A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening.

Science.gov (United States)

Fowler, Karen B; McCollister, Faye P; Sabo, Diane L; Shoup, Angela G; Owen, Kris E; Woodruff, Julie L; Cox, Edith; Mohamed, Lisa S; Choo, Daniel I; Boppana, Suresh B

2017-02-01

Congenital cytomegalovirus (cCMV) infection remains a leading cause of childhood hearing loss. Currently universal CMV screening at birth does not exist in the United States. An alternative approach could be testing infants who do not pass their newborn hearing screening (NHS) for cCMV. This study was undertaken to evaluate whether a targeted approach will identify infants with CMV-related sensorineural hearing loss (SNHL). Infants born at 7 US medical centers received NHS and were also screened for cCMV while in the newborn nursery. Infants who tested positive for CMV received further diagnostic audiologic evaluations to identify or confirm hearing loss. Between 2007 and 2012, 99 945 newborns were screened for both hearing impairment and cCMV. Overall, 7.0% of CMV-positive infants did not pass NHS compared with 0.9% of CMV-negative infants (P CMV-infected infants who passed their NHS had SNHL confirmed by further evaluation during early infancy. NHS in this cohort identified 57% of all CMV-related SNHL that occurred in the neonatal period. A targeted CMV approach that tests newborns who fail their NHS identified the majority of infants with CMV-related SNHL at birth. However, 43% of the infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk for late onset SNHL were not identified by NHS. Copyright © 2017 by the American Academy of Pediatrics.

Oral cancer screening: serum Raman spectroscopic approach

Science.gov (United States)

Sahu, Aditi K.; Dhoot, Suyash; Singh, Amandeep; Sawant, Sharada S.; Nandakumar, Nikhila; Talathi-Desai, Sneha; Garud, Mandavi; Pagare, Sandeep; Srivastava, Sanjeeva; Nair, Sudhir; Chaturvedi, Pankaj; Murali Krishna, C.

2015-11-01

Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe. Spectral findings suggest changes in amino acids, lipids, protein, DNA, and β-carotene across the groups. A patient-wise approach was employed for data analysis using principal component linear discriminant analysis. In the first step, the classification among premalignant, disease control (nonoral cancer), oral cancer, and normal samples was evaluated in binary classification models. Thereafter, two screening-friendly classification approaches were explored to further evaluate the clinical utility of serum RS: a single four-group model and normal versus abnormal followed by determining the type of abnormality model. Results demonstrate the feasibility of premalignant and specific cancer detection. The normal versus abnormal model yields better sensitivity and specificity rates of 64 and 80% these rates are comparable to standard screening approaches. Prospectively, as the current screening procedure of visual inspection is useful mainly for high-risk populations, serum RS may serve as a useful adjunct for early and specific detection of oral precancers and cancer.

Lead identification for the K-Ras protein: virtual screening and combinatorial fragment-based approaches

Directory of Open Access Journals (Sweden)

Pathan AAK

2016-05-01

Full Text Available Akbar Ali Khan Pathan,1,2,* Bhavana Panthi,3,* Zahid Khan,1 Purushotham Reddy Koppula,4–6 Mohammed Saud Alanazi,1 Sachchidanand,3 Narasimha Reddy Parine,1 Mukesh Chourasia3,* 1Genome Research Chair (GRC, Department of Biochemistry, College of Science, King Saud University, 2Integrated Gulf Biosystems, Riyadh, Kingdom of Saudi Arabia; 3Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Hajipur, India; 4Department of Internal Medicine, School of Medicine, 5Harry S. Truman Memorial Veterans Affairs Hospital, 6Department of Radiology, School of Medicine, Columbia, MO, USA *These authors contributed equally to this work Objective: Kirsten rat sarcoma (K-Ras protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods: In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results: Interestingly, the designed compounds exhibit a binding preference for the �

A practical approach to screen for authorised and unauthorised genetically modified plants.

Science.gov (United States)

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.

The influence of the negative-positive ratio and screening database size on the performance of machine learning-based virtual screening.

Science.gov (United States)

Kurczab, Rafał; Bojarski, Andrzej J

2017-01-01

The machine learning-based virtual screening of molecular databases is a commonly used approach to identify hits. However, many aspects associated with training predictive models can influence the final performance and, consequently, the number of hits found. Thus, we performed a systematic study of the simultaneous influence of the proportion of negatives to positives in the testing set, the size of screening databases and the type of molecular representations on the effectiveness of classification. The results obtained for eight protein targets, five machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest), two types of molecular fingerprints (MACCS and CDK FP) and eight screening databases with different numbers of molecules confirmed our previous findings that increases in the ratio of negative to positive training instances greatly influenced most of the investigated parameters of the ML methods in simulated virtual screening experiments. However, the performance of screening was shown to also be highly dependent on the molecular library dimension. Generally, with the increasing size of the screened database, the optimal training ratio also increased, and this ratio can be rationalized using the proposed cost-effectiveness threshold approach. To increase the performance of machine learning-based virtual screening, the training set should be constructed in a way that considers the size of the screening database.

iScreen: Image-Based High-Content RNAi Screening Analysis Tools.

Science.gov (United States)

Zhong, Rui; Dong, Xiaonan; Levine, Beth; Xie, Yang; Xiao, Guanghua

2015-09-01

High-throughput RNA interference (RNAi) screening has opened up a path to investigating functional genomics in a genome-wide pattern. However, such studies are often restricted to assays that have a single readout format. Recently, advanced image technologies have been coupled with high-throughput RNAi screening to develop high-content screening, in which one or more cell image(s), instead of a single readout, were generated from each well. This image-based high-content screening technology has led to genome-wide functional annotation in a wider spectrum of biological research studies, as well as in drug and target discovery, so that complex cellular phenotypes can be measured in a multiparametric format. Despite these advances, data analysis and visualization tools are still largely lacking for these types of experiments. Therefore, we developed iScreen (image-Based High-content RNAi Screening Analysis Tool), an R package for the statistical modeling and visualization of image-based high-content RNAi screening. Two case studies were used to demonstrate the capability and efficiency of the iScreen package. iScreen is available for download on CRAN (http://cran.cnr.berkeley.edu/web/packages/iScreen/index.html). The user manual is also available as a supplementary document. © 2014 Society for Laboratory Automation and Screening.

A semi-supervised approach using label propagation to support citation screening.

Science.gov (United States)

Kontonatsios, Georgios; Brockmeier, Austin J; Przybyła, Piotr; McNaught, John; Mu, Tingting; Goulermas, John Y; Ananiadou, Sophia

2017-08-01

Citation screening, an integral process within systematic reviews that identifies citations relevant to the underlying research question, is a time-consuming and resource-intensive task. During the screening task, analysts manually assign a label to each citation, to designate whether a citation is eligible for inclusion in the review. Recently, several studies have explored the use of active learning in text classification to reduce the human workload involved in the screening task. However, existing approaches require a significant amount of manually labelled citations for the text classification to achieve a robust performance. In this paper, we propose a semi-supervised method that identifies relevant citations as early as possible in the screening process by exploiting the pairwise similarities between labelled and unlabelled citations to improve the classification performance without additional manual labelling effort. Our approach is based on the hypothesis that similar citations share the same label (e.g., if one citation should be included, then other similar citations should be included also). To calculate the similarity between labelled and unlabelled citations we investigate two different feature spaces, namely a bag-of-words and a spectral embedding based on the bag-of-words. The semi-supervised method propagates the classification codes of manually labelled citations to neighbouring unlabelled citations in the feature space. The automatically labelled citations are combined with the manually labelled citations to form an augmented training set. For evaluation purposes, we apply our method to reviews from clinical and public health. The results show that our semi-supervised method with label propagation achieves statistically significant improvements over two state-of-the-art active learning approaches across both clinical and public health reviews. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Ecological risk assessment of agricultural soils for the definition of soil screening values: A comparison between substance-based and matrix-based approaches

Directory of Open Access Journals (Sweden)

Alberto Pivato

2017-04-01

Full Text Available The Italian legislation on contaminated soils does not include the Ecological Risk Assessment (ERA and this deficiency has important consequences for the sustainable management of agricultural soils. The present research compares the results of two ERA procedures applied to agriculture (i one based on the “substance-based” approach and (ii a second based on the “matrix-based” approach. In the former the soil screening values (SVs for individual substances were derived according to institutional foreign guidelines. In the latter, the SVs characterizing the whole-matrix were derived originally by the authors by means of experimental activity.The results indicate that the “matrix-based” approach can be efficiently implemented in the Italian legislation for the ERA of agricultural soils. This method, if compared to the institutionalized “substance based” approach is (i comparable in economic terms and in testing time, (ii is site specific and assesses the real effect of the investigated soil on a battery of bioassays, (iii accounts for phenomena that may radically modify the exposure of the organisms to the totality of contaminants and (iv can be considered sufficiently conservative. Keyword: Environmental science

Screening for EIA in India: enhancing effectiveness through ecological carrying capacity approach.

Science.gov (United States)

Rajaram, T; Das, Ashutosh

2011-01-01

Developing countries across the world have embraced the policy of high economic growth as a means to reduce poverty. This economic growth largely based on industrial output is fast degrading the ecosystems, jeopardizing their long term sustainability. Environmental Impact Assessment (EIA) has long been recognized as a tool which can help in protecting the ecosystems and aid sustainable development. The Screening guidelines for EIA reflect the level of commitment the nation displays towards tightening its environmental protection system. The paper analyses the screening process for EIA in India and dissects the rationale behind the exclusions and thresholds set in the screening process. The screening process in India is compared with that of the European Union with the aim of understanding the extent of deviations from a screening approach in the context of better economic development. It is found that the Indian system excludes many activities from the purview of screening itself when compared to the EU. The constraints responsible for these exclusions are discussed and the shortcomings of the current command and control system of environmental management in India are also explained. It is suggested that an ecosystem carrying capacity based management system can provide significant inputs to enhance the effectiveness of EIA process from screening to monitoring. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comfortably engaging: which approach to alcohol screening should we use?

Science.gov (United States)

Vinson, Daniel C; Galliher, James M; Reidinger, Carol; Kappus, Jennifer A

2004-01-01

We wanted to compare 2 screening instruments for problem drinking, the CAGE and a single question, assessing frequency of use, patient and clinician comfort, and patient engagement in change. The study was a crossover, cluster-randomized clinical trial with 31 clinicians in Missouri and 13 in the American Academy of Family Physicians (AAFP) National Network for Family Practice and Primary Care Research; 2,800 patients provided data. The clinician was the unit of randomization. Clinicians decided whether to screen each patient; if they chose to screen, they used the screening approach assigned for that block of patients. The clinician and patient separately completed questionnaires immediately after the office visit to assess each one's comfort with screening (and any ensuing discussion) and the patient's engagement in change. Missouri clinicians screened more patients when assigned the single question (81%) than the CAGE (69%, P = .001 in weighted analysis). There was no difference among AAFP network clinicians (96% of patients screened with the CAGE, 97% with the single question). Eighty percent to 90% of clinicians and 70% of patients reported being comfortable with screening and the ensuing discussion, with no difference between approaches in either network. About one third of patients who were identified as problem drinkers reported thinking about or planning to change their drinking behavior, with no difference in engagement between screening approaches. Clinicians and patients reported similar comfort with the CAGE questions and the single-question screening tools for problem drinking, and the 2 instruments were equal in their ability to engage the patient. In Missouri, the single question was more likely to be used.

Population-based screening versus case detection.

Directory of Open Access Journals (Sweden)

Thomas Ravi

2002-01-01

Full Text Available India has a large burden of blindness and population-based screening is a strategy commonly employed to detect disease and prevent morbidity. However, not all diseases are amenable to screening. This communication examines the issue of "population-based screening" versus "case detection" in the Indian scenario. Using the example of glaucoma, it demonstrates that given the poor infrastructure, for a "rare" disease, case detection is more effective than population-based screening.

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

International Nuclear Information System (INIS)

Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan; Durmus, Naside Gozde

2011-01-01

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

Energy Technology Data Exchange (ETDEWEB)

Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan [Department of Medicine, Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Durmus, Naside Gozde, E-mail: udemirci@rics.bwh.harvard.edu [School of Engineering and Division of Biology and Medicine, Brown University, Providence, RI (United States)

2011-09-15

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.

A graph-based approach to construct target-focused libraries for virtual screening.

Science.gov (United States)

Naderi, Misagh; Alvin, Chris; Ding, Yun; Mukhopadhyay, Supratik; Brylinski, Michal

2016-01-01

Due to exorbitant costs of high-throughput screening, many drug discovery projects commonly employ inexpensive virtual screening to support experimental efforts. However, the vast majority of compounds in widely used screening libraries, such as the ZINC database, will have a very low probability to exhibit the desired bioactivity for a given protein. Although combinatorial chemistry methods can be used to augment existing compound libraries with novel drug-like compounds, the broad chemical space is often too large to be explored. Consequently, the trend in library design has shifted to produce screening collections specifically tailored to modulate the function of a particular target or a protein family. Assuming that organic compounds are composed of sets of rigid fragments connected by flexible linkers, a molecule can be decomposed into its building blocks tracking their atomic connectivity. On this account, we developed eSynth, an exhaustive graph-based search algorithm to computationally synthesize new compounds by reconnecting these building blocks following their connectivity patterns. We conducted a series of benchmarking calculations against the Directory of Useful Decoys, Enhanced database. First, in a self-benchmarking test, the correctness of the algorithm is validated with the objective to recover a molecule from its building blocks. Encouragingly, eSynth can efficiently rebuild more than 80 % of active molecules from their fragment components. Next, the capability to discover novel scaffolds is assessed in a cross-benchmarking test, where eSynth successfully reconstructed 40 % of the target molecules using fragments extracted from chemically distinct compounds. Despite an enormous chemical space to be explored, eSynth is computationally efficient; half of the molecules are rebuilt in less than a second, whereas 90 % take only about a minute to be generated. eSynth can successfully reconstruct chemically feasible molecules from molecular fragments

Spherical harmonics coefficients for ligand-based virtual screening of cyclooxygenase inhibitors.

Science.gov (United States)

Wang, Quan; Birod, Kerstin; Angioni, Carlo; Grösch, Sabine; Geppert, Tim; Schneider, Petra; Rupp, Matthias; Schneider, Gisbert

2011-01-01

Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort.

New approach for high-throughput screening of drug activity on Plasmodium liver stages.

NARCIS (Netherlands)

Gego, A.; Silvie, O.; Franetich, J.F.; Farhati, K.; Hannoun, L.; Luty, A.J.F.; Sauerwein, R.W.; Boucheix, C.; Rubinstein, E.; Mazier, D.

2006-01-01

Plasmodium liver stages represent potential targets for antimalarial prophylactic drugs. Nevertheless, there is a lack of molecules active on these stages. We have now developed a new approach for the high-throughput screening of drug activity on Plasmodium liver stages in vitro, based on an

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

Science.gov (United States)

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.

The screening approach for review of accident management programmes

International Nuclear Information System (INIS)

Misak, J.

1999-01-01

In this lecture the screening approach for review of accident management programmes are presented. It contains objective trees for accident management: logic structure of the approach; objectives and safety functions for accident management; safety principles

Promoting community practitioners' use of evidence-based approaches to increase breast cancer screening.

Science.gov (United States)

Leeman, Jennifer; Moore, Alexis; Teal, Randall; Barrett, Nadine; Leighton, Ashely; Steckler, Allan

2013-07-01

Many women do not get mammography screenings at the intervals recommended for early detection and treatment of breast cancer. The Guide to Community Preventive Services (Community Guide) recommends a range of evidence-based strategies to improve mammography rates. However, nurses and others working in community-based settings make only limited use of these strategies. We report on a dissemination intervention that partnered the University of North Carolina with the Susan G. Komen Triangle Affiliate to disseminate Community Guide breast cancer screening strategies to community organizations. The intervention was guided by social marketing and diffusion of innovation theory and was designed to provide evidence and support via Komen's existing relationships with grantee organizations. The present study reports the findings from a formative evaluation of the intervention, which included a content analysis of 46 grant applications pre- and post intervention and focus groups with 20 grant recipients. © 2013 Wiley Periodicals, Inc.

Pregnant Women's Perceptions of the Risks and Benefits of Disclosure During Web-Based Mental Health E-Screening Versus Paper-Based Screening: Randomized Controlled Trial.

Science.gov (United States)

Kingston, Dawn; Biringer, Anne; Veldhuyzen van Zanten, Sander; Giallo, Rebecca; McDonald, Sarah; MacQueen, Glenda; Vermeyden, Lydia; Austin, Marie-Paule

2017-10-20

Pregnant women's perceptions of the risks and benefits during mental health screening impact their willingness to disclose concerns. Early research in violence screening suggests that such perceptions may vary by mode of screening, whereby women view the anonymity of e-screening as less risky than other approaches. Understanding whether mode of screening influences perceptions of risk and benefit of disclosure is important in screening implementation. The objective of this randomized controlled trial was to compare the perceptions of pregnant women randomized to a Web-based screening intervention group and a paper-based screening control group on the level of risk and benefit they perceive in disclosing mental health concerns to their prenatal care provider. A secondary objective was to identify factors associated with women's perceptions of risk and benefit of disclosure. Pregnant women recruited from maternity clinics, hospitals, and prenatal classes were computer-randomized to a fully automated Web-based e-screening intervention group or a paper-based control. The intervention group completed the Antenatal Psychosocial Health Assessment and the Edinburgh Postnatal Depression Scale on a computer tablet, whereas the control group completed them on paper. The primary outcome was women's perceptions of the risk and benefits of mental health screening using the Disclosure Expectations Scale (DES). A completer analysis was conducted. Statistical significance was set at Pcontrol (n=331) groups. There were no significant baseline differences between groups. The mode of screening was not associated with either perceived risk or benefit of screening. There were no differences in groups in the mean scores of the risk and benefit of disclosure subscales. Over three-quarters of women in both intervention and control groups perceived that mental health screening was beneficial. However, 43.1% (272/631) of women in both groups reported feeling very, moderately, or somewhat

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

Science.gov (United States)

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.

A first approach to a neuropsychological screening tool using eye-tracking for bedside cognitive testing based on the Edinburgh Cognitive and Behavioural ALS Screen.

Science.gov (United States)

Keller, Jürgen; Krimly, Amon; Bauer, Lisa; Schulenburg, Sarah; Böhm, Sarah; Aho-Özhan, Helena E A; Uttner, Ingo; Gorges, Martin; Kassubek, Jan; Pinkhardt, Elmar H; Abrahams, Sharon; Ludolph, Albert C; Lulé, Dorothée

2017-08-01

Reliable assessment of cognitive functions is a challenging task in amyotrophic lateral sclerosis (ALS) patients unable to speak and write. We therefore present an eye-tracking based neuropsychological screening tool based on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a standard screening tool for cognitive deficits in ALS. In total, 46 ALS patients and 50 healthy controls matched for age, gender and education were tested with an oculomotor based and a standard paper-and-pencil version of the ECAS. Significant correlation between both versions was observed for ALS patients and healthy controls in the ECAS total score and in all of its ALS-specific domains (all r > 0.3; all p ALS patients and healthy controls in the ECAS total score (p ALS patients who are unable to speak or write.

Bead-based screening in chemical biology and drug discovery

DEFF Research Database (Denmark)

Komnatnyy, Vitaly V.; Nielsen, Thomas Eiland; Qvortrup, Katrine

2018-01-01

libraries for early drug discovery. Among the various library forms, the one-bead-one-compound (OBOC) library, where each bead carries many copies of a single compound, holds the greatest potential for the rapid identification of novel hits against emerging drug targets. However, this potential has not yet...... been fully realized due to a number of technical obstacles. In this feature article, we review the progress that has been made towards bead-based library screening and applications to the discovery of bioactive compounds. We identify the key challenges of this approach and highlight key steps needed......High-throughput screening is an important component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds requires assays amanable to miniaturisation and automization. Combinatorial chemistry holds a unique promise to deliver structural diverse...

First-trimester screening for chromosomal abnormalities: advantages of an instant results approach.

Science.gov (United States)

Norton, Mary E

2010-09-01

Protocols that include first trimester screening for fetal chromosome abnormalities have become standard of care throughout the United States. Earlier screening allows for first trimester diagnostic testing in cases found to be at increased risk. However, first trimester screening requires coordination of the nuchal translucency ultrasound screening (NT) and biochemical screening, during early, specific, narrow, but slightly different gestational age ranges. Instant results can often be provided at the time of the NT ultrasound if preceded by the programs that perform the biochemical analyses; this optimizes the benefits of the first trimester approach while improving efficiency and communication with the patient. This article discusses the benefits and logistics of such an approach. Copyright 2010 Elsevier Inc. All rights reserved.

A web-based platform for virtual screening.

Science.gov (United States)

Watson, Paul; Verdonk, Marcel; Hartshorn, Michael J

2003-09-01

A fully integrated, web-based, virtual screening platform has been developed to allow rapid virtual screening of large numbers of compounds. ORACLE is used to store information at all stages of the process. The system includes a large database of historical compounds from high throughput screenings (HTS) chemical suppliers, ATLAS, containing over 3.1 million unique compounds with their associated physiochemical properties (ClogP, MW, etc.). The database can be screened using a web-based interface to produce compound subsets for virtual screening or virtual library (VL) enumeration. In order to carry out the latter task within ORACLE a reaction data cartridge has been developed. Virtual libraries can be enumerated rapidly using the web-based interface to the cartridge. The compound subsets can be seamlessly submitted for virtual screening experiments, and the results can be viewed via another web-based interface allowing ad hoc querying of the virtual screening data stored in ORACLE.

Approaches to virtual screening and screening library selection.

Science.gov (United States)

Wildman, Scott A

2013-01-01

The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. This review aims to identify many of the common difficulties associated with virtual screening and allow researchers to better assess the reliability of their virtual screening effort.

Influence of approach velocity and mesh size on the entrainment and contact of a lowland river fish assemblage at a screened irrigation pump.

Directory of Open Access Journals (Sweden)

Craig A Boys

Full Text Available Fish screens can help prevent the entrainment or injury of fish at irrigation diversions, but only when designed appropriately. Design criteria cannot simply be transferred between sites or pump systems and need to be developed using an evidence-based approach with the needs of local species in mind. Laboratory testing is typically used to quantify fish responses at intake screens, but often limits the number of species that can studied and creates artificial conditions not directly applicable to screens in the wild. In this study a field-based approach was used to assess the appropriateness of different screen design attributes for the protection of a lowland river fish assemblage at an experimental irrigation pump. Direct netting of entrained fish was used along with sonar technology to quantify the probability of screen contact for a Murray-Darling Basin (Australia fish species. Two approach velocities (0.1 and 0.5 m.sec(-1 and different sizes of woven mesh (5, 10 and 20 mm were evaluated. Smaller fish (<150 mm in the assemblage were significantly more susceptible to entrainment and screen contact, especially at higher approach velocities. Mesh size appeared to have little impact on screen contact and entrainment, suggesting that approach velocity rather than mesh size is likely to be the primary consideration when developing screens. Until the effects of screen contacts on injury and survival of these species are better understood, it is recommended that approach velocities not exceed 0.1 m.sec(-1 when the desire is to protect the largest range of species and size classes for lowland river fish assemblages in the Murray-Darling Basin. The field method tested proved to be a useful approach that could compliment laboratory studies to refine fish screen design and facilitate field validation.

Innovative approaches to cervical cancer screening for sex trade workers: an international scoping review.

Science.gov (United States)

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

Hierarchical screening for multiple mental disorders.

Science.gov (United States)

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.

Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial.

Science.gov (United States)

Denny, Lynette; Kuhn, Louise; De Souza, Michelle; Pollack, Amy E; Dupree, William; Wright, Thomas C

2005-11-02

Non-cytology-based screen-and-treat approaches for cervical cancer prevention have been developed for low-resource settings, but few have directly addressed efficacy. To determine the safety and efficacy of 2 screen-and-treat approaches for cervical cancer prevention that were designed to be more resource-appropriate than conventional cytology-based screening programs. Randomized clinical trial of 6555 nonpregnant women, aged 35 to 65 years, recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women's health clinics in Khayelitsha, South Africa. All patients were screened using human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Women were subsequently randomized to 1 of 3 groups: cryotherapy if she had a positive HPV DNA test result; cryotherapy if she had a positive VIA test result; or to delayed evaluation. Biopsy-confirmed high-grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation (control) group; complications after cryotherapy. The prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) was significantly lower in the 2 screen-and-treat groups at 6 months after randomization than in the delayed evaluation group. At 6 months, CIN 2+ was diagnosed in 0.80% (95% confidence interval [CI], 0.40%-1.20%) of the women in the HPV DNA group and 2.23% (95% CI, 1.57%-2.89%) in the VIA group compared with 3.55% (95% CI, 2.71%-4.39%) in the delayed evaluation group (Pcryotherapy, major complications were rare. Both screen-and-treat approaches are safe and result in a lower prevalence of high-grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months. Trial Registration http://clinicaltrials.gov Identifier: NCT00233727.

Young men's views toward the barriers and facilitators of Internet-based Chlamydia trachomatis screening: qualitative study.

Science.gov (United States)

Lorimer, Karen; McDaid, Lisa

2013-12-03

There is a growing number of Internet-based approaches that offer young people screening for sexually transmitted infections. This paper explores young men's views towards the barriers and facilitators of implementing an Internet-based screening approach. The study sought to consider ways in which the proposed intervention would reach and engage men across ages and socioeconomic backgrounds. This qualitative study included 15 focus groups with 60 heterosexual young men (aged 16-24 years) across central Scotland, drawn across age and socioeconomic backgrounds. Focus groups began by obtaining postcode data to allocate participants to a high/low deprivation category. Focus group discussions involved exploration of men's knowledge of chlamydia, use of technology, and views toward Internet-based screening. Men were shown sample screening invitation letters, test kits, and existing screening websites to facilitate discussions. Transcripts from audio recordings were analyzed with "Framework Analysis". Men's Internet and technology use was heterogeneous in terms of individual practices, with greater use among older men (aged 20-24 years) than teenagers and some deprivation-related differences in use. We detail three themes related to barriers to successful implementation: acceptability, confidentiality and privacy concerns, and language, style, and content. These themes identify ways Internet-based screening approaches may fail to engage some men, such as by raising anxiety and failing to convey confidentiality. Men wanted screening websites to frame screening as a serious issue, rather than using humorous images and text. Participants were encouraged to reach a consensus within their groups on their broad design and style preferences for a screening website; this led to a set of common preferences that they believed were likely to engage men across age and deprivation groups and lead to greater screening uptake. The Internet provides opportunities for re-evaluating how we

Office-based ultrasound screening for abdominal aortic aneurysm.

Science.gov (United States)

Blois, Beau

2012-03-01

To assess the efficacy of an office-based, family physician–administered ultrasound examination to screen for abdominal aortic aneurysm (AAA). A prospective observational study. Consecutive patients were approached by nonphysician staff. Rural family physician offices in Grand Forks and Revelstoke, BC. The Canadian Society for Vascular Surgery screening recommendations for AAA were used to help select patients who were at risk of AAA. All men 65 years of age or older were included. Women 65 years of age or older were included if they were current smokers or had diabetes, hypertension, a history of coronary artery disease, or a family history of AAA. A focused “quick screen”, which measured the maximal diameter of the abdominal aorta using point-of-care ultrasound technology, was performed in the office by a resident physician trained in emergency ultrasonography. Each patient was then booked for a criterion standard scan (i.e., a conventional abdominal ultrasound scan performed by a technician and interpreted by a radiologist). The maximal abdominal aortic diameter measured by ultrasound in the office was compared with that measured by the criterion standard method. The time to screen each patient was recorded. Forty-five patients were included in data analysis; 62% of participants were men. The mean age was 73 years. The mean pairwise difference between the office-based ultrasound scan and the criterion standard scan was not statistically significant. The mean absolute difference between the 2 scans was 0.20 cm (95% CI 0.15 to 0.25 cm). Correlation between the scans was 0.81. The office-based ultrasound scan had both a sensitivity and a specificity of 100%. The mean time to screen each patient was 212 seconds (95% CI 194 to 230 seconds). Abdominal aortic aneurysm screening can be safely performed in the office by family physicians who are trained to use point-of- care ultrasound technology. The screening test can be completed within the time constraints of a

Fragment-based lead generation: identification of seed fragments by a highly efficient fragment screening technology

Science.gov (United States)

Neumann, Lars; Ritscher, Allegra; Müller, Gerhard; Hafenbradl, Doris

2009-08-01

For the detection of the precise and unambiguous binding of fragments to a specific binding site on the target protein, we have developed a novel reporter displacement binding assay technology. The application of this technology for the fragment screening as well as the fragment evolution process with a specific modelling based design strategy is demonstrated for inhibitors of the protein kinase p38alpha. In a fragment screening approach seed fragments were identified which were then used to build compounds from the deep-pocket towards the hinge binding area of the protein kinase p38alpha based on a modelling approach. BIRB796 was used as a blueprint for the alignment of the fragments. The fragment evolution of these deep-pocket binding fragments towards the fully optimized inhibitor BIRB796 included the modulation of the residence time as well as the affinity. The goal of our study was to evaluate the robustness and efficiency of our novel fragment screening technology at high fragment concentrations, compare the screening data with biochemical activity data and to demonstrate the evolution of the hit fragments with fast kinetics, into slow kinetic inhibitors in an in silico approach.

Development of fluorescence imaging-based assay for screening cardioprotective compounds from medicinal plants.

Science.gov (United States)

Wang, Yi; Zhao, Xiaoping; Gao, Xiumei; Nie, Xiaojing; Yang, Yingxin; Fan, Xiaohui

2011-09-19

Medicinal plants have been widely recognized as a renewable resource for the discovery of novel leads and drug. In this study, an approach for screening and identification compounds with cardioprotective activity from medicinal plant extracts by cellular-fluorescence imaging technique was developed. It is a cell-based assay for measuring mitochondrial membrane potential changes in H9c2 cardiac muscle cells exposed to H(2)O(2) by using a fluorescence automatic microscopy screening platform. Rhodamine 123 was used as the fluorescent dye to indicate the change of mitochondrial membrane potential. The sensitivity and linear range of the proposed approach were evaluated and validated using vitamin C, an antioxidative compound. The method was applied to screen active components with potent cardioprotective effects from a traditional Chinese formula. The potential cardioprotective components were identified by liquid chromatography coupled with mass spectrometry (LC/MS). Moreover, the utility of the proposed approach was further validated by three compounds (salvianolic acid B, protocatechuic aldehyde, and tanshinone II A) identified from the formula which showed cardioprotective effects in a dose-dependent manner. These applications suggested that the proposed rapid and sensitive screening approach offers an efficient way to discover active components or compounds from medicinal plants. Copyright © 2011 Elsevier B.V. All rights reserved.

NMR-Fragment Based Virtual Screening: A Brief Overview.

Science.gov (United States)

Singh, Meenakshi; Tam, Benjamin; Akabayov, Barak

2018-01-25

Fragment-based drug discovery (FBDD) using NMR has become a central approach over the last twenty years for development of small molecule inhibitors against biological macromolecules, to control a variety of cellular processes. Yet, several considerations should be taken into account for obtaining a therapeutically relevant agent. In this review, we aim to list the considerations that make NMR fragment screening a successful process for yielding potent inhibitors. Factors that may govern the competence of NMR in fragment based drug discovery are discussed, as well as later steps that involve optimization of hits obtained by NMR-FBDD.

NMR-Fragment Based Virtual Screening: A Brief Overview

Directory of Open Access Journals (Sweden)

Meenakshi Singh

2018-01-01

Full Text Available Fragment-based drug discovery (FBDD using NMR has become a central approach over the last twenty years for development of small molecule inhibitors against biological macromolecules, to control a variety of cellular processes. Yet, several considerations should be taken into account for obtaining a therapeutically relevant agent. In this review, we aim to list the considerations that make NMR fragment screening a successful process for yielding potent inhibitors. Factors that may govern the competence of NMR in fragment based drug discovery are discussed, as well as later steps that involve optimization of hits obtained by NMR-FBDD.

Identification of LasR Ligands through a Virtual Screening Approach

DEFF Research Database (Denmark)

Skovstrup, Søren; Le Quement, Sebastian Thordal; Hansen, Thomas

2013-01-01

as an attractive therapeutic target for the next generation of antimicrobial agents. In the present study, a virtual screening workflow combining pharmacophore‐ and structure‐based approaches was used to identify new LasR ligands. Five novel inducers and three inhibitors of LasR activity were validated...... experimentally by use of a cell‐based assay. Interestingly, these compounds are molecularly distinct from the native signal molecule, N‐3‐oxododecanoyl‐L‐homoserine lactone (OHN), and may serve as lead structures for the design of new drugs. The binding modes of these compounds to the OHN binding site in Las......R were predicted and used to identify the key interactions that contribute to the induction and inhibition of LasR activity....

Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening

DEFF Research Database (Denmark)

Markt, Patrick; Petersen, Rasmus K; Flindt, Esben N

2008-01-01

Peroxisome proliferator-activated receptors (PPARs) are important targets for drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type 2 diabetes, and other diseases caused by abnormal regulation of the glucose and lipid metabolism. We applied a virtual screening workflow base...

Screening the sequence selectivity of DNA-binding molecules using a gold nanoparticle-based colorimetric approach.

Science.gov (United States)

Hurst, Sarah J; Han, Min Su; Lytton-Jean, Abigail K R; Mirkin, Chad A

2007-09-15

We have developed a novel competition assay that uses a gold nanoparticle (Au NP)-based, high-throughput colorimetric approach to screen the sequence selectivity of DNA-binding molecules. This assay hinges on the observation that the melting behavior of DNA-functionalized Au NP aggregates is sensitive to the concentration of the DNA-binding molecule in solution. When short, oligomeric hairpin DNA sequences were added to a reaction solution consisting of DNA-functionalized Au NP aggregates and DNA-binding molecules, these molecules may either bind to the Au NP aggregate interconnects or the hairpin stems based on their relative affinity for each. This relative affinity can be measured as a change in the melting temperature (Tm) of the DNA-modified Au NP aggregates in solution. As a proof of concept, we evaluated the selectivity of 4',6-diamidino-2-phenylindone (an AT-specific binder), ethidium bromide (a nonspecific binder), and chromomycin A (a GC-specific binder) for six sequences of hairpin DNA having different numbers of AT pairs in a five-base pair variable stem region. Our assay accurately and easily confirmed the known trends in selectivity for the DNA binders in question without the use of complicated instrumentation. This novel assay will be useful in assessing large libraries of potential drug candidates that work by binding DNA to form a drug/DNA complex.

Are we ready for the challenge of implementing risk-based breast cancer screening and primary prevention?

NARCIS (Netherlands)

Rainey, L.; Waal, D. van der; Jervaeus, A.; Wengstrom, Y.; Evans, D.G.; Donnelly, L.S.; Broeders, M.J.M.

2018-01-01

BACKGROUND: Increased knowledge of breast cancer risk factors provides opportunities to shift from a one-size-fits-all screening programme to a personalised approach, where screening and prevention is based on a woman's risk of developing breast cancer. However, potential implementation of this new

Young Men’s Views Toward the Barriers and Facilitators of Internet-Based Chlamydia Trachomatis Screening: Qualitative Study

Science.gov (United States)

McDaid, Lisa

2013-01-01

Background There is a growing number of Internet-based approaches that offer young people screening for sexually transmitted infections. Objective This paper explores young men’s views towards the barriers and facilitators of implementing an Internet-based screening approach. The study sought to consider ways in which the proposed intervention would reach and engage men across ages and socioeconomic backgrounds. Methods This qualitative study included 15 focus groups with 60 heterosexual young men (aged 16-24 years) across central Scotland, drawn across age and socioeconomic backgrounds. Focus groups began by obtaining postcode data to allocate participants to a high/low deprivation category. Focus group discussions involved exploration of men’s knowledge of chlamydia, use of technology, and views toward Internet-based screening. Men were shown sample screening invitation letters, test kits, and existing screening websites to facilitate discussions. Transcripts from audio recordings were analyzed with "Framework Analysis". Results Men’s Internet and technology use was heterogeneous in terms of individual practices, with greater use among older men (aged 20-24 years) than teenagers and some deprivation-related differences in use. We detail three themes related to barriers to successful implementation: acceptability, confidentiality and privacy concerns, and language, style, and content. These themes identify ways Internet-based screening approaches may fail to engage some men, such as by raising anxiety and failing to convey confidentiality. Men wanted screening websites to frame screening as a serious issue, rather than using humorous images and text. Participants were encouraged to reach a consensus within their groups on their broad design and style preferences for a screening website; this led to a set of common preferences that they believed were likely to engage men across age and deprivation groups and lead to greater screening uptake. Conclusions The

Advancing early detection of autism spectrum disorder by applying an integrated two-stage screening approach

NARCIS (Netherlands)

Oosterling, Iris J.; Wensing, Michel; Swinkels, Sophie H.; van der Gaag, Rutger Jan; Visser, Janne C.; Woudenberg, Tim; Minderaa, Ruud; Steenhuis, Mark-Peter; Buitelaar, Jan K.

Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of

Evaluation of a population-based approach to familial colorectal cancer.

Science.gov (United States)

Parfrey, P S; Dicks, E; Parfrey, O; McNicholas, P J; Noseworthy, H; Woods, M O; Negriin, C; Green, J

2017-05-01

As Newfoundland has the highest rate of familial colorectal cancer (CRC) in the world, we started a population-based clinic to provide colonoscopic and Lynch syndrome (LS) screening recommendations to families of CRC patients based on family risk. Of 1091 incident patients 51% provided a family history. Seventy-two percent of families were at low or intermediate-low risk of CRC and colonoscopic screening recommendations were provided by letter. Twenty-eight percent were at high and intermediate-high risk and were referred to the genetic counsellor, but only 30% (N = 48) were interviewed by study end. Colonoscopy was recommended more frequently than every 5 years in 35% of families. Lower family risk was associated with older age of proband but the frequency of screening colonoscopy recommendations varied across all age groups, driven by variability in family history. Twenty-four percent had a high MMR predict score for a Lynch syndrome mutation, and 23% fulfilled the Provincial Program criteria for LS screening. A population-based approach in the provision of colonoscopic screening recommendations to families at risk of CRC was limited by the relatively low response rate. A family history first approach to the identification of LS families was inefficient. © 2016 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fluorescence-based assay as a new screening tool for toxic chemicals

Science.gov (United States)

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.

Testing for direct genetic effects using a screening step in family-based association studies

Directory of Open Access Journals (Sweden)

Sharon M Lutz

2013-11-01

Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm [1]. Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.

Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge

Science.gov (United States)

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.

Determining potential locations for biomass valorization using a macro screening approach

Energy Technology Data Exchange (ETDEWEB)

Van Dael, M.; Van Passel, S.; Schreurs, E. [Research Group of Environmental Economics, Centre for Environmental Sciences, Hasselt University, Agoralaan Gebouw D, 3590 Diepenbeek (Belgium); Pelkmans, L.; Guisson, R. [VITO, Boeretang 200, 2400 Mol (Belgium); Swinnen, G. [Research Group of Marketing, Hasselt University, Agoralaan Gebouw D, 3590 Diepenbeek (Belgium)

2012-10-15

European policy states that by 2020 at least 20% of final energy consumption should come from renewable energy sources. Biomass as a renewable energy source cannot be disregarded in order to attain this target. In this study a macro screening approach is developed to determine potential locations for biomass valorization in a specified region. The approach consists of five steps: (1) criteria determination, (2) data gathering, (3) weight assignment, (4) final score, (5) spatial representation. The resulting outcome provides a first well balanced scan of the possibilities for energy production using regional biomass. This way policy makers and investors can be supported and motivated to study the possibilities of building energy production plants at specific locations in more detail, which can be described as a 'micro-screening'. In our case study the approach is applied to determine the potentially interesting locations to establish a biomass project. The region has been limited to the forty-four communities in the province of Limburg (Belgium). The macro screening approach has shown to be very effective since the amount of interesting locations has been reduced drastically.

Virtual screening by a new Clustering-based Weighted Similarity Extreme Learning Machine approach.

Science.gov (United States)

Pasupa, Kitsuchart; Kudisthalert, Wasu

2018-01-01

Machine learning techniques are becoming popular in virtual screening tasks. One of the powerful machine learning algorithms is Extreme Learning Machine (ELM) which has been applied to many applications and has recently been applied to virtual screening. We propose the Weighted Similarity ELM (WS-ELM) which is based on a single layer feed-forward neural network in a conjunction of 16 different similarity coefficients as activation function in the hidden layer. It is known that the performance of conventional ELM is not robust due to random weight selection in the hidden layer. Thus, we propose a Clustering-based WS-ELM (CWS-ELM) that deterministically assigns weights by utilising clustering algorithms i.e. k-means clustering and support vector clustering. The experiments were conducted on one of the most challenging datasets-Maximum Unbiased Validation Dataset-which contains 17 activity classes carefully selected from PubChem. The proposed algorithms were then compared with other machine learning techniques such as support vector machine, random forest, and similarity searching. The results show that CWS-ELM in conjunction with support vector clustering yields the best performance when utilised together with Sokal/Sneath(1) coefficient. Furthermore, ECFP_6 fingerprint presents the best results in our framework compared to the other types of fingerprints, namely ECFP_4, FCFP_4, and FCFP_6.

Virtual drug screen schema based on multiview similarity integration and ranking aggregation.

Science.gov (United States)

Kang, Hong; Sheng, Zhen; Zhu, Ruixin; Huang, Qi; Liu, Qi; Cao, Zhiwei

2012-03-26

The current drug virtual screen (VS) methods mainly include two categories. i.e., ligand/target structure-based virtual screen and that, utilizing protein-ligand interaction fingerprint information based on the large number of complex structures. Since the former one focuses on the one-side information while the later one focuses on the whole complex structure, they are thus complementary and can be boosted by each other. However, a common problem faced here is how to present a comprehensive understanding and evaluation of the various virtual screen results derived from various VS methods. Furthermore, there is still an urgent need for developing an efficient approach to fully integrate various VS methods from a comprehensive multiview perspective. In this study, our virtual screen schema based on multiview similarity integration and ranking aggregation was tested comprehensively with statistical evaluations, providing several novel and useful clues on how to perform drug VS from multiple heterogeneous data sources. (1) 18 complex structures of HIV-1 protease with ligands from the PDB were curated as a test data set and the VS was performed with five different drug representations. Ritonavir ( 1HXW ) was selected as the query in VS and the weighted ranks of the query results were aggregated from multiple views through four similarity integration approaches. (2) Further, one of the ranking aggregation methods was used to integrate the similarity ranks calculated by gene ontology (GO) fingerprint and structural fingerprint on the data set from connectivity map, and two typical HDAC and HSP90 inhibitors were chosen as the queries. The results show that rank aggregation can enhance the result of similarity searching in VS when two or more descriptions are involved and provide a more reasonable similarity rank result. Our study shows that integrated VS based on multiple data fusion can achieve a remarkable better performance compared to that from individual ones and

The health system and population health implications of large-scale diabetes screening in India: a microsimulation model of alternative approaches.

Directory of Open Access Journals (Sweden)

Sanjay Basu

2015-05-01

Full Text Available Like a growing number of rapidly developing countries, India has begun to develop a system for large-scale community-based screening for diabetes. We sought to identify the implications of using alternative screening instruments to detect people with undiagnosed type 2 diabetes among diverse populations across India.We developed and validated a microsimulation model that incorporated data from 58 studies from across the country into a nationally representative sample of Indians aged 25-65 y old. We estimated the diagnostic and health system implications of three major survey-based screening instruments and random glucometer-based screening. Of the 567 million Indians eligible for screening, depending on which of four screening approaches is utilized, between 158 and 306 million would be expected to screen as "high risk" for type 2 diabetes, and be referred for confirmatory testing. Between 26 million and 37 million of these people would be expected to meet international diagnostic criteria for diabetes, but between 126 million and 273 million would be "false positives." The ratio of false positives to true positives varied from 3.9 (when using random glucose screening to 8.2 (when using a survey-based screening instrument in our model. The cost per case found would be expected to be from US$5.28 (when using random glucose screening to US$17.06 (when using a survey-based screening instrument, presenting a total cost of between US$169 and US$567 million. The major limitation of our analysis is its dependence on published cohort studies that are unlikely fully to capture the poorest and most rural areas of the country. Because these areas are thought to have the lowest diabetes prevalence, this may result in overestimation of the efficacy and health benefits of screening.Large-scale community-based screening is anticipated to produce a large number of false-positive results, particularly if using currently available survey-based screening

Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

Science.gov (United States)

Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

2013-01-01

Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having

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

Science.gov (United States)

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.

Cost Analysis of Universal Screening vs. Risk Factor-Based Screening for Methicillin-Resistant Staphylococcus aureus (MRSA.

Directory of Open Access Journals (Sweden)

Virginia R Roth

Full Text Available The literature remains conflicted regarding the most effective way to screen for MRSA. This study was designed to assess costs associated with universal versus risk factor-based screening for the reduction of nosocomial MRSA transmission.The study was conducted at The Ottawa Hospital, a large multi-centre tertiary care facility with approximately 47,000 admissions annually. From January 2006-December 2007, patients underwent risk factor-based screening for MRSA on admission. From January 2008 to August 2009 universal MRSA screening was implemented. A comparison of costs incurred during risk factor-based screening and universal screening was conducted. The model incorporated probabilities relating to the likelihood of being tested and the results of polymerase chain reaction (PCR testing with associated effects in terms of MRSA bacteremia and true positive and negative test results. Inputted costs included laboratory testing, contact precautions and infection control, private room costs, housekeeping, and length of hospital stay. Deterministic sensitivity analyses were conducted.The risk factor-based MRSA screening program screened approximately 30% of admitted patients and cost the hospital over $780 000 annually. The universal screening program screened approximately 83% of admitted patients and cost over $1.94 million dollars, representing an excess cost of $1.16 million per year. The estimated additional cost per patient screened was $17.76.This analysis demonstrated that a universal MRSA screening program was costly from a hospital perspective and was previously known to not be clinically effective at reducing MRSA transmission. These results may be useful to inform future model-based economic analyses of MRSA interventions.

Tiered High-Throughput Screening Approach to Identify ...

Science.gov (United States)

High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the US EPA ToxCast screening assay portfolio. To fill one critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast Phase I and II chemical libraries, comprised of 1,074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single concentration screen were retested in concentration-response. Due to high false positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed two additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using

Cost-effectiveness and harm-benefit analyses of risk-based screening strategies for breast cancer.

Directory of Open Access Journals (Sweden)

Ester Vilaprinyo

Full Text Available The one-size-fits-all paradigm in organized screening of breast cancer is shifting towards a personalized approach. The present study has two objectives: 1 To perform an economic evaluation and to assess the harm-benefit ratios of screening strategies that vary in their intensity and interval ages based on breast cancer risk; and 2 To estimate the gain in terms of cost and harm reductions using risk-based screening with respect to the usual practice. We used a probabilistic model and input data from Spanish population registries and screening programs, as well as from clinical studies, to estimate the benefit, harm, and costs over time of 2,624 screening strategies, uniform or risk-based. We defined four risk groups, low, moderate-low, moderate-high and high, based on breast density, family history of breast cancer and personal history of breast biopsy. The risk-based strategies were obtained combining the exam periodicity (annual, biennial, triennial and quinquennial, the starting ages (40, 45 and 50 years and the ending ages (69 and 74 years in the four risk groups. Incremental cost-effectiveness and harm-benefit ratios were used to select the optimal strategies. Compared to risk-based strategies, the uniform ones result in a much lower benefit for a specific cost. Reductions close to 10% in costs and higher than 20% in false-positive results and overdiagnosed cases were obtained for risk-based strategies. Optimal screening is characterized by quinquennial or triennial periodicities for the low or moderate risk-groups and annual periodicity for the high-risk group. Risk-based strategies can reduce harm and costs. It is necessary to develop accurate measures of individual risk and to work on how to implement risk-based screening strategies.

Patterns of screen-based sedentary behavior and physical activity and associations with overweight among Norwegian adolescents: a latent profile approach

Directory of Open Access Journals (Sweden)

Ole Melkevik

2011-03-01

Full Text Available Background: Physical activity and screen based sedentary behaviors are both related to energy balance and to risk for becoming overweight. The aim of this study is to find out if these behaviors cluster together in order to find out whether groups of adolescents have particularly unfortunate levels of both physical activity and screen-based sedentary behaviors. Methods: Data are from the Norwegian 2005/2006 sample of the international "Health Behaviour in School-aged Children (HBSC study; A WHO cross-National Survey". Data were collected through questionnaires from 13-, 15- and 16-year-olds. The final sample included 4848 adolescents. Gender-stratified latent profile analysis was used to identify the different profiles. Results: Six profiles were identified for both boys and girls. Less than 30% of adolescents were found to have behavioral patterns which were associated with higher risk for overweight relative to the most healthy behavioral profile. Physical activity and screen-based sedentary behaviors cluster together in different ways suggesting independence between the behaviors. Low levels of physical activity was the most important predictor for overweight among boys. Screen-based sedentary behaviors were more important predictors of overweight among girls. Conclusions: Physical activity and screen-based sedentary behaviors are independent behaviors and may cluster together in manners which lead to low energy expenditure and subsequent increased risk for overweight among adolescents.

Polyglutamine Disease Modeling: Epitope Based Screen for Homologous Recombination using CRISPR/Cas9 System.

Science.gov (United States)

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.

Virtual screening approach to identifying influenza virus neuraminidase inhibitors using molecular docking combined with machine-learning-based scoring function.

Science.gov (United States)

Zhang, Li; Ai, Hai-Xin; Li, Shi-Meng; Qi, Meng-Yuan; Zhao, Jian; Zhao, Qi; Liu, Hong-Sheng

2017-10-10

In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0.707 in a 5-fold cross-validation study. The performance of RF-NA-Score in a docking-based virtual screening of NA inhibitors was evaluated with a dataset containing 281 NA inhibitors and 322 noninhibitors. Compared with other docking-rescoring virtual screening strategies, rescoring with RF-NA-Score significantly improved the efficiency of virtual screening, and a strategy that averaged the scores given by RF-NA-Score, based on the binding conformations predicted with AutoDock, AutoDock Vina, and LeDock, was shown to be the best strategy. This strategy was then applied to the virtual screening of NA inhibitors in the SPECS database. The 100 selected compounds were tested in an in vitro H7N9 NA inhibition assay, and two compounds with novel scaffolds showed moderate inhibitory activities. These results indicate that RF-NA-Score improves the efficiency of virtual screening for NA inhibitors, and can be used successfully to identify new NA inhibitor scaffolds. Scoring functions specific for other drug targets could also be established with the same method.

Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.

Science.gov (United States)

Hübner, Joachim; Waldmann, Annika; Eisemann, Nora; Noftz, Maria; Geller, Alan C; Weinstock, Martin A; Volkmer, Beate; Greinert, Rüdiger; Breitbart, Eckhard W; Katalinic, Alexander

2017-07-07

Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany project conducted in the German state of Schleswig-Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR): 17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR: 5.3; 95% CI: 3.6-7.6), and multiple (≥40) common nevi (OR: 1.3; 95% CI: 1.1-1.6) were associated with an increased risk of melanoma detection. Family history and congenital nevi were not significantly associated with melanoma detection in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany population. The effects of several risk-adapted screening strategies were evaluated. Hypothesizing a screening of individuals aged more than or equal to 35 years, irrespective of risk factors (age approach), the number needed to screen is 559 (95% CI: 514-612), whereas a screening of adults (aged ≥20) with at least one risk factor (risk approach) leads to an number needed to screen of 178 (95% CI: 163-196). Converted into one screen-detected melanoma, the number of missed melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI: 0.19-0.26) with the risk approach. The results indicate that focusing on individuals at high risk for melanoma may improve the cost-effectiveness and the benefit-to-harm balance of melanoma screening programs.

A Systematic Protein Refolding Screen Method using the DGR Approach Reveals that Time and Secondary TSA are Essential Variables.

Science.gov (United States)

Wang, Yuanze; van Oosterwijk, Niels; Ali, Ameena M; Adawy, Alaa; Anindya, Atsarina L; Dömling, Alexander S S; Groves, Matthew R

2017-08-24

Refolding of proteins derived from inclusion bodies is very promising as it can provide a reliable source of target proteins of high purity. However, inclusion body-based protein production is often limited by the lack of techniques for the detection of correctly refolded protein. Thus, the selection of the refolding conditions is mostly achieved using trial and error approaches and is thus a time-consuming process. In this study, we use the latest developments in the differential scanning fluorimetry guided refolding approach as an analytical method to detect correctly refolded protein. We describe a systematic buffer screen that contains a 96-well primary pH-refolding screen in conjunction with a secondary additive screen. Our research demonstrates that this approach could be applied for determining refolding conditions for several proteins. In addition, it revealed which "helper" molecules, such as arginine and additives are essential. Four different proteins: HA-RBD, MDM2, IL-17A and PD-L1 were used to validate our refolding approach. Our systematic protocol evaluates the impact of the "helper" molecules, the pH, buffer system and time on the protein refolding process in a high-throughput fashion. Finally, we demonstrate that refolding time and a secondary thermal shift assay buffer screen are critical factors for improving refolding efficiency.

Towards novel therapeutics for HIV through fragment-based screening and drug design.

Science.gov (United States)

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.

Free-Form Deformation Approach for Registration of Visible and Infrared Facial Images in Fever Screening

Directory of Open Access Journals (Sweden)

Yedukondala Narendra Dwith Chenna

2018-01-01

Full Text Available Fever screening based on infrared (IR thermographs (IRTs is an approach that has been implemented during infectious disease pandemics, such as Ebola and Severe Acute Respiratory Syndrome. A recently published international standard indicates that regions medially adjacent to the inner canthi provide accurate estimates of core body temperature and are preferred sites for fever screening. Therefore, rapid, automated identification of the canthi regions within facial IR images may greatly facilitate rapid fever screening of asymptomatic travelers. However, it is more difficult to accurately identify the canthi regions from IR images than from visible images that are rich with exploitable features. In this study, we developed and evaluated techniques for multi-modality image registration (MMIR of simultaneously captured visible and IR facial images for fever screening. We used free form deformation (FFD models based on edge maps to improve registration accuracy after an affine transformation. Two widely used FFD models in medical image registration based on the Demons and cubic B-spline algorithms were qualitatively compared. The results showed that the Demons algorithm outperformed the cubic B-spline algorithm, likely due to overfitting of outliers by the latter method. The quantitative measure of registration accuracy, obtained through selected control point correspondence, was within 2.8 ± 1.2 mm, which enables accurate and automatic localization of canthi regions in the IR images for temperature measurement.

Estimation of the applicability domain of kernel-based machine learning models for virtual screening

Directory of Open Access Journals (Sweden)

Fechner Nikolas

2010-03-01

Full Text Available Abstract Background The virtual screening of large compound databases is an important application of structural-activity relationship models. Due to the high structural diversity of these data sets, it is impossible for machine learning based QSAR models, which rely on a specific training set, to give reliable results for all compounds. Thus, it is important to consider the subset of the chemical space in which the model is applicable. The approaches to this problem that have been published so far mostly use vectorial descriptor representations to define this domain of applicability of the model. Unfortunately, these cannot be extended easily to structured kernel-based machine learning models. For this reason, we propose three approaches to estimate the domain of applicability of a kernel-based QSAR model. Results We evaluated three kernel-based applicability domain estimations using three different structured kernels on three virtual screening tasks. Each experiment consisted of the training of a kernel-based QSAR model using support vector regression and the ranking of a disjoint screening data set according to the predicted activity. For each prediction, the applicability of the model for the respective compound is quantitatively described using a score obtained by an applicability domain formulation. The suitability of the applicability domain estimation is evaluated by comparing the model performance on the subsets of the screening data sets obtained by different thresholds for the applicability scores. This comparison indicates that it is possible to separate the part of the chemspace, in which the model gives reliable predictions, from the part consisting of structures too dissimilar to the training set to apply the model successfully. A closer inspection reveals that the virtual screening performance of the model is considerably improved if half of the molecules, those with the lowest applicability scores, are omitted from the screening

Estimation of the applicability domain of kernel-based machine learning models for virtual screening.

Science.gov (United States)

Fechner, Nikolas; Jahn, Andreas; Hinselmann, Georg; Zell, Andreas

2010-03-11

The virtual screening of large compound databases is an important application of structural-activity relationship models. Due to the high structural diversity of these data sets, it is impossible for machine learning based QSAR models, which rely on a specific training set, to give reliable results for all compounds. Thus, it is important to consider the subset of the chemical space in which the model is applicable. The approaches to this problem that have been published so far mostly use vectorial descriptor representations to define this domain of applicability of the model. Unfortunately, these cannot be extended easily to structured kernel-based machine learning models. For this reason, we propose three approaches to estimate the domain of applicability of a kernel-based QSAR model. We evaluated three kernel-based applicability domain estimations using three different structured kernels on three virtual screening tasks. Each experiment consisted of the training of a kernel-based QSAR model using support vector regression and the ranking of a disjoint screening data set according to the predicted activity. For each prediction, the applicability of the model for the respective compound is quantitatively described using a score obtained by an applicability domain formulation. The suitability of the applicability domain estimation is evaluated by comparing the model performance on the subsets of the screening data sets obtained by different thresholds for the applicability scores. This comparison indicates that it is possible to separate the part of the chemspace, in which the model gives reliable predictions, from the part consisting of structures too dissimilar to the training set to apply the model successfully. A closer inspection reveals that the virtual screening performance of the model is considerably improved if half of the molecules, those with the lowest applicability scores, are omitted from the screening. The proposed applicability domain formulations

Evidence-based medicine: the value of vision screening.

Science.gov (United States)

Beauchamp, George R; Ellepola, Chalani; Beauchamp, Cynthia L

2010-01-01

To review the literature for evidence-based medicine (EBM), to assess the evidence for effectiveness of vision screening, and to propose moving toward value-based medicine (VBM) as a preferred basis for comparative effectiveness research. Literature based evidence is applied to five core questions concerning vision screening: (1) Is vision valuable (an inherent good)?; (2) Is screening effective (finding amblyopia)?; (3) What are the costs of screening?; (4) Is treatment effective?; and (5) Is amblyopia detection beneficial? Based on EBM literature and clinical experience, the answers to the five questions are: (1) yes; (2) based on literature, not definitively so; (3) relatively inexpensive, although some claim benefits for more expensive options such as mandatory exams; (4) yes, for compliant care, although treatment processes may have negative aspects such as "bullying"; and (5) economic productive values are likely very high, with returns of investment on the order of 10:1, while human value returns need further elucidation. Additional evidence is required to ascertain the degree to which vision screening is effective. The processes of screening are multiple, sequential, and complicated. The disease is complex, and good visual outcomes require compliance. The value of outcomes is appropriately analyzed in clinical, human, and economic terms.

Simple approach for the fabrication of screen-printed carbon-based electrode for amperometric detection on microchip electrophoresis

International Nuclear Information System (INIS)

Petroni, Jacqueline Marques; Lucca, Bruno Gabriel; Ferreira, Valdir Souza

2017-01-01

This paper describes a simple method for the fabrication of screen-printed based electrodes for amperometric detection on microchip electrophoresis (ME) devices. The procedure developed is quite simple and does not require expensive instrumentation or sophisticated protocols commonly employed on the production of amperometric sensors, such as photolithography or sputtering steps. The electrodes were fabricated through manual deposition of home-made conductive carbon ink over patterned acrylic substrate. Morphological structure and electrochemical behavior of the carbon electrodes were investigated by scanning electron microscopy and cyclic voltammetry. The produced amperometric sensors were coupled to polydimethylsiloxane (PDMS) microchips at end-channel configuration in order to evaluate their analytical performance. For this purpose, electrophoretic experiments were carried out using nitrite and ascorbic acid as model analytes. Separation of these substances was successfully performed within 50s with good resolution (R = 1.2) and sensitivities (713.5 pA/μM for nitrite and 255.4 pA/μM for ascorbate). The reproducibility of the fabrication method was evaluated and revealed good values concerning the peak currents obtained (8.7% for nitrite and 9.3% for ascorbate). The electrodes obtained through this method exhibited satisfactory lifetime (ca. 400 runs) over low fabrication cost (less than $1 per piece). The feasibility of the proposed device for real analysis was demonstrated through the determination of nitrite concentration levels in drinking water samples. Based on the results achieved, the approach proposed here shows itself as an interesting alternative for simple fabrication of carbon-based electrodes. Furthermore, the devices indicate great promise for other kind of analytical applications involving ME devices. - Highlights: • A novel method to fabricate screen-printed electrodes for amperometric detection in ME is demonstrated. • No sophisticated

Simple approach for the fabrication of screen-printed carbon-based electrode for amperometric detection on microchip electrophoresis

Energy Technology Data Exchange (ETDEWEB)

Petroni, Jacqueline Marques [Instituto de Química, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, 79074-460 (Brazil); Lucca, Bruno Gabriel, E-mail: bruno.lucca@ufes.br [Departamento de Ciências Naturais, Universidade Federal do Espírito Santo, São Mateus, ES, 29932-540 (Brazil); Ferreira, Valdir Souza [Instituto de Química, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, 79074-460 (Brazil)

2017-02-15

This paper describes a simple method for the fabrication of screen-printed based electrodes for amperometric detection on microchip electrophoresis (ME) devices. The procedure developed is quite simple and does not require expensive instrumentation or sophisticated protocols commonly employed on the production of amperometric sensors, such as photolithography or sputtering steps. The electrodes were fabricated through manual deposition of home-made conductive carbon ink over patterned acrylic substrate. Morphological structure and electrochemical behavior of the carbon electrodes were investigated by scanning electron microscopy and cyclic voltammetry. The produced amperometric sensors were coupled to polydimethylsiloxane (PDMS) microchips at end-channel configuration in order to evaluate their analytical performance. For this purpose, electrophoretic experiments were carried out using nitrite and ascorbic acid as model analytes. Separation of these substances was successfully performed within 50s with good resolution (R = 1.2) and sensitivities (713.5 pA/μM for nitrite and 255.4 pA/μM for ascorbate). The reproducibility of the fabrication method was evaluated and revealed good values concerning the peak currents obtained (8.7% for nitrite and 9.3% for ascorbate). The electrodes obtained through this method exhibited satisfactory lifetime (ca. 400 runs) over low fabrication cost (less than $1 per piece). The feasibility of the proposed device for real analysis was demonstrated through the determination of nitrite concentration levels in drinking water samples. Based on the results achieved, the approach proposed here shows itself as an interesting alternative for simple fabrication of carbon-based electrodes. Furthermore, the devices indicate great promise for other kind of analytical applications involving ME devices. - Highlights: • A novel method to fabricate screen-printed electrodes for amperometric detection in ME is demonstrated. • No sophisticated

Rationale, design, and results of the first screening round of a comprehensive, register-based, Chlamydia screening implementation programme in the Netherlands

Directory of Open Access Journals (Sweden)

Koekenbier Rik H

2010-10-01

Full Text Available Abstract Background Implementing Chlamydia trachomatis screening in the Netherlands has been a point of debate for several years. The National Health Council advised against implementing nationwide screening until additional data collected from a pilot project in 2003 suggested that screening by risk profiles could be effective. A continuous increase in infections recorded in the national surveillance database affirmed the need for a more active approach. Here, we describe the rationale, design, and implementation of a Chlamydia screening demonstration programme. Methods A systematic, selective, internet-based Chlamydia screening programme started in April 2008. Letters are sent annually to all 16 to 29-year-old residents of Amsterdam, Rotterdam, and selected municipalities of South Limburg. The letters invite sexually active persons to login to http://www.chlamydiatest.nl with a personal code and to request a test kit. In the lower prevalence area of South Limburg, test kits can only be requested if the internet-based risk assessment exceeds a predefined value. Results We sent invitations to 261,025 people in the first round. One-fifth of the invitees requested a test kit, of whom 80% sent in a sample for testing. The overall positivity rate was 4.2%. Conclusions This programme advances Chlamydia control activities in the Netherlands. Insight into the feasibility, effectiveness, cost-effectiveness, and impact of this large-scale screening programme will determine whether the programme will be implemented nationally.

Mass spectrometric-based stable isotopic 2-aminobenzoic acid glycan mapping for rapid glycan screening of biotherapeutics.

Science.gov (United States)

Prien, Justin M; Prater, Bradley D; Qin, Qiang; Cockrill, Steven L

2010-02-15

Fast, sensitive, robust methods for "high-level" glycan screening are necessary during various stages of a biotherapeutic product's lifecycle, including clone selection, process changes, and quality control for lot release testing. Traditional glycan screening involves chromatographic or electrophoretic separation-based methods, and, although reproducible, these methods can be time-consuming. Even ultrahigh-performance chromatographic and microfluidic integrated LC/MS systems, which work on the tens of minute time scale, become lengthy when hundreds of samples are to be analyzed. Comparatively, a direct infusion mass spectrometry (MS)-based glycan screening method acquires data on a millisecond time scale, exhibits exquisite sensitivity and reproducibility, and is amenable to automated peak annotation. In addition, characterization of glycan species via sequential mass spectrometry can be performed simultaneously. Here, we demonstrate a quantitative high-throughput MS-based mapping approach using stable isotope 2-aminobenzoic acid (2-AA) for rapid "high-level" glycan screening.

Library fingerprints: a novel approach to the screening of virtual libraries.

Science.gov (United States)

Klon, Anthony E; Diller, David J

2007-01-01

We propose a novel method to prioritize libraries for combinatorial synthesis and high-throughput screening that assesses the viability of a particular library on the basis of the aggregate physical-chemical properties of the compounds using a naïve Bayesian classifier. This approach prioritizes collections of related compounds according to the aggregate values of their physical-chemical parameters in contrast to single-compound screening. The method is also shown to be useful in screening existing noncombinatorial libraries when the compounds in these libraries have been previously clustered according to their molecular graphs. We show that the method used here is comparable or superior to the single-compound virtual screening of combinatorial libraries and noncombinatorial libraries and is superior to the pairwise Tanimoto similarity searching of a collection of combinatorial libraries.

In Vivo RNAi-Based Screens: Studies in Model Organisms

Directory of Open Access Journals (Sweden)

Miki Yamamoto-Hino

2013-11-01

Full Text Available RNA interference (RNAi is a technique widely used for gene silencing in organisms and cultured cells, and depends on sequence homology between double-stranded RNA (dsRNA and target mRNA molecules. Numerous cell-based genome-wide screens have successfully identified novel genes involved in various biological processes, including signal transduction, cell viability/death, and cell morphology. However, cell-based screens cannot address cellular processes such as development, behavior, and immunity. Drosophila and Caenorhabditis elegans are two model organisms whose whole bodies and individual body parts have been subjected to RNAi-based genome-wide screening. Moreover, Drosophila RNAi allows the manipulation of gene function in a spatiotemporal manner when it is implemented using the Gal4/UAS system. Using this inducible RNAi technique, various large-scale screens have been performed in Drosophila, demonstrating that the method is straightforward and valuable. However, accumulated results reveal that the results of RNAi-based screens have relatively high levels of error, such as false positives and negatives. Here, we review in vivo RNAi screens in Drosophila and the methods that could be used to remove ambiguity from screening results.

Lessons Learned From A Study Of Genomics-Based Carrier Screening For Reproductive Decision Making.

Science.gov (United States)

Wilfond, Benjamin S; Kauffman, Tia L; Jarvik, Gail P; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Gilmore, Marian; Himes, Patricia; Kraft, Stephanie A; Porter, Kathryn M; Schneider, Jennifer L; Punj, Sumit; Leo, Michael C; Dickerson, John F; Lynch, Frances L; Clarke, Elizabeth; Rope, Alan F; Lutz, Kevin; Goddard, Katrina A B

2018-05-01

Genomics-based carrier screening is one of many opportunities to use genomic information to inform medical decision making, but clinicians, health care delivery systems, and payers need to determine whether to offer screening and how to do so in an efficient, ethical way. To shed light on this issue, we conducted a study in the period 2014-17 to inform the design of clinical screening programs and guide further health services research. Many of our results have been published elsewhere; this article summarizes the lessons we learned from that study and offers policy insights. Our experience can inform understanding of the potential impact of expanded carrier screening services on health system workflows and workforces-impacts that depend on the details of the screening approach. We found limited patient or health system harms from expanded screening. We also found that some patients valued the information they learned from the process. Future policy discussions should consider the value of offering such expanded carrier screening in health delivery systems with limited resources.

A multi-substrate approach for functional metagenomics-based screening for (hemi)cellulases in two wheat straw-degrading microbial consortia unveils novel thermoalkaliphilic enzymes.

Science.gov (United States)

Maruthamuthu, Mukil; Jiménez, Diego Javier; Stevens, Patricia; van Elsas, Jan Dirk

2016-01-28

Functional metagenomics is a promising strategy for the exploration of the biocatalytic potential of microbiomes in order to uncover novel enzymes for industrial processes (e.g. biorefining or bleaching pulp). Most current methodologies used to screen for enzymes involved in plant biomass degradation are based on the use of single substrates. Moreover, highly diverse environments are used as metagenomic sources. However, such methods suffer from low hit rates of positive clones and hence the discovery of novel enzymatic activities from metagenomes has been hampered. Here, we constructed fosmid libraries from two wheat straw-degrading microbial consortia, denoted RWS (bred on untreated wheat straw) and TWS (bred on heat-treated wheat straw). Approximately 22,000 clones from each library were screened for (hemi)cellulose-degrading enzymes using a multi-chromogenic substrate approach. The screens yielded 71 positive clones for both libraries, giving hit rates of 1:440 and 1:1,047 for RWS and TWS, respectively. Seven clones (NT2-2, T5-5, NT18-17, T4-1, 10BT, NT18-21 and T17-2) were selected for sequence analyses. Their inserts revealed the presence of 18 genes encoding enzymes belonging to twelve different glycosyl hydrolase families (GH2, GH3, GH13, GH17, GH20, GH27, GH32, GH39, GH53, GH58, GH65 and GH109). These encompassed several carbohydrate-active gene clusters traceable mainly to Klebsiella related species. Detailed functional analyses showed that clone NT2-2 (containing a beta-galactosidase of ~116 kDa) had highest enzymatic activity at 55 °C and pH 9.0. Additionally, clone T5-5 (containing a beta-xylosidase of ~86 kDa) showed > 90% of enzymatic activity at 55 °C and pH 10.0. This study employed a high-throughput method for rapid screening of fosmid metagenomic libraries for (hemi)cellulose-degrading enzymes. The approach, consisting of screens on multi-substrates coupled to further analyses, revealed high hit rates, as compared with recent other studies. Two

A high-resolution peak fractionation approach for streamlined screening of nuclear-factor-E2-related factor-2 activators in Salvia miltiorrhiza.

Science.gov (United States)

Zhang, Hui; Luo, Li-Ping; Song, Hui-Peng; Hao, Hai-Ping; Zhou, Ping; Qi, Lian-Wen; Li, Ping; Chen, Jun

2014-01-24

Generation of a high-purity fraction library for efficiently screening active compounds from natural products is challenging because of their chemical diversity and complex matrices. In this work, a strategy combining high-resolution peak fractionation (HRPF) with a cell-based assay was proposed for target screening of bioactive constituents from natural products. In this approach, peak fractionation was conducted under chromatographic conditions optimized for high-resolution separation of the natural product extract. The HRPF approach was automatically performed according to the predefinition of certain peaks based on their retention times from a reference chromatographic profile. The corresponding HRPF database was collected with a parallel mass spectrometer to ensure purity and characterize the structures of compounds in the various fractions. Using this approach, a set of 75 peak fractions on the microgram scale was generated from 4mg of the extract of Salvia miltiorrhiza. After screening by an ARE-luciferase reporter gene assay, 20 diterpene quinones were selected and identified, and 16 of these compounds were reported to possess novel Nrf2 activation activity. Compared with conventional fixed-time interval fractionation, the HRPF approach could significantly improve the efficiency of bioactive compound discovery and facilitate the uncovering of minor active components. Copyright © 2013 Elsevier B.V. All rights reserved.

High-throughput Screening for Protein-based Inheritance in S. cerevisiae.

Science.gov (United States)

Byers, James S; Jarosz, Daniel F

2017-08-08

The encoding of biological information that is accessible to future generations is generally achieved via changes to the DNA sequence. Long-lived inheritance encoded in protein conformation (rather than sequence) has long been viewed as paradigm-shifting but rare. The best characterized examples of such epigenetic elements are prions, which possess a self-assembling behavior that can drive the heritable manifestation of new phenotypes. Many archetypal prions display a striking N/Q-rich sequence bias and assemble into an amyloid fold. These unusual features have informed most screening efforts to identify new prion proteins. However, at least three known prions (including the founding prion, PrP Sc ) do not harbor these biochemical characteristics. We therefore developed an alternative method to probe the scope of protein-based inheritance based on a property of mass action: the transient overexpression of prion proteins increases the frequency at which they acquire a self-templating conformation. This paper describes a method for analyzing the capacity of the yeast ORFeome to elicit protein-based inheritance. Using this strategy, we previously found that >1% of yeast proteins could fuel the emergence of biological traits that were long-lived, stable, and arose more frequently than genetic mutation. This approach can be employed in high throughput across entire ORFeomes or as a targeted screening paradigm for specific genetic networks or environmental stimuli. Just as forward genetic screens define numerous developmental and signaling pathways, these techniques provide a methodology to investigate the influence of protein-based inheritance in biological processes.

Pesticide Cumulative Risk Assessment: Framework for Screening Analysis

Science.gov (United States)

This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two-step approach: begin with evaluation of available toxicological information and, if necessary, follow up with a risk-based screening approach.

Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing

Science.gov (United States)

Yafia, Mohamed; Shukla, Saurabh; Najjaran, Homayoun

2015-05-01

In this work, a new fabrication method is presented for digital microfluidic (DMF) devices in which the electrodes are generated using the screen printing technique. This method is applicable to both rigid and flexible substrates. The proposed screen printing approach, as a batch printing technique, is advantageous to the widely reported DMF fabrication methods in terms of fabrication time, cost and capability of mass production. Screen printing provides an effective means for printing different types of conductive materials on a variety of substrates. Specifically, screen printing of conductive silver and carbon based inks is performed on paper, glass and wax paper. As a result, the fabricated DMF devices are characterized by being flexible, disposable and incinerable. Hence, the main advantage of screen printing carbon based inks on paper substrates is more pronounced for point-of-care applications that require a large number of low cost DMF chips, and laboratory setups that lack sophisticated microfabrication facilities. The resolution of the printed DMF electrodes generated by this technique is examined for proof of concept using manual screen printing, but higher resolution screens and automated machines are available off-the-shelf, if needed. Another contribution of this research is the improved actuation techniques that facilitate droplet transport in electrode configurations with relatively large electrode spacing to alleviate the disadvantage of lower resolution screens. Thus, we were able to reduce the cost of fabrication significantly without compromising the DMF performance. The paper-based devices have already shown to be effective in continuous microfluidics domain, so the investigation of their applicability in DMF systems is worthwhile. With this in mind, successful integration of a paper-based microchannel with paper-based digital microfluidic chip is demonstrated in this work.

Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing

International Nuclear Information System (INIS)

Yafia, Mohamed; Shukla, Saurabh; Najjaran, Homayoun

2015-01-01

In this work, a new fabrication method is presented for digital microfluidic (DMF) devices in which the electrodes are generated using the screen printing technique. This method is applicable to both rigid and flexible substrates. The proposed screen printing approach, as a batch printing technique, is advantageous to the widely reported DMF fabrication methods in terms of fabrication time, cost and capability of mass production. Screen printing provides an effective means for printing different types of conductive materials on a variety of substrates. Specifically, screen printing of conductive silver and carbon based inks is performed on paper, glass and wax paper. As a result, the fabricated DMF devices are characterized by being flexible, disposable and incinerable. Hence, the main advantage of screen printing carbon based inks on paper substrates is more pronounced for point-of-care applications that require a large number of low cost DMF chips, and laboratory setups that lack sophisticated microfabrication facilities. The resolution of the printed DMF electrodes generated by this technique is examined for proof of concept using manual screen printing, but higher resolution screens and automated machines are available off-the-shelf, if needed. Another contribution of this research is the improved actuation techniques that facilitate droplet transport in electrode configurations with relatively large electrode spacing to alleviate the disadvantage of lower resolution screens. Thus, we were able to reduce the cost of fabrication significantly without compromising the DMF performance. The paper-based devices have already shown to be effective in continuous microfluidics domain, so the investigation of their applicability in DMF systems is worthwhile. With this in mind, successful integration of a paper-based microchannel with paper-based digital microfluidic chip is demonstrated in this work. (note)

Identification of New Natural DNA G-Quadruplex Binders Selected by a Structure-Based Virtual Screening Approach

Directory of Open Access Journals (Sweden)

Stefano Alcaro

2013-09-01

Full Text Available The G-quadruplex DNA structures are mainly present at the terminal portion of telomeres and can be stabilized by ligands able to recognize them in a specific manner. The recognition process is usually related to the inhibition of the enzyme telomerase indirectly involved and over-expressed in a high percentage of human tumors. There are several ligands, characterized by different chemical structures, already reported in the literature for their ability to bind and stabilize the G-quadruplex structures. Using the structural and biological information available on these structures; we performed a high throughput in silico screening of commercially natural compounds databases by means of a structure-based approach followed by docking experiments against the human telomeric sequence d[AG3(T2AG33]. We identified 12 best hits characterized by different chemical scaffolds and conformational and physicochemical properties. All of them were associated to an improved theoretical binding affinity with respect to that of known selective G-binders. Among these hits there is a chalcone derivative; structurally very similar to the polyphenol butein; known to remarkably inhibit the telomerase activity.

Knowledge of Chlamydia trachomatis among men and women approached to participate in community-based screening, Scotland, UK

Directory of Open Access Journals (Sweden)

Hart Graham J

2010-12-01

Full Text Available Abstract Background Poor awareness and knowledge of Chlamydia trachomatis could be a barrier to uptake of screening. This study aimed to determine the level of awareness and knowledge of chlamydia among young people who were being approached in a variety of community settings and offered opportunistic screening. Methods Men and women aged 16-24 years were approached in education, health and fitness, and workplace settings and invited to complete a self-administered questionnaire then provide a urine sample for chlamydia testing. Follow-up semi-structured interviews with 24 respondents were carried out after test results were received. Results 363 questionnaires were completed (43.5% from men. Whilst awareness of chlamydia was high, knowledge decreased as questions became increasingly focussed so that around half of respondents were unaware of the asymptomatic nature of chlamydia infections. Men's knowledge of symptoms was consistently lower than women's, with most men failing to identify unusual discharge as a symptom in men (men 58.3%, female 45.8%, p = 0.019; fewer men knew unusual discharge was a symptom among women (men 65.3% female 21.4%, p Conclusions Despite scientific gains in understanding chlamydia infection, public understanding remains limited. Greater efforts are required to translate scientific evidence to the public. An improvement in knowledge may maximise gains from interventions to improve detection.

Knowledge of Chlamydia trachomatis among men and women approached to participate in community-based screening, Scotland, UK.

Science.gov (United States)

Lorimer, Karen; Hart, Graham J

2010-12-30

Poor awareness and knowledge of Chlamydia trachomatis could be a barrier to uptake of screening. This study aimed to determine the level of awareness and knowledge of chlamydia among young people who were being approached in a variety of community settings and offered opportunistic screening. Men and women aged 16-24 years were approached in education, health and fitness, and workplace settings and invited to complete a self-administered questionnaire then provide a urine sample for chlamydia testing. Follow-up semi-structured interviews with 24 respondents were carried out after test results were received. 363 questionnaires were completed (43.5% from men). Whilst awareness of chlamydia was high, knowledge decreased as questions became increasingly focussed so that around half of respondents were unaware of the asymptomatic nature of chlamydia infections. Men's knowledge of symptoms was consistently lower than women's, with most men failing to identify unusual discharge as a symptom in men (men 58.3%, female 45.8%, p = 0.019); fewer men knew unusual discharge was a symptom among women (men 65.3% female 21.4%, p participation in the study. Despite scientific gains in understanding chlamydia infection, public understanding remains limited. Greater efforts are required to translate scientific evidence to the public. An improvement in knowledge may maximise gains from interventions to improve detection.

Fragment-based approaches to the discovery of kinase inhibitors.

Science.gov (United States)

Mortenson, Paul N; Berdini, Valerio; O'Reilly, Marc

2014-01-01

Protein kinases are one of the most important families of drug targets, and aberrant kinase activity has been linked to a large number of disease areas. Although eminently targetable using small molecules, kinases present a number of challenges as drug targets, not least obtaining selectivity across such a large and relatively closely related target family. Fragment-based drug discovery involves screening simple, low-molecular weight compounds to generate initial hits against a target. These hits are then optimized to more potent compounds via medicinal chemistry, usually facilitated by structural biology. Here, we will present a number of recent examples of fragment-based approaches to the discovery of kinase inhibitors, detailing the construction of fragment-screening libraries, the identification and validation of fragment hits, and their optimization into potent and selective lead compounds. The advantages of fragment-based methodologies will be discussed, along with some of the challenges associated with using this route. Finally, we will present a number of key lessons derived both from our own experience running fragment screens against kinases and from a large number of published studies.

A screening approach for classroom acoustics using web-based listening tests and subjective ratings.

Science.gov (United States)

Persson Waye, Kerstin; Magnusson, Lennart; Fredriksson, Sofie; Croy, Ilona

2015-01-01

Perception of speech is crucial in school where speech is the main mode of communication. The aim of the study was to evaluate whether a web based approach including listening tests and questionnaires could be used as a screening tool for poor classroom acoustics. The prime focus was the relation between pupils' comprehension of speech, the classroom acoustics and their description of the acoustic qualities of the classroom. In total, 1106 pupils aged 13-19, from 59 classes and 38 schools in Sweden participated in a listening study using Hagerman's sentences administered via Internet. Four listening conditions were applied: high and low background noise level and positions close and far away from the loudspeaker. The pupils described the acoustic quality of the classroom and teachers provided information on the physical features of the classroom using questionnaires. In 69% of the classes, at least three pupils described the sound environment as adverse and in 88% of the classes one or more pupil reported often having difficulties concentrating due to noise. The pupils' comprehension of speech was strongly influenced by the background noise level (pcomprehension. Of the pupils' descriptions of acoustic qualities, clattery significantly (pcomprehension. Clattery was furthermore associated to difficulties understanding each other, while the description noisy was associated to concentration difficulties. The majority of classrooms do not seem to have an optimal sound environment. The pupil's descriptions of acoustic qualities and listening tests can be one way of predicting sound conditions in the classroom.

4D Flexible Atom-Pairs: An efficient probabilistic conformational space comparison for ligand-based virtual screening

Science.gov (United States)

2011-01-01

Background The performance of 3D-based virtual screening similarity functions is affected by the applied conformations of compounds. Therefore, the results of 3D approaches are often less robust than 2D approaches. The application of 3D methods on multiple conformer data sets normally reduces this weakness, but entails a significant computational overhead. Therefore, we developed a special conformational space encoding by means of Gaussian mixture models and a similarity function that operates on these models. The application of a model-based encoding allows an efficient comparison of the conformational space of compounds. Results Comparisons of our 4D flexible atom-pair approach with over 15 state-of-the-art 2D- and 3D-based virtual screening similarity functions on the 40 data sets of the Directory of Useful Decoys show a robust performance of our approach. Even 3D-based approaches that operate on multiple conformers yield inferior results. The 4D flexible atom-pair method achieves an averaged AUC value of 0.78 on the filtered Directory of Useful Decoys data sets. The best 2D- and 3D-based approaches of this study yield an AUC value of 0.74 and 0.72, respectively. As a result, the 4D flexible atom-pair approach achieves an average rank of 1.25 with respect to 15 other state-of-the-art similarity functions and four different evaluation metrics. Conclusions Our 4D method yields a robust performance on 40 pharmaceutically relevant targets. The conformational space encoding enables an efficient comparison of the conformational space. Therefore, the weakness of the 3D-based approaches on single conformations is circumvented. With over 100,000 similarity calculations on a single desktop CPU, the utilization of the 4D flexible atom-pair in real-world applications is feasible. PMID:21733172

Practical application of in silico fragmentation based residue screening with ion mobility high-resolution mass spectrometry.

Science.gov (United States)

Kaufmann, Anton; Butcher, Patrick; Maden, Kathry; Walker, Stephan; Widmer, Mirjam

2017-07-15

A screening concept for residues in complex matrices based on liquid chromatography coupled to ion mobility high-resolution mass spectrometry LC/IMS-HRMS is presented. The comprehensive four-dimensional data (chromatographic retention time, drift time, mass-to-charge and ion abundance) obtained in data-independent acquisition (DIA) mode was used for data mining. An in silico fragmenter utilizing a molecular structure database was used for suspect screening, instead of targeted screening with reference substances. The utilized data-independent acquisition mode relies on the MS E concept; where two constantly alternating HRMS scans (low and high fragmentation energy) are acquired. Peak deconvolution and drift time alignment of ions from the low (precursor ion) and high (product ion) energy scan result in relatively clean product ion spectra. A bond dissociation in silico fragmenter (MassFragment) supplied with mol files of compounds of interest was used to explain the observed product ions of each extracted candidate component (chromatographic peak). Two complex matrices (fish and bovine liver extract) were fortified with 98 veterinary drugs. Out of 98 screened compounds 94 could be detected with the in silico based screening approach. The high correlation among drift time and m/z value of equally charged ions was utilized for an orthogonal filtration (ranking). Such an orthogonal ion mobility based filter removes multiply charged ions (e.g. peptides and proteins from the matrix) as well as noise and artefacts. Most significantly, this filtration dramatically reduces false positive findings but hardly increases false negative findings. The proposed screening approach may offer new possibilities for applications where reference compounds are hardly or not at all commercially available. Such areas may be the analysis of metabolites of drugs, pyrrolizidine alkaloids, marine toxins, derivatives of sildenafil or novel designer drugs (new psychoactive substances

Screening of Riboflavin-Producing Lactobacilli by a Polymerase-Chain-Reaction-Based Approach and Microbiological Assay.

Science.gov (United States)

Thakur, Kiran; Tomar, Sudhir Kumar; Brahma, Biswajit; De, Sachinandan

2016-03-09

Riboflavin has an important role in various cellular metabolic activities through its participation in oxidation-reduction reactions. In this study, as many as 60 lactobacilli were screened for the presence or absence of riboflavin biosynthesis genes and riboflavin production. Of these, only 14 strains were able to grow in a commercial riboflavin-free medium. We observed that the presence of riboflavin biosynthesis genes is strain-specific across different species of lactobacilli. The microbiological assay was found to be appreciably reproducible, sensitive, rapid, and inexpensive and, hence, can be employed for screening the riboflavin-producing strains. The study thus represents a convenient and efficient method for selection of novel riboflavin producers. These riboflavin(+) strains thus identified and characterized could be explored as potent candidates for the development of a wide range of dairy- and cereal-based foods for the delivery of in situ riboflavin to consumers.

Application of microarray and functional-based screening methods for the detection of antimicrobial resistance genes in the microbiomes of healthy humans.

Directory of Open Access Journals (Sweden)

Roderick M Card

Full Text Available The aim of this study was to screen for the presence of antimicrobial resistance genes within the saliva and faecal microbiomes of healthy adult human volunteers from five European countries. Two non-culture based approaches were employed to obviate potential bias associated with difficult to culture members of the microbiota. In a gene target-based approach, a microarray was employed to screen for the presence of over 70 clinically important resistance genes in the saliva and faecal microbiomes. A total of 14 different resistance genes were detected encoding resistances to six antibiotic classes (aminoglycosides, β-lactams, macrolides, sulphonamides, tetracyclines and trimethoprim. The most commonly detected genes were erm(B, blaTEM, and sul2. In a functional-based approach, DNA prepared from pooled saliva samples was cloned into Escherichia coli and screened for expression of resistance to ampicillin or sulphonamide, two of the most common resistances found by array. The functional ampicillin resistance screen recovered genes encoding components of a predicted AcrRAB efflux pump. In the functional sulphonamide resistance screen, folP genes were recovered encoding mutant dihydropteroate synthase, the target of sulphonamide action. The genes recovered from the functional screens were from the chromosomes of commensal species that are opportunistically pathogenic and capable of exchanging DNA with related pathogenic species. Genes identified by microarray were not recovered in the activity-based screen, indicating that these two methods can be complementary in facilitating the identification of a range of resistance mechanisms present within the human microbiome. It also provides further evidence of the diverse reservoir of resistance mechanisms present in bacterial populations in the human gut and saliva. In future the methods described in this study can be used to monitor changes in the resistome in response to antibiotic therapy.

Quality management in European screening laboratories in blood establishments: A view of current approaches and trends.

Science.gov (United States)

Pereira, Paulo; Westgard, James O; Encarnação, Pedro; Seghatchian, Jerard; de Sousa, Gracinda

2015-04-01

The screening laboratory has a critical role in the post-transfusion safety. The success of its targets and efficiency depends on the management system used. Even though the European Union directive 2002/98/EC requires a quality management system in blood establishments, its requirements for screening laboratories are generic. Complementary approaches are needed to implement a quality management system focused on screening laboratories. This article briefly discusses the current good manufacturing practices and good laboratory practices, as well as the trends in quality management system standards. ISO 9001 is widely accepted in some European Union blood establishments as the quality management standard, however this is not synonymous of its successful application. The ISO "risk-based thinking" is interrelated with the quality risk-management process of the EuBIS "Standards and criteria for the inspection of blood establishments". ISO 15189 should be the next step on the quality assurance of a screening laboratory, since it is focused on medical laboratory. To standardize the quality management systems in blood establishments' screening laboratories, new national and European claims focused on technical requirements following ISO 15189 is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Computer Screen Use Detection Using Smart Eyeglasses

Directory of Open Access Journals (Sweden)

Florian Wahl

2017-05-01

Full Text Available Screen use can influence the circadian phase and cause eye strain. Smart eyeglasses with an integrated color light sensor can detect screen use. We present a screen use detection approach based on a light sensor embedded into the bridge of smart eyeglasses. By calculating the light intensity at the user’s eyes for different screens and content types, we found only computer screens to have a significant impact on the circadian phase. Our screen use detection is based on ratios between color channels and used a linear support vector machine to detect screen use. We validated our detection approach in three studies. A test bench was built to detect screen use under different ambient light sources and intensities in a controlled environment. In a lab study, we evaluated recognition performance for different ambient light intensities. By using participant-independent models, we achieved an ROC AUC above 0.9 for ambient light intensities below 200 lx. In a study of typical ADLs, screen use was detected with an average ROC AUC of 0.83 assuming screen use for 30% of the time.

Is screen-and-treat approach suited for screening and management of precancerous cervical lesions in Sub-Saharan Africa?

Science.gov (United States)

Fokom-Domgue, Joël; Vassilakos, Pierre; Petignat, Patrick

2014-08-01

The World Health Organization guidelines for screening and management of cervical precancerous lesions updated in 2013 made an emphasis on the use of the 'screen-and-treat' approach for cervical cancer prevention. In order to facilitate scaling-up in low income settings, most of these screen-and-treat strategies do not involve confirmatory biopsy. This yields a certain rate of overtreatment. In other words, a majority of people undergoing screen-and-treat intervention who are treated does not necessarily benefit from the treatment. Therefore, the issue of potential short term and long term complications of the recommended treatment procedures (cryotherapy and Loop Electrosurgical Excision Procedure) arises. This question has seldom been studied in resource poor countries, particularly in Sub-Saharan Africa where Human Immunodeficiency Virus infection is rampant in an epidemic fashion and where the procreative capacities are socially rewarding for women. We draw the attention of the scientific community and policy makers to the fact that the lack of evidence supporting the safety of these treatment procedures in African populations may have an impact on the acceptability of these strategies and therefore on the effectiveness of screening programs. Copyright © 2014 Elsevier Inc. All rights reserved.

Tele-cytology: An innovative approach for cervical cancer screening in resource-poor settings.

Science.gov (United States)

Singh, Sandeep; Badaya, Sorabh

2016-01-01

Carcinoma cervix remains a leading cause of cancer mortality among women in countries lacking any screening program. The existing screening policy and approach via conventional cytology centered mainly in Tertiary Care Center, is totally unaffordable to Indian women, especially in the remote areas. This suggests the need of depolarizing the resources via generating the near real time modalities which could be used at the door step of the needy ones. For any screening modality to be effective it should be adequately sensitive, specific, reproducible, cheap, simple, affordable, and the most important is should be real time to ensure wide coverage and curtail loss to follow-up. Incorporating telecytology as a screening tool could make the dream come true. Telecytology is the interpretation of cytology material at a distance using digital images. Use of mobile telecytology unit housed in a van carrying satellite equipment and the automated image capturing systems is the central theme behind this idea. The imaging equipment would be carrying out the imaging of Papanicolaou smears prepared at the screening site and sending the images to the central laboratories situated at some tertiary care level. This concept could overcome the hindrance of trained cytology infrastructure in the resource poor settings and could provide an efficient and economical way of screening patients. There is possibility that the designed approach may not detect the entire women positive for the disease but if the desired objective was to diagnose as many cases as possible in resource poor setting, then this process offers an advantage over no screening at all.

[Risk assessment for fetal trisomy 21 based on nuchal translucency measurement and biochemical screening at 11-13 weeks.].

Science.gov (United States)

Harðardóttir, H

2001-05-01

Screening for fetal aneuploidy during the first trimester using fetal nuchal translucency measurement and maternal serum free ss-hCG (ss-human chorionic gonadotropin) and PAPP-A (pregnancy associated plasma protein A) is commonly practised. An approach with a one stop clinic for assessment of risk for fetal anomalies, where pre-test counseling, blood test, ultrasound and post-test counseling is offered in one hour visit is described. Based on maternal age, biochemistry and fetal nuchal translucency measurement an estimated risk for fetal trisomies 13,18 and 21 is calculated. The main benefit of this approach in screening for fetal aneuploidy is the short turnaround time, with immediate results and a low screen positive rate. This approach leads to diagnosis of the majority (95%) of fetal aneuploidy cases. If screening is positive a diagnostic test is available with chorionic villous sampling or amniocentesis. In Iceland, fetal karyotyping is offered to women 35 years and older and performed during the second trimester, but by using this approach prenatal diagnosis can be moved to the first trimester and also offered to women of all ages. A screening approach with a series of steps from 10-15 weeks, including maternal blood test at 10 and again at 15 weeks, as well as an ultrasound and nuchal translucency measurement at 11-13 weeks, with integrated results at 15+ weeks has been proposed. This method offers even lower screen positive rate (1%) while detection rates of fetal aneuploides are high (>90%) but it requires four visits instead of one and the prolonged approach is likely to cause excess anxiety for the parents to be. If all women are to be offered prenatal sreening in the first trimester the structure of prenatal care in Iceland needs some modifications including scheduling the first prenatal visit at 8-10 weeks and teaching healthcare providers counseling regarding prenatal testing.

A Ligand-observed Mass Spectrometry Approach Integrated into the Fragment Based Lead Discovery Pipeline

Science.gov (United States)

Chen, Xin; Qin, Shanshan; Chen, Shuai; Li, Jinlong; Li, Lixin; Wang, Zhongling; Wang, Quan; Lin, Jianping; Yang, Cheng; Shui, Wenqing

2015-01-01

In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially for tough targets. In this study, this approach was integrated into a FBLD program targeting the HCV RNA polymerase NS5B. Our ligand-observed mass spectrometry analysis resulted in the discovery of 10 hits from a 384-member fragment library through two independent screens of complex cocktails and a follow-up validation assay. Moreover, this MS-based approach enabled quantitative measurement of weak binding affinities of fragments which was in general consistent with SPR analysis. Five out of the ten hits were then successfully translated to X-ray structures of fragment-bound complexes to lay a foundation for structure-based inhibitor design. With distinctive strengths in terms of high capacity and speed, minimal method development, easy sample preparation, low material consumption and quantitative capability, this MS-based assay is anticipated to be a valuable addition to the repertoire of current fragment screening techniques. PMID:25666181

Method for screening prevention and control measures and technologies based on groundwater pollution intensity assessment

Energy Technology Data Exchange (ETDEWEB)

Li, Juan, E-mail: lijuan@craes.org.cn [College of Water Sciences, Beijing Normal University, Beijing 100875 (China); Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Yang, Yang [College of Environment, Beijing Normal University, Beijing 100875 (China); Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Huan, Huan; Li, Mingxiao [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Xi, Beidou, E-mail: xibd413@yeah.net [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Lanzhou Jiaotong University, Lanzhou 730070 (China); Lv, Ningqing [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Wu, Yi [Guizhou Academy of Environmental Science and Designing, Guizhou 550000 (China); Xie, Yiwen, E-mail: qin3201@126.com [School of Chemical and Environmental Engineering, Dongguan University of Technology, Dongguan, 523808 (China); Li, Xiang; Yang, Jinjin [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China)

2016-05-01

This paper presents a system for determining the evaluation and gradation indices of groundwater pollution intensity (GPI). Considering the characteristics of the vadose zone and pollution sources, the system decides which anti-seepage measures should be implemented at the contaminated site. The pollution sources hazards (PSH) and groundwater intrinsic vulnerability (GIV) are graded by the revised Nemerow Pollution Index and an improved DRTAS model, respectively. GPI is evaluated and graded by a double-sided multi-factor coupling model, which is constructed by the matrix method. The contaminated sites are categorized as prior, ordinary, or common sites. From the GPI results, we develop guiding principles for preventing and removing pollution sources, procedural interruption and remediation, and end treatment and monitoring. Thus, we can select appropriate prevention and control technologies (PCT). To screen the technological schemes and optimize the traditional analytical hierarchy process (AHP), we adopt the technique for order preference by the similarity to ideal solution (TOPSIS) method. Our GPI approach and PCT screening are applied to three types of pollution sites: the refuse dump of a rare earth mine development project (a potential pollution source), a chromium slag dump, and a landfill (existing pollution sources). These three sites are identified as ordinary, prior, and ordinary sites, respectively. The anti-seepage materials at the refuse dump should perform as effectively as a 1.5-m-thick clay bed. The chromium slag dump should be preferentially treated by soil flushing and in situ chemical remediation. The landfill should be treated by natural attenuation technology. The proposed PCT screening approach was compared with conventional screening methods results at the three sites and proved feasible and effective. The proposed method can provide technical support for the monitoring and management of groundwater pollution in China. - Highlights: • An

Method for screening prevention and control measures and technologies based on groundwater pollution intensity assessment

International Nuclear Information System (INIS)

Li, Juan; Yang, Yang; Huan, Huan; Li, Mingxiao; Xi, Beidou; Lv, Ningqing; Wu, Yi; Xie, Yiwen; Li, Xiang; Yang, Jinjin

2016-01-01

This paper presents a system for determining the evaluation and gradation indices of groundwater pollution intensity (GPI). Considering the characteristics of the vadose zone and pollution sources, the system decides which anti-seepage measures should be implemented at the contaminated site. The pollution sources hazards (PSH) and groundwater intrinsic vulnerability (GIV) are graded by the revised Nemerow Pollution Index and an improved DRTAS model, respectively. GPI is evaluated and graded by a double-sided multi-factor coupling model, which is constructed by the matrix method. The contaminated sites are categorized as prior, ordinary, or common sites. From the GPI results, we develop guiding principles for preventing and removing pollution sources, procedural interruption and remediation, and end treatment and monitoring. Thus, we can select appropriate prevention and control technologies (PCT). To screen the technological schemes and optimize the traditional analytical hierarchy process (AHP), we adopt the technique for order preference by the similarity to ideal solution (TOPSIS) method. Our GPI approach and PCT screening are applied to three types of pollution sites: the refuse dump of a rare earth mine development project (a potential pollution source), a chromium slag dump, and a landfill (existing pollution sources). These three sites are identified as ordinary, prior, and ordinary sites, respectively. The anti-seepage materials at the refuse dump should perform as effectively as a 1.5-m-thick clay bed. The chromium slag dump should be preferentially treated by soil flushing and in situ chemical remediation. The landfill should be treated by natural attenuation technology. The proposed PCT screening approach was compared with conventional screening methods results at the three sites and proved feasible and effective. The proposed method can provide technical support for the monitoring and management of groundwater pollution in China. - Highlights: • An

Quality is the key for emerging issues of population-based colonoscopy screening

Directory of Open Access Journals (Sweden)

Jin Young Yoon

2018-01-01

Full Text Available Colonoscopy is currently regarded as the gold standard and preferred method of screening for colorectal cancer (CRC. However, the benefit of colonoscopy screening may be blunted by low participation rates in population-based screening programs. Harmful effects of population-based colonoscopy screening may include complications induced by colonoscopy itself and by sedation, psychosocial distress, potential over-diagnosis, and socioeconomic burden. In addition, harmful effects of colonoscopy may increase with age and comorbidities. As the risk of adverse events in population-based colonoscopy screening may offset the benefit, the adverse events should be managed and monitored. To adopt population-based colonoscopy screening, consensus on the risks and benefits should be developed, focusing on potential harm, patient preference, socioeconomic considerations, and quality improvement of colonoscopy, as well as efficacy for CRC prevention. As suboptimal colonoscopy quality is a major pitfall of population-based screening, adequate training and regulation of screening colonoscopists should be the first step in minimizing variations in quality. Gastroenterologists should promote quality improvement, auditing, and training for colonoscopy in a population-based screening program.

Single-item screening for agoraphobic symptoms : validation of a web-based audiovisual screening instrument

NARCIS (Netherlands)

van Ballegooijen, Wouter; Riper, Heleen; Donker, Tara; Martin Abello, Katherina; Marks, Isaac; Cuijpers, Pim

2012-01-01

The advent of web-based treatments for anxiety disorders creates a need for quick and valid online screening instruments, suitable for a range of social groups. This study validates a single-item multimedia screening instrument for agoraphobia, part of the Visual Screener for Common Mental Disorders

Phenotype-Based Screening of Small Molecules to Modify Plant Cell Walls Using BY-2 Cells.

Science.gov (United States)

Okubo-Kurihara, Emiko; Matsui, Minami

2018-01-01

The plant cell wall is an important and abundant biomass with great potential for use as a modern recyclable resource. For effective utilization of this cellulosic biomass, its ability to degrade efficiently is key point. With the aim of modifying the cell wall to allow easy decomposition, we used chemical biological technology to alter its structure. As a first step toward evaluating the chemicals in the cell wall we employed a phenotype-based approach using high-throughput screening. As the plant cell wall is essential in determining cell morphology, phenotype-based screening is particularly effective in identifying compounds that bring about alterations in the cell wall. For rapid and reproducible screening, tobacco BY-2 cell is an excellent system in which to observe cell morphology. In this chapter, we provide a detailed chemical biological methodology for studying cell morphology using tobacco BY-2 cells.

Approaching the Hard-to-Reach in Organized Colorectal Cancer Screening: an Overview of Individual, Provider and System Level Coping Strategies

Directory of Open Access Journals (Sweden)

Jason Liwen Huang

2017-06-01

Full Text Available Background: Despite the proven effectiveness of colorectal cancer (CRC screening on reduction of CRC mortality, the uptake of CRC screening remains low. Participation rate is one of determinants for the success of organized population-based screening program. This review aims to identify those who are hard-to-reach, and summarize the strategies to increase their screening rate from individual, provider and system levels. Methods: A systematic search of electronic English databases was conducted on the factors and strategies of uptake in CRC screening for the hard-to-reach population up to May 2017. Discussion: The coverage rate and participation rate are two indexes to identify the hard-to-reach population in organized CRC screening program. However, the homeless, new immigrants, people with severe mental illness, the jail intimates, and people with characteristics including lower education levels and/or low socioeconomic status, living in rural/remote areas, without insurance, and racial minorities are usually recognized as hard-to-reach populations. For them, organized screening programs offer a better coverage, while novel invitation approaches for eligible individuals and multiple strategies from primary care physicians are still needed to enhance screening rates among subjects who are hard-to-reach. Suggestions implied the effectiveness of interventions at the system level, including linkages to general practice; use of decision making tools; enlisting supports from coalition; and the continuum from screening to diagnosis and treatment. Conclusion: Organized CRC screening offers a system access to approach the hard-to-reach populations. To increase their uptake, multiple and novel strategies from individual, provider and system levels should be applied. For policymakers, public healthcare providers and community stakeholders, it is a test to tailor their potential needs and increase their participation rates through continuous efforts to

Discovery of Novel Inhibitors for Nek6 Protein through Homology Model Assisted Structure Based Virtual Screening and Molecular Docking Approaches

Directory of Open Access Journals (Sweden)

P. Srinivasan

2014-01-01

Full Text Available Nek6 is a member of the NIMA (never in mitosis, gene A-related serine/threonine kinase family that plays an important role in the initiation of mitotic cell cycle progression. This work is an attempt to emphasize the structural and functional relationship of Nek6 protein based on homology modeling and binding pocket analysis. The three-dimensional structure of Nek6 was constructed by molecular modeling studies and the best model was further assessed by PROCHECK, ProSA, and ERRAT plot in order to analyze the quality and consistency of generated model. The overall quality of computed model showed 87.4% amino acid residues under the favored region. A 3 ns molecular dynamics simulation confirmed that the structure was reliable and stable. Two lead compounds (Binding database ID: 15666, 18602 were retrieved through structure-based virtual screening and induced fit docking approaches as novel Nek6 inhibitors. Hence, we concluded that the potential compounds may act as new leads for Nek6 inhibitors designing.

COSMO-RS-based extractant screening for phenol extraction as model system

NARCIS (Netherlands)

Burghoff, B.; Goetheer, E.L.V.; Haan, A.B. de

2008-01-01

The focus of this investigation is the development of a fast and reliable extractant screening approach. Phenol extraction is selected as the model process. A quantum chemical conductor-like screening model for real solvents (COSMO-RS) is combined with molecular design considerations. For this

Photoprotection in Plants Optical Screening-based Mechanisms

CERN Document Server

Solovchenko, Alexei

2010-01-01

Optical screening of excessive and potentially harmful solar radiation is an important photoprotective mechanism, though it has received much less attention in comparison with other systems preventing photooxidative damage to photoautotrophic organisms. This photoprotection in the form of screening appears to be especially important for juvenile and senescing plants as well as under environmental stresses—i.e. in situations where the efficiency of enzymatic ROS elimination, DNA repair and other ‘classical’ photoprotective systems could be impaired. This book represents an attempt to develop an integral view of optical screening-based photoprotection in microalgae and higher plants. Towards this end, the key groups of pigments involved in the screening of ultraviolet and visible components of solar radiation in microalgae and higher plants, and the patterns of their accumulation and distribution within plant cells and tissues, are described. Special attention is paid to the manifestations of screening pi...

Targeted Screening With Combined Age- and Morphology-Based Criteria Enriches Detection of Lynch Syndrome in Endometrial Cancer.

Science.gov (United States)

Lin, Douglas I; Hecht, Jonathan L

2016-06-01

Endometrial cancer is associated with Lynch syndrome in 2% to 6% of cases. Adequate screening may prevent of a second cancer and incident cancers in family members via risk-reducing strategies. The goal of the study was to evaluate the detection rate of Lynch syndrome via a targeted screening approach. In 2009, we incorporated targeted Lynch syndrome screening via immunohistochemistry for MLH1, PMS2, MSH2, and MSH6, followed by MLH1 promoter hypermethylation, in select cases of endometrial carcinoma. Criteria for patient selection included (1) all patients Lynch syndrome. Therefore, targeted screening with combined age and morphology based criteria enriches detection of Lynch syndrome in endometrial cancer. However, the detection rate is lower than the rates from published series that offer universal screening. © The Author(s) 2016.

Variable screening and ranking using sampling-based sensitivity measures

International Nuclear Information System (INIS)

Wu, Y-T.; Mohanty, Sitakanta

2006-01-01

This paper presents a methodology for screening insignificant random variables and ranking significant important random variables using sensitivity measures including two cumulative distribution function (CDF)-based and two mean-response based measures. The methodology features (1) using random samples to compute sensitivities and (2) using acceptance limits, derived from the test-of-hypothesis, to classify significant and insignificant random variables. Because no approximation is needed in either the form of the performance functions or the type of continuous distribution functions representing input variables, the sampling-based approach can handle highly nonlinear functions with non-normal variables. The main characteristics and effectiveness of the sampling-based sensitivity measures are investigated using both simple and complex examples. Because the number of samples needed does not depend on the number of variables, the methodology appears to be particularly suitable for problems with large, complex models that have large numbers of random variables but relatively few numbers of significant random variables

SELEX-Based Screening of Exosome-Tropic RNA.

Science.gov (United States)

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.

Screening for chronic comorbid diseases in people with HIV: the need for a strategic approach.

Science.gov (United States)

Peters, B; Post, F; Wierzbicki, A S; Phillips, A; Power, L; Das, S; Johnson, M; Moyle, G; Hughes, L; Wilkins, E; McCloskey, E; Compston, J; Di Angelantonio, E

2013-01-01

Among people living with HIV, the proportion of deaths attributed to chronic noninfectious comorbid diseases has increased over the past 15 years. This is partly a result of increased longevity in the era of highly active antiretroviral therapy (HAART), and also because HIV infection is related, causally or otherwise, to several chronic conditions. These comorbidities include conditions that are strongly associated with modifiable risk factors, such as cardiovascular disease (CVD), diabetes, and renal and bone diseases, and increasingly management guidelines for HIV recommend risk evaluation for these conditions. The uptake of these screening approaches is often limited by the resources required for their application, and hence the management of risk reduction in most HIV-infected populations falls below a reasonable standard. The situation is compounded by the fact that few risk calculators have been adjusted for specific use in HIV infection. There is substantial overlap of risk factors for the four common comorbid diseases listed above that are especially relevant in HIV infection, and this offers an opportunity to develop a simple screening approach that encompasses the key risk factors for lifestyle-related chronic disease in people with HIV infection. This would identify those patients who require more in-depth investigation, and facilitate a stepwise approach to targeted management. Such a tool could improve communication between patient and clinician. A significant proportion of people with HIV are sufficiently engaged with their care to participate in health promotion and take the lead in using patient-centric screening measures. Health-based social networking offers a mechanism for dissemination of such a tool and is able to embed educational messages and support within the process. © 2012 British HIV Association.

The Cost-Effectiveness of School-Based Eating Disorder Screening

Science.gov (United States)

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

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

Science.gov (United States)

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-based activities and physical complaints among adolescents from the Nordic countries

Directory of Open Access Journals (Sweden)

Bjarnason Thoroddur

2010-06-01

Full Text Available Abstract Background A positive association between time spent on sedentary screen-based activities and physical complaints has been reported, but the cumulative association between different types of screen-based activities and physical complaints has not been examined thoroughly. Methods The cross-sectional association between screen-based activity and physical complaints (backache and headache among students was examined in a sample of 31022 adolescents from Denmark, Sweden, Norway, Finland, Iceland and Greenland, as part of the Health behaviour in school-aged children 2005/06 (HBSC study. Daily hours spent on screen-based activities and levels of physical complaints were assessed using self-reports. Results Logistic regression analysis indicated that computer use, computer gaming and TV viewing contributed uniquely to prediction of weekly backache and headache. The magnitude of associations was consistent across types of screen based activities, and across gender. Conclusion The observed associations indicate that time spent on screen-based activity is a contributing factor to physical complaints among young people, and that effects accumulate across different types of screen-based activities.

Novel colchicine-site binders with a cyclohexanedione scaffold identified through a ligand-based virtual screening approach.

Science.gov (United States)

Canela, María-Dolores; Pérez-Pérez, María-Jesús; Noppen, Sam; Sáez-Calvo, Gonzalo; Díaz, J Fernando; Camarasa, María-José; Liekens, Sandra; Priego, Eva-María

2014-05-22

Vascular disrupting agents (VDAs) constitute an innovative anticancer therapy that targets the tumor endothelium, leading to tumor necrosis. Our approach for the identification of new VDAs has relied on a ligand 3-D shape similarity virtual screening (VS) approach using the ROCS program as the VS tool and as query colchicine and TN-16, which both bind the α,β-tubulin dimer. One of the hits identified, using TN-16 as query, has been explored by the synthesis of its structural analogues, leading to 2-(1-((2-methoxyphenyl)amino)ethylidene)-5-phenylcyclohexane-1,3-dione (compound 16c) with an IC50 = 0.09 ± 0.01 μM in HMEC-1 and BAEC, being 100-fold more potent than the initial hit. Compound 16c caused cell cycle arrest in the G2/M phase and interacted with the colchicine-binding site in tubulin, as confirmed by a competition assay with N,N'-ethylenebis(iodoacetamide) and by fluorescence spectroscopy. Moreover, 16c destroyed an established endothelial tubular network at 1 μM and inhibited the migration and invasion of human breast carcinoma cells at 0.4 μM. In conclusion, our approach has led to a new chemotype of promising antiproliferative compounds with antimitotic and potential VDA properties.

Systematic review of model-based cervical screening evaluations.

Science.gov (United States)

Mendes, Diana; Bains, Iren; Vanni, Tazio; Jit, Mark

2015-05-01

Optimising population-based cervical screening policies is becoming more complex due to the expanding range of screening technologies available and the interplay with vaccine-induced changes in epidemiology. Mathematical models are increasingly being applied to assess the impact of cervical cancer screening strategies. We systematically reviewed MEDLINE®, Embase, Web of Science®, EconLit, Health Economic Evaluation Database, and The Cochrane Library databases in order to identify the mathematical models of human papillomavirus (HPV) infection and cervical cancer progression used to assess the effectiveness and/or cost-effectiveness of cervical cancer screening strategies. Key model features and conclusions relevant to decision-making were extracted. We found 153 articles meeting our eligibility criteria published up to May 2013. Most studies (72/153) evaluated the introduction of a new screening technology, with particular focus on the comparison of HPV DNA testing and cytology (n = 58). Twenty-eight in forty of these analyses supported HPV DNA primary screening implementation. A few studies analysed more recent technologies - rapid HPV DNA testing (n = 3), HPV DNA self-sampling (n = 4), and genotyping (n = 1) - and were also supportive of their introduction. However, no study was found on emerging molecular markers and their potential utility in future screening programmes. Most evaluations (113/153) were based on models simulating aggregate groups of women at risk of cervical cancer over time without accounting for HPV infection transmission. Calibration to country-specific outcome data is becoming more common, but has not yet become standard practice. Models of cervical screening are increasingly used, and allow extrapolation of trial data to project the population-level health and economic impact of different screening policy. However, post-vaccination analyses have rarely incorporated transmission dynamics. Model calibration to country

New approaches to screening infrastructure investments in multi-reservoir systems- Evaluating proposed dams in Ethiopia and Kenya

Science.gov (United States)

Harou, J. J.; Geressu, R. T.; Hurford, A. P.

2014-12-01

Two approaches have been used traditionally to screen infrastructure investments in multi-reservoir systems: scenario analysis of a few simulated designs and deterministic optimization, sometimes using hydro-economic models or screening optimization models. Simulation models realistically represent proposed water systems and can easily include multiple performance metrics; however each prospective system operating rules need to be formulated and simulated for each proposed design (time consuming. Optimization models have been used to overcome this burden. Screening optimization models use integer or non-linear programming and can be challenging to apply to large and/or multi-objective systems. Hydro-economic models that use deterministic (implicit stochastic) optimization must be modified to examine each different plan and they cannot always reproduce realistic or politically acceptable system operations. In this presentation we demonstrate the application of a new screening approach to multi-reservoir systems where operating rules and new assets (dams) are simultaneously optimized in a multi-criteria context. Results are not least cost investment plans that satisfy reliability or other engineering constraints, but rather Pareto-optimal sets of asset portfolios that work well under historical and/or future scenarios. This is achieved by using stakeholder-built simulation models linked to multi-criteria search algorithms (e.g. many objective evolutionary algorithms, MOEA). Typical output is demonstrated through two case-studies on the Tana and Blue Nile rivers where operating rules and reservoir assets are efficiently screened together considering stakeholder-defined metrics. The focus on the Tana system is how reservoir operating rules and new irrigation schemes should be co-managed to limit ecological damages. On the Nile system, we identify Blue Nile river reservoir capacities that least negatively impact downstream Nile nations. Limitations and new directions of

A new approach to data evaluation in the non-target screening of organic trace substances in water analysis.

Science.gov (United States)

Müller, Alexander; Schulz, Wolfgang; Ruck, Wolfgang K L; Weber, Walter H

2011-11-01

Non-target screening via high performance liquid chromatography-mass spectrometry (HPLC-MS) has gained increasingly in importance for monitoring organic trace substances in water resources targeted for the production of drinking water. In this article a new approach for evaluating the data from non-target HPLC-MS screening in water is introduced and its advantages are demonstrated using the supply of drinking water as an example. The crucial difference between this and other approaches is the comparison of samples based on compounds (features) determined by their full scan data. In so doing, we take advantage of the temporal, spatial, or process-based relationships among the samples by applying the set operators, UNION, INTERSECT, and COMPLEMENT to the features of each sample. This approach regards all compounds, detectable by the used analytical method. That is the fundamental meaning of non-target screening, which includes all analytical information from the applied technique for further data evaluation. In the given example, in just one step, all detected features (1729) of a landfill leachate sample could be examined for their relevant influences on water purification respectively drinking water. This study shows that 1721 out of 1729 features were not relevant for the water purification. Only eight features could be determined in the untreated water and three of them were found in the final drinking water after ozonation. In so doing, it was possible to identify 1-adamantylamine as contamination of the landfill in the drinking water at a concentration in the range of 20 ng L(-1). To support the identification of relevant compounds and their transformation products, the DAIOS database (Database-Assisted Identification of Organic Substances) was used. This database concept includes some functions such as product ion search to increase the efficiency of the database query after the screening. To identify related transformation products the database function

Prediction of the PCDD/F and dl-PCB 2005-WHO-TEQ content based on the contribution of six congeners: Toward a new screening approach for fish samples?

International Nuclear Information System (INIS)

Cariou, Ronan; Marchand, Philippe; Venisseau, Anais; Brosseaud, Aline; Bertrand, Dominique; Qannari, El Mostafa; Antignac, Jean-Philippe; Le Bizec, Bruno

2010-01-01

Current European Union regulation regarding polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in food and feed is based on Toxic Equivalent Quotient (TEQ) concept. For confirmatory purpose, the isotope-dilution method associated to a measurement by gas chromatography coupled with high resolution mass spectrometry is usually the method of choice for precisely measuring the 29 target congeners in three separated fractions. Time and cost related to these analyses are very significant. Various kinds of screening concepts can be considered. In the present study, we elaborated and validated a prediction model for the 2005 World Health Organization TEQ in fish, based on the measurement of 4 PCDD/F and 2 non-ortho dl-PCB congeners, potentially analyzable in a single extracted fraction by gas chromatography coupled with mass spectrometry. Large independent datasets have been used for model elaboration (n = 108) and validation (n = 363, n = 357 and n = 6). - This study describes a statistical regression model approach for screening PCDD/Fs and dl-PCBs in fish.

Impact of gender on decisions to participate in faecal immunochemical test-based colorectal cancer screening: a qualitative study.

Science.gov (United States)

Clarke, Nicholas; Gallagher, Pamela; Kearney, Patricia M; McNamara, Deirdre; Sharp, Linda

2016-12-01

Faecal immunochemical tests (FITs) are increasingly being used in population-based colorectal cancer-screening programmes. Uptake of FIT is lower in men than women; however, the reasons for this are not well understood. We aimed to explore gender differences in influences on decisions to participate in FIT screening. This is a qualitative study using in-depth face-to-face interviews of four groups of screening invitees (male and female screening users and male and female screening non-users), purposively sampled from the database of a population-based FIT screening programme. Recruitment continued until saturation was reached. Interviews were audio recorded and transcribed verbatim. Thematic analysis using the framework approach was employed with the theoretical domains framework guiding analysis. Forty-seven screening invitees were interviewed. Six theoretical domains influenced screening uptake: 'environmental context and resources', 'beliefs about capabilities', 'beliefs about consequences', 'emotions', 'social influences' and 'knowledge'. Male non-users were often fatalistic, less knowledgeable and misinformed about cancer and FIT screening compared with other groups. Female non-users expressed negative attitudes, beliefs and emotions towards FIT screening, cancer, social influences and the medical profession and were over-confident about their health. Negative attitudes and emotions to screening dominated non-user decision-making but differed by gender. Opportunities to improve uptake in men and women exist. Greater national discussions on the benefits of FIT screening, and development of screening materials tackling negative attitudes and beliefs while recognising male/female differences, may improve screening uptake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Performance of machine learning methods for ligand-based virtual screening.

Science.gov (United States)

Plewczynski, Dariusz; Spieser, Stéphane A H; Koch, Uwe

2009-05-01

Computational screening of compound databases has become increasingly popular in pharmaceutical research. This review focuses on the evaluation of ligand-based virtual screening using active compounds as templates in the context of drug discovery. Ligand-based screening techniques are based on comparative molecular similarity analysis of compounds with known and unknown activity. We provide an overview of publications that have evaluated different machine learning methods, such as support vector machines, decision trees, ensemble methods such as boosting, bagging and random forests, clustering methods, neuronal networks, naïve Bayesian, data fusion methods and others.

Using ontology-based semantic similarity to facilitate the article screening process for systematic reviews.

Science.gov (United States)

Ji, Xiaonan; Ritter, Alan; Yen, Po-Yin

2017-05-01

Systematic Reviews (SRs) are utilized to summarize evidence from high quality studies and are considered the preferred source of evidence-based practice (EBP). However, conducting SRs can be time and labor intensive due to the high cost of article screening. In previous studies, we demonstrated utilizing established (lexical) article relationships to facilitate the identification of relevant articles in an efficient and effective manner. Here we propose to enhance article relationships with background semantic knowledge derived from Unified Medical Language System (UMLS) concepts and ontologies. We developed a pipelined semantic concepts representation process to represent articles from an SR into an optimized and enriched semantic space of UMLS concepts. Throughout the process, we leveraged concepts and concept relations encoded in biomedical ontologies (SNOMED-CT and MeSH) within the UMLS framework to prompt concept features of each article. Article relationships (similarities) were established and represented as a semantic article network, which was readily applied to assist with the article screening process. We incorporated the concept of active learning to simulate an interactive article recommendation process, and evaluated the performance on 15 completed SRs. We used work saved over sampling at 95% recall (WSS95) as the performance measure. We compared the WSS95 performance of our ontology-based semantic approach to existing lexical feature approaches and corpus-based semantic approaches, and found that we had better WSS95 in most SRs. We also had the highest average WSS95 of 43.81% and the highest total WSS95 of 657.18%. We demonstrated using ontology-based semantics to facilitate the identification of relevant articles for SRs. Effective concepts and concept relations derived from UMLS ontologies can be utilized to establish article semantic relationships. Our approach provided a promising performance and can easily apply to any SR topics in the

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

Science.gov (United States)

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

Evaluation of two-year Jewish genetic disease screening program in Atlanta: insight into community genetic screening approaches.

Science.gov (United States)

Shao, Yunru; Liu, Shuling; Grinzaid, Karen

2015-04-01

Improvements in genetic testing technologies have led to the development of expanded carrier screening panels for the Ashkenazi Jewish population; however, there are major inconsistencies in current screening practices. A 2-year pilot program was launched in Atlanta in 2010 to promote and facilitate screening for 19 Jewish genetic diseases. We analyzed data from this program, including participant demographics and outreach efforts. This retrospective analysis is based on a de-identified dataset of 724 screenees. Data were obtained through medical chart review and questionnaires and included demographic information, screening results, response to outreach efforts, and follow-up behavior and preferences. We applied descriptive analysis, chi-square tests, and logistic regression to analyze the data and compare findings with published literature. The majority of participants indicated that they were not pregnant or did not have a partner who was pregnant were affiliated with Jewish organizations and reported 100 % AJ ancestry. Overall, carrier frequency was 1 in 3.9. Friends, rabbis, and family members were the most common influencers of the decision to receive screening. People who were older, had a history of pregnancy, and had been previously screened were more likely to educate others (all p influencers who then encouraged screening in the target population. Educating influencers and increasing overall awareness were the most effective outreach strategies.

Simple approach for the fabrication of screen-printed carbon-based electrode for amperometric detection on microchip electrophoresis.

Science.gov (United States)

Petroni, Jacqueline Marques; Lucca, Bruno Gabriel; Ferreira, Valdir Souza

2017-02-15

This paper describes a simple method for the fabrication of screen-printed based electrodes for amperometric detection on microchip electrophoresis (ME) devices. The procedure developed is quite simple and does not require expensive instrumentation or sophisticated protocols commonly employed on the production of amperometric sensors, such as photolithography or sputtering steps. The electrodes were fabricated through manual deposition of home-made conductive carbon ink over patterned acrylic substrate. Morphological structure and electrochemical behavior of the carbon electrodes were investigated by scanning electron microscopy and cyclic voltammetry. The produced amperometric sensors were coupled to polydimethylsiloxane (PDMS) microchips at end-channel configuration in order to evaluate their analytical performance. For this purpose, electrophoretic experiments were carried out using nitrite and ascorbic acid as model analytes. Separation of these substances was successfully performed within 50s with good resolution (R = 1.2) and sensitivities (713.5 pA/μM for nitrite and 255.4 pA/μM for ascorbate). The reproducibility of the fabrication method was evaluated and revealed good values concerning the peak currents obtained (8.7% for nitrite and 9.3% for ascorbate). The electrodes obtained through this method exhibited satisfactory lifetime (ca. 400 runs) over low fabrication cost (less than $1 per piece). The feasibility of the proposed device for real analysis was demonstrated through the determination of nitrite concentration levels in drinking water samples. Based on the results achieved, the approach proposed here shows itself as an interesting alternative for simple fabrication of carbon-based electrodes. Furthermore, the devices indicate great promise for other kind of analytical applications involving ME devices. Copyright © 2016 Elsevier B.V. All rights reserved.

Reaching the Unreachable: Novel Approaches to Telemedicine Screening of Underserved Populations for Vitreoretinal Disease.

Science.gov (United States)

Murchison, Ann P; Haller, Julia A; Mayro, Eileen; Hark, Lisa; Gower, Emily; Huisingh, Carrie; Rhodes, Lindsay; Friedman, David S; Lee, David J; Lam, Byron L

2017-07-01

Telemedicine involves electronic communication between a physician in one location and a patient in another location to provide remote medical care. Ophthalmologists are increasingly employing telemedicine, particularly in retinal disease screening and monitoring. Telemedicine has been utilized to decrease barriers to care and yield greater patient satisfaction and lower costs, while maintaining high sensitivity and specificity. This review discusses common patient barriers to eye care, innovative approaches to retinal disease screening and monitoring using telemedicine, and eye care policy initiatives needed to enact large-scale telemedicine eye disease screening programs.

Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia

Science.gov (United States)

Wen, Qiang; Goldenson, Benjamin; Silver, Serena J.; Schenone, Monica; Dancik, Vladimir; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy; An, W. Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S.; Moore, Christopher B.; Bliss-Moreau, Meghan; VerPlank, Lynn; Tolliday, Nicola J.; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K.; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D. Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S.; Smith, Franklin O.; Woods, William G.; Taub, Jeffrey; Scherer, Christina A.; Bradner, James; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E.; Gould, Robert J.; Clemons, Paul A.; Carr, Steven A.; Root, David E.; Schreiber, Stuart L.; Stern, Andrew M.; Crispino, John D.

2012-01-01

Summary The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. We found that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. A broadly applicable, highly integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora A kinase (AURKA), which has not been studied extensively in megakaryocytes. Moreover, we discovered that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in AMKL blasts and displayed potent anti-AMKL activity in vivo. This research provides the rationale to support clinical trials of MLN8237 and other inducers of polyploidization in AMKL. Finally, we have identified five networks of kinases that regulate the switch to polyploidy. PMID:22863010

New approach for risk based inspection of H2S based Process Plants

International Nuclear Information System (INIS)

Vinod, Gopika; Sharma, Pavan K.; Santosh, T.V.; Hari Prasad, M.; Vaze, K.K.

2014-01-01

Highlights: • Study looks into improving the consequence evaluation in risk based inspection. • Ways to revise the quantity factors used in qualitative approach. • New approach based on computational fluid dynamics along with probit mathematics. • Demonstrated this methodology along with a suitable case study for the said issue. - Abstract: Recent trend in risk informed and risk based approaches in life management issues have certainly put the focus on developing estimation methods for real risk. Idea of employing risk as an optimising measure for in-service inspection, termed as risk based inspection, was accepted in principle from late 80s. While applying risk based inspection, consequence of failure from each component needs to be assessed. Consequence evaluation in a Process Plant is a crucial task. It may be noted that, in general, the number of components to be considered for life management is very large and hence the consequence evaluation resulting from their failures (individually) is a laborious task. Screening of critical components is usually carried out using simplified qualitative approach, which primarily uses influence factors for categorisation. This necessitates logical formulation of influence factors and their ranges with a suitable technical basis for acceptance from regulators. This paper describes application of risk based inspection for H 2 S based Process Plant along with the approach devised for handling the influence factor related to the quantity of H 2 S released

An efficient route to selective bio-oxidation catalysts: an iterative approach comprising modeling, diversification, and screening, based on CYP102A1.

Science.gov (United States)

Seifert, Alexander; Antonovici, Mihaela; Hauer, Bernhard; Pleiss, Jürgen

2011-06-14

Perillyl alcohol is the terminal hydroxylation product of the cheap and readily available terpene, limonene. It has high potential as an anti-tumor substance, but is of limited availability. In principle, cytochrome P450 monooxygenases, such as the self-sufficient CYP102A1, are promising catalysts for the oxidation of limonene or other inert hydrocarbons. The wild-type enzyme converts (4R)-limonene to four different oxidation products; however, terminal hydroxylation at the allylic C7 is not observed. Here we describe a generic strategy to engineer this widely used enzyme to hydroxylate exclusively the exposed, but chemically less reactive, primary C7 in the presence of other reactive positions. The approach presented here turns CYP102A1 into a highly selective catalyst with a shifted product spectra by successive rounds of modeling, the design of small focused libraries, and screening. In the first round a minimal CYP102A1 mutant library was rationally designed. It contained variants with improved or strongly shifted regio-, stereo- and chemoselectivity, compared to wild-type. From this library the variant with the highest perillyl alcohol ratio was fine-tuned by two additional rounds of molecular modeling, diversification, and screening. In total only 29 variants needed to be screened to identify the triple mutant A264V/A238V/L437F that converts (4R)-limonene to perillyl alcohol with a selectivity of 97 %. Focusing mutagenesis on a small number of relevant positions identified by computational approaches is the key for efficient screening for enzyme selectivity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NASA Conjunction Assessment Organizational Approach and the Associated Determination of Screening Volume Sizes

Science.gov (United States)

Newman, Lauri K.; Hejduk, Matthew D.

2015-01-01

NASA is committed to safety of flight for all of its operational assets Performed by CARA at NASA GSFC for robotic satellites Focus of this briefing Performed by TOPO at NASA JSC for human spaceflight he Conjunction Assessment Risk Analysis (CARA) was stood up to offer this service to all NASA robotic satellites Currently provides service to 70 operational satellites NASA unmanned operational assets Other USG assets (USGS, USAF, NOAA) International partner assets Conjunction Assessment (CA) is the process of identifying close approaches between two orbiting objects; sometimes called conjunction screening The Joint Space Operations Center (JSpOC) a USAF unit at Vandenberg AFB, maintains the high accuracy catalog of space objects, screens CARA-supported assets against the catalog, performs OD tasking, and generates close approach data.

Determinants of successful implementation of population-based cancer screening programmes

DEFF Research Database (Denmark)

Lynge, Elsebeth; Törnberg, Sven; von Karsa, Lawrence

2012-01-01

consider when planning, implementing and running population based cancer screening programmes. The list is general and is applicable to breast, cervical and colorectal cancer screening. It is based on evidence presented in the three European Union guidelines on quality assurance in cancer screening...... and diagnosis, supplemented with other literature and expert experience presented at a European Science Advisory Network for Health workshop. The implementation of a cancer screening programme should be divided into the following seven phases: (1) before planning, (2) planning, (3) feasibility testing, (4......) piloting or trial implementation, (5) scaling up from pilot to service, (6) running of full-scale programme, and (7) sustainability. For each phase, a substantial number of specified conditions have to be met. Successful implementation of a cancer screening programme requires societal acceptance and local...

A prediction model-based algorithm for computer-assisted database screening of adverse drug reactions in the Netherlands.

Science.gov (United States)

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.

A knowledge-based approach for identification of drugs against vivapain-2 protein of Plasmodium vivax through pharmacophore-based virtual screening with comparative modelling.

Science.gov (United States)

Yadav, Manoj Kumar; Singh, Amisha; Swati, D

2014-08-01

Malaria is one of the most infectious diseases in the world. Plasmodium vivax, the pathogen causing endemic malaria in humans worldwide, is responsible for extensive disease morbidity. Due to the emergence of resistance to common anti-malarial drugs, there is a continuous need to develop a new class of drugs for this pathogen. P. vivax cysteine protease, also known as vivapain-2, plays an important role in haemoglobin hydrolysis and is considered essential for the survival of the parasite. The three-dimensional (3D) structure of vivapain-2 is not predicted experimentally, so its structure is modelled by using comparative modelling approach and further validated by Qualitative Model Energy Analysis (QMEAN) and RAMPAGE tools. The potential binding site of selected vivapain-2 structure has been detected by grid-based function prediction method. Drug targets and their respective drugs similar to vivapain-2 have been identified using three publicly available databases: STITCH 3.1, DrugBank and Therapeutic Target Database (TTD). The second approach of this work focuses on docking study of selected drug E-64 against vivapain-2 protein. Docking reveals crucial information about key residues (Asn281, Cys283, Val396 and Asp398) that are responsible for holding the ligand in the active site. The similarity-search criterion is used for the preparation of our in-house database of drugs, obtained from filtering the drugs from the DrugBank database. A five-point 3D pharmacophore model is generated for the docked complex of vivapain-2 with E-64. This study of 3D pharmacophore-based virtual screening results in identifying three new drugs, amongst which one is approved and the other two are experimentally proved. The ADMET properties of these drugs are found to be in the desired range. These drugs with novel scaffolds may act as potent drugs for treating malaria caused by P. vivax.

Computer-aided diagnostics of screening mammography using content-based image retrieval

Science.gov (United States)

Deserno, Thomas M.; Soiron, Michael; de Oliveira, Júlia E. E.; de A. Araújo, Arnaldo

2012-03-01

Breast cancer is one of the main causes of death among women in occidental countries. In the last years, screening mammography has been established worldwide for early detection of breast cancer, and computer-aided diagnostics (CAD) is being developed to assist physicians reading mammograms. A promising method for CAD is content-based image retrieval (CBIR). Recently, we have developed a classification scheme of suspicious tissue pattern based on the support vector machine (SVM). In this paper, we continue moving towards automatic CAD of screening mammography. The experiments are based on in total 10,509 radiographs that have been collected from different sources. From this, 3,375 images are provided with one and 430 radiographs with more than one chain code annotation of cancerous regions. In different experiments, this data is divided into 12 and 20 classes, distinguishing between four categories of tissue density, three categories of pathology and in the 20 class problem two categories of different types of lesions. Balancing the number of images in each class yields 233 and 45 images remaining in each of the 12 and 20 classes, respectively. Using a two-dimensional principal component analysis, features are extracted from small patches of 128 x 128 pixels and classified by means of a SVM. Overall, the accuracy of the raw classification was 61.6 % and 52.1 % for the 12 and the 20 class problem, respectively. The confusion matrices are assessed for detailed analysis. Furthermore, an implementation of a SVM-based CBIR system for CADx in screening mammography is presented. In conclusion, with a smarter patch extraction, the CBIR approach might reach precision rates that are helpful for the physicians. This, however, needs more comprehensive evaluation on clinical data.

A novel decision tree approach based on transcranial Doppler sonography to screen for blunt cervical vascular injuries.

Science.gov (United States)

Purvis, Dianna; Aldaghlas, Tayseer; Trickey, Amber W; Rizzo, Anne; Sikdar, Siddhartha

2013-06-01

Early detection and treatment of blunt cervical vascular injuries prevent adverse neurologic sequelae. Current screening criteria can miss up to 22% of these injuries. The study objective was to investigate bedside transcranial Doppler sonography for detecting blunt cervical vascular injuries in trauma patients using a novel decision tree approach. This prospective pilot study was conducted at a level I trauma center. Patients undergoing computed tomographic angiography for suspected blunt cervical vascular injuries were studied with transcranial Doppler sonography. Extracranial and intracranial vasculatures were examined with a portable power M-mode transcranial Doppler unit. The middle cerebral artery mean flow velocity, pulsatility index, and their asymmetries were used to quantify flow patterns and develop an injury decision tree screening protocol. Student t tests validated associations between injuries and transcranial Doppler predictive measures. We evaluated 27 trauma patients with 13 injuries. Single vertebral artery injuries were most common (38.5%), followed by single internal carotid artery injuries (30%). Compared to patients without injuries, mean flow velocity asymmetry was higher for single internal carotid artery (P = .003) and single vertebral artery (P = .004) injuries. Similarly, pulsatility index asymmetry was higher in single internal carotid artery (P = .015) and single vertebral artery (P = .042) injuries, whereas the lowest pulsatility index was elevated for bilateral vertebral artery injuries (P = .006). The decision tree yielded 92% specificity, 93% sensitivity, and 93% correct classifications. In this pilot feasibility study, transcranial Doppler measures were significantly associated with the blunt cervical vascular injury status, suggesting that transcranial Doppler sonography might be a viable bedside screening tool for trauma. Patient-specific hemodynamic information from transcranial Doppler assessment has the potential to alter

Digital screen visits in home care services

DEFF Research Database (Denmark)

Zarakit, Mohamad; Nors Hansen, Louise; Evron, Lotte Orr

2017-01-01

with participant observation of three selected screen visits with older patients with a minority ethnic background. Analysis: thematic analysis based on a hermeneutic approach. Primarily results indicate that older patients with a minority ethnic background are screened out during the recruitment phase for digital...

Virtual screening filters for the design of type II p38 MAP kinase inhibitors: a fragment based library generation approach.

Science.gov (United States)

Badrinarayan, Preethi; Sastry, G Narahari

2012-04-01

In this work, we introduce the development and application of a three-step scoring and filtering procedure for the design of type II p38 MAP kinase leads using allosteric fragments extracted from virtual screening hits. The design of the virtual screening filters is based on a thorough evaluation of docking methods, DFG-loop conformation, binding interactions and chemotype specificity of the 138 p38 MAP kinase inhibitors from Protein Data Bank bound to DFG-in and DFG-out conformations using Glide, GOLD and CDOCKER. A 40 ns molecular dynamics simulation with the apo, type I with DFG-in and type II with DFG-out forms was carried out to delineate the effects of structural variations on inhibitor binding. The designed docking-score and sub-structure filters were first tested on a dataset of 249 potent p38 MAP kinase inhibitors from seven diverse series and 18,842 kinase inhibitors from PDB, to gauge their capacity to discriminate between kinase and non-kinase inhibitors and likewise to selectively filter-in target-specific inhibitors. The designed filters were then applied in the virtual screening of a database of ten million (10⁷) compounds resulting in the identification of 100 hits. Based on their binding modes, 98 allosteric fragments were extracted from the hits and a fragment library was generated. New type II p38 MAP kinase leads were designed by tailoring the existing type I ATP site binders with allosteric fragments using a common urea linker. Target specific virtual screening filters can thus be easily developed for other kinases based on this strategy to retrieve target selective compounds. Copyright © 2012 Elsevier Inc. All rights reserved.

HDAT: web-based high-throughput screening data analysis tools

International Nuclear Information System (INIS)

Liu, Rong; Hassan, Taimur; Rallo, Robert; Cohen, Yoram

2013-01-01

The increasing utilization of high-throughput screening (HTS) in toxicity studies of engineered nano-materials (ENMs) requires tools for rapid and reliable processing and analyses of large HTS datasets. In order to meet this need, a web-based platform for HTS data analyses tools (HDAT) was developed that provides statistical methods suitable for ENM toxicity data. As a publicly available computational nanoinformatics infrastructure, HDAT provides different plate normalization methods, various HTS summarization statistics, self-organizing map (SOM)-based clustering analysis, and visualization of raw and processed data using both heat map and SOM. HDAT has been successfully used in a number of HTS studies of ENM toxicity, thereby enabling analysis of toxicity mechanisms and development of structure–activity relationships for ENM toxicity. The online approach afforded by HDAT should encourage standardization of and future advances in HTS as well as facilitate convenient inter-laboratory comparisons of HTS datasets. (paper)

Impact of non-clinical community-based promotional campaigns on bowel cancer screening engagement: An integrative literature review.

Science.gov (United States)

Martini, Angelita; Morris, Julia N; Preen, David

2016-10-01

This paper reviewed the relationship between non-clinical, client-oriented promotional campaigns to raise bowel cancer awareness and screening engagement. An integrative literature review using predefined search terms was conducted to summarise the accumulated knowledge. Data was analysed by coding and categorising, then synthesized through development of themes. Eighteen of 116 studies met inclusion criteria. Promotional campaigns had varying impact on screening uptake for bowel cancer. Mass media was found to moderately increase screening, predominately amongst "worried well". Small media used in conjunction with other promotional activities, thus its effect on screening behaviours was unclear. One-on-one education was less effective and less feasible than group education in increasing intention to screen. Financial support was ineffective in increasing screening rates when compared to other promotional activities. Screening engagement increased because of special events and celebrity endorsement. Non-clinical promotional campaigns did impact uptake of bowel cancer screening engagement. However, little is evident on the effect of single types of promotion and most research is based on clinician-directed campaigns. Cancer awareness and screening promotions should be implemented at community and clinical level to maximize effectiveness. Such an approach will ensure promotional activities are targeting consumers, thus strengthening screening engagement. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

Science.gov (United States)

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.

High-throughput fragment screening by affinity LC-MS.

Science.gov (United States)

Duong-Thi, Minh-Dao; Bergström, Maria; Fex, Tomas; Isaksson, Roland; Ohlson, Sten

2013-02-01

Fragment screening, an emerging approach for hit finding in drug discovery, has recently been proven effective by its first approved drug, vemurafenib, for cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon resonance, and isothemal titration calorimetry, with their own pros and cons, have been employed for screening fragment libraries. As an alternative approach, screening based on high-performance liquid chromatography separation has been developed. In this work, we present weak affinity LC/MS as a method to screen fragments under high-throughput conditions. Affinity-based capillary columns with immobilized thrombin were used to screen a collection of 590 compounds from a fragment library. The collection was divided into 11 mixtures (each containing 35 to 65 fragments) and screened by MS detection. The primary screening was performed in 3500 fragments per day). Thirty hits were defined, which subsequently entered a secondary screening using an active site-blocked thrombin column for confirmation of specificity. One hit showed selective binding to thrombin with an estimated dissociation constant (K (D)) in the 0.1 mM range. This study shows that affinity LC/MS is characterized by high throughput, ease of operation, and low consumption of target and fragments, and therefore it promises to be a valuable method for fragment screening.

Maximizing gain in high-throughput screening using conformal prediction.

Science.gov (United States)

Svensson, Fredrik; Afzal, Avid M; Norinder, Ulf; Bender, Andreas

2018-02-21

Iterative screening has emerged as a promising approach to increase the efficiency of screening campaigns compared to traditional high throughput approaches. By learning from a subset of the compound library, inferences on what compounds to screen next can be made by predictive models, resulting in more efficient screening. One way to evaluate screening is to consider the cost of screening compared to the gain associated with finding an active compound. In this work, we introduce a conformal predictor coupled with a gain-cost function with the aim to maximise gain in iterative screening. Using this setup we were able to show that by evaluating the predictions on the training data, very accurate predictions on what settings will produce the highest gain on the test data can be made. We evaluate the approach on 12 bioactivity datasets from PubChem training the models using 20% of the data. Depending on the settings of the gain-cost function, the settings generating the maximum gain were accurately identified in 8-10 out of the 12 datasets. Broadly, our approach can predict what strategy generates the highest gain based on the results of the cost-gain evaluation: to screen the compounds predicted to be active, to screen all the remaining data, or not to screen any additional compounds. When the algorithm indicates that the predicted active compounds should be screened, our approach also indicates what confidence level to apply in order to maximize gain. Hence, our approach facilitates decision-making and allocation of the resources where they deliver the most value by indicating in advance the likely outcome of a screening campaign.

[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].

Science.gov (United States)

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, PHPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z= 6.16, PHPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ(2)=132.00, PHPV 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.

Benefits of computer screen-based simulation in learning cardiac arrest procedures.

Science.gov (United States)

Bonnetain, Elodie; Boucheix, Jean-Michel; Hamet, Maël; Freysz, Marc

2010-07-01

What is the best way to train medical students early so that they acquire basic skills in cardiopulmonary resuscitation as effectively as possible? Studies have shown the benefits of high-fidelity patient simulators, but have also demonstrated their limits. New computer screen-based multimedia simulators have fewer constraints than high-fidelity patient simulators. In this area, as yet, there has been no research on the effectiveness of transfer of learning from a computer screen-based simulator to more realistic situations such as those encountered with high-fidelity patient simulators. We tested the benefits of learning cardiac arrest procedures using a multimedia computer screen-based simulator in 28 Year 2 medical students. Just before the end of the traditional resuscitation course, we compared two groups. An experiment group (EG) was first asked to learn to perform the appropriate procedures in a cardiac arrest scenario (CA1) in the computer screen-based learning environment and was then tested on a high-fidelity patient simulator in another cardiac arrest simulation (CA2). While the EG was learning to perform CA1 procedures in the computer screen-based learning environment, a control group (CG) actively continued to learn cardiac arrest procedures using practical exercises in a traditional class environment. Both groups were given the same amount of practice, exercises and trials. The CG was then also tested on the high-fidelity patient simulator for CA2, after which it was asked to perform CA1 using the computer screen-based simulator. Performances with both simulators were scored on a precise 23-point scale. On the test on a high-fidelity patient simulator, the EG trained with a multimedia computer screen-based simulator performed significantly better than the CG trained with traditional exercises and practice (16.21 versus 11.13 of 23 possible points, respectively; p<0.001). Computer screen-based simulation appears to be effective in preparing learners to

Screen-based process control in nuclear plants

International Nuclear Information System (INIS)

Hinz, W.; Arnoldt, C.; Hessler, C.

1993-01-01

Requirements, development and conceptual design of a screen-based control room for nuclear power plants are outlined. The control room consists of three or four equally equipped operator workstations comprising screens for process information and manual process control. A plant overview will assist the coordination among the operators. A safety classified backup system (safety control area) is provided to cover postulated failures of the control means. Some aspects of ergonomical validation and of future development trends are discussed. (orig.) [de

Stage distribution of breast cancer diagnosed before and after implementation of population-based mammographic screening

International Nuclear Information System (INIS)

Hofvind, S.; Skaane, P.

2012-01-01

Purpose: The German mammographic screening program is very similar to the Norwegian Breast Cancer Screening Program (NBCSP), which started about 10 years earlier. This study analyzes the stage distribution of invasive breast cancers diagnosed in the pre-screening and screening period, and evaluates the overall mortality in women aged 55 - 74 in the pilot and non-pilot counties of the NBCSP. Materials and Methods: The NBCSP invites women aged 50 - 69 to participate in two-view mammography biennially. Chi-square statistics were used to compare percentages of the stage and treatment of invasive breast cancers diagnosed in women residing in the four pilot counties in the pre-screening (1984 - 1995) and screening (1996 - 2007) period. An ecological approach was used to analyze the age-specific mortality in the pilot and non-pilot counties for the period 1970 - 2007. Results: 50 % of the breast cancers diagnosed in the pre-screening period, 70 % of the cases detected with screening, 43 % of the interval cancers, and 52 % of the cancers diagnosed outside the NBCSP were stage I. Stage III + was present in 11 % of the cancers in the pre-screening period, and in 1 % of the cancers detected with screening. In the screening period, the breast cancer mortality rate decreased substantially more in the pilot counties than in the non-pilot counties. Conclusion: The stage distribution of breast cancer diagnosed in the NBCSP is prognostically favorable compared to cancers diagnosed outside the screening program. The reduction in the breast cancer mortality rate was more pronounced in the four pilot counties compared to the non-pilot counties. It is necessary to evaluate the program based on individual data. (orig.)

Estimating radionuclide air concentrations near buildings: a screening approach

International Nuclear Information System (INIS)

Miller, C.W.; Yildiran, M.

1984-01-01

For some facilities that routinely release small amounts of radionuclides to the atmosphere, such as hospitals, research laboratories, contaminated clothing laundries, and others, it is necessary to estimate the dose to persons very near the buildings from which the releases occur. Such facilities need simple screening procedures which provide reasonable assurance that as long as the calculated dose is less than some fraction of a relevant dose limit no individual will receive a dose in excess of that limit. Screening procedures have been proposed for persons living within hundreds of meters to a few kilometers from a source of radioactive effluent. This paper examines a screening technique for estimating long-term average radionuclide air concentrations within approximately 100 m of a building from which the release occurs. The technique is based on a modified gaussion plume model (HB model) which considers the influence of the tallest building within 100 m and is independant of atmospheric stability and downwind distance. 4 references, 2 tables

How should we screen for depression following a natural disaster? An ROC approach to post-disaster screening in adolescents and adults.

Science.gov (United States)

Cohen, Joseph R; Adams, Zachary W; Menon, Suvarna V; Youngstrom, Eric A; Bunnell, Brian E; Acierno, Ron; Ruggiero, Kenneth J; Danielson, Carla Kmett

2016-09-15

The present study's aim was to provide the foundation for an efficient, empirically based protocol for depression screening following a natural disaster. Utilizing a Receiver Operating Characteristic (ROC) analytic approach, the study tested a) what specific disaster-related stressors (i.e., property damage, loss of basic services) and individual-related constructs (i.e., PTSD symptoms, trauma history, social support) conveyed the greatest risk for post-natural disaster depression, b) specific cutoff scores across these measures, and c) whether the significance or cutoff scores for each construct varied between adolescents and adults. Structured phone-based clinical interviews were conducted with 2000 adolescents who lived through a tornado and 1543 adults who survived a hurricane. Findings suggested that in both adolescents and adults, individual-related constructs forecasted greater risk for depressive symptoms following a natural disaster compared to disaster-related stressors. Furthermore, trauma history and PTSD symptoms were particularly strong indicators for adolescent depressive symptoms compared to adult depressive symptoms. Adolescents and adults who reported vulnerable scores for social support, trauma history, and lifetime PTSD symptoms were approximately twice as likely to present as depressed following the natural disaster. Findings from the present study were limited to post-disaster assessments and based on self-reported functioning 6-12 months following the natural disaster. The present study synthesizes the extensive body of research on post-disaster functioning by providing a clear framework for which questions may be most important to ask when screening for depression following a natural disaster. Copyright © 2016 Elsevier B.V. All rights reserved.

Protocol for population testing of an Internet-based Personalised Decision Support system for colorectal cancer screening

Directory of Open Access Journals (Sweden)

Wilson Carlene J

2010-09-01

Full Text Available Abstract Background Australia has a comparatively high incidence of colorectal (bowel cancer; however, population screening uptake using faecal occult blood test (FOBT remains low. This study will determine the impact on screening participation of a novel, Internet-based Personalised Decision Support (PDS package. The PDS is designed to measure attitudes and cognitive concerns and provide people with individually tailored information, in real time, that will assist them with making a decision to screen. The hypothesis is that exposure to (tailored PDS will result in greater participation in screening than participation following exposure to non-tailored PDS or resulting from the current non-tailored, paper-based approach. Methods/design A randomised parallel trial comprising three arms will be conducted. Men and women aged 50-74 years (N = 3240 will be recruited. They must have access to the Internet; have not had an FOBT within the previous 12 months, or sigmoidoscopy or colonoscopy within the previous 5 years; have had no clinical diagnosis of bowel cancer. Groups 1 and 2 (PDS arms will access a website and complete a baseline survey measuring decision-to-screen stage, attitudes and cognitive concerns and will receive immediate feedback; Group 1 will receive information 'tailored' to their responses in the baseline survey and group 2 will received 'non-tailored' bowel cancer information. Respondents in both groups will subsequently receive an FOBT kit. Group 3 (usual practice arm will complete a paper-based version of the baseline survey and respondents will subsequently receive 'non-tailored' paper-based bowel cancer information with accompanying FOBT kit. Following despatch of FOBTs, all respondents will be requested to complete an endpoint survey. Main outcome measures are (1 completion of FOBT and (2 change in decision-to-screen stage. Secondary outcomes include satisfaction with decision and change in attitudinal scores from baseline to

Ecosystem screening approach for pathogen-associated microorganisms affecting host disease.

Science.gov (United States)

Galiana, Eric; Marais, Antoine; Mura, Catherine; Industri, Benoît; Arbiol, Gilles; Ponchet, Michel

2011-09-01

The microbial community in which a pathogen evolves is fundamental to disease outcome. Species interacting with a pathogen on the host surface shape the distribution, density, and genetic diversity of the inoculum, but the role of these species is rarely determined. The screening method developed here can be used to characterize pathogen-associated species affecting disease. This strategy involves three steps: (i) constitution of the microbial community, using the pathogen as a trap; (ii) community selection, using extracts from the pathogen as the sole nutrient source; and (iii) molecular identification and the screening of isolates focusing on their effects on the growth of the pathogen in vitro and host disease. This approach was applied to a soilborne plant pathogen, Phytophthora parasitica, structured in a biofilm, for screening the microbial community from the rhizosphere of Nicotiana tabacum (the host). Two of the characterized eukaryotes interfered with the oomycete cycle and may affect the host disease. A Vorticella species acted through a mutualistic interaction with P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma species established an amensal interaction with P. parasitica, strongly suppressing disease by inhibiting P. parasitica germination. This screening method is appropriate for all nonobligate pathogens. It allows the definition of microbial species as promoters or suppressors of a disease for a given biotope. It should also help to identify important microbial relationships for ecology and evolution of pathogens.

A multicopy suppressor screening approach as a means to identify antibiotic resistance determinant candidates in Yersinia pestis

Directory of Open Access Journals (Sweden)

Moy Richard L

2008-07-01

Full Text Available Abstract Background Yersinia pestis is the causative agent of plague and a potential agent of bioterrorism and biowarfare. The plague biothreat and the emergence of multidrug-resistant plague underscore the need to increase our understanding of the intrinsic potential of Y. pestis for developing antimicrobial resistance and to anticipate the mechanisms of resistance that may emerge in Y. pestis. Identification of Y. pestis genes that, when overexpressed, are capable of reducing antibiotic susceptibility is a useful strategy to expose genes that this pathogen may rely upon to evolve antibiotic resistance via a vertical modality. In this study, we explored the use of a multicopy suppressor, Escherichia coli host-based screening approach as a means to expose antibiotic resistance determinant candidates in Y. pestis. Results We constructed a multicopy plasmid-based, Y. pestis genome-wide expression library of nearly 16,000 clones in E. coli and screened the library for suppressors of the antimicrobial activity of ofloxacin, a fluoroquinolone antibiotic. The screen permitted the identification of a transcriptional regulator-encoding gene (robAYp that increased the MIC99 of ofloxacin by 23-fold when overexpressed from a multicopy plasmid in Y. pestis. Additionally, we found that robAYp overexpression in Y. pestis conferred low-level resistance to many other antibiotics and increased organic solvent tolerance. Overexpression of robAYp also upregulated the expression of several efflux pumps in Y. pestis. Conclusion Our study provides proof of principle for the use of multicopy suppressor screening based on the tractable and easy-to-manipulate E. coli host as a means to identify antibiotic resistance determinant candidates of Y. pestis.

The competitor-introduced Ggamma recruitment system, a new approach for screening affinity-enhanced proteins.

Science.gov (United States)

Fukuda, Nobuo; Ishii, Jun; Tanaka, Tsutomu; Kondo, Akihiko

2010-04-01

We have developed a new approach based on the Ggamma recruitment system to screen affinity-enhanced proteins by expressing a binding competitor. The previously established Ggamma recruitment system is a yeast two-hybrid (Y2H) system that utilizes G-protein signaling, and is based on the fact that membrane localization of the G-protein gamma subunit (Ggamma) is essential for signal transduction in yeast. In the original Y2H system, an engineered Ggamma that lacks membrane localization upon deletion of the lipid modification site (Ggamma(cyto)) is produced, and a candidate protein with an artificial lipidation site and its counterpart fused with Ggamma(cyto) are expressed. As protein-protein interactions bring Ggamma(cyto) towards the plasma membrane, G-protein signaling can be activated, and the interaction is detected by various cellular responses as the readout. In the current study, we expressed a third cytosolic protein that competes with the candidate protein to specifically isolate affinity-enhanced mutants from a mutation library of the candidate protein. Enhancing the affinity of the protein candidate guides the counterpart-Ggamma(cyto) fusion protein towards the plasma membrane and activates signaling. Using mutants of the Z domain derived from Staphylococcus aureus protein A as candidate proteins or competitors, and the Fc portion of human immunoglobulin G (IgG) as the counterpart, we demonstrate that affinity-enhanced proteins can be effectively screened from a library containing a 10 000-fold excess of non-enhanced proteins. This new approach, called the competitor-introduced Ggamma recruitment system, will be useful for efficient discovery of rare valuable candidates hidden among excess ordinary ones.

Cost Effective Community Based Dementia Screening: A Markov Model Simulation

Directory of Open Access Journals (Sweden)

Erin Saito

2014-01-01

Full Text Available Background. Given the dementia epidemic and the increasing cost of healthcare, there is a need to assess the economic benefit of community based dementia screening programs. Materials and Methods. Markov model simulations were generated using data obtained from a community based dementia screening program over a one-year period. The models simulated yearly costs of caring for patients based on clinical transitions beginning in pre dementia and extending for 10 years. Results. A total of 93 individuals (74 female, 19 male were screened for dementia and 12 meeting clinical criteria for either mild cognitive impairment (n=7 or dementia (n=5 were identified. Assuming early therapeutic intervention beginning during the year of dementia detection, Markov model simulations demonstrated 9.8% reduction in cost of dementia care over a ten-year simulation period, primarily through increased duration in mild stages and reduced time in more costly moderate and severe stages. Discussion. Community based dementia screening can reduce healthcare costs associated with caring for demented individuals through earlier detection and treatment, resulting in proportionately reduced time in more costly advanced stages.

Methodology for the Model-based Small Area Estimates of Cancer Risk Factors and Screening Behaviors - Small Area Estimates

Science.gov (United States)

This model-based approach uses data from both the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS) to produce estimates of the prevalence rates of cancer risk factors and screening behaviors at the state, health service area, and county levels.

Defined PEG smears as an alternative approach to enhance the search for crystallization conditions and crystal-quality improvement in reduced screens

Energy Technology Data Exchange (ETDEWEB)

Chaikuad, Apirat, E-mail: apirat.chaikuad@sgc.ox.ac.uk [University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ (United Kingdom); Knapp, Stefan [University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ (United Kingdom); Johann Wolfgang Goethe-University, Building N240 Room 3.03, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main (Germany); Delft, Frank von, E-mail: apirat.chaikuad@sgc.ox.ac.uk [University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ (United Kingdom)

2015-07-28

An alternative strategy for PEG sampling is suggested through the use of four newly defined PEG smears to enhance chemical space in reduced screens with a benefit towards protein crystallization. The quest for an optimal limited set of effective crystallization conditions remains a challenge in macromolecular crystallography, an issue that is complicated by the large number of chemicals which have been deemed to be suitable for promoting crystal growth. The lack of rational approaches towards the selection of successful chemical space and representative combinations has led to significant overlapping conditions, which are currently present in a multitude of commercially available crystallization screens. Here, an alternative approach to the sampling of widely used PEG precipitants is suggested through the use of PEG smears, which are mixtures of different PEGs with a requirement of either neutral or cooperatively positive effects of each component on crystal growth. Four newly defined smears were classified by molecular-weight groups and enabled the preservation of specific properties related to different polymer sizes. These smears not only allowed a wide coverage of properties of these polymers, but also reduced PEG variables, enabling greater sampling of other parameters such as buffers and additives. The efficiency of the smear-based screens was evaluated on more than 220 diverse recombinant human proteins, which overall revealed a good initial crystallization success rate of nearly 50%. In addition, in several cases successful crystallizations were only obtained using PEG smears, while various commercial screens failed to yield crystals. The defined smears therefore offer an alternative approach towards PEG sampling, which will benefit the design of crystallization screens sampling a wide chemical space of this key precipitant.

Pharmacological screening technologies for venom peptide discovery.

Science.gov (United States)

Prashanth, Jutty Rajan; Hasaballah, Nojod; Vetter, Irina

2017-12-01

Venomous animals occupy one of the most successful evolutionary niches and occur on nearly every continent. They deliver venoms via biting and stinging apparatuses with the aim to rapidly incapacitate prey and deter predators. This has led to the evolution of venom components that act at a number of biological targets - including ion channels, G-protein coupled receptors, transporters and enzymes - with exquisite selectivity and potency, making venom-derived components attractive pharmacological tool compounds and drug leads. In recent years, plate-based pharmacological screening approaches have been introduced to accelerate venom-derived drug discovery. A range of assays are amenable to this purpose, including high-throughput electrophysiology, fluorescence-based functional and binding assays. However, despite these technological advances, the traditional activity-guided fractionation approach is time-consuming and resource-intensive. The combination of screening techniques suitable for miniaturization with sequence-based discovery approaches - supported by advanced proteomics, mass spectrometry, chromatography as well as synthesis and expression techniques - promises to further improve venom peptide discovery. Here, we discuss practical aspects of establishing a pipeline for venom peptide drug discovery with a particular emphasis on pharmacology and pharmacological screening approaches. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

A convolutional neural network-based screening tool for X-ray serial crystallography.

Science.gov (United States)

Ke, Tsung Wei; Brewster, Aaron S; Yu, Stella X; Ushizima, Daniela; Yang, Chao; Sauter, Nicholas K

2018-05-01

A new tool is introduced for screening macromolecular X-ray crystallography diffraction images produced at an X-ray free-electron laser light source. Based on a data-driven deep learning approach, the proposed tool executes a convolutional neural network to detect Bragg spots. Automatic image processing algorithms described can enable the classification of large data sets, acquired under realistic conditions consisting of noisy data with experimental artifacts. Outcomes are compared for different data regimes, including samples from multiple instruments and differing amounts of training data for neural network optimization. open access.

Smartphone-Based Hearing Screening in Noisy Environments

Directory of Open Access Journals (Sweden)

Youngmin Na

2014-06-01

Full Text Available 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.

Web-based newborn screening system for metabolic diseases: machine learning versus clinicians.

Science.gov (United States)

Chen, Wei-Hsin; Hsieh, Sheau-Ling; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

2013-05-23

predicting cases. The feature selection strategies were implemented and the optimal markers for PKU, hypermethioninemia, and 3-MCC deficiency were obtained. The results of the machine learning approach were compared with the cutoff scheme. The number of the false positive cases were reduced from 21 to 2 for PKU, from 30 to 10 for hypermethioninemia, and 209 to 46 for 3-MCC deficiency. This SOA Web service-based newborn screening system can accelerate screening procedures effectively and efficiently. An SVM learning methodology for PKU, hypermethioninemia, and 3-MCC deficiency metabolic diseases classification, including optimal feature selection strategies, is presented. By adopting the results of this study, the number of suspected cases could be reduced dramatically.

Structure-Based Virtual Screening of Commercially Available Compound Libraries.

Science.gov (United States)

Kireev, Dmitri

2016-01-01

Virtual screening (VS) is an efficient hit-finding tool. Its distinctive strength is that it allows one to screen compound libraries that are not available in the lab. Moreover, structure-based (SB) VS also enables an understanding of how the hit compounds bind the protein target, thus laying ground work for the rational hit-to-lead progression. SBVS requires a very limited experimental effort and is particularly well suited for academic labs and small biotech companies that, unlike pharmaceutical companies, do not have physical access to quality small-molecule libraries. Here, we describe SBVS of commercial compound libraries for Mer kinase inhibitors. The screening protocol relies on the docking algorithm Glide complemented by a post-docking filter based on structural protein-ligand interaction fingerprints (SPLIF).

Automated Cervical Screening and Triage, Based on HPV Testing and Computer-Interpreted Cytology.

Science.gov (United States)

Yu, Kai; Hyun, Noorie; Fetterman, Barbara; Lorey, Thomas; Raine-Bennett, Tina R; Zhang, Han; Stamps, Robin E; Poitras, Nancy E; Wheeler, William; Befano, Brian; Gage, Julia C; Castle, Philip E; Wentzensen, Nicolas; Schiffman, Mark

2018-04-11

State-of-the-art cervical cancer prevention includes human papillomavirus (HPV) vaccination among adolescents and screening/treatment of cervical precancer (CIN3/AIS and, less strictly, CIN2) among adults. HPV testing provides sensitive detection of precancer but, to reduce overtreatment, secondary "triage" is needed to predict women at highest risk. Those with the highest-risk HPV types or abnormal cytology are commonly referred to colposcopy; however, expert cytology services are critically lacking in many regions. To permit completely automatable cervical screening/triage, we designed and validated a novel triage method, a cytologic risk score algorithm based on computer-scanned liquid-based slide features (FocalPoint, BD, Burlington, NC). We compared it with abnormal cytology in predicting precancer among 1839 women testing HPV positive (HC2, Qiagen, Germantown, MD) in 2010 at Kaiser Permanente Northern California (KPNC). Precancer outcomes were ascertained by record linkage. As additional validation, we compared the algorithm prospectively with cytology results among 243 807 women screened at KPNC (2016-2017). All statistical tests were two-sided. Among HPV-positive women, the algorithm matched the triage performance of abnormal cytology. Combined with HPV16/18/45 typing (Onclarity, BD, Sparks, MD), the automatable strategy referred 91.7% of HPV-positive CIN3/AIS cases to immediate colposcopy while deferring 38.4% of all HPV-positive women to one-year retesting (compared with 89.1% and 37.4%, respectively, for typing and cytology triage). In the 2016-2017 validation, the predicted risk scores strongly correlated with cytology (P < .001). High-quality cervical screening and triage performance is achievable using this completely automated approach. Automated technology could permit extension of high-quality cervical screening/triage coverage to currently underserved regions.

BeeDoctor, a versatile MLPA-based diagnostic tool for screening bee viruses.

Science.gov (United States)

De Smet, Lina; Ravoet, Jorgen; de Miranda, Joachim R; Wenseleers, Tom; Mueller, Matthias Y; Moritz, Robin F A; de Graaf, Dirk C

2012-01-01

The long-term decline of managed honeybee hives in the world has drawn significant attention to the scientific community and bee-keeping industry. A high pathogen load is believed to play a crucial role in this phenomenon, with the bee viruses being key players. Most of the currently characterized honeybee viruses (around twenty) are positive stranded RNA viruses. Techniques based on RNA signatures are widely used to determine the viral load in honeybee colonies. High throughput screening for viral loads necessitates the development of a multiplex polymerase chain reaction approach in which different viruses can be targeted simultaneously. A new multiparameter assay, called "BeeDoctor", was developed based on multiplex-ligation probe dependent amplification (MLPA) technology. This assay detects 10 honeybee viruses in one reaction. "BeeDoctor" is also able to screen selectively for either the positive strand of the targeted RNA bee viruses or the negative strand, which is indicative for active viral replication. Due to its sensitivity and specificity, the MLPA assay is a useful tool for rapid diagnosis, pathogen characterization, and epidemiology of viruses in honeybee populations. "BeeDoctor" was used for screening 363 samples from apiaries located throughout Flanders; the northern half of Belgium. Using the "BeeDoctor", virus infections were detected in almost eighty percent of the colonies, with deformed wing virus by far the most frequently detected virus and multiple virus infections were found in 26 percent of the colonies.

BeeDoctor, a versatile MLPA-based diagnostic tool for screening bee viruses.

Directory of Open Access Journals (Sweden)

Lina De Smet

Full Text Available The long-term decline of managed honeybee hives in the world has drawn significant attention to the scientific community and bee-keeping industry. A high pathogen load is believed to play a crucial role in this phenomenon, with the bee viruses being key players. Most of the currently characterized honeybee viruses (around twenty are positive stranded RNA viruses. Techniques based on RNA signatures are widely used to determine the viral load in honeybee colonies. High throughput screening for viral loads necessitates the development of a multiplex polymerase chain reaction approach in which different viruses can be targeted simultaneously. A new multiparameter assay, called "BeeDoctor", was developed based on multiplex-ligation probe dependent amplification (MLPA technology. This assay detects 10 honeybee viruses in one reaction. "BeeDoctor" is also able to screen selectively for either the positive strand of the targeted RNA bee viruses or the negative strand, which is indicative for active viral replication. Due to its sensitivity and specificity, the MLPA assay is a useful tool for rapid diagnosis, pathogen characterization, and epidemiology of viruses in honeybee populations. "BeeDoctor" was used for screening 363 samples from apiaries located throughout Flanders; the northern half of Belgium. Using the "BeeDoctor", virus infections were detected in almost eighty percent of the colonies, with deformed wing virus by far the most frequently detected virus and multiple virus infections were found in 26 percent of the colonies.

The anterior interhemispheric approach: a safe and effective approach to anterior skull base lesions.

Science.gov (United States)

Mielke, Dorothee; Mayfrank, Lothar; Psychogios, Marios Nikos; Rohde, Veit

2014-04-01

Many approaches to the anterior skull base have been reported. Frequently used are the pterional, the unilateral or bilateral frontobasal, the supraorbital and the frontolateral approach. Recently, endoscopic transnasal approaches have become more popular. The benefits of each approach has to be weighted against its complications and limitations. The aim of this study was to investigate if the anterior interhemispheric approach (AIA) could be a safe and effective alternative approach to tumorous and non-tumorous lesions of the anterior skull base. We screened the operative records of all patients with an anterior skull base lesion undergoing transcranial surgery. We have used the AIA in 61 patients. These were exclusively patients with either olfactory groove meningioma (OGM) (n = 43), ethmoidal dural arteriovenous fistula (dAVF) ( n = 6) or frontobasal fractures of the anterior midline with cerebrospinal fluid (CSF) leakage ( n = 12). Patient records were evaluated concerning accessibility of the lesion, realization of surgical aims (complete tumor removal, dAVF obliteration, closure of the dural tear), and approach related complications. The use of the AIA exclusively in OGMs, ethmoidal dAVFs and midline frontobasal fractures indicated that we considered lateralized frontobasal lesions not suitable to be treated successfully. If restricted to these three pathologies, the AIA is highly effective and safe. The surgical aim (complete tumor removal, complete dAVF occlusion, no rhinorrhea) was achieved in all patients. The complication rate was 11.5 % (wound infection (n = 2; 3.2 %), contusion of the genu of the corpus callosum, subdural hygroma, epileptic seizure, anosmia and asymptomatic bleed into the tumor cavity (n = 1 each). Only the contusion of the corpus callosum was directly related to the approach (1.6 %). Olfaction, if present before surgery, was preserved in all patients, except one (1.6 %). The AIA is an effective and a safe approach

Mass spectrometry for fragment screening.

Science.gov (United States)

Chan, Daniel Shiu-Hin; Whitehouse, Andrew J; Coyne, Anthony G; Abell, Chris

2017-11-08

Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography. In this context, MS is a relatively underutilized technique in fragment screening for drug discovery. MS-based techniques have the advantage of high sensitivity, low sample consumption and being label-free. This review highlights recent examples of the emerging use of MS-based techniques in fragment screening. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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

Science.gov (United States)

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.

Evolutions in fragment-based drug design: the deconstruction–reconstruction approach

Science.gov (United States)

Chen, Haijun; Zhou, Xiaobin; Wang, Ailan; Zheng, Yunquan; Gao, Yu; Zhou, Jia

2014-01-01

Recent advances in the understanding of molecular recognition and protein–ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction–reconstruction strategy by utilizing privileged fragments of reported ligands. PMID:25263697

The effect of omitting an early population-based vision screen in the Netherlands : A micro-simulation model approach

NARCIS (Netherlands)

F. Sloot; E. Heijnsdijk; F. Goudsmit; E.W. Steyerberg; H.J. de Koning; H.J. Simonsz; Dr. J.H. Groenewoud

2016-01-01

To estimate the effect of omitting an individual screen from a child vision screening programme on the detection of amblyopia in the Netherlands. A previous study (Rotterdam Amblyopia Screening Effectiveness Study) suggested that the three screens carried out between 6 and 24 months contributed

Superior performance of liquid-based versus conventional cytology in a population-based cervical cancer screening program

NARCIS (Netherlands)

Beerman, H.; van Dorst, E. B. L.; Kuenen-Boumeester, V.; Hogendoorn, P. C. W.

Objective. Liquid-based cytology may offer improvements over conventional cytology for cervical cancer screening. The two cytology techniques were compared in a group of 86,469 women who participated in a population-based screening program. Using a nation-wide pathology database containing both

Modeling thrombin generation: plasma composition based approach.

Science.gov (United States)

Brummel-Ziedins, Kathleen E; Everse, Stephen J; Mann, Kenneth G; Orfeo, Thomas

2014-01-01

Thrombin has multiple functions in blood coagulation and its regulation is central to maintaining the balance between hemorrhage and thrombosis. Empirical and computational methods that capture thrombin generation can provide advancements to current clinical screening of the hemostatic balance at the level of the individual. In any individual, procoagulant and anticoagulant factor levels together act to generate a unique coagulation phenotype (net balance) that is reflective of the sum of its developmental, environmental, genetic, nutritional and pharmacological influences. Defining such thrombin phenotypes may provide a means to track disease progression pre-crisis. In this review we briefly describe thrombin function, methods for assessing thrombin dynamics as a phenotypic marker, computationally derived thrombin phenotypes versus determined clinical phenotypes, the boundaries of normal range thrombin generation using plasma composition based approaches and the feasibility of these approaches for predicting risk.

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

Directory of Open Access Journals (Sweden)

Amelia Acera

Full Text Available 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.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.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

Understanding and Creating Accessible Touch Screen Interactions for Blind People

Science.gov (United States)

Kane, Shaun K.

2011-01-01

Using touch screens presents a number of usability and accessibility challenges for blind people. Most touch screen-based user interfaces are optimized for visual interaction, and are therefore difficult or impossible to use without vision. This dissertation presents an approach to redesigning gesture-based user interfaces to enable blind people…

Cervical cancer screening and treatment of cervical intraepithelial neoplasia in female sex workers using “screen and treat” approach

Directory of Open Access Journals (Sweden)

Joshi S

2015-05-01

Full Text Available Smita Joshi,1 Vinay Kulkarni,2 Trupti Darak,2 Uma Mahajan,1 Yogesh Srivastava,3 Sanjay Gupta,3 Sumitra Krishnan,1 Mahesh Mandolkar,2 Alok Chandra Bharti31Hirabai Cowasji Jehangir Medical Research Institute (HCJMRI, Jehangir Hospital Premises, Pune, Maharashtra, India; 2Prayas Health Group, Amrita Clinic, Pune, India; 3Institute for Cytology and Preventive Oncology, Indian Council of Medical Research, New Delhi, IndiaObjective: Female sex workers (FSWs are at an increased risk of human immunodeficiency virus (HIV as well as human papillomavirus (HPV infections and thus have an increased risk of cervical intraepithelial neoplasia (CIN and cervical cancer. We evaluated the feasibility of “screen and treat approach” for cervical cancer prevention and the performance of different screening tests among FSWs.Methods: Women were screened using cytology, VIA (visual inspection with acetic acid, and VILI (visual inspection with Lugol’s iodine and underwent colposcopy, biopsy, and immediate treatment using cold coagulation, if indicated, at the same visit.Results: We screened 300 FSWs of whom 200 (66.67% were HIV uninfected and 100 (33.34% were HIV infected. The overall prevalence of CIN 2–3 lesions was 4.7%. But all women with CIN 2–3 lesions were HIV infected, and thus the prevalence of CIN 2–3 lesions in HIV-infected FSWs was 14/100 (14%, 95% confidence interval: 7.2–20.8. All of them screened positive by all three screening tests. Cold coagulation was well tolerated, with no appreciable side effects.Conclusion: Cervical cancer prevention by “screen and treat” approach using VIA, followed by ablative treatment, in this high-risk group of women is feasible and can be implemented through various targeted intervention programs. Keywords: cytology, VIA, VILI, CIN, cold coagulation, cervical cancer, HPV, FSWs

Eurogin 2016 Roadmap: how HPV knowledge is changing screening practice.

Science.gov (United States)

Wentzensen, Nicolas; Arbyn, Marc; Berkhof, Johannes; Bower, Mark; Canfell, Karen; Einstein, Mark; Farley, Christopher; Monsonego, Joseph; Franceschi, Silvia

2017-05-15

Human papillomaviruses (HPVs) are the necessary cause of most cervical cancers, a large proportion of other anogenital cancers, and a subset of oropharyngeal cancers. The knowledge about HPV has led to development of novel HPV-based prevention strategies with important impact on clinical and public health practice. Two complementary reviews have been prepared following the 2015 Eurogin Conference to evaluate how knowledge about HPV is changing practice in HPV infection and disease control through vaccination and screening. This review focuses on screening for cervical and anal cancers in increasingly vaccinated populations. The introduction of HPV vaccines a decade ago has led to reductions in HPV infections and early cancer precursors in countries with wide vaccination coverage. Despite the high efficacy of HPV vaccines, cervical cancer screening will remain important for many decades. Many healthcare systems are considering switching to primary HPV screening, which has higher sensitivity for cervical precancers and allows extending screening intervals. We describe different approaches to implementing HPV-based screening efforts in different healthcare systems with a focus in high-income countries. While the population prevalence for other anogenital cancers is too low for population-based screening, anal cancer incidence is very high in HIV-infected men who have sex with men, warranting consideration of early detection approaches. We summarize the current evidence on HPV-based prevention of anal cancers and highlight important evidence gaps. © 2016 UICC.

A Wide-Field Fluorescence Microscope Extension for Ultrafast Screening of One-Bead One-Compound Libraries Using a Spectral Image Subtraction Approach.

Science.gov (United States)

Heusermann, Wolf; Ludin, Beat; Pham, Nhan T; Auer, Manfred; Weidemann, Thomas; Hintersteiner, Martin

2016-05-09

The increasing involvement of academic institutions and biotech companies in drug discovery calls for cost-effective methods to identify new bioactive molecules. Affinity-based on-bead screening of combinatorial one-bead one-compound libraries combines a split-mix synthesis design with a simple protein binding assay operating directly at the bead matrix. However, one bottleneck for academic scale on-bead screening is the unavailability of a cheap, automated, and robust screening platform that still provides a quantitative signal related to the amount of target protein binding to individual beads for hit bead ranking. Wide-field fluorescence microscopy has long been considered unsuitable due to significant broad spectrum autofluorescence of the library beads in conjunction with low detection sensitivity. Herein, we demonstrate how such a standard microscope equipped with LED-based excitation and a modern CMOS camera can be successfully used for selecting hit beads. We show that the autofluorescence issue can be overcome by an optical image subtraction approach that yields excellent signal-to-noise ratios for the detection of bead-associated target proteins. A polymer capillary attached to a semiautomated bead-picking device allows the operator to efficiently isolate individual hit beads in less than 20 s. The system can be used for ultrafast screening of >200,000 bead-bound compounds in 1.5 h, thereby making high-throughput screening accessible to a wider group within the scientific community.

Automation-assisted cervical cancer screening in manual liquid-based cytology with hematoxylin and eosin staining.

Science.gov (United States)

Zhang, Ling; Kong, Hui; Ting Chin, Chien; Liu, Shaoxiong; Fan, Xinmin; Wang, Tianfu; Chen, Siping

2014-03-01

Current automation-assisted technologies for screening cervical cancer mainly rely on automated liquid-based cytology slides with proprietary stain. This is not a cost-efficient approach to be utilized in developing countries. In this article, we propose the first automation-assisted system to screen cervical cancer in manual liquid-based cytology (MLBC) slides with hematoxylin and eosin (H&E) stain, which is inexpensive and more applicable in developing countries. This system consists of three main modules: image acquisition, cell segmentation, and cell classification. First, an autofocusing scheme is proposed to find the global maximum of the focus curve by iteratively comparing image qualities of specific locations. On the autofocused images, the multiway graph cut (GC) is performed globally on the a* channel enhanced image to obtain cytoplasm segmentation. The nuclei, especially abnormal nuclei, are robustly segmented by using GC adaptively and locally. Two concave-based approaches are integrated to split the touching nuclei. To classify the segmented cells, features are selected and preprocessed to improve the sensitivity, and contextual and cytoplasm information are introduced to improve the specificity. Experiments on 26 consecutive image stacks demonstrated that the dynamic autofocusing accuracy was 2.06 μm. On 21 cervical cell images with nonideal imaging condition and pathology, our segmentation method achieved a 93% accuracy for cytoplasm, and a 87.3% F-measure for nuclei, both outperformed state of the art works in terms of accuracy. Additional clinical trials showed that both the sensitivity (88.1%) and the specificity (100%) of our system are satisfyingly high. These results proved the feasibility of automation-assisted cervical cancer screening in MLBC slides with H&E stain, which is highly desirable in community health centers and small hospitals. © 2013 International Society for Advancement of Cytometry.

Population-based mammography screening: comparison of screen-film and full-field digital mammography with soft-copy reading--Oslo I study.

Science.gov (United States)

Skaane, Per; Young, Kari; Skjennald, Arnulf

2003-12-01

To compare screen-film and full-field digital mammography with soft-copy reading in a population-based screening program. Full-field digital and screen-film mammography were performed in 3,683 women aged 50-69 years. Two standard views of each breast were acquired with each modality. Images underwent independent double reading with use of a five-point rating scale for probability of cancer. Recall rates and positive predictive values were calculated. Cancer detection rates determined with both modalities were compared by using the McNemar test for paired proportions. Retrospective side-by-side analysis for conspicuity of cancers was performed by an external independent radiologist group with experience in both modalities. In 3,683 cases, 31 cancers were detected. Screen-film mammography depicted 28 (0.76%) malignancies, and full-field digital mammography depicted 23 (0.62%) malignancies. The difference between cancer detection rates was not significant (P =.23). The recall rate for full-field digital mammography (4.6%; 168 of 3,683 cases) was slightly higher than that for screen-film mammography (3.5%; 128 of 3,683 cases). The positive predictive value based on needle biopsy results was 46% for screen-film mammography and 39% for full-field digital mammography. Side-by-side image comparison for cancer conspicuity led to classification of 19 cancers as equal for probability of malignancy, six cancers as slightly better demonstrated at screen-film mammography, and six cancers as slightly better demonstrated at full-field digital mammography. There was no statistically significant difference in cancer detection rate between screen-film and full-field digital mammography. Cancer conspicuity was equal with both modalities. Full-field digital mammography with soft-copy reading is comparable to screen-film mammography in population-based screening.

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

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

Aaron J. Oakley

2012-10-01

Full Text Available 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.

Developments in SPR Fragment Screening.

Science.gov (United States)

Chavanieu, Alain; Pugnière, Martine

2016-01-01

Fragment-based approaches have played an increasing role alongside high-throughput screening in drug discovery for 15 years. The label-free biosensor technology based on surface plasmon resonance (SPR) is now sensitive and informative enough to serve during primary screens and validation steps. In this review, the authors discuss the role of SPR in fragment screening. After a brief description of the underlying principles of the technique and main device developments, they evaluate the advantages and adaptations of SPR for fragment-based drug discovery. SPR can also be applied to challenging targets such as membrane receptors and enzymes. The high-level of immobilization of the protein target and its stability are key points for a relevant screening that can be optimized using oriented immobilized proteins and regenerable sensors. Furthermore, to decrease the rate of false negatives, a selectivity test may be performed in parallel on the main target bearing the binding site mutated or blocked with a low-off-rate ligand. Fragment-based drug design, integrated in a rational workflow led by SPR, will thus have a predominant role for the next wave of drug discovery which could be greatly enhanced by new improvements in SPR devices.

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

Science.gov (United States)

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.

Population-based cancer screening programmes in low-income and middle-income countries: regional consultation of the International Cancer Screening Network in India.

Science.gov (United States)

Sivaram, Sudha; Majumdar, Gautam; Perin, Douglas; Nessa, Ashrafun; Broeders, Mireille; Lynge, Elsebeth; Saraiya, Mona; Segnan, Nereo; Sankaranarayanan, Rengaswamy; Rajaraman, Preetha; Trimble, Edward; Taplin, Stephen; Rath, G K; Mehrotra, Ravi

2018-02-01

The reductions in cancer morbidity and mortality afforded by population-based cancer screening programmes have led many low-income and middle-income countries to consider the implementation of national screening programmes in the public sector. Screening at the population level, when planned and organised, can greatly benefit the population, whilst disorganised screening can increase costs and reduce benefits. The International Cancer Screening Network (ICSN) was created to share lessons, experience, and evidence regarding cancer screening in countries with organised screening programmes. Organised screening programmes provide screening to an identifiable target population and use multidisciplinary delivery teams, coordinated clinical oversight committees, and regular review by a multidisciplinary evaluation board to maximise benefit to the target population. In this Series paper, we report outcomes of the first regional consultation of the ICSN held in Agartala, India (Sept 5-7, 2016), which included discussions from cancer screening programmes from Denmark, the Netherlands, USA, and Bangladesh. We outline six essential elements of population-based cancer screening programmes, and share recommendations from the meeting that policy makers might want to consider before implementation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of putative estrogen receptor-mediated endocrine disrupting chemicals using QSAR- and structure-based virtual screening approaches

Energy Technology Data Exchange (ETDEWEB)

Zhang, Liying; Sedykh, Alexander; Tripathi, Ashutosh [Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC (United States); Zhu, Hao [The Rutgers Center for Computational and Integrative Biology, Rutgers University, Camden, NJ (United States); Department of Chemistry, Rutgers University, Camden, NJ (United States); Afantitis, Antreas; Mouchlis, Varnavas D.; Melagraki, Georgia [NovaMechanics Ltd., Nicosia (Cyprus); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC (United States)

2013-10-01

Identification of endocrine disrupting chemicals is one of the important goals of environmental chemical hazard screening. We report on the development of validated in silico predictors of chemicals likely to cause estrogen receptor (ER)-mediated endocrine disruption to facilitate their prioritization for future screening. A database of relative binding affinity of a large number of ERα and/or ERβ ligands was assembled (546 for ERα and 137 for ERβ). Both single-task learning (STL) and multi-task learning (MTL) continuous quantitative structure–activity relationship (QSAR) models were developed for predicting ligand binding affinity to ERα or ERβ. High predictive accuracy was achieved for ERα binding affinity (MTL R{sup 2} = 0.71, STL R{sup 2} = 0.73). For ERβ binding affinity, MTL models were significantly more predictive (R{sup 2} = 0.53, p < 0.05) than STL models. In addition, docking studies were performed on a set of ER agonists/antagonists (67 agonists and 39 antagonists for ERα, 48 agonists and 32 antagonists for ERβ, supplemented by putative decoys/non-binders) using the following ER structures (in complexes with respective ligands) retrieved from the Protein Data Bank: ERα agonist (PDB ID: 1L2I), ERα antagonist (PDB ID: 3DT3), ERβ agonist (PDB ID: 2NV7), and ERβ antagonist (PDB ID: 1L2J). We found that all four ER conformations discriminated their corresponding ligands from presumed non-binders. Finally, both QSAR models and ER structures were employed in parallel to virtually screen several large libraries of environmental chemicals to derive a ligand- and structure-based prioritized list of putative estrogenic compounds to be used for in vitro and in vivo experimental validation. - Highlights: • This is the largest curated dataset inclusive of ERα and β (the latter is unique). • New methodology that for the first time affords acceptable ERβ models. • A combination of QSAR and docking enables prediction of affinity and function. �

Identification of putative estrogen receptor-mediated endocrine disrupting chemicals using QSAR- and structure-based virtual screening approaches

International Nuclear Information System (INIS)

Zhang, Liying; Sedykh, Alexander; Tripathi, Ashutosh; Zhu, Hao; Afantitis, Antreas; Mouchlis, Varnavas D.; Melagraki, Georgia; Rusyn, Ivan; Tropsha, Alexander

2013-01-01

Identification of endocrine disrupting chemicals is one of the important goals of environmental chemical hazard screening. We report on the development of validated in silico predictors of chemicals likely to cause estrogen receptor (ER)-mediated endocrine disruption to facilitate their prioritization for future screening. A database of relative binding affinity of a large number of ERα and/or ERβ ligands was assembled (546 for ERα and 137 for ERβ). Both single-task learning (STL) and multi-task learning (MTL) continuous quantitative structure–activity relationship (QSAR) models were developed for predicting ligand binding affinity to ERα or ERβ. High predictive accuracy was achieved for ERα binding affinity (MTL R 2 = 0.71, STL R 2 = 0.73). For ERβ binding affinity, MTL models were significantly more predictive (R 2 = 0.53, p < 0.05) than STL models. In addition, docking studies were performed on a set of ER agonists/antagonists (67 agonists and 39 antagonists for ERα, 48 agonists and 32 antagonists for ERβ, supplemented by putative decoys/non-binders) using the following ER structures (in complexes with respective ligands) retrieved from the Protein Data Bank: ERα agonist (PDB ID: 1L2I), ERα antagonist (PDB ID: 3DT3), ERβ agonist (PDB ID: 2NV7), and ERβ antagonist (PDB ID: 1L2J). We found that all four ER conformations discriminated their corresponding ligands from presumed non-binders. Finally, both QSAR models and ER structures were employed in parallel to virtually screen several large libraries of environmental chemicals to derive a ligand- and structure-based prioritized list of putative estrogenic compounds to be used for in vitro and in vivo experimental validation. - Highlights: • This is the largest curated dataset inclusive of ERα and β (the latter is unique). • New methodology that for the first time affords acceptable ERβ models. • A combination of QSAR and docking enables prediction of affinity and function. • The results

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

Science.gov (United States)

Pron, G

2015-01-01

Background Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate-specific antigen (PSA) testing for PC has been in common practice for more than 20 years. Objectives A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system. Data Sources A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA-based population screening programs for PC. Review Methods A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality. Results The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67–0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87–1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ-confined PCs in the screening arm. Conclusions There was no

A Community-Based Randomized Trial of Hepatitis B Screening Among High-Risk Vietnamese Americans.

Science.gov (United States)

Ma, Grace X; Fang, Carolyn Y; Seals, Brenda; Feng, Ziding; Tan, Yin; Siu, Philip; Yeh, Ming Chin; Golub, Sarit A; Nguyen, Minhhuyen T; Tran, Tam; Wang, Minqi

2017-03-01

To evaluate the effectiveness of a community-based liver cancer prevention program on hepatitis B virus (HBV) screening among low-income, underserved Vietnamese Americans at high risk. We conducted a cluster randomized trial involving 36 Vietnamese community-based organizations and 2337 participants in Pennsylvania, New Jersey, and New York City between 2009 and 2014. We randomly assigned 18 community-based organizations to a community-based multilevel HBV screening intervention (n = 1131). We randomly assigned the remaining 18 community-based organizations to a general cancer education program (n = 1206), which included information about HBV-related liver cancer prevention. We assessed HBV screening rates at 6-month follow-up. Intervention participants were significantly more likely to have undergone HBV screening (88.1%) than were control group participants (4.6%). In a Cochran-Mantel-Haenszel analysis, the intervention effect on screening outcomes remained statistically significant after adjustment for demographic and health care access variables, including income, having health insurance, having a regular health provider, and English proficiency. A community-based, culturally appropriate, multilevel HBV screening intervention effectively increases screening rates in a high-risk, hard-to-reach Vietnamese American population.

Binding-site assessment by virtual fragment screening.

Directory of Open Access Journals (Sweden)

Niu Huang

2010-04-01

Full Text Available 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 approximately 11,000 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.

poolHiTS: A Shifted Transversal Design based pooling strategy for high-throughput drug screening

Directory of Open Access Journals (Sweden)

Woolf Peter J

2008-05-01

Full Text Available Abstract Background A key goal of drug discovery is to increase the throughput of small molecule screens without sacrificing screening accuracy. High-throughput screening (HTS in drug discovery involves testing a large number of compounds in a biological assay to identify active compounds. Normally, molecules from a large compound library are tested individually to identify the activity of each molecule. Usually a small number of compounds are found to be active, however the presence of false positive and negative testing errors suggests that this one-drug one-assay screening strategy can be significantly improved. Pooling designs are testing schemes that test mixtures of compounds in each assay, thereby generating a screen of the whole compound library in fewer tests. By repeatedly testing compounds in different combinations, pooling designs also allow for error-correction. These pooled designs, for specific experiment parameters, can be simply and efficiently created using the Shifted Transversal Design (STD pooling algorithm. However, drug screening contains a number of key constraints that require specific modifications if this pooling approach is to be useful for practical screen designs. Results In this paper, we introduce a pooling strategy called poolHiTS (Pooled High-Throughput Screening which is based on the STD algorithm. In poolHiTS, we implement a limit on the number of compounds that can be mixed in a single assay. In addition, we show that the STD-based pooling strategy is limited in the error-correction that it can achieve. Due to the mixing constraint, we show that it is more efficient to split a large library into smaller blocks of compounds, which are then tested using an optimized strategy repeated for each block. We package the optimal block selection algorithm into poolHiTS. The MATLAB codes for the poolHiTS algorithm and the corresponding decoding strategy are also provided. Conclusion We have produced a practical version

Cost-Effectiveness of a School-Based Emotional Health Screening Program

Science.gov (United States)

Kuo, Elena; Stoep, Ann Vander; McCauley, Elizabeth; Kernic, Mary A.

2009-01-01

Background: School-based screening for health conditions can help extend the reach of health services to underserved populations. Screening for mental health conditions is growing in acceptability, but evidence of cost-effectiveness is lacking. This study assessed costs and effectiveness associated with the Developmental Pathways Screening…

Referral criteria for school-based hearing screening in South Africa ...

African Journals Online (AJOL)

Referral criteria for school-based hearing screening in South Africa: Considerations for resource-limited contexts. ... Diagnostic audiometry confirmed that almost half (47%) of the referred children had a hearing loss. Conclusion: A screening intensity of 25 dB HL andimmediate rescreen reduces the referral rate significantly ...

"Thanks for Letting Us All Share Your Mammogram Experience Virtually": Developing a Web-Based Hub for Breast Cancer Screening.

Science.gov (United States)

Galpin, Adam; Meredith, Joanne; Ure, Cathy; Robinson, Leslie

2017-10-27

The decision around whether to attend breast cancer screening can often involve making sense of confusing and contradictory information on its risks and benefits. The Word of Mouth Mammogram e-Network (WoMMeN) project was established to create a Web-based resource to support decision making regarding breast cancer screening. This paper presents data from our user-centered approach in engaging stakeholders (both health professionals and service users) in the design of this Web-based resource. Our novel approach involved creating a user design group within Facebook to allow them access to ongoing discussion between researchers, radiographers, and existing and potential service users. This study had two objectives. The first was to examine the utility of an online user design group for generating insight for the creation of Web-based health resources. We sought to explore the advantages and limitations of this approach. The second objective was to analyze what women want from a Web-based resource for breast cancer screening. We recruited a user design group on Facebook and conducted a survey within the group, asking questions about design considerations for a Web-based breast cancer screening hub. Although the membership of the Facebook group varied over time, there were 71 members in the Facebook group at the end point of analysis. We next conducted a framework analysis on 70 threads from Facebook and a thematic analysis on the 23 survey responses. We focused additionally on how the themes were discussed by the different stakeholders within the context of the design group. Two major themes were found across both the Facebook discussion and the survey data: (1) the power of information and (2) the hub as a place for communication and support. Information was considered as empowering but also recognized as threatening. Communication and the sharing of experiences were deemed important, but there was also recognition of potential miscommunication within online

In vitro flow cytometry-based screening platform for cellulase engineering

Science.gov (United States)

Körfer, Georgette; Pitzler, Christian; Vojcic, Ljubica; Martinez, Ronny; Schwaneberg, Ulrich

2016-01-01

Ultrahigh throughput screening (uHTS) plays an essential role in directed evolution for tailoring biocatalysts for industrial applications. Flow cytometry-based uHTS provides an efficient coverage of the generated protein sequence space by analysis of up to 107 events per hour. Cell-free enzyme production overcomes the challenge of diversity loss during the transformation of mutant libraries into expression hosts, enables directed evolution of toxic enzymes, and holds the promise to efficiently design enzymes of human or animal origin. The developed uHTS cell-free compartmentalization platform (InVitroFlow) is the first report in which a flow cytometry-based screened system has been combined with compartmentalized cell-free expression for directed cellulase enzyme evolution. InVitroFlow was validated by screening of a random cellulase mutant library employing a novel screening system (based on the substrate fluorescein-di-β-D-cellobioside), and yielded significantly improved cellulase variants (e.g. CelA2-H288F-M1 (N273D/H288F/N468S) with 13.3-fold increased specific activity (220.60 U/mg) compared to CelA2 wildtype: 16.57 U/mg). PMID:27184298

Assessing the efficacy of cancer screening

Directory of Open Access Journals (Sweden)

Gemma Jacklyn

2017-07-01

Full Text Available Background: Population-based cancer screening has been established for several types of cancer in Australia and internationally. Screening may perform differently in practice from randomised controlled trials, which makes evaluating programs complex. Materials and methods: We discuss how to assess the evidence of benefits and harms of cancer screening, including the main biases that can mislead clinicians and policy makers (such as volunteer, lead-time, length-time and overdiagnosis bias. We also discuss ways in which communication of risks can inform or mislead the community. Results: The evaluation of cancer screening programs should involve balancing the benefits and harms. When considering the overall worth of an intervention and allocation of scarce health resources, decisions should focus on the net benefits and be informed by systematic reviews. Communication of screening outcomes can be misleading. Many messages highlight the benefits while downplaying the harms, and often use relative risks and 5-year survival to persuade people to screen rather than support informed choice. Lessons learned: An evidence based approach is essential when evaluating and communicating the benefits and harms of cancer screening, to minimise misleading biases and the reliance on intuition.

An improved single cell ultrahigh throughput screening method based on in vitro compartmentalization.

Directory of Open Access Journals (Sweden)

Fuqiang Ma

Full Text Available High-throughput screening is a key technique in discovery and engineering of enzymes. In vitro compartmentalization based fluorescence-activated cell sorting (IVC-FACS has recently emerged as a powerful tool for ultrahigh-throughput screening of biocatalysts. However, the accuracy of current IVC-FACS assays is severely limited by the wide polydispersity of micro-reactors generated by homogenizing. Here, an improved protocol based on membrane-extrusion technique was reported to generate the micro-reactors in a more uniform manner. This crucial improvement enables ultrahigh-throughput screening of enzymatic activity at a speed of >10⁸ clones/day with an accuracy that could discriminate as low as two-fold differences in enzymatic activity inside the micro-reactors, which is higher than similar IVC-FACS systems ever have reported. The enzymatic reaction in the micro-reactors has very similar kinetic behavior compared to the bulk reaction system and shows wide dynamic range. By using the modified IVC-FACS, E. coli cells with esterase activity could be enriched 330-fold from large excesses of background cells through a single round of sorting. The utility of this new IVC-FACS system was further illustrated by the directed evolution of thermophilic esterase AFEST. The catalytic activity of the very efficient esterase was further improved by ∼2-fold, resulting in several improved mutants with k(cat/K(M values approaching the diffusion-limited efficiency of ∼10⁸ M⁻¹s⁻¹.

Screening Risk Evaluation methodology

International Nuclear Information System (INIS)

Hopper, K.M.

1994-01-01

The Screening Risk Evaluation (SRE) Guidance document is a set of guidelines provided for the uniform implementation of SREs performed on D ampersand D facilities. These guidelines are designed specifically for the completion of the second (semi-quantitative screening) phase of the D ampersand D Risk-Based Process. The SRE Guidance produces screening risk scores reflecting levels of risk through the use of risk ranking indices. Five types of possible risk are calculated from the SRE: current releases, worker exposures, future releases, physical hazards, and criticality. The Current Release Index (CRI) calculates the risk to human health and the environment from ongoing or probable releases within a one year time period. The Worker Exposure Index (WEI) calculates the risk to workers, occupants, and visitors in D ampersand D facilities of contaminant exposure. The Future Release Index (FRI) calculates the risk of future releases of contaminants, after one year, to human health and the environment. The Physical Hazards Index (PHI) calculates the risk-to human health due to factors other than that of contaminants. The index of Criticality is approached as a modifying factor to the entire SRE, due to the fact that criticality issues are strictly regulated under DOE. Screening risk results will be tabulated in matrix form and Total Risk will be calculated (weighted equation) to produce a score on which to base early action recommendations. Other recommendations from the screening risk scores will be made based either on individual index scores or from reweighted Total Risk calculations. All recommendations based on the SRE will be made based on a combination of screening risk scores, decision drivers, and other considerations, determined on a project by project basis. The SRE is the first and most important step in the overall D ampersand D project level decision making process

Optical touch screen based on waveguide sensing

DEFF Research Database (Denmark)

Pedersen, Henrik Chresten; Jakobsen, Michael Linde; Hanson, Steen Grüner

2011-01-01

We disclose a simple, optical touch screen technique based on a planar injection molded polymer waveguide, a single laser, and a small linear detector array. The solution significantly reduces the complexity and cost as compared to existing optical touch technologies. Force detection of a touching...

Register-based studies of cancer screening effects

DEFF Research Database (Denmark)

Von Euler-Chelpin, My; Lynge, Elsebeth; Rebolj, Matejka

2011-01-01

INTRODUCTION: There are two organised cancer screening programmes in Denmark, against cervical and breast cancers. The aim with this study was to give an overview of the available register-based research regarding these two programmes, to demonstrate the usefulness of data from the national regis...

Machine-learning scoring functions to improve structure-based binding affinity prediction and virtual screening.

Science.gov (United States)

Ain, Qurrat Ul; Aleksandrova, Antoniya; Roessler, Florian D; Ballester, Pedro J

2015-01-01

Docking tools to predict whether and how a small molecule binds to a target can be applied if a structural model of such target is available. The reliability of docking depends, however, on the accuracy of the adopted scoring function (SF). Despite intense research over the years, improving the accuracy of SFs for structure-based binding affinity prediction or virtual screening has proven to be a challenging task for any class of method. New SFs based on modern machine-learning regression models, which do not impose a predetermined functional form and thus are able to exploit effectively much larger amounts of experimental data, have recently been introduced. These machine-learning SFs have been shown to outperform a wide range of classical SFs at both binding affinity prediction and virtual screening. The emerging picture from these studies is that the classical approach of using linear regression with a small number of expert-selected structural features can be strongly improved by a machine-learning approach based on nonlinear regression allied with comprehensive data-driven feature selection. Furthermore, the performance of classical SFs does not grow with larger training datasets and hence this performance gap is expected to widen as more training data becomes available in the future. Other topics covered in this review include predicting the reliability of a SF on a particular target class, generating synthetic data to improve predictive performance and modeling guidelines for SF development. WIREs Comput Mol Sci 2015, 5:405-424. doi: 10.1002/wcms.1225 For further resources related to this article, please visit the WIREs website.

Screen-based sedentary behaviours in Italian school children: the ZOOM8 study

Directory of Open Access Journals (Sweden)

Myriam Galfo

2014-07-01

Full Text Available Normal 0 14 Background: screen-based sedentary behaviours likely have a negative impact on many aspects of youth health and development. The purpose of this study was to describe the screen-based sedentary behaviours and to examine factors associated in a sample of Italian school children. Methods: 2129 children, aged 8-9 years, from the three main geographical areas of Italy were involved. Body weight and height were measured. Screen-based sedentary behaviours were evaluated using a parent-reported questionnaire that included items about the time spent watching television (TV and using computer/playstation and other electronic games. Pearson’s chi-square test and logistic regression analysis were conducted to study possible associated factors.Results: more time was spent in screen-based sedentary activities during non-school days rather than on school days. More males than females watched television more than the recommended 2 hours a day and spent the same time using computer (PC, playstation and other electronic games.  The presence of a TV in the child’s bedroom was significantly associated with geographical area, and inversely associated with mother’s education. Moreover, children with a TV in the bedroom had higher odds of being overweight/obese and watching TV more than 2 hours a day than those without a TV. According to multiple logistic regression gender, mother’s age and mother’s education were predictors of the total screen time.Conclusions: Italian children spent a significant amount of time in screen-based sedentary behaviours, exceeding media recommendations. In addition gender, mother’s age and mother’s education were predictors of the total screen time.

Continuous Membrane-Based Screening System for Biocatalysis

Directory of Open Access Journals (Sweden)

Matthias Kraume

2011-02-01

Full Text Available The use of membrane reactors for enzymatic and co-factor regenerating reactions offers versatile advantages such as higher conversion rates and space-time-yields and is therefore often applied in industry. However, currently available screening and kinetics characterization systems are based on batch and fed-batch operated reactors and were developed for whole cell biotransformations rather than for enzymatic catalysis. Therefore, the data obtained from such systems has only limited transferability for continuous membrane reactors. The aim of this study is to evaluate and to improve a novel screening and characterization system based on the membrane reactor concept using the enzymatic hydrolysis of cellulose as a model reaction. Important aspects for the applicability of the developed system such as long-term stability and reproducibility of continuous experiments were very high. The concept used for flow control and fouling suppression allowed control of the residence time with a high degree of precision (±1% accuracy in a long-term study (>100 h.

Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.

Science.gov (United States)

Han, Byeonggu; Ahn, Hee-Chul

2016-01-01

During the past decade fragment-based drug discovery (FBDD) has rapidly evolved and several drugs or drug candidates developed by FBDD approach are clinically in use or in clinical trials. For example, vemurafenib, a V600E mutated BRAF inhibitor, was developed by utilizing FBDD approach and approved by FDA in 2011. In FBDD, screening of fragments is the starting step for identification of hits and lead generation. Fragment screening usually relies on biophysical techniques by which the protein-bound small molecules can be detected. NMR spectroscopy has been extensively used to study the molecular interaction between the protein and the ligand, and has many advantages in fragment screening over other biophysical techniques. This chapter describes the practical aspects of fragment screening by saturation transfer difference NMR.

Automated NMR fragment based screening identified a novel interface blocker to the LARG/RhoA complex.

Directory of Open Access Journals (Sweden)

Jia Gao

Full Text Available The small GTPase cycles between the inactive GDP form and the activated GTP form, catalyzed by the upstream guanine exchange factors. The modulation of such process by small molecules has been proven to be a fruitful route for therapeutic intervention to prevent the over-activation of the small GTPase. The fragment based approach emerging in the past decade has demonstrated its paramount potential in the discovery of inhibitors targeting such novel and challenging protein-protein interactions. The details regarding the procedure of NMR fragment screening from scratch have been rarely disclosed comprehensively, thus restricts its wider applications. To achieve a consistent screening applicable to a number of targets, we developed a highly automated protocol to cover every aspect of NMR fragment screening as possible, including the construction of small but diverse libray, determination of the aqueous solubility by NMR, grouping compounds with mutual dispersity to a cocktail, and the automated processing and visualization of the ligand based screening spectra. We exemplified our streamlined screening in RhoA alone and the complex of the small GTPase RhoA and its upstream guanine exchange factor LARG. Two hits were confirmed from the primary screening in cocktail and secondary screening over individual hits for LARG/RhoA complex, while one of them was also identified from the screening for RhoA alone. HSQC titration of the two hits over RhoA and LARG alone, respectively, identified one compound binding to RhoA.GDP at a 0.11 mM affinity, and perturbed the residues at the switch II region of RhoA. This hit blocked the formation of the LARG/RhoA complex, validated by the native gel electrophoresis, and the titration of RhoA to ¹⁵N labeled LARG in the absence and presence the compound, respectively. It therefore provides us a starting point toward a more potent inhibitor to RhoA activation catalyzed by LARG.

Psychiatric screening and interventions for minor refugees in Europe: an overview of approaches and tools.

Science.gov (United States)

Horlings, Annerieke; Hein, Irma

2018-02-01

Currently hundreds of thousands of minor refugees entered Europe. This group has been exposed to traumatic events pre-, during, and post-migration and is at increased risk of developing psychiatric disorders. In this article, we describe the results of our literature search on screening and interventions for post-traumatic stress disorder (PTSD) in minor refugees, in order to make recommendations for clinical practice. Results show that studies on diagnostic accuracy of assessment instruments and efficacy of mental healthcare interventions in this population are lacking. Traumatic experiences pre-flight, during the flight and at resettlement, superimposed by parental PTSD, and other contextual factors, might lead to more than 25% of minor refugees developing PTSD. To enhance the number of minor refugees recognized with PTSD, we recommend the use of a brief screening instrument. A public health approach, focusing on environmental supportive factors is the first step in treatment for this group, followed by short-term psychological group interventions focusing on psycho-education and stress reduction. Minor refugees with no improvement in PTSD symptoms by these interventions need referral to specialized mental health care services. Mental health providers should be culturally competent. What is Known: • Post-traumatic stress disorder, anxiety, sleeping problems, and depression are the most common psychiatric disorders in minor refugees. • Evidence based methods on screening and interventions in minor refugees with psychiatric disorders are lacking. What is New: • In the absence of validated screening tools a best practice reliable, quick and child-friendly tool is presented. • A layered system for mental health care and psychosocial support in minor refugees is explained.

A new system for parallel drug screening against multiple-resistant HIV mutants based on lentiviral self-inactivating (SIN vectors and multi-colour analyses

Directory of Open Access Journals (Sweden)

Prokofjeva Maria M

2013-01-01

Full Text Available Abstract 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.

Newborn screening for congenital cytomegalovirus: Options for hospital-based and public health programs.

Science.gov (United States)

Grosse, Scott D; Dollard, Sheila; Ross, Danielle S; Cannon, Michael

2009-12-01

Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL) and developmental disability in children. Early identification of infected children through screening could allow for early intervention and improvement in functional outcomes among the subset who develop sequelae. To outline potential options and strategies for screening newborns for congenital CMV infection and to discuss barriers to screening and data needs to inform future policy decisions. Commentary based on the literature and expert opinion on newborn dried blood spot screening, newborn hearing screening/Early Hearing Detection and Intervention (EHDI) programs, and congenital CMV. Although no population-based screening for congenital CMV is underway, pilot newborn screening studies using a variety of assays with urine or dried blood spot specimens are underway. Challenges to screening are both practical-uncertain sensitivity of blood spot assays suitable for large-scale screening and lack of infrastructure for collection of urine specimens; and evidentiary-the need to demonstrate improved outcomes and value of screening to offset the expense and potential adverse psychosocial consequences for children and families whose children require periodic monitoring but never develop sequelae. Screening for congenital CMV infection is a potentially important intervention that merits additional research, including the logistical feasibility of different screening options and psychosocial consequences for families.

Estimating time and travel costs incurred in clinic based screening: flexible sigmoidoscopy screening for colorectal cancer.

Science.gov (United States)

Frew, E; Wolstenholme, J L; Atkin, W; Whynes, D K

1999-01-01

To identify the characteristics of mode of travel to screening clinics; to estimate the time and travel costs incurred in attending; to investigate whether such costs are likely to bias screening compliance. Twelve centres in the trial of flexible sigmoidoscopy screening for colorectal cancer, drawn from across Great Britain. Analysis of 3525 questionnaires completed by screening subjects while attending clinics. Information supplied included sociodemographic characteristics, modes of travel, expenses, activities foregone owing to attendance, and details of companions. More than 80% of subjects arrived at the clinics by car, and about two thirds were accompanied. On average, the clinic visit involved a 14.4 mile (22.8 km) round trip, requiring 130 minutes. Mean travel costs amounted to 6.10 Pounds per subject. The mean gross direct non-medical and indirect cost per subject amounted to 16.90 Pounds, and the mean overall gross cost per attendance was 22.40 Pounds. Compared with the Great Britain population as a whole, non-manual classes were more strongly represented, and the self employed less strongly represented, among the attendees. In relation to direct medical costs, the time and travel costs of clinic based screening can be substantial, may influence the overall cost effectiveness of a screening programme, and may deter potential subjects from attending.

Diabetes and Hypertension in Marshallese Adults: Results from Faith-Based Health Screenings.

Science.gov (United States)

McElfish, Pearl Anna; Rowland, Brett; Long, Christopher R; Hudson, Jonell; Piel, Michelle; Buron, Bill; Riklon, Sheldon; Bing, Williamina Ioanna; Warmack, T Scott

2017-12-01

The Pacific Islander population in the USA is growing rapidly. However, research on Pacific Islanders in the USA is limited, or sometimes misleading due to aggregation with Asian Americans. This project seeks to add to the dearth of health literature by conducting a health assessment of Marshallese in northwest Arkansas. Using a community-based participatory research approach, nine health screening events were conducted at local Marshallese churches. Participants completed the Behavioral Risk Factors Surveillance Survey core questionnaire and diabetes module if applicable. Biometric data, including Hemoglobin A1c, blood pressure, and body mass index, were gathered by an interprofessional team. Four hundred one participants completed health screenings. High proportions of diabetes, obesity, and hypertension were found. A high percentage of participants were uninsured, and multiple barriers to health care were found within the sample. This project represents one of the first broad health assessments of Pacific Islanders in the USA. Proportions of diabetes, hypertension, obesity, and uninsured found in the sample are much higher than national proportions.

Drug and bioactive molecule screening based on a bioelectrical impedance cell culture platform

Directory of Open Access Journals (Sweden)

Ramasamy S

2014-12-01

Full Text Available Sakthivel Ramasamy,1 Devasier Bennet,1 Sanghyo Kim1,2 1Department of Bionanotechnology, Gachon University, Gyeonggi-Do, Republic of Korea; 2Graduate Gachon Medical Research Institute, Gil Medical Center, Incheon, Republic of Korea Abstract: This review will present a brief discussion on the recent advancements of bioelectrical impedance cell-based biosensors, especially the electric cell-substrate impedance sensing (ECIS system for screening of various bioactive molecules. The different technical integrations of various chip types, working principles, measurement systems, and applications for drug targeting of molecules in cells are highlighted in this paper. Screening of bioactive molecules based on electric cell-substrate impedance sensing is a trial-and-error process toward the development of therapeutically active agents for drug discovery and therapeutics. In general, bioactive molecule screening can be used to identify active molecular targets for various diseases and toxicity at the cellular level with nanoscale resolution. In the innovation and screening of new drugs or bioactive molecules, the activeness, the efficacy of the compound, and safety in biological systems are the main concerns on which determination of drug candidates is based. Further, drug discovery and screening of compounds are often performed in cell-based test systems in order to reduce costs and save time. Moreover, this system can provide more relevant results in in vivo studies, as well as high-throughput drug screening for various diseases during the early stages of drug discovery. Recently, MEMS technologies and integration with image detection techniques have been employed successfully. These new technologies and their possible ongoing transformations are addressed. Select reports are outlined, and not all the work that has been performed in the field of drug screening and development is covered. Keywords: screening of bioactive agents, impedance-based cell

How Phenotypic Screening Influenced Drug Discovery: Lessons from Five Years of Practice.

Science.gov (United States)

Haasen, Dorothea; Schopfer, Ulrich; Antczak, Christophe; Guy, Chantale; Fuchs, Florian; Selzer, Paul

Since 2011, phenotypic screening has been a trend in the pharmaceutical industry as well as in academia. This renaissance was triggered by analyses that suggested that phenotypic screening is a superior strategy to discover first-in-class drugs. Despite these promises and considerable investments, pharmaceutical research organizations have encountered considerable challenges with the approach. Few success stories have emerged in the past 5 years and companies are questioning their investment in this area. In this contribution, we outline what we have learned about success factors and challenges of phenotypic screening. We then describe how our efforts in phenotypic screening have influenced our approach to drug discovery in general. We predict that concepts from phenotypic screening will be incorporated into target-based approaches and will thus remain influential beyond the current trend.

Isolation of xylose isomerases by sequence- and function-based screening from a soil metagenomic library

Directory of Open Access Journals (Sweden)

Parachin Nádia

2011-05-01

Full Text Available Abstract Background Xylose isomerase (XI catalyses the isomerisation of xylose to xylulose in bacteria and some fungi. Currently, only a limited number of XI genes have been functionally expressed in Saccharomyces cerevisiae, the microorganism of choice for lignocellulosic ethanol production. The objective of the present study was to search for novel XI genes in the vastly diverse microbial habitat present in soil. As the exploitation of microbial diversity is impaired by the ability to cultivate soil microorganisms under standard laboratory conditions, a metagenomic approach, consisting of total DNA extraction from a given environment followed by cloning of DNA into suitable vectors, was undertaken. Results A soil metagenomic library was constructed and two screening methods based on protein sequence similarity and enzyme activity were investigated to isolate novel XI encoding genes. These two screening approaches identified the xym1 and xym2 genes, respectively. Sequence and phylogenetic analyses revealed that the genes shared 67% similarity and belonged to different bacterial groups. When xym1 and xym2 were overexpressed in a xylA-deficient Escherichia coli strain, similar growth rates to those in which the Piromyces XI gene was expressed were obtained. However, expression in S. cerevisiae resulted in only one-fourth the growth rate of that obtained for the strain expressing the Piromyces XI gene. Conclusions For the first time, the screening of a soil metagenomic library in E. coli resulted in the successful isolation of two active XIs. However, the discrepancy between XI enzyme performance in E. coli and S. cerevisiae suggests that future screening for XI activity from soil should be pursued directly using yeast as a host.

The Impact of a Population-Based Screening Program on Income- and Immigration-Related Disparities in Colorectal Cancer Screening.

Science.gov (United States)

Kiran, Tara; Glazier, Richard H; Moineddin, Rahim; Gu, Sumei; Wilton, Andrew S; Paszat, Lawrence

2017-09-01

Background: A population-based program promoting the Fecal Occult Blood Test (FOBT) for colorectal cancer screening was introduced in 2008 in Ontario, Canada, where opportunistic screening with colonoscopy had been increasing in frequency. We evaluated the impact of the program on income and immigration-related disparities in screening. Methods: We used linked administrative data to calculate colorectal cancer screening rates for eligible Ontarians in each year between 2001/02 ( n = 2,852,619) and 2013/14 ( n = 4,139,304). We quantified disparities using an "inequality ratio" of screening rates in the most disadvantaged group relative to the most advantaged group. We performed segmented logistic regression analyses stratified by screening modality and adjusted for age, sex, rurality, comorbidity, and morbidity. Results: Between 2001/02 and 2013/14, the income and immigration inequality ratios narrowed from 0.74 to 0.80 and 0.55 to 0.69, respectively. Before the screening program, the income inequality ratio was widening by 1% per year (95% CI 1% to 1%); in the year it was introduced, it narrowed by 4% (95% CI 2% to 7%) and in the years following, it remained stable [0% decrease (95% CI 1% decrease to 0% decrease) per year]. Results were similar for immigration-related disparities. After program introduction, disparities in receiving FOBT were narrowing at a faster rate while disparities in receiving colonoscopy were widening at a slower rate. Conclusions: Introduction of a population-based screening program promoting FOBT for colorectal cancer was associated with only modest improvements in immigration and income-related disparities. Impact: Reducing immigration and income-related disparities should be a focus for future research and policy work. Disparities in Ontario seem to be driven by a higher uptake of colonoscopy among more advantaged groups. Cancer Epidemiol Biomarkers Prev; 26(9); 1401-10. ©2017 AACR . ©2017 American Association for Cancer Research.

Just-in-Time Compound Pooling Increases Primary Screening Capacity without Compromising Screening Quality.

Science.gov (United States)

Elkin, L L; Harden, D G; Saldanha, S; Ferguson, H; Cheney, D L; Pieniazek, S N; Maloney, D P; Zewinski, J; O'Connell, J; Banks, M

2015-06-01

Compound pooling, or multiplexing more than one compound per well during primary high-throughput screening (HTS), is a controversial approach with a long history of limited success. Many issues with this approach likely arise from long-term storage of library plates containing complex mixtures of compounds at high concentrations. Due to the historical difficulties with using multiplexed library plates, primary HTS often uses a one-compound-one-well approach. However, as compound collections grow, innovative strategies are required to increase the capacity of primary screening campaigns. Toward this goal, we have developed a novel compound pooling method that increases screening capacity without compromising data quality. This method circumvents issues related to the long-term storage of complex compound mixtures by using acoustic dispensing to enable "just-in-time" compound pooling directly in the assay well immediately prior to assay. Using this method, we can pool two compounds per well, effectively doubling the capacity of a primary screen. Here, we present data from pilot studies using just-in-time pooling, as well as data from a large >2-million-compound screen using this approach. These data suggest that, for many targets, this method can be used to vastly increase screening capacity without significant reduction in the ability to detect screening hits. © 2015 Society for Laboratory Automation and Screening.

A cloud-based system for automatic glaucoma screening.

Science.gov (United States)

Fengshou Yin; Damon Wing Kee Wong; Ying Quan; Ai Ping Yow; Ngan Meng Tan; Gopalakrishnan, Kavitha; Beng Hai Lee; Yanwu Xu; Zhuo Zhang; Jun Cheng; Jiang Liu

2015-08-01

In recent years, there has been increasing interest in the use of automatic computer-based systems for the detection of eye diseases including glaucoma. However, these systems are usually standalone software with basic functions only, limiting their usage in a large scale. In this paper, we introduce an online cloud-based system for automatic glaucoma screening through the use of medical image-based pattern classification technologies. It is designed in a hybrid cloud pattern to offer both accessibility and enhanced security. Raw data including patient's medical condition and fundus image, and resultant medical reports are collected and distributed through the public cloud tier. In the private cloud tier, automatic analysis and assessment of colour retinal fundus images are performed. The ubiquitous anywhere access nature of the system through the cloud platform facilitates a more efficient and cost-effective means of glaucoma screening, allowing the disease to be detected earlier and enabling early intervention for more efficient intervention and disease management.

The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador.

Science.gov (United States)

Campos, Nicole G; Maza, Mauricio; Alfaro, Karla; Gage, Julia C; Castle, Philip E; Felix, Juan C; Cremer, Miriam L; Kim, Jane J

2015-08-15

Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP. © 2015 UICC.

Opportunistic pathology-based screening for diabetes

Science.gov (United States)

Simpson, Aaron J; Krowka, Renata; Kerrigan, Jennifer L; Southcott, Emma K; Wilson, J Dennis; Potter, Julia M; Nolan, Christopher J; Hickman, Peter E

2013-01-01

Objective To determine the potential of opportunistic glycated haemoglobin (HbA1c) testing of pathology samples to detect previously unknown diabetes. Design Pathology samples from participants collected for other reasons and suitable for HbA1c testing were utilised for opportunistic diabetes screening. HbA1c was measured with a Biorad Variant II turbo analyser and HbA1c levels of ≥6.5% (48 mmol/mol) were considered diagnostic for diabetes. Confirmation of previously unknown diabetes status was obtained by a review of hospital medical records and phone calls to general practitioners. Setting Hospital pathology laboratory receiving samples from hospital-based and community-based (CB) settings. Participants Participants were identified based on the blood sample collection location in the CB, emergency department (ED) and inpatient (IP) groups. Exclusions pretesting were made based on the electronic patient history of: age <18 years, previous diabetes diagnosis, query for diabetes status in the past 12 months, evidence of pregnancy and sample collected postsurgery or transfusion. Only one sample per individual participant was tested. Results Of the 22 396 blood samples collected, 4505 (1142 CB, 1113 ED, 2250 IP) were tested of which 327 (7.3%) had HbA1c levels ≥6.5% (48 mmol/mol). Of these 120 (2.7%) were determined to have previously unknown diabetes (11 (1%) CB, 21 (1.9%) ED, 88 (3.9%) IP). The prevalence of previously unknown diabetes was substantially higher (5.4%) in hospital-based (ED and IP) participants aged over 54 years. Conclusions Opportunistic testing of referred pathology samples can be an effective method of screening for diabetes, especially in hospital-based and older persons. PMID:24065696

A rational approach to heavy-atom derivative screening

International Nuclear Information System (INIS)

Joyce, M. Gordon; Radaev, Sergei; Sun, Peter D.

2010-01-01

In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom-derivative screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. Despite the development in recent times of a range of techniques for phasing macromolecules, the conventional heavy-atom derivatization method still plays a significant role in protein structure determination. However, this method has become less popular in modern high-throughput oriented crystallography, mostly owing to its trial-and-error nature, which often results in lengthy empirical searches requiring large numbers of well diffracting crystals. In addition, the phasing power of heavy-atom derivatives is often compromised by lack of isomorphism or even loss of diffraction. In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom derivative-screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. The method includes three basic steps: (i) the selection of likely reactive compounds for a given protein and specific crystallization conditions based on pre-defined heavy-atom compound reactivity profiles, (ii) screening of the chosen heavy-atom compounds for their ability to form protein adducts using mass spectrometry and (iii) derivatization of crystals with selected heavy-metal compounds using the quick-soak method to maximize diffraction quality and minimize non-isomorphism. Overall, this system streamlines the process of heavy-atom compound identification and minimizes the problem of non-isomorphism in phasing

A rational approach to heavy-atom derivative screening

Energy Technology Data Exchange (ETDEWEB)

Joyce, M. Gordon; Radaev, Sergei; Sun, Peter D., E-mail: psun@nih.gov [Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, Maryland 20852 (United States)

2010-04-01

In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom-derivative screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. Despite the development in recent times of a range of techniques for phasing macromolecules, the conventional heavy-atom derivatization method still plays a significant role in protein structure determination. However, this method has become less popular in modern high-throughput oriented crystallography, mostly owing to its trial-and-error nature, which often results in lengthy empirical searches requiring large numbers of well diffracting crystals. In addition, the phasing power of heavy-atom derivatives is often compromised by lack of isomorphism or even loss of diffraction. In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom derivative-screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. The method includes three basic steps: (i) the selection of likely reactive compounds for a given protein and specific crystallization conditions based on pre-defined heavy-atom compound reactivity profiles, (ii) screening of the chosen heavy-atom compounds for their ability to form protein adducts using mass spectrometry and (iii) derivatization of crystals with selected heavy-metal compounds using the quick-soak method to maximize diffraction quality and minimize non-isomorphism. Overall, this system streamlines the process of heavy-atom compound identification and minimizes the problem of non-isomorphism in phasing.

Machine Learning Approaches Toward Building Predictive Models for Small Molecule Modulators of miRNA and Its Utility in Virtual Screening of Molecular Databases.

Science.gov (United States)

Periwal, Vinita; Scaria, Vinod

2017-01-01

The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules. Here, we describe a computational strategy based on machine learning for creation of predictive models from high-throughput biological screens for virtual screening of small molecules with the potential to inhibit microRNAs. Such models could be potentially used for computational prioritization of small molecules before performing high-throughput biological assay.

Patient-completed or symptom-based screening tools for endometriosis: a scoping review.

Science.gov (United States)

Surrey, Eric; Carter, Cathryn M; Soliman, Ahmed M; Khan, Shahnaz; DiBenedetti, Dana B; Snabes, Michael C

2017-08-01

The objective of this review was to evaluate existing patient-completed screening questionnaires and/or symptom-based predictive models with respect to their potential for use as screening tools for endometriosis in adult women. Validated instruments were of particular interest. We conducted structured searches of PubMed and targeted searches of the gray literature to identify studies reporting on screening instruments used in endometriosis. Studies were screened according to inclusion and exclusion criteria that followed the PICOS (population, intervention, comparison, outcomes, study design) framework. A total of 16 studies were identified, of which 10 described measures for endometriosis in general, 2 described measures for endometriosis at specific sites, and 4 described measures for deep-infiltrating endometriosis. Only 1 study evaluated a questionnaire that was solely patient-completed. Most measures required physician, imaging, or laboratory assessments in addition to patient-completed questionnaires, and several measures relied on complex scoring. Validation for use as a screening tool in adult women with potential endometriosis was lacking in all studies, as most studies focused on diagnosis versus screening. This literature review did not identify any fully validated, symptom-based, patient-reported questionnaires for endometriosis screening in adult women.

Screening sensitivity theory

International Nuclear Information System (INIS)

Oblow, E.M.; Perey, F.G.

1984-01-01

A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

[Methodology of Screening New Antibiotics: Present Status and Prospects].

Science.gov (United States)

Trenin, A S

2015-01-01

Due to extensive distribution of pathogen resistance to available pharmaceuticals and serious problems in the treatment of various infections and tumor diseases, the necessity of new antibiotics is urgent. The basic methodological approaches to chemical synthesis of antibiotics and screening of new antibiotics among natural products, mainly among microbial secondary metabolites, are considered in the review. Since the natural compounds are very much diverse, screening of such substances gives a good opportunity to discover antibiotics of various chemical structure and mechanism of action. Such an approach followed by chemical or biological transformation, is capable of providing the health care with new effective pharmaceuticals. The review is mainly concentrated on screening of natural products and methodological problems, such as: isolation of microbial producers from the habitats, cultivation of microorganisms producing appropriate substances, isolation and chemical characterization of microbial metabolites, identification of the biological activity of the metabolites. The main attention is paid to the problems of microbial secondary metabolism and design of new models for screening biologically active compounds. The last achievements in the field of antibiotics and most perspective approaches to future investigations are discussed. The main methodological approach to isolation and cultivation of the producers remains actual and needs constant improvement. The increase of the screening efficiency can be achieved by more rapid chemical identification of antibiotics and design of new screening models based on the biological activity detection.

An approximate-reasoning-based method for screening flammable gas tanks

International Nuclear Information System (INIS)

Eisenhawer, S.W.; Bott, T.F.; Smith, R.E.

1998-03-01

High-level waste (HLW) produces flammable gases as a result of radiolysis and thermal decomposition of organics. Under certain conditions, these gases can accumulate within the waste for extended periods and then be released quickly into the dome space of the storage tank. As part of the effort to reduce the safety concerns associated with flammable gas in HLW tanks at Hanford, a flammable gas watch list (FGWL) has been established. Inclusion on the FGWL is based on criteria intended to measure the risk associated with the presence of flammable gas. It is important that all high-risk tanks be identified with high confidence so that they may be controlled. Conversely, to minimize operational complexity, the number of tanks on the watchlist should be reduced as near to the true number of flammable risk tanks as the current state of knowledge will support. This report presents an alternative to existing approaches for FGWL screening based on the theory of approximate reasoning (AR) (Zadeh 1976). The AR-based model emulates the inference process used by an expert when asked to make an evaluation. The FGWL model described here was exercised by performing two evaluations. (1) A complete tank evaluation where the entire algorithm is used. This was done for two tanks, U-106 and AW-104. U-106 is a single shell tank with large sludge and saltcake layers. AW-104 is a double shell tank with over one million gallons of supernate. Both of these tanks had failed the screening performed by Hodgson et al. (2) Partial evaluations using a submodule for the predictor likelihood for all of the tanks on the FGWL that had been flagged previously by Whitney (1995)

Screen printing as a scalable and low-cost approach for rigid and flexible thin-film transistors using separated carbon nanotubes.

Science.gov (United States)

Cao, Xuan; Chen, Haitian; Gu, Xiaofei; Liu, Bilu; Wang, Wenli; Cao, Yu; Wu, Fanqi; Zhou, Chongwu

2014-12-23

Semiconducting single-wall carbon nanotubes are very promising materials in printed electronics due to their excellent mechanical and electrical property, outstanding printability, and great potential for flexible electronics. Nonetheless, developing scalable and low-cost approaches for manufacturing fully printed high-performance single-wall carbon nanotube thin-film transistors remains a major challenge. Here we report that screen printing, which is a simple, scalable, and cost-effective technique, can be used to produce both rigid and flexible thin-film transistors using separated single-wall carbon nanotubes. Our fully printed top-gated nanotube thin-film transistors on rigid and flexible substrates exhibit decent performance, with mobility up to 7.67 cm2 V(-1) s(-1), on/off ratio of 10(4)∼10(5), minimal hysteresis, and low operation voltage (transistors (bent with radius of curvature down to 3 mm) and driving capability for organic light-emitting diode have been demonstrated. Given the high performance of the fully screen-printed single-wall carbon nanotube thin-film transistors, we believe screen printing stands as a low-cost, scalable, and reliable approach to manufacture high-performance nanotube thin-film transistors for application in display electronics. Moreover, this technique may be used to fabricate thin-film transistors based on other materials for large-area flexible macroelectronics, and low-cost display electronics.

Breast Cancer Screening in an Era of Personalized Regimens

Science.gov (United States)

Onega, Tracy; Beaber, Elisabeth F.; Sprague, Brian L.; Barlow, William E.; Haas, Jennifer S.; Tosteson, Anna N.A.; Schnall, Mitchell D.; Armstrong, Katrina; Schapira, Marilyn M.; Geller, Berta; Weaver, Donald L.; Conant, Emily F.

2014-01-01

Breast cancer screening holds a prominent place in public health, health care delivery, policy, and women’s health care decisions. Several factors are driving shifts in how population-based breast cancer screening is approached, including advanced imaging technologies, health system performance measures, health care reform, concern for “overdiagnosis,” and improved understanding of risk. Maximizing benefits while minimizing the harms of screening requires moving from a “1-size-fits-all” guideline paradigm to more personalized strategies. A refined conceptual model for breast cancer screening is needed to align women’s risks and preferences with screening regimens. A conceptual model of personalized breast cancer screening is presented herein that emphasizes key domains and transitions throughout the screening process, as well as multilevel perspectives. The key domains of screening awareness, detection, diagnosis, and treatment and survivorship are conceptualized to function at the level of the patient, provider, facility, health care system, and population/policy arena. Personalized breast cancer screening can be assessed across these domains with both process and outcome measures. Identifying, evaluating, and monitoring process measures in screening is a focus of a National Cancer Institute initiative entitled PROSPR (Population-based Research Optimizing Screening through Personalized Regimens), which will provide generalizable evidence for a risk-based model of breast cancer screening, The model presented builds on prior breast cancer screening models and may serve to identify new measures to optimize benefits-to-harms tradeoffs in population-based screening, which is a timely goal in the era of health care reform. PMID:24830599

A comprehensive platform for highly multiplexed mammalian functional genetic screens

Directory of Open Access Journals (Sweden)

Cheung-Ong Kahlin

2011-05-01

Full Text Available Abstract Background Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens. Results Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens. Conclusion Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray based deconvolution methods.

The health indicators associated with screen-based sedentary behavior among adolescent girls: a systematic review.

Science.gov (United States)

Costigan, Sarah A; Barnett, Lisa; Plotnikoff, Ronald C; Lubans, David R

2013-04-01

Evidence suggests sitting time is independently associated with a range of health issues in adults, yet the relationship between sedentary behavior and health indicators in young people is less clear. Age-related increases in sedentary behavior are well-documented; the behavioral patterns of adolescent girls are of particular concern. More than one third of adolescent girls' sedentary behavior time is accumulated through use of recreational screen-based behaviors. The objective of this review was to investigate the association between recreational screen-based sedentary behavior and the physical, behavioral, and psychosocial health indicators for adolescent girls. A secondary objective was to identify studies that have adjusted sedentary behavior indicators for physical activity. A structured electronic search of all publication years (through December 2011) was conducted to identify studies in: CINAHL, Communications and Mass Media Complete, ERIC, MEDLINE with Full Text, PsycINFO, and SPORTDiscus with Full Text. Included publications were observational and interventional studies involving adolescent girls (12-18 years) that examined associations between screen-based, sedentary behavior and health indicators (physical, psychosocial, and/or behavioral). The search identified 33 studies that evaluated health indicators of screen-based sedentary behaviors among adolescent girls. Strong evidence for a positive association between screen-based sedentary behavior and weight status was found. A positive association was observed between screen-time and sleep problems, musculoskeletal pain and depression. Negative associations were identified between screen time and physical activity/fitness, screen time and psychological well-being, and screen time and social support. The relationship between screen-based sedentary behavior and diet quality was inconclusive. Less than half of the studies adjusted sedentary behavior indicators for physical activity. Screen-based sedentary

Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test.

Science.gov (United States)

Zorzi, Manuel; Fedeli, Ugo; Schievano, Elena; Bovo, Emanuela; Guzzinati, Stefano; Baracco, Susanna; Fedato, Chiara; Saugo, Mario; Dei Tos, Angelo Paolo

2015-05-01

Colorectal cancer (CRC) screening programmes based on the guaiac faecal occult blood test (gFOBT) reduce CRC-specific mortality. Several studies have shown higher sensitivity with the faecal immunochemical test (FIT) compared with gFOBT. We carried out an ecological study to evaluate the impact of FIT-based screening programmes on CRC mortality. In the Veneto Region (Italy), biennial FIT-based screening programmes that invited 50-69-year-old residents were introduced in different areas between 2002 and 2009. We compared CRC mortality rates from 1995 to 2011 between the areas where screening started in 2002-2004 (early screening areas (ESA)) and areas that introduced the screening in 2008-2009 (late screening areas (LSA)) using Poisson regression models. We also compared available data on CRC incidence rates (1995-2007) and surgical resection rates (2001-2012). Before the introduction of screening, CRC mortality and incidence rates in the two areas were similar. Compared with 1995-2000, 2006-2011 mortality rates were 22% lower in the ESA than in the LSA (rate ratio (RR)=0.78; 95% CI 0.68 to 0.89). The reduction was larger in women (RR=0.64; CI 0.51 to 0.80) than in men (RR=0.87; CI 0.73 to 1.04). In the ESA, incidence and surgery rates peaked during the introduction of the screening programme and then returned to the baseline (2006-2007 incidence) or dropped below initial values (surgery after 2007). FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Field-based evaluations of horizontal flat-plate fish screens, II: Testing of a unique off-stream channel device - The Farmers Screen

Science.gov (United States)

Mesa, Matthew G.; Rose, Brien P.; Copeland, Elizabeth S.

2012-01-01

Screens are installed at water diversion sites to reduce entrainment of fish. Recently, the Farmers Irrigation District (Oregon) developed a unique flat-plate screen (the “Farmers Screen”) that operates passively and may offer reduced installation and operating costs. To evaluate the effectiveness of this screen on fish, we conducted two separate field experiments. First, juvenile coho salmon Oncorhynchus kisutch were released over a working version of this screen under a range of inflows (0.02–0.42 m3/s) and diversion flows (0.02–0.34 m3/s) at different water depths. Mean approach velocities ranged from 0 to 5 cm/s and sweeping velocities ranged from 36 to 178 cm/s. Water depths over the screen surface ranged from 1 to 25 cm and were directly related to inflow. Passage of fish over the screen under these conditions did not severely injure them or cause delayed mortality, and no fish were observed becoming impinged on the screen surface. Second, juvenile coho salmon and steelhead O. mykiss were released at the upstream end of a 34-m flume and allowed to volitionally move downstream and pass over a 3.5-m section of the Farmers Screen to determine whether fish would refuse to pass over the screen after encountering its leading edge. For coho salmon, 75–95% of the fish passed over the screen within 5 min and 82–98% passed within 20 min, depending on hydraulic conditions. For steelhead, 47–90% of the fish passed over the screen within 5 min and 79–95% passed within 20 min. Our results indicate that when operated within its design criteria, the Farmers Screen provides safe and efficient downstream passage of juvenile salmonids under a variety of hydraulic conditions.

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

Science.gov (United States)

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 Pscreen-detected nodule characterization appears extremely promising however independent external validation is needed.

American Indian Men's Perceptions of Breast Cancer Screening for American Indian Women.

Science.gov (United States)

Filippi, Melissa K; Pacheco, Joseph; James, Aimee S; Brown, Travis; Ndikum-Moffor, Florence; Choi, Won S; Greiner, K Allen; Daley, Christine M

2014-01-01

Screening, especially screening mammography, is vital for decreasing breast cancer incidence and mortality. Screening rates in American Indian women are low compared to other racial/ethnic groups. In addition, American Indian women are diagnosed at more advanced stages and have lower 5-year survival rate than others. To better address the screening rates of American Indian women, focus groups (N=8) were conducted with American Indian men (N=42) to explore their perceptions of breast cancer screening for American Indian women. Our intent was to understand men's support level toward screening. Using a community-based participatory approach, focus groups were audio-taped, transcribed verbatim, and analyzed using a text analysis approach developed by our team. Topics discussed included breast cancer and screening knowledge, barriers to screening, and suggestions to improve screening rates. These findings can guide strategies to improve knowledge and awareness, communication among families and health care providers, and screening rates in American Indian communities.

The WISDOM Study: breaking the deadlock in the breast cancer screening debate.

Science.gov (United States)

Esserman, Laura J

2017-01-01

There are few medical issues that have generated as much controversy as screening for breast cancer. In science, controversy often stimulates innovation; however, the intensely divisive debate over mammographic screening has had the opposite effect and has stifled progress. The same two questions-whether it is better to screen annually or bi-annually, and whether women are best served by beginning screening at 40 or some later age-have been debated for 20 years, based on data generated three to four decades ago. The controversy has continued largely because our current approach to screening assumes all women have the same risk for the same type of breast cancer. In fact, we now know that cancers vary tremendously in terms of timing of onset, rate of growth, and probability of metastasis. In an era of personalized medicine, we have the opportunity to investigate tailored screening based on a woman's specific risk for a specific tumor type, generating new data that can inform best practices rather than to continue the rancorous debate. It is time to move from debate to wisdom by asking new questions and generating new knowledge. The WISDOM Study (Women Informed to Screen Depending On Measures of risk) is a pragmatic, adaptive, randomized clinical trial comparing a comprehensive risk-based, or personalized approach to traditional annual breast cancer screening. The multicenter trial will enroll 100,000 women, powered for a primary endpoint of non-inferiority with respect to the number of late stage cancers detected. The trial will determine whether screening based on personalized risk is as safe, less morbid, preferred by women, will facilitate prevention for those most likely to benefit, and adapt as we learn who is at risk for what kind of cancer. Funded by the Patient Centered Outcomes Research Institute, WISDOM is the product of a multi-year stakeholder engagement process that has brought together consumers, advocates, primary care physicians, specialists, policy

Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase.

Science.gov (United States)

Zhang, Baofeng; D'Erasmo, Michael P; Murelli, Ryan P; Gallicchio, Emilio

2016-09-30

We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 individual absolute alchemical binding free energy parallel molecular dynamics calculations and over 1 million CPU hours on national computing clusters and a local campus computational grid. The thermodynamic and structural measures obtained in this work rationalize a series of characteristics of this system useful for guiding future synthetic and biochemical efforts. The free energy model identified key ligand-dependent entropic and conformational reorganization processes difficult to capture using standard docking and scoring approaches. Binding free energy-based optimization of the lead compounds emerging from the virtual screen has yielded four compounds with very favorable binding properties, which will be the subject of further experimental investigations. This work is one of the few reported applications of advanced-binding free energy models to large-scale virtual screening and optimization projects. It further demonstrates that, with suitable algorithms and automation, advanced-binding free energy models can have a useful role in early-stage drug-discovery programs.

Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF.

Science.gov (United States)

Baz-Lomba, J A; Reid, Malcolm J; Thomas, Kevin V

2016-03-31

The quantification of illicit drug and pharmaceutical residues in sewage has been shown to be a valuable tool that complements existing approaches in monitoring the patterns and trends of drug use. The present work delineates the development of a novel analytical tool and dynamic workflow for the analysis of a wide range of substances in sewage-based samples. The validated method can simultaneously quantify 51 target psychoactive substances and pharmaceuticals in sewage-based samples using an off-line automated solid phase extraction (SPE-DEX) method, using Oasis HLB disks, followed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) in MS(e). Quantification and matrix effect corrections were overcome with the use of 25 isotopic labeled internal standards (ILIS). Recoveries were generally greater than 60% and the limits of quantification were in the low nanogram-per-liter range (0.4-187 ng L(-1)). The emergence of new psychoactive substances (NPS) on the drug scene poses a specific analytical challenge since their market is highly dynamic with new compounds continuously entering the market. Suspect screening using high-resolution mass spectrometry (HRMS) simultaneously allowed the unequivocal identification of NPS based on a mass accuracy criteria of 5 ppm (of the molecular ion and at least two fragments) and retention time (2.5% tolerance) using the UNIFI screening platform. Applying MS(e) data against a suspect screening database of over 1000 drugs and metabolites, this method becomes a broad and reliable tool to detect and confirm NPS occurrence. This was demonstrated through the HRMS analysis of three different sewage-based sample types; influent wastewater, passive sampler extracts and pooled urine samples resulting in the concurrent quantification of known psychoactive substances and the identification of NPS and pharmaceuticals. Copyright © 2016 Elsevier B.V. All rights reserved.

Screening of pollution control and clean-up materials for river chemical spills using the multiple case-based reasoning method with a difference-driven revision strategy.

Science.gov (United States)

Liu, Rentao; Jiang, Jiping; Guo, Liang; Shi, Bin; Liu, Jie; Du, Zhaolin; Wang, Peng

2016-06-01

In-depth filtering of emergency disposal technology (EDT) and materials has been required in the process of environmental pollution emergency disposal. However, an urgent problem that must be solved is how to quickly and accurately select the most appropriate materials for treating a pollution event from the existing spill control and clean-up materials (SCCM). To meet this need, the following objectives were addressed in this study. First, the material base and a case base for environment pollution emergency disposal were established to build a foundation and provide material for SCCM screening. Second, the multiple case-based reasoning model method with a difference-driven revision strategy (DDRS-MCBR) was applied to improve the original dual case-based reasoning model method system, and screening and decision-making was performed for SCCM using this model. Third, an actual environmental pollution accident from 2012 was used as a case study to verify the material base, case base, and screening model. The results demonstrated that the DDRS-MCBR method was fast, efficient, and practical. The DDRS-MCBR method changes the passive situation in which the choice of SCCM screening depends only on the subjective experience of the decision maker and offers a new approach to screening SCCM.

Validation approach for a fast and simple targeted screening method for 75 antibiotics in meat and aquaculture products using LC-MS/MS.

Science.gov (United States)

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.

Novel high-throughput cell-based hybridoma screening methodology using the Celigo Image Cytometer.

Science.gov (United States)

Zhang, Haohai; Chan, Leo Li-Ying; Rice, William; Kassam, Nasim; Longhi, Maria Serena; Zhao, Haitao; Robson, Simon C; Gao, Wenda; Wu, Yan

2017-08-01

Hybridoma screening is a critical step for antibody discovery, which necessitates prompt identification of potential clones from hundreds to thousands of hybridoma cultures against the desired immunogen. Technical issues associated with ELISA- and flow cytometry-based screening limit accuracy and diminish high-throughput capability, increasing time and cost. Conventional ELISA screening with coated antigen is also impractical for difficult-to-express hydrophobic membrane antigens or multi-chain protein complexes. Here, we demonstrate novel high-throughput screening methodology employing the Celigo Image Cytometer, which avoids nonspecific signals by contrasting antibody binding signals directly on living cells, with and without recombinant antigen expression. The image cytometry-based high-throughput screening method was optimized by detecting the binding of hybridoma supernatants to the recombinant antigen CD39 expressed on Chinese hamster ovary (CHO) cells. Next, the sensitivity of the image cytometer was demonstrated by serial dilution of purified CD39 antibody. Celigo was used to measure antibody affinities of commercial and in-house antibodies to membrane-bound CD39. This cell-based screening procedure can be completely accomplished within one day, significantly improving throughput and efficiency of hybridoma screening. Furthermore, measuring direct antibody binding to living cells eliminated both false positive and false negative hits. The image cytometry method was highly sensitive and versatile, and could detect positive antibody in supernatants at concentrations as low as ~5ng/mL, with concurrent K d binding affinity coefficient determination. We propose that this screening method will greatly facilitate antibody discovery and screening technologies. Copyright © 2017 Elsevier B.V. All rights reserved.

Feed particle size evaluation: conventional approach versus digital holography based image analysis

Directory of Open Access Journals (Sweden)

Vittorio Dell’Orto

2010-01-01

Full Text Available The aim of this study was to evaluate the application of image analysis approach based on digital holography in defining particle size in comparison with the sieve shaker method (sieving method as reference method. For this purpose ground corn meal was analyzed by a sieve shaker Retsch VS 1000 and by image analysis approach based on digital holography. Particle size from digital holography were compared with results obtained by screen (sieving analysis for each of size classes by a cumulative distribution plot. Comparison between particle size values obtained by sieving method and image analysis indicated that values were comparable in term of particle size information, introducing a potential application for digital holography and image analysis in feed industry.

Team-Based Interprofessional Competency Training for Dementia Screening and Management.

Science.gov (United States)

Tan, Zaldy S; Damron-Rodriguez, JoAnn; Cadogan, Mary; Gans, Daphna; Price, Rachel M; Merkin, Sharon S; Jennings, Lee; Schickedanz, Heather; Shimomura, Sam; Osterweil, Dan; Chodosh, Joshua

2017-01-01

As many as 50% of people satisfying diagnostic criteria for dementia are undiagnosed. A team-based training program for dementia screening and management was developed targeting four professions (medicine, nursing, pharmacy, social work) whose scope of practice involves dementia care. An interprofessional group of 10 faculty members was trained to facilitate four interactive competency stations on dementia screening, differential diagnoses, dementia management and team care planning, and screening for and managing caregiver stress. Registrants were organized into teams of five members, with at least one member of each profession per team. The teams rotated through all stations, completing assigned tasks through interprofessional collaboration. A total of 117 professionals (51 physicians, 11 nurses, 20 pharmacists, 24 social workers, 11 others) successfully completed the program. Change scores showed significant improvements in overall competence in dementia assessment and intervention (very low = 1; very high = 5; average change 1.12, P managing medication (average change 0.86, P team-based interprofessional competency training is a team teaching model that can be used to enhance competency in dementia screening and management in medical, nursing, pharmacy, and social work practitioners. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

A multiplex degenerate PCR analytical approach targeting to eight genes for screening GMOs.

Science.gov (United States)

Guo, Jinchao; Chen, Lili; Liu, Xin; Gao, Ying; Zhang, Dabing; Yang, Litao

2012-06-01

Currently, the detection methods with lower cost and higher throughput are the major trend in screening genetically modified (GM) food or feed before specific identification. In this study, we developed a quadruplex degenerate PCR screening approach for more than 90 approved GMO events. This assay is consisted of four PCR systems targeting on nine DNA sequences from eight trait genes widely introduced into GMOs, such as CP4-EPSPS derived from Acetobacterium tumefaciens sp. strain CP4, phosphinothricin acetyltransferase gene derived from Streptomyceshygroscopicus (bar) and Streptomyces viridochromogenes (pat), and Cry1Ab, Cry1Ac, Cry1A(b/c), mCry3A, and Cry3Bb1 derived from Bacillus thuringiensis. The quadruplex degenerate PCR assay offers high specificity and sensitivity with the absolute limit of detection (LOD) of approximate 80targetcopies. Furthermore, the applicability of the quadruplex PCR assay was confirmed by screening either several artificially prepared samples or samples of Grain Inspection, Packers and Stockyards Administration (GIPSA) proficiency program. Copyright © 2011 Elsevier Ltd. All rights reserved.

Service Use by At-Risk Youth after School-Based Suicide Screening

Science.gov (United States)

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

RBCA-based approaches to ecological risk assessment for TPH-contaminated areas

International Nuclear Information System (INIS)

Hummell, R.; Vedagiri, U.

1995-01-01

The RBCA guidelines proposed by ASTM form an evaluation and decision-making framework for sites potentially contaminated by petroleum releases. They present a three-tiered approach of decreasing conservatism and increasing site-specificity that primarily evaluates risks to human health. While RBCA includes consideration of environmental impacts, there are no specific recommendations on how this is to be achieved. A RBCA-based ecological risk assessment approach was developed for TPH-contaminated areas in Alaska. The approach presents a habitat-based selection process for surrogate chemicals and indicator chemicals of ecological relevance, evaluation of ecotoxicity, derivation of matrix-specific Tier 1 RBSLs (including soils) and determination of Tier 2 and 3 SSTLS. Chemicals are considered by class, aquatic (freshwater and saltwater) and terrestrial habitats are evaluated independently, and chemical concentrations are screened in all media of concern (air, soil, water, sediment). Data needs and decision points specific to ecological receptors are identified for each tier of the approach. Other aspects of the approach include consideration of contaminant migration pathways and habitats that are typical of Arctic conditions. Areas where ecological and human risk concerns may overlap are identified

Orbitrap technology for comprehensive metabolite-based liquid chromatographic–high resolution-tandem mass spectrometric urine drug screening – Exemplified for cardiovascular drugs

International Nuclear Information System (INIS)

Helfer, Andreas G.; Michely, Julian A.; Weber, Armin A.; Meyer, Markus R.; Maurer, Hans H.

2015-01-01

LC–high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC–HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC–HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing. - Highlights: • First study on the application of Orbitrap technology for comprehensive drug screening in clinical and forensic toxicology. • Simple workup, sufficient separation, and powerful screening and identification using modern high resolution MS. • Validation of the assay according to guidelines for qualitative approaches. • Elucidation of the power of new data evaluation software in combination with a new reference drug and metabolite library. • Great relevance for science and practice in clinical and forensic

Orbitrap technology for comprehensive metabolite-based liquid chromatographic–high resolution-tandem mass spectrometric urine drug screening – Exemplified for cardiovascular drugs

Energy Technology Data Exchange (ETDEWEB)

Helfer, Andreas G.; Michely, Julian A.; Weber, Armin A.; Meyer, Markus R.; Maurer, Hans H., E-mail: hans.maurer@uks.eu

2015-09-03

LC–high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC–HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC–HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing. - Highlights: • First study on the application of Orbitrap technology for comprehensive drug screening in clinical and forensic toxicology. • Simple workup, sufficient separation, and powerful screening and identification using modern high resolution MS. • Validation of the assay according to guidelines for qualitative approaches. • Elucidation of the power of new data evaluation software in combination with a new reference drug and metabolite library. • Great relevance for science and practice in clinical and forensic

Screening agars for MRSA: evaluation of a stepwise diagnostic approach with two different selective agars for the screening for methicillin-resistant Staphylococcus aureus (MRSA).

Science.gov (United States)

Micheel, Volker; Hogan, Benedikt; Köller, Thomas; Warnke, Philipp; Crusius, Sabine; Hinz, Rebecca; Hagen, Ralf Matthias; Schwarz, Norbert Georg; Frickmann, Hagen

2015-01-01

Colonization with methicillin-resistant Staphylococcus aureus (MRSA) poses a hygiene risk that does not spare field hospitals or military medical field camps during military deployments. Diagnostic options for unambiguously identifying MRSA isolates are usually scarce in military environments. In this study, we assessed the stepwise application of two different selective agars for the specific identification of MRSA in screening analyses. Nasal swabs from 1541 volunteers were subjected to thioglycollate broth enrichment and subsequently screened on CHROMagar MRSA selective agar for the identification of MRSA. The MRSA identity of suspicious-looking colonies was confirmed afterwards or excluded by another selective agar, chromID MRSA. All isolates from the selective agars with MRSA-specific colony morphology were identified by biochemical methods and mass spectrometry. The initial CHROMagar MRSA screening identified suspicious colonies in 36 out of 1541 samples. A total of 25 of these 36 isolates showed MRSA-like growth on chromID agar. Out of these 25 isolates, 24 were confirmed as MRSA, while one isolate was identified as Staphylococcus kloosii. From the 11 strains that did not show suspicious growth on chromID agar, 3 were methicillin-sensitive Staphylococcus aureus (MSSA, with one instance of co-colonization with Corynebacterium spp.), 2 were confirmed as MRSA (with 1 instance of co-colonization with MSSA), 2 were lost during passaging and could not be re-cultured, one could not be identified by the applied approaches, and the remaining 3 strains were identified as Staphylococcus saprophyticus, Staphylococcus hominis (co-colonized with Macrococcus caseolyticus) and Staphylococcus cohnii, respectively. The application of the selective agar CHROMagar MRSA alone proved to be too non-specific to allow for a reliable diagnosis of the presence of MRSA. The combined use of two selective agars in a stepwise approach reduced this non-specificity with an acceptably low

Newborn Congenital Cytomegalovirus Screening Based on Clinical Manifestations and Evaluation of DNA-based Assays for In Vitro Diagnostics.

Science.gov (United States)

Fujii, Tomoyuki; Oka, Akira; Morioka, Ichiro; Moriuchi, Hiroyuki; Koyano, Shin; Yamada, Hideto; Saito, Shigeru; Sameshima, Hiroshi; Nagamatsu, Takeshi; Tsuchida, Shinya; Inoue, Naoki

2017-10-01

To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as in vitro diagnostics by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences. Newborns with clinical manifestations considered to be consequences of cCMV infection (n = 575) were screened for the presence of cytomegalovirus (CMV) DNA in urine specimens collected onto filter paper placed in their diapers using the polymerase chain reaction-based assay reported previously. Liquid urine specimens were obtained from all of 20 CMV-positive newborns and 107 of the CMV-negative newborns identified in the screening. We used these 127 specimens, as well as 12 from cCMV cases identified in a previous study and 41 from healthy newborns, to compare the performance of 2 commercial assays and 1 in-house assay. The risk-based screening allowed the identification of cCMV cases at least 10-fold more efficiently than our previous universal screening, although there appears to be a limit to the identification of asymptomatically infected newborns. Although CMV-specific IgM during pregnancy was found frequently in mothers of cCMV newborns, CMV-IgM alone is not an effective diagnostic marker. The urine-filter-based assay and the 3 diagnostic assays yielded identical results. Although risk-based and universal newborn screening strategies for cCMV infection each have their respective advantages and disadvantages, urine-filter-based assay followed by confirmatory in vitro diagnostics assays is able to identify cCMV cases efficiently.

A tailored intervention to promote uptake of retinal screening among young adults with type 2 diabetes - an intervention mapping approach.

Science.gov (United States)

Lake, Amelia J; Browne, Jessica L; Abraham, Charles; Tumino, Dee; Hines, Carolyn; Rees, Gwyneth; Speight, Jane

2018-05-31

Young adults (18-39 years) with type 2 diabetes are at risk of early development and rapid progression of diabetic retinopathy, a leading cause of vision loss and blindness in working-age adults. Retinal screening is key to the early detection of diabetic retinopathy, with risk of vision loss significantly reduced by timely treatment thereafter. Despite this, retinal screening rates are low among this at-risk group. The objective of this study was to develop a theoretically-grounded, evidence-based retinal screening promotion leaflet, tailored to young adults with type 2 diabetes. Utilising the six steps of Intervention Mapping, our multidisciplinary planning team conducted a mixed-methods needs assessment (Step 1); identified modifiable behavioural determinants of screening behaviour and constructed a matrix of change objectives (Step 2); designed, reviewed and debriefed leaflet content with stakeholders (Steps 3 and 4); and developed program implementation and evaluation plans (Steps 5 and 6). Step 1 included in-depth qualitative interviews (N = 10) and an online survey that recruited a nationally-representative sample (N = 227), both informed by literature review. The needs assessment highlighted the crucial roles of knowledge (about diabetic retinopathy and screening), perception of personal risk, awareness of the approval of significant others and engagement with healthcare team, on retinal screening intentions and uptake. In Step 2, we selected five modifiable behavioural determinants to be targeted: knowledge, attitudes, normative beliefs, intention, and behavioural skills. In Steps 3 and 4, the "Who is looking after your eyes?" leaflet was developed, containing persuasive messages targeting each determinant and utilising engaging, cohort-appropriate imagery. In Steps 5 and 6, we planned Statewide implementation and designed a randomised controlled trial to evaluate the leaflet. This research provides an example of a systematic, evidence-based

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

Science.gov (United States)

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 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 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.

Receptor-based screening assays for the detection of antibiotics residues - A review.

Science.gov (United States)

Ahmed, Saeed; Ning, Jianan; Cheng, Guyue; Ahmad, Ijaz; Li, Jun; Mingyue, Liu; Qu, Wei; Iqbal, Mujahid; Shabbir, M A B; Yuan, Zonghui

2017-05-01

Consumer and regulatory agencies have a high concern to antibiotic residues in food producing animals, so appropriate screening assays of fast, sensitive, low cost, and easy sample preparation for the identification of these residues are essential for the food-safety insurance. Great efforts in the development of a high-throughput antibiotic screening assay have been made in recent years. Concerning the screening of antibiotic residue, this review elaborate an overview on the availability, advancement and applicability of antibiotic receptor based screening assays for the safety assessment of antibiotics usage (i.e. radio receptor assay, enzyme labeling assays, colloidal gold receptor assay, enzyme colorimetry assay and biosensor assay). This manuscript also tries to shed a light on the selection, preparation and future perspective of receptor protein for antibiotic residue detection. These assays have been introduced for the screening of numerous food samples. Receptor based screening technology for antibiotic detection has high accuracy. It has been concluded that at the same time, it can detect a class of drugs for certain receptor, and realize the multi-residue detection. These assays offer fast, easy and precise detection of antibiotics. Copyright © 2017 Elsevier B.V. All rights reserved.

Psychosis screening practices in schools: A survey of school-based mental health providers.

Science.gov (United States)

Kline, Emily R; Chokran, Cole; Rodenhiser-Hill, Janine; Seidman, Larry J; Woodberry, Kristen A

2018-05-04

Many school districts in the United States employ mental health professionals to provide assessment, counselling and crisis interventions within the school setting; however, little is known about actual clinical practices of psychosis screening in schools. The aim of the present study is to examine attitudes and practices regarding psychosis screening among school mental health providers in metropolitan Boston, Massachusetts. School-based mental health clinicians (N = 100) completed an anonymous survey assessing familiarity, screening, and involvement with psychosis and psychosis risk prior to attending trainings on psychosis. Providers reported screening for psychosis less often than other mental health problems and rated themselves as less confident treating psychosis relative to other mental health concerns. Frequency of screening for psychosis was significantly associated with familiarity with psychosis assessment and case management, confidence providing treatment for individuals experiencing psychosis, and the number of students with or at risk for psychosis with whom providers had been involved. Frequency of screening for psychosis was not associated with years of practice, suggesting that both novice and experienced school-based providers may benefit from training on this issue. Community outreach via school-based provider training on assessment and management of psychosis may help to increase providers' understanding of psychosis and increase the practice of verbal or written screening for psychosis and psychosis risk within schools. © 2018 John Wiley & Sons Australia, Ltd.

SPR-based fragment screening with neurotensin receptor 1 generates novel small molecule ligands

Science.gov (United States)

Huber, Sylwia; Casagrande, Fabio; Hug, Melanie N.; Wang, Lisha; Heine, Philipp; Kummer, Lutz; Plückthun, Andreas; Hennig, Michael

2017-01-01

The neurotensin receptor 1 represents an important drug target involved in various diseases of the central nervous system. So far, the full exploitation of potential therapeutic activities has been compromised by the lack of compounds with favorable physicochemical and pharmacokinetic properties which efficiently penetrate the blood-brain barrier. Recent progress in the generation of stabilized variants of solubilized neurotensin receptor 1 and its subsequent purification and successful structure determination presents a solid starting point to apply the approach of fragment-based screening to extend the chemical space of known neurotensin receptor 1 ligands. In this report, surface plasmon resonance was used as primary method to screen 6369 compounds. Thereby 44 hits were identified and confirmed in competition as well as dose-response experiments. Furthermore, 4 out of 8 selected hits were validated using nuclear magnetic resonance spectroscopy as orthogonal biophysical method. Computational analysis of the compound structures, taking the known crystal structure of the endogenous peptide agonist into consideration, gave insight into the potential fragment-binding location and interactions and inspires chemistry efforts for further exploration of the fragments. PMID:28510609

Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening

Science.gov (United States)

Halim, Sobia A.; Khan, Shanza; Khan, Ajmal; Wadood, Abdul; Mabood, Fazal; Hussain, Javid; Al-Harrasi, Ahmed

2017-10-01

Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, twenty five compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase in silico, and can be helpful in the treatment of Dengue.

In silico structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening

Directory of Open Access Journals (Sweden)

Junichi Taira

2017-01-01

Full Text Available Background: Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1 is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. Materials and Methods: We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS. Following the selection of such compounds, their antimycobacterial activity was examined. Results: With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug. Conclusion: The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores.

Screening uptake rates and the clinical and cost effectiveness of screening for gestational diabetes mellitus in primary versus secondary care: study protocol for a randomised controlled trial.

LENUS (Irish Health Repository)

O Dea, Angela

2014-01-17

The risks associated with gestational diabetes mellitus (GDM) are well recognized, and there is increasing evidence to support treatment of the condition. However, clear guidance on the ideal approach to screening for GDM is lacking. Professional groups continue to debate whether selective screening (based on risk factors) or universal screening is the most appropriate approach. Additionally, there is ongoing debate about what levels of glucose abnormalities during pregnancy respond best to treatment and which maternal and neonatal outcomes benefit most from treatment. Furthermore, the implications of possible screening options on health care costs are not well established. In response to this uncertainty there have been repeated calls for well-designed, randomised trials to determine the efficacy of screening, diagnosis, and management plans for GDM. We describe a randomised controlled trial to investigate screening uptake rates and the clinical and cost effectiveness of screening in primary versus secondary care settings. The objective of this study is to assess screening uptake rates, and the clinical and cost effectiveness of screening for GDM in primary versus secondary care.

Localization-based super-resolution imaging meets high-content screening.

Science.gov (United States)

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.

Design and Polarization Characteristics Analysis of Dihedral Based on Salisbury Screen

Directory of Open Access Journals (Sweden)

Zhang Ran

2016-12-01

Full Text Available Salisbury screens have a number of unique electromagnetic scattering characteristics. When appropriately designed, the Salisbury screen can reach the radar target signature transform. Based on the electromagnetic scattering characteristics of the Salisbury screen, we designed a novel dihedral corner, and theoretically analyzed and simulated its electromagnetic scattering characteristics in this study. The results reveal the monostatic radar cross section curves of the 90°and 60° Salisbury screen dihedral and metal dihedral, respectively. Taking an orthogonal dihedral corner as an example, we obtained the polarization scattering matrixes for different incident degrees. In addition, we investigated the influence of illumination frequency, target gestures, and other key factors on the polarization characteristics of the Salisbury screen dihedral corner. The theoretical and simulation analysis results show that compared with the conventional metal dihedral corner, the Salisbury screen dihedral corner significantly influences the scattering characteristics and will have potential application in electronic warfare.

Screening history in women with cervical cancer in a Danish population-based screening program

DEFF Research Database (Denmark)

Kirschner, Benny; Poll, Susanne; Rygaard, Carsten

2011-01-01

The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer.......The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer....

Availability and accessibility of subsidized mammogram screening program in peninsular Malaysia: A preliminary study using travel impedance approach.

Science.gov (United States)

Mahmud, Aidalina; Aljunid, Syed Mohamed

2018-01-01

lived in sub-urban and rural areas. In summary, availability of mammogram facilities was good in the central and west coast of the peninsula. The overall provider-to-population ratio was lower than recommended. Based on the travel impedance approach used, accessibility to subsidised mammogram screening among the respondents was good in urban areas but deprived in other areas. This study was a preliminary study with limitations. Nonetheless, the evidence suggests that actions have to be taken to improve the accessibility to opportunistic mammogram screening in Malaysia in pursuit of universal health coverage.

Screening for cerebrovascular disease in microcephalic osteodysplastic primordial dwarfism type II (MOPD II): an evidence-based proposal.

Science.gov (United States)

Perry, Luke D; Robertson, Fergus; Ganesan, Vijeya

2013-04-01

Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720) is a rare autosomal recessive condition frequently associated with early-onset cerebrovascular disease. Presymptomatic detection and intervention could prevent the adverse consequences associated with this. We reviewed published cases of microcephalic osteodysplastic primordial dwarfism type II to ascertain prevalence and characteristics of cerebrovascular disease and use these data to propose an evidence-based approach to cerebrovascular screening. Of 147 cases identified, 47 had cerebrovascular disease (32%), including occlusive arteriopathy (including moyamoya) and cerebral aneurysmal disease. Occlusive disease occurred in younger individuals, and progression can be both rapid and clinically silent. A reasonable screening approach would be magnetic resonance imaging and angiography of the cervical and intracranial circulation at diagnosis, repeated at yearly intervals until 10 years, and every 2 years thereafter, unless clinical concerns occur earlier. At present it would appear that this needs to be life-long. Families and professionals should be alerted to the potential significance of neurologic symptoms and measures should be taken to maintain good vascular health in affected individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

Science.gov (United States)

Racher, Hilary; Phelps, Ian G.; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A.; Sorusch, Nasrin; Abdelhamed, Zakia A.; Natarajan, Subaashini; Herridge, Warren; van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A.; Letteboer, Stef J.F.; Roosing, Susanne; Adams, Matthew; Bell, Sandra M.; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E.; Tomlinson, Darren C.; Slaats, Gisela G.; van Dam, Teunis J. P.; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V.; Boyle, Evan A.; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A.; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A.; Chodirker, Bernard N.; Chudley, Albert E.; Lamont, Ryan; Bernier, Francois P.; Beaulieu, Chandree L.; Gordon, Paul; Pon, Richard T.; Donahue, Clem; Barkovich, A. James; Wolf, Louis; Toomes, Carmel; Thiel, Christian T.; Boycott, Kym M.; McKibbin, Martin; Inglehearn, Chris F.; Stewart, Fiona; Omran, Heymut; Huynen, Martijn A.; Sergouniotis, Panagiotis I.; Alkuraya, Fowzan S.; Parboosingh, Jillian S.; Innes, A Micheil; Willoughby, Colin E.; Giles, Rachel H.; Webster, Andrew R.; Ueffing, Marius; Blacque, Oliver; Gleeson, Joseph G.; Wolfrum, Uwe; Beales, Philip L.; Gibson, Toby

2015-01-01

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and three pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localise to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1/CEP90 and C21orf2/LRRC76 as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2-variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease. PMID:26167768

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

Energy Technology Data Exchange (ETDEWEB)

Barngkgei, Imad; Al Haffar, Iyad; Khattab, Razan [Faculty of Dentistry, Damascus University, Damascus (Syrian Arab Republic); Halboub, Esam; Almashraqi, Abeer Abdulkareem [Dept. of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan (Saudi Arabia)

2016-09-15

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. 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. 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%). 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.

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

Science.gov (United States)

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

2016-09-01

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. 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. 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%). 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.

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

International Nuclear Information System (INIS)

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

2016-01-01

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. 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. 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%). 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

Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study.

Science.gov (United States)

Yoon, Christina; Semitala, Fred C; Atuhumuza, Elly; Katende, Jane; Mwebe, Sandra; Asege, Lucy; Armstrong, Derek T; Andama, Alfred O; Dowdy, David W; Davis, J Luke; Huang, Laurence; Kamya, Moses; Cattamanchi, Adithya

2017-12-01

Symptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination. We assessed the performance of C-reactive protein (CRP) measured with a point-of-care assay as a screening tool for active pulmonary tuberculosis. For this prospective study, we enrolled adults (aged ≥18 years) living with HIV with CD4 cell count less than or equal to 350 cells per μL who were initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda. CRP concentrations were measured at study entry with a point-of-care assay using whole blood obtained by fingerprick (concentration ≥10 mg/L defined as screen positive for tuberculosis). Sputum samples were collected for Xpert MTB/RIF testing and culture. We calculated the sensitivity and specificity of point-of-care CRP and WHO symptom-based screening in reference to culture results. We repeated the sensitivity analysis with Xpert MTB/RIF as the reference standard. Between July 8, 2013, and Dec 15, 2015, 1237 HIV-infected adults were enrolled and underwent point-of-care CRP testing. 60 (5%) patients with incomplete or contaminated cultures were excluded from the analysis. Of the remaining 1177 patients (median CD4 count 165 cells per μL [IQR 75-271]), 163 (14%) had culture-confirmed tuberculosis. Point-of-care CRP testing had 89% sensitivity (145 of 163, 95% CI 83-93) and 72% specificity (731 of 1014, 95% CI 69-75) for culture-confirmed tuberculosis. Compared with WHO symptom-based screening, point-of-care CRP testing had lower sensitivity (difference -7%, 95% CI -12 to -2; p=0·002) but substantially higher specificity (difference 58%, 95% CI 55 to 61; ptuberculosis screening test

Developing a Bacteroides System for Function-Based Screening of DNA from the Human Gut Microbiome.

Science.gov (United States)

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

High resolution melting curve analysis targeting the HBB gene mutational hot-spot offers a reliable screening approach for all common as well as most of the rare beta-globin gene mutations in Bangladesh.

Science.gov (United States)

Islam, Md Tarikul; Sarkar, Suprovath Kumar; Sultana, Nusrat; Begum, Mst Noorjahan; Bhuyan, Golam Sarower; Talukder, Shezote; Muraduzzaman, A K M; Alauddin, Md; Islam, Mohammad Sazzadul; Biswas, Pritha Promita; Biswas, Aparna; Qadri, Syeda Kashfi; Shirin, Tahmina; Banu, Bilquis; Sadya, Salma; Hussain, Manzoor; Sarwardi, Golam; Khan, Waqar Ahmed; Mannan, Mohammad Abdul; Shekhar, Hossain Uddin; Chowdhury, Emran Kabir; Sajib, Abu Ashfaqur; Akhteruzzaman, Sharif; Qadri, Syed Saleheen; Qadri, Firdausi; Mannoor, Kaiissar

2018-01-02

Bangladesh lies in the global thalassemia belt, which has a defined mutational hot-spot in the beta-globin gene. The high carrier frequencies of beta-thalassemia trait and hemoglobin E-trait in Bangladesh necessitate a reliable DNA-based carrier screening approach that could supplement the use of hematological and electrophoretic indices to overcome the barriers of carrier screening. With this view in mind, the study aimed to establish a high resolution melting (HRM) curve-based rapid and reliable mutation screening method targeting the mutational hot-spot of South Asian and Southeast Asian countries that encompasses exon-1 (c.1 - c.92), intron-1 (c.92 + 1 - c.92 + 130) and a portion of exon-2 (c.93 - c.217) of the HBB gene which harbors more than 95% of mutant alleles responsible for beta-thalassemia in Bangladesh. Our HRM approach could successfully differentiate ten beta-globin gene mutations, namely c.79G > A, c.92 + 5G > C, c.126_129delCTTT, c.27_28insG, c.46delT, c.47G > A, c.92G > C, c.92 + 130G > C, c.126delC and c.135delC in heterozygous states from the wild type alleles, implying the significance of the approach for carrier screening as the first three of these mutations account for ~85% of total mutant alleles in Bangladesh. Moreover, different combinations of compound heterozygous mutations were found to generate melt curves that were distinct from the wild type alleles and from one another. Based on the findings, sixteen reference samples were run in parallel to 41 unknown specimens to perform direct genotyping of the beta-thalassemia specimens using HRM. The HRM-based genotyping of the unknown specimens showed 100% consistency with the sequencing result. Targeting the mutational hot-spot, the HRM approach could be successfully applied for screening of beta-thalassemia carriers in Bangladesh as well as in other countries of South Asia and Southeast Asia. The approach could be a useful supplement of hematological and

One step versus two step approach for gestational diabetes screening: systematic review and meta-analysis of the randomized trials.

Science.gov (United States)

Saccone, Gabriele; Caissutti, Claudia; Khalifeh, Adeeb; Meltzer, Sara; Scifres, Christina; Simhan, Hyagriv N; Kelekci, Sefa; Sevket, Osman; Berghella, Vincenzo

2017-12-03

To compare both the prevalence of gestational diabetes mellitus (GDM) as well as maternal and neonatal outcomes by either the one-step or the two-step approaches. Electronic databases were searched from their inception until June 2017. We included all randomized controlled trials (RCTs) comparing the one-step with the two-step approaches for the screening and diagnosis of GDM. The primary outcome was the incidence of GDM. Three RCTs (n = 2333 participants) were included in the meta-analysis. 910 were randomized to the one step approach (75 g, 2 hrs), and 1423 to the two step approach. No significant difference in the incidence of GDM was found comparing the one step versus the two step approaches (8.4 versus 4.3%; relative risk (RR) 1.64, 95%CI 0.77-3.48). Women screened with the one step approach had a significantly lower risk of preterm birth (PTB) (3.7 versus 7.6%; RR 0.49, 95%CI 0.27-0.88), cesarean delivery (16.3 versus 22.0%; RR 0.74, 95%CI 0.56-0.99), macrosomia (2.9 versus 6.9%; RR 0.43, 95%CI 0.22-0.82), neonatal hypoglycemia (1.7 versus 4.5%; RR 0.38, 95%CI 0.16-0.90), and admission to neonatal intensive care unit (NICU) (4.4 versus 9.0%; RR 0.49, 95%CI 0.29-0.84), compared to those randomized to screening with the two step approach. The one and the two step approaches were not associated with a significant difference in the incidence of GDM. However, the one step approach was associated with better maternal and perinatal outcomes.

Glucose biosensor based on disposable electrochemical paper-based transducers fully fabricated by screen-printing.

Science.gov (United States)

Lamas-Ardisana, P J; Martínez-Paredes, G; Añorga, L; Grande, H J

2018-06-30

This paper describes a new approach for the massive production of electrochemical paper-based analytical devices (ePADs). These devices are fully fabricated by screen-printing technology and consist of a lineal microfluidic channel delimited by hydrophobic walls (patterned with diluted ultraviolet screen-printing ink in chromatographic paper grade 4) and a three-electrode system (printed with carbon and/or Ag/AgCl conductive inks). The printing process was characterised and optimized for pattern each layer with only one squeeze sweep. These ePADs were used as transducers to develop a glucose biosensor. Ionic strength/pH buffering salts, electrochemical mediator (ferricyanide) and enzyme (glucose dehydrogenase FAD-dependent) were separately stored along the microfluidic channel in order to be successively dissolved and mixed after the sample dropping at the entrance. The analyses required only 10 µl and the biosensors showed good reproducibility (RSD = 6.2%, n = 10) and sensitivity (0.426 C/M cm 2 ), wide linear range (0.5-50 mM; r 2 = 0.999) and low limit of detection (0.33 mM). Furthermore, the new biosensor was applied for glucose determination in five commercial soft-drinks without any sample treatment before the analysis. These samples were also analysed with a commercial enzymatic-kit assay. The results indicated that both methods provide accurate results. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of first-tier cell-free DNA screening for common aneuploidies with conventional publically funded screening.

Science.gov (United States)

Langlois, Sylvie; Johnson, JoAnn; Audibert, François; Gekas, Jean; Forest, Jean-Claude; Caron, André; Harrington, Keli; Pastuck, Melanie; Meddour, Hasna; Tétu, Amélie; Little, Julian; Rousseau, François

2017-12-01

This study evaluates the impact of offering cell-free DNA (cfDNA) screening as a first-tier test for trisomies 21 and 18. This is a prospective study of pregnant women undergoing conventional prenatal screening who were offered cfDNA screening in the first trimester with clinical outcomes obtained on all pregnancies. A total of 1198 pregnant women were recruited. The detection rate of trisomy 21 with standard screening was 83% with a false positive rate (FPR) of 5.5% compared with 100% detection and 0% FPR for cfDNA screening. The FPR of cfDNA screening for trisomies 18 and 13 was 0.09% for each. Two percent of women underwent an invasive diagnostic procedure based on screening or ultrasound findings; without the cfDNA screening, it could have been as high as 6.8%. Amongst the 640 women with negative cfDNA results and a nuchal translucency (NT) ultrasound, only 3 had an NT greater or equal to 3.5 mm: one had a normal outcome and two lost their pregnancy before 20 weeks. cfDNA screening has the potential to be a highly effective first-tier screening approach leading to a significant reduction of invasive diagnostic procedures. For women with a negative cfDNA screening result, NT measurement has limited clinical utility. © 2017 John Wiley & Sons, Ltd.

An unbiased method to build benchmarking sets for ligand-based virtual screening and its application to GPCRs.

Science.gov (United States)

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.

Microarray-based cancer prediction using soft computing approach.

Science.gov (United States)

Wang, Xiaosheng; Gotoh, Osamu

2009-05-26

One of the difficulties in using gene expression profiles to predict cancer is how to effectively select a few informative genes to construct accurate prediction models from thousands or ten thousands of genes. We screen highly discriminative genes and gene pairs to create simple prediction models involved in single genes or gene pairs on the basis of soft computing approach and rough set theory. Accurate cancerous prediction is obtained when we apply the simple prediction models for four cancerous gene expression datasets: CNS tumor, colon tumor, lung cancer and DLBCL. Some genes closely correlated with the pathogenesis of specific or general cancers are identified. In contrast with other models, our models are simple, effective and robust. Meanwhile, our models are interpretable for they are based on decision rules. Our results demonstrate that very simple models may perform well on cancerous molecular prediction and important gene markers of cancer can be detected if the gene selection approach is chosen reasonably.

Indicators for monitoring screening programs with primary HPV test.

Science.gov (United States)

Zorzi, Manuel; Giorgi Rossi, Paolo

2017-01-01

following scientific evidence produced in numerous studies, as well as national and international guidelines, organized cervical cancer screening programs in Italy have gradually introduced the HPV test as primary screening test, replacing cytology. As public health interventions, screening programs must ensure equity, improvement in quality of life, and adequate information for the population involved with regards to benefits and possible risks; therefore, it is essential for quality to be constantly checked at every phase of the project.The Italian Cervical Screening Group (Gruppo Italiano per lo Screening Cervicale, GISCi) has written a handbook for the calculation and interpretation of cervical screening program monitoring indicators that take into account the new protocol based on primary HPV test with cytology triage. based on the European guidelines and Italian recommendations on primary HPVbased screening, the working group, which includes professionals from all the fields involved in cervical screening, identified the essential points needed to monitor the screening process, the accuracy of individual tests, and early outcomes, defining a specific indicator for each aspect. The indicators were grouped as follows: baseline indicators, indicators for test repeat after one year, cumulative indicators, and waiting times. For every indicator, the source of data, calculation formula, any standards or critical thresholds, and interpretation were defined. The standards are based on the results of NTCC trials or Italian pilot studies. the main indicators proposed for the organization are the following: number of invitations, compliance with first invitation, with one-year test repeat and with colposcopy; for test and process accuracy, a cohort approach was utilised, where indicators are based on women who must be followed for at least one year, so as to integrate the results obtained after the first HPV test with the outcome of the test's repetition after one year

Examining the Cervical Screening Behaviour of Women Aged 50 or above and Its Predicting Factors: A Population-Based Survey.

Science.gov (United States)

Chan, Carmen W H; Choi, Kai Chow; Wong, Rosa S; Chow, Ka Ming; So, Winnie K W; Leung, Doris Y P; Lam, Wendy W T; Goggins, William

2016-12-02

Under-screening may increase the risk of cervical cancer in middle-aged women. This study aimed to investigate cervical cancer screening behaviour and its predictors among women aged 50 years or above. A population-based sample of 959 women was recruited by telephone from domestic households in Hong Kong, using random methods, and a structured questionnaire developed to survey participants. Multivariable logistic regressions were performed to examine the factors independently associated with cervical screening behaviour. Nearly half the sample (48%) had never had a cervical smear test. Multivariable analyses showed that age, educational level, marital status, family history of cancer, smoking status, use of complementary therapy, recommendation from health professionals, and believing that regular visits to a doctor or a Chinese herbalist were good for their health were predictors of cervical screening behaviour. Misconceptions concerned with menopause may reduce women's perceived susceptibility to cervical cancer, especially if they are 50 or above, and exert a negative effect on their screening behaviour. Healthcare professionals should actively approach these high-risk groups-older unmarried women, smokers, those less educated and who are generally not much concerned with their health.

Examining the Cervical Screening Behaviour of Women Aged 50 or above and Its Predicting Factors: A Population-Based Survey

Directory of Open Access Journals (Sweden)

Carmen W. H. Chan

2016-12-01

Full Text Available Under-screening may increase the risk of cervical cancer in middle-aged women. This study aimed to investigate cervical cancer screening behaviour and its predictors among women aged 50 years or above. A population-based sample of 959 women was recruited by telephone from domestic households in Hong Kong, using random methods, and a structured questionnaire developed to survey participants. Multivariable logistic regressions were performed to examine the factors independently associated with cervical screening behaviour. Nearly half the sample (48% had never had a cervical smear test. Multivariable analyses showed that age, educational level, marital status, family history of cancer, smoking status, use of complementary therapy, recommendation from health professionals, and believing that regular visits to a doctor or a Chinese herbalist were good for their health were predictors of cervical screening behaviour. Misconceptions concerned with menopause may reduce women’s perceived susceptibility to cervical cancer, especially if they are 50 or above, and exert a negative effect on their screening behaviour. Healthcare professionals should actively approach these high-risk groups–older unmarried women, smokers, those less educated and who are generally not much concerned with their health.

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

Science.gov (United States)

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.

Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF

Energy Technology Data Exchange (ETDEWEB)

Baz-Lomba, J.A., E-mail: jba@niva.no [Norwegian Institute for Water Research, Gaustadalléen 21, NO-0349, Oslo (Norway); Faculty of Medicine, University of Oslo, PO box 1078 Blindern, 0316, Oslo (Norway); Reid, Malcolm J.; Thomas, Kevin V. [Norwegian Institute for Water Research, Gaustadalléen 21, NO-0349, Oslo (Norway)

2016-03-31

The quantification of illicit drug and pharmaceutical residues in sewage has been shown to be a valuable tool that complements existing approaches in monitoring the patterns and trends of drug use. The present work delineates the development of a novel analytical tool and dynamic workflow for the analysis of a wide range of substances in sewage-based samples. The validated method can simultaneously quantify 51 target psychoactive substances and pharmaceuticals in sewage-based samples using an off-line automated solid phase extraction (SPE-DEX) method, using Oasis HLB disks, followed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) in MS{sup e}. Quantification and matrix effect corrections were overcome with the use of 25 isotopic labeled internal standards (ILIS). Recoveries were generally greater than 60% and the limits of quantification were in the low nanogram-per-liter range (0.4–187 ng L{sup −1}). The emergence of new psychoactive substances (NPS) on the drug scene poses a specific analytical challenge since their market is highly dynamic with new compounds continuously entering the market. Suspect screening using high-resolution mass spectrometry (HRMS) simultaneously allowed the unequivocal identification of NPS based on a mass accuracy criteria of 5 ppm (of the molecular ion and at least two fragments) and retention time (2.5% tolerance) using the UNIFI screening platform. Applying MS{sup e} data against a suspect screening database of over 1000 drugs and metabolites, this method becomes a broad and reliable tool to detect and confirm NPS occurrence. This was demonstrated through the HRMS analysis of three different sewage-based sample types; influent wastewater, passive sampler extracts and pooled urine samples resulting in the concurrent quantification of known psychoactive substances and the identification of NPS and pharmaceuticals. - Highlights: • A novel reiterative workflow

Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF

International Nuclear Information System (INIS)

Baz-Lomba, J.A.; Reid, Malcolm J.; Thomas, Kevin V.

2016-01-01

The quantification of illicit drug and pharmaceutical residues in sewage has been shown to be a valuable tool that complements existing approaches in monitoring the patterns and trends of drug use. The present work delineates the development of a novel analytical tool and dynamic workflow for the analysis of a wide range of substances in sewage-based samples. The validated method can simultaneously quantify 51 target psychoactive substances and pharmaceuticals in sewage-based samples using an off-line automated solid phase extraction (SPE-DEX) method, using Oasis HLB disks, followed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) in MS"e. Quantification and matrix effect corrections were overcome with the use of 25 isotopic labeled internal standards (ILIS). Recoveries were generally greater than 60% and the limits of quantification were in the low nanogram-per-liter range (0.4–187 ng L"−"1). The emergence of new psychoactive substances (NPS) on the drug scene poses a specific analytical challenge since their market is highly dynamic with new compounds continuously entering the market. Suspect screening using high-resolution mass spectrometry (HRMS) simultaneously allowed the unequivocal identification of NPS based on a mass accuracy criteria of 5 ppm (of the molecular ion and at least two fragments) and retention time (2.5% tolerance) using the UNIFI screening platform. Applying MS"e data against a suspect screening database of over 1000 drugs and metabolites, this method becomes a broad and reliable tool to detect and confirm NPS occurrence. This was demonstrated through the HRMS analysis of three different sewage-based sample types; influent wastewater, passive sampler extracts and pooled urine samples resulting in the concurrent quantification of known psychoactive substances and the identification of NPS and pharmaceuticals. - Highlights: • A novel reiterative workflow based on three

Consolidated principles for screening based on a systematic review and consensus process.

Science.gov (United States)

Dobrow, Mark J; Hagens, Victoria; Chafe, Roger; Sullivan, Terrence; Rabeneck, Linda

2018-04-09

In 1968, Wilson and Jungner published 10 principles of screening that often represent the de facto starting point for screening decisions today; 50 years on, are these principles still the right ones? Our objectives were to review published work that presents principles for population-based screening decisions since Wilson and Jungner's seminal publication, and to conduct a Delphi consensus process to assess the review results. We conducted a systematic review and modified Delphi consensus process. We searched multiple databases for articles published in English in 1968 or later that were intended to guide population-based screening decisions, described development and modification of principles, and presented principles as a set or list. Identified sets were compared for basic characteristics (e.g., number, categorization), a citation analysis was conducted, and principles were iteratively synthesized and consolidated into categories to assess evolution. Participants in the consensus process assessed the level of agreement with the importance and interpretability of the consolidated screening principles. We identified 41 sets and 367 unique principles. Each unique principle was coded to 12 consolidated decision principles that were further categorized as disease/condition, test/intervention or program/system principles. Program or system issues were the focus of 3 of Wilson and Jungner's 10 principles, but comprised almost half of all unique principles identified in the review. The 12 consolidated principles were assessed through 2 rounds of the consensus process, leading to specific refinements to improve their relevance and interpretability. No gaps or missing principles were identified. Wilson and Jungner's principles are remarkably enduring, but increasingly reflect a truncated version of contemporary thinking on screening that does not fully capture subsequent focus on program or system principles. Ultimately, this review and consensus process provides a

Consolidated principles for screening based on a systematic review and consensus process

Science.gov (United States)

Hagens, Victoria; Chafe, Roger; Sullivan, Terrence; Rabeneck, Linda

2018-01-01

BACKGROUND: In 1968, Wilson and Jungner published 10 principles of screening that often represent the de facto starting point for screening decisions today; 50 years on, are these principles still the right ones? Our objectives were to review published work that presents principles for population-based screening decisions since Wilson and Jungner’s seminal publication, and to conduct a Delphi consensus process to assess the review results. METHODS: We conducted a systematic review and modified Delphi consensus process. We searched multiple databases for articles published in English in 1968 or later that were intended to guide population-based screening decisions, described development and modification of principles, and presented principles as a set or list. Identified sets were compared for basic characteristics (e.g., number, categorization), a citation analysis was conducted, and principles were iteratively synthesized and consolidated into categories to assess evolution. Participants in the consensus process assessed the level of agreement with the importance and interpretability of the consolidated screening principles. RESULTS: We identified 41 sets and 367 unique principles. Each unique principle was coded to 12 consolidated decision principles that were further categorized as disease/condition, test/intervention or program/system principles. Program or system issues were the focus of 3 of Wilson and Jungner’s 10 principles, but comprised almost half of all unique principles identified in the review. The 12 consolidated principles were assessed through 2 rounds of the consensus process, leading to specific refinements to improve their relevance and interpretability. No gaps or missing principles were identified. INTERPRETATION: Wilson and Jungner’s principles are remarkably enduring, but increasingly reflect a truncated version of contemporary thinking on screening that does not fully capture subsequent focus on program or system principles

A highly efficient approach to protein interactome mapping based on collaborative filtering framework.

Science.gov (United States)

Luo, Xin; You, Zhuhong; Zhou, Mengchu; Li, Shuai; Leung, Hareton; Xia, Yunni; Zhu, Qingsheng

2015-01-09

The comprehensive mapping of protein-protein interactions (PPIs) is highly desired for one to gain deep insights into both fundamental cell biology processes and the pathology of diseases. Finely-set small-scale experiments are not only very expensive but also inefficient to identify numerous interactomes despite their high accuracy. High-throughput screening techniques enable efficient identification of PPIs; yet the desire to further extract useful knowledge from these data leads to the problem of binary interactome mapping. Network topology-based approaches prove to be highly efficient in addressing this problem; however, their performance deteriorates significantly on sparse putative PPI networks. Motivated by the success of collaborative filtering (CF)-based approaches to the problem of personalized-recommendation on large, sparse rating matrices, this work aims at implementing a highly efficient CF-based approach to binary interactome mapping. To achieve this, we first propose a CF framework for it. Under this framework, we model the given data into an interactome weight matrix, where the feature-vectors of involved proteins are extracted. With them, we design the rescaled cosine coefficient to model the inter-neighborhood similarity among involved proteins, for taking the mapping process. Experimental results on three large, sparse datasets demonstrate that the proposed approach outperforms several sophisticated topology-based approaches significantly.

A high-throughput screening approach to discovering good forms of biologically inspired visual representation.

Science.gov (United States)

Pinto, Nicolas; Doukhan, David; DiCarlo, James J; Cox, David D

2009-11-01

While many models of biological object recognition share a common set of "broad-stroke" properties, the performance of any one model depends strongly on the choice of parameters in a particular instantiation of that model--e.g., the number of units per layer, the size of pooling kernels, exponents in normalization operations, etc. Since the number of such parameters (explicit or implicit) is typically large and the computational cost of evaluating one particular parameter set is high, the space of possible model instantiations goes largely unexplored. Thus, when a model fails to approach the abilities of biological visual systems, we are left uncertain whether this failure is because we are missing a fundamental idea or because the correct "parts" have not been tuned correctly, assembled at sufficient scale, or provided with enough training. Here, we present a high-throughput approach to the exploration of such parameter sets, leveraging recent advances in stream processing hardware (high-end NVIDIA graphic cards and the PlayStation 3's IBM Cell Processor). In analogy to high-throughput screening approaches in molecular biology and genetics, we explored thousands of potential network architectures and parameter instantiations, screening those that show promising object recognition performance for further analysis. We show that this approach can yield significant, reproducible gains in performance across an array of basic object recognition tasks, consistently outperforming a variety of state-of-the-art purpose-built vision systems from the literature. As the scale of available computational power continues to expand, we argue that this approach has the potential to greatly accelerate progress in both artificial vision and our understanding of the computational underpinning of biological vision.

A high-throughput screening approach to discovering good forms of biologically inspired visual representation.

Directory of Open Access Journals (Sweden)

Nicolas Pinto

2009-11-01

Full Text Available While many models of biological object recognition share a common set of "broad-stroke" properties, the performance of any one model depends strongly on the choice of parameters in a particular instantiation of that model--e.g., the number of units per layer, the size of pooling kernels, exponents in normalization operations, etc. Since the number of such parameters (explicit or implicit is typically large and the computational cost of evaluating one particular parameter set is high, the space of possible model instantiations goes largely unexplored. Thus, when a model fails to approach the abilities of biological visual systems, we are left uncertain whether this failure is because we are missing a fundamental idea or because the correct "parts" have not been tuned correctly, assembled at sufficient scale, or provided with enough training. Here, we present a high-throughput approach to the exploration of such parameter sets, leveraging recent advances in stream processing hardware (high-end NVIDIA graphic cards and the PlayStation 3's IBM Cell Processor. In analogy to high-throughput screening approaches in molecular biology and genetics, we explored thousands of potential network architectures and parameter instantiations, screening those that show promising object recognition performance for further analysis. We show that this approach can yield significant, reproducible gains in performance across an array of basic object recognition tasks, consistently outperforming a variety of state-of-the-art purpose-built vision systems from the literature. As the scale of available computational power continues to expand, we argue that this approach has the potential to greatly accelerate progress in both artificial vision and our understanding of the computational underpinning of biological vision.

Quality assurance target for community-based breast cancer screening in China: a model simulation.

Science.gov (United States)

Yang, Lan; Wang, Jing; Cheng, Juan; Wang, Yuan; Lu, Wenli

2018-03-07

We aimed to clarify the feasibility of a community-based screening strategy for breast cancer in Tianjin, China; to identify the factors that most significantly influenced its feasibility; and to identify the reference range for quality control. A state-transition Markov model simulated a hypothetical cohort of 100,000 healthy women, the start aged was set at 35 years and the time horizon was set to 50 years. The primary outcome for the model was the incremental cost-utility ratio (ICUR), defined as the program's cost per quality-adjusted life year (QALY) gained. Three screening strategies providing by community health service for women aged 35 to 69 years was compared regarding to different intervals. The probability of the ICUR being below 20 272USD (i.e., triple the annual gross domestic product [3 GDPs]) per QALY saved was 100% for annual screening strategy and screening every three years. Only when the attendance rate was > 50%, the probability for annual screening would be cost effective > 95%. The probability for the annual screening strategy being cost effective could reach to 95% for a willingness-to-pay (WTP) of 2 GDPs when the compliance rate for transfer was > 80%. When 10% stage I tumors were detected by screening, the probability of the annual screening strategy being cost effective would be up to 95% for a WTP > 3 GDPs. Annual community-based breast cancer screening was cost effective for a WTP of 3 GDP based on the incidence of breast cancer in Tianjin, China. Measures are needed to ensure performance indicators to a desirable level for the cost-effectiveness of breast cancer screening.

Elder abuse: The role of general practitioners in community-based screening and multidisciplinary action

Science.gov (United States)

Ries, Nola M; Mansfield, Elise

2018-04-01

There are growing calls for elder abuse screening to be conducted by a range of community-based service providers, including general practitioners (GPs), practice nurses, home care workers and lawyers. Improved screening may be a valuable first step towards improving elder abuse detection and response; however, practitioners need evidence-based strategies for screening and follow-up. This article summarises several brief screening tools for various forms of elder abuse. Screening tool properties and evidence gaps are noted. As elder abuse often requires multidisciplinary responses, initiatives to connect health, legal and other service providers are highlighted. GPs are trusted professionals who are well placed to identify older patients at risk of, or experiencing, various forms of abuse. They should be aware of available screening tools and consider how best to incorporate them into their own practice. They also play an important role in multidisciplinary action to address elder abuse.  .

N-screen aware multicriteria hybrid recommender system using weight based subspace clustering.

Science.gov (United States)

Ullah, Farman; Sarwar, Ghulam; Lee, Sungchang

2014-01-01

This paper presents a recommender system for N-screen services in which users have multiple devices with different capabilities. In N-screen services, a user can use various devices in different locations and time and can change a device while the service is running. N-screen aware recommendation seeks to improve the user experience with recommended content by considering the user N-screen device attributes such as screen resolution, media codec, remaining battery time, and access network and the user temporal usage pattern information that are not considered in existing recommender systems. For N-screen aware recommendation support, this work introduces a user device profile collaboration agent, manager, and N-screen control server to acquire and manage the user N-screen devices profile. Furthermore, a multicriteria hybrid framework is suggested that incorporates the N-screen devices information with user preferences and demographics. In addition, we propose an individual feature and subspace weight based clustering (IFSWC) to assign different weights to each subspace and each feature within a subspace in the hybrid framework. The proposed system improves the accuracy, precision, scalability, sparsity, and cold start issues. The simulation results demonstrate the effectiveness and prove the aforementioned statements.

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing

Science.gov (United States)

Fang, Ye; Ding, Yun; Feinstein, Wei P.; Koppelman, David M.; Moreno, Juana; Jarrell, Mark; Ramanujam, J.; Brylinski, Michal

2016-01-01

Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

Directory of Open Access Journals (Sweden)

Ye Fang

Full Text Available Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU. First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.

High-throughput screening for various classes of doping agents using a new 'dilute-and-shoot' liquid chromatography-tandem mass spectrometry multi-target approach.

Science.gov (United States)

Guddat, S; Solymos, E; Orlovius, A; Thomas, A; Sigmund, G; Geyer, H; Thevis, M; Schänzer, W

2011-01-01

A new multi-target approach based on liquid chromatography--electrospray ionization tandem mass spectrometry (LC-(ESI)-MS/MS) is presented to screen for various classes of prohibited substances using direct injection of urine specimens. With a highly sensitive new generation hybrid mass spectrometer classic groups of drugs--for example, diuretics, beta2-agonists--stimulants and narcotics are detectable at concentration levels far below the required limits. Additionally, more challenging and various new target compounds could be implemented. Model compounds of stimulant conjugates were studied to investigate a possible screening without complex sample preparation. As a main achievement, the integration of the plasma volume expanders dextran and hydroxyethyl starch (HES), commonly analyzed in time-consuming, stand-alone procedures, is accomplished. To screen for relatively new prohibited compounds, a common metabolite of the selective androgen receptor modulator (SARMs) andarine, a metabolite of growth hormone releasing peptide (GHRP-2), and 5-amino-4-imidazolecarboxyamide ribonucleoside (AICAR) are analyzed. Following a completely new approach, conjugates of di(2-ethylhexyl) phthalate (DEHP) metabolites are monitored to detect abnormally high levels of plasticizers indicating for illicit blood transfusion. The assay was fully validated for qualitative purposes considering the parameters specificity, intra- (3.2-16.6%) and inter-day precision (0.4-19.9%) at low, medium and high concentration, robustness, limit of detection (1-70 ng/ml, dextran: 30 µg/ml, HES: 10 µg/ml) and ion suppression/enhancement effects. The analyses of post-administration and routine doping control samples demonstrates the applicability of the method for sports drug testing. This straightforward and reliable approach accomplishes the combination of different screening procedures resulting in a high-throughput method that increases the efficiency of the labs daily work. Copyright © 2011 John

Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.

Science.gov (United States)

Kutchukian, Peter S; Wassermann, Anne Mai; Lindvall, Mika K; Wright, S Kirk; Ottl, Johannes; Jacob, Jaison; Scheufler, Clemens; Marzinzik, Andreas; Brooijmans, Natasja; Glick, Meir

2015-06-01

A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits. © 2014 Society for Laboratory Automation and Screening.

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

Directory of Open Access Journals (Sweden)

Chen C

2014-09-01

Full Text Available Can Chen,1,2,* Ting Wang,1,3,* Fengbo Wu,1,* Wei Huang,4 Gu He,1 Liang Ouyang,1 Mingli Xiang,1 Cheng Peng,4 Qinglin Jiang1,2 1State Key Laboratory of Biotherapy and Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 2College of Pharmacy and the First Affiliated Hospital, Chengdu Medical College, Chengdu, 3Department of Cardiology, Genenal Hospital of Chengdu Military Command, Chengdu, 4State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workAbstract: 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

A nuclear magnetic resonance based approach to accurate functional annotation of putative enzymes in the methanogen Methanosarcina acetivorans

Directory of Open Access Journals (Sweden)

Nikolau Basil J

2011-06-01

Full Text Available Abstract Background Correct annotation of function is essential if one is to take full advantage of the vast amounts of genomic sequence data. The accuracy of sequence-based functional annotations is often variable, particularly if the sequence homology to a known function is low. Indeed recent work has shown that even proteins with very high sequence identity can have different folds and functions, and therefore caution is needed in assigning functions by sequence homology in the absence of experimental validation. Experimental methods are therefore needed to efficiently evaluate annotations in a way that complements current high throughput technologies. Here, we describe the use of nuclear magnetic resonance (NMR-based ligand screening as a tool for testing functional assignments of putative enzymes that may be of variable reliability. Results The target genes for this study are putative enzymes from the methanogenic archaeon Methanosarcina acetivorans (MA that have been selected after manual genome re-annotation and demonstrate detectable in vivo expression at the level of the transcriptome. The experimental approach begins with heterologous E. coli expression and purification of individual MA gene products. An NMR-based ligand screen of the purified protein then identifies possible substrates or products from a library of candidate compounds chosen from the putative pathway and other related pathways. These data are used to determine if the current sequence-based annotation is likely to be correct. For a number of case studies, additional experiments (such as in vivo genetic complementation were performed to determine function so that the reliability of the NMR screen could be independently assessed. Conclusions In all examples studied, the NMR screen was indicative of whether the functional annotation was correct. Thus, the case studies described demonstrate that NMR-based ligand screening is an effective and rapid tool for confirming or

Invitation strategies and coverage in the population-based cancer screening programmes in the European Union.

Science.gov (United States)

Vale, Diama B; Anttila, Ahti; Ponti, Antonio; Senore, Carlo; Sankaranaryanan, Rengaswamy; Ronco, Guglielmo; Segnan, Nereo; Tomatis, Mariano; Žakelj, Maja P; Elfström, Klara M; Lönnberg, Stefan; Dillner, Joakim; Basu, Partha

2018-03-21

The aim of this study was to describe the compliance of the population-based cancer screening programmes in the European Union Member States to the invitation strategies enumerated in the European Guidelines and the impact of such strategies on the invitational coverage. Experts in screening programme monitoring from the respective countries provided data. Coverage by invitation was calculated as the proportion of individuals in the target age range receiving a screening invitation over the total number of annualized eligible population. The invitation strategies of 30 breasts, 25 cervical and 27 colorectal national or regional population-based screening programmes are described. Individual mail invitations are sent by 28 breasts, 20 cervical and 25 colorectal screening programmes. Faecal occult blood test kits are sent by post in 17 of the colorectal cancer screening programmes. The majority of programmes claimed to have a population registry, although some use health insurance data as the database for sending invitations. At least 95% invitation coverage was reached by 16 breast, six cervical and five colorectal screening programmes. Majority of the programmes comply with the invitation strategies enumerated in the European guidelines, although there is still scope for improvements. Coverage by invitation is below the desirable level in many population-based cancer screening programmes in European Union.

Chemogenomics profiling of drug targets of peptidoglycan biosynthesis pathway in Leptospira interrogans by virtual screening approaches.

Science.gov (United States)

Bhattacharjee, Biplab; Simon, Rose Mary; Gangadharaiah, Chaithra; Karunakar, Prashantha

2013-06-28

Leptospirosis is a worldwide zoonosis of global concern caused by Leptospira interrogans. The availability of ligand libraries has facilitated the search for novel drug targets using chemogenomics approaches, compared with the traditional method of drug discovery, which is time consuming and yields few leads with little intracellular information for guiding target selection. Recent subtractive genomics studies have revealed the putative drug targets in peptidoglycan biosynthesis pathways in Leptospira interrogans. Aligand library for the murD ligase enzyme in the peptidoglycan pathway has also been identified. Our approach in this research involves screening of the pre-existing ligand library of murD with related protein family members in the putative drug target assembly in the peptidoglycan biosynthesis pathway. A chemogenomics approach has been implemented here, which involves screening of known ligands of a protein family having analogous domain architecture for identification of leads for existing druggable protein family members. By means of this approach, one murC and one murF inhibitor were identified, providing a platform for developing an antileptospirosis drug targeting the peptidoglycan biosynthesis pathway. Given that the peptidoglycan biosynthesis pathway is exclusive to bacteria, the in silico identified mur ligase inhibitors are expected to be broad-spectrum Gram-negative inhibitors if synthesized and tested in in vitro and in vivo assays.

Comparative analysis of machine learning methods in ligand-based virtual screening of large compound libraries.

Science.gov (United States)

Ma, Xiao H; Jia, Jia; Zhu, Feng; Xue, Ying; Li, Ze R; Chen, Yu Z

2009-05-01

Machine learning methods have been explored as ligand-based virtual screening tools for facilitating drug lead discovery. These methods predict compounds of specific pharmacodynamic, pharmacokinetic or toxicological properties based on their structure-derived structural and physicochemical properties. Increasing attention has been directed at these methods because of their capability in predicting compounds of diverse structures and complex structure-activity relationships without requiring the knowledge of target 3D structure. This article reviews current progresses in using machine learning methods for virtual screening of pharmacodynamically active compounds from large compound libraries, and analyzes and compares the reported performances of machine learning tools with those of structure-based and other ligand-based (such as pharmacophore and clustering) virtual screening methods. The feasibility to improve the performance of machine learning methods in screening large libraries is discussed.

[Generalized neonatal screening based on laboratory tests].

Science.gov (United States)

Ardaillou, Raymond; Le Gall, Jean-Yves

2006-11-01

Implementation of a generalized screening program for neonatal diseases must obey precise rules. The disease must be severe, recognizable at an early stage, amenable to an effective treatment, detectable with a non expensive and widely applicable test; it must also be a significant public health problem. Subjects with positive results must be offered immediate treatment or prevention. All screening programs must be regularly evaluated. In France, since 1978, a national screening program has been organized by a private association ("Association française pour le dépistage et la prévention des handicaps de l'enfant") and supervised by the "Caisse nationale d'assurance maladie" and "Direction Générale de la Sante". Five diseases are now included in the screening program: phenylketonuria, hypothyroidism, congenital adrenal hyperplasia, cystic fibrosis and sickle cell disease (the latter only in at-risk newborns). Toxoplasmosis is a particular problem because only the children of mothers who were not tested during the pregnancy or who seroconverted are screened. Neonatal screening for phenylketonuria and hypothyrodism is unanimously recommended. Screening for congenital adrenal hyperplasia is approved in most countries. Cases of sickle cell disease and cystic fibrosis are more complex because--not all children who carry the mutations develop severe forms;--there is no curative treatment;--parents may become anxious, even though the phenotype is sometimes mild or even asymptomatic. Supporters of screening stress the benefits of early diagnosis (which extends the life expectancy of these children, particularly in the case of sickle cell disease), the fact that it opens up the possibility of prenatal screening of future pregnancies, and the utility of informing heterozygous carriers identified by familial screening. Neonatal screening for other diseases is under discussion. Indeed, technical advances such as tandem mass spectrometry make it possible to detect about 50

State of the Art High-Throughput Approaches to Genotoxicity: Flow Micronucleus, Ames II, GreenScreen and Comet

Science.gov (United States)

State of the Art High-Throughput Approaches to Genotoxicity: Flow Micronucleus, Ames II, GreenScreen and Comet (Presented by Dr. Marilyn J. Aardema, Chief Scientific Advisor, Toxicology, Dr. Leon Stankowski, et. al. (6/28/2012)

iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.

Science.gov (United States)

Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

2011-06-01

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

Science.gov (United States)

Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

2011-06-01

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

Molecular genetic approach for screening of hereditary non-polyposis colorectal cancer

Directory of Open Access Journals (Sweden)

Metka Ravnik-Glavač

2005-07-01

Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based

Using lessons from breast, cervical, and colorectal cancer screening to inform the development of lung cancer screening programs.

Science.gov (United States)

Armstrong, Katrina; Kim, Jane J; Halm, Ethan A; Ballard, Rachel M; Schnall, Mitchell D

2016-05-01

Multiple advisory groups now recommend that high-risk smokers be screened for lung cancer by low-dose computed tomography. Given that the development of lung cancer screening programs will face many of the same issues that have challenged other cancer screening programs, the National Cancer Institute-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium was used to identify lessons learned from the implementation of breast, cervical, and colorectal cancer screening that should inform the introduction of lung cancer screening. These lessons include the importance of developing systems for identifying and recruiting eligible individuals in primary care, ensuring that screening centers are qualified and performance is monitored, creating clear communication standards for reporting screening results to referring physicians and patients, ensuring follow-up is available for individuals with abnormal test results, avoiding overscreening, remembering primary prevention, and leveraging advances in cancer genetics and immunology. Overall, this experience emphasizes that effective cancer screening is a multistep activity that requires robust strategies to initiate, report, follow up, and track each step as well as a dynamic and ongoing oversight process to revise current screening practices as new evidence regarding screening is created, new screening technologies are developed, new biological markers are identified, and new approaches to health care delivery are disseminated. Cancer 2016;122:1338-1342. © 2016 American Cancer Society. © 2016 American Cancer Society.

The Novel Language-Systematic Aphasia Screening SAPS: Screening-Based Therapy in Combination with Computerised Home Training

Science.gov (United States)

Krzok, Franziska; Rieger, Verena; Niemann, Katharina; Nobis-Bosch, Ruth; Radermacher, Irmgard; Huber, Walter; Willmes, Klaus; Abel, Stefanie

2018-01-01

Background: SAPS--'Sprachsystematisches Aphasiescreening'--is a novel language-systematic aphasia screening developed for the German language, which already had been positively evaluated. It offers a fast assessment of modality-specific psycholinguistic components at different levels of complexity and the derivation of impairment-based treatment…

Design and analysis of a piezoelectric material based touch screen with additional pressure and its acceleration measurement functions

International Nuclear Information System (INIS)

Chu, Xiang-Cheng; Liu, Jia-Yi; Gao, Ren-Long; Chang, Jie; Li, Long-Tu

2013-01-01

Touch screens are becoming more and more prevalent in everyday environments due to their convenience and humanized operation. In this paper, a piezoelectric material based touch screen is developed and investigated. Piezoelectric ceramics arrayed under the touch panel at the edges or corners are used as tactile sensors to measure the touch positioning point similarly to conventional touch screens. However, additional touch pressure and its acceleration performance can also be obtained to obtain a higher-level human–machine interface. The piezoelectric ceramics can also be added to a traditional touch screen structure, or they can be used independently to construct a novel touch screen with a high light transmittance approach to a transparent glass. The piezoelectric ceramics were processed from PZT piezoelectric ceramic powder into a round or rectangular shape. According to the varied touch position and physical press strength of a finger, or even a gloved hand or fingernail, the piezoelectric tactile sensors will have different output voltage responses. By calculating the ratio of different piezoelectric tactile sensors’ responses and summing up all piezoelectric tactile sensors’ output voltages, the touch point position, touch pressure and touch force acceleration can be detected. A prototype of such a touch screen is manufactured and its position accuracy, touch pressure and response speed are measured in detail. The experimental results show that the prototype has many advantages such as high light transmittance, low energy cost and high durability. (paper)

Complex Approach to Thyroid Screening In Regions Adjacent to the Semipalatinsk Test Site Area

International Nuclear Information System (INIS)

Zhumadilov, Zh.Sh.; Musinov, D.R.; Vasikovsky, G.G.; Bobokhidze, D.A.; Zhigitaev, T.K.; Abisheva, G.N.

1998-01-01

It has been well documented that the thyroid gland is one of the most radiosensitive of organs, especially when exposure occurs during childhood. It is known as well that childhood exposure to radioactive iodine increases thyroid cancer risk. Conducting thyroid screening in regions adjacent to the Semipalatinsk Test Site (STS) area is very important for medical examination, data management and thyroid dose reconstruction. Our experience of thyroid screening based on our screening projects in Kurchatov and several regions adjacent to STS (more than 4,000 screened patients) allowed to work out the most appropriate screening protocol. A retrospective analysis of the results of surgical treatment of the 7,271 patients with thyroid abnormalities in the Semipalatinsk, Pavlodar and Ust-Kamenogorsk regions of Kazakstan and study the histological staging of 7,271 surgically removed thyroid glands was preceded by our thyroid screening projects. Ours is the first study in the Semipalatinsk region that covers the period 1966-1998.Taking into account the onset of population effective doses during 1962, it was decided to distinguish 6 periods of observation. It is known that basic effective equivalent doses for the majority of the region's population were established by radioactive events in the period 1949-1962. This explains our focus on the year 1962, but thyroid dose reconstruction matter as well as other radiation related problems are still in the progress. We need to get the accurate dosimetry data. Selection of study subjects based on the appropriate criteria needed to be adjusted and clarified in accordance with the main goal of the project and radiation related information. All specialists involved in the thyroid screening project, data management, data analyses and interpretation of the results must be trained and must be highly qualified specialists in this field of science and practice. The experiences in Nagasaki, Hiroshima and Chernobyl, and discussions with

How to Achieve Better Results Using PASS-Based Virtual Screening: Case Study for Kinase Inhibitors

Directory of Open Access Journals (Sweden)

Pavel V. Pogodin

2018-04-01

Full Text Available Discovery of new pharmaceutical substances is currently boosted by the possibility of utilization of the Synthetically Accessible Virtual Inventory (SAVI library, which includes about 283 million molecules, each annotated with a proposed synthetic one-step route from commercially available starting materials. The SAVI database is well-suited for ligand-based methods of virtual screening to select molecules for experimental testing. In this study, we compare the performance of three approaches for the analysis of structure-activity relationships that differ in their criteria for selecting of “active” and “inactive” compounds included in the training sets. PASS (Prediction of Activity Spectra for Substances, which is based on a modified Naïve Bayes algorithm, was applied since it had been shown to be robust and to provide good predictions of many biological activities based on just the structural formula of a compound even if the information in the training set is incomplete. We used different subsets of kinase inhibitors for this case study because many data are currently available on this important class of drug-like molecules. Based on the subsets of kinase inhibitors extracted from the ChEMBL 20 database we performed the PASS training, and then applied the model to ChEMBL 23 compounds not yet present in ChEMBL 20 to identify novel kinase inhibitors. As one may expect, the best prediction accuracy was obtained if only the experimentally confirmed active and inactive compounds for distinct kinases in the training procedure were used. However, for some kinases, reasonable results were obtained even if we used merged training sets, in which we designated as inactives the compounds not tested against the particular kinase. Thus, depending on the availability of data for a particular biological activity, one may choose the first or the second approach for creating ligand-based computational tools to achieve the best possible results in

Reevaluation of 1999 Health-Based Environmental Screening Levels (HBESLs) for Chemical Warfare Agents

Energy Technology Data Exchange (ETDEWEB)

Watson, Annetta Paule [ORNL; Dolislager, Fredrick G [ORNL

2007-05-01

This report evaluates whether new information and updated scientific models require that changes be made to previously published health-based environmental soil screening levels (HBESLs) and associated environmental fate/breakdown information for chemical warfare agents (USACHPPM 1999). Specifically, the present evaluation describes and compares changes that have been made since 1999 to U.S. Environmental Protection Agency (EPA) risk assessment models, EPA exposure assumptions, as well as to specific chemical warfare agent parameters (e.g., toxicity values). Comparison was made between screening value estimates recalculated with current assumptions and earlier health-based environmental screening levels presented in 1999. The chemical warfare agents evaluated include the G-series and VX nerve agents and the vesicants sulfur mustard (agent HD) and Lewisite (agent L). In addition, key degradation products of these agents were also evaluated. Study findings indicate that the combined effect of updates and/or changes to EPA risk models, EPA default exposure parameters, and certain chemical warfare agent toxicity criteria does not result in significant alteration to the USACHPPM (1999) health-based environmental screening level estimates for the G-series and VX nerve agents or the vesicant agents HD and L. Given that EPA's final position on separate Tier 1 screening levels for indoor and outdoor worker screening assessments has not yet been released as of May 2007, the study authors find that the 1999 screening level estimates (see Table ES.1) are still appropriate and protective for screening residential as well as nonresidential sites. As such, risk management decisions made on the basis of USACHPPM (1999) recommendations do not require reconsideration. While the 1999 HBESL values are appropriate for continued use as general screening criteria, the updated '2007' estimates (presented below) that follow the new EPA protocols currently under development

Effects of population based screening for Chlamydia infections in the Netherlands limited by declining participation rates.

Directory of Open Access Journals (Sweden)

Boris V Schmid

Full Text Available BACKGROUND: A large trial to investigate the effectiveness of population based screening for chlamydia infections was conducted in the Netherlands in 2008-2012. The trial was register based and consisted of four rounds of screening of women and men in the age groups 16-29 years in three regions in the Netherlands. Data were collected on participation rates and positivity rates per round. A modeling study was conducted to project screening effects for various screening strategies into the future. METHODS AND FINDINGS: We used a stochastic network simulation model incorporating partnership formation and dissolution, aging and a sexual life course perspective. Trends in baseline rates of chlamydia testing and treatment were used to describe the epidemiological situation before the start of the screening program. Data on participation rates was used to describe screening uptake in rural and urban areas. Simulations were used to project the effectiveness of screening on chlamydia prevalence for a time period of 10 years. In addition, we tested alternative screening strategies, such as including only women, targeting different age groups, and biennial screening. Screening reduced prevalence by about 1% in the first two screening rounds and leveled off after that. Extrapolating observed participation rates into the future indicated very low participation in the long run. Alternative strategies only marginally changed the effectiveness of screening. Higher participation rates as originally foreseen in the program would have succeeded in reducing chlamydia prevalence to very low levels in the long run. CONCLUSIONS: Decreasing participation rates over time profoundly impact the effectiveness of population based screening for chlamydia infections. Using data from several consecutive rounds of screening in a simulation model enabled us to assess the future effectiveness of screening on prevalence. If participation rates cannot be kept at a sufficient level

Discovery of technical methanation catalysts based on computational screening

DEFF Research Database (Denmark)

Sehested, Jens; Larsen, Kasper Emil; Kustov, Arkadii

2007-01-01

Methanation is a classical reaction in heterogeneous catalysis and significant effort has been put into improving the industrially preferred nickel-based catalysts. Recently, a computational screening study showed that nickel-iron alloys should be more active than the pure nickel catalyst and at ...

Interval Cancers in a Population-Based Screening Program for Colorectal Cancer in Catalonia, Spain

Directory of Open Access Journals (Sweden)

M. Garcia

2015-01-01

Full Text Available 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.

An obstructive sleep apnea detection approach using kernel density classification based on single-lead electrocardiogram.

Science.gov (United States)

Chen, Lili; Zhang, Xi; Wang, Hui

2015-05-01

Obstructive sleep apnea (OSA) is a common sleep disorder that often remains undiagnosed, leading to an increased risk of developing cardiovascular diseases. Polysomnogram (PSG) is currently used as a golden standard for screening OSA. However, because it is time consuming, expensive and causes discomfort, alternative techniques based on a reduced set of physiological signals are proposed to solve this problem. This study proposes a convenient non-parametric kernel density-based approach for detection of OSA using single-lead electrocardiogram (ECG) recordings. Selected physiologically interpretable features are extracted from segmented RR intervals, which are obtained from ECG signals. These features are fed into the kernel density classifier to detect apnea event and bandwidths for density of each class (normal or apnea) are automatically chosen through an iterative bandwidth selection algorithm. To validate the proposed approach, RR intervals are extracted from ECG signals of 35 subjects obtained from a sleep apnea database ( http://physionet.org/cgi-bin/atm/ATM ). The results indicate that the kernel density classifier, with two features for apnea event detection, achieves a mean accuracy of 82.07 %, with mean sensitivity of 83.23 % and mean specificity of 80.24 %. Compared with other existing methods, the proposed kernel density approach achieves a comparably good performance but by using fewer features without significantly losing discriminant power, which indicates that it could be widely used for home-based screening or diagnosis of OSA.

Effectiveness of a Web-Based Protocol for the Screening and Phenotyping of Individuals with Tourette Syndrome for Genetic Studies

Science.gov (United States)

Egan, Crystelle; Marakovitz, Susan; O’Rourke, Julia; Osiecki, Lisa; Illmann, Cornelia; Barton, Lauren; McLaughlin, Elizabeth; Proujansky, Rachel; Royal, Justin; Cowley, Heather; Rangel-Lugo, Martha; Pauls, David; Scharf, Jeremiah M.; Mathews, Carol A.

2014-01-01

Genome-wide association studies (GWAS) and other emerging technologies offer great promise for the identification of genetic risk factors for complex psychiatric disorders, yet such studies are constrained by the need for large sample sizes. Web-based collection offers a relatively untapped resource for increasing participant recruitment. Therefore, we developed and implemented a novel web-based screening and phenotyping protocol for genetic studies of Tourette Syndrome (TS), a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. Participants were recruited over a 13 month period through the membership of the Tourette Syndrome Association (TSA) (n=28,878). Of the TSA members contacted, 4.3% (1,242) initiated the questionnaire, and 79.5% (987) of these were enrollment eligible. 63.9% (631) of enrolled participants completed the study by submitting phenotypic data and blood specimens. Age was the only variable that predicted study completion; children and young adults were significantly less likely to be study completers than adults 26 and older. Compared to a clinic-based study conducted over the same time period, the web-based method yielded a 60% larger sample. Web-based participants were older and more often female; otherwise, the sample characteristics did not differ significantly. TS diagnoses based on the web-screen demonstrated 100% accuracy compared to those derived from in-depth clinical interviews. Our results suggest that a web-based approach is effective for increasing the sample size for genetic studies of a relatively rare disorder and that our web-based screen is valid for diagnosing TS. Findings from this study should aid in the development of web-based protocols for other disorders. PMID:23090870

The use of twin-screen-based WIMPS in spacecraft control

Science.gov (United States)

Klim, R. D.

1990-10-01

The ergonomic problems of designing a sophisticated Windows Icons Mouse Pop-up (WIMP) based twin screen workstation are outlined. These same problems will be encountered by future spacecraft controllers. The design of a modern, advanced workstation for use on a distributed multicontrol center in a multisatellite control system is outlined. The system uses access control mechanisms to ensure that only authorized personnel can undertake certain operations on the workstation. Rules governing the use of windowing features, screen attributes, icons, keyboard and mouse in spacecraft control are discussed.

Community-Based Multidisciplinary Computed Tomography Screening Program Improves Lung Cancer Survival.

Science.gov (United States)

Miller, Daniel L; Mayfield, William R; Luu, Theresa D; Helms, Gerald A; Muster, Alan R; Beckler, Vickie J; Cann, Aaron

2016-05-01

Lung cancer is the most common cause of cancer deaths in the United States. Overall survival is less than 20%, with the majority of patients presenting with advanced disease. The National Lung Screening Trial, performed mainly in academic medical centers, showed that cancer mortality can be reduced with computed tomography (CT) screening compared with chest radiography in high-risk patients. To determine whether this survival advantage can be duplicated in a community-based multidisciplinary thoracic oncology program, we initiated a CT scan screening program for lung cancer within an established health care system. In 2008, we launched a lung cancer CT screening program within the WellStar Health System (WHS) consisting of five hospitals, three health parks, 140 outpatient medical offices, and 12 imaging centers that provide care in a five-county area of approximately 1.4 million people in Metro-Atlanta. Screening criteria incorporated were the International Early Lung Cancer Action Program (2008 to 2010) and National Comprehensive Cancer Network guidelines (2011 to 2013) for moderate- and high-risk patients. A total of 1,267 persons underwent CT lung cancer screening in WHS from 2008 through 2013; 53% were men, 87% were 50 years of age or older, and 83% were current or former smokers. Noncalcified indeterminate pulmonary nodules were found in 518 patients (41%). Thirty-six patients (2.8%) underwent a diagnostic procedure for positive findings on their CT scan; 30 proved to have cancer, 28 (2.2%) primary lung cancer and 2 metastatic cancer, and 6 had benign disease. Fourteen patients (50%) had their lung cancer discovered on their initial CT scan, 11 on subsequent scans associated with indeterminate pulmonary nodules growth and 3 patients who had a new indeterminate pulmonary nodules. Only 15 (54%) of these 28 patients would have qualified as a National Lung Screening Trial high-risk patient; 75% had stage I or II disease. Overall 5-year survival was 64% and 5-year

A Learning Collaborative Approach to Improve Primary Care STI Screening.

Science.gov (United States)

McKee, M Diane; Alderman, Elizabeth; York, Deborah V; Blank, Arthur E; Briggs, Rahil D; Hoidal, Kelsey E S; Kus, Christopher; Lechuga, Claudia; Mann, Marie; Meissner, Paul; Patel, Nisha; Racine, Andrew D

2017-10-01

The Bronx Ongoing Pediatric Screening (BOPS) project sought to improve screening for sexual activity and sexually transmitted infections (gonorrhea and chlamydia [GCC] and HIV) in a primary care network, employing a modified learning collaborative, real-time clinical data feedback to practices, improvement coaching, and a pay-for-quality monetary incentive. Outcomes are compared for 11 BOPS-participating sites and 10 non-participating sites. The quarterly median rate for documenting sexual activity status increased from 55% to 88% (BOPS sites) and from 13% to 74% (non-BOPS sites). GCC screening of sexually active youth increased at BOPS and non-BOPS sites. Screening at non-health care maintenance visits improved more at BOPS than non-BOPS sites. Data from nonparticipating sites suggests that introduction of an adolescent EMR template or other factors improved screening rates regardless of BOPS participation; BOPS activities appear to promote additional improvement of screening during non-health maintenance visits.

Correlates of Community-Based Colorectal Cancer Screening in a Rural Population: The Role of Fatalism.

Science.gov (United States)

Crosby, Richard A; Collins, Tom

2017-09-01

One largely unexplored barrier to colorectal cancer (CRC) screening is fatalistic beliefs about cancer. The purpose of this study was to identify correlates of ever having endoscopy screenings for CRC and to determine whether fatalism plays a unique role. Because evidence suggests that cancer-associated fatalistic beliefs may be particularly common among rural Americans, the study was conducted in a medically underserved area of rural Appalachia.  METHODS: Rural residents (N = 260) between 51 and 75 years of age, from a medically underserved area of Appalachia, Kentucky, were recruited for a cross-sectional study. The outcome measure was assessed by a single item asking whether participants ever had a colonoscopy or flexible sigmoidoscopy. Demographic and health-related correlates of this outcome were selected based on past studies of rural populations. A single item assessed perceptions of fatalism regarding CRC. Age-adjusted analyses of correlates testing significant at the bivariate level were conducted.  RESULTS: The analytic sample was limited to 135 rural residents indicating they had ever had CRC endoscopy and 107 indicating never having endoscopy. In age-adjusted analyses, only the measure of fatalism had a significant association with having endoscopy. Those endorsing the statement pertaining to fatalism were 2.3 times more likely (95% CI = 1.24-4.27, P = .008) than the remainder to indicate never having endoscopy.  CONCLUSIONS: A community-based approach to the promotion of endoscopy for CRC screening could focus on overcoming CRC-associated fatalism, thereby potentially bringing more unscreened people to endoscopy clinics. © 2017 National Rural Health Association.

PATTERN BASED DETECTION OF POTENTIALLY DRUGGABLE BINDING SITES BY LIGAND SCREENING

Directory of Open Access Journals (Sweden)

Uttam Pal

2018-03-01

Full Text Available This article describes an innovative way of finding the potentially druggable sites on a target protein, which can be used for orthosteric and allosteric lead detection in a single virtual screening setup. Druggability estimation for an alternate binding site other than the canonical ligand-binding pocket of an enzyme is rewarding for several inherent benefits. Allostery is a direct and efficient way of regulating biomacromolecule function. The allosteric modulators can fine-tune protein mechanics. Besides, allosteric sites are evolutionarily less conserved/more diverse even in very similarly related proteins, thus, provides high degree of specificity in targeting a particular protein. Therefore, targeting of allosteric sites is gaining attention as an emerging strategy in rational drug design. However, the experimental approaches provide a limited degree of characterization of new allosteric sites. Computational approaches are useful to analyze and select potential allosteric sites for drug discovery. Here, the use of molecular docking, which has become an integral part of the drug discovery process, has been discussed to predict the druggability of novel allosteric sites as well as the active site on target proteins by ligand screening. Genetic algorithm was used for docking and the whole protein was placed in the search space. For each ligand in the library of small molecules, the genetic algorithm was run for multiple times to populate all the druggable sites in the target protein, which was then translated into two dimensional density maps or “patterns”. High density clusters were observed for lead like molecules in these pattern diagrams. Each cluster in such a pattern diagram indicated a plausible binding site and the density gave its druggability score in terms of weighted probabilities. The patterns were filtered to find the leads for each of the druggable sites on the target protein. Such a novel pattern based analysis of the

Development of a community-based participatory colorectal cancer screening intervention to address disparities, Arkansas, 2008-2009.

Science.gov (United States)

Yeary, Karen; Flowers, Eric; Ford, Gemessia; Burroughs, Desiree; Burton, Jackie; Woods, Delores; Stewart, Chara; Mehta, Paulette; Greene, Paul; Henry-Tillman, Ronda

2011-03-01

The death rate from colorectal cancer is high and affects poor and medically underserved populations disproportionately. In the United States, health disparities are particularly acute in the Lower Mississippi River Delta region. Because many in the region have limited access to basic health care resources, they are not screened for cancer, even though screening is one of the most effective strategies to prevent colorectal cancer. Community-based participatory research is a promising approach to prevent colorectal cancer in this population. The Empowering Communities for Life program was implemented in 2 underserved counties in the Arkansas Lower Mississippi River Delta. The program arose from a 9-year partnership between the University of Arkansas for Medical Sciences and 9 cancer councils across Arkansas. Empowering Communities for Life is a community-based participatory intervention designed to increase colorectal cancer screening in rural, underserved communities through fecal occult blood testing. Community and academic partners collaborated to develop research infrastructure, intervention materials and methods, and the assessment instrument. Project outcomes were strengthened community-academic partnerships, certification of community partners in conducting human subjects research, development of a randomized controlled design to test the intervention's efficacy, an interactive PowerPoint presentation, an informational pamphlet, the certification of 6 lay health advisors and 22 role models to provide the intervention, and an assessment tool using an audience response system. Lessons learned in working collaboratively with diverse groups include the importance of meeting face to face and listening.

Interval breast cancers in the 'screening with tomosynthesis or standard mammography' (STORM) population-based trial.

Science.gov (United States)

Houssami, Nehmat; Bernardi, Daniela; Caumo, Francesca; Brunelli, Silvia; Fantò, Carmine; Valentini, Marvi; Romanucci, Giovanna; Gentilini, Maria A; Zorzi, Manuel; Macaskill, Petra

2018-04-01

The prospective 'screening with tomosynthesis or standard mammography' (STORM) trial recruited women participating in biennial breast screening in Italy (2011-2012), and compared sequential screen-readings based on 2D-mammography alone or based on tomosynthesis (integrated 2D/3D-mammography). The STORM trial showed that tomosynthesis screen-reading significantly increased breast cancer detection compared to 2D-mammography alone. The present study completes reporting of the trial by examining interval breast cancers ascertained at two year follow-up. 9 interval breast cancers were identified; the estimated interval cancer rate was 1.23/1000 screens [9/7292] (95%CI 0.56 to 2.34) or 1.24/1000 negative screens [9/7235] (95%CI 0.57 to 2.36). In concurrently screened women who attended the same screening services and received 2D-mammography, interval cancer rate was 1.60/1000 screens [40/25,058] (95% CI 1.14 to 2.17) or 1.61/1000 negative screens [40/24,922] (95% CI 1.15 to 2.18). Estimated screening sensitivity for the STORM trial was 85.5% [59/69] (95%CI 75.0%-92.8%), and that for 2D-mammography screening was 77.3% [136/176] (95%CI 70.4%-83.2%). Interval breast cancer rate amongst screening participants in the STORM trial was marginally lower (and screening sensitivity higher) than estimates amongst 2D-screened women; these findings should be interpreted with caution given the small number of interval cases and the sample size of the trial. Much larger screening studies, or pooled analyses, are required to examine interval cancer rates arising after breast tomosynthesis screening versus digital mammography screening. Copyright © 2018 Elsevier Ltd. All rights reserved.

Barriers to and facilitators of compliance with clinic-based cervical cancer screening: population-based cohort study of women aged 23-60 years.

Science.gov (United States)

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

2015-01-01

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. 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. 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. 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

Barriers to and facilitators of compliance with clinic-based cervical cancer screening: population-based cohort study of women aged 23-60 years.

Directory of Open Access Journals (Sweden)

Ellinor Östensson

Full Text Available 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.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.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.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

Designing airport checked-baggage-screening strategies considering system capability and reliability

International Nuclear Information System (INIS)

Feng Qianmei; Sahin, Hande; Kapur, Kailash C.

2009-01-01

Emerging image-based technologies are critical components of airport security for screening checked baggage. Since these new technologies differ widely in cost and accuracy, a comprehensive mathematical framework should be developed for selecting technology or combination of technologies for efficient 100% baggage screening. This paper addresses the problem of setting threshold values of these screening technologies and determining the optimal combination of technologies in a two-level screening system by considering system capability and human reliability. Probability and optimization techniques are used to quantify and evaluate the cost- and risk-effectiveness of various deployment configurations, which is captured by using a system life-cycle cost model that incorporates the deployment cost, operating cost, and costs associated with system decisions. Two system decision rules are studied for a two-level screening system. For each decision rule, two different optimization approaches are formulated and investigated from practitioner's perspective. Numerical examples for different decision rules, optimization approaches and system arrangements are demonstrated

Breast Cancer Screening in Denmark

DEFF Research Database (Denmark)

Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Kalager, Mette

2017-01-01

Background: Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Objective: To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Design......) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing...... rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted...

Development of droplets‐based microfluidic systems for single­‐cell high‐throughput screening

DEFF Research Database (Denmark)

Chen, Jun; Jensen, Thomas Glasdam; Godina, Alexei

2014-01-01

High-throughput screening (HTS) plays an important role in the development of microbial cell factories. One of the most popular approaches is to use microplates combined with the application of robotics, liquid handling and sophisticated detection methods. However, these workstations require large...... investment, and a logarithmic increase to screen large combinatorial libraries over the decades also makes it gradually out of depth. Here, we are trying to develop a feasible high‐throughput system that uses microfluidics to compartmentalize a single cell for propagation and analysis in monodisperse...... picoliter aqueous droplets surround by an immiscible fluorinated oil phase. Our aim is to use this system to facilitate the screening process for both the biotechnology and food industry....

Variations in screening outcome among pairs of screening radiologists at non-blinded double reading of screening mammograms: a population-based study

NARCIS (Netherlands)

Klompenhouwer, E. G.; Duijm, L. E. M.; Voogd, A. C.; den Heeten, G. J.; Nederend, J.; Jansen, F. H.; Broeders, M. J. M.

2014-01-01

Substantial inter-observer variability in screening mammography interpretation has been reported at single reading. However, screening results of pairs of screening radiologists have not yet been published. We determined variations in screening performances among pairs of screening radiologists at

Screening and syndromic approaches to identify gonorrhea and chlamydial infection among women.

Science.gov (United States)

Sloan, N L; Winikoff, B; Haberland, N; Coggins, C; Elias, C

2000-03-01

The standard diagnostic tools to identify sexually transmitted infections are often expensive and have laboratory and infrastructure requirements that make them unavailable to family planning and primary health-care clinics in developing countries. Therefore, inexpensive, accessible tools that rely on symptoms, signs, and/or risk factors have been developed to identify and treat reproductive tract infections without the need for laboratory diagnostics. Studies were reviewed that used standard diagnostic tests to identify gonorrhea and cervical chlamydial infection among women and that provided adequate information about the usefulness of the tools for screening. Aggregation of the studies' results suggest that risk factors, algorithms, and risk scoring for syndromic management are poor indicators of gonorrhea and chlamydial infection in samples of both low and high prevalence and, consequently, are not effective mechanisms with which to identify or manage these conditions. The development and evaluation of other approaches to identify gonorrhea and chlamydial infections, including inexpensive and simple laboratory screening tools, periodic universal treatment, and other alternatives must be given priority.

Internet-based recruitment system for HIV and STI screening for men who have sex with men in Estonia, 2013: analysis of preliminary outcomes.

Science.gov (United States)

Ruutel, K; Lohmus, L; Janes, J

2015-04-16

The aim of the current project was to develop an Internet-based recruitment system for HIV and sexually transmitted infection (STI) screening for men who have sex with men (MSM) in Estonia in order to collect biological samples during behavioural studies. In 2013, an Internet-based HIV risk-behaviour survey was conducted among MSM living in Estonia. After completing the questionnaire, all participants were offered anonymous and free-of-charge STI testing. They could either order a urine sample kit by post to screen for chlamydia infections (including lymphogranuloma venereum (LGV)), trichomoniasis, gonorrhoea and Mycoplasma genitalium infections, or visit a laboratory for HIV, hepatitis A virus, hepatitis B virus,hepatitis C virus and syphilis screening. Of 301 participants who completed the questionnaire, 265 (88%),reported that they were MSM. Of these 265 MSM,68 (26%) underwent various types of testing. In the multiple regression analysis, Russian as the first language,previous HIV testing and living in a city or town increased the odds of testing during the study. Linking Internet-based behavioural data collection with biological sample collection is a promising approach. As there are no specific STI services for MSM in Estonia,this system could also be used as an additional option for anonymous and free-of-charge STI screening.

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Aman C. Kaushik

2018-02-01

Full Text Available GPR142 (G protein receptor 142 is a novel orphan GPCR (G protein coupled receptor belonging to “Class A” of GPCR family and expressed in β cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling, and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

Science.gov (United States)

Kaushik, Aman C.; Kumar, Sanjay; Wei, Dong Q.; Sahi, Shakti

2018-02-01

GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to ‘Class A’ of GPCR family and expressed in beta cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Estimates of over-diagnosis of breast cancer due to population-based mammography screening in South Australia after adjustment for lead time effects.

Science.gov (United States)

Beckmann, Kerri; Duffy, Stephen W; Lynch, John; Hiller, Janet; Farshid, Gelareh; Roder, David

2015-09-01

To estimate over-diagnosis due to population-based mammography screening using a lead time adjustment approach, with lead time measures based on symptomatic cancers only. Women aged 40-84 in 1989-2009 in South Australia eligible for mammography screening. Numbers of observed and expected breast cancer cases were compared, after adjustment for lead time. Lead time effects were modelled using age-specific estimates of lead time (derived from interval cancer rates and predicted background incidence, using maximum likelihood methods) and screening sensitivity, projected background breast cancer incidence rates (in the absence of screening), and proportions screened, by age and calendar year. Lead time estimates were 12, 26, 43 and 53 months, for women aged 40-49, 50-59, 60-69 and 70-79 respectively. Background incidence rates were estimated to have increased by 0.9% and 1.2% per year for invasive and all breast cancer. Over-diagnosis among women aged 40-84 was estimated at 7.9% (0.1-12.0%) for invasive cases and 12.0% (5.7-15.4%) when including ductal carcinoma in-situ (DCIS). We estimated 8% over-diagnosis for invasive breast cancer and 12% inclusive of DCIS cancers due to mammography screening among women aged 40-84. These estimates may overstate the extent of over-diagnosis if the increasing prevalence of breast cancer risk factors has led to higher background incidence than projected. © The Author(s) 2015.

Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial.

Science.gov (United States)

Skaane, Per; Sebuødegård, Sofie; Bandos, Andriy I; Gur, David; Østerås, Bjørn Helge; Gullien, Randi; Hofvind, Solveig

2018-02-10

Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening. Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting women 50-69 years biennially, comparing full-field digital mammography (FFDM) plus DBT with FFDM alone. Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds. 24,301 consenting women underwent FFDM + DBT screening over a 2-year period. Results were compared with 59,877 FFDM examinations during prior rounds. Addition of DBT resulted in a non-significant increase in sensitivity (76.2%, 378/496, vs. 80.8%, 227/281, p = 0.151) and a significant increase in specificity (96.4%, 57229/59381 vs. 97.5%, 23427/24020, p < .001). Number of recalls per screen-detected cancer decreased from 6.7 (2530/378) to 3.6 (820/227) with DBT (p < .001). Cancer detection per 1000 women screened increased (6.3, 378/59877, vs. 9.3, 227/24301, p < .001). Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds (2.1, 51/24301 vs. 2.0, 118/59877, p = 0.734). Interval cancers post-DBT were comparable to prior rounds but significantly different in size, grade, and node status from cancers detected only using DBT. 39.6% (19/48) of interval cancers had positive nodes compared with only 3.9% (2/51) of additional DBT-only-detected cancers. DBT-supplemented screening resulted in significant increases in screen-detected cancers and specificity. However, no significant change was observed in the rate, size, node status, or grade of interval cancers. ClinicalTrials.gov: NCT01248546.

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

Science.gov (United States)

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 (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.

A fluorescence-based rapid screening assay for cytotoxic compounds

International Nuclear Information System (INIS)

Montoya, Jessica; Varela-Ramirez, Armando; Estrada, Abril; Martinez, Luis E.; Garza, Kristine; Aguilera, Renato J.

2004-01-01

A simple fluorescence-based assay was developed for the rapid screening of potential cytotoxic compounds generated by combinatorial chemistry. The assay is based on detection of nuclear green fluorescent protein (GFP) staining of a human cervical cancer cell line (HeLa) carrying an integrated histone H2B-GFP fusion gene. Addition of a cytotoxic compound to the HeLa-GFP cells results in the eventual degradation of DNA and loss of the GFP nuclear fluorescence. Using this assay, we screened 11 distinct quinone derivatives and found that several of these compounds were cytotoxic. These compounds are structurally related to plumbagin an apoptosis-inducing naphthoquinone isolated from Black Walnut. In order to determine the mechanism by which cell death was induced, we performed additional experiments with the most cytotoxic quinones. These compounds were found to induce morphological changes (blebbing and nuclear condensation) consistent with induction of apoptosis. Additional tests revealed that the cytotoxic compounds induce both necrotic and apoptotic modes of death

Screen printed Y and Bi-based superconductors

Science.gov (United States)

Haertling, Gene H.; Hsi, Chi-Shiung

1992-01-01

High T(sub c) superconducting thick film was prepared by screen printing process. Y-based (YBa2Cu3O(7 - x)) superconducting thick films were printed on 211/Al2O3, SNT/Al2O3, and YSZ substrates. Because of poor adhesion of the superconducting thick films to 211/Al2O3 and SNT/Al2O3 substrates, relatively low T(sub c) and J(sub c) values were obtained from the films printed on these substrates. Critical temperatures of YBa2Cu3O(7 - x) thick films deposited on 211/Al2O3 and SNT/Al2O3 substrates were about 80 K. The critical current densities of these films were less than 2 A/cm(exp 2). Higher T(sub c) and J(sub c) films were printed on the YSZ substrates; T(sub c) = 86.4 K and J(sub c) = 50.4 A/cm(exp 2). Multiple lead samples were also prepared on the YSZ substrates. These showed lower T(sub c) and J(sub c) values than plain samples. The heat treatment conditions of the multiple lead samples are still under investigation. Bi-based superconductor thick films have been obtained so far. Improving the superconducting properties of the BSCCO screen printed thick films will be emphasized in future work.

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

Science.gov (United States)

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

A Tiered Approach to Retinopathy of Prematurity Screening (TARP) Using a Weight Gain Predictive Model and a Telemedicine System.

Science.gov (United States)

Gurwin, Jaclyn; Tomlinson, Lauren A; Quinn, Graham E; Ying, Gui-Shuang; Baumritter, Agnieshka; Binenbaum, Gil

2017-01-05

The Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study telemedicine system of remote fundus image grading and The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP-ROP) postnatal weight gain predictive model are 2 approaches for improving ROP screening efficiency. Current screening has low specificity for severe ROP. To describe a tiered approach to ROP screening (TARP) for identifying children who develop severe ROP using telemedicine and a predictive model synergistically. This investigation was a post hoc analysis of a cohort in the e-ROP Study (a multicenter prospective telemedicine study) and the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study (a multicenter retrospective cohort study). The setting was neonatal intensive care units at The Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Participants in the e-ROP Study were premature infants with a birth weight less than 1251 g and a known ROP outcome enrolled between May 25, 2011, and October 31, 2013. The G-ROP Study enrolled all infants undergoing ROP examinations with a known ROP outcome who were born between January 1, 2006, and December 31, 2011. The mean outcomes were the sensitivity for type 1 ROP, reductions in infants requiring imaging or examinations, numbers of imaging sessions and examinations, and total clinical encounters (imaging sessions and examinations combined). The following 4 screening approaches were evaluated: ROUTINE (only diagnostic examinations by an ophthalmologist), CHOP-ROP (birth weight and gestational age, with weekly weight gain initiating examinations when the risk cut point is surpassed), e-ROP IMAGING (trained reader grading of type 1 or 2 ROP initiates diagnostic examinations), and TARP (CHOP-ROP alarm initiates imaging, and imaging finding of severe ROP initiates diagnostic examinations). A total of 242 infants were included in the study, with a median birth

The In Situ Enzymatic Screening (ISES) Approach to Reaction Discovery and Catalyst Identification.

Science.gov (United States)

Swyka, Robert A; Berkowitz, David B

2017-12-14

The importance of discovering new chemical transformations and/or optimizing catalytic combinations has led to a flurry of activity in reaction screening. The in situ enzymatic screening (ISES) approach described here utilizes biological tools (enzymes/cofactors) to advance chemistry. The protocol interfaces an organic reaction layer with an adjacent aqueous layer containing reporting enzymes that act upon the organic reaction product, giving rise to a spectroscopic signal. ISES allows the experimentalist to rapidly glean information on the relative rates of a set of parallel organic/organometallic reactions under investigation, without the need to quench the reactions or draw aliquots. In certain cases, the real-time enzymatic readout also provides information on sense and magnitude of enantioselectivity and substrate specificity. This article contains protocols for single-well (relative rate) and double-well (relative rate/enantiomeric excess) ISES, in addition to a colorimetric ISES protocol and a miniaturized double-well procedure. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

3D mosquito screens to create window double screen traps for mosquito control.

Science.gov (United States)

Khattab, Ayman; Jylhä, Kaisa; Hakala, Tomi; Aalto, Mikko; Malima, Robert; Kisinza, William; Honkala, Markku; Nousiainen, Pertti; Meri, Seppo

2017-08-29

Mosquitoes are vectors for many diseases such as malaria. Insecticide-treated bed nets and indoor residual spraying of insecticides are the principal malaria vector control tools used to prevent malaria in the tropics. Other interventions aim at reducing man-vector contact. For example, house screening provides additive or synergistic effects to other implemented measures. We used commercial screen materials made of polyester, polyethylene or polypropylene to design novel mosquito screens that provide remarkable additional benefits to those commonly used in house screening. The novel design is based on a double screen setup made of a screen with 3D geometric structures parallel to a commercial mosquito screen creating a trap between the two screens. Owing to the design of the 3D screen, mosquitoes can penetrate the 3D screen from one side but cannot return through the other side, making it a unidirectional mosquito screen. Therefore, the mosquitoes are trapped inside the double screen system. The permissiveness of both sides of the 3D screens for mosquitoes to pass through was tested in a wind tunnel using the insectary strain of Anopheles stephensi. Among twenty-five tested 3D screen designs, three designs from the cone, prism, or cylinder design groups were the most efficient in acting as unidirectional mosquito screens. The three cone-, prism-, and cylinder-based screens allowed, on average, 92, 75 and 64% of Anopheles stephensi mosquitoes released into the wind tunnel to penetrate the permissive side and 0, 0 and 6% of mosquitoes to escape through the non-permissive side, respectively. A cone-based 3D screen fulfilled the study objective. It allowed capturing 92% of mosquitoes within the double screen setup inside the wind tunnel and blocked 100% from escaping. Thus, the cone-based screen effectively acted as a unidirectional mosquito screen. This 3D screen-based trap design could therefore be used in house screening as a means of avoiding infective bites and

Societal costs and effects of implementing population-based mammography screening in Greenland

DEFF Research Database (Denmark)

Christensen, Maria Klitgaard; Niclasen, Birgit; Moesgaard Iburg, Kim

2017-01-01

With a low breast cancer incidence and low population density, Greenland is geographically and organisationally challenged in implementing a cost effective breast cancer screening programme where a large proportion of the Greenlandic women will have to travel far to attend. The aim of this paper ...... transportation and accommodation costs and loss of productivity, and none would be accepted as cost-effective per YLS/QALY gained within a conventional threshold level. The least expensive strategy was regional screening with hotel accommodation.......With a low breast cancer incidence and low population density, Greenland is geographically and organisationally challenged in implementing a cost effective breast cancer screening programme where a large proportion of the Greenlandic women will have to travel far to attend. The aim of this paper...... is to evaluate the cost effectiveness and cost utility of different strategies for implementing population-based breast cancer screening in Greenland. Two strategies were evaluated: Centralised screening in the capital Nuuk and decentralised screening in the five municipal regions of Greenland. A cost...

Non-visit-based cancer screening using a novel population management system.

Science.gov (United States)

Atlas, Steven J; Zai, Adrian H; Ashburner, Jeffrey M; Chang, Yuchiao; Percac-Lima, Sanja; Levy, Douglas E; Chueh, Henry C; Grant, Richard W

2014-01-01

Advances in information technology (IT) now permit population-based preventive screening, but the best methods remain uncertain. We evaluated whether involving primary care providers (PCPs) in a visit-independent population management IT application led to more effective cancer screening. We conducted a cluster-randomized trial involving 18 primary care practice sites and 169 PCPs from June 15, 2011, to June 14, 2012. Participants included adults eligible for breast, cervical, and/or colorectal cancer screening. In practices randomized to the intervention group, PCPs reviewed real-time rosters of their patients overdue for screening and provided individualized contact (via a letter, practice delegate, or patient navigator) or deferred screening (temporarily or permanently). In practices randomized to the comparison group, overdue patients were automatically sent reminder letters and transferred to practice delegate lists for follow-up. Intervention patients without PCP action within 8 weeks defaulted to the automated control version. The primary outcome was adjusted average cancer screening completion rates over 1-year follow-up, accounting for clustering by physician or practice. Baseline cancer screening rates (80.8% vs 80.3%) were similar among patients in the intervention (n = 51,071) and comparison group (n = 52,799). Most intervention providers used the IT application (88 of 101, 87%) and users reviewed 7984 patients overdue for at least 1 cancer screening (73% sent reminder letter, 6% referred directly to a practice delegate or patient navigator, and 21% deferred screening). In addition, 6128 letters were automatically sent to patients in the intervention group (total of 12,002 letters vs 16,378 letters in comparison practices; P management IT application resulted in similar cancer screening rates compared with an automated reminder system, but fewer patients were sent reminder letters. This suggests that PCPs were able to identify and exclude from contact

Design and evaluation of a theory-based, culturally relevant outreach model for breast and cervical cancer screening for Latina immigrants.

Science.gov (United States)

White, Kari; Garces, Isabel C; Bandura, Lisa; McGuire, Allison A; Scarinci, Isabel C

2012-01-01

Breast and cervical cancer are common among Latinas, but screening rates among foreign-born Latinas are relatively low. In this article we describe the design and implementation of a theory-based (PEN-3) outreach program to promote breast and cervical cancer screening to Latina immigrants, and evaluate the program's effectiveness. We used data from self-administered questionnaires completed at six annual outreach events to examine the sociodemographic characteristics of attendees and evaluate whether the program reached the priority population - foreign-born Latina immigrants with limited access to health care and screening services. To evaluate the program's effectiveness in connecting women to screening, we examined the proportion and characteristics of women who scheduled and attended Pap smear and mammography appointments. Among the 782 Latinas who attended the outreach program, 60% and 83% had not had a Pap smear or mammogram, respectively, in at least a year. Overall, 80% scheduled a Pap smear and 78% scheduled a mammogram. Women without insurance, who did not know where to get screening and had not been screened in the last year were more likely to schedule appointments (P < .05). Among women who scheduled appointments, 65% attended their Pap smear and 79% attended the mammogram. We did not identify significant differences in sociodemographic characteristics associated with appointment attendance. Using a theoretical approach to outreach design and implementation, it is possible to reach a substantial number of Latina immigrants and connect them to cancer screening services.

Accelerometry-based gait analysis, an additional objective approach to screen subjects at risk for falling.

Science.gov (United States)

Senden, R; Savelberg, H H C M; Grimm, B; Heyligers, I C; Meijer, K

2012-06-01

This study investigated whether the Tinetti scale, as a subjective measure for fall risk, is associated with objectively measured gait characteristics. It is studied whether gait parameters are different for groups that are stratified for fall risk using the Tinetti scale. Moreover, the discriminative power of gait parameters to classify elderly according to the Tinetti scale is investigated. Gait of 50 elderly with a Tinneti>24 and 50 elderly with a Tinetti≤24 was analyzed using acceleration-based gait analysis. Validated algorithms were used to derive spatio-temporal gait parameters, harmonic ratio, inter-stride amplitude variability and root mean square (RMS) from the accelerometer data. Clear differences in gait were found between the groups. All gait parameters correlated with the Tinetti scale (r-range: 0.20-0.73). Only walking speed, step length and RMS showed moderate to strong correlations and high discriminative power to classify elderly according to the Tinetti scale. It is concluded that subtle gait changes that have previously been related to fall risk are not captured by the subjective assessment. It is therefore worthwhile to include objective gait assessment in fall risk screening. Copyright © 2012 Elsevier B.V. All rights reserved.

Machine Learning Consensus Scoring Improves Performance Across Targets in Structure-Based Virtual Screening.

Science.gov (United States)

Ericksen, Spencer S; Wu, Haozhen; Zhang, Huikun; Michael, Lauren A; Newton, Michael A; Hoffmann, F Michael; Wildman, Scott A

2017-07-24

In structure-based virtual screening, compound ranking through a consensus of scores from a variety of docking programs or scoring functions, rather than ranking by scores from a single program, provides better predictive performance and reduces target performance variability. Here we compare traditional consensus scoring methods with a novel, unsupervised gradient boosting approach. We also observed increased score variation among active ligands and developed a statistical mixture model consensus score based on combining score means and variances. To evaluate performance, we used the common performance metrics ROCAUC and EF1 on 21 benchmark targets from DUD-E. Traditional consensus methods, such as taking the mean of quantile normalized docking scores, outperformed individual docking methods and are more robust to target variation. The mixture model and gradient boosting provided further improvements over the traditional consensus methods. These methods are readily applicable to new targets in academic research and overcome the potentially poor performance of using a single docking method on a new target.

Pediatric-based intervention to motivate mothers to seek follow-up for depression screens: The Motivating Our Mothers (MOM) trial.

Science.gov (United States)

Fernandez y Garcia, Erik; Joseph, Jill; Wilson, Machelle D; Hinton, Ladson; Simon, Gregory; Ludman, Evette; Scott, Fiona; Kravitz, Richard L

2015-01-01

To determine the initial effectiveness of a novel, pediatric office-based intervention in motivating mothers to seek further assessment of positive depression screens. In this pilot randomized controlled trial, English-speaking mothers (n = 104) with positive 2-question depression screens and presenting with children 0 to 12 years old for well-child care to a general pediatric training clinic received interventions from a trained research assistant. The Motivating Our Mothers (MOM) intervention included office-based written and verbal targeted depression education and motivational messages encouraging further depression assessment and a semistructured telephone booster delivered 2 days later. The control intervention included nontargeted written and verbal messages and 2 days later, an attention control telephone survey. Both groups received a list of depression care resources. The primary outcome was the proportion of mothers in each group who reported trying to contact any of 6 types of resources to discuss the positive screen at 2 weeks after intervention (ClinicalTrials.gov NCT01453790). Despite 6 contact attempts, 10 MOM and 9 control mothers were lost to follow-up. More mothers in the MOM intervention tried to contact a resource compared to control (73.8% vs 53.5%, difference 20.3%, 95% confidence interval for difference -0.1 to 38.5, P = .052). Mothers receiving the MOM intervention made more attempts to contact a resource for follow-up of positive depression screens. If found effective in larger studies, MOM may prove a promising approach for motivating depression screen-positive mothers identified in general pediatric settings within and beyond the postpartum period to seek further depression assessment and support. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Human papillomavirus self-sampling for screening nonattenders

DEFF Research Database (Denmark)

Lam, Janni Uyen Hoa; Rebolj, Matejka; Ejegod, Ditte Møller

2017-01-01

was well-accepted among nonattenders. Adopting modern technology-based platforms into the current organized screening program would serve as a convenient communication method between health authority and citizens, allowing easy access for the citizen and reducing the work load in administrating self-sampling......In organized cervical screening programs, typically 25% of the invited women do not attend. The Copenhagen Self-sampling Initiative (CSi) aimed to gain experiences on participation among screening nonattenders in the Capital Region of Denmark. Here, we report on the effectiveness of different...... communication platforms used in the pilot with suggestions for strategies prior to a full-implementation. Moreover, an innovative approach using self-sampling brushes with unique radio frequency identification chips allowed for unprecedented levels patient identification safety. Nonattenders from the capital...

Screening for Inborn Errors of Metabolism

Directory of Open Access Journals (Sweden)

F.A. Elshaari

2013-09-01

Full Text Available Inborn errors of metabolism (IEM are a heterogeneous group of monogenic diseases that affect the metabolic pathways. The detection of IEM relies on a high index of clinical suspicion and co-ordinated access to specialized laboratory services. Biochemical analysis forms the basis of the final confirmed diagnosis in several of these disorders. The investigations fall into four main categories1.General metabolic screening tests2.Specific metabolite assays3.Enzyme studies4.DNA analysis The first approach to the diagnosis is by a multi-component analysis of body fluids in clinically selected patients, referred to as metabolic screening tests. These include simple chemical tests in the urine, blood glucose, acid-base profile, lactate, ammonia and liver function tests. The results of these tests can help to suggest known groups of metabolic disorders so that specific metabolites such as amino acids, organic acids, etc. can be estimated. However, not all IEM needs the approach of general screening. Lysosomal, peroxisomal, thyroid and adrenal disorders are suspected mainly on clinical grounds and pertinent diagnostic tests can be performed. The final diagnosis relies on the demonstration of the specific enzyme defect, which can be further confirmed by DNA studies.

Computational approaches to screen candidate ligands with anti- Parkinson's activity using R programming.

Science.gov (United States)

Jayadeepa, R M; Niveditha, M S

2012-01-01

It is estimated that by 2050 over 100 million people will be affected by the Parkinson's disease (PD). We propose various computational approaches to screen suitable candidate ligand with anti-Parkinson's activity from phytochemicals. Five different types of dopamine receptors have been identified in the brain, D1-D5. Dopamine receptor D3 was selected as the target receptor. The D3 receptor exists in areas of the brain outside the basal ganglia, such as the limbic system, and thus may play a role in the cognitive and emotional changes noted in Parkinson's disease. A ligand library of 100 molecules with anti-Parkinson's activity was collected from literature survey. Nature is the best combinatorial chemist and possibly has answers to all diseases of mankind. Failure of some synthetic drugs and its side effects have prompted many researches to go back to ancient healing methods which use herbal medicines to give relief. Hence, the candidate ligands with anti-Parkinson's were selected from herbal sources through literature survey. Lipinski rules were applied to screen the suitable molecules for the study, the resulting 88 molecules were energy minimized, and subjected to docking using Autodock Vina. The top eleven molecules were screened according to the docking score generated by Autodock Vina Commercial drug Ropinirole was computed similarly and was compared with the 11 phytochemicals score, the screened molecules were subjected to toxicity analysis and to verify toxic property of phytochemicals. R Programming was applied to remove the bias from the top eleven molecules. Using cluster analysis and Confusion Matrix two phytochemicals were computationally selected namely Rosmarinic acid and Gingkolide A for further studies on the disease Parkinson's.

Infrared Thermography Approach for Effective Shielding Area of Field Smoke Based on Background Subtraction and Transmittance Interpolation.

Science.gov (United States)

Tang, Runze; Zhang, Tonglai; Chen, Yongpeng; Liang, Hao; Li, Bingyang; Zhou, Zunning

2018-05-06

Effective shielding area is a crucial indicator for the evaluation of the infrared smoke-obscuring effectiveness on the battlefield. The conventional methods for assessing the shielding area of the smoke screen are time-consuming and labor intensive, in addition to lacking precision. Therefore, an efficient and convincing technique for testing the effective shielding area of the smoke screen has great potential benefits in the smoke screen applications in the field trial. In this study, a thermal infrared sensor with a mid-wavelength infrared (MWIR) range of 3 to 5 μm was first used to capture the target scene images through clear as well as obscuring smoke, at regular intervals. The background subtraction in motion detection was then applied to obtain the contour of the smoke cloud at each frame. The smoke transmittance at each pixel within the smoke contour was interpolated based on the data that was collected from the image. Finally, the smoke effective shielding area was calculated, based on the accumulation of the effective shielding pixel points. One advantage of this approach is that it utilizes only one thermal infrared sensor without any other additional equipment in the field trial, which significantly contributes to the efficiency and its convenience. Experiments have been carried out to demonstrate that this approach can determine the effective shielding area of the field infrared smoke both practically and efficiently.

Infrared Thermography Approach for Effective Shielding Area of Field Smoke Based on Background Subtraction and Transmittance Interpolation

Directory of Open Access Journals (Sweden)

Runze Tang

2018-05-01

Full Text Available Effective shielding area is a crucial indicator for the evaluation of the infrared smoke-obscuring effectiveness on the battlefield. The conventional methods for assessing the shielding area of the smoke screen are time-consuming and labor intensive, in addition to lacking precision. Therefore, an efficient and convincing technique for testing the effective shielding area of the smoke screen has great potential benefits in the smoke screen applications in the field trial. In this study, a thermal infrared sensor with a mid-wavelength infrared (MWIR range of 3 to 5 μm was first used to capture the target scene images through clear as well as obscuring smoke, at regular intervals. The background subtraction in motion detection was then applied to obtain the contour of the smoke cloud at each frame. The smoke transmittance at each pixel within the smoke contour was interpolated based on the data that was collected from the image. Finally, the smoke effective shielding area was calculated, based on the accumulation of the effective shielding pixel points. One advantage of this approach is that it utilizes only one thermal infrared sensor without any other additional equipment in the field trial, which significantly contributes to the efficiency and its convenience. Experiments have been carried out to demonstrate that this approach can determine the effective shielding area of the field infrared smoke both practically and efficiently.

A novel Antibody based approach to Cancer Treatment

Directory of Open Access Journals (Sweden)

Yoshikazu Kurosawa

2010-01-01

Full Text Available Cancer is one of the leading causes of death among the human race. No valid modalities of treatment other than surgical treatment have been established for this disease. We aimed to identify and to characterize cancer using large number of human monoclonal antibodies (mAbs which are specific against their surface for new molecular targeted immunotherapy. In order to find proper targets for therapeutic antibodies against cancers we developed a screening strategy. We used a huge phage library of human antibodies. At the first step we comprehensively isolated many monoclonal antibodies (mAbs that specifically bound to surface of cancer cells. Development of ICOS (Isolation of antigen/antibody complexes through organic solvent method allowed us to succeed in isolation of a huge number of mAbs with various characteristics (Y Akahori et al. 2009. At the next step we selected clones that showed tumor-specific staining patterns in immunohistochemical (IHC analysis by using many fresh cancer tissues reseted. Many surgeons took part in this project. Finally the antigens recognized by these clones were identified by immunoprecipitation (IP followed by analysis with mass (MS spectrometry (G Kurosawa et al. 2009. We have succeeded in identification of 29 tumor-associated antigens (TAAs and in isolation of 441 human mAbs that specifically bound to one of the 29 TAAs (G Kurosawa et al. 2008. In these screenings of the library, rounds of the selection process, mixing of cells and phage particles centrifugation growth of phages, were repeated three to four times in each screening. Therefore, numbers of phages of the clones whose antigens were abundantly present on the cell surface increased during the screenings. Recently we developed a new method for isolation of clones whose antigens were less abundantly present on the cell surface. Hence, we would like to talk on these methodology and discuss regarding this “A novel antibody based approach to Cancer

Novel approaches for targeting the adenosine A2A receptor.

Science.gov (United States)

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.

Using screen-based simulation of inhaled anaesthetic delivery to improve patient care.

Science.gov (United States)

Philip, J H

2015-12-01

Screen-based simulation can improve patient care by giving novices and experienced clinicians insight into drug behaviour. Gas Man(®) is a screen-based simulation program that depicts pictorially and graphically the anaesthetic gas and vapour tension from the vaporizer to the site of action, namely the brain and spinal cord. The gases and vapours depicted are desflurane, enflurane, ether, halothane, isoflurane, nitrogen, nitrous oxide, sevoflurane, and xenon. Multiple agents can be administered simultaneously or individually and the results shown on an overlay graph. Practice exercises provide in-depth knowledge of the subject matter. Experienced clinicians can simulate anaesthesia occurrences and practices for application to their clinical practice, and publish the results to benefit others to improve patient care. Published studies using this screen-based simulation have led to a number of findings, as follows: changing from isoflurane to desflurane toward the end of anaesthesia does not accelerate recovery in humans; vital capacity induction can produce loss of consciousness in 45 s; simulated context-sensitive decrement times explain recovery profiles; hyperventilation does not dramatically speed emergence; high fresh gas flow is wasteful; fresh gas flow and not the vaporizer setting should be reduced during intubation; re-anaesthetization can occur with severe hypoventilation after extubation; and in re-anaesthetization, the anaesthetic redistributes from skeletal muscle. Researchers using screen-based simulations can study fewer subjects to reach valid conclusions that impact clinical care. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effectiveness of a two-step population-based osteoporosis screening program using FRAX

DEFF Research Database (Denmark)

Rubin, K H; Rothmann, M J; Holmberg, T

2018-01-01

The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in fractures from systematic screening compared to the current case-finding strategy. The group of moderate......- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program. INTRODUCTION: The purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self......-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed. METHODS: Participants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion...

[Population-based breast cancer screening: certainties, controversies, and future perspectives].

Science.gov (United States)

Apesteguía Ciriza, Luis; Pina Insausti, Luis Javier

2014-01-01

Population-based breast cancer screening programs based on mammography must maintain a high level of quality, so the results must be constantly monitored. Although most authors consider that these programs have decreased the mortality due to breast cancer by about 30%, others claim that the mortality has decreased by only about 12% due to errors in the randomization of patients, because the rate of advanced tumors has hardly decreased and because adjuvant treatment also improves survival. Other criticisms focus on overdiagnosis and overtreatment. We believe that despite the unquestionable value of mammographic screening, we should be open to certain changes such as the stratification of patients by their level of risk and the introduction of complementary techniques like tomosynthesis, ultrasonography, and magnetic resonance imaging in selected cases. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Critical Evaluation of Native Electrospray Ionization Mass Spectrometry for Fragment-Based Screening.

Science.gov (United States)

Göth, Melanie; Badock, Volker; Weiske, Jörg; Pagel, Kevin; Kuropka, Benno

2017-08-08

Fragment-based screening presents a promising alternative to high-throughput screening and has gained great attention in recent years. So far, only a few studies have discussed mass spectrometry as a screening technology for fragments. Herein, we report the application of native electrospray ionization mass spectrometry (MS) for screening defined sets of fragments against four different target proteins. Fragments were selected from a primary screening conducted with a thermal shift assay (TSA) and represented different binding categories. Our data indicated that, beside specific complex formation, many fragments show extensive multiple binding and also charge-state shifts. Both of these factors complicate automated data analysis and decrease the attractiveness of native MS as a primary screening tool for fragments. A comparison of the hits identified by native MS and TSA showed good agreement for two of the proteins. Furthermore, we discuss general challenges, including the determination of an optimal fragment concentration and the question of how to rank fragment hits according to their affinity. In conclusion, we consider native MS to be a highly valuable tool for the validation and deeper investigation of promising fragment hits rather than a method for primary screening. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of a fluorescence-based method for antibabesial drug screening.

Science.gov (United States)

Guswanto, Azirwan; Sivakumar, Thillaiampalam; Rizk, Mohamed Abdo; Elsayed, Shimaa Abd Elsalam; Youssef, Mohamed Ahmed; ElSaid, ElSaid El Shirbini; Yokoyama, Naoaki; Igarashi, Ikuo

2014-08-01

In vitro evaluation of chemotherapeutic agents against Babesia and Theileria parasites has become routine, and the effectiveness of these chemicals is usually determined by comparing the parasitemia dynamics of untreated and treated parasites. Although microscopy is widely used to calculate parasitemia, several disadvantages are associated with this technique. The present study evaluated a fluorescence-based method using SYBR green I stain (SG I) to screen antibabesial agents in in vitro cultures of Babesia bovis. The linearity between relative fluorescence units (RFU) and parasitemia was found to be well correlated with a 0.9944 goodness-of-fit (r(2)) value. Subsequently, 50% inhibitory concentration (IC50) values were calculated for 3 antiprotozoan agents, diminazene aceturate, nimbolide, and gedunin, by this method. For diminazene aceturate and nimbolide, the IC(50)s determined by the fluorescence-based method (408 nM and 8.13 μM, respectively) and microscopy (400.3 nM and 9.4 μM, respectively) were in agreement. Furthermore, the IC50 of gedunin determined by the fluorescence-based method (19 μM) was similar to the recently described microscopy-based value (21.7 μM) for B. bovis. Additionally, the Z' factor (0.80 to 0.90), signal-to-noise (S/N) ratio (44.15 to 87.64), coefficient of variation at the maximum signal (%CVmax) (0.50 to 2.85), and coefficient of variation at the minimum signal (%CVmin) (1.23 to 2.21) calculated for the fluorescence method using diminazene aceturate were comparable to those previously determined in malaria research for this assay. These findings suggest that the fluorescence-based method might be useful for antibabesial drug screening and may have potential to be developed into a high-throughput screening (HTS) assay. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers.

Science.gov (United States)

Horeweg, Nanda; Scholten, Ernst Th; de Jong, Pim A; van der Aalst, Carlijn M; Weenink, Carla; Lammers, Jan-Willem J; Nackaerts, Kristiaan; Vliegenthart, Rozemarijn; ten Haaf, Kevin; Yousaf-Khan, Uraujh A; Heuvelmans, Marjolein A; Thunnissen, Erik; Oudkerk, Matthijs; Mali, Willem; de Koning, Harry J

2014-11-01

Low-dose CT screening is recommended for individuals at high risk of developing lung cancer. However, CT screening does not detect all lung cancers: some might be missed at screening, and others can develop in the interval between screens. The NELSON trial is a randomised trial to assess the effect of screening with increasing screening intervals on lung cancer mortality. In this prespecified analysis, we aimed to assess screening test performance, and the epidemiological, radiological, and clinical characteristics of interval cancers in NELSON trial participants assigned to the screening group. Eligible participants in the NELSON trial were those aged 50-75 years, who had smoked 15 or more cigarettes per day for more than 25 years or ten or more cigarettes for more than 30 years, and were still smoking or had quit less than 10 years ago. We included all participants assigned to the screening group who had attended at least one round of screening. Screening test results were based on volumetry using a two-step approach. Initially, screening test results were classified as negative, indeterminate, or positive based on nodule presence and volume. Subsequently, participants with an initial indeterminate result underwent follow-up screening to classify their final screening test result as negative or positive, based on nodule volume doubling time. We obtained information about all lung cancer diagnoses made during the first three rounds of screening, plus an additional 2 years of follow-up from the national cancer registry. We determined epidemiological, radiological, participant, and tumour characteristics by reassessing medical files, screening CTs, and clinical CTs. The NELSON trial is registered at www.trialregister.nl, number ISRCTN63545820. 15,822 participants were enrolled in the NELSON trial, of whom 7915 were assigned to low-dose CT screening with increasing interval between screens, and 7907 to no screening. We included 7155 participants in our study, with

Automatic Tortuosity-Based Retinopathy of Prematurity Screening System

Science.gov (United States)

Sukkaew, Lassada; Uyyanonvara, Bunyarit; Makhanov, Stanislav S.; Barman, Sarah; Pangputhipong, Pannet

Retinopathy of Prematurity (ROP) is an infant disease characterized by increased dilation and tortuosity of the retinal blood vessels. Automatic tortuosity evaluation from retinal digital images is very useful to facilitate an ophthalmologist in the ROP screening and to prevent childhood blindness. This paper proposes a method to automatically classify the image into tortuous and non-tortuous. The process imitates expert ophthalmologists' screening by searching for clearly tortuous vessel segments. First, a skeleton of the retinal blood vessels is extracted from the original infant retinal image using a series of morphological operators. Next, we propose to partition the blood vessels recursively using an adaptive linear interpolation scheme. Finally, the tortuosity is calculated based on the curvature of the resulting vessel segments. The retinal images are then classified into two classes using segments characterized by the highest tortuosity. For an optimal set of training parameters the prediction is as high as 100%.

Status of implementation and organization of cancer screening in The European Union Member States-Summary results from the second European screening report.

Science.gov (United States)

Basu, Partha; Ponti, Antonio; Anttila, Ahti; Ronco, Guglielmo; Senore, Carlo; Vale, Diama Bhadra; Segnan, Nereo; Tomatis, Mariano; Soerjomataram, Isabelle; Primic Žakelj, Maja; Dillner, Joakim; Elfström, Klara Miriam; Lönnberg, Stefan; Sankaranarayanan, Rengaswamy

2018-01-01

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N = 80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only. Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3 and 51.3% in 2016 and 2007, respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2-111% for breast cancer, 7.6-105% for cervical cancer and 1.8-127% for colorectal cancer in the target populations. In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes. © 2017 UICC.

Fluorescence-based high-throughput screening of dicer cleavage activity.

Science.gov (United States)

Podolska, Katerina; Sedlak, David; Bartunek, Petr; Svoboda, Petr

2014-03-01

Production of small RNAs by ribonuclease III Dicer is a key step in microRNA and RNA interference pathways, which employ Dicer-produced small RNAs as sequence-specific silencing guides. Further studies and manipulations of microRNA and RNA interference pathways would benefit from identification of small-molecule modulators. Here, we report a study of a fluorescence-based in vitro Dicer cleavage assay, which was adapted for high-throughput screening. The kinetic assay can be performed under single-turnover conditions (35 nM substrate and 70 nM Dicer) in a small volume (5 µL), which makes it suitable for high-throughput screening in a 1536-well format. As a proof of principle, a small library of bioactive compounds was analyzed, demonstrating potential of the assay.

Yield and Efficiency of Mental Health Screening: A Comparison of Screening Protocols at Intake to Prison.

Science.gov (United States)

Martin, Michael S; Potter, Beth K; Crocker, Anne G; Wells, George A; Colman, Ian

2016-01-01

The value of screening for mental illness has increasingly been questioned in low prevalence settings due to high false positive rates. However, since false positive rates are related to prevalence, screening may be more effective in higher prevalence settings, including correctional institutions. We compared the yield (i.e. newly detected cases) and efficiency (i.e. false positives) of five screening protocols to detect mental illness in prisons against the use of mental health history taking (the prior approach to detecting mental illness). We estimated the accuracy of the six approaches to detect an Axis I disorder among a sample of 467 newly admitted male inmates (83.1% participation rate). Mental health history taking identified only 41.0% (95% CI 32.1, 50.6) of all inmates with mental illness. Screening protocols identified between 61.9 and 85.7% of all cases, but referred between 2 and 3 additional individuals who did not have a mental illness for every additional case detected compared to the mental health history taking approach. In low prevalence settings (i.e. 10% or less) the screening protocols would have had between 4.6 and 16.2 false positives per true positive. While screening may not be practical in low prevalence settings, it may be beneficial in jails and prisons where the prevalence of mental illness is higher. Further consideration of the context in which screening is being implemented, and of the impacts of policies and clinical practices on the benefits and harms of screening is needed to determine the effectiveness of screening in these settings.

Yield and Efficiency of Mental Health Screening: A Comparison of Screening Protocols at Intake to Prison.