and expressed viruses with similar coreceptor usage profiles to subjects with no or ineffective cART therapy (i.e., significant plasma viral load at death). The study suggests that tissue microenvironments provide a sanctuary for the continued evolution of HIV despite cART. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Tenofovir Disoproxil Fumarate on Incidence of Chronic Kidney Disease and Rate of Estimated Glomerular Filtration Rate Decrement in HIV-1-Infected Treatment-Naïve Asian Patients: Results from 12-Year Observational Cohort.

PubMed

Suzuki, Soichiro; Nishijima, Takeshi; Kawasaki, Yohei; Kurosawa, Takuma; Mutoh, Yoshikazu; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

2017-03-01

Little evidence is available for the incidence of chronic kidney disease (CKD) and rate of estimated glomerular filtration rate (eGFR) decrement among Asians with low body weight who are susceptible to tenofovir disoproxil fumarate (TDF) nephrotoxicity. In this 12-year observational cohort in Tokyo, we examined 1383 treatment-naïve HIV-1-infected Asians [720 started TDF-containing (TDF group) and 663 started non-TDF-containing (control) combination antiretroviral therapy (cART)]. The CKD incidence was calculated, and the effect of TDF use on CKD development was estimated using logistic regression. The eGFR slopes, before and after cART initiation, were estimated using mixed-effects linear spline models. Most patients were males (median weight, 62.6 kg; 83% started ritonavir-boosted protease inhibitors; median observation duration, 5.08 years). CKD developed in 150 patients (10.8%), with an incidence of 20.6 per 1000 person-years [confidence interval (95% CI), 17.6-24.2]. None developed end-stage renal disease. TDF use was associated with CKD [odds ratio (OR), 1.8; 95% CI, 1.00-3.13; p = 0.052]. The cumulative mean loss in the TDF group, relative to the control, increased over time after 1, 4, and 8 years of TDF exposure (-3.8, -5.5, and -9.0 mL/min/1.73 m 2 , respectively; p < 0.0001). The eGFR rapidly declined during the first 3 months of cART, particularly in the TDF group (-26.4 vs. -7.4 mL/min/1.73 m 2 /year in the control). In the TDF group, cART introduction was significantly associated with a faster rate of eGFR decline (from -0.44 to -2.11 mL/min/1.73 m 2 /year; p = 0.010), whereas in the control, the difference was not significant. For HIV-1-infected Asian patients with low body weight, TDF-containing cART is associated with CKD and faster eGFR declines.

CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: a multinational, multicohort European study.

PubMed

Wittkop, Linda; Arsandaux, Julie; Trevino, Ana; Schim van der Loeff, Maarten; Anderson, Jane; van Sighem, Ard; Böni, Jürg; Brun-Vezinet, Françoise; Soriano, Vicente; Boufassa, Faroudy; Brockmeyer, Norbert; Calmy, Alexandra; Dabis, François; Jarrin, Inma; Dorrucci, Maria; Duque, Vitor; Fätkenheuer, Gerd; Zangerle, Robert; Ferrer, Elena; Porter, Kholoud; Judd, Ali; Sipsas, Nikolaos V; Lambotte, Olivier; Shepherd, Leah; Leport, Catherine; Morrison, Charles; Mussini, Cristina; Obel, Niels; Ruelle, Jean; Schwarze-Zander, Carolyne; Sonnerborg, Anders; Teira, Ramon; Torti, Carlo; Valadas, Emilia; Colin, Celine; Friis-Møller, Nina; Costagliola, Dominique; Thiebaut, Rodolphe; Chene, Geneviève; Matheron, Sophie

2017-10-01

CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12 months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P = 0.0127) in HIV-2+ patients compared with HIV-1+ patients. A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Proportion and factors associated with recent HIV infection in a cohort of patients seen for care in Italy over 1996-2014: Data from the ICONA Foundation Study cohort.

PubMed

Nozza, Silvia; Cozzi-Lepri, Alessandro; Bai, Francesca; Rusconi, Stefano; Gori, Andrea; Cinque, Paola; Ammassari, Adriana; Caramello, Pietro; Tambussi, Giuseppe; D'Arminio Monforte, Antonella; Marchetti, Giulia

2017-01-01

In Italy the prevalence of recent HIV infection (RHI) isn't currently monitored. Early diagnosis is crucial to allow introduction of antiretroviral therapy (cART) in the recent phase of infection. We aimed to estimate the proportion and the determinants of RHI among patients enrolled in the ICONA cohort; we explored differences in the median time from HIV diagnosis to cART initiation and in the viro-immunological response between RHI and Less Recent HIV infections (NRHI). We included antiretroviral-naïve HIV-positive patients enrolled in the cohort with documented dates of HIV-negative and positive antibodies tests, grouped in RHI (estimated date of seroconversion within 12 months of enrolment) and NRHI. Proportion of RHI and the trend of this proportion by calendar period (1996-2014) were investigated (Chi-square test). Logistic regression analysis was employed to identify factors associated with RHI. The time from seroconversion to cART initiation was compared in RHI and NRHI overall and after stratification by calendar period (survival analysis). We finally explored the time from starting cART to HIV-RNA <50 copies/mL and to CD4+ gain ≥200 cells/mmc by Cox regression. HIV seroconversion could be estimated for 2608/12,616 patients: 981/2608 (37.6%) were RHI. Proportion of RHI increased in recent calendar periods and was associated with younger age, baseline higher HIV-RNA and CD4+ count. There wasn't difference in the 2-year estimates of cART start between RHI and NRHI, regardless of calendar period. Rates and hazards of virological response were similar in RHI versus NRHI. RHI showed a 1.5-fold higher probability of CD4+ gain, also following adjustment for calendar period and cART regimen, and for age, HCV and smoking; the difference in probability was however attenuated after further controlling for baseline HIV-RNA and CD4+ T-cells. The increased proportion of RHI over time suggests that in recent years in Italy HIV infections are more likely to be detected earlier than before. The similar rates of cART introduction and viro-immunological response in RHI and NRHI probably reflect the efficacy of the modern cART regimens. An improvement of the prevention services is warranted to allow an early cART access, also in the perspective of therapy as prevention.

Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts

PubMed Central

Cohen, Sophie; Innes, Steve; Geelen, Sibyl P. M.; Wells, Jonathan C. K.; Smit, Colette; Wolfs, Tom F. W.; van Eck-Smit, Berthe L. F.; Kuijpers, Taco W.; Reiss, Peter; Scherpbier, Henriette J.

2015-01-01

Objective Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment. Methods We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time. Results In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003). Conclusions Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally. PMID:26148119

Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts.

PubMed

Cohen, Sophie; Innes, Steve; Geelen, Sibyl P M; Wells, Jonathan C K; Smit, Colette; Wolfs, Tom F W; van Eck-Smit, Berthe L F; Kuijpers, Taco W; Reiss, Peter; Scherpbier, Henriette J; Pajkrt, Dasja; Bunders, Madeleine J

2015-01-01

Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment. We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time. In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003). Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.

Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells

PubMed Central

Sloan, Derek D.; Lam, Chia-Ying Kao; Irrinki, Alivelu; Liu, Liqin; Tsai, Angela; Pace, Craig S.; Kaur, Jasmine; Murry, Jeffrey P.; Balakrishnan, Mini; Moore, Paul A.; Johnson, Syd; Nordstrom, Jeffrey L.; Cihlar, Tomas; Koenig, Scott

2015-01-01

HIV reservoirs and production of viral antigens are not eliminated in chronically infected participants treated with combination antiretroviral therapy (cART). Novel therapeutic strategies aiming at viral reservoir elimination are needed to address chronic immune dysfunction and non-AIDS morbidities that exist despite effective cART. The HIV envelope protein (Env) is emerging as a highly specific viral target for therapeutic elimination of the persistent HIV-infected reservoirs via antibody-mediated cell killing. Dual-Affinity Re-Targeting (DART) molecules exhibit a distinct mechanism of action via binding the cell surface target antigen and simultaneously engaging CD3 on cytotoxic T lymphocytes (CTLs). We designed and evaluated Env-specific DARTs (HIVxCD3 DARTs) derived from known antibodies recognizing diverse Env epitopes with or without broadly neutralizing activity. HIVxCD3 DARTs derived from PGT121, PGT145, A32, and 7B2, but not VRC01 or 10E8 antibodies, mediated potent CTL-dependent killing of quiescent primary CD4 T cells infected with diverse HIV isolates. Similar killing activity was also observed with DARTs structurally modified for in vivo half-life extension. In an ex vivo model using cells isolated from HIV-infected participants on cART, combinations of the most potent HIVxCD3 DARTs reduced HIV expression both in quiescent and activated peripheral blood mononuclear cell cultures isolated from HIV-infected participants on suppressive cART. Importantly, HIVxCD3 DARTs did not induce cell-to-cell virus spread in resting or activated CD4 T cell cultures. Collectively, these results provide support for further development of HIVxCD3 DARTs as a promising therapeutic strategy for targeting HIV reservoirs. PMID:26539983

Effect of treatment course of comprehensive intervention with Traditional Chinese Medicine on mortality of acquired immunodeficiency syndrome patients treated with combined antiretroviral therapy.

PubMed

Guo, Huijun; Wang, Jian; Li, Zhengwei; Jiang, Ziqiang; Xu, Qianlei; Xu, Liran

2016-08-01

To investigate the effect of a treatment course of comprehensive intervention with Traditional Chinese Medicine (TCM) on the mortality of patients with acquired immunodeficiency syndrome (AIDS) treated with combined antiretroviral therapy (cART). AIDS patients who had taken cART in a national TCM human immunodeficiency virus treatment trial program (NTCMTP) before 2009 were enrolled in this study and followed for 36 months from November 2009. Patients enrolled in the NTCMTP in 2004 were taken as the first group, those enrolled in 2006 as the second group, and those enrolled in 2009 as the third group. Cumulative survival rates were calculated by the life table method. Survival curves for subgroups were compared by the log-rank test. Hazard ratios were calculated with a Cox proportional hazards model. A total of 1443 AIDS patients were followed for 3 years (4198 person-years). During this period, 91 (6.3%) patients died and 13 (0.9%) were lost to follow-up. The total mortality rate was 2.17/ 100 person-years. The mortality rate of patients enrolled in the NTCMTP in 2004 was 1.49/100 person- years, which was lower than that of patients enrolled in 2006 (2.23/100 person-years) and 2009 (3.48/100 person-years). After adjusting for other factors, a shorter time of treatment with TCM, male sex, older age, lower CD4 + T-cell counts, and long-term treatment with cART were risk factors of mortality. Long-term treatment with TCM decreased the mortality risk of AIDS patients. Factors such as being male, older age, CD4 + T-cell counts, and time of treatment with TCM and cART were correlated with mortality.

Cascade of care and factors associated with virological suppression among HIV-positive persons linked to care in the Test and Keep in Care (TAK) project.

PubMed

Kowalska, Justyna D; Ankiersztejn-Bartczak, Magdalena; Shepherd, Leah; Mocroft, Amanda

2018-05-21

Early treatment remains the most effective HIV prevention strategy; poor linkage to care after HIV diagnosis may compromise this benefit. We sought to better understand patient characteristics and their association with virological suppression (VS) following cART initiation. The TAK project collects pre-linkage to care and clinical data on patients diagnosed with HIV in voluntary testing facilities in central Poland. Data collected for persons diagnosed in 2010-2013 were linked with HIV clinic records. Individuals linked to care who commenced cART were followed from until the earliest of first VS (HIV RNA < 50 copies/ml), last visit, death or 6 January 2016. Cox-proportional hazard models were used to identify factors associated with first viral suppression. 232 persons were HIV positive, 144 (62%, 95% CI 55, 68%) linked to care, 116 (81% of those linked to care, 95% CI 73, 87%) started cART during follow up, of which 113 (97%, 95% CI 93, 99%) achieved VS. Non-PI based regimen (for integrase inhibitors aHR: 5.03: 1.90, 13.32) and HLA B5701-positive (aHR: 3.97: 1.33, 11.85) were associated with higher chance of VS. Unknown syphilis status (aHR: 0.27: 0.13, 0.57) and higher HIV RNA (aHR a tenfold increase: 0.56: 0.42, 0.75) remained associated with lower chance of VS. Although a low proportion of persons were linked to care, almost all those linked to care started cART and achieved rapid VS. The high rates of VS were irrespective of prior HIV-associated risk behaviours. Linkage to care remains the highest priority in prevention strategies in central Poland.

Adoptive immunotherapy for B-cell malignancies using CD19-targeted chimeric antigen receptor T-cells: A systematic review of efficacy and safety.

PubMed

Hao, Lu; Li, Tongtong; Chang, Lung-Ji; Chen, Xiaochuan

2017-08-01

Adoptive infusion of chimeric antigen receptor transduced T-cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results. In this report, we performed a meta-analysis to evaluate the efficacy and side effects of CAR-T on relapsed B-cell malignancies, including leukemia and lymphoma. Clinical studies investigating efficacy and safety of CAR-T in acute and chronic lymphocytic leukemia and lymphoma were identified by searching PubMed and EMBASE. Outcomes of efficacy subjected to analysis were the rates of complete remission (CR) and partial remission (PR). The safety parameters were the prevalence of adverse effects including fever, hypotension, and acute renal failure. Meta analyses were performed using R software. Weighted hazard ratio (HR) with 95% confidence intervals was calculated for each outcome. Fixed or random-effects models were employed depending on the heterogeneity across the included studies. Nineteen published clinical studies, with a total of 391 patients were included for the meta-analysis. The pooled rate of complete remission was 55% (95% CI 41%-69%); the pooled rate of partial remission was 25% (95% CI: 19%-33%). The prevalence of fever was 62% (95% CI: 41%-79%); the hypotension was 22% (95% CI: 15%-31%); acute renal failure was 24% (95% CI: 16%-34%). All adverse effects were manageable and no death was reported due to toxicity. CD19-targeted CAR-T is an effective modality in treating refractory B-cell malignancies including acute and chronic lymphatic leukemia, Hodjkin's and non-Hodjkin's lymphoma. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A comparison of virological suppression and rebound between Indigenous and non-Indigenous persons initiating combination antiretroviral therapy in a multisite cohort of individuals living with HIV in Canada.

PubMed

Benoit, Anita C; Younger, Jaime; Beaver, Kerrigan; Jackson, Randy; Loutfy, Mona; Masching, Renée; Nobis, Tony; Nowgesic, Earl; O'Brien-Teengs, Doe; Whitebird, Wanda; Zoccole, Art; Hull, Mark; Jaworsky, Denise; Rachlis, Anita; Rourke, Sean; Burchell, Ann N; Cooper, Curtis; Hogg, Robert; Klein, Marina B; Machouf, Nima; Montaner, Julio; Tsoukas, Chris; Raboud, Janet

2017-01-01

This study compared time to virological suppression and rebound between Indigenous and non-Indigenous individuals living with HIV in Canada initiating combination antiretroviral therapy (cART). Data were from the Canadian Observational Cohort collaboration; eight studies of treatment-naive persons with HIV initiating cART after 1/1/2000. Fine and Gray models were used to estimate the effect of ethnicity on time to virological suppression (two consecutive viral loads [VLs] <50 copies/ml at least 3 months apart) after adjusting for the competing risk of death and time until virological rebound (two consecutive VLs >200 copies/ml at least 3 months apart) following suppression. Among 7,080 participants were 497 Indigenous persons of whom 413 (83%) were from British Columbia. The cumulative incidence of suppression 1 year after cART initiation was 54% for Indigenous persons, 77% for Caucasian and 80% for African, Caribbean or Black (ACB) persons. The cumulative incidence of rebound 1 year after suppression was 13% for Indigenous persons, 6% for Caucasian and 7% for ACB persons. Indigenous persons were less likely to achieve suppression than Caucasian participants (aHR=0.58, 95% CI 0.50, 0.68), but not more likely to experience rebound (aHR=1.03, 95% CI 0.84, 1.27) after adjusting for age, gender, injection drug use, men having sex with men status, province of residence, baseline VL and CD4 + T-cell count, antiretroviral class and year of cART initiation. Lower suppression rates among Indigenous persons suggest a need for targeted interventions to improve HIV health outcomes during the first year of treatment when suppression is usually achieved.

Preconceptional folic acid-containing supplement use in the National Birth Defects Prevention Study.

PubMed

Khodr, Zeina G; Lupo, Philip J; Agopian, A J; Canfield, Mark A; Case, Amy P; Carmichael, Suzan L; Mitchell, Laura E

2014-06-01

Despite public health campaigns encouraging women to take a daily folic acid supplement, the proportion of reproductive age women, in the United States, who comply with this recommendation is less than optimal. The objective of this analysis was to identify predictors of preconceptional folic acid-containing supplement use to define subgroups of women who may benefit from targeted folic acid campaigns. This study included 6570 mothers of live born infants from the control population of National Birth Defects Prevention Study (1997-2005). Logistic regression analyses were used to identify predictors of preconceptional folic acid supplementation. A classification and regression tree (CART) analysis was used to define subgroups of women with different patterns of preconceptional folic acid supplementation. Race/ethnicity, education, age at delivery, nativity, employment, income, number of dependents, smoking, and birth control use were significantly associated with preconceptional folic acid-containing supplement use. Based on a CART analysis, education, race/ethnicity, and age were the most distinguishing factors between women with different preconceptional supplementation patterns. Non-white women with <4 years of a college education were the least likely to use folic acid-containing supplements (11%). However, even in the most compliant subgroup (women with ≥4 years of college), only 60% of women supplemented with folic acid. These results demonstrate the need for continued efforts to increase folic acid supplementation among all reproductive aged women. However, the success of such efforts may be improved if maternal characteristics such as education, race/ethnicity, and age, are considered in the development of future interventions. © 2014 Wiley Periodicals, Inc.

Hydrologic classification of rivers based on cluster analysis of dimensionless hydrologic signatures: Applications for environmental instream flows

NASA Astrophysics Data System (ADS)

Praskievicz, S. J.; Luo, C.

2017-12-01

Classification of rivers is useful for a variety of purposes, such as generating and testing hypotheses about watershed controls on hydrology, predicting hydrologic variables for ungaged rivers, and setting goals for river management. In this research, we present a bottom-up (based on machine learning) river classification designed to investigate the underlying physical processes governing rivers' hydrologic regimes. The classification was developed for the entire state of Alabama, based on 248 United States Geological Survey (USGS) stream gages that met criteria for length and completeness of records. Five dimensionless hydrologic signatures were derived for each gage: slope of the flow duration curve (indicator of flow variability), baseflow index (ratio of baseflow to average streamflow), rising limb density (number of rising limbs per unit time), runoff ratio (ratio of long-term average streamflow to long-term average precipitation), and streamflow elasticity (sensitivity of streamflow to precipitation). We used a Bayesian clustering algorithm to classify the gages, based on the five hydrologic signatures, into distinct hydrologic regimes. We then used classification and regression trees (CART) to predict each gaged river's membership in different hydrologic regimes based on climatic and watershed variables. Using existing geospatial data, we applied the CART analysis to classify ungaged streams in Alabama, with the National Hydrography Dataset Plus (NHDPlus) catchment (average area 3 km2) as the unit of classification. The results of the classification can be used for meeting management and conservation objectives in Alabama, such as developing statewide standards for environmental instream flows. Such hydrologic classification approaches are promising for contributing to process-based understanding of river systems.

Multiple Food-Animal-Borne Route in Transmission of Antibiotic-Resistant Salmonella Newport to Humans

PubMed Central

Pan, Hang; Paudyal, Narayan; Li, Xiaoliang; Fang, Weihuan; Yue, Min

2018-01-01

Characterization of transmission routes of Salmonella among various food-animal reservoirs and their antibiogram is crucial for appropriate intervention and medical treatment. Here, we analyzed 3728 Salmonella enterica serovar Newport (S. Newport) isolates collected from various food-animals, retail meats and humans in the United States between 1996 and 2015, based on their minimum inhibitory concentration (MIC) toward 27 antibiotics. Random Forest and Hierarchical Clustering statistic was used to group the isolates according to their MICs. Classification and Regression Tree (CART) analysis was used to identify the appropriate antibiotic and its cut-off value between human- and animal-population. Two distinct populations were revealed based on the MICs of individual strain by both methods, with the animal population having significantly higher MICs which correlates to antibiotic-resistance (AR) phenotype. Only ∼9.7% (267/2763) human isolates could be attributed to food–animal origins. Furthermore, the isolates of animal origin had less diverse antibiogram than human isolates (P < 0.001), suggesting multiple sources involved in human infections. CART identified trimethoprim-sulfamethoxazole to be the best classifier for differentiating the animal and human isolates. Additionally, two typical AR patterns, MDR-Amp and Tet-SDR dominant in bovine- or turkey-population, were identified, indicating that distinct food-animal sources could be involved in human infections. The AR analysis suggested fluoroquinolones (i.e., ciprofloxacin), but not extended-spectrum cephalosporins (i.e., ceftriaxone, cefoxitin), is the adaptive choice for empirical therapy. Antibiotic-resistant S. Newport from humans has multiple origins, with distinct food-animal-borne route contributing to a significant proportion of heterogeneous isolates. PMID:29410657

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia.

PubMed

Cai, Bo; Guo, Mei; Wang, Yao; Zhang, Yajing; Yang, Jun; Guo, Yelei; Dai, Hanren; Yu, Changlin; Sun, Qiyun; Qiao, Jianhui; Hu, Kaixun; Zuo, Hongli; Dong, Zheng; Zhang, Zechuan; Feng, Mingxing; Li, Bingxia; Sun, Yujing; Liu, Tieqiang; Liu, Zhiqing; Wang, Yi; Huang, Yajing; Yao, Bo; Han, Weidong; Ai, Huisheng

2016-11-25

Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT02799550.

Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T-lymphocytes

PubMed Central

Caruana, Ignazio; Savoldo, Barbara; Hoyos, Valentina; Weber, Gerrit; Liu, Hao; Kim, Eugene S.; Ittmann, Michael M.; Marchetti, Dario; Dotti, Gianpietro

2015-01-01

Adoptive transfer of chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR-T cells) has had less striking effects in solid tumors1–3 than in lymphoid malignancies4, 5. Although active tumor-mediated immunosuppression may play a role in limiting efficacy6, functional changes in T lymphocytes following their ex vivo manipulation may also account for cultured CAR-T cells’ reduced ability to penetrate stroma-rich solid tumors. We therefore studied the capacity of human in vitro-cultured CAR-T cells to degrade components of the extracellular matrix (ECM). In contrast to freshly isolated T lymphocytes, we found that in vitro-cultured T lymphocytes lack expression of the enzyme heparanase (HPSE) that degrades heparan sulphate proteoglycans, which are main components of ECM. We found that HPSE mRNA is down regulated in in vitro-expanded T cells, which may be a consequence of p53 binding to the HPSE gene promoter. We therefore engineered CAR-T cells to express HPSE and showed improved capacity to degrade ECM, which promoted tumor T-cell infiltration and antitumor activity. Employing this strategy may enhance the activity of CAR-T cells in individuals with stroma-rich solid tumors. PMID:25849134

Application of a water quality model in the White Cart water catchment, Glasgow, UK.

PubMed

Liu, S; Tucker, P; Mansell, M; Hursthouse, A

2003-03-01

Water quality models of urban systems have previously focused on point source (sewerage system) inputs. Little attention has been given to diffuse inputs and research into diffuse pollution has been largely confined to agriculture sources. This paper reports on new research that is aimed at integrating diffuse inputs into an urban water quality model. An integrated model is introduced that is made up of four modules: hydrology, contaminant point sources, nutrient cycling and leaching. The hydrology module, T&T consists of a TOPMODEL (a TOPography-based hydrological MODEL), which simulates runoff from pervious areas and a two-tank model, which simulates runoff from impervious urban areas. Linked into the two-tank model, the contaminant point source module simulates the overflow from the sewerage system in heavy rain. The widely known SOILN (SOIL Nitrate model) is the basis of nitrogen cycle module. Finally, the leaching module consists of two functions: the production function and the transfer function. The production function is based on SLIM (Solute Leaching Intermediate Model) while the transfer function is based on the 'flushing hypothesis' which postulates a relationship between contaminant concentrations in the receiving water course and the extent to which the catchment is saturated. This paper outlines the modelling methodology and the model structures that have been developed. An application of this model in the White Cart catchment (Glasgow) is also included.

Dealing with deep uncertainties in landslide modelling for disaster risk reduction under climate change

NASA Astrophysics Data System (ADS)

Almeida, Susana; Holcombe, Elizabeth Ann; Pianosi, Francesca; Wagener, Thorsten

2017-02-01

Landslides have large negative economic and societal impacts, including loss of life and damage to infrastructure. Slope stability assessment is a vital tool for landslide risk management, but high levels of uncertainty often challenge its usefulness. Uncertainties are associated with the numerical model used to assess slope stability and its parameters, with the data characterizing the geometric, geotechnic and hydrologic properties of the slope, and with hazard triggers (e.g. rainfall). Uncertainties associated with many of these factors are also likely to be exacerbated further by future climatic and socio-economic changes, such as increased urbanization and resultant land use change. In this study, we illustrate how numerical models can be used to explore the uncertain factors that influence potential future landslide hazard using a bottom-up strategy. Specifically, we link the Combined Hydrology And Stability Model (CHASM) with sensitivity analysis and Classification And Regression Trees (CART) to identify critical thresholds in slope properties and climatic (rainfall) drivers that lead to slope failure. We apply our approach to a slope in the Caribbean, an area that is naturally susceptible to landslides due to a combination of high rainfall rates, steep slopes, and highly weathered residual soils. For this particular slope, we find that uncertainties regarding some slope properties (namely thickness and effective cohesion of topsoil) are as important as the uncertainties related to future rainfall conditions. Furthermore, we show that 89 % of the expected behaviour of the studied slope can be characterized based on only two variables - the ratio of topsoil thickness to cohesion and the ratio of rainfall intensity to duration.

The GRACE Checklist: A Validated Assessment Tool for High Quality Observational Studies of Comparative Effectiveness.

PubMed

Dreyer, Nancy A; Bryant, Allison; Velentgas, Priscilla

2016-10-01

Recognizing the growing need for robust evidence about treatment effectiveness in real-world populations, the Good Research for Comparative Effectiveness (GRACE) guidelines have been developed for noninterventional studies of comparative effectiveness to determine which studies are sufficiently rigorous to be reliable enough for use in health technology assessments. To evaluate which aspects of the GRACE Checklist contribute most strongly to recognition of quality. We assembled 28 observational comparative effectiveness articles published from 2001 to 2010 that compared treatment effectiveness and/or safety of drugs, medical devices, and medical procedures. Twenty-two volunteers from academia, pharmaceutical companies, and government agencies applied the GRACE Checklist to those articles, providing 56 assessments. Ten senior academic and industry experts provided assessments of overall article quality for the purpose of decision support. We also rated each article based on the number of annual citations and impact factor of the journal in which the article was published. To identify checklist items that were most predictive of quality, classification and regression tree (CART) analysis, a binary, recursive, partitioning methodology, was used to create 3 decision trees, which compared the 56 article assessments with 3 external quality outcomes: (1) expert assessment of overall quality, (2) citation frequency, and (3) impact factor. A fourth tree looked at the composite outcome of all 3 quality indicators. The best predictors of quality included the following: use of concurrent comparators, limiting the study to new initiators of the study drug, equivalent measurement of outcomes in study groups, collecting data on most if not all known confounders or effect modifiers, accounting for immortal time bias in the analysis, and use of sensitivity analyses to test how much effect estimates depended on various assumptions. Only sensitivity analyses appeared consistently as a predictor of quality in all 4 trees. When a composite outcome of the 3 quality measures was used, the GRACE Checklist showed high sensitivity and specificity (71.43% and 80.95%, respectively). The GRACE Checklist stands out from other consensus-driven and expert guidance documents because of its extensive validation efforts. This most recent work shows that the checklist has strong sensitivity and specificity, increasing its utility as a screening tool to identify high-quality observational comparative effectiveness research worthy of in-depth review and applicability for decision support. No outside funding supported this research. All authors are full-time employees of Quintiles, which provides research and consulting services to the biopharmaceutical industry. The authors have no other disclosures to report. Two of the 3 CART trees were presented at the International Society of Pharmacepidemiology in 2015 ("Article Citations per Year" and "Journal Impact Factor"). The original validation study was published in the March 2014 issue of the Journal of Managed Care & Specialty Pharmacy. The checklist questions and scoring were included using a table that was originally published by this journal in 2014. Study concept and design were primarily contributed by Dreyer and Velentgas, along with Bryant. Bryant took the lead in data collection and analysis, along with Dreyer and Velentgas, and data interpretation was performed by Dreyer, Velentgas, and Bryant. The manuscript was written and revised primarily by Dreyer, along with Bryant and Velentgas.

Apparatus for microbiological sampling. [including automatic swabbing

NASA Technical Reports Server (NTRS)

Wilkins, J. R.; Mills, S. M. (Inventor)

1974-01-01

An automatic apparatus is described for microbiologically sampling surface using a cotton swab which eliminates human error. The apparatus includes a self-powered transport device, such as a motor-driven wheeled cart, which mounts a swabbing motor drive for a crank arm which supports a swab in the free end thereof. The swabbing motor is pivotably mounted and an actuator rod movable responsive to the cart traveling a predetermined distance provides lifting of the swab from the surface being sampled and reversal of the direction of travel of the cart.

Short-Term High-Fat Diet Increases Leptin Activation of CART Neurons and Advances Puberty in Female Mice.

PubMed

Venancio, Jade Cabestre; Margatho, Lisandra Oliveira; Rorato, Rodrigo; Rosales, Roberta Ribeiro Costa; Debarba, Lucas Kniess; Coletti, Ricardo; Antunes-Rodrigues, Jose; Elias, Carol F; Elias, Lucila Leico K

2017-11-01

Leptin is a permissive factor for puberty initiation, participating as a metabolic cue in the activation of the kisspeptin (Kiss1)-gonadotropin-releasing hormone neuronal circuitry; however, it has no direct effect on Kiss1 neurons. Leptin acts on hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons, participating in the regulation of energy homeostasis. We investigated the influence of a short-term high-fat diet (HFD) on the effect of leptin on puberty timing. Kiss1-hrGFP female mice received a HFD or regular diet (RD) after weaning at postnatal day (PN)21 and were studied at PN28 and PN32. The HFD increased body weight and plasma leptin concentrations and decreased the age at vaginal opening (HFD, 32 ± 0.53 days; RD, 38 ± 0.67 days). Similar colocalization of neurokinin B and dynorphin in Kiss1-hrGFP neurons of the arcuate nucleus (ARC) was observed between the HFD and RD groups. The HFD increased CART expression in the ARC and Kiss1 messenger RNA expression in the anteroventral periventricular (AVPV)/anterior periventricular (Pe). The HFD also increased the number of ARC CART neurons expressing leptin-induced phosphorylated STAT3 (signal transducer and activator of transcription 3) at PN32. Close apposition of CART fibers to Kiss1-hrGFP neurons was observed in the ARC of both RD- and HFD-fed mice. In conclusion, these data reinforce the notion that a HFD increases kisspeptin expression in the AVPV/Pe and advances puberty initiation. Furthermore, we have demonstrated that the HFD-induced earlier puberty is associated with an increase in CART expression in the ARC. Therefore, these data indicate that CART neurons in the ARC can mediate the effect of leptin on Kiss1 neurons in early puberty induced by a HFD. Copyright © 2017 Endocrine Society.

Hypothalamic interactions between neuropeptide Y, agouti-related protein, cocaine- and amphetamine-regulated transcript and alpha-melanocyte-stimulating hormone in vitro in male rats.

PubMed

Dhillo, W S; Small, C J; Stanley, S A; Jethwa, P H; Seal, L J; Murphy, K G; Ghatei, M A; Bloom, S R

2002-09-01

A number of neuropeptides implicated in the hypothalamic regulation of appetite are synthesized in the arcuate nucleus (Arc). Neuropeptide Y (NPY) and agouti-related protein (Agrp) are orexigenic. The pro-opiomelanocortin (POMC) product alpha-melanocyte-stimulating hormone (alpha-MSH) is anorectic. Intracerebroventricular administration of cocaine- and amphetamine-regulated transcript (CART) decreases food intake. However, recent results show that CART is orexigenic when injected into discrete hypothalamic nuclei. There is almost complete coexpression of NPY and Agrp mRNA in Arc neurones, and the majority of CART-containing neurones in the Arc also contain POMC mRNA. We investigated possible interactions between these neuropeptides in vitro using a rat hypothalamic explant system. Administration of 1, 10 and 100 nm of NPY to hypothalamic explants significantly increased release of Agrp(83-132)-immunoreactivity (IR). NPY (10 and 100 nm) significantly increased the release of CART(55-102)-IR and alpha-MSH-IR from hypothalamic explants. Agrp(83-132) (10 nm) administered to hypothalamic explants significantly increased the release of NPY-IR. Agrp(83-132) (10 and 100 nm) significantly decreased the release of CART(55-102)-IR from hypothalamic explants. Administration of 1, 10 and 100 nm CART(55-102) to hypothalamic explants resulted in a significant increase in NPY-IR release. Administration of 10 nm CART(55-102) to hypothalamic explants significantly increased the release of Agrp(83-132)-IR. NDP-MSH (10 nm) administered to hypothalamic explants significantly increased the release of NPY-IR. NDP-MSH (10 and 100 nm) significantly increased the release of Agrp(83-132)-IR from hypothalamic explants. These data suggest that orexigenic neuropeptides in the arcuate nucleus stimulate the release of each other, perhaps reinforcing orexigenic behaviour via a positive-feedback loop. Our results are also in keeping with the possibility that the melanocortin-3 receptor in the arcuate nucleus may influence the release of arcuate neuropeptides.