Web-Based Versus Conventional Training for Medical Students on Infant Gross Motor Screening.

PubMed

Pusponegoro, Hardiono D; Soebadi, Amanda; Surya, Raymond

2015-12-01

Early detection of developmental abnormalities is important for early intervention. A simple screening method is needed for use by general practitioners, as is an effective and efficient training method. This study aims to evaluate the effectiveness, acceptability, and usability of Web-based training for medical students on a simple gross motor screening method in infants. Fifth-year medical students at University of Indonesia in Jakarta were randomized into two groups. A Web-based training group received online video modules, discussions, and assessments (at www.schoology.com ). A conventional training group received a 1-day live training using the same module. Both groups completed identical pre- and posttests and the User Satisfaction Questionnaire (USQ). The Web-based group also completed the System Usability Scale (SUS). The module was based on a gross motor screening method used in the World Health Organization Multicentre Growth Reference Study. There were 39 and 32 subjects in the Web-based and conventional groups, respectively. Mean pretest versus posttest scores (correct answers out of 20) were 9.05 versus 16.95 (p=0.0001) in the Web-based group and 9.31 versus 16.88 (p=0.0001) in the conventional group. Mean difference between pre- and posttest scores did not differ significantly between the Web-based and conventional groups (mean [standard deviation], 7.56 [3.252] versus 7.90 [5.170]; p=0.741]. Both training methods were acceptable based on USQ scores. Based on SUS scores, the Web-based training had good usability. Web-based training is an effective, efficient, and acceptable training method for medical students on simple infant gross motor screening and is as effective as conventional training.

Diabetic retinopathy screening: global and local perspective.

PubMed

Gangwani, R A; Lian, J X; McGhee, S M; Wong, D; Li, K Kw

2016-10-01

Diabetes mellitus has become a global epidemic. It causes significant macrovascular complications such as coronary artery disease, peripheral artery disease, and stroke; as well as microvascular complications such as retinopathy, nephropathy, and neuropathy. Diabetic retinopathy is known to be the leading cause of blindness in the working-age population and may be asymptomatic until vision loss occurs. Screening for diabetic retinopathy has been shown to reduce blindness by timely detection and effective laser treatment. Diabetic retinopathy screening is being done worldwide either as a national screening programme or hospital-based project or as a community-based screening programme. In this article, we review different methods of screening including grading used to detect the severity of sight-threatening retinopathy and the newer screening methods. This review also includes the method of systematic screening being carried out in Hong Kong, a system that has helped to identify diabetic retinopathy among all attendees in public primary care clinics using a Hong Kong-wide public patients' database.

Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening

PubMed Central

Kuo, Ming-Jeng; Chen, Hsiu-Hsi; Chen, Chi-Ling; Fann, Jean Ching-Yuan; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Lin, Yu-Min; Liao, Chao-Sheng; Chang, Hung-Chuen; Lin, Yueh-Shih; Yen, Amy Ming-Fang

2016-01-01

AIM: To assess the cost-effectiveness of two population-based hepatocellular carcinoma (HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography (AUS). METHODS: In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The results show that the mass screening using AUS was associated with an incremental cost-effectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening. CONCLUSION: Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval. PMID:27022228

Preferences for Mental Health Screening Among Pregnant Women: A Cross-Sectional Study.

PubMed

Kingston, Dawn E; Biringer, Anne; McDonald, Sheila W; Heaman, Maureen I; Lasiuk, Gerri C; Hegadoren, Kathy M; McDonald, Sarah D; Veldhuyzen van Zanten, Sander; Sword, Wendy; Kingston, Joshua J; Jarema, Karly M; Vermeyden, Lydia; Austin, Marie-Paule

2015-10-01

The process of mental health screening can influence disclosure, uptake of referral, and treatment; however, no studies have explored pregnant women's views of methods of mental health screening. The objectives of this study are to determine pregnant women's comfort and preferences regarding mental health screening. Pregnant women were recruited (May-December 2013) for this cross-sectional descriptive survey from prenatal classes and maternity clinics in Alberta, Canada, if they were aged >16 years and spoke/read English. Descriptive statistics summarized acceptability of screening, and multivariable logistic regression identified factors associated with women's comfort with screening methods. Analysis was conducted in January-December 2014. The participation rate was 92% (N=460/500). Overall, 97.6% of women reported that they were very (74.8%) or somewhat (22.8%) comfortable with mental health screening in pregnancy. Women were most comfortable with completing paper- (>90%) and computer-based (>82%) screening in a clinic or at home, with fewest reporting comfort with telephone-based screening (62%). The majority of women were very/somewhat comfortable with provider-initiated (97.4%) versus self-initiated (68.7%) approaches. Women's ability to be honest with their provider about emotional health was most strongly associated with comfort with each method of screening. The majority of pregnant women viewed prenatal mental health screening favorably and were comfortable with a variety of screening methods. These findings provide evidence of high acceptability of screening--a key criterion for implementation of universal screening--and suggest that providers can select from a variety of screening methods best suited for their clinical setting. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Experimental cocrystal screening and solution based scale-up cocrystallization methods.

PubMed

Malamatari, Maria; Ross, Steven A; Douroumis, Dennis; Velaga, Sitaram P

2017-08-01

Cocrystals are crystalline single phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio which are neither solvates nor simple salts. If one of the components is an active pharmaceutical ingredient (API), the term pharmaceutical cocrystal is often used. There is a growing interest among drug development scientists in exploring cocrystals, as means to address physicochemical, biopharmaceutical and mechanical properties and expand solid form diversity of the API. Conventionally, coformers are selected based on crystal engineering principles, and the equimolar mixtures of API and coformers are subjected to solution-based crystallization that are commonly employed in polymorph and salt screening. However, the availability of new knowledge on cocrystal phase behaviour in solid state and solutions has spurred the development and implementation of more rational experimental cocrystal screening as well as scale-up methods. This review aims to provide overview of commonly employed solid form screening techniques in drug development with an emphasis on cocrystal screening methodologies. The latest developments in understanding and the use of cocrystal phase diagrams in both screening and solution based scale-up methods are also presented. Final section is devoted to reviewing the state of the art research covering solution based scale-up cocrystallization process for different cocrystals besides more recent continuous crystallization methods. Copyright © 2017 Elsevier B.V. All rights reserved.

A Monte-Carlo method which is not based on Markov chain algorithm, used to study electrostatic screening of ion potential

NASA Astrophysics Data System (ADS)

Šantić, Branko; Gracin, Davor

2017-12-01

A new simple Monte Carlo method is introduced for the study of electrostatic screening by surrounding ions. The proposed method is not based on the generally used Markov chain method for sample generation. Each sample is pristine and there is no correlation with other samples. As the main novelty, the pairs of ions are gradually added to a sample provided that the energy of each ion is within the boundaries determined by the temperature and the size of ions. The proposed method provides reliable results, as demonstrated by the screening of ion in plasma and in water.

Three-dimensional compound comparison methods and their application in drug discovery.

PubMed

Shin, Woong-Hee; Zhu, Xiaolei; Bures, Mark Gregory; Kihara, Daisuke

2015-07-16

Virtual screening has been widely used in the drug discovery process. Ligand-based virtual screening (LBVS) methods compare a library of compounds with a known active ligand. Two notable advantages of LBVS methods are that they do not require structural information of a target receptor and that they are faster than structure-based methods. LBVS methods can be classified based on the complexity of ligand structure information utilized: one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D). Unlike 1D and 2D methods, 3D methods can have enhanced performance since they treat the conformational flexibility of compounds. In this paper, a number of 3D methods will be reviewed. In addition, four representative 3D methods were benchmarked to understand their performance in virtual screening. Specifically, we tested overall performance in key aspects including the ability to find dissimilar active compounds, and computational speed.

Inhibition of Retinoblastoma Protein Inactivation

DTIC Science & Technology

2016-09-01

Retinoblastoma protein, E2F transcription factor, high throughput screen, drug discovery, x-ray crystallography 16. SECURITY CLASSIFICATION OF: 17...developed a method to perform fragment based screening by x-ray crystallography . 2.0 KEYWORDS Retinoblastoma (Rb) pathway, E2F transcription factor...cancer, cell-cycle inhibition, activation, modulation, inhibition, high throughput screening, fragment-based screening, x-ray crystallography

Terbium-sensitized luminescence screening method for fluoroquinolones in beef serum

USDA-ARS?s Scientific Manuscript database

Enrofloxacin is one of only two fluoroquinolone antibiotics approved for use in cattle in the U.S. Microbial screening methods commonly used for monitoring veterinary drug residues are not sensitive or selective for fluoroquinolones. In this work, a luminescence-based screening assay was developed...

Hierarchical screening for multiple mental disorders.

PubMed

Batterham, Philip J; Calear, Alison L; Sunderland, Matthew; Carragher, Natacha; Christensen, Helen; Mackinnon, Andrew J

2013-10-01

There is a need for brief, accurate screening when assessing multiple mental disorders. Two-stage hierarchical screening, consisting of brief pre-screening followed by a battery of disorder-specific scales for those who meet diagnostic criteria, may increase the efficiency of screening without sacrificing precision. This study tested whether more efficient screening could be gained using two-stage hierarchical screening than by administering multiple separate tests. Two Australian adult samples (N=1990) with high rates of psychopathology were recruited using Facebook advertising to examine four methods of hierarchical screening for four mental disorders: major depressive disorder, generalised anxiety disorder, panic disorder and social phobia. Using K6 scores to determine whether full screening was required did not increase screening efficiency. However, pre-screening based on two decision tree approaches or item gating led to considerable reductions in the mean number of items presented per disorder screened, with estimated item reductions of up to 54%. The sensitivity of these hierarchical methods approached 100% relative to the full screening battery. Further testing of the hierarchical screening approach based on clinical criteria and in other samples is warranted. The results demonstrate that a two-phase hierarchical approach to screening multiple mental disorders leads to considerable increases efficiency gains without reducing accuracy. Screening programs should take advantage of prescreeners based on gating items or decision trees to reduce the burden on respondents. © 2013 Elsevier B.V. All rights reserved.

Using iterative cluster merging with improved gap statistics to perform online phenotype discovery in the context of high-throughput RNAi screens

PubMed Central

Yin, Zheng; Zhou, Xiaobo; Bakal, Chris; Li, Fuhai; Sun, Youxian; Perrimon, Norbert; Wong, Stephen TC

2008-01-01

Background The recent emergence of high-throughput automated image acquisition technologies has forever changed how cell biologists collect and analyze data. Historically, the interpretation of cellular phenotypes in different experimental conditions has been dependent upon the expert opinions of well-trained biologists. Such qualitative analysis is particularly effective in detecting subtle, but important, deviations in phenotypes. However, while the rapid and continuing development of automated microscope-based technologies now facilitates the acquisition of trillions of cells in thousands of diverse experimental conditions, such as in the context of RNA interference (RNAi) or small-molecule screens, the massive size of these datasets precludes human analysis. Thus, the development of automated methods which aim to identify novel and biological relevant phenotypes online is one of the major challenges in high-throughput image-based screening. Ideally, phenotype discovery methods should be designed to utilize prior/existing information and tackle three challenging tasks, i.e. restoring pre-defined biological meaningful phenotypes, differentiating novel phenotypes from known ones and clarifying novel phenotypes from each other. Arbitrarily extracted information causes biased analysis, while combining the complete existing datasets with each new image is intractable in high-throughput screens. Results Here we present the design and implementation of a novel and robust online phenotype discovery method with broad applicability that can be used in diverse experimental contexts, especially high-throughput RNAi screens. This method features phenotype modelling and iterative cluster merging using improved gap statistics. A Gaussian Mixture Model (GMM) is employed to estimate the distribution of each existing phenotype, and then used as reference distribution in gap statistics. This method is broadly applicable to a number of different types of image-based datasets derived from a wide spectrum of experimental conditions and is suitable to adaptively process new images which are continuously added to existing datasets. Validations were carried out on different dataset, including published RNAi screening using Drosophila embryos [Additional files 1, 2], dataset for cell cycle phase identification using HeLa cells [Additional files 1, 3, 4] and synthetic dataset using polygons, our methods tackled three aforementioned tasks effectively with an accuracy range of 85%–90%. When our method is implemented in the context of a Drosophila genome-scale RNAi image-based screening of cultured cells aimed to identifying the contribution of individual genes towards the regulation of cell-shape, it efficiently discovers meaningful new phenotypes and provides novel biological insight. We also propose a two-step procedure to modify the novelty detection method based on one-class SVM, so that it can be used to online phenotype discovery. In different conditions, we compared the SVM based method with our method using various datasets and our methods consistently outperformed SVM based method in at least two of three tasks by 2% to 5%. These results demonstrate that our methods can be used to better identify novel phenotypes in image-based datasets from a wide range of conditions and organisms. Conclusion We demonstrate that our method can detect various novel phenotypes effectively in complex datasets. Experiment results also validate that our method performs consistently under different order of image input, variation of starting conditions including the number and composition of existing phenotypes, and dataset from different screens. In our findings, the proposed method is suitable for online phenotype discovery in diverse high-throughput image-based genetic and chemical screens. PMID:18534020

Probe molecules (PrM) approach in adverse outcome pathway (AOP) based high throughput screening (HTS): in vivo discovery for developing in vitro target methods

EPA Science Inventory

Efficient and accurate adverse outcome pathway (AOP) based high-throughput screening (HTS) methods use a systems biology based approach to computationally model in vitro cellular and molecular data for rapid chemical prioritization; however, not all HTS assays are grounded by rel...

SELEX-Based Screening of Exosome-Tropic RNA.

PubMed

Yamashita, Takuma; Shinotsuka, Haruka; Takahashi, Yuki; Kato, Kana; Nishikawa, Makiya; Takakura, Yoshinobu

2017-01-01

Cell-derived nanosized vesicles or exosomes are expected to become delivery carriers for functional RNAs, such as small interfering RNA (siRNA). A method to efficiently load functional RNAs into exosomes is required for the development of exosome-based delivery carriers of functional RNAs. However, there is no method to find exosome-tropic exogenous RNA sequences. In this study, we used a systematic evolution of ligands by exponential enrichment (SELEX) method to screen exosome-tropic RNAs that can be used to load functional RNAs into exosomes by conjugation. Pooled single stranded 80-base RNAs, each of which contains a randomized 40-base sequence, were transfected into B16-BL6 murine melanoma cells and exosomes were collected from the cells. RNAs extracted from the exosomes were subjected to next round of SELEX. Cloning and sequencing of RNAs in SELEX-screened RNA pools showed that 29 of 56 clones had a typical RNA sequence. The sequence found by SELEX was enriched in exosomes after transfection to B16-BL6 cells. The results show that the SELEX-based method can be used for screening of exosome-tropic RNAs.

Enrichment assessment of multiple virtual screening strategies for Toll-like receptor 8 agonists based on a maximal unbiased benchmarking data set.

PubMed

Pei, Fen; Jin, Hongwei; Zhou, Xin; Xia, Jie; Sun, Lidan; Liu, Zhenming; Zhang, Liangren

2015-11-01

Toll-like receptor 8 agonists, which activate adaptive immune responses by inducing robust production of T-helper 1-polarizing cytokines, are promising candidates for vaccine adjuvants. As the binding site of toll-like receptor 8 is large and highly flexible, virtual screening by individual method has inevitable limitations; thus, a comprehensive comparison of different methods may provide insights into seeking effective strategy for the discovery of novel toll-like receptor 8 agonists. In this study, the performance of knowledge-based pharmacophore, shape-based 3D screening, and combined strategies was assessed against a maximum unbiased benchmarking data set containing 13 actives and 1302 decoys specialized for toll-like receptor 8 agonists. Prior structure-activity relationship knowledge was involved in knowledge-based pharmacophore generation, and a set of antagonists was innovatively used to verify the selectivity of the selected knowledge-based pharmacophore. The benchmarking data set was generated from our recently developed 'mubd-decoymaker' protocol. The enrichment assessment demonstrated a considerable performance through our selected three-layer virtual screening strategy: knowledge-based pharmacophore (Phar1) screening, shape-based 3D similarity search (Q4_combo), and then a Gold docking screening. This virtual screening strategy could be further employed to perform large-scale database screening and to discover novel toll-like receptor 8 agonists. © 2015 John Wiley & Sons A/S.

Time-resolved luminescence screening method for enrofloxacin in beef serum

USDA-ARS?s Scientific Manuscript database

Enrofloxacin is one of only two fluoroquinolone antibiotics approved for use in cattle in the U.S. Microbial screening methods currently used in the U.S. for monitoring veterinary drug residues are not sensitive or selective for fluoroquinolones. In this work, a luminescence-based screening assay ...

Computer-aided diagnosis workstation and network system for chest diagnosis based on multislice CT images

NASA Astrophysics Data System (ADS)

Satoh, Hitoshi; Niki, Noboru; Mori, Kiyoshi; Eguchi, Kenji; Kaneko, Masahiro; Kakinuma, Ryutarou; Moriyama, Noriyuki; Ohmatsu, Hironobu; Masuda, Hideo; Machida, Suguru

2007-03-01

Multislice CT scanner advanced remarkably at the speed at which the chest CT images were acquired for mass screening. Mass screening based on multislice CT images requires a considerable number of images to be read. It is this time-consuming step that makes the use of helical CT for mass screening impractical at present. To overcome this problem, we have provided diagnostic assistance methods to medical screening specialists by developing a lung cancer screening algorithm that automatically detects suspected lung cancers in helical CT images and a coronary artery calcification screening algorithm that automatically detects suspected coronary artery calcification. Moreover, we have provided diagnostic assistance methods to medical screening specialists by using a lung cancer screening algorithm built into mobile helical CT scanner for the lung cancer mass screening done in the region without the hospital. We also have developed electronic medical recording system and prototype internet system for the community health in two or more regions by using the Virtual Private Network router and Biometric fingerprint authentication system and Biometric face authentication system for safety of medical information. Based on these diagnostic assistance methods, we have now developed a new computer-aided workstation and database that can display suspected lesions three-dimensionally in a short time. This paper describes basic studies that have been conducted to evaluate this new system.

Evaluation of parameters of color profile models of LCD and LED screens

NASA Astrophysics Data System (ADS)

Zharinov, I. O.; Zharinov, O. O.

2017-12-01

The purpose of the research relates to the problem of parametric identification of the color profile model of LCD (liquid crystal display) and LED (light emitting diode) screens. The color profile model of a screen is based on the Grassmann’s Law of additive color mixture. Mathematically the problem is to evaluate unknown parameters (numerical coefficients) of the matrix transformation between different color spaces. Several methods of evaluation of these screen profile coefficients were developed. These methods are based either on processing of some colorimetric measurements or on processing of technical documentation data.

Native State Mass Spectrometry, Surface Plasmon Resonance, and X-ray Crystallography Correlate Strongly as a Fragment Screening Combination.

PubMed

Woods, Lucy A; Dolezal, Olan; Ren, Bin; Ryan, John H; Peat, Thomas S; Poulsen, Sally-Ann

2016-03-10

Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.

SensiScreen® KRAS exon 2-sensitive simplex and multiplex real-time PCR-based assays for detection of KRAS exon 2 mutations

PubMed Central

Guldmann-Christensen, Mariann; Hauge Kyneb, Majbritt; Voogd, Kirsten; Andersen, Christina; Epistolio, Samantha; Merlo, Elisabetta; Yding Wolff, Tine; Hamilton-Dutoit, Stephen; Lorenzen, Jan; Christensen, Ulf Bech

2017-01-01

Activating mutations in codon 12 and codon 13 of the KRAS (Kirsten rat sarcoma viral oncogene homolog) gene are implicated in the development of several human cancer types and influence their clinical evaluation, treatment and prognosis. Numerous different methods for KRAS genotyping are currently available displaying a wide range of sensitivities, time to answer and requirements for laboratory equipment and user skills. Here we present SensiScreen® KRAS exon 2 simplex and multiplex CE IVD assays, that use a novel real-time PCR-based method for KRAS mutation detection based on PentaBase’s proprietary DNA analogue technology and designed to work on standard real-time PCR instruments. By means of the included BaseBlocker™ technology, we show that SensiScreen® specifically amplifies the mutated alleles of interest with no or highly subdued amplification of the wild type allele. Furthermore, serial dilutions of mutant DNA in a wild type background demonstrate that all SensiScreen® assays display a limit of detection that falls within the range of 0.25–1%. Finally, in three different colorectal cancer patient populations, SensiScreen® assays confirmed the KRAS genotype previously determined by commonly used methods for KRAS mutation testing, and notably, in two of the populations, SensiScreen® identified additional mutant positive cases not detected by common methods. PMID:28636636

Improving the accuracy of ultrafast ligand-based screening: incorporating lipophilicity into ElectroShape as an extra dimension.

PubMed

Armstrong, M Stuart; Finn, Paul W; Morris, Garrett M; Richards, W Graham

2011-08-01

In a previous paper, we presented the ElectroShape method, which we used to achieve successful ligand-based virtual screening. It extended classical shape-based methods by applying them to the four-dimensional shape of the molecule where partial charge was used as the fourth dimension to capture electrostatic information. This paper extends the approach by using atomic lipophilicity (alogP) as an additional molecular property and validates it using the improved release 2 of the Directory of Useful Decoys (DUD). When alogP replaced partial charge, the enrichment results were slightly below those of ElectroShape, though still far better than purely shape-based methods. However, when alogP was added as a complement to partial charge, the resulting five-dimensional enrichments shows a clear improvement in performance. This demonstrates the utility of extending the ElectroShape virtual screening method by adding other atom-based descriptors.

A mix-and-read drop-based in vitro two-hybrid method for screening high-affinity peptide binders

PubMed Central

Cui, Naiwen; Zhang, Huidan; Schneider, Nils; Tao, Ye; Asahara, Haruichi; Sun, Zhiyi; Cai, Yamei; Koehler, Stephan A.; de Greef, Tom F. A.; Abbaspourrad, Alireza; Weitz, David A.; Chong, Shaorong

2016-01-01

Drop-based microfluidics have recently become a novel tool by providing a stable linkage between phenotype and genotype for high throughput screening. However, use of drop-based microfluidics for screening high-affinity peptide binders has not been demonstrated due to the lack of a sensitive functional assay that can detect single DNA molecules in drops. To address this sensitivity issue, we introduced in vitro two-hybrid system (IVT2H) into microfluidic drops and developed a streamlined mix-and-read drop-IVT2H method to screen a random DNA library. Drop-IVT2H was based on the correlation between the binding affinity of two interacting protein domains and transcriptional activation of a fluorescent reporter. A DNA library encoding potential peptide binders was encapsulated with IVT2H such that single DNA molecules were distributed in individual drops. We validated drop-IVT2H by screening a three-random-residue library derived from a high-affinity MDM2 inhibitor PMI. The current drop-IVT2H platform is ideally suited for affinity screening of small-to-medium-sized libraries (103–106). It can obtain hits within a single day while consuming minimal amounts of reagents. Drop-IVT2H simplifies and accelerates the drop-based microfluidics workflow for screening random DNA libraries, and represents a novel alternative method for protein engineering and in vitro directed protein evolution. PMID:26940078

Sensitive fluorimetric assays for α-glucosidase activity and inhibitor screening based on β-cyclodextrin-coated quantum dots.

PubMed

Liu, Si-Yao; Wang, Huan; He, Tian; Qi, Liang; Zhang, Zhi-Qi

2016-02-01

A fluorescence method was established for a α-glucosidase activity assay and inhibitor screening based on β-cyclodextrin-coated quantum dots. p-Nitrophenol, the hydrolysis product of the α-glucosidase reaction, could quench the fluorescence of β-cyclodextrin-coated quantum dots via an electron transfer process, leading to fluorescence turn-off, whereas the fluorescence of the system turned on in the presence of α-glucosidase inhibitors. Taking advantage of the excellent properties of quantum dots, this method provided a very simple, rapid and sensitive screening method for α-glucosidase inhibitors. Two α-glucosidase inhibitors, 2,4,6-tribromophenol and acarbose, were used to evaluate the feasibility of this screening model, and IC50 values of 24 μM and 0.55 mM were obtained respectively, which were lower than those previously reported. The method may have potential application in screening α-glucosidase inhibitors. Copyright © 2015 John Wiley & Sons, Ltd.

Component analysis and target cell-based neuroactivity screening of Panax ginseng by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

PubMed

Yuan, Jinbin; Chen, Yang; Liang, Jian; Wang, Chong-Zhi; Liu, Xiaofei; Yan, Zhihong; Tang, Yi; Li, Jiankang; Yuan, Chun-Su

2016-12-01

Ginseng is one of the most widely used natural medicines in the world. Recent studies have suggested Panax ginseng has a wide range of beneficial effects on aging, central nervous system disorders, and neurodegenerative diseases. However, knowledge about the specific bioactive components of ginseng is still limited. This work aimed to screen for the bioactive components in Panax ginseng that act against neurodegenerative diseases, using the target cell-based bioactivity screening method. Firstly, component analysis of Panax ginseng extracts was performed by UPLC-QTOF-MS, and a total of 54 compounds in white ginseng were characterized and identified according to the retention behaviors, accurate MW, MS characteristics, parent nucleus, aglycones, side chains, and literature data. Then target cell-based bioactivity screening method was developed to predict the candidate compounds in ginseng with SH-SY5Y cells. Four ginsenosides, Rg 2 , Rh 1 , Ro, and Rd, were observed to be active. The target cell-based bioactivity screening method coupled with UPLC-QTOF-MS technique has suitable sensitivity and it can be used as a screening tool for low content bioactive constituents in natural products. Copyright © 2016 Elsevier B.V. All rights reserved.

Adapting Document Similarity Measures for Ligand-Based Virtual Screening.

PubMed

Himmat, Mubarak; Salim, Naomie; Al-Dabbagh, Mohammed Mumtaz; Saeed, Faisal; Ahmed, Ali

2016-04-13

Quantifying the similarity of molecules is considered one of the major tasks in virtual screening. There are many similarity measures that have been proposed for this purpose, some of which have been derived from document and text retrieving areas as most often these similarity methods give good results in document retrieval and can achieve good results in virtual screening. In this work, we propose a similarity measure for ligand-based virtual screening, which has been derived from a text processing similarity measure. It has been adopted to be suitable for virtual screening; we called this proposed measure the Adapted Similarity Measure of Text Processing (ASMTP). For evaluating and testing the proposed ASMTP we conducted several experiments on two different benchmark datasets: the Maximum Unbiased Validation (MUV) and the MDL Drug Data Report (MDDR). The experiments have been conducted by choosing 10 reference structures from each class randomly as queries and evaluate them in the recall of cut-offs at 1% and 5%. The overall obtained results are compared with some similarity methods including the Tanimoto coefficient, which are considered to be the conventional and standard similarity coefficients for fingerprint-based similarity calculations. The achieved results show that the performance of ligand-based virtual screening is better and outperforms the Tanimoto coefficients and other methods.

An evaluation of authentication methods for smartphone based on users’ preferences

NASA Astrophysics Data System (ADS)

Sari, P. K.; Ratnasari, G. S.; Prasetio, A.

2016-04-01

This study discusses about smartphone screen lock preferences using some types of authentication methods. The purpose is to determine the user behaviours based on the perceived security and convenience, as well as the preferences for different types of authentication methods. Variables used are the considerations for locking the screens and the types of authentication methods. The population consists of the smartphone users with the total samples of 400 respondents within a nonprobability sampling method. Data analysis method used is the descriptive analysis. The results showed that the convenience factor is still the major consideration for locking the smartphone screens. Majority of the users chose the pattern unlock as the most convenient method to use. Meanwhile, fingerprint unlock becomes the most secure method in the users’ perceptions and as the method chosen to be used in the future.

Cocrystal screening of hydroxybenzamides with benzoic acid derivatives: a comparative study of thermal and solution-based methods.

PubMed

Manin, Alex N; Voronin, Alexander P; Drozd, Ksenia V; Manin, Nikolay G; Bauer-Brandl, Annette; Perlovich, German L

2014-12-18

The main problem occurring at the early stages of cocrystal search is the choice of an effective screening technique. Among the most popular techniques of obtaining cocrystals are crystallization from solution, crystallization from melt and solvent-drop grinding. This paper represents a comparative analysis of the following screening techniques: DSC cocrystal screening method, thermal microscopy and saturation temperature method. The efficiency of different techniques of cocrystal screening was checked in 18 systems. Benzamide and benzoic acid derivatives were chosen as model systems due to their ability to form acid-amide supramolecular heterosynthon. The screening has confirmed the formation of 6 new cocrystals. The screening by the saturation temperature method has the highest screen-out rate but the smallest range of application. DSC screening has a satisfactory accuracy and allows screening over a short time. Thermal microscopy is most efficient as an additional technique used to interpret ambiguous DSC screening results. The study also included an analysis of the influence of solvent type and component solubility on cocrystal formation. Copyright © 2014 Elsevier B.V. All rights reserved.

Parent Reactions to a School-Based Body Mass Index Screening Program

ERIC Educational Resources Information Center

Johnson, Suzanne Bennett; Pilkington, Lorri L.; Lamp, Camilla; He, Jianghua; Deeb, Larry C.

2009-01-01

Background: This study assessed parent reactions to school-based body mass index (BMI) screening. Methods: After a K-8 BMI screening program, parents were sent a letter detailing their child's BMI results. Approximately 50 parents were randomly selected for interview from each of 4 child weight-classification groups (overweight, at risk of…

Development of purely structure-based pharmacophores for the topoisomerase I-DNA-ligand binding pocket

NASA Astrophysics Data System (ADS)

Drwal, Malgorzata N.; Agama, Keli; Pommier, Yves; Griffith, Renate

2013-12-01

Purely structure-based pharmacophores (SBPs) are an alternative method to ligand-based approaches and have the advantage of describing the entire interaction capability of a binding pocket. Here, we present the development of SBPs for topoisomerase I, an anticancer target with an unusual ligand binding pocket consisting of protein and DNA atoms. Different approaches to cluster and select pharmacophore features are investigated, including hierarchical clustering and energy calculations. In addition, the performance of SBPs is evaluated retrospectively and compared to the performance of ligand- and complex-based pharmacophores. SBPs emerge as a valid method in virtual screening and a complementary approach to ligand-focussed methods. The study further reveals that the choice of pharmacophore feature clustering and selection methods has a large impact on the virtual screening hit lists. A prospective application of the SBPs in virtual screening reveals that they can be used successfully to identify novel topoisomerase inhibitors.

Whole Organism High-Content Screening by Label-Free, Image-Based Bayesian Classification for Parasitic Diseases

PubMed Central

Paveley, Ross A.; Mansour, Nuha R.; Hallyburton, Irene; Bleicher, Leo S.; Benn, Alex E.; Mikic, Ivana; Guidi, Alessandra; Gilbert, Ian H.; Hopkins, Andrew L.; Bickle, Quentin D.

2012-01-01

Sole reliance on one drug, Praziquantel, for treatment and control of schistosomiasis raises concerns about development of widespread resistance, prompting renewed interest in the discovery of new anthelmintics. To discover new leads we designed an automated label-free, high content-based, high throughput screen (HTS) to assess drug-induced effects on in vitro cultured larvae (schistosomula) using bright-field imaging. Automatic image analysis and Bayesian prediction models define morphological damage, hit/non-hit prediction and larval phenotype characterization. Motility was also assessed from time-lapse images. In screening a 10,041 compound library the HTS correctly detected 99.8% of the hits scored visually. A proportion of these larval hits were also active in an adult worm ex-vivo screen and are the subject of ongoing studies. The method allows, for the first time, screening of large compound collections against schistosomes and the methods are adaptable to other whole organism and cell-based screening by morphology and motility phenotyping. PMID:22860151

Histology Verification Demonstrates That Biospectroscopy Analysis of Cervical Cytology Identifies Underlying Disease More Accurately than Conventional Screening: Removing the Confounder of Discordance

PubMed Central

Gajjar, Ketan; Ahmadzai, Abdullah A.; Valasoulis, George; Trevisan, Júlio; Founta, Christina; Nasioutziki, Maria; Loufopoulos, Aristotelis; Kyrgiou, Maria; Stasinou, Sofia Melina; Karakitsos, Petros; Paraskevaidis, Evangelos; Da Gama-Rose, Bianca; Martin-Hirsch, Pierre L.; Martin, Francis L.

2014-01-01

Background Subjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation. Methods Within a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn’s test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease. Results Conventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening. Scores plots of IR spectra exhibit marked crossover of spectral points between different cytological categories. Although, significant differences between spectral bands in different categories are noted, crossover samples point to the potential for poor specificity and hampers the development of biospectroscopy as a diagnostic tool. However, when histology-based categories are used to conduct analyses, the scores plot of IR spectra exhibit markedly better segregation. Conclusions Histology demonstrates that ATR-FTIR spectroscopy of liquid-based cytology identifies the presence of underlying atypia or disease missed in conventional cytology screening. This study points to an urgent need for a future biospectroscopy study where categories are based on such histology. It will allow for the validation of this approach as a screening tool. PMID:24404130

Modeling Individual Patient Preferences for Colorectal Cancer Screening Based on Their Tolerance for Complications Risk.

PubMed

Taksler, Glen B; Perzynski, Adam T; Kattan, Michael W

2017-04-01

Recommendations for colorectal cancer screening encourage patients to choose among various screening methods based on individual preferences for benefits, risks, screening frequency, and discomfort. We devised a model to illustrate how individuals with varying tolerance for screening complications risk might decide on their preferred screening strategy. We developed a discrete-time Markov mathematical model that allowed hypothetical individuals to maximize expected lifetime utility by selecting screening method, start age, stop age, and frequency. Individuals could choose from stool-based testing every 1 to 3 years, flexible sigmoidoscopy every 1 to 20 years with annual stool-based testing, colonoscopy every 1 to 20 years, or no screening. We compared the life expectancy gained from the chosen strategy with the life expectancy available from a benchmark strategy of decennial colonoscopy. For an individual at average risk of colorectal cancer who was risk neutral with respect to screening complications (and therefore was willing to undergo screening if it would actuarially increase life expectancy), the model predicted that he or she would choose colonoscopy every 10 years, from age 53 to 73 years, consistent with national guidelines. For a similar individual who was moderately averse to screening complications risk (and therefore required a greater increase in life expectancy to accept potential risks of colonoscopy), the model predicted that he or she would prefer flexible sigmoidoscopy every 12 years with annual stool-based testing, with 93% of the life expectancy benefit of decennial colonoscopy. For an individual with higher risk aversion, the model predicted that he or she would prefer 2 lifetime flexible sigmoidoscopies, 20 years apart, with 70% of the life expectancy benefit of decennial colonoscopy. Mathematical models may formalize how individuals with different risk attitudes choose between various guideline-recommended colorectal cancer screening strategies.

Eliciting women's cervical screening preferences: a mixed methods systematic review protocol.

PubMed

Wood, Brianne; Van Katwyk, Susan Rogers; El-Khatib, Ziad; McFaul, Susan; Taljaard, Monica; Wright, Erica; Graham, Ian D; Little, Julian

2016-08-11

With the accumulation of evidence regarding potential harms of cancer screening in recent years, researchers, policy-makers, and the public are becoming more critical of population-based cancer screening. Consequently, a high-quality cancer screening program should consider individuals' values and preferences when determining recommendations. In cervical cancer screening, offering women autonomy is considered a "person-centered" approach to health care services; however, it may impact the effectiveness of the program should women choose to not participate. As part of a larger project to investigate women's cervical screening preferences and correlates of these preferences, this systematic review will capture quantitative and qualitative investigations of women's cervical screening preferences and the methods used to elicit them. This mixed methods synthesis will use a thematic analysis approach to synthesize qualitative, quantitative, and mixed methods evidence. This protocol describes the methods that will be used in this investigation. A search strategy has been developed with a health librarian and peer reviewed using PRESS. Based on this strategy, five databases and the gray literature will be searched for studies that meet the inclusion criteria. The quality of the included individual studies will be examined using the Mixed Methods Appraisal Tool. Three reviewers will extract data from the primary studies on the tools or instruments used to elicit women's preferences regarding cervical cancer screening, theoretical frameworks used, outcomes measured, the outstanding themes from quantitative and qualitative evidence, and the identified preferences for cervical cancer screening. We will describe the relationships between study results and the study population, "intervention" (e.g., tool or instrument), and context. We will follow the PRISMA reporting guideline. We will compare findings across studies and between study methods (e.g., qualitative versus quantitative study designs). The strength of the synthesized findings will be assessed using the validated GRADE and CERQual tool. This review will inform the development of a tool to elicit women's cervical screening preferences. Understanding the methods used to elicit women's preferences and what is known about women's cervical screening preferences will be useful for guideline developers who wish to incorporate a woman-centered approach specifically for cervical screening guidelines. PROSPERO CRD42016035737.

Economic Evaluation of Screening Strategies Combined with HPV Vaccination of Preadolescent Girls for the Prevention of Cervical Cancer in Vientiane, Lao PDR

PubMed Central

2016-01-01

Background Several approaches to reduce the incidence of invasive cervical cancers exist. The approach adopted should take into account contextual factors that influence the cost-effectiveness of the available options. Objective To determine the cost-effectiveness of screening strategies combined with a vaccination program for 10-year old girls for cervical cancer prevention in Vientiane, Lao PDR. Methods A population-based dynamic compartment model was constructed. The interventions consisted of a 10-year old girl vaccination program only, or this program combined with screening strategies, i.e., visual inspection with acetic acid (VIA), cytology-based screening, rapid human papillomavirus (HPV) DNA testing, or combined VIA and cytology testing. Simulations were run over 100 years. In base-case scenario analyses, we assumed a 70% vaccination coverage with lifelong protection and a 50% screening coverage. The outcome of interest was the incremental cost per Disability-Adjusted Life Year (DALY) averted. Results In base-case scenarios, compared to the next best strategy, the model predicted that VIA screening of women aged 30–65 years old every three years, combined with vaccination, was the most attractive option, costing 2 544 international dollars (I$) per DALY averted. Meanwhile, rapid HPV DNA testing was predicted to be more attractive than cytology-based screening or its combination with VIA. Among cytology-based screening options, combined VIA with conventional cytology testing was predicted to be the most attractive option. Multi-way sensitivity analyses did not change the results. Compared to rapid HPV DNA testing, VIA had a probability of cost-effectiveness of 73%. Compared to the vaccination only option, the probability that a program consisting of screening women every five years would be cost-effective was around 60% and 80% if the willingness-to-pay threshold is fixed at one and three GDP per capita, respectively. Conclusions A VIA screening program in addition to a girl vaccination program was predicted to be the most attractive option in the health care context of Lao PDR. When compared with other screening methods, VIA was the primary recommended method for combination with vaccination in Lao PDR. PMID:27631732

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

PubMed

Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

2015-09-18

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

PubMed Central

Guyon, Laurent; Lajaunie, Christian; fer, Frédéric; bhajun, Ricky; sulpice, Eric; pinna, Guillaume; campalans, Anna; radicella, J. Pablo; rouillier, Philippe; mary, Mélissa; combe, Stéphanie; obeid, Patricia; vert, Jean-Philippe; gidrol, Xavier

2015-01-01

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID:26382112

Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge

NASA Astrophysics Data System (ADS)

Kumar, Ashutosh; Zhang, Kam Y. J.

2012-05-01

SAMPL3 fragment based virtual screening challenge provides a valuable opportunity for researchers to test their programs, methods and screening protocols in a blind testing environment. We participated in SAMPL3 challenge and evaluated our virtual fragment screening protocol, which involves RosettaLigand as the core component by screening a 500 fragments Maybridge library against bovine pancreatic trypsin. Our study reaffirmed that the real test for any virtual screening approach would be in a blind testing environment. The analyses presented in this paper also showed that virtual screening performance can be improved, if a set of known active compounds is available and parameters and methods that yield better enrichment are selected. Our study also highlighted that to achieve accurate orientation and conformation of ligands within a binding site, selecting an appropriate method to calculate partial charges is important. Another finding is that using multiple receptor ensembles in docking does not always yield better enrichment than individual receptors. On the basis of our results and retrospective analyses from SAMPL3 fragment screening challenge we anticipate that chances of success in a fragment screening process could be increased significantly with careful selection of receptor structures, protein flexibility, sufficient conformational sampling within binding pocket and accurate assignment of ligand and protein partial charges.

A Metric for Reducing False Positives in the Computer-Aided Detection of Breast Cancer from Dynamic Contrast-Enhanced Magnetic Resonance Imaging Based Screening Examinations of High-Risk Women.

PubMed

Levman, Jacob E D; Gallego-Ortiz, Cristina; Warner, Ellen; Causer, Petrina; Martel, Anne L

2016-02-01

Magnetic resonance imaging (MRI)-enabled cancer screening has been shown to be a highly sensitive method for the early detection of breast cancer. Computer-aided detection systems have the potential to improve the screening process by standardizing radiologists to a high level of diagnostic accuracy. This retrospective study was approved by the institutional review board of Sunnybrook Health Sciences Centre. This study compares the performance of a proposed method for computer-aided detection (based on the second-order spatial derivative of the relative signal intensity) with the signal enhancement ratio (SER) on MRI-based breast screening examinations. Comparison is performed using receiver operating characteristic (ROC) curve analysis as well as free-response receiver operating characteristic (FROC) curve analysis. A modified computer-aided detection system combining the proposed approach with the SER method is also presented. The proposed method provides improvements in the rates of false positive markings over the SER method in the detection of breast cancer (as assessed by FROC analysis). The modified computer-aided detection system that incorporates both the proposed method and the SER method yields ROC results equal to that produced by SER while simultaneously providing improvements over the SER method in terms of false positives per noncancerous exam. The proposed method for identifying malignancies outperforms the SER method in terms of false positives on a challenging dataset containing many small lesions and may play a useful role in breast cancer screening by MRI as part of a computer-aided detection system.

HPV vaccination impact on a cervical cancer screening program: methods of the FASTER-Tlalpan Study in Mexico.

PubMed

Salmerón, Jorge; Torres-Ibarra, Leticia; Bosch, F Xavier; Cuzick, Jack; Lörincz, Attila; Wheeler, Cosette M; Castle, Philip E; Robles, Claudia; Lazcano-Ponce, Eduardo

2016-04-01

To outline the design of a clinical trial to evaluate the impact of HPV vaccination as part of a hrHPV-based primary screening program to extend screening intervals. A total of 18,000 women aged 25-45 years, attending the regular cervical cancer-screening program in primary health care services in Tlalpan, Mexico City, will be invited to the study. Eligible participants will be assigned to one of three comparison groups: 1) HPV16/18 vaccine and hrHPV-based screening; 2) HPV6/11/16/18 vaccine and hrHPV-based screening; 3) Control group who will receive only hrHPV-based screening. Strict surveillance of hrHPV persistent infection and occurrence of precancerous lesions will be conducted to estimate safety profiles at different screening intervals; participants will undergo diagnosis confirmation and treatment as necessary. The FASTER-Tlalpan Study will provide insights into new approaches of cervical cancer prevention programs. It will offer valuable information on potential benefits of combining HPV vaccination and hrHPV-based screening to safety extend screening intervals.

A permutation-based non-parametric analysis of CRISPR screen data.

PubMed

Jia, Gaoxiang; Wang, Xinlei; Xiao, Guanghua

2017-07-19

Clustered regularly-interspaced short palindromic repeats (CRISPR) screens are usually implemented in cultured cells to identify genes with critical functions. Although several methods have been developed or adapted to analyze CRISPR screening data, no single specific algorithm has gained popularity. Thus, rigorous procedures are needed to overcome the shortcomings of existing algorithms. We developed a Permutation-Based Non-Parametric Analysis (PBNPA) algorithm, which computes p-values at the gene level by permuting sgRNA labels, and thus it avoids restrictive distributional assumptions. Although PBNPA is designed to analyze CRISPR data, it can also be applied to analyze genetic screens implemented with siRNAs or shRNAs and drug screens. We compared the performance of PBNPA with competing methods on simulated data as well as on real data. PBNPA outperformed recent methods designed for CRISPR screen analysis, as well as methods used for analyzing other functional genomics screens, in terms of Receiver Operating Characteristics (ROC) curves and False Discovery Rate (FDR) control for simulated data under various settings. Remarkably, the PBNPA algorithm showed better consistency and FDR control on published real data as well. PBNPA yields more consistent and reliable results than its competitors, especially when the data quality is low. R package of PBNPA is available at: https://cran.r-project.org/web/packages/PBNPA/ .

School-Based BMI and Body Composition Screening and Parent Notification in California: Methods and Messages

ERIC Educational Resources Information Center

Madsen, Kristine A.; Linchey, Jennifer

2012-01-01

Background: School-based body mass index (BMI) or body composition screening is increasing, but little is known about the process of parent notification. Since 2001, California has required annual screening of body composition via the FITNESSGRAM, with optional notification. This study sought to identify the prevalence of parental notification…

How to benchmark methods for structure-based virtual screening of large compound libraries.

PubMed

Christofferson, Andrew J; Huang, Niu

2012-01-01

Structure-based virtual screening is a useful computational technique for ligand discovery. To systematically evaluate different docking approaches, it is important to have a consistent benchmarking protocol that is both relevant and unbiased. Here, we describe the designing of a benchmarking data set for docking screen assessment, a standard docking screening process, and the analysis and presentation of the enrichment of annotated ligands among a background decoy database.

Measuring lip force by oral screens. Part 1: Importance of screen size and individual variability.

PubMed

Wertsén, Madeleine; Stenberg, Manne

2017-06-01

To reduce drooling and facilitate food transport in rehabilitation of patients with oral motor dysfunction, lip force can be trained using an oral screen. Longitudinal studies evaluating the effect of training require objective methods. The aim of this study was to evaluate a method for measuring lip strength, to investigate normal values and fluctuation of lip force in healthy adults on 1 occasion and over time, to study how the size of the screen affects the force, to evaluate the most appropriate measure of reliability, and to identify force performed in relation to gender. Three different sizes of oral screens were used to measure the lip force for 24 healthy adults on 3 different occasions, during a period of 6 months, using an apparatus based on strain gauge. The maximum lip force as evaluated with this method depends on the area of the screen size. By calculating the projected area of the screen, the lip force could be normalized to an oral screen pressure quantity expressed in kPa, which can be used for comparing measurements from screens with different sizes. Both the mean value and standard deviation were shown to vary between individuals. The study showed no differences regarding gender and only small variation with age. Normal variation over time (months) may be up to 3 times greater than the standard error of measurement at a certain occasion. The lip force increases in relation to the projected area of the screen. No general standard deviation can be assigned to the method and all measurements should be analyzed individually based on oral screen pressure to compensate for different screen sizes.

Comparing methods for measuring peak look duration: are individual differences observed on screen-based tasks also found in more ecologically valid contexts?

PubMed

Wass, Sam V

2014-08-01

Convergent research points to the importance of studying the ontogenesis of sustained attention during the early years of life, but little research hitherto has compared and contrasted different techniques available for measuring sustained attention. Here, we compare methods that have been used to assess one parameter of sustained attention, namely infants' peak look duration to novel stimuli. Our focus was to assess whether individual differences in peak look duration are stable across different measurement techniques. In a single cohort of 42 typically developing 11-month-old infants we assessed peak look duration using six different measurement paradigms (four screen-based, two naturalistic). Zero-order correlations suggested that individual differences in peak look duration were stable across all four screen-based paradigms, but no correlations were found between peak look durations observed on the screen-based and the naturalistic paradigms. A factor analysis conducted on the dependent variable of peak look duration identified two factors. All four screen-based tasks loaded onto the first factor, but the two naturalistic tasks did not relate, and mapped onto a different factor. Our results question how individual differences observed on screen-based tasks manifest in more ecologically valid contexts. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Comparing methods for measuring peak look duration: Are individual differences observed on screen-based tasks also found in more ecologically valid contexts?

PubMed Central

Wass, Sam V.

2014-01-01

Convergent research points to the importance of studying the ontogenesis of sustained attention during the early years of life, but little research hitherto has compared and contrasted different techniques available for measuring sustained attention. Here, we compare methods that have been used to assess one parameter of sustained attention, namely infants’ peak look duration to novel stimuli. Our focus was to assess whether individual differences in peak look duration are stable across different measurement techniques. In a single cohort of 42 typically developing 11-month-old infants we assessed peak look duration using six different measurement paradigms (four screen-based, two naturalistic). Zero-order correlations suggested that individual differences in peak look duration were stable across all four screen-based paradigms, but no correlations were found between peak look durations observed on the screen-based and the naturalistic paradigms. A factor analysis conducted on the dependent variable of peak look duration identified two factors. All four screen-based tasks loaded onto the first factor, but the two naturalistic tasks did not relate, and mapped onto a different factor. Our results question how individual differences observed on screen-based tasks manifest in more ecologically valid contexts. PMID:24905901

[Ideas and methods on efficient screening of traditional medicines for anti-osteoporosis activity based on M-Act/Tox integrated evaluation using zebrafish].

PubMed

Wang, Mo; Ling, Jie; Chen, Ying; Song, Jie; Sun, E; Shi, Zi-Qi; Feng, Liang; Jia, Xiao-Bin; Wei, Ying-Jie

2017-11-01

The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabolic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxicity(M-Act/Tox) for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds(including metabolites) severely restrict efficient screening in vivo. By referring to previous relevant research and domestic and abroad literature, zebrafish M-Act/Tox integrative method was put forward for efficiently screening anti-osteoporosis herb medicines, which has organically integrated zebrafish metabolism model, osteoporosis model and toxicity evaluation method. This method can break through the bottleneck and blind spots that trace compositions can't achieve efficient and integrated in vivo evaluation, and realize both efficient and comprehensive screening on anti-osteoporosis traditional medicines based on in vivo process taking both safety and effectiveness into account, which is significant to accelerate discovery of effective and safe innovative traditional Chinese medicines for osteoporosis. Copyright© by the Chinese Pharmaceutical Association.

Recruitment methods employed in the prostate, lung, colorectal, and ovarian cancer screening trial

PubMed Central

Gren, Lisa; Broski, Karen; Childs, Jeffery; Cordes, Jill; Engelhard, Deborah; Gahagan, Betsy; Gamito, Eduard; Gardner, Vivien; Geisser, Mindy; Higgins, Darlene; Jenkins, Victoria; Lamerato, Lois; Lappe, Karen; Lowery, Heidi; McGuire, Colleen; Miedzinski, Mollie; Ogden, Sheryl; Tenorio, Sally; Watt, Gavin; Wohlers, Bonita; Marcus, Pamela

2015-01-01

Background The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) is a US National Cancer Institute (NCI)-funded randomized controlled trial designed to evaluate whether certain screening tests reduce mortality from prostate, lung, colorectal, and ovarian cancer. To obtain adequate statistical power, it was necessary to enroll over 150,000 healthy volunteers. Recruitment began in 1993 and ended in 2001. Purpose Our goal is to evaluate the success of recruitment methods employed by the 10 PLCO screening centers. We also provide estimates of recruitment yield and cost for our most successful strategy, direct mail. Methods Each screening center selected its own methods of recruitment. Methods changed throughout the recruitment period as needed. For this manuscript, representatives from each screening center provided information on methods utilized and their success. Results In the United States between 1993 and 2001, ten screening centers enrolled 154,934 study participants. Based on participant self-report, an estimated 95% of individuals were recruited by direct mail. Overall, enrollment yield for direct mail was 1.0%. Individual center enrollment yield ranged from 0.7% to 3.8%. Cost per enrolled participant was $9.64–35.38 for direct mail, excluding personnel costs. Limitations Numeric data on recruitment processes were not kept consistently at individual screening centers. Numeric data in this manuscript are based on the experiences of 5 of the 10 centers. Conclusions Direct mail, using rosters of names and addresses from profit and not-for-profit (including government) organizations, was the most successful and most often used recruitment method. Other recruitment strategies, such as community outreach and use of mass media, can be an important adjunct to direct mail in recruiting minority populations. PMID:19254935

Challenges to be overcome using population-based sampling methods to recruit veterans for a study of post-traumatic stress disorder and traumatic brain injury.

PubMed

Bayley, Peter J; Kong, Jennifer Y; Helmer, Drew A; Schneiderman, Aaron; Roselli, Lauren A; Rosse, Stephanie M; Jackson, Jordan A; Baldwin, Janet; Isaac, Linda; Nolasco, Michael; Blackman, Marc R; Reinhard, Matthew J; Ashford, John Wesson; Chapman, Julie C

2014-04-08

Many investigators are interested in recruiting veterans from recent conflicts in Afghanistan and Iraq with Traumatic Brain Injury (TBI) and/or Post Traumatic Stress Disorder (PTSD). Researchers pursuing such studies may experience problems in recruiting sufficient numbers unless effective strategies are used. Currently, there is very little information on recruitment strategies for individuals with TBI and/or PTSD. It is known that groups of patients with medical conditions may be less likely to volunteer for clinical research. This study investigated the feasibility of recruiting veterans returning from recent military conflicts--Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF)--using a population-based sampling method. Individuals were sampled from a previous epidemiological study. Three study sites focused on recruiting survey respondents (n = 445) who lived within a 60 mile radius of one of the sites. Overall, the successful recruitment of veterans using a population-based sampling method was dependent on the ability to contact potential participants following mass mailing. Study enrollment of participants with probable TBI and/or PTSD had a recruitment yield (enrolled/total identified) of 5.4%. We were able to contact 146 individuals, representing a contact rate of 33%. Sixty-six of the individuals contacted were screened. The major reasons for not screening included a stated lack of interest in the study (n = 37), a failure to answer screening calls after initial contact (n = 30), and an unwillingness or inability to travel to a study site (n = 10). Based on the phone screening, 36 veterans were eligible for the study. Twenty-four veterans were enrolled, (recruitment yield = 5.4%) and twelve were not enrolled for a variety of reasons. Our experience with a population-based sampling method for recruitment of recent combat veterans illustrates the challenges encountered, particularly contacting and screening potential participants. The screening and enrollment data will help guide recruitment for future studies using population-based methods.

Visual detection technique for efficient screening and isolation of Salmonella based on a novel enrichment assay using chromatography membrane.

PubMed

Tang, F; Xiong, Y; Zhang, H; Wu, K; Xiang, Y; Shao, J-B; Ai, H-W; Xiang, Y-P; Zheng, X-L; Lv, J-R; Sun, H; Bao, L-S; Zhang, Z; Hu, H-B; Zhang, J-Y; Chen, L; Lu, J; Liu, W-Y; Mei, H; Ma, Y; Xu, C-F; Fang, A-Y; Gu, M; Xu, C-Y; Chen, Y; Chen, Z; Sun, Z-Y

2016-03-01

To detect Salmonella more efficiently and isolate strains more easily, a novel and simple detection method that uses an enrichment assay and two chromogenic reactions on a chromatography membrane was developed. Grade 3 chromatography paper is used as functionalized solid phase support (SPS), which contains specially optimized medium. One reaction for screening is based on the sulfate-reducing capacity of Salmonella. Hydrogen sulfide (H2S) generated by Salmonella reacts with ammonium ferric citrate to produce black colored ferrous sulfide. Another reaction is based on Salmonella C8 esterase that is unique for Enterobacteriaceae except Serratia and interacts with 4-methylumbelliferyl caprylate (MUCAP) to produce fluorescent umbelliferone, which is visible under ultraviolet light. A very low detection limit (10(1) CFU ml(-1)) for Salmonella was achieved on the background of 10(5) CFU ml(-1) Escherichia coli. More importantly, testing with more than 1,000 anal samples indicated that our method has a high positive detection rate and is relatively low cost, compared with the traditional culture-based method. It took only 1 day for the preliminary screening and 2 days to efficiently isolate the Salmonella cells, indicating that the new assay is specific, rapid, and simple for Salmonella detection. In contrast to the traditional culture-based method, this method can be easily used to screen and isolate targeted strains with the naked eye. The results of quantitative and comparative experiments showed that the visual detection technique is an efficient alternative method for the screening of Salmonella spp. in many applications of large-sized samples related to public health surveillance.

Rapid automated method for screening of enteric pathogens from stool specimens.

PubMed Central

Villasante, P A; Agulla, A; Merino, F J; Pérez, T; Ladrón de Guevara, C; Velasco, A C

1987-01-01

A total of 800 colonies suggestive of Salmonella, Shigella, or Yersinia species isolated on stool differential agar media were inoculated onto both conventional biochemical test media (triple sugar iron agar, urea agar, and phenylalanine agar) and Entero Pathogen Screen cards of the AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.). Based on the conventional tests, the AutoMicrobic system method yielded the following results: 587 true-negatives, 185 true-positives, 2 false-negatives, and 26 false-positives (sensitivity, 99%; specificity, 96%). Both true-positive and true-negative results were achieved considerably earlier than false results (P less than 0.001). The Entero Pathogen Screen card method is a fast, easy, and sensitive method for screening for Salmonella, Shigella, or Yersinia species. The impossibility of screening for oxidase-positive pathogens is a minor disadvantage of this method. PMID:3553230

Biosensor-based small molecule fragment screening with biolayer interferometry

NASA Astrophysics Data System (ADS)

Wartchow, Charles A.; Podlaski, Frank; Li, Shirley; Rowan, Karen; Zhang, Xiaolei; Mark, David; Huang, Kuo-Sen

2011-07-01

Biosensor-based fragment screening is a valuable tool in the drug discovery process. This method is advantageous over many biochemical methods because primary hits can be distinguished from non-specific or non-ideal interactions by examining binding profiles and responses, resulting in reduced false-positive rates. Biolayer interferometry (BLI), a technique that measures changes in an interference pattern generated from visible light reflected from an optical layer and a biolayer containing proteins of interest, is a relatively new method for monitoring small molecule interactions. The BLI format is based on a disposable sensor that is immersed in 96-well or 384-well plates. BLI has been validated for small molecule detection and fragment screening with model systems and well-characterized targets where affinity constants and binding profiles are generally similar to those obtained with surface plasmon resonsance (SPR). Screens with challenging targets involved in protein-protein interactions including BCL-2, JNK1, and eIF4E were performed with a fragment library of 6,500 compounds, and hit rates were compared for these targets. For eIF4E, a protein containing a PPI site and a nucleotide binding site, results from a BLI fragment screen were compared to results obtained in biochemical HTS screens. Overlapping hits were observed for the PPI site, and hits unique to the BLI screen were identified. Hit assessments with SPR and BLI are described.

Estimating the Effect of Targeted Screening Strategies: An Application to Colonoscopy and Colorectal Cancer.

PubMed

Thomas, Duncan C

2017-07-01

Screening behavior depends on previous screening history and family members' behaviors, which can act as both confounders and intermediate variables on a causal pathway from screening to disease risk. Conventional analyses that adjust for these variables can lead to incorrect inferences about the causal effect of screening if high-risk individuals are more likely to be screened. Analyzing the data in a manner that treats screening as randomized conditional on covariates allows causal parameters to be estimated; inverse probability weighting based on propensity of exposure scores is one such method considered here. I simulated family data under plausible models for the underlying disease process and for screening behavior to assess the performance of alternative methods of analysis and whether a targeted screening approach based on individuals' risk factors would lead to a greater reduction in cancer incidence in the population than a uniform screening policy. Simulation results indicate that there can be a substantial underestimation of the effect of screening on subsequent cancer risk when using conventional analysis approaches, which is avoided by using inverse probability weighting. A large case-control study of colonoscopy and colorectal cancer from Germany shows a strong protective effect of screening, but inverse probability weighting makes this effect even stronger. Targeted screening approaches based on either fixed risk factors or family history yield somewhat greater reductions in cancer incidence with fewer screens needed to prevent one cancer than population-wide approaches, but the differences may not be large enough to justify the additional effort required. See video abstract at, http://links.lww.com/EDE/B207.

CORALINA: a universal method for the generation of gRNA libraries for CRISPR-based screening.

PubMed

Köferle, Anna; Worf, Karolina; Breunig, Christopher; Baumann, Valentin; Herrero, Javier; Wiesbeck, Maximilian; Hutter, Lukas H; Götz, Magdalena; Fuchs, Christiane; Beck, Stephan; Stricker, Stefan H

2016-11-14

The bacterial CRISPR system is fast becoming the most popular genetic and epigenetic engineering tool due to its universal applicability and adaptability. The desire to deploy CRISPR-based methods in a large variety of species and contexts has created an urgent need for the development of easy, time- and cost-effective methods enabling large-scale screening approaches. Here we describe CORALINA (comprehensive gRNA library generation through controlled nuclease activity), a method for the generation of comprehensive gRNA libraries for CRISPR-based screens. CORALINA gRNA libraries can be derived from any source of DNA without the need of complex oligonucleotide synthesis. We show the utility of CORALINA for human and mouse genomic DNA, its reproducibility in covering the most relevant genomic features including regulatory, coding and non-coding sequences and confirm the functionality of CORALINA generated gRNAs. The simplicity and cost-effectiveness make CORALINA suitable for any experimental system. The unprecedented sequence complexities obtainable with CORALINA libraries are a necessary pre-requisite for less biased large scale genomic and epigenomic screens.

Benefits of an Android Based Tablet Application in Primary Screening for Eye Diseases in a Rural Population, India.

PubMed

Imtiaz, Sayed Ahmed; Krishnaiah, Sannapaneni; Yadav, Sunil Kumar; Bharath, Balasubramaniam; Ramani, Ramanathan V

2017-04-01

To investigate the effectiveness, efficiency and cost gains in collecting patient eye health information from remote rural villages of India by trained field investigators through an Android Based Tablet Application namely 'Sankara Electronic Remote Vision Information System (SERVIS)". During January and March 2016, a population based cross-sectional study was conducted in three Indian states employing SERVIS and manual method. The SERVIS application has a 48-items survey instrument programed into the application. Data on 281 individuals were collected for each of these methods as part of screening. The demographic details of individuals between both screening methods were comparable (P>0.05). The mean time (in minutes) to screen an individual by SERVIS was significantly less when compared to manual method (6.57±1.46 versus 11.93±1.53) (P<0.0001). The efficiency of SERVIS in screening was significantly evident as 26% (n = 73) of the patients screened have been referred to campsite and 69.8% (n = 51) of those referred were visited the campsite for a detailed eye examination by an ophthalmologist. The cost of screening through SERVIS is significantly less when compared to manual method; INR 7,633 (USD 113.9) Versus INR 24,780 (USD 370). SERVIS is an effective and efficient tool in terms of patients' referral conversion to the camp site leading to timely detection of potential blinding eye conditions and their appropriate treatment. This ensures timely prevention of avoidable blindness and visual impairment. In addition, the storage and access of eye health epidemiological quality data is helpful to plan appropriate blindness prevention initiatives in rural India.

Parameter screening: the use of a dummy parameter to identify non-influential parameters in a global sensitivity analysis

NASA Astrophysics Data System (ADS)

Khorashadi Zadeh, Farkhondeh; Nossent, Jiri; van Griensven, Ann; Bauwens, Willy

2017-04-01

Parameter estimation is a major concern in hydrological modeling, which may limit the use of complex simulators with a large number of parameters. To support the selection of parameters to include in or exclude from the calibration process, Global Sensitivity Analysis (GSA) is widely applied in modeling practices. Based on the results of GSA, the influential and the non-influential parameters are identified (i.e. parameters screening). Nevertheless, the choice of the screening threshold below which parameters are considered non-influential is a critical issue, which has recently received more attention in GSA literature. In theory, the sensitivity index of a non-influential parameter has a value of zero. However, since numerical approximations, rather than analytical solutions, are utilized in GSA methods to calculate the sensitivity indices, small but non-zero indices may be obtained for the indices of non-influential parameters. In order to assess the threshold that identifies non-influential parameters in GSA methods, we propose to calculate the sensitivity index of a "dummy parameter". This dummy parameter has no influence on the model output, but will have a non-zero sensitivity index, representing the error due to the numerical approximation. Hence, the parameters whose indices are above the sensitivity index of the dummy parameter can be classified as influential, whereas the parameters whose indices are below this index are within the range of the numerical error and should be considered as non-influential. To demonstrated the effectiveness of the proposed "dummy parameter approach", 26 parameters of a Soil and Water Assessment Tool (SWAT) model are selected to be analyzed and screened, using the variance-based Sobol' and moment-independent PAWN methods. The sensitivity index of the dummy parameter is calculated from sampled data, without changing the model equations. Moreover, the calculation does not even require additional model evaluations for the Sobol' method. A formal statistical test validates these parameter screening results. Based on the dummy parameter screening, 11 model parameters are identified as influential. Therefore, it can be denoted that the "dummy parameter approach" can facilitate the parameter screening process and provide guidance for GSA users to define a screening-threshold, with only limited additional resources. Key words: Parameter screening, Global sensitivity analysis, Dummy parameter, Variance-based method, Moment-independent method

Novel microscopy-based screening method reveals regulators of contact-dependent intercellular transfer

PubMed Central

Michael Frei, Dominik; Hodneland, Erlend; Rios-Mondragon, Ivan; Burtey, Anne; Neumann, Beate; Bulkescher, Jutta; Schölermann, Julia; Pepperkok, Rainer; Gerdes, Hans-Hermann; Kögel, Tanja

2015-01-01

Contact-dependent intercellular transfer (codeIT) of cellular constituents can have functional consequences for recipient cells, such as enhanced survival and drug resistance. Pathogenic viruses, prions and bacteria can also utilize this mechanism to spread to adjacent cells and potentially evade immune detection. However, little is known about the molecular mechanism underlying this intercellular transfer process. Here, we present a novel microscopy-based screening method to identify regulators and cargo of codeIT. Single donor cells, carrying fluorescently labelled endocytic organelles or proteins, are co-cultured with excess acceptor cells. CodeIT is quantified by confocal microscopy and image analysis in 3D, preserving spatial information. An siRNA-based screening using this method revealed the involvement of several myosins and small GTPases as codeIT regulators. Our data indicates that cellular protrusions and tubular recycling endosomes are important for codeIT. We automated image acquisition and analysis to facilitate large-scale chemical and genetic screening efforts to identify key regulators of codeIT. PMID:26271723

Constraint factor graph cut-based active contour method for automated cellular image segmentation in RNAi screening.

PubMed

Chen, C; Li, H; Zhou, X; Wong, S T C

2008-05-01

Image-based, high throughput genome-wide RNA interference (RNAi) experiments are increasingly carried out to facilitate the understanding of gene functions in intricate biological processes. Automated screening of such experiments generates a large number of images with great variations in image quality, which makes manual analysis unreasonably time-consuming. Therefore, effective techniques for automatic image analysis are urgently needed, in which segmentation is one of the most important steps. This paper proposes a fully automatic method for cells segmentation in genome-wide RNAi screening images. The method consists of two steps: nuclei and cytoplasm segmentation. Nuclei are extracted and labelled to initialize cytoplasm segmentation. Since the quality of RNAi image is rather poor, a novel scale-adaptive steerable filter is designed to enhance the image in order to extract long and thin protrusions on the spiky cells. Then, constraint factor GCBAC method and morphological algorithms are combined to be an integrated method to segment tight clustered cells. Compared with the results obtained by using seeded watershed and the ground truth, that is, manual labelling results by experts in RNAi screening data, our method achieves higher accuracy. Compared with active contour methods, our method consumes much less time. The positive results indicate that the proposed method can be applied in automatic image analysis of multi-channel image screening data.

A ranking method for the concurrent learning of compounds with various activity profiles.

PubMed

Dörr, Alexander; Rosenbaum, Lars; Zell, Andreas

2015-01-01

In this study, we present a SVM-based ranking algorithm for the concurrent learning of compounds with different activity profiles and their varying prioritization. To this end, a specific labeling of each compound was elaborated in order to infer virtual screening models against multiple targets. We compared the method with several state-of-the-art SVM classification techniques that are capable of inferring multi-target screening models on three chemical data sets (cytochrome P450s, dehydrogenases, and a trypsin-like protease data set) containing three different biological targets each. The experiments show that ranking-based algorithms show an increased performance for single- and multi-target virtual screening. Moreover, compounds that do not completely fulfill the desired activity profile are still ranked higher than decoys or compounds with an entirely undesired profile, compared to other multi-target SVM methods. SVM-based ranking methods constitute a valuable approach for virtual screening in multi-target drug design. The utilization of such methods is most helpful when dealing with compounds with various activity profiles and the finding of many ligands with an already perfectly matching activity profile is not to be expected.

An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs.

PubMed

Kim, Wooseong; Hendricks, Gabriel Lambert; Lee, Kiho; Mylonakis, Eleftherios

2017-06-01

The emergence of antibiotic-resistant and -tolerant bacteria is a major threat to human health. Although efforts for drug discovery are ongoing, conventional bacteria-centered screening strategies have thus far failed to yield new classes of effective antibiotics. Therefore, new paradigms for discovering novel antibiotics are of critical importance. Caenorhabditis elegans, a model organism used for in vivo, offers a promising solution for identification of anti-infective compounds. Areas covered: This review examines the advantages of C. elegans-based high-throughput screening over conventional, bacteria-centered in vitro screens. It discusses major anti-infective compounds identified from large-scale C. elegans-based screens and presents the first clinically-approved drugs, then known bioactive compounds, and finally novel small molecules. Expert opinion: There are clear advantages of using a C. elegans-infection based screening method. A C. elegans-based screen produces an enriched pool of non-toxic, efficacious, potential anti-infectives, covering: conventional antimicrobial agents, immunomodulators, and anti-virulence agents. Although C. elegans-based screens do not denote the mode of action of hit compounds, this can be elucidated in secondary studies by comparing the results to target-based screens, or conducting subsequent target-based screens, including the genetic knock-down of host or bacterial genes.

A Novel Quantum Dots-Based Point of Care Test for Syphilis

NASA Astrophysics Data System (ADS)

Yang, Hao; Li, Ding; He, Rong; Guo, Qin; Wang, Kan; Zhang, Xueqing; Huang, Peng; Cui, Daxiang

2010-05-01

One-step lateral flow test is recommended as the first line screening of syphilis for primary healthcare settings in developing countries. However, it generally shows low sensitivity. We describe here the development of a novel fluorescent POC (Point Of Care) test method to be used for screening for syphilis. The method was designed to combine the rapidness of lateral flow test and sensitiveness of fluorescent method. 50 syphilis-positive specimens and 50 healthy specimens conformed by Treponema pallidum particle agglutination (TPPA) were tested with Quantum Dot-labeled and colloidal gold-labeled lateral flow test strips, respectively. The results showed that both sensitivity and specificity of the quantum dots-based method reached up to 100% (95% confidence interval [CI], 91-100%), while those of the colloidal gold-based method were 82% (95% CI, 68-91%) and 100% (95% CI, 91-100%), respectively. In addition, the naked-eye detection limit of quantum dot-based method could achieve 2 ng/ml of anti-TP47 polyclonal antibodies purified by affinity chromatography with TP47 antigen, which was tenfold higher than that of colloidal gold-based method. In conclusion, the quantum dots were found to be suitable for labels of lateral flow test strip. Its ease of use, sensitiveness and low cost make it well-suited for population-based on-the-site syphilis screening.

Colorectal Cancer Deaths Attributable to Nonuse of Screening in the United States

PubMed Central

Meester, Reinier G.S.; Doubeni, Chyke A.; Lansdorp-Vogelaar, Iris; Goede, S.L.; Levin, Theodore R.; Quinn, Virginia P.; van Ballegooijen, Marjolein; Corley, Douglas A.; Zauber, Ann G.

2015-01-01

Purpose Screening is a major contributor to colorectal cancer (CRC) mortality reductions in the U.S., but is underutilized. We estimated the fraction of CRC deaths attributable to nonuse of screening to demonstrate the potential benefits from targeted interventions. Methods The established MISCAN-colon microsimulation model was used to estimate the population attributable fraction (PAF) in people aged ≥50 years. The model incorporates long-term patterns and effects of screening by age and type of screening test. PAF for 2010 was estimated using currently available data on screening uptake; PAF was also projected assuming constant future screening rates to incorporate lagged effects from past increases in screening uptake. We also computed PAF using Levin's formula to gauge how this simpler approach differs from the model-based approach. Results There were an estimated 51,500 CRC deaths in 2010, about 63% (N∼32,200) of which were attributable to non-screening. The PAF decreases slightly to 58% in 2020. Levin's approach yielded a considerably more conservative PAF of 46% (N∼23,600) for 2010. Conclusions The majority of current U.S. CRC deaths are attributable to non-screening. This underscores the potential benefits of increasing screening uptake in the population. Traditional methods of estimating PAF underestimated screening effects compared with model-based approaches. PMID:25721748

Design and fabrication of semi-transparent screen based on micro-patterns for direct-view type head-up display in automobiles

NASA Astrophysics Data System (ADS)

Lee, Jae-Yong; Kim, Hyo-Jun; Kim, Young-Joo

2016-02-01

A semi-transparent screen with hemisphere micro-patterns was proposed and designed to enhance the brightness uniformity of the display image toward the driver for a direct-view type head-up display. The hemisphere micro-patterns were designed to consider the inclined angle of the windshield for efficient reflection and scattering toward to the driver. The density and radius of the hemisphere micro-patterns were adjusted as a function of position on the screen based on the geometrical calculation and analyzed by the commercial optical simulation tool based on a ray-tracing method. The designed hemisphere micro-patterns was fabricated by the thermal reflow method and evaluated to confirm the uniform illumination. From the results, the semi-transparent screen with variable micro-patterns shows the 91.9 % of brightness uniformity with the enhanced luminance compare to a screen without micro-patterns. A luminance of fabricated screen also shows good agreement with the simulation result to reflect the clear and bright driving information to the driver.

Application of clustering analysis in the prediction of photovoltaic power generation based on neural network

NASA Astrophysics Data System (ADS)

Cheng, K.; Guo, L. M.; Wang, Y. K.; Zafar, M. T.

2017-11-01

In order to select effective samples in the large number of data of PV power generation years and improve the accuracy of PV power generation forecasting model, this paper studies the application of clustering analysis in this field and establishes forecasting model based on neural network. Based on three different types of weather on sunny, cloudy and rainy days, this research screens samples of historical data by the clustering analysis method. After screening, it establishes BP neural network prediction models using screened data as training data. Then, compare the six types of photovoltaic power generation prediction models before and after the data screening. Results show that the prediction model combining with clustering analysis and BP neural networks is an effective method to improve the precision of photovoltaic power generation.

Terminate Lung Cancer (TLC) Study - A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky

PubMed Central

Cardarelli, Roberto; Reese, David; Roper, Karen L.; Cardarelli, Kathryn; Feltner, Frances J.; Studts, Jamie L.; Knight, Jennifer R.; Armstrong, Debra; Weaver, Anthony; Shaffer, Dana

2017-01-01

For low dose CT lung cancer screening to be effective in curbing disease mortality, efforts are needed to overcome barriers to awareness and facilitate uptake of the current evidence-based screening guidelines. A sequential mixed-methods approach was employed to design a screening campaign utilizing messages developed from community focus groups, followed by implementation of the outreach campaign intervention in two high-risk Kentucky regions. This study reports on rates of awareness and screening in intervention regions, as compared to a control region. PMID:27866066

Response: Reading between the lines of cancer screening trials: using modeling to understand the evidence.

PubMed

Etzioni, Ruth; Gulati, Roman

2013-04-01

In our article about limitations of basing screening policy on screening trials, we offered several examples of ways in which modeling, using data from large screening trials and population trends, provided insights that differed somewhat from those based only on empirical trial results. In this editorial, we take a step back and consider the general question of whether randomized screening trials provide the strongest evidence for clinical guidelines concerning population screening programs. We argue that randomized trials provide a process that is designed to protect against certain biases but that this process does not guarantee that inferences based on empirical results from screening trials will be unbiased. Appropriate quantitative methods are key to obtaining unbiased inferences from screening trials. We highlight several studies in the statistical literature demonstrating that conventional survival analyses of screening trials can be misleading and list a number of key questions concerning screening harms and benefits that cannot be answered without modeling. Although we acknowledge the centrality of screening trials in the policy process, we maintain that modeling constitutes a powerful tool for screening trial interpretation and screening policy development.

Virtual screening applications: a study of ligand-based methods and different structure representations in four different scenarios.

PubMed

Hristozov, Dimitar P; Oprea, Tudor I; Gasteiger, Johann

2007-01-01

Four different ligand-based virtual screening scenarios are studied: (1) prioritizing compounds for subsequent high-throughput screening (HTS); (2) selecting a predefined (small) number of potentially active compounds from a large chemical database; (3) assessing the probability that a given structure will exhibit a given activity; (4) selecting the most active structure(s) for a biological assay. Each of the four scenarios is exemplified by performing retrospective ligand-based virtual screening for eight different biological targets using two large databases--MDDR and WOMBAT. A comparison between the chemical spaces covered by these two databases is presented. The performance of two techniques for ligand--based virtual screening--similarity search with subsequent data fusion (SSDF) and novelty detection with Self-Organizing Maps (ndSOM) is investigated. Three different structure representations--2,048-dimensional Daylight fingerprints, topological autocorrelation weighted by atomic physicochemical properties (sigma electronegativity, polarizability, partial charge, and identity) and radial distribution functions weighted by the same atomic physicochemical properties--are compared. Both methods were found applicable in scenario one. The similarity search was found to perform slightly better in scenario two while the SOM novelty detection is preferred in scenario three. No method/descriptor combination achieved significant success in scenario four.

Incorporating Virtual Reactions into a Logic-based Ligand-based Virtual Screening Method to Discover New Leads

PubMed Central

Reynolds, Christopher R; Muggleton, Stephen H; Sternberg, Michael J E

2015-01-01

The use of virtual screening has become increasingly central to the drug development pipeline, with ligand-based virtual screening used to screen databases of compounds to predict their bioactivity against a target. These databases can only represent a small fraction of chemical space, and this paper describes a method of exploring synthetic space by applying virtual reactions to promising compounds within a database, and generating focussed libraries of predicted derivatives. A ligand-based virtual screening tool Investigational Novel Drug Discovery by Example (INDDEx) is used as the basis for a system of virtual reactions. The use of virtual reactions is estimated to open up a potential space of 1.21×1012 potential molecules. A de novo design algorithm known as Partial Logical-Rule Reactant Selection (PLoRRS) is introduced and incorporated into the INDDEx methodology. PLoRRS uses logical rules from the INDDEx model to select reactants for the de novo generation of potentially active products. The PLoRRS method is found to increase significantly the likelihood of retrieving molecules similar to known actives with a p-value of 0.016. Case studies demonstrate that the virtual reactions produce molecules highly similar to known actives, including known blockbuster drugs. PMID:26583052

GPURFSCREEN: a GPU based virtual screening tool using random forest classifier.

PubMed

Jayaraj, P B; Ajay, Mathias K; Nufail, M; Gopakumar, G; Jaleel, U C A

2016-01-01

In-silico methods are an integral part of modern drug discovery paradigm. Virtual screening, an in-silico method, is used to refine data models and reduce the chemical space on which wet lab experiments need to be performed. Virtual screening of a ligand data model requires large scale computations, making it a highly time consuming task. This process can be speeded up by implementing parallelized algorithms on a Graphical Processing Unit (GPU). Random Forest is a robust classification algorithm that can be employed in the virtual screening. A ligand based virtual screening tool (GPURFSCREEN) that uses random forests on GPU systems has been proposed and evaluated in this paper. This tool produces optimized results at a lower execution time for large bioassay data sets. The quality of results produced by our tool on GPU is same as that on a regular serial environment. Considering the magnitude of data to be screened, the parallelized virtual screening has a significantly lower running time at high throughput. The proposed parallel tool outperforms its serial counterpart by successfully screening billions of molecules in training and prediction phases.

Socio-Cognitive Determinants of the Mammography Screening Uptake among Iranian Women

PubMed

Mirzaei-Alavijeh, Mehdi; Ghorbani, Parvaneh; Jalilian, Farzad

2018-05-26

Background: Mammography screening uptake is the most effective method in breast cancer screening. The aim of this study was to determine the determinants related to mammography screening uptake among Iranian women based on the theory of planned behavior. Materials and Methods: This cross-sectional study was conducted among 408 women who referred to health centers in Kermanshah city, the western of Iran, during 2016. Participants filled out a self-administered questionnaire. Data were analyzed by SPSS version 21 using Pearson correlation, linear and logistic regression statistical tests at 95% significant level. Results: The mean age of participants was 39.61 years [SD: 8.28], ranged from 30 to 60 years. Almost 13% of the participants had already mammography screening uptake at least once. Perceived behavioral control (OR=1.229) and behavioral intention (OR=1.283) were the more influential predictors on mammography screening uptake. Conclusions: Based on result, it seems increase perceived behavior control toward mammography screening uptake may be usefulness in promotion of mammography screening uptake among Iranian women. Creative Commons Attribution License

DNA-conjugated gold nanoparticles based colorimetric assay to assess helicase activity: a novel route to screen potential helicase inhibitors

NASA Astrophysics Data System (ADS)

Deka, Jashmini; Mojumdar, Aditya; Parisse, Pietro; Onesti, Silvia; Casalis, Loredana

2017-03-01

Helicase are essential enzymes which are widespread in all life-forms. Due to their central role in nucleic acid metabolism, they are emerging as important targets for anti-viral, antibacterial and anti-cancer drugs. The development of easy, cheap, fast and robust biochemical assays to measure helicase activity, overcoming the limitations of the current methods, is a pre-requisite for the discovery of helicase inhibitors through high-throughput screenings. We have developed a method which exploits the optical properties of DNA-conjugated gold nanoparticles (AuNP) and meets the required criteria. The method was tested with the catalytic domain of the human RecQ4 helicase and compared with a conventional FRET-based assay. The AuNP-based assay produced similar results but is simpler, more robust and cheaper than FRET. Therefore, our nanotechnology-based platform shows the potential to provide a useful alternative to the existing conventional methods for following helicase activity and to screen small-molecule libraries as potential helicase inhibitors.

Protective Factors Based Model for Screening for Posttraumatic Distress in Adolescents

ERIC Educational Resources Information Center

Pat-Horenczyk, Ruth; Kenan, Avraham Max; Achituv, Michal; Bachar, Eytan

2014-01-01

Background: There is growing application of school-based screening to identify post-traumatic distress in students following exposure to trauma. The consensus method is based on self-report questionnaires that assess posttraumatic symptoms, functional impairment, depression or anxiety. Objective: The current research explored the possibility of…

Metabolomics Approach for Toxicity Screening of Volatile Substances

EPA Science Inventory

In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However, the ch...

Assessment of circulating copy number variant detection for cancer screening.

PubMed

Molparia, Bhuvan; Nichani, Eshaan; Torkamani, Ali

2017-01-01

Current high-sensitivity cancer screening methods, largely utilizing correlative biomarkers, suffer from false positive rates that lead to unnecessary medical procedures and debatable public health benefit overall. Detection of circulating tumor DNA (ctDNA), a causal biomarker, has the potential to revolutionize cancer screening. Thus far, the majority of ctDNA studies have focused on detection of tumor-specific point mutations after cancer diagnosis for the purpose of post-treatment surveillance. However, ctDNA point mutation detection methods developed to date likely lack either the scope or analytical sensitivity necessary to be useful for cancer screening, due to the low (<1%) ctDNA fraction derived from early stage tumors. On the other hand, tumor-derived copy number variant (CNV) detection is hypothetically a superior means of ctDNA-based cancer screening for many tumor types, given that, relative to point mutations, each individual tumor CNV contributes a much larger number of ctDNA fragments to the overall pool of circulating free DNA (cfDNA). A small number of studies have demonstrated the potential of ctDNA CNV-based screening in select cancer types. Here we perform an in silico assessment of the potential for ctDNA CNV-based cancer screening across many common cancers, and suggest ctDNA CNV detection shows promise as a broad cancer screening methodology.

Novel approaches for targeting the adenosine A2A receptor.

PubMed

Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

2015-01-01

The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells.

PubMed

Zhou, Yuexin; Zhu, Shiyou; Cai, Changzu; Yuan, Pengfei; Li, Chunmei; Huang, Yanyi; Wei, Wensheng

2014-05-22

Targeted genome editing technologies are powerful tools for studying biology and disease, and have a broad range of research applications. In contrast to the rapid development of toolkits to manipulate individual genes, large-scale screening methods based on the complete loss of gene expression are only now beginning to be developed. Here we report the development of a focused CRISPR/Cas-based (clustered regularly interspaced short palindromic repeats/CRISPR-associated) lentiviral library in human cells and a method of gene identification based on functional screening and high-throughput sequencing analysis. Using knockout library screens, we successfully identified the host genes essential for the intoxication of cells by anthrax and diphtheria toxins, which were confirmed by functional validation. The broad application of this powerful genetic screening strategy will not only facilitate the rapid identification of genes important for bacterial toxicity but will also enable the discovery of genes that participate in other biological processes.

Can streamlined multi-criteria decision analysis be used to implement shared decision making for colorectal cancer screening?

PubMed Central

Dolan, James G.; Boohaker, Emily; Allison, Jeroan; Imperiale, Thomas F.

2013-01-01

Background Current US colorectal cancer screening guidelines that call for shared decision making regarding the choice among several recommended screening options are difficult to implement. Multi-criteria decision analysis (MCDA) is an established methodology well suited for supporting shared decision making. Our study goal was to determine if a streamlined form of MCDA using rank order based judgments can accurately assess patients’ colorectal cancer screening priorities. Methods We converted priorities for four decision criteria and three sub-criteria regarding colorectal cancer screening obtained from 484 average risk patients using the Analytic Hierarchy Process (AHP) in a prior study into rank order-based priorities using rank order centroids. We compared the two sets of priorities using Spearman rank correlation and non-parametric Bland-Altman limits of agreement analysis. We assessed the differential impact of using the rank order-based versus the AHP-based priorities on the results of a full MCDA comparing three currently recommended colorectal cancer screening strategies. Generalizability of the results was assessed using Monte Carlo simulation. Results Correlations between the two sets of priorities for the seven criteria ranged from 0.55 to 0.92. The proportions of absolute differences between rank order-based and AHP-based priorities that were more than ± 0.15 ranged from 1% to 16%. Differences in the full MCDA results were minimal and the relative rankings of the three screening options were identical more than 88% of the time. The Monte Carlo simulation results were similar. Conclusion Rank order-based MCDA could be a simple, practical way to guide individual decisions and assess population decision priorities regarding colorectal cancer screening strategies. Additional research is warranted to further explore the use of these methods for promoting shared decision making. PMID:24300851

Optimizing Associative Experimental Design for Protein Crystallization Screening

PubMed Central

Dinç, Imren; Pusey, Marc L.; Aygün, Ramazan S.

2016-01-01

The goal of protein crystallization screening is the determination of the main factors of importance to crystallizing the protein under investigation. One of the major issues about determining these factors is that screening is often expanded to many hundreds or thousands of conditions to maximize combinatorial chemical space coverage for maximizing the chances of a successful (crystalline) outcome. In this paper, we propose an experimental design method called “Associative Experimental Design (AED)” and an optimization method includes eliminating prohibited combinations and prioritizing reagents based on AED analysis of results from protein crystallization experiments. AED generates candidate cocktails based on these initial screening results. These results are analyzed to determine those screening factors in chemical space that are most likely to lead to higher scoring outcomes, crystals. We have tested AED on three proteins derived from the hyperthermophile Thermococcus thioreducens, and we applied an optimization method to these proteins. Our AED method generated novel cocktails (count provided in parentheses) leading to crystals for three proteins as follows: Nucleoside diphosphate kinase (4), HAD superfamily hydrolase (2), Nucleoside kinase (1). After getting promising results, we have tested our optimization method on four different proteins. The AED method with optimization yielded 4, 3, and 20 crystalline conditions for holo Human Transferrin, archaeal exosome protein, and Nucleoside diphosphate kinase, respectively. PMID:26955046

Mathematic model analysis of Gaussian beam propagation through an arbitrary thickness random phase screen.

PubMed

Tian, Yuzhen; Guo, Jin; Wang, Rui; Wang, Tingfeng

2011-09-12

In order to research the statistical properties of Gaussian beam propagation through an arbitrary thickness random phase screen for adaptive optics and laser communication application in the laboratory, we establish mathematic models of statistical quantities, which are based on the Rytov method and the thin phase screen model, involved in the propagation process. And the analytic results are developed for an arbitrary thickness phase screen based on the Kolmogorov power spectrum. The comparison between the arbitrary thickness phase screen and the thin phase screen shows that it is more suitable for our results to describe the generalized case, especially the scintillation index.

Advances in biosensor development for the screening of antibiotic residues in food products of animal origin - A comprehensive review.

PubMed

Gaudin, Valérie

2017-04-15

Antibiotic residues may be found in food of animal origin, since veterinary drugs are used for preventive and curative purposes to treat animals. The control of veterinary drug residues in food is necessary to ensure consumer safety. Screening methods are the first step in the control of antibiotic residues in food of animal origin. Conventional screening methods are based on different technologies, microbiological methods, immunological methods or physico-chemical methods (e.g. thin-layer chromatography, HPLC, LC-MS/MS). Screening methods should be simple, quick, inexpensive and specific, with low detection limits and high sample throughput. Biosensors can meet some of these requirements. Therefore, the development of biosensors for the screening of antibiotic residues has been increasing since the 1980s. The present review provides extensive and up-to-date findings on biosensors for the screening of antibiotic residues in food products of animal origin. Biosensors are constituted of a bioreceptor and a transducer. In the detection of antibiotic residues, even though antibodies were the first bioreceptors to be used, new kinds of bioreceptors are being developed more and more (enzymes, aptamers, MIPs); their advantages and drawbacks are discussed in this review. The different categories of transducers (electrochemical, mass-based biosensors, optical and thermal) and their potential applications for the screening of antibiotic residues in food are presented. Moreover, the advantages and drawbacks of the different types of transducers are discussed. Lastly, outlook and the future development of biosensors for the control of antibiotic residues in food are highlighted. Copyright © 2016. Published by Elsevier B.V.

Binding-Site Assessment by Virtual Fragment Screening

PubMed Central

Huang, Niu; Jacobson, Matthew P.

2010-01-01

The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules) would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock ∼11000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors. PMID:20404926

Development and application of hybrid structure based method for efficient screening of ligands binding to G-protein coupled receptors

NASA Astrophysics Data System (ADS)

Kortagere, Sandhya; Welsh, William J.

2006-12-01

G-protein coupled receptors (GPCRs) comprise a large superfamily of proteins that are targets for nearly 50% of drugs in clinical use today. In the past, the use of structure-based drug design strategies to develop better drug candidates has been severely hampered due to the absence of the receptor's three-dimensional structure. However, with recent advances in molecular modeling techniques and better computing power, atomic level details of these receptors can be derived from computationally derived molecular models. Using information from these models coupled with experimental evidence, it has become feasible to build receptor pharmacophores. In this study, we demonstrate the use of the Hybrid Structure Based (HSB) method that can be used effectively to screen and identify prospective ligands that bind to GPCRs. Essentially; this multi-step method combines ligand-based methods for building enriched libraries of small molecules and structure-based methods for screening molecules against the GPCR target. The HSB method was validated to identify retinal and its analogues from a random dataset of ˜300,000 molecules. The results from this study showed that the 9 top-ranking molecules are indeed analogues of retinal. The method was also tested to identify analogues of dopamine binding to the dopamine D2 receptor. Six of the ten top-ranking molecules are known analogues of dopamine including a prodrug, while the other thirty-four molecules are currently being tested for their activity against all dopamine receptors. The results from both these test cases have proved that the HSB method provides a realistic solution to bridge the gap between the ever-increasing demand for new drugs to treat psychiatric disorders and the lack of efficient screening methods for GPCRs.

Lead screening in DBS by solid sampling high-resolution continuum source graphite furnace atomic absorption spectrometry: application to newborns and pregnant women.

PubMed

Rello, Luis; Aramendía, Maite; Belarra, Miguel A; Resano, Martín

2015-01-01

DBS have become a clinical specimen especially adequate for establishing home-based collection protocols. In this work, high-resolution continuum source graphite furnace atomic absorption spectrometry is evaluated for the direct monitoring of Pb in DBS, both as a quantitative tool and a screening method. The development of the screening model is based on the establishment of the unreliability region around the threshold limits, 100 or 50 μg l(-1). More than 500 samples were analyzed to validate the model. The screening method demonstrated high sensitivity (the rate of true positives detected was always higher than 95%), an excellent LOD (1 µg l(-1)) and high throughput (10 min per sample).

Evaluation of dysphagia in early stroke patients by bedside, endoscopic, and electrophysiological methods.

PubMed

Umay, Ebru Karaca; Unlu, Ece; Saylam, Guleser Kılıc; Cakci, Aytul; Korkmaz, Hakan

2013-09-01

We aimed in this study to evaluate dysphagia in early stroke patients using a bedside screening test and flexible fiberoptic endoscopic evaluation of swallowing (FFEES) and electrophysiological evaluation (EE) methods and to compare the effectiveness of these methods. Twenty-four patients who were hospitalized in our clinic within the first 3 months after stroke were included in this study. Patients were evaluated using a bedside screening test [including bedside dysphagia score (BDS), neurological examination dysphagia score (NEDS), and total dysphagia score (TDS)] and FFEES and EE methods. Patients were divided into normal-swallowing and dysphagia groups according to the results of the evaluation methods. Patients with dysphagia as determined by any of these methods were compared to the patients with normal swallowing based on the results of the other two methods. Based on the results of our study, a high BDS was positively correlated with dysphagia identified by FFEES and EE methods. Moreover, the FFEES and EE methods were positively correlated. There was no significant correlation between NEDS and TDS levels and either EE or FFEES method. Bedside screening tests should be used mainly as an initial screening test; then FFEES and EE methods should be combined in patients who show risks. This diagnostic algorithm may provide a practical and fast solution for selected stroke patients.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers.

PubMed

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J; Brown, Powel H; Dannenberg, Andrew J; Szabo, Eva

2012-09-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. Published by Elsevier Inc.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers

PubMed Central

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J.; Brown, Powel H.; Dannenberg, Andrew J.; Szabo, Eva

2012-01-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. PMID:22771576

Quantum probability ranking principle for ligand-based virtual screening.

PubMed

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Quantum probability ranking principle for ligand-based virtual screening

NASA Astrophysics Data System (ADS)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Solid-phase assays for small molecule screening using sol-gel entrapped proteins.

PubMed

Lebert, Julie M; Forsberg, Erica M; Brennan, John D

2008-04-01

With compound libraries exceeding one million compounds, the ability to quickly and effectively screen these compounds against relevant pharmaceutical targets has become crucial. Solid-phase assays present several advantages over solution-based methods. For example, a higher degree of miniaturization can be achieved, functional- and affinity-based studies are possible, and a variety of detection methods can be used. Unfortunately, most protein immobilization methods are either too harsh or require recombinant proteins and thus are not amenable to delicate proteins such as kinases and membrane-bound receptors. Sol-gel encapsulation of proteins in an inorganic silica matrix has emerged as a novel solid-phase assay platform. In this minireview, we discuss the development of sol-gel derived protein microarrays and sol-gel based monolithic bioaffinity columns for the high-throughput screening of small molecule libraries and mixtures.

Next-generation libraries for robust RNA interference-based genome-wide screens

PubMed Central

Kampmann, Martin; Horlbeck, Max A.; Chen, Yuwen; Tsai, Jordan C.; Bassik, Michael C.; Gilbert, Luke A.; Villalta, Jacqueline E.; Kwon, S. Chul; Chang, Hyeshik; Kim, V. Narry; Weissman, Jonathan S.

2015-01-01

Genetic screening based on loss-of-function phenotypes is a powerful discovery tool in biology. Although the recent development of clustered regularly interspaced short palindromic repeats (CRISPR)-based screening approaches in mammalian cell culture has enormous potential, RNA interference (RNAi)-based screening remains the method of choice in several biological contexts. We previously demonstrated that ultracomplex pooled short-hairpin RNA (shRNA) libraries can largely overcome the problem of RNAi off-target effects in genome-wide screens. Here, we systematically optimize several aspects of our shRNA library, including the promoter and microRNA context for shRNA expression, selection of guide strands, and features relevant for postscreen sample preparation for deep sequencing. We present next-generation high-complexity libraries targeting human and mouse protein-coding genes, which we grouped into 12 sublibraries based on biological function. A pilot screen suggests that our next-generation RNAi library performs comparably to current CRISPR interference (CRISPRi)-based approaches and can yield complementary results with high sensitivity and high specificity. PMID:26080438

Screening Systems and Decision Making at the Preschool Level: Application of a Comprehensive Validity Framework

ERIC Educational Resources Information Center

Kettler, Ryan J.; Feeney-Kettler, Kelly A.

2011-01-01

Universal screening is designed to be an efficient method for identifying preschool students with mental health problems, but prior to use, screening systems must be evaluated to determine their appropriateness within a specific setting. In this article, an evidence-based validity framework is applied to four screening systems for identifying…

Mixture-based combinatorial libraries from small individual peptide libraries: a case study on α1-antitrypsin deficiency.

PubMed

Chang, Yi-Pin; Chu, Yen-Ho

2014-05-16

The design, synthesis and screening of diversity-oriented peptide libraries using a "libraries from libraries" strategy for the development of inhibitors of α1-antitrypsin deficiency are described. The major buttress of the biochemical approach presented here is the use of well-established solid-phase split-and-mix method for the generation of mixture-based libraries. The combinatorial technique iterative deconvolution was employed for library screening. While molecular diversity is the general consideration of combinatorial libraries, exquisite design through systematic screening of small individual libraries is a prerequisite for effective library screening and can avoid potential problems in some cases. This review will also illustrate how large peptide libraries were designed, as well as how a conformation-sensitive assay was developed based on the mechanism of the conformational disease. Finally, the combinatorially selected peptide inhibitor capable of blocking abnormal protein aggregation will be characterized by biophysical, cellular and computational methods.

Hierarchical virtual screening approaches in small molecule drug discovery.

PubMed

Kumar, Ashutosh; Zhang, Kam Y J

2015-01-01

Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Copyright © 2014 Elsevier Inc. All rights reserved.

Screening Tools to Estimate Mold Burdens in Homes

EPA Science Inventory

Objective: The objective of this study was to develop screening tools that could be used to estimate the mold burden in a home which would indicate whether more detailed testing might be useful. Methods: Previously, in the American Healthy Home Survey, a DNA-based method of an...

Applicability of a gene expression based prediction method to SD and Wistar rats: an example of CARCINOscreen®.

PubMed

Matsumoto, Hiroshi; Saito, Fumiyo; Takeyoshi, Masahiro

2015-12-01

Recently, the development of several gene expression-based prediction methods has been attempted in the fields of toxicology. CARCINOscreen® is a gene expression-based screening method to predict carcinogenicity of chemicals which target the liver with high accuracy. In this study, we investigated the applicability of the gene expression-based screening method to SD and Wistar rats by using CARCINOscreen®, originally developed with F344 rats, with two carcinogens, 2,4-diaminotoluen and thioacetamide, and two non-carcinogens, 2,6-diaminotoluen and sodium benzoate. After the 28-day repeated dose test was conducted with each chemical in SD and Wistar rats, microarray analysis was performed using total RNA extracted from each liver. Obtained gene expression data were applied to CARCINOscreen®. Predictive scores obtained by the CARCINOscreen® for known carcinogens were > 2 in all strains of rats, while non-carcinogens gave prediction scores below 0.5. These results suggested that the gene expression based screening method, CARCINOscreen®, can be applied to SD and Wistar rats, widely used strains in toxicological studies, by setting of an appropriate boundary line of prediction score to classify the chemicals into carcinogens and non-carcinogens.

A Quantum-Based Similarity Method in Virtual Screening.

PubMed

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2015-10-02

One of the most widely-used techniques for ligand-based virtual screening is similarity searching. This study adopted the concepts of quantum mechanics to present as state-of-the-art similarity method of molecules inspired from quantum theory. The representation of molecular compounds in mathematical quantum space plays a vital role in the development of quantum-based similarity approach. One of the key concepts of quantum theory is the use of complex numbers. Hence, this study proposed three various techniques to embed and to re-represent the molecular compounds to correspond with complex numbers format. The quantum-based similarity method that developed in this study depending on complex pure Hilbert space of molecules called Standard Quantum-Based (SQB). The recall of retrieved active molecules were at top 1% and top 5%, and significant test is used to evaluate our proposed methods. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Simulated virtual screening experiment show that the effectiveness of SQB method was significantly increased due to the role of representational power of molecular compounds in complex numbers forms compared to Tanimoto benchmark similarity measure.

Virtual screening of mandelate racemase mutants with enhanced activity based on binding energy in the transition state.

PubMed

Gu, Jiali; Liu, Min; Guo, Fei; Xie, Wenping; Lu, Wenqiang; Ye, Lidan; Chen, Zhirong; Yuan, Shenfeng; Yu, Hongwei

2014-02-05

Mandelate racemase (MR) is a promising candidate for the dynamic kinetic resolution of racemates. However, the poor activity of MR towards most of its non-natural substrates limits its widespread application. In this work, a virtual screening method based on the binding energy in the transition state was established to assist in the screening of MR mutants with enhanced catalytic efficiency. Using R-3-chloromandelic acid as a model substrate, a total of 53 mutants were constructed based on rational design in the two rounds of screening. The number of mutants for experimental validation was brought down to 17 by the virtual screening method, among which 14 variants turned out to possess improved catalytic efficiency. The variant V26I/Y54V showed 5.2-fold higher catalytic efficiency (k(cat)/K(m)) towards R-3-chloromandelic acid than that observed for the wild-type enzyme. Using this strategy, mutants were successfully obtained for two other substrates, R-mandelamide and R-2-naphthylglycolate (V26I and V29L, respectively), both with a 2-fold improvement in catalytic efficiency. These results demonstrated that this method could effectively predict the trend of mutational effects on catalysis. Analysis from the energetic and structural assays indicated that the enhanced interactions between the active sites and the substrate in the transition state led to improved catalytic efficiency. It was concluded that this virtual screening method based on the binding energy in the transition state was beneficial in enzyme rational redesign and helped to better understand the catalytic properties of the enzyme. Copyright © 2013 Elsevier Inc. All rights reserved.

In Vitro Toxicity Screening Technique for Volatile Substances Using Flow-Through System#

EPA Science Inventory

In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However the cha...

NMR screening in fragment-based drug design: a practical guide.

PubMed

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (<300-350 Da) and lower initial potency but higher ligand efficiency when compared to those from high-throughput screening. NMR spectroscopy has been widely used for FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

Smartphone-Based Hearing Screening in Noisy Environments

PubMed Central

Na, Youngmin; Joo, Hyo Sung; Yang, Hyejin; Kang, Soojin; Hong, Sung Hwa; Woo, Jihwan

2014-01-01

It is important and recommended to detect hearing loss as soon as possible. If it is found early, proper treatment may help improve hearing and reduce the negative consequences of hearing loss. In this study, we developed smartphone-based hearing screening methods that can ubiquitously test hearing. However, environmental noise generally results in the loss of ear sensitivity, which causes a hearing threshold shift (HTS). To overcome this limitation in the hearing screening location, we developed a correction algorithm to reduce the HTS effect. A built-in microphone and headphone were calibrated to provide the standard units of measure. The HTSs in the presence of either white or babble noise were systematically investigated to determine the mean HTS as a function of noise level. When the hearing screening application runs, the smartphone automatically measures the environmental noise and provides the HTS value to correct the hearing threshold. A comparison to pure tone audiometry shows that this hearing screening method in the presence of noise could closely estimate the hearing threshold. We expect that the proposed ubiquitous hearing test method could be used as a simple hearing screening tool and could alert the user if they suffer from hearing loss. PMID:24926692

Comparative effectiveness and acceptability of home-based and clinic-based sampling methods for sexually transmissible infections screening in females aged 14-50 years: a systematic review and meta-analysis.

PubMed

Odesanmi, Tolulope Y; Wasti, Sharada P; Odesanmi, Omolola S; Adegbola, Omololu; Oguntuase, Olubukola O; Mahmood, Sajid

2013-12-01

Home-based sampling is a strategy to enhance uptake of sexually transmissible infection (STI) screening. This review aimed to compare the screening uptake levels of home-based self-sampling and clinic-based specimen collection for STIs (chlamydia (Chlamydia trachomatis), gonorrhoea (Neisseria gonorrhoeae) and trichomoniasis) in females aged 14-50 years. Acceptability and effect on specimen quality were determined. Sixteen electronic databases were searched from inception to September 2012. Randomised controlled trials (RCTs) comparing the uptake levels of home-based self-sampling and clinic-based sampling for chlamydia, gonorrhoea and trichomoniasis in females aged 14-50 years were eligible for inclusion. The risk of bias in the trials was assessed. Risk ratios (RRs) for dichotomous outcomes were meta-analysed. Of 3065 papers, six studies with seven RCTs contributed to the final review. Compared with clinic-based methods, home-based screening increased uptake significantly (P=0.001-0.05) in five trials and was substantiated in a meta-analysis (RR: 1.55; 95% confidence interval: 1.30-1.85; P=0.00001) of two trials. In three trials, a significant preference for home-based testing (P=0.001-0.05) was expressed. No significant difference was observed in specimen quality. Sampling was rated as easy by a significantly higher number of women (P=0.01) in the clinic group in one trial. The review provides evidence that home-based testing results in greater uptake of STI screening in females (14-50 years) than clinic-based testing without compromising quality in the developed world. Home collection strategies should be added to clinic-based screening programs to enhance uptake.

Web-based depression screening and psychiatric consultation for college students: a feasibility and acceptability study.

PubMed

Williams, Aya; Larocca, Rachel; Chang, Trina; Trinh, Nhi-Ha; Fava, Maurizio; Kvedar, Joseph; Yeung, Albert

2014-01-01

Background. A steady rise in the prevalence of depression among college students has negatively affected student quality of life. This study investigates the feasibility and acceptability of a Web-based model, including Skype, to screen and provide psychiatric consultation to depressed college students. Methods. Students completed the 9-item Patient Health Questionnaire (PHQ-9) online; those who screened positive (PHQ-9 ≥ 10) or endorsed any level of suicidal ideation were offered Web-based psychiatric consultation using Skype. After the consultation, students filled out a 7-item satisfaction questionnaire to report on the acceptability of this Web-based method. Results. A total of 972 students consented to the online depression screening and 285 screened positive. Of those, 69 students consented and 17 students successfully completed the psychiatric consultation via Skype. Thirteen (76.4%) students found the interview useful in helping them understand their depression. Fifteen (88.2%) students thought that psychologists and psychiatrists could successfully see patients via videoconferencing. Conclusions. Current online technologies can provide depression screening and psychiatric consultation to college students; those who participated reported a positive experience. Future studies will need to address the low levels of participation among college students and attract students who are underserved, as well as use a videoconferencing platform that adequately protects data confidentiality.

Web-Based Depression Screening and Psychiatric Consultation for College Students: A Feasibility and Acceptability Study

PubMed Central

Williams, Aya; LaRocca, Rachel; Chang, Trina; Trinh, Nhi-Ha; Fava, Maurizio

2014-01-01

Background. A steady rise in the prevalence of depression among college students has negatively affected student quality of life. This study investigates the feasibility and acceptability of a Web-based model, including Skype, to screen and provide psychiatric consultation to depressed college students. Methods. Students completed the 9-item Patient Health Questionnaire (PHQ-9) online; those who screened positive (PHQ-9 ≥ 10) or endorsed any level of suicidal ideation were offered Web-based psychiatric consultation using Skype. After the consultation, students filled out a 7-item satisfaction questionnaire to report on the acceptability of this Web-based method. Results. A total of 972 students consented to the online depression screening and 285 screened positive. Of those, 69 students consented and 17 students successfully completed the psychiatric consultation via Skype. Thirteen (76.4%) students found the interview useful in helping them understand their depression. Fifteen (88.2%) students thought that psychologists and psychiatrists could successfully see patients via videoconferencing. Conclusions. Current online technologies can provide depression screening and psychiatric consultation to college students; those who participated reported a positive experience. Future studies will need to address the low levels of participation among college students and attract students who are underserved, as well as use a videoconferencing platform that adequately protects data confidentiality. PMID:24799895

In person versus Computer Screening for Intimate Partner Violence Among Pregnant Patients

PubMed Central

Dado, Diane; Schussler, Sara; Hawker, Lynn; Holland, Cynthia L.; Burke, Jessica G.; Cluss, Patricia A.

2012-01-01

Objective To compare in person versus computerized screening for intimate partner violence (IPV) in a hospital-based prenatal clinic and explore women’s assessment of the screening methods. Methods We compared patient IPV disclosures on a computerized questionnaire to audio-taped first obstetric visits with an obstetric care provider and performed semi-structured interviews with patient participants who reported experiencing IPV. Results Two-hundred and fifty patient participants and 52 provider participants were in the study. Ninety-one (36%) patients disclosed IPV either via computer or in person. Of those who disclosed IPV, 60 (66%) disclosed via both methods, but 31 (34%) disclosed IPV via only one of the two methods. Twenty-three women returned for interviews. They recommended using both types together. While computerized screening was felt to be non-judgmental and more anonymous, in person screening allowed for tailored questioning and more emotional connection with the provider. Conclusion Computerized screening allowed disclosure without fear of immediate judgment. In person screening allows more flexibility in wording of questions regarding IPV and opportunity for interpersonal rapport. Practice Implications Both computerized or self-completed screening and in person screening is recommended. Providers should address IPV using non-judgmental, descriptive language, include assessments for psychological IPV, and repeat screening in person, even if no patient disclosure occurs via computer. PMID:22770815

Computed Tomography Screening for Lung Cancer in the National Lung Screening Trial

PubMed Central

Black, William C.

2016-01-01

The National Lung Screening Trial (NLST) demonstrated that screening with low-dose CT versus chest radiography reduced lung cancer mortality by 16% to 20%. More recently, a cost-effectiveness analysis (CEA) of CT screening for lung cancer versus no screening in the NLST was performed. The CEA conformed to the reference-case recommendations of the US Panel on Cost-Effectiveness in Health and Medicine, including the use of the societal perspective and an annual discount rate of 3%. The CEA was based on several important assumptions. In this paper, I review the methods and assumptions used to obtain the base case estimate of $81,000 per quality-adjusted life-year gained. In addition, I show how this estimate varied widely among different subsets and when some of the base case assumptions were changed and speculate on the cost-effectiveness of CT screening for lung cancer outside the NLST. PMID:25635704

Pharmacy diabetes care program: analysis of two screening methods for undiagnosed type 2 diabetes in Australian community pharmacy.

PubMed

Krass, I; Mitchell, B; Clarke, P; Brillant, M; Dienaar, R; Hughes, J; Lau, P; Peterson, G; Stewart, K; Taylor, S; Wilkinson, J; Armour, C

2007-03-01

To compare the efficacy and cost-effectiveness of two methods of screening for undiagnosed type 2 diabetes in Australian community pharmacy. A random sample of 30 pharmacies were allocated into two groups: (i) tick test only (TTO); or (ii) sequential screening (SS) method. Both methods used the same initial risk assessment for type 2 diabetes. Subjects with one or more risk factors in the TTO group were offered a referral to their general practitioner (GP). Under the SS method, patients with risk factors were offered a capillary blood glucose test and those identified as being at risk referred to a GP. The effectiveness and cost-effectiveness of these approaches was assessed. A total of 1286 people were screened over a period of 3 months. The rate of diagnosis of diabetes was significantly higher for SS compared with the TTO method (1.7% versus 0.2%; p=0.008). The SS method resulted in fewer referrals to the GP and a higher uptake of referrals than the TTO method and so was the more cost-effective screening method. SS is the superior method from a cost and efficacy perspective. It should be considered as the preferred option for screening by community based pharmacists in Australia.

Molecular testing for familial hypercholesterolaemia-associated mutations in a UK-based cohort: development of an NGS-based method and comparison with multiplex polymerase chain reaction and oligonucleotide arrays.

PubMed

Reiman, Anne; Pandey, Sarojini; Lloyd, Kate L; Dyer, Nigel; Khan, Mike; Crockard, Martin; Latten, Mark J; Watson, Tracey L; Cree, Ian A; Grammatopoulos, Dimitris K

2016-11-01

Background Detection of disease-associated mutations in patients with familial hypercholesterolaemia is crucial for early interventions to reduce risk of cardiovascular disease. Screening for these mutations represents a methodological challenge since more than 1200 different causal mutations in the low-density lipoprotein receptor has been identified. A number of methodological approaches have been developed for screening by clinical diagnostic laboratories. Methods Using primers targeting, the low-density lipoprotein receptor, apolipoprotein B, and proprotein convertase subtilisin/kexin type 9, we developed a novel Ion Torrent-based targeted re-sequencing method. We validated this in a West Midlands-UK small cohort of 58 patients screened in parallel with other mutation-targeting methods, such as multiplex polymerase chain reaction (Elucigene FH20), oligonucleotide arrays (Randox familial hypercholesterolaemia array) or the Illumina next-generation sequencing platform. Results In this small cohort, the next-generation sequencing method achieved excellent analytical performance characteristics and showed 100% and 89% concordance with the Randox array and the Elucigene FH20 assay. Investigation of the discrepant results identified two cases of mutation misclassification of the Elucigene FH20 multiplex polymerase chain reaction assay. A number of novel mutations not previously reported were also identified by the next-generation sequencing method. Conclusions Ion Torrent-based next-generation sequencing can deliver a suitable alternative for the molecular investigation of familial hypercholesterolaemia patients, especially when comprehensive mutation screening for rare or unknown mutations is required.

Fragment screening by SPR and advanced application to GPCRs.

PubMed

Shepherd, Claire A; Hopkins, Andrew L; Navratilova, Iva

2014-01-01

Surface plasmon resonance (SPR) is one of the primary biophysical methods for the screening of low molecular weight 'fragment' libraries, due to its low protein consumption and 'label-free' methodology. SPR biosensor interaction analysis is employed to both screen and confirm the binding of compounds in fragment screening experiments, as it provides accurate information on the affinity and kinetics of molecular interactions. The most advanced application of the use of SPR for fragment screening is against membrane protein drug targets, such G-protein coupled receptors (GPCRs). Biophysical GPCR assays using SPR have been validated with pharmacological measurements approximate to cell-based methods, yet provide the advantage of biophysical methods in their ability to measure the weak affinities of low molecular weight fragments. A number of SPR fragment screens against GPCRs have now been disclosed in the literature. SPR fragment screening is proving versatile to screen both thermostabilised GPCRs and solubilised wild type receptors. In this chapter, we discuss the state-of-the-art in GPCR fragment screening by SPR and the technical considerations in performing such experiments. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Address entry while driving: speech recognition versus a touch-screen keyboard.

PubMed

Tsimhoni, Omer; Smith, Daniel; Green, Paul

2004-01-01

A driving simulator experiment was conducted to determine the effects of entering addresses into a navigation system during driving. Participants drove on roads of varying visual demand while entering addresses. Three address entry methods were explored: word-based speech recognition, character-based speech recognition, and typing on a touch-screen keyboard. For each method, vehicle control and task measures, glance timing, and subjective ratings were examined. During driving, word-based speech recognition yielded the shortest total task time (15.3 s), followed by character-based speech recognition (41.0 s) and touch-screen keyboard (86.0 s). The standard deviation of lateral position when performing keyboard entry (0.21 m) was 60% higher than that for all other address entry methods (0.13 m). Degradation of vehicle control associated with address entry using a touch screen suggests that the use of speech recognition is favorable. Speech recognition systems with visual feedback, however, even with excellent accuracy, are not without performance consequences. Applications of this research include the design of in-vehicle navigation systems as well as other systems requiring significant driver input, such as E-mail, the Internet, and text messaging.

mRAISE: an alternative algorithmic approach to ligand-based virtual screening

NASA Astrophysics Data System (ADS)

von Behren, Mathias M.; Bietz, Stefan; Nittinger, Eva; Rarey, Matthias

2016-08-01

Ligand-based virtual screening is a well established method to find new lead molecules in todays drug discovery process. In order to be applicable in day to day practice, such methods have to face multiple challenges. The most important part is the reliability of the results, which can be shown and compared in retrospective studies. Furthermore, in the case of 3D methods, they need to provide biologically relevant molecular alignments of the ligands, that can be further investigated by a medicinal chemist. Last but not least, they have to be able to screen large databases in reasonable time. Many algorithms for ligand-based virtual screening have been proposed in the past, most of them based on pairwise comparisons. Here, a new method is introduced called mRAISE. Based on structural alignments, it uses a descriptor-based bitmap search engine (RAISE) to achieve efficiency. Alignments created on the fly by the search engine get evaluated with an independent shape-based scoring function also used for ranking of compounds. The correct ranking as well as the alignment quality of the method are evaluated and compared to other state of the art methods. On the commonly used Directory of Useful Decoys dataset mRAISE achieves an average area under the ROC curve of 0.76, an average enrichment factor at 1 % of 20.2 and an average hit rate at 1 % of 55.5. With these results, mRAISE is always among the top performing methods with available data for comparison. To access the quality of the alignments calculated by ligand-based virtual screening methods, we introduce a new dataset containing 180 prealigned ligands for 11 diverse targets. Within the top ten ranked conformations, the alignment closest to X-ray structure calculated with mRAISE has a root-mean-square deviation of less than 2.0 Å for 80.8 % of alignment pairs and achieves a median of less than 2.0 Å for eight of the 11 cases. The dataset used to rate the quality of the calculated alignments is freely available at http://www.zbh.uni-hamburg.de/mraise-dataset.html. The table of all PDB codes contained in the ensembles can be found in the supplementary material. The software tool mRAISE is freely available for evaluation purposes and academic use (see http://www.zbh.uni-hamburg.de/raise).

Development and evaluation of nursing user interface screens using multiple methods.

PubMed

Hyun, Sookyung; Johnson, Stephen B; Stetson, Peter D; Bakken, Suzanne

2009-12-01

Building upon the foundation of the Structured Narrative Electronic Health Record (EHR) model, we applied theory-based (combined Technology Acceptance Model and Task-Technology Fit Model) and user-centered methods to explore nurses' perceptions of functional requirements for an electronic nursing documentation system, design user interface screens reflective of the nurses' perspectives, and assess nurses' perceptions of the usability of the prototype user interface screens. The methods resulted in user interface screens that were perceived to be easy to use, potentially useful, and well-matched to nursing documentation tasks associated with Nursing Admission Assessment, Blood Administration, and Nursing Discharge Summary. The methods applied in this research may serve as a guide for others wishing to implement user-centered processes to develop or extend EHR systems. In addition, some of the insights obtained in this study may be informative to the development of safe and efficient user interface screens for nursing document templates in EHRs.

Computationally assisted screening and design of cell-interactive peptides by a cell-based assay using peptide arrays and a fuzzy neural network algorithm.

PubMed

Kaga, Chiaki; Okochi, Mina; Tomita, Yasuyuki; Kato, Ryuji; Honda, Hiroyuki

2008-03-01

We developed a method of effective peptide screening that combines experiments and computational analysis. The method is based on the concept that screening efficiency can be enhanced from even limited data by use of a model derived from computational analysis that serves as a guide to screening and combining the model with subsequent repeated experiments. Here we focus on cell-adhesion peptides as a model application of this peptide-screening strategy. Cell-adhesion peptides were screened by use of a cell-based assay of a peptide array. Starting with the screening data obtained from a limited, random 5-mer library (643 sequences), a rule regarding structural characteristics of cell-adhesion peptides was extracted by fuzzy neural network (FNN) analysis. According to this rule, peptides with unfavored residues in certain positions that led to inefficient binding were eliminated from the random sequences. In the restricted, second random library (273 sequences), the yield of cell-adhesion peptides having an adhesion rate more than 1.5-fold to that of the basal array support was significantly high (31%) compared with the unrestricted random library (20%). In the restricted third library (50 sequences), the yield of cell-adhesion peptides increased to 84%. We conclude that a repeated cycle of experiments screening limited numbers of peptides can be assisted by the rule-extracting feature of FNN.

Efficient exploration of chemical space by fragment-based screening.

PubMed

Hall, Richard J; Mortenson, Paul N; Murray, Christopher W

2014-01-01

Screening methods seek to sample a vast chemical space in order to identify starting points for further chemical optimisation. Fragment based drug discovery exploits the superior sampling of chemical space that can be achieved when the molecular weight is restricted. Here we show that commercially available fragment space is still relatively poorly sampled and argue for highly sensitive screening methods to allow the detection of smaller fragments. We analyse the properties of our fragment library versus the properties of X-ray hits derived from the library. We particularly consider properties related to the degree of planarity of the fragments. Copyright © 2014 Elsevier Ltd. All rights reserved.

A spectrophotometric screening method for avermectin oxidizing microorganisms.

PubMed

Wang, Yuan-Shan; Hu, Qi-Wei; Zheng, Xing-Chang; Zhang, Jian-Fen; Zheng, Yu-Guo

2017-04-01

A spectrophotometric screening method for avermectin oxidizing microbes by determination of 4″-oxo-avermectin was established based on the reaction between 4″-oxo-avermectin and 2,4-dinitrophenylhydrazine. Combined with a gradient HPLC assay, microorganisms capable of regioselectively oxidizing avermectin to 4″-oxo-avermectin were successfully obtained by this method. Copyright © 2017 Elsevier B.V. All rights reserved.

A high-throughput AO/PI-based cell concentration and viability detection method using the Celigo image cytometry.

PubMed

Chan, Leo Li-Ying; Smith, Tim; Kumph, Kendra A; Kuksin, Dmitry; Kessel, Sarah; Déry, Olivier; Cribbes, Scott; Lai, Ning; Qiu, Jean

2016-10-01

To ensure cell-based assays are performed properly, both cell concentration and viability have to be determined so that the data can be normalized to generate meaningful and comparable results. Cell-based assays performed in immuno-oncology, toxicology, or bioprocessing research often require measuring of multiple samples and conditions, thus the current automated cell counter that uses single disposable counting slides is not practical for high-throughput screening assays. In the recent years, a plate-based image cytometry system has been developed for high-throughput biomolecular screening assays. In this work, we demonstrate a high-throughput AO/PI-based cell concentration and viability method using the Celigo image cytometer. First, we validate the method by comparing directly to Cellometer automated cell counter. Next, cell concentration dynamic range, viability dynamic range, and consistency are determined. The high-throughput AO/PI method described here allows for 96-well to 384-well plate samples to be analyzed in less than 7 min, which greatly reduces the time required for the single sample-based automated cell counter. In addition, this method can improve the efficiency for high-throughput screening assays, where multiple cell counts and viability measurements are needed prior to performing assays such as flow cytometry, ELISA, or simply plating cells for cell culture.

Practical Considerations for Optic Nerve Estimation in Telemedicine

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

Karnowski, Thomas Paul; Aykac, Deniz; Chaum, Edward

The projected increase in diabetes in the United States and worldwide has created a need for broad-based, inexpensive screening for diabetic retinopathy (DR), an eye disease which can lead to vision impairment. A telemedicine network with retina cameras and automated quality control, physiological feature location, and lesion / anomaly detection is a low-cost way of achieving broad-based screening. In this work we report on the effect of quality estimation on an optic nerve (ON) detection method with a confidence metric. We report on an improvement of the fusion technique using a data set from an ophthalmologists practice then show themore » results of the method as a function of image quality on a set of images from an on-line telemedicine network collected in Spring 2009 and another broad-based screening program. We show that the fusion method, combined with quality estimation processing, can improve detection performance and also provide a method for utilizing a physician-in-the-loop for images that may exceed the capabilities of automated processing.« less

HPPD: ligand- and target-based virtual screening on a herbicide target.

PubMed

López-Ramos, Miriam; Perruccio, Francesca

2010-05-24

Hydroxyphenylpyruvate dioxygenase (HPPD) has proven to be a very successful target for the development of herbicides with bleaching properties, and today HPPD inhibitors are well established in the agrochemical market. Syngenta has a long history of HPPD-inhibitor research, and HPPD was chosen as a case study for the validation of diverse ligand- and target-based virtual screening approaches to identify compounds with inhibitory properties. Two-dimensional extended connectivity fingerprints, three-dimensional shape-based tools (ROCS, EON, and Phase-shape) and a pharmacophore approach (Phase) were used as ligand-based methods; Glide and Gold were used as target-based. Both the virtual screening utility and the scaffold-hopping ability of the screening tools were assessed. Particular emphasis was put on the specific pitfalls to take into account for the design of a virtual screening campaign in an agrochemical context, as compared to a pharmaceutical environment.

Screen-viewing among preschoolers in childcare: a systematic review

PubMed Central

2014-01-01

Background Screen-viewing is one of the most common sedentary behaviors among preschoolers. Despite the high prevalence of sedentary behaviors in childcare, little research exists on the context and/or type of activities that account for these particular behaviors. Accordingly, if the amount of screen-viewing accumulated by preschoolers in childcare is not considered, researchers may be underestimating total screen time among this population, as only a portion of their day is being captured (i.e., the home environment). This systematic review provides a synthesis of research on the levels of screen-viewing among preschool-aged children (2.5-5 years) attending childcare (i.e., centre- and home-based childcare). This review also examined the correlates of screen-viewing among preschoolers in this setting. To provide additional contextual information, availability of screen activities was used to help ameliorate the understanding of preschoolers’ screen-viewing behaviors in childcare. Methods Twelve electronic databases were searched to retrieve relevant articles for inclusion (dating from 2000 onwards). Additional studies were identified via manual searching techniques (i.e., hand searching and citation tracking). Only English, published peer-reviewed articles that examined preschoolers’ screen-viewing behaviors in childcare (i.e., rates of screen-viewing and access to/opportunities for related activities) were included. No restrictions to study design were applied. Results Seventeen international studies (4 experimental; 12 cross-sectional; 1 mixed-methods) published between 2004 and 2014 were examined. Of those, eight studies reported rates of screen-viewing and found that preschoolers spent approximately 0.1 to 1.3 hrs/day and 1.8 to 2.4 hrs/day engaged in this behavior in center- and home-based childcare, respectively. High staff education (negative association) and type of childcare arrangement (notably, home-based childcare in comparison to center-based childcare; positive association) were identified as two correlates in relation to preschoolers’ screen-viewing in childcare. Nine studies spoke to the availability of screen-viewing activities in childcare, and found the childcare environment to be conducive to this behavior. Conclusions Despite some variability, preschoolers appear to engage in somewhat high levels of screen-viewing while in childcare, particularly within home-based facilities. This paper also highlighted the conduciveness of the childcare environment with regard to screen-viewing among preschoolers. Additional exploration into the correlates of screen-viewing in childcare is required. (PROSPORO registration: CRD42013005552). PMID:25129567

The East London glaucoma prediction score: web-based validation of glaucoma risk screening tool

PubMed Central

Stephen, Cook; Benjamin, Longo-Mbenza

2013-01-01

AIM It is difficult for Optometrists and General Practitioners to know which patients are at risk. The East London glaucoma prediction score (ELGPS) is a web based risk calculator that has been developed to determine Glaucoma risk at the time of screening. Multiple risk factors that are available in a low tech environment are assessed to provide a risk assessment. This is extremely useful in settings where access to specialist care is difficult. Use of the calculator is educational. It is a free web based service. Data capture is user specific. METHOD The scoring system is a web based questionnaire that captures and subsequently calculates the relative risk for the presence of Glaucoma at the time of screening. Three categories of patient are described: Unlikely to have Glaucoma; Glaucoma Suspect and Glaucoma. A case review methodology of patients with known diagnosis is employed to validate the calculator risk assessment. RESULTS Data from the patient records of 400 patients with an established diagnosis has been captured and used to validate the screening tool. The website reports that the calculated diagnosis correlates with the actual diagnosis 82% of the time. Biostatistics analysis showed: Sensitivity = 88%; Positive predictive value = 97%; Specificity = 75%. CONCLUSION Analysis of the first 400 patients validates the web based screening tool as being a good method of screening for the at risk population. The validation is ongoing. The web based format will allow a more widespread recruitment for different geographic, population and personnel variables. PMID:23550097

Fragment-based virtual screening approach and molecular dynamics simulation studies for identification of BACE1 inhibitor leads.

PubMed

Manoharan, Prabu; Ghoshal, Nanda

2018-05-01

Traditional structure-based virtual screening method to identify drug-like small molecules for BACE1 is so far unsuccessful. Location of BACE1, poor Blood Brain Barrier permeability and P-glycoprotein (Pgp) susceptibility of the inhibitors make it even more difficult. Fragment-based drug design method is suitable for efficient optimization of initial hit molecules for target like BACE1. We have developed a fragment-based virtual screening approach to identify/optimize the fragment molecules as a starting point. This method combines the shape, electrostatic, and pharmacophoric features of known fragment molecules, bound to protein conjugate crystal structure, and aims to identify both chemically and energetically feasible small fragment ligands that bind to BACE1 active site. The two top-ranked fragment hits were subjected for a 53 ns MD simulation. Principle component analysis and free energy landscape analysis reveal that the new ligands show the characteristic features of established BACE1 inhibitors. The potent method employed in this study may serve for the development of potential lead molecules for BACE1-directed Alzheimer's disease therapeutics.

Comparison of 2 resident learning tools-interactive screen-based simulated case scenarios versus problem-based learning discussions: a prospective quasi-crossover cohort study.

PubMed

Rajan, Shobana; Khanna, Ashish; Argalious, Maged; Kimatian, Stephen J; Mascha, Edward J; Makarova, Natalya; Nada, Eman M; Elsharkawy, Hesham; Firoozbakhsh, Farhad; Avitsian, Rafi

2016-02-01

Simulation-based learning is emerging as an alternative educational tool in this era of a relative shortfall of teaching anesthesiologists. The objective of the study is to assess whether screen-based (interactive computer simulated) case scenarios are more effective than problem-based learning discussions (PBLDs) in improving test scores 4 and 8 weeks after these interventions in anesthesia residents during their first neuroanesthesia rotation. Prospective, nonblinded quasi-crossover study. Cleveland Clinic. Anesthesiology residents. Two case scenarios were delivered from the Anesoft software as screen-based sessions, and parallel scripts were developed for 2 PBLDs. Each resident underwent both types of training sessions, starting with the PBLD session, and the 2 cases were alternated each month (ie, in 1 month, the screen-based intervention used case 1 and the PBLD used case 2, and vice versa for the next month). Test scores before the rotation (baseline), immediately after the rotation (4 weeks after the start of the rotation), and 8 weeks after the start of rotation were collected on each topic from each resident. The effect of training method on improvement in test scores was assessed using a linear mixed-effects model. Compared to the departmental standard of PBLD, the simulation method did not improve either the 4- or 8-week mean test scores (P = .41 and P = .40 for training method effect on 4- and 8-week scores, respectively). Resident satisfaction with the simulation module on a 5-point Likert scale showed subjective evidence of a positive impact on resident education. Screen-based simulators were not more effective than PBLD for education during the neuroanesthesia rotation in anesthesia residency. Copyright © 2016 Elsevier Inc. All rights reserved.

Testing the Untestable: A Vision Screening Program for Exceptional Children.

ERIC Educational Resources Information Center

Bishop, Virginia E.; Godolphin, Vivienne

Based on a longitudinal study of vision screening techniques for handicapped children at the Chester County (Pennsylvania) Child Development Center, the paper reports on the development of a battery of effective vision screening methods for children with low functioning handicapped children. Specific tests are described, including the Sheridan…

Optically Based Rapid Screening Method for Proven Optimal Treatment Strategies Before Treatment Begins

DTIC Science & Technology

to rapidly test /screen breast cancer therapeutics as a strategy to streamline drug development and provide individualized treatment. The results...system can therefore be used to streamline pre-clinical drug development, by reducing the number of animals , cost, and time required to screen new drugs

A simple and sensitive high-throughput GFP screening in woody and herbaceous plants.

PubMed

Hily, Jean-Michel; Liu, Zongrang

2009-03-01

Green fluorescent protein (GFP) has been used widely as a powerful bioluminescent reporter, but its visualization by existing methods in tissues or whole plants and its utilization for high-throughput screening remains challenging in many species. Here, we report a fluorescence image analyzer-based method for GFP detection and its utility for high-throughput screening of transformed plants. Of three detection methods tested, the Typhoon fluorescence scanner was able to detect GFP fluorescence in all Arabidopsis thaliana tissues and apple leaves, while regular fluorescence microscopy detected it only in Arabidopsis flowers and siliques but barely in the leaves of either Arabidopsis or apple. The hand-held UV illumination method failed in all tissues of both species. Additionally, the Typhoon imager was able to detect GFP fluorescence in both green and non-green tissues of Arabidopsis seedlings as well as in imbibed seeds, qualifying it as a high-throughput screening tool, which was further demonstrated by screening the seedlings of primary transformed T(0) seeds. Of the 30,000 germinating Arabidopsis seedlings screened, at least 69 GFP-positive lines were identified, accounting for an approximately 0.23% transformation efficiency. About 14,000 seedlings grown in 16 Petri plates could be screened within an hour, making the screening process significantly more efficient and robust than any other existing high-throughput screening method for transgenic plants.

A graft-based chemotherapy method for screening effective molecules and rescuing Huanglongbing (HLB)-affected citrus plants

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB), the most devastating disease of citrus worldwide, is associated with three species of fastidious and phloem-limited a-Proteobacteria in the genus of ‘Candidatus Liberibacter’. We previously reported a regeneration-based chemical screening system using periwinkle cuttings. In ...

Economic Evaluation of Screening Strategies Combined with HPV Vaccination of Preadolescent Girls for the Prevention of Cervical Cancer in Vientiane, Lao PDR.

PubMed

Chanthavilay, Phetsavanh; Reinharz, Daniel; Mayxay, Mayfong; Phongsavan, Keokedthong; Marsden, Donald E; Moore, Lynne; White, Lisa J

2016-01-01

Several approaches to reduce the incidence of invasive cervical cancers exist. The approach adopted should take into account contextual factors that influence the cost-effectiveness of the available options. To determine the cost-effectiveness of screening strategies combined with a vaccination program for 10-year old girls for cervical cancer prevention in Vientiane, Lao PDR. A population-based dynamic compartment model was constructed. The interventions consisted of a 10-year old girl vaccination program only, or this program combined with screening strategies, i.e., visual inspection with acetic acid (VIA), cytology-based screening, rapid human papillomavirus (HPV) DNA testing, or combined VIA and cytology testing. Simulations were run over 100 years. In base-case scenario analyses, we assumed a 70% vaccination coverage with lifelong protection and a 50% screening coverage. The outcome of interest was the incremental cost per Disability-Adjusted Life Year (DALY) averted. In base-case scenarios, compared to the next best strategy, the model predicted that VIA screening of women aged 30-65 years old every three years, combined with vaccination, was the most attractive option, costing 2 544 international dollars (I$) per DALY averted. Meanwhile, rapid HPV DNA testing was predicted to be more attractive than cytology-based screening or its combination with VIA. Among cytology-based screening options, combined VIA with conventional cytology testing was predicted to be the most attractive option. Multi-way sensitivity analyses did not change the results. Compared to rapid HPV DNA testing, VIA had a probability of cost-effectiveness of 73%. Compared to the vaccination only option, the probability that a program consisting of screening women every five years would be cost-effective was around 60% and 80% if the willingness-to-pay threshold is fixed at one and three GDP per capita, respectively. A VIA screening program in addition to a girl vaccination program was predicted to be the most attractive option in the health care context of Lao PDR. When compared with other screening methods, VIA was the primary recommended method for combination with vaccination in Lao PDR.

Understanding wax screen-printing: a novel patterning process for microfluidic cloth-based analytical devices.

PubMed

Liu, Min; Zhang, Chunsun; Liu, Feifei

2015-09-03

In this work, we first introduce the fabrication of microfluidic cloth-based analytical devices (μCADs) using a wax screen-printing approach that is suitable for simple, inexpensive, rapid, low-energy-consumption and high-throughput preparation of cloth-based analytical devices. We have carried out a detailed study on the wax screen-printing of μCADs and have obtained some interesting results. Firstly, an analytical model is established for the spreading of molten wax in cloth. Secondly, a new wax screen-printing process has been proposed for fabricating μCADs, where the melting of wax into the cloth is much faster (∼5 s) and the heating temperature is much lower (75 °C). Thirdly, the experimental results show that the patterning effects of the proposed wax screen-printing method depend to a certain extent on types of screens, wax melting temperatures and melting time. Under optimized conditions, the minimum printing width of hydrophobic wax barrier and hydrophilic channel is 100 μm and 1.9 mm, respectively. Importantly, the developed analytical model is also well validated by these experiments. Fourthly, the μCADs fabricated by the presented wax screen-printing method are used to perform a proof-of-concept assay of glucose or protein in artificial urine with rapid high-throughput detection taking place on a 48-chamber cloth-based device and being performed by a visual readout. Overall, the developed cloth-based wax screen-printing and arrayed μCADs should provide a new research direction in the development of advanced sensor arrays for detection of a series of analytes relevant to many diverse applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications.

PubMed

Xu, Feng; Wu, JinHui; Wang, ShuQi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

2011-09-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

Microengineering Methods for Cell Based Microarrays and High-Throughput Drug Screening Applications

PubMed Central

Xu, Feng; Wu, JinHui; Wang, ShuQi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

2011-01-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time-consuming and often face ethical concerns due to extensive use of animals. To improve cost-effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems have facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell based drug-screening models, which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell based drug screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds a great potential to provide repeatable 3D cell based constructs with high temporal, spatial control and versatility. PMID:21725152

Fabricating Simple Wax Screen-Printing Paper-Based Analytical Devices to Demonstrate the Concept of Limiting Reagent in Acid- Base Reactions

ERIC Educational Resources Information Center

Namwong, Pithakpong; Jarujamrus, Purim; Amatatongchai, Maliwan; Chairam, Sanoe

2018-01-01

In this article, a low-cost, simple, and rapid fabrication of paper-based analytical devices (PADs) using a wax screen-printing method is reported here. The acid-base reaction is implemented in the simple PADs to demonstrate to students the chemistry concept of a limiting reagent. When a fixed concentration of base reacts with a gradually…

Virtual Screening with AutoDock: Theory and Practice

PubMed Central

Cosconati, Sandro; Forli, Stefano; Perryman, Alex L.; Harris, Rodney; Goodsell, David S.; Olson, Arthur J.

2011-01-01

Importance to the field Virtual screening is a computer-based technique for identifying promising compounds to bind to a target molecule of known structure. Given the rapidly increasing number of protein and nucleic acid structures, virtual screening continues to grow as an effective method for the discovery of new inhibitors and drug molecules. Areas covered in this review We describe virtual screening methods that are available in the AutoDock suite of programs, and several of our successes in using AutoDock virtual screening in pharmaceutical lead discovery. What the reader will gain A general overview of the challenges of virtual screening is presented, along with the tools available in the AutoDock suite of programs for addressing these challenges. Take home message Virtual screening is an effective tool for the discovery of compounds for use as leads in drug discovery, and the free, open source program AutoDock is an effective tool for virtual screening. PMID:21532931

Comparison of cytology, HPV DNA testing and HPV 16/18 genotyping alone or combined targeting to the more balanced methodology for cervical cancer screening.

PubMed

Chatzistamatiou, Kimon; Moysiadis, Theodoros; Moschaki, Viktoria; Panteleris, Nikolaos; Agorastos, Theodoros

2016-07-01

The objective of the present study was to identify the most effective cervical cancer screening algorithm incorporating different combinations of cytology, HPV testing and genotyping. Women 25-55years old recruited for the "HERMES" (HEllenic Real life Multicentric cErvical Screening) study were screened in terms of cytology and high-risk (hr) HPV testing with HPV 16/18 genotyping. Women positive for cytology or/and hrHPV were referred for colposcopy, biopsy and treatment. Ten screening algorithms based on different combinations of cytology, HPV testing and HPV 16/18 genotyping were investigated in terms of diagnostic accuracy. Three clusters of algorithms were formed according to the balance between effectiveness and harm caused by screening. The cluster showing the best balance included two algorithms based on co-testing and two based on HPV primary screening with HPV 16/18 genotyping. Among these, hrHPV testing with HPV 16/18 genotyping and reflex cytology (atypical squamous cells of undetermined significance - ASCUS threshold) presented the optimal combination of sensitivity (82.9%) and specificity relative to cytology alone (0.99) with 1.26 false positive rate relative to cytology alone. HPV testing with HPV 16/18 genotyping, referring HPV 16/18 positive women directly to colposcopy, and hrHPV (non 16/18) positive women to reflex cytology (ASCUS threshold), as a triage method to colposcopy, reflects the best equilibrium between screening effectiveness and harm. Algorithms, based on cytology as initial screening method, on co-testing or HPV primary without genotyping, and on HPV primary with genotyping but without cytology triage, are not supported according to the present analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Colorimetric micro-assay for accelerated screening of mould inhibitors

Treesearch

Carol A. Clausen; Vina W. Yang

2013-01-01

Since current standard laboratory methods are time-consuming macro-assays that rely on subjective visual ratings of mould growth, rapid and quantitative laboratory methods are needed to screen potential mould inhibitors for use in and on cellulose-based products. A colorimetric micro-assay has been developed that uses XTT tetrazolium salt to enzymatically assess...

Applying under-sampling techniques and cost-sensitive learning methods on risk assessment of breast cancer.

PubMed

Hsu, Jia-Lien; Hung, Ping-Cheng; Lin, Hung-Yen; Hsieh, Chung-Ho

2015-04-01

Breast cancer is one of the most common cause of cancer mortality. Early detection through mammography screening could significantly reduce mortality from breast cancer. However, most of screening methods may consume large amount of resources. We propose a computational model, which is solely based on personal health information, for breast cancer risk assessment. Our model can be served as a pre-screening program in the low-cost setting. In our study, the data set, consisting of 3976 records, is collected from Taipei City Hospital starting from 2008.1.1 to 2008.12.31. Based on the dataset, we first apply the sampling techniques and dimension reduction method to preprocess the testing data. Then, we construct various kinds of classifiers (including basic classifiers, ensemble methods, and cost-sensitive methods) to predict the risk. The cost-sensitive method with random forest classifier is able to achieve recall (or sensitivity) as 100 %. At the recall of 100 %, the precision (positive predictive value, PPV), and specificity of cost-sensitive method with random forest classifier was 2.9 % and 14.87 %, respectively. In our study, we build a breast cancer risk assessment model by using the data mining techniques. Our model has the potential to be served as an assisting tool in the breast cancer screening.

Prostate-Specific Antigen (PSA)–Based Population Screening for Prostate Cancer: An Economic Analysis

PubMed Central

Tawfik, A

2015-01-01

Background The prostate-specific antigen (PSA) blood test has become widely used in Canada to test for prostate cancer (PC), the most common cancer among Canadian men. Data suggest that population-based PSA screening may not improve overall survival. Objectives This analysis aimed to review existing economic evaluations of population-based PSA screening, determine current spending on opportunistic PSA screening in Ontario, and estimate the cost of introducing a population-based PSA screening program in the province. Methods A systematic literature search was performed to identify economic evaluations of population-based PSA screening strategies published from 1998 to 2013. Studies were assessed for their methodological quality and applicability to the Ontario setting. An original cost analysis was also performed, using data from Ontario administrative sources and from the published literature. One-year costs were estimated for 4 strategies: no screening, current (opportunistic) screening of men aged 40 years and older, current (opportunistic) screening of men aged 50 to 74 years, and population-based screening of men aged 50 to 74 years. The analysis was conducted from the payer perspective. Results The literature review demonstrated that, overall, population-based PSA screening is costly and cost-ineffective but may be cost-effective in specific populations. Only 1 Canadian study, published 15 years ago, was identified. Approximately $119.2 million is being spent annually on PSA screening of men aged 40 years and older in Ontario, including close to $22 million to screen men younger than 50 and older than 74 years of age (i.e., outside the target age range for a population-based program). A population-based screening program in Ontario would cost approximately $149.4 million in the first year. Limitations Estimates were based on the synthesis of data from a variety of sources, requiring several assumptions and causing uncertainty in the results. For example, where Ontario-specific data were unavailable, data from the United States were used. Conclusions PSA screening is associated with significant costs to the health care system when the cost of the PSA test itself is considered in addition to the costs of diagnosis, staging, and treatment of screen-detected PCs. PMID:26366237

Multi-modality image registration for effective thermographic fever screening

NASA Astrophysics Data System (ADS)

Dwith, C. Y. N.; Ghassemi, Pejhman; Pfefer, Joshua; Casamento, Jon; Wang, Quanzeng

2017-02-01

Fever screening based on infrared thermographs (IRTs) is a viable mass screening approach during infectious disease pandemics, such as Ebola and Severe Acute Respiratory Syndrome (SARS), for temperature monitoring in public places like hospitals and airports. IRTs have been found to be powerful, quick and non-invasive methods for detecting elevated temperatures. Moreover, regions medially adjacent to the inner canthi (called the canthi regions in this paper) are preferred sites for fever screening. Accurate localization of the canthi regions can be achieved through multi-modality registration of infrared (IR) and white-light images. Here we propose a registration method through a coarse-fine registration strategy using different registration models based on landmarks and edge detection on eye contours. We have evaluated the registration accuracy to be within +/- 2.7 mm, which enables accurate localization of the canthi regions.

Cost-effectiveness analysis of colorectal cancer screening methods in Iran.

PubMed

Allameh, Zahra; Davari, Majid; Emami, Mohammad Hasan

2011-03-01

Screening can prevent colorectal cancer from becoming advanced by early detection of precancerous lesions. Cost-effectiveness analysis of colorectal cancer screening methods is highly necessary due to increased prevalence, decreased age at onset and the limited budget in Iran. Methods of screening currently available in Iran were selected. A systematic search revealed the sensitivity and specificity of each method. For this study, a model for a 20 year screening period of a population of 100,000 apparently healthy persons of ages 45-65 years in Isfahan Province was used. The cost-effectiveness of each method and the ratio of cost-effectiveness were calculated based on this model. The most and the least effective methods were CT colonography and fecal occult blood test, respectively. The highest and lowest expenditures in the governmental sector were related to fecal occult blood test and flexible sigmoidoscopy and in the private sector, to CT colonography and fecal occult blood test, respectively. The cost per cancer detected in 20 years of screening in the governmental sector was 0.28, 0.22 and 0.42 billion Rials, respectively for screening by colonoscopy, flexible sigmoidoscopy and fecal occult blood test. In the private sector, these were 1.54 (colonoscopy), 1.68 (flexible sigmoidoscopy), and 1.60 (fecal occult blood test) billion and 2.58 billion Rials for CT colonography, respectively. Although CT colonography is the most effective method, it needs a budget of 2.58 billion Rials for each screened patient. If costs in the governmental sector are considered, flexible sigmoidoscopy would be the most cost-effective method for screening the 45 - 65-year-old population in Iran.

A high throughput screen for biomining cellulase activity from metagenomic libraries.

PubMed

Mewis, Keith; Taupp, Marcus; Hallam, Steven J

2011-02-01

Cellulose, the most abundant source of organic carbon on the planet, has wide-ranging industrial applications with increasing emphasis on biofuel production (1). Chemical methods to modify or degrade cellulose typically require strong acids and high temperatures. As such, enzymatic methods have become prominent in the bioconversion process. While the identification of active cellulases from bacterial and fungal isolates has been somewhat effective, the vast majority of microbes in nature resist laboratory cultivation. Environmental genomic, also known as metagenomic, screening approaches have great promise in bridging the cultivation gap in the search for novel bioconversion enzymes. Metagenomic screening approaches have successfully recovered novel cellulases from environments as varied as soils (2), buffalo rumen (3) and the termite hind-gut (4) using carboxymethylcellulose (CMC) agar plates stained with congo red dye (based on the method of Teather and Wood (5)). However, the CMC method is limited in throughput, is not quantitative and manifests a low signal to noise ratio (6). Other methods have been reported (7,8) but each use an agar plate-based assay, which is undesirable for high-throughput screening of large insert genomic libraries. Here we present a solution-based screen for cellulase activity using a chromogenic dinitrophenol (DNP)-cellobioside substrate (9). Our library was cloned into the pCC1 copy control fosmid to increase assay sensitivity through copy number induction (10). The method uses one-pot chemistry in 384-well microplates with the final readout provided as an absorbance measurement. This readout is quantitative, sensitive and automated with a throughput of up to 100X 384-well plates per day using a liquid handler and plate reader with attached stacking system.

Enhanced HTS hit selection via a local hit rate analysis.

PubMed

Posner, Bruce A; Xi, Hualin; Mills, James E J

2009-10-01

The postprocessing of high-throughput screening (HTS) results is complicated by the occurrence of false positives (inactive compounds misidentified as active by the primary screen) and false negatives (active compounds misidentified as inactive by the primary screen). An activity cutoff is frequently used to select "active" compounds from HTS data; however, this approach is insensitive to both false positives and false negatives. An alternative method that can minimize the occurrence of these artifacts will increase the efficiency of hit selection and therefore lead discovery. In this work, rather than merely using the activity of a given compound, we look at the presence and absence of activity among all compounds in its "chemical space neighborhood" to give a degree of confidence in its activity. We demonstrate that this local hit rate (LHR) analysis method outperforms hit selection based on ranking by primary screen activity values across ten diverse high throughput screens, spanning both cell-based and biochemical assay formats of varying biology and robustness. On average, the local hit rate analysis method was approximately 2.3-fold and approximately 1.3-fold more effective in identifying active compounds and active chemical series, respectively, than selection based on primary activity alone. Moreover, when applied to finding false negatives, this method was 2.3-fold better than ranking by primary activity alone. In most cases, novel hit series were identified that would have otherwise been missed. Additional uses of and observations regarding this HTS analysis approach are also discussed.

A Comparison of Protein Kinases Inhibitor Screening Methods Using Both Enzymatic Activity and Binding Affinity Determination

PubMed Central

Rudolf, Amalie Frederikke; Skovgaard, Tine; Knapp, Stefan; Jensen, Lars Juhl; Berthelsen, Jens

2014-01-01

Binding assays are increasingly used as a screening method for protein kinase inhibitors; however, as yet only a weak correlation with enzymatic activity-based assays has been demonstrated. We show that the correlation between the two types of assays can be improved using more precise screening conditions. Furthermore a marked improvement in the correlation was found by using kinase constructs containing the catalytic domain in presence of additional domains or subunits. PMID:24915177

Quantitative digital image analysis of chromogenic assays for high throughput screening of alpha-amylase mutant libraries.

PubMed

Shankar, Manoharan; Priyadharshini, Ramachandran; Gunasekaran, Paramasamy

2009-08-01

An image analysis-based method for high throughput screening of an alpha-amylase mutant library using chromogenic assays was developed. Assays were performed in microplates and high resolution images of the assay plates were read using the Virtual Microplate Reader (VMR) script to quantify the concentration of the chromogen. This method is fast and sensitive in quantifying 0.025-0.3 mg starch/ml as well as 0.05-0.75 mg glucose/ml. It was also an effective screening method for improved alpha-amylase activity with a coefficient of variance of 18%.

A high-throughput liquid bead array-based screening technology for Bt presence in GMO manipulation.

PubMed

Fu, Wei; Wang, Huiyu; Wang, Chenguang; Mei, Lin; Lin, Xiangmei; Han, Xueqing; Zhu, Shuifang

2016-03-15

The number of species and planting areas of genetically modified organisms (GMOs) has been rapidly developed during the past ten years. For the purpose of GMO inspection, quarantine and manipulation, we have now devised a high-throughput Bt-based GMOs screening method based on the liquid bead array. This novel method is based on the direct competitive recognition between biotinylated antibodies and beads-coupled antigens, searching for Bt presence in samples if it contains Bt Cry1 Aa, Bt Cry1 Ab, Bt Cry1 Ac, Bt Cry1 Ah, Bt Cry1 B, Bt Cry1 C, Bt Cry1 F, Bt Cry2 A, Bt Cry3 or Bt Cry9 C. Our method has a wide GMO species coverage so that more than 90% of the whole commercialized GMO species can be identified throughout the world. Under our optimization, specificity, sensitivity, repeatability and availability validation, the method shows a high specificity and 10-50 ng/mL sensitivity of quantification. We then assessed more than 1800 samples in the field and food market to prove capacity of our method in performing a high throughput screening work for GMO manipulation. Our method offers an applicant platform for further inspection and research on GMO plants. Copyright © 2015 Elsevier B.V. All rights reserved.

Single-cell analysis of population context advances RNAi screening at multiple levels

PubMed Central

Snijder, Berend; Sacher, Raphael; Rämö, Pauli; Liberali, Prisca; Mench, Karin; Wolfrum, Nina; Burleigh, Laura; Scott, Cameron C; Verheije, Monique H; Mercer, Jason; Moese, Stefan; Heger, Thomas; Theusner, Kristina; Jurgeit, Andreas; Lamparter, David; Balistreri, Giuseppe; Schelhaas, Mario; De Haan, Cornelis A M; Marjomäki, Varpu; Hyypiä, Timo; Rottier, Peter J M; Sodeik, Beate; Marsh, Mark; Gruenberg, Jean; Amara, Ali; Greber, Urs; Helenius, Ari; Pelkmans, Lucas

2012-01-01

Isogenic cells in culture show strong variability, which arises from dynamic adaptations to the microenvironment of individual cells. Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image-based RNAi screens. We developed a comprehensive computational approach that employs Bayesian and multivariate methods at the single-cell level. We applied these methods to 45 RNA interference screens of various sizes, including 7 druggable genome and 2 genome-wide screens, analysing 17 different mammalian virus infections and four related cell physiological processes. Analysing cell-based screens at this depth reveals widespread RNAi-induced changes in the population context of individual cells leading to indirect RNAi effects, as well as perturbations of cell-to-cell variability regulators. We find that accounting for indirect effects improves the consistency between siRNAs targeted against the same gene, and between replicate RNAi screens performed in different cell lines, in different labs, and with different siRNA libraries. In an era where large-scale RNAi screens are increasingly performed to reach a systems-level understanding of cellular processes, we show that this is often improved by analyses that account for and incorporate the single-cell microenvironment. PMID:22531119

Screening of a Brassica napus bacterial artificial chromosome library using highly parallel single nucleotide polymorphism assays

PubMed Central

2013-01-01

Background Efficient screening of bacterial artificial chromosome (BAC) libraries with polymerase chain reaction (PCR)-based markers is feasible provided that a multidimensional pooling strategy is implemented. Single nucleotide polymorphisms (SNPs) can be screened in multiplexed format, therefore this marker type lends itself particularly well for medium- to high-throughput applications. Combining the power of multiplex-PCR assays with a multidimensional pooling system may prove to be especially challenging in a polyploid genome. In polyploid genomes two classes of SNPs need to be distinguished, polymorphisms between accessions (intragenomic SNPs) and those differentiating between homoeologous genomes (intergenomic SNPs). We have assessed whether the highly parallel Illumina GoldenGate® Genotyping Assay is suitable for the screening of a BAC library of the polyploid Brassica napus genome. Results A multidimensional screening platform was developed for a Brassica napus BAC library which is composed of almost 83,000 clones. Intragenomic and intergenomic SNPs were included in Illumina’s GoldenGate® Genotyping Assay and both SNP classes were used successfully for screening of the multidimensional BAC pools of the Brassica napus library. An optimized scoring method is proposed which is especially valuable for SNP calling of intergenomic SNPs. Validation of the genotyping results by independent methods revealed a success of approximately 80% for the multiplex PCR-based screening regardless of whether intra- or intergenomic SNPs were evaluated. Conclusions Illumina’s GoldenGate® Genotyping Assay can be efficiently used for screening of multidimensional Brassica napus BAC pools. SNP calling was specifically tailored for the evaluation of BAC pool screening data. The developed scoring method can be implemented independently of plant reference samples. It is demonstrated that intergenomic SNPs represent a powerful tool for BAC library screening of a polyploid genome. PMID:24010766

Microfluidics for cell-based high throughput screening platforms - A review.

PubMed

Du, Guansheng; Fang, Qun; den Toonder, Jaap M J

2016-01-15

In the last decades, the basic techniques of microfluidics for the study of cells such as cell culture, cell separation, and cell lysis, have been well developed. Based on cell handling techniques, microfluidics has been widely applied in the field of PCR (Polymerase Chain Reaction), immunoassays, organ-on-chip, stem cell research, and analysis and identification of circulating tumor cells. As a major step in drug discovery, high-throughput screening allows rapid analysis of thousands of chemical, biochemical, genetic or pharmacological tests in parallel. In this review, we summarize the application of microfluidics in cell-based high throughput screening. The screening methods mentioned in this paper include approaches using the perfusion flow mode, the droplet mode, and the microarray mode. We also discuss the future development of microfluidic based high throughput screening platform for drug discovery. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of an ELA-DRA gene typing method based on pyrosequencing technology.

PubMed

Díaz, S; Echeverría, M G; It, V; Posik, D M; Rogberg-Muñoz, A; Pena, N L; Peral-García, P; Vega-Pla, J L; Giovambattista, G

2008-11-01

The polymorphism of equine lymphocyte antigen (ELA) class II DRA gene had been detected by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and reference strand-mediated conformation analysis. These methodologies allowed to identify 11 ELA-DRA exon 2 sequences, three of which are widely distributed among domestic horse breeds. Herein, we describe the development of a pyrosequencing-based method applicable to ELA-DRA typing, by screening samples from eight different horse breeds previously typed by PCR-SSCP. This sequence-based method would be useful in high-throughput genotyping of major histocompatibility complex genes in horses and other animal species, making this system interesting as a rapid screening method for animal genotyping of immune-related genes.

Screening of the key volatile organic compounds of Tuber melanosporum fermentation by aroma sensory evaluation combination with principle component analysis

PubMed Central

Liu, Rui-Sang; Jin, Guang-Huai; Xiao, Deng-Rong; Li, Hong-Mei; Bai, Feng-Wu; Tang, Ya-Jie

2015-01-01

Aroma results from the interplay of volatile organic compounds (VOCs) and the attributes of microbial-producing aromas are significantly affected by fermentation conditions. Among the VOCs, only a few of them contribute to aroma. Thus, screening and identification of the key VOCs is critical for microbial-producing aroma. The traditional method is based on gas chromatography-olfactometry (GC-O), which is time-consuming and laborious. Considering the Tuber melanosporum fermentation system as an example, a new method to screen and identify the key VOCs by combining the aroma evaluation method with principle component analysis (PCA) was developed in this work. First, an aroma sensory evaluation method was developed to screen 34 potential favorite aroma samples from 504 fermentation samples. Second, PCA was employed to screen nine common key VOCs from these 34 samples. Third, seven key VOCs were identified by the traditional method. Finally, all of the seven key VOCs identified by the traditional method were also identified, along with four others, by the new strategy. These results indicate the reliability of the new method and demonstrate it to be a viable alternative to the traditional method. PMID:26655663

Study on the millimeter-wave scale absorber based on the Salisbury screen

NASA Astrophysics Data System (ADS)

Yuan, Liming; Dai, Fei; Xu, Yonggang; Zhang, Yuan

2018-03-01

In order to solve the problem on the millimeter-wave scale absorber, the Salisbury screen absorber is employed and designed based on the RL. By optimizing parameters including the sheet resistance of the surface resistive layer, the permittivity and the thickness of the grounded dielectric layer, the RL of the Salisbury screen absorber could be identical with that of the theoretical scale absorber. An example is given to verify the effectiveness of the method, where the Salisbury screen absorber is designed by the proposed method and compared with the theoretical scale absorber. Meanwhile, plate models and tri-corner reflector (TCR) models are constructed according to the designed result and their scattering properties are simulated by FEKO. Results reveal that the deviation between the designed Salisbury screen absorber and the theoretical scale absorber falls within the tolerance of radar Cross section (RCS) measurement. The work in this paper has important theoretical and practical significance in electromagnetic measurement of large scale ratio.

24 CFR 35.1320 - Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and...

Code of Federal Regulations, 2010 CFR

2010-04-01

... POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and reevaluations. 35.1320 Section 35.1320 Housing and...

24 CFR 35.1320 - Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and...

Code of Federal Regulations, 2014 CFR

2014-04-01

... POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and reevaluations. 35.1320 Section 35.1320 Housing and...

24 CFR 35.1320 - Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and...

Code of Federal Regulations, 2013 CFR

2013-04-01

... POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and reevaluations. 35.1320 Section 35.1320 Housing and...

24 CFR 35.1320 - Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and...

Code of Federal Regulations, 2012 CFR

2012-04-01

... POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and reevaluations. 35.1320 Section 35.1320 Housing and...

24 CFR 35.1320 - Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and...

Code of Federal Regulations, 2011 CFR

2011-04-01

... POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Lead-based paint inspections, paint testing, risk assessments, lead-hazard screens, and reevaluations. 35.1320 Section 35.1320 Housing and...

Barriers to Breast and Cervical Cancer Screening in Singapore: a Mixed Methods Analysis.

PubMed

Malhotra, Chetna; Bilger, Marcel; Liu, Joy; Finkelstein, Eric

2016-01-01

In order to increase breast and cervical cancer screening uptake in Singapore, women's perceived barriers to screening need to be identified and overcome. Using data from both focus groups and surveys, we aimed to assess perceived barriers and motivations for breast and cervical cancer screening. We conducted 8 focus groups with 64 women, using thematic analysis to identify overarching themes related to women's attitudes towards screening. Based on recurring themes from focus groups, several hypotheses regarding potential barriers and motivations to screen were generated and tested through a national survey of 801 women aged 25-64. Focus group participants had misconceptions related to screening, believing that the procedures were painful. Cost was an issue, as well as efficacy and fatalism. By identifying barriers to and motivators for screening through a mixed-method design that has both nuance and external validity, this study offers valuable suggestions to policymakers to improve breast and cervical cancer screening uptake in Singapore.

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

Belinsky, Steven A; Palmisano, William A

A molecular marker-based method for monitoring and detecting cancer in humans. Aberrant methylation of gene promoters is a marker for cancer risk in humans. A two-stage, or "nested" polymerase chain reaction method is disclosed for detecting methylated DNA sequences at sufficiently high levels of sensitivity to permit cancer screening in biological fluid samples, such as sputum, obtained non-invasively. The method is for detecting the aberrant methylation of the p16 gene, O 6-methylguanine-DNA methyltransferase gene, Death-associated protein kinase gene, RAS-associated family 1 gene, or other gene promoters. The method offers a potentially powerful approach to population-based screening for the detection ofmore » lung and other cancers.« less

Methodology for a randomised controlled trial of preschool vision screening. A new approach with the 'ALSPAC' project.

PubMed

Williams, C; Harrad, R A; Harvey, I; Frankel, S; Golding, J

1996-06-01

We present the methodology of a population-based Randomised Controlled Trial, comparing an intensive programme of primary preschool vision screening by orthoptists with the usual non-specialist screening. The aims of the trial are to compare the effectiveness and costs of intensive orthoptic screening with non-specialist measures. The orthoptic screening programme will be evaluated both as a composite package and in terms of the screening value of the individual tests at specific ages. This trial is nested within a large population-based longitudinal study. Additional demographic and developmental data on the children in the trial are therefore available. The results of the trial will be used to help clarify which methods of preschool ophthalmic population screening are best in terms of disease detection and cost efficiency.

Computer-aided diagnosis workstation and database system for chest diagnosis based on multi-helical CT images

NASA Astrophysics Data System (ADS)

Satoh, Hitoshi; Niki, Noboru; Mori, Kiyoshi; Eguchi, Kenji; Kaneko, Masahiro; Kakinuma, Ryutarou; Moriyama, Noriyuki; Ohmatsu, Hironobu; Masuda, Hideo; Machida, Suguru; Sasagawa, Michizou

2006-03-01

Multi-helical CT scanner advanced remarkably at the speed at which the chest CT images were acquired for mass screening. Mass screening based on multi-helical CT images requires a considerable number of images to be read. It is this time-consuming step that makes the use of helical CT for mass screening impractical at present. To overcome this problem, we have provided diagnostic assistance methods to medical screening specialists by developing a lung cancer screening algorithm that automatically detects suspected lung cancers in helical CT images and a coronary artery calcification screening algorithm that automatically detects suspected coronary artery calcification. We also have developed electronic medical recording system and prototype internet system for the community health in two or more regions by using the Virtual Private Network router and Biometric fingerprint authentication system and Biometric face authentication system for safety of medical information. Based on these diagnostic assistance methods, we have now developed a new computer-aided workstation and database that can display suspected lesions three-dimensionally in a short time. This paper describes basic studies that have been conducted to evaluate this new system. The results of this study indicate that our computer-aided diagnosis workstation and network system can increase diagnostic speed, diagnostic accuracy and safety of medical information.

Nested methylation-specific polymerase chain reaction cancer detection method

DOEpatents

Belinsky, Steven A [Albuquerque, NM; Palmisano, William A [Edgewood, NM

2007-05-08

A molecular marker-based method for monitoring and detecting cancer in humans. Aberrant methylation of gene promoters is a marker for cancer risk in humans. A two-stage, or "nested" polymerase chain reaction method is disclosed for detecting methylated DNA sequences at sufficiently high levels of sensitivity to permit cancer screening in biological fluid samples, such as sputum, obtained non-invasively. The method is for detecting the aberrant methylation of the p16 gene, O 6-methylguanine-DNA methyltransferase gene, Death-associated protein kinase gene, RAS-associated family 1 gene, or other gene promoters. The method offers a potentially powerful approach to population-based screening for the detection of lung and other cancers.

PhAST: pharmacophore alignment search tool.

PubMed

Hähnke, Volker; Hofmann, Bettina; Grgat, Tomislav; Proschak, Ewgenij; Steinhilber, Dieter; Schneider, Gisbert

2009-04-15

We present a ligand-based virtual screening technique (PhAST) for rapid hit and lead structure searching in large compound databases. Molecules are represented as strings encoding the distribution of pharmacophoric features on the molecular graph. In contrast to other text-based methods using SMILES strings, we introduce a new form of text representation that describes the pharmacophore of molecules. This string representation opens the opportunity for revealing functional similarity between molecules by sequence alignment techniques in analogy to homology searching in protein or nucleic acid sequence databases. We favorably compared PhAST with other current ligand-based virtual screening methods in a retrospective analysis using the BEDROC metric. In a prospective application, PhAST identified two novel inhibitors of 5-lipoxygenase product formation with minimal experimental effort. This outcome demonstrates the applicability of PhAST to drug discovery projects and provides an innovative concept of sequence-based compound screening with substantial scaffold hopping potential. 2008 Wiley Periodicals, Inc.

Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits.

PubMed

Blaazer, Antoni R; Orrling, Kristina M; Shanmugham, Anitha; Jansen, Chimed; Maes, Louis; Edink, Ewald; Sterk, Geert Jan; Siderius, Marco; England, Paul; Bailey, David; de Esch, Iwan J P; Leurs, Rob

2015-01-01

Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint. Fragment-based drug discovery is a target-based approach that typically involves the screening of a relatively small number of fragment-like (molecular weight <300) molecules that efficiently cover chemical space. Here, we report a fragment screening on TbrPDEB1, an essential cyclic nucleotide phosphodiesterase (PDE) from Trypanosoma brucei, and human PDE4D, an off-target, in a workflow in which fragment hits and a series of close analogs are subsequently screened for antiparasitic activity in a phenotypic panel. The phenotypic panel contained T. brucei, Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum, the causative agents of human African trypanosomiasis (sleeping sickness), Chagas disease, leishmaniasis, and malaria, respectively, as well as MRC-5 human lung cells. This hybrid screening workflow has resulted in the discovery of various benzhydryl ethers with antiprotozoal activity and low toxicity, representing interesting starting points for further antiparasitic optimization. © 2014 Society for Laboratory Automation and Screening.

School-Based Screening to Identify At-Risk Students Not Already Known to School Professionals: The Columbia Suicide Screen

PubMed Central

Wilcox, Holly C.; Schonfeld, Irvin Sam; Davies, Mark; Hicks, Roger C.; Turner, J. Blake; Shaffer, David

2009-01-01

Objectives. We sought to determine the degree of overlap between students identified through school-based suicide screening and those thought to be at risk by school administrative and clinical professionals. Methods. Students from 7 high schools in the New York metropolitan area completed the Columbia Suicide Screen; 489 of the 1729 students screened had positive results. The clinical status of 641 students (73% of those who had screened positive and 23% of those who had screened negative) was assessed with modules from the Diagnostic Interview Schedule for Children. School professionals nominated by their principal and unaware of students' screening and diagnostic status were asked to indicate whether they were concerned about the emotional well-being of each participating student. Results. Approximately 34% of students with significant mental health problems were identified only through screening, 13.0% were identified only by school professionals, 34.9% were identified both through screening and by school professionals, and 18.3% were identified neither through screening nor by school professionals. The corresponding percentages among students without mental health problems were 9.1%, 24.0%, 5.5%, and 61.3%. Conclusions. School-based screening can identify suicidal and emotionally troubled students not recognized by school professionals. PMID:19059865

Discovery of novel mGluR1 antagonists: a multistep virtual screening approach based on an SVM model and a pharmacophore hypothesis significantly increases the hit rate and enrichment factor.

PubMed

Li, Guo-Bo; Yang, Ling-Ling; Feng, Shan; Zhou, Jian-Ping; Huang, Qi; Xie, Huan-Zhang; Li, Lin-Li; Yang, Sheng-Yong

2011-03-15

Development of glutamate non-competitive antagonists of mGluR1 (Metabotropic glutamate receptor subtype 1) has increasingly attracted much attention in recent years due to their potential therapeutic application for various nervous disorders. Since there is no crystal structure reported for mGluR1, ligand-based virtual screening (VS) methods, typically pharmacophore-based VS (PB-VS), are often used for the discovery of mGluR1 antagonists. Nevertheless, PB-VS usually suffers a lower hit rate and enrichment factor. In this investigation, we established a multistep ligand-based VS approach that is based on a support vector machine (SVM) classification model and a pharmacophore model. Performance evaluation of these methods in virtual screening against a large independent test set, M-MDDR, show that the multistep VS approach significantly increases the hit rate and enrichment factor compared with the individual SB-VS and PB-VS methods. The multistep VS approach was then used to screen several large chemical libraries including PubChem, Specs, and Enamine. Finally a total of 20 compounds were selected from the top ranking compounds, and shifted to the subsequent in vitro and in vivo studies, which results will be reported in the near future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genome-scale deletion screening of human long non-coding RNAs using a paired-guide RNA CRISPR library

PubMed Central

Zhu, Shiyou; Li, Wei; Liu, Jingze; Chen, Chen-Hao; Liao, Qi; Xu, Ping; Xu, Han; Xiao, Tengfei; Cao, Zhongzheng; Peng, Jingyu; Yuan, Pengfei; Brown, Myles; Liu, Xiaole Shirley; Wei, Wensheng

2017-01-01

CRISPR/Cas9 screens have been widely adopted to analyse coding gene functions, but high throughput screening of non-coding elements using this method is more challenging, because indels caused by a single cut in non-coding regions are unlikely to produce a functional knockout. A high-throughput method to produce deletions of non-coding DNA is needed. Herein, we report a high throughput genomic deletion strategy to screen for functional long non-coding RNAs (lncRNAs) that is based on a lentiviral paired-guide RNA (pgRNA) library. Applying our screening method, we identified 51 lncRNAs that can positively or negatively regulate human cancer cell growth. We individually validated 9 lncRNAs using CRISPR/Cas9-mediated genomic deletion and functional rescue, CRISPR activation or inhibition, and gene expression profiling. Our high-throughput pgRNA genome deletion method should enable rapid identification of functional mammalian non-coding elements. PMID:27798563

Depth detection in interactive projection system based on one-shot black-and-white stripe pattern.

PubMed

Zhou, Qian; Qiao, Xiaorui; Ni, Kai; Li, Xinghui; Wang, Xiaohao

2017-03-06

A novel method enabling estimation of not only the screen surface as the conventional one, but the depth information from two-dimensional coordinates in an interactive projection system was proposed in this research. In this method, a one-shot black-and-white stripe pattern from a projector is projected on a screen plane, where the deformed pattern is captured by a charge-coupled device camera. An algorithm based on object/shadow simultaneous detection is proposed for fulfillment of the correspondence. The depth information of the object is then calculated using the triangulation principle. This technology provides a more direct feeling of virtual interaction in three dimensions without using auxiliary equipment or a special screen as interaction proxies. Simulation and experiments are carried out and the results verified the effectiveness of this method in depth detection.

[Screening for risk of child abuse and neglect. A practicable method?].

PubMed

Kindler, H

2010-10-01

Selective primary prevention programs for child abuse and neglect depend on risk screening instruments that have the goal of systematically identifying families who can profit most from early help. Based on a systematic review of longitudinal studies, a set of established risk factors for early child abuse and neglect is presented. Nearly half of the items included in screening instruments can be seen as validated. Available studies indicate a high sensitivity of risk screening instruments. Positive predictive values, however, are low. Overall, the use of risk screening instruments in the area of primary prevention for families at risk represents a feasible method, as long as stigmatizing effects can be avoided and participating families also benefit beyond preventing endangerment.

In person versus computer screening for intimate partner violence among pregnant patients.

PubMed

Chang, Judy C; Dado, Diane; Schussler, Sara; Hawker, Lynn; Holland, Cynthia L; Burke, Jessica G; Cluss, Patricia A

2012-09-01

To compare in person versus computerized screening for intimate partner violence (IPV) in a hospital-based prenatal clinic and explore women's assessment of the screening methods. We compared patient IPV disclosures on a computerized questionnaire to audio-taped first obstetric visits with an obstetric care provider and performed semi-structured interviews with patient participants who reported experiencing IPV. Two-hundred and fifty patient participants and 52 provider participants were in the study. Ninety-one (36%) patients disclosed IPV either via computer or in person. Of those who disclosed IPV, 60 (66%) disclosed via both methods, but 31 (34%) disclosed IPV via only one of the two methods. Twenty-three women returned for interviews. They recommended using both types together. While computerized screening was felt to be non-judgmental and more anonymous, in person screening allowed for tailored questioning and more emotional connection with the provider. Computerized screening allowed disclosure without fear of immediate judgment. In person screening allows more flexibility in wording of questions regarding IPV and opportunity for interpersonal rapport. Both computerized or self-completed screening and in person screening is recommended. Providers should address IPV using non-judgmental, descriptive language, include assessments for psychological IPV, and repeat screening in person, even if no patient disclosure occurs via computer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

TINS, target immobilized NMR screening: an efficient and sensitive method for ligand discovery.

PubMed

Vanwetswinkel, Sophie; Heetebrij, Robert J; van Duynhoven, John; Hollander, Johan G; Filippov, Dmitri V; Hajduk, Philip J; Siegal, Gregg

2005-02-01

We propose a ligand screening method, called TINS (target immobilized NMR screening), which reduces the amount of target required for the fragment-based approach to drug discovery. Binding is detected by comparing 1D NMR spectra of compound mixtures in the presence of a target immobilized on a solid support to a control sample. The method has been validated by the detection of a variety of ligands for protein and nucleic acid targets (K(D) from 60 to 5000 muM). The ligand binding capacity of a protein was undiminished after 2000 different compounds had been applied, indicating the potential to apply the assay for screening typical fragment libraries. TINS can be used in competition mode, allowing rapid characterization of the ligand binding site. TINS may allow screening of targets that are difficult to produce or that are insoluble, such as membrane proteins.

How should hearing screening tests be offered?

PubMed

Koopman, Jan; Davey, Elizabeth; Thomas, Neil; Wittkop, Thomas; Verschuure, Hans

2008-05-01

This paper deals with the question of how the general public should be addressed when offering hearing screening. Postal-based questionnaires in the United Kingdom, Germany, and The Netherlands were sent to users of hearing devices, those that are in the process of obtaining one, or those that have indicated that they have special interest in hearing. Results of the survey indicated that respondents were enthusiastic about the idea of being able to carry out hearing self-screening tests via the internet, telephone, or questionnaires. A questionnaire as a method to screen on hearing was generally preferred above using the internet, which was preferred over using the telephone for the test. About 27% of the respondents indicated to use exclusively one method. Most respondents indicated that either method provided would be of interest (41%), 17% indicated not to be interested in conducting screening tests using the internet.

Detection of Antibiotics and Evaluation of Antibacterial Activity with Screen-Printed Electrodes

PubMed Central

Titoiu, Ana Maria; Marty, Jean-Louis

2018-01-01

This review provides a brief overview of the fabrication and properties of screen-printed electrodes and details the different opportunities to apply them for the detection of antibiotics, detection of bacteria and antibiotic susceptibility. Among the alternative approaches to costly chromatographic or ELISA methods for antibiotics detection and to lengthy culture methods for bacteria detection, electrochemical biosensors based on screen-printed electrodes present some distinctive advantages. Chemical and (bio)sensors for the detection of antibiotics and assays coupling detection with screen-printed electrodes with immunomagnetic separation are described. With regards to detection of bacteria, the emphasis is placed on applications targeting viable bacterial cells. While the electrochemical sensors and biosensors face many challenges before replacing standard analysis methods, the potential of screen-printed electrodes is increasingly exploited and more applications are anticipated to advance towards commercial analytical tools. PMID:29562637

Screening methods for assessment of biodegradability of chemicals in seawater--results from a ring test

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

Nyholm, N.; Kristensen, P.

1992-04-01

An international ring test involving 14 laboratories was organized on behalf of the Commission of the European Economic Communities (EEC) with the purpose of evaluating two proposed screening methods for assessment of biodegradability in seawater: (a) a shake flask die-away test based primarily on analysis of dissolved organic carbon and (b) a closed bottle test based on determination of dissolved oxygen. Both tests are performed with nutrient-enriched natural seawater as the test medium and with no inoculum added other than the natural seawater microflora. The test methods are seawater versions of the modified OECD screening test and the closed bottlemore » test, respectively, adopted by the Organization for Economic Cooperation and Development (OECD) and by the EEC as tests for ready biodegradability.' The following five chemicals were examined: sodium benzoate, aniline, diethylene glycol, pentaerythritol, and 4-nitrophenol. Sodium benzoate and aniline, which are known to be generally readily biodegradable consistently degraded in practically all tests, thus demonstrating the technical feasibility of the methods. Like in previous ring tests with freshwater screening methods variable results were obtained with the other three compounds, which is believed primarily to be due to site-specific differences between the microflora of the different seawater samples used and to some extent also to differences in the applied concentrations of test material. A positive result with the screening methods indicates that the test substance will most likely degrade relatively rapidly in seawater from the site of collection, while a negative test result does not preclude biodegradability under environmental conditions where the concentrations of chemicals are much lower than the concentrations applied for analytical reasons in screening tests.« less

The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors.

PubMed

Santos, Radleigh G; Appel, Jon R; Giulianotti, Marc A; Edwards, Bruce S; Sklar, Larry A; Houghten, Richard A; Pinilla, Clemencia

2013-05-30

In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays.

CSBB-ConeExclusion, adapting structure based solution virtual screening to libraries on solid support.

PubMed

Shave, Steven; Auer, Manfred

2013-12-23

Combinatorial chemical libraries produced on solid support offer fast and cost-effective access to a large number of unique compounds. If such libraries are screened directly on-bead, the speed at which chemical space can be explored by chemists is much greater than that addressable using solution based synthesis and screening methods. Solution based screening has a large supporting body of software such as structure-based virtual screening tools which enable the prediction of protein-ligand complexes. Use of these techniques to predict the protein bound complexes of compounds synthesized on solid support neglects to take into account the conjugation site on the small molecule ligand. This may invalidate predicted binding modes, the linker may be clashing with protein atoms. We present CSBB-ConeExclusion, a methodology and computer program which provides a measure of the applicability of solution dockings to solid support. Output is given in the form of statistics for each docking pose, a unique 2D visualization method which can be used to determine applicability at a glance, and automatically generated PyMol scripts allowing visualization of protein atom incursion into a defined exclusion volume. CSBB-ConeExclusion is then exemplarically used to determine the optimum attachment point for a purine library targeting cyclin-dependent kinase 2 CDK2.

Activity-Based Screening of Metagenomic Libraries for Hydrogenase Enzymes.

PubMed

Adam, Nicole; Perner, Mirjam

2017-01-01

Here we outline how to identify hydrogenase enzymes from metagenomic libraries through an activity-based screening approach. A metagenomic fosmid library is constructed in E. coli and the fosmids are transferred into a hydrogenase deletion mutant of Shewanella oneidensis (ΔhyaB) via triparental mating. If a fosmid exhibits hydrogen uptake activity, S. oneidensis' phenotype is restored and hydrogenase activity is indicated by a color change of the medium from yellow to colorless. This new method enables screening of 48 metagenomic fosmid clones in parallel.

Going direct to the consumer: Examining treatment preferences for veterans with insomnia, PTSD, and depression.

PubMed

Gutner, Cassidy A; Pedersen, Eric R; Drummond, Sean P A

2018-05-01

Inclusion of consumer preferences to disseminate evidence-based psychosocial treatment (EBPT) is crucial to effectively bridge the science-to-practice quality chasm. We examined this treatment gap for insomnia, posttraumatic stress disorder (PTSD), depression, and comorbid symptoms in a sample of 622 young adult veterans through preference in symptom focus, treatment modality, and related gender differences among those screening positive for each problem. Data were collected from veteran drinkers recruited through targeted Facebook advertisements as part of a brief online alcohol intervention. Analyses demonstrated that veterans reported greater willingness to seek insomnia-focused treatment over PTSD- or depression-focused care. Notably, even when participants screened negative for insomnia, they preferred sleep-focused care to PTSD- or depression-focused care. Although one in five veterans with a positive screen would not consider care, veterans screening for both insomnia and PTSD who would consider care had a preference for in-person counseling, and those screening for both insomnia and depression had similar preferences for in-person and mobile app-based/computer self-help treatment. Marginal gender differences were found. Incorporating direct-to-consumer methods into research can help educate stakeholders about methods to expand EBPT access. Though traditional in-person counseling was often preferred, openness to app-based/computer interventions offers alternative methods to provide veterans with EBPTs. Published by Elsevier B.V.

Development and Interlaboratory Validation of a Simple Screening Method for Genetically Modified Maize Using a ΔΔC(q)-Based Multiplex Real-Time PCR Assay.

PubMed

Noguchi, Akio; Nakamura, Kosuke; Sakata, Kozue; Sato-Fukuda, Nozomi; Ishigaki, Takumi; Mano, Junichi; Takabatake, Reona; Kitta, Kazumi; Teshima, Reiko; Kondo, Kazunari; Nishimaki-Mogami, Tomoko

2016-04-19

A number of genetically modified (GM) maize events have been developed and approved worldwide for commercial cultivation. A screening method is needed to monitor GM maize approved for commercialization in countries that mandate the labeling of foods containing a specified threshold level of GM crops. In Japan, a screening method has been implemented to monitor approved GM maize since 2001. However, the screening method currently used in Japan is time-consuming and requires generation of a calibration curve and experimental conversion factor (C(f)) value. We developed a simple screening method that avoids the need for a calibration curve and C(f) value. In this method, ΔC(q) values between the target sequences and the endogenous gene are calculated using multiplex real-time PCR, and the ΔΔC(q) value between the analytical and control samples is used as the criterion for determining analytical samples in which the GM organism content is below the threshold level for labeling of GM crops. An interlaboratory study indicated that the method is applicable independently with at least two models of PCR instruments used in this study.

Avalanche for shape and feature-based virtual screening with 3D alignment

NASA Astrophysics Data System (ADS)

Diller, David J.; Connell, Nancy D.; Welsh, William J.

2015-11-01

This report introduces a new ligand-based virtual screening tool called Avalanche that incorporates both shape- and feature-based comparison with three-dimensional (3D) alignment between the query molecule and test compounds residing in a chemical database. Avalanche proceeds in two steps. The first step is an extremely rapid shape/feature based comparison which is used to narrow the focus from potentially millions or billions of candidate molecules and conformations to a more manageable number that are then passed to the second step. The second step is a detailed yet still rapid 3D alignment of the remaining candidate conformations to the query conformation. Using the 3D alignment, these remaining candidate conformations are scored, re-ranked and presented to the user as the top hits for further visualization and evaluation. To provide further insight into the method, the results from two prospective virtual screens are presented which show the ability of Avalanche to identify hits from chemical databases that would likely be missed by common substructure-based or fingerprint-based search methods. The Avalanche method is extended to enable patent landscaping, i.e., structural refinements to improve the patentability of hits for deployment in drug discovery campaigns.

Prevalence of autosomal dominant polycystic kidney disease in the European Union.

PubMed

Willey, Cynthia J; Blais, Jaime D; Hall, Anthony K; Krasa, Holly B; Makin, Andrew J; Czerwiec, Frank S

2017-08-01

Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease, but estimates of its prevalence vary by >10-fold. The objective of this study was to examine the public health impact of ADPKD in the European Union (EU) by estimating minimum prevalence (point prevalence of known cases) and screening prevalence (minimum prevalence plus cases expected after population-based screening). A review of the epidemiology literature from January 1980 to February 2015 identified population-based studies that met criteria for methodological quality. These examined large German and British populations, providing direct estimates of minimum prevalence and screening prevalence. In a second approach, patients from the 2012 European Renal Association‒European Dialysis and Transplant Association (ERA-EDTA) Registry and literature-based inflation factors that adjust for disease severity and screening yield were used to estimate prevalence across 19 EU countries (N = 407 million). Population-based studies yielded minimum prevalences of 2.41 and 3.89/10 000, respectively, and corresponding estimates of screening prevalences of 3.3 and 4.6/10 000. A close correspondence existed between estimates in countries where both direct and registry-derived methods were compared, which supports the validity of the registry-based approach. Using the registry-derived method, the minimum prevalence was 3.29/10 000 (95% confidence interval 3.27-3.30), and if ADPKD screening was implemented in all countries, the expected prevalence was 3.96/10 000 (3.94-3.98). ERA-EDTA-based prevalence estimates and application of a uniform definition of prevalence to population-based studies consistently indicate that the ADPKD point prevalence is <5/10 000, the threshold for rare disease in the EU. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

A method of measuring and correcting tilt of anti - vibration wind turbines based on screening algorithm

NASA Astrophysics Data System (ADS)

Xiao, Zhongxiu

2018-04-01

A Method of Measuring and Correcting Tilt of Anti - vibration Wind Turbines Based on Screening Algorithm is proposed in this paper. First of all, we design a device which the core is the acceleration sensor ADXL203, the inclination is measured by installing it on the tower of the wind turbine as well as the engine room. Next using the Kalman filter algorithm to filter effectively by establishing a state space model for signal and noise. Then we use matlab for simulation. Considering the impact of the tower and nacelle vibration on the collected data, the original data and the filtering data are classified and stored by the Screening algorithm, then filter the filtering data to make the output data more accurate. Finally, we eliminate installation errors by using algorithm to achieve the tilt correction. The device based on this method has high precision, low cost and anti-vibration advantages. It has a wide range of application and promotion value.

Correction factors for self-selection when evaluating screening programmes.

PubMed

Spix, Claudia; Berthold, Frank; Hero, Barbara; Michaelis, Jörg; Schilling, Freimut H

2016-03-01

In screening programmes there is recognized bias introduced through participant self-selection (the healthy screenee bias). Methods used to evaluate screening programmes include Intention-to-screen, per-protocol, and the "post hoc" approach in which, after introducing screening for everyone, the only evaluation option is participants versus non-participants. All methods are prone to bias through self-selection. We present an overview of approaches to correct for this bias. We considered four methods to quantify and correct for self-selection bias. Simple calculations revealed that these corrections are actually all identical, and can be converted into each other. Based on this, correction factors for further situations and measures were derived. The application of these correction factors requires a number of assumptions. Using as an example the German Neuroblastoma Screening Study, no relevant reduction in mortality or stage 4 incidence due to screening was observed. The largest bias (in favour of screening) was observed when comparing participants with non-participants. Correcting for bias is particularly necessary when using the post hoc evaluation approach, however, in this situation not all required data are available. External data or further assumptions may be required for estimation. © The Author(s) 2015.

Cheminformatics meets molecular mechanics: a combined application of knowledge-based pose scoring and physical force field-based hit scoring functions improves the accuracy of structure-based virtual screening.

PubMed

Hsieh, Jui-Hua; Yin, Shuangye; Wang, Xiang S; Liu, Shubin; Dokholyan, Nikolay V; Tropsha, Alexander

2012-01-23

Poor performance of scoring functions is a well-known bottleneck in structure-based virtual screening (VS), which is most frequently manifested in the scoring functions' inability to discriminate between true ligands vs known nonbinders (therefore designated as binding decoys). This deficiency leads to a large number of false positive hits resulting from VS. We have hypothesized that filtering out or penalizing docking poses recognized as non-native (i.e., pose decoys) should improve the performance of VS in terms of improved identification of true binders. Using several concepts from the field of cheminformatics, we have developed a novel approach to identifying pose decoys from an ensemble of poses generated by computational docking procedures. We demonstrate that the use of target-specific pose (scoring) filter in combination with a physical force field-based scoring function (MedusaScore) leads to significant improvement of hit rates in VS studies for 12 of the 13 benchmark sets from the clustered version of the Database of Useful Decoys (DUD). This new hybrid scoring function outperforms several conventional structure-based scoring functions, including XSCORE::HMSCORE, ChemScore, PLP, and Chemgauss3, in 6 out of 13 data sets at early stage of VS (up 1% decoys of the screening database). We compare our hybrid method with several novel VS methods that were recently reported to have good performances on the same DUD data sets. We find that the retrieved ligands using our method are chemically more diverse in comparison with two ligand-based methods (FieldScreen and FLAP::LBX). We also compare our method with FLAP::RBLB, a high-performance VS method that also utilizes both the receptor and the cognate ligand structures. Interestingly, we find that the top ligands retrieved using our method are highly complementary to those retrieved using FLAP::RBLB, hinting effective directions for best VS applications. We suggest that this integrative VS approach combining cheminformatics and molecular mechanics methodologies may be applied to a broad variety of protein targets to improve the outcome of structure-based drug discovery studies.

Outcomes of Community-Based Screening for Depression and Suicide Prevention among Japanese Elders

ERIC Educational Resources Information Center

Oyama, Hirofumi; Fujita, Motoi; Goto, Masahiro; Shibuya, Hiroshi; Sakashita, Tomoe

2006-01-01

Purpose: In this study we evaluate outcomes of a community-based program to prevent suicide among elderly individuals aged 65 and older. Design and Methods: We used a quasi-experimental design with intervention and referent municipalities. The program included a 7-year implementation of depression screening with follow-up by general practitioners…

Clinical guideline representation in a CDS: a human information processing method.

PubMed

Kilsdonk, Ellen; Riezebos, Rinke; Kremer, Leontien; Peute, Linda; Jaspers, Monique

2012-01-01

The Dutch Childhood Oncology Group (DCOG) has developed evidence-based guidelines for screening childhood cancer survivors for possible late complications of treatment. These paper-based guidelines appeared to not suit clinicians' information retrieval strategies; it was thus decided to communicate the guidelines through a Computerized Decision Support (CDS) tool. To ensure high usability of this tool, an analysis of clinicians' cognitive strategies in retrieving information from the paper-based guidelines was used as requirements elicitation method. An information processing model was developed through an analysis of think aloud protocols and used as input for the design of the CDS user interface. Usability analysis of the user interface showed that the navigational structure of the CDS tool fitted well with the clinicians' mental strategies employed in deciding on survivors screening protocols. Clinicians were more efficient and more complete in deciding on patient-tailored screening procedures when supported by the CDS tool than by the paper-based guideline booklet. The think-aloud method provided detailed insight into users' clinical work patterns that supported the design of a highly usable CDS system.

The role of community pharmacists in screening and subsequent management of chronic respiratory diseases: a systematic review

PubMed Central

Fathima, Mariam; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol L.

Objective The purpose of this review was to evaluate the role of community pharmacists in provision of screening with/without subsequent management of undiagnosed chronic obstructive pulmonary disease (COPD) and uncontrolled asthma. Methods An extensive literature search using four databases (ie. Medline, PubMed, International Pharmaceutical Abstracts (IPA) and Scopus) with search terms pharmacy, screening, asthma or COPD was conducted. Searches were limited to the years 2003-2013, those in English and those reporting research with humans. Data retrieval, analysis and result presentation employed a scoping review method. Results Seventeen articles met the inclusion/exclusion criteria, of which fifteen studies were based on people with asthma and two were based on people with COPD. Only seven asthma studies and one COPD study involved screening followed by subsequent management. More than half of the people screened were found to be poorly controlled and up to 62% of people were identified at high risk for COPD by community pharmacists. The studies varied in the method and type of asthma control assessment/screening, the type of intervention provided and the outcomes measured. The limitations of the reviewed studies included varying definitions of asthma control, different study methodologies, and the lack of long-term follow-up. While many different methods were used for risk assessment and management services by the pharmacists, all the studies demonstrated that community pharmacists were capable of identifying people with poorly controlled asthma and undiagnosed COPD and providing them with suitable interventions. Conclusions The literature review identified that community pharmacists can play an effective role in screening of people with poorly controlled asthma and undiagnosed COPD along with delivering management interventions. However, there is very little literature available on screening for these chronic respiratory conditions. Future research should focus on development of patient care delivery model incorporating a screening protocol followed by targeted management interventions delivered by the community pharmacist. PMID:24367463

Developmental dysplasia of the hip: impact of sonographic newborn hip screening on the outcome of early treated decentered hip joints-a single center retrospective comparative cohort study based on Graf's method of hip ultrasonography.

PubMed

Tschauner, Christian; Fürntrath, Frank; Saba, Yasaman; Berghold, Andrea; Radl, Roman

2011-12-01

PURPOSE/BACKGROUND/INTRODUCTION: The aim of this study was to retrospectively evaluate the impact of neonatal sonographic hip screening using Graf's method for the management and outcome of orthopaedic treatment of decentered hip joints with developmental dysplasia of the hip (DDH), using three decades (1978-2007) of clinical information compiled in a medical database. Three representative cohorts of consecutive cases of decentered hip joints were selected according to different search criteria and inclusion and exclusion parameters: (1) cohort 1 (1978-1982; n = 80), without sonographic screening; (2) cohort 2.1 (1994-1996; n = 91), with nationwide established general sonographic screening according to the Graf-method; (3) cohort 2.2 (2003-2005; n = 91), with sonographic screening including referred cases for open reduction from non-screened populations. These three cohorts were compared for the following parameters: age at initial treatment, successful closed reduction, necessary overhead traction, necessary adductor-tenotomy, rate of open reduction, rate of avascular necrosis (AVN) and rate of secondary acetabuloplasty. The age at initial treatment was reduced from 5.5 months in the first cohort to 2 months in the two subsequent two cohorts and the rate of successful closed reduction increased from 88.7 to 98.9 and 95.6%, respectively. There was a statistically significant improvement in six out of seven parameters with sonographic hip screening; only the rate of secondary acetabuloplasty did not improve significantly. Compared to the era before the institution of a sonographic hip screening programme according to the Graf-method in Austria in 1992, ultrasound screening based-treatment of decentered hip joints has become safer, shorter and simpler: "safer" means lower rate of AVN, "shorter" means less treatment time due to earlier onset and "simpler" means that the devices are now less invasive and highly standardized.

Comparison of array comparative genomic hybridization and quantitative real-time PCR-based aneuploidy screening of blastocyst biopsies.

PubMed

Capalbo, Antonio; Treff, Nathan R; Cimadomo, Danilo; Tao, Xin; Upham, Kathleen; Ubaldi, Filippo Maria; Rienzi, Laura; Scott, Richard T

2015-07-01

Comprehensive chromosome screening (CCS) methods are being extensively used to select chromosomally normal embryos in human assisted reproduction. Some concerns related to the stage of analysis and which aneuploidy screening method to use still remain. In this study, the reliability of blastocyst-stage aneuploidy screening and the diagnostic performance of the two mostly used CCS methods (quantitative real-time PCR (qPCR) and array comparative genome hybridization (aCGH)) has been assessed. aCGH aneuploid blastocysts were rebiopsied, blinded, and evaluated by qPCR. Discordant cases were subsequently rebiopsied, blinded, and evaluated by single-nucleotide polymorphism (SNP) array-based CCS. Although 81.7% of embryos showed the same diagnosis when comparing aCGH and qPCR-based CCS, 18.3% (22/120) of embryos gave a discordant result for at least one chromosome. SNP array reanalysis showed that a discordance was reported in ten blastocysts for aCGH, mostly due to false positives, and in four cases for qPCR. The discordant aneuploidy call rate per chromosome was significantly higher for aCGH (5.7%) compared with qPCR (0.6%; P<0.01). To corroborate these findings, 39 embryos were simultaneously biopsied for aCGH and qPCR during blastocyst-stage aneuploidy screening cycles. 35 matched including all 21 euploid embryos. Blinded SNP analysis on rebiopsies of the four embryos matched qPCR. These findings demonstrate the high reliability of diagnosis performed at the blastocyst stage with the use of different CCS methods. However, the application of aCGH can be expected to result in a higher aneuploidy rate than other contemporary methods of CCS.

Condorcet and borda count fusion method for ligand-based virtual screening.

PubMed

Ahmed, Ali; Saeed, Faisal; Salim, Naomie; Abdo, Ammar

2014-01-01

It is known that any individual similarity measure will not always give the best recall of active molecule structure for all types of activity classes. Recently, the effectiveness of ligand-based virtual screening approaches can be enhanced by using data fusion. Data fusion can be implemented using two different approaches: group fusion and similarity fusion. Similarity fusion involves searching using multiple similarity measures. The similarity scores, or ranking, for each similarity measure are combined to obtain the final ranking of the compounds in the database. The Condorcet fusion method was examined. This approach combines the outputs of similarity searches from eleven association and distance similarity coefficients, and then the winner measure for each class of molecules, based on Condorcet fusion, was chosen to be the best method of searching. The recall of retrieved active molecules at top 5% and significant test are used to evaluate our proposed method. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Simulated virtual screening experiments with the standard two data sets show that the use of Condorcet fusion provides a very simple way of improving the ligand-based virtual screening, especially when the active molecules being sought have a lowest degree of structural heterogeneity. However, the effectiveness of the Condorcet fusion was increased slightly when structural sets of high diversity activities were being sought.

Condorcet and borda count fusion method for ligand-based virtual screening

PubMed Central

2014-01-01

Background It is known that any individual similarity measure will not always give the best recall of active molecule structure for all types of activity classes. Recently, the effectiveness of ligand-based virtual screening approaches can be enhanced by using data fusion. Data fusion can be implemented using two different approaches: group fusion and similarity fusion. Similarity fusion involves searching using multiple similarity measures. The similarity scores, or ranking, for each similarity measure are combined to obtain the final ranking of the compounds in the database. Results The Condorcet fusion method was examined. This approach combines the outputs of similarity searches from eleven association and distance similarity coefficients, and then the winner measure for each class of molecules, based on Condorcet fusion, was chosen to be the best method of searching. The recall of retrieved active molecules at top 5% and significant test are used to evaluate our proposed method. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Conclusions Simulated virtual screening experiments with the standard two data sets show that the use of Condorcet fusion provides a very simple way of improving the ligand-based virtual screening, especially when the active molecules being sought have a lowest degree of structural heterogeneity. However, the effectiveness of the Condorcet fusion was increased slightly when structural sets of high diversity activities were being sought. PMID:24883114

Ensemble pharmacophore meets ensemble docking: a novel screening strategy for the identification of RIPK1 inhibitors

NASA Astrophysics Data System (ADS)

Fayaz, S. M.; Rajanikant, G. K.

2014-07-01

Programmed cell death has been a fascinating area of research since it throws new challenges and questions in spite of the tremendous ongoing research in this field. Recently, necroptosis, a programmed form of necrotic cell death, has been implicated in many diseases including neurological disorders. Receptor interacting serine/threonine protein kinase 1 (RIPK1) is an important regulatory protein involved in the necroptosis and inhibition of this protein is essential to stop necroptotic process and eventually cell death. Current structure-based virtual screening methods involve a wide range of strategies and recently, considering the multiple protein structures for pharmacophore extraction has been emphasized as a way to improve the outcome. However, using the pharmacophoric information completely during docking is very important. Further, in such methods, using the appropriate protein structures for docking is desirable. If not, potential compound hits, obtained through pharmacophore-based screening, may not have correct ranks and scores after docking. Therefore, a comprehensive integration of different ensemble methods is essential, which may provide better virtual screening results. In this study, dual ensemble screening, a novel computational strategy was used to identify diverse and potent inhibitors against RIPK1. All the pharmacophore features present in the binding site were captured using both the apo and holo protein structures and an ensemble pharmacophore was built by combining these features. This ensemble pharmacophore was employed in pharmacophore-based screening of ZINC database. The compound hits, thus obtained, were subjected to ensemble docking. The leads acquired through docking were further validated through feature evaluation and molecular dynamics simulation.

Child and teacher acceptability of school-based echocardiographic screening for rheumatic heart disease in Uganda.

PubMed

Ploutz, Michelle; Aliku, Twalib; Bradley-Hewitt, Tyler; Dantin, Andrea; Lemley, Bethan; Gillespie, Catherine W; Lwabi, Peter; Sable, Craig; Beaton, Andrea

2017-01-01

Introduction Rheumatic heart disease causes substantial morbidity in children in low-income countries. School-based echocardiographic screening has been suggested as a means to identify children with latent disease; however, little is known about the experience of children and teachers participating in screenings. The aim of our study was to assess students' and teachers' experience of school-based echocardiographic screening and identify areas for improvement. Materials and methods A school-based echocardiographic screening programme was conducted in five schools in Northern Uganda in 2013. After 8 months, an age- and gender-stratified population that included 5% of the participating students and teachers completed a questionnaire via an in-person interview. Responses were reviewed by question and coded to identify key themes. A total of 255 students (mean 10.7 years; 48% male) and 35 teachers participated in our study. In total, 95% of the students and 100% of the teachers were happy to have participated in the screening; however, students reported feeling scared (35%) and nervous (48%) during the screening process. Programmatic strengths included the following: knowing one's health status, opportunity to receive treatment, and staff interactions. Although 43% of the patients did not suggest a change with open-ended questioning, concerns regarding privacy, fear of the screening process, and a desire to include others in the community were noted. Discussion School-based echocardiographic rheumatic heart disease screening was well received by students and teachers. Future programmes would likely benefit from improved pre-screening education regarding the screening process and diagnosis of rheumatic heart disease. Furthermore, education of teachers and students could improve screening perception and establish realistic expectations regarding the scope of screening.

Prioritizing chemicals for environmental management in China based on screening of potential risks

NASA Astrophysics Data System (ADS)

Yu, Xiangyi; Mao, Yan; Sun, Jinye; Shen, Yingwa

2014-03-01

The rapid development of China's chemical industry has created increasing pressure to improve the environmental management of chemicals. To bridge the large gap between the use and safe management of chemicals, we performed a comprehensive review of the international methods used to prioritize chemicals for environmental management. By comparing domestic and foreign methods, we confirmed the presence of this gap and identified potential solutions. Based on our literature review, we developed an appropriate screening method that accounts for the unique characteristics of chemical use within China. The proposed method is based on an evaluation using nine indices of the potential hazard posed by a chemical: three environmental hazard indices (persistence, bioaccumulation, and eco-toxicity), four health hazard indices (acute toxicity, carcinogenicity, mutagenicity, and reproductive and developmental toxicity), and two environmental exposure hazard indices (chemical amount and utilization pattern). The results of our screening agree with results of previous efforts from around the world, confirming the validity of the new system. The classification method will help decisionmakers to prioritize and identify the chemicals with the highest environmental risk, thereby providing a basis for improving chemical management in China.

An effective method to screen sodium-based layered materials for sodium ion batteries

NASA Astrophysics Data System (ADS)

Zhang, Xu; Zhang, Zihe; Yao, Sai; Chen, An; Zhao, Xudong; Zhou, Zhen

2018-03-01

Due to the high cost and insufficient resource of lithium, sodium-ion batteries are widely investigated for large-scale applications. Typically, insertion-type materials possess better cyclic stability than alloy-type and conversion-type ones. Therefore, in this work, we proposed a facile and effective method to screen sodium-based layered materials based on Materials Project database as potential candidate insertion-type materials for sodium ion batteries. The obtained Na-based layered materials contains 38 kinds of space group, which reveals that the credibility of our screening approach would not be affected by the space group. Then, some important indexes of the representative materials, including the average voltage, volume change and sodium ion mobility, were further studied by means of density functional theory computations. Some materials with extremely low volume changes and Na diffusion barriers are promising candidates for sodium ion batteries. We believe that our classification algorithm could also be used to search for other alkali and multivalent ion-based layered materials, to accelerate the development of battery materials.

Screen Space Ambient Occlusion Based Multiple Importance Sampling for Real-Time Rendering

NASA Astrophysics Data System (ADS)

Zerari, Abd El Mouméne; Babahenini, Mohamed Chaouki

2018-03-01

We propose a new approximation technique for accelerating the Global Illumination algorithm for real-time rendering. The proposed approach is based on the Screen-Space Ambient Occlusion (SSAO) method, which approximates the global illumination for large, fully dynamic scenes at interactive frame rates. Current algorithms that are based on the SSAO method suffer from difficulties due to the large number of samples that are required. In this paper, we propose an improvement to the SSAO technique by integrating it with a Multiple Importance Sampling technique that combines a stratified sampling method with an importance sampling method, with the objective of reducing the number of samples. Experimental evaluation demonstrates that our technique can produce high-quality images in real time and is significantly faster than traditional techniques.

Development of a Novel Screening Method for the Isolation of “Cronobacter” spp. (Enterobacter sakazakii)▿

PubMed Central

Iversen, Carol; Druggan, Patrick; Schumacher, Sandra; Lehner, Angelika; Feer, Claudia; Gschwend, Karl; Joosten, Han; Stephan, Roger

2008-01-01

A differential medium, “Cronobacter” screening broth, has been designed to complement agars based on hydrolysis of chromogenic α-glucopyranoside substrates. The broth was evaluated using 329 Enterobacteriaceae strains (229 target isolates), spiked/naturally contaminated samples, and a parallel comparison with current methods for raw materials, line/end products, and factory environment samples. PMID:18310415

Synthesis and screening of one-bead-one-compound cyclic peptide libraries.

PubMed

Qian, Ziqing; Upadhyaya, Punit; Pei, Dehua

2015-01-01

Cyclic peptides have been a rich source of biologically active molecules. Herein we present a method for the combinatorial synthesis and screening of large one-bead-one-compound (OBOC) libraries of cyclic peptides against biological targets such as proteins. Up to ten million different cyclic peptides are rapidly synthesized on TentaGel microbeads by the split-and-pool synthesis method and subjected to a multistage screening protocol which includes magnetic sorting, on-bead enzyme-linked and fluorescence-based assays, and in-solution binding analysis of cyclic peptides selectively released from single beads by fluorescence anisotropy. Finally, the most active hit(s) is identified by the partial Edman degradation-mass spectrometry (PED-MS) method. This method allows a single researcher to synthesize and screen up to ten million cyclic peptides and identify the most active ligand(s) in ~1 month, without the time-consuming and expensive hit resynthesis or the use of any special equipment.

Screening, diagnosis, and treatment of post-traumatic stress disorder.

PubMed

Wisco, Blair E; Marx, Brian P; Keane, Terence M

2012-08-01

Post-traumatic stress disorder (PTSD) is a prevalent problem among military personnel and veterans. Identification of effective screening tools, diagnostic technologies, and treatments for PTSD is essential to ensure that all individuals in need of treatment are offered interventions with proven efficacy. Well-validated methods for screening and diagnosing PTSD are now available, and effective pharmacological and psychological treatments can be offered. Despite these advances, many military personnel and veterans do not receive evidence-based care. We review the literature on screening, diagnosis, and treatment of PTSD in military populations, and discuss the challenges to implementing the best evidence-based practices in clinical settings.

Factors affecting attendance to cervical cancer screening among women in the Paracentral Region of El Salvador: a nested study within the CAPE HPV screening program.

PubMed

Alfaro, Karla M; Gage, Julia C; Rosenbaum, Alan J; Ditzian, Lauren R; Maza, Mauricio; Scarinci, Isabel C; Miranda, Esmeralda; Villalta, Sofia; Felix, Juan C; Castle, Philip E; Cremer, Miriam L

2015-10-16

Cervical cancer is the third most commonly occurring cancer among women and the fourth leading cause of cancer-related deaths in women worldwide, with more than 85 % of these cases occurring in developing countries. These global disparities reflect the differences in cervical cancer screening rates between high-income and medium- and low-income countries. At 19 %, El Salvador has the lowest reported screening coverage of all Latin American countries. The purpose of this study is to identify factors affecting public sector HPV DNA-based cervical cancer screening participation in El Salvador. This study was nested within a public sector screening program where health promoters used door-to-door outreach to recruit women aged 30-49 years to attend educational sessions about HPV screening. A subgroup of these participants was chosen randomly and questioned about demographic factors, healthcare utilization, previous cervical cancer screening, and HPV knowledge. Women then scheduled screening appointments at their public health clinics. Screening participants were adherent if they attended their scheduled appointment or rescheduled and were screened within 6 months. The association between non-adherence and demographic variables, medical history, history of cancer, sexual history, birth control methods, and screening barriers was assessed using Chi-square tests of significance and logistic regression. All women (n = 409) enrolled in the study scheduled HPV screening appointments, and 88 % attended. Non-adherence was associated with a higher number of lifetime partners and being under-screened-defined as not having participated in cervical cancer screening within the previous 3 years (p = 0.03 and p = 0.04, respectively); 22.8 % of participants in this study were under-screened. Adherence to cervical cancer screening after educational sessions was higher than expected, in part due to interactions with the community-based health promoters as well as the educational session itself. More effective recruitment methods targeted toward under-screened women are required.

A rotation-translation invariant molecular descriptor of partial charges and its use in ligand-based virtual screening

PubMed Central

2014-01-01

Background Measures of similarity for chemical molecules have been developed since the dawn of chemoinformatics. Molecular similarity has been measured by a variety of methods including molecular descriptor based similarity, common molecular fragments, graph matching and 3D methods such as shape matching. Similarity measures are widespread in practice and have proven to be useful in drug discovery. Because of our interest in electrostatics and high throughput ligand-based virtual screening, we sought to exploit the information contained in atomic coordinates and partial charges of a molecule. Results A new molecular descriptor based on partial charges is proposed. It uses the autocorrelation function and linear binning to encode all atoms of a molecule into two rotation-translation invariant vectors. Combined with a scoring function, the descriptor allows to rank-order a database of compounds versus a query molecule. The proposed implementation is called ACPC (AutoCorrelation of Partial Charges) and released in open source. Extensive retrospective ligand-based virtual screening experiments were performed and other methods were compared with in order to validate the method and associated protocol. Conclusions While it is a simple method, it performed remarkably well in experiments. At an average speed of 1649 molecules per second, it reached an average median area under the curve of 0.81 on 40 different targets; hence validating the proposed protocol and implementation. PMID:24887178

New approaches to cervical cancer screening in Latin America and the Caribbean.

PubMed

Herrero, Rolando; Ferreccio, Catterina; Salmerón, Jorge; Almonte, Maribel; Sánchez, Gloria Ines; Lazcano-Ponce, Eduardo; Jerónimo, José

2008-08-19

Cervical cancer remains an important public health problem in the Latin America and Caribbean region (LAC), with an expected significant increase in disease burden in the next decades as a result of population ageing. Prophylactic human papillomavirus (HPV) vaccine is currently unaffordable in LAC countries. However, even if vaccination was implemented, an additional two decades will be required to observe its impact on HPV related disease and cancer. With some exceptions, cytology-based screening programs have been largely ineffective to control the problem in the region, and there is a need for new approaches to the organization of screening and for use of newly developed techniques. Several research groups in LAC have conducted research on new screening methods, some of which are summarized in this paper. A recommendation to reorganize screening programs is presented considering visual inspection for very low resource areas, improvement of cytology where it is operating successfully and HPV DNA testing followed by visual inspection with acetic acid (VIA) or cytology as soon as this method becomes technically and economically sustainable. This could be facilitated by the incorporation of new, low-cost HPV DNA testing methods and the use of self-collected vaginal specimens for selected groups of the population. An important requisite for screening based on HPV testing will be the quality assurance of the laboratory and the technique by validation and certification measures.

Discovery of novel Pim-1 kinase inhibitors by a hierarchical multistage virtual screening approach based on SVM model, pharmacophore, and molecular docking.

PubMed

Ren, Ji-Xia; Li, Lin-Li; Zheng, Ren-Lin; Xie, Huan-Zhang; Cao, Zhi-Xing; Feng, Shan; Pan, You-Li; Chen, Xin; Wei, Yu-Quan; Yang, Sheng-Yong

2011-06-27

In this investigation, we describe the discovery of novel potent Pim-1 inhibitors by employing a proposed hierarchical multistage virtual screening (VS) approach, which is based on support vector machine-based (SVM-based VS or SB-VS), pharmacophore-based VS (PB-VS), and docking-based VS (DB-VS) methods. In this approach, the three VS methods are applied in an increasing order of complexity so that the first filter (SB-VS) is fast and simple, while successive ones (PB-VS and DB-VS) are more time-consuming but are applied only to a small subset of the entire database. Evaluation of this approach indicates that it can be used to screen a large chemical library rapidly with a high hit rate and a high enrichment factor. This approach was then applied to screen several large chemical libraries, including PubChem, Specs, and Enamine as well as an in-house database. From the final hits, 47 compounds were selected for further in vitro Pim-1 inhibitory assay, and 15 compounds show nanomolar level or low micromolar inhibition potency against Pim-1. In particular, four of them were found to have new scaffolds which have potential for the chemical development of Pim-1 inhibitors.

Maternal age–based prenatal screening for chromosomal disorders

PubMed Central

Carroll, June C.; Rideout, Andrea; Wilson, Brenda J.; Allanson, Judith; Blaine, Sean; Esplen, Mary Jane; Farrell, Sandra; Graham, Gail E.; MacKenzie, Jennifer; Meschino, Wendy S.; Prakash, Preeti; Shuman, Cheryl; Taylor, Sherry; Tobin, Stasey

2013-01-01

Objective To explore views of women and health care providers (HCPs) about the changing recommendations regarding maternal age–based prenatal screening. Design Mixed-methods design. Setting Ontario. Participants A sample of women who had given birth within the previous 2 years and who had attended a family medicine centre, midwifery practice, or baby and mother wellness program (n = 42); and a random sample of family physicians (n = 1600), and all Ontario obstetricians (n = 694) and midwives (n = 334) who provided prenatal care. Methods We used focus groups (FGs) to explore women's views. Content analysis was used to uncover themes and delineate meaning. To explore HCPs' views, we conducted a cross-sectional self-completion survey. Main findings All FG participants (42 women in 6 FGs) expressed the importance of individual choice of prenatal screening modality, regardless of age. They described their perception that society considers women older than 35 to be at high obstetric risk and raised concerns that change in the maternal age–related screening policy would require education. The HCP survey response rate was 40%. Results showed 24% of HCPs agreed that women of any age should be eligible for invasive diagnostic testing regardless of prenatal screening results; 15% agreed that the age for diagnostic testing should be increased to 40 years, 14% agreed that diagnostic testing should be reserved for women with positive prenatal screening results, and 45% agreed that prenatal screening should remain unchanged. Conclusion Maternity care organizations have recommended that maternal age–based prenatal screening is no longer appropriate. Informed choice is of paramount importance to women and should be part of any change. Health care providers need to be engaged in and educated about any change to screening guidelines to offer women informed choices. PMID:23341678

Electrochemical estrogen screen method based on the electrochemical behavior of MCF-7 cells.

PubMed

Li, Jinlian; Song, Jia; Bi, Sheng; Zhou, Shi; Cui, Jiwen; Liu, Jiguang; Wu, Dongmei

2016-08-05

It was an urgent task to develop quick, cheap and accurate estrogen screen method for evaluating the estrogen effect of the booming chemicals. In this study, the voltammetric behavior between the estrogen-free and normal fragmented MCF-7 cell suspensions were compared, and the electrochemical signal (about 0.68V attributed by xanthine and guanine) of the estrogen-free fragmented MCF-7 cell suspension was obviously lower than that of the normal one. The electrochemistry detection of ex-secretion purines showed that the ability of ex-secretion purines of cells sharp decreased due to the removing of endogenous estrogen. The results indicated that the electrochemical signal of MCF-7 cells was related to the level of intracellular estrogen. When the level of intracellular estrogen was down-regulated, the concentrations of the xanthine and hypoxanthine decreased, which led to the electrochemical signal of MCF-7 cells fall. Based on the electrochemical signal, the electrochemical estrogen screen method was established. The estrogen effect of estradiol, nonylphenol and bisphenol A was evaluated with the electrochemical method, and the result was accordant with that of MTT assay. The electrochemical estrogen screen method was simple, quickly, cheap, objective, and it exploits a new way for the evaluation of estrogenic effects of chemicals. Copyright © 2016. Published by Elsevier B.V.

Screening for small molecule inhibitors of Toxoplasma gondii.

PubMed

Kortagere, Sandhya

2012-12-01

Toxoplasma gondii, the agent that causes toxoplasmosis, is an opportunistic parasite that infects many mammalian species. It is an obligate intracellular parasite that causes severe congenital neurological and ocular disease mostly in immunocompromised humans. The current regimen of therapy includes only a few medications that often lead to hypersensitivity and toxicity. In addition, there are no vaccines available to prevent the transmission of this agent. Therefore, safer and more effective medicines to treat toxoplasmosis are urgently needed. The author presents in silico and in vitro strategies that are currently used to screen for novel targets and unique chemotypes against T. gondii. Furthermore, this review highlights the screening technologies and characterization of some novel targets and new chemical entities that could be developed into highly efficacious treatments for toxoplasmosis. A number of diverse methods are being used to design inhibitors against T. gondii. These include ligand-based methods, in which drugs that have been shown to be efficacious against other Apicomplexa parasites can be repurposed to identify lead molecules against T. gondii. In addition, structure-based methods use currently available repertoire of structural information in various databases to rationally design small-molecule inhibitors of T. gondii. Whereas the screening methods have their advantages and limitations, a combination of methods is ideally suited to design small-molecule inhibitors of complex parasites such as T. gondii.

Computer-aided diagnosis workstation and network system for chest diagnosis based on multislice CT images

NASA Astrophysics Data System (ADS)

Satoh, Hitoshi; Niki, Noboru; Eguchi, Kenji; Moriyama, Noriyuki; Ohmatsu, Hironobu; Masuda, Hideo; Machida, Suguru

2008-03-01

Mass screening based on multi-helical CT images requires a considerable number of images to be read. It is this time-consuming step that makes the use of helical CT for mass screening impractical at present. To overcome this problem, we have provided diagnostic assistance methods to medical screening specialists by developing a lung cancer screening algorithm that automatically detects suspected lung cancers in helical CT images, a coronary artery calcification screening algorithm that automatically detects suspected coronary artery calcification and a vertebra body analysis algorithm for quantitative evaluation of osteoporosis likelihood by using helical CT scanner for the lung cancer mass screening. The function to observe suspicious shadow in detail are provided in computer-aided diagnosis workstation with these screening algorithms. We also have developed the telemedicine network by using Web medical image conference system with the security improvement of images transmission, Biometric fingerprint authentication system and Biometric face authentication system. Biometric face authentication used on site of telemedicine makes "Encryption of file" and Success in login" effective. As a result, patients' private information is protected. Based on these diagnostic assistance methods, we have developed a new computer-aided workstation and a new telemedicine network that can display suspected lesions three-dimensionally in a short time. The results of this study indicate that our radiological information system without film by using computer-aided diagnosis workstation and our telemedicine network system can increase diagnostic speed, diagnostic accuracy and security improvement of medical information.

ALTERNATIVE REMEDIATION TECHNOLOGY STUDY FOR GROUNDWATER TREATMENT AT 200-PO-1 OPERABLE UNIT AT HANFORD SITE

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

DADO MA

2008-07-31

This study focuses on the remediation methods and technologies applicable for use at 200-PO-I Groundwater Operable Unit (OU) at the Hanford Site. The 200-PO-I Groundwater au requires groundwater remediation because of the existence of contaminants of potential concern (COPC). A screening was conducted on alternative technologies and methods of remediation to determine which show the most potential for remediation of groundwater contaminants. The possible technologies were screened to determine which would be suggested for further study and which were not applicable for groundwater remediation. COPCs determined by the Hanford Site groundwater monitoring were grouped into categories based on properties linkingmore » them by remediation methods applicable to each COPC group. The screening considered the following criteria. (1) Determine if the suggested method or technology can be used for the specific contaminants found in groundwater and if the technology can be applied at the 200-PO-I Groundwater au, based on physical characteristics such as geology and depth to groundwater. (2) Evaluate screened technologies based on testing and development stages, effectiveness, implementability, cost, and time. This report documents the results of an intern research project conducted by Mathew Dado for Central Plateau Remediation in the Soil and Groundwater Remediation Project. The study was conducted under the technical supervision of Gloria Cummins and management supervision of Theresa Bergman and Becky Austin.« less

Using in Vitro Evolution and Whole Genome Analysis To Discover Next Generation Targets for Antimalarial Drug Discovery

PubMed Central

2018-01-01

Although many new anti-infectives have been discovered and developed solely using phenotypic cellular screening and assay optimization, most researchers recognize that structure-guided drug design is more practical and less costly. In addition, a greater chemical space can be interrogated with structure-guided drug design. The practicality of structure-guided drug design has launched a search for the targets of compounds discovered in phenotypic screens. One method that has been used extensively in malaria parasites for target discovery and chemical validation is in vitro evolution and whole genome analysis (IVIEWGA). Here, small molecules from phenotypic screens with demonstrated antiparasitic activity are used in genome-based target discovery methods. In this Review, we discuss the newest, most promising druggable targets discovered or further validated by evolution-based methods, as well as some exceptions. PMID:29451780

Screening-Level Ecological Risk Assessment Methods, Revision 3

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

Mirenda, Richard J.

2012-08-16

This document provides guidance for screening-level assessments of potential adverse impacts to ecological resources from release of environmental contaminants at the Los Alamos National Laboratory (LANL or the Laboratory). The methods presented are based on two objectives, namely: to provide a basis for reaching consensus with regulators, managers, and other interested parties on how to conduct screening-level ecological risk investigations at the Laboratory; and to provide guidance for ecological risk assessors under the Environmental Programs (EP) Directorate. This guidance promotes consistency, rigor, and defensibility in ecological screening investigations and in reporting those investigation results. The purpose of the screening assessmentmore » is to provide information to the risk managers so informed riskmanagement decisions can be made. This document provides examples of recommendations and possible risk-management strategies.« less

Identification of novel drug scaffolds for inhibition of SARS-CoV 3-Chymotrypsin-like protease using virtual and high-throughput screenings.

PubMed

Lee, Hyun; Mittal, Anuradha; Patel, Kavankumar; Gatuz, Joseph L; Truong, Lena; Torres, Jaime; Mulhearn, Debbie C; Johnson, Michael E

2014-01-01

We have used a combination of virtual screening (VS) and high-throughput screening (HTS) techniques to identify novel, non-peptidic small molecule inhibitors against human SARS-CoV 3CLpro. A structure-based VS approach integrating docking and pharmacophore based methods was employed to computationally screen 621,000 compounds from the ZINC library. The screening protocol was validated using known 3CLpro inhibitors and was optimized for speed, improved selectivity, and for accommodating receptor flexibility. Subsequently, a fluorescence-based enzymatic HTS assay was developed and optimized to experimentally screen approximately 41,000 compounds from four structurally diverse libraries chosen mainly based on the VS results. False positives from initial HTS hits were eliminated by a secondary orthogonal binding analysis using surface plasmon resonance (SPR). The campaign identified a reversible small molecule inhibitor exhibiting mixed-type inhibition with a K(i) value of 11.1 μM. Together, these results validate our protocols as suitable approaches to screen virtual and chemical libraries, and the newly identified compound reported in our study represents a promising structural scaffold to pursue for further SARS-CoV 3CLpro inhibitor development. Copyright © 2013. Published by Elsevier Ltd.

The Cost-Effectiveness of School-Based Eating Disorder Screening

PubMed Central

Austin, S. Bryn; LeAnn Noh, H.; Jiang, Yushan; Sonneville, Kendrin R.

2014-01-01

Objectives. We aimed to assess the value of school-based eating disorder (ED) screening for a hypothetical cohort of US public school students. Methods. We used a decision-analytic microsimulation model to model the effectiveness (life-years with ED and quality-adjusted life-years [QALYs]), total direct costs, and cost-effectiveness (cost per QALY gained) of screening relative to current practice. Results. The screening strategy cost $2260 (95% confidence interval [CI] = $1892, $2668) per student and resulted in a per capita gain of 0.25 fewer life-years with ED (95% CI = 0.21, 0.30) and 0.04 QALYs (95% CI = 0.03, 0.05) relative to current practice. The base case cost-effectiveness of the intervention was $9041 per life-year with ED avoided (95% CI = $6617, $12 344) and $56 500 per QALY gained (95% CI = $38 805, $71 250). Conclusions. At willingness-to-pay thresholds of $50 000 and $100 000 per QALY gained, school-based ED screening is 41% and 100% likely to be cost-effective, respectively. The cost-effectiveness of ED screening is comparable to many other accepted pediatric health interventions, including hypertension screening. PMID:25033131

Effectively Communicating Colorectal Cancer Screening Information to Primary Care Providers: Application for State, Tribe or Territory Comprehensive Cancer Control Coalitions

ERIC Educational Resources Information Center

Redmond, Jennifer; Vanderpool, Robin; McClung, Rebecca

2012-01-01

Background: Patients are more likely to be screened for colorectal cancer if it is recommended by a health care provider. Therefore, it is imperative that providers have access to the latest screening guidelines. Purpose: This practice-based project sought to identify Kentucky primary care providers' preferred sources and methods of receiving…

The Mathematics of a Successful Deconvolution: A Quantitative Assessment of Mixture-Based Combinatorial Libraries Screened Against Two Formylpeptide Receptors

PubMed Central

Santos, Radleigh G.; Appel, Jon R.; Giulianotti, Marc A.; Edwards, Bruce S.; Sklar, Larry A.; Houghten, Richard A.; Pinilla, Clemencia

2014-01-01

In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays. PMID:23722730

A cancer screening intervention for underserved Latina women by lay educators.

PubMed

Larkey, Linda K; Herman, Patricia M; Roe, Denise J; Garcia, Francisco; Lopez, A M; Gonzalez, J; Perera, Prasadini N; Saboda, Kathylynn

2012-05-01

Inadequate screening adherence for breast, cervical, and colorectal cancer among Latinas places them at greater risk for poor survival rates, once diagnosed. The purpose of this study was to examine two delivery methods of lay health educators (promotoras de salud) to increase screening behavior and evaluate costs. This community-based group randomized trial assigned Latinas due for breast, cervical, or colorectal cancer screening (n=1006) to promotora-taught cancer screening/prevention classes delivered individually (IND) or in social support groups (SSG) over 8 weeks. Screening behaviors were assessed immediately after and 3 and 15 months after intervention. Intervention costs per study arm were compared. Screening and maintenance behaviors were not significantly different between SSG and IND for any one type of cancer screening, but with a study entry requirement that participants were either never screened or due for screening, postintervention screening rates (that is, completing a screening that was due) were notable (39.4% and 45.5%, respectively). The cost of achieving any one screening was much higher for IND participants. SSG vs. IND delivery did not significantly affect cancer screening behaviors, but both interventions produced robust achievement of screenings for previously nonadherent participants. Group-based promotora-led interventions supporting social involvement are recommended as a more cost-effective approach to achieving cancer screening among Latina women.

In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen

PubMed Central

Plouffe, David; Brinker, Achim; McNamara, Case; Henson, Kerstin; Kato, Nobutaka; Kuhen, Kelli; Nagle, Advait; Adrián, Francisco; Matzen, Jason T.; Anderson, Paul; Nam, Tae-gyu; Gray, Nathanael S.; Chatterjee, Arnab; Janes, Jeff; Yan, S. Frank; Trager, Richard; Caldwell, Jeremy S.; Schultz, Peter G.; Zhou, Yingyao; Winzeler, Elizabeth A.

2008-01-01

The growing resistance to current first-line antimalarial drugs represents a major health challenge. To facilitate the discovery of new antimalarials, we have implemented an efficient and robust high-throughput cell-based screen (1,536-well format) based on proliferation of Plasmodium falciparum (Pf) in erythrocytes. From a screen of ≈1.7 million compounds, we identified a diverse collection of ≈6,000 small molecules comprised of >530 distinct scaffolds, all of which show potent antimalarial activity (<1.25 μM). Most known antimalarials were identified in this screen, thus validating our approach. In addition, we identified many novel chemical scaffolds, which likely act through both known and novel pathways. We further show that in some cases the mechanism of action of these antimalarials can be determined by in silico compound activity profiling. This method uses large datasets from unrelated cellular and biochemical screens and the guilt-by-association principle to predict which cellular pathway and/or protein target is being inhibited by select compounds. In addition, the screening method has the potential to provide the malaria community with many new starting points for the development of biological probes and drugs with novel antiparasitic activities. PMID:18579783

Six-degrees-of-freedom sensing based on pictures taken by single camera.

PubMed

Zhongke, Li; Yong, Wang; Yongyuan, Qin; Peijun, Lu

2005-02-01

Two six-degrees-of-freedom sensing methods are presented. In the first method, three laser beams are employed to set up Descartes' frame on a rigid body and a screen is adopted to form diffuse spots. In the second method, two superimposed grid screens and two laser beams are used. A CCD camera is used to take photographs in both methods. Both approaches provide a simple and error-free method to record the positions and the attitudes of a rigid body in motion continuously.

Screening for Pancreatic Cancer

PubMed Central

Brand, Randall E.

2007-01-01

Despite improvements in the clinical and surgical management of pancreatic cancer, limited strides have been made in the early detection of this highly lethal malignancy. The majority of localized pancreatic tumors are asymptomatic, and the recognized presenting symptoms of pancreatic adenocarcinoma are often vague and heterogeneous in nature. These factors, coupled with the lack of a sensitive and noninvasive screening method, have made population-based screening for pancreatic cancer impossible. Nevertheless, at least two large institutions have performed multimodality-screening protocols for individuals with high risk of pancreatic cancer based on genetic predisposition and strong family history. Abnormalities noted during these screening protocols prompted further investigation or surgery that resulted in the discovery of benign, potentially malignant, and malignant pancreatic lesions. In addition to ductal epithelial pancreatic intraepithelial neoplasia, greater sensitivity has recently been achieved in the identification and characterization of precancerous mucinous pancreatic tumors. Advancements in proteomics and DNA microarray technology may confirm serum-based biomarkers that could be incorporated into future screening algorithms for pancreatic cancer. PMID:21960811

Mammographic screening: measurement of the cost in a population based programme in Victoria, Australia.

PubMed

Hurley, S F; Livingston, P M; Thane, N; Quang, L

1994-08-01

To estimate the cost per woman participating in a mammographic screening programme, and to describe methods for measuring costs. Expenditure, resource usage, and throughput were monitored over a 12 month period. Unit costs for each phase of the screening process were estimated and linked with the probabilities of each screening outcome to obtain the cost per woman screened and the cost per breast cancer detected. A pilot, population based Australian programme offering free two-view mammographic screening. A total of 5986 women aged 50-69 years who lived in the target area, were listed on the electoral roll, had no previous breast cancer, and attended the programme. Unit costs for recruitment, screening, and recall mammography were $17.54, $60.04, and $175.54, respectively. The costs of clinical assessment for women with subsequent clear, benign, malignant (palpable), and malignant (impalpable) diagnoses were $173.71, $527.29, $436.62, and $567.22, respectively. The cost per woman screened was $117.70, and the cost per breast cancer detected was $11,550. The cost per woman screened is a key variable in assessment of the cost effectiveness of mammographic screening, and is likely to vary between health care settings. Its measurement is justified if decisions about health care services are to be based on cost effectiveness criteria.

A calibration method for fringe reflection technique based on the analytical phase-slope description

NASA Astrophysics Data System (ADS)

Wu, Yuxiang; Yue, Huimin; Pan, Zhipeng; Liu, Yong

2018-05-01

The fringe reflection technique (FRT) has been one of the most popular methods to measure the shape of specular surface these years. The existing system calibration methods of FRT usually contain two parts, which are camera calibration and geometric calibration. In geometric calibration, the liquid crystal display (LCD) screen position calibration is one of the most difficult steps among all the calibration procedures, and its accuracy is affected by the factors such as the imaging aberration, the plane mirror flatness, and LCD screen pixel size accuracy. In this paper, based on the deduction of FRT analytical phase-slope description, we present a novel calibration method with no requirement to calibrate the position of LCD screen. On the other hand, the system can be arbitrarily arranged, and the imaging system can either be telecentric or non-telecentric. In our experiment of measuring the 5000mm radius sphere mirror, the proposed calibration method achieves 2.5 times smaller measurement error than the geometric calibration method. In the wafer surface measuring experiment, the measurement result with the proposed calibration method is closer to the interferometer result than the geometric calibration method.

NEW FRONTIERS IN DRUGGABILITY

PubMed Central

Kozakov, Dima; Hall, David R.; Napoleon, Raeanne L.; Yueh, Christine; Whitty, Adrian; Vajda, Sandor

2016-01-01

A powerful early approach to evaluating the druggability of proteins involved determining the hit rate in NMR-based screening of a library of small compounds. Here we show that a computational analog of this method, based on mapping proteins using small molecules as probes, can reliably reproduce druggability results from NMR-based screening, and can provide a more meaningful assessment in cases where the two approaches disagree. We apply the method to a large set of proteins. The results show that, because the method is based on the biophysics of binding rather than on empirical parameterization, meaningful information can be gained about classes of proteins and classes of compounds beyond those resembling validated targets and conventionally druglike ligands. In particular, the method identifies targets that, while not druggable by druglike compounds, may become druggable using compound classes such as macrocycles or other large molecules beyond the rule-of-five limit. PMID:26230724

A new concept and a comprehensive evaluation of SYSMEX UF-1000i  flow cytometer to identify culture-negative urine specimens in patients with UTI.

PubMed

Monsen, T; Ryden, P

2017-09-01

Urinary tract infections (UTIs) are among the most common bacterial infections in men and urine culture is gold standard for diagnosis. Considering the high prevalence of culture-negative specimens, any method that identifies such specimens is of interest. The aim was to evaluate a new screening concept for flow cytometry analysis (FCA). The outcomes were evaluated against urine culture, uropathogen species and three conventional screening methods. A prospective, consecutive study examined 1,312 urine specimens, collected during January and February 2012. The specimens were analyzed using the Sysmex UF1000i FCA. Based on the FCA data culture negative specimens were identified in a new model by use of linear discriminant analysis (FCA-LDA). In total 1,312 patients were included. In- and outpatients represented 19.6% and 79.4%, respectively; 68.3% of the specimens originated from women. Of the 610 culture-positive specimens, Escherichia coli represented 64%, enterococci 8% and Klebsiella spp. 7%. Screening with FCA-LDA at 95% sensitivity identified 42% (552/1312) as culture negative specimens when UTI was defined according to European guidelines. The proposed screening method was either superior or similar in comparison to the three conventional screening methods. In conclusion, the proposed/suggested and new FCA-LDA screening method was superior or similar to three conventional screening methods. We recommend the proposed screening method to be used in clinic to exclude culture negative specimens, to reduce workload, costs and the turnaround time. In addition, the FCA data may add information that enhance handling and support diagnosis of patients with suspected UTI pending urine culture [corrected].

A new method to evaluate the biocontrol potential of single spore isolates of fungal entomopathogens

PubMed Central

Posada, Francisco J.; Vega, Fernando E.

2005-01-01

Fifty Beauveria bassiana (Balsamo) Vuillemin (Ascomycota: Hypocreales) strains isolated from the coffee berry borer were used to develop a novel screening method aimed at selecting strains with the highest biocontrol potential. The screening method is based on percent insect mortality, average survival time, mortality distribution, percent spore germination, fungal life cycle duration, and spore production on the insect. Based on these parameters, only 11 strains merited further study. The use of a sound scientific protocol for the selection of promising fungal entomopathogens should lead to more efficient use of time, labor, and financial resources in biological control programs. PMID:17119619

Association between background parenchymal enhancement of breast MRI and BIRADS rating change in the subsequent screening

NASA Astrophysics Data System (ADS)

Aghaei, Faranak; Mirniaharikandehei, Seyedehnafiseh; Hollingsworth, Alan B.; Stoug, Rebecca G.; Pearce, Melanie; Liu, Hong; Zheng, Bin

2018-03-01

Although breast magnetic resonance imaging (MRI) has been used as a breast cancer screening modality for high-risk women, its cancer detection yield remains low (i.e., <= 3%). Thus, increasing breast MRI screening efficacy and cancer detection yield is an important clinical issue in breast cancer screening. In this study, we investigated association between the background parenchymal enhancement (BPE) of breast MRI and the change of diagnostic (BIRADS) status in the next subsequent breast MRI screening. A dataset with 65 breast MRI screening cases was retrospectively assembled. All cases were rated BIRADS-2 (benign findings). In the subsequent screening, 4 cases were malignant (BIRADS-6), 48 remained BIRADS-2 and 13 were downgraded to negative (BIRADS-1). A computer-aided detection scheme was applied to process images of the first set of breast MRI screening. Total of 33 features were computed including texture feature and global BPE features. Texture features were computed from either a gray-level co-occurrence matrix or a gray level run length matrix. Ten global BPE features were also initially computed from two breast regions and bilateral difference between the left and right breasts. Box-plot based analysis shows positive association between texture features and BIRADS rating levels in the second screening. Furthermore, a logistic regression model was built using optimal features selected by a CFS based feature selection method. Using a leave-one-case-out based cross-validation method, classification yielded an overall 75% accuracy in predicting the improvement (or downgrade) of diagnostic status (to BIRAD-1) in the subsequent breast MRI screening. This study demonstrated potential of developing a new quantitative imaging marker to predict diagnostic status change in the short-term, which may help eliminate a high fraction of unnecessary repeated breast MRI screenings and increase the cancer detection yield.

Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening electrophilic dermal sensitizers

PubMed Central

Chipinda, Itai; Mbiya, Wilbes; Adigun, Risikat Ajibola; Morakinyo, Moshood K.; Law, Brandon F.; Simoyi, Reuben H.; Siegel, Paul D.

2015-01-01

Chemical allergens bind directly, or after metabolic or abiotic activation, to endogenous proteins to become allergenic. Assessment of this initial binding has been suggested as a target for development of assays to screen chemicals for their allergenic potential. Recently we reported a nitrobenzenethiol (NBT) based method for screening thiol reactive skin sensitizers, however, amine selective sensitizers are not detected by this assay. In the present study we describe an amine (pyridoxylamine (PDA)) based kinetic assay to complement the NBT assay for identification of amine-selective and non-selective skin sensitizers. UV-Vis spectrophotometry and fluorescence were used to measure PDA reactivity for 57 chemicals including anhydrides, aldehydes, and quinones where reaction rates ranged from 116 to 6.2 × 10−6 M−1 s−1 for extreme to weak sensitizers, respectively. No reactivity towards PDA was observed with the thiol-selective sensitizers, non-sensitizers and prohaptens. The PDA rate constants correlated significantly with their respective murine local lymph node assay (LLNA) threshold EC3 values (R2 = 0.76). The use of PDA serves as a simple, inexpensive amine based method that shows promise as a preliminary screening tool for electrophilic, amine-selective skin sensitizers. PMID:24333919

Microplate-based method to screen inhibitors of isozymes of cyclic nucleotide phosphodiesterase fused to SUMO.

PubMed

Chen, Chunyan; Liu, Miaomiao; Wu, Jing; Yang, Xiaolan; Hu, Xiaolei; Pu, Jun; Long, Gaobo; Xie, Yanling; Jiang, Hairong; Yuan, Yonghua; Liao, Fei

2014-12-01

The feasibility for microplate-based screening of inhibitors of isozymes of cyclic nucleotide phosphodiesterase (PDE) was tested via the coupled action of a phosphatase on adenosine-5'-monophosphate and an improved malachite green assay of phosphate. Human full-length PDE4B2 and truncated mutant (152-528aa) were expressed in Escherichia coli via fusion to SUMO, which after purification through Ni-NTA column exhibited specific activities >0.017 U mg(-1). In the presence of proteins <30 mg L(-1), absorbance for 10 µΜ phosphate was measurable; a PDE isozyme of specific activity over 0.008 U mg(-1) after reaction for 20 min thus suited for microplate-based screening of inhibitors. By using Biotek ELX 800 microplate reader, affinities of two forms of PEDE4B2 for cAMP, rolipram and papaverine varied over three magnitudes and were consistent with those by routine assay, respectively. Hence, the proposed method was promising for high-throughput-screening of inhibitors of phosphate-releasing enzymes bearing specific activities over 0.008 U mg(-1).

Screening a fragment cocktail library using ultrafiltration

PubMed Central

Shibata, Sayaka; Zhang, Zhongsheng; Korotkov, Konstantin V.; Delarosa, Jaclyn; Napuli, Alberto; Kelley, Angela M.; Mueller, Natasha; Ross, Jennifer; Zucker, Frank H.; Buckner, Frederick S.; Merritt, Ethan A.; Verlinde, Christophe L. M. J.; Van Voorhis, Wesley C.; Hol, Wim G. J.; Fan, Erkang

2011-01-01

Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar Kd, the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins. PMID:21750879

Barriers to asymptomatic screening and other STD services for adolescents and young adults: focus group discussions

PubMed Central

Tilson, Elizabeth C; Sanchez, Victoria; Ford, Chandra L; Smurzynski, Marlene; Leone, Peter A; Fox, Kimberley K; Irwin, Kathleen; Miller, William C

2004-01-01

Background Sexually transmitted diseases (STDs) are a major public health problem among young people and can lead to the spread of HIV. Previous studies have primarily addressed barriers to STD care for symptomatic patients. The purpose of our study was to identify perceptions about existing barriers to and ideal services for STDs, especially asymptomatic screening, among young people in a southeastern community. Methods Eight focus group discussions including 53 White, African American, and Latino youth (age 14–24) were conducted. Results Perceived barriers to care included lack of knowledge of STDs and available services, cost, shame associated with seeking services, long clinic waiting times, discrimination, and urethral specimen collection methods. Perceived features of ideal STD services included locations close to familiar places, extended hours, and urine-based screening. Television was perceived as the most effective route of disseminating STD information. Conclusions Further research is warranted to evaluate improving convenience, efficiency, and privacy of existing services; adding urine-based screening and new services closer to neighborhoods; and using mass media to disseminate STD information as strategies to increase STD screening. PMID:15189565

Testing the convergent validity of the contingent valuation and travel cost methods in valuing the benefits of health care.

PubMed

Clarke, Philip M

2002-03-01

In this study, the convergent validity of the contingent valuation method (CVM) and travel cost method (TCM) is tested by comparing estimates of the willingness to pay (WTP) for improving access to mammographic screening in rural areas of Australia. It is based on a telephone survey of 458 women in 19 towns, in which they were asked about their recent screening behaviour and their WTP to have a mobile screening unit visit their nearest town. After eliminating missing data and other non-usable responses the contingent valuation experiment and travel cost model were based on information from 372 and 319 women, respectively. Estimates of the maximum WTP for the use of mobile screening units were derived using both methods and compared. The highest mean WTP estimated using the TCM was $83.10 (95% C.I. $99.06-$68.53), which is significantly less than the estimate of $148.09 ($131.13-$166.60) using the CVM. This could be due to the CVM estimates also reflecting non-use values such as altruism, or a range of potential biases that are known to affect both methods. Further tests of validity are required in order to gain a greater understanding of the relationship between these two methods of estimating WTP. Copyright 2001 John Wiley & Sons, Ltd.

Bridging the Gap: Using School-Based Health Services to Improve Chlamydia Screening Among Young Women

PubMed Central

Provost, Jackie M.

2010-01-01

Objectives. We implemented a chlamydia screening program targeted at young women accessing reproductive health care services in a school-based setting, and we assessed racial/ethnic factors associated with infection. Methods. The California Family Health Council partnered with 9 health care agencies receiving federal Title X family planning funding and 19 educational institutions to implement the Educational Partnerships to Increase Chlamydia Screening (EPICS) program from January 2008 through December 2008. Results. EPICS agencies provided reproductive health services to 3396 unique sexually active females, 85% of whom self-reported no other source for reproductive health care. Chlamydia screening was provided to 3026 clients (89.1% chlamydia screening coverage). Of those screened for chlamydia, 5.6% tested positive. Clients who were African American (odds ratio [OR] = 7.5; 95% confidence interval [CI] = 3.9, 14.3), Pacific Islander (OR = 4.1; 95% CI = 1.1, 15.5), or Asian (OR = 3.3; 95% CI = 1.4, 8.1) were more likely to have a positive test than were White clients. Conclusions. Chlamydia screening programs implemented in school-based settings have the capacity to identify and treat a significant amount of asymptomatic infection in a population that otherwise may not be reached. To facilitate screening, school-based clinics should implement outreach strategies that target their school population and clinical strategies that maximize opportunities for screening. PMID:20634446

Computational design of auxotrophy-dependent microbial biosensors for combinatorial metabolic engineering experiments.

PubMed

Tepper, Naama; Shlomi, Tomer

2011-01-21

Combinatorial approaches in metabolic engineering work by generating genetic diversity in a microbial population followed by screening for strains with improved phenotypes. One of the most common goals in this field is the generation of a high rate chemical producing strain. A major hurdle with this approach is that many chemicals do not have easy to recognize attributes, making their screening expensive and time consuming. To address this problem, it was previously suggested to use microbial biosensors to facilitate the detection and quantification of chemicals of interest. Here, we present novel computational methods to: (i) rationally design microbial biosensors for chemicals of interest based on substrate auxotrophy that would enable their high-throughput screening; (ii) predict engineering strategies for coupling the synthesis of a chemical of interest with the production of a proxy metabolite for which high-throughput screening is possible via a designed bio-sensor. The biosensor design method is validated based on known genetic modifications in an array of E. coli strains auxotrophic to various amino-acids. Predicted chemical production rates achievable via the biosensor-based approach are shown to potentially improve upon those predicted by current rational strain design approaches. (A Matlab implementation of the biosensor design method is available via http://www.cs.technion.ac.il/~tomersh/tools).

Barriers to and Facilitators of Compliance with Clinic-Based Cervical Cancer Screening: Population-Based Cohort Study of Women Aged 23-60 Years

PubMed Central

Östensson, Ellinor; Alder, Susanna; Elfström, K. Miriam; Sundström, Karin; Zethraeus, Niklas; Arbyn, Marc; Andersson, Sonia

2015-01-01

Objective This study aims to identify possible barriers to and facilitators of cervical cancer screening by (a) estimating time and travel costs and other direct non-medical costs incurred in attending clinic-based cervical cancer screening, (b) investigating screening compliance and reasons for noncompliance, (c) determining women’s knowledge of human papillomavirus (HPV), its relationship to cervical cancer, and HPV and cervical cancer prevention, and (d) investigating correlates of HPV knowledge and screening compliance. Materials and Methods 1510 women attending the clinic-based cervical cancer screening program in Stockholm, Sweden were included. Data on sociodemographic characteristics, time and travel costs and other direct non-medical costs incurred in attending (e.g., indirect cost of time needed for the screening visit, transportation costs, child care costs, etc.), mode(s) of travel, time, distance, companion’s attendance, HPV knowledge, and screening compliance were obtained via self-administered questionnaire. Results Few respondents had low socioeconomic status. Mean total time and travel costs and direct non-medical cost per attendance, including companion (if any) were €55.6. Over half (53%) of the respondents took time off work to attend screening (mean time 147 minutes). A large portion (44%) of the respondents were noncompliant (i.e., did not attend screening within 1 year of the initial invitation), 51% of whom stated difficulties in taking time off work. 64% of all respondents knew that HPV vaccination was available; only 34% knew it was important to continue to attend screening following vaccination. Age, education, and income were the most important correlates of HPV knowledge and compliance; and additional factors associated with compliance were time off work, accompanying companion and HPV knowledge. Conclusion Time and travel costs and other direct non-medical costs for clinic-based screening can be considerable, may affect the cost-effectiveness of a screening program, and may constitute barriers to screening while HPV knowledge may facilitate compliance with screening. PMID:26011051

Accuracy and Cost-Effectiveness of Cervical Cancer Screening by High-Risk HPV DNA Testing of Self-Collected Vaginal Samples

PubMed Central

Balasubramanian, Akhila; Kulasingam, Shalini L.; Baer, Atar; Hughes, James P.; Myers, Evan R.; Mao, Constance; Kiviat, Nancy B.; Koutsky, Laura A.

2010-01-01

Objective Estimate the accuracy and cost-effectiveness of cervical cancer screening strategies based on high-risk HPV DNA testing of self-collected vaginal samples. Materials and Methods A subset of 1,665 women (18-50 years of age) participating in a cervical cancer screening study were screened by liquid-based cytology and by high-risk HPV DNA testing of both self-collected vaginal swab samples and clinician-collected cervical samples. Women with positive/abnormal screening test results and a subset of women with negative screening test results were triaged to colposcopy. Based on individual and combined test results, five screening strategies were defined. Estimates of sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or worse were calculated and a Markov model was used to estimate the incremental cost-effectiveness ratios (ICERs) for each strategy. Results Compared to cytology-based screening, high-risk HPV DNA testing of self-collected vaginal samples was more sensitive (68%, 95%CI=58%-78% versus 85%, 95%CI=76%-94%) but less specific (89%, 95%CI=86%-91% versus 73%, 95%CI=67%-79%). A strategy of high-risk HPV DNA testing of self-collected vaginal samples followed by cytology triage of HPV positive women, was comparably sensitive (75%, 95%CI=64%-86%) and specific (88%, 95%CI=85%-92%) to cytology-based screening. In-home self-collection for high-risk HPV DNA detection followed by in-clinic cytology triage had a slightly lower lifetime cost and a slightly higher quality-adjusted life expectancy than did cytology-based screening (ICER of triennial screening compared to no screening was $9,871/QALY and $12,878/QALY, respectively). Conclusions Triennial screening by high-risk HPV DNA testing of in-home, self-collected vaginal samples followed by in-clinic cytology triage was cost-effective. PMID:20592553

Design of an off-axis visual display based on a free-form projection screen to realize stereo vision

NASA Astrophysics Data System (ADS)

Zhao, Yuanming; Cui, Qingfeng; Piao, Mingxu; Zhao, Lidong

2017-10-01

A free-form projection screen is designed for an off-axis visual display, which shows great potential in applications such as flight training for providing both accommodation and convergence cues for pilots. The method based on point cloud is proposed for the design of the free-form surface, and the design of the point cloud is controlled by a program written in the macro-language. In the visual display based on the free-form projection screen, when the error of the screen along Z-axis is 1 mm, the error of visual distance at each filed is less than 1%. And the resolution of the design for full field is better than 1‧, which meet the requirement of resolution for human eyes.

Highly sensitive screening method for nitroaromatic, nitramine and nitrate ester explosives by high performance liquid chromatography-atmospheric pressure ionization-mass spectrometry (HPLC-API-MS) in forensic applications.

PubMed

Xu, Xiaoma; van de Craats, Anick M; de Bruyn, Peter C A M

2004-11-01

A highly sensitive screening method based on high performance liquid chromatography atmospheric pressure ionization mass spectrometry (HPLC-API-MS) has been developed for the analysis of 21 nitroaromatic, nitramine and nitrate ester explosives, which include the explosives most commonly encountered in forensic science. Two atmospheric pressure ionization (API) methods, atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI), and various experimental conditions have been applied to allow for the detection of all 21 explosive compounds. The limit of detection (LOD) in the full-scan mode has been found to be 0.012-1.2 ng on column for the screening of most explosives investigated. For nitrobenzene, an LOD of 10 ng was found with the APCI method in the negative mode. Although the detection of nitrobenzene, 2-, 3-, and 4-nitrotoluene is hindered by the difficult ionization of these compounds, we have found that by forming an adduct with glycine, LOD values in the range of 3-16 ng on column can be achieved. Compared with previous screening methods with thermospray ionization, the API method has distinct advantages, including simplicity and stability of the method applied, an extended screening range and a low detection limit for the explosives studied.

One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists.

PubMed

Schiebel, Johannes; Radeva, Nedyalka; Köster, Helene; Metz, Alexander; Krotzky, Timo; Kuhnert, Maren; Diederich, Wibke E; Heine, Andreas; Neumann, Lars; Atmanene, Cedric; Roecklin, Dominique; Vivat-Hannah, Valérie; Renaud, Jean-Paul; Meinecke, Robert; Schlinck, Nina; Sitte, Astrid; Popp, Franziska; Zeeb, Markus; Klebe, Gerhard

2015-09-01

Fragment-based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit-to-lead-to-drug optimization, the screening process should distinguish reliably between binders and non-binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease-relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361-entry library by using a reporter-displacement assay, saturation-transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immunochemical faecal occult blood test for colorectal cancer screening: a systematic review.

PubMed

Syful Azlie, M F; Hassan, M R; Junainah, S; Rugayah, B

2015-02-01

A systematic review on the effectiveness and costeffectiveness of Immunochemical faecal occult IFOBT for CRC screening was carried out. A total of 450 relevant titles were identified, 41 abstracts were screened and 18 articles were included in the results. There was fair level of retrievable evidence to suggest that the sensitivity and specificity of IFOBT varies with the cut-off point of haemoglobin, whereas the diagnostic accuracy performance was influenced by high temperature and haemoglobin stability. A screening programme using IFOBT can be effective for prevention of advanced CRC and reduced mortality. There was also evidence to suggest that IFOBT is cost-effective in comparison with no screening, whereby a two-day faecal collection method was found to be costeffective as a means of screening for CRC. Based on the review, quantitative IFOBT method can be used in Malaysia as a screening test for CRC. The use of fully automated IFOBT assay would be highly desirable.

A multivariate cure model for left-censored and right-censored data with application to colorectal cancer screening patterns.

PubMed

Hagar, Yolanda C; Harvey, Danielle J; Beckett, Laurel A

2016-08-30

We develop a multivariate cure survival model to estimate lifetime patterns of colorectal cancer screening. Screening data cover long periods of time, with sparse observations for each person. Some events may occur before the study begins or after the study ends, so the data are both left-censored and right-censored, and some individuals are never screened (the 'cured' population). We propose a multivariate parametric cure model that can be used with left-censored and right-censored data. Our model allows for the estimation of the time to screening as well as the average number of times individuals will be screened. We calculate likelihood functions based on the observations for each subject using a distribution that accounts for within-subject correlation and estimate parameters using Markov chain Monte Carlo methods. We apply our methods to the estimation of lifetime colorectal cancer screening behavior in the SEER-Medicare data set. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Systematic screening and characterization of flavonoid glycosides in Carthamus tinctorius L. by liquid chromatography/UV diode-array detection/electrospray ionization tandem mass spectrometry.

PubMed

Jin, Yu; Xiao, Yuan-sheng; Zhang, Fei-fang; Xue, Xing-ya; Xu, Qing; Liang, Xin-miao

2008-02-13

The traditional Chinese medicine (TCM) is a complex system, which always consists of numerous compounds with significant difference in the content and physical and chemical properties. In this paper, a screening method based on target molecular weights was developed to characterize the flavonoid glycosides in the flower of Carthamus tinctorius L. The screening tables of aglycone and glycan were designed, respectively, in order to select and combine freely. The multiple reaction monitoring (MRM) scan mode with higher sensitivity and selectivity was adopted in the screening, which benefit the characterization for the minor components. Seventy-seven flavonoid glycosides were screened out finally, and their structures were characterized by tandem mass spectrometric method in both positive and negative ion modes. The glycosylation mode, aglycone, sequence and/or the interglycosidic linkages of the glycan portion and glycosylation position were elucidated by the fragmentation rule in the MS. Numerous compounds screened out with this method showed the structure variety in secondary plant metabolites, and the purposeful screening systemically and subsequent structure characterization offered more information about the chemical constitutions of TCM.

GWASinlps: Nonlocal prior based iterative SNP selection tool for genome-wide association studies.

PubMed

Sanyal, Nilotpal; Lo, Min-Tzu; Kauppi, Karolina; Djurovic, Srdjan; Andreassen, Ole A; Johnson, Valen E; Chen, Chi-Hua

2018-06-19

Multiple marker analysis of the genome-wide association study (GWAS) data has gained ample attention in recent years. However, because of the ultra high-dimensionality of GWAS data, such analysis is challenging. Frequently used penalized regression methods often lead to large number of false positives, whereas Bayesian methods are computationally very expensive. Motivated to ameliorate these issues simultaneously, we consider the novel approach of using nonlocal priors in an iterative variable selection framework. We develop a variable selection method, named, iterative nonlocal prior based selection for GWAS, or GWASinlps, that combines, in an iterative variable selection framework, the computational efficiency of the screen-and-select approach based on some association learning and the parsimonious uncertainty quantification provided by the use of nonlocal priors. The hallmark of our method is the introduction of 'structured screen-and-select' strategy, that considers hierarchical screening, which is not only based on response-predictor associations, but also based on response-response associations, and concatenates variable selection within that hierarchy. Extensive simulation studies with SNPs having realistic linkage disequilibrium structures demonstrate the advantages of our computationally efficient method compared to several frequentist and Bayesian variable selection methods, in terms of true positive rate, false discovery rate, mean squared error, and effect size estimation error. Further, we provide empirical power analysis useful for study design. Finally, a real GWAS data application was considered with human height as phenotype. An R-package for implementing the GWASinlps method is available at https://cran.r-project.org/web/packages/GWASinlps/index.html. Supplementary data are available at Bioinformatics online.

Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand

PubMed Central

Lew, Jie-Bin; Simms, Kate; Smith, Megan; Lewis, Hazel; Neal, Harold; Canfell, Karen

2016-01-01

Background New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20–69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). Methods A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. Results Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25–69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12–16% and to save 4–13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. Conclusion Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ. PMID:27187495

EVALUATION OF LITERATURE ESTABLISHING SCREENING LEVELS FOR TERRESTRIAL PLANTS/INVERTEBRATES

EPA Science Inventory

Scientific publications often lack key information on experimental design or do not follow appropriate test methods and therefore cannot be used in deriving reliable benchmarks. Risk based soil screening levels (Eco-SSLs) are being established for chemicals of concern to terrestr...

Developing science gateways for drug discovery in a grid environment.

PubMed

Pérez-Sánchez, Horacio; Rezaei, Vahid; Mezhuyev, Vitaliy; Man, Duhu; Peña-García, Jorge; den-Haan, Helena; Gesing, Sandra

2016-01-01

Methods for in silico screening of large databases of molecules increasingly complement and replace experimental techniques to discover novel compounds to combat diseases. As these techniques become more complex and computationally costly we are faced with an increasing problem to provide the research community of life sciences with a convenient tool for high-throughput virtual screening on distributed computing resources. To this end, we recently integrated the biophysics-based drug-screening program FlexScreen into a service, applicable for large-scale parallel screening and reusable in the context of scientific workflows. Our implementation is based on Pipeline Pilot and Simple Object Access Protocol and provides an easy-to-use graphical user interface to construct complex workflows, which can be executed on distributed computing resources, thus accelerating the throughput by several orders of magnitude.

Modelling, simulation and verification of the screening process of a swing-bar sieve based on the DEM

NASA Astrophysics Data System (ADS)

Wang, Yang; Yu, Jianqun; Yu, Yajun

2018-05-01

To solve the problems in the DEM simulations of the screening process of a swing-bar sieve, in this paper we propose the real-virtual boundary method to build the geometrical model of the screen deck on a swing-bar sieve. The motion of the swing-bar sieve is modelled by the planer multi-body kinematics. A coupled model of the discrete element method (DEM) with multi-body kinematics (MBK) is presented to simulate the flowing and passing processes of soybean particles on the screen deck. By the comparison of the simulated results with the experimental results of the screening process of the LA-LK laboratory scale swing-bar sieve, the feasibility and validity of the real-virtual boundary method and the coupled DEM-MBK model we proposed in this paper can be verified. This work provides the basis for the optimization design of the swing-bar sieve with circular apertures and complex motion.

How to select the correct education strategy: when not to go online.

PubMed

Klingbeil, Carol G; Johnson, Norah L; Totka, Joan P; Doyle, Lynn

2009-01-01

Screening for intimate partner violence is an important injury prevention strategy. Nurses who develop staff education, to promote screening, need to select a method that is sensitive to learners. Online learning, although convenient, is not well suited to sensitive topics such as screening for intimate partner violence. The purpose of this article is to describe a curriculum for intimate partner violence screening based on self-efficacy theory, which includes a hospital-produced video, a role play, and a discussion.

Determination of a Screening Metric for High Diversity DNA Libraries.

PubMed

Guido, Nicholas J; Handerson, Steven; Joseph, Elaine M; Leake, Devin; Kung, Li A

2016-01-01

The fields of antibody engineering, enzyme optimization and pathway construction rely increasingly on screening complex variant DNA libraries. These highly diverse libraries allow researchers to sample a maximized sequence space; and therefore, more rapidly identify proteins with significantly improved activity. The current state of the art in synthetic biology allows for libraries with billions of variants, pushing the limits of researchers' ability to qualify libraries for screening by measuring the traditional quality metrics of fidelity and diversity of variants. Instead, when screening variant libraries, researchers typically use a generic, and often insufficient, oversampling rate based on a common rule-of-thumb. We have developed methods to calculate a library-specific oversampling metric, based on fidelity, diversity, and representation of variants, which informs researchers, prior to screening the library, of the amount of oversampling required to ensure that the desired fraction of variant molecules will be sampled. To derive this oversampling metric, we developed a novel alignment tool to efficiently measure frequency counts of individual nucleotide variant positions using next-generation sequencing data. Next, we apply a method based on the "coupon collector" probability theory to construct a curve of upper bound estimates of the sampling size required for any desired variant coverage. The calculated oversampling metric will guide researchers to maximize their efficiency in using highly variant libraries.

Introducing Bayesian thinking to high-throughput screening for false-negative rate estimation.

PubMed

Wei, Xin; Gao, Lin; Zhang, Xiaolei; Qian, Hong; Rowan, Karen; Mark, David; Peng, Zhengwei; Huang, Kuo-Sen

2013-10-01

High-throughput screening (HTS) has been widely used to identify active compounds (hits) that bind to biological targets. Because of cost concerns, the comprehensive screening of millions of compounds is typically conducted without replication. Real hits that fail to exhibit measurable activity in the primary screen due to random experimental errors will be lost as false-negatives. Conceivably, the projected false-negative rate is a parameter that reflects screening quality. Furthermore, it can be used to guide the selection of optimal numbers of compounds for hit confirmation. Therefore, a method that predicts false-negative rates from the primary screening data is extremely valuable. In this article, we describe the implementation of a pilot screen on a representative fraction (1%) of the screening library in order to obtain information about assay variability as well as a preliminary hit activity distribution profile. Using this training data set, we then developed an algorithm based on Bayesian logic and Monte Carlo simulation to estimate the number of true active compounds and potential missed hits from the full library screen. We have applied this strategy to five screening projects. The results demonstrate that this method produces useful predictions on the numbers of false negatives.

Assessing HTS Performance Using BioAssay Ontology: Screening and Analysis of a Bacterial Phospho-N-Acetylmuramoyl-Pentapeptide Translocase Campaign

PubMed Central

Moberg, Andreas; Hansson, Eva; Boyd, Helen

2014-01-01

Abstract With the public availability of biochemical assays and screening data constantly increasing, new applications for data mining and method analysis are evolving in parallel. One example is BioAssay Ontology (BAO) for systematic classification of assays based on screening setup and metadata annotations. In this article we report a high-throughput screening (HTS) against phospho-N-acetylmuramoyl-pentapeptide translocase (MraY), an attractive antibacterial drug target involved in peptidoglycan synthesis. The screen resulted in novel chemistry identification using a fluorescence resonance energy transfer assay. To address a subset of the false positive hits, a frequent hitter analysis was performed using an approach in which MraY hits were compared with hits from similar assays, previously used for HTS. The MraY assay was annotated according to BAO and three internal reference assays, using a similar assay design and detection technology, were identified. Analyzing the assays retrospectively, it was clear that both MraY and the three reference assays all showed a high false positive rate in the primary HTS assays. In the case of MraY, false positives were efficiently identified by applying a method to correct for compound interference at the hit-confirmation stage. Frequent hitter analysis based on the three reference assays with similar assay method identified additional false actives in the primary MraY assay as frequent hitters. This article demonstrates how assays annotated using BAO terms can be used to identify closely related reference assays, and that analysis based on these assays clearly can provide useful data to influence assay design, technology, and screening strategy. PMID:25415593

Improving the delivery of brief interventions for heavy drinking in primary health care: outcome results of the Optimizing Delivery of Health Care Intervention (ODHIN) five-country cluster randomized factorial trial.

PubMed

Anderson, Peter; Bendtsen, Preben; Spak, Fredrik; Reynolds, Jillian; Drummond, Colin; Segura, Lidia; Keurhorst, Myrna N; Palacio-Vieira, Jorge; Wojnar, Marcin; Parkinson, Kathryn; Colom, Joan; Kłoda, Karolina; Deluca, Paolo; Baena, Begoña; Newbury-Birch, Dorothy; Wallace, Paul; Heinen, Maud; Wolstenholme, Amy; van Steenkiste, Ben; Mierzecki, Artur; Okulicz-Kozaryn, Katarzyna; Ronda, Gaby; Kaner, Eileen; Laurant, Miranda G H; Coulton, Simon; Gual, Toni

2016-11-01

To test if training and support, financial reimbursement and option of referring screen-positive patients to an internet-based method of giving advice (eBI) can increase primary health-care providers' delivery of Alcohol Use Disorders Identification Test (AUDIT)-C-based screening and advice to heavy drinkers. Cluster randomized factorial trial with 12-week implementation and measurement period. Primary health-care units (PHCU) in different locations throughout Catalonia, England, the Netherlands, Poland and Sweden. A total of 120 PHCU, 24 in each of Catalonia, England, the Netherlands, Poland and Sweden. PHCUs were randomized to one of eight groups: care as usual, training and support (TS), financial reimbursement (FR) and eBI; paired combinations of TS, FR and eBI, and all of FR, TS and eBI. The primary outcome measure was the proportion of eligible adult (age 18+ years) patients screened during a 12-week implementation period. Secondary outcome measures were proportion of screen-positive patients advised; and proportion of consulting adult patients given an intervention (screening and advice to screen-positives) during the same 12-week implementation period. During a 4-week baseline measurement period, the proportion of consulting adult patients who were screened for their alcohol consumption was 0.059 per PHCU (95% CI 0.034 to 0.084). Based on the factorial design, the ratio of the logged proportion screened during the 12-week implementation period was 1.48 (95% CI = 1.13-1.95) in PHCU that received TS versus PHCU that did not receive TS; for FR, the ratio was 2.00 (95% CI = 1.56-2.56). The option of referral to eBI did not lead to a higher proportion of patients screened. The ratio for TS plus FR was 2.34 (95% CI = 1.77-3.10), and the ratio for TS plus FR plus eBI was1.68 (95% CI = 1.11-2.53). Providing primary health-care units with training, support and financial reimbursement for delivering Alcohol Use Disorders Identification Test-C-based screening and advice to heavy drinkers increases screening for alcohol consumption. Providing primary health-care units with the option of referring screen-positive patients to an internet-based method of giving advice does not appear to increase screening for alcohol consumption. © 2016 Society for the Study of Addiction.

Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy

PubMed Central

Sharp, L; Tilson, L; Whyte, S; O'Ceilleachair, A; Walsh, C; Usher, C; Tappenden, P; Chilcott, J; Staines, A; Barry, M; Comber, H

2012-01-01

Background: Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55–74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55–74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60. Methods: A state-transition model was used to estimate costs and outcomes for each screening scenario vs no screening. A third party payer perspective was adopted. Probabilistic sensitivity analyses were undertaken. Results: All scenarios would be considered highly cost-effective compared with no screening. The lowest incremental cost-effectiveness ratio (ICER vs no screening €589 per quality-adjusted life-year (QALY) gained) was found for FSIG, followed by FIT (€1696) and gFOBT (€4428); gFOBT was dominated. Compared with FSIG, FIT was associated with greater gains in QALYs and reductions in lifetime cancer incidence and mortality, but was more costly, required considerably more colonoscopies and resulted in more complications. Results were robust to variations in parameter estimates. Conclusion: Population-based screening based on FIT is expected to result in greater health gains than a policy of gFOBT (with reflex FIT) or once-only FSIG, but would require significantly more colonoscopy resources and result in more individuals experiencing adverse effects. Weighing these advantages and disadvantages presents a considerable challenge to policy makers. PMID:22343624

Cost Effectiveness of Interventions to Promote Screening for Colorectal Cancer: A Randomized Trial

PubMed Central

Misra, Swati; Chan, Wenyaw; Chang, Yu-Chia; Bartholomew, L. Kay; Greisinger, Anthony; McQueen, Amy; Vernon, Sally W.

2011-01-01

Objectives Screening for colorectal cancer is considered cost effective, but is underutilized in the U.S. Information on the efficiency of "tailored interventions" to promote colorectal cancer screening in primary care settings is limited. The paper reports the results of a cost effectiveness analysis that compared a survey-only control group to a Centers for Disease Control (CDC) web-based intervention (screen for life) and to a tailored interactive computer-based intervention. Methods A randomized controlled trial of people 50 and over, was conducted to test the interventions. The sample was 1224 partcipants 50-70 years of age, recruited from Kelsey-Seybold Clinic, a large multi-specialty clinic in Houston, Texas. Screening status was obtained by medical chart review after a 12-month follow-up period. An "intention to treat" analysis and micro costing from the patient and provider perspectives were used to estimate the costs and effects. Analysis of statistical uncertainty was conducted using nonparametric bootstrapping. Results The estimated cost of implementing the web-based intervention was $40 per person and the cost of the tailored intervention was $45 per person. The additional cost per person screened for the web-based intervention compared to no intervention was $2602 and the tailored intervention was no more effective than the web-based strategy. Conclusions The tailored intervention was less cost-effective than the web-based intervention for colorectal cancer screening promotion. The web-based intervention was less cost-effective than previous studies of in-reach colorectal cancer screening promotion. Researchers need to continue developing and evaluating the effectiveness and cost-effectiveness of interventions to increase colorectal cancer screening. PMID:21617335

Immobilized enzyme reactors in HPLC and its application in inhibitor screening: A review

PubMed Central

Fang, Si-Meng; Wang, Hai-Na; Zhao, Zhong-Xi; Wang, Wei-Hong

2011-01-01

This paper sets out to summarize the literatures based on immobilized enzyme bio-chromatography and its application in inhibitors screening in the last decade. In order to screen enzyme inhibitors from a mass of compounds in preliminary screening, multi-pore materials with good biocompatibility are used for the supports of immobilizing enzymes, and then the immobilized enzyme reactor applied as the immobilized enzyme stationary phase in HPLC. Therefore, a technology platform of high throughput screening is gradually established to screen the enzyme inhibitors as new anti-tumor drugs. Here, we briefly summarize the selective methods of supports, immobilization techniques, co-immobilized enzymes system and the screening model. PMID:29403726

Budget Impact Analysis of Switching to Digital Mammography in a Population-Based Breast Cancer Screening Program: A Discrete Event Simulation Model

PubMed Central

Comas, Mercè; Arrospide, Arantzazu; Mar, Javier; Sala, Maria; Vilaprinyó, Ester; Hernández, Cristina; Cots, Francesc; Martínez, Juan; Castells, Xavier

2014-01-01

Objective To assess the budgetary impact of switching from screen-film mammography to full-field digital mammography in a population-based breast cancer screening program. Methods A discrete-event simulation model was built to reproduce the breast cancer screening process (biennial mammographic screening of women aged 50 to 69 years) combined with the natural history of breast cancer. The simulation started with 100,000 women and, during a 20-year simulation horizon, new women were dynamically entered according to the aging of the Spanish population. Data on screening were obtained from Spanish breast cancer screening programs. Data on the natural history of breast cancer were based on US data adapted to our population. A budget impact analysis comparing digital with screen-film screening mammography was performed in a sample of 2,000 simulation runs. A sensitivity analysis was performed for crucial screening-related parameters. Distinct scenarios for recall and detection rates were compared. Results Statistically significant savings were found for overall costs, treatment costs and the costs of additional tests in the long term. The overall cost saving was 1,115,857€ (95%CI from 932,147 to 1,299,567) in the 10th year and 2,866,124€ (95%CI from 2,492,610 to 3,239,638) in the 20th year, representing 4.5% and 8.1% of the overall cost associated with screen-film mammography. The sensitivity analysis showed net savings in the long term. Conclusions Switching to digital mammography in a population-based breast cancer screening program saves long-term budget expense, in addition to providing technical advantages. Our results were consistent across distinct scenarios representing the different results obtained in European breast cancer screening programs. PMID:24832200

Incorporating genomics into breast and prostate cancer screening: assessing the implications

PubMed Central

Chowdhury, Susmita; Dent, Tom; Pashayan, Nora; Hall, Alison; Lyratzopoulos, Georgios; Hallowell, Nina; Hall, Per; Pharoah, Paul; Burton, Hilary

2013-01-01

Individual risk prediction and stratification based on polygenic profiling may be useful in disease prevention. Risk-stratified population screening based on multiple factors including a polygenic risk profile has the potential to be more efficient than age-stratified screening. In this article, we summarize the implications of personalized screening for breast and prostate cancers. We report the opinions of multidisciplinary international experts who have explored the scientific, ethical, and logistical aspects of stratified screening. We have identified (i) the need to recognize the benefits and harms of personalized screening as compared with existing screening methods, (ii) that the use of genetic data highlights complex ethical issues including discrimination against high-risk individuals by insurers and employers and patient autonomy in relation to genetic testing of minors, (iii) the need for transparency and clear communication about risk scores, about harms and benefits, and about reasons for inclusion and exclusion from the risk-based screening process, and (iv) the need to develop new professional competences and to assess cost-effectiveness and acceptability of stratified screening programs before implementation. We conclude that health professionals and stakeholders need to consider the implications of incorporating genetic information in intervention strategies for health-care planning in the future. Genet Med 2013:15(6):423–432 PMID:23412607

Collaborative trial validation studies of real-time PCR-based GMO screening methods for detection of the bar gene and the ctp2-cp4epsps construct.

PubMed

Grohmann, Lutz; Brünen-Nieweler, Claudia; Nemeth, Anne; Waiblinger, Hans-Ulrich

2009-10-14

Polymerase Chain Reaction (PCR)-based screening methods targeting genetic elements commonly used in genetically modified (GM) plants are important tools for the detection of GM materials in food, feed, and seed samples. To expand and harmonize the screening capability of enforcement laboratories, the German Federal Office of Consumer Protection and Food Safety conducted collaborative trials for interlaboratory validation of real-time PCR methods for detection of the phosphinothricin acetyltransferase (bar) gene from Streptomyces hygroscopicus and a construct containing the 5-enolpyruvylshikimate-3-phosphate synthase gene from Agrobacterium tumefaciens sp. strain CP4 (ctp2-cp4epsps), respectively. To assess the limit of detection, precision, and accuracy of the methods, laboratories had to analyze two sets of 18 coded genomic DNA samples of events LLRice62 and MS8 with the bar method and NK603 and GT73 with the ctp2-cp4epsps method at analyte levels of 0, 0.02, and 0.1% GM content, respectively. In addition, standard DNAs were provided to the laboratories to generate calibration curves for copy number quantification of the bar and ctp2-cp4epsps target sequences present in the test samples. The study design and the results obtained are discussed with respect to the difficult issue of developing general guidelines and concepts for the collaborative trial validation of qualitative PCR screening methods.

Design of a projection display screen with vanishing color shift for rear-projection HDTV

NASA Astrophysics Data System (ADS)

Liu, Xiu; Zhu, Jin-lin

1996-09-01

Using bi-convex cylinder lens with matrix structure, the transmissive projection display screen with high contrast and wider viewing angle has been widely used in large rear projection TV and video projectors, it obtained a inhere color shift and puzzled the designer of display screen for RGB projection tube in-line adjustment. Based on the method of light beam racing, the general software of designing projection display screen has been developed and the computer model of vanishing color shift for rear projection HDTV has bee completed. This paper discussed the practical designing method to vanish the defect of color shift and mentioned the relations between the primary optical parameters of display screen and relative geometry sizes of lens' surface. The distributions of optical gain to viewing angle and the influences on engineering design are briefly analyzed.

Screening for Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus, and Treponema pallidum by Blood Testing Using a Bio-Flash Technology-Based Algorithm before Gastrointestinal Endoscopy

PubMed Central

Zhen, Chen; QuiuLi, Zhang; YuanQi, An; Casado, Verónica Vocero; Fan, Yuan

2016-01-01

Currently, conventional enzyme immunoassays which use manual gold immunoassays and colloidal tests (GICTs) are used as screening tools to detect Treponema pallidum (syphilis), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and HIV-2 in patients undergoing surgery. The present observational, cross-sectional study compared the sensitivity, specificity, and work flow characteristics of the conventional algorithm with manual GICTs with those of a newly proposed algorithm that uses the automated Bio-Flash technology as a screening tool in patients undergoing gastrointestinal (GI) endoscopy. A total of 956 patients were examined for the presence of serological markers of infection with HIV-1/2, HCV, HBV, and T. pallidum. The proposed algorithm with the Bio-Flash technology was superior for the detection of all markers (100.0% sensitivity and specificity for detection of anti-HIV and anti-HCV antibodies, HBV surface antigen [HBsAg], and T. pallidum) compared with the conventional algorithm based on the manual method (80.0% sensitivity and 98.6% specificity for the detection of anti-HIV, 75.0% sensitivity for the detection of anti-HCV, 94.7% sensitivity for the detection of HBsAg, and 100% specificity for the detection of anti-HCV and HBsAg) in these patients. The automated Bio-Flash technology-based screening algorithm also reduced the operation time by 85.0% (205 min) per day, saving up to 24 h/week. In conclusion, the use of the newly proposed screening algorithm based on the automated Bio-Flash technology can provide an advantage over the use of conventional algorithms based on manual methods for screening for HIV, HBV, HCV, and syphilis before GI endoscopy. PMID:27707942

Screening for Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus, and Treponema pallidum by Blood Testing Using a Bio-Flash Technology-Based Algorithm before Gastrointestinal Endoscopy.

PubMed

Jun, Zhou; Zhen, Chen; QuiuLi, Zhang; YuanQi, An; Casado, Verónica Vocero; Fan, Yuan

2016-12-01

Currently, conventional enzyme immunoassays which use manual gold immunoassays and colloidal tests (GICTs) are used as screening tools to detect Treponema pallidum (syphilis), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and HIV-2 in patients undergoing surgery. The present observational, cross-sectional study compared the sensitivity, specificity, and work flow characteristics of the conventional algorithm with manual GICTs with those of a newly proposed algorithm that uses the automated Bio-Flash technology as a screening tool in patients undergoing gastrointestinal (GI) endoscopy. A total of 956 patients were examined for the presence of serological markers of infection with HIV-1/2, HCV, HBV, and T. pallidum The proposed algorithm with the Bio-Flash technology was superior for the detection of all markers (100.0% sensitivity and specificity for detection of anti-HIV and anti-HCV antibodies, HBV surface antigen [HBsAg], and T. pallidum) compared with the conventional algorithm based on the manual method (80.0% sensitivity and 98.6% specificity for the detection of anti-HIV, 75.0% sensitivity for the detection of anti-HCV, 94.7% sensitivity for the detection of HBsAg, and 100% specificity for the detection of anti-HCV and HBsAg) in these patients. The automated Bio-Flash technology-based screening algorithm also reduced the operation time by 85.0% (205 min) per day, saving up to 24 h/week. In conclusion, the use of the newly proposed screening algorithm based on the automated Bio-Flash technology can provide an advantage over the use of conventional algorithms based on manual methods for screening for HIV, HBV, HCV, and syphilis before GI endoscopy. Copyright © 2016 Jun et al.

Recruitment, screening, and baseline participant characteristics in the WALK 2.0 study: A randomized controlled trial using web 2.0 applications to promote physical activity.

PubMed

Caperchione, Cristina M; Duncan, Mitch J; Rosenkranz, Richard R; Vandelanotte, Corneel; Van Itallie, Anetta K; Savage, Trevor N; Hooker, Cindy; Maeder, Anthony J; Mummery, W Kerry; Kolt, Gregory S

2016-04-15

To describe in detail the recruitment methods and enrollment rates, the screening methods, and the baseline characteristics of a sample of adults participating in the Walk 2.0 Study, an 18 month, 3-arm randomized controlled trial of a Web 2.0 based physical activity intervention. A two-fold recruitment plan was developed and implemented, including a direct mail-out to an extract from the Australian Electoral Commission electoral roll, and other supplementary methods including email and telephone. Physical activity screening involved two steps: a validated single-item self-report instrument and the follow-up Active Australia Questionnaire. Readiness for physical activity participation was also based on a two-step process of administering the Physical Activity Readiness Questionnaire and, where needed, further clearance from a medical practitioner. Across all recruitment methods, a total of 1244 participants expressed interest in participating, of which 656 were deemed eligible. Of these, 504 were later enrolled in the Walk 2.0 trial (77% enrollment rate) and randomized to the Walk 1.0 group (n = 165), the Walk 2.0 group (n = 168), or the Logbook group (n = 171). Mean age of the total sample was 50.8 years, with 65.2% female and 79.1% born in Australia. The results of this recruitment process demonstrate the successful use of multiple strategies to obtain a diverse sample of adults eligible to take part in a web-based physical activity promotion intervention. The use of dual screening processes ensured safe participation in the intervention. This approach to recruitment and physical activity screening can be used as a model for further trials in this area.

Cost and detection rate of glaucoma screening with imaging devices in a primary care center

PubMed Central

Anton, Alfonso; Fallon, Monica; Cots, Francesc; Sebastian, María A; Morilla-Grasa, Antonio; Mojal, Sergi; Castells, Xavier

2017-01-01

Purpose To analyze the cost and detection rate of a screening program for detecting glaucoma with imaging devices. Materials and methods In this cross-sectional study, a glaucoma screening program was applied in a population-based sample randomly selected from a population of 23,527. Screening targeted the population at risk of glaucoma. Examinations included optic disk tomography (Heidelberg retina tomograph [HRT]), nerve fiber analysis, and tonometry. Subjects who met at least 2 of 3 endpoints (HRT outside normal limits, nerve fiber index ≥30, or tonometry ≥21 mmHg) were referred for glaucoma consultation. The currently established (“conventional”) detection method was evaluated by recording data from primary care and ophthalmic consultations in the same population. The direct costs of screening and conventional detection were calculated by adding the unit costs generated during the diagnostic process. The detection rate of new glaucoma cases was assessed. Results The screening program evaluated 414 subjects; 32 cases were referred for glaucoma consultation, 7 had glaucoma, and 10 had probable glaucoma. The current detection method assessed 677 glaucoma suspects in the population, of whom 29 were diagnosed with glaucoma or probable glaucoma. Glaucoma screening and the conventional detection method had detection rates of 4.1% and 3.1%, respectively, and the cost per case detected was 1,410 and 1,435€, respectively. The cost of screening 1 million inhabitants would be 5.1 million euros and would allow the detection of 4,715 new cases. Conclusion The proposed screening method directed at population at risk allows a detection rate of 4.1% and a cost of 1,410 per case detected. PMID:28243057

Computer-aided diagnosis workstation and telemedicine network system for chest diagnosis based on multislice CT images

NASA Astrophysics Data System (ADS)

Satoh, Hitoshi; Niki, Noboru; Eguchi, Kenji; Ohmatsu, Hironobu; Kakinuma, Ryutaru; Moriyama, Noriyuki

2009-02-01

Mass screening based on multi-helical CT images requires a considerable number of images to be read. It is this time-consuming step that makes the use of helical CT for mass screening impractical at present. Moreover, the doctor who diagnoses a medical image is insufficient in Japan. To overcome these problems, we have provided diagnostic assistance methods to medical screening specialists by developing a lung cancer screening algorithm that automatically detects suspected lung cancers in helical CT images, a coronary artery calcification screening algorithm that automatically detects suspected coronary artery calcification and a vertebra body analysis algorithm for quantitative evaluation of osteoporosis likelihood by using helical CT scanner for the lung cancer mass screening. The functions to observe suspicious shadow in detail are provided in computer-aided diagnosis workstation with these screening algorithms. We also have developed the telemedicine network by using Web medical image conference system with the security improvement of images transmission, Biometric fingerprint authentication system and Biometric face authentication system. Biometric face authentication used on site of telemedicine makes "Encryption of file" and "Success in login" effective. As a result, patients' private information is protected. We can share the screen of Web medical image conference system from two or more web conference terminals at the same time. An opinion can be exchanged mutually by using a camera and a microphone that are connected with workstation. Based on these diagnostic assistance methods, we have developed a new computer-aided workstation and a new telemedicine network that can display suspected lesions three-dimensionally in a short time. The results of this study indicate that our radiological information system without film by using computer-aided diagnosis workstation and our telemedicine network system can increase diagnostic speed, diagnostic accuracy and security improvement of medical information.

Robust Microplate-Based Methods for Culturing and in Vivo Phenotypic Screening of Chlamydomonas reinhardtii

PubMed Central

Haire, Timothy C.; Bell, Cody; Cutshaw, Kirstin; Swiger, Brendan; Winkelmann, Kurt; Palmer, Andrew G.

2018-01-01

Chlamydomonas reinhardtii (Cr), a unicellular alga, is routinely utilized to study photosynthetic biochemistry, ciliary motility, and cellular reproduction. Its minimal culture requirements, unicellular morphology, and ease of transformation have made it a popular model system. Despite its relatively slow doubling time, compared with many bacteria, it is an ideal eukaryotic system for microplate-based studies utilizing either, or both, absorbance as well as fluorescence assays. Such microplate assays are powerful tools for researchers in the areas of toxicology, pharmacology, chemical genetics, biotechnology, and more. However, while microplate-based assays are valuable tools for screening biological systems, these methodologies can significantly alter the conditions in which the organisms are cultured and their subsequent physiology or morphology. Herein we describe a novel method for the microplate culture and in vivo phenotypic analysis of growth, viability, and photosynthetic pigments of C. reinhardtii. We evaluated the utility of our assay by screening silver nanoparticles for their effects on growth and viability. These methods are amenable to a wide assortment of studies and present a significant advancement in the methodologies available for research involving this model organism. PMID:29623083

Robust Microplate-Based Methods for Culturing and in Vivo Phenotypic Screening of Chlamydomonas reinhardtii.

PubMed

Haire, Timothy C; Bell, Cody; Cutshaw, Kirstin; Swiger, Brendan; Winkelmann, Kurt; Palmer, Andrew G

2018-01-01

Chlamydomonas reinhardtii (Cr), a unicellular alga, is routinely utilized to study photosynthetic biochemistry, ciliary motility, and cellular reproduction. Its minimal culture requirements, unicellular morphology, and ease of transformation have made it a popular model system. Despite its relatively slow doubling time, compared with many bacteria, it is an ideal eukaryotic system for microplate-based studies utilizing either, or both, absorbance as well as fluorescence assays. Such microplate assays are powerful tools for researchers in the areas of toxicology, pharmacology, chemical genetics, biotechnology, and more. However, while microplate-based assays are valuable tools for screening biological systems, these methodologies can significantly alter the conditions in which the organisms are cultured and their subsequent physiology or morphology. Herein we describe a novel method for the microplate culture and in vivo phenotypic analysis of growth, viability, and photosynthetic pigments of C. reinhardtii . We evaluated the utility of our assay by screening silver nanoparticles for their effects on growth and viability. These methods are amenable to a wide assortment of studies and present a significant advancement in the methodologies available for research involving this model organism.

Discrete Fourier Transform-Based Multivariate Image Analysis: Application to Modeling of Aromatase Inhibitory Activity.

PubMed

Barigye, Stephen J; Freitas, Matheus P; Ausina, Priscila; Zancan, Patricia; Sola-Penna, Mauro; Castillo-Garit, Juan A

2018-02-12

We recently generalized the formerly alignment-dependent multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR) method through the application of the discrete Fourier transform (DFT), allowing for its application to noncongruent and structurally diverse chemical compound data sets. Here we report the first practical application of this method in the screening of molecular entities of therapeutic interest, with human aromatase inhibitory activity as the case study. We developed an ensemble classification model based on the two-dimensional (2D) DFT MIA-QSAR descriptors, with which we screened the NCI Diversity Set V (1593 compounds) and obtained 34 chemical compounds with possible aromatase inhibitory activity. These compounds were docked into the aromatase active site, and the 10 most promising compounds were selected for in vitro experimental validation. Of these compounds, 7419 (nonsteroidal) and 89 201 (steroidal) demonstrated satisfactory antiproliferative and aromatase inhibitory activities. The obtained results suggest that the 2D-DFT MIA-QSAR method may be useful in ligand-based virtual screening of new molecular entities of therapeutic utility.

In Vitro Toxicity Screening Technique for Volatile Substances Using Flow-Through System@@

EPA Science Inventory

In 2007, the National Research Council envisioned the need for inexpensive, rapid, cell-based toxicity testing methods relevant to human health. in vitro screening approaches have largely addressed these problems by using robotics and automation. However, the challenge is that ma...

Exploiting Defect Clustering to Screen Bare Die for Infant Mortality Failure: An Experimental Study

NASA Technical Reports Server (NTRS)

Lakin, David R., II; Singh, Adit D.

1999-01-01

We present the first experimental results to establish that a binning strategy based on defect clustering can be used to screen bare die for early life failures. The data for this study comes from the SEMATECH test methods experiment.

A review on EEG-based methods for screening and diagnosing alcohol use disorder.

PubMed

Mumtaz, Wajid; Vuong, Pham Lam; Malik, Aamir Saeed; Rashid, Rusdi Bin Abd

2018-04-01

The screening test for alcohol use disorder (AUD) patients has been of subjective nature and could be misleading in particular cases such as a misreporting the actual quantity of alcohol intake. Although the neuroimaging modality such as electroencephalography (EEG) has shown promising research results in achieving objectivity during the screening and diagnosis of AUD patients. However, the translation of these findings for clinical applications has been largely understudied and hence less clear. This study advocates the use of EEG as a diagnostic and screening tool for AUD patients that may help the clinicians during clinical decision making. In this context, a comprehensive review on EEG-based methods is provided including related electrophysiological techniques reported in the literature. More specifically, the EEG abnormalities associated with the conditions of AUD patients are summarized. The aim is to explore the potentials of objective techniques involving quantities/features derived from resting EEG, event-related potentials or event-related oscillations data.

A Xylenol Orange-Based Screening Assay for the Substrate Specificity of Flavin-Dependent para-Phenol Oxidases.

PubMed

Ewing, Tom A; van Noord, Aster; Paul, Caroline E; van Berkel, Willem J H

2018-01-14

Vanillyl alcohol oxidase (VAO) and eugenol oxidase (EUGO) are flavin-dependent enzymes that catalyse the oxidation of para -substituted phenols. This makes them potentially interesting biocatalysts for the conversion of lignin-derived aromatic monomers to value-added compounds. To facilitate their biocatalytic exploitation, it is important to develop methods by which variants of the enzymes can be rapidly screened for increased activity towards substrates of interest. Here, we present the development of a screening assay for the substrate specificity of para -phenol oxidases based on the detection of hydrogen peroxide using the ferric-xylenol orange complex method. The assay was used to screen the activity of VAO and EUGO towards a set of twenty-four potential substrates. This led to the identification of 4-cyclopentylphenol as a new substrate of VAO and EUGO and 4-cyclohexylphenol as a new substrate of VAO. Screening of a small library of VAO and EUGO active-site variants for alterations in their substrate specificity led to the identification of a VAO variant (T457Q) with increased activity towards vanillyl alcohol (4-hydroxy-3-methoxybenzyl alcohol) and a EUGO variant (V436I) with increased activity towards chavicol (4-allylphenol) and 4-cyclopentylphenol. This assay provides a quick and efficient method to screen the substrate specificity of para -phenol oxidases, facilitating the enzyme engineering of known para- phenol oxidases and the evaluation of the substrate specificity of novel para -phenol oxidases.

Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23): a study protocol.

PubMed

Thamsborg, Lise Holst; Andersen, Berit; Larsen, Lise Grupe; Christensen, Jette; Johansen, Tonje; Hariri, Jalil; Christiansen, Sanne; Rygaard, Carsten; Lynge, Elsebeth

2018-05-26

The first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated women. These women are better protected against cervical cancer and could therefore be offered less intensive screening. Primary HPV testing is more sensitive than cytology, allowing for a longer screening interval. The aim of Trial23 is to investigate if primary HPV testing with cytology triage of HPV positive samples is a reasonable screening scheme for women offered HPV vaccination as girls. Trial23 is a method study embedded in the existing cervical screening programme in four out of five Danish regions. Without affecting the screening programme, women born in 1994 are randomised to present screening with liquid-based cytology every third year (present programme arm) or present screening plus an HPV test (HPV arm). The study started 1 February 2017 and will run over three screening rounds corresponding to 7-8 years. The primary endpoint is cervical intraepithelial neoplasia grade 3 or above. The trial is undertaken as a non-inferiority study including intention-to-treat and per-protocol analyses. The potential effect of primary HPV screening with a 6-year interval will be calculated from the observed data. The study protocol has been submitted to the ethical committee and deemed a method study. All women are screened according to routine guidelines. The study will contribute new evidence on the future screening of HPV vaccinated birth cohorts of women. All results will be published in open-access journal. NCT03049553; Pre-results. © 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.

Increasing Cervical Cancer Screening Coverage: A Randomised, Community-Based Clinical Trial

PubMed Central

Acera, Amelia; Manresa, Josep Maria; Rodriguez, Diego; Rodriguez, Ana; Bonet, Josep Maria; Trapero-Bertran, Marta; Hidalgo, Pablo; Sànchez, Norman

2017-01-01

Background Opportunistic cervical cancer screening can lead to suboptimal screening coverage. Coverage could be increased after a personalised invitation to the target population. We present a community randomized intervention study with three strategies aiming to increase screening coverage. Methods The CRICERVA study is a community-based clinical trial to improve coverage of population-based screening in the Cerdanyola SAP area in Barcelona.A total of 32,858 women residing in the study area, aged 30 to 70 years were evaluated. A total of 15,965 women were identified as having no registration of a cervical cytology in the last 3.5 years within the Public Health data base system. Eligible women were assigned to one of four community randomized intervention groups (IGs): (1) (IG1 N = 4197) personalised invitation letter, (2) (IG2 N = 3601) personalised invitation letter + informative leaflet, (3) (IG3 N = 6088) personalised invitation letter + informative leaflet + personalised phone call and (4) (Control N = 2079) based on spontaneous demand of cervical cancer screening as officially recommended. To evaluate screening coverage, we used heterogeneity tests to compare impact of the interventions and mixed logistic regression models to assess the age effect. We refer a “rescue” visit as the screening visit resulting from the study invitation. Results Among the 13,886 women in the IGs, 2,862 were evaluated as having an adequate screening history after the initial contact; 4,263 were lost to follow-up and 5,341 were identified as having insufficient screening and thus being eligible for a rescue visit. All intervention strategies significantly increased participation to screening compared to the control group. Coverage after the intervention reached 84.1% while the control group reached 64.8%. The final impact of our study was an increase of 20% in the three IGs and of 9% in the control group (p<0.001). Within the intervention arms, age was an important determinant of rescue visits showing a statistical interaction with the coverage attained in the IGs. Within the intervention groups, final screening coverage was significantly higher in IG3 (84.4%) (p<0.001). However, the differences were more substantial in the age groups 50–59 and those 60+. The highest impact of the IG3 intervention was observed among women 60+ y.o with 32.0% of them being rescued for screening. The lowest impact of the interventions was in younger women. Conclusions The study confirms that using individual contact methods and assigning a fixed screening date notably increases participation in screening. The response to the invitation is strongly dependent on age. Trial Registration ClinicalTrials.gov NCT01373723 PMID:28118410

School-based BMI and body composition screening and parent notification in California: methods and messages.

PubMed

Madsen, Kristine A; Linchey, Jennifer

2012-06-01

School-based body mass index (BMI) or body composition screening is increasing, but little is known about the process of parent notification. Since 2001, California has required annual screening of body composition via the FITNESSGRAM, with optional notification. This study sought to identify the prevalence of parental notification when screening is required but notification is optional, and the methods and messages used. Researchers conducted phone interviews with 851 school districts (89%) in California and reviewed notification materials from 54 districts. As of 2008, 53% of California districts notified parents of screening results. Many districts (24%) did not know the reason for their notification policy. Most districts notified parents via a letter mailed home (70%) or sent home with the child (18%). Whereas 79% of sample letters provided students' BMI, only 12% provided an explanation of BMI, and only half provided tips on what parents should do if concerned about their child's results. In California, where body composition screening is required but parent notification is not, approximately half of school districts elect to notify parents of results, most commonly via letter. Most letters do not explain BMI or percent body fat scores, nor do they suggest what parents should do for a child identified as at-risk. Further research to identify interpretable and actionable notification messages for parents will be critical if school-based BMI and body composition screening and notification is to reduce childhood obesity. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Measuring and improving cervical, breast, and colorectal cancer screening rates in a multi-site urban practice in Toronto, Canada.

PubMed

Feldman, Joshua; Davie, Sam; Kiran, Tara

2017-01-01

Our Family Health Team is located in Toronto, Canada and provides care to over 35 000 patients. Like many practices in Canada, we took an opportunistic approach to cervical, breast, and colorectal cancer screening. We wanted to shift to a proactive, population-based approach but were unable to systematically identify patients overdue for screening or calculate baseline screening rates. Our initiative had two goals: (1) to develop a method for systematically identifying patients eligible for screening and whether they were overdue and (2) to increase screening rates for cervical, breast, and colorectal cancer. Using external government data in combination with our practice's electronic medical record, we developed a process to identify patients eligible and overdue for cancer screening. After generating baseline data, we implemented an evidence-based, multifaceted intervention to improve cancer screening rates. We sent a personalized reminder letter to overdue patients, provided physicians with practice-level audit and feedback, and improved our electronic reminder function by updating charts with accurate data on the Fecal Occult Blood Test (FOBT). Following our initial intervention, we sought to maintain and further improve our screening rates by experimenting with alternative recall methods and collecting patient feedback. Screening rates significantly improved for all three cancers. Between March 2014 and December 2016, the cervical cancer screening rate increased from 60% to 71% (p<0.05), the breast cancer screening rate increased from 56% to 65% (p<0.05), and the overall colorectal screening rate increased from 59% to 70% (p<0.05). The increase in colorectal screening rates was largely due to an increase in FOBT screening from 18% to 25%, while colonoscopy screening remained relatively unchanged, shifting from 45% to 46%. We also found that patients living in low income neighbourhoods were less likely to be screened. Following our intervention, this equity gap narrowed modestly for breast and colorectal cancer but did not change for cervical cancer screening. Our future improvement efforts will be focused on reducing the gap in screening between patients living in low-income and high-income neighbourhoods while maintaining overall gains.

FAITH – Fast Assembly Inhibitor Test for HIV

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

Hadravová, Romana; Rumlová, Michaela, E-mail: michaela.rumlova@vscht.cz; Department of Biotechnology, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague

Due to the high number of drug-resistant HIV-1 mutants generated by highly active antiretroviral therapy (HAART), there is continuing demand for new types of inhibitors. Both the assembly of the Gag polyprotein into immature and mature HIV-1 particles are attractive candidates for the blocking of the retroviral life cycle. Currently, no therapeutically-used assembly inhibitor is available. One possible explanation is the lack of a reliable and simple assembly inhibitor screening method. To identify compounds potentially inhibiting the formation of both types of HIV-1 particles, we developed a new fluorescent high-throughput screening assay. This assay is based on the quantification ofmore » the assembly efficiency in vitro in a 96-well plate format. The key components of the assay are HIV-1 Gag-derived proteins and a dual-labelled oligonucleotide, which emits fluorescence only when the assembly of retroviral particles is inhibited. The method was validated using three (CAI, BM2, PF74) reported assembly inhibitors. - Highlights: • Allows screening of assembly inhibitors of both mature and immature HIV-1 particles. • Based on Gag-derived proteins with CA in mature or immature conformation. • Simple and sensitive method suitable for high-throughput screening of inhibitors. • Unlike in other HIV assembly methods, works under physiological conditions. • No washing steps are necessary.« less

In silico approaches to identify novel myeloid cell leukemia-1 (Mcl-1) inhibitors for treatment of cancer.

PubMed

Ren, Ji-Xia; Li, Cheng-Ping; Zhou, Xiu-Ling; Cao, Xue-Song; Xie, Yong

2017-08-22

Myeloid cell leukemia-1 (Mcl-1) has been a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to the resistance to current chemotherapeutics. Here, we identified new Mcl-1 inhibitors using a multi-step virtual screening approach. First, based on two different ligand-receptor complexes, 20 pharmacophore models were established by simultaneously using 'Receptor-Ligand Pharmacophore Generation' method and manual build feature method, and then carefully validated by a test database. Then, pharmacophore-based virtual screening (PB-VS) could be performed by using the 20 pharmacophore models. In addition, docking study was used to predict the possible binding poses of compounds, and the docking parameters were optimized before performing docking-based virtual screening (DB-VS). Moreover, a 3D QSAR model was established by applying the 55 aligned Mcl-1 inhibitors. The 55 inhibitors sharing the same scaffold were docked into the Mcl-1 active site before alignment, then the inhibitors with possible binding conformations were aligned. For the training set, the 3D QSAR model gave a correlation coefficient r 2 of 0.996; for the test set, the correlation coefficient r 2 was 0.812. Therefore, the developed 3D QSAR model was a good model, which could be applied for carrying out 3D QSAR-based virtual screening (QSARD-VS). After the above three virtual screening methods orderly filtering, 23 potential inhibitors with novel scaffolds were identified. Furthermore, we have discussed in detail the mapping results of two potent compounds onto pharmacophore models, 3D QSAR model, and the interactions between the compounds and active site residues.

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization.

PubMed

Xu, Juanjuan; Fang, Rui; Chen, Li; Chen, Daozhen; Xiao, Jian-Ping; Yang, Weimin; Wang, Honghua; Song, Xiaoqing; Ma, Ting; Bo, Shiping; Shi, Chong; Ren, Jun; Huang, Lei; Cai, Li-Yi; Yao, Bing; Xie, X Sunney; Lu, Sijia

2016-10-18

Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.

Medicare Cancer Screening in the Context of Clinical Guidelines: 2000 to 2012.

PubMed

Maroongroge, Sean; Yu, James B

2018-04-01

Cancer screening is a ubiquitous and controversial public health issue, particularly in the elderly population. Despite extensive evidence-based guidelines for screening, it is unclear how cancer screening has changed in the Medicare population over time. We characterize trends in cancer screening for the most common cancer types in the Medicare fee-for-service (FFS) program in the context of conflicting guidelines from 2000 to 2012. We performed a descriptive analysis of retrospective claims data from the Medicare FFS program based on billing codes. Our data include all claims for Medicare part B beneficiaries who received breast, colorectal (CRC), or prostate cancer screening from 2000 to 2012 based on billing codes. We utilize a Monte Carlo permutation method to detect changes in screening trends. In total, 231,416,732 screening tests were analyzed from 2000 to 2012, representing an average of 436.8 tests per 1000 beneficiaries per year. Mammography rates declined 7.4%, with digital mammography extensively replacing film. CRC cancer screening rates declined overall. As a percentage of all CRC screening tests, colonoscopy grew from 32% to 71%. Prostate screening rates increased 16% from 2000 to 2007, and then declined to 7% less than its 2000 rate by 2012. Both the aggressiveness of screening guidelines and screening rates for the Medicare FFS population peaked and then declined from 2000 to 2012. However, guideline publications did not consistently precede utilization trend shifts. Technology adoption, practical and financial concerns, and patient preferences may have also contributed to the observed trends. Further research should be performed on the impact of multiple, conflicting guidelines in cancer screening.

High-throughput detection and screening of plants modified by gene editing using quantitative real-time polymerase chain reaction.

PubMed

Peng, Cheng; Wang, Hua; Xu, Xiaoli; Wang, Xiaofu; Chen, Xiaoyun; Wei, Wei; Lai, Yongmin; Liu, Guoquan; Godwin, Ian Douglas; Li, Jieqin; Zhang, Ling; Xu, Junfeng

2018-05-15

Gene editing techniques are becoming powerful tools for modifying target genes in organisms. Although several methods have been developed to detect gene-edited organisms, these techniques are time and labour intensive. Meanwhile, few studies have investigated high-throughput detection and screening strategies for plants modified by gene editing. In this study, we developed a simple, sensitive and high-throughput quantitative real-time (qPCR)-based method. The qPCR-based method exploits two differently labelled probes that are placed within one amplicon at the gene editing target site to simultaneously detect the wild-type and a gene-edited mutant. We showed that the qPCR-based method can accurately distinguish CRISPR/Cas9-induced mutants from the wild-type in several different plant species, such as Oryza sativa, Arabidopsis thaliana, Sorghum bicolor, and Zea mays. Moreover, the method can subsequently determine the mutation type by direct sequencing of the qPCR products of mutations due to gene editing. The qPCR-based method is also sufficiently sensitive to distinguish between heterozygous and homozygous mutations in T 0 transgenic plants. In a 384-well plate format, the method enabled the simultaneous analysis of up to 128 samples in three replicates without handling the post-polymerase chain reaction (PCR) products. Thus, we propose that our method is an ideal choice for screening plants modified by gene editing from many candidates in T 0 transgenic plants, which will be widely used in the area of plant gene editing. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Molecular Building Block-Based Electronic Charges for High-Throughput Screening of Metal-Organic Frameworks for Adsorption Applications.

PubMed

Argueta, Edwin; Shaji, Jeena; Gopalan, Arun; Liao, Peilin; Snurr, Randall Q; Gómez-Gualdrón, Diego A

2018-01-09

Metal-organic frameworks (MOFs) are porous crystalline materials with attractive properties for gas separation and storage. Their remarkable tunability makes it possible to create millions of MOF variations but creates the need for fast material screening to identify promising structures. Computational high-throughput screening (HTS) is a possible solution, but its usefulness is tied to accurate predictions of MOF adsorption properties. Accurate adsorption simulations often require an accurate description of electrostatic interactions, which depend on the electronic charges of the MOF atoms. HTS-compatible methods to assign charges to MOF atoms need to accurately reproduce electrostatic potentials (ESPs) and be computationally affordable, but current methods present an unsatisfactory trade-off between computational cost and accuracy. We illustrate a method to assign charges to MOF atoms based on ab initio calculations on MOF molecular building blocks. A library of building blocks with built-in charges is thus created and used by an automated MOF construction code to create hundreds of MOFs with charges "inherited" from the constituent building blocks. The molecular building block-based (MBBB) charges are similar to REPEAT charges-which are charges that reproduce ESPs obtained from ab initio calculations on crystallographic unit cells of nanoporous crystals-and thus similar predictions of adsorption loadings, heats of adsorption, and Henry's constants are obtained with either method. The presented results indicate that the MBBB method to assign charges to MOF atoms is suitable for use in computational high-throughput screening of MOFs for applications that involve adsorption of molecules such as carbon dioxide.

Prediction of Phase Behavior of Spray-Dried Amorphous Solid Dispersions: Assessment of Thermodynamic Models, Standard Screening Methods and a Novel Atomization Screening Device with Regard to Prediction Accuracy

PubMed Central

Chavez, Pierre-François; Meeus, Joke; Robin, Florent; Schubert, Martin Alexander; Somville, Pascal

2018-01-01

The evaluation of drug–polymer miscibility in the early phase of drug development is essential to ensure successful amorphous solid dispersion (ASD) manufacturing. This work investigates the comparison of thermodynamic models, conventional experimental screening methods (solvent casting, quench cooling), and a novel atomization screening device based on their ability to predict drug–polymer miscibility, solid state properties (Tg value and width), and adequate polymer selection during the development of spray-dried amorphous solid dispersions (SDASDs). Binary ASDs of four drugs and seven polymers were produced at 20:80, 40:60, 60:40, and 80:20 (w/w). Samples were systematically analyzed using modulated differential scanning calorimetry (mDSC) and X-ray powder diffraction (XRPD). Principal component analysis (PCA) was used to qualitatively assess the predictability of screening methods with regards to SDASD development. Poor correlation was found between theoretical models and experimentally-obtained results. Additionally, the limited ability of usual screening methods to predict the miscibility of SDASDs did not guarantee the appropriate selection of lead excipient for the manufacturing of robust SDASDs. Contrary to standard approaches, our novel screening device allowed the selection of optimal polymer and drug loading and established insight into the final properties and performance of SDASDs at an early stage, therefore enabling the optimization of the scaled-up late-stage development. PMID:29518936

Interval cancers in a population-based screening program for colorectal cancer in catalonia, Spain.

PubMed

Garcia, M; Domènech, X; Vidal, C; Torné, E; Milà, N; Binefa, G; Benito, L; Moreno, V

2015-01-01

Objective. To analyze interval cancers among participants in a screening program for colorectal cancer (CRC) during four screening rounds. Methods. The study population consisted of participants of a fecal occult blood test-based screening program from February 2000 to September 2010, with a 30-month follow-up (n = 30,480). We used hospital administration data to identify CRC. An interval cancer was defined as an invasive cancer diagnosed within 30 months of a negative screening result and before the next recommended examination. Gender, age, stage, and site distribution of interval cancers were compared with those in the screen-detected group. Results. Within the study period, 97 tumors were screen-detected and 74 tumors were diagnosed after a negative screening. In addition, 17 CRC (18.3%) were found after an inconclusive result and 2 cases were diagnosed within the surveillance interval (2.1%). There was an increase of interval cancers over the four rounds (from 32.4% to 46.0%). When compared with screen-detected cancers, interval cancers were found predominantly in the rectum (OR: 3.66; 95% CI: 1.51-8.88) and at more advanced stages (P = 0.025). Conclusion. There are large numbers of cancer that are not detected through fecal occult blood test-based screening. The low sensitivity should be emphasized to ensure that individuals with symptoms are not falsely reassured.

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved

PubMed Central

Inrig, Stephen J.; Tiro, Jasmin A.; Melhado, Trisha V.; Argenbright, Keith E.; Craddock Lee, Simon J.

2017-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. Objectives To better understand how to implement a decentralized regional delivery “hub & spoke” model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow’s RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Methods and Design The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow’s RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. Discussion This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting. PMID:28713882

Fragment based drug discovery: practical implementation based on ¹⁹F NMR spectroscopy.

PubMed

Jordan, John B; Poppe, Leszek; Xia, Xiaoyang; Cheng, Alan C; Sun, Yax; Michelsen, Klaus; Eastwood, Heather; Schnier, Paul D; Nixey, Thomas; Zhong, Wenge

2012-01-26

Fragment based drug discovery (FBDD) is a widely used tool for discovering novel therapeutics. NMR is a powerful means for implementing FBDD, and several approaches have been proposed utilizing (1)H-(15)N heteronuclear single quantum coherence (HSQC) as well as one-dimensional (1)H and (19)F NMR to screen compound mixtures against a target of interest. While proton-based NMR methods of fragment screening (FBS) have been well documented and are widely used, the use of (19)F detection in FBS has been only recently introduced (Vulpetti et al. J. Am. Chem. Soc.2009, 131 (36), 12949-12959) with the aim of targeting "fluorophilic" sites in proteins. Here, we demonstrate a more general use of (19)F NMR-based fragment screening in several areas: as a key tool for rapid and sensitive detection of fragment hits, as a method for the rapid development of structure-activity relationship (SAR) on the hit-to-lead path using in-house libraries and/or commercially available compounds, and as a quick and efficient means of assessing target druggability.

Automated assessment of aortic and main pulmonary arterial diameters using model-based blood vessel segmentation for predicting chronic thromboembolic pulmonary hypertension in low-dose CT lung screening

NASA Astrophysics Data System (ADS)

Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Sugiura, Toshihiko; Tanabe, Nobuhiro; Kusumoto, Masahiko; Eguchi, Kenji; Kaneko, Masahiro

2018-02-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of the pulmonary vasculature by residual organized thrombi. A morphological abnormality inside mediastinum of CTEPH patient is enlargement of pulmonary artery. This paper presents an automated assessment of aortic and main pulmonary arterial diameters for predicting CTEPH in low-dose CT lung screening. The distinctive feature of our method is to segment aorta and main pulmonary artery using both of prior probability and vascular direction which were estimated from mediastinal vascular region using principal curvatures of four-dimensional hyper surface. The method was applied to two datasets, 64 lowdose CT scans of lung cancer screening and 19 normal-dose CT scans of CTEPH patients through the training phase with 121 low-dose CT scans. This paper demonstrates effectiveness of our method for predicting CTEPH in low-dose CT screening.

High-throughput screening of high Monascus pigment-producing strain based on digital image processing.

PubMed

Xia, Meng-lei; Wang, Lan; Yang, Zhi-xia; Chen, Hong-zhang

2016-04-01

This work proposed a new method which applied image processing and support vector machine (SVM) for screening of mold strains. Taking Monascus as example, morphological characteristics of Monascus colony were quantified by image processing. And the association between the characteristics and pigment production capability was determined by SVM. On this basis, a highly automated screening strategy was achieved. The accuracy of the proposed strategy is 80.6 %, which is compatible with the existing methods (81.1 % for microplate and 85.4 % for flask). Meanwhile, the screening of 500 colonies only takes 20-30 min, which is the highest rate among all published results. By applying this automated method, 13 strains with high-predicted production were obtained and the best one produced as 2.8-fold (226 U/mL) of pigment and 1.9-fold (51 mg/L) of lovastatin compared with the parent strain. The current study provides us with an effective and promising method for strain improvement.

Clinical perspective of cell-free DNA testing for fetal aneuploidies.

PubMed

Gratacós, Eduard; Nicolaides, Kypros

2014-01-01

Cell-free DNA testing in maternal blood provides the most effective method of screening for trisomy 21, with a reported detection rate of 99% and a false positive rate of less than 0.1%. After many years of research, this method is now commercially available and is carried out in an increasing number of patients, and there is an expanding number of conditions that can be screened for. However, the application of these methods in clinical practice requires a careful analysis. Current first-trimester screening strategies are based on a complex combination of tests, aiming at detecting fetal defects and predicting the risk of main pregnancy complications. It is therefore necessary to define the optimal way of combining cell-free DNA testing with current first-trimester screening methods. In this concise review we describe the basis of cell-free DNA testing and discuss the potential approaches for its implementation in combination with current tests in the first trimester. © 2014 S. Karger AG, Basel.

Determining diabetic retinopathy screening interval based on time from no retinopathy to laser therapy.

PubMed

Hughes, Daniel; Nair, Sunil; Harvey, John N

2017-12-01

Objectives To determine the necessary screening interval for retinopathy in diabetic patients with no retinopathy based on time to laser therapy and to assess long-term visual outcome following screening. Methods In a population-based community screening programme in North Wales, 2917 patients were followed until death or for approximately 12 years. At screening, 2493 had no retinopathy; 424 had mostly minor degrees of non-proliferative retinopathy. Data on timing of first laser therapy and visual outcome following screening were obtained from local hospitals and ophthalmology units. Results Survival analysis showed that very few of the no retinopathy at screening group required laser therapy in the early years compared with the non-proliferative retinopathy group ( p < 0.001). After two years, <0.1% of the no retinopathy at screening group required laser therapy, and at three years 0.2% (cumulative), lower rates of treatment than have been suggested by analyses of sight-threatening retinopathy determined photographically. At follow-up (mean 7.8 ± 4.6 years), mild to moderate visual impairment in one or both eyes due to diabetic retinopathy was more common in those with retinopathy at screening (26% vs. 5%, p < 0.001), but blindness due to diabetes occurred in only 1 in 1000. Conclusions Optimum screening intervals should be determined from time to active treatment. Based on requirement for laser therapy, the screening interval for diabetic patients with no retinopathy can be extended to two to three years. Patients who attend for retinal screening and treatment who have no or non-proliferative retinopathy now have a very low risk of eventual blindness from diabetes.

Interval cancers in a guaiac-based colorectal cancer screening programme: Consequences on sensitivity.

PubMed

Blom, Johannes; Törnberg, Sven

2017-09-01

Objective To evaluate interval cancers in the population-based colorectal cancer screening programme of Stockholm/Gotland, Sweden. Methods From 2008, individuals aged 60-69 were invited to colorectal cancer screening using biennial guaiac-based faecal occult blood test (Hemoccult®). Interval cancers, defined as colorectal cancer among participants not diagnosed by the screening programme but registered in the Swedish cancer register, were evaluated by cross-checking the screening histories for all cancers in the region 2008-2012. Results Of 203,848 individuals from nine different birth cohorts who participated (∼60%), 4530 (2.2%) tested positive. All invited individuals were followed up for 24 months after invitation. The cancer register reported 557 colorectal cancer, 219 (39.3%) screen-detected cancers and 338 (60.7%) interval cancers, generating both test- and episode sensitivities of approximately 40% and an interval cancer-rate of 17.1/10,000 tests. Among individuals with positive tests without colorectal cancer diagnosed at work-up colonoscopy, 37 interval cancers (10.9%) occurred. There was statistically significant lower sensitivity in women, ranging 22.4-32.2%, compared with 43.2-52.0% in men. Age-group and tumour location were not strongly correlated to screen-detected cancer rates. The programme sensitivity increased by year (20.3-25.0%), with successively more colorectal cancers diagnosed within the expanding programme (11.6-16.2%). Conclusion Interval cancer is a quality indicator of a screening programme. As the interval cancer-rate determined in a well-organized population-based screening programme was actually higher than the screen-detected cancer rate, a change to a more sensitive screening test is indicated. The lower screen-detected cancers among women, and compliance and quality of work-up colonoscopies also need attention.

Inhibitors of Helicobacter pylori Protease HtrA Found by ‘Virtual Ligand’ Screening Combat Bacterial Invasion of Epithelia

PubMed Central

Schneider, Petra; Hoy, Benjamin; Wessler, Silja; Schneider, Gisbert

2011-01-01

Background The human pathogen Helicobacter pylori (H. pylori) is a main cause for gastric inflammation and cancer. Increasing bacterial resistance against antibiotics demands for innovative strategies for therapeutic intervention. Methodology/Principal Findings We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. Pharmacophoric features of the map are clustered and transformed in a correlation vector (‘virtual ligand’) for rapid virtual screening of compound databases. This computer-based technique was validated for 18 different targets of pharmaceutical interest in a retrospective screening experiment. Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. Among 22 tested compounds six block E-cadherin cleavage by HtrA in vitro and result in reduced scattering and wound healing of gastric epithelial cells, thereby preventing bacterial infiltration of the epithelium. Conclusions/Significance This study demonstrates that receptor-based virtual screening with a permissive (‘fuzzy’) pharmacophore model can help identify small bioactive agents for combating bacterial infection. PMID:21483848

Fragment-based screening by protein crystallography: successes and pitfalls.

PubMed

Chilingaryan, Zorik; Yin, Zhou; Oakley, Aaron J

2012-10-08

Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.

Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls

PubMed Central

Chilingaryan, Zorik; Yin, Zhou; Oakley, Aaron J.

2012-01-01

Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality. PMID:23202926

A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila

NASA Astrophysics Data System (ADS)

Apostol, Barbara L.; Kazantsev, Alexsey; Raffioni, Simona; Illes, Katalin; Pallos, Judit; Bodai, Laszlo; Slepko, Natalia; Bear, James E.; Gertler, Frank B.; Hersch, Steven; Housman, David E.; Marsh, J. Lawrence; Michels Thompson, Leslie

2003-05-01

The formation of polyglutamine-containing aggregates and inclusions are hallmarks of pathogenesis in Huntington's disease that can be recapitulated in model systems. Although the contribution of inclusions to pathogenesis is unclear, cell-based assays can be used to screen for chemical compounds that affect aggregation and may provide therapeutic benefit. We have developed inducible PC12 cell-culture models to screen for loss of visible aggregates. To test the validity of this approach, compounds that inhibit aggregation in the PC12 cell-based screen were tested in a Drosophila model of polyglutamine-repeat disease. The disruption of aggregation in PC12 cells strongly correlates with suppression of neuronal degeneration in Drosophila. Thus, the engineered PC12 cells coupled with the Drosophila model provide a rapid and effective method to screen and validate compounds.

Current issues and future perspectives of gastric cancer screening

PubMed Central

Hamashima, Chisato

2014-01-01

Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries, which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques, namely, upper gastrointestinal endoscopy, serological testing, and “screen and treat” method were extensively reviewed. Moreover, the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand, serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date, the effectiveness of new techniques for gastric cancer screening has remained limited. However, endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening. To effectively introduce new techniques for gastric cancer screening in a community, incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies. In addition to effectiveness evaluation, the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening. PMID:25320514

Label-free screening of foodborne Salmonella using surface plasmon resonance imaging

USDA-ARS?s Scientific Manuscript database

Since 15 pathogens cause approximately 95% of the foodborne infections, it is desirable to develop rapid and simultaneous screening methods for these major pathogens. In this study, we developed an immunoassay for Salmonella based on surface plasmon resonance imaging (SPRi). The sensor surface modif...

QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.

EPA Science Inventory

New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. Whi...

A screening method based on UV-Visible spectroscopy and multivariate analysis to assess addition of filler juices and water to pomegranate juices.

PubMed

Boggia, Raffaella; Casolino, Maria Chiara; Hysenaj, Vilma; Oliveri, Paolo; Zunin, Paola

2013-10-15

Consumer demand for pomegranate juice has considerably grown, during the last years, for its potential health benefits. Since it is an expensive functional food, cheaper fruit juices addition (i.e., grape and apple juices) or its simple dilution, or polyphenols subtraction are deceptively used. At present, time-consuming analyses are used to control the quality of this product. Furthermore these analyses are expensive and require well-trained analysts. Thus, the purpose of this study was to propose a high-speed and easy-to-use shortcut. Based on UV-VIS spectroscopy and chemometrics, a screening method is proposed to quickly screening some common fillers of pomegranate juice that could decrease the antiradical scavenging capacity of pure products. The analytical method was applied to laboratory prepared juices, to commercial juices and to representative experimental mixtures at different levels of water and filler juices. The outcomes were evaluated by means of multivariate exploratory analysis. The results indicate that the proposed strategy can be a useful screening tool to assess addition of filler juices and water to pomegranate juices. Copyright © 2012 Elsevier Ltd. All rights reserved.

Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

NASA Astrophysics Data System (ADS)

Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

2014-03-01

Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

Promotion and Provision of Colorectal Cancer Screening: A Comparison of Colorectal Cancer Control Program Grantees and Nongrantees, 2011–2012

PubMed Central

Hannon, Peggy A.; Escoffery, Cam; Vu, Thuy; Kohn, Marlana; Vernon, Sally W.; DeGroff, Amy

2014-01-01

Introduction Since 2009, the Centers for Disease Control and Prevention (CDC) has awarded nearly $95 million to 29 states and tribes through the Colorectal Cancer Control Program (CRCCP) to fund 2 program components: 1) providing colorectal cancer (CRC) screening to uninsured and underinsured low-income adults and 2) promoting population-wide CRC screening through evidence-based interventions identified in the Guide to Community Preventive Services (Community Guide). CRCCP is a new model for disseminating and promoting use of evidence-based interventions. If the program proves successful, CDC may adopt the model for future cancer control programs. The objective of our study was to compare the colorectal cancer screening practices of recipients of CRCCP funding (grantees) with those of nonrecipients (nongrantees). Methods We conducted parallel Web-based surveys in 2012 with CRCCP grantees (N = 29) and nongrantees (N = 24) to assess promotion and provision of CRC screening, including the use of evidence-based interventions. Results CRCCP grantees were significantly more likely than nongrantees to use Community Guide-recommended evidence-based interventions (mean, 3.14 interventions vs 1.25 interventions, P < .001) and to use patient navigation services (eg, transportion or language translation services) (72% vs 17%, P < .001) for promoting CRC screening. Both groups were equally likely to use other strategies. CRCCP grantees were significantly more likely to provide CRC screening than were nongrantees (100% versus 50%, P < .001). Conclusion Results suggest that CRCCP funding and support increases use of evidence-based interventions to promote CRC screening, indicating the program’s potential to increase population-wide CRC screening rates. PMID:25275807

Fragment screening of cyclin G-associated kinase by weak affinity chromatography.

PubMed

Meiby, Elinor; Knapp, Stefan; Elkins, Jonathan M; Ohlson, Sten

2012-11-01

Fragment-based drug discovery (FBDD) has become a new strategy for drug discovery where lead compounds are evolved from small molecules. These fragments form low affinity interactions (dissociation constant (K(D)) = mM - μM) with protein targets, which require fragment screening methods of sufficient sensitivity. Weak affinity chromatography (WAC) is a promising new technology for fragment screening based on selective retention of fragments by a drug target. Kinases are a major pharmaceutical target, and FBDD has been successfully applied to several of these targets. In this work, we have demonstrated the potential to use WAC in combination with mass spectrometry (MS) detection for fragment screening of a kinase target-cyclin G-associated kinase (GAK). One hundred seventy fragments were selected for WAC screening by virtual screening of a commercial fragment library against the ATP-binding site of five different proteins. GAK protein was immobilized on a capillary HPLC column, and compound binding was characterized by frontal affinity chromatography. Compounds were screened in sets of 13 or 14, in combination with MS detection for enhanced throughput. Seventy-eight fragments (46 %) with K(D) < 200 μM were detected, including a few highly efficient GAK binders (K(D) of 2 μM; ligand efficiency = 0.51). Of special interest is that chiral screening by WAC may be possible, as two stereoisomeric fragments, which both contained one chiral center, demonstrated twin peaks. This ability, in combination with the robustness, sensitivity, and simplicity of WAC makes it a new method for fragment screening of considerable potential.

A novel screen-printed microfluidic paper-based electrochemical device for detection of glucose and uric acid in urine.

PubMed

Yao, Yong; Zhang, Chunsun

2016-10-01

A novel screen-printed microfluidic paper-based analytical device with all-carbon electrode-enabled electrochemical assay (SP-ACE-EC-μPAD) has been developed. The fabrication of these devices involved wax screen-printing, which was simple, low-cost and energy-efficient. The working, counter and reference electrodes were screen-printed using carbon ink on the patterned paper devices. Different wax screen-printing processes were examined and optimized, which led to an improved method with a shorter heating time (~5 s) and a lower heating temperature (75 °C). Different printing screens were examined, with a 300-mesh polyester screen yielding the highest quality wax screen-prints. The carbon electrodes were screen-printed on the μPADs and then examined using cyclic voltammetry. The analytical performance of the SP-ACE-EC-μPADs for the detection of glucose and uric acid in standard solutions was investigated. The results were reproducible, with a linear relationship [R(2) = 0.9987 (glucose) or 0.9997 (uric acid)] within the concentration range of interest, and with detection limits as low as 0.35 mM (glucose) and 0.08 mM (uric acid). To determine the clinical utility of the μPADs, chronoamperometry was used to analyze glucose and uric acid in real urine samples using the standard addition method. Our devices were able to detect the analytes of interest in complex real-world biological samples, and have the potential for use in a wide variety of applications.

Community-based screening for obstetric fistula in Nigeria: a novel approach

PubMed Central

2014-01-01

Background Obstetric fistula continues to have devastating effects on the physical, social, and economic lives of thousands of women in many low-resource settings. Governments require credible estimates of the backlog of existing cases requiring care to effectively plan for the treatment of fistula cases. Our study aims to quantify the backlog of obstetric fistula cases within two states via community-based screenings and to assess the questions in the Demographic Health Survey (DHS) fistula module. Methods The screening sites, all lower level health facilities, were selected based on their geographic coverage, prior relationships with the communities and availability of fistula surgery facilities in the state. This cross-sectional study included women who presented for fistula screenings at study facilities based on their perceived fistula-like symptoms. Research assistants administered the pre-screening questionnaire. Nurse-midwives then conducted a medical exam. Univariate and bivariate analyses are presented. Results A total of 268 women attended the screenings. Based on the pre-screening interview, the backlog of fistula cases reported was 75 (28% of women screened). The backlog identified after the medical exam was 26 fistula cases (29.5% of women screened) in Kebbi State sites and 12 cases in Cross River State sites (6.7%). Verification assessment showed that the DHS questionnaire had 92% sensitivity, 83% specificity with 47% positive predictive value and 98% negative predictive value for identifying women afflicted by fistula among women who came for the screenings. Conclusions This methodology, involving effective, locally appropriate messaging and community outreach followed up with medical examination by nurse-midwives at lower level facilities, is challenging, but represents a promising approach to identify the backlog of women needing surgery and to link them with surgical facilities. PMID:24456506

The Japanese Guidelines for Breast Cancer Screening.

PubMed

Hamashima, Chisato; Hamashima C, Chisato; Hattori, Masakazu; Honjo, Satoshi; Kasahara, Yoshio; Katayama, Takafumi; Nakai, Masahiro; Nakayama, Tomio; Morita, Takako; Ohta, Koji; Ohnuki, Koji; Sagawa, Motoyasu; Saito, Hiroshi; Sasaki, Seiju; Shimada, Tomoyuki; Sobue, Tomotaka; Suto, Akihiko

2016-05-01

The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported age-standardized rate of 63.6 per 100 000 women. The Japanese guidelines for breast cancer screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screenings were formulated. Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of community pharmacists in screening and subsequent management of chronic respiratory diseases: a systematic review.

PubMed

Fathima, Mariam; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol L

2013-10-01

The purpose of this review was to evaluate the role of community pharmacists in provision of screening with/without subsequent management of undiagnosed chronic obstructive pulmonary disease (COPD) and uncontrolled asthma. An extensive literature search using four databases (ie. Medline, PubMed, International Pharmaceutical Abstracts (IPA) and Scopus) with search terms pharmacy, screening, asthma or COPD was conducted. Searches were limited to the years 2003-2013, those in English and those reporting research with humans. Data retrieval, analysis and result presentation employed a scoping review method. Seventeen articles met the inclusion/exclusion criteria, of which fifteen studies were based on people with asthma and two were based on people with COPD. Only seven asthma studies and one COPD study involved screening followed by subsequent management. More than half of the people screened were found to be poorly controlled and up to 62% of people were identified at high risk for COPD by community pharmacists. The studies varied in the method and type of asthma control assessment/screening, the type of intervention provided and the outcomes measured. The limitations of the reviewed studies included varying definitions of asthma control, different study methodologies, and the lack of long-term follow-up. While many different methods were used for risk assessment and management services by the pharmacists, all the studies demonstrated that community pharmacists were capable of identifying people with poorly controlled asthma and undiagnosed COPD and providing them with suitable interventions. The literature review identified that community pharmacists can play an effective role in screening of people with poorly controlled asthma and undiagnosed COPD along with delivering management interventions. However, there is very little literature available on screening for these chronic respiratory conditions. Future research should focus on development of patient care delivery model incorporating a screening protocol followed by targeted management interventions delivered by the community pharmacist.

High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists.

PubMed

Wu, Bainan; Barile, Elisa; De, Surya K; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

2015-01-01

In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications.

High-throughput screening by Nuclear Magnetic Resonance (HTS by NMR) for the identification of PPIs antagonists

PubMed Central

Wu, Bainan; Barile, Elisa; De, Surya K.; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

2015-01-01

In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications. PMID:25986689

Two-colored fluorescence correlation spectroscopy screening for LC3-P62 interaction inhibitors.

PubMed

Tsuganezawa, Keiko; Shinohara, Yoshiyasu; Ogawa, Naoko; Tsuboi, Shun; Okada, Norihisa; Mori, Masumi; Yokoyama, Shigeyuki; Noda, Nobuo N; Inagaki, Fuyuhiko; Ohsumi, Yoshinori; Tanaka, Akiko

2013-10-01

The fluorescence correlation spectroscopy (FCS)-based competitive binding assay to screen for protein-protein interaction inhibitors is a highly sensitive method as compared with the fluorescent polarization assay used conventionally. However, the FCS assay identifies many false-positive compounds, which requires specifically designed orthogonal screenings. A two-colored application of the FCS-based screening was newly developed, and inhibitors of a protein-protein interaction, involving selective autophagy, were selected. We focused on the interaction of LC3 with the adaptor protein p62, because the interaction is crucial to degrade the specific target proteins recruited by p62. First, about 10,000 compounds were subjected to the FCS-based competitive assay using a TAMRA-labeled p62-derived probe, and 29 hit compounds were selected. Next, the obtained hits were evaluated by the second FCS assay, using an Alexa647-labeled p62-derived probe to remove the false-positive compounds, and six hit compounds inhibited the interaction. Finally, we tested all 29 compounds by surface plasmon resonance-based competitive binding assay to evaluate their inhibition of the LC3-p62 interaction and selected two inhibitors with IC50 values less than 2 µM. The two-colored FCS-based screening was shown to be effective to screen for protein-protein interaction inhibitors.

Combining structure-based pharmacophore modeling, virtual screening, and in silico ADMET analysis to discover novel tetrahydro-quinoline based pyruvate kinase isozyme M2 activators with antitumor activity

PubMed Central

Chen, Can; Wang, Ting; Wu, Fengbo; Huang, Wei; He, Gu; Ouyang, Liang; Xiang, Mingli; Peng, Cheng; Jiang, Qinglin

2014-01-01

Compared with normal differentiated cells, cancer cells upregulate the expression of pyruvate kinase isozyme M2 (PKM2) to support glycolytic intermediates for anabolic processes, including the synthesis of nucleic acids, amino acids, and lipids. In this study, a combination of the structure-based pharmacophore modeling and a hybrid protocol of virtual screening methods comprised of pharmacophore model-based virtual screening, docking-based virtual screening, and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis were used to retrieve novel PKM2 activators from commercially available chemical databases. Tetrahydroquinoline derivatives were identified as potential scaffolds of PKM2 activators. Thus, the hybrid virtual screening approach was applied to screen the focused tetrahydroquinoline derivatives embedded in the ZINC database. Six hit compounds were selected from the final hits and experimental studies were then performed. Compound 8 displayed a potent inhibitory effect on human lung cancer cells. Following treatment with Compound 8, cell viability, apoptosis, and reactive oxygen species (ROS) production were examined in A549 cells. Finally, we evaluated the effects of Compound 8 on mice xenograft tumor models in vivo. These results may provide important information for further research on novel PKM2 activators as antitumor agents. PMID:25214764

A chemical genetic screen for mTOR pathway inhibitors based on 4E-BP-dependent nuclear accumulation of eIF4E.

PubMed

Livingstone, Mark; Larsson, Ola; Sukarieh, Rami; Pelletier, Jerry; Sonenberg, Nahum

2009-12-24

The signal transduction pathway wherein mTOR regulates cellular growth and proliferation is an active target for drug discovery. The search for new mTOR inhibitors has recently yielded a handful of promising compounds that hold therapeutic potential. This search has been limited by the lack of a high-throughput assay to monitor the phosphorylation of a direct rapamycin-sensitive mTOR substrate in cells. Here we describe a novel cell-based chemical genetic screen useful for efficiently monitoring mTOR signaling to 4E-BPs in response to stimuli. The screen is based on the nuclear accumulation of eIF4E, which occurs in a 4E-BP-dependent manner specifically upon inhibition of mTOR signaling. Using this assay in a small-scale screen, we have identified several compounds not previously known to inhibit mTOR signaling, demonstrating that this method can be adapted to larger screens. Copyright 2009 Elsevier Ltd. All rights reserved.

IDIOS: An innovative index for evaluating dental imaging-based osteoporosis screening indices

PubMed Central

Halboub, Esam; Almashraqi, Abeer Abdulkareem; Khattab, Razan; Al Haffar, Iyad

2016-01-01

Purpose The goal of this study was to develop a new index as an objective reference for evaluating current and newly developed indices used for osteoporosis screening based on dental images. Its name; IDIOS, stands for Index of Dental-imaging Indices of Osteoporosis Screening. Materials and Methods A comprehensive PubMed search was conducted to retrieve studies on dental imaging-based indices for osteoporosis screening. The results of the eligible studies, along with other relevant criteria, were used to develop IDIOS, which has scores ranging from 0 (0%) to 15 (100%). The indices presented in the studies we included were then evaluated using IDIOS. Results The 104 studies that were included utilized 24, 4, and 9 indices derived from panoramic, periapical, and computed tomographic/cone-beam computed tomographic techniques, respectively. The IDIOS scores for these indices ranged from 0 (0%) to 11.75 (78.32%). Conclusion IDIOS is a valuable reference index that facilitates the evaluation of other dental imaging-based osteoporosis screening indices. Furthermore, IDIOS can be utilized to evaluate the accuracy of newly developed indices. PMID:27672615

A colorimetric assay of 1-aminocyclopropane-1-carboxylate (ACC) based on ninhydrin reaction for rapid screening of bacteria containing ACC deaminase.

PubMed

Li, Z; Chang, S; Lin, L; Li, Y; An, Q

2011-08-01

1-Aminocyclopropane-1-carboxylate (ACC) deaminase activity is an efficient marker for bacteria to promote plant growth by lowering ethylene levels in plants. We aim to develop a method for rapidly screening bacteria containing ACC deaminase, based on a colorimetric ninhydrin assay of ACC. A reliable colorimetric ninhydrin assay was developed to quantify ACC using heat-resistant polypropylene chimney-top 96-well PCR plates, having the wells evenly heated in boiling water, preventing accidental contamination from boiling water and limiting evaporation. With this method to measure bacterial consumption of ACC, 44 ACC-utilizing bacterial isolates were rapidly screened out from 311 bacterial isolates that were able to grow on minimal media containing ACC as the sole nitrogen source. The 44 ACC-utilizing bacterial isolates showed ACC deaminase activities and belonged to the genus Burkholderia, Pseudomonas or Herbaspirillum. Determination of bacterial ACC consumption by the PCR-plate ninhydrin-ACC assay is a rapid and efficient method for screening bacteria containing ACC deaminase from a large number of bacterial isolates. The PCR-plate ninhydrin-ACC assay extends the utility of the ninhydrin reaction and enables a rapid screening of bacteria containing ACC deaminase from large numbers of bacterial isolates. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

[Study of Cervical Exfoliated Cell's DNA Quantitative Analysis Based on Multi-Spectral Imaging Technology].

PubMed

Wu, Zheng; Zeng, Li-bo; Wu, Qiong-shui

2016-02-01

The conventional cervical cancer screening methods mainly include TBS (the bethesda system) classification method and cellular DNA quantitative analysis, however, by using multiple staining method in one cell slide, which is staining the cytoplasm with Papanicolaou reagent and the nucleus with Feulgen reagent, the study of achieving both two methods in the cervical cancer screening at the same time is still blank. Because the difficulty of this multiple staining method is that the absorbance of the non-DNA material may interfere with the absorbance of DNA, so that this paper has set up a multi-spectral imaging system, and established an absorbance unmixing model by using multiple linear regression method based on absorbance's linear superposition character, and successfully stripped out the absorbance of DNA to run the DNA quantitative analysis, and achieved the perfect combination of those two kinds of conventional screening method. Through a series of experiment we have proved that between the absorbance of DNA which is calculated by the absorbance unmixxing model and the absorbance of DNA which is measured there is no significant difference in statistics when the test level is 1%, also the result of actual application has shown that there is no intersection between the confidence interval of the DNA index of the tetraploid cells which are screened by using this paper's analysis method when the confidence level is 99% and the DNA index's judging interval of cancer cells, so that the accuracy and feasibility of the quantitative DNA analysis with multiple staining method expounded by this paper have been verified, therefore this analytical method has a broad application prospect and considerable market potential in early diagnosis of cervical cancer and other cancers.

HIV coreceptor phenotyping in the clinical setting.

PubMed

Low, Andrew J; Swenson, Luke C; Harrigan, P Richard

2008-01-01

The introduction of CCR5 antagonists increases the options available for constructing antiretroviral regimens. However, this option is coupled with the caveat that patients should be tested for HIV coreceptor tropism prior to initiating CCR5 antagonist-based therapy. Failure to screen for CXCR4 usage increases the risk of using an ineffective drug, thus reducing the likelihood of viral suppression and increasing their risk for developing antiretroviral resistance. This review discusses current and future methods of determining HIV tropism, with a focus on their utility in the clinical setting for screening purposes. Some of these methods include recombinant phenotypic tests, such as the Monogram Trofile assay, as well as genotype-based predictors, heteroduplex tracking assays, and flow cytometry based methods. Currently, the best evidence supports the use of phenotypic methods, although other methods of screening for HIV coreceptor usage prior to the administration of CCR5 antagonists may reduce costs and increase turnaround time over phenotypic methods. The presence of low levels of X4 virus is a challenge to all assay methods, resulting in reduced sensitivity in clinical, patient-derived samples when compared to clonally derived samples. Gaining a better understanding of the output of these assays and correlating them with clinical progression and therapy response will provide some indication on how both genotype-based, and phenotypic assays for determining HIV coreceptor usage can be improved. In addition, leveraging new technologies capable of detecting low-level minority species may provide the most significant advances in ensuring that individuals with low levels of dual/mixed tropic virus are not inadvertently prescribed CCR5 antagonists.

A choice-based screening method for compulsive drug users in rats.

PubMed

Lenoir, Magalie; Augier, Eric; Vouillac, Caroline; Ahmed, Serge H

2013-07-01

We describe a protocol for screening compulsive drug users among cocaine self-administering rats, the most frequently used animal model in addiction research. Rats are first trained on several alternating days to self-administer either cocaine (i.v.) or saccharin-sweetened water (by mouth)--a potent, albeit nonessential, nondrug reward. Then rats are allowed to choose between the two rewards over several days until the preference stabilizes. Most rats choose to stop using cocaine and pursue the alternative reward. Only a minority of Wistar strain rats (generally 15%) persist in taking the drug, regardless of the severity of past cocaine use and even when made hungry and offered the possibility to relieve their physiological need. Persistence of cocaine use in the face of a high-stakes choice is a core defining feature of compulsion. This choice-based screening method for compulsive drug users is easy to implement, has several important applications, and compares well with other methods in the field. 2013 by John Wiley & Sons, Inc.

Isolation, screening, and characterization of surface-active agent-producing, oil-degrading marine bacteria of Mumbai Harbor.

PubMed

Mohanram, Rajamani; Jagtap, Chandrakant; Kumar, Pradeep

2016-04-15

Diverse marine bacterial species predominantly found in oil-polluted seawater produce diverse surface-active agents. Surface-active agents produced by bacteria are classified into two groups based on their molecular weights, namely biosurfactants and bioemulsifiers. In this study, surface-active agent-producing, oil-degrading marine bacteria were isolated using a modified Bushnell-Haas medium with high-speed diesel as a carbon source from three oil-polluted sites of Mumbai Harbor. Surface-active agent-producing bacterial strains were screened using nine widely used methods. The nineteen bacterial strains showed positive results for more than four surface-active agent screening methods; further, these strains were characterized using biochemical and nucleic acid sequencing methods. Based on the results, the organisms belonged to the genera Acinetobacter, Alcanivorax, Bacillus, Comamonas, Chryseomicrobium, Halomonas, Marinobacter, Nesterenkonia, Pseudomonas, and Serratia. The present study confirmed the prevalence of surface-active agent-producing bacteria in the oil-polluted waters of Mumbai Harbor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reducing DNA context dependence in bacterial promoters

PubMed Central

Carr, Swati B.; Densmore, Douglas M.

2017-01-01

Variation in the DNA sequence upstream of bacterial promoters is known to affect the expression levels of the products they regulate, sometimes dramatically. While neutral synthetic insulator sequences have been found to buffer promoters from upstream DNA context, there are no established methods for designing effective insulator sequences with predictable effects on expression levels. We address this problem with Degenerate Insulation Screening (DIS), a novel method based on a randomized 36-nucleotide insulator library and a simple, high-throughput, flow-cytometry-based screen that randomly samples from a library of 436 potential insulated promoters. The results of this screen can then be compared against a reference uninsulated device to select a set of insulated promoters providing a precise level of expression. We verify this method by insulating the constitutive, inducible, and repressible promotors of a four transcriptional-unit inverter (NOT-gate) circuit, finding both that order dependence is largely eliminated by insulation and that circuit performance is also significantly improved, with a 5.8-fold mean improvement in on/off ratio. PMID:28422998

The novel measuring method for screening and assessing chromium content in clothes and shoes materials

NASA Astrophysics Data System (ADS)

Salerno-Kochan, R.

2017-10-01

The aim of this paper is to propose the bioindicative measuring method for screening and assessing the safety of textile and leather materials in relation to chemical threats. This method is based on toxicological assay in which Tetrahymena pyriformis, unicellular organism belonging to protozoans, is used as a test organism. For the realization of the research goal the sensitivity threshold of test organisms to chromium(VI) solutions was identified. The changes in cell development of test organisms in chromium solutions were registered by colorimetric measurements in the presence of alamarBlue® cell viability reagent. Empirical data enabled to fit logistic curves on the base of which the level of chromium toxicity was estimated. In the second step, harmfulness of aqueous extracts obtained from textile and leather samples containing chromium in relation to test organisms was evaluated. The performed research confirmed the high efficiency of the proposed method in screening and assessing chromium content in clothes and shoes materials and showed possibilities of using it in safety assessment of products with regard to chemical risks.

Newborn hearing screening update for midwifery practice.

PubMed

Narrigan, D

2000-01-01

Neonatal identification of congenital hearing impairment allows interventions during the first 3 years, the critical period for language and speech development. Two recently developed biophysical testing methods offer simple, accurate, and relatively inexpensive means to identify the one to three in 1,000 healthy newborns with hearing loss. Universal screening for auditory system integrity is advocated, because almost half of all newborns with hearing impairment have no risk factors associated with this impairment. Critics of universal screening cite the high rate of false positive tests (up to 7%), which increases program costs from follow-up and re-testing large numbers of infants to ensure identifying the few affected infants. As of early 2000, 24 states had introduced some type of auditory screening program, and the U.S. Congress had passed legislation with appropriations mandating state-based auditory screening for all newborns. Midwives practicing in states already mandating biophysical screening need to comply with their local requirements; those in other states may voluntarily incorporate new auditory test methods into practice.

Novel citation-based search method for scientific literature: application to meta-analyses.

PubMed

Janssens, A Cecile J W; Gwinn, M

2015-10-13

Finding eligible studies for meta-analysis and systematic reviews relies on keyword-based searching as the gold standard, despite its inefficiency. Searching based on direct citations is not sufficiently comprehensive. We propose a novel strategy that ranks articles on their degree of co-citation with one or more "known" articles before reviewing their eligibility. In two independent studies, we aimed to reproduce the results of literature searches for sets of published meta-analyses (n = 10 and n = 42). For each meta-analysis, we extracted co-citations for the randomly selected 'known' articles from the Web of Science database, counted their frequencies and screened all articles with a score above a selection threshold. In the second study, we extended the method by retrieving direct citations for all selected articles. In the first study, we retrieved 82% of the studies included in the meta-analyses while screening only 11% as many articles as were screened for the original publications. Articles that we missed were published in non-English languages, published before 1975, published very recently, or available only as conference abstracts. In the second study, we retrieved 79% of included studies while screening half the original number of articles. Citation searching appears to be an efficient and reasonably accurate method for finding articles similar to one or more articles of interest for meta-analysis and reviews.

A microscopy-based screen employing multiplex genome sequencing identifies cargo-specific requirements for dynein velocity

PubMed Central

Tan, Kaeling; Roberts, Anthony J.; Chonofsky, Mark; Egan, Martin J.; Reck-Peterson, Samara L.

2014-01-01

The timely delivery of membranous organelles and macromolecules to specific locations within the majority of eukaryotic cells depends on microtubule-based transport. Here we describe a screening method to identify mutations that have a critical effect on intracellular transport and its regulation using mutagenesis, multicolor-fluorescence microscopy, and multiplex genome sequencing. This screen exploits the filamentous fungus Aspergillus nidulans, which has many of the advantages of yeast molecular genetics but uses long-range microtubule-based transport in a manner more similar to metazoan cells. Using this method, we identified seven mutants that represent novel alleles of components of the intracellular transport machinery: specifically, kinesin-1, cytoplasmic dynein, and the dynein regulators Lis1 and dynactin. The two dynein mutations identified in our screen map to dynein's AAA+ catalytic core. Single-molecule studies reveal that both mutations reduce dynein's velocity in vitro. In vivo these mutants severely impair the distribution and velocity of endosomes, a known dynein cargo. In contrast, another dynein cargo, the nucleus, is positioned normally in these mutants. These results reveal that different dynein functions have distinct stringencies for motor performance. PMID:24403603

[Fragment-based drug discovery: concept and aim].

PubMed

Tanaka, Daisuke

2010-03-01

Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically <300 Da), have not been employed in conventional high-throughput screening (HTS), the recent significant progress in the biophysical screening methods enables fragment screening at a practical level. The intention of FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to "undruggable targets" (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.

Orbitals for classical arbitrary anisotropic colloidal potentials

NASA Astrophysics Data System (ADS)

Girard, Martin; Nguyen, Trung Dac; de la Cruz, Monica Olvera

2017-11-01

Coarse-grained potentials are ubiquitous in mesoscale simulations. While various methods to compute effective interactions for spherically symmetric particles exist, anisotropic interactions are seldom used, due to their complexity. Here we describe a general formulation, based on a spatial decomposition of the density fields around the particles, akin to atomic orbitals. We show that anisotropic potentials can be efficiently computed in numerical simulations using Fourier-based methods. We validate the field formulation and characterize its computational efficiency with a system of colloids that have Gaussian surface charge distributions. We also investigate the phase behavior of charged Janus colloids immersed in screened media, with screening lengths comparable to the colloid size. The system shows rich behaviors, exhibiting vapor, liquid, gel, and crystalline morphologies, depending on temperature and screening length. The crystalline phase only appears for symmetric Janus particles. For very short screening lengths, the system undergoes a direct transition from a vapor to a crystal on cooling; while, for longer screening lengths, a vapor-liquid-crystal transition is observed. The proposed formulation can be extended to model force fields that are time or orientation dependent, such as those in systems of polymer-grafted particles and magnetic colloids.

Validity, efficacy and reliability of 3 nutritional screening tools regarding the nutritional assessment in different social and health areas.

PubMed

Castro-Vega, Iciar; Veses Martín, Silvia; Cantero Llorca, Juana; Barrios Marta, Cristina; Bañuls, Celia; Hernández-Mijares, Antonio

2018-03-09

Nutritional screening allows for the detection of nutritional risk. Validated tools should be implemented, and their usefulness should be contrasted with a gold standard. The aim of this study is to discover the validity, efficacy and reliability of 3 nutritional screening tools in relation to complete nutritional assessment. A sub-analysis of a cross-sectional and descriptive study on the prevalence of disease-related malnutrition. The sample was selected from outpatients, hospitalized and institutionalized patients. MUST, MNAsf and MST screening were employed. A nutritional assessment of all the patients was undertaken. The SENPE-SEDOM consensus was used for the diagnosis. In the outpatients, both MUST and MNAsf have a similar validity in relation to the nutritional assessment (AUC 0.871 and 0.883, respectively). In the institutionalized patients, the MUST screening method is the one that shows the greatest validity (AUC 0.815), whereas in the hospitalized patients, the most valid methods are both MUST and MST (AUC 0.868 and 0.853, respectively). It is essential to use nutritional screening to invest the available resources wisely. Based on our results, MUST is the most suitable screening method in hospitalized and institutionalized patients. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

A modified reverse one-hybrid screen identifies transcriptional activation in Phyochrome-Interacting Factor 3

USDA-ARS?s Scientific Manuscript database

Transcriptional activation domains (TAD) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast-based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput...

Empirical Data Collection and Analysis Using Camtasia and Transana

ERIC Educational Resources Information Center

Thorsteinsson, Gisli; Page, Tom

2009-01-01

One of the possible techniques for collecting empirical data is video recordings of a computer screen with specific screen capture software. This method for collecting empirical data shows how students use the BSCWII (Be Smart Cooperate Worldwide--a web based collaboration/groupware environment) to coordinate their work and collaborate in…

Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Model Applications to Screen Environmental Hazards.

EPA Science Inventory

This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. A...

Screening and identification of glyceollins and their metabolites by electrospray ionization tandem mass spectrometry with precursor ion scanning

USDA-ARS?s Scientific Manuscript database

A method has been developed for screening glyceollins and their metabolites based upon precursor ion scanning. Under higher-energy collision conditions, employing a triple quadrupole mass spectrometer in the negative ion mode, deprotonated glyceollin precursors yield a diagnostic radical product ion...

Semiautomated TaqMan PCR screening of GMO labelled samples for (unauthorised) GMOs.

PubMed

Scholtens, Ingrid M J; Molenaar, Bonnie; van Hoof, Richard A; Zaaijer, Stephanie; Prins, Theo W; Kok, Esther J

2017-06-01

In most countries, systems are in place to analyse food products for the potential presence of genetically modified organisms (GMOs), to enforce labelling requirements and to screen for the potential presence of unauthorised GMOs. With the growing number of GMOs on the world market, a larger diversity of methods is required for informative analyses. In this paper, the specificity of an extended screening set consisting of 32 screening methods to identify different crop species (endogenous genes) and GMO elements was verified against 59 different GMO reference materials. In addition, a cost- and time-efficient strategy for DNA isolation, screening and identification is presented. A module for semiautomated analysis of the screening results and planning of subsequent event-specific tests for identification has been developed. The Excel-based module contains information on the experimentally verified specificity of the element methods and of the EU authorisation status of the GMO events. If a detected GMO element cannot be explained by any of the events as identified in the same sample, this may indicate the presence of an unknown unauthorised GMO that may not yet have been assessed for its safety for humans, animals or the environment.

Technologic advances for evaluation of cervical cytology: is newer better?

PubMed

Hartmann, K E; Nanda, K; Hall, S; Myers, E

2001-12-01

Among those women who have cervical cancer and have been screened, 14% to 33% of the cases represent failure to detect abnormalities that existed at the time of screening. New technologies intended to improve detection of cytologic abnormalities include liquid-based, thin-layer cytology (ThinPrep, AutoCyte), computerized rescreening (PAPNET), and algorithm-based computer rescreening (AutoPap). This report combines evidence reviews conducted for the U.S. Preventive Services Task Force and the Agency for Healthcare Research and Quality, in which we systematically identified articles on cervical neoplasia, cervical dysplasia, and screening published between January 1966 and March 2001. We note the challenges for improving screening methods, providing an overview of methods for collecting and evaluating cytologic samples, and examining the evidence about the diagnostic performance of new technologies for detecting cervical lesions. Using standard criteria for evaluation of the diagnostic tests, we determined that knowledge about the sensitivity, specificity, and predictive values of new technologies is meager. Only one study of liquid-based cytology used a reference standard of colposcopy, with histology as indicated, to assess participants with normal screening results. Lack of an adequate reference standard is the overwhelming reason that test characteristics cannot be properly assessed or compared. Most publications compare results of screening using the new technology with expert panel review of the cytologic specimen. In that case, the tests are not independent measures and do nothing to relate the screening test findings to the true status of the cervix, making determination of false-negatives, and thus sensitivity, specificity, and negative predictive value, impossible. We did not identify any literature about health outcomes or cost effectiveness of using these tools in a system of screening. For the purposes of guiding decision making about choice of screening tools, the current evidence is inadequate to gauge whether new technologies are "better" than conventional cytology..

A deep learning method for early screening of lung cancer

NASA Astrophysics Data System (ADS)

Zhang, Kunpeng; Jiang, Huiqin; Ma, Ling; Gao, Jianbo; Yang, Xiaopeng

2018-04-01

Lung cancer is the leading cause of cancer-related deaths among men. In this paper, we propose a pulmonary nodule detection method for early screening of lung cancer based on the improved AlexNet model. In order to maintain the same image quality as the existing B/S architecture PACS system, we convert the original CT image into JPEG format image by analyzing the DICOM file firstly. Secondly, in view of the large size and complex background of CT chest images, we design the convolution neural network on basis of AlexNet model and sparse convolution structure. At last we train our models on the software named DIGITS which is provided by NVIDIA. The main contribution of this paper is to apply the convolutional neural network for the early screening of lung cancer and improve the screening accuracy by combining the AlexNet model with the sparse convolution structure. We make a series of experiments on the chest CT images using the proposed method, of which the sensitivity and specificity indicates that the method presented in this paper can effectively improve the accuracy of early screening of lung cancer and it has certain clinical significance at the same time.

Development and interlaboratory validation of quantitative polymerase chain reaction method for screening analysis of genetically modified soybeans.

PubMed

Takabatake, Reona; Onishi, Mari; Koiwa, Tomohiro; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi

2013-01-01

A novel real-time polymerase chain reaction (PCR)-based quantitative screening method was developed for three genetically modified soybeans: RRS, A2704-12, and MON89788. The 35S promoter (P35S) of cauliflower mosaic virus is introduced into RRS and A2704-12 but not MON89788. We then designed a screening method comprised of the combination of the quantification of P35S and the event-specific quantification of MON89788. The conversion factor (Cf) required to convert the amount of a genetically modified organism (GMO) from a copy number ratio to a weight ratio was determined experimentally. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDR), respectively. The determined RSDR values for the method were less than 25% for both targets. We consider that the developed method would be suitable for the simple detection and approximate quantification of GMO.

A phase screen model for simulating numerically the propagation of a laser beam in rain

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

Lukin, I P; Rychkov, D S; Falits, A V

2009-09-30

The method based on the generalisation of the phase screen method for a continuous random medium is proposed for simulating numerically the propagation of laser radiation in a turbulent atmosphere with precipitation. In the phase screen model for a discrete component of a heterogeneous 'air-rain droplet' medium, the amplitude screen describing the scattering of an optical field by discrete particles of the medium is replaced by an equivalent phase screen with a spectrum of the correlation function of the effective dielectric constant fluctuations that is similar to the spectrum of a discrete scattering component - water droplets in air. Themore » 'turbulent' phase screen is constructed on the basis of the Kolmogorov model, while the 'rain' screen model utiises the exponential distribution of the number of rain drops with respect to their radii as a function of the rain intensity. Theresults of the numerical simulation are compared with the known theoretical estimates for a large-scale discrete scattering medium. (propagation of laser radiation in matter)« less

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

Taylor-Pashow, K.; Fondeur, F.; White, T.

Savannah River National Laboratory (SRNL) was tasked with identifying and developing at least one, but preferably two methods for quantifying the suppressor in the Next Generation Solvent (NGS) system. The suppressor is a guanidine derivative, N,N',N"-tris(3,7-dimethyloctyl)guanidine (TiDG). A list of 10 possible methods was generated, and screening experiments were performed for 8 of the 10 methods. After completion of the screening experiments, the non-aqueous acid-base titration was determined to be the most promising, and was selected for further development as the primary method. {sup 1}H NMR also showed promising results from the screening experiments, and this method was selected formore » further development as the secondary method. Other methods, including {sup 36}Cl radiocounting and ion chromatography, also showed promise; however, due to the similarity to the primary method (titration) and the inability to differentiate between TiDG and TOA (tri-n-ocytlamine) in the blended solvent, {sup 1}H NMR was selected over these methods. Analysis of radioactive samples obtained from real waste ESS (extraction, scrub, strip) testing using the titration method showed good results. Based on these results, the titration method was selected as the method of choice for TiDG measurement. {sup 1}H NMR has been selected as the secondary (back-up) method, and additional work is planned to further develop this method and to verify the method using radioactive samples. Procedures for analyzing radioactive samples of both pure NGS and blended solvent were developed and issued for the both methods.« less

Exploring the Perceptions of Anal Cancer Screening and Behaviors Among Gay and Bisexual Men Infected With HIV

PubMed Central

Koskan, Alexis M.; LeBlanc, Natalie; Rosa-Cunha, Isabella

2016-01-01

Background The incidence of anal cancer is on the rise among HIV-infected men who have sex with men (MSM). Given the increasing availability of screening, this study explored anal cancer screening awareness and behaviors among MSM infected with HIV. Methods In-depth interviews were conducted with 58 MSM infected with HIV. Results Other than 2 participants treated for anal cancer and 3 treated for precancerous anal lesions, the majority of participants had never heard of anal cancer. Men reported lack of awareness and recommendations from their health care professionals as the greatest barriers to screening. Upon learning about their risk for anal cancer and the availability of screening, the men were eager to discuss screening with their physicians. Participants provided numerous recommendations for future interventions, including training health care professionals to promote screening, disseminating information pertaining to anal cancer through social networks, and creating media campaigns to raise awareness about the need to screen for this type of cancer. Conclusions Future intervention work should focus on ensuring that health care professionals, particularly among HIV/primary care specialists, promote screening for anal dysplasia. It is critical that intervention methods use a community-based approach to raise awareness about the need to screen for anal cancer, especially among MSM infected with HIV. PMID:27009457

Identification of a ligand for tumor necrosis factor receptor from Chinese herbs by combination of surface plasmon resonance biosensor and UPLC-MS.

PubMed

Cao, Yan; Li, Ying-Hua; Lv, Di-Ya; Chen, Xiao-Fei; Chen, Lang-Dong; Zhu, Zhen-Yu; Chai, Yi-Feng; Zhang, Jun-Ping

2016-07-01

Identification of bioactive compounds directly from complex herbal extracts is a key issue in the study of Chinese herbs. The present study describes the establishment and application of a sensitive, efficient, and convenient method based on surface plasmon resonance (SPR) biosensors for screening active ingredients targeting tumor necrosis factor receptor type 1 (TNF-R1) from Chinese herbs. Concentration-adjusted herbal extracts were subjected to SPR binding assay, and a remarkable response signal was observed in Rheum officinale extract. Then, the TNF-R1-bound ingredients were recovered, enriched, and analyzed by UPLC-QTOF/MS. As a result, physcion-8-O-β-D-monoglucoside (PMG) was identified as a bioactive compound, and the affinity constant of PMG to TNF-R1 was determined by SPR affinity analysis (K D  = 376 nM). Pharmacological assays revealed that PMG inhibited TNF-α-induced cytotoxicity and apoptosis in L929 cells via TNF-R1. Although PMG was a trace component in the chemical constituents of the R. officinale extract, it had considerable anti-inflammatory activities. It was found for the first time that PMG was a ligand for TNF receptor from herbal medicines. The proposed SPR-based screening method may prove to be an effective solution to analyzing bioactive components of Chinese herbs and other complex drug systems. Graphical abstract Scheme of the method based on SPR biosensor for screening and recovering active ingredients from complex herbal extracts and UPLC-MS for identifying them. Scheme of the method based on SPR biosensor for screening and recovering active ingredients from complex herbal extracts and UPLC-MS for identifying them.

Conditional screening for ultra-high dimensional covariates with survival outcomes

PubMed Central

Hong, Hyokyoung G.; Li, Yi

2017-01-01

Identifying important biomarkers that are predictive for cancer patients’ prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization. The recently developed variable screening methods, though powerful in many practical setting, fail to incorporate prior information on the importance of each biomarker and are less powerful in detecting marginally weak while jointly important signals. We propose a new conditional screening method for survival outcome data by computing the marginal contribution of each biomarker given priorily known biological information. This is based on the premise that some biomarkers are known to be associated with disease outcomes a priori. Our method possesses sure screening properties and a vanishing false selection rate. The utility of the proposal is further confirmed with extensive simulation studies and analysis of a diffuse large B-cell lymphoma dataset. We are pleased to dedicate this work to Jack Kalbfleisch, who has made instrumental contributions to the development of modern methods of analyzing survival data. PMID:27933468

Benchmarking methods and data sets for ligand enrichment assessment in virtual screening.

PubMed

Xia, Jie; Tilahun, Ermias Lemma; Reid, Terry-Elinor; Zhang, Liangren; Wang, Xiang Simon

2015-01-01

Retrospective small-scale virtual screening (VS) based on benchmarking data sets has been widely used to estimate ligand enrichments of VS approaches in the prospective (i.e. real-world) efforts. However, the intrinsic differences of benchmarking sets to the real screening chemical libraries can cause biased assessment. Herein, we summarize the history of benchmarking methods as well as data sets and highlight three main types of biases found in benchmarking sets, i.e. "analogue bias", "artificial enrichment" and "false negative". In addition, we introduce our recent algorithm to build maximum-unbiased benchmarking sets applicable to both ligand-based and structure-based VS approaches, and its implementations to three important human histone deacetylases (HDACs) isoforms, i.e. HDAC1, HDAC6 and HDAC8. The leave-one-out cross-validation (LOO CV) demonstrates that the benchmarking sets built by our algorithm are maximum-unbiased as measured by property matching, ROC curves and AUCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Benchmarking Methods and Data Sets for Ligand Enrichment Assessment in Virtual Screening

PubMed Central

Xia, Jie; Tilahun, Ermias Lemma; Reid, Terry-Elinor; Zhang, Liangren; Wang, Xiang Simon

2014-01-01

Retrospective small-scale virtual screening (VS) based on benchmarking data sets has been widely used to estimate ligand enrichments of VS approaches in the prospective (i.e. real-world) efforts. However, the intrinsic differences of benchmarking sets to the real screening chemical libraries can cause biased assessment. Herein, we summarize the history of benchmarking methods as well as data sets and highlight three main types of biases found in benchmarking sets, i.e. “analogue bias”, “artificial enrichment” and “false negative”. In addition, we introduced our recent algorithm to build maximum-unbiased benchmarking sets applicable to both ligand-based and structure-based VS approaches, and its implementations to three important human histone deacetylase (HDAC) isoforms, i.e. HDAC1, HDAC6 and HDAC8. The Leave-One-Out Cross-Validation (LOO CV) demonstrates that the benchmarking sets built by our algorithm are maximum-unbiased in terms of property matching, ROC curves and AUCs. PMID:25481478

Road screening and distribution route multi-objective robust optimization for hazardous materials based on neural network and genetic algorithm.

PubMed

Ma, Changxi; Hao, Wei; Pan, Fuquan; Xiang, Wang

2018-01-01

Route optimization of hazardous materials transportation is one of the basic steps in ensuring the safety of hazardous materials transportation. The optimization scheme may be a security risk if road screening is not completed before the distribution route is optimized. For road screening issues of hazardous materials transportation, a road screening algorithm of hazardous materials transportation is built based on genetic algorithm and Levenberg-Marquardt neural network (GA-LM-NN) by analyzing 15 attributes data of each road network section. A multi-objective robust optimization model with adjustable robustness is constructed for the hazardous materials transportation problem of single distribution center to minimize transportation risk and time. A multi-objective genetic algorithm is designed to solve the problem according to the characteristics of the model. The algorithm uses an improved strategy to complete the selection operation, applies partial matching cross shift and single ortho swap methods to complete the crossover and mutation operation, and employs an exclusive method to construct Pareto optimal solutions. Studies show that the sets of hazardous materials transportation road can be found quickly through the proposed road screening algorithm based on GA-LM-NN, whereas the distribution route Pareto solutions with different levels of robustness can be found rapidly through the proposed multi-objective robust optimization model and algorithm.

Global Sensitivity Analysis of Environmental Models: Convergence, Robustness and Validation

NASA Astrophysics Data System (ADS)

Sarrazin, Fanny; Pianosi, Francesca; Khorashadi Zadeh, Farkhondeh; Van Griensven, Ann; Wagener, Thorsten

2015-04-01

Global Sensitivity Analysis aims to characterize the impact that variations in model input factors (e.g. the parameters) have on the model output (e.g. simulated streamflow). In sampling-based Global Sensitivity Analysis, the sample size has to be chosen carefully in order to obtain reliable sensitivity estimates while spending computational resources efficiently. Furthermore, insensitive parameters are typically identified through the definition of a screening threshold: the theoretical value of their sensitivity index is zero but in a sampling-base framework they regularly take non-zero values. There is little guidance available for these two steps in environmental modelling though. The objective of the present study is to support modellers in making appropriate choices, regarding both sample size and screening threshold, so that a robust sensitivity analysis can be implemented. We performed sensitivity analysis for the parameters of three hydrological models with increasing level of complexity (Hymod, HBV and SWAT), and tested three widely used sensitivity analysis methods (Elementary Effect Test or method of Morris, Regional Sensitivity Analysis, and Variance-Based Sensitivity Analysis). We defined criteria based on a bootstrap approach to assess three different types of convergence: the convergence of the value of the sensitivity indices, of the ranking (the ordering among the parameters) and of the screening (the identification of the insensitive parameters). We investigated the screening threshold through the definition of a validation procedure. The results showed that full convergence of the value of the sensitivity indices is not necessarily needed to rank or to screen the model input factors. Furthermore, typical values of the sample sizes that are reported in the literature can be well below the sample sizes that actually ensure convergence of ranking and screening.

Targeting regional pediatric congenital hearing loss using a spatial scan statistic.

PubMed

Bush, Matthew L; Christian, Warren Jay; Bianchi, Kristin; Lester, Cathy; Schoenberg, Nancy

2015-01-01

Congenital hearing loss is a common problem, and timely identification and intervention are paramount for language development. Patients from rural regions may have many barriers to timely diagnosis and intervention. The purpose of this study was to examine the spatial and hospital-based distribution of failed infant hearing screening testing and pediatric congenital hearing loss throughout Kentucky. Data on live births and audiological reporting of infant hearing loss results in Kentucky from 2009 to 2011 were analyzed. The authors used spatial scan statistics to identify high-rate clusters of failed newborn screening tests and permanent congenital hearing loss (PCHL), based on the total number of live births per county. The authors conducted further analyses on PCHL and failed newborn hearing screening tests, based on birth hospital data and method of screening. The authors observed four statistically significant (p < 0.05) high-rate clusters with failed newborn hearing screenings in Kentucky, including two in the Appalachian region. Hospitals using two-stage otoacoustic emission testing demonstrated higher rates of failed screening (p = 0.009) than those using two-stage automated auditory brainstem response testing. A significant cluster of high rate of PCHL was observed in Western Kentucky. Five of the 54 birthing hospitals were found to have higher relative risk of PCHL, and two of those hospitals are located in a very rural region of Western Kentucky within the cluster. This spatial analysis in children in Kentucky has identified specific regions throughout the state with high rates of congenital hearing loss and failed newborn hearing screening tests. Further investigation regarding causative factors is warranted. This method of analysis can be useful in the setting of hearing health disparities to focus efforts on regions facing high incidence of congenital hearing loss.

Fragment length analysis screening for detection of CEBPA mutations in intermediate-risk karyotype acute myeloid leukemia.

PubMed

Fuster, Oscar; Barragán, Eva; Bolufer, Pascual; Such, Esperanza; Valencia, Ana; Ibáñez, Mariam; Dolz, Sandra; de Juan, Inmaculada; Jiménez, Antonio; Gómez, Maria Teresa; Buño, Ismael; Martínez, Joaquín; Cervera, José; Montesinos, Pau; Moscardó, Federico; Sanz, Miguel Ángel

2012-01-01

During last years, molecular markers have been increased as prognostic factors routinely screened in acute myeloid leukemia (AML). Recently, an increasing interest has been reported in introducing to clinical practice screening for mutations in the CCAAT/enhancer-binding protein α (CEBPA) gene in AML, as it seems to be a good prognostic factor. However, there is no reliable established method for assessing CEBPA mutations during the diagnostic work-up of AMLs. We describe here a straightforward and reliable fragment analysis method based in PCR capillary electrophoresis (PCR-CE) for screening of CEBPA mutations; moreover, we present the results obtained in 151 intermediate-risk karyotype AML patients (aged 16-80 years). The method gave a specificity of 100% and sensitivity of 93% with a lower detection limit of 1-5% for CEBPA mutations. The series found 19 mutations and four polymorphisms in 12 patients, seven of whom (58%) presented two mutations. The overall frequency of CEBPA mutations in AML was 8% (n = 12). CEBPA mutations showed no coincidence with FLT3-ITD or NPM1 mutations. CEBPA mutation predicted better disease-free survival in the group of patients without FLT3-ITD, NPM, or both genes mutated (HR 3.6, IC 95%; 1.0-13.2, p = 0.05) and better overall survival in patients younger than 65 of this group without molecular markers (HR 4.0, IC 95%; 1.0-17.4, p = 0.05). In conclusion, the fragment analysis method based in PCR-CE is a rapid, specific, and sensitive method for CEBPA mutation screening and our results confirm that CEBPA mutations can identify a subgroup of patients with favorable prognosis in AML with intermediate-risk karyotype.

Screening and clustering of sparse regressions with finite non-Gaussian mixtures.

PubMed

Zhang, Jian

2017-06-01

This article proposes a method to address the problem that can arise when covariates in a regression setting are not Gaussian, which may give rise to approximately mixture-distributed errors, or when a true mixture of regressions produced the data. The method begins with non-Gaussian mixture-based marginal variable screening, followed by fitting a full but relatively smaller mixture regression model to the selected data with help of a new penalization scheme. Under certain regularity conditions, the new screening procedure is shown to possess a sure screening property even when the population is heterogeneous. We further prove that there exists an elbow point in the associated scree plot which results in a consistent estimator of the set of active covariates in the model. By simulations, we demonstrate that the new procedure can substantially improve the performance of the existing procedures in the content of variable screening and data clustering. By applying the proposed procedure to motif data analysis in molecular biology, we demonstrate that the new method holds promise in practice. © 2016, The International Biometric Society.

A Versatile Cell Death Screening Assay Using Dye-Stained Cells and Multivariate Image Analysis.

PubMed

Collins, Tony J; Ylanko, Jarkko; Geng, Fei; Andrews, David W

2015-11-01

A novel dye-based method for measuring cell death in image-based screens is presented. Unlike conventional high- and medium-throughput cell death assays that measure only one form of cell death accurately, using multivariate analysis of micrographs of cells stained with the inexpensive mix, red dye nonyl acridine orange, and a nuclear stain, it was possible to quantify cell death induced by a variety of different agonists even without a positive control. Surprisingly, using a single known cytotoxic agent as a positive control for training a multivariate classifier allowed accurate quantification of cytotoxicity for mechanistically unrelated compounds enabling generation of dose-response curves. Comparison with low throughput biochemical methods suggested that cell death was accurately distinguished from cell stress induced by low concentrations of the bioactive compounds Tunicamycin and Brefeldin A. High-throughput image-based format analyses of more than 300 kinase inhibitors correctly identified 11 as cytotoxic with only 1 false positive. The simplicity and robustness of this dye-based assay makes it particularly suited to live cell screening for toxic compounds.

A Versatile Cell Death Screening Assay Using Dye-Stained Cells and Multivariate Image Analysis

PubMed Central

Collins, Tony J.; Ylanko, Jarkko; Geng, Fei

2015-01-01

Abstract A novel dye-based method for measuring cell death in image-based screens is presented. Unlike conventional high- and medium-throughput cell death assays that measure only one form of cell death accurately, using multivariate analysis of micrographs of cells stained with the inexpensive mix, red dye nonyl acridine orange, and a nuclear stain, it was possible to quantify cell death induced by a variety of different agonists even without a positive control. Surprisingly, using a single known cytotoxic agent as a positive control for training a multivariate classifier allowed accurate quantification of cytotoxicity for mechanistically unrelated compounds enabling generation of dose–response curves. Comparison with low throughput biochemical methods suggested that cell death was accurately distinguished from cell stress induced by low concentrations of the bioactive compounds Tunicamycin and Brefeldin A. High-throughput image-based format analyses of more than 300 kinase inhibitors correctly identified 11 as cytotoxic with only 1 false positive. The simplicity and robustness of this dye-based assay makes it particularly suited to live cell screening for toxic compounds. PMID:26422066

Estimating Development Cost of an Interactive Website Based Cancer Screening Promotion Program

PubMed Central

Lairson, David R.; Chung, Tong Han; Smith, Lisa G.; Springston, Jeffrey K.; Champion, Victoria L.

2015-01-01

Objectives The aim of this study was to estimate the initial development costs for an innovative talk show format tailored intervention delivered via the interactive web, for increasing cancer screening in women 50 to 75 who were non-adherent to screening guidelines for colorectal cancer and/or breast cancer. Methods The cost of the intervention development was estimated from a societal perspective. Micro costing methods plus vendor contract costs were used to estimate cost. Staff logs were used to track personnel time. Non-personnel costs include all additional resources used to produce the intervention. Results Development cost of the interactive web based intervention was $.39 million, of which 77% was direct cost. About 98% of the cost was incurred in personnel time cost, contract cost and overhead cost. Conclusions The new web-based disease prevention medium required substantial investment in health promotion and media specialist time. The development cost was primarily driven by the high level of human capital required. The cost of intervention development is important information for assessing and planning future public and private investments in web-based health promotion interventions. PMID:25749548

Anthropometric methods for obesity screening in schoolchildren: the Ouro Preto Study.

PubMed

Cándido, A P C; Alosta, J P S; Oliveira, C T; Freitas, R N; Freitas, S N; Machado-Coelho, G L L

2012-01-01

Childhood obesity is increasing dramatically in last decades. To evaluate the usefulness of body mass index (BMI), skinfold thickness (ST), waist circumference (WC), and foot-to-foot bioelectrical impedance (BIA-FF) for screening for obesity in mixed-race population, using the tetrapolar bioelectrical impedance (BIA-T) technique as reference method. A cross-sectional-based population study was performed in the city of Ouro Preto, Brazil, in 2006. Schoolchildren aged 6-15 years (n = 788) was randomly selected according to age and sex stratified by the proportion of students in each schools of the city. Nonparametric receiver operating characteristic (ROC) analysis was used to define the sensitivity and specificity for each method studied using the tetrapolar method as reference. The BMI and the BIA-FF were the most suitable for adiposity screening in pre-pubertal and pubertal stages because they present a better balance between sensitivity and specificity, and smaller misclassification. For post-pubertal boys, the BF-ST-D was the best body fat assessment method. The results suggest that BIA-FF and BMI are choice methods for obesity screening in mixed population and that the method choice for body fat screening must be done according to sexual maturity of boys and girls. The present study demonstrates the need to perform studies in wider mixed-race population to determine anthropometric parameters and to examine the predictive ability of methods and cut-offs here elucidated in the development of obesity.

Persuasive Interventions for Controversial Cancer Screening Recommendations: Testing a Novel Approach to Help Patients Make Evidence-Based Decisions

PubMed Central

Saver, Barry G.; Mazor, Kathleen M.; Luckmann, Roger; Cutrona, Sarah L.; Hayes, Marcela; Gorodetsky, Tatyana; Esparza, Nancy; Bacigalupe, Gonzalo

2017-01-01

PURPOSE We wanted to evaluate novel decision aids designed to help patients trust and accept the controversial, evidence-based, US Preventive Services Task Force recommendations about prostate cancer screening (from 2012) and mammography screening for women aged 40 to 49 years (from 2009). METHODS We created recorded vignettes of physician-patient discussions about prostate cancer screening and mammography, accompanied by illustrative slides, based on principles derived from preceding qualitative work and behavioral science literature. We conducted a randomized crossover study with repeated measures with 27 men aged 50 to 74 years and 35 women aged 40 to 49 years. All participants saw a video intervention and a more traditional, paper-based decision aid intervention in random order. At entry and after seeing each intervention, they were surveyed about screening intentions, perceptions of benefits and harm, and decisional conflict. RESULTS Changes in screening intentions were analyzed without regard to order of intervention after an initial analyses showed no evidence of an order effect. At baseline, 69% of men and 86% of women reported wanting screening, with 31% and 6%, respectively, unsure. Mean change on a 3-point, yes, unsure, no scale was −0.93 (P = <.001) for men and −0.50 (P = <.001) for women after seeing the video interventions vs 0.0 and −0.06 (P = .75) after seeing the print interventions. At the study end, 33% of men and 49% of women wanted screening, and 11% and 20%, respectively, were unsure. CONCLUSIONS Our novel, persuasive video interventions significantly changed the screening intentions of substantial proportions of viewers. Our approach needs further testing but may provide a model for helping patients to consider and accept evidence-based, counterintuitive recommendations. PMID:28376460

An Unbiased Method To Build Benchmarking Sets for Ligand-Based Virtual Screening and its Application To GPCRs

PubMed Central

2015-01-01

Benchmarking data sets have become common in recent years for the purpose of virtual screening, though the main focus had been placed on the structure-based virtual screening (SBVS) approaches. Due to the lack of crystal structures, there is great need for unbiased benchmarking sets to evaluate various ligand-based virtual screening (LBVS) methods for important drug targets such as G protein-coupled receptors (GPCRs). To date these ready-to-apply data sets for LBVS are fairly limited, and the direct usage of benchmarking sets designed for SBVS could bring the biases to the evaluation of LBVS. Herein, we propose an unbiased method to build benchmarking sets for LBVS and validate it on a multitude of GPCRs targets. To be more specific, our methods can (1) ensure chemical diversity of ligands, (2) maintain the physicochemical similarity between ligands and decoys, (3) make the decoys dissimilar in chemical topology to all ligands to avoid false negatives, and (4) maximize spatial random distribution of ligands and decoys. We evaluated the quality of our Unbiased Ligand Set (ULS) and Unbiased Decoy Set (UDS) using three common LBVS approaches, with Leave-One-Out (LOO) Cross-Validation (CV) and a metric of average AUC of the ROC curves. Our method has greatly reduced the “artificial enrichment” and “analogue bias” of a published GPCRs benchmarking set, i.e., GPCR Ligand Library (GLL)/GPCR Decoy Database (GDD). In addition, we addressed an important issue about the ratio of decoys per ligand and found that for a range of 30 to 100 it does not affect the quality of the benchmarking set, so we kept the original ratio of 39 from the GLL/GDD. PMID:24749745

An unbiased method to build benchmarking sets for ligand-based virtual screening and its application to GPCRs.

PubMed

Xia, Jie; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Wang, Xiang Simon

2014-05-27

Benchmarking data sets have become common in recent years for the purpose of virtual screening, though the main focus had been placed on the structure-based virtual screening (SBVS) approaches. Due to the lack of crystal structures, there is great need for unbiased benchmarking sets to evaluate various ligand-based virtual screening (LBVS) methods for important drug targets such as G protein-coupled receptors (GPCRs). To date these ready-to-apply data sets for LBVS are fairly limited, and the direct usage of benchmarking sets designed for SBVS could bring the biases to the evaluation of LBVS. Herein, we propose an unbiased method to build benchmarking sets for LBVS and validate it on a multitude of GPCRs targets. To be more specific, our methods can (1) ensure chemical diversity of ligands, (2) maintain the physicochemical similarity between ligands and decoys, (3) make the decoys dissimilar in chemical topology to all ligands to avoid false negatives, and (4) maximize spatial random distribution of ligands and decoys. We evaluated the quality of our Unbiased Ligand Set (ULS) and Unbiased Decoy Set (UDS) using three common LBVS approaches, with Leave-One-Out (LOO) Cross-Validation (CV) and a metric of average AUC of the ROC curves. Our method has greatly reduced the "artificial enrichment" and "analogue bias" of a published GPCRs benchmarking set, i.e., GPCR Ligand Library (GLL)/GPCR Decoy Database (GDD). In addition, we addressed an important issue about the ratio of decoys per ligand and found that for a range of 30 to 100 it does not affect the quality of the benchmarking set, so we kept the original ratio of 39 from the GLL/GDD.

A chemical family-based strategy for uncovering hidden bioactive molecules and multicomponent interactions in herbal medicines.

PubMed

Song, Hui-Peng; Wu, Si-Qi; Hao, Haiping; Chen, Jun; Lu, Jun; Xu, Xiaojun; Li, Ping; Yang, Hua

2016-03-30

Two concepts involving natural products were proposed and demonstrated in this paper. (1) Natural product libraries (e.g. herbal extract) are not perfect for bioactivity screening because of the vast complexity of compound compositions, and thus a library reconstruction procedure is necessary before screening. (2) The traditional mode of "screening single compound" could be improved to "screening single compound, drug combination and multicomponent interaction" due to the fact that herbal medicines work by integrative effects of multi-components rather than single effective constituents. Based on the two concepts, we established a novel strategy aiming to make screening easier and deeper. Using thrombin as the model enzyme, we firstly uncovered the minor lead compounds, potential drug combinations and multicomponent interactions in an herbal medicine of Dan-Qi pair, showing a significant advantage over previous methods. This strategy was expected to be a new and promising mode for investigation of herbal medicines.

Storyboard method of end-user programming with natural language configuration

DOEpatents

Bouchard, Ann M; Osbourn, Gordon C

2013-11-19

A technique for end-user programming includes populating a template with graphically illustrated actions and then invoking a command to generate a screen element based on the template. The screen element is rendered within a computing environment and provides a mechanism for triggering execution of a sequence of user actions. The sequence of user actions is based at least in part on the graphically illustrated actions populated into the template.

Rapid review of cognitive screening instruments in MCI: proposal for a process-based approach modification of overlapping tasks in select widely used instruments.

PubMed

Díaz-Orueta, Unai; Blanco-Campal, Alberto; Burke, Teresa

2018-05-01

ABSTRACTBackground:A detailed neuropsychological assessment plays an important role in the diagnostic process of Mild Cognitive Impairment (MCI). However, available brief cognitive screening tests for this clinical population are administered and interpreted based mainly, or exclusively, on total achievement scores. This score-based approach can lead to erroneous clinical interpretations unless we also pay attention to the test taking behavior or to the type of errors committed during test performance. The goal of the current study is to perform a rapid review of the literature regarding cognitive screening tools for dementia in primary and secondary care; this will include revisiting previously published systematic reviews on screening tools for dementia, extensive database search, and analysis of individual references cited in selected studies. A subset of representative screening tools for dementia was identified that covers as many cognitive functions as possible. How these screening tools overlap with each other (in terms of the cognitive domains being measured and the method used to assess them) was examined and a series of process-based approach (PBA) modifications for these overlapping features was proposed, so that the changes recommended in relation to one particular cognitive task could be extrapolated to other screening tools. It is expected that future versions of cognitive screening tests, modified using a PBA, will highlight the benefits of attending to qualitative features of test performance when trying to identify subtle features suggestive of MCI and/or dementia.

Achieving accurate compound concentration in cell-based screening: validation of acoustic droplet ejection technology.

PubMed

Grant, Richard John; Roberts, Karen; Pointon, Carly; Hodgson, Clare; Womersley, Lynsey; Jones, Darren Craig; Tang, Eric

2009-06-01

Compound handling is a fundamental and critical step in compound screening throughout the drug discovery process. Although most compound-handling processes within compound management facilities use 100% DMSO solvent, conventional methods of manual or robotic liquid-handling systems in screening workflows often perform dilutions in aqueous solutions to maintain solvent tolerance of the biological assay. However, the use of aqueous media in these applications can lead to suboptimal data quality due to compound carryover or precipitation during the dilution steps. In cell-based assays, this effect is worsened by the unpredictable physical characteristics of compounds and the low DMSO tolerance within the assay. In some cases, the conventional approaches using manual or automated liquid handling resulted in variable IC(50) dose responses. This study examines the cause of this variability and evaluates the accuracy of screening data in these case studies. A number of liquid-handling options have been explored to address the issues and establish a generic compound-handling workflow to support cell-based screening across our screening functions. The authors discuss the validation of the Labcyte Echo reformatter as an effective noncontact solution for generic compound-handling applications against diverse compound classes using triple-quad liquid chromatography/mass spectrometry. The successful validation and implementation challenges of this technology for direct dosing onto cells in cell-based screening is discussed.

Similarities among receptor pockets and among compounds: analysis and application to in silico ligand screening.

PubMed

Fukunishi, Yoshifumi; Mikami, Yoshiaki; Nakamura, Haruki

2005-09-01

We developed a new method to evaluate the distances and similarities between receptor pockets or chemical compounds based on a multi-receptor versus multi-ligand docking affinity matrix. The receptors were classified by a cluster analysis based on calculations of the distance between receptor pockets. A set of low homologous receptors that bind a similar compound could be classified into one cluster. Based on this line of reasoning, we proposed a new in silico screening method. According to this method, compounds in a database were docked to multiple targets. The new docking score was a slightly modified version of the multiple active site correction (MASC) score. Receptors that were at a set distance from the target receptor were not included in the analysis, and the modified MASC scores were calculated for the selected receptors. The choice of the receptors is important to achieve a good screening result, and our clustering of receptors is useful to this purpose. This method was applied to the analysis of a set of 132 receptors and 132 compounds, and the results demonstrated that this method achieves a high hit ratio, as compared to that of a uniform sampling, using a receptor-ligand docking program, Sievgene, which was newly developed with a good docking performance yielding 50.8% of the reconstructed complexes at a distance of less than 2 A RMSD.

Tox21 Enricher: Web-based Chemical/Biological Functional Annotation Analysis Tool Based on Tox21 Toxicity Screening Platform.

PubMed

Hur, Junguk; Danes, Larson; Hsieh, Jui-Hua; McGregor, Brett; Krout, Dakota; Auerbach, Scott

2018-05-01

The US Toxicology Testing in the 21st Century (Tox21) program was established to develop more efficient and human-relevant toxicity assessment methods. The Tox21 program screens >10,000 chemicals using quantitative high-throughput screening (qHTS) of assays that measure effects on toxicity pathways. To date, more than 70 assays have yielded >12 million concentration-response curves. The patterns of activity across assays can be used to define similarity between chemicals. Assuming chemicals with similar activity profiles have similar toxicological properties, we may infer toxicological properties based on its neighbourhood. One approach to inference is chemical/biological annotation enrichment analysis. Here, we present Tox21 Enricher, a web-based chemical annotation enrichment tool for the Tox21 toxicity screening platform. Tox21 Enricher identifies over-represented chemical/biological annotations among lists of chemicals (neighbourhoods), facilitating the identification of the toxicological properties and mechanisms in the chemical set. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Automated image-based phenotypic analysis in zebrafish embryos

PubMed Central

Vogt, Andreas; Cholewinski, Andrzej; Shen, Xiaoqiang; Nelson, Scott; Lazo, John S.; Tsang, Michael; Hukriede, Neil A.

2009-01-01

Presently, the zebrafish is the only vertebrate model compatible with contemporary paradigms of drug discovery. Zebrafish embryos are amenable to automation necessary for high-throughput chemical screens, and optical transparency makes them potentially suited for image-based screening. However, the lack of tools for automated analysis of complex images presents an obstacle to utilizing the zebrafish as a high-throughput screening model. We have developed an automated system for imaging and analyzing zebrafish embryos in multi-well plates regardless of embryo orientation and without user intervention. Images of fluorescent embryos were acquired on a high-content reader and analyzed using an artificial intelligence-based image analysis method termed Cognition Network Technology (CNT). CNT reliably detected transgenic fluorescent embryos (Tg(fli1:EGFP)y1) arrayed in 96-well plates and quantified intersegmental blood vessel development in embryos treated with small molecule inhibitors of anigiogenesis. The results demonstrate it is feasible to adapt image-based high-content screening methodology to measure complex whole organism phenotypes. PMID:19235725

Health literacy screening instruments for eHealth applications: a systematic review.

PubMed

Collins, Sarah A; Currie, Leanne M; Bakken, Suzanne; Vawdrey, David K; Stone, Patricia W

2012-06-01

To systematically review current health literacy (HL) instruments for use in consumer-facing and mobile health information technology screening and evaluation tools. The databases, PubMed, OVID, Google Scholar, Cochrane Library and Science Citation Index, were searched for health literacy assessment instruments using the terms "health", "literacy", "computer-based," and "psychometrics". All instruments identified by this method were critically appraised according to their reported psychometric properties and clinical feasibility. Eleven different health literacy instruments were found. Screening questions, such as asking a patient about his/her need for assistance in navigating health information, were evaluated in seven different studies and are promising for use as a valid, reliable, and feasible computer-based approach to identify patients that struggle with low health literacy. However, there was a lack of consistency in the types of screening questions proposed. There is also a lack of information regarding the psychometric properties of computer-based health literacy instruments. Only English language health literacy assessment instruments were reviewed and analyzed. Current health literacy screening tools demonstrate varying benefits depending on the context of their use. In many cases, it seems that a single screening question may be a reliable, valid, and feasible means for establishing health literacy. A combination of screening questions that assess health literacy and technological literacy may enable tailoring eHealth applications to user needs. Further research should determine the best screening question(s) and the best synthesis of various instruments' content and methodologies for computer-based health literacy screening and assessment. Copyright © 2012 Elsevier Inc. All rights reserved.

Health Literacy Screening Instruments for eHealth Applications: A Systematic Review

PubMed Central

Collins, Sarah A.; Currie, Leanne M.; Bakken, Suzanne; Vawdrey, David K.; Stone, Patricia W.

2012-01-01

Objective To systematically review current health literacy (HL) instruments for use in consumer-facing and mobile health information technology screening and evaluation tools. Design The databases, PubMed, OVID, Google Scholar, Cochrane Library and Science Citation Index, were searched for health literacy assessment instruments using the terms “health”, “literacy”, “computer-based,” and “psychometrics”. All instruments identified by this method were critically appraised according to their reported psychometric properties and clinical feasibility. Results Eleven different health literacy instruments were found. Screening questions, such as asking a patient about his/her need for assistance in navigating health information, were evaluated in 7 different studies and are promising for use as a valid, reliable, and feasible computer-based approach to identify patients that struggle with low health literacy. However, there was a lack of consistency in the types of screening questions proposed. There is also a lack of information regarding the psychometric properties of computer-based health literacy instruments. Limitations Only English language health literacy assessment instruments were reviewed and analyzed. Conclusions Current health literacy screening tools demonstrate varying benefits depending on the context of their use. In many cases, it seems that a single screening question may be a reliable, valid, and feasible means for establishing health literacy. A combination of screening questions that assess health literacy and technological literacy may enable tailoring eHealth applications to user needs. Further research should determine the best screening question(s) and the best synthesis of various instruments’ content and methodologies for computer-based health literacy screening and assessment. PMID:22521719

Improving Community Health While Satisfying a Critical Community Need: A Case Study for Nonprofit Hospitals

PubMed Central

Kephart, Donna K.; Dillon, Judith F.; McCullough, Jody R.; Blatt, Barbara J.; Kraschnewski, Jennifer L.

2015-01-01

Background School-based student health screenings identify issues that may affect physical and intellectual development and are an important way to maintain student health. Nonprofit hospitals can provide a unique resource to school districts by assisting in the timely completion of school-based screenings and meet requirements of the Affordable Care Act. This case study describes the collaboration between an academic medical center and a local school district to conduct school-based health screenings. Community Context Penn State Milton S. Hershey Medical Center and Penn State Hershey PRO Wellness Center collaborated with Lebanon School District to facilitate student health screenings, a need identified in part by a community health needs assessment. Methods From June 2012 through February 2013, district-wide student health screenings were planned and implemented by teams of hospital nursing leadership, school district leadership, and school nurses. In fall 2013, students were screened through standardized procedures for height, weight, scoliosis, vision, and hearing. Outcomes In 2 days, 3,105 students (67% of all students in the district) were screened. Letters explaining screening results were mailed to parents of all students screened. Debriefing meetings and follow-up surveys for the participating nurses provided feedback for future screenings. Interpretation The 2-day collaborative screening event decreased the amount of time spent by school nurses in screening students throughout the year and allowed them more time in their role as school wellness champion. Additionally, parents found out early in the school year whether their child needed physician follow-up. Partnerships between school districts and hospitals to conduct student health screenings are a practical option for increasing outreach while satisfying community needs. PMID:26513441

Prospective performance evaluation of selected common virtual screening tools. Case study: Cyclooxygenase (COX) 1 and 2.

PubMed

Kaserer, Teresa; Temml, Veronika; Kutil, Zsofia; Vanek, Tomas; Landa, Premysl; Schuster, Daniela

2015-01-01

Computational methods can be applied in drug development for the identification of novel lead candidates, but also for the prediction of pharmacokinetic properties and potential adverse effects, thereby aiding to prioritize and identify the most promising compounds. In principle, several techniques are available for this purpose, however, which one is the most suitable for a specific research objective still requires further investigation. Within this study, the performance of several programs, representing common virtual screening methods, was compared in a prospective manner. First, we selected top-ranked virtual screening hits from the three methods pharmacophore modeling, shape-based modeling, and docking. For comparison, these hits were then additionally predicted by external pharmacophore- and 2D similarity-based bioactivity profiling tools. Subsequently, the biological activities of the selected hits were assessed in vitro, which allowed for evaluating and comparing the prospective performance of the applied tools. Although all methods performed well, considerable differences were observed concerning hit rates, true positive and true negative hits, and hitlist composition. Our results suggest that a rational selection of the applied method represents a powerful strategy to maximize the success of a research project, tightly linked to its aims. We employed cyclooxygenase as application example, however, the focus of this study lied on highlighting the differences in the virtual screening tool performances and not in the identification of novel COX-inhibitors. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Development and testing of monoclonal antibody-based rapid immunodiagnostic test kits for direct detection of Vibrio cholerae O139 synonym Bengal.

PubMed

Hasan, J A; Huq, A; Nair, G B; Garg, S; Mukhopadhyay, A K; Loomis, L; Bernstein, D; Colwell, R R

1995-11-01

We report on the development and testing of two monoclonal antibody-based rapid immunodiagnostic test kits, BengalScreen, a coagglutination test, and Bengal DFA, a direct fluorescent-antibody test, for direct detection of Vibrio cholerae O139 synonym Bengal in clinical and environmental specimens. The BengalScreen test requires less than 5 min to complete and can be used in the field. Bengal DFA, being more sensitive than BengalScreen, requires only one reagent and less than 20 min for detection and enumeration of V. cholerae O139 synonym Bengal. In tests for specificity, all 40 strains of V. cholerae O139 reacted with both test kits, whereas 157 strains of heterologous species examined did not, yielding 100% specificity in this study. A field trial was conducted in with both BengalScreen and Bengal DFA, and the results were compared with those obtained by conventional culture methods. BengalScreen demonstrated a sensitivity of 95%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 94%. Results obtained by Bengal DFA, on the other hand, were 100% sensitive and 100% specific and yielded 100% positive and negative predictive values compared with culture methods. In a second evaluation, 93 stool specimens from Mexico that were negative for V. cholerae O139 by culture were also tested with both the BengalScreen and Bengal DFA kits. None of the 93 specimens were positive for V. cholerae O139 by both tests. A concentration method was optimized for screening of environmental water samples for V. cholerae O139 synonym Bengal with rapid test kits. BengalScreen results were unequivocally positive when water samples contained at least 2.0 x 10(3) CFU/ml, whereas Bengal DFA demonstrated an unequivocally positive reaction when the water sample contained at least 1.5 x 10(2) CFU/ml. When Bengal DFA was compared with conventional culture methods for enumeration of V. cholerae O139 synonym Bengal organisms, no difference was observed.

Effect of transient liquid flow on retention characteristics of screen acquisition systems. [design of Space Shuttle feed system

NASA Technical Reports Server (NTRS)

Cady, E. C.

1977-01-01

A design analysis, is developed based on experimental data, to predict the effects of transient flow and pressure surges (caused either by valve or pump operation, or by boiling of liquids in warm lines) on the retention performance of screen acquisition systems. A survey of screen liquid acquisition system applications was performed to determine appropriate system environment and classification. A screen model was developed which assumed that the screen device was a uniformly distributed composite orthotropic structure, and which accounted for liquid inflow/outflow, gas ingestion quality, screen stress, and liquid spill. A series of 177 tests using 13 specimens (5 screen meshes, 4 screen device construction/backup methods, and 2 orientations) with three test fluids (isopropyl alcohol, Freon 114, and LH2) provided data which verified important features of the screen model and resulted in a design tool which could accurately predict the transient startup performance acquisition devices.

Cervical cancer screening programs in Latin America and the Caribbean.

PubMed

Murillo, Raul; Almonte, Maribel; Pereira, Ana; Ferrer, Elena; Gamboa, Oscar A; Jerónimo, José; Lazcano-Ponce, Eduardo

2008-08-19

Latin America and the Caribbean (LAC) have a significant burden of cervical cancer. Prophylactic human papillomavirus (HPV) vaccines are an opportunity for primary prevention and new screening methods, such as new HPV DNA testing, are promising alternatives to cytology screening that should be analyzed in the context of regional preventive programs. Cytology-based screening programs have not fulfilled their expectations and coverage does not sufficiently explain the lack of impact on screening in LAC. While improved evaluation of screening programs is necessary to increase the impact of screening on the reduction of incidence and mortality, other programmatic aspects will need to be addressed such as follow-up of positive tests and quality control. The implementation of new technologies might enhance screening performance and reduce mortality in the region. The characteristics, performance and impact of cervical cancer screening programs in LAC are reviewed in this article.

AMIGAS: Building a Cervical Cancer Screening Intervention for Public Health Practice

PubMed Central

Smith, Judith Lee; Wilson, Katherine M.; Orians, Carlyn E.; Byrd, Theresa L.

2015-01-01

Background Many barriers to cervical cancer screening for Hispanic women have been documented, but few effective interventions exist. The Community Preventive Services Task Force recommends increasing cervical cancer screening through various methods. Building on this evidence, the Centers for Disease Control and Prevention funded the research and testing phases for an evidence-based and theoretically grounded intervention designed to increase cervical cancer screening among never and rarely screened Hispanic women of Mexican descent. In this article, we describe the development process of the AMIGAS (Ayudando a las Mujeres con Información, Guía, y Amor para su Salud) intervention, highlight the integration of scientific evidence and community-based participatory research principles, and identify opportunities for dissemination, adaptation, and implementation of this intervention. Methods The AMIGAS team was a collaboration among researchers, promotoras (community health workers), and program administrators. The multiyear, multiphase project was conducted in Houston, Texas; El Paso, Texas; and Yakima, Washington. The team completed several rounds of formative research, designed intervention materials and methodology, conducted a randomized controlled trial, created a guide for program administrators, and developed an intervention dissemination plan. Results Trial results demonstrated that AMIGAS was successful in increasing cervical cancer screening among Hispanic women. Adaptation of AMIGAS showed minimal reduction of outcomes. Dissemination efforts are underway to make AMIGAS available in a downloadable format via the Internet. Conclusions Developing a community-based intervention that is evidence-based and theoretically grounded is challenging, time-intensive, and requires collaboration among multiple disciplines. Inclusion of key stakeholders—in particular program deliverers and administrators—and planning for dissemination and translation to practice are integral components of successful intervention design. By providing explicit directions for adaptation for program deliverers, relevant information for program administrators, and access to the intervention via the Internet, AMIGAS is available to help increase cervical cancer screening among Hispanic women and other women disproportionately affected by cervical cancer. PMID:23930983

Docking and scoring in virtual screening for drug discovery: methods and applications.

PubMed

Kitchen, Douglas B; Decornez, Hélène; Furr, John R; Bajorath, Jürgen

2004-11-01

Computational approaches that 'dock' small molecules into the structures of macromolecular targets and 'score' their potential complementarity to binding sites are widely used in hit identification and lead optimization. Indeed, there are now a number of drugs whose development was heavily influenced by or based on structure-based design and screening strategies, such as HIV protease inhibitors. Nevertheless, there remain significant challenges in the application of these approaches, in particular in relation to current scoring schemes. Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches.

Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase.

PubMed

Jordan, John B; Whittington, Douglas A; Bartberger, Michael D; Sickmier, E Allen; Chen, Kui; Cheng, Yuan; Judd, Ted

2016-04-28

Fragment-based drug discovery (FBDD) has become a widely used tool in small-molecule drug discovery efforts. One of the most commonly used biophysical methods in detecting weak binding of fragments is nuclear magnetic resonance (NMR) spectroscopy. In particular, FBDD performed with (19)F NMR-based methods has been shown to provide several advantages over (1)H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of (19)F-based fragment screening by detailing the identification of a second-site fragment through (19)F NMR screening that binds to a specific pocket of the aspartic acid protease, β-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a molecule exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallographic studies of the molecules demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and molecular modeling.

Concentration solar power optimization system and method of using the same

DOEpatents

Andraka, Charles E

2014-03-18

A system and method for optimizing at least one mirror of at least one CSP system is provided. The system has a screen for displaying light patterns for reflection by the mirror, a camera for receiving a reflection of the light patterns from the mirror, and a solar characterization tool. The solar characterization tool has a characterizing unit for determining at least one mirror parameter of the mirror based on an initial position of the camera and the screen, and a refinement unit for refining the determined parameter(s) based on an adjusted position of the camera and screen whereby the mirror is characterized. The system may also be provided with a solar alignment tool for comparing at least one mirror parameter of the mirror to a design geometry whereby an alignment error is defined, and at least one alignment unit for adjusting the mirror to reduce the alignment error.

Results of a Community-Based Randomized Trial to Increase Colorectal Cancer Screening Among Filipino Americans

PubMed Central

Bastani, Roshan; Danao, Leda L.; Antonio, Cynthia; Garcia, Gabriel M.; Crespi, Catherine M.

2010-01-01

Objectives. We conducted 1 of the first community-based trials to develop a multicomponent intervention that would increase colorectal cancer screening among an Asian American population. Methods. Filipino Americans (n = 548) nonadherent to colorectal cancer (CRC) screening guidelines were randomized into an intervention group that received an education session on CRC screening and free fecal occult blood test (FOBT) kits; a second intervention group that received an education session but no free FOBT kits; and a control group that received an education session on the health benefits of physical activity. Results. Self-reported CRC screening rates during the 6-month follow-up period were 30%, 25%, and 9% for participants assigned to intervention with FOBT kit, intervention without the kit, and control group, respectively. Participants in either of the 2 intervention groups were significantly more likely to report screening at follow-up than were participants in the control group. Conclusions. A multicomponent intervention that includes an educational group session in a community setting can significantly increase CRC screening among Filipino Americans, even when no free FOBT kits are distributed. PMID:20864724

SeaWiFS Technical Report Series. Volume 7: Cloud screening for polar orbiting visible and infrared (IR) satellite sensors

NASA Technical Reports Server (NTRS)

Darzi, Michael; Hooker, Stanford B. (Editor); Firestone, Elaine R. (Editor)

1992-01-01

Methods for detecting and screening cloud contamination from satellite derived visible and infrared data are reviewed in this document. The methods are applicable to past, present, and future polar orbiting satellite radiometers. Such instruments include the Coastal Zone Color Scanner (CZCS), operational from 1978 through 1986; the Advanced Very High Resolution Radiometer (AVHRR); the Sea-viewing Wide Field-of-view Sensor (SeaWiFS), scheduled for launch in August 1993; and the Moderate Resolution Imaging Spectrometer (IMODIS). Constant threshold methods are the least demanding computationally, and often provide adequate results. An improvement to these methods are the least demanding computationally, and often provide adequate results. An improvement to these methods is to determine the thresholds dynamically by adjusting them according to the areal and temporal distributions of the surrounding pixels. Spatial coherence methods set thresholds based on the expected spatial variability of the data. Other statistically derived methods and various combinations of basic methods are also reviewed. The complexity of the methods is ultimately limited by the computing resources. Finally, some criteria for evaluating cloud screening methods are discussed.

Impact of endoscopic screening on mortality reduction from gastric cancer

PubMed Central

Hamashima, Chisato; Ogoshi, Kazuei; Narisawa, Rintarou; Kishi, Tomoki; Kato, Toshiyuki; Fujita, Kazutaka; Sano, Masatoshi; Tsukioka, Satoshi

2015-01-01

AIM: To investigate mortality reduction from gastric cancer based on the results of endoscopic screening. METHODS: The study population consisted of participants of gastric cancer screening by endoscopy, regular radiography, and photofluorography at Niigata city in 2005. The observed numbers of cumulative deaths from gastric cancers and other cancers were accumulated by linkage with the Niigata Prefectural Cancer Registry. The standardized mortality ratio (SMR) of gastric cancer and other cancer deaths in each screening group was calculated by applying the mortality rate of the reference population. RESULTS: Based on the results calculated from the mortality rate of the population of Niigata city, the SMRs of gastric cancer death were 0.43 (95%CI: 0.30-0.57) for the endoscopic screening group, 0.68 (95%CI: 0.55-0.79) for the regular radiographic screening group, and 0.85 (95%CI: 0.71-0.94) for the photofluorography screening group. The mortality reduction from gastric cancer was higher in the endoscopic screening group than in the regular radiographic screening group despite the nearly equal mortality rates of all cancers except gastric cancer. CONCLUSION: The 57% mortality reduction from gastric cancer might indicate the effectiveness of endoscopic screening for gastric cancer. Further studies and prudent interpretation of results are needed. PMID:25741155

Plate-based diversity subset screening generation 2: an improved paradigm for high-throughput screening of large compound files.

PubMed

Bell, Andrew S; Bradley, Joseph; Everett, Jeremy R; Loesel, Jens; McLoughlin, David; Mills, James; Peakman, Marie-Claire; Sharp, Robert E; Williams, Christine; Zhu, Hongyao

2016-11-01

High-throughput screening (HTS) is an effective method for lead and probe discovery that is widely used in industry and academia to identify novel chemical matter and to initiate the drug discovery process. However, HTS can be time consuming and costly and the use of subsets as an efficient alternative to screening entire compound collections has been investigated. Subsets may be selected on the basis of chemical diversity, molecular properties, biological activity diversity or biological target focus. Previously, we described a novel form of subset screening: plate-based diversity subset (PBDS) screening, in which the screening subset is constructed by plate selection (rather than individual compound cherry-picking), using algorithms that select for compound quality and chemical diversity on a plate basis. In this paper, we describe a second-generation approach to the construction of an updated subset: PBDS2, using both plate and individual compound selection, that has an improved coverage of the chemical space of the screening file, whilst only selecting the same number of plates for screening. We describe the validation of PBDS2 and its successful use in hit and lead discovery. PBDS2 screening became the default mode of singleton (one compound per well) HTS for lead discovery in Pfizer.

Breast Cancer Screening Programmes across the WHO European Region: Differences among Countries Based on National Income Level.

PubMed

Altobelli, Emma; Rapacchietta, Leonardo; Angeletti, Paolo Matteo; Barbante, Luca; Profeta, Filippo Valerio; Fagnano, Roberto

2017-04-23

Breast cancer (BC) is the most frequent tumour affecting women all over the world. In low- and middle-income countries, where its incidence is expected to rise further, BC seems set to become a public health emergency. The aim of the present study is to provide a systematic review of current BC screening programmes in WHO European Region to identify possible patterns. Multiple correspondence analysis was performed to evaluate the association among: measures of occurrence; GNI level; type of BC screening programme; organization of public information and awareness campaigns regarding primary prevention of modifiable risk factors; type of BC screening services; year of screening institution; screening coverage and data quality. A key difference between High Income (HI) and Low and Middle Income (LMI) States, emerging from the present data, is that in the former screening programmes are well organized, with approved screening centres, the presence of mobile units to increase coverage, the offer of screening tests free of charge; the fairly high quality of occurrence data based on high-quality sources, and the adoption of accurate methods to estimate incidence and mortality. In conclusion, the governments of LMI countries should allocate sufficient resources to increase screening participation and they should improve the accuracy of incidence and mortality rates.

Cost-effectiveness of Population Screening for BRCA Mutations in Ashkenazi Jewish Women Compared With Family History–Based Testing

PubMed Central

Manchanda, Ranjit; Legood, Rosa; Burnell, Matthew; McGuire, Alistair; Raikou, Maria; Loggenberg, Kelly; Wardle, Jane; Sanderson, Saskia; Gessler, Sue; Side, Lucy; Balogun, Nyala; Desai, Rakshit; Kumar, Ajith; Dorkins, Huw; Wallis, Yvonne; Chapman, Cyril; Taylor, Rohan; Jacobs, Chris; Tomlinson, Ian; Beller, Uziel; Menon, Usha

2015-01-01

Background: Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)–based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women. Methods: A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty. Results: Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days’ gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy. Conclusion: Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older. PMID:25435542

Screening and Brief Intervention for Tobacco Use by Student Health Providers on College Campuses

ERIC Educational Resources Information Center

Sutfin, Erin L.; McNamara, Robert S.; Blocker, Jill N.; Ip, Edward H.; O'Brien, Mary Claire; Wolfson, Mark

2012-01-01

Objective: This study assessed college students' reports of tobacco screening and brief intervention by student health center providers. Participants: Participants were 3,800 students from 8 universities in North Carolina. Methods: Web-based survey of a stratified random sample of undergraduates. Results: Fifty-three percent reported ever visiting…

Inconsistencies between alcohol screening results based on AUDIT-C scores and reported drinking on the AUDIT-C questions: prevalence in two US national samples

PubMed Central

2014-01-01

Background The AUDIT-C is an extensively validated screen for unhealthy alcohol use (i.e. drinking above recommended limits or alcohol use disorder), which consists of three questions about alcohol consumption. AUDIT-C scores ≥4 points for men and ≥3 for women are considered positive screens based on US validation studies that compared the AUDIT-C to “gold standard” measures of unhealthy alcohol use from independent, detailed interviews. However, results of screening—positive or negative based on AUDIT-C scores—can be inconsistent with reported drinking on the AUDIT-C questions. For example, individuals can screen positive based on the AUDIT-C score while reporting drinking below US recommended limits on the same AUDIT-C. Alternatively, they can screen negative based on the AUDIT-C score while reporting drinking above US recommended limits. Such inconsistencies could complicate interpretation of screening results, but it is unclear how often they occur in practice. Methods This study used AUDIT-C data from respondents who reported past-year drinking on one of two national US surveys: a general population survey (N = 26,610) and a Veterans Health Administration (VA) outpatient survey (N = 467,416). Gender-stratified analyses estimated the prevalence of AUDIT-C screen results—positive or negative screens based on the AUDIT-C score—that were inconsistent with reported drinking (above or below US recommended limits) on the same AUDIT-C. Results Among men who reported drinking, 13.8% and 21.1% of US general population and VA samples, respectively, had screening results based on AUDIT-C scores (positive or negative) that were inconsistent with reported drinking on the AUDIT-C questions (above or below US recommended limits). Among women who reported drinking, 18.3% and 20.7% of US general population and VA samples, respectively, had screening results that were inconsistent with reported drinking. Limitations This study did not include an independent interview gold standard for unhealthy alcohol use and therefore cannot address how often observed inconsistencies represent false positive or negative screens. Conclusions Up to 21% of people who drink alcohol had alcohol screening results based on the AUDIT-C score that were inconsistent with reported drinking on the same AUDIT-C. This needs to be addressed when training clinicians to use the AUDIT-C. PMID:24468406

Rapid Screening of Ergot Alkaloids in Sclerotia by MALDI-TOF Mass Spectrometry.

PubMed

Sivagnanam, Kumaran; Komatsu, Emy; Patrick, Susan; Rampitsch, Christoph; Perreault, Hélène; Gräfenhan, Tom

2016-07-01

Ergot is a common disease of wheat and other cereal grains that is predominantly caused by Claviceps purpurea in the field, often affecting crop yield in addition to the environment. Infected grain can be contaminated with dark sclerotia, which contain fungal metabolites such as ergot alkaloids. The occurrence of ergot alkaloids in cereal grain is a major health concern for humans and livestock. Effective and rapid screening of these mycotoxins is crucial for producers, processors, and consumers of cereal-based food and feed grain. Established methods of ergot alkaloid screening based on LC-MS or GC-MS require laborious processes. A novel method using matrix-assisted laser desorption ionization (MALDI)-time-of-flight (TOF) MS was developed to identify four ergot alkaloids. Using dihydroxybenzoic acid as the matrix, ergosine, ergocornine, ergocryptine, and ergocristine were readily detected in individual sclerotia of C. purpurea. The accuracy of the identified ergot alkaloids was further confirmed by tandem MS analysis. MALDI-TOF MS is suitable for high-throughput screening of ergot alkaloids because it permits rapid and accurate identification, simple sample preparation, and no derivatization or chromatographic separation.

Fluorescence-based assay as a new screening tool for toxic chemicals

PubMed Central

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-01-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients. PMID:27653274

Fluorescence-based assay as a new screening tool for toxic chemicals.

PubMed

Moczko, Ewa; Mirkes, Evgeny M; Cáceres, César; Gorban, Alexander N; Piletsky, Sergey

2016-09-22

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Fluorescence-based assay as a new screening tool for toxic chemicals

NASA Astrophysics Data System (ADS)

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-09-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Modeling Test and Treatment Strategies for Presymptomatic Alzheimer Disease

PubMed Central

Burke, James F.; Langa, Kenneth M.; Hayward, Rodney A.; Albin, Roger L.

2014-01-01

Objectives In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. Methods Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. Findings In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. Conclusions Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment. PMID:25474698

Sensitivity and specificity of digital retinal imaging for screening diabetic retinopathy.

PubMed

Lopez-Bastida, J; Cabrera-Lopez, F; Serrano-Aguilar, P

2007-04-01

To assess the effectiveness of a non-mydriatic digital camera (45 degrees -30 degrees photographs) compared with the reference method for screening diabetic retinopathy. Type 1 and 2 diabetic patients (n = 773; 1546 eyes) underwent screening for diabetic retinopathy in a prospective observational study. Hospital-based non-mydriatic digital retinal imaging by a consultant specialist in retinal diseases was compared with slit-lamp biomicroscopy and indirect ophthalmoscopy through dilated pupils, as a gold standard, previously performed in a community health centre by another consultant specialist in retinal diseases. The main outcome measures were sensitivity and specificity of screening methods and prevalence of diabetic retinopathy. The prevalence of any form of diabetic retinopathy was 42.4% (n = 328); the prevalence of sight-threatening including macular oedema and proliferative retinopathy was 9.6% (n = 74). Sensitivity of detection of any diabetic retinopathy by digital imaging was 92% (95% confidence interval 90, 94). Specificity of detection of any diabetic retinopathy was 96% (95, 98). The predictive value of the negative tests was 94% and of a positive test 95%. For sight-threatening retinopathy digital imaging had a sensitivity of 100%. A high sensitivity and specificity are essential for an effective screening programme. These results confirm digital retinal imaging with a non-mydriatic camera as an effective option in community-based screening programmes for diabetic retinopathy.

A combined enrichment/polymerase chain reaction based method for the routine screening of Streptococcus agalactiae in pregnant women.

PubMed

Munari, F M; De-Paris, F; Salton, G D; Lora, P S; Giovanella, P; Machado, A B M P; Laybauer, L S; Oliveira, K R P; Ferri, C; Silveira, J L S; Laurino, C C F C; Xavier, R M; Barth, A L; Echeverrigaray, S; Laurino, J P

2012-01-01

Group B Streptococcus (GBS) is the most common cause of life-threatening infection in neonates. Guidelines from CDC recommend universal screening of pregnant women for rectovaginal GBS colonization. The objective of this study was to compare the performance of a combined enrichment/PCR based method targeting the atr gene in relation to culture using enrichment with selective broth medium (standard method) to identify the presence of GBS in pregnant women. Rectovaginal GBS samples from women at ≥36 weeks of pregnancy were obtained with a swab and analyzed by the two methods. A total of 89 samples were evaluated. The prevalence of positive results for GBS detection was considerable higher when assessed by the combined enrichment/PCR method than with the standard method (35.9% versus 22.5%, respectively). The results demonstrated that the use of selective enrichment broth followed by PCR targeting the atr gene is a highly sensitive, specific and accurate test for GBS screening in pregnant women, allowing the detection of the bacteria even in lightly colonized patients. This PCR methodology may provide a useful diagnostic tool for GBS detection and contributes for a more accurate and effective intrapartum antibiotic and lower newborn mortality and morbidity.

COMPARISON OF TAXONOMIC, COLONY MORPHOTYPE AND PCR-RFLP METHODS TO CHARACTERIZE MICROFUNGAL DIVERSITY

EPA Science Inventory

We compared three methods for estimating fungal species diversity in soil samples. A rapid screening method based on gross colony morphological features and color reference standards was compared with traditional fungal taxonomic methods and PCR-RFLP for estimation of ecological ...

Effect of vibration on retention characteristics of screen acquisition systems. [for surface tension propellant acquisition

NASA Technical Reports Server (NTRS)

Tegart, J. R.; Aydelott, J. C.

1978-01-01

The design of surface tension propellant acquisition systems using fine-mesh screen must take into account all factors that influence the liquid pressure differentials within the system. One of those factors is spacecraft vibration. Analytical models to predict the effects of vibration have been developed. A test program to verify the analytical models and to allow a comparative evaluation of the parameters influencing the response to vibration was performed. Screen specimens were tested under conditions simulating the operation of an acquisition system, considering the effects of such parameters as screen orientation and configuration, screen support method, screen mesh, liquid flow and liquid properties. An analytical model, based on empirical coefficients, was most successful in predicting the effects of vibration.

Solvent shift method for anti-precipitant screening of poorly soluble drugs using biorelevant medium and dimethyl sulfoxide.

PubMed

Yamashita, Taro; Ozaki, Shunsuke; Kushida, Ikuo

2011-10-31

96-well plate based anti-precipitant screening using bio-relevant medium FaSSIF (fasted-state simulated small intestinal fluid) is a useful technique for discovering anti-precipitants that maintain supersaturation of poorly soluble drugs. In a previous report, two disadvantages of the solvent evaporation method (solvent casting method) were mentioned: precipitation during the evaporation process and the use of volatile solvents to dissolve compounds. In this report, we propose a solvent shift method using DMSO (dimethyl sulfoxide). Initially, the drug substance was dissolved in DMSO at a high concentration and diluted with FaSSIF that contained anti-precipitants. To evaluate the validity of the method, itraconazole (ITZ) was used as the poorly soluble model drug. The solvent shift method resolved the disadvantages of the evaporation method, and AQOAT (HPMC-AS) was found as the most appropriate anti-precipitant for ITZ in a facile and expeditious manner when compared with the solvent evaporation method. In the large scale JP paddle method, AQOAT-based solid dispersion maintained a higher concentration than Tc-5Ew (HPMC)-based formulation; this result corresponded well with the small scale of the solvent shift method. Copyright © 2011 Elsevier B.V. All rights reserved.

Towards novel therapeutics for HIV through fragment-based screening and drug design.

PubMed

Tiefendbrunn, Theresa; Stout, C David

2014-01-01

Fragment-based drug discovery has been applied with varying levels of success to a number of proteins involved in the HIV (Human Immunodeficiency Virus) life cycle. Fragment-based approaches have led to the discovery of novel binding sites within protease, reverse transcriptase, integrase, and gp41. Novel compounds that bind to known pockets within CCR5 have also been identified via fragment screening, and a fragment-based approach to target the TAR-Tat interaction was explored. In the context of HIV-1 reverse transcriptase (RT), fragment-based approaches have yielded fragment hits with mid-μM activity in an in vitro activity assay, as well as fragment hits that are active against drug-resistant variants of RT. Fragment-based drug discovery is a powerful method to elucidate novel binding sites within proteins, and the method has had significant success in the context of HIV proteins.

Automatic classification of transiently evoked otoacoustic emissions using an artificial neural network.

PubMed

Buller, G; Lutman, M E

1998-08-01

The increasing use of transiently evoked otoacoustic emissions (TEOAE) in large neonatal hearing screening programmes makes a standardized method of response classification desirable. Until now methods have been either subjective or based on arbitrary response characteristics. This study takes an expert system approach to standardize the subjective judgements of an experienced scorer. The method that is developed comprises three stages. First, it transforms TEOAEs from waveforms in the time domain into a simplified parameter set. Second, the parameter set is classified by an artificial neural network that has been taught on a large database TEOAE waveforms and corresponding expert scores. Third, additional fuzzy logic rules automatically detect probable artefacts in the waveforms and synchronized spontaneous emission components. In this way, the knowledge of the experienced scorer is encapsulated in the expert system software and thereafter can be accessed by non-experts. Teaching and evaluation of the neural network was based on TEOAEs from a database totalling 2190 neonatal hearing screening tests. The database was divided into learning and test groups with 820 and 1370 waveforms respectively. From each recorded waveform a set of 12 parameters was calculated, representing signal static and dynamic properties. The artifical network was taught with parameter sets of only the learning groups. Reproduction of the human scorer classification by the neural net in the learning group showed a sensitivity for detecting screen fails of 99.3% (299 from 301 failed results on subjective scoring) and a specificity for detecting screen passes of 81.1% (421 of 519 pass results). To quantify the post hoc performance of the net (generalization), the test group was then presented to the network input. Sensitivity was 99.4% (474 from 477) and specificity was 87.3% (780 from 893). To check the efficiency of the classification method, a second learning group was selected out of the previous test group, and the previous learning group was used as the test group. Repeating learning and test procedures yielded 99.3% sensitivity and 80.7% specificity for reproduction, and 99.4% sensitivity and 86.7% specificity for generalization. In all respects, performance was better than for a previously optimized method based simply on cross-correlation between replicate non-linear waveforms. It is concluded that classification methods based on neural networks show promise for application to large neonatal screening programmes utilizing TEOAEs.

Quantification and clustering of phenotypic screening data using time-series analysis for chemotherapy of schistosomiasis

PubMed Central

2012-01-01

Background Neglected tropical diseases, especially those caused by helminths, constitute some of the most common infections of the world's poorest people. Development of techniques for automated, high-throughput drug screening against these diseases, especially in whole-organism settings, constitutes one of the great challenges of modern drug discovery. Method We present a method for enabling high-throughput phenotypic drug screening against diseases caused by helminths with a focus on schistosomiasis. The proposed method allows for a quantitative analysis of the systemic impact of a drug molecule on the pathogen as exhibited by the complex continuum of its phenotypic responses. This method consists of two key parts: first, biological image analysis is employed to automatically monitor and quantify shape-, appearance-, and motion-based phenotypes of the parasites. Next, we represent these phenotypes as time-series and show how to compare, cluster, and quantitatively reason about them using techniques of time-series analysis. Results We present results on a number of algorithmic issues pertinent to the time-series representation of phenotypes. These include results on appropriate representation of phenotypic time-series, analysis of different time-series similarity measures for comparing phenotypic responses over time, and techniques for clustering such responses by similarity. Finally, we show how these algorithmic techniques can be used for quantifying the complex continuum of phenotypic responses of parasites. An important corollary is the ability of our method to recognize and rigorously group parasites based on the variability of their phenotypic response to different drugs. Conclusions The methods and results presented in this paper enable automatic and quantitative scoring of high-throughput phenotypic screens focused on helmintic diseases. Furthermore, these methods allow us to analyze and stratify parasites based on their phenotypic response to drugs. Together, these advancements represent a significant breakthrough for the process of drug discovery against schistosomiasis in particular and can be extended to other helmintic diseases which together afflict a large part of humankind. PMID:22369037

Evidence-based Guidelines for Precision Risk Stratification-Based Screening (PRSBS) for Colorectal Cancer: Lessons learned from the US Armed Forces: Consensus and Future Directions

PubMed Central

Avital, Itzhak; Langan, Russell C.; Summers, Thomas A.; Steele, Scott R.; Waldman, Scott A.; Backman, Vadim; Yee, Judy; Nissan, Aviram; Young, Patrick; Womeldorph, Craig; Mancusco, Paul; Mueller, Renee; Noto, Khristian; Grundfest, Warren; Bilchik, Anton J.; Protic, Mladjan; Daumer, Martin; Eberhardt, John; Man, Yan Gao; Brücher, Björn LDM; Stojadinovic, Alexander

2013-01-01

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U.S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however, these numerical estimates of incidence and disease-specific mortality have remained stable from years prior. Technological, genetic profiling, molecular and surgical advances in our modern era should allow us to improve risk stratification of patients with CRC and identify those who may benefit from preventive measures, early aggressive treatment, alternative treatment strategies, and/or frequent surveillance for the early detection of disease recurrence. To better negotiate future economic constraints and enhance patient outcomes, ultimately, we propose to apply the principals of personalized and precise cancer care to risk-stratify patients for CRC screening (Precision Risk Stratification-Based Screening, PRSBS). We believe that genetic, molecular, ethnic and socioeconomic disparities impact oncological outcomes in general, those related to CRC, in particular. This document highlights evidence-based screening recommendations and risk stratification methods in response to our CRC working group private-public consensus meeting held in March 2012. Our aim was to address how we could improve CRC risk stratification-based screening, and to provide a vision for the future to achieving superior survival rates for patients diagnosed with CRC. PMID:23459409

Performance of prenatal screening using maternal serum and ultrasound markers for Down syndrome in Chinese women: a systematic review and meta-analysis.

PubMed

Tu, S; Rosenthal, M; Wang, D; Huang, J; Chen, Y

2016-09-01

Controversies about the performance of conventional prenatal screening using maternal serum and ultrasound markers (PSMSUM) in detecting Down syndrome (DS) have been raised as a result of a recently available noninvasive prenatal test based on cell-free fetal DNA sequencing. To evaluate the screening performance of PSMSUM in detecting DS in Chinese women. An exhaustive literature search of MEDLINE, Embase, the Cochrane Library, ISI Web of Science and China BioMedical Disc. Primary studies, published from January 2004 to November 2014, which examined the screening accuracy of PSMSUM in pregnant Chinese women, compared with a reference standard, either chromosomal verification or inspection of the newborn. Data were extracted as screening positive/negative results for Down and non-Down syndrome pregnancies, allowing estimation of sensitivities and specificities. Risks of bias within and across studies were assessed. Screening accuracy measures were pooled using a bivariate random effects regression model. Seventy-eight studies, involving six categories of PSMSUM, were included. Second-trimester double serum [pooled sensitivity (SEN) = 0.80, pooled specificity (SPE) = 0.95] and triple-serum (pooled SEN = 0.79, pooled SPE = 0.96) screening were the predominant PSMSUM methods. The screening performances of these methods achieved the national standard but varied enormously across studies. First-trimester combined screening (pooled SEN = 0.92, pooled SPE = 0.93) and second-trimester quadruple serum screening (median SEN = 0.86, median SPE = 0.96) performed better, but were rarely used. Second-trimester maternal serum screening has the potential to achieve satisfactory screening performance in middle- and low-income countries. The reported enormous range in screening performance of second-trimester PSMSUM calls for urgent implementation of methods for performance optimization. Meta-analysis results show good accuracy of maternal serum and ultrasound screening for trisomy 21 in Chinese women. © 2016 Royal College of Obstetricians and Gynaecologists.

Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer screening in asymptomatic individuals.

PubMed

Holme, Øyvind; Bretthauer, Michael; Fretheim, Atle; Odgaard-Jensen, Jan; Hoff, Geir

2013-10-01

Colorectal cancer is the third most frequent cancer in the world. As the sojourn time for this cancer is several years and a good prognosis is associated with early stage diagnosis, screening has been implemented in a number of countries. Both screening with faecal occult blood test and flexible sigmoidoscopy have been shown to reduce mortality from colorectal cancer in randomised controlled trials. The comparative effectiveness of these tests on colorectal cancer mortality has, however, never been evaluated, and controversies exist over which test to choose. To compare the effectiveness of screening for colorectal cancer with flexible sigmoidoscopy to faecal occult blood testing. We searched MEDLINE and EMBASE (November 16, 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11) and reference lists for eligible studies. Randomised controlled trials comparing screening with flexible sigmoidoscopy or faecal occult blood testing to each other or to no screening. Only studies reporting mortality from colorectal cancer were included. Faecal occult blood testing had to be repeated (annually or biennially). Data retrieval and assessment of risk of bias were performed independently by two review authors. Standard meta-analyses using a random-effects model were conducted for flexible sigmoidoscopy and faecal occult blood testing (FOBT) separately and we calculated relative risks with 95% confidence intervals (CI). We used a Bayesian approach (a contrast-based network meta-analysis method) for indirect analyses and presented the results as posterior median relative risk with 95% credibility intervals. We assessed the quality of evidence using GRADE. We identified nine studies comprising 338,467 individuals randomised to screening and 405,919 individuals to the control groups. Five studies compared flexible sigmoidoscopy to no screening and four studies compared repetitive guaiac-based FOBT (annually and biennially) to no screening. We did not consider that study risk of bias reduced our confidence in our results. We did not identify any studies comparing the two screening methods directly. When compared with no screening, colorectal cancer mortality was lower with flexible sigmoidoscopy (relative risk 0.72; 95% CI 0.65 to 0.79, high quality evidence) and FOBT (relative risk 0.86; 95% CI 0.80 to 0.92, high quality evidence). In the analyses based on indirect comparison of the two screening methods, the relative risk of dying from colorectal cancer was 0.85 (95% credibility interval 0.72 to 1.01, low quality evidence) for flexible sigmoidoscopy screening compared to FOBT. No complications occurred after the FOBT test itself, but 0.03% of participants suffered a major complication after follow-up. Among more than 60,000 flexible sigmoidoscopy screening procedures and almost 6000 work-up colonoscopies, a major complication was recorded in 0.08% of participants. Adverse event data should be interpreted with caution as the reporting of adverse effects was incomplete. There is high quality evidence that both flexible sigmoidoscopy and faecal occult blood testing reduce colorectal cancer mortality when applied as screening tools. There is low quality indirect evidence that screening with either approach reduces colorectal cancer deaths more than the other. Major complications associated with screening require validation from studies with more complete reporting of harms

Sense and sensibility: the use of cell death biomarker assays in high-throughput anticancer drug screening and monitoring treatment responses.

PubMed

Shoshan, Maria C; Havelka, Associate Professor Principal Investigator Aleksandra Mandic; Neumann, Frank; Linder, Stig

2006-11-01

Cell-based screening allows identification of biologically active compounds, for example, potential anticancer drugs. In this review, various screening assays are discussed in terms of what they measure and how this affects interpretation and relevance. High-throughput (HT) assays of viability based on the reduction of exogenous substrates do not always reflect viability or cell number levels. Membrane integrity assays can be used for HT quantification of cell death, but are non-specific as to the death mode. Several HT assays monitor end point apoptosis. Screening libraries at a single concentration (micromolar) can prevent detection of potent apoptosis inducers, as high concentrations may induce mainly necrosis. Using monolayer cultures limits the significance of cell-based screening as the properties of monolayer cells differ from tumours in vivo. Spheroid cultures are more physiological, but are impractical for screening by conventional methods. The authors have developed an assay quantifying accumulation of a caspase-cleaved protein specific for epithelial cells. It provides an integrated measure of apoptosis in two- and three-dimensional cultures and can be used as a blood biomarker assay for tumour apoptosis in vivo.

A method to identify differential expression profiles of time-course gene data with Fourier transformation.

PubMed

Kim, Jaehee; Ogden, Robert Todd; Kim, Haseong

2013-10-18

Time course gene expression experiments are an increasingly popular method for exploring biological processes. Temporal gene expression profiles provide an important characterization of gene function, as biological systems are both developmental and dynamic. With such data it is possible to study gene expression changes over time and thereby to detect differential genes. Much of the early work on analyzing time series expression data relied on methods developed originally for static data and thus there is a need for improved methodology. Since time series expression is a temporal process, its unique features such as autocorrelation between successive points should be incorporated into the analysis. This work aims to identify genes that show different gene expression profiles across time. We propose a statistical procedure to discover gene groups with similar profiles using a nonparametric representation that accounts for the autocorrelation in the data. In particular, we first represent each profile in terms of a Fourier basis, and then we screen out genes that are not differentially expressed based on the Fourier coefficients. Finally, we cluster the remaining gene profiles using a model-based approach in the Fourier domain. We evaluate the screening results in terms of sensitivity, specificity, FDR and FNR, compare with the Gaussian process regression screening in a simulation study and illustrate the results by application to yeast cell-cycle microarray expression data with alpha-factor synchronization.The key elements of the proposed methodology: (i) representation of gene profiles in the Fourier domain; (ii) automatic screening of genes based on the Fourier coefficients and taking into account autocorrelation in the data, while controlling the false discovery rate (FDR); (iii) model-based clustering of the remaining gene profiles. Using this method, we identified a set of cell-cycle-regulated time-course yeast genes. The proposed method is general and can be potentially used to identify genes which have the same patterns or biological processes, and help facing the present and forthcoming challenges of data analysis in functional genomics.

Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.

PubMed

Kobayashi, Masakazu; Retra, Kim; Figaroa, Francis; Hollander, Johan G; Ab, Eiso; Heetebrij, Robert J; Irth, Hubertus; Siegal, Gregg

2010-09-01

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ligands with affinity weaker than 1 mM K(D) is limited. Similarly, they find that SPR detection is most suited to ligands that bind with K(D) better than 1 mM. However, the good correlation between SPR and potency in a bioassay makes this a good method for hit validation and characterization studies.

Colorectal Cancer Control Program Grantees’ Use of Evidence-Based Interventions

PubMed Central

Hannon, Peggy A.; Maxwell, Annette E.; Escoffery, Cam; Vu, Thuy; Kohn, Marlana; Leeman, Jennifer; Carvalho, Michelle L.; Pfeiffer, Debbie J.; Dwyer, Andrea; Fernandez, Maria E.; Vernon, Sally W.; Liang, Lily; DeGroff, Amy

2015-01-01

Background Colorectal cancer (CRC) screening is recommended for adults aged 50–75 years, yet screening rates are low, especially among the uninsured. The CDC initiated the Colorectal Cancer Control Program (CRCCP) in 2009 with the goal of increasing CRC screening rates to 80% by 2014. A total of 29 grantees (states and tribal organizations) receive CRCCP funding to (1) screen uninsured adults and (2) promote CRC screening at the population level. Purpose CRCCP encourages grantees to use one or more of five evidence-based interventions (EBIs) recommended by the Guide to Community Preventive Services. The purpose of the study was to evaluate grantees’ EBI use. Methods A web-based survey was conducted in 2011 measuring grantees’ use of CRC screening EBIs and identifying their implementation partners. Data were analyzed in 2012. Results Twenty-eight grantees (97%) completed the survey. Most respondents (96%) used small media. Fewer used client reminders (75%); reduction of structural barriers (50%); provider reminders (32%); or provider assessment and feedback (50%). Provider-oriented EBIs were rated as harder to implement than client-oriented EBIs. Grantees partnered with several types of organizations to implement EBIs, many with county- or state-wide reach. Conclusions Almost all grantees implement EBIs to promote CRC screening, but the EBIs that may have the greatest impact with CRC screening are implemented by fewer grantees in the first 2 years of the CRCCP. PMID:24139779

Global sensitivity analysis for urban water quality modelling: Terminology, convergence and comparison of different methods

NASA Astrophysics Data System (ADS)

Vanrolleghem, Peter A.; Mannina, Giorgio; Cosenza, Alida; Neumann, Marc B.

2015-03-01

Sensitivity analysis represents an important step in improving the understanding and use of environmental models. Indeed, by means of global sensitivity analysis (GSA), modellers may identify both important (factor prioritisation) and non-influential (factor fixing) model factors. No general rule has yet been defined for verifying the convergence of the GSA methods. In order to fill this gap this paper presents a convergence analysis of three widely used GSA methods (SRC, Extended FAST and Morris screening) for an urban drainage stormwater quality-quantity model. After the convergence was achieved the results of each method were compared. In particular, a discussion on peculiarities, applicability, and reliability of the three methods is presented. Moreover, a graphical Venn diagram based classification scheme and a precise terminology for better identifying important, interacting and non-influential factors for each method is proposed. In terms of convergence, it was shown that sensitivity indices related to factors of the quantity model achieve convergence faster. Results for the Morris screening method deviated considerably from the other methods. Factors related to the quality model require a much higher number of simulations than the number suggested in literature for achieving convergence with this method. In fact, the results have shown that the term "screening" is improperly used as the method may exclude important factors from further analysis. Moreover, for the presented application the convergence analysis shows more stable sensitivity coefficients for the Extended-FAST method compared to SRC and Morris screening. Substantial agreement in terms of factor fixing was found between the Morris screening and Extended FAST methods. In general, the water quality related factors exhibited more important interactions than factors related to water quantity. Furthermore, in contrast to water quantity model outputs, water quality model outputs were found to be characterised by high non-linearity.

Screen-viewing among preschoolers in childcare: a systematic review.

PubMed

Vanderloo, Leigh M

2014-08-16

Screen-viewing is one of the most common sedentary behaviors among preschoolers. Despite the high prevalence of sedentary behaviors in childcare, little research exists on the context and/or type of activities that account for these particular behaviors. Accordingly, if the amount of screen-viewing accumulated by preschoolers in childcare is not considered, researchers may be underestimating total screen time among this population, as only a portion of their day is being captured (i.e., the home environment). This systematic review provides a synthesis of research on the levels of screen-viewing among preschool-aged children (2.5-5 years) attending childcare (i.e., centre- and home-based childcare). This review also examined the correlates of screen-viewing among preschoolers in this setting. To provide additional contextual information, availability of screen activities was used to help ameliorate the understanding of preschoolers' screen-viewing behaviors in childcare. Twelve electronic databases were searched to retrieve relevant articles for inclusion (dating from 2000 onwards). Additional studies were identified via manual searching techniques (i.e., hand searching and citation tracking). Only English, published peer-reviewed articles that examined preschoolers' screen-viewing behaviors in childcare (i.e., rates of screen-viewing and access to/opportunities for related activities) were included. No restrictions to study design were applied. Seventeen international studies (4 experimental; 12 cross-sectional; 1 mixed-methods) published between 2004 and 2014 were examined. Of those, eight studies reported rates of screen-viewing and found that preschoolers spent approximately 0.1 to 1.3 hrs/day and 1.8 to 2.4 hrs/day engaged in this behavior in center- and home-based childcare, respectively. High staff education (negative association) and type of childcare arrangement (notably, home-based childcare in comparison to center-based childcare; positive association) were identified as two correlates in relation to preschoolers' screen-viewing in childcare. Nine studies spoke to the availability of screen-viewing activities in childcare, and found the childcare environment to be conducive to this behavior. Despite some variability, preschoolers appear to engage in somewhat high levels of screen-viewing while in childcare, particularly within home-based facilities. This paper also highlighted the conduciveness of the childcare environment with regard to screen-viewing among preschoolers. Additional exploration into the correlates of screen-viewing in childcare is required. (PROSPORO registration: CRD42013005552).

A New Versatile Microarray-based Method for High Throughput Screening of Carbohydrate-active Enzymes*

PubMed Central

Vidal-Melgosa, Silvia; Pedersen, Henriette L.; Schückel, Julia; Arnal, Grégory; Dumon, Claire; Amby, Daniel B.; Monrad, Rune Nygaard; Westereng, Bjørge; Willats, William G. T.

2015-01-01

Carbohydrate-active enzymes have multiple biological roles and industrial applications. Advances in genome and transcriptome sequencing together with associated bioinformatics tools have identified vast numbers of putative carbohydrate-degrading and -modifying enzymes including glycoside hydrolases and lytic polysaccharide monooxygenases. However, there is a paucity of methods for rapidly screening the activities of these enzymes. By combining the multiplexing capacity of carbohydrate microarrays with the specificity of molecular probes, we have developed a sensitive, high throughput, and versatile semiquantitative enzyme screening technique that requires low amounts of enzyme and substrate. The method can be used to assess the activities of single enzymes, enzyme mixtures, and crude culture broths against single substrates, substrate mixtures, and biomass samples. Moreover, we show that the technique can be used to analyze both endo-acting and exo-acting glycoside hydrolases, polysaccharide lyases, carbohydrate esterases, and lytic polysaccharide monooxygenases. We demonstrate the potential of the technique by identifying the substrate specificities of purified uncharacterized enzymes and by screening enzyme activities from fungal culture broths. PMID:25657012

Quantitative assessment of smoking-induced emphysema progression in longitudinal CT screening for lung cancer

NASA Astrophysics Data System (ADS)

Suzuki, H.; Mizuguchi, R.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

2015-03-01

Computed tomography has been used for assessing structural abnormalities associated with emphysema. It is important to develop a robust CT based imaging biomarker that would allow quantification of emphysema progression in early stage. This paper presents effect of smoking on emphysema progression using annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in longitudinal screening for lung cancer. The percentage of LAV (LAV%) was measured after applying CT value threshold method and small noise reduction. Progression of emphysema was assessed by statistical analysis of the annual changes represented by linear regression of LAV%. This method was applied to 215 participants in lung cancer CT screening for five years (18 nonsmokers, 85 past smokers, and 112 current smokers). The results showed that LAV% is useful to classify current smokers with rapid progression of emphysema (0.2%/year, p<0.05). This paper demonstrates effectiveness of the proposed method in diagnosis and prognosis of early emphysema in CT screening for lung cancer.

Comparison of methods for in-house screening of HLA-B*57:01 to prevent abacavir hypersensitivity in HIV-1 care.

PubMed

De Spiegelaere, Ward; Philippé, Jan; Vervisch, Karen; Verhofstede, Chris; Malatinkova, Eva; Kiselinova, Maja; Trypsteen, Wim; Bonczkowski, Pawel; Vogelaers, Dirk; Callens, Steven; Ruelle, Jean; Kabeya, Kabamba; De Wit, Stephane; Van Acker, Petra; Van Sandt, Vicky; Emonds, Marie-Paule; Coucke, Paul; Sermijn, Erica; Vandekerckhove, Linos

2015-01-01

Abacavir is a nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy in HIV-1-infected patients. Because this drug can cause a hypersensitivity reaction that is correlated with the presence of the HLA-B*57:01 allotype, screening for the presence of HLA-B*57:01 is recommended before abacavir initiation. Different genetic assays have been developed for HLA-B*57:01 screening, each with specific sensitivity, turnaround time and assay costs. Here, a new real-time PCR (qPCR) based analysis is described and compared to sequence specific primer PCR with capillary electrophoresis (SSP PCR CE) on 149 patient-derived samples, using sequence specific oligonucleotide hybridization combined with high resolution SSP PCR as gold standard. In addition to these PCR based methods, a complementary approach was developed using flow cytometry with an HLA-B17 specific monoclonal antibody as a pre-screening assay to diminish the number of samples for genetic testing. All three assays had a maximum sensitivity of >99. However, differences in specificity were recorded, i.e. 84.3%, 97.2% and >99% for flow cytometry, qPCR and SSP PCR CE respectively. Our data indicate that the most specific and sensitive of the compared methods is the SSP PCR CE. Flow cytometry pre-screening can substantially decrease the number of genetic tests for HLA-B*57:01 typing in a clinical setting.

Development and Validation of a P-35S, T-nos, T-35S and P-FMV Tetraplex Real-time PCR Screening Method to Detect Regulatory Genes of Genetically Modified Organisms in Food.

PubMed

Eugster, Albert; Murmann, Petra; Kaenzig, Andre; Breitenmoser, Alda

2014-10-01

In routine analysis screening methods based on real-time PCR (polymerase chain reaction) are most commonly used for the detection of genetically modified (GM) plant material in food and feed. Screening tests are based on sequences frequently used for GM development, allowing the detection of a large number of GMOs (genetically modified organisms). Here, we describe the development and validation of a tetraplex real-time PCR screening assay comprising detection systems for the regulatory genes Cauliflower Mosaic Virus 35S promoter, Agrobacterium tumefaciens nos terminator, Cauliflower Mosaic Virus 35S terminator and Figwort Mosaic Virus 34S promoter. Three of the four primer and probe combinations have already been published elsewhere, whereas primers and probe for the 35S terminator have been developed in-house. Adjustment of primer and probe concentrations revealed a high PCR sensitivity with insignificant physical cross-talk between the four detection channels. The sensitivity of each PCR-system is sufficient to detect a GMO concentration as low as 0.05% of the containing respective element. The specificity of the described tetraplex is high when tested on DNA from GM maize, soy, rapeseed and tomato. We also demonstrate the robustness of the system by inter-laboratory tests. In conclusion, this method provides a sensitive and reliable screening procedure for the detection of the most frequently used regulatory elements present in GM crops either authorised or unauthorised for food.

Depression screening among older adults attending low-vision rehabilitation and eye-care services: Characteristics of those who screen positive and client acceptability of screening.

PubMed

Holloway, Edith E; Sturrock, Bonnie A; Lamoureux, Ecosse L; Keeffe, Jill E; Rees, Gwyneth

2015-12-01

To investigate characteristics associated with screening positive for depressive symptoms among older adults accessing low-vision rehabilitation and eye-care services and to determine client acceptability of depression screening using the Patient Health Questionnaire-2 (PHQ-2) in these settings. One-hundred and twenty-four older adults (mean = 77.02 years, SD = 9.12) attending low-vision rehabilitation and eye-care services across Australia were screened for depression and invited to complete a telephone-administered questionnaire to determine characteristics associated with depressive symptoms and client acceptability of screening in these settings. Thirty-seven per cent (n = 46/124) of participants screened positive for depressive symptoms, and the majority considered the new depression screening method to be a 'good idea' in vision services (85%). Severe vision loss (<6/60 in the better eye) was associated with an increased odds of screening positive for depressive symptoms (odds ratio 2.37; 95% confidence interval 1.08-6.70) even after adjusting for potential confounders. Participants who screened positive had a preference for 'talking' therapy or a combination of medication and 'talking therapy' delivered within their own home (73%) or via telephone (67%). The PHQ-2 appears to be an acceptable method for depression screening in eye-care settings among older adults. Targeted interventions that incorporate home-based or telephone delivered therapy sessions may improve outcomes for depression in this group. © 2014 ACOTA.

Polyglutamine Disease Modeling: Epitope Based Screen for Homologous Recombination using CRISPR/Cas9 System.

PubMed

An, Mahru C; O'Brien, Robert N; Zhang, Ningzhe; Patra, Biranchi N; De La Cruz, Michael; Ray, Animesh; Ellerby, Lisa M

2014-04-15

We have previously reported the genetic correction of Huntington's disease (HD) patient-derived induced pluripotent stem cells using traditional homologous recombination (HR) approaches. To extend this work, we have adopted a CRISPR-based genome editing approach to improve the efficiency of recombination in order to generate allelic isogenic HD models in human cells. Incorporation of a rapid antibody-based screening approach to measure recombination provides a powerful method to determine relative efficiency of genome editing for modeling polyglutamine diseases or understanding factors that modulate CRISPR/Cas9 HR.

Mass spectrometric screening of ligands with lower off-rate from a clicked-based pooled library.

PubMed

Arai, Satoshi; Hirosawa, Shota; Oguchi, Yusuke; Suzuki, Madoka; Murata, Atsushi; Ishiwata, Shin'ichi; Takeoka, Shinji

2012-08-13

This paper describes a convenient screening method using ion trap electrospray ionization mass spectrometry to classify ligands to a target molecule in terms of kinetic parameters. We demonstrate this method in the screening of ligands to a hexahistidine tag from a pooled library synthesized by click chemistry. The ion trap mass spectrometry analysis revealed that higher stabilities of ligand-target complexes in the gas phase were related to lower dissociation rate constants, i.e., off-rates in solution. Finally, we prepared a fluorescent probe utilizing the ligand with lowest off-rate and succeeded in performing single molecule observations of hexahistidine-tagged myosin V walking on actin filaments.

Identifying Novel Molecular Structures for Advanced Melanoma by Ligand-Based Virtual Screening

PubMed Central

Wang, Zhao; Lu, Yan; Seibel, William; Miller, Duane D.; Li, Wei

2009-01-01

We recently discovered a new class of thiazole analogs that are highly potent against melanoma cells. To expand the structure-activity relationship study and to explore potential new molecular scaffolds, we performed extensive ligand-based virtual screening against a compound library containing 342,910 small molecules. Two different approaches of virtual screening were carried out using the structure of our lead molecule: 1) connectivity-based search using Scitegic Pipeline Pilot from Accelerys and 2) molecular shape similarity search using Schrodinger software. Using a testing compound library, both approaches can rank similar compounds very high and rank dissimilar compounds very low, thus validating our screening methods. Structures identified from these searches were analyzed, and selected compounds were tested in vitro to assess their activity against melanoma cancer cell lines. Several molecules showed good anticancer activity. While none of the identified compounds showed better activity than our lead compound, they provided important insight into structural modifications for our lead compound and also provided novel platforms on which we can optimize new classes of anticancer compounds. One of the newly synthesized analogs based on this virtual screening has improved potency and selectivity against melanoma. PMID:19445498

Enzymatically Generated CRISPR Libraries for Genome Labeling and Screening

PubMed Central

Lane, Andrew B.; Strzelecka, Magdalena; Ettinger, Andreas; Grenfell, Andrew W.; Wittmann, Torsten; Heald, Rebecca

2015-01-01

Summary CRISPR-based technologies have emerged as powerful tools to alter genomes and mark chromosomal loci, but an inexpensive method for generating large numbers of RNA guides for whole genome screening and labeling is lacking. Using a method that permits library construction from any source of DNA, we generated guide libraries that label repetitive loci or a single chromosomal locus in Xenopus egg extracts and show that a complex library can target the E. coli genome at high frequency. PMID:26212133

Statistical studies of animal response data from USF toxicity screening test method

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Machado, A. M.

1978-01-01

Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

Evaluating the Predictivity of Virtual Screening for Abl Kinase Inhibitors to Hinder Drug Resistance

PubMed Central

Gani, Osman A B S M; Narayanan, Dilip; Engh, Richard A

2013-01-01

Virtual screening methods are now widely used in early stages of drug discovery, aiming to rank potential inhibitors. However, any practical ligand set (of active or inactive compounds) chosen for deriving new virtual screening approaches cannot fully represent all relevant chemical space for potential new compounds. In this study, we have taken a retrospective approach to evaluate virtual screening methods for the leukemia target kinase ABL1 and its drug-resistant mutant ABL1-T315I. ‘Dual active’ inhibitors against both targets were grouped together with inactive ligands chosen from different decoy sets and tested with virtual screening approaches with and without explicit use of target structures (docking). We show how various scoring functions and choice of inactive ligand sets influence overall and early enrichment of the libraries. Although ligand-based methods, for example principal component analyses of chemical properties, can distinguish some decoy sets from active compounds, the addition of target structural information via docking improves enrichment, and explicit consideration of multiple target conformations (i.e. types I and II) achieves best enrichment of active versus inactive ligands, even without assuming knowledge of the binding mode. We believe that this study can be extended to other therapeutically important kinases in prospective virtual screening studies. PMID:23746052

HTS techniques for patch clamp-based ion channel screening - advances and economy.

PubMed

Farre, Cecilia; Fertig, Niels

2012-06-01

Ten years ago, the first publication appeared showing patch clamp recordings performed on a planar glass chip instead of using a conventional patch clamp pipette. "Going planar" proved to revolutionize ion channel drug screening as we know it, by allowing high quality measurements of ion channels and their effectors at a higher throughput and at the same time de-skilling the highly laborious technique. Over the years, platforms evolved in response to user requirements regarding experimental features, data handling plus storage, and suitable target diversity. This article gives a snapshot image of patch clamp-based ion channel screening with focus on platforms developed to meet requirements of high-throughput screening environments. The commercially available platforms are described, along with their benefits and drawbacks in ion channel drug screening. Automated patch clamp (APC) platforms allow faster investigation of a larger number of ion channel active compounds or cell clones than previously possible. Since patch clamp is the only method allowing direct, real-time measurements of ion channel activity, APC holds the promise of picking up high quality leads, where they otherwise would have been overseen using indirect methods. In addition, drug candidate safety profiling can be performed earlier in the drug discovery process, avoiding late-phase compound withdrawal due to safety liability issues, which is highly costly and inefficient.

A New Method for Rapid Screening of End-Point PCR Products: Application to Single Genome Amplified HIV and SIV Envelope Amplicons

PubMed Central

Houzet, Laurent; Deleage, Claire; Satie, Anne-Pascale; Merlande, Laetitia; Mahe, Dominique; Dejucq-Rainsford, Nathalie

2015-01-01

PCR is the most widely applied technique for large scale screening of bacterial clones, mouse genotypes, virus genomes etc. A drawback of large PCR screening is that amplicon analysis is usually performed using gel electrophoresis, a step that is very labor intensive, tedious and chemical waste generating. Single genome amplification (SGA) is used to characterize the diversity and evolutionary dynamics of virus populations within infected hosts. SGA is based on the isolation of single template molecule using limiting dilution followed by nested PCR amplification and requires the analysis of hundreds of reactions per sample, making large scale SGA studies very challenging. Here we present a novel approach entitled Long Amplicon Melt Profiling (LAMP) based on the analysis of the melting profile of the PCR reactions using SYBR Green and/or EvaGreen fluorescent dyes. The LAMP method represents an attractive alternative to gel electrophoresis and enables the quick discrimination of positive reactions. We validate LAMP for SIV and HIV env-SGA, in 96- and 384-well plate formats. Because the melt profiling allows the screening of several thousands of PCR reactions in a cost-effective, rapid and robust way, we believe it will greatly facilitate any large scale PCR screening. PMID:26053379

Current Technologies and Recent Developments for Screening of HPV-Associated Cervical and Oropharyngeal Cancers

PubMed Central

Shah, Sunny S.; Senapati, Satyajyoti; Klacsmann, Flora; Miller, Daniel L.; Johnson, Jeff J.; Chang, Hsueh-Chia; Stack, M. Sharon

2016-01-01

Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, predominantly represented by cervical cancer and oropharyngeal squamous cell carcinoma. Because of the prevalence of the virus, persistence of infection, and long latency period, novel and low-cost methods are needed for effective population level screening and monitoring. We review established methods for screening of cervical and oral cancer as well as commercially-available techniques for detection of HPV DNA. We then describe the ongoing development of microfluidic nucleic acid-based biosensors to evaluate circulating host microRNAs that are produced in response to an oncogenic HPV infection. The goal is to develop an ideal screening platform that is low-cost, portable, and easy to use, with appropriate signal stability, sensitivity and specificity. Advances in technologies for sample lysis, pre-treatment and concentration, and multiplexed nucleic acid detection are provided. Continued development of these devices provides opportunities for cancer screening in low resource settings, for point-of-care diagnostics and self-screening, and for monitoring response to vaccination or surgical treatment. PMID:27618102

A practical approach to screen for authorised and unauthorised genetically modified plants.

PubMed

Waiblinger, Hans-Ulrich; Grohmann, Lutz; Mankertz, Joachim; Engelbert, Dirk; Pietsch, Klaus

2010-03-01

In routine analysis, screening methods based on real-time PCR are most commonly used for the detection of genetically modified (GM) plant material in food and feed. In this paper, it is shown that the combination of five DNA target sequences can be used as a universal screening approach for at least 81 GM plant events authorised or unauthorised for placing on the market and described in publicly available databases. Except for maize event LY038, soybean events DP-305423 and BPS-CV127-9 and cotton event 281-24-236 x 3006-210-23, at least one of the five genetic elements has been inserted in these GM plants and is targeted by this screening approach. For the detection of these sequences, fully validated real-time PCR methods have been selected. A screening table is presented that describes the presence or absence of the target sequences for most of the listed GM plants. These data have been verified either theoretically according to available databases or experimentally using available reference materials. The screening table will be updated regularly by a network of German enforcement laboratories.

A prediction model-based algorithm for computer-assisted database screening of adverse drug reactions in the Netherlands.

PubMed

Scholl, Joep H G; van Hunsel, Florence P A M; Hak, Eelko; van Puijenbroek, Eugène P

2018-02-01

The statistical screening of pharmacovigilance databases containing spontaneously reported adverse drug reactions (ADRs) is mainly based on disproportionality analysis. The aim of this study was to improve the efficiency of full database screening using a prediction model-based approach. A logistic regression-based prediction model containing 5 candidate predictors was developed and internally validated using the Summary of Product Characteristics as the gold standard for the outcome. All drug-ADR associations, with the exception of those related to vaccines, with a minimum of 3 reports formed the training data for the model. Performance was based on the area under the receiver operating characteristic curve (AUC). Results were compared with the current method of database screening based on the number of previously analyzed associations. A total of 25 026 unique drug-ADR associations formed the training data for the model. The final model contained all 5 candidate predictors (number of reports, disproportionality, reports from healthcare professionals, reports from marketing authorization holders, Naranjo score). The AUC for the full model was 0.740 (95% CI; 0.734-0.747). The internal validity was good based on the calibration curve and bootstrapping analysis (AUC after bootstrapping = 0.739). Compared with the old method, the AUC increased from 0.649 to 0.740, and the proportion of potential signals increased by approximately 50% (from 12.3% to 19.4%). A prediction model-based approach can be a useful tool to create priority-based listings for signal detection in databases consisting of spontaneous ADRs. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Reliability and Validity of Observational Risk Screening in Evaluating Dynamic Knee Valgus

PubMed Central

Ekegren, Christina L.; Miller, William C.; Celebrini, Richard G.; Eng, Janice J.; MacIntyre, Donna L.

2012-01-01

Study Design Nonexperimental methodological study. Objectives To determine the interrater and intrarater reliability and validity of using observational risk screening guidelines to evaluate dynamic knee valgus. Background A deficiency in the neuromuscular control of the hip has been identified as a key risk factor for non-contact anterior cruciate ligament (ACL) injury in post pubescent females. This deficiency can manifest itself as a valgus knee alignment during tasks involving hip and knee flexion. There are currently no scientifically tested methods to screen for dynamic knee valgus in the clinic or on the field. Methods Three physiotherapists used observational risk screening guidelines to rate 40 adolescent female soccer players according to their risk of ACL injury. The rating was based on the amount of dynamic knee valgus observed on a drop jump landing. Ratings were evaluated for intrarater and interrater agreement using kappa coefficients. Sensitivity and specificity of ratings were evaluated by comparing observational ratings with measurements obtained using 3-dimensional (3D) motion analysis. Results Kappa coefficients for intrarater and interrater agreement ranged from 0.75 to 0.85, indicating that ratings were reasonably consistent over time and between physiotherapists. Sensitivity values were inadequate, ranging from 67–87%. This indicated that raters failed to detect up to a third of “truly high risk” individuals. Specificity values ranged from 60–72% which was considered adequate for the purposes of the screen. Conclusion Observational risk screening is a practical and cost-effective method of screening for ACL injury risk. Rater agreement and specificity were acceptable for this method but sensitivity was not. To detect a greater proportion of individuals at risk of ACL injury, coaches and clinicians should ensure that they include additional tests for other high risk characteristics in their screening protocols. PMID:19721212

Independence screening for high dimensional nonlinear additive ODE models with applications to dynamic gene regulatory networks.

PubMed

Xue, Hongqi; Wu, Shuang; Wu, Yichao; Ramirez Idarraga, Juan C; Wu, Hulin

2018-05-02

Mechanism-driven low-dimensional ordinary differential equation (ODE) models are often used to model viral dynamics at cellular levels and epidemics of infectious diseases. However, low-dimensional mechanism-based ODE models are limited for modeling infectious diseases at molecular levels such as transcriptomic or proteomic levels, which is critical to understand pathogenesis of diseases. Although linear ODE models have been proposed for gene regulatory networks (GRNs), nonlinear regulations are common in GRNs. The reconstruction of large-scale nonlinear networks from time-course gene expression data remains an unresolved issue. Here, we use high-dimensional nonlinear additive ODEs to model GRNs and propose a 4-step procedure to efficiently perform variable selection for nonlinear ODEs. To tackle the challenge of high dimensionality, we couple the 2-stage smoothing-based estimation method for ODEs and a nonlinear independence screening method to perform variable selection for the nonlinear ODE models. We have shown that our method possesses the sure screening property and it can handle problems with non-polynomial dimensionality. Numerical performance of the proposed method is illustrated with simulated data and a real data example for identifying the dynamic GRN of Saccharomyces cerevisiae. Copyright © 2018 John Wiley & Sons, Ltd.

Use of short messaging services to assess depressive symptoms among refugees in South Africa: Implications for social services providing mental health care in resource-poor settings

PubMed Central

Tomita, Andrew; Kandolo, Ka Muzombo; Susser, Ezra; Burns, Jonathan K

2016-01-01

Few studies in developing nations have assessed the use of short messaging services (SMS) to identify psychological challenges in refugee populations. This study aimed to assess the feasibility of SMS-based methods to screen for depression risk among refugees in South Africa attending mental health services, and to compare its reliability and acceptability with face-to-face consultation. Of the 153 refugees enrolled at baseline, 135 were available for follow-up assessments in our cohort study. Depression symptomatology was assessed using the 16-item Quick Inventory of Depressive Symptomatology (QIDS) instrument. Nearly everyone possessed a mobile phone and utilized SMS. Furthermore, low incomplete item response in QIDS and high perceived ease of interacting via SMS with service providers supported the feasibility of this method. There was a fair level of reliability between face-to-face and SMS-based screening methods, but no significant difference in preference rating between the two methods. Despite potential implementation barriers (network delay/phone theft), depression screening using SMS may be viable for refugee mental health services in low-resource settings. PMID:26407989

Tactile objects based on an amplitude disturbed diffraction pattern method

NASA Astrophysics Data System (ADS)

Liu, Yuan; Nikolovski, Jean-Pierre; Mechbal, Nazih; Hafez, Moustapha; Vergé, Michel

2009-12-01

Tactile sensing is becoming widely used in human-computer interfaces. Recent advances in acoustic approaches demonstrated the possibilities to transform ordinary solid objects into interactive interfaces. This letter proposes a static finger contact localization process using an amplitude disturbed diffraction pattern method. The localization method is based on the following physical phenomenon: a finger contact modifies the energy distribution of acoustic wave in a solid; these variations depend on the wave frequency and the contact position. The presented method first consists of exciting the object with an acoustic signal with plural frequency components. In a second step, a measured acoustic signal is compared with prerecorded values to deduce the contact position. This position is then used for human-machine interaction (e.g., finger tracking on computer screen). The selection of excitation signals is discussed and a frequency choice criterion based on contrast value is proposed. Tests on a sandwich plate (liquid crystal display screen) prove the simplicity and easiness to apply the process in various solids.

Validation and cost-effectiveness of a home-based screening system for amblyopia.

PubMed

Lan, Weizhong; Zhao, Feng; Li, Zhen; Zeng, Junwen; Liu, Wenyan; Lu, Jinhua; Zheng, Dehui; Lin, Lixia; Ge, Jian; Yang, Zhikuan

2012-06-01

To investigate the cost-effectiveness of a novel home-based screening system for amblyopia and amblyogenic risk factors. Evaluation of diagnostic test or technology. Two thousand four hundred forty-two preschoolers 3 to 6 years of age from 10 kindergartens randomly selected from Guangzhou participated in the study in 2009. Preschoolers were assessed for amblyopia and amblyogenic risk factors by their parents using the home-based screening system and were re-evaluated by professionals who conducted a comprehensive eye examination. Sensitivity, specificity, positive predictive value, negative predictive value, and the cost-benefit of the home-based screening system were calculated by comparing the results from the home-assessed model and those from the professional evaluation. Three thousand three hundred children were invited to participate in the study, and 2308 (1216 boys and 1092 girls) completed all of the procedures. Twenty-four amblyopes were found by professional examinations. Fifteen of these amblyopes had not been diagnosed previously, and 12 of them were detected by the home-assessment model. The sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 94.1%, 8.2%, and 99.9%, respectively. Professional examinations cost an average of US $1131.00 per case of amblyopia detected, whereas the cost was only US $266.00 per case for the home-based method. For amblyogenic factors, 50, 87, and 96 children were classified into grade I, II, or III according to the professional examinations. The corresponding numbers in the home-based system were 23, 29, and 15, respectively. Accordingly, the true positive rates were 46.0%, 33.3%, and 15.6% for each grade. The home-based amblyopia screening system was found to be a simple, effective, and cost-beneficial method for amblyopia screening and amblyogenic risk factors. The approach offers a practical option for developing areas with large populations. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

RAIM availability for supplemental GPS navigation

DOT National Transportation Integrated Search

1992-06-29

This paper examines GPS receiver autonomous integrity monitoring (RAIM) availability for supplemental navigation based on the approximate radial-error protection (ARP) method. This method applies ceiling levels for the ARP figure of merit to screen o...

Identification of effective screening strategies for cardiovascular disease prevention in a developing country: using cardiovascular risk-estimation and risk-reduction tools for policy recommendations

PubMed Central

2013-01-01

Background Recent increases in cardiovascular risk-factor prevalences have led to new national policy recommendations of universal screening for primary prevention of cardiovascular disease in Malaysia. This study assessed whether the current national policy recommendation of universal screening was optimal, by comparing the effectiveness and impact of various cardiovascular screening strategies. Methods Data from a national population based survey of 24 270 participants aged 30 to 74 was used. Five screening strategies were modelled for the overall population and by gender; universal and targeted screening (four age cut-off points). Screening strategies were assessed based on the ability to detect high cardiovascular risk populations (effectiveness), incremental effectiveness, impact on cardiovascular event prevention and cost of screening. Results 26.7% (95% confidence limits 25.7, 27.7) were at high cardiovascular risk, men 34.7% (33.6, 35.8) and women 18.9% (17.8, 20). Universal screening identified all those at high-risk and resulted in one high-risk individual detected for every 3.7 people screened, with an estimated cost of USD60. However, universal screening resulted in screening an additional 7169 persons, with an incremental cost of USD115,033 for detection of one additional high-risk individual in comparison to targeted screening of those aged ≥35 years. The cost, incremental cost and impact of detection of high-risk individuals were more for women than men for all screening strategies. The impact of screening women aged ≥45 years was similar to universal screening in men. Conclusions Targeted gender- and age-specific screening strategies would ensure more optimal utilisation of scarce resources compared to the current policy recommendations of universal screening. PMID:23442728

Fluorescence imaging technology (FI) for high-throughput screening of selenide-modified nano-TiO2 catalysts.

PubMed

Wang, Liping; Lee, Jianchao; Zhang, Meijuan; Duan, Qiannan; Zhang, Jiarui; Qi, Hailang

2016-02-18

A high-throughput screening (HTS) method based on fluorescence imaging (FI) was implemented to evaluate the catalytic performance of selenide-modified nano-TiO2. Chemical ink-jet printing (IJP) technology was reformed to fabricate a catalyst library comprising 1405 (Ni(a)Cu(b)Cd(c)Ce(d)In(e)Y(f))Se(x)/TiO2 (M6Se/Ti) composite photocatalysts. Nineteen M6Se/Tis were screened out from the 1405 candidates efficiently.

ScreenCube: A 3D Printed System for Rapid and Cost-Effective Chemical Screening in Adult Zebrafish.

PubMed

Monstad-Rios, Adrian T; Watson, Claire J; Kwon, Ronald Y

2018-02-01

Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish. Using prefilled screening plates, the system enables dosing of 96 fish in ∼3 min, with a 10-fold reduction in drug quantity compared to that used in previous chemical screens in adult zebrafish. We characterize water quality kinetics during immersion in the system and use these kinetics to rationally design intermittent dosing regimens that result in 100% fish survival. As a demonstration of system fidelity, we show the potential to identify two known chemical inhibitors of adult tail fin regeneration, cyclopamine and dorsomorphin. By developing methods for rapid and cost-effective chemical administration in adult zebrafish, this study expands the potential for small molecule discovery in postembryonic models of development, disease, and regeneration.

Public stated preferences and predicted uptake for genome-based colorectal cancer screening

PubMed Central

2014-01-01

Background Emerging developments in nanomedicine allow the development of genome-based technologies for non-invasive and individualised screening for diseases such as colorectal cancer. The main objective of this study was to measure user preferences for colorectal cancer screening using a nanopill. Methods A discrete choice experiment was used to estimate the preferences for five competing diagnostic techniques including the nanopill and iFOBT. Alternative screening scenarios were described using five attributes namely: preparation involved, sensitivity, specificity, complication rate and testing frequency. Fourteen random and two fixed choice tasks, each consisting of three alternatives, were offered to 2225 individuals. Data were analysed using the McFadden conditional logit model. Results Thirteen hundred and fifty-six respondents completed the questionnaire. The most important attributes (and preferred levels) were the screening technique (nanopill), sensitivity (100%) and preparation (no preparation). Stated screening uptake for the nanopill was 79%, compared to 76% for iFOBT. In the case of screening with the nanopill, the percentage of people preferring not to be screened would be reduced from 19.2% (iFOBT) to 16.7%. Conclusions Although the expected benefits of nanotechnology based colorectal cancer screening are improved screening uptake, assuming more accurate test results and less preparation involved, the relative preference of the nanopill is only slightly higher than the iFOBT. Estimating user preferences during the development of diagnostic technologies could be used to identify relative performance, including perceived benefits and harms compared to competitors allowing for significant changes to be made throughout the process of development. PMID:24642027

Factors affecting reproducibility between genome-scale siRNA-based screens

PubMed Central

Barrows, Nicholas J.; Le Sommer, Caroline; Garcia-Blanco, Mariano A.; Pearson, James L.

2011-01-01

RNA interference-based screening is a powerful new genomic technology which addresses gene function en masse. To evaluate factors influencing hit list composition and reproducibility, we performed two identically designed small interfering RNA (siRNA)-based, whole genome screens for host factors supporting yellow fever virus infection. These screens represent two separate experiments completed five months apart and allow the direct assessment of the reproducibility of a given siRNA technology when performed in the same environment. Candidate hit lists generated by sum rank, median absolute deviation, z-score, and strictly standardized mean difference were compared within and between whole genome screens. Application of these analysis methodologies within a single screening dataset using a fixed threshold equivalent to a p-value ≤ 0.001 resulted in hit lists ranging from 82 to 1,140 members and highlighted the tremendous impact analysis methodology has on hit list composition. Intra- and inter-screen reproducibility was significantly influenced by the analysis methodology and ranged from 32% to 99%. This study also highlighted the power of testing at least two independent siRNAs for each gene product in primary screens. To facilitate validation we conclude by suggesting methods to reduce false discovery at the primary screening stage. In this study we present the first comprehensive comparison of multiple analysis strategies, and demonstrate the impact of the analysis methodology on the composition of the “hit list”. Therefore, we propose that the entire dataset derived from functional genome-scale screens, especially if publicly funded, should be made available as is done with data derived from gene expression and genome-wide association studies. PMID:20625183

Radiologic findings of screen-detected cancers in an organized population-based screening mammography program in Turkey

PubMed Central

Kayhan, Arda; Arıbal, Erkin; Şahin, Cennet; Taşçı, Ömür Can; Gürdal, Sibel Özkan; Öztürk, Enis; Hatipoğlu, Hayat Halide; Özaydın, Nilüfer; Cabioğlu, Neslihan; Özçınar, Beyza; Özmen, Vahit

2016-01-01

PURPOSE Bahçeşehir Breast Cancer Screening Program is a population based organized screening program in Turkey, where asymptomatic women aged 40–69 years are screened biannually. In this prospective study, we aimed to determine the mammographic findings of screen-detected cancers and discuss the efficacy of breast cancer screening in a developing country. METHODS A total of 6912 women were screened in three rounds. The radiologic findings were grouped as mass, focal asymmetry, calcification, and architectural distortion. Masses were classified according to shape, border, and density. Calcifications were grouped according to morphology and distribution. Cancers were grouped according to the clinical stage. RESULTS Seventy cancers were detected with an incidence of 4.8/1000. Two cancers were detected in other centers and three were not visualized mammographically. Mammographic presentations of the remaining 65 cancers were mass (47.7%, n=31), calcification (30.8%, n=20), focal asymmetry (16.9%, n=11), architectural distortion (3.1%, n=2), and skin thickening (1.5%, n=1). The numbers of stage 0, 1, 2, 3, and 4 cancers were 13 (20.0%), 34 (52.3%), 14 (21.5%), 3 (4.6%), and 1 (1.5%), respectively. The numbers of interval and missed cancers were 5 (7.4%) and 7 (10.3%), respectively. CONCLUSION A high incidence of early breast cancer has been detected. The incidence of missed and interval cancers did not show major differences from western screening trials. We believe that this study will pioneer implementation of efficient population-based mammographic screenings in developing countries. PMID:27705880

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

PubMed

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

2018-01-01

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

Development of a Colorectal Cancer Screening Intervention for Iranian Adults: Appling Intervention Mapping

PubMed

Besharati, Fereshteh; Karimi-Shahanjarini, Akram; Hazavehei, Seyed Mohammad Mehdi; Bashirian, Saeid; Bagheri, Fahimeh; Faradmal, Javad

2017-08-27

Background: While the incidence rate of the colorectal cancer (CRC) has been increasing over the last three decades in Iran, very limited interventions to increase CRC screening have been developed for Iranian population. The purpose of this study was to describe the use of Intervention Mapping (IM) for applying theory and evidence and considering local contexts to develop a CRC screening program among adults in Iran. Materials and Methods: From April 2014 to July 2016 following the IM process, six steps were formulated and implemented. First a need assessment was conducted involving relevant stakeholders and using focus groups discussions (n=10), individual interviews (n=20), and a household survey (n= 480). Then a matrix of change objectives was developed for each behavioral outcome and theoretical methods and their practical applications were identified to guide intervention development and implementation. A multi-component intervention was developed and piloted. Decision on suitable parts of intervention was made based on feedback of pilot study. Finally, evaluation plan including process and outcome evaluation was generated and conducted to inform future scale up. Results: The needs assessment highlighted factors affecting CRC screening including knowledge, self efficacy, social support and perceived benefit and barriers (financial problems, fear of detection of cancer and etc). Results of needs assessment were used to develop next steps IM. The program utilized methods like information delivery, modeling, and persuasion. Practical applications included video presentation, group discussion, role playing and postcards.This program was assessed through a cluster-randomized controlled trial. Results showed that there were significant differences in CRC screening uptake between intervention groups and control (P<0.001). Conclusions: IM is a useful process in the design of a theory-based intervention addressing CRC screening among Iranian population. Creative Commons Attribution License

A high-throughput colorimetric assay for glucose detection based on glucose oxidase-catalyzed enlargement of gold nanoparticles

NASA Astrophysics Data System (ADS)

Xiong, Yanmei; Zhang, Yuyan; Rong, Pengfei; Yang, Jie; Wang, Wei; Liu, Dingbin

2015-09-01

We developed a simple high-throughput colorimetric assay to detect glucose based on the glucose oxidase (GOx)-catalysed enlargement of gold nanoparticles (AuNPs). Compared with the currently available glucose kit method, the AuNP-based assay provides higher clinical sensitivity at lower cost, indicating its great potential to be a powerful tool for clinical screening of glucose.We developed a simple high-throughput colorimetric assay to detect glucose based on the glucose oxidase (GOx)-catalysed enlargement of gold nanoparticles (AuNPs). Compared with the currently available glucose kit method, the AuNP-based assay provides higher clinical sensitivity at lower cost, indicating its great potential to be a powerful tool for clinical screening of glucose. Electronic supplementary information (ESI) available: Experimental section and additional figures. See DOI: 10.1039/c5nr03758a

The Harvard Clean Energy Project: High-throughput screening of organic photovoltaic materials using cheminformatics, machine learning, and pattern recognition

NASA Astrophysics Data System (ADS)

Olivares-Amaya, Roberto; Hachmann, Johannes; Amador-Bedolla, Carlos; Daly, Aidan; Jinich, Adrian; Atahan-Evrenk, Sule; Boixo, Sergio; Aspuru-Guzik, Alán

2012-02-01

Organic photovoltaic devices have emerged as competitors to silicon-based solar cells, currently reaching efficiencies of over 9% and offering desirable properties for manufacturing and installation. We study conjugated donor polymers for high-efficiency bulk-heterojunction photovoltaic devices with a molecular library motivated by experimental feasibility. We use quantum mechanics and a distributed computing approach to explore this vast molecular space. We will detail the screening approach starting from the generation of the molecular library, which can be easily extended to other kinds of molecular systems. We will describe the screening method for these materials which ranges from descriptor models, ubiquitous in the drug discovery community, to eventually reaching first principles quantum chemistry methods. We will present results on the statistical analysis, based principally on machine learning, specifically partial least squares and Gaussian processes. Alongside, clustering methods and the use of the hypergeometric distribution reveal moieties important for the donor materials and allow us to quantify structure-property relationships. These efforts enable us to accelerate materials discovery in organic photovoltaics through our collaboration with experimental groups.

Developing a Bacteroides System for Function-Based Screening of DNA from the Human Gut Microbiome.

PubMed

Lam, Kathy N; Martens, Eric C; Charles, Trevor C

2018-01-01

Functional metagenomics is a powerful method that allows the isolation of genes whose role may not have been predicted from DNA sequence. In this approach, first, environmental DNA is cloned to generate metagenomic libraries that are maintained in Escherichia coli, and second, the cloned DNA is screened for activities of interest. Typically, functional screens are carried out using E. coli as a surrogate host, although there likely exist barriers to gene expression, such as lack of recognition of native promoters. Here, we describe efforts to develop Bacteroides thetaiotaomicron as a surrogate host for screening metagenomic DNA from the human gut. We construct a B. thetaiotaomicron-compatible fosmid cloning vector, generate a fosmid clone library using DNA from the human gut, and show successful functional complementation of a B. thetaiotaomicron glycan utilization mutant. Though we were unable to retrieve the physical fosmid after complementation, we used genome sequencing to identify the complementing genes derived from the human gut microbiome. Our results demonstrate that the use of B. thetaiotaomicron to express metagenomic DNA is promising, but they also exemplify the challenges that can be encountered in the development of new surrogate hosts for functional screening. IMPORTANCE Human gut microbiome research has been supported by advances in DNA sequencing that make it possible to obtain gigabases of sequence data from metagenomes but is limited by a lack of knowledge of gene function that leads to incomplete annotation of these data sets. There is a need for the development of methods that can provide experimental data regarding microbial gene function. Functional metagenomics is one such method, but functional screens are often carried out using hosts that may not be able to express the bulk of the environmental DNA being screened. We expand the range of current screening hosts and demonstrate that human gut-derived metagenomic libraries can be introduced into the gut microbe Bacteroides thetaiotaomicron to identify genes based on activity screening. Our results support the continuing development of genetically tractable systems to obtain information about gene function.

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland

PubMed Central

2013-01-01

Background Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. Methods A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55–74 years, and (c) biennial faecal immunochemical tests (FIT) at 55–74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55–64 years) and staggered age-based roll-out across the 55–74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55–74). Results FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381–1,053 with FSIG-based, and 967–1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. Conclusions While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning. PMID:23510135

[Comparison of screening performance between primary high-risk HPV screening and high-risk HPV screening plus liquid-based cytology cotesting in diagnosis of cervical precancerous or cancerous lesions].

PubMed

Zhao, X L; Remila, Rezhake; Hu, S Y; Zhang, L; Xu, X Q; Chen, F; Pan, Q J; Zhang, X; Zhao, F H

2018-05-06

Objective: To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+). Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups. Results: Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ(2)=19.00, P< 0.001), and the specificity were 86.2% and 78.8% (χ(2)=2 067.00, P< 0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z= 6.16, P< 0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ(2)=132.00, P< 0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting. Conclusion: Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

Post processing of protein-compound docking for fragment-based drug discovery (FBDD): in-silico structure-based drug screening and ligand-binding pose prediction.

PubMed

Fukunishi, Yoshifumi

2010-01-01

For fragment-based drug development, both hit (active) compound prediction and docking-pose (protein-ligand complex structure) prediction of the hit compound are important, since chemical modification (fragment linking, fragment evolution) subsequent to the hit discovery must be performed based on the protein-ligand complex structure. However, the naïve protein-compound docking calculation shows poor accuracy in terms of docking-pose prediction. Thus, post-processing of the protein-compound docking is necessary. Recently, several methods for the post-processing of protein-compound docking have been proposed. In FBDD, the compounds are smaller than those for conventional drug screening. This makes it difficult to perform the protein-compound docking calculation. A method to avoid this problem has been reported. Protein-ligand binding free energy estimation is useful to reduce the procedures involved in the chemical modification of the hit fragment. Several prediction methods have been proposed for high-accuracy estimation of protein-ligand binding free energy. This paper summarizes the various computational methods proposed for docking-pose prediction and their usefulness in FBDD.

Delivering colonoscopy screening for low-income populations in Suffolk County: strategies, outcomes, and benchmarks.

PubMed

Lane, Dorothy S; Messina, Catherine R; Cavanagh, Mary F; Anderson, Joseph C

2013-08-01

Current and pending legislation provides colorectal cancer screening reimbursement for previously uninsured populations. Colonoscopy is currently the screening method most frequently recommended by physicians for insured patients. The experience of the SCOPE (Suffolk County Preventive Endoscopy) demonstration project (Project SCOPE) at Stony Brook University Medical Center provides a model for delivering colonoscopy screening to low-income populations to meet anticipated increasing demands. Project SCOPE, based in the Department of Preventive Medicine, featured internal collaboration with the academic medical center's large gastroenterology practice and external collaboration with the Suffolk County Department of Health Services' network of community health centers. Colonoscopies were performed by faculty gastroenterologists or supervised fellows. Measures of colonoscopy performance were compared with quality indicators and differences between faculty and supervised fellows were identified. During a 40-month screening period, 800 initial colonoscopies were performed. Approximately 21% of women screened were found to have adenomatous polyps compared with 36% of men. Five cancers were detected. The majority of the population screened (70%) were members of minority populations. African American individuals had a higher percentage of proximally located adenomas (78%) compared with white individuals (65%) and Hispanics (49%), based on the location of the most advanced lesion. Hispanic individuals had a 36% lower risk of adenomas compared with white individuals. Performance measures including the percentage of procedures with adequate bowel preparation, cecum reached, scope withdrawal time, and adenoma detection rate met quality benchmarks when performed by either faculty or supervised fellows. Project SCOPE's operational strategies demonstrated a feasible method for an academic medical center to provide high-quality screening colonoscopy for low-income populations. © 2013 American Cancer Society.

Exploring Disparities and Variability in Perceptions and Self-Reported Colorectal Cancer Screening Among Three Ethnic Subgroups of U.S. Blacks

PubMed Central

Gwede, Clement K.; William, Claire M.; Thomas, Kamilah B.; Tarver, Will L.; Quinn, Gwendolyn P.; Vadaparampil, Susan T.; Kim, Jongphil; Lee, Ji-Hyun; Meade, Cathy D.

2010-01-01

Purpose/Objectives To explore perceptions of colorectal cancer (CRC) and self-reported CRC screening behaviors among ethnic subgroups of U.S. blacks. Design Descriptive, cross-sectional, exploratory, developmental pilot. Setting Medically underserved areas in Hillsborough County, FL. Sample 62 men and women aged 50 years or older. Ethnic subgroup distribution included 22 African American, 20 English-speaking Caribbean-born, and 20 Haitian-born respondents. Methods Community-based participatory research methods were used to conduct face-to-face individual interviews in the community. Main Research Variables Ethnic subgroup, health access, perceptions of CRC (e.g., awareness of screening tests, perceived risk, perceived barriers to screening), healthcare provider recommendation, and self-reported CRC screening. Findings Awareness of CRC screening tests, risk perception, healthcare provider recommendation, and self-reported use of screening were low across all subgroups. However, only 55% of Haitian-born participants had heard about the fecal occult blood test compared to 84% for English-speaking Caribbean-born participants and 91% for African Americans. Similarly, only 15% of Haitian-born respondents had had a colonoscopy compared to 50% for the English-speaking Caribbean and African American subgroups. Conclusions This exploratory, developmental pilot study identified lack of awareness, low risk perception, and distinct barriers to screening. The findings support the need for a larger community-based study to elucidate and address disparities among subgroups. Implications for Nursing Nurses play a major role in reducing cancer health disparities through research, education, and quality care. Recognition of the cultural diversity of the U.S. black population can help nurses address health disparities and contribute to the health of the community. PMID:20797950

Quantification and clustering of phenotypic screening data using time-series analysis for chemotherapy of schistosomiasis.

PubMed

Lee, Hyokyeong; Moody-Davis, Asher; Saha, Utsab; Suzuki, Brian M; Asarnow, Daniel; Chen, Steven; Arkin, Michelle; Caffrey, Conor R; Singh, Rahul

2012-01-01

Neglected tropical diseases, especially those caused by helminths, constitute some of the most common infections of the world's poorest people. Development of techniques for automated, high-throughput drug screening against these diseases, especially in whole-organism settings, constitutes one of the great challenges of modern drug discovery. We present a method for enabling high-throughput phenotypic drug screening against diseases caused by helminths with a focus on schistosomiasis. The proposed method allows for a quantitative analysis of the systemic impact of a drug molecule on the pathogen as exhibited by the complex continuum of its phenotypic responses. This method consists of two key parts: first, biological image analysis is employed to automatically monitor and quantify shape-, appearance-, and motion-based phenotypes of the parasites. Next, we represent these phenotypes as time-series and show how to compare, cluster, and quantitatively reason about them using techniques of time-series analysis. We present results on a number of algorithmic issues pertinent to the time-series representation of phenotypes. These include results on appropriate representation of phenotypic time-series, analysis of different time-series similarity measures for comparing phenotypic responses over time, and techniques for clustering such responses by similarity. Finally, we show how these algorithmic techniques can be used for quantifying the complex continuum of phenotypic responses of parasites. An important corollary is the ability of our method to recognize and rigorously group parasites based on the variability of their phenotypic response to different drugs. The methods and results presented in this paper enable automatic and quantitative scoring of high-throughput phenotypic screens focused on helmintic diseases. Furthermore, these methods allow us to analyze and stratify parasites based on their phenotypic response to drugs. Together, these advancements represent a significant breakthrough for the process of drug discovery against schistosomiasis in particular and can be extended to other helmintic diseases which together afflict a large part of humankind.

Estimating the influenza vaccine effectiveness in elderly on a yearly basis using the Spanish influenza surveillance network--pilot case-control studies using different control groups, 2008-2009 season, Spain.

PubMed

Savulescu, Camelia; Valenciano, Marta; de Mateo, Salvador; Larrauri, Amparo

2010-04-01

We conducted a case-control and screening method studies to estimate influenza vaccine effectiveness (IVE) in the age group >or=65 years, based on the Spanish Influenza Sentinel Surveillance System (SISSS). Cases (influenza laboratory-confirmed) were compared to influenza-negative ILI patients (test-negative) and patients without ILI since the beginning of the season (non-ILI). For the screening method, cases' vaccination coverage was compared to the vaccination coverage of the GPs' catchment population. The results suggested a protective effect of the vaccine against laboratory-confirmed influenza in elderly in 2008-2009. The screening method and the test-negative control designs enable estimating IVE using exclusively SISSS data. (c) 2010 Elsevier Ltd. All rights reserved.

Screening for heat transport by groundwater in closed geothermal systems.

PubMed

Ferguson, Grant

2015-01-01

Heat transfer due to groundwater flow can significantly affect closed geothermal systems. Here, a screening method is developed, based on Peclet numbers for these systems and Darcy's law. Conduction-only conditions should not be expected where specific discharges exceed 10(-8)  m/s. Constraints on hydraulic gradients allow for preliminary screening for advection based on rock or soil types. Identification of materials with very low hydraulic conductivity, such as shale and intact igneous and metamorphic rock, allow for analysis with considering conduction only. Variability in known hydraulic conductivity allows for the possibility of advection in most other rocks and soil types. Further screening relies on refinement of estimates of hydraulic gradients and hydraulic conductivity through site investigations and modeling until the presence or absence of conduction can be confirmed. © 2014, National Ground Water Association.

Validation approach for a fast and simple targeted screening method for 75 antibiotics in meat and aquaculture products using LC-MS/MS.

PubMed

Dubreil, Estelle; Gautier, Sophie; Fourmond, Marie-Pierre; Bessiral, Mélaine; Gaugain, Murielle; Verdon, Eric; Pessel, Dominique

2017-04-01

An approach is described to validate a fast and simple targeted screening method for antibiotic analysis in meat and aquaculture products by LC-MS/MS. The strategy of validation was applied for a panel of 75 antibiotics belonging to different families, i.e., penicillins, cephalosporins, sulfonamides, macrolides, quinolones and phenicols. The samples were extracted once with acetonitrile, concentrated by evaporation and injected into the LC-MS/MS system. The approach chosen for the validation was based on the Community Reference Laboratory (CRL) guidelines for the validation of screening qualitative methods. The aim of the validation was to prove sufficient sensitivity of the method to detect all the targeted antibiotics at the level of interest, generally the maximum residue limit (MRL). A robustness study was also performed to test the influence of different factors. The validation showed that the method is valid to detect and identify 73 antibiotics of the 75 antibiotics studied in meat and aquaculture products at the validation levels.

Mobile Phone Text Messaging Intervention for Cervical Cancer Screening: Changes in Knowledge and Behavior Pre-Post Intervention

PubMed Central

2014-01-01

Background Cervical cancer poses a significant threat to Korean American women, who are reported to have one of the highest cervical cancer mortality rates in the United States. Studies consistently report that Korean American women have the lowest Pap test screening rates across US ethnic groups. Objective In response to the need to enhance cervical cancer screening in this vulnerable population, we developed and tested a 7-day mobile phone text message-based cervical cancer Screening (mScreening) intervention designed to promote the receipt of Pap tests by young Korean American women. Methods We developed and assessed the acceptability and feasibility of a 1-week mScreening intervention to increase knowledge of cervical cancer screening, intent to receive screening, and the receipt of a Pap test. Fogg’s Behavior Model was the conceptual framework that guided the development of the mScreening intervention. A series of focus groups were conducted to inform the development of the intervention. The messages were individually tailored for each participant and delivered to them for a 7-day period at each participant’s preferred time. A quasi-experimental research design of 30 Korean American women aged 21 to 29 years was utilized with baseline, post (1 week after the completion of mScreening), and follow-up (3 months after the completion of mScreening) testing. Results Findings revealed a significant increase in participants’ knowledge of cervical cancer (P<.001) and guidelines for cervical cancer screening (P=.006). A total of 23% (7/30) (95% CI 9.9-42.3) of the mScreening participants received a Pap test; 83% (25/30) of the participants expressed satisfaction with the intervention and 97% (29/30) reported that they would recommend the program to their friends, indicating excellent acceptability and feasibility of the intervention. Conclusions This study provides evidence of the effectiveness and feasibility of the mScreening intervention. Mobile technology is a promising tool to increase both knowledge and receipt of cervical cancer screening. Given the widespread usage of mobile phones among young adults, a mobile phone-based health intervention could be a low-cost and effective method of reaching populations with low cervical cancer screening rates, using individually tailored messages that cover broad content areas and overcome restrictions to place and time of delivery. PMID:25164545

A Network-Based Method to Assess the Statistical Significance of Mild Co-Regulation Effects

PubMed Central

Horvát, Emőke-Ágnes; Zhang, Jitao David; Uhlmann, Stefan; Sahin, Özgür; Zweig, Katharina Anna

2013-01-01

Recent development of high-throughput, multiplexing technology has initiated projects that systematically investigate interactions between two types of components in biological networks, for instance transcription factors and promoter sequences, or microRNAs (miRNAs) and mRNAs. In terms of network biology, such screening approaches primarily attempt to elucidate relations between biological components of two distinct types, which can be represented as edges between nodes in a bipartite graph. However, it is often desirable not only to determine regulatory relationships between nodes of different types, but also to understand the connection patterns of nodes of the same type. Especially interesting is the co-occurrence of two nodes of the same type, i.e., the number of their common neighbours, which current high-throughput screening analysis fails to address. The co-occurrence gives the number of circumstances under which both of the biological components are influenced in the same way. Here we present SICORE, a novel network-based method to detect pairs of nodes with a statistically significant co-occurrence. We first show the stability of the proposed method on artificial data sets: when randomly adding and deleting observations we obtain reliable results even with noise exceeding the expected level in large-scale experiments. Subsequently, we illustrate the viability of the method based on the analysis of a proteomic screening data set to reveal regulatory patterns of human microRNAs targeting proteins in the EGFR-driven cell cycle signalling system. Since statistically significant co-occurrence may indicate functional synergy and the mechanisms underlying canalization, and thus hold promise in drug target identification and therapeutic development, we provide a platform-independent implementation of SICORE with a graphical user interface as a novel tool in the arsenal of high-throughput screening analysis. PMID:24039936

Photovoltaic and Impedance Spectroscopy Study of Screen-Printed TiO₂ Based CdS Quantum Dot Sensitized Solar Cells.

PubMed

Atif, M; Farooq, W A; Fatehmulla, Amanullah; Aslam, M; Ali, Syed Mansoor

2015-01-19

Cadmium sulphide (CdS) quantum dot sensitized solar cells (QDSSCs) based on screen-printed TiO₂ were assembled using a screen-printing technique. The CdS quantum dots (QDs) were grown by using the Successive Ionic Layer Adsorption and Reaction (SILAR) method. The optical properties were studied by UV-Vis absorbance spectroscopy. Photovoltaic characteristics and impedance spectroscopic measurements of CdS QDSSCs were carried out under air mass 1.5 illuminations. The experimental results of capacitance against voltage indicate a trend from positive to negative capacitance because of the injection of electrons from the Fluorine doped tin oxide (FTO) electrode into TiO₂.

Fully automated screening of immunocytochemically stained specimens for early cancer detection

NASA Astrophysics Data System (ADS)

Bell, André A.; Schneider, Timna E.; Müller-Frank, Dirk A. C.; Meyer-Ebrecht, Dietrich; Böcking, Alfred; Aach, Til

2007-03-01

Cytopathological cancer diagnoses can be obtained less invasive than histopathological investigations. Cells containing specimens can be obtained without pain or discomfort, bloody biopsies are avoided, and the diagnosis can, in some cases, even be made earlier. Since no tissue biopsies are necessary these methods can also be used in screening applications, e.g., for cervical cancer. Among the cytopathological methods a diagnosis based on the analysis of the amount of DNA in individual cells achieves high sensitivity and specificity. Yet this analysis is time consuming, which is prohibitive for a screening application. Hence, it will be advantageous to retain, by a preceding selection step, only a subset of suspicious specimens. This can be achieved using highly sensitive immunocytochemical markers like p16 ink4a for preselection of suspicious cells and specimens. We present a method to fully automatically acquire images at distinct positions at cytological specimens using a conventional computer controlled microscope and an autofocus algorithm. Based on the thus obtained images we automatically detect p16 ink4a-positive objects. This detection in turn is based on an analysis of the color distribution of the p16 ink4a marker in the Lab-colorspace. A Gaussian-mixture-model is used to describe this distribution and the method described in this paper so far achieves a sensitivity of up to 90%.

Innovative approaches to cervical cancer screening for sex trade workers: an international scoping review.

PubMed

Thulien, Naomi S

2014-03-01

Female sex trade workers are among those at highest risk for developing and dying of cervical cancer, and yet many-particularly the most marginalized-are less likely than other women to be screened. This review summarizes global findings on innovative approaches to cervical cancer screening for female sex trade workers, highlights current gaps in the delivery of cervical cancer screening for female sex trade workers globally, and suggests areas for future research and policy development. A scoping review of peer-reviewed publications and grey literature was conducted. Medline (OVID), PubMed, EMBASE, and SCOPUS were searched for relevant studies written in English. There were no limitations placed on dates. Grey literature was identified by hand searching and through discussion with health care providers and community outreach workers currently working with sex trade workers. Twenty-five articles were deemed suitable for review. Articles detailing innovative ways for female sex trade workers to access cervical cancer screening were included. Articles about screening for sexually transmitted infections were also included if the findings could be generalized to screening for cervical cancer. Articles limited to exploring risk factors, knowledge, awareness, education, prevalence, and incidence of cervical cancer among sex trade workers were excluded from the review. Successful screening initiatives identified in the studies reviewed had unconventional hours of operation, understood the difference between street-based and venue-based sex trade workers, and/or used peers for outreach. Two significant gaps in health care service delivery were highlighted in this review: the limited use of unorthodox hours and the nearly exclusive practice of providing sexually transmitted infection screening for female sex trade workers without cervical cancer screening. In addition, although street-based (as opposed to venue-based) sex trade workers are likely at higher risk for developing cervical cancer, they are much less likely than other eligible women to participate in screening programs, meaning traditional outreach methods are unlikely to be successful.

Uptake of community-based, self-collected HPV testing vs. visual inspection with acetic acid for cervical cancer screening in Kampala, Uganda: preliminary results of a randomised controlled trial.

PubMed

Moses, Erin; Pedersen, Heather N; Mitchell, Sheona M; Sekikubo, Musa; Mwesigwa, David; Singer, Joel; Biryabarema, Christine; Byamugisha, Josaphat K; Money, Deborah M; Ogilvie, Gina S

2015-10-01

To compare two cervical cancer screening methods: community-based self-collection of high-risk human papillomavirus (HR-HPV) testing and visual inspection with acetic acid (VIA). Pilot randomised controlled trial of 500 women aged 30-65 in the community of Kisenyi, Uganda. Women randomised to self-collection-based HR-HPV testing provided a cervico-vaginal swab for HR-HPV, and results were provided by phone after laboratory testing. Women who tested HPV positive were referred for VIA at the local health unit. Women randomised to VIA underwent screening at the local health unit, where women who tested positive with VIA were provided cryotherapy at time of screening, as per local standard of care. Women were referred for colposcopy when indicated. Outcome measures were uptake of screening, HR-HPV prevalence, VIA result and treatment rates. In the HR-HPV arm, 248 of 250 (p < 0.01) women provided samples, while in the VIA arm, 121 of 250 (48.4%) women attended screening. Among the 73 of 248 HR-HPV-positive women, 45.2% (N = 33) attended VIA screening for follow-up, 21.2% (N = 7) of whom screened positive; five received treatment and two were missing clinical follow-up records. Of the 121 women in the VIA arm who attended screening, 13.2% (N = 16) screened positive; seven received cryotherapy, three refused treatment, five were referred to colposcopy; and one woman had suspected cervical cancer and received treatment after confirmatory testing. This pilot study demonstrated trial feasibility and willingness of the women to participate and be randomised successfully into the two arms. Self-collection-based cervical cancer screening had a higher uptake than VIA. © 2015 John Wiley & Sons Ltd.

Applying systematic review search methods to the grey literature: a case study examining guidelines for school-based breakfast programs in Canada.

PubMed

Godin, Katelyn; Stapleton, Jackie; Kirkpatrick, Sharon I; Hanning, Rhona M; Leatherdale, Scott T

2015-10-22

Grey literature is an important source of information for large-scale review syntheses. However, there are many characteristics of grey literature that make it difficult to search systematically. Further, there is no 'gold standard' for rigorous systematic grey literature search methods and few resources on how to conduct this type of search. This paper describes systematic review search methods that were developed and applied to complete a case study systematic review of grey literature that examined guidelines for school-based breakfast programs in Canada. A grey literature search plan was developed to incorporate four different searching strategies: (1) grey literature databases, (2) customized Google search engines, (3) targeted websites, and (4) consultation with contact experts. These complementary strategies were used to minimize the risk of omitting relevant sources. Since abstracts are often unavailable in grey literature documents, items' abstracts, executive summaries, or table of contents (whichever was available) were screened. Screening of publications' full-text followed. Data were extracted on the organization, year published, who they were developed by, intended audience, goal/objectives of document, sources of evidence/resources cited, meals mentioned in the guidelines, and recommendations for program delivery. The search strategies for identifying and screening publications for inclusion in the case study review was found to be manageable, comprehensive, and intuitive when applied in practice. The four search strategies of the grey literature search plan yielded 302 potentially relevant items for screening. Following the screening process, 15 publications that met all eligibility criteria remained and were included in the case study systematic review. The high-level findings of the case study systematic review are briefly described. This article demonstrated a feasible and seemingly robust method for applying systematic search strategies to identify web-based resources in the grey literature. The search strategy we developed and tested is amenable to adaptation to identify other types of grey literature from other disciplines and answering a wide range of research questions. This method should be further adapted and tested in future research syntheses.

A marine bacterial adhesion microplate test using the DAPI fluorescent dye: a new method to screen antifouling agents.

PubMed

Leroy, C; Delbarre-Ladrat, C; Ghillebaert, F; Rochet, M J; Compère, C; Combes, D

2007-04-01

To develop a method to screen antifouling agents against marine bacterial adhesion as a sensitive, rapid and quantitative microplate fluorescent test. Our experimental method is based on a natural biofilm formed by mono-incubation of the marine bacterium Pseudoalteromonas sp. D41 in sterile natural sea water in a 96-well polystyrene microplate. The 4'6-diamidino-2-phenylindole dye was used to quantify adhered bacteria in each well. The total measured fluorescence in the wells was correlated with the amount of bacteria showing a detection limit of one bacterium per 5 microm(2) and quantifying 2 x 10(7) to 2 x 10(8) bacteria adhered per cm(2). The antifouling properties of three commercial surface-active agents and chlorine were tested by this method in the prevention of adhesion and also in the detachment of already adhered bacteria. The marine bacterial adhesion inhibition rate depending on the agent concentration showed a sigmoid shaped dose-response curve. This test is well adapted for a rapid and quantitative first screening of antifouling agents directly in seawater in the early steps of marine biofilm formation. In contrast to the usual screenings of antifouling products which detect a bactericidal activity, this test is more appropriate to screen antifouling agents for bacterial adhesion removal or bacterial adhesion inhibition activities. This screening test focuses on the antifouling properties of the products, especially the initial steps of marine biofilm formation.

A theoretical introduction to "combinatory SYBRGreen qPCR screening", a matrix-based approach for the detection of materials derived from genetically modified plants.

PubMed

Van den Bulcke, Marc; Lievens, Antoon; Barbau-Piednoir, Elodie; MbongoloMbella, Guillaume; Roosens, Nancy; Sneyers, Myriam; Casi, Amaya Leunda

2010-03-01

The detection of genetically modified (GM) materials in food and feed products is a complex multi-step analytical process invoking screening, identification, and often quantification of the genetically modified organisms (GMO) present in a sample. "Combinatory qPCR SYBRGreen screening" (CoSYPS) is a matrix-based approach for determining the presence of GM plant materials in products. The CoSYPS decision-support system (DSS) interprets the analytical results of SYBRGREEN qPCR analysis based on four values: the C(t)- and T(m) values and the LOD and LOQ for each method. A theoretical explanation of the different concepts applied in CoSYPS analysis is given (GMO Universe, "Prime number tracing", matrix/combinatory approach) and documented using the RoundUp Ready soy GTS40-3-2 as an example. By applying a limited set of SYBRGREEN qPCR methods and through application of a newly developed "prime number"-based algorithm, the nature of subsets of corresponding GMO in a sample can be determined. Together, these analyses provide guidance for semi-quantitative estimation of GMO presence in a food and feed product.

Simple and fast screening of G-quadruplex ligands with electrochemical detection system.

PubMed

Fan, Qiongxuan; Li, Chao; Tao, Yaqin; Mao, Xiaoxia; Li, Genxi

2016-11-01

Small molecules that may facilitate and stabilize the formation of G-quadruplexes can be used for cancer treatments, because the G-quadruplex structure can inhibit the activity of telomerase, an enzyme over-expressed in many cancer cells. Therefore, there is considerable interest in developing a simple and high-performance method for screening small molecules binding to G-quadruplex. Here, we have designed a simple electrochemical approach to screen such ligands based on the fact that the formation and stabilization of G-quadruplex by ligand may inhibit electron transfer of redox species to electrode surface. As a proof-of-concept study, two types of classical G-quadruplex ligands, TMPyP4 and BRACO-19, are studied in this work, which demonstrates that this method is fast and robust and it may be applied to screen G-quadruplex ligands for anticancer drugs testing and design in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Lung Cancer Screening Participation: Developing a Conceptual Model to Guide Research

PubMed Central

Carter-Harris, Lisa; Davis, Lorie L.; Rawl, Susan M.

2017-01-01

Purpose To describe the development of a conceptual model to guide research focused on lung cancer screening participation from the perspective of the individual in the decision-making process. Methods Based on a comprehensive review of empirical and theoretical literature, a conceptual model was developed linking key psychological variables (stigma, medical mistrust, fatalism, worry, and fear) to the health belief model and precaution adoption process model. Results Proposed model concepts have been examined in prior research of either lung or other cancer screening behavior. To date, a few studies have explored a limited number of variables that influence screening behavior in lung cancer specifically. Therefore, relationships among concepts in the model have been proposed and future research directions presented. Conclusion This proposed model is an initial step to support theoretically based research. As lung cancer screening becomes more widely implemented, it is critical to theoretically guide research to understand variables that may be associated with lung cancer screening participation. Findings from future research guided by the proposed conceptual model can be used to refine the model and inform tailored intervention development. PMID:28304262

Associations between Screen-Based Sedentary Behaviour and Anxiety Symptoms in Mothers with Young Children

PubMed Central

Teychenne, Megan; Hinkley, Trina

2016-01-01

Objectives Anxiety is a serious illness and women (including mothers with young children) are at particular risk. Although physical activity (PA) may reduce anxiety risk, little research has investigated the link between sedentary behaviour and anxiety risk. The aim of this study was to examine the association between screen-based sedentary behaviour and anxiety symptoms, independent of PA, amongst mothers with young children. Methods During 2013–2014, 528 mothers with children aged 2–5 years completed self-report measures of recreational screen-based sedentary behaviour (TV/DVD/video viewing, computer/e-games/hand held device use) and anxiety symptoms (using the Hospital Anxiety and Depression Scale, HADS-A). Linear regression analyses examined the cross-sectional association between screen-based sedentary behaviour and anxiety symptoms. Results In models that adjusted for key demographic and behavioural covariates (including moderate- to vigorous-intensity PA, MVPA), computer/device use (B = 0.212; 95% CI = 0.048, 0.377) and total screen time (B = 0.109; 95% CI = 0.014, 0.205) were positively associated with heightened anxiety symptoms. TV viewing was not associated with anxiety symptoms in either model. Conclusions Higher levels of recreational computer or handheld device use and overall screen time may be linked to higher risk of anxiety symptoms in mothers with young children, independent of MVPA. Further longitudinal and intervention research is required to determine temporal associations. PMID:27191953

Fluorometric method for inorganic pyrophosphatase activity detection and inhibitor screening based on click chemistry.

PubMed

Xu, Kefeng; Chen, Zhonghui; Zhou, Ling; Zheng, Ou; Wu, Xiaoping; Guo, Longhua; Qiu, Bin; Lin, Zhenyu; Chen, Guonan

2015-01-06

A fluorometric method for pyrophosphatase (PPase) activity detection was developed based on click chemistry. Cu(II) can coordinate with pyrophosphate (PPi), the addition of pyrophosphatase (PPase) into the above system can destroy the coordinate compound because PPase catalyzes the hydrolysis of PPi into inorganic phosphate and produces free Cu(II), and free Cu(II) can be reduced by sodium ascorbate (SA) to form Cu(I), which in turn initiates the ligating reaction between nonfluorescent 3-azidocoumarins and terminal alkynes to produce a highly fluorescent triazole complex, based on which, a simple and sensitive turn on fluorometric method for PPase can be developed. The fluorescence intensity of the system has a linear relationship with the logarithm of the PPase concentration in the range of 0.5 and 10 mU with a detection limit down to 0.2 mU (S/N = 3). This method is cost-effective and convenient without any labels or complicated operations. The proposed system was applied to screen the potential PPase inhibitor with high efficiency. The proposed method can be applied to diagnosis of PPase-related diseases.

Rectal swab sampling followed by an enrichment culture-based real-time PCR assay to detect Salmonella enterocolitis in children.

PubMed

Lin, L-H; Tsai, C-Y; Hung, M-H; Fang, Y-T; Ling, Q-D

2011-09-01

Although routine bacterial culture is the traditional reference standard method for the detection of Salmonella infection in children with diarrhoea, it is a time-consuming procedure that usually only gives results after 3-4 days. Some molecular detection methods can improve the turn-around time to within 24 h, but these methods are not applied directly from stool or rectal swab specimens as routine diagnostic methods for the detection of gastrointestinal pathogens. In this study, we tested the feasibility of a bacterial enrichment culture-based real-time PCR assay method for detecting and screening for diarrhoea in children caused by Salmonella. Our results showed that the minimum real-time PCR assay time required to detect enriched bacterial culture from a swab was 3 h. In all children with suspected Salmonella diarrhoea, the enrichment culture-based real-time PCR achieved 85.4% sensitivity and 98.1% specificity, as compared with the 53.7% sensitivity and 100% specificity of detection with the routine bacterial culture method. We suggest that rectal swab sampling followed by enrichment culture-based real-time PCR is suitable as a rapid method for detecting and screening for Salmonella in paediatric patients. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Interprofessional collaborative practice incorporating training for alcohol and drug use screening for healthcare providers in rural areas.

PubMed

Puskar, Kathy; Mitchell, Ann M; Albrecht, Susan A; Frank, Linda R; Kane, Irene; Hagle, Holly; Lindsay, Dawn; Lee, Heeyoung; Fioravanti, Marie; Talcott, Kimberly S

2016-07-01

Interprofessional collaborative practice expands resources in rural and underserved communities. This article explores the impact of an online education programme on the perceptions of healthcare providers about interprofessional care within alcohol and drug use screening for rural residents. Nurses, behavioural health counsellors, and public health professionals participated in an evidence-based practice (screening, brief intervention, and referral to treatment-SBIRT) model that targets individuals who use alcohol and other drugs in a risky manner. SBIRT is recommended by the United States Preventive Services Task Force as a universal, evidence-based screening tool. Online modules, case simulation practice, and interprofessional dialogues are used to deliver practice-based learning experiences. A quasi-experimental method with pre-tests and post-tests was utilised. Results indicate increased perceptions of professional competence, need for cooperation, actual cooperation, and role values pre-to-post training. Implications suggest that online interprofessional education is useful but the added component of professional dialogues regarding patient cases offers promise in promoting collaborative practice.

[Effectiveness of FTA Elute® indicating cartridge in combination with hybrid capture 2 for cervical cancer screening].

PubMed

Chen, Feng; Zhang, Xi; Wang, Shaoming; Hu, Shangying; Chen, Wen; Zhao, Fanghui; He, Wei; Zhang, Yuqing; Qiao, Youlin

2015-02-01

To evaluate the effectiveness of FTA Elute® Cartridge (GE healthcare, Kent, UK) in combination with hybrid capture 2 (HC2) testing for cervical cancer screening. From May to June 2012, 412 women aged 25 to 65 years in Jiangxi Tonggu were enrolled in the study. We used pathological outcome as the gold standard, and the accuracy of the FTA card in combination with HC2 testing was investigated from both physician- and self-sampling, respectively. Physician sampling using the FTA card in combination with HC2 testing showed a comparable sensitivity (12/13) with the liquid based medium, but a higher specificity 69.5% (266/383) vs (77.8%, 298/383) (P < 0.001).When self sampling method was used, the sensitivity and specificity of using the FTA card in combination with HC2 testing with liquid based medium was 10/13 vs 8/13(P = 0.625) and (62.3%, 238/382) vs (75.7%, 289/382) (P < 0.001). The agreement of detection results for HC2 between FTA and liquid-based sampling medium was 86.1% (340/395) and 79.5% (314/395). For physician-collected samples used for HC2 testing to detect CIN2+, the accuracy of the FTA card was superior to that of the liquid-based medium (area under the receiver operating characteristic curve (AUC) = 0.898, 95%CI:0.838-0.958). FTA Elute® cartridge in combination with HC2 testing is a promising method of specimen transport for cervical cancer screening programs with a good precision.With further optimization, it could become an effective method for cervical cancer screening in various economic levels of areas.

A Smartphone App to Screen for HIV-Related Neurocognitive Impairment

PubMed Central

Robbins, Reuben N.; Brown, Henry; Ehlers, Andries; Joska, John A.; Thomas, Kevin G.F.; Burgess, Rhonda; Byrd, Desiree; Morgello, Susan

2014-01-01

Background Neurocognitive Impairment (NCI) is one of the most common complications of HIV-infection, and has serious medical and functional consequences. However, screening for it is not routine and NCI often goes undiagnosed. Screening for NCI in HIV disease faces numerous challenges, such as limited screening tests, the need for specialized equipment and apparatuses, and highly trained personnel to administer, score and interpret screening tests. To address these challenges, we developed a novel smartphone-based screening tool, NeuroScreen, to detect HIV-related NCI that includes an easy-to-use graphical user interface with ten highly automated neuropsychological tests. Aims To examine NeuroScreen’s: 1) acceptability among patients and different potential users; 2) test construct and criterion validity; and 3) sensitivity and specificity to detect NCI. Methods Fifty HIV+ individuals were administered a gold-standard neuropsychological test battery, designed to detect HIV-related NCI, and NeuroScreen. HIV+ test participants and eight potential provider-users of NeuroScreen were asked about its acceptability. Results There was a high level of acceptability of NeuroScreen by patients and potential provider-users. Moderate to high correlations between individual NeuroScreen tests and paper-and-pencil tests assessing the same cognitive domains were observed. NeuroScreen also demonstrated high sensitivity to detect NCI. Conclusion NeuroScreen, a highly automated, easy-to-use smartphone-based screening test to detect NCI among HIV patients and usable by a range of healthcare personnel could help make routine screening for HIV-related NCI feasible. While NeuroScreen demonstrated robust psychometric properties and acceptability, further testing with larger and less neurocognitively impaired samples is warranted. PMID:24860624

Do Men and Women Need to Be Screened Differently with Fecal Immunochemical Testing? A Cost-Effectiveness Analysis.

PubMed

Meulen, Miriam P van der; Kapidzic, Atija; Leerdam, Monique E van; van der Steen, Alex; Kuipers, Ernst J; Spaander, Manon C W; de Koning, Harry J; Hol, Lieke; Lansdorp-Vogelaar, Iris

2017-08-01

Background: Several studies suggest that test characteristics for the fecal immunochemical test (FIT) differ by gender, triggering a debate on whether men and women should be screened differently. We used the microsimulation model MISCAN-Colon to evaluate whether screening stratified by gender is cost-effective. Methods: We estimated gender-specific FIT characteristics based on first-round positivity and detection rates observed in a FIT screening pilot (CORERO-1). Subsequently, we used the model to estimate harms, benefits, and costs of 480 gender-specific FIT screening strategies and compared them with uniform screening. Results: Biennial FIT screening from ages 50 to 75 was less effective in women than men [35.7 vs. 49.0 quality-adjusted life years (QALY) gained, respectively] at higher costs (€42,161 vs. -€5,471, respectively). However, the incremental QALYs gained and costs of annual screening compared with biennial screening were more similar for both genders (8.7 QALYs gained and €26,394 for women vs. 6.7 QALYs gained and €20,863 for men). Considering all evaluated screening strategies, optimal gender-based screening yielded at most 7% more QALYs gained than optimal uniform screening and even resulted in equal costs and QALYs gained from a willingness-to-pay threshold of €1,300. Conclusions: FIT screening is less effective in women, but the incremental cost-effectiveness is similar in men and women. Consequently, screening stratified by gender is not more cost-effective than uniform FIT screening. Impact: Our conclusions support the current policy of uniform FIT screening. Cancer Epidemiol Biomarkers Prev; 26(8); 1328-36. ©2017 AACR . ©2017 American Association for Cancer Research.

Rapid screening of bioactive compounds from natural products by integrating 5-channel parallel chromatography coupled with on-line mass spectrometry and microplate based assays.

PubMed

Zhang, Yufeng; Xiao, Shun; Sun, Lijuan; Ge, Zhiwei; Fang, Fengkai; Zhang, Wen; Wang, Yi; Cheng, Yiyu

2013-05-13

A high throughput method was developed for rapid screening and identification of bioactive compounds from traditional Chinese medicine, marine products and other natural products. The system, integrated with five-channel chromatographic separation and dual UV-MS detection, is compatible with in vitro 96-well microplate based bioassays. The stability and applicability of the proposed method was validated by testing radical scavenging capability of a mixture of seven known compounds (rutin, dihydroquercetin, salvianolic acid A, salvianolic acid B, glycyrrhizic acid, rubescensin A and tangeretin). Moreover, the proposed method was successfully applied to the crude extracts of traditional Chinese medicine and a marine sponge from which 12 bioactive compounds were screened and characterized based on their anti-oxidative or anti-tumor activities. In particular, two diterpenoid derivatives, agelasine B and (-)-agelasine D, were identified for the first time as anti-tumor compounds from the sponge Agelas mauritiana, showing a considerable activity toward MCF-7 cells (IC50 values of 7.84±0.65 and 10.48±0.84 μM, respectively). Our findings suggested that the integrated system of 5-channel parallel chromatography coupled with on-line mass spectrometry and microplate based assays can be a versatile and high efficient approach for the discovery of active compounds from natural products. Copyright © 2013 Elsevier B.V. All rights reserved.

Large-Scale Chemical Similarity Networks for Target Profiling of Compounds Identified in Cell-Based Chemical Screens

PubMed Central

Lo, Yu-Chen; Senese, Silvia; Li, Chien-Ming; Hu, Qiyang; Huang, Yong; Damoiseaux, Robert; Torres, Jorge Z.

2015-01-01

Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are limited to single or sequential ligand analysis that have limited capabilities for accurate deconvolution of a large number of compounds with diverse chemical structures. Here, we present CSNAP (Chemical Similarity Network Analysis Pulldown), a new computational target identification method that utilizes chemical similarity networks for large-scale chemotype (consensus chemical pattern) recognition and drug target profiling. Our benchmark study showed that CSNAP can achieve an overall higher accuracy (>80%) of target prediction with respect to representative chemotypes in large (>200) compound sets, in comparison to the SEA approach (60–70%). Additionally, CSNAP is capable of integrating with biological knowledge-based databases (Uniprot, GO) and high-throughput biology platforms (proteomic, genetic, etc) for system-wise drug target validation. To demonstrate the utility of the CSNAP approach, we combined CSNAP's target prediction with experimental ligand evaluation to identify the major mitotic targets of hit compounds from a cell-based chemical screen and we highlight novel compounds targeting microtubules, an important cancer therapeutic target. The CSNAP method is freely available and can be accessed from the CSNAP web server (http://services.mbi.ucla.edu/CSNAP/). PMID:25826798

A new system for parallel drug screening against multiple-resistant HIV mutants based on lentiviral self-inactivating (SIN) vectors and multi-colour analyses

PubMed Central

2013-01-01

Background Despite progress in the development of combined antiretroviral therapies (cART), HIV infection remains a significant challenge for human health. Current problems of cART include multi-drug-resistant virus variants, long-term toxicity and enormous treatment costs. Therefore, the identification of novel effective drugs is urgently needed. Methods We developed a straightforward screening approach for simultaneously evaluating the sensitivity of multiple HIV gag-pol mutants to antiviral drugs in one assay. Our technique is based on multi-colour lentiviral self-inactivating (SIN) LeGO vector technology. Results We demonstrated the successful use of this approach for screening compounds against up to four HIV gag-pol variants (wild-type and three mutants) simultaneously. Importantly, the technique was adapted to Biosafety Level 1 conditions by utilising ecotropic pseudotypes. This allowed upscaling to a large-scale screening protocol exploited by pharmaceutical companies in a successful proof-of-concept experiment. Conclusions The technology developed here facilitates fast screening for anti-HIV activity of individual agents from large compound libraries. Although drugs targeting gag-pol variants were used here, our approach permits screening compounds that target several different, key cellular and viral functions of the HIV life-cycle. The modular principle of the method also allows the easy exchange of various mutations in HIV sequences. In conclusion, the methodology presented here provides a valuable new approach for the identification of novel anti-HIV drugs. PMID:23286882

Erythropoietin abuse and erythropoietin gene doping: detection strategies in the genomic era.

PubMed

Diamanti-Kandarakis, Evanthia; Konstantinopoulos, Panagiotis A; Papailiou, Joanna; Kandarakis, Stylianos A; Andreopoulos, Anastasios; Sykiotis, Gerasimos P

2005-01-01

The administration of recombinant human erythropoietin (rhEPO) increases the maximum oxygen consumption capacity, and is therefore abused as a doping method in endurance sports. The detection of erythropoietin (EPO) abuse is based on direct pharmacological and indirect haematological approaches, both of which have several limitations. In addition, current detection methods cannot cope with the emerging doping strategies of EPO mimicry, analogues and gene doping, and thus novel detection strategies are urgently needed. Direct detection methods for EPO misuse can be either pharmacological approaches that identify exogenous substances based on their physicochemical properties, or molecular methods that recognise EPO transgenes or gene transfer vectors. Since direct detection with molecular methods requires invasive procedures, it is not appropriate for routine screening of large numbers of athletes. In contrast, novel indirect methods based on haematological and/or molecular profiling could be better suited as screening tools, and athletes who are suspect of doping would then be submitted to direct pharmacological and molecular tests. This article reviews the current state of the EPO doping field, discusses available detection methods and their shortcomings, outlines emerging pharmaceutical and genetic technologies in EPO misuse, and proposes potential directions for the development of novel detection strategies.

Screening and determination of polycyclic aromatic hydrocarbons in seafoods using QuEChERS-based extraction and high-performance liquid chromatography with fluorescence detection.

PubMed

Gratz, Samuel R; Ciolino, Laura A; Mohrhaus, Angela S; Gamble, Bryan M; Gracie, Jill M; Jackson, David S; Roetting, John P; McCauley, Heather A; Heitkemper, Douglas T; Fricke, Fred L; Krol, Walter J; Arsenault, Terri L; White, Jason C; Flottmeyer, Michele M; Johnson, Yoko S

2011-01-01

A rapid, sensitive, and accurate method for the screening and determination of polycyclic aromatic hydrocarbons (PAHs) in edible seafood is described. The method uses quick, easy, cheap, effective, rugged, and safe (QuEChERS)-based extraction and HPLC with fluorescence detection (FLD). The method was developed and validated in response to the massive Deepwater Horizon oil spill in the Gulf of Mexico. Rapid and highly sensitive PAH screening methods are critical tools needed for oil spill response; they help to assess when seafood is safe for harvesting and consumption. Sample preparation involves SPE of edible seafood portions with acetonitrile, followed by the addition of salts to induce water partitioning. After centrifugation, a portion of the acetonitrile layer is filtered prior to analysis via HPLC-FLD. The chromatographic method uses a polymeric C18 stationary phase designed for PAH analysis with gradient elution, and it resolves 15 U.S. Environmental Protection Agency priority parent PAHs in fewer than 20 min. The procedure was validated in three laboratories for the parent PAHs using spike recovery experiments at PAH fortification levels ranging from 25 to 10 000 microg/kg in oysters, shrimp, crab, and finfish, with recoveries ranging from 78 to 99%. Additional validation was conducted for a series of alkylated homologs of naphthalene, dibenzothiophene, and phenanthrene, with recoveries ranging from 87 to 128%. Method accuracy was further assessed based on analysis of National Institute of Standards and Technology Standard Reference Material 1974b. The method provides method detection limits in the sub to low ppb (microg/kg) range, and practical LOQs in the low ppb (microg/kg) range for most of the PAH compounds studied.

Potential biases in colorectal cancer screening using faecal occult blood test.

PubMed

Riboe, Dea Grip; Dogan, Tilde Steen; Brodersen, John

2013-04-01

Colorectal cancer (CRC) is one of the most common types of cancer in European countries and associated with a high mortality rate. A 16% relative risk reduction (RRR) of mortality was found in a meta-analysis based on four randomized controlled trials (RCT) on CRC screening. The aim of this paper was to scrutinize these trials for potential biases and assess their influence on the screening trials. The four RCTs were reviewed based on the principles of 'Critical Appraisal of the Medical Literature'. Principal investigators of the four RCTs were contacted to clarify uncertainties in their study. Data were collected from The Danish Data Archives. Authors of the Cochrane review were contacted. Six biases were identified, of which five favour screening. Three of the biases identified were specific to CRC screening: type of diagnostic method, place of surgery and diagnostic delay. The 16% RRR in CRC mortality found in the updated Cochrane review's meta-analysis is overestimated. © 2012 Blackwell Publishing Ltd.

A universal array-based multiplexed test for cystic fibrosis carrier screening.

PubMed

Amos, Jean A; Bridge-Cook, Philippa; Ponek, Victor; Jarvis, Michael R

2006-01-01

Cystic fibrosis is a multisystem autosomal recessive disorder with high carrier frequencies in caucasians and significant, but lower, carrier frequencies in other ethnicities. Based on technology that allows high detection of mutations in caucasians and significant detection in other ethnic groups, the American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG) have recommended pan-ethnic cystic fibrosis carrier screening for all reproductive couples. This paper discusses carrier screening using the Tag-It multiplex mutation platform and the Cystic Fibrosis Mutation Detection Kit. The Tag-It cystic fibrosis assay is a multiplexed genotyping assay that detects a panel of 40 cystic fibrosis transmembrane conductance regulator mutations including the 23 mutations recommended by the ACMG and ACOG for population screening. A total of 16 additional mutations detected by the Tag-It cystic fibrosis assay may also be common. The assay method is described in detail, and its performance in a genetics reference laboratory performing high-volume cystic fibrosis carrier screening is assessed.

High impact technologies for natural products screening.

PubMed

Koehn, Frank E

2008-01-01

Natural products have historically been a rich source of lead molecules in drug discovery. However, natural products have been de-emphasized as high throughput screening resources in the recent past, in part because of difficulties in obtaining high quality natural products screening libraries, or in applying modern screening assays to these libraries. In addition, natural products programs based on screening of extract libraries, bioassay-guided isolation, structure elucidation and subsequent production scale-up are challenged to meet the rapid cycle times that are characteristic of the modern HTS approach. Fortunately, new technologies in mass spectrometry, NMR and other spectroscopic techniques can greatly facilitate the first components of the process - namely the efficient creation of high-quality natural products libraries, bimolecular target or cell-based screening, and early hit characterization. The success of any high throughput screening campaign is dependent on the quality of the chemical library. The construction and maintenance of a high quality natural products library, whether based on microbial, plant, marine or other sources is a costly endeavor. The library itself may be composed of samples that are themselves mixtures - such as crude extracts, semi-pure mixtures or single purified natural products. Each of these library designs carries with it distinctive advantages and disadvantages. Crude extract libraries have lower resource requirements for sample preparation, but high requirements for identification of the bioactive constituents. Pre-fractionated libraries can be an effective strategy to alleviate interferences encountered with crude libraries, and may shorten the time needed to identify the active principle. Purified natural product libraries require substantial resources for preparation, but offer the advantage that the hit detection process is reduced to that of synthetic single component libraries. Whether the natural products library consists of crude or partially fractionated mixtures, the library contents should be profiled to identify the known components present - a process known as dereplication. The use of mass spectrometry and HPLC-mass spectrometry together with spectral databases is a powerful tool in the chemometric profiling of bio-sources for natural product production. High throughput, high sensitivity flow NMR is an emerging tool in this area as well. Whether by cell based or biomolecular target based assays, screening of natural product extract libraries continues to furnish novel lead molecules for further drug development, despite challenges in the analysis and prioritization of natural products hits. Spectroscopic techniques are now being used to directly screen natural product and synthetic libraries. Mass spectrometry in the form of methods such as ESI-ICRFTMS, and FACS-MS as well as NMR methods such as SAR by NMR and STD-NMR have been utilized to effectively screen molecular libraries. Overall, emerging advances in mass spectrometry, NMR and other technologies are making it possible to overcome the challenges encountered in screening natural products libraries in today's drug discovery environment. As we apply these technologies and develop them even further, we can look forward to increased impact of natural products in the HTS based drug discovery.

Continuous flow immobilized enzyme reactor-tandem mass spectrometry for screening of AChE inhibitors in complex mixtures.

PubMed

Forsberg, Erica M; Green, James R A; Brennan, John D

2011-07-01

A method is described for identifying bioactive compounds in complex mixtures based on the use of capillary-scale monolithic enzyme-reactor columns for rapid screening of enzyme activity. A two-channel nanoLC system was used to continuously infuse substrate coupled with automated injections of substrate/small molecule mixtures, optionally containing the chromogenic Ellman reagent, through sol-gel derived acetylcholinesterase (AChE) doped monolithic columns. This is the first report of AChE encapsulated in monolithic silica for use as an immobilized enzyme reactor (IMER), and the first use of such IMERs for mixture screening. AChE IMER columns were optimized to allow rapid functional screening of compound mixtures based on changes in the product absorbance or the ratio of mass spectrometric peaks for product and substrate ions in the eluent. The assay had robust performance and produced a Z' factor of 0.77 in the presence of 2% (v/v) DMSO. A series of 52 mixtures consisting of 1040 compounds from the Canadian Compound Collection of bioactives was screened and two known inhibitors, physostigmine and 9-aminoacridine, were identified from active mixtures by manual deconvolution. The activity of the compounds was confirmed using the enzyme reactor format, which allowed determination of both IC(50) and K(I) values. Screening results were found to correlate well with a recently published fluorescence-based microarray screening assay for AChE inhibitors.

Service Use by At-Risk Youth after School-Based Suicide Screening

PubMed Central

2009-01-01

Objective We sought to examine follow-up service use by students identified at risk for suicidal behavior in a school-based screening program, and assess barriers to seeking services as perceived by youth and parents. Method We conducted a longitudinal study of 317 at-risk youth identified by a school-based suicide screening in six high schools in New York State. The at-risk teenagers and their parents were interviewed approximately two years after the initial screen to assess service use during the intervening period and identify barriers that may have interfered with seeking treatment. Results At the time of the screen, 72% of the at-risk students were not receiving any type of mental health service. Of these students, 51% were deemed in need of services and subsequently referred by us to a mental health professional. Nearly 70% followed through with the screening’s referral recommendations. Youth and their parents reported perceptions about mental health problems, specifically relating to the need for treatment, as the primary reasons for not seeking service. Conclusions Screening appears to be effective in enhancing the likelihood that students at risk for suicidal behavior will get into treatment. Well developed and systematic planning is needed to ensure that screening and referral services are coordinated so as to facilitate access for youth into timely treatment. PMID:19858758

A pre-classification strategy based on UPLC-Triple-TOF/MS for metabolic screening and identification of Radix glehniae in rats.

PubMed

Wang, Shuang; Qi, Pengcheng; Zhou, Na; Zhao, Minmin; Ding, Weijing; Li, Song; Liu, Minyan; Wang, Qiao; Jin, Shumin

2016-10-01

Traditional Chinese Medicines (TCMs) have gained increasing popularity in modern society. However, the profiles of TCMs in vivo are still unclear owing to their complexity and low level in vivo. In this study, UPLC-Triple-TOF techniques were employed for data acquiring, and a novel pre-classification strategy was developed to rapidly and systematically screen and identify the absorbed constituents and metabolites of TCMs in vivo using Radix glehniae as the research object. In this strategy, pre-classification for absorbed constituents was first performed according to the similarity of their structures. Then representative constituents were elected from every class and analyzed separately to screen non-target absorbed constituents and metabolites in biosamples. This pre-classification strategy is basing on target (known) constituents to screen non-target (unknown) constituents from the massive data acquired by mass spectrometry. Finally, the screened candidate compounds were interpreted and identified based on a predicted metabolic pathway, well - studied fragmentation rules, a predicted metabolic pathway, polarity and retention time of the compounds, and some related literature. With this method, a total of 111 absorbed constituents and metabolites of Radix glehniae in rats' urine, plasma, and bile samples were screened and identified or tentatively characterized successfully. This strategy provides an idea for the screening and identification of the metabolites of other TCMs.

3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors.

PubMed

Fu, Ying; Sun, Yi-Na; Yi, Ke-Han; Li, Ming-Qiang; Cao, Hai-Feng; Li, Jia-Zhong; Ye, Fei

2017-06-09

p -Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD inhibitors. The complex-based pharmacophore model (CBP) with 0.721 of ROC used for screening compounds showed remarkable ability to retrieve known active ligands from among decoy molecules. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5 (DS 2.5) to discern interactions with key residues at the active site of HPPD. Four compounds with top rankings in the HipHop model and well-known binding model were finally chosen as lead compounds with potential inhibitory effects on the active site of target. The results provided powerful insight into the development of novel HPPD inhibitors herbicides using computational techniques.

Is a Perceived Activity-Friendly Environment Associated with More Physical Activity and Fewer Screen-Based Activities in Adolescents?

PubMed

Kopcakova, Jaroslava; Dankulincova Veselska, Zuzana; Madarasova Geckova, Andrea; Bucksch, Jens; Nalecz, Hanna; Sigmundova, Dagmar; van Dijk, Jitse P; Reijneveld, Sijmen A

2017-01-03

Background: The aim of this study is to explore if perception of an activity-friendly environment is associated with more physical activity and fewer screen-based activities among adolescents. Methods: We collected self-reported data in 2014 via the Health Behavior in School-aged Children cross-sectional study from four European countries ( n = 13,800, mean age = 14.4, 49.4% boys). We explored the association of perceived environment (e.g., "There are other children nearby home to go out and play with") with physical activity and screen-based activities using a binary logistic regression model adjusted for age, gender, family affluence and country. Results: An environment perceived as activity-friendly was associated with higher odds that adolescents meet recommendations for physical activity (odds ratio (OR) for one standard deviation (SD) change = 1.11, 95% confidence interval (CI) 1.05-1.18) and lower odds for excessive screen-based activities (OR for 1 SD better = 0.93, 95% CI 0.88-0.98). Conclusions: Investment into an activity-friendly environment may support the promotion of active life styles in adolescence.

Using model-based screening to help discover unknown environmental contaminants.

PubMed

McLachlan, Michael S; Kierkegaard, Amelie; Radke, Michael; Sobek, Anna; Malmvärn, Anna; Alsberg, Tomas; Arnot, Jon A; Brown, Trevor N; Wania, Frank; Breivik, Knut; Xu, Shihe

2014-07-01

Of the tens of thousands of chemicals in use, only a small fraction have been analyzed in environmental samples. To effectively identify environmental contaminants, methods to prioritize chemicals for analytical method development are required. We used a high-throughput model of chemical emissions, fate, and bioaccumulation to identify chemicals likely to have high concentrations in specific environmental media, and we prioritized these for target analysis. This model-based screening was applied to 215 organosilicon chemicals culled from industrial chemical production statistics. The model-based screening prioritized several recognized organosilicon contaminants and generated hypotheses leading to the selection of three chemicals that have not previously been identified as potential environmental contaminants for target analysis. Trace analytical methods were developed, and the chemicals were analyzed in air, sewage sludge, and sediment. All three substances were found to be environmental contaminants. Phenyl-tris(trimethylsiloxy)silane was present in all samples analyzed, with concentrations of ∼50 pg m(-3) in Stockholm air and ∼0.5 ng g(-1) dw in sediment from the Stockholm archipelago. Tris(trifluoropropyl)trimethyl-cyclotrisiloxane and tetrakis(trifluoropropyl)tetramethyl-cyclotetrasiloxane were found in sediments from Lake Mjøsa at ∼1 ng g(-1) dw. The discovery of three novel environmental contaminants shows that models can be useful for prioritizing chemicals for exploratory assessment.

Review of the Potential of the Ni/Cu Plating Technique for Crystalline Silicon Solar Cells

PubMed Central

Rehman, Atteq ur; Lee, Soo Hong

2014-01-01

Developing a better method for the metallization of silicon solar cells is integral part of realizing superior efficiency. Currently, contact realization using screen printing is the leading technology in the silicon based photovoltaic industry, as it is simple and fast. However, the problem with metallization of this kind is that it has a lower aspect ratio and higher contact resistance, which limits solar cell efficiency. The mounting cost of silver pastes and decreasing silicon wafer thicknesses encourages silicon solar cell manufacturers to develop fresh metallization techniques involving a lower quantity of silver usage and not relying pressing process of screen printing. In recent times nickel/copper (Ni/Cu) based metal plating has emerged as a metallization method that may solve these issues. This paper offers a detailed review and understanding of a Ni/Cu based plating technique for silicon solar cells. The formation of a Ni seed layer by adopting various deposition techniques and a Cu conducting layer using a light induced plating (LIP) process are appraised. Unlike screen-printed metallization, a step involving patterning is crucial for opening the masking layer. Consequently, experimental procedures involving patterning methods are also explicated. Lastly, the issues of adhesion, back ground plating, process complexity and reliability for industrial applications are also addressed. PMID:28788516

Review of the Potential of the Ni/Cu Plating Technique for Crystalline Silicon Solar Cells.

PubMed

Rehman, Atteq Ur; Lee, Soo Hong

2014-02-18

Developing a better method for the metallization of silicon solar cells is integral part of realizing superior efficiency. Currently, contact realization using screen printing is the leading technology in the silicon based photovoltaic industry, as it is simple and fast. However, the problem with metallization of this kind is that it has a lower aspect ratio and higher contact resistance, which limits solar cell efficiency. The mounting cost of silver pastes and decreasing silicon wafer thicknesses encourages silicon solar cell manufacturers to develop fresh metallization techniques involving a lower quantity of silver usage and not relying pressing process of screen printing. In recent times nickel/copper (Ni/Cu) based metal plating has emerged as a metallization method that may solve these issues. This paper offers a detailed review and understanding of a Ni/Cu based plating technique for silicon solar cells. The formation of a Ni seed layer by adopting various deposition techniques and a Cu conducting layer using a light induced plating (LIP) process are appraised. Unlike screen-printed metallization, a step involving patterning is crucial for opening the masking layer. Consequently, experimental procedures involving patterning methods are also explicated. Lastly, the issues of adhesion, back ground plating, process complexity and reliability for industrial applications are also addressed.

Feature Screening for Ultrahigh Dimensional Categorical Data with Applications.

PubMed

Huang, Danyang; Li, Runze; Wang, Hansheng

2014-01-01

Ultrahigh dimensional data with both categorical responses and categorical covariates are frequently encountered in the analysis of big data, for which feature screening has become an indispensable statistical tool. We propose a Pearson chi-square based feature screening procedure for categorical response with ultrahigh dimensional categorical covariates. The proposed procedure can be directly applied for detection of important interaction effects. We further show that the proposed procedure possesses screening consistency property in the terminology of Fan and Lv (2008). We investigate the finite sample performance of the proposed procedure by Monte Carlo simulation studies, and illustrate the proposed method by two empirical datasets.

Nurse's Desk: food bank-based outreach and screening to decrease unmet referral needs.

PubMed

Larsson, Laura S; Kuster, Emilie

2013-01-01

The Nurse's Desk health screening project used the Intervention Wheel model to conduct outreach, screening, education, and referral for food bank clients (n = 506). Blood glucose, blood pressure, health care utilization, and unmet referral needs were assessed. Screening results identified 318 clients (62.8%) with 1 or more unmet referral needs, including 6 clients (3.16%) with capillary blood glucose more than 199 mg/dL and 132 (31.9%) with hypertension. Clients had higher-than-average systolic and diastolic blood pressures and undiagnosed diabetes than in the general population. A client-approved method for tracking completed referrals is needed for this potentially high-risk population.

A Field Test of Web-Based Screening for Dry Eye Disease to Enhance Awareness of Eye Problems Among General Internet Users: A Latent Strategy to Promote Health

PubMed Central

Uchino, Miki; Kawazoe, Takashi; Kamiyashiki, Masaaki; Sano, Kokoro; Tsubota, Kazuo

2013-01-01

Background A Web-based self-check system including a brief questionnaire would seem to be a suitable tool for rapid disease screening. Objective The purpose of this preliminary study was to test a Web-based self-screening questionnaire for drawing attention to dry eye disease among general Internet users and identifying those with a higher risk of developing the condition. Methods A survey website was launched and used to recruit participants from general Internet users. In the first phase, volunteers were asked to complete a Web-based self-screening questionnaire containing 12 questions on dry eye symptoms. The second phase focused on the respondents who reported five or more dry eye symptoms and expressed their intention to seek medical attention. These participants performed the Schirmer test, for evaluating tear production, and completed a paper-based lifestyle questionnaire to provide relevant background data. Results Of the 1689 visitors to the website, 980 (58.0%) volunteers completed the Web-based self-screening questionnaire. Among these, 355 (36.2%) respondents reported five or more dry eye symptoms. Then, 99 (27.9%) of the symptomatic participants performed the Schirmer test and completed the paper-based lifestyle questionnaire. Out of these, 32 (32.2%) had abnormal tear production (≤5 mm). Conclusions The proposed Web-based self-screening questionnaire seems to be a promising tool for raising awareness of dry eye disease among general Internet users and identifying those with a higher risk of developing the condition, although further research is needed to validate its effectiveness. PMID:24072379

Localization-based super-resolution imaging meets high-content screening.

PubMed

Beghin, Anne; Kechkar, Adel; Butler, Corey; Levet, Florian; Cabillic, Marine; Rossier, Olivier; Giannone, Gregory; Galland, Rémi; Choquet, Daniel; Sibarita, Jean-Baptiste

2017-12-01

Single-molecule localization microscopy techniques have proven to be essential tools for quantitatively monitoring biological processes at unprecedented spatial resolution. However, these techniques are very low throughput and are not yet compatible with fully automated, multiparametric cellular assays. This shortcoming is primarily due to the huge amount of data generated during imaging and the lack of software for automation and dedicated data mining. We describe an automated quantitative single-molecule-based super-resolution methodology that operates in standard multiwell plates and uses analysis based on high-content screening and data-mining software. The workflow is compatible with fixed- and live-cell imaging and allows extraction of quantitative data like fluorophore photophysics, protein clustering or dynamic behavior of biomolecules. We demonstrate that the method is compatible with high-content screening using 3D dSTORM and DNA-PAINT based super-resolution microscopy as well as single-particle tracking.

Multi-component identification and target cell-based screening of potential bioactive compounds in toad venom by UPLC coupled with high-resolution LTQ-Orbitrap MS and high-sensitivity Qtrap MS.

PubMed

Ren, Wei; Han, Lingyu; Luo, Mengyi; Bian, Baolin; Guan, Ming; Yang, Hui; Han, Chao; Li, Na; Li, Tuo; Li, Shilei; Zhang, Yangyang; Zhao, Zhenwen; Zhao, Haiyu

2018-04-28

Traditional Chinese medicines (TCMs) are undoubtedly treasured natural resources for discovering effective medicines in treating and preventing various diseases. However, it is still extremely difficult for screening the bioactive compounds due to the tremendous constituents in TCMs. In this work, the chemical composition of toad venom was comprehensively analyzed using ultra-high performance liquid chromatography (UPLC) coupled with high-resolution LTQ-Orbitrap mass spectrometry and 93 compounds were detected. Among them, 17 constituents were confirmed by standard substances and 8 constituents were detected in toad venom for the first time. Further, a compound database of toad venom containing the fullest compounds was further constructed using UPLC coupled with high-sensitivity Qtrap MS. Then a target cell-based approach for screening potential bioactive compounds from toad venom was developed by analyzing the target cell extracts. The reliability of this method was validated by negative controls and positive controls. In total, 17 components in toad venom were discovered to interact with the target cancer cells. Further, in vitro pharmacological trials were performed to confirm the anti-cancer activity of four of them. The results showed that the six bufogenins and seven bufotoxins detected in our research represented a promising resource to explore bufogenins/bufotoxins-based anticancer agents with low cardiotoxic effect. The target cell-based screening method coupled with the compound database of toad venom constructed by UPLC-Qtrap-MS with high sensitivity provide us a new strategy to rapidly screen and identify the potential bioactive constituents with low content in natural products, which was beneficial for drug discovery from other TCMs. ᅟ Graphical abstract.

Method and apparatus for making absolute range measurements

DOEpatents

Earl, Dennis D [Knoxville, TN; Allison, Stephen W [Knoxville, TN; Cates, Michael R [Oak Ridge, TN; Sanders, Alvin J [Knoxville, TN

2002-09-24

This invention relates to a method and apparatus for making absolute distance or ranging measurements using Fresnel diffraction. The invention employs a source of electromagnetic radiation having a known wavelength or wavelength distribution, which sends a beam of electromagnetic radiation through a screen at least partially opaque at the wavelength. The screen has an aperture sized so as to produce a Fresnel diffraction pattern. A portion of the beam travels through the aperture to a detector spaced some distance from the screen. The detector detects the central intensity of the beam as well as a set of intensities displaced from a center of the aperture. The distance from the source to the target can then be calculated based upon the known wavelength, aperture radius, and beam intensity.

Real-time detection method and system for identifying individual aerosol particles

DOEpatents

Gard, Eric E [San Francisco, CA; Coffee, Keith R [Patterson, CA; Frank, Matthias [Oakland, CA; Tobias, Herbert J [Kensington, CA; Fergenson, David P [Alamo, CA; Madden, Norm [Livermore, CA; Riot, Vincent J [Berkeley, CA; Steele, Paul T [Livermore, CA; Woods, Bruce W [Livermore, CA

2007-08-21

An improved method and system of identifying individual aerosol particles in real time. Sample aerosol particles are collimated, tracked, and screened to determine which ones qualify for mass spectrometric analysis based on predetermined qualification or selection criteria. Screening techniques include one or more of determining particle size, shape, symmetry, and fluorescence. Only qualifying particles passing all screening criteria are subject to desorption/ionization and single particle mass spectrometry to produce corresponding test spectra, which is used to determine the identities of each of the qualifying aerosol particles by comparing the test spectra against predetermined spectra for known particle types. In this manner, activation cycling of a particle ablation laser of a single particle mass spectrometer is reduced.

Proposal for a new protein therapeutic immunogenicity titer assay cutpoint.

PubMed

Wakshull, Eric; Hendricks, Robert; Amaya, Caroline; Coleman, Daniel

2011-12-01

Generally, immunogenicity assessment strategies follow this assay triage schema: screen→confirm→titer. Each requires the determination of a threshold value (cutpoint) for decision making. No guidance documents exist for the determination of a specific titration assay cutpoint. The default practice is to use the screening assay cutpoint, frequently leading to controls or samples not reaching this cutpoint. We propose a method for determination of a titration cutpoint based upon the variance of the negative-control sample. Positive-control samples that did not cross a screening cutpoint did cross the titer cutpoint, albeit generating slightly lower titer values. Our approach is consistent with the statistical methods currently recommended for the screening and confirmatory assay cutpoints and is operationally simple and efficient.

Display screen and method of manufacture therefor

NASA Technical Reports Server (NTRS)

Dubin, Matthew B. (Inventor); Larson, Brent D. (Inventor)

2002-01-01

A screen assembly that combines an angle re-distributing prescreen with a conventional diffusion screen. The prescreen minimizes or eliminates the sensitivity of the screen assembly to projector location. The diffusion screen provides other desirable screen characteristics. Compatible screen structures, along with methods for fabricating high resolution prescreens and methods and devices for maintaining the desired relationship between the prescreen and the diffusion screen are contemplated.

An ultrasensitive chemiluminescence immunoassay of chloramphenicol based on gold nanoparticles and magnetic beads.

PubMed

Tao, Xiaoqi; Jiang, Haiyang; Yu, Xuezhi; Zhu, Jinghui; Wang, Xia; Wang, Zhanhui; Niu, Lanlan; Wu, Xiaoping; Shen, Jianzhong

2013-05-01

A competitive, direct, chemiluminescent immunoassay based on a magnetic beads (MBs) separation and gold nanoparticles (AuNPs) labelling technique to detect chloramphenicol (CAP) has been developed. Horseradish peroxidase (HRP)-labelled anti-CAP monoclonal antibody conjugated with AuNPs and antigen-immobilized MBs were prepared. After optimization parameters of immunocomplex MBs, the IC50 values of chemiluminescence magnetic nanoparticles immunoassay (CL-MBs-nano-immunoassay) were 0.017 µg L(-1) for extract method I and 0.17 µg L(-1) for extract method II. The immunoassay with two extract methods was applied to detect CAP in milk. Comparison of these two extract methods showed that extract method I was advantageous in better sensitivity, in which the sensitivity was 10 times compared to that of extract method II, while extract method II was superior in simple operation, suitable for high throughout screen. The recoveries were 86.7-98.0% (extract method I) and 80.0-103.0% (extract method II), and the coefficients of variation (CVs) were all <15%. The satisfactory recovery with both extract methods and high correlation with traditional ELISA kit in milk system confirmed that the immunomagnetic assay based on AuNPs exhibited promising potential in rapid field screening for trace CAP analysis. Copyright © 2013 John Wiley & Sons, Ltd.

Cost-effectiveness of population-based vascular disease screening and intervention in men from the Viborg Vascular (VIVA) trial.

PubMed

Søgaard, R; Lindholt, J S

2018-04-25

Population-based screening and intervention for abdominal aortic aneurysm, peripheral artery disease and hypertension was recently reported to reduce the relative risk of mortality among Danish men by 7 per cent. The aim of this study was to investigate the cost-effectiveness of vascular screening versus usual care (ad hoc primary care-based risk assessment) from a national health service perspective. A cost-effectiveness evaluation was conducted alongside an RCT involving all men from a region in Denmark (50 156) who were allocated to screening (25 078) or no screening (25 078) and followed for up to 5 years. Mobile nurse teams provided screening locally and, for individuals with positive test results, referrals were made to general practices or hospital-based specialized centres for vascular surgery. Intention-to-treat-based, censoring-adjusted incremental costs (2014 euros), life-years and quality-adjusted life-years (QALYs) were estimated using Lin's average estimator method. Incremental net benefit was estimated using Willan's estimator and sensitivity analyses were conducted. The cost of screening was estimated at €148 (95 per cent c.i. 126 to 169), and the effectiveness at 0·022 (95 per cent c.i. 0·006 to 0·038) life-years and 0·069 (0·054 to 0·083) QALYs, generating average costs of €6872 per life-year and €2148 per QALY. At a willingness-to-pay threshold of €40 000 per QALY, the probabilities of cost-effectiveness were 98 and 99 per cent respectively. The probability of cost-effectiveness was 71 per cent when all the sensitivity analyses were combined into one conservative scenario. Vascular screening appears to be cost-effective and compares favourably with current screening programmes. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Comparison of enzyme-linked immunosorbent assay, surface plasmon resonance and biolayer interferometry for screening of deoxynivalenol in wheat and wheat dust

USDA-ARS?s Scientific Manuscript database

A sample preparation method was developed for the screening of deoxynivalenol (DON) in wheat and wheat dust. Extraction was carried out with water and was successful due to the polar character of DON. For detection, an enzyme-linked immunosorbent assay (ELISA) was compared to the sensor-based techni...

Outcomes of a Breast Health Project for Hmong Women and Men in California

PubMed Central

Tanjasiri, Sora Park; Valdez, Annalyn; Yu, Hongjian; Foo, Mary Anne

2009-01-01

Objectives. We used a community-based research approach to test a culturally based breast cancer screening program among low-income Hmong women in central and southern California. Methods. We designed a culturally informed educational program with measures at baseline and 1-year follow-up in 2 intervention cities and 1 comparison city. Measures included changes in breast cancer screening, knowledge, and attitudes. Results. Compared with women in the comparison community, women in the intervention community significantly improved their attitudes toward, and increased their knowledge and receipt of, breast cancer screenings. Odds of women in the intervention group having had a mammogram, having had a clinical breast examination, and having performed breast self-examination was 6.75, 12.16, and 20.06, respectively, compared with women in the comparison group. Conclusions. Culturally informed education materials and intervention design were effective methods in conveying the importance of maintaining and monitoring proper breast health. The strength of community collaboration in survey development and intervention design highlighted the challenges of early detection and screening programs among newer immigrants, who face significant language and cultural barriers to care, and identified promising practices to overcome these health literacy challenges. PMID:19443830

A utility/cost analysis of breast cancer risk prediction algorithms

NASA Astrophysics Data System (ADS)

Abbey, Craig K.; Wu, Yirong; Burnside, Elizabeth S.; Wunderlich, Adam; Samuelson, Frank W.; Boone, John M.

2016-03-01

Breast cancer risk prediction algorithms are used to identify subpopulations that are at increased risk for developing breast cancer. They can be based on many different sources of data such as demographics, relatives with cancer, gene expression, and various phenotypic features such as breast density. Women who are identified as high risk may undergo a more extensive (and expensive) screening process that includes MRI or ultrasound imaging in addition to the standard full-field digital mammography (FFDM) exam. Given that there are many ways that risk prediction may be accomplished, it is of interest to evaluate them in terms of expected cost, which includes the costs of diagnostic outcomes. In this work we perform an expected-cost analysis of risk prediction algorithms that is based on a published model that includes the costs associated with diagnostic outcomes (true-positive, false-positive, etc.). We assume the existence of a standard screening method and an enhanced screening method with higher scan cost, higher sensitivity, and lower specificity. We then assess expected cost of using a risk prediction algorithm to determine who gets the enhanced screening method under the strong assumption that risk and diagnostic performance are independent. We find that if risk prediction leads to a high enough positive predictive value, it will be cost-effective regardless of the size of the subpopulation. Furthermore, in terms of the hit-rate and false-alarm rate of the of the risk prediction algorithm, iso-cost contours are lines with slope determined by properties of the available diagnostic systems for screening.