[Preference on screening frequency and willingness-to-pay for multiple-cancer packaging screening programs in urban populations in China].

Science.gov (United States)

Zhu, J; Huang, H Y; Mao, A Y; Sun, Z X; Qiu, W Q; Lei, H K; Dong, P; Huang, J W; Bai, Y N; Sun, X J; Liu, G X; Wang, D B; Liao, X Z; Ren, J S; Guo, L W; Lan, L; Zhou, Q; Song, B B; Liu, Y Q; Du, L B; Zhu, L; Cao, R; Wang, J L; Mai, L; Ren, Y; Zhou, J Y; Sun, X H; Wu, S L; Qi, X; Lou, P A; Cai, B; Li, N; Zhang, K; He, J; Dai, M; Shi, J F

2018-02-10

Objective: From an actual cancer screening service demanders' perspective, we tried to understand the preference on screening frequency and willingness-to-pay for the packaging screening program on common cancers and to evaluate its long-term sustainability in urban populations in China. Methods: From 2012 to 2014, a multi-center cross-sectional survey was conducted among the actual screening participants from 13 provinces covered by the Cancer Screening Program in Urban China (CanSPUC). By face-to-face interview, information regarding to preference to screening frequency, willingness-to-pay for packaging screening program, maximum amount on payment and related reasons for unwillingness were investigated. Results: A total of 31 029 participants were included in this survey, with an average age as (55.2±7.5) years and median annual income per family as 25 000 Chinese Yuan. People's preference to screening frequency varied under different assumptions ( " totally free" and "self-paid" ). When the packaging screening was assumed totally free, 93.9% of residents would prefer to take the screening program every 1 to 3 years. However, the corresponding proportion dropped to 67.3% when assuming a self-paid pattern. 76.7% of the participants had the willingness-to-pay for the packaging screening, but only 11.2% of them would like to pay more than 500 Chinese Yuan (the expenditure of the particular packaging screening were about 1 500 Chinese Yuan). The remaining 23.3% of residents showed no willingness-to-pay, and the main reasons were unaffordable expenditure (71.7%) and feeling'no need'(40.4%). Conclusions: People who participated in the CanSPUC program generally tended to choose high-frequency packaging screening program, indicating the high potential acceptance for scale-up packaging screening, while it needs cautious assessments and rational guidance to the public. Although about seven in ten of the residents were willing to pay, the payment amount was limited

Functional analysis screening for multiple topographies of problem behavior.

Science.gov (United States)

Bell, Marlesha C; Fahmie, Tara A

2018-04-23

The current study evaluated a screening procedure for multiple topographies of problem behavior in the context of an ongoing functional analysis. Experimenters analyzed the function of a topography of primary concern while collecting data on topographies of secondary concern. We used visual analysis to predict the function of secondary topographies and a subsequent functional analysis to test those predictions. Results showed that a general function was accurately predicted for five of six (83%) secondary topographies. A specific function was predicted and supported for a subset of these topographies. The experimenters discuss the implication of these results for clinicians who have limited time for functional assessment. © 2018 Society for the Experimental Analysis of Behavior.

Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth

Directory of Open Access Journals (Sweden)

Charalampos Rallis

2014-01-01

Target of rapamycin complex 1 (TORC1, which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We screened a deletion library, comprising ∼84% of all non-essential fission yeast genes, for drug-resistant mutants. This screen identified 33 genes encoding functions such as transcription, kinases, mitochondrial respiration, biosynthesis, intra-cellular trafficking, and stress response. Among the corresponding mutants, 5 showed shortened and 21 showed increased maximal chronological lifespans; 15 of the latter mutants showed no further lifespan increase with rapamycin and might thus represent key targets downstream of TORC1. We pursued the long-lived sck2 mutant with additional functional analyses, revealing that the Sck2p kinase functions within the TORC1 network and is required for normal cell growth, global protein translation, and ribosomal S6 protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth was associated with all long-lived mutants while oxidative-stress resistance was not.

Revealing molecular mechanisms by integrating high-dimensional functional screens with protein interaction data.

Directory of Open Access Journals (Sweden)

Angela Simeone

2014-09-01

Full Text Available Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes. However, they suffer from problems like noise, and often provide little insight into molecular mechanisms. A bottleneck for addressing these issues is the lack of computational methods for the systematic integration of multi-parametric phenotypic datasets with molecular interactions. Here, we present Integrative Multi Profile Analysis of Cellular Traits (IMPACT. The main goal of IMPACT is to identify the most consistent phenotypic profile among interacting genes. This approach utilizes two types of external information: sets of related genes (IMPACT-sets and network information (IMPACT-modules. Based on the notion that interacting genes are more likely to be involved in similar functions than non-interacting genes, this data is used as a prior to inform the filtering of phenotypic profiles that are similar among interacting genes. IMPACT-sets selects the most frequent profile among a set of related genes. IMPACT-modules identifies sub-networks containing genes with similar phenotype profiles. The statistical significance of these selections is subsequently quantified via permutations of the data. IMPACT (1 handles multiple profiles per gene, (2 rescues genes with weak phenotypes and (3 accounts for multiple biases e.g. caused by the network topology. Application to a genome-wide RNAi screen on endocytosis showed that IMPACT improved the recovery of known endocytosis-related genes, decreased off-target effects, and detected consistent phenotypes. Those findings were confirmed by rescreening 468 genes. Additionally we validated an unexpected influence of the IGF-receptor on EGF-endocytosis. IMPACT facilitates the selection of high-quality phenotypic profiles using different types of independent information, thereby supporting the molecular interpretation of functional screens.

Screens

OpenAIRE

2016-01-01

This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).

Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening

Science.gov (United States)

Machutta, Carl A.; Kollmann, Christopher S.; Lind, Kenneth E.; Bai, Xiaopeng; Chan, Pan F.; Huang, Jianzhong; Ballell, Lluis; Belyanskaya, Svetlana; Besra, Gurdyal S.; Barros-Aguirre, David; Bates, Robert H.; Centrella, Paolo A.; Chang, Sandy S.; Chai, Jing; Choudhry, Anthony E.; Coffin, Aaron; Davie, Christopher P.; Deng, Hongfeng; Deng, Jianghe; Ding, Yun; Dodson, Jason W.; Fosbenner, David T.; Gao, Enoch N.; Graham, Taylor L.; Graybill, Todd L.; Ingraham, Karen; Johnson, Walter P.; King, Bryan W.; Kwiatkowski, Christopher R.; Lelièvre, Joël; Li, Yue; Liu, Xiaorong; Lu, Quinn; Lehr, Ruth; Mendoza-Losana, Alfonso; Martin, John; McCloskey, Lynn; McCormick, Patti; O'Keefe, Heather P.; O'Keeffe, Thomas; Pao, Christina; Phelps, Christopher B.; Qi, Hongwei; Rafferty, Keith; Scavello, Genaro S.; Steiginga, Matt S.; Sundersingh, Flora S.; Sweitzer, Sharon M.; Szewczuk, Lawrence M.; Taylor, Amy; Toh, May Fern; Wang, Juan; Wang, Minghui; Wilkins, Devan J.; Xia, Bing; Yao, Gang; Zhang, Jean; Zhou, Jingye; Donahue, Christine P.; Messer, Jeffrey A.; Holmes, David; Arico-Muendel, Christopher C.; Pope, Andrew J.; Gross, Jeffrey W.; Evindar, Ghotas

2017-07-01

The identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus. The success of this effort led to the hypothesis that the relative number of ELT binders alone could be used to assess the ligandability of large sets of proteins. This concept was further explored by screening 42 targets from Mycobacterium tuberculosis. Active chemical series for six targets from our initial effort as well as three chemotypes for DHFR from M. tuberculosis are reported. The findings demonstrate that parallel ELT selections can be used to assess ligandability and highlight opportunities for successful lead and tool discovery.

Reliability and validity of a Danish version of the multiple sclerosis neuropsychological screening Questionnaire

DEFF Research Database (Denmark)

Sejbæk, Tobias; Blaabjerg, Morten; Sprogøe, Pippi

2018-01-01

. The Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) has previously shown good validity in American, Argentinean, and Dutch MS cohorts. We sought to test reliability and validity of a Danish translation of the MSNQ compared with formal neuropsychological testing, and measures of depression...... the Expanded Disability Status Scale and MS Impairment Scale. Results: The test-retest reliability of the MSNQ-P was significant (R2 = 0.79, P ... that the MSNQ-P measures these items more than the cognitive abilities of the patients. Conclusions: This study does not support use of the MSNQ as a sensitive or valid screening tool for cognitive impairment in Danish patients with MS....

Decision-making and cancer screening: a qualitative study of older adults with multiple chronic conditions.

Science.gov (United States)

Gross, Cary P; Fried, Terri R; Tinetti, Mary E; Ross, Joseph S; Genao, Inginia; Hossain, Sabina; Wolf, Elizabeth; Lewis, Carmen L

2015-03-01

To understand how older persons with multiple chronic conditions (MCC) approach decisions about cancer screening. We conducted interviews with adults >65 years old with at least two chronic conditions who were taking ≥five medications daily. Patients were first asked how age and multimorbidity influence their cancer screening decisions. After showing them an educational prompt that explained the relationship between life expectancy and the benefits of cancer screening, respondents were then asked about screening in the context of specific health scenarios. Using grounded theory, three independent readers coded responses for salient themes. Sample size was determined by thematic saturation. Most respondents (26 of 28) initially indicated that their overall health or medical conditions do not influence their cancer screening decisions. After viewing the educational prompt, respondents described two broad approaches to cancer screening in the setting of increasing age or multi-morbidity. The first was a "benefits versus harms" approach in which participants weighed direct health benefits (e.g. reducing cancer incidence or mortality) and harms (e.g. complications or inconvenience). The second was a heuristic approach. Some heuristics favored screening, such as a persistent belief in unspecified benefits from screening, value of knowledge about cancer status, and not wanting to "give up", whereas other heuristics discouraged screening, such as fatalism or a reluctance to learn about their cancer status. When considering cancer screening, some older persons with MCC employ heuristics which circumvent the traditional quantitative comparison of risks and benefits, providing an important challenge to informed decision making. Copyright © 2014 Elsevier Inc. All rights reserved.

X-ray diffraction imaging with the Multiple Inverse Fan Beam topology: Principles, performance and potential for security screening

Energy Technology Data Exchange (ETDEWEB)

Harding, G., E-mail: Geoffrey.Harding@Morphodetection.com [Morpho Detection Germany GmbH, Heselstuecken 3, 22453 Hamburg (Germany); Fleckenstein, H.; Kosciesza, D.; Olesinski, S.; Strecker, H.; Theedt, T.; Zienert, G. [Morpho Detection Germany GmbH, Heselstuecken 3, 22453 Hamburg (Germany)

2012-07-15

The steadily increasing number of explosive threat classes, including home-made explosives (HMEs), liquids, amorphous and gels (LAGs), is forcing up the false-alarm rates of security screening equipment. This development can best be countered by increasing the number of features available for classification. X-ray diffraction intrinsically offers multiple features for both solid and LAGs explosive detection, and is thus becoming increasingly important for false-alarm and cost reduction in both carry-on and checked baggage security screening. Following a brief introduction to X-ray diffraction imaging (XDI), which synthesizes in a single modality the image-forming and material-analysis capabilities of X-rays, the Multiple Inverse Fan Beam (MIFB) XDI topology is described. Physical relationships obtaining in such MIFB XDI components as the radiation source, collimators and room-temperature detectors are presented with experimental performances that have been achieved. Representative X-ray diffraction profiles of threat substances measured with a laboratory MIFB XDI system are displayed. The performance of Next-Generation (MIFB) XDI relative to that of the 2nd Generation XRD 3500{sup TM} screener (Morpho Detection Germany GmbH) is assessed. The potential of MIFB XDI, both for reducing the exorbitant cost of false alarms in hold baggage screening (HBS), as well as for combining 'in situ' liquid and solid explosive detection in carry-on luggage screening is outlined. - Highlights: Black-Right-Pointing-Pointer X-ray diffraction imaging (XDI) synthesizes analysis and imaging in one x-ray modality. Black-Right-Pointing-Pointer A novel XDI beam topology comprising multiple inverse fan-beams (MIFB) is described. Black-Right-Pointing-Pointer The MIFB topology is technically easy to realize and has high photon collection efficiency. Black-Right-Pointing-Pointer Applications are envisaged in checkpoint, hold baggage and cargo screening.

Screening of freshwater fungi for decolorizing multiple synthetic dyes.

Science.gov (United States)

Yang, Panpan; Shi, Wenxiao; Wang, Hongkai; Liu, Hongmei

The biodegradation of synthetic dyes by fungi is emerging as an effective and promising approach. In the present study, freshwater fungal strains isolated from submerged woods were screened for the decolorization of 7 synthetic dyes. Subsequently, 13 isolates with high decolorization capability were assessed in a liquid system; they belonged to 9 different fungal species. Several strains exhibited a highly effective decolorization of multiple types of dyes. New absorbance peaks appeared after the treatment with 3 fungal strains, which suggests that a biotransformation process occurred through fungal biodegradation. These results showed the unexploited and valuable capability of freshwater fungi for the treatment of dye-containing effluents. The ability of certain fungi to decolorize dyes is reported here for the first time. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development.

Science.gov (United States)

Covassin, L D; Siekmann, A F; Kacergis, M C; Laver, E; Moore, J C; Villefranc, J A; Weinstein, B M; Lawson, N D

2009-05-15

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.

Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

International Nuclear Information System (INIS)

Liu, Yaou; Duan, Yunyun; He, Yong; Yu, Chunshui; Wang, Jun; Huang, Jing; Ye, Jing; Parizel, Paul M.; Li, Kuncheng; Shu, Ni

2012-01-01

Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS

Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

Energy Technology Data Exchange (ETDEWEB)

Liu, Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Duan, Yunyun, E-mail: xiaoyun81.love@163.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); He, Yong, E-mail: yong.h.he@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Yu, Chunshui, E-mail: csyuster@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Wang, Jun, E-mail: jun_wang@bnu.edu.cn [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Huang, Jing, E-mail: sainthj@126.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Ye, Jing, E-mail: jingye.2007@yahoo.com.cn [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Parizel, Paul M., E-mail: paul.parizel@ua.ac.be [Department of Radiology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, 8 Belgium (Belgium); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni, E-mail: nshu55@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China)

2012-10-15

Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS.

X-ray diffraction imaging with the Multiple Inverse Fan Beam topology: principles, performance and potential for security screening.

Science.gov (United States)

Harding, G; Fleckenstein, H; Kosciesza, D; Olesinski, S; Strecker, H; Theedt, T; Zienert, G

2012-07-01

The steadily increasing number of explosive threat classes, including home-made explosives (HMEs), liquids, amorphous and gels (LAGs), is forcing up the false-alarm rates of security screening equipment. This development can best be countered by increasing the number of features available for classification. X-ray diffraction intrinsically offers multiple features for both solid and LAGs explosive detection, and is thus becoming increasingly important for false-alarm and cost reduction in both carry-on and checked baggage security screening. Following a brief introduction to X-ray diffraction imaging (XDI), which synthesizes in a single modality the image-forming and material-analysis capabilities of X-rays, the Multiple Inverse Fan Beam (MIFB) XDI topology is described. Physical relationships obtaining in such MIFB XDI components as the radiation source, collimators and room-temperature detectors are presented with experimental performances that have been achieved. Representative X-ray diffraction profiles of threat substances measured with a laboratory MIFB XDI system are displayed. The performance of Next-Generation (MIFB) XDI relative to that of the 2nd Generation XRD 3500TM screener (Morpho Detection Germany GmbH) is assessed. The potential of MIFB XDI, both for reducing the exorbitant cost of false alarms in hold baggage screening (HBS), as well as for combining "in situ" liquid and solid explosive detection in carry-on luggage screening is outlined. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

Science.gov (United States)

Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

2009-07-01

The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

Multiple-Layer Parking with Screening

NARCIS (Netherlands)

van Enter, Aernout; Fleurke, Sjoert; Rudas, Imre J.

2015-01-01

In this article a multilayer parking system with screening of size n = 3 is studied with a focus on the time-dependent particle density. We prove that the asymptotic limit of the particle density increases from an average density of 1/3 on the first layer to the value of (10 − √5 )/19 ≈ 0.4086 in

Genomic screening for dissection of a complex disease: The multiple sclerosis phenotype

Energy Technology Data Exchange (ETDEWEB)

Haines, J.L.; Bazyk, A.; Gusella, J.F. [Massachusetts General Hospital, Boston, MA (United States)] [and others

1994-09-01

Application of positional cloning to diseases with a complex etiology is fraught with problems. These include undefined modes of inheritance, heterogeneity, and epistasis. Although microsatellite markers now make genotyping the genome a straightforward task, no single analytical method is available to efficiently and accurately use these data for a complex disease. We have developed a multi-stage genomic screening strategy which uses a combination of non-parametric approaches (Affected Pedigree Member (APM) linkage analysis and robust sib pair analysis (SP)), and the parametric lod score approach (using four different genetic models). To warrant follow-up, a marker must have two or more of: a nominal P value of 0.05 or less on the non-parametric tests, or a lod score greater than 1.0 for any model. Two adjacent markers each fulfilling one criterion are also considered for follow-up. These criteria were determined both by simulation studies and our empirical experience in screening a large number of other disorders. We applied this approach to multiple sclerosis (MS), a complex neurological disorder with a strong but ill-defined genetic component. Analysis of the first 91 markers from our screen of 55 multiplex families found 5 markers which met the SP criteria, 13 markers which met the APM criteria, and 8 markers which met the lod score criteria. Five regions (on chromosomes 2, 4, 7, 14, and 19) met our overall criteria. However, no single method identified all of these regions, suggesting that each method is sensitive to various (unknown) influences. The chromosome 14 results were not supported by follow-up typing and analysis of markers in that region, but the chromosome 19 results remain well supported. Updated screening results will be presented.

Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

Science.gov (United States)

Lebensohn, Andres M; Dubey, Ramin; Neitzel, Leif R; Tacchelly-Benites, Ofelia; Yang, Eungi; Marceau, Caleb D; Davis, Eric M; Patel, Bhaven B; Bahrami-Nejad, Zahra; Travaglini, Kyle J; Ahmed, Yashi; Lee, Ethan; Carette, Jan E; Rohatgi, Rajat

2016-01-01

The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway. These include a requirement for the transcription factor AP-4, a role for the DAX domain of AXIN2 in controlling β-catenin transcriptional activity, a contribution of glycophosphatidylinositol anchor biosynthesis and glypicans to R-spondin-potentiated WNT signaling, and two different mechanisms that regulate signaling when distinct components of the β-catenin destruction complex are lost. The conceptual and methodological framework we describe should enable the comprehensive understanding of other signaling systems. DOI: http://dx.doi.org/10.7554/eLife.21459.001 PMID:27996937

Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

Science.gov (United States)

Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

2016-08-18

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

Big pharma screening collections: more of the same or unique libraries? The AstraZeneca-Bayer Pharma AG case.

Science.gov (United States)

Kogej, Thierry; Blomberg, Niklas; Greasley, Peter J; Mundt, Stefan; Vainio, Mikko J; Schamberger, Jens; Schmidt, Georg; Hüser, Jörg

2013-10-01

In this study, the screening collections of two major pharmaceutical companies (AstraZeneca and Bayer Pharma AG) have been compared using a 2D molecular fingerprint by a nearest neighborhood approach. Results revealed a low overlap between both collections in terms of compound identity and similarity. This emphasizes the value of screening multiple compound collections to expand the chemical space that can be accessed by high-throughput screening (HTS). Copyright © 2012 Elsevier Ltd. All rights reserved.

Alkylation sensitivity screens reveal a conserved cross-species functionome

Science.gov (United States)

Svilar, David; Dyavaiah, Madhu; Brown, Ashley R.; Tang, Jiang-bo; Li, Jianfeng; McDonald, Peter R.; Shun, Tong Ying; Braganza, Andrea; Wang, Xiao-hong; Maniar, Salony; St Croix, Claudette M.; Lazo, John S.; Pollack, Ian F.; Begley, Thomas J.; Sobol, Robert W.

2013-01-01

To identify genes that contribute to chemotherapy resistance in glioblastoma, we conducted a synthetic lethal screen in a chemotherapy-resistant glioblastoma derived cell line with the clinical alkylator temozolomide (TMZ) and an siRNA library tailored towards “druggable” targets. Select DNA repair genes in the screen were validated independently, confirming the DNA glycosylases UNG and MYH as well as MPG to be involved in the response to high dose TMZ. The involvement of UNG and MYH is likely the result of a TMZ-induced burst of reactive oxygen species. We then compared the human TMZ sensitizing genes identified in our screen with those previously identified from alkylator screens conducted in E. coli and S. cerevisiae. The conserved biological processes across all three species composes an Alkylation Functionome that includes many novel proteins not previously thought to impact alkylator resistance. This high-throughput screen, validation and cross-species analysis was then followed by a mechanistic analysis of two essential nodes: base excision repair (BER) DNA glycosylases (UNG, human and mag1, S. cerevisiae) and protein modification systems, including UBE3B and ICMT in human cells or pby1, lip22, stp22 and aim22 in S. cerevisiae. The conserved processes of BER and protein modification were dual targeted and yielded additive sensitization to alkylators in S. cerevisiae. In contrast, dual targeting of BER and protein modification genes in human cells did not increase sensitivity, suggesting an epistatic relationship. Importantly, these studies provide potential new targets to overcome alkylating agent resistance. PMID:23038810

[Exome sequencing revealed Allan-Herndon-Dudley syndrome underlying multiple disabilities].

Science.gov (United States)

Arvio, Maria; Philips, Anju K; Ahvenainen, Minna; Somer, Mirja; Kalscheuer, Vera; Järvelä, Irma

2014-01-01

Normal function of the thyroid gland is the cornerstone of a child's mental development and physical growth. We describe a Finnish family, in which the diagnosis of three brothers became clear after investigations that lasted for more than 30 years. Two of the sons have already died. DNA analysis of the third one, a 16-year-old boy, revealed in exome sequencing of the complete X chromosome a mutation in the SLC16A2 gene, i.e. MCT8, coding for a thyroid hormone transport protein. Allan-Herndon-Dudley syndrome was thus shown to be the cause of multiple disabilities.

Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

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Xiaoke Ma

2015-06-01

Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

Revealing the uncultivated majority: combining DNA stable-isotope probing, multiple displacement amplification and metagenomic analyses of uncultivated Methylocystis in acidic peatlands.

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Chen, Yin; Dumont, Marc G; Neufeld, Josh D; Bodrossy, Levente; Stralis-Pavese, Nancy; McNamara, Niall P; Ostle, Nick; Briones, Maria J I; Murrell, J Colin

2008-10-01

Peatlands represent an enormous carbon reservoir and have a potential impact on the global climate because of the active methanogenesis and methanotrophy in these soils. Uncultivated methanotrophs from seven European peatlands were studied using a combination of molecular methods. Screening for methanotroph diversity using a particulate methane monooxygenase-based diagnostic gene array revealed that Methylocystis-related species were dominant in six of the seven peatlands studied. The abundance and methane oxidation activity of Methylocystis spp. were further confirmed by DNA stable-isotope probing analysis of a sample taken from the Moor House peatland (England). After ultracentrifugation, (13)C-labelled DNA, containing genomic DNA of these Methylocystis spp., was separated from (12)C DNA and subjected to multiple displacement amplification (MDA) to generate sufficient DNA for the preparation of a fosmid metagenomic library. Potential bias of MDA was detected by fingerprint analysis of 16S rRNA using denaturing gradient gel electrophoresis for low-template amplification (0.01 ng template). Sufficient template (1-5 ng) was used in MDA to circumvent this bias and chimeric artefacts were minimized by using an enzymatic treatment of MDA-generated DNA with S1 nuclease and DNA polymerase I. Screening of the metagenomic library revealed one fosmid containing methanol dehydrogenase and two fosmids containing 16S rRNA genes from these Methylocystis-related species as well as one fosmid containing a 16S rRNA gene related to that of Methylocella/Methylocapsa. Sequencing of the 14 kb methanol dehydrogenase-containing fosmid allowed the assembly of a gene cluster encoding polypeptides involved in bacterial methanol utilization (mxaFJGIRSAC). This combination of DNA stable-isotope probing, MDA and metagenomics provided access to genomic information of a relatively large DNA fragment of these thus far uncultivated, predominant and active methanotrophs in peatland soil.

Subtitle Synchronization across Multiple Screens and Devices

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Aitor Rodriguez-Alsina

2012-06-01

Full Text Available Ambient Intelligence is a new paradigm in which environments are sensitive and responsive to the presence of people. This is having an increasing importance in multimedia applications, which frequently rely on sensors to provide useful information to the user. In this context, multimedia applications must adapt and personalize both content and interfaces in order to reach acceptable levels of context-specific quality of service for the user, and enable the content to be available anywhere and at any time. The next step is to make content available to everybody in order to overcome the existing access barriers to content for users with specific needs, or else to adapt to different platforms, hence making content fully usable and accessible. Appropriate access to video content, for instance, is not always possible due to the technical limitations of traditional video packaging, transmission and presentation. This restricts the flexibility of subtitles and audio-descriptions to be adapted to different devices, contexts and users. New Web standards built around HTML5 enable more featured applications with better adaptation and personalization facilities, and thus would seem more suitable for accessible AmI environments. This work presents a video subtitling system that enables the customization, adaptation and synchronization of subtitles across different devices and multiple screens. The benefits of HTML5 applications for building the solution are analyzed along with their current platform support. Moreover, examples of the use of the application in three different cases are presented. Finally, the user experience of the solution is evaluated.

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

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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.

Utility of multiple rule out CT screening of high-risk atraumatic patients in an emergency department-a feasibility study

DEFF Research Database (Denmark)

Pries-Heje, Mia M; Hasselbalch, Rasmus B; Raaschou, Henriette

2018-01-01

malignant tumors in 10 (10%) cases. The mean size specific radiation dose was 15.9 mSv (± 3.1 mSv). CONCLUSION: Screening with a multi-rule out CT scan of high-risk patients in an ED is feasible and result in discovery of clinically unrecognized diagnoses and malignant tumors, but at the cost of radiation......BACKGROUND: Several large trials have evaluated the effect of CT screening based on specific symptoms, with varying outcomes. Screening of patients with CT based on their prognosis alone has not been examined before. For moderate-to-high risk patients presenting in the emergency department (ED......), the potential gain from a CT scan might outweigh the risk of radiation exposure. We hypothesized that an accelerated "multiple rule out" CT screening of moderate-to-high risk patients will detect many clinically unrecognized diagnoses that affect change in treatment. METHOD: Patients ≥ 40 years, triaged as high...

Genome-Wide RNAi Ionomics Screen Reveals New Genes and Regulation of Human Trace Element Metabolism

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Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei; Lutsenko, Svetlana; Gladyshev, Vadim N.

2017-01-01

Trace elements are essential for human metabolism and dysregulation of their homeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundamental differences in the regulation of different trace elements. Specifically, selenium levels are controlled through the selenocysteine machinery and expression of abundant selenoproteins; copper balance is affected by lipid metabolism and requires machinery involved in protein trafficking and posttranslational modifications; and the iron levels are influenced by iron import and expression of the iron/heme-containing enzymes. Our approach can be applied to a variety of disease models and/or nutritional conditions, and the generated dataset opens new directions for studies of human trace element metabolism. PMID:24522796

Dual gene activation and knockout screen reveals directional dependencies in genetic networks. | Office of Cancer Genomics

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Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.

A Multiplexed Assay That Monitors Effects of Multiple Compound Treatment Times Reveals Candidate Immune-Enhancing Compounds.

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Zhao, Ziyan; Henowitz, Liza; Zweifach, Adam

2018-05-01

We previously developed a flow cytometry assay that monitored lytic granule exocytosis in cytotoxic T lymphocytes stimulated by contacting beads coated with activating anti-CD3 antibodies. That assay was multiplexed in that responses of cells that did or did not receive the activating stimulus were distinguished via changes in light scatter accompanying binding of cells to beads, allowing us to discriminate compounds that activate responses on their own from compounds that enhance responses in cells that received the activating stimulus, all within a single sample. Here we add a second dimension of multiplexing by developing means to assess in a single sample the effects of treating cells with test compounds for different times. Bar-coding cells before adding them to test wells lets us determine compound treatment time while also monitoring activation status and response amplitude at the point of interrogation. This multiplexed assay is suitable for screening 96-well plates. We used it to screen compounds from the National Cancer Institute, identifying several compounds that enhance anti-LAMP1 responses. Multiple-treatment-time (MTT) screening enabled by bar-coding and read via high-throughput flow cytometry may be a generally useful method for facilitating the discovery of compounds of interest.

A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1.

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Karen M Chisholm

Full Text Available Alu-mediated rearrangement of tumor suppressor genes occurs frequently during carcinogenesis. In breast cancer, this mechanism contributes to loss of the wild-type BRCA1 allele in inherited disease and to loss of heterozygosity in sporadic cancer. To identify genes required for suppression of Alu-mediated recombination we performed a genomewide screen of a collection of 4672 yeast gene deletion mutants using a direct repeat recombination assay. The primary screen and subsequent analysis identified 12 candidate genes including TSA, ELG1, and RRM3, which are known to play a significant role in maintaining genomic stability. Genetic analysis of the corresponding human homologs was performed in sporadic breast tumors and in inherited BRCA1-associated carcinomas. Sequencing of these genes in high risk breast cancer families revealed a potential role for the helicase PIF1 in cancer predisposition. PIF1 variant L319P was identified in three breast cancer families; importantly, this variant, which is predicted to be functionally damaging, was not identified in a large series of controls nor has it been reported in either dbSNP or the 1000 Genomes Project. In Schizosaccharomyces pombe, Pfh1 is required to maintain both mitochondrial and nuclear genomic integrity. Functional studies in yeast of human PIF1 L319P revealed that this variant cannot complement the essential functions of Pfh1 in either the nucleus or mitochondria. Our results provide a global view of nonessential genes involved in suppressing Alu-mediated recombination and implicate variation in PIF1 in breast cancer predisposition.

Multiple skeletal muscle metastases revealing a cardiac intimal sarcoma

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Crombe, Amandine [Institut Bergonie, Department of Radiology, Bordeaux (France); Lintingre, Pierre-Francois; Dallaudiere, Benjamin [Clinique du Sport de Bordeaux-Merignac, Department of Musculoskeletal Radiology, Merignac (France); Le Loarer, Francois [Institut Bergonie, Department of Pathology, Bordeaux (France); Lachatre, Denis [Dupuytren University Hospital, Department of Radiology, Limoges (France)

2018-01-15

We report the case of a 59-year-old female with progressive bilateral painful swelling of the thighs. MRI revealed multiple intramuscular necrotic masses with similar morphologic patterns. Whole-body CT and 18-FDG PET-CT scans demonstrated additional hypermetabolic muscular masses and a lobulated lesion within the left atrial cavity. As biopsy of a muscular mass was compatible with a poorly differentiated sarcoma with MDM2 oncogene amplification, two diagnoses were discussed: a dedifferentiated liposarcoma with muscle and heart metastases or a primary cardiac sarcoma, mainly a cardiac intimal sarcoma, with muscular metastases, which was finally confirmed by array-comparative genomic hybridization (aCGH) in a sarcoma reference center. This case emphasizes the potential for intimal sarcoma to disseminate in skeletal muscle prior to any other organ and the need for a genomic approach in addition to classical radiopathologic analyses to distinguish primary from secondary locations facing simultaneous tumors of the heart and skeletal muscles with MDM2 amplification. (orig.)

Functional Genomic Screening Reveals Core Modulators of Echinocandin Stress Responses in Candida albicans

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Tavia Caplan

2018-05-01

Full Text Available Summary: Candida albicans is a leading cause of death due to fungal infection. Treatment of systemic candidiasis often relies on echinocandins, which disrupt cell wall synthesis. Resistance is readily acquired via mutations in the drug target gene, FKS1. Both basal tolerance and resistance to echinocandins require cellular stress responses. We performed a systematic analysis of 3,030 C. albicans mutants to define circuitry governing cellular responses to echinocandins. We identified 16 genes for which deletion or transcriptional repression enhanced echinocandin susceptibility, including components of the Pkc1-MAPK signaling cascade. We discovered that the molecular chaperone Hsp90 is required for the stability of Pkc1 and Bck1, establishing key mechanisms through which Hsp90 mediates echinocandin resistance. We also discovered that perturbation of the CCT chaperonin complex causes enhanced echinocandin sensitivity, altered cell wall architecture, and aberrant septin localization. Thus, we provide insights into the mechanisms by which cellular chaperones enable crucial responses to echinocandin-induced stress. : Caplan et al. screen 3,030 Candida albicans mutants to define circuitry governing cellular responses to echinocandins, the first-line therapy for systemic candidiasis. They reveal that the molecular chaperone Hsp90 is required for stability of Pkc1 and Bck1 and that the CCT chaperonin complex is a key modulator of echinocandin susceptibility. Keywords: fungal pathogen, Candida albicans, echinocandins, Hsp90, Pkc1, CCT complex, client protein, stress response, functional genomic screen, drug resistance

The development of an observational screening tool to assess safe, effective and appropriate walking aid use in people with multiple sclerosis.

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Eitzen, Abby; Finlayson, Marcia; Carolan-Laing, Leanne; Nacionales, Arthur Junn; Walker, Christie; O'Connor, Josephine; Asano, Miho; Coote, Susan

2017-08-01

The purpose of this study was to identify potential items for an observational screening tool to assess safe, effective and appropriate walking aid use among people with multiple sclerosis (MS). Such a tool is needed because of the association between fall risk and mobility aid use in this population. Four individuals with MS were videotaped using a one or two straight canes, crutches or a rollator in different settings. Seventeen health care professionals from Canada, Ireland and the United States were recruited, and viewed the videos, and were then interviewed about the use of the devices by the individuals in the videos. Interview questions addressed safety, effectiveness and appropriateness of the device in the setting. Data were analyzed qualitatively. Coding consistency across raters was evaluated and confirmed. Nineteen codes were identified as possible items for the screening tool. The most frequent issues raised regardless of setting and device were "device used for duration/abandoned", "appropriate device", "balance and stability", "device technique", "environmental modification" and "hands free." With the identification of a number of potential tool items, researchers can now move forward with the development of the tool. This will involve consultation with both healthcare professionals and people with MS. Implications for rehabilitation Falls among people with multiple sclerosis are associated with mobility device use and use of multiple devices is associated with greater falls risk. The ability to assess for safe, effective and efficient use of walking aids is therefore important, no tools currently exist for this purpose. The codes arising from this study will be used to develop a screening tool for safe, effective and efficient walking aid use with the aim of reducing falls risk.

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

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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.

A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia

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Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

2014-01-01

In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia. PMID:24860163

Primary care colorectal cancer screening correlates with breast cancer screening: implications for colorectal cancer screening improvement interventions.

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Weiss, Jennifer M; Pandhi, Nancy; Kraft, Sally; Potvien, Aaron; Carayon, Pascale; Smith, Maureen A

2018-04-25

National colorectal cancer (CRC) screening rates have plateaued. To optimize interventions targeting those unscreened, a better understanding is needed of how this preventive service fits in with multiple preventive and chronic care needs managed by primary care providers (PCPs). This study examines whether PCP practices of other preventive and chronic care needs correlate with CRC screening. We performed a retrospective cohort study of 90 PCPs and 33,137 CRC screening-eligible patients. Five PCP quality metrics (breast cancer screening, cervical cancer screening, HgbA1c and LDL testing, and blood pressure control) were measured. A baseline correlation test was performed between these metrics and PCP CRC screening rates. Multivariable logistic regression with clustering at the clinic-level estimated odds ratios and 95% confidence intervals for these PCP quality metrics, patient and PCP characteristics, and their relationship to CRC screening. PCP CRC screening rates have a strong correlation with breast cancer screening rates (r = 0.7414, p < 0.001) and a weak correlation with the other quality metrics. In the final adjusted model, the only PCP quality metric that significantly predicted CRC screening was breast cancer screening (OR 1.25; 95% CI 1.11-1.42; p < 0.001). PCP CRC screening rates are highly concordant with breast cancer screening. CRC screening is weakly concordant with cervical cancer screening and chronic disease management metrics. Efforts targeting PCPs to increase CRC screening rates could be bundled with breast cancer screening improvement interventions to increase their impact and success.

Pathway-based analysis of genome-wide siRNA screens reveals the regulatory landscape of APP processing.

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Luiz Miguel Camargo

Full Text Available The progressive aggregation of Amyloid-β (Aβ in the brain is a major trait of Alzheimer's Disease (AD. Aβ is produced as a result of proteolytic processing of the β-amyloid precursor protein (APP. Processing of APP is mediated by multiple enzymes, resulting in the production of distinct peptide products: the non-amyloidogenic peptide sAPPα and the amyloidogenic peptides sAPPβ, Aβ40, and Aβ42. Using a pathway-based approach, we analyzed a large-scale siRNA screen that measured the production of different APP proteolytic products. Our analysis identified many of the biological processes/pathways that are known to regulate APP processing and have been implicated in AD pathogenesis, as well as revealing novel regulatory mechanisms. Furthermore, we also demonstrate that some of these processes differentially regulate APP processing, with some mechanisms favouring production of certain peptide species over others. For example, synaptic transmission having a bias towards regulating Aβ40 production over Aβ42 as well as processes involved in insulin and pancreatic biology having a bias for sAPPβ production over sAPPα. In addition, some of the pathways identified as regulators of APP processing contain genes (CLU, BIN1, CR1, PICALM, TREM2, SORL1, MEF2C, DSG2, EPH1A recently implicated with AD through genome wide association studies (GWAS and associated meta-analysis. In addition, we provide supporting evidence and a deeper mechanistic understanding of the role of diabetes in AD. The identification of these processes/pathways, their differential impact on APP processing, and their relationships to each other, provide a comprehensive systems biology view of the "regulatory landscape" of APP.

Screening for Intimate Partner Violence in Orthopedic Patients: A Comparison of Three Screening Tools

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Sprague, Sheila; Madden, Kim; Dosanjh, Sonia; Petrisor, Brad; Schemitsch, Emil H.; Bhandari, Mohit

2012-01-01

Accurately identifying victims of intimate partner violence (IPV) can be a challenge for clinicians and clinical researchers. Multiple instruments have been developed and validated to identify IPV in patients presenting to health care practitioners, including the Woman Abuse Screening Tool (WAST) and the Partner Violence Screen (PVS). The purpose…

The correlates of preschoolers' compliance with screen recommendations exist across multiple domains.

Science.gov (United States)

Hinkley, Trina; Salmon, Jo; Okely, Anthony D; Crawford, David

2013-09-01

To investigate the individual, social and physical environment correlates of preschool children's compliance with Australian/Canadian and American Academy of Pediatrics (AAP) screen recommendations. An Ecological Model (EM) was used to identify constructs potentially associated with children's screen time. In 2008-2009, parents in Melbourne, Australia, reported their child's screen time and on a range of potential correlates. Children (n = 935; 54% boys, mean age 4.54 ± 0.70 years) were assessed as meeting or not meeting each of the screen recommendations. Logistic regression assessed bivariable and multivariable associations. In total, 15 explanatory variables, across the three domains of the EM were associated with boys' and/or girls' compliance with either Australian/Canadian or AAP recommendations. Correlates varied by sex and recommendation. Maternal television viewing time was the only consistent correlate for both boys' and girls' compliance with both recommendations. No demographic groups were identified as being less likely to comply with screen recommendations. Public health programs should take account of the sex-specific nature of correlates of preschool children's screen time. Preschool children across all demographic groups need support to engage in less screen use. Parents may benefit from education and parenting skills to minimize potentially harmful effects of excessive screen time for their child. Copyright © 2013 Elsevier Inc. All rights reserved.

Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis

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Giaever Guri

2009-01-01

Full Text Available Abstract Background Single genome-wide screens for the effect of altered gene dosage on drug sensitivity in the model organism Saccharomyces cerevisiae provide only a partial picture of the mechanism of action of a drug. Results Using the example of the tumor cell invasion inhibitor dihydromotuporamine C, we show that a more complete picture of drug action can be obtained by combining different chemical genomics approaches – analysis of the sensitivity of ρ0 cells lacking mitochondrial DNA, drug-induced haploinsufficiency, suppression of drug sensitivity by gene overexpression and chemical-genetic synthetic lethality screening using strains deleted of nonessential genes. Killing of yeast by this chemical requires a functional mitochondrial electron-transport chain and cytochrome c heme lyase function. However, we find that it does not require genes associated with programmed cell death in yeast. The chemical also inhibits endocytosis and intracellular vesicle trafficking and interferes with vacuolar acidification in yeast and in human cancer cells. These effects can all be ascribed to inhibition of sphingolipid biosynthesis by dihydromotuporamine C. Conclusion Despite their similar conceptual basis, namely altering drug sensitivity by modifying gene dosage, each of the screening approaches provided a distinct set of information that, when integrated, revealed a more complete picture of the mechanism of action of a drug on cells.

RNAi screen reveals an Abl kinase-dependent host cell pathway involved in Pseudomonas aeruginosa internalization.

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Julia F Pielage

2008-03-01

Full Text Available Internalization of the pathogenic bacterium Pseudomonas aeruginosa by non-phagocytic cells is promoted by rearrangements of the actin cytoskeleton, but the host pathways usurped by this bacterium are not clearly understood. We used RNAi-mediated gene inactivation of approximately 80 genes known to regulate the actin cytoskeleton in Drosophila S2 cells to identify host molecules essential for entry of P. aeruginosa. This work revealed Abl tyrosine kinase, the adaptor protein Crk, the small GTPases Rac1 and Cdc42, and p21-activated kinase as components of a host signaling pathway that leads to internalization of P. aeruginosa. Using a variety of complementary approaches, we validated the role of this pathway in mammalian cells. Remarkably, ExoS and ExoT, type III secreted toxins of P. aeruginosa, target this pathway by interfering with GTPase function and, in the case of ExoT, by abrogating P. aeruginosa-induced Abl-dependent Crk phosphorylation. Altogether, this work reveals that P. aeruginosa utilizes the Abl pathway for entering host cells and reveals unexpected complexity by which the P. aeruginosa type III secretion system modulates this internalization pathway. Our results furthermore demonstrate the applicability of using RNAi screens to identify host signaling cascades usurped by microbial pathogens that may be potential targets for novel therapies directed against treatment of antibiotic-resistant infections.

SCREENING FOR PERSONALITY DISORDERS

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Morse, Jennifer Q.; Pilkonis, Paul A.

2010-01-01

A brief but valid self-report measure to screen for personality disorders (PDs) would be a valuable tool in making decisions about further assessment and in planning optimal treatments. In psychiatric and nonpsychiatric samples, we compared the validity of three screening measures: the PD scales from the Inventory of Interpersonal Problems, a self-report version of the Iowa Personality Disorder Screen, and the self-directedness scale of the Temperament and Character Inventory. Despite their different theoretical origins, the screeners were highly correlated in a range from .71 to .77. As a result, the use of multiple screeners was not a significant improvement over any individual screener, and no single screener stood out as clearly superior to the others. Each performed modestly in predicting the presence of any PD diagnosis in both the psychiatric and nonpsychiatric groups. Performance was best when predicting a more severe PD diagnosis in the psychiatric sample. The results also highlight the potential value of multiple assessments when relying on self-reports. PMID:17492920

A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma

International Nuclear Information System (INIS)

Palumbo, Tiziana; Poultsides, George A.; Kouraklis, Grigorios; Liakakos, Theodore; Drakaki, Alexandra; Peros, George; Hatziapostolou, Maria; Iliopoulos, Dimitrios

2016-01-01

Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma. The online version of this article (doi:10.1186/s12885-016-2384-0) contains supplementary material, which is available to authorized users

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

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

2009-12-01

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

Mycobacterium malmesburyense sp. nov., a non-tuberculous species of the genus Mycobacterium revealed by multiple gene sequence characterization

CSIR Research Space (South Africa)

Gcebe, N

2017-04-01

Full Text Available Journal of Systematic and Evolutionary Microbiology: DOI 10.1099/ijsem.0.001678 Mycobacterium malmesburyense sp. nov., a non-tuberculous species of the genus Mycobacterium revealed by multiple gene sequence characterization Gcebe N Rutten V Gey...

Breast Cancer Screening

International Nuclear Information System (INIS)

Altaf, Fadwa J.

2004-01-01

Breast cancer is a very common health problem in Saudi females that can be reduced by early detection through introducing breast cancer screening. Literature review reveals significant reduction in breast cancer incidence and outcome after the beginning of breast cancer screening. The objectives of this article are to highlight the significance of breast cancer screening in different international societies and to write the major guidelines of breast cancer screening in relation to other departments involved with more emphasis on the Pathology Department guidelines in tissue handling, diagnostic criteria and significance of the diagnosis. This article summaries and acknowledges major work carried out before, and recommends similar modified work in order to meet the requirement for the Saudi society. (author)

Multiple surveys employing a new sample-processing protocol reveal the genetic diversity of placozoans in Japan.

Science.gov (United States)

Miyazawa, Hideyuki; Nakano, Hiroaki

2018-03-01

Placozoans, flat free-living marine invertebrates, possess an extremely simple bauplan lacking neurons and muscle cells and represent one of the earliest-branching metazoan phyla. They are widely distributed from temperate to tropical oceans. Based on mitochondrial 16S rRNA sequences, 19 haplotypes forming seven distinct clades have been reported in placozoans to date. In Japan, placozoans have been found at nine locations, but 16S genotyping has been performed at only two of these locations. Here, we propose a new processing protocol, "ethanol-treated substrate sampling," for collecting placozoans from natural environments. We also report the collection of placozoans from three new locations, the islands of Shikine-jima, Chichi-jima, and Haha-jima, and we present the distribution of the 16S haplotypes of placozoans in Japan. Multiple surveys conducted at multiple locations yielded five haplotypes that were not reported previously, revealing high genetic diversity in Japan, especially at Shimoda and Shikine-jima Island. The observed geographic distribution patterns were different among haplotypes; some were widely distributed, while others were sampled only from a single location. However, samplings conducted on different dates at the same sites yielded different haplotypes, suggesting that placozoans of a given haplotype do not inhabit the same site constantly throughout the year. Continued sampling efforts conducted during all seasons at multiple locations worldwide and the development of molecular markers within the haplotypes are needed to reveal the geographic distribution pattern and dispersal history of placozoans in greater detail.

Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.

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Mohan Babu

2014-02-01

Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.

Zebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.

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Yaping Sun

Full Text Available Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na(+/K(+ ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na(+/K(+ ATPase α3 subunit (ATP1A3. Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxidants protects DA neurons from Neriifolin-induced death. These results reveal a previously unknown effect of cardiac glycosides on DA neuronal survival and suggest that it is mediated through ATP1A3 inhibition, oxidative stress, and p53. They also elucidate potential approaches for counteracting the neurotoxicity of this valuable class of medications.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

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David Judah

Full Text Available Integrin-linked kinase (ILK is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

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Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

CLAD DEGRADATION - FEPS SCREENING ARGUMENTS

International Nuclear Information System (INIS)

R. Schreiner

2004-01-01

The purpose of this report is to evaluate and document the screening of the clad degradation features, events, and processes (FEPs) with respect to modeling used to support the Total System Performance Assessment-License Application (TSPA-LA). This report also addresses the effect of certain FEPs on both the cladding and the commercial spent nuclear fuel (CSNF), DOE-owned spent nuclear fuel (DSNF), and defense high-level waste (DHLW) waste forms, as appropriate to address the effects on multiple materials and both components (FEPs 2.1.09.09.0A, 2.1.09.11.0A, 2.1.11.05.0A, 2.1.12.02.0A, and 2.1.12.03.0A). These FEPs are expected to affect the repository performance during the postclosure regulatory period of 10,000 years after permanent closure. Table 1-1 provides the list of cladding FEPs, including their screening decisions (include or exclude). The primary purpose of this report is to identify and document the analysis, screening decision, and TSPA-LA disposition (for included FEPs) or screening argument (for excluded FEPs) for these FEPs related to clad degradation. In some cases, where a FEP covers multiple technical areas and is shared with other FEP reports, this report may provide only a partial technical basis for the screening of the FEP. The full technical basis for shared FEPs is addressed collectively by the sharing FEP reports. The screening decisions and associated TSPA-LA dispositions or screening arguments from all of the FEP reports are cataloged in a project-specific FEPs database

Systematic analysis of off-target effects in an RNAi screen reveals microRNAs affecting sensitivity to TRAIL-induced apoptosis

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Enright Anton J

2010-03-01

Full Text Available Abstract Background RNA inhibition by siRNAs is a frequently used approach to identify genes required for specific biological processes. However RNAi screening using siRNAs is hampered by non-specific or off target effects of the siRNAs, making it difficult to separate genuine hits from false positives. It is thought that many of the off-target effects seen in RNAi experiments are due to siRNAs acting as microRNAs (miRNAs, causing a reduction in gene expression of unintended targets via matches to the 6 or 7 nt 'seed' sequence. We have conducted a careful examination of off-target effects during an siRNA screen for novel regulators of the TRAIL apoptosis induction pathway(s. Results We identified 3 hexamers and 3 heptamer seed sequences that appeared multiple times in the top twenty siRNAs in the TRAIL apoptosis screen. Using a novel statistical enrichment approach, we systematically identified a further 17 hexamer and 13 heptamer seed sequences enriched in high scoring siRNAs. The presence of one of these seeds sequences (which could explain 6 of 8 confirmed off-target effects is sufficient to elicit a phenotype. Three of these seed sequences appear in the human miRNAs miR-26a, miR-145 and miR-384. Transfection of mimics of these miRNAs protects several cell types from TRAIL-induced cell death. Conclusions We have demonstrated a role for miR-26a, miR-145 and miR-26a in TRAIL-induced apoptosis. Further these results show that RNAi screening enriches for siRNAs with relevant off-target effects. Some of these effects can be identified by the over-representation of certain seed sequences in high-scoring siRNAs and we demonstrate the usefulness of such systematic analysis of enriched seed sequences.

A Genetic Screen Reveals that Synthesis of 1,4-Dihydroxy-2-Naphthoate (DHNA), but Not Full-Length Menaquinone, Is Required for Listeria monocytogenes Cytosolic Survival.

Science.gov (United States)

Chen, Grischa Y; McDougal, Courtney E; D'Antonio, Marc A; Portman, Jonathan L; Sauer, John-Demian

2017-03-21

Through unknown mechanisms, the host cytosol restricts bacterial colonization; therefore, only professional cytosolic pathogens are adapted to colonize this host environment. Listeria monocytogenes is a Gram-positive intracellular pathogen that is highly adapted to colonize the cytosol of both phagocytic and nonphagocytic cells. To identify L. monocytogenes determinants of cytosolic survival, we designed and executed a novel screen to isolate L. monocytogenes mutants with cytosolic survival defects. Multiple mutants identified in the screen were defective for synthesis of menaquinone (MK), an essential molecule in the electron transport chain. Analysis of an extensive set of MK biosynthesis and respiratory chain mutants revealed that cellular respiration was not required for cytosolic survival of L. monocytogenes but that, instead, synthesis of 1,4-dihydroxy-2-naphthoate (DHNA), an MK biosynthesis intermediate, was essential. Recent discoveries showed that modulation of the central metabolism of both host and pathogen can influence the outcome of host-pathogen interactions. Our results identify a potentially novel function of the MK biosynthetic intermediate DHNA and specifically highlight how L. monocytogenes metabolic adaptations promote cytosolic survival and evasion of host immunity. IMPORTANCE Cytosolic bacterial pathogens, such as Listeria monocytogenes and Francisella tularensis , are exquisitely evolved to colonize the host cytosol in a variety of cell types. Establishing an intracellular niche shields these pathogens from effectors of humoral immunity, grants access to host nutrients, and is essential for pathogenesis. Through yet-to-be-defined mechanisms, the host cytosol restricts replication of non-cytosol-adapted bacteria, likely through a combination of cell autonomous defenses (CADs) and nutritional immunity. Utilizing a novel genetic screen, we identified determinants of L. monocytogenes cytosolic survival and virulence and identified a role

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

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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/.

Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase

Energy Technology Data Exchange (ETDEWEB)

Duan, Hongying; Takagi, Akira [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Kayano, Hidekazu [Department of Pathology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Koyama, Isamu [Department of Digestive and General Surgery, Saitama International Medical Center, Faculty of Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298 (Japan); Morisseau, Christophe; Hammock, Bruce D. [Department of Entomology and Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616-8584 (United States); Akatsuka, Toshitaka, E-mail: akatsuka@saitama-med.ac.jp [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan)

2012-04-01

In a previous study, we developed five kinds of monoclonal antibodies against different portions of human mEH: three, anti-N-terminal; one, anti-C-terminal; one, anti-conformational epitope. Using them, we stained the intact and the permeabilized human cells of various kinds and performed flow cytometric analysis. Primary hepatocytes and peripheral blood mononuclear cells (PBMC) showed remarkable differences. On the surface, hepatocytes exhibited 4 out of 5 epitopes whereas PBMC did not show any of the epitopes. mEH was detected inside both cell types, but the most prominent expression was observed for the conformational epitope in the hepatocytes and the two N-terminal epitopes in PBMC. These differences were also observed between hepatocyte-derived cell lines and mononuclear cell-derived cell lines. In addition, among each group, there were several differences which may be related to the cultivation, the degree of differentiation, or the original cell subsets. We also noted that two glioblastoma cell lines reveal marked expression of the conformational epitope on the surface which seemed to correlate with the brain tumor-associated antigen reported elsewhere. Several cell lines also underwent selective permeabilization before flow cytometric analysis, and we noticed that the topological orientation of mEH on the ER membrane in those cells was in accordance with the previous report. However, the orientation on the cell surface was inconsistent with the report and had a great variation between the cells. These findings show the multiple mode of expression of mEH which may be possibly related to the multiple roles that mEH plays in different cells. -- Highlights: ► We examine expression of five mEH epitopes in human cells. ► Remarkable differences exist between hepatocytes and PBMC. ► mEH expression in cell lines differs depending on several factors. ► Some glioblastoma cell lines reveal marked surface expression of mEH. ► Topology of mEH on the cell

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

Science.gov (United States)

Roy, Sarah H; Tobin, David V; Memar, Nadin; Beltz, Eleanor; Holmen, Jenna; Clayton, Joseph E; Chiu, Daniel J; Young, Laura D; Green, Travis H; Lubin, Isabella; Liu, Yuying; Conradt, Barbara; Saito, R Mako

2014-02-28

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development. Copyright © 2014 Roy et al.

Signature-tagged mutagenesis screening revealed a novel smooth-to-rough transition determinant of Salmonella enterica serovar Enteritidis.

Science.gov (United States)

Jiao, Yang; Guo, Rongxian; Tang, Peipei; Kang, Xilong; Yin, Junlei; Wu, Kaiyue; Geng, Shizhong; Li, Qiuchun; Sun, Jun; Xu, Xiulong; Zhou, Xiaohui; Gan, Junji; Jiao, Xinan; Liu, Xiufan; Pan, Zhiming

2017-03-03

Salmonella enterica serovar Enteritidis (S. Enteritidis) has emerged as one of the most important food-borne pathogens for humans. Lipopolysaccharide (LPS), as a component of the outer membrane, is responsible for the virulence and smooth-to-rough transition in S. Enteritidis. In this study, we screened S. Enteritidis signature-tagged transposon mutant library using monoclonal antibody against somatic O 9 antigen (O 9 MAb) and O 9 factor rabbit antiserum to identify novel genes that are involved in smooth-to-rough transition. A total of 480 mutants were screened and one mutant with transposon insertion in rfbG gene had smooth-to-rough transition phenotype. In order to verify the role of rfbG gene, an rfbG insertion or deletion mutant was constructed using λ-Red recombination system. Phenotypic and biological analysis revealed that rfbG insertion or deletion mutants were similar to the wild-type strain in growth rate and biochemical properties, but the swimming motility was reduced. SE Slide Agglutination test and ELISA test showed that rfbG mutants do not stimulate animals to produce agglutinating antibody. In addition, the half-lethal dose (LD 50 ) of the rfbG deletion mutant strain was 10 6.6 -fold higher than that of the parent strain in a mouse model when injected intraperitoneally. These data indicate that the rfbG gene is involved in smooth-to-rough transition, swimming motility and virulence of S. Enteritidis. Furthermore, somatic O-antigen antibody-based approach to screen signature-tagged transposon mutants is feasible to clarify LPS biosynthesis and to find suitable markers in DIVA-vaccine research.

Effect of Fee on Cervical Cancer Screening Attendance--ScreenFee, a Swedish Population-Based Randomised Trial.

Science.gov (United States)

Alfonzo, Emilia; Andersson Ellström, Agneta; Nemes, Szilard; Strander, Björn

2016-01-01

Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (≈11 €). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85-1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas. ClinicalTrials.gov NCT02378324.

Mobile Screens: The Visual Regime of Navigation

NARCIS (Netherlands)

Verhoeff, N.

2012-01-01

In this book on screen media, space, and mobility I compare synchronically, as well as diachronically, diverse and variegated screen media - their technologies and practices – as sites for virtual mobility and navigation. Mobility as a central trope can be found on the multiple levels that are

Latino risk-adjusted mortality in the men screened for the Multiple Risk Factor Intervention Trial.

Science.gov (United States)

Thomas, Avis J; Eberly, Lynn E; Neaton, James D; Smith, George Davey

2005-09-15

Latinos are now the largest minority in the United States, but their distinctive health needs and mortality patterns remain poorly understood. Proportional hazards regressions were used to compare Latino versus White risk- and income-adjusted mortality over 25 years' follow-up from 5,846 Latino and 300,647 White men screened for the Multiple Risk Factor Intervention Trial. Men were aged 35-57 years and residing in 14 states when screened in 1973-1975. Data on coronary heart disease risk factors, self-reported race/ethnicity, and home addresses were obtained at baseline; income was estimated by linking addresses to census data. Mortality follow-up through 1999 was obtained using the National Death Index. The fully adjusted Latino/White hazard ratio for all-cause mortality was 0.82 (95% confidence interval (CI): 0.77, 0.87), based on 1,085 Latino and 73,807 White deaths; this pattern prevailed over time and across states (thus, likely across Latino subgroups). Hazard ratios were significantly greater than one for stroke (hazard ratio = 1.30, 95% CI: 1.01, 1.68), liver cancer (hazard ratio = 2.02, 95% CI: 1.21, 3.37), and infection (hazard ratio = 1.69, 95% CI: 1.24, 2.32). A substudy found only minor racial/ethnic differences in the quality of Social Security numbers, birth dates, soundex-adjusted names, and National Death Index searches. Results were not likely an artifact of return migration or incomplete mortality data.

Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

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Scott B Vafai

Full Text Available Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS. Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.

The Role of Effective Communication to Enhance Participation in Screening Mammography: A New Zealand Case

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Margaret A. Brunton

2009-02-01

Full Text Available Changes in the organisation of health care have dominated policy initiatives over the past two decades in many countries. An increasing reliance on public health initiatives to prevent or detect disease early has resulted in an increase in programs that screen for cancer in the community. In turn, this accentuates the need to persuasively communicate the value of such initiatives to encourage continued participation. Merely placing screening programs into a community setting is not sufficient to ensure that adequate numbers will voluntarily participate regularly to achieve anticipated cost and mortality savings in the population. In this research the influence of managing communication in a public screening mammography program was investigated. The results revealed that significant opportunities were overlooked for reassurance and information during the physical mammography process. In turn, this highlights the influence of constraints imposed by the structure of the screening program and the resources allocated to the process. This research suggests that it is important to address multiple influences, including ethnic differences, when asking questions about the effectiveness of public health policy, particularly when considering the choices women make about ongoing participation in breast screening programs.

Genomic library screening for viruses from the human dental plaque revealed pathogen-specific lytic phage sequences.

Science.gov (United States)

Al-Jarbou, Ahmed Nasser

2012-01-01

Bacterial pathogenesis presents an astounding arsenal of virulence factors that allow them to conquer many different niches throughout the course of infection. Principally fascinating is the fact that some bacterial species are able to induce different diseases by expression of different combinations of virulence factors. Nevertheless, studies aiming at screening for the presence of bacteriophages in humans have been limited. Such screening procedures would eventually lead to identification of phage-encoded properties that impart increased bacterial fitness and/or virulence in a particular niche, and hence, would potentially be used to reverse the course of bacterial infections. As the human oral cavity represents a rich and dynamic ecosystem for several upper respiratory tract pathogens. However, little is known about virus diversity in human dental plaque which is an important reservoir. We applied the culture-independent approach to characterize virus diversity in human dental plaque making a library from a virus DNA fraction amplified using a multiple displacement method and sequenced 80 clones. The resulting sequence showed 44% significant identities to GenBank databases by TBLASTX analysis. TBLAST homology comparisons showed that 66% was viral; 18% eukarya; 10% bacterial; 6% mobile elements. These sequences were sorted into 6 contigs and 45 single sequences in which 4 contigs and a single sequence showed significant identity to a small region of a putative prophage in the Corynebacterium diphtheria genome. These findings interestingly highlight the uniqueness of over half of the sequences, whilst the dominance of a pathogen-specific prophage sequences imply their role in virulence.

Genome-Wide Screening of Cytogenetic Abnormalities in Multiple Myeloma Patients Using Array-CGH Technique: A Czech Multicenter Experience

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Jan Smetana

2014-01-01

Full Text Available Characteristic recurrent copy number aberrations (CNAs play a key role in multiple myeloma (MM pathogenesis and have important prognostic significance for MM patients. Array-based comparative genomic hybridization (aCGH provides a powerful tool for genome-wide classification of CNAs and thus should be implemented into MM routine diagnostics. We demonstrate the possibility of effective utilization of oligonucleotide-based aCGH in 91 MM patients. Chromosomal aberrations associated with effect on the prognosis of MM were initially evaluated by I-FISH and were found in 93.4% (85/91. Incidence of hyperdiploidy was 49.5% (45/91; del(13(q14 was detected in 57.1% (52/91; gain(1(q21 occurred in 58.2% (53/91; del(17(p13 was observed in 15.4% (14/91; and t(4;14(p16;q32 was found in 18.6% (16/86. Genome-wide screening using Agilent 44K aCGH microarrays revealed copy number alterations in 100% (91/91. Most common deletions were found at 13q (58.9%, 1p (39.6%, and 8p (31.1%, whereas gain of whole 1q was the most often duplicated region (50.6%. Furthermore, frequent homozygous deletions of genes playing important role in myeloma biology such as TRAF3, BIRC1/BIRC2, RB1, or CDKN2C were observed. Taken together, we demonstrated the utilization of aCGH technique in clinical diagnostics as powerful tool for identification of unbalanced genomic abnormalities with prognostic significance for MM patients.

Elaborate cellulosome architecture of Acetivibrio cellulolyticus revealed by selective screening of cohesin–dockerin interactions

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Yuval Hamberg

2014-10-01

cellulosome’s total cohesin and dockerin sequence diversity, emphasizing the testing of unusual and previously-unknown protein modules. The screen revealed several novel cell-bound cellulosome architectures, thus expanding on those previously known, as well as soluble cellulose systems that are not bound to the bacterial cell surface. This study sets the stage for screening the entire complement of cellulosomal components from A. cellulolyticus and other organisms with large cellulosome systems. The knowledge gained by such efforts brings us closer to understanding the exceptional catalytic abilities of cellulosomes and will allow the use of novel cellulosomal components in artificial assemblies and in enzyme cocktails for sustainable energy-related research programs.

Phytochemical Screening, Antibacterial and Toxicological Activities ...

African Journals Online (AJOL)

The phytochemical screening, antibacterial and toxicological activities of extracts of the stem bark of Acacia senegal were investigated. The phytochemical analyses according to standard screening tests using conventional protocols revealed the presence of tannins, saponins and sterols in the stem bark of the plant.

Proximate composition, phytochemical screening and antianaemic ...

African Journals Online (AJOL)

In this study, the phytochemical screening and anti-anaemic effect of Aloe barbadensis leaves was investigated in nutritionally stressed rats. Preliminary phytochemical screening test of the plant revealed that it contained tannins, flavonoids, anthraquinones, saponins, alkaloids and cardiac glycosides. Sets of male albino ...

Effect of Fee on Cervical Cancer Screening Attendance—ScreenFee, a Swedish Population-Based Randomised Trial

Science.gov (United States)

Alfonzo, Emilia; Andersson Ellström, Agneta; Nemes, Szilard; Strander, Björn

2016-01-01

Background Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. Method Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (≈11 €). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. Results Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85–1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. Conclusion Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas. Trial Registration ClinicalTrials.gov NCT02378324 PMID:26986848

Comparison and clinical utility evaluation of four multiple allergen simultaneous tests including two newly introduced fully automated analyzers

Directory of Open Access Journals (Sweden)

John Hoon Rim

2016-04-01

Full Text Available Background: We compared the diagnostic performances of two newly introduced fully automated multiple allergen simultaneous tests (MAST analyzers with two conventional MAST assays. Methods: The serum samples from a total of 53 and 104 patients were tested for food panels and inhalant panels, respectively, in four analyzers including AdvanSure AlloScreen (LG Life Science, Korea, AdvanSure Allostation Smart II (LG Life Science, PROTIA Allergy-Q (ProteomeTech, Korea, and RIDA Allergy Screen (R-Biopharm, Germany. We compared not only the total agreement percentages but also positive propensities among four analyzers. Results: Evaluation of AdvanSure Allostation Smart II as upgraded version of AdvanSure AlloScreen revealed good concordance with total agreement percentages of 93.0% and 92.2% in food and inhalant panel, respectively. Comparisons of AdvanSure Allostation Smart II or PROTIA Allergy-Q with RIDA Allergy Screen also showed good concordance performance with positive propensities of two new analyzers for common allergens (Dermatophagoides farina and Dermatophagoides pteronyssinus. The changes of cut-off level resulted in various total agreement percentage fluctuations among allergens by different analyzers, although current cut-off level of class 2 appeared to be generally suitable. Conclusions: AdvanSure Allostation Smart II and PROTIA Allergy-Q presented favorable agreement performances with RIDA Allergy Screen, although positive propensities were noticed in common allergens. Keywords: Multiple allergen simultaneous test, Automated analyzer

Phytochemical screening and antiproliferative effects of methanol ...

African Journals Online (AJOL)

Preliminary Phytochemical screening. Thin layer chromatographic profile (TLC) of methanol crude extract and antiproliferative studies were carried out in this research. Phytochemical screening revealed the presence of carbohydrate, glycoside, anthraquinone, steroid, triterpenes, saponin, tannins, flavonoids and alkaloid.

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.

The Cannabis Abuse Screening Test and the DSM-5 in the general population: Optimal thresholds and underlying common structure using multiple factor analysis.

Science.gov (United States)

Legleye, Stéphane

2017-11-10

The Cannabis Abuse Screening Test (CAST) aims at screening the problematic use of cannabis. It has never been validated against the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and its relationships with this latter have never been studied. We used a probabilistic telephone survey collected in 2014 (1351 past-year cannabis users aged 15-64) implementing the CAST and a DSM-5 adaptation of the Munich Composite International Diagnostic Interview assessing cannabis use disorders. Data were weighted, and CAST items were considered categorical. Factorial structures were assessed with confirmatory factor analyses; the relationships between the instruments were studied with multiple factor analysis (MFA). One factor for the DSM-5 and two correlated factors for the CAST were the best confirmatory factor analyses solutions. The CAST thresholds for screening moderate/severe and severe cannabis use disorders were 5 (sensitivity = 78.2% and specificity = 79.6%) and 8 (sensitivity = 86.0% and specificity = 86.7%), respectively. The MFA identified two orthogonal dimensions: The first was equally shared by both instruments; the second was the second CAST dimension (extreme frequencies of use before midday and alone, memory problems, and reproaches from friends/family). The CAST structure and screening properties were confirmed. The MFA explains its screening performances by its first dimension and identified the problematic patterns (the second dimension) that are not captured by the DSM-5. Copyright © 2017 John Wiley & Sons, Ltd.

In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling.

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Juan Du

Full Text Available Hedgehog (Hh signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12 that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci, the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.

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.

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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.

Evaluation of three rapid oral fluid test devices on the screening of multiple drugs of abuse including ketamine.

Science.gov (United States)

Tang, Magdalene H Y; Ching, C K; Poon, Simon; Chan, Suzanne S S; Ng, W Y; Lam, M; Wong, C K; Pao, Ronnie; Lau, Angus; Mak, Tony W L

2018-05-01

Rapid oral fluid testing (ROFT) devices have been extensively evaluated for their ability to detect common drugs of abuse; however, the performance of such devices on simultaneous screening for ketamine has been scarcely investigated. The present study evaluated three ROFT devices (DrugWipe ® 6S, Ora-Check ® and SalivaScreen ® ) on the detection of ketamine, opiates, methamphetamine, cannabis, cocaine and MDMA. A liquid chromatography tandem mass spectrometry (LCMS) assay was firstly established and validated for confirmation analysis of the six types of drugs and/or their metabolites. In the field test, the three ROFT devices were tested on subjects recruited from substance abuse clinics/rehabilitation centre. Oral fluid was also collected using Quantisal ® for confirmation analysis. A total of 549 samples were collected in the study. LCMS analysis on 491 samples revealed the following drugs: codeine (55%), morphine (49%), heroin (40%), methamphetamine (35%), THC (8%), ketamine (4%) and cocaine (2%). No MDMA-positive cases were observed. Results showed that the overall specificity and accuracy were satisfactory and met the DRUID standard of >80% for all 3 devices. Ora-Check ® had poor sensitivities (ketamine 36%, methamphetamine 63%, opiates 53%, cocaine 60%, THC 0%). DrugWipe ® 6S showed good sensitivities in the methamphetamine (83%) and opiates (93%) tests but performed relatively poorly for ketamine (41%), cocaine (43%) and THC (22%). SalivaScreen ® also demonstrated good sensitivities in the methamphetamine (83%) and opiates (100%) tests, and had the highest sensitivity for ketamine (76%) and cocaine (71%); however, it failed to detect any of the 28 THC-positive cases. The test completion rate (proportion of tests completed with quality control passed) were: 52% (Ora-Check ® ), 78% (SalivaScreen ® ) and 99% (DrugWipe ® 6S). Copyright © 2018 Elsevier B.V. All rights reserved.

A kinome-wide RNAi screen in Drosophila Glia reveals that the RIO kinases mediate cell proliferation and survival through TORC2-Akt signaling in glioblastoma.

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Renee D Read

Full Text Available Glioblastoma, the most common primary malignant brain tumor, is incurable with current therapies. Genetic and molecular analyses demonstrate that glioblastomas frequently display mutations that activate receptor tyrosine kinase (RTK and Pi-3 kinase (PI3K signaling pathways. In Drosophila melanogaster, activation of RTK and PI3K pathways in glial progenitor cells creates malignant neoplastic glial tumors that display many features of human glioblastoma. In both human and Drosophila, activation of the RTK and PI3K pathways stimulates Akt signaling along with other as-yet-unknown changes that drive oncogenesis. We used this Drosophila glioblastoma model to perform a kinome-wide genetic screen for new genes required for RTK- and PI3K-dependent neoplastic transformation. Human orthologs of novel kinases uncovered by these screens were functionally assessed in mammalian glioblastoma models and human tumors. Our results revealed that the atypical kinases RIOK1 and RIOK2 are overexpressed in glioblastoma cells in an Akt-dependent manner. Moreover, we found that overexpressed RIOK2 formed a complex with RIOK1, mTor, and mTor-complex-2 components, and that overexpressed RIOK2 upregulated Akt signaling and promoted tumorigenesis in murine astrocytes. Conversely, reduced expression of RIOK1 or RIOK2 disrupted Akt signaling and caused cell cycle exit, apoptosis, and chemosensitivity in glioblastoma cells by inducing p53 activity through the RpL11-dependent ribosomal stress checkpoint. These results imply that, in glioblastoma cells, constitutive Akt signaling drives RIO kinase overexpression, which creates a feedforward loop that promotes and maintains oncogenic Akt activity through stimulation of mTor signaling. Further study of the RIO kinases as well as other kinases identified in our Drosophila screen may reveal new insights into defects underlying glioblastoma and related cancers and may reveal new therapeutic opportunities for these cancers.

Characteristics of the Danish families with multiple endocrine neoplasia type 1

DEFF Research Database (Denmark)

Jäger, Anne Charlotte; Friis-Hansen, Lennart; Hansen, Thomas v.O.

2006-01-01

Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier...... reported mutation. The mutations were predominantly found in exons 9 and 10 encoding the C-terminal part of menin. Seven of the mutations were missense mutations, changing conserved residues. Furthermore screening of 93 out of 153 consecutive patients with primary hyperparathyroidism (pHPT) identified five...... mutation carriers. Two of these belonged to known MEN1 families, whereas the only MEN1-related disease in the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut endocrine tumours revealed five mutation carries out of 28 patients with sporadic gastrinomas, whereas no mutations were...

Cost-effectiveness of breast cancer screening policies using simulation.

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Gocgun, Y; Banjevic, D; Taghipour, S; Montgomery, N; Harvey, B J; Jardine, A K S; Miller, A B

2015-08-01

In this paper, we study breast cancer screening policies using computer simulation. We developed a multi-state Markov model for breast cancer progression, considering both the screening and treatment stages of breast cancer. The parameters of our model were estimated through data from the Canadian National Breast Cancer Screening Study as well as data in the relevant literature. Using computer simulation, we evaluated various screening policies to study the impact of mammography screening for age-based subpopulations in Canada. We also performed sensitivity analysis to examine the impact of certain parameters on number of deaths and total costs. The analysis comparing screening policies reveals that a policy in which women belonging to the 40-49 age group are not screened, whereas those belonging to the 50-59 and 60-69 age groups are screened once every 5 years, outperforms others with respect to cost per life saved. Our analysis also indicates that increasing the screening frequencies for the 50-59 and 60-69 age groups decrease mortality, and that the average number of deaths generally decreases with an increase in screening frequency. We found that screening annually for all age groups is associated with the highest costs per life saved. Our analysis thus reveals that cost per life saved increases with an increase in screening frequency. Copyright © 2015 Elsevier Ltd. All rights reserved.

Women's knowledge, attitudes and practice about breast cancer screening in the region of Monastir (Tunisia).

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El Mhamdi, Sana; Bouanene, Ines; Mhirsi, Amel; Sriha, Asma; Ben Salem, Kamel; Soltani, Mohamed Soussi

2013-01-01

Breast cancer remains a worldwide public health problem. In Tunisia, it is considered to be the primary women's cancer and causes high morbidity and mortality. This study aimed to investigate female knowledge, attitudes and practice of breast cancer screening in the region of Monastir (Tunisia). We conducted a descriptive cross-sectional design exploring knowledge, attitudes and practices of women in the region of Monastir on breast cancer screening. The study was conducted in health centres of this region from 1 March 2009 to 30 June 2009. Data were collected via a structured questionnaire containing 15 items on demographic status, knowledge of risk factors and screening methods and attitudes towards the relevance and effectiveness of breast cancer screening. A scoring scheme was used to score women's responses. A total of 900 women agreed to take part in the study. Their mean age was 41.6±12.4 years and 64% did not exceed the primary level of education. According to the constructed scores, 92% of participants had poor knowledge of the specific risk factors for breast cancer and 63.2% had poor knowledge of the screening methods. Proper practice of breast cancer screening was observed in 14.3% of cases. Multiple logistic regression analysis showed that good knowledge of risk factors and screening methods, higher level of education and positive family history of breast cancer were independently correlated with breast cancer screening practice. This study revealed poor knowledge of breast cancer and the screening methods as well as low levels of practice of breast cancer screening among women in the region of Monastir. Results justify educational programs to raise women's adherence to breast cancer screening programs in Tunisia.

Pointright: a system to redirect mouse and keyboard control among multiple machines

Science.gov (United States)

Johanson, Bradley E [Palo Alto, CA; Winograd, Terry A [Stanford, CA; Hutchins, Gregory M [Mountain View, CA

2008-09-30

The present invention provides a software system, PointRight, that allows for smooth and effortless control of pointing and input devices among multiple displays. With PointRight, a single free-floating mouse and keyboard can be used to control multiple screens. When the cursor reaches the edge of a screen it seamlessly moves to the adjacent screen and keyboard control is simultaneously redirected to the appropriate machine. Laptops may also redirect their keyboard and pointing device, and multiple pointers are supported simultaneously. The system automatically reconfigures itself as displays go on, go off, or change the machine they display.

Population Screening Using Sewage Reveals Pan-Resistant Bacteria in Hospital and Community Samples.

Science.gov (United States)

Meir-Gruber, Lital; Manor, Yossi; Gefen-Halevi, Shiraz; Hindiyeh, Musa Y; Mileguir, Fernando; Azar, Roberto; Smollan, Gill; Belausov, Natasha; Rahav, Galia; Shamiss, Ari; Mendelson, Ella; Keller, Nathan

2016-01-01

The presence of pan-resistant bacteria worldwide possesses a threat to global health. It is difficult to evaluate the extent of carriage of resistant bacteria in the population. Sewage sampling is a possible way to monitor populations. We evaluated the presence of pan-resistant bacteria in Israeli sewage collected from all over Israel, by modifying the pour plate method for heterotrophic plate count technique using commercial selective agar plates. This method enables convenient and fast sewage sampling and detection. We found that sewage in Israel contains multiple pan-resistant bacteria including carbapenemase resistant Enterobacteriacae carrying blaKPC and blaNDM-1, MRSA and VRE. blaKPC carrying Klebsiella pneumonia and Enterobacter cloacae were the most common Enterobacteriacae drug resistant bacteria found in the sewage locations we sampled. Klebsiella pneumonia, Enterobacter spp., Escherichia coli and Citrobacter spp. were the 4 main CRE isolated from Israeli sewage and also from clinical samples in our clinical microbiology laboratory. Hospitals and Community sewage had similar percentage of positive samplings for blaKPC and blaNDM-1. VRE was found to be more abundant in sewage in Israel than MRSA but there were more locations positive for MRSA and VRE bacteria in Hospital sewage than in the Community. Therefore, our upgrade of the pour plate method for heterotrophic plate count technique using commercial selective agar plates can be a useful tool for routine screening and monitoring of the population for pan-resistant bacteria using sewage.

Patterns of cervical coinfection with multiple human papilloma virus types in a screening population in Denmark

DEFF Research Database (Denmark)

Goldman, Bryan; Rebolj, Matejka; Rygaard, Carsten

2013-01-01

Patterns of cervical human papillomavirus (HPV) infection suggest that HPV genotypes are not independent of each other. This may be explained by risk factors common to all HPV infections, but type-specific biological factors may also play a role. This raises the question of whether widespread use...... of the quadrivalent vaccine (covering HPV6, 11, 16, 18) may indirectly affect the prevalence of any non-vaccine types. Routine screening samples from 5014 Danish women were tested for 35 HPV genotypes (including 13 high-risk) using the Genomica CLART(®) HPV2 kit, which is a low-density microarray based on PCR...... amplification. Simulation studies were performed both under independence between genotypes and under a common dependence structure as would arise from common risk factors, and simulation results were compared to observed coinfection patterns. Overall HPV prevalence was 37.4%, with multiple infections in 17...

Everyday multiscreening : How the simultaneous usage of multiple screens affects information processing and advertising effectiveness

NARCIS (Netherlands)

Segijn, C.M.

2017-01-01

Today, people have access to a variety of screens, such as a television, laptop, smartphone, and tablet. Screen saturation and the convergence of these technologies have led to an increase in combining different screens simultaneously, also known as multiscreening. With so many new devices and

Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity

Science.gov (United States)

Schoggins, John W.; MacDuff, Donna A.; Imanaka, Naoko; Gainey, Maria D.; Shrestha, Bimmi; Eitson, Jennifer L.; Mar, Katrina B.; Richardson, R. Blake; Ratushny, Alexander V.; Litvak, Vladimir; Dabelic, Rea; Manicassamy, Balaji; Aitchison, John D.; Aderem, Alan; Elliott, Richard M.; García-Sastre, Adolfo; Racaniello, Vincent; Snijder, Eric J.; Yokoyama, Wayne M.; Diamond, Michael S.; Virgin, Herbert W.; Rice, Charles M.

2014-01-01

The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors. Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses. However, antiviral ISG specificity across multiple distinct classes of viruses remains largely unexplored. Here we used an ectopic expression assay to screen a library of more than 350 human ISGs for effects on 14 viruses representing 7 families and 11 genera. We show that 47 genes inhibit one or more viruses, and 25 genes enhance virus infectivity. Comparative analysis reveals that the screened ISGs target positive-sense single-stranded RNA viruses more effectively than negative-sense single-stranded RNA viruses. Gene clustering highlights the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression also broadly inhibits several RNA viruses. In vitro, lentiviral delivery of enzymatically active cGAS triggers a STING-dependent, IRF3-mediated antiviral program that functions independently of canonical IFN/STAT1 signalling. In vivo, genetic ablation of murine cGAS reveals its requirement in the antiviral response to two DNA viruses, and an unappreciated contribution to the innate control of an RNA virus. These studies uncover new paradigms for the preferential specificity of IFN-mediated antiviral pathways spanning several virus families.

Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

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Maria Liguori

Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

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Cohn AL

2017-02-01

Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

ScreenBEAM: a novel meta-analysis algorithm for functional genomics screens via Bayesian hierarchical modeling.

Science.gov (United States)

Yu, Jiyang; Silva, Jose; Califano, Andrea

2016-01-15

Functional genomics (FG) screens, using RNAi or CRISPR technology, have become a standard tool for systematic, genome-wide loss-of-function studies for therapeutic target discovery. As in many large-scale assays, however, off-target effects, variable reagents' potency and experimental noise must be accounted for appropriately control for false positives. Indeed, rigorous statistical analysis of high-throughput FG screening data remains challenging, particularly when integrative analyses are used to combine multiple sh/sgRNAs targeting the same gene in the library. We use large RNAi and CRISPR repositories that are publicly available to evaluate a novel meta-analysis approach for FG screens via Bayesian hierarchical modeling, Screening Bayesian Evaluation and Analysis Method (ScreenBEAM). Results from our analysis show that the proposed strategy, which seamlessly combines all available data, robustly outperforms classical algorithms developed for microarray data sets as well as recent approaches designed for next generation sequencing technologies. Remarkably, the ScreenBEAM algorithm works well even when the quality of FG screens is relatively low, which accounts for about 80-95% of the public datasets. R package and source code are available at: https://github.com/jyyu/ScreenBEAM. ac2248@columbia.edu, jose.silva@mssm.edu, yujiyang@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A cross docking pipeline for improving pose prediction and virtual screening performance

Science.gov (United States)

Kumar, Ashutosh; Zhang, Kam Y. J.

2018-01-01

Pose prediction and virtual screening performance of a molecular docking method depend on the choice of protein structures used for docking. Multiple structures for a target protein are often used to take into account the receptor flexibility and problems associated with a single receptor structure. However, the use of multiple receptor structures is computationally expensive when docking a large library of small molecules. Here, we propose a new cross-docking pipeline suitable to dock a large library of molecules while taking advantage of multiple target protein structures. Our method involves the selection of a suitable receptor for each ligand in a screening library utilizing ligand 3D shape similarity with crystallographic ligands. We have prospectively evaluated our method in D3R Grand Challenge 2 and demonstrated that our cross-docking pipeline can achieve similar or better performance than using either single or multiple-receptor structures. Moreover, our method displayed not only decent pose prediction performance but also better virtual screening performance over several other methods.

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.

Screening Sex: revelando e dissimulando o sexo Screening Sex

Directory of Open Access Journals (Sweden)

Linda Williams

2012-06-01

Full Text Available Neste texto, procura-se contar a história da exibição do sexo em filmes majoritariamente produzidos nos Estados Unidos no período de quase um século. Ao se perguntar quando, porque e como os Estados Unidos se transformaram de uma cultura que não exibia o sexo em uma que o exibe, a autora insiste no duplo significado do verbo screen (tanto como uma revelação quanto uma dissimulação. Exibir é revelar em uma tela. Mas um segundo e igualmente importante significado, como diz o dicionário é "proteger ou esconder atrás de uma tela". Os filmes tanto revelam como escondem. O artigo analisa a forma como mudanças sociais ocorridas nos Estados Unidos, como, por exemplo, a Revolução sexual dos anos 60 e novas visões a respeito da sexualidade, possibilitaram novas maneiras de representação do sexo no cinema, reorganizando a relação entre o público e o privado. O artigo se pergunta também sobre como nossos corpos e sentidos reagem ao encontro com o sexo na tela, introduzindo a ideia de "saber carnal" (carnal knowledge.In this paper, we try to tell the history of the exhibition of sex in movies mainly produced in the United States in almost a century. Asking when, why and how the United States became - from a culture that did not exhibit sex - into a culture that exhibits it, the author insists in the double sense of the verb to screen (as both a revelation and a dissimulation. To exhibit is to reveal in a screen. But another, and important, sense, as says the dictionary, is "to protect or hide behind a screen". Movies show as well as they reveal. The paper analyzes the way social change in the United States, for example the sexual revolution of the sixties and new views on sexuality allowed new ways of representing sex in the movies, creating a new relation between public and private. The paper also asks how our bodies and senses react to sex in the screen, introducing the idea of "carnal knowledge".

Predictors of hyperglycaemic individuals who do not follow up with physicians after screening in Japan: a cohort study.

Science.gov (United States)

Tsujimura, Yuka; Takahashi, Yoshimitsu; Ishizaki, Tatsuro; Kuriyama, Akira; Miyazaki, Kikuko; Satoh, Toshihiko; Ikeda, Shunya; Kimura, Shinya; Nakayama, Takeo

2014-08-01

Although people screened as being hyperglycaemic often fail to follow up with physicians for clinical assessment, epidemiologic findings on the frequency and predictors of not following up (hereafter, "no follow-up") are lacking. The purpose of this study was to examine the no follow-up rate with physicians after screening for diabetes and predictors of no follow-up. We assessed cases of no follow-up with physicians within six months after screening based on medical claims data from employee-based social health insurance programs in Japan, for people aged 20 to 68 years from 2005 to 2010. Among 3878 screened participants with hyperglycaemia, 2527 (65%) did not follow up with their physicians within six months after screening. Multiple logistic regression analysis revealed that younger age and lower blood glucose level predicted no follow-up among both men and women, while lower body mass index and negative proteinuria also predicted no follow-up among men. Treatment for dyslipidaemia facilitated follow-up among both genders, and treatment for hypertension or depression facilitated follow-up among men. Approximately two thirds of individuals screened as having hyperglycaemia did not follow up with their physicians within six months after screening. Predictors of no follow-up were younger age and milder hyperglycaemia. Being on treatment for co-morbidities tended to facilitate follow-up. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Screening and Invasive Testing in Twins

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Giovanni Monni

2014-07-01

Full Text Available Prenatal screening and testing for trisomy 21 in twin pregnancies poses a number of challenges: the exact estimate of the a priori risk of trisomy 21, the choice of prenatal screening test and/or invasive techniques to employ for the diagnosis and the impact of the result on the options of treatment in case of discordant results within a twin pair or among multiples. These different aspects are discussed below while recognizing that many issues remain unresolved.

A Tendon Cell Specific RNAi Screen Reveals Novel Candidates Essential for Muscle Tendon Interaction.

Directory of Open Access Journals (Sweden)

Prabhat Tiwari

Full Text Available Tendons are fibrous connective tissue which connect muscles to the skeletal elements thus acting as passive transmitters of force during locomotion and provide appropriate body posture. Tendon-derived cues, albeit poorly understood, are necessary for proper muscle guidance and attachment during development. In the present study, we used dorsal longitudinal muscles of Drosophila and their tendon attachment sites to unravel the molecular nature of interactions between muscles and tendons. We performed a genetic screen using RNAi-mediated knockdown in tendon cells to find out molecular players involved in the formation and maintenance of myotendinous junction and found 21 candidates out of 2507 RNAi lines screened. Of these, 19 were novel molecules in context of myotendinous system. Integrin-βPS and Talin, picked as candidates in this screen, are known to play important role in the cell-cell interaction and myotendinous junction formation validating our screen. We have found candidates with enzymatic function, transcription activity, cell adhesion, protein folding and intracellular transport function. Tango1, an ER exit protein involved in collagen secretion was identified as a candidate molecule involved in the formation of myotendinous junction. Tango1 knockdown was found to affect development of muscle attachment sites and formation of myotendinous junction. Tango1 was also found to be involved in secretion of Viking (Collagen type IV and BM-40 from hemocytes and fat cells.

How Do Multiple-Star Systems Form? VLA Study Reveals "Smoking Gun"

Science.gov (United States)

2006-12-01

system, all the antennas could provide data for us. In addition, we improved the level of detail by using the Pie Town, NM, antenna of the Very Long Baseline Array, as part of an expanded system," Lim said. The implementation and improvement of the 43 GHz receiving system was a collaborative program among the German Max Planck Institute, the Mexican National Autonomous University, and the U.S. National Radio Astronomy Observatory. Two popular theoretical models for the formation of multiple-star systems are, first, that the two protostars and their surrounding dusty disks fragment from a larger parent disk, and, second, that the protostars form independently and then one captures the other into a mutual orbit. "Our new study shows that the disks of the two main protostars are aligned with each other, and also are aligned with the larger, surrounding disk. In addition, their orbital motion resembles the rotation of the larger disk. This is a 'smoking gun' supporting the fragmentation model," Lim said. However, the new study also revealed a third young star with a dust disk. "The disk of this one is misaligned with those of the other two, so it may be the result of either fragmentation or capture," Takakuwa said. The misalignment of the third disk could have come through gravitational interactions with the other two, larger, protostars, the scientists said. They plan further observations to try to resolve the question. "We have a very firm indication that two of these protostars and their dust disks formed from the same, larger disk-like cloud, then broke out from it in a fragmentation process. That strongly supports one theoretical model for how multiple-star systems are formed. The misalignment of the third protostar and its disk leaves open the possibility that it could have formed elsewhere and been captured, and we'll continue to work on reconstructing the history of this fascinating system," Lim summarized. The National Radio Astronomy Observatory is a facility of

Lung cancer screening: Update

International Nuclear Information System (INIS)

Kim, Hyea Young

2015-01-01

Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers

Lung cancer screening: Update

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

2015-09-15

Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

Mathematics revealed

CERN Document Server

Berman, Elizabeth

1979-01-01

Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

Multiple dislocation pile-ups in small grains at small strains: implications for the Hall-Petch relationship and backstress screening

International Nuclear Information System (INIS)

Schouwenaars, R; Jacobo, V H; Ortiz, A

2014-01-01

A classic explanation for the Hall-Petch relationship is given by the stress field of a single dislocation pile-up perpendicular to the grain boundary. Similarly, the gradual compensation of the stress fields of pile-ups on both sides of the boundary has been invoked to explain the transitory effects observed in the stress- strain curves of ultrafine grained polycrystals. This paper studies the effects of introducing deviations of the highly simplified geometry mentioned above, using the proper mathematical approximations of linear elastic dislocation theory. Multiple pile-ups invalidate the conclusions drawn from the single pile-up model. Pile-ups in multiple grains are assessed by a highly idealised model of an infinite array of periodical pile-ups. In the latter case, screening is always perfect. By considering the Peach-Köhler force between dislocations mutually disoriented grains, the magnitude of the fluctuations around such ideal case can be estimated. However, using sound probabilistic arguments to calculate the free path for dislocation slip in fine-grained polycrystals, it is found that the amount of dislocations that can be stored in the pile- ups is generally too small to explain the strong grain size effects observed experimentally

Pennsylvania's experience in mass screening

International Nuclear Information System (INIS)

Gerusky, T.M.

1975-01-01

A policy statement issued in 1972 by the Assistant Secretary for Health and Scientific Affairs of the Department of Health, Education, and Welfare recommended that community chest x-ray surveys should not be used as a screening procedure for the detection of cardiopulmonary disorders and that when chest x-ray screening programs are justified for selected population groups, the full size photograph, rather than the miniature film, is preferred. A survey conducted in 1974--75 revealed that chest x rays were required for prisoners, prison employees, school employees, food handlers, and students who wished to participate in sports. Meetings were held with medical associations in the hope of stopping the local mass-screening operations. Of 27 groups in Pennsylvania involved in tuberculosis screening, 12 groups refused or were unwilling to phase out their photofluorographic procedures. The problem will be resolved by regulation

Pain during mammography: Implications for breast screening programmes

International Nuclear Information System (INIS)

Andrews, F.J.

2001-01-01

Pain experienced during mammography can deter women from attending for breast cancer screening. Review of the current literature on pain experienced during mammography reveals three main areas of interest: reports of the frequency of pain, identification of predictors of pain and strategies for responding to pain. Implications of this literature for breast screening programmes include the need for appropriate measurements of pain during mammography that are valid for screening populations, a further understanding of organizational factors involved in screening programmes that may be predictors of pain and for the development of valid strategies for responding to pain within breast screening programmes. Copyright (2001) Blackwell Science Pty Ltd

Screening Mixtures of Small Molecules for Binding to Multiple Sites on the Surface Tetanus Toxin C Fragment by Bioaffinity NMR

International Nuclear Information System (INIS)

Cosman, M; Zeller, L; Lightstone, F C; Krishnan, V V; Balhorn, R

2002-01-01

also contains 3-sialyllactose (another predicted site 1 binder) and bisbenzimide 33342 (non-binder). A series of five predicted Site-2 binders were then screened sequentially in the presence of the Site-1 binder doxorubicin. These experiments showed that the compounds lavendustin A and naphthofluorescein-di-(β-D-galactopyranoside) binds along with doxorubicin to TetC. Further experiments indicate that doxorubicin and lavendustin are potential candidates to use in preparing a bidendate inhibitor specific for TetC. The simultaneous binding of two different predicted Site-2 ligands to TetC suggests that they may bind multiple sites. Another possibility is that the conformations of the binding sites are dynamic and can bind multiple diverse ligands at a single site depending on the pre-existing conformation of the protein, especially when doxorubicin is already bound

A Review of Different Behavior Modification Strategies Designed to Reduce Sedentary Screen Behaviors in Children

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Jeremy A. Steeves

2012-01-01

Full Text Available Previous research suggests that reducing sedentary screen behaviors may be a strategy for preventing and treating obesity in children. This systematic review describes strategies used in interventions designed to either solely target sedentary screen behaviors or multiple health behaviors, including sedentary screen behaviors. Eighteen studies were included in this paper; eight targeting sedentary screen behaviors only, and ten targeting multiple health behaviors. All studies used behavior modification strategies for reducing sedentary screen behaviors in children (aged 1–12 years. Nine studies only used behavior modification strategies, and nine studies supplemented behavior modification strategies with an electronic device to enhance sedentary screen behaviors reductions. Many interventions (50% significantly reduced sedentary screen behaviors; however the magnitude of the significant reductions varied greatly (−0.44 to −3.1 h/day and may have been influenced by the primary focus of the intervention, number of behavior modification strategies used, and other tools used to limit sedentary screen behaviors.

A review of different behavior modification strategies designed to reduce sedentary screen behaviors in children.

Science.gov (United States)

Steeves, Jeremy A; Thompson, Dixie L; Bassett, David R; Fitzhugh, Eugene C; Raynor, Hollie A

2012-01-01

Previous research suggests that reducing sedentary screen behaviors may be a strategy for preventing and treating obesity in children. This systematic review describes strategies used in interventions designed to either solely target sedentary screen behaviors or multiple health behaviors, including sedentary screen behaviors. Eighteen studies were included in this paper; eight targeting sedentary screen behaviors only, and ten targeting multiple health behaviors. All studies used behavior modification strategies for reducing sedentary screen behaviors in children (aged 1-12 years). Nine studies only used behavior modification strategies, and nine studies supplemented behavior modification strategies with an electronic device to enhance sedentary screen behaviors reductions. Many interventions (50%) significantly reduced sedentary screen behaviors; however the magnitude of the significant reductions varied greatly (-0.44 to -3.1 h/day) and may have been influenced by the primary focus of the intervention, number of behavior modification strategies used, and other tools used to limit sedentary screen behaviors.

Risk modeling and screening for BRCA1 mutations among Filipino breast cancer patients

International Nuclear Information System (INIS)

Nato, Alejandro Q. Jr.

2003-03-01

Breast cancer susceptibility gene, type 1(BRCA1) has been thought to be responsible for ∼45% of families with multiple breast carcinomas and for ∼80% of breast and ovarian cancer families. In this study, we investigated 34 familial Filipino breast cancer (BC) patients to: (a) estimate breast cancer risks and BRCA1/2 mutation carrier probabilities using risk assessment and prior probability models, respectively; (b) screen for putative polymorphisms at selected smaller exons of BRCA1 by single-strand conformation polymorphism (SSCP) analysis; (c) screen for truncated mutations at BRCA1 exon 11 by radioactive protein truncation test (PTT); and (d) estimate posterior probabilities upon incorporation of screening results. SSCP analysis revealed 8 unique putative polymorphisms. Low prevalence of unique putative polymorphisms at exon 2, 5, 17, and 22 may indicate probable mutations. Contrastingly, high prevalence of unique putative polymorphisms at exons 13, 15, and 16 may suggest true polymorphisms which are biologically insignificant. PTT, DHPLC, and sequence analyses revealed a novel mutation in exon 11 involving GT insertion that resulted to a stop codon which generated a 29.7 kDa truncated protein product. This is the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. Initial genotype-phenotype correlations in Filipino BC patients may be elucidated based on screening tests performed. Our results corroborate the findings of a study on unselected incident Filipino BC cases where the reported prevalence of BRCA1 mutation is low. The higher prevalence of putative polypmorphisms may be attributed to the increased stringency in patient prospecting. The Gail, Claus, and BRCAPRO models can be utilized to estimate BC risk in unaffected high-risk individuals but validation is needed. Most of the BRCAPRO and Myriad.com prior probability estimates coincide with the presence of BRCA1 mutation and/or putative polymorphisms. This pioneering

Risk modeling and screening for BRCA1 mutations among Filipino breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Nato, Jr, Alejandro Q

2003-03-01

Breast cancer susceptibility gene, type 1(BRCA1) has been thought to be responsible for {approx}45% of families with multiple breast carcinomas and for {approx}80% of breast and ovarian cancer families. In this study, we investigated 34 familial Filipino breast cancer (BC) patients to: (a) estimate breast cancer risks and BRCA1/2 mutation carrier probabilities using risk assessment and prior probability models, respectively; (b) screen for putative polymorphisms at selected smaller exons of BRCA1 by single-strand conformation polymorphism (SSCP) analysis; (c) screen for truncated mutations at BRCA1 exon 11 by radioactive protein truncation test (PTT); and (d) estimate posterior probabilities upon incorporation of screening results. SSCP analysis revealed 8 unique putative polymorphisms. Low prevalence of unique putative polymorphisms at exon 2, 5, 17, and 22 may indicate probable mutations. Contrastingly, high prevalence of unique putative polymorphisms at exons 13, 15, and 16 may suggest true polymorphisms which are biologically insignificant. PTT, DHPLC, and sequence analyses revealed a novel mutation in exon 11 involving GT insertion that resulted to a stop codon which generated a 29.7 kDa truncated protein product. This is the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. Initial genotype-phenotype correlations in Filipino BC patients may be elucidated based on screening tests performed. Our results corroborate the findings of a study on unselected incident Filipino BC cases where the reported prevalence of BRCA1 mutation is low. The higher prevalence of putative polypmorphisms may be attributed to the increased stringency in patient prospecting. The Gail, Claus, and BRCAPRO models can be utilized to estimate BC risk in unaffected high-risk individuals but validation is needed. Most of the BRCAPRO and Myriad.com prior probability estimates coincide with the presence of BRCA1 mutation and/or putative polymorphisms. This

Screening for thalassemia and other hemoglobinopathies in a tertiary care hospital of West Bengal: implications for population screening.

Science.gov (United States)

Jain, Bhawna Bhutoria; Roy, Rabindra Nath; Ghosh, Sulekha; Ghosh, Tapan; Banerjee, Uma; Bhattacharya, Subodh Kumar

2012-01-01

Hemoglobinopathies are common genetic disorders of hemoglobin, which can be prevented by population screening and offering genetic counseling. In absence of population-based screening for hemoglobinopathies, the hospital-based diagnosis register provide idea about the extent of problem in the community. The present study was undertaken to find out the burden of hemoglobinopathies and spectrum of this disorders among the population who were screened in the hospital-based screening program. A record-basedanalysis of subjects who underwent screening for hemoglobinopathies in Burdwan Medical College and Hospital over a period of 3 years and 4 months revealed that overall 29.3% of subjects were positive for hemoglobinopathies. Beta thalassemia heterozygous was the most commonhemoglobinopathy in this region closely followed by hemoglobin E heterozygous. In view of high prevalence of hemoglobinopathies in this region, a routine premarital screening program is needed for identification and prevention of high-risk marriages.

Visual screening for localized RNAs in yeast revealed novel RNAs at the bud-tip

International Nuclear Information System (INIS)

Andoh, Tomoko; Oshiro, Yukiko; Hayashi, Sachiko; Takeo, Hideki; Tani, Tokio

2006-01-01

Several RNAs, including rRNAs, snRNAs, snoRNAs, and some mRNAs, are known to be localized at specific sites in a cell. Although methods have been established to visualize RNAs in a living cell, no large-scale visual screening of localized RNAs has been performed. In this study, we constructed a genomic library in which random genomic fragments were inserted downstream of U1A-tag sequences under a GAL1 promoter. In a living yeast cell, transcribed U1A-tagged RNAs were visualized by U1A-GFP that binds the RNA sequence of the U1A-tag. In this screening, many RNAs showed nuclear signals. Since the nuclear signals of some RNAs were not seen when the U1A-tag was connected to the 3' ends of the RNAs, it is suggested that their nuclear signals correspond to nascent transcripts on GAL1 promoter plasmids. Using this screening method, we successfully identified two novel localized mRNAs, CSR2 and DAL81, which showed bud-tip localization

Influencing Cancer Screening Participation Rates—Providing a Combined Cancer Screening Program (a ‘One Stop’ Shop Could Be a Potential Answer

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Amanda Bobridge

2017-12-01

Full Text Available IntroductionParticipation in established cancer screening programs remains variable. Therefore, a renewed focus on how to increase screening uptake, including addressing structural barriers such as time, travel, and cost is needed. One approach could be the provision of combined cancer screening, where multiple screening tests are provided at the same time and location (essentially a ‘One Stop’ screening shop. This cohort study explored both cancer screening behavior and the acceptability of a combined screening approach.MethodsParticipants of the North Western Adelaide Health Study (NWAHS, South Australia were invited to participate in a questionnaire about cancer screening behaviors and the acceptability of a proposed ‘One Stop’ cancer screening shop. Data were collected from 10th August 2015 to 18th January 2016, weighted for selection probability, age, and sex and analyzed using descriptive and multivariable logistic regression analysis.Results1,562 people, 52% female (mean age 54.1 years ± 15.2 participated. Reported screening participation was low, the highest being for Pap Smear (34.4%. Common reasons for screening participation were preventing sickness (56.1%, CI 53.2–59.0%, maintaining health (51%, CI 48–53.9%, and free program provision (30.9%, CI 28.2–33.6%. Females were less likely to state that screening is not beneficial [OR 0.37 (CI 0.21–0.66, p < 0.001] and to cite sickness prevention [OR 2.10 (CI 1.46–3.00, p < 0.001] and free program [OR 1.75 (CI 1.22–2.51, p < 0.003] as reasons for screening participation. Of those who did not participate, 34.6% (CI 30.3–39.1% stated that there was nothing that discouraged them from participation, with 55- to 64-year olds [OR 0.24 (CI 0.07–0.74, p < 0.04] being less likely to cite this reason. 21% (CI 17.2–24.8% thought they did not need screening, while a smaller proportion stated not having time (6.9%, CI 4.9–9.7% and the costs associated

A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

Directory of Open Access Journals (Sweden)

Sabine M Hölter

Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

A prospective multiple case study of the impact of emerging scientific evidence on established colorectal cancer screening programs: a study protocol.

Science.gov (United States)

Geddie, Hannah; Dobrow, Mark J; Hoch, Jeffrey S; Rabeneck, Linda

2012-06-01

Health-policy decision making is a complex and dynamic process, for which strong evidentiary support is required. This includes scientifically produced research, as well as information that relates to the context in which the decision takes place. Unlike scientific evidence, this "contextual evidence" is highly variable and often includes information that is not scientifically produced, drawn from sources such as political judgement, program management experience and knowledge, or public values. As the policy decision-making process is variable and difficult to evaluate, it is often unclear how this heterogeneous evidence is identified and incorporated into "evidence-based policy" decisions. Population-based colorectal cancer screening poses an ideal context in which to examine these issues. In Canada, colorectal cancer screening programs have been established in several provinces over the past five years, based on the fecal occult blood test (FOBT) or the fecal immunochemical test. However, as these programs develop, new scientific evidence for screening continues to emerge. Recently published randomized controlled trials suggest that the use of flexible sigmoidoscopy for population-based screening may pose a greater reduction in mortality than the FOBT. This raises the important question of how policy makers will address this evidence, given that screening programs are being established or are already in place. This study will examine these issues prospectively and will focus on how policy makers monitor emerging scientific evidence and how both scientific and contextual evidence are identified and applied for decisions about health system improvement. This study will employ a prospective multiple case study design, involving participants from Ontario, Alberta, Manitoba, Nova Scotia, and Quebec. In each province, data will be collected via document analysis and key informant interviews. Documents will include policy briefs, reports, meeting minutes, media

RAS - Screens & Assays - Drug Discovery

Science.gov (United States)

The RAS Drug Discovery group aims to develop assays that will reveal aspects of RAS biology upon which cancer cells depend. Successful assay formats are made available for high-throughput screening programs to yield potentially effective drug compounds.

Long-term comparison of temperature measurements by the multi-plate shield and Czech-Slovak thermometer screen

Energy Technology Data Exchange (ETDEWEB)

Mozny, Martin; Stepanek, Petr; Hajkova, Lenka; Bares, Daniel [Doksany Observatory, Doksany (Czech Republic). Czech Hydrometeorological Inst.; Trnka, Mirek [Academy of Science of the Czech Republic, Brno (Czech Republic). Global Change Research Centre; Zalud, Zdenek; Semeradova, Daniela [Mendel Univ., Brno (Czech Republic). Agrosystems and Bioclimatology; Koznarova, Vera [Czech Univ. of Life Sciences, Prague (Czech Republic). Dept. of Agroecology and Biometeorology

2012-04-15

Differences between measurements taken with the Czech-Slovak thermometer screen (TS) and the multiplate radiation shield (MRS) should not be neglected. The average difference between the TS and the MRS measurements varied between 0.3 and 2.8 C during suitable weather conditions (wind speed less than 3 m/s, bright and sunny day) throughout the year, during both daytime and nighttime hours. A 10-year time series of comparative measurements in Doksany, Czech Republic, showed that relative to TS, measurements from MRS yielded average and minimum air temperatures that were lower in the winter and higher in the summer. Daily maximum air temperatures were lower for MRS than TS throughout the year. The greatest differences were observed in the maximum air temperatures; only 62 % of all differences between the TS and MRS were less than 0.5 C, and 70 % were less than 1 C. Among minimum air temperatures, 60 % of differences were less than 0.5 C, and 79 % were less than 1 C. In contrast, 74 % of all differences in average daily temperature were less than 0.5 C, and 97 % were less than 1 C. The use of temperature measurements from multiple equipments may negatively affect inference from climate and hydro-meteorological models. Irregular temperature data could be corrected using a simulation of temperature differences (SITEDI) model, which incorporates differences between the MRS and the TS. It is important to consider whether temperature data in the Czech Republic and Slovakia come from the TS or the MRS when analyzing and modeling temperature in Central Europe. (orig.)

Conceptual understanding of screen media parenting: Report of a working group

Science.gov (United States)

Screen media (television, computers, and videogames) use has been linked to multiple child outcomes, including obesity. Parents can be an important influence on children's screen use. There has been an increase in the number of instruments available to assess parenting in feeding and physical activi...

Active versus Passive Screen Time for Young Children

Science.gov (United States)

Sweetser, Penelope; Johnson, Daniel; Ozdowska, Anne; Wyeth, Peta

2012-01-01

In this paper we report some initial findings from our investigations into the Australian Government's Longitudinal Study of Australian Children dataset. It is revealed that the majority of Australian children are exceeding the government's Screen Time recommendations and that most of their screen time is spent as TV viewing, as opposed to video…

Screening in larval zebrafish reveals tissue-specific distribution of fifteen fluorescent compounds

Directory of Open Access Journals (Sweden)

Yuxiao Yao

2017-09-01

Full Text Available The zebrafish is a prominent vertebrate model for low-cost in vivo whole organism screening. In our recent screening of the distribution patterns of fluorescent compounds in live zebrafish larvae, fifteen compounds with tissue-specific distributions were identified. Several compounds were observed to accumulate in tissues where they were reported to induce side-effects, and compounds with similar structures tended to be enriched in the same tissues, with minor differences. In particular, we found three novel red fluorescent bone-staining dyes: purpurin, lucidin and 3-hydroxy-morindone; purpurin can effectively label bones in both larval and adult zebrafish, as well as in postnatal mice, without significantly affecting bone mass and density. Moreover, two structurally similar chemotherapeutic compounds, doxorubicin and epirubicin, were observed to have distinct distribution preferences in zebrafish. Epirubicin maintained a relatively higher concentration in the liver, and performed better in inhibiting hepatic hyperplasia caused by the over-expression of krasG12V. In total, our study suggests that the transparent zebrafish larvae serve as valuable tools for identifying tissue-specific distributions of fluorescent compounds.

Quantifying and resolving multiple vector transformants in S. cerevisiae plasmid libraries.

Science.gov (United States)

Scanlon, Thomas C; Gray, Elizabeth C; Griswold, Karl E

2009-11-20

In addition to providing the molecular machinery for transcription and translation, recombinant microbial expression hosts maintain the critical genotype-phenotype link that is essential for high throughput screening and recovery of proteins encoded by plasmid libraries. It is known that Escherichia coli cells can be simultaneously transformed with multiple unique plasmids and thusly complicate recombinant library screening experiments. As a result of their potential to yield misleading results, bacterial multiple vector transformants have been thoroughly characterized in previous model studies. In contrast to bacterial systems, there is little quantitative information available regarding multiple vector transformants in yeast. Saccharomyces cerevisiae is the most widely used eukaryotic platform for cell surface display, combinatorial protein engineering, and other recombinant library screens. In order to characterize the extent and nature of multiple vector transformants in this important host, plasmid-born gene libraries constructed by yeast homologous recombination were analyzed by DNA sequencing. It was found that up to 90% of clones in yeast homologous recombination libraries may be multiple vector transformants, that on average these clones bear four or more unique mutant genes, and that these multiple vector cells persist as a significant proportion of library populations for greater than 24 hours during liquid outgrowth. Both vector concentration and vector to insert ratio influenced the library proportion of multiple vector transformants, but their population frequency was independent of transformation efficiency. Interestingly, the average number of plasmids born by multiple vector transformants did not vary with their library population proportion. These results highlight the potential for multiple vector transformants to dominate yeast libraries constructed by homologous recombination. The previously unrecognized prevalence and persistence of multiply

Quantifying and resolving multiple vector transformants in S. cerevisiae plasmid libraries

Directory of Open Access Journals (Sweden)

Gray Elizabeth C

2009-11-01

Full Text Available Abstract Background In addition to providing the molecular machinery for transcription and translation, recombinant microbial expression hosts maintain the critical genotype-phenotype link that is essential for high throughput screening and recovery of proteins encoded by plasmid libraries. It is known that Escherichia coli cells can be simultaneously transformed with multiple unique plasmids and thusly complicate recombinant library screening experiments. As a result of their potential to yield misleading results, bacterial multiple vector transformants have been thoroughly characterized in previous model studies. In contrast to bacterial systems, there is little quantitative information available regarding multiple vector transformants in yeast. Saccharomyces cerevisiae is the most widely used eukaryotic platform for cell surface display, combinatorial protein engineering, and other recombinant library screens. In order to characterize the extent and nature of multiple vector transformants in this important host, plasmid-born gene libraries constructed by yeast homologous recombination were analyzed by DNA sequencing. Results It was found that up to 90% of clones in yeast homologous recombination libraries may be multiple vector transformants, that on average these clones bear four or more unique mutant genes, and that these multiple vector cells persist as a significant proportion of library populations for greater than 24 hours during liquid outgrowth. Both vector concentration and vector to insert ratio influenced the library proportion of multiple vector transformants, but their population frequency was independent of transformation efficiency. Interestingly, the average number of plasmids born by multiple vector transformants did not vary with their library population proportion. Conclusion These results highlight the potential for multiple vector transformants to dominate yeast libraries constructed by homologous recombination. The

Discovery of small molecules binding to the normal conformation of prion by combining virtual screening and multiple biological activity evaluation methods

Science.gov (United States)

Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun

2017-12-01

Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.

BMI and breast cancer prognosis benefit: mammography screening reveals differences between normal weight and overweight women.

Science.gov (United States)

Crispo, Anna; Grimaldi, Maria; D'Aiuto, Massimiliano; Rinaldo, Massimo; Capasso, Immacolata; Amore, Alfonso; D'Aiuto, Giuseppe; Giudice, Aldo; Ciliberto, Gennaro; Montella, Maurizio

2015-02-01

Few studies are available on the potential impact of body weight on breast cancer prognosis in screen-detected patients. Moreover, it is not known whether body mass index (BMI) could have a different prognostic impact in screen-detected versus symptomatic breast cancer patients. To investigate these unsolved issues, we carried out a retrospective study evaluating the effect of BMI on breast cancer prognosis in screen-detected vs symptomatic breast cancer patients. We conducted a follow-up study on 448 women diagnosed with incident, histologically-confirmed breast cancer. Patients were categorized according to their BMI as normal weight, overweight and obese. Disease free survival (DFS), overall survival (OS), and BMI curves were compared according to mode of cancer detection. Among screen-detected patients, higher BMI was associated with a significant lower DFS, whereas no significant difference was observed among symptomatic patients. OS showed similar results. In the multivariate analysis adjusting for age, education, tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR) and menopausal status, the risk for high level of BMI among screen-detected patients did not reach the statistical significance for either recurrence or survival. Our study highlights the potential impact of high bodyweight in breast cancer prognosis, the findings confirm that obesity plays a role in women breast cancer prognosis independently from diagnosis mode. Copyright © 2014 Elsevier Ltd. All rights reserved.

A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome.

Science.gov (United States)

Cuykendall, Tawny N; Satyaki, P; Ji, Shuqing; Clay, Derek M; Edelman, Nathaniel B; Kimchy, Alexandra; Li, Ling-Hei; Nuzzo, Erin A; Parekh, Neil; Park, Suna; Barbash, Daniel A

2014-10-27

Hybrid sons between Drosophila melanogaster females and D. simulans males die as 3rd instar larvae. Two genes, D. melanogaster Hybrid male rescue (Hmr) on the X chromosome, and D. simulans Lethal hybrid rescue (Lhr) on chromosome II, interact to cause this lethality. Loss-of-function mutations in either gene suppress lethality, but several pieces of evidence suggest that additional factors are required for hybrid lethality. Here we screen the D. melanogaster autosomal genome by using the Bloomington Stock Center Deficiency kit to search for additional regions that can rescue hybrid male lethality. Our screen is designed to identify putative hybrid incompatibility (HI) genes similar to Hmr and Lhr which, when removed, are dominant suppressors of lethality. After screening 89% of the autosomal genome, we found no regions that rescue males to the adult stage. We did, however, identify several regions that rescue up to 13% of males to the pharate adult stage. This weak rescue suggests the presence of multiple minor-effect HI loci, but we were unable to map these loci to high resolution, presumably because weak rescue can be masked by genetic background effects. We attempted to test one candidate, the dosage compensation gene male specific lethal-3 (msl-3), by using RNA interference with short hairpin microRNA constructs targeted specifically against D. simulans msl-3 but failed to achieve knockdown, in part due to off-target effects. We conclude that the D. melanogaster autosomal genome likely does not contain additional major-effect HI loci. We also show that Hmr is insufficient to fully account for the lethality associated with the D. melanogaster X chromosome, suggesting that additional X-linked genes contribute to hybrid lethality. Copyright © 2014 Cuykendall et al.

The significance of X-ray mammography for breast cancer screening

International Nuclear Information System (INIS)

Schulz-Wendtland, R.; Kraemer, S.; Doeinghaus, K.; Saebel, M.; Lang, N.; Bautz, W.

1997-01-01

One high-priority health problem in our society are the high, age-specifically standardized mortality rates of breast cancer. Breast-conserving therapies are increasingly applied today whenever appropriate, as the patient outcome depends less on the local size of the tumor than on the existing micrometastases and general spreading of the tumor in terms of a systemic tumor lesion at the time of diagnosis and primary therapy. Among the available diagnostic methods, X-ray mammography is the modality of choice for detection of small, pre-clinical carcinoma or pre-invasive stages. Although one should not overestimate the true correct findings in detection of tumors less than 1 cm of size, the proportion of correct findings indicating T1-tumors or minimal cancer obtained in multiple screening projects is surprising. The fact that the number of detected cases involving the lymph nodes is 50% in patients with clinical symptoms and only 20% or even less in diognoses obtained by screening gives reason enough to speak of ''early detection'' in the latter case. Finally, the results of the HIP study, (reduction of mortality rates for women over 50 by 40%), and of the Oestergoetland study (for women between 40 and 70 years of age, 31%) are very convincing. Furthermore, a meta-analysis on the value of breast cancer screening reveals a mortality reduction of 22% in women between 40 and 49 years of age. Further improvement of the mammographic method and quality control in medical evaluation hopefully will contribute to more widespread screening activities also in Germany, and hence to a further reduction of mortality rates. (Orig./vhe) [de

Validation of Screening Questions for Hyperacusis in Chronic Tinnitus

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Martin Schecklmann

2015-01-01

Full Text Available Background. We investigated the validity of the two hyperacusis items of the TSCHQ (Tinnitus Sample Case History Questionnaire from the TRI (Tinnitus Research Initiative database by comparing them with the German hyperacusis questionnaire GÜF. Methods. We investigated the association of the GÜF with the TSCHQ screening questions for both the sum score and the single items with correlation, contrast, principal component, and discriminant analysis in a sample of 161 patients with chronic tinnitus. Results. TSCHQ items and the GÜF total score were significantly associated with a special focus on fear and pain related hyperacusis. Factor analysis of the GÜF revealed the three factors “fear and pain related hyperacusis,” “hearing related problems,” and “problems in quality of life.” A discriminant analysis showed a sensitivity of 64% and a specificity of 71% of the TSCHQ items for the establishment of tinnitus patient subgroups with and without hyperacusis. Discussion. Both hyperacusis TSCHQ items can serve as screening questions with respect to self-reported hyperacusis in chronic tinnitus with a specific focus on fear and pain related hyperacusis. However, the multiple dimensions of hyperacusis should be considered for diagnosis and treatment in both scientific and clinical contexts.

Genetics Home Reference: multiple epiphyseal dysplasia

Science.gov (United States)

... Hamel BC, Spranger J, Zabel B, Cohn DH, Cole WG, Hecht JT, Superti-Furga A. Recessive multiple ... medicine? What is newborn screening? New Pages Lyme disease Fibromyalgia White-Sutton syndrome All New & Updated Pages ...

Visual field abnormalities in multiple sclerosis.

OpenAIRE

Patterson, V H; Heron, J R

1980-01-01

Visual fields were examined with a tangent screen in 54 patients with multiple sclerosis (MS) or optic neuritis (ON). Visual fields were abnormal in all patients with definite MS, 94% with probable MS and 81% with possible MS. Three-quarters of the MS patients with no history of visual symptoms had abnormal fields. The commonest defect found was an arcuate scotoma. As a diagnostic test of visual pathway involvement in MS, tangent screen examination compares favourably with more sophisticated ...

Impurity screening of scrape-off plasma in a tokamak

International Nuclear Information System (INIS)

Kishimoto, Hiroshi; Tani, Keiji; Nakamura, Hiroo

1981-11-01

Impurity screening effect of a scrape-off layer has been studied in a tokamak, based on a simple model of wall-released impurity behavior. Wall-sputtered impurities are stopped effectively by the scrape-off plasma for a medium-Z or high-Z wall system while major part of impurities enters the main plasma in a low-Z wall system. The screening becomes inefficient with increase of scrape-off plasma temperature. Successive multiplication of recycling impurities in the scrape-off layer is large for a high-Z wall and is enhanced by a rise of scrape-off plasma temperature. The stability of plasma-wall interaction is determined by a multiplication factor of recycling impurities. (author)

Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening.

Science.gov (United States)

Beaber, Elisabeth F; Kim, Jane J; Schapira, Marilyn M; Tosteson, Anna N A; Zauber, Ann G; Geiger, Ann M; Kamineni, Aruna; Weaver, Donald L; Tiro, Jasmin A

2015-06-01

General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Screening for a Chronic Disease: A Multiple Stage Duration Model with Partial Observability.

Science.gov (United States)

Mroz, Thomas A; Picone, Gabriel; Sloan, Frank; Yashkin, Arseniy P

2016-08-01

We estimate a dynamic multi-stage duration model to investigate how early detection of diabetes can delay the onset of lower extremity complications and death. We allow for partial observability of the disease stage, unmeasured heterogeneity, and endogenous timing of diabetes screening. Timely diagnosis appears important. We evaluate the effectiveness of two potential policies to reduce the monetary costs of frequent screening in terms of lost longevity. Compared to the status quo, the more restrictive policy yields an implicit value for an additional year of life of about $50,000, while the less restrictive policy implies a value of about $120,000.

Ethical issues in cancer screening and prevention.

Science.gov (United States)

Plutynski, Anya

2012-06-01

November 2009's announcement of the USPSTF's recommendations for screening for breast cancer raised a firestorm of objections. Chief among them were that the panel had insufficiently valued patients' lives or allowed cost considerations to influence recommendations. The publicity about the recommendations, however, often either simplified the actual content of the recommendations or bypassed significant methodological issues, which a philosophical examination of both the science behind screening recommendations and their import reveals. In this article, I discuss two of the leading ethical considerations at issue in screening recommendations: respect for patient autonomy and beneficence and then turn to the most significant methodological issues raised by cancer screening: the potential biases that may infect a trial of screening effectiveness, the problem of base rates in communicating risk, and the trade-offs involved in a judgment of screening effectiveness. These issues reach more broadly, into the use of "evidence-based" medicine generally, and have important implications for informed consent.

Quick screening of cognitive function in Indian multiple sclerosis patients using Montreal cognitive assessment test-short version

Directory of Open Access Journals (Sweden)

Darshpreet Kaur

2013-01-01

Full Text Available Background: Cognitive impairments in multiple sclerosis (MS are now well recognized worldwide, but unfortunately this domain has been less explored in India due to many undermining factors. The aim of this study was to evaluate cognitive impairments in Indian MS patients with visual or upper limb motor problems with the help of short version of Montreal cognitive assessment test (MoCA. Subjects and Methods: Thirty MS patients and 50 matched controls were recruited for the 12 points MoCA task. Receiver operating characteristic curve (ROC analysis was performed to determine optimal sensitivity and specificity of the 12 points MoCA in differentiating cognitively impaired patients and controls. Results: The mean 12 points MoCA scores of the controls and MS patients were 11.56 ± 0.67 and 8.06 ± 1.99, respectively. In our study, the optimal cut-off value for 12 points MoCA to be able to differentiate patients with cognitive impairments from controls is 10/12. Accordingly, 73.3% patients fell below the cut off value. Both the groups did not have significant statistical differences with regard to age and educational years. Conclusion: The 12 points, short version of MoCA, is a useful brief screening tool for quick and early detection of mild cognitive impairments in subjects with MS. It can be administered to patients having visual and motor problems. It is of potential use by primary care physicians, nurses, and other allied health professionals who need a quick screening test. No formal training for administration is required. Financial and time constraints should not limit the use of the proposed instrument.

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

Science.gov (United States)

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

2008-01-01

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

Providing floating capabilities in latest-generation sand screens

Energy Technology Data Exchange (ETDEWEB)

Bowen, E.G.; Coronado, M.P. [Society of Petroleum Engineers, Richardson, TX (United States)]|[Baker Hughes, Houston, TX (United States)

2008-10-15

Alternative production methods are needed for the massive reserves located in the bitumen region of Canada's tar sands. The area has over 100 installations of sand screens/slotted liners in both injection and production legs using steam-assisted gravity drainage (SAGD) technology. Multiple wells must be drilled from a single pad because of the sensitive nature of the environment. With significant depths of these wells, a floating sand screen provides assurance that the sand screen will reach the desired depth. Paraffin is generally used to plug the flow access of the screen during installation. This paper discussed a new technology that has been developed to allow for sand screen installations without relying on paraffin wax to withstand differential pressure. The new technology uses a hydro-mechanical valving system incorporated into the screen design to temporarily close off the screen while being run in the hole. The paper described how the technology could provide a reliable, time-saving solution for SAGD installations when floating sand control screens are needed. The paper discussed current technology and its limitations, sand screen installation, screen design for floating applications, and additional applications. It was concluded that this technology solution provides a unique alternative to the methods currently used to install sand screens with SAGD technology in the fast growing Canadian market for bitumen recovery. 2 refs., 5 figs.

A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia

Science.gov (United States)

Bray, Walter M.; White, Pamela M.; Ruybal, Jordan; Lokey, R. Scott; Debec, Alain; Sullivan, William

2012-01-01

Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular Wolbachia titer both in Drosophila melanogaster and Brugia malayi, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt Drosophila microtubule organization, suggesting that this compound reduces titer through direct targeting of Wolbachia. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces Wolbachia elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their Wolbachia endosymbionts. PMID:23028321

Multifractal fluctuations in joint angles during infant spontaneous kicking reveal multiplicativity-driven coordination

International Nuclear Information System (INIS)

Stephen, Damian G.; Hsu, Wen-Hao; Young, Diana; Saltzman, Elliot L.; Holt, Kenneth G.; Newman, Dava J.; Weinberg, Marc; Wood, Robert J.; Nagpal, Radhika; Goldfield, Eugene C.

2012-01-01

Previous research has considered infant spontaneous kicking as a form of exploration. According to this view, spontaneous kicking provides information about motor degrees of freedom and may shape multijoint coordinations for more complex movement patterns such as gait. Recent work has demonstrated that multifractal, multiplicative fluctuations in exploratory movements index energy flows underlying perceptual-motor information. If infant spontaneous kicking is exploratory and occasions an upstream flow of information from the motor periphery, we expected not only that multiplicativity of fluctuations at the hip should promote multiplicativity of fluctuations at more distal joints (i.e., reflecting downstream effects of neural control) but also that multiplicativity at more distal joints should promote multiplicativity at the hip. Multifractal analysis demonstrated that infant spontaneous kicking in four typically developing infants for evidence of multiplicative fluctuations in multiple joint angles along the leg (i.e., hip, knee, and ankle) exhibited multiplicativity. Vector autoregressive modeling demonstrated that only one leg exhibited downstream effects but that both legs exhibited upstream effects. These results confirm the exploratory aspect of infant spontaneous kicking and suggest chaotic dynamics in motor coordination. They also resonate with existing models of chaos-controlled robotics and noise-based interventions for rehabilitating motor coordination in atypically developing patients.

Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

Directory of Open Access Journals (Sweden)

Britta Stadelmann

2016-03-01

Full Text Available The metacestode (larval stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE, a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV, comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

Mammography screening services: market segments and messages.

Science.gov (United States)

Scammon, D L; Smith, J A; Beard, T

1991-01-01

Mammography has become a vital tool for the early detection of breast cancer. Although many organizations and health care facilities are working to educate and motivate women to take advantage of the life saving opportunity that is offered through screening mammography, only twenty percent of women who should be screened actually have the procedure performed. In order to reach women who have not been screened, it is important to learn which factors most strongly motivate those women who do choose to have a mammogram. Depth interviews with 18 women attending a mobile mammography unit were conducted to explore the decision making process of women obtaining mammography screening services and to develop a profile of prevalent emotions, attitudes, and feelings associated with receiving breast cancer screening services. Analysis of the interview transcripts revealed several important themes to which health care professionals can direct marketing and health promotion strategies.

Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

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Yoon-Dong Park

2016-08-01

Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

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Maleeha Maria

Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

Generalized Linear Mixed Model Analysis of Urban-Rural Differences in Social and Behavioral Factors for Colorectal Cancer Screening

Science.gov (United States)

Wang, Ke-Sheng; Liu, Xuefeng; Ategbole, Muyiwa; Xie, Xin; Liu, Ying; Xu, Chun; Xie, Changchun; Sha, Zhanxin

2017-09-27

Objective: Screening for colorectal cancer (CRC) can reduce disease incidence, morbidity, and mortality. However, few studies have investigated the urban-rural differences in social and behavioral factors influencing CRC screening. The objective of the study was to investigate the potential factors across urban-rural groups on the usage of CRC screening. Methods: A total of 38,505 adults (aged ≥40 years) were selected from the 2009 California Health Interview Survey (CHIS) data - the latest CHIS data on CRC screening. The weighted generalized linear mixed-model (WGLIMM) was used to deal with this hierarchical structure data. Weighted simple and multiple mixed logistic regression analyses in SAS ver. 9.4 were used to obtain the odds ratios (ORs) and their 95% confidence intervals (CIs). Results: The overall prevalence of CRC screening was 48.1% while the prevalence in four residence groups - urban, second city, suburban, and town/rural, were 45.8%, 46.9%, 53.7% and 50.1%, respectively. The results of WGLIMM analysis showed that there was residence effect (pregression analysis revealed that age, race, marital status, education level, employment stats, binge drinking, and smoking status were associated with CRC screening (p<0.05). Stratified by residence regions, age and poverty level showed associations with CRC screening in all four residence groups. Education level was positively associated with CRC screening in second city and suburban. Infrequent binge drinking was associated with CRC screening in urban and suburban; while current smoking was a protective factor in urban and town/rural groups. Conclusions: Mixed models are useful to deal with the clustered survey data. Social factors and behavioral factors (binge drinking and smoking) were associated with CRC screening and the associations were affected by living areas such as urban and rural regions. Creative Commons Attribution License

High-Throughput Genetic Screen Reveals that Early Attachment and Biofilm Formation Are Necessary for Full Pyoverdine Production by Pseudomonas aeruginosa

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Donghoon Kang

2017-09-01

Full Text Available Pseudomonas aeruginosa is a re-emerging, multidrug-resistant, opportunistic pathogen that threatens the lives of immunocompromised patients, patients with cystic fibrosis, and those in critical care units. One of the most important virulence factors in this pathogen is the siderophore pyoverdine. Pyoverdine serves several critical roles during infection. Due to its extremely high affinity for ferric iron, pyoverdine gives the pathogen a significant advantage over the host in their competition for iron. In addition, pyoverdine can regulate the production of multiple bacterial virulence factors and perturb host mitochondrial homeostasis. Inhibition of pyoverdine biosynthesis decreases P. aeruginosa pathogenicity in multiple host models. To better understand the regulation of pyoverdine production, we developed a high-throughput genetic screen that uses the innate fluorescence of pyoverdine to identify genes necessary for its biosynthesis. A substantial number of hits showing severe impairment of pyoverdine production were in genes responsible for early attachment and biofilm formation. In addition to genetic disruption of biofilm, both physical and chemical perturbations also attenuated pyoverdine production. This regulatory relationship between pyoverdine and biofilm is particularly significant in the context of P. aeruginosa multidrug resistance, where the formation of biofilm is a key mechanism preventing access to antimicrobials and the immune system. Furthermore, we demonstrate that the biofilm inhibitor 2-amino-5,6-dimethylbenzimidazole effectively attenuates pyoverdine production and rescues Caenorhabditis elegans from P. aeruginosa-mediated pathogenesis. Our findings suggest that targeting biofilm formation in P. aeruginosa infections may have multiple therapeutic benefits and that employing an unbiased, systems biology-based approach may be useful for understanding the regulation of specific virulence factors and identifying novel anti

The paradox of screening: Rural women's views on screening for postnatal depression

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Small Rhonda E

2010-12-01

Full Text Available Abstract Background Universal screening for postnatal depression is currently being promoted in Australia to assist detection and treatment of affected women, yet debate continues internationally about the effectiveness of screening. One rural shire in Victoria has been screening all women for postnatal depression at maternal and child health checks for many years. This paper explores the views of women affected by this intervention. Methods A postal survey was sent to an entire one year cohort of women resident in the shire and eligible for this program [n = 230]. Women were asked whether they recalled having been screened for postnatal depression and what their experience had been, including any referrals made as a result of screening. Women interested in providing additional information were invited to give a phone number for further contact. Twenty women were interviewed in-depth about their experiences. The interview sample was selected to include both depressed and non-depressed women living in town and on rural properties, who represented the range of circumstances of women living in the shire. Results The return rate for the postal survey was 62% [n = 147/230]. Eighty-seven women indicated that they were interested in further contact, 80 of whom were able to be reached by telephone and 20 were interviewed in-depth. Women had diverse views and experiences of screening. The EPDS proved to be a barrier for some women, and a facilitator for others, in accessing support and referrals. The mediating factor appeared to be a trusting relationship with the nurse able to communicate her concern for the woman and offer support and referrals if required. Conclusions Detection of maternal depression requires more than administration of a screening tool at a single time point. While this approach did work for some women, for others it actually made appropriate care and support more difficult. Rather, trained and empathic healthcare providers working

Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei

Energy Technology Data Exchange (ETDEWEB)

Begley, Darren W.; Hartley, Robert C.; Davies, Douglas R.; Edwards, Thomas E.; Leonard, Jess T.; Abendroth, Jan; Burris, Courtney A.; Bhandari, Janhavi; Myler, Peter J.; Staker, Bart L.; Stewart, Lance J. (UWASH); (Emerald)

2011-09-28

As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification of several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme.

Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

Energy Technology Data Exchange (ETDEWEB)

Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M.; Shell, Scott A.; Bacus, Sarah

2015-05-15

Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks. Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in

Enhancing Reproducibility in Cancer Drug Screening: How Do We Move Forward?

DEFF Research Database (Denmark)

Shi, Leming; Haibe-Kains, Benjamin; Birkbak, Nicolai Juul

2014-01-01

Large-scale pharmacogenomic high-throughput screening (HTS) studies hold great potential for generating robust genomic predictors of drug response. Two recent large-scale HTS studies have reported results of such screens, revealing several known and novel drug sensitivities and biomarkers...

Barriers to Mammography Screening: How to Overcome Them

Directory of Open Access Journals (Sweden)

Yasmin Hassoun

2015-10-01

Full Text Available Background: Screening mammography is an established intervention that leads to early breast cancer detection and reduced mortality. The Lebanese Ministry of Health has initiated yearly awareness campaigns and provided free mammography in multiple centers around the country. Methods: The study took place in two major areas of Lebanon - Beirut and South Lebanon. This cross-sectional survey aimed to assess knowledge about breast cancer screening and screening behaviors in the Lebanese population. The primary outcome of the study was to assess the reasons that prevented women from performing screening mammography based on our categories of questions: lack of knowledge about breast cancer, lack of access to screening facilities, failure of primary care physician to encourage screening behavior, and other reasons. Results: The major barriers to seek screening that had statistically significant P-values, in order of prevalence, included: lack of knowledge about breast cancer, followed by social reasons and lack of access. Conclusion: Given the prevalence of breast cancer in our population, it is important to understand the pitfalls that we experience in promoting awareness. Our study is the first study to reach out to the community to assess perceived barriers against screening and provide solutions for such barriers.

Assessing the Effectiveness of Functional Genetic Screens for the Identification of Bioactive Metabolites

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Staffan Kjelleberg

2012-12-01

Full Text Available A common limitation for the identification of novel activities from functional (meta genomic screens is the low number of active clones detected relative to the number of clones screened. Here we demonstrate that constructing libraries with strains known to produce bioactives can greatly enhance the screening efficiency, by increasing the “hit-rate” and unmasking multiple activities from the same bacterial source.

On the representation of electron multiple elastic-scattering distributions for Monte Carlo calculations

International Nuclear Information System (INIS)

Kawrakow, I.; Bielajew, A.F.

1998-01-01

A new representation of elastic electron-nucleus (Coulomb) multiple-scattering distributions is developed. Using the screened Rutherford cross section with the Moliere screening parameter as an example, a simple analytic angular transformation of the Goudsmit-Saunderson multiple-scattering distribution accounts for most of the structure of the angular distribution leaving a residual 3-parameter (path-length, transformed angle and screening parameter) function that is reasonably slowly varying and suitable for rapid, accurate interpolation in a computer-intensive algorithm. The residual function is calculated numerically for a wide range of Moliere screening parameters and path-lengths suitable for use in a general-purpose condensed-history Monte Carlo code. Additionally, techniques are developed that allow the distributions to be scaled to account for energy loss. This new representation allows ''''on-the-fly'''' sampling of Goudsmit-Saunderson angular distributions in a screened Rutherford approximation suitable for class II condensed-history Monte Carlo codes. (orig.)

Recycled incomplete identification procedures for blood screening

NARCIS (Netherlands)

Bar-Lev, S.K.; Boxma, O.J.; Kleiner, I.; Perry, D.; Stadje, W.

2017-01-01

The operation of blood banks aims at the cost-efficient supply of uncontaminated human blood. Each unit of donated blood goes through multiple testing for the presence of various pathogens which are able to cause transfusion-transmitted diseases. The blood screening process is comprised of two

Population-based colorectal cancer screening by fecal immunochemical testing over multiple rounds

NARCIS (Netherlands)

van der Vlugt, M.

2017-01-01

Colorectal cancer (CRC) is one of the major causes of death in the Netherlands, accounting for over 5100 deaths in 2015. Population screening aims to detect CRC or its precursors, advanced adenoma, in an early phase, thereby reducing CRC morbidity and mortality. A recent observational study

Screening the budding yeast genome reveals unique factors affecting K2 toxin susceptibility.

Science.gov (United States)

Servienė, Elena; Lukša, Juliana; Orentaitė, Irma; Lafontaine, Denis L J; Urbonavičius, Jaunius

2012-01-01

Understanding how biotoxins kill cells is of prime importance in biomedicine and the food industry. The budding yeast (S. cerevisiae) killers serve as a convenient model to study the activity of biotoxins consistently supplying with significant insights into the basic mechanisms of virus-host cell interactions and toxin entry into eukaryotic target cells. K1 and K2 toxins are active at the cell wall, leading to the disruption of the plasma membrane and subsequent cell death by ion leakage. K28 toxin is active in the cell nucleus, blocking DNA synthesis and cell cycle progression, thereby triggering apoptosis. Genome-wide screens in the budding yeast S. cerevisiae identified several hundred effectors of K1 and K28 toxins. Surprisingly, no such screen had been performed for K2 toxin, the most frequent killer toxin among industrial budding yeasts. We conducted several concurrent genome-wide screens in S. cerevisiae and identified 332 novel K2 toxin effectors. The effectors involved in K2 resistance and hypersensitivity largely map in distinct cellular pathways, including cell wall and plasma membrane structure/biogenesis and mitochondrial function for K2 resistance, and cell wall stress signaling and ion/pH homeostasis for K2 hypersensitivity. 70% of K2 effectors are different from those involved in K1 or K28 susceptibility. Our work demonstrates that despite the fact that K1 and K2 toxins share some aspects of their killing strategies, they largely rely on different sets of effectors. Since the vast majority of the host factors identified here is exclusively active towards K2, we conclude that cells have acquired a specific K2 toxin effectors set. Our work thus indicates that K1 and K2 have elaborated different biological pathways and provides a first step towards the detailed characterization of K2 mode of action.

In Vivo Screening Using Transgenic Zebrafish Embryos Reveals New Effects of HDAC Inhibitors Trichostatin A and Valproic Acid on Organogenesis.

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Ling Li

Full Text Available The effects of endocrine disrupting chemicals (EDCs on reproduction are well known, whereas their developmental effects are much less characterized. However, exposure to endocrine disruptors during organogenesis may lead to deleterious and permanent problems later in life. Zebrafish (Danio rerio transgenic lines expressing the green fluorescent protein (GFP in specific organs and tissues are powerful tools to uncover developmental defects elicited by EDCs. Here, we used seven transgenic lines to visualize in vivo whether a series of EDCs and other pharmaceutical compounds can alter organogenesis in zebrafish. We used transgenic lines expressing GFP in pancreas, liver, blood vessels, inner ear, nervous system, pharyngeal tooth and pectoral fins. This screen revealed that four of the tested chemicals have detectable effects on different organs, which shows that the range of effects elicited by EDCs is wider than anticipated. The endocrine disruptor tetrabromobisphenol-A (TBBPA, as well as the three drugs diclofenac, trichostatin A (TSA and valproic acid (VPA induced abnormalities in the embryonic vascular system of zebrafish. Moreover, TSA and VPA induced specific alterations during the development of pancreas, an observation that was confirmed by in situ hybridization with specific markers. Developmental delays were also induced by TSA and VPA in the liver and in pharyngeal teeth, resulting in smaller organ size. Our results show that EDCs can induce a large range of developmental alterations during embryogenesis of zebrafish and establish GFP transgenic lines as powerful tools to screen for EDCs effects in vivo.

High-throughput screening reveals alsterpaullone, 2-cyanoethyl as a potent p27Kip1 transcriptional inhibitor.

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Brandon J Walters

Full Text Available p27Kip1 is a cell cycle inhibitor that prevents cyclin dependent kinase (CDK/cyclin complexes from phosphorylating their targets. p27Kip1 is a known tumor suppressor, as the germline loss of p27Kip1 results in sporadic pituitary formation in aged rodents, and its presence in human cancers is indicative of a poor prognosis. In addition to its role in cancer, loss of p27Kip1 results in regenerative phenotypes in some tissues and maintenance of stem cell pluripotency, suggesting that p27Kip1 inhibitors could be beneficial for tissue regeneration. Because p27Kip1 is an intrinsically disordered protein, identifying direct inhibitors of the p27Kip1 protein is difficult. Therefore, we pursued a high-throughput screening strategy to identify novel p27Kip1 transcriptional inhibitors. We utilized a luciferase reporter plasmid driven by the p27Kip1 promoter to transiently transfect HeLa cells and used cyclohexamide as a positive control for non-specific inhibition. We screened a "bioactive" library consisting of 8,904 (4,359 unique compounds, of which 830 are Food and Drug Administration (FDA approved. From this screen, we successfully identified 111 primary hits with inhibitory effect against the promoter of p27Kip1. These hits were further refined using a battery of secondary screens. Here we report four novel p27Kip1 transcriptional inhibitors, and further demonstrate that our most potent hit compound (IC50 = 200 nM Alsterpaullone 2-cyanoethyl, inhibits p27Kip1 transcription by preventing FoxO3a from binding to the p27Kip1 promoter. This screen represents one of the first attempts to identify inhibitors of p27Kip1 and may prove useful for future tissue regeneration studies.

Reasons for never and intermittent completion of colorectal cancer screening after receiving multiple rounds of mailed fecal tests.

Science.gov (United States)

Green, Beverly B; BlueSpruce, June; Tuzzio, Leah; Vernon, Sally W; Aubree Shay, L; Catz, Sheryl L

2017-05-30

Long-term adherence to colorectal cancer (CRC) screening is particularly important for fecal testing. Some U.S. studies report that only 25% of individuals repeat fecal testing annually. The purpose of this qualitative study was to identify barriers and facilitators reported by patients with suboptimal screening adherence to refine interventions for starting ongoing adherence to CRC screening. We also explored whether participants, particularly never screeners, would be willing to do a CRC screening blood test. Forty-one patients who previously enrolled in the Systems of Support to Increase CRC Screening (SOS) trial were interviewed 4-5 years later. Participants were purposively selected to include men and women with diverse race/ethnicities who had either been inconsistent screeners or had never screened during the first three years of SOS despite receiving at least two rounds of mailed fecal tests. Two interviewers conducted 30-min telephone interviews using a semi-structured interview guide. An iterative thematic analysis approach was used. Themes related to screening barriers were more pervasive among never screeners including: (1) Avoidance (inattention, procrastination) (2) Concerns about handling stool; (3) Health concerns; (4) Fear of a cancer diagnosis or positive test results. Themes related to screening facilitators were more often mentioned by participants who screened at least once including: (1) Use of a simpler 1-sample fecal test; (2) Convenience of mailings and doing the test at home; (3) Salience of prevention, especially as one got older; and (4) Influence of recommendations from providers, family and friends. Participants had diverse preferences for the number (3 on average) and types (phone, mail, text) of screening reminders. Some participants did not prefer e-mail links to the patient shared electronic health record because of difficulties remembering their password. It was acceptable for a nurse or medical assistant not from their clinic to

Individual decision making in relation to participation in cardiovascular screening: a study of revealed and stated preferences.

Science.gov (United States)

Søgaard, Rikke; Lindholt, Jes; Gyrd-Hansen, Dorte

2013-02-01

The (cost-)effectiveness of a screening programme may be strongly influenced by the participation rate. The objective of this study was to compare participants' and non-participants' motives for the attendance decision as well as their overall preferences for participation in cardiovascular disease screening. This study sampled 1053 participants and 1006 non-participants from a screening trial and randomly allocated the participants to receive different levels of additional information about the screening programme. An ad hoc survey questionnaire about doubt and arguments in relation to the participation decision was given to participants and non-participants along with a contingent valuation task. Among participants, 5% had doubt about participation and the most frequent argument was that they did not want the test result. Among non-participants, 40% would reconsider their non-participation decision after having received additional information while the remainder 60% stood by their decision and provided explicit arguments for it. After having received additional information the participants still valued the programme significantly higher than non-participants, but the difference was relatively small. Participants and non-participants in cardiovascular screening programmes seem to have different strengths of preferences, which signals that their behavioural choice is founded in rational thinking. Furthermore, it appears that additional information and a second reflection about the participation decision may affect a substantial proportion of non-participants to reverse their decision, a finding that should receive policy interest.

A functional screen reveals an extensive layer of transcriptional and splicing control underlying RAS/MAPK signaling in Drosophila.

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Dariel Ashton-Beaucage

2014-03-01

Full Text Available The small GTPase RAS is among the most prevalent oncogenes. The evolutionarily conserved RAF-MEK-MAPK module that lies downstream of RAS is one of the main conduits through which RAS transmits proliferative signals in normal and cancer cells. Genetic and biochemical studies conducted over the last two decades uncovered a small set of factors regulating RAS/MAPK signaling. Interestingly, most of these were found to control RAF activation, thus suggesting a central regulatory role for this event. Whether additional factors are required at this level or further downstream remains an open question. To obtain a comprehensive view of the elements functionally linked to the RAS/MAPK cascade, we used a quantitative assay in Drosophila S2 cells to conduct a genome-wide RNAi screen for factors impacting RAS-mediated MAPK activation. The screen led to the identification of 101 validated hits, including most of the previously known factors associated to this pathway. Epistasis experiments were then carried out on individual candidates to determine their position relative to core pathway components. While this revealed several new factors acting at different steps along the pathway--including a new protein complex modulating RAF activation--we found that most hits unexpectedly work downstream of MEK and specifically influence MAPK expression. These hits mainly consist of constitutive splicing factors and thereby suggest that splicing plays a specific role in establishing MAPK levels. We further characterized two representative members of this group and surprisingly found that they act by regulating mapk alternative splicing. This study provides an unprecedented assessment of the factors modulating RAS/MAPK signaling in Drosophila. In addition, it suggests that pathway output does not solely rely on classical signaling events, such as those controlling RAF activation, but also on the regulation of MAPK levels. Finally, it indicates that core splicing

Structural motif screening reveals a novel, conserved carbohydrate-binding surface in the pathogenesis-related protein PR-5d

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Moffatt Barbara A

2010-08-01

Full Text Available Abstract Background Aromatic amino acids play a critical role in protein-glycan interactions. Clusters of surface aromatic residues and their features may therefore be useful in distinguishing glycan-binding sites as well as predicting novel glycan-binding proteins. In this work, a structural bioinformatics approach was used to screen the Protein Data Bank (PDB for coplanar aromatic motifs similar to those found in known glycan-binding proteins. Results The proteins identified in the screen were significantly associated with carbohydrate-related functions according to gene ontology (GO enrichment analysis, and predicted motifs were found frequently within novel folds and glycan-binding sites not included in the training set. In addition to numerous binding sites predicted in structural genomics proteins of unknown function, one novel prediction was a surface motif (W34/W36/W192 in the tobacco pathogenesis-related protein, PR-5d. Phylogenetic analysis revealed that the surface motif is exclusive to a subfamily of PR-5 proteins from the Solanaceae family of plants, and is absent completely in more distant homologs. To confirm PR-5d's insoluble-polysaccharide binding activity, a cellulose-pulldown assay of tobacco proteins was performed and PR-5d was identified in the cellulose-binding fraction by mass spectrometry. Conclusions Based on the combined results, we propose that the putative binding site in PR-5d may be an evolutionary adaptation of Solanaceae plants including potato, tomato, and tobacco, towards defense against cellulose-containing pathogens such as species of the deadly oomycete genus, Phytophthora. More generally, the results demonstrate that coplanar aromatic clusters on protein surfaces are a structural signature of glycan-binding proteins, and can be used to computationally predict novel glycan-binding proteins from 3 D structure.

Structural motif screening reveals a novel, conserved carbohydrate-binding surface in the pathogenesis-related protein PR-5d.

Science.gov (United States)

Doxey, Andrew C; Cheng, Zhenyu; Moffatt, Barbara A; McConkey, Brendan J

2010-08-03

Aromatic amino acids play a critical role in protein-glycan interactions. Clusters of surface aromatic residues and their features may therefore be useful in distinguishing glycan-binding sites as well as predicting novel glycan-binding proteins. In this work, a structural bioinformatics approach was used to screen the Protein Data Bank (PDB) for coplanar aromatic motifs similar to those found in known glycan-binding proteins. The proteins identified in the screen were significantly associated with carbohydrate-related functions according to gene ontology (GO) enrichment analysis, and predicted motifs were found frequently within novel folds and glycan-binding sites not included in the training set. In addition to numerous binding sites predicted in structural genomics proteins of unknown function, one novel prediction was a surface motif (W34/W36/W192) in the tobacco pathogenesis-related protein, PR-5d. Phylogenetic analysis revealed that the surface motif is exclusive to a subfamily of PR-5 proteins from the Solanaceae family of plants, and is absent completely in more distant homologs. To confirm PR-5d's insoluble-polysaccharide binding activity, a cellulose-pulldown assay of tobacco proteins was performed and PR-5d was identified in the cellulose-binding fraction by mass spectrometry. Based on the combined results, we propose that the putative binding site in PR-5d may be an evolutionary adaptation of Solanaceae plants including potato, tomato, and tobacco, towards defense against cellulose-containing pathogens such as species of the deadly oomycete genus, Phytophthora. More generally, the results demonstrate that coplanar aromatic clusters on protein surfaces are a structural signature of glycan-binding proteins, and can be used to computationally predict novel glycan-binding proteins from 3 D structure.

Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway

International Nuclear Information System (INIS)

Drakaki, Alexandra; Hatziapostolou, Maria; Polytarchou, Christos; Vorvis, Christina; Poultsides, George A.; Souglakos, John; Georgoulias, Vassilis; Iliopoulos, Dimitrios

2015-01-01

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors. MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets. A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3′UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3′UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels. Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis. The online version of this article (doi:10.1186/s12885-015-1562-9) contains supplementary material, which is

Added value of second biopsy target in screen-detected widespread suspicious breast calcifications.

Science.gov (United States)

Falkner, Nathalie M; Hince, Dana; Porter, Gareth; Dessauvagie, Ben; Jeganathan, Sanjay; Bulsara, Max; Lo, Glen

2018-06-01

There is controversy on the optimal work-up of screen-detected widespread breast calcifications: whether to biopsy a single target or multiple targets. This study evaluates agreement between multiple biopsy targets within the same screen-detected widespread (≥25 mm) breast calcification to determine if the second biopsy adds value. Retrospective observational study of women screened in a statewide general population risk breast cancer mammographic screening program from 2009 to 2016. Screening episodes recalled for widespread calcifications where further views indicated biopsy, and two or more separate target areas were sampled within the same lesion were included. Percentage agreement and Cohen's Kappa were calculated. A total of 293317 women were screened during 761124 separate episodes with recalls for widespread calcifications in 2355 episodes. In 171 women, a second target was biopsied within the same lesion. In 149 (86%) cases, the second target biopsy result agreed with the first biopsy (κ = 0.6768). Agreement increased with increasing mammography score (85%, 86% and 92% for score 3, 4 and 5 lesions). Same day multiple biopsied lesions were three times more likely to yield concordant results compared to post-hoc second target biopsy cases. While a single target biopsy is sufficient to discriminate a benign vs. malignant diagnosis in most cases, in 14% there is added value in performing a second target biopsy. Biopsies performed prospectively are more likely to yield concordant results compared to post-hoc second target biopsy cases, suggesting a single prospective biopsy may be sufficient when results are radiological-pathological concordant; discordance still requires repeat sampling. © 2018 The Royal Australian and New Zealand College of Radiologists.

Identifying the trauma recovery needs of maltreated children: An examination of child welfare workers' effectiveness in screening for traumatic stress.

Science.gov (United States)

Whitt-Woosley, Adrienne; Sprang, Ginny; Royse, David G

2018-07-01

Children in the child welfare system comprise a group characterized by exposure to trauma via experiences of maltreatment, under circumstances presenting multiple risk factors for traumatic stress. High rates of posttraumatic stress have been observed in this population. However, there is currently no standard for the universal screening of children in child welfare for trauma exposure and traumatic stress. This study examined the trauma experiences of a sample of maltreated children and whether their child welfare workers were effective screeners of traumatic stress symptoms. Descriptive and correlational analyses were conducted regarding a sample of children (N = 131) with trauma screenings completed by their child welfare workers and clinical measures of traumatic stress symptoms. Four hierarchical regression models were also examined to determine whether workers' screening information regarding child age, trauma exposure history and symptoms of traumatic stress were predictive of outcomes on clinical measures. The analyses revealed complex trauma exposure histories and high rates of traumatic stress symptoms among this generally younger sample of maltreated children. Additionally, the models supported workers' efficacy in screening for symptoms of total posttraumatic stress and specific trauma symptoms of intrusion and avoidance. Workers were less effective in screening for the symptoms of arousal. These findings support the importance of identifying the trauma recovery needs of maltreated children and the utility of child protection workers in assisting with the trauma screening process. Implications are provided for related practice, policy and training efforts in child welfare. Published by Elsevier Ltd.

Development of novel vaccines using DNA shuffling and screening strategies.

Science.gov (United States)

Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha

2004-02-01

DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.

Integrating evidence-based practices for increasing cancer screenings in safety net health systems: a multiple case study using the Consolidated Framework for Implementation Research.

Science.gov (United States)

Liang, Shuting; Kegler, Michelle C; Cotter, Megan; Emily, Phillips; Beasley, Derrick; Hermstad, April; Morton, Rentonia; Martinez, Jeremy; Riehman, Kara

2016-08-02

Implementing evidence-based practices (EBPs) to increase cancer screenings in safety net primary care systems has great potential for reducing cancer disparities. Yet there is a gap in understanding the factors and mechanisms that influence EBP implementation within these high-priority systems. Guided by the Consolidated Framework for Implementation Research (CFIR), our study aims to fill this gap with a multiple case study of health care safety net systems that were funded by an American Cancer Society (ACS) grants program to increase breast and colorectal cancer screening rates. The initiative funded 68 safety net systems to increase cancer screening through implementation of evidence-based provider and client-oriented strategies. Data are from a mixed-methods evaluation with nine purposively selected safety net systems. Fifty-two interviews were conducted with project leaders, implementers, and ACS staff. Funded safety net systems were categorized into high-, medium-, and low-performing cases based on the level of EBP implementation. Within- and cross-case analyses were performed to identify CFIR constructs that influenced level of EBP implementation. Of 39 CFIR constructs examined, six distinguished levels of implementation. Two constructs were from the intervention characteristics domain: adaptability and trialability. Three were from the inner setting domain: leadership engagement, tension for change, and access to information and knowledge. Engaging formally appointed internal implementation leaders, from the process domain, also distinguished level of implementation. No constructs from the outer setting or individual characteristics domain differentiated systems by level of implementation. Our study identified a number of influential CFIR constructs and illustrated how they impacted EBP implementation across a variety of safety net systems. Findings may inform future dissemination efforts of EBPs for increasing cancer screening in similar settings. Moreover

An Efficient Approach to Screening Epigenome-Wide Data

Directory of Open Access Journals (Sweden)

Meredith A. Ray

2016-01-01

Full Text Available Screening cytosine-phosphate-guanine dinucleotide (CpG DNA methylation sites in association with some covariate(s is desired due to high dimensionality. We incorporate surrogate variable analyses (SVAs into (ordinary or robust linear regressions and utilize training and testing samples for nested validation to screen CpG sites. SVA is to account for variations in the methylation not explained by the specified covariate(s and adjust for confounding effects. To make it easier to users, this screening method is built into a user-friendly R package, ttScreening, with efficient algorithms implemented. Various simulations were implemented to examine the robustness and sensitivity of the method compared to the classical approaches controlling for multiple testing: the false discovery rates-based (FDR-based and the Bonferroni-based methods. The proposed approach in general performs better and has the potential to control both types I and II errors. We applied ttScreening to 383,998 CpG sites in association with maternal smoking, one of the leading factors for cancer risk.

A Desktop Screen Sharing System based on Various Connection Methods

Science.gov (United States)

Negishi, Yuya; Kawaguchi, Nobuo

Recently it became very common to use information devices such as PCs during presentations and discussions. In these situations, a need arises for techniques that allow a smooth switch of presenters without changing cables, or an easy screen sharing in case of remote videoconferences. In this paper, we propose a desktop screen sharing system that can be used for such purposes and situations. For that, we designed an automatic control of connections in the VNC system that can be operated remotely over the network. We also suggested an interface that assigns a role such as “Screen sender" or “Screen receiver" to each terminal. In the proposed system, while sharing a screen between multiple terminals, one can easily display and browse the screen without having to understand how the others are connected. We also implemented a “role card" using contactless IC card, where roles are assigned only by placing the card in the IC reader.

[Cost-effectiveness of multiple screening modalities on breast cancer in Chinese women from Shanghai].

Science.gov (United States)

Wu, F; Mo, M; Qin, X X; Fang, H; Zhao, G M; Liu, G Y; Chen, Y Y; Cao, Z G; Yan, Y J; Lyu, L L; Xu, W H; Shao, Z M

2017-12-10

Objective: To determine the most cost-effective modality for breast cancer screening in women living in Shanghai. Methods: A Markov model for breast cancer was redeveloped based on true effect which was derived from a project for detection of women at high risk of breast cancer and an organized breast cancer screening program conducted simultaneously in Minhang district, Shanghai, during 2008 to 2012. Parameters of the model were derived from literatures. General principles related to cost-effectiveness analysis were used to compare the costs and effects of 12 different screening modalities in a simulated cohort involving 100 000 women aged 45 years. Incremental cost-effectiveness ratio (ICER) was used to determine the most cost-effective modality. Sensitivity analysis was conducted to evaluate how these factors affected the estimated cost-effectiveness. Results: The modality of biennial CBE followed by ultrasonic and mammography among those with positive CBE was observed as the most cost-effective one. The costs appeared as 182 526 Yuan RMB per life year gained and 144 386 Yuan RMB per quality adjusted life-year (QALY) saved, which were within the threshold of 2-3 times of local per capita Gross Domestic Product. Results from sensitivity analysis showed that, due to higher incidence rate of breast cancer in Shanghai, the cost per QALY would be 64 836 Yuan RMB lower in Shanghai than the average level in China. Conclusion: Our research findings showed that the biennial CBE program followed by ultrasonic and mammography for those with positive CBE results might serve as the optimal breast cancer screening modality for Chinese women living in Shanghai, and thus be widely promoted in this population elsewhere.

Politics and patriarchy: barriers to health screening for socially disadvantaged women.

Science.gov (United States)

Peters, Kathleen

2012-10-01

Health screening and early detection of cancer results in significantly better health outcomes and lower mortality. However barriers to such screening are multiple and complex. This paper specifically addresses barriers to women's health screening for socially disadvantaged women in an economically and service disadvantaged area. In this qualitative study, women's healthcare workers and consumers of women's health screening were interviewed and data related to issues for women who had special needs were analysed. Findings indicate there is a lack of access to appropriate services for socially disadvantaged women which affects their screening uptake rates. This study also highlights the difficulties socially disadvantaged women encountered when they were able to access these services which also influenced their decisions regarding subsequent health screening. Implications for nurses and other healthcare professionals are manifold and include advocating for greater access to services and more sensitive care in the delivery of health screening services for socially disadvantaged women.

First trimester prenatal screening among women pregnant after IVF/ICSI

DEFF Research Database (Denmark)

Anne Cathrine, Gjerris; Tabor, Ann; Loft, Anne

2012-01-01

BACKGROUND Prenatal screening and diagnosis of chromosomal abnormalities especially Down's syndrome in IVF pregnancies are complicated by higher maternal age, a high multiple pregnancy rate, a high risk of a vanishing twin and an increased risk of chromosomal abnormalities, particularly in pregna......BACKGROUND Prenatal screening and diagnosis of chromosomal abnormalities especially Down's syndrome in IVF pregnancies are complicated by higher maternal age, a high multiple pregnancy rate, a high risk of a vanishing twin and an increased risk of chromosomal abnormalities, particularly...... in pregnancies after ICSI. The aim of the present systematic review was to evaluate the findings of first trimester screening for chromosomal abnormalities in IVF/ICSI singleton and twin pregnancies. METHODS A systematic MESH-term search in MEDLINE using PubMed and the Cochrane Library was performed until May...... 2011, with no earlier date limit. RESULTS The electronic search retrieved 562 citations, 96 of which were evaluated in detail and 57 were then excluded for not meeting the selection criteria. A total of 61 articles were finally selected for review. Our analysis of the data shows that, for IVF...

Family structure as a predictor of screen time among youth.

Science.gov (United States)

McMillan, Rachel; McIsaac, Michael; Janssen, Ian

2015-01-01

The family plays a central role in the development of health-related behaviors among youth. The objective of this study was to determine whether non-traditional parental structure and shared custody arrangements predict how much time youth spend watching television, using a computer recreationally, and playing video games. Participants were a nationally representative sample of Canadian youth (N = 26,068) in grades 6-10 who participated in the 2009/10 Health Behaviour in School-aged Children Survey. Screen time in youth from single parent and reconstituted families, with or without regular visitation with their non-residential parent, was compared to that of youth from traditional dual-parent families. Multiple imputation was used to account for missing data. After multiple imputation, the relative odds of being in the highest television, computer use, video game, and total screen time quartiles were not different in boys and girls from non-traditional families by comparison to boys and girls from traditional dual-parent families. In conclusion, parental structure and child custody arrangements did not have a meaningful impact on screen time among youth.

Family structure as a predictor of screen time among youth

Directory of Open Access Journals (Sweden)

Rachel McMillan

2015-06-01

Full Text Available The family plays a central role in the development of health-related behaviors among youth. The objective of this study was to determine whether non-traditional parental structure and shared custody arrangements predict how much time youth spend watching television, using a computer recreationally, and playing video games. Participants were a nationally representative sample of Canadian youth (N = 26,068 in grades 6–10 who participated in the 2009/10 Health Behaviour in School-aged Children Survey. Screen time in youth from single parent and reconstituted families, with or without regular visitation with their non-residential parent, was compared to that of youth from traditional dual-parent families. Multiple imputation was used to account for missing data. After multiple imputation, the relative odds of being in the highest television, computer use, video game, and total screen time quartiles were not different in boys and girls from non-traditional families by comparison to boys and girls from traditional dual-parent families. In conclusion, parental structure and child custody arrangements did not have a meaningful impact on screen time among youth.

MRI screening on bone ischemia of hip and knee in recovered SARS patients

International Nuclear Information System (INIS)

Cheng Xiaoguang; Qu Hui; Liu Wei; Sun Jing; Cheng Kebin; Feng Suchen; Li Xiaosong

2004-01-01

screening the osteonecrosis in recovered SARS patients with steroid usage. MRI screening revealed high prevalence of osteonecrosis of hip and knee in SARS patients with steroid treatment. Most of SARS patients had multiple joint pains, and the cause for the pain was not clear

Latent fingerprints on different type of screen protective films

Directory of Open Access Journals (Sweden)

Yuttana Sudjaroen

2016-07-01

Full Text Available The purpose of this research was to study the quality of latent fingerprint on different types of screen protective films including screen protector, matte screen protector, anti-fingerprint clear screen protector and anti-fingerprint matte screen protector by using black powder method in developing latent fingerprints. The fingerprints were performed by 10 volunteers whose fingers (right index, right thumb, left index and left thumb were stubbing at different types of screen protective films and subsequently latent fingerprints were developed by brushing with black powder. Automated Fingerprint Identification System (AFIS counted the numbers of minutiae points from 320 latent fingerprints. Anti-fingerprint matte screen protective film produced the best quality of latent fingerprint with an average minutiae point 72.65, followed by matte screen protective film, clear screen protective film and anti-fingerprint clear screen protective film with an average minutiae point of 155.2, 135.0 and 72.65 respectively. The quality of latent fingerprints developed between a clear and a matte surface of screen protective films showed a significant difference (sig>0.05, whereas the coat and the non-coat with anti-fingerprint chemical revealed a non-significant difference (sig<0.05 in their number of minutiae points.

A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation

NARCIS (Netherlands)

Paul, Petra; van den Hoorn, Tineke; Jongsma, Marlieke L. M.; Bakker, Mark J.; Hengeveld, Rutger; Janssen, Lennert; Cresswell, Peter; Egan, David A.; van Ham, Marieke; ten Brinke, Anja; Ovaa, Huib; Beijersbergen, Roderick L.; Kuijl, Coenraad; Neefjes, Jacques

2011-01-01

MHC class II molecules (MHC-II) present peptides to T helper cells to facilitate immune responses and are strongly linked to autoimmune diseases. To unravel processes controlling MHC-II antigen presentation, we performed a genome-wide flow cytometry-based RNAi screen detecting MHC-II expression and

Depressive symptoms in adolescence: the association with multiple health risk behaviors.

Science.gov (United States)

Katon, Wayne; Richardson, Laura; Russo, Joan; McCarty, Carolyn A; Rockhill, Carol; McCauley, Elizabeth; Richards, Julie; Grossman, David C

2010-01-01

Although multiple studies of adolescents have examined the association of depression with individual health risk behaviors such as obesity or smoking, this is one of the few studies that examined the association between depression and multiple risk behaviors. A brief mail questionnaire, which screened for age, gender, weight, height, sedentary behaviors, physical activity, perception of general health, functional impairment and depressive symptoms, was completed by a sample of 2291 youth (60.7% response rate) aged 13-17 enrolled in a health care plan. A subset of youth who screened positive on the two-item depression screen and a random sample of those screening negative were approached to participate in a telephone interview with more in-depth information obtained on smoking and at-risk behaviors associated with drug and alcohol use. Youth screening positive for high levels of depressive symptoms compared to those with few or no depressive symptoms were significantly more likely to meet criteria for obesity, had a poorer perception of health, spent more time on the computer, got along less well with parents and friends, had more problems completing school work and were more likely to have experimented with smoking and a wide array of behaviors associated with drug and alcohol use. Because many adverse health behaviors that develop in adolescence continue into adulthood, the association of depressive symptoms with multiple risk behaviors and poor functioning suggest that early interventions are needed at an individual, school, community and primary care level. Copyright 2010 Elsevier Inc. All rights reserved.

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

Phosphate solubilization and multiple plant growth promoting ...

African Journals Online (AJOL)

Phosphate solubilizing efficiencies of the strains were analyzed using different insoluble phosphorus sources and the results show that most isolates released a substantial amount of soluble phosphate from tricalcium phosphate, rock phosphate and bone meal. Screening for multiple plant growth promoting attributes ...

The "DOC" screen: Feasible and valid screening for depression, Obstructive Sleep Apnea (OSA) and cognitive impairment in stroke prevention clinics.

Science.gov (United States)

Swartz, Richard H; Cayley, Megan L; Lanctôt, Krista L; Murray, Brian J; Cohen, Ashley; Thorpe, Kevin E; Sicard, Michelle N; Lien, Karen; Sahlas, Demetrios J; Herrmann, Nathan

2017-01-01

Post-stroke Depression, Obstructive sleep apnea (OSA) and Cognitive impairment ("DOC") are associated with greater mortality, worse recovery and poorer quality of life. Best practice recommendations endorse routine screening for each condition; yet, all are under-assessed, diagnosed and treated. We seek to determine the feasibility and validity of an integrated tool ("DOC" screen) to identify stroke clinic patients at high-risk of depression, OSA, and cognitive impairment. All consecutive new referrals to a regional Stroke Prevention Clinic who were English-speaking and non-aphasic were eligible to be screened. Time for screen completion was logged. DOC screen results were compared to the neuropsychological battery and polysomnogram assessments using a modified receiver operator characteristic and area under the curve analysis. Data is reported to conform to STARD guidelines. 1503 people were screened over 2 years. 89% of eligible patients completed the screen in 5 minutes or less (mean 4.2 minutes), less than half the time it takes to complete the Montreal Cognitive Assessment (MoCA). 437 people consented to detailed testing. Of those, 421 completed the Structured Clinical Interview for Depression within 3 months of screening, 387 completed detailed neuropsychological testing within 3 months, and 88 had overnight polysomnograms. Screening scores combined with demographic variables (age, sex, education, body mass index), had excellent validity compared to gold standard diagnoses: DOC-Mood AUC 0.90; DOC-Apnea AUC 0.80; DOC-Cog AUC 0.81. DOC screen scores can reliably categorize patients in to low-, intermediate- or high-risk groups for further action and can do so with comparable accuracy to more time-consuming screens. Systematic screening of depression, obstructive sleep apnea, and cognitive impairment in 5 minutes or less is feasible and valid in a high volume stroke clinic using the DOC screen. The DOC screen may facilitate improved identification and treatment

Breast, prostate, and thyroid cancer screening tests and overdiagnosis.

Science.gov (United States)

Jung, Minsoo

The purpose of this study was to examine overdiagnosis and overtreatment related to cancer screening and to review relevant reports and studies. A comprehensive search of peer-reviewed and gray literature was conducted for relevant studies published between January 2000 and December 2015 reporting breast, prostate, and thyroid cancer screening tests and overdiagnosis. This study revealed no dichotomy on where screening would lower risk or cause overdiagnosis and overtreatment. Many screening tests did both, that is, at population level, there were both benefit (decreased disease-specific mortality) and harm (overdiagnosis and overtreatment). Therefore, we need to consider a balanced argument with citations for the potential benefits of screening along with the harms associated with screening. Although the benefits and harms can only be tested through randomized trials, important data from cohort studies, diagnostic accuracy studies, and modeling work can help define the extent of benefits and harms in the population. The health care cycle that prompt patients to undergo periodic screening tests is self-reinforcing. In most developed countries, screening test recommendations encourage periodic testing. Therefore, patients are continuing their screening. It is necessary for patients to become wise consumers of screening tests and make decisions with their physicians regarding further testing and treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigating ethnic variations in reporting of psychotic symptoms: a multiple-group confirmatory factor analysis of the Psychosis Screening Questionnaire.

Science.gov (United States)

Heuvelman, Hein; Nazroo, James; Rai, Dheeraj

2018-03-12

Epidemiological evidence suggests risk for psychosis varies with ethnicity in Western countries. However, there is little evidence to date on the cross-cultural validity of screening instruments used for such comparisons. Combining two existing UK population-based cohorts, we examined risk for reporting psychotic symptoms across White British (n = 3467), White Irish (n = 851), Caribbean (n = 1899), Indian (n = 2590), Pakistani (n = 1956) and Bangladeshi groups (n = 1248). We assessed the psychometric properties of the Psychosis Screening Questionnaire (PSQ) with a multiple-group confirmatory factor analysis, assessing the equivalence of factor loadings, response thresholds and residual variances in an analysis of measurement non-invariance. Compared with prevalence among British Whites (5.4%), the prevalence of self-reported psychotic symptoms was greater in the Caribbean group (12.7%, adjusted OR = 2.38 [95% CI 1.84-3.07]). Prevalence was also increased among Pakistani individuals (8.3%, adjusted OR = 1.36 [1.01-1.84]) although this difference was driven by a greater likelihood of reporting paranoid symptoms. PSQ items for thought interference, strange experience and hallucination were measured in equivalent ways across ethnic groups. However, our measurement models suggested that paranoid symptoms were measured less reliably among ethnic minorities than among British Whites and appeared to exaggerate latent differences between Pakistani and White British groups when measurement non-invariance was not accounted for. Notwithstanding evidence for measurement non-invariance, the greater risk for reporting psychotic symptoms among Caribbean individuals is unlikely to be an artefact of measurement. Greater residual variance in the recording of paranoid symptoms among ethnic minority respondents warrants caution in using this item to investigate ethnic variation in psychosis risk.

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.

Phytochemical Screening, Proximate and Mineral Composition of ...

African Journals Online (AJOL)

Leaves of sweet potato (Ipomoea batatas) grown in Tepi area was studied for their class of phytochemicals, mineral and proximate composition using standard analytical methods. The phytochemical screening revealed the presence of alkaloids, flavonoid, terpenoids, saponins, quinones, phenol, tannins, amino acid and ...

Multiple sclerosis

International Nuclear Information System (INIS)

Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

1986-01-01

Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases.

Science.gov (United States)

Kline, Rachel A; Kaifer, Kevin A; Osman, Erkan Y; Carella, Francesco; Tiberi, Ariana; Ross, Jolill; Pennetta, Giuseppa; Lorson, Christian L; Murray, Lyndsay M

2017-03-01

The term "motor neuron disease" encompasses a spectrum of disorders in which motor neurons are the primary pathological target. However, in both patients and animal models of these diseases, not all motor neurons are equally vulnerable, in that while some motor neurons are lost very early in disease, others remain comparatively intact, even at late stages. This creates a valuable system to investigate the factors that regulate motor neuron vulnerability. In this study, we aim to use this experimental paradigm to identify potential transcriptional modifiers. We have compared the transcriptome of motor neurons from healthy wild-type mice, which are differentially vulnerable in the childhood motor neuron disease Spinal Muscular Atrophy (SMA), and have identified 910 transcriptional changes. We have compared this data set with published microarray data sets on other differentially vulnerable motor neurons. These neurons were differentially vulnerable in the adult onset motor neuron disease Amyotrophic Lateral Sclerosis (ALS), but the screen was performed on the equivalent population of neurons from neurologically normal human, rat and mouse. This cross species comparison has generated a refined list of differentially expressed genes, including CELF5, Col5a2, PGEMN1, SNCA, Stmn1 and HOXa5, alongside a further enrichment for synaptic and axonal transcripts. As an in vivo validation, we demonstrate that the manipulation of a significant number of these transcripts can modify the neurodegenerative phenotype observed in a Drosophila line carrying an ALS causing mutation. Finally, we demonstrate that vector-mediated expression of alpha-synuclein (SNCA), a transcript decreased in selectively vulnerable motor neurons in all four screens, can extend life span, increase weight and decrease neuromuscular junction pathology in a mouse model of SMA. In summary, we have combined multiple data sets to identify transcripts, which are strong candidates for being phenotypic modifiers

Screening for pulmonary arterial hypertension in systemic sclerosis

Directory of Open Access Journals (Sweden)

J-L. Vachiéry

2009-09-01

Full Text Available The onset and progression of pulmonary arterial hypertension (PAH in patients with systemic sclerosis (SSc can be particularly aggressive; however, effective treatments are available. Therefore, early identification of patients with suspected PAH, confirmation of diagnosis, and intervention is essential. PAH may be challenging to diagnose in its earliest stages, particularly in populations that have multiple causes of breathlessness, and, therefore, screening is required. The optimal screening tools and methodology are, as yet, unknown, and this is confounded by a lack of consensus over which patients to screen. Current practice favours annual screening of all SSc patients using Doppler echocardiography to detect elevated right heart pressures. This will typically identify most patients with the various forms of pulmonary hypertension found in SSc. The optimum thresholds for Doppler echocardiography are still subject to investigation, especially for patients with mild pulmonary hypertension, and this technique may, therefore, yield a significant number of false-positives and a currently unknown number of false-negatives. Confirmatory right heart catheterisation remains necessary in all suspected cases. Further research is needed to identify the optimal tools and the screening approach with greatest specificity and selectivity.

Cost implications of PSA screening differ by age.

Science.gov (United States)

Rao, Karthik; Liang, Stella; Cardamone, Michael; Joshu, Corinne E; Marmen, Kyle; Bhavsar, Nrupen; Nelson, William G; Ballentine Carter, H; Albert, Michael C; Platz, Elizabeth A; Pollack, Craig E

2018-05-09

Multiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups-including the costs of screening and subsequent diagnosis, treatment, and adverse events-remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios. We determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate). Under the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively. With constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with

Biomarker screening of oral cancer cell lines revealed sub-populations of CD133-, CD44-, CD24- and ALDH1- positive cancer stem cells

Directory of Open Access Journals (Sweden)

Kendall K

2013-05-01

Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth worldwide for cancer-related mortality. For the past several decades the mainstay of treatment for HNSCC has been surgery and external beam radiation, although more recent trials combining chemotherapy and radiation have demonstrated improvements. However, cancer recurrence and treatment failures continue to occur in a significant percentage of patients. Recent advances in tumor biology have led to the discovery that many cancers, including HNSCC, may contain subpopulations of cells with stem cell-like properties that may explain relapse and recurrence. The objective of this study was to screen existing oral cancer cell lines for biomarkers specific for cells with stem cell-like properties. RNA was isolated for RT-PCR screening using primers for specific mRNA of the biomarkers: CD44, CD24, CD133, NANOG, Nestin, ALDH1, and ABCG2 in CAL27, SCC25 and SCC15 cells. This analysis revealed that some oral cancer cell lines (CAL27 and SCC25 may contain small subpopulations of adhesion- and contact-independent cells (AiDC that also express tumor stem cell markers, including CD44, CD133, and CD24. In addition, CAL27 cells also expressed the intracellular tumor stem cell markers, ALDH1 and ABCG2. Isolation and culture of the adhesion- and contact-independent cells from CAL27 and SCC25 populations revealed differential proliferation rates and more robust inhibition by the MEK inhibitor PD98059, as well as the chemotherapeutic agents Cisplatin and Paclitaxel, within the AiDC CAL27 cells. At least one oral cancer cell line (CAL27 contained subpopulations of cells that express specific biomarkers associated with tumor stem cells which were morphologically and phenotypically distinct from other cells within this cell line.

Parental perspectives of screening for adverse childhood experiences in pediatric primary care.

Science.gov (United States)

Conn, Anne-Marie; Szilagyi, Moira A; Jee, Sandra H; Manly, Jody T; Briggs, Rahil; Szilagyi, Peter G

2018-03-01

Pediatricians recognize a need to mitigate the negative impact that adverse childhood experiences (ACEs) can have on health and development. However, ACEs screening and interventions in primary care pediatrics may be inhibited by concerns about parental perceptions. We assessed parent perspectives of screening for ACEs in the pediatric primary care setting, to understand their views on the potential impact of their ACEs on their parenting and to identify opportunities for pediatric anticipatory guidance. We used purposive sampling to recruit parents of children <6 years receiving care at an urban, pediatric clinic. Semistructured questions guided 1:1 interviews that were later coded by multiple researchers to verify reliability. A thematic framework approach guided analysis and identified main themes and subthemes. We reached thematic saturation after 15 parent interviews, which consistently revealed 3 interrelated themes. First, parents strongly supported ACEs screening as a bridge to needed services, and they recommended using a trauma-sensitive, person-centered approach in pediatric practices. Second, parents understood the intergenerational impact of ACEs and expressed a desire to break the cycle of adversity. Finally, parents saw their child's pediatrician as a potential change-agent who could provide support to meet their parenting goals. Parents want to discuss their ACEs and receive help and guidance from pediatricians. Furthermore, they perceive their child's pediatrician as having an important role to play in meeting their parenting goals. It is important to ensure that pediatricians have the training, skills and familiarity with available resources to meet parental expectations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

OpenAIRE

Rausch, Keiko; Hackett, Brent A.; Weinbren, Nathan L.; Reeder, Sophia M.; Sadovsky, Yoel; Hunter, Christopher A.; Schultz, David C.; Coyne, Carolyn B.; Cherry, Sara

2017-01-01

Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from in...

Screening in new credit markets: can individual lenders infer borrower creditworthiness in peer-to-peer lending?

NARCIS (Netherlands)

Iyer, R.; Khwaja, A.I.; Luttmer, E.F.P.; Shue, K.

2009-01-01

The current banking crisis highlights the challenges faced in the traditional lending model, particularly in terms of screening smaller borrowers. The recent growth in online peer-to-peer lending marketplaces offers opportunities to examine different lending models that rely on screening by multiple

Screening for psychological distress in cancer: renewing the research agenda.

Science.gov (United States)

Salmon, Peter; Clark, Louise; McGrath, Elly; Fisher, Peter

2015-03-01

Although health policy for cancer care promotes screening of patients for emotional distress, the utility and validity of screening have been questioned. Continued research to refine detection of distress or to evaluate outcomes of screening programmes is unlikely to end this controversy. Instead, we need to identify more fundamental research questions that address the validity or utility of screening in this context. We critically and selectively review research and policy literature on psychological screening in cancer care, drawing also from research literature about the nature of psychological needs in cancer care and from relevant literature on psychological screening in mental health. We identify three broad research questions: (i) Apart from intensity of distress, what further information should screening seek about the context of distress, psychological processes that promote distress and patients' own perspective on their needs? (ii) What are the implications of the contextual dependence of disclosure of emotional feelings, given that screening questions can be asked in contexts ranging from an impersonal questionnaire to dialogue with a trusted practitioner? (iii) How should a screen be responded to, given the inherent uncertainty associated with screening results and given that distress in a cancer context can indicate instrumental as well as psychological needs? Examining these questions will mean exchanging a diagnostic framework for screening, in which health need is indicated by the presence of a psychological disorder, for a public health framework, in which health need is identified from multiple perspectives. Copyright © 2014 John Wiley & Sons, Ltd.

Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells

Directory of Open Access Journals (Sweden)

Chad M. Toledo

2015-12-01

Full Text Available To identify therapeutic targets for glioblastoma (GBM, we performed genome-wide CRISPR-Cas9 knockout (KO screens in patient-derived GBM stem-like cells (GSCs and human neural stem/progenitors (NSCs, non-neoplastic stem cell controls, for genes required for their in vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of molecular networks commonly altered in GBM and GSCs (e.g., oncogenic drivers. In vitro and in vivo validation of GSC-specific targets revealed several strong hits, including the wee1-like kinase, PKMYT1/Myt1. Mechanistic studies demonstrated that PKMYT1 acts redundantly with WEE1 to inhibit cyclin B-CDK1 activity via CDK1-Y15 phosphorylation and to promote timely completion of mitosis in NSCs. However, in GSCs, this redundancy is lost, most likely as a result of oncogenic signaling, causing GBM-specific lethality.

Decision trees and integrated features for computer aided mammographic screening

Energy Technology Data Exchange (ETDEWEB)

Kegelmeyer, W.P. Jr.; Groshong, B.; Allmen, M.; Woods, K.

1997-02-01

Breast cancer is a serious problem, which in the United States causes 43,000 deaths a year, eventually striking 1 in 9 women. Early detection is the only effective countermeasure, and mass mammography screening is the only reliable means for early detection. Mass screening has many shortcomings which could be addressed by a computer-aided mammographic screening system. Accordingly, we have applied the pattern recognition methods developed in earlier investigations of speculated lesions in mammograms to the detection of microcalcifications and circumscribed masses, generating new, more rigorous and uniform methods for the detection of both those signs. We have also improved the pattern recognition methods themselves, through the development of a new approach to combinations of multiple classifiers.

Newborn screening by tandem mass spectrometry: ethical and social issues.

Science.gov (United States)

Avard, Denise; Vallance, Hilary; Greenberg, Cheryl; Potter, Beth

2007-01-01

Emerging technologies like Tandem Mass Spectrometry (TMS) enable multiple tests on a single blood sample and allow the expansion of Newborn Screening (NBS) to include various metabolic diseases. Introducing TMS for NBS raises important social and ethical questions: what are the criteria for adding disorders to screening panels? What evidence justifies expansion of screening? How can equity in NBS access and standards be ensured? How can policy standards be set, given the multiplicity of stakeholders? To address emerging issues, policy-makers, patient advocates, clinicians and researchers had a workshop during the 2005 Garrod Symposium. The participants received a summary of the discussion and understood the workshop's goal was to provide a basis for further discussion. This article contributes to this ongoing discussion. Several proposed recommendations assert the centrality of including social and ethical issues in the assessment of whether or not to introduce TMS. The article outlines five key recommendations for advancing the NBS agenda: national public health leadership; transparency; increased national consistency in NBS strategy, including minimum standards; collaboration between the federal and provincial/territorial governments and diverse stakeholders; and supporting research and/or programs based on effectiveness, which integrate ethical and social issues into assessment.

Memory-Context Effects of Screen Color in Multiple-Choice and Fill-In Tests

Science.gov (United States)

Prestera, Gustavo E.; Clariana, Roy; Peck, Andrew

2005-01-01

In this experimental study, 44 undergraduates completed five computer-based instructional lessons and either two multiplechoice tests or two fill-in-the-blank tests. Color-coded borders were displayed during the lesson, adjacent to the screen text and illustrations. In the experimental condition, corresponding border colors were shown at posttest.…

Core-level photoemission revealing the Mott transition

International Nuclear Information System (INIS)

Kim, Hyeong-Do; Noh, Han-Jin; Kim, K.H.; Oh, S.-J.

2005-01-01

Ru 3d core-level X-ray photoemission spectra of various ruthenates are examined. They show in general two-peak structures, which can be assigned as the screened and unscreened peaks. The screened peak is absent in a Mott insulator, but develops into a main peak as the correlation strength becomes weak. This spectral behavior is well explained by the dynamical mean-field theory calculation for the single-band Hubbard model with the on-site core-hole potential using the exact diagonalization method. The new mechanism of the core-level photoemission satellite can be utilized to reveal the Mott transition phenomenon in various strongly correlated electron systems

Preparticipation Screening of Athletic Officials: SEC Football Referees at Risk.

Science.gov (United States)

Turner, John L; Walters, Rod; Leski, Mark J; Saywell, Robert M; Wooldridge, J Scott

2003-03-01

Although preparticipation screening for athletes is commonplace, few studies have addressed the issue for those officiating at games. To review current data on physiologic stress on sports officials, to obtain prevalence data on health parameters for football officials, and to determine the outcomes when screening criteria are applied in preseason exams. A protocol was established using health history questionnaires and physical exams with laboratory screening to assess the health of all football officials working in the Southeastern Conference (SEC) from 1997 to 2000. The main outcome measure was the prevalence of cardiac risk factors as determined by American College of Sports Medicine guidelines. Initial screening of 102 football officials revealed that 10.1% of SEC referees had elevated systolic blood pressure, 13.9% had elevated diastolic blood pressure, and 3.8% had resting tachycardia. Average body mass index (BMI) was 28.6 kg/m2, with 87.3% having a BMI that exceeded 25 (overweight). About one-third (31.6%) had a BMI greater than 30 (obese). Total fasting cholesterol exceeded 200 mg/dL in 44.2%, HDL levels were below 35 mg/dL in 34.3%, and LDL levels were above 120 mg/dL in 62.3%. Compared with age-adjusted national data, there were more overweight and more obese officials, but they had lower systolic and diastolic blood pressures and lower mean total cholesterol levels. Using the Framingham Study prediction model to estimate coronary heart disease (CHD) risk, analysis revealed that referees had a lower risk than the national 10-year CHD risk but a higher risk compared with that of the low-risk population. These data reveal a greater need for graded exercise testing. The higher rates of obesity among officials will promote further screening for CHD risk factors.

Evolution of MHC class I genes in the endangered loggerhead sea turtle (Caretta caretta) revealed by 454 amplicon sequencing.

Science.gov (United States)

Stiebens, Victor A; Merino, Sonia E; Chain, Frédéric J J; Eizaguirre, Christophe

2013-04-30

In evolutionary and conservation biology, parasitism is often highlighted as a major selective pressure. To fight against parasites and pathogens, genetic diversity of the immune genes of the major histocompatibility complex (MHC) are particularly important. However, the extensive degree of polymorphism observed in these genes makes it difficult to conduct thorough population screenings. We utilized a genotyping protocol that uses 454 amplicon sequencing to characterize the MHC class I in the endangered loggerhead sea turtle (Caretta caretta) and to investigate their evolution at multiple relevant levels of organization. MHC class I genes revealed signatures of trans-species polymorphism across several reptile species. In the studied loggerhead turtle individuals, it results in the maintenance of two ancient allelic lineages. We also found that individuals carrying an intermediate number of MHC class I alleles are larger than those with either a low or high number of alleles. Multiple modes of evolution seem to maintain MHC diversity in the loggerhead turtles, with relatively high polymorphism for an endangered species.

Fecal Molecular Markers for Colorectal Cancer Screening

Directory of Open Access Journals (Sweden)

Rani Kanthan

2012-01-01

Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

Advances in Predictive Toxicology for Discovery Safety through High Content Screening.

Science.gov (United States)

Persson, Mikael; Hornberg, Jorrit J

2016-12-19

High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.

Phytochemical screening and thin layer chromatography of the ...

African Journals Online (AJOL)

Phytochemical constituents of the leaves of Khaya senegalensis (dry zone mahogany) were determined in petroleum ether, chloroform, acetone and ethanol extracts. The screening revealed the presence of flavonoids, carbohydrates, glycosides, saponins, tannins, alkaloids and anthraquinones. Saponins and cardiac ...

Multiple spectroscopic analyses reveal the fate and metabolism of sulfamide herbicide triafamone in agricultural environments

International Nuclear Information System (INIS)

Wang, Mengcen; Qian, Yuan; Liu, Xiaoyu; Wei, Peng; Deng, Man; Wang, Lei; Wu, Huiming; Zhu, Guonian

2017-01-01

Triafamone, a sulfamide herbicide, has been extensively utilized for weed control in rice paddies in Asia. However, its fate and transformation in the environment have not been established. Through a rice paddy microcosm-based simulation trial combined with multiple spectroscopic analyses, we isolated and identified three novel metabolites of triafamone, including hydroxyl triafamone (HTA), hydroxyl triafamone glycoside (HTAG), and oxazolidinedione triafamone (OTA). When triafamone was applied to rice paddies at a concentration of 34.2 g active ingredient/ha, this was predominantly distributed in the paddy soil and water, and then rapidly dissipated in accordance with the first-order rate model, with half-lives of 4.3–11.0 days. As the main transformation pathway, triafamone was assimilated by the rice plants and was detoxified into HTAG, whereas the rest was reduced into HTA with subsequent formation of OTA. At the senescence stage, brown rice had incurred triafamone at a concentration of 0.0016 mg/kg, but the hazard quotient was <1, suggesting that long-term consumption of the triafamone-containing brown rice is relatively safe. The findings of the present study indicate that triafamone is actively metabolized in the agricultural environment, and elucidation of the link between environmental exposure to these triazine or oxazolidinedione moieties that contain metabolites and their potential impacts is warranted. - Highlights: • Multiple spectroscopic analyses were applied to investigate agrochemicals transformation in environment. • Three novel compounds were isolated and identified as triafamone metabolites. • The fate and transformation pathway of triafamone in rice paddy were revealed. • Long-term consumption of the triafamone-containing brown rice is relatively safe. • Elucidation of environmental impacts by exposure to these triazine or oxazolidinedione metabolites is warranted. - Triafamone rapidly dissipates in agricultural environments

Oral cancer screening: knowledge is not enough.

Science.gov (United States)

Tax, C L; Haslam, S Kim; Brillant, Mgs; Doucette, H J; Cameron, J E; Wade, S E

2017-08-01

The purpose of this cross-sectional study was to investigate whether dental hygienists are transferring their knowledge of oral cancer screening into practice. This study also wanted to gain insight into the barriers that might prevent dental hygienists from performing these screenings. A 27-item survey instrument was constructed to study the oral cancer screening practices of licensed dental hygienists in Nova Scotia. A total of 623 practicing dental hygienists received the survey. The response rate was 34% (n = 212) yielding a maximum margin of error of 5.47 at a 95% confidence level. Descriptive statistics were calculated using IBM SPSS Statistics v21 software (Armonk, NY:IBM Corp). Qualitative thematic analysis was performed on any open-ended responses. This study revealed that while dental hygienists perceived themselves as being knowledgeable about oral cancer screening, they were not transferring this knowledge to actual practice. Only a small percentage (13%) of respondents were performing a comprehensive extra-oral examination, and 7% were performing a comprehensive intra-oral examination. The respondents identified several barriers that prevented them from completing a comprehensive oral cancer screening. Early detection of oral cancer reduces mortality rates so there is a professional responsibility to ensure that comprehensive oral cancer screenings are being performed on patients. Dental hygienists may not have the authority in a dental practice to overcome all of the barriers that are preventing them from performing these screenings. Public awareness about oral cancer screenings could increase the demand for screenings and thereby play a role in changing practice norms. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Breast screening policy: Are we heading in the right direction?

International Nuclear Information System (INIS)

Evans, A.; Whelehan, P.

2011-01-01

There is a large body of evidence supporting 2-yearly screening of women aged 50-69 years. There is good evidence for a mortality reduction from mammographic screening in women aged 40 to 49 years but a 1-year interval is required. The lack of specificity of screening in young women does remain a problem. There is no evidence to suggest that a single screen between the ages of 47 and 50 years within a programme screening at 3-year intervals will reduce mortality; the trials showing a mortality benefit in women in their 40s included multiple screening episodes and shorter screening intervals. There is no randomized, controlled trial evidence to support screening in women aged above 70 years and screening this age group will cause greater harm than in younger women through higher rates of over-diagnosis and consequent over-treatment. The randomized phase of the screening age extension, which at the moment is planned to last only 6 years, should not be immediately followed by general implementation of the policy. Only if and when additional mortality reductions and an acceptable balance between benefit and harms are shown to be achieved by the extra screens should the 2007 Cancer Reform Strategy policy on age extension be implemented. Resources saved by delaying or abandoning the roll-out of the age extension could potentially be redirected towards reducing the current 3 year screening interval to 2 years in women aged 50-69 years. However, reducing the screening interval to 2 years for women aged 50-69 years would require significantly more screening invitations and resources than the proposed age extension.

Breast screening policy: Are we heading in the right direction?

Energy Technology Data Exchange (ETDEWEB)

Evans, A., E-mail: a.z.evans@dundee.ac.uk [Dundee Cancer Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee (United Kingdom); Whelehan, P. [Dundee Cancer Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee (United Kingdom)

2011-10-15

There is a large body of evidence supporting 2-yearly screening of women aged 50-69 years. There is good evidence for a mortality reduction from mammographic screening in women aged 40 to 49 years but a 1-year interval is required. The lack of specificity of screening in young women does remain a problem. There is no evidence to suggest that a single screen between the ages of 47 and 50 years within a programme screening at 3-year intervals will reduce mortality; the trials showing a mortality benefit in women in their 40s included multiple screening episodes and shorter screening intervals. There is no randomized, controlled trial evidence to support screening in women aged above 70 years and screening this age group will cause greater harm than in younger women through higher rates of over-diagnosis and consequent over-treatment. The randomized phase of the screening age extension, which at the moment is planned to last only 6 years, should not be immediately followed by general implementation of the policy. Only if and when additional mortality reductions and an acceptable balance between benefit and harms are shown to be achieved by the extra screens should the 2007 Cancer Reform Strategy policy on age extension be implemented. Resources saved by delaying or abandoning the roll-out of the age extension could potentially be redirected towards reducing the current 3 year screening interval to 2 years in women aged 50-69 years. However, reducing the screening interval to 2 years for women aged 50-69 years would require significantly more screening invitations and resources than the proposed age extension.

The West Midlands breast cancer screening status algorithm - methodology and use as an audit tool.

Science.gov (United States)

Lawrence, Gill; Kearins, Olive; O'Sullivan, Emma; Tappenden, Nancy; Wallis, Matthew; Walton, Jackie

2005-01-01

To illustrate the ability of the West Midlands breast screening status algorithm to assign a screening status to women with malignant breast cancer, and its uses as a quality assurance and audit tool. Breast cancers diagnosed between the introduction of the National Health Service [NHS] Breast Screening Programme and 31 March 2001 were obtained from the West Midlands Cancer Intelligence Unit (WMCIU). Screen-detected tumours were identified via breast screening units, and the remaining cancers were assigned to one of eight screening status categories. Multiple primaries and recurrences were excluded. A screening status was assigned to 14,680 women (96% of the cohort examined), 110 cancers were not registered at the WMCIU and the cohort included 120 screen-detected recurrences. The West Midlands breast screening status algorithm is a robust simple tool which can be used to derive data to evaluate the efficacy and impact of the NHS Breast Screening Programme.

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.

Comparison of characteristics between frequent participants and non-participants in screening program for stomach cancer.

Science.gov (United States)

Fukao, A; Hisamichi, S; Komatsu, S; Shimizu, H; Satoh, H; Nakatsuka, H; Watanabe, T; Fujisaku, S; Ichinowatari, Y; Kuroda, S

1992-04-01

To clarify the differences in characteristics between participants and non-participants in the screening program for stomach cancer, life-style and medical histories were compared among 20, 169 subjects who lived in an urban area (Sendai) and a rural area (Wakuya and Tajiri) in Miyagi Prefecture, Japan. All subjects were classified into three groups according to the frequency of participation in the screening program during the last 5 years; i.e., frequent participating group (FPG) for 4 or 5 times, reference group (RG) for 1-3 times and non-participating group (NPG) for 0 times. Subjects in the FPG consumed more milk and green-yellow vegetable whereas those in the NPG consumed less these foods. The age-adjusted proportions of present smokers were higher in the NPG but lower in the FPG significantly. The proportions of subjects who had parental histories of all cancers and stomach cancer and past history of gastro-duodenal ulcer were higher in the FPG and lower in the NPG. To control influences among the variables a stepwise multiple regression analysis was done, and it revealed that smoking and parental history of cancers were strong predictors to explain the frequency of participation.

Cervical Cancer Screening Service Uptake and Associated Factors among Age Eligible Women in Mekelle Zone, Northern Ethiopia, 2015: A Community Based Study Using Health Belief Model.

Directory of Open Access Journals (Sweden)

Hinsermu Bayu

Full Text Available Cervical cancer is the third most common cancer among women worldwide, with about 500,000 new patients diagnosed and over 250,000 deaths every year. Cervical cancer screening offers protective benefits and is associated with a reduction in the incidence of invasive cervical cancer and cervical cancer mortality. But there is very low participation rate in screening for cervical cancer among low and middle-income countries.This study aimed to determine cervical cancer screening service uptake and its associated factor among age eligible women in Mekelle zone, northern Ethiopia, 2015.A community based cross-sectional study was conducted in Mekelle zone among age eligible women from February to June 2015. Systematic sampling technique was used to select 1286 women in to the study. A pre-tested structured questionnaire was used to collect relevant data. Data was entered and cleaned using EPINFO and analyzed using SPSS version 20 software package. Bivariate and Multivariate logistic regression was performed to assess association between dependent and independent variables with 95% CI and p-value less than 0.05 was set for association.The study revealed that among 1186 age eligible women, only 235(19.8% have been screened for cervical cancer. Age (AOR = 1.799, 95%CI = 1.182-2.739, history of multiple sexual partners (AOR = 1.635, 95%CI = 1.094-2.443, history of sexually transmitted disease (AOR = 1.635,95%CI = 1.094-2.443, HIV sero status (AOR = 5.614, 95%CI = 2.595-12.144, perceived susceptibility to cervical cancer (AOR = 2.225, 95%CI = 1.308-3.783, perceived barriers to premalignant cervical lesions screening (AOR = 2.256, 95%CI = 1.447-3.517 and knowledge on cervical cancer and screening (AOR = 2.355, 95%CI = 1.155-4.802 were significant predictors of cervical cancer screening service uptake.Magnitude of cervical cancer screening service uptake among age eligible women is still unacceptably low. Age of the women, history of multiple sexual partners

Phytochemical screening and mineral composition of chewing sticks ...

African Journals Online (AJOL)

Phytochemical screening of the stems of Garcinia kola, Dennettia tripetala, Acioa barteri, Dialium guineense, Maesobotrya barteri, Mallotus oppositifolius and Psidium guajava which are commonly used as chewing sticks in southern Nigeria revealed the presence of bioactive compounds comprising saponins, tannins, ...

Development and Validation of a POSIT-Short Form: Screening for Problem Behaviors among Adolescents at Risk for Substance Use.

Science.gov (United States)

Danseco, Evangeline R.; Marques, Paul R.

2002-01-01

The Problem-Oriented Screening Instrument for Teenagers (POSIT) screens for multiple problems among adolescents at risk for substance use. A shortened version of the POSIT was developed, using factor analysis, and correlational and reliability analyses. The POSIT-SF shows potential for a reliable and cost-efficient screen for youth with substance…

Older Korean American men's prostate cancer screening behavior: the prime role of culture.

Science.gov (United States)

Lee, Hee Yun; Jung, Yunkyung

2013-12-01

East and South Asian male immigrants show markedly low odds of prostate cancer screening as compared to U.S.-born men. However, knowledge about these immigrants' culture-based screening behavior and barriers to screening is extremely limited. This study investigates factors influencing receipt of prostate cancer screening among Korean American immigrant men, particularly investigating culture's impact on screening behaviors. Data were collected through a convenience and purposive sampling technique from 134 Korean American males aged 50 and older recruited in New York City. A structured questionnaire was used and cultural variables were measured by adopting items from Tang and colleagues' work. Approximately 60 % of the sample had received a prostate-specific antigen (PSA) test in their lifetime, and of these, about 66 % reported having done so in the previous 12 months. Logistic regression analysis revealed that a crisis-oriented intervention approach was associated with a substantially reduced likelihood of screening. A positive correlation was noted between the use of Eastern medicine and PSA test receipt. Further analysis revealed a significant interaction effect between use of Eastern medicine and age in predicting PSA test uptake. Culture-specific intervention strategies for increasing prostate cancer screening in this group are discussed, with particular attention to increasing pertinent health literacy. Health professionals should consider the cultural domain when working with Korean immigrant men in order to provide culturally competent care.

Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

Directory of Open Access Journals (Sweden)

Tia DiTommaso

2014-10-01

Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

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.

Multiple variables data sets visualization in ROOT

International Nuclear Information System (INIS)

Couet, O

2008-01-01

The ROOT graphical framework provides support for many different functions including basic graphics, high-level visualization techniques, output on files, 3D viewing etc. They use well-known world standards to render graphics on screen, to produce high-quality output files, and to generate images for Web publishing. Many techniques allow visualization of all the basic ROOT data types, but the graphical framework was still a bit weak in the visualization of multiple variables data sets. This paper presents latest developments done in the ROOT framework to visualize multiple variables (>4) data sets

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Knudsen, L; Jensen, K

1994-01-01

In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

The impact of aviation checkpoint queues on optimizing security screening effectiveness

Energy Technology Data Exchange (ETDEWEB)

Lee, Adrian J., E-mail: ajlee@citeri.or [Central Illinois Technology and Education Research Institute, 2312 Connie Drive, Springfield, IL 62704-8722 (United States); Jacobson, Sheldon H., E-mail: shj@illinois.ed [Department of Computer Science, University of Illinois at Urbana-Champaign, 201 N. Goodwin Ave. M/C 258, Urbana, IL 61801-2302 (United States)

2011-08-15

Passenger screening at aviation security checkpoints is a critical component in protecting airports and aircraft from terrorist threats. Recent developments in screening device technology have increased the ability to detect these threats; however, the average amount of time it takes to screen a passenger still remains a concern. This paper models the queueing process for a multi-level airport checkpoint security system, where multiple security classes are formed through subsets of specialized screening devices. An optimal static assignment policy is obtained which minimizes the steady-state expected amount of time a passenger spends in the security system. Then, an optimal dynamic assignment policy is obtained through a transient analysis that balances the expected number of true alarms with the expected amount of time a passenger spends in the security system. Performance of a two-class system is compared to that of a selective security system containing primary and secondary levels of screening. The key contribution is that the resulting optimal assignment policies increase security and passenger throughput by efficiently and effectively utilizing available screening resources.

The impact of aviation checkpoint queues on optimizing security screening effectiveness

International Nuclear Information System (INIS)

Lee, Adrian J.; Jacobson, Sheldon H.

2011-01-01

Passenger screening at aviation security checkpoints is a critical component in protecting airports and aircraft from terrorist threats. Recent developments in screening device technology have increased the ability to detect these threats; however, the average amount of time it takes to screen a passenger still remains a concern. This paper models the queueing process for a multi-level airport checkpoint security system, where multiple security classes are formed through subsets of specialized screening devices. An optimal static assignment policy is obtained which minimizes the steady-state expected amount of time a passenger spends in the security system. Then, an optimal dynamic assignment policy is obtained through a transient analysis that balances the expected number of true alarms with the expected amount of time a passenger spends in the security system. Performance of a two-class system is compared to that of a selective security system containing primary and secondary levels of screening. The key contribution is that the resulting optimal assignment policies increase security and passenger throughput by efficiently and effectively utilizing available screening resources.

Adenoma detection in patients undergoing a comprehensive colonoscopy screening

International Nuclear Information System (INIS)

Raju, Gottumukkala S; Vadyala, Vikram; Slack, Rebecca; Krishna, Somashekar G; Ross, William A; Lynch, Patrick M; Bresalier, Robert S; Hawk, Ernest; Stroehlein, John R

2013-01-01

Measures shown to improve the adenoma detection during colonoscopy (excellent bowel preparation, cecal intubation, cap fitted colonoscope to examine behind folds, patient position change to optimize colon distention, trained endoscopy team focusing on detection of subtle flat lesions, and incorporation of optimum endoscopic examination with adequate withdrawal time) are applicable to clinical practice and, if incorporated are projected to facilitate comprehensive colonoscopy screening program for colon cancer prevention. To determine adenoma and serrated polyp detection rate under conditions designed to optimize quality parameters for comprehensive screening colonoscopy. Retrospective analysis of data obtained from a comprehensive colon cancer screening program designed to optimize quality parameters. Academic medical center. Three hundred and forty-three patients between the ages of 50 years and 75 years who underwent first screening colonoscopy between 2009 and 2011 among 535 consecutive patients undergoing colonoscopy. Comprehensive colonoscopy screening program was utilized to screen all patients. Cecal intubation was successful in 98.8% of patients. The Boston Bowel Preparation Scale for quality of colonoscopy was 8.97 (95% confidence interval [CI]; 8.94, 9.00). The rate of adenoma detection was 60% and serrated lesion (defined as serrated adenomas or hyperplastic polyps proximal to the splenic flexure) detection was 23%. The rate of precancerous lesion detection (adenomas and serrated lesions) was 66%. The mean number of adenomas per screening procedure was 1.4 (1.2, 1.6) and the mean number of precancerous lesions (adenomas or serrated lesions) per screening procedure was 1.6 (1.4, 1.8). Retrospective study and single endoscopist experience. A comprehensive colonoscopy screening program results in high-quality screening with high detection of adenomas, advanced adenomas, serrated adenomas, and multiple adenomas

The influence of time perspective on cervical cancer screening among Latinas in the United States.

Science.gov (United States)

Roncancio, Angelica M; Ward, Kristy K; Fernandez, Maria E

2014-12-01

To develop effective interventions to increase cervical cancer screening among Latinas, we should understand the role of cultural factors, such as time perspective, in the decision to be screened. We examined the relation between present time orientation, future time orientation, and self-reported cervical cancer screening among Latinas. A group of 206 Latinas completed a survey measuring factors associated with screening. Logistic regression analyses revealed that future time orientation was significantly associated with self-reported screening. Understanding the influence of time orientation on cervical cancer screening will assist us in developing interventions that effectively target time perspective and screening. © The Author(s) 2013.

Phytochemical Screening and Evaluation of Analgesic Activity of Oroxylum indicum

OpenAIRE

Das, B. K.; Al-Amin, M. M.; Russel, S. M.; Kabir, S.; Bhattacherjee, R.; Hannan, J. M. A.

2014-01-01

We aimed to study phytochemical screening and analgesic activity of ethanol extract of Oroxylum indicum. The dried powder of the barks of the plant was extracted with 95% ethanol and was subjected to various phytochemical tests to ascertain the principle constituents contained in the extract. The result revealed the presence of alkaloids, flavonoids, tannins, glycosides in the ethanol extract of Oroxylum indicum. The extract was screened for analgesic activity by using hot plate, acetic acid-...

Cross sectional associations of screen time and outdoor play with social skills in preschool children.

Science.gov (United States)

Hinkley, Trina; Brown, Helen; Carson, Valerie; Teychenne, Megan

2018-01-01

Screen time and physical activity behaviours develop during the crucial early childhood period (0-5 years) and impact multiple health and developmental outcomes, including psychosocial wellbeing. Social skills, one component of psychosocial wellbeing, are vital for children's school readiness and future mental health. This study investigates potential associations of screen time and outdoor play (as a proxy for physical activity) with social skills. Cross sectional data were available for 575 mothers with a child (54% boys) aged 2-5 years. Mothers reported their child's screen time, outdoor play time and social skills (Adaptive Social Behavior Inventory; ASBI). Multiple linear regression analyses assessed associations of screen and outdoor play time (Model 1) and compliance with screen time and physical activity recommendations (Model 2) with three ASBI subscales. Boys and girls spent a mean of 2.0 and 2.2 hours per day in screen time, and 3.3 and 2.9 hours per day in outdoor play, respectively. Girls scores for express and comply skills were significantly higher than boys (p<0.005). After applying the Benjamini-Hochberg Procedure to adjust for multiple associations, children's television/DVD/video viewing was inversely associated with their compliant scores (B = -0.35 95% CI -0.26, -0.14; p = 0.001) and outdoor play time was positively associated with both expressive (B = 0.20 95% CI 0.07, 0.34; p = 0.004) and compliant (B = 0.22 95% CI 0.08, 0.36; p = 0.002) scores. Findings indicate that television/DVD/video viewing may be adversely, and outdoor play favourably, associated with preschool children's social skills. Future research is required to identify the direction of causation and explore potential mechanisms of association.

The “DOC” screen: Feasible and valid screening for depression, Obstructive Sleep Apnea (OSA) and cognitive impairment in stroke prevention clinics

Science.gov (United States)

Swartz, Richard H.; Cayley, Megan L.; Lanctôt, Krista L.; Murray, Brian J.; Cohen, Ashley; Thorpe, Kevin E.; Sicard, Michelle N.; Lien, Karen; Sahlas, Demetrios J.; Herrmann, Nathan

2017-01-01

Background Post-stroke Depression, Obstructive sleep apnea (OSA) and Cognitive impairment (“DOC”) are associated with greater mortality, worse recovery and poorer quality of life. Best practice recommendations endorse routine screening for each condition; yet, all are under-assessed, diagnosed and treated. We seek to determine the feasibility and validity of an integrated tool (“DOC” screen) to identify stroke clinic patients at high-risk of depression, OSA, and cognitive impairment. Methods All consecutive new referrals to a regional Stroke Prevention Clinic who were English-speaking and non-aphasic were eligible to be screened. Time for screen completion was logged. DOC screen results were compared to the neuropsychological battery and polysomnogram assessments using a modified receiver operator characteristic and area under the curve analysis. Data is reported to conform to STARD guidelines. Findings 1503 people were screened over 2 years. 89% of eligible patients completed the screen in 5 minutes or less (mean 4.2 minutes), less than half the time it takes to complete the Montreal Cognitive Assessment (MoCA). 437 people consented to detailed testing. Of those, 421 completed the Structured Clinical Interview for Depression within 3 months of screening, 387 completed detailed neuropsychological testing within 3 months, and 88 had overnight polysomnograms. Screening scores combined with demographic variables (age, sex, education, body mass index), had excellent validity compared to gold standard diagnoses: DOC-Mood AUC 0.90; DOC-Apnea AUC 0.80; DOC-Cog AUC 0.81. DOC screen scores can reliably categorize patients in to low-, intermediate- or high-risk groups for further action and can do so with comparable accuracy to more time-consuming screens. Conclusions Systematic screening of depression, obstructive sleep apnea, and cognitive impairment in 5 minutes or less is feasible and valid in a high volume stroke clinic using the DOC screen. The DOC screen may

A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.

Science.gov (United States)

Modrzynska, Katarzyna; Pfander, Claudia; Chappell, Lia; Yu, Lu; Suarez, Catherine; Dundas, Kirsten; Gomes, Ana Rita; Goulding, David; Rayner, Julian C; Choudhary, Jyoti; Billker, Oliver

2017-01-11

A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony. We describe non-essential functions for AP2-O and AP2-SP proteins in blood stages, and identify AP2-G2 as a repressor active in both asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages revealed clusters of co-regulated genes with shared cis promoter elements, whose expression can be controlled positively or negatively by different ApiAP2 factors. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

Science.gov (United States)

Schiebler, Mark; Brown, Karen; Hegyi, Krisztina; Newton, Sandra M; Renna, Maurizio; Hepburn, Lucy; Klapholz, Catherine; Coulter, Sarah; Obregón-Henao, Andres; Henao Tamayo, Marcela; Basaraba, Randall; Kampmann, Beate; Henry, Katherine M; Burgon, Joseph; Renshaw, Stephen A; Fleming, Angeleen; Kay, Robert R; Anderson, Karen E; Hawkins, Phillip T; Ordway, Diane J; Rubinsztein, David C; Floto, Rodrigo Andres

2015-02-01

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Multiplexed screening of natural humoral immunity identifies antibodies at fine specificity for complex and dynamic viral targets.

Science.gov (United States)

McCutcheon, Krista M; Gray, Julia; Chen, Natalie Y; Liu, Keyi; Park, Minha; Ellsworth, Stote; Tripp, Ralph A; Tompkins, S Mark; Johnson, Scott K; Samet, Shelly; Pereira, Lenore; Kauvar, Lawrence M

2014-01-01

Viral entry targets with therapeutic neutralizing potential are subject to multiple escape mechanisms, including antigenic drift, immune dominance of functionally irrelevant epitopes, and subtle variations in host cell mechanisms. A surprising finding of recent years is that potent neutralizing antibodies to viral epitopes independent of strain exist, but are poorly represented across the diverse human population. Identifying these antibodies and understanding the biology mediating the specific immune response is thus difficult. An effective strategy for meeting this challenge is to incorporate multiplexed antigen screening into a high throughput survey of the memory B cell repertoire from immune individuals. We used this approach to discover suites of cross-clade antibodies directed to conformational epitopes in the stalk region of the influenza A hemagglutinin (HA) protein and to select high-affinity anti-peptide antibodies to the glycoprotein B (gB) of human cytomegalovirus. In each case, our screens revealed a restricted VH and VL germline usage, including published and previously unidentified gene families. The in vivo evolution of paratope specificity with optimal neutralizing activity was understandable after correlating biological activities with kinetic binding and epitope recognition. Iterative feedback between antigen probe design based on structure and function information with high throughput multiplexed screening demonstrated a generally applicable strategy for efficient identification of safe, native, finely tuned antibodies with the potential for high genetic barriers to viral escape.

Multiple myeloma

International Nuclear Information System (INIS)

Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

1994-01-01

Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus.

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Kit Curtius

2015-05-01

Full Text Available Barrett's esophagus (BE patients are routinely screened for high grade dysplasia (HGD and esophageal adenocarcinoma (EAC through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1 the probability that small cancers are missed during biopsy-based screening, (2 the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3 the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence.

Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge

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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.

Evaluation of e-liquid toxicity using an open-source high-throughput screening assay

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Keating, James E.; Zorn, Bryan T.; Kochar, Tavleen K.; Wolfgang, Matthew C.; Glish, Gary L.; Tarran, Robert

2018-01-01

The e-liquids used in electronic cigarettes (E-cigs) consist of propylene glycol (PG), vegetable glycerin (VG), nicotine, and chemical additives for flavoring. There are currently over 7,700 e-liquid flavors available, and while some have been tested for toxicity in the laboratory, most have not. Here, we developed a 3-phase, 384-well, plate-based, high-throughput screening (HTS) assay to rapidly triage and validate the toxicity of multiple e-liquids. Our data demonstrated that the PG/VG vehicle adversely affected cell viability and that a large number of e-liquids were more toxic than PG/VG. We also performed gas chromatography–mass spectrometry (GC-MS) analysis on all tested e-liquids. Subsequent nonmetric multidimensional scaling (NMDS) analysis revealed that e-liquids are an extremely heterogeneous group. Furthermore, these data indicated that (i) the more chemicals contained in an e-liquid, the more toxic it was likely to be and (ii) the presence of vanillin was associated with higher toxicity values. Further analysis of common constituents by electron ionization revealed that the concentration of cinnamaldehyde and vanillin, but not triacetin, correlated with toxicity. We have also developed a publicly available searchable website (www.eliquidinfo.org). Given the large numbers of available e-liquids, this website will serve as a resource to facilitate dissemination of this information. Our data suggest that an HTS approach to evaluate the toxicity of multiple e-liquids is feasible. Such an approach may serve as a roadmap to enable bodies such as the Food and Drug Administration (FDA) to better regulate e-liquid composition. PMID:29584716

Evaluation of French version of the Vulnerability to abuse screen scale (VASS), a elder abuse screening tool.

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Grenier, Florian; Capriz, Françoise; Lacroix-Hugues, Virginie; Paysant, François; Pradier, Christian; Franco, Alain

2016-06-01

The elder abuse is a major public health problem. In the world, almost 4 to 10% of people of more than 65 years would be abuse. The generalist practitioners report only 2% of the elder abuse. Furthermore, the evaluations of elder abuse screenings test found in the scientist literature were unsatisfactory. Evaluate the elder abuse screening capacities of the Vulnerability to abuse screen scale (VASS) in order to propose it to the doctors. VASS was translated in French. It's a quantitative and a forward-looking study whose the answers of people of more than 65 years old were analysed and compared in blind way to the answers of socials workers. 200 patients were included between March and May 2012 in the CHU of Cimiez, Nice. We found 104 patients in danger of abuse, 40 cases of abuse revealed by the socials workers, so 20% of abuses were reported by the gold standard. It means a sensibility of 90,9%, a specificity of 49,7% and a predictive value of 96,1% to a score of 1 to the test. The screening test VASS shown it useful to detect elder people in danger of abuse but a few discriminants and not adapted to patients who have cognitive pathologies. It's a screening tool usable by default, more sensitive than others tests in the scientist literature. However, these results ask the question of the useful of these tools of elder abuse screening in comparison with the education of doctors which made proofs of success in this subject.

Reactions, accuracy and response complexity of numerical typing on touch screens.

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Lin, Cheng-Jhe; Wu, Changxu

2013-01-01

Touch screens are popular nowadays as seen on public kiosks, industrial control panels and personal mobile devices. Numerical typing is one frequent task performed on touch screens, but this task on touch screen is subject to human errors and slow responses. This study aims to find innate differences of touch screens from standard physical keypads in the context of numerical typing by eliminating confounding issues. Effects of precise visual feedback and urgency of numerical typing were also investigated. The results showed that touch screens were as accurate as physical keyboards, but reactions were indeed executed slowly on touch screens as signified by both pre-motor reaction time and reaction time. Provision of precise visual feedback caused more errors, and the interaction between devices and urgency was not found on reaction time. To improve usability of touch screens, designers should focus more on reducing response complexity and be cautious about the use of visual feedback. The study revealed that slower responses on touch screens involved more complex human cognition to formulate motor responses. Attention should be given to designing precise visual feedback appropriately so that distractions or visual resource competitions can be avoided to improve human performance on touch screens.

Screening for psychosocial problems in children attending the pediatric clinic at king Khalid university hospital (KKUH in Riyadh (KSA

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Ibrahim H Al-Ayed

2008-01-01

Conclusion: This study revealed the feasibility of screening for behavioral problems of children in an outpatient setting. It is necessary to implement screening procedures for psycho-behavioral problems, and train pediatricians to screen children presenting at clinics.

The Use of TOC Reconciliation as a Means of Establishing the Degree to Which Chromatographic Screening of Plastic Material Extracts for Organic Extractables Is Complete.

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Jenke, Dennis; Couch, Thomas R; Robinson, Sarah J; Volz, Trent J; Colton, Raymond H

2014-01-01

Extracts of plastic packaging, manufacturing, and delivery systems (or their materials of construction) are analyzed by chromatographic methods to establish the system's extractables profile. The testing strategy consists of multiple orthogonal chromatographic methods, for example, gas and liquid chromatography with multiple detection strategies. Although this orthogonal testing strategy is comprehensive, it is not necessarily complete and members of the extractables profile can elude detection and/or accurate identification/quantification. Because the chromatographic methods rarely indicate that some extractables have been missed, another means of assessing the completeness of the profiling activity must be established. If the extracts are aqueous and contain no organic additives (e.g., pH buffers), then they can be analyzed for their total organic carbon content (TOC). Additionally, the TOC of an extract can be calculated based on the extractables revealed by the screening analyses. The measured and calculated TOC can be reconciled to establish the completeness and accuracy of the extractables profile. If the reconciliation is poor, then the profile is either incomplete or inaccurate and additional testing is needed to establish the complete and accurate profile. Ten test materials and components of systems were extracted and their extracts characterized for organic extractables using typical screening procedures. Measured and calculated TOC was reconciled to establish the completeness of the revealed extractables profile. When the TOC reconciliation was incomplete, the profiling was augmented with additional analytical testing to reveal the missing members of the organic extractables profile. This process is illustrated via two case studies involving aqueous extracts of sterile filters. Plastic materials and systems used to manufacture, contain, store, and deliver pharmaceutical products are extracted and the extracts analyzed to establish the materials' (or

[Studies of marker screening efficiency and corresponding influencing factors in QTL composite interval mapping].

Science.gov (United States)

Gao, Yong-Ming; Wan, Ping

2002-06-01

Screening markers efficiently is the foundation of mapping QTLs by composite interval mapping. Main and interaction markers distinguished, besides using background control for genetic variation, could also be used to construct intervals of two-way searching for mapping QTLs with epistasis, which can save a lot of calculation time. Therefore, the efficiency of marker screening would affect power and precision of QTL mapping. A doubled haploid population with 200 individuals and 5 chromosomes was constructed, with 50 markers evenly distributed at 10 cM space. Among a total of 6 QTLs, one was placed on chromosome I, two linked on chromosome II, and the other three linked on chromosome IV. QTL setting included additive effects and epistatic effects of additive x additive, the corresponding QTL interaction effects were set if data were collected under multiple environments. The heritability was assumed to be 0.5 if no special declaration. The power of marker screening by stepwise regression, forward regression, and three methods for random effect prediction, e.g. best linear unbiased prediction (BLUP), linear unbiased prediction (LUP) and adjusted unbiased prediction (AUP), was studied and compared through 100 Monte Carlo simulations. The results indicated that the marker screening power by stepwise regression at 0.1, 0.05 and 0.01 significant level changed from 2% to 68%, the power changed from 2% to 72% by forward regression. The larger the QTL effects, the higher the marker screening power. While the power of marker screening by three random effect prediction was very low, the maximum was only 13%. That suggested that regression methods were much better than those by using the approaches of random effect prediction to identify efficient markers flanking QTLs, and forward selection method was more simple and efficient. The results of simulation study on heritability showed that heightening of both general heritability and interaction heritability of genotype x

Enhancing citizen engagement in cancer screening through deliberative democracy.

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Rychetnik, Lucie; Carter, Stacy M; Abelson, Julia; Thornton, Hazel; Barratt, Alexandra; Entwistle, Vikki A; Mackenzie, Geraldine; Salkeld, Glenn; Glasziou, Paul

2013-03-20

Cancer screening is widely practiced and participation is promoted by various social, technical, and commercial drivers, but there are growing concerns about the emerging harms, risks, and costs of cancer screening. Deliberative democracy methods engage citizens in dialogue on substantial and complex problems: especially when evidence and values are important and people need time to understand and consider the relevant issues. Information derived from such deliberations can provide important guidance to cancer screening policies: citizens' values are made explicit, revealing what really matters to people and why. Policy makers can see what informed, rather than uninformed, citizens would decide on the provision of services and information on cancer screening. Caveats can be elicited to guide changes to existing policies and practices. Policies that take account of citizens' opinions through a deliberative democracy process can be considered more legitimate, justifiable, and feasible than those that don't.

Vertical dielectric screening of few-layer van der Waals semiconductors.

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Koo, Jahyun; Gao, Shiyuan; Lee, Hoonkyung; Yang, Li

2017-10-05

Vertical dielectric screening is a fundamental parameter of few-layer van der Waals two-dimensional (2D) semiconductors. However, unlike the widely-accepted wisdom claiming that the vertical dielectric screening is sensitive to the thickness, our first-principles calculation based on the linear response theory (within the weak field limit) reveals that this screening is independent of the thickness and, in fact, it is the same as the corresponding bulk value. This conclusion is verified in a wide range of 2D paraelectric semiconductors, covering narrow-gap ones and wide-gap ones with different crystal symmetries, providing an efficient and reliable way to calculate and predict static dielectric screening of reduced-dimensional materials. Employing this conclusion, we satisfactorily explain the tunable band gap in gated 2D semiconductors. We further propose to engineer the vertical dielectric screening by changing the interlayer distance via vertical pressure or hybrid structures. Our predicted vertical dielectric screening can substantially simplify the understanding of a wide range of measurements and it is crucial for designing 2D functional devices.

Design and Polarization Characteristics Analysis of Dihedral Based on Salisbury Screen

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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.

Adiposity and different types of screen time.

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Falbe, Jennifer; Rosner, Bernard; Willett, Walter C; Sonneville, Kendrin R; Hu, Frank B; Field, Alison E

2013-12-01

Few prospective studies have examined separate forms of screen time in relation to adiposity. Our objective was to assess independent relations of television, electronic games (video/computer), and digital versatile disc (DVD)/videos and total screen time with change in adolescent BMI. Using data from the 2004, 2006, and 2008 waves of the ongoing Growing up Today Study II, we assessed baseline and 2-year change in reported screen time in relation to concurrent change in BMI among 4287 girls and 3505 boys aged 9 to 16 years in 2004. Gender-specific models adjusted for previous BMI, age, race/ethnicity, growth/development, months between questionnaires, and physical activity. Among girls and boys, each hour per day increase in reported television viewing was associated with a 0.09 increase in BMI (Ps food advertising, was most consistently associated with BMI gains. Among girls, electronic games and DVDs/videos were also related to increased BMI, possibly due to influences of product placements and advergames on diet and/or distracted eating. Adolescents, especially overweight adolescents, may benefit from reduced time with multiple types of media.

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

Participation and barriers to colorectal cancer screening in Malaysia.

Science.gov (United States)

Yusoff, Harmy Mohamed; Daud, Norwati; Noor, Norhayati Mohd; Rahim, Amry Abdul

2012-01-01

In Malaysia, colorectal cancer is the most common cancer in males and the third most common in females. Mortality due to colorectal cancer can be effectively reduced with early diagnosis. This study was designed to look into colorectal cancer screening participation and its barriers among average risk individuals in Malaysia. A cross sectional study was conducted from August 2009 till April 2010 involving average risk individuals from 44 primary care clinics in West Malaysia. Each individual was asked whether they have performed any of the colorectal cancer screening methods in the past five years. The barrier questions had three domains: patient factors, test factors and health care provider factors. Descriptive analysis was achieved using Statistical Program for Social Sciences (SPSS) version 12.0. A total of 1,905 average risk individuals responded making a response rate of 93.8%. Only 13 (0.7%) respondents had undergone any of the colorectal cancer screening methods in the past five years. The main patient and test factors for not participating were embarrassment (35.2%) and feeling uncomfortable (30.0%), respectively. There were 11.2% of respondents who never received any advice to do screening. The main reason for them to undergo screening was being advised by health care providers (84.6%). The study showed that participation in colorectal cancer screening in Malaysia is extremely low and multiple factors contribute to this situation. Given the importance of the disease, efforts should be made to increase colorectal cancer screening activities in Malaysia.

Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins

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Kahlem Pascal

2006-06-01

Full Text Available Abstract Background Trisomy of human chromosome 21 (Chr21 results in Down's syndrome, a complex developmental and neurodegenerative disease. Molecular analysis of Down's syndrome, however, poses a particular challenge, because the aneuploid region of Chr21 contains many genes of unknown function. Subcellular localization of human Chr21 proteins may contribute to further understanding of the functions and regulatory mechanisms of the genes that code for these proteins. Following this idea, we used a transfected-cell array technique to perform a rapid and cost-effective analysis of the intracellular distribution of Chr 21 proteins. Results We chose 89 genes that were distributed over the majority of 21q, ranging from RBM11 (14.5 Mb to MCM3AP (46.6 Mb, with part of them expressed aberrantly in the Down's syndrome mouse model. Open reading frames of these genes were cloned into a mammalian expression vector with an amino-terminal His6 tag. All of the constructs were arrayed on glass slides and reverse transfected into HEK293T cells for protein expression. Co-localization detection using a set of organelle markers was carried out for each Chr21 protein. Here, we report the subcellular localization properties of 52 proteins. For 34 of these proteins, their localization is described for the first time. Furthermore, the alteration in cell morphology and growth as a result of protein over-expression for claudin-8 and claudin-14 genes has been characterized. Conclusion The cell array-based protein expression and detection approach is a cost-effective platform for large-scale functional analyses, including protein subcellular localization and cell phenotype screening. The results from this study reveal novel functional features of human Chr21 proteins, which should contribute to further understanding of the molecular pathology of Down's syndrome.

Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives: A Feasibility Study.

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Bingley, Polly J; Rafkin, Lisa E; Matheson, Della; Steck, Andrea K; Yu, Liping; Henderson, Courtney; Beam, Craig A; Boulware, David C

2015-12-01

Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot-based screening to identify islet autoantibody-positive relatives potentially eligible for inclusion in prevention trials. Dried blood spot (DBS) and venous samples were collected from 229 relatives participating in the TrialNet Pathway to Prevention Study. Both samples were tested for glutamic acid decarboxylase, islet antigen 2, and zinc transporter 8 autoantibodies, and venous samples were additionally tested for insulin autoantibodies and islet cell antibodies. We defined multiple autoantibody positive as two or more autoantibodies in venous serum and DBS screen positive if one or more autoantibodies were detected. Participant questionnaires compared the sample collection methods. Of 44 relatives who were multiple autoantibody positive in venous samples, 42 (95.5%) were DBS screen positive, and DBS accurately detected 145 of 147 autoantibody-negative relatives (98.6%). Capillary blood sampling was perceived as more painful than venous blood draw, but 60% of participants would prefer initial screening using home fingerstick with clinic visits only required if autoantibodies were found. Capillary blood sampling could facilitate screening for type 1 diabetes prevention studies.

Depression Screening

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... Depression Screening Substance Abuse Screening Alcohol Use Screening Depression Screening (PHQ-9) - Instructions The following questions are ... this tool, there is also text-only version . Depression Screening - Manual Instructions The following questions are a ...

[The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies--will a global change start in Israel?].

Science.gov (United States)

Bronshtein, Moshe; Solt, Ido; Blumenfeld, Zeev

2014-06-01

Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries

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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 limi...

A reliable computational workflow for the selection of optimal screening libraries.

Science.gov (United States)

Gilad, Yocheved; Nadassy, Katalin; Senderowitz, Hanoch

2015-01-01

components, it can be easily adapted and reproduced by computational groups interested in rational selection of screening libraries. Furthermore, the workflow could be readily modified to include additional components. This workflow has been routinely used in our laboratory for the selection of libraries in multiple projects and consistently selects libraries which are well balanced across multiple parameters.Graphical abstract.

Biosensor reveals multiple sources for mitochondrial NAD⁺.

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Cambronne, Xiaolu A; Stewart, Melissa L; Kim, DongHo; Jones-Brunette, Amber M; Morgan, Rory K; Farrens, David L; Cohen, Michael S; Goodman, Richard H

2016-06-17

Nicotinamide adenine dinucleotide (NAD(+)) is an essential substrate for sirtuins and poly(adenosine diphosphate-ribose) polymerases (PARPs), which are NAD(+)-consuming enzymes localized in the nucleus, cytosol, and mitochondria. Fluctuations in NAD(+) concentrations within these subcellular compartments are thought to regulate the activity of NAD(+)-consuming enzymes; however, the challenge in measuring compartmentalized NAD(+) in cells has precluded direct evidence for this type of regulation. We describe the development of a genetically encoded fluorescent biosensor for directly monitoring free NAD(+) concentrations in subcellular compartments. We found that the concentrations of free NAD(+) in the nucleus, cytoplasm, and mitochondria approximate the Michaelis constants for sirtuins and PARPs in their respective compartments. Systematic depletion of enzymes that catalyze the final step of NAD(+) biosynthesis revealed cell-specific mechanisms for maintaining mitochondrial NAD(+) concentrations. Copyright © 2016, American Association for the Advancement of Science.

The screening pelvic radiograph in pediatric trauma

International Nuclear Information System (INIS)

Rees, M.J.; Aickin, R.; Kolbe, A.; Teele, R.L.

2001-01-01

Background. Pelvic radiographs are routinely obtained in adult trauma to optimise early management. In adults, pelvic fractures are associated with high early transfusion requirement, high injury severity scores and an increased incidence of other abdominal and thoracic injuries. It is unclear whether this holds true in children. Objective. To determine whether the screening pelvic radiograph is necessary in paediatric trauma. Materials and methods. The notes of all patients who presented after trauma to the Starship Children's Hospital and were triaged to the resuscitation room during 1997 were reviewed. Results of initial radiography were obtained and correlated with later imaging. Results. Our review of 444 injured children seen over a period of 1 year revealed that of 347 children who had screening pelvic radiographs, only 1 had a pelvic fracture. The fracture in this child was clinically apparent and required no specific treatment. Conclusions. The presence of a pelvic fracture is rare in injured children. By omitting screening pelvic radiographs there are potential benefits, including reduced radiation exposure to children and cost savings. Uninterpretable or abnormal clinical examination or haematuria requires further investigation, but routine screening for pelvic fracture is unnecessary. (orig.)

The incremental role of trait emotional intelligence on perceived cervical screening barriers.

Science.gov (United States)

Costa, Sebastiano; Barberis, Nadia; Larcan, Rosalba; Cuzzocrea, Francesca

2018-02-13

Researchers have become increasingly interested in investigating the role of the psychological aspects related to the perception of cervical screening barriers. This study investigates the influence of trait EI on perceived cervical screening barriers. Furthermore, this study investigates the incremental validity of trait EI beyond the Big Five, as well as emotion regulation in the perceived barrier towards the Pap test as revealed in a sample of 206 Italian women that were undergoing cervical screening. Results have shown that trait EI is negatively related to cervical screening barriers. Furthermore, trait EI can be considered as a strong incremental predictor of a woman's perception of screening over and above the Big Five, emotion regulation, age, sexual intercourse experience and past Pap test. Detailed information on the study findings and future research directions are discussed.

Exploring general practitioners' experience of informing women about prenatal screening tests for foetal abnormalities: A qualitative focus group study

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Meiser Bettina

2008-05-01

Full Text Available Abstract Background Recent developments have made screening tests for foetal abnormalities available earlier in pregnancy and women have a range of testing options accessible to them. It is now recommended that all women, regardless of their age, are provided with information on prenatal screening tests. General Practitioners (GPs are often the first health professionals a woman consults in pregnancy. As such, GPs are well positioned to inform women of the increasing range of prenatal screening tests available. The aim of this study was to explore GPs experience of informing women of prenatal genetic screening tests for foetal abnormality. Methods A qualitative study consisting of four focus groups was conducted in metropolitan and rural Victoria, Australia. A discussion guide was used and the audio-taped transcripts were independently coded by two researchers using thematic analysis. Multiple coders and analysts and informant feedback were employed to reduce the potential for researcher bias and increase the validity of the findings. Results Six themes were identified and classified as 'intrinsic' if they occurred within the context of the consultation or 'extrinsic' if they consisted of elements that impacted on the GP beyond the scope of the consultation. The three intrinsic themes were the way GPs explained the limitations of screening, the extent to which GPs provided information selectively and the time pressures at play. The three extrinsic factors were GPs' attitudes and values towards screening, the conflict they experienced in offering screening information and the sense of powerlessness within the screening test process and the health care system generally. Extrinsic themes reveal GPs' attitudes and values to screening and to disability, as well as raising questions about the fundamental premise of testing. Conclusion The increasing availability and utilisation of screening tests, in particular first trimester tests, has expanded GPs

Risk Prediction Models for Other Cancers or Multiple Sites

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Developing statistical models that estimate the probability of developing other multiple cancers over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

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.

Symptom overlap in anxiety and multiple sclerosis.

LENUS (Irish Health Repository)

O Donnchadha, Seán

2013-02-14

BACKGROUND: The validity of self-rated anxiety inventories in people with multiple sclerosis (pwMS) is unclear. However, the appropriateness of self-reported depression scales has been widely examined. Given somatic symptom overlap between depression and MS, research emphasises caution when using such scales. OBJECTIVE: This study evaluates symptom overlap between anxiety and MS in a group of 33 individuals with MS, using the Beck Anxiety Inventory (BAI). METHODS: Participants underwent a neurological examination and completed the BAI. RESULTS: A novel procedure using hierarchical cluster analysis revealed three distinct symptom clusters. Cluster one (\\'wobbliness\\' and \\'unsteady\\') grouped separately from all other BAI items. These symptoms are well-recognised MS-related symptoms and we question whether their endorsement in pwMS can be considered to reflect anxiety. A modified 19-item BAI (mBAI) was created which excludes cluster one items. This removal reduced the number of MS participants considered \\'anxious\\' by 21.21% (low threshold) and altered the level of anxiety severity for a further 27.27%. CONCLUSION: Based on these data, it is suggested that, as with depression measures, researchers and clinicians should exercise caution when using brief screening measures for anxiety in pwMS.

Brain transcriptome-wide screen for HIV-1 Nef protein interaction partners reveals various membrane-associated proteins.

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Ellen C Kammula

Full Text Available HIV-1 Nef protein contributes essentially to the pathology of AIDS by a variety of protein-protein-interactions within the host cell. The versatile functionality of Nef is partially attributed to different conformational states and posttranslational modifications, such as myristoylation. Up to now, many interaction partners of Nef have been identified using classical yeast two-hybrid screens. Such screens rely on transcriptional activation of reporter genes in the nucleus to detect interactions. Thus, the identification of Nef interaction partners that are integral membrane proteins, membrane-associated proteins or other proteins that do not translocate into the nucleus is hampered. In the present study, a split-ubiquitin based yeast two-hybrid screen was used to identify novel membrane-localized interaction partners of Nef. More than 80% of the hereby identified interaction partners of Nef are transmembrane proteins. The identified hits are GPM6B, GPM6A, BAP31, TSPAN7, CYB5B, CD320/TCblR, VSIG4, PMEPA1, OCIAD1, ITGB1, CHN1, PH4, CLDN10, HSPA9, APR-3, PEBP1 and B3GNT, which are involved in diverse cellular processes like signaling, apoptosis, neurogenesis, cell adhesion and protein trafficking or quality control. For a subfraction of the hereby identified proteins we present data supporting their direct interaction with HIV-1 Nef. We discuss the results with respect to many phenotypes observed in HIV infected cells and patients. The identified Nef interaction partners may help to further elucidate the molecular basis of HIV-related diseases.

Systematic analysis of fly models with multiple drivers reveals different effects of ataxin-1 and huntingtin in neuron subtype-specific expression.

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Risa Shiraishi

Full Text Available The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases.

Iterative Cellular Screening System for Nanoparticle Safety Testing

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Franziska Sambale

2015-01-01

Full Text Available Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide and titanium dioxide nanoparticles. They were used as benchmarks to set up our methods and to examine their effects on mammalian cell lines. Different biological processes such as cell viability, gene expression of interleukin-8 and heat shock protein 70, as well as morphology changes were investigated. Within our screening system, both nanoparticle suspensions and coatings can be tested. Electric cell impedance measurements revealed to be a good method for online monitoring of cellular behavior. The implementation of three-dimensional cell culture is essential to better mimic in vivo conditions. In conclusion, our screening system is highly efficient, cost minimizing, and reduces the need for animal studies.

Persistent demographic differences in colorectal cancer screening utilization despite Medicare reimbursement

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Kreuter William

2005-03-01

Full Text Available Abstract Background Colorectal cancer screening is widely recommended, but often under-utilized. In addition, significant demographic differences in screening utilization exist. Insurance coverage may be one factor influencing utilization of colorectal cancer screening tests. Methods We conducted a retrospective analysis of claims for outpatient services for Washington state Medicare beneficiaries in calendar year 2000. We determined the proportion of beneficiaries utilizing screening fecal occult blood tests, flexible sigmoidoscopy, colonoscopy, or double contrast barium enema in the overall population and various demographic subgroups. Multiple logistic regression analysis was used to determine the relative odds of screening in different demographic groups. Results Approximately 9.2% of beneficiaries had fecal occult blood tests, 7.2% had any colonoscopy, flexible sigmoidoscopy, or barium enema (invasive colon tests, and 3.5% had invasive tests for screening indications. Colonoscopy accounted for 41% of all invasive tests for screening indications. Women were more likely to receive fecal occult blood test screening (OR 1.18; 95%CI 1.15, 1.21 and less likely to receive invasive tests for screening indications than men (OR 0.80, 95%CI 0.77, 0.83. Whites were more likely than other racial groups to receive any type of screening. Rural residents were more likely than urban residents to have fecal occult blood tests (OR 1.20, 95%CI 1.17, 1.23 but less likely to receive invasive tests for screening indications (OR 0.89; 95%CI 0.85, 0.93. Conclusion Reported use of fecal occult blood testing remains modest. Overall use of the more invasive tests for screening indications remains essentially unchanged, but there has been a shift toward increased use of screening colonoscopy. Significant demographic differences in screening utilization persist despite consistent insurance coverage.

Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

Energy Technology Data Exchange (ETDEWEB)

Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Tajima, Shigeru [Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640 (Japan); Hikono, Hirokazu; Saito, Takehiko [Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

2014-07-18

Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC{sub 50} values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets.

Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

International Nuclear Information System (INIS)

Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn; Tajima, Shigeru; Hikono, Hirokazu; Saito, Takehiko; Aida, Yoko

2014-01-01

Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC 50 values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets

Parkinson disease: α-synuclein mutational screening and new clinical insight into the p.E46K mutation.

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Pimentel, Márcia M G; Rodrigues, Fabíola C; Leite, Marco Antônio A; Campos Júnior, Mário; Rosso, Ana Lucia; Nicaretta, Denise H; Pereira, João S; Silva, Delson José; Della Coletta, Marcus V; Vasconcellos, Luiz Felipe R; Abreu, Gabriella M; Dos Santos, Jussara M; Santos-Rebouças, Cíntia B

2015-06-01

Amongst Parkinson's disease-causing genetic factors, missense mutations and genomic multiplications in the gene encoding α-synuclein are well established causes of the disease, although genetic data in populations with a high degree of admixture, such as the Brazilian one, are still scarce. In this study, we conducted a molecular screening of α-synuclein point mutations and copy number variation in the largest cohort of Brazilian patients with Parkinson's disease (n = 549) and also in twelve Portuguese and one Bolivian immigrants. Genomic DNA was isolated from peripheral blood leukocytes or saliva, and the mutational screening was performed by quantitative and qualitative real-time PCR. The only alteration identified was the p.E46K mutation in a 60-year-old man, born in Bolivia, with a familial history of autosomal dominant Parkinson's disease. This is the second family ever reported, in which this rare pathogenic mutation is segregating. The same mutation was firstly described ten years ago in a Spanish family with a neurodegenerative syndrome combining parkinsonism, dementia and visual hallucinations. The clinical condition of our proband reveals a less aggressive phenotype than previously described and reinforces that marked phenotypic heterogeneity is common among patients with Parkinson's disease, even among those carriers sharing the same mutation. Our findings add new insight into the preexisting information about α-synuclein p.E46K, improving our understanding about the endophenotypes associated to this mutation and corroborate that missense alterations and multiplications in α-synuclein are uncommon among Brazilian patients with Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Screening and large-scale expression of membrane proteins in mammalian cells for structural studies

OpenAIRE

Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H.; Michel, Jennifer Carlisle; Claxton, Derek P.; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K. Christopher; Gouaux, Eric

2014-01-01

Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in over-expression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient productio...

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

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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.

WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures

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Kenyon Colin

2009-05-01

Full Text Available Abstract Background Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the Plasmodium parasite, some are promising targets to carry out rational drug discovery. Motivation Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR, and on a new promising one, glutathione-S-transferase. Methods In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate in silico docking and in information technology to design and operate large scale grid infrastructures. Results On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, In vitro results are underway for all the targets against which screening is performed. Conclusion The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software

Genetic screening of EXT1 and EXT2 in Cypriot families with ...

Indian Academy of Sciences (India)

RESEARCH NOTE. Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary .... on samples from the HMO patient's parents in an attempt to establish .... Intragenic deletions involving single or multiple EXT1 or. EXT2 exons are ...

The influence of year-end bonuses on colorectal cancer screening.

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Armour, Brian S; Friedman, Carol; Pitts, M Melinda; Wike, Jennifer; Alley, Linda; Etchason, Jeff

2004-09-01

To estimate the effect of physician bonus eligibility on colorectal cancer (CRC) screening, controlling for patient and primary care physician characteristics. Retrospective study using managed care plan claims data from 2000 and 2001. Data on 50-year-old commercially insured patients in a managed care health plan were linked to enrollment and provider files. The data included information on 6749 patients (3058 in 2000 and 3691 in 2001). Multivariate logistic regression models were used to assess the association between CRC screening receipt and physician bonus eligibility. From 2000 to 2001, CRC screening use increased from 23.4% to 26.4% (P analysis revealed that the probability that a patient received a CRC screening was approximately 3 percentage points higher in the bonus year, 2001 (P < .01). Bonuses targeted at individual physicians were associated with increased use of CRC screening tests. However, more research is needed to examine the effect of performance-based incentives on resource use and the quality of medical care. Specifically, there is a need to determine whether explicit financial incentives are effective in reducing racial disparities in the quality of patient care. This has particular relevance for CRC screening given that black patients are less likely to be screened, they have higher CRC incidence and mortality rates compared with other racial groups, and screening has been shown to be more cost effective in this population.

Rational polypharmacology: systematically identifying and engaging multiple drug targets to promote axon growth

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Al-Ali, Hassan; Lee, Do-Hun; Danzi, Matt C.; Nassif, Houssam; Gautam, Prson; Wennerberg, Krister; Zuercher, Bill; Drewry, David H.; Lee, Jae K.; Lemmon, Vance P.; Bixby, John L.

2016-01-01

Mammalian Central Nervous System (CNS) neurons regrow their axons poorly following injury, resulting in irreversible functional losses. Identifying therapeutics that encourage CNS axon repair has been difficult, in part because multiple etiologies underlie this regenerative failure. This suggests a particular need for drugs that engage multiple molecular targets. Although multi-target drugs are generally more effective than highly selective alternatives, we lack systematic methods for discovering such drugs. Target-based screening is an efficient technique for identifying potent modulators of individual targets. In contrast, phenotypic screening can identify drugs with multiple targets; however, these targets remain unknown. To address this gap, we combined the two drug discovery approaches using machine learning and information theory. We screened compounds in a phenotypic assay with primary CNS neurons and also in a panel of kinase enzyme assays. We used learning algorithms to relate the compounds’ kinase inhibition profiles to their influence on neurite outgrowth. This allowed us to identify kinases that may serve as targets for promoting neurite outgrowth, as well as others whose targeting should be avoided. We found that compounds that inhibit multiple targets (polypharmacology) promote robust neurite outgrowth in vitro. One compound with exemplary polypharmacology, was found to promote axon growth in a rodent spinal cord injury model. A more general applicability of our approach is suggested by its ability to deconvolve known targets for a breast cancer cell line, as well as targets recently shown to mediate drug resistance. PMID:26056718

Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

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Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

2016-11-01

Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

More comprehensive discussion of CRC screening associated with higher screening.

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Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

2013-04-01

Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

Participants, Physicians or Programmes: Participants' educational level and initiative in cancer screening.

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Willems, Barbara; Bracke, Piet

2018-04-01

This study is an in-depth examination of at whose initiative (participant, physician or screening programme) individuals participate in cervical, breast and colorectal cancer screening across the EU-28. Special attention is paid to (1) the association with educational attainment and (2) the country's cancer screening strategy (organised, pilot/regional or opportunistic) for each type of cancer screened. Data were obtained from Eurobarometer 66.2 'Health in the European Union' (2006). Final samples consisted of 10,186; 5443 and 9851 individuals for cervical, breast, and colorectal cancer, respectively. Multinomial logistic regressions were performed. Surprisingly, even in countries with organised screening programmes, participation in screenings for cervical, breast and colorectal cancer was most likely to be initiated by the general practitioner (GP) or the participant. In general, GPs were found to play a crucial role in making referrals to screenings, regardless of the country's screening strategy. The results also revealed differences between educational groups with regard to their incentive to participate in cervical and breast cancer screening and, to a lesser extent, in colorectal cancer screening. People with high education are more likely to participate in cancer screening at their own initiative, while people with less education are more likely to participate at the initiative of a physician or a screening programme. Albeit, the results varied according to type of cancer screening and national screening strategy. Copyright © 2018 Elsevier B.V. All rights reserved.

Field screening of experimental corn hybrids and inbred lines for multiple ear-feeding insect resistance.

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Ni, Xinzhi; Xu, Wenwei; Krakowsky, Matthew D; Buntin, G David; Brown, Steve L; Lee, R Dewey; Coy, Anton E

2007-10-01

Identifying and using native insect resistance genes is the core of integrated pest management. In this study, 10 experimental corn, Zea mays L., hybrids and 10 inbred lines were screened for resistance to major ear-feeding insects in the southeastern Coastal Plain region of the United States during 2004 and 2005. Ear-feeding insect damage was assessed at harvest by visual damage rating for the corn earworm, Helicoverpa zea (Boddie), and by the percentage of kernels damaged by the maize weevil, Sitophilus zeamais Motschulsky, and stink bugs [combination of Euschistus servus (Say) and southern green stink bug, Nezara viridula (L.)]. Among the eight inbred lines and two control populations examined, C3S1B73-5b was resistant to corn earworm, maize weevil, and stink bugs. In contrast, C3S1B73-4 was resistant to corn earworm and stink bugs, but not to maize weevil. In a similar manner, the corn hybrid S1W*CML343 was resistant to all three ear-feeding insects, whereas hybrid C3S1B73-3*Tx205 was resistant to corn earworm and maize weevil in both growing seasons, but susceptible to stink bugs in 2005. The silk-feeding bioassay showed that corn earworm developed better on corn silk than did fall armyworm. Among all phenotypic traits examined (i.e., corn ear size, husk extension, and husk tightness), only corn ear size was negatively correlated to corn earworm damage in the inbred lines examined, whereas only husk extension (i.e., coverage) was negatively correlated to both corn earworm and maize weevil damage on the experimental hybrids examined. Such information could be used to establish a baseline for developing agronomically elite corn germplasm that confers multiple ear-feeding insect resistance.

Breast and Cervical Cancer Screening Among Medicaid Beneficiaries: The Role of Physician Payment and Managed Care.

Science.gov (United States)

Sabik, Lindsay M; Dahman, Bassam; Vichare, Anushree; Bradley, Cathy J

2018-05-01

Medicaid-insured women have low rates of cancer screening. There are multiple policy levers that may influence access to preventive services such as screening, including physician payment and managed care. We examine the relationship between each of these factors and breast and cervical cancer screening among nonelderly nondisabled adult Medicaid enrollees. We combine individual-level data on Medicaid enrollment, demographics, and use of screening services from the Medicaid Analytic eXtract files with data on states' Medicaid-to-Medicare fee ratios and estimate their impact on screening services. Higher physician fees are associated with greater screening for comprehensive managed care enrollees; for enrollees in fee-for-service Medicaid, the findings are mixed. Patient participation in primary care case management is a significant moderator of the relationship between physician fees and the rate of screening, as interactions between enrollee primary care case management status and the Medicaid fee ratio are consistently positive across models of screening.

Multiple insect resistance in 59 commmerical corn hybrids - 2017

Science.gov (United States)

Commercial corn hybrids were screened for ear- and kernel-feeding insect resistance under field conditions at Tifton, GA. Nine hybrids were rated Very Good (VG), the highest rating for multiple insect resistance in 2017 (see following table). Thirteen were Good (G), 19 were Fair (F), and 13 were Poo...

From screen to structure with a harvestable microfluidic device

International Nuclear Information System (INIS)

Stojanoff, Vivian; Jakoncic, Jean; Oren, Deena A.; Nagarajan, V.; Navarro Poulsen, Jens-Christian; Adams-Cioaba, Melanie A.; Bergfors, Terese; Sommer, Morten O. A.

2011-01-01

Microfluidic crystallization using the Crystal Former improves the identification of initial crystallization conditions relative to screening via vapour diffusion. Advances in automation have facilitated the widespread adoption of high-throughput vapour-diffusion methods for initial crystallization screening. However, for many proteins, screening thousands of crystallization conditions fails to yield crystals of sufficient quality for structural characterization. Here, the rates of crystal identification for thaumatin, catalase and myoglobin using microfluidic Crystal Former devices and sitting-drop vapour-diffusion plates are compared. It is shown that the Crystal Former results in a greater number of identified initial crystallization conditions compared with vapour diffusion. Furthermore, crystals of thaumatin and lysozyme obtained in the Crystal Former were used directly for structure determination both in situ and upon harvesting and cryocooling. On the basis of these results, a crystallization strategy is proposed that uses multiple methods with distinct kinetic trajectories through the protein phase diagram to increase the output of crystallization pipelines

The attitudes of primary care providers towards screening for colorectal cancer

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Jesús López-Torres Hidalgo

2013-06-01

Full Text Available Background and objective: the scientific community supports the appropriateness of colorectal cancer screening, and there is consensus on the need to raise awareness about the significance of prevention among both health care professionals and the population. The goal was to record the attitude of primary care providers towards colorectal cancer screening, as well as the main barriers to both patient and provider participation. Methods: a cross-sectional, observational study was performed of 511 professionals in Albacete Health District. Variables included views on screening effectiveness and cost-effectiveness, acceptance by providers and patients, barriers to participation, frequency of prevention recommendations, and education needs. Results: most (76 % considered screening was effective; 85 % said acceptance of fecal occult blood testing was intermediate or high, and 68.2 % this is also the case for colonoscopy when needed; 71.9 % would recommend screening should a population-based program be implemented (currently only 9.7 % recommends this. Correspondence analysis revealed that recommendation is more common when assigned populations are smaller. Conclusions: most providers consider screening is both effective and acceptable for patients. In today's situation, where screening is only performed in an opportunistic manner, the proportion of professionals who commonly recommend screening for the mid-risk population is low, especially when assigned populations are huge.

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

Science.gov (United States)

Maroongroge, Sean; Yu, James B

2018-04-01

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

Screensaver: an open source lab information management system (LIMS for high throughput screening facilities

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Nale Jennifer

2010-05-01

Full Text Available Abstract Background Shared-usage high throughput screening (HTS facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. Results We have developed Screensaver, a free, open source, web-based lab information management system (LIMS, to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. Conclusions The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities.

Screensaver: an open source lab information management system (LIMS) for high throughput screening facilities.

Science.gov (United States)

Tolopko, Andrew N; Sullivan, John P; Erickson, Sean D; Wrobel, David; Chiang, Su L; Rudnicki, Katrina; Rudnicki, Stewart; Nale, Jennifer; Selfors, Laura M; Greenhouse, Dara; Muhlich, Jeremy L; Shamu, Caroline E

2010-05-18

Shared-usage high throughput screening (HTS) facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. We have developed Screensaver, a free, open source, web-based lab information management system (LIMS), to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities.

"I'm on it 24/7 at the moment": A qualitative examination of multi-screen viewing behaviours among UK 10-11 year olds

Directory of Open Access Journals (Sweden)

Cillero Itziar

2011-08-01

Full Text Available Abstract Background Screen-viewing has been associated with increased body mass, increased risk of metabolic syndrome and lower psychological well-being among children and adolescents. There is a shortage of information about the nature of contemporary screen-viewing amongst children especially given the rapid advances in screen-viewing equipment technology and their widespread availability. Anecdotal evidence suggests that large numbers of children embrace the multi-functionality of current devices to engage in multiple forms of screen-viewing at the same time. In this paper we used qualitative methods to assess the nature and extent of multiple forms of screen-viewing in UK children. Methods Focus groups were conducted with 10-11 year old children (n = 63 who were recruited from five primary schools in Bristol, UK. Topics included the types of screen-viewing in which the participants engaged; whether the participants ever engaged in more than one form of screen-viewing at any time and if so the nature of this multiple viewing; reasons for engaging in multi-screen-viewing; the room within the house where multi-screen-viewing took place and the reasons for selecting that room. All focus groups were transcribed verbatim, anonymised and thematically analysed. Results Multi-screen viewing was a common behaviour. Although multi-screen viewing often involved watching TV, TV viewing was often the background behaviour with attention focussed towards a laptop, handheld device or smart-phone. There were three main reasons for engaging in multi-screen viewing: 1 tempering impatience that was associated with a programme loading; 2 multi-screen facilitated filtering out unwanted content such as advertisements; and 3 multi-screen viewing was perceived to be enjoyable. Multi-screen viewing occurred either in the child's bedroom or in the main living area of the home. There was considerable variability in the level and timing of viewing and this appeared to be

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.

Text Messaging Interventions on Cancer Screening Rates: A Systematic Review.

Science.gov (United States)

Uy, Catherine; Lopez, Jennifer; Trinh-Shevrin, Chau; Kwon, Simona C; Sherman, Scott E; Liang, Peter S

2017-08-24

Despite high-quality evidence demonstrating that screening reduces mortality from breast, cervical, colorectal, and lung cancers, a substantial portion of the population remains inadequately screened. There is a critical need to identify interventions that increase the uptake and adoption of evidence-based screening guidelines for preventable cancers at the community practice level. Text messaging (short message service, SMS) has been effective in promoting behavioral change in various clinical settings, but the overall impact and reach of text messaging interventions on cancer screening are unknown. The objective of this systematic review was to assess the effect of text messaging interventions on screening for breast, cervical, colorectal, and lung cancers. We searched multiple databases for studies published between the years 2000 and 2017, including PubMed, EMBASE, and the Cochrane Library, to identify controlled trials that measured the effect of text messaging on screening for breast, cervical, colorectal, or lung cancers. Study quality was evaluated using the Cochrane risk of bias tool. Our search yielded 2238 citations, of which 31 underwent full review and 9 met inclusion criteria. Five studies examined screening for breast cancer, one for cervical cancer, and three for colorectal cancer. No studies were found for lung cancer screening. Absolute screening rates for individuals who received text message interventions were 0.6% to 15.0% higher than for controls. Unadjusted relative screening rates for text message recipients were 4% to 63% higher compared with controls. Text messaging interventions appear to moderately increase screening rates for breast and cervical cancer and may have a small effect on colorectal cancer screening. Benefit was observed in various countries, including resource-poor and non-English-speaking populations. Given the paucity of data, additional research is needed to better quantify the effectiveness of this promising intervention

Why are Tailored Messages More Effective? A Multiple Mediation Analysis of a Breast Cancer Screening Intervention.

Science.gov (United States)

Jensen, Jakob D; King, Andy J; Carcioppolo, Nicholas; Davis, LaShara

2012-10-01

Past research has found that tailoring increases the persuasive effectiveness of a message. However, the observed effect has been small and the explanatory mechanism remains unknown. To address these shortcomings, a tailoring software program was created that personalized breast cancer screening pamphlets according to risk, health belief model constructs, and visual preference. Women aged 40 and older ( N = 119) participated in a 2 (tailored vs. stock message) × 2 (charts/graphs vs. illustrated visuals) × 3 (nested replications of the visuals) experiment. Participants provided with tailored illustrated pamphlets expressed greater breast cancer screening intentions than those provided with other pamphlets. In a test of 10 different mediators, perceived message relevance was found to fully mediate the tailoring × visual interaction.

Cross sectional associations of screen time and outdoor play with social skills in preschool children

Science.gov (United States)

Carson, Valerie

2018-01-01

Screen time and physical activity behaviours develop during the crucial early childhood period (0–5 years) and impact multiple health and developmental outcomes, including psychosocial wellbeing. Social skills, one component of psychosocial wellbeing, are vital for children’s school readiness and future mental health. This study investigates potential associations of screen time and outdoor play (as a proxy for physical activity) with social skills. Cross sectional data were available for 575 mothers with a child (54% boys) aged 2–5 years. Mothers reported their child’s screen time, outdoor play time and social skills (Adaptive Social Behavior Inventory; ASBI). Multiple linear regression analyses assessed associations of screen and outdoor play time (Model 1) and compliance with screen time and physical activity recommendations (Model 2) with three ASBI subscales. Boys and girls spent a mean of 2.0 and 2.2 hours per day in screen time, and 3.3 and 2.9 hours per day in outdoor play, respectively. Girls scores for express and comply skills were significantly higher than boys (poutdoor play time was positively associated with both expressive (B = 0.20 95% CI 0.07, 0.34; p = 0.004) and compliant (B = 0.22 95% CI 0.08, 0.36; p = 0.002) scores. Findings indicate that television/DVD/video viewing may be adversely, and outdoor play favourably, associated with preschool children’s social skills. Future research is required to identify the direction of causation and explore potential mechanisms of association. PMID:29617366

SWIMS: a small-angle multiple scattering computer code

International Nuclear Information System (INIS)

Sayer, R.O.

1976-07-01

SWIMS (Sigmund and WInterbon Multiple Scattering) is a computer code for calculation of the angular dispersion of ion beams that undergo small-angle, incoherent multiple scattering by gaseous or solid media. The code uses the tabulated angular distributions of Sigmund and Winterbon for a Thomas-Fermi screened Coulomb potential. The fraction of the incident beam scattered into a cone defined by the polar angle α is computed as a function of α for reduced thicknesses over the range 0.01 less than or equal to tau less than or equal to 10.0. 1 figure, 2 tables

Computer screen photo-excited surface plasmon resonance imaging.

Science.gov (United States)

Filippini, Daniel; Winquist, Fredrik; Lundström, Ingemar

2008-09-12

Angle and spectra resolved surface plasmon resonance (SPR) images of gold and silver thin films with protein deposits is demonstrated using a regular computer screen as light source and a web camera as detector. The screen provides multiple-angle illumination, p-polarized light and controlled spectral radiances to excite surface plasmons in a Kretchmann configuration. A model of the SPR reflectances incorporating the particularities of the source and detector explain the observed signals and the generation of distinctive SPR landscapes is demonstrated. The sensitivity and resolution of the method, determined in air and solution, are 0.145 nm pixel(-1), 0.523 nm, 5.13x10(-3) RIU degree(-1) and 6.014x10(-4) RIU, respectively, encouraging results at this proof of concept stage and considering the ubiquity of the instrumentation.

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.

A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues.

Science.gov (United States)

Parsons, Linda M; Grzeschik, Nicola A; Amaratunga, Kasun; Burke, Peter; Quinn, Leonie M; Richardson, Helena E

2017-08-07

In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila "cell polarity" eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the "nutrient sensing" kinases Salt Inducible Kinase 2 and 3 ( SIK2 and 3 ) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development. Copyright © 2017 Parsons et al.

Screening Genetic Resources of Capsicum Peppers in Their Primary Center of Diversity in Bolivia and Peru.

Science.gov (United States)

van Zonneveld, Maarten; Ramirez, Marleni; Williams, David E; Petz, Michael; Meckelmann, Sven; Avila, Teresa; Bejarano, Carlos; Ríos, Llermé; Peña, Karla; Jäger, Matthias; Libreros, Dimary; Amaya, Karen; Scheldeman, Xavier

2015-01-01

For most crops, like Capsicum, their diversity remains under-researched for traits of interest for food, nutrition and other purposes. A small investment in screening this diversity for a wide range of traits is likely to reveal many traditional varieties with distinguished values. One objective of this study was to demonstrate, with Capsicum as model crop, the application of indicators of phenotypic and geographic diversity as effective criteria for selecting promising genebank accessions for multiple uses from crop centers of diversity. A second objective was to evaluate the expression of biochemical and agromorphological properties of the selected Capsicum accessions in different conditions. Four steps were involved: 1) Develop the necessary diversity by expanding genebank collections in Bolivia and Peru; 2) Establish representative subsets of ~100 accessions for biochemical screening of Capsicum fruits; 3) Select promising accessions for different uses after screening; and 4) Examine how these promising accessions express biochemical and agromorphological properties when grown in different environmental conditions. The Peruvian Capsicum collection now contains 712 accessions encompassing all five domesticated species (C. annuum, C. chinense, C. frutescens, C. baccatum, and C. pubescens). The collection in Bolivia now contains 487 accessions, representing all five domesticates plus four wild taxa (C. baccatum var. baccatum, C. caballeroi, C. cardenasii, and C. eximium). Following the biochemical screening, 44 Bolivian and 39 Peruvian accessions were selected as promising, representing wide variation in levels of antioxidant capacity, capsaicinoids, fat, flavonoids, polyphenols, quercetins, tocopherols, and color. In Peru, 23 promising accessions performed well in different environments, while each of the promising Bolivian accessions only performed well in a certain environment. Differences in Capsicum diversity and local contexts led to distinct outcomes in

A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria.

Science.gov (United States)

Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P

2015-09-01

Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. © FASEB.

Single-copy nuclear genes place haustorial Hydnoraceae within piperales and reveal a cretaceous origin of multiple parasitic angiosperm lineages.

Directory of Open Access Journals (Sweden)

Julia Naumann

Full Text Available Extreme haustorial parasites have long captured the interest of naturalists and scientists with their greatly reduced and highly specialized morphology. Along with the reduction or loss of photosynthesis, the plastid genome often decays as photosynthetic genes are released from selective constraint. This makes it challenging to use traditional plastid genes for parasitic plant phylogenetics, and has driven the search for alternative phylogenetic and molecular evolutionary markers. Thus, evolutionary studies, such as molecular clock-based age estimates, are not yet available for all parasitic lineages. In the present study, we extracted 14 nuclear single copy genes (nSCG from Illumina transcriptome data from one of the "strangest plants in the world", Hydnora visseri (Hydnoraceae. A ~15,000 character molecular dataset, based on all three genomic compartments, shows the utility of nSCG for reconstructing phylogenetic relationships in parasitic lineages. A relaxed molecular clock approach with the same multi-locus dataset, revealed an ancient age of ~91 MYA for Hydnoraceae. We then estimated the stem ages of all independently originated parasitic angiosperm lineages using a published dataset, which also revealed a Cretaceous origin for Balanophoraceae, Cynomoriaceae and Apodanthaceae. With the exception of Santalales, older parasite lineages tend to be more specialized with respect to trophic level and have lower species diversity. We thus propose the "temporal specialization hypothesis" (TSH implementing multiple independent specialization processes over time during parasitic angiosperm evolution.

Discovery of novel selenium derivatives as Pin1 inhibitors by high-throughput screening

International Nuclear Information System (INIS)

Subedi, Amit; Shimizu, Takeshi; Ryo, Akihide; Sanada, Emiko; Watanabe, Nobumoto; Osada, Hiroyuki

2016-01-01

Peptidyl prolyl cis/trans isomerization by Pin1 regulates various oncogenic signals during cancer progression, and its inhibition through multiple approaches has established Pin1 as a therapeutic target. However, lack of simplified screening systems has limited the discovery of potent Pin1 inhibitors. We utilized phosphorylation-dependent binding of Pin1 to its specific substrate to develop a screening system for Pin1 inhibitors. Using this system, we screened a chemical library, and identified a novel selenium derivative as Pin1 inhibitor. Based on structure-activity guided chemical synthesis, we developed more potent Pin1 inhibitors that inhibited cancer cell proliferation. -- Highlights: •Novel screening for Pin1 inhibitors based on Pin1 binding is developed. •A novel selenium compound is discovered as Pin1 inhibitor. •Activity guided chemical synthesis of selenium derivatives resulted potent Pin1 inhibitors.

Colon cancer screening

Science.gov (United States)

Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

Proteotyping of laboratory-scale biogas plants reveals multiple steady-states in community composition.

Science.gov (United States)

Kohrs, F; Heyer, R; Bissinger, T; Kottler, R; Schallert, K; Püttker, S; Behne, A; Rapp, E; Benndorf, D; Reichl, U

2017-08-01

Complex microbial communities are the functional core of anaerobic digestion processes taking place in biogas plants (BGP). So far, however, a comprehensive characterization of the microbiomes involved in methane formation is technically challenging. As an alternative, enriched communities from laboratory-scale experiments can be investigated that have a reduced number of organisms and are easier to characterize by state of the art mass spectrometric-based (MS) metaproteomic workflows. Six parallel laboratory digesters were inoculated with sludge from a full-scale BGP to study the development of enriched microbial communities under defined conditions. During the first three month of cultivation, all reactors (R1-R6) were functionally comparable regarding biogas productions (375-625 NL L reactor volume -1 d -1 ), methane yields (50-60%), pH values (7.1-7.3), and volatile fatty acids (VFA, 1 gNH 3 L -1 ) showed an increase to pH 7.5-8.0, accumulation of acetate (>10 mM), and decreasing biogas production (<125 NL L reactor volume -1 d -1 ). Tandem MS (MS/MS)-based proteotyping allowed the identification of taxonomic abundances and biological processes. Although all reactors showed similar performances, proteotyping and terminal restriction fragment length polymorphisms (T-RFLP) fingerprinting revealed significant differences in the composition of individual microbial communities, indicating multiple steady-states. Furthermore, cellulolytic enzymes and cellulosomal proteins of Clostridium thermocellum were identified to be specific markers for the thermophilic reactors (R3, R4). Metaproteins found in R3 indicated hydrogenothrophic methanogenesis, whereas metaproteins of acetoclastic methanogenesis were identified in R4. This suggests not only an individual evolution of microbial communities even for the case that BGPs are started at the same initial conditions under well controlled environmental conditions, but also a high compositional variance of microbiomes under

An experience of qualified preventive screening: shiraz smart screening software.

Science.gov (United States)

Islami Parkoohi, Parisa; Zare, Hashem; Abdollahifard, Gholamreza

2015-01-01

Computerized preventive screening software is a cost effective intervention tool to address non-communicable chronic diseases. Shiraz Smart Screening Software (SSSS) was developed as an innovative tool for qualified screening. It allows simultaneous smart screening of several high-burden chronic diseases and supports reminder notification functionality. The extent in which SSSS affects screening quality is also described. Following software development, preventive screening and annual health examinations of 261 school staff (Medical School of Shiraz, Iran) was carried out in a software-assisted manner. To evaluate the quality of the software-assisted screening, we used quasi-experimental study design and determined coverage, irregular attendance and inappropriateness proportions in relation with the manual and software-assisted screening as well as the corresponding number of requested tests. In manual screening method, 27% of employees were covered (with 94% irregular attendance) while by software-assisted screening, the coverage proportion was 79% (attendance status will clear after the specified time). The frequency of inappropriate screening test requests, before the software implementation, was 41.37% for fasting plasma glucose, 41.37% for lipid profile, 0.84% for occult blood, 0.19% for flexible sigmoidoscopy/colonoscopy, 35.29% for Pap smear, 19.20% for mammography and 11.2% for prostate specific antigen. All of the above were corrected by the software application. In total, 366 manual screening and 334 software-assisted screening tests were requested. SSSS is an innovative tool to improve the quality of preventive screening plans in terms of increased screening coverage, reduction in inappropriateness and the total number of requested tests.

Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association

Directory of Open Access Journals (Sweden)

Vidya Nair

2016-01-01

Full Text Available Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%, but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently.

Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease

DEFF Research Database (Denmark)

Fu, Jing; Li, Shirong; Feng, Rentian

2016-01-01

Multiple myeloma (MM) cells secrete osteoclastogenic factors that promote osteolytic lesions; however, the identity of these factors is largely unknown. Here, we performed a screen of human myeloma cells to identify pro-osteoclastogenic agents that could potentially serve as therapeutic targets...

Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing

Science.gov (United States)

Shinde, Mansi Y.; Sidoli, Simone; Kulej, Katarzyna; Mallory, Michael J.; Radens, Caleb M.; Reicherter, Amanda L.; Myers, Rebecca L.; Barash, Yoseph; Lynch, Kristen W.; Garcia, Benjamin A.; Klein, Peter S.

2017-01-01

Glycogen synthase kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif ((pS/pT)XXX(S/T)), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and MS techniques to analyze the repertoire of GSK-3–dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ∼2.4% of (pS/pT)XXX(S/T) sites are phosphorylated in a GSK-3–dependent manner. A comparison of WT and Gsk3a;Gsk3b knock-out (Gsk3 DKO) ESCs revealed prominent GSK-3–dependent phosphorylation of multiple splicing factors and regulators of RNA biosynthesis as well as proteins that regulate transcription, translation, and cell division. Gsk3 DKO reduced phosphorylation of the splicing factors RBM8A, SRSF9, and PSF as well as the nucleolar proteins NPM1 and PHF6, and recombinant GSK-3β phosphorylated these proteins in vitro. RNA-Seq of WT and Gsk3 DKO ESCs identified ∼190 genes that are alternatively spliced in a GSK-3–dependent manner, supporting a broad role for GSK-3 in regulating alternative splicing. The MS data also identified posttranscriptional regulation of protein abundance by GSK-3, with ∼47 proteins (1.4%) whose levels increased and ∼78 (2.4%) whose levels decreased in the absence of GSK-3. This study provides the first unbiased analysis of the GSK-3 phosphoproteome and strong evidence that GSK-3 broadly regulates alternative splicing. PMID:28916722

Transport and screen blockage characteristics of reflective metallic insulation materials

International Nuclear Information System (INIS)

Brocard, D.N.

1984-01-01

In the event of a LOCA within a nuclear power plant, it is possible for insulation debris to be generated by the break jet. Such debris has the potential for PWR sump screen (or BWR RHR suction inlet) blockage and thus can affect the long-term recirculation capability. In addition to the variables of break jet location and orientation, the types and quantities of debris which could be generated are dependent on the insulation materials employed. This experimental investigation was limited to reflective metallic insulation and components thereof. The study was aimed at determining the flow velocities needed to transport the insulation debris to the sump screens and the resulting modes of screen blockage. The tests revealed that thin metallic foils (0.0025 in. and 0.004 in.) could transport at low flow velocities, 0.2 to 0.5 ft/sec. Thicker foils (0.008 in.) transported at higher velocities, 0.4 to 0.8 ft/sec, and as fabricated half cylinder insulation units required velocities in excess of 1.0 ft/sec for transport. The tests also provided information on screen blockage patterns that showed blockage could occur at the lower portion of the screen as foils readily flipped on the screen when reaching it

Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

Directory of Open Access Journals (Sweden)

S Birla

2016-01-01

Full Text Available Background and Objectives: Primary hyperparathyroidism (PHPT can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1 is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.

A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance

NARCIS (Netherlands)

van der Tol, L.; Smid, B. E.; Poorthuis, B. J. H. M.; Biegstraaten, M.; Deprez, R. H. Lekanne; Linthorst, G. E.; Hollak, C. E. M.

2014-01-01

Screening for Fabry disease (FD) reveals a high prevalence of individuals with α-galactosidase A (GLA) genetic variants of unknown significance (GVUS). These individuals often do not express characteristic features of FD. A systematic review on FD screening studies was performed to interpret the

The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program

Energy Technology Data Exchange (ETDEWEB)

Roman, M., E-mail: Marta.Roman@kreftregisteret.no [Cancer Registry of Norway, Oslo (Norway); Department of Women and Children’s Health, Oslo University Hospital, Oslo (Norway); Skaane, P., E-mail: PERSK@ous-hf.no [Department of Radiology, Oslo University Hospital Ullevaal, University of Oslo, Oslo (Norway); Hofvind, S., E-mail: Solveig.Hofvind@kreftregisteret.no [Cancer Registry of Norway, Oslo (Norway); Oslo and Akershus University College of Applied Sciences, Faculty of Health Science, Oslo (Norway)

2014-09-15

Highlights: • We found variation in early performance measures across screening centres. • Radiologists’ performance may play a key role in the variability. • Potential to improve the effectiveness of breast cancer screening programs. • Continuous surveillance of screening centres and radiologists is essential. - Abstract: Background: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. Methods: We studied 618,636 women aged 50–69 years who underwent 2,090,575 screening exams (1996–2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. Results: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4–12.0%) to 41.5% (95% CI: 34.1–48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7–4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0–4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0–12.9%) and 19.9% (95% CI: 18.3–21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5–1.9). Conclusions: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the

The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program

International Nuclear Information System (INIS)

Roman, M.; Skaane, P.; Hofvind, S.

2014-01-01

Highlights: • We found variation in early performance measures across screening centres. • Radiologists’ performance may play a key role in the variability. • Potential to improve the effectiveness of breast cancer screening programs. • Continuous surveillance of screening centres and radiologists is essential. - Abstract: Background: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. Methods: We studied 618,636 women aged 50–69 years who underwent 2,090,575 screening exams (1996–2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. Results: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4–12.0%) to 41.5% (95% CI: 34.1–48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7–4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0–4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0–12.9%) and 19.9% (95% CI: 18.3–21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5–1.9). Conclusions: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the

Alcohol Use Screening

Science.gov (United States)

... Depression Screening Substance Abuse Screening Alcohol Use Screening Alcohol Use Screening (AUDIT-C) - Instructions The following questions ... this tool, there is also text-only version . Alcohol Use Screening (AUDIT-C) - Manual Instructions The following ...

Metagenomics of the Svalbard reindeer rumen microbiome reveals abundance of polysaccharide utilization loci.

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Phillip B Pope

Full Text Available Lignocellulosic biomass remains a largely untapped source of renewable energy predominantly due to its recalcitrance and an incomplete understanding of how this is overcome in nature. We present here a compositional and comparative analysis of metagenomic data pertaining to a natural biomass-converting ecosystem adapted to austere arctic nutritional conditions, namely the rumen microbiome of Svalbard reindeer (Rangifer tarandus platyrhynchus. Community analysis showed that deeply-branched cellulolytic lineages affiliated to the Bacteroidetes and Firmicutes are dominant, whilst sequence binning methods facilitated the assemblage of metagenomic sequence for a dominant and novel Bacteroidales clade (SRM-1. Analysis of unassembled metagenomic sequence as well as metabolic reconstruction of SRM-1 revealed the presence of multiple polysaccharide utilization loci-like systems (PULs as well as members of more than 20 glycoside hydrolase and other carbohydrate-active enzyme families targeting various polysaccharides including cellulose, xylan and pectin. Functional screening of cloned metagenome fragments revealed high cellulolytic activity and an abundance of PULs that are rich in endoglucanases (GH5 but devoid of other common enzymes thought to be involved in cellulose degradation. Combining these results with known and partly re-evaluated metagenomic data strongly indicates that much like the human distal gut, the digestive system of herbivores harbours high numbers of deeply branched and as-yet uncultured members of the Bacteroidetes that depend on PUL-like systems for plant biomass degradation.

Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval

NARCIS (Netherlands)

Yousaf-Khan, U.; Aalst, C. van der; Jong, P.A. de; Heuvelmans, M.; Scholten, E.T.; Lammers, J.-W.J.; Ooijen, P. van; Nackaerts, K.; Weenink, C.; Groen, H.; Vliegenthart, R.; Haaf, K. Ten; Oudkerk, M.; Koning, H. de

2016-01-01

In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

NARCIS (Netherlands)

Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

BACKGROUND: In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

NARCIS (Netherlands)

Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A.; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

Background In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

The Edinburgh Cognitive and Behavioural ALS Screen in a Chinese Amyotrophic Lateral Sclerosis Population.

Directory of Open Access Journals (Sweden)

Shan Ye

Full Text Available The existing screening batteries assessing multiple neuropsychological functions are not specific to amyotrophic lateral sclerosis (ALS patients and are limited to their physical dysfunctions, whereas category cognitive tests are too time-consuming to assess all the domains. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS was recently developed as a fast and easy cognitive screening tool specifically designed for patients. The purpose of the study was to validate the effectiveness of the Chinese version in Chinese ALS populations.Eighty-four ALS patients and 84 age-, gender- and education-matched healthy controls were included in this cross-sectional study. All the participants took the ECAS, Mini-Mental State Examination (MMSE and Frontal Assessment Battery (FAB. Primary caregivers of patients were interviewed for behavioural and psychiatric changes.Significant differences were noted in language (p = 0.01, fluency, executive function, ALS-specific functions, and ECAS total score (p<0.01 between ALS patients and controls. The cut-off value of the total ECAS score was 81.92. Cognitive impairment was observed in 35.71% of patients, and 27.38% exhibited behavioural abnormalities. The ECAS total score had a medium correlation with education year. Memory was more easily impaired in the lower education group, whereas verbal fluency and language function tended to be preserved in the higher education group. The average time of ECAS was only 18 minutes.The Chinese version of the ECAS is the first screening battery assessing multiple neuropsychological functions specially designed for the ALS population in China, which provides an effective and rapid tool to screen cognitive and behavioural impairments.

Development of the multiple sclerosis (MS) early mobility impairment questionnaire (EMIQ).

Science.gov (United States)

Ziemssen, Tjalf; Phillips, Glenn; Shah, Ruchit; Mathias, Adam; Foley, Catherine; Coon, Cheryl; Sen, Rohini; Lee, Andrew; Agarwal, Sonalee

2016-10-01

The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews. Data from an observational study was used to make additional updates to the instrument based on exploratory factor analysis (EFA) and item response theory (IRT) analysis, and psychometric analyses were performed to evaluate the reliability and validity of the final instrument's scores and screening properties (i.e., sensitivity and specificity). Based on qualitative interview analyses, a revised 15-item EMIQ was included in the observational study. EFA, IRT and item-to-item correlation analyses revealed redundant items which were removed leading to the final nine-item EMIQ. The nine-item EMIQ performed well with respect to: test-retest reliability (ICC = 0.858); internal consistency (α = 0.893); convergent validity; and known-groups methods for construct validity. A cut-point of 41 on the 0-to-100 scale resulted in sufficient sensitivity and specificity statistics for viably identifying patients with mobility impairment. The EMIQ is a content valid and psychometrically sound instrument for capturing MS patients' experience with mobility impairments in a clinical practice setting. Additional research is suggested to further confirm the EMIQ's screening properties over time.

Preflight screening techniques for centrifuge-simulated suborbital spaceflight.

Science.gov (United States)

Pattarini, James M; Blue, Rebecca S; Castleberry, Tarah L; Vanderploeg, James M

2014-12-01

Historically, space has been the venue of the healthy individual. With the advent of commercial spaceflight, we face the novel prospect of routinely exposing spaceflight participants (SPFs) with multiple comorbidities to the space environment. Preflight screening procedures must be developed to identify those individuals at increased risk during flight. We examined the responses of volunteers to centrifuge accelerations mimicking commercial suborbital spaceflight profiles to evaluate how potential SFPs might tolerate such forces. We evaluated our screening process for medical approval of subjects for centrifuge participation for applicability to commercial spaceflight operations. All registered subjects completed a medical questionnaire, physical examination, and electrocardiogram. Subjects with identified concerns including cardiopulmonary disease, hypertension, and diabetes were required to provide documentation of their conditions. There were 335 subjects who registered for the study, 124 who completed all prescreening, and 86 subjects who participated in centrifuge trials. Due to prior medical history, five subjects were disqualified, most commonly for psychiatric reasons or uncontrolled medical conditions. Of the subjects approved, four individuals experienced abnormal physiological responses to centrifuge profiles, including one back strain and three with anxiety reactions. The screening methods used were judged to be sufficient to identify individuals physically capable of tolerating simulated suborbital flight. Improved methods will be needed to identify susceptibility to anxiety reactions. While severe or uncontrolled disease was excluded, many subjects successfully participated in centrifuge trials despite medical histories of disease that are disqualifying under historical spaceflight screening regimes. Such screening techniques are applicable for use in future commercial spaceflight operations.

Pharmacophore-based screening of differentially-expressed PGF, DDIT4, COMP and CHI3L1 from hMSC cell lines reveals five novel therapeutic compounds for primary osteoporosis

Directory of Open Access Journals (Sweden)

Catherine Jessica Lai

2016-06-01

Full Text Available As many societies age, primary osteoporosis (PO is increasingly a major health problem. Current drug treatments such as alendronate and risedronate have known side effects. We took an agnostic empirical approach to find PO therapeutic compounds. We examined 13,548,960 probe data-points from mesenchymal stromal cell (hMSC lines and found that PGF, DDIT4, and COMP to be up-regulated, and CHI3L1, down-regulated. We then identified their druggable domains. For the up-regulated differentially-expressed genes, we used protein–protein interactions to find residue clusters as binding surfaces. We then employed pharmacophore models to screen 15,407,096 conformations of 22,723,923 compounds, which identified (6R,9R-6-(2-furyl-9-(1H-indol-3-yl-2-(trifluoromethyl-5,6,7, 9-tetrahydro-4H[1,2,4]triazolo[5,1],(2S-N1-[2-[2-(methylamino-2-oxo-ethyl]phenyl]-N2-phenylpyrrolidine-1,2-dicarboxamide, and 2-furyl-(1H-indol-3-yl-methyl-BLAHone as candidate compounds. For the down-regulated CH13L1, we relied on genome-wide disease signatures to identify (11alpha-9-fluoro-11,17,21-trihydroxypregn-4-ene-3,20-dione and Genistein as candidate compounds. Our approach differs from previous research as we did not confine our drug targets to hypothesized compounds in the existing literature. Instead, we allowed the full expression profile of PO cell lines to reveal the most desirable targets. Second, our differential gene analysis revealed both up- and down-regulated genes, in contrast to the literature, which has focused on inhibiting only up-regulated genes. Third, our virtual screening universe of 22,723,923 compounds was more than 100 times larger than those in the known literature.

Effect of the LHC Beam Screen Baffle on the Electron Cloud Buildup

CERN Document Server

Romano, Annalisa; Li, Kevin; Rumolo, Giovanni

2016-01-01

Electron Cloud (EC) has been identified as one of the major intensity-limiting factors in the CERN Large Hadron Collider (LHC). Due to the EC, an additional heat load is deposited on the perforated LHC beam screen, for which only a small cooling capacity is available. In order to preserve the superconducting state of the magnets, pumping slots shields were added on the outer side of the beam screens. In the framework of the design of the beam screens of the new HL-LHC triplets, the impact of these shields on the multipacting process was studied with macroparticle simulations. For this purpose multiple new features had to be introduced in the PyECLOUD code. This contribution will describe the implemented simulation model and summarize the outcome of this study.

Evaluation of Estimating Missed Answers in Conners Adult ADHD Rating Scale (Screening Version)

Science.gov (United States)

Ghassemi, Farnaz; Moradi, Mohammad Hassan; Tehrani-Doost, Mehdi

2010-01-01

Objective Conners Adult ADHD Rating Scale (CAARS) is among the valid questionnaires for evaluating Attention-Deficit/Hyperactivity Disorder in adults. The aim of this paper is to evaluate the validity of the estimation of missed answers in scoring the screening version of the Conners questionnaire, and to extract its principal components. Method This study was performed on 400 participants. Answer estimation was calculated for each question (assuming the answer was missed), and then a Kruskal-Wallis test was performed to evaluate the difference between the original answer and its estimation. In the next step, principal components of the questionnaire were extracted by means of Principal Component Analysis (PCA). Finally the evaluation of differences in the whole groups was provided using the Multiple Comparison Procedure (MCP). Results Findings indicated that a significant difference existed between the original and estimated answers for some particular questions. However, the results of MCP showed that this estimation, when evaluated in the whole group, did not show a significant difference with the original value in neither of the questionnaire subscales. The results of PCA revealed that there are eight principal components in the CAARS questionnaire. Conclusion The obtained results can emphasize the fact that this questionnaire is mainly designed for screening purposes, and this estimation does not change the results of groups when a question is missed randomly. Notwithstanding this finding, more considerations should be paid when the missed question is a critical one. PMID:22952502

BioSig3D: High Content Screening of Three-Dimensional Cell Culture Models.

Directory of Open Access Journals (Sweden)

Cemal Cagatay Bilgin

Full Text Available BioSig3D is a computational platform for high-content screening of three-dimensional (3D cell culture models that are imaged in full 3D volume. It provides an end-to-end solution for designing high content screening assays, based on colony organization that is derived from segmentation of nuclei in each colony. BioSig3D also enables visualization of raw and processed 3D volumetric data for quality control, and integrates advanced bioinformatics analysis. The system consists of multiple computational and annotation modules that are coupled together with a strong use of controlled vocabularies to reduce ambiguities between different users. It is a web-based system that allows users to: design an experiment by defining experimental variables, upload a large set of volumetric images into the system, analyze and visualize the dataset, and either display computed indices as a heatmap, or phenotypic subtypes for heterogeneity analysis, or download computed indices for statistical analysis or integrative biology. BioSig3D has been used to profile baseline colony formations with two experiments: (i morphogenesis of a panel of human mammary epithelial cell lines (HMEC, and (ii heterogeneity in colony formation using an immortalized non-transformed cell line. These experiments reveal intrinsic growth properties of well-characterized cell lines that are routinely used for biological studies. BioSig3D is being released with seed datasets and video-based documentation.

Evaluation of Estimating Missed Answers in Conners Adult ADHD Rating Scale (Screening Version

Directory of Open Access Journals (Sweden)

Vahid Abootalebi

2010-08-01

Full Text Available "n Objective: Conners Adult ADHD Rating Scale (CAARS is among the valid questionnaires for evaluating Attention-Deficit/Hyperactivity Disorder in adults. The aim of this paper is to evaluate the validity of the estimation of missed answers in scoring the screening version of the Conners questionnaire, and to extract its principal components. "n Method: This study was performed on 400 participants. Answer estimation was calculated for each question (assuming the answer was missed, and then a Kruskal-Wallis test was performed to evaluate the difference between the original answer and its estimation. In the next step, principal components of the questionnaire were extracted by means of Principal Component Analysis (PCA. Finally the evaluation of differences in the whole groups was provided using the Multiple Comparison Procedure (MCP. Results: Findings indicated that a significant difference existed between the original and estimated answers for some particular questions. However, the results of MCP showed that this estimation, when evaluated in the whole group, did not show a significant difference with the original value in neither of the questionnaire subscales. The results of PCA revealed that there are eight principal components in the CAARS questionnaire. Conclusion: The obtained results can emphasize the fact that this questionnaire is mainly designed for screening purposes, and this estimation does not change the results of groups when a question is missed randomly. Notwithstanding this finding, more considerations should be paid when the missed question is a critical one.

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.

Breast cancer screening with mammography as part of our comprehensive medical check-up

International Nuclear Information System (INIS)

Ishii, Kaname; Kaburaki, Tomonori; Iwata, Keiko; Tsuneda, Atsushi; Mori, Kazuhiro; Takeyama, Shigeru; Tsuji, Hiroshi

2012-01-01

In the breast cancer screening program adopted by our hospital's Health Care Center as part of a comprehensive medical check-up, mammography (MMG) is performed in addition to a clinical breast examination to provide better screening quality. The clinical breast examination is performed by our surgeons. Two-view MMG is performed for women in their 40's and one-view MMG for the others. If any abnormality is detected in the clinical breast examination, or if MMG reveals abnormalities of category 3 or over, a more thorough diagnostic work-up is recommended. Each year, 1,400 or more women undergo breast cancer screening at the center, with an average recall rate of 12% and an average breast cancer detection rate of 0.14%. The high recall rate indicates the need for improvement of screening accuracy. Although the breast cancer detection rate and positive predictive value are somewhat low, the majority of the detected cases are early-stage breast cancer, thus demonstrating the efficacy of the screening. Herein, we describe the current state of MMG screening in our comprehensive medical check-up, along with a discussion of the screening procedure. However, further efforts are needed to improve screening accuracy. (author)

Radiation protection in screening children's hips

International Nuclear Information System (INIS)

Heribanova, A.; Skokanova, K.; Sevc, J.; Paskova, Z.; Mundilova, M.

1987-01-01

Repeat hygienic investigation of the conditions of radiation protection in preventive screening of children's hips (at a time interval of 10 years) in the Central Bohemian Region revealed certain improvement in covering children's gonads (in the frequency of using protective devices), in the protection of the accompanying person and the equipment of the workplaces with modern X-ray apparatus and automatic developers. Large differences between individual workplaces were seen in the selection of technical parameters (voltage, power, focus, size of irradiated field); that is why up to nine-fold differences existed in irradiation of children. (The mean gonadal dose was 22.6 μGy and the mean weighted whole-body dose was 71.2 μGy.) A conservative estimate of the effective dose equivalent was used in comparing the social cost and benefit in preventive screening of children's hips which had shown that at least one preventive X-ray picture in all children in the 3rd to 4th month after birth was quite reasonable. The analysis of the problems outlined revealed that particular attention must be paid to the protection of the children's gonads by using suitable protective devices and to minimize irradiation of children by a suitable adjustment of technical parameters of the examination and also by exclusive use of quality film material. (author). 4 tabs., 18 refs

High Content Screening: Understanding Cellular Pathway

International Nuclear Information System (INIS)

Mohamed Zaffar Ali Mohamed Amiroudine; Daryl Jesus Arapoc; Zainah Adam; Shafii Khamis

2015-01-01

High content screening (HCS) is the convergence between cell-based assays, high-resolution fluorescence imaging, phase-contrast imaging of fixed- or live-cell assays, tissues and small organisms. It has been widely adopted in the pharmaceutical and biotech industries for target identification and validation and as secondary screens to reveal potential toxicities or to elucidate a drugs mechanism of action. By using the ImageXpress® Micro XLS System HCS, the complex network of key players controlling proliferation and apoptosis can be reduced to several sentinel markers for analysis. Cell proliferation and apoptosis are two key areas in cell biology and drug discovery research. Understanding the signaling pathways in cell proliferation and apoptosis is important for new therapeutic discovery because the imbalance between these two events is predominant in the progression of many human diseases, including cancer. The DNA binding dye DAPI is used to determine the nuclear size and nuclear morphology as well as cell cycle phases by DNA content. Images together with MetaXpress® analysis results provide a convenient and easy to use solution to high volume image management. In particular, HCS platform is beginning to have an important impact on early drug discovery, basic research in systems cell biology, and is expected to play a role in personalized medicine or revealing off-target drug effects. (author)

Population Screening for Hereditary Haemochromatosis in Australia: Construction and Validation of a State-Transition Cost-Effectiveness Model.

Science.gov (United States)

de Graaff, Barbara; Si, Lei; Neil, Amanda L; Yee, Kwang Chien; Sanderson, Kristy; Gurrin, Lyle C; Palmer, Andrew J

2017-03-01

HFE-associated haemochromatosis, the most common monogenic disorder amongst populations of northern European ancestry, is characterised by iron overload. Excess iron is stored in parenchymal tissues, leading to morbidity and mortality. Population screening programmes are likely to improve early diagnosis, thereby decreasing associated disease. Our aim was to develop and validate a health economics model of screening using utilities and costs from a haemochromatosis cohort. A state-transition model was developed with Markov states based on disease severity. Australian males (aged 30 years) and females (aged 45 years) of northern European ancestry were the target populations. The screening strategy was the status quo approach in Australia; the model was run over a lifetime horizon. Costs were estimated from the government perspective and reported in 2015 Australian dollars ($A); costs and quality-adjusted life-years (QALYs) were discounted at 5% annually. Model validity was assessed using goodness-of-fit analyses. Second-order Monte-Carlo simulation was used to account for uncertainty in multiple parameters. For validity, the model reproduced mortality, life expectancy (LE) and prevalence rates in line with published data. LE for C282Y homozygote males and females were 49.9 and 40.2 years, respectively, slightly lower than population rates. Mean (95% confidence interval) QALYS were 15.7 (7.7-23.7) for males and 14.4 (6.7-22.1) for females. Mean discounted lifetime costs for C282Y homozygotes were $A22,737 (3670-85,793) for males and $A13,840 (1335-67,377) for females. Sensitivity analyses revealed discount rates and prevalence had the greatest impacts on outcomes. We have developed a transparent, validated health economics model of C282Y homozygote haemochromatosis. The model will be useful to decision makers to identify cost-effective screening strategies.

Community cholesterol screening. Impact of labeling on participant behavior.

Science.gov (United States)

Gordon, R L; Klag, M J; Whelton, P K

1990-09-01

To investigate the effect of screening for an elevated cholesterol level and compliance with follow-up recommendations, we surveyed 375 participants in a free screening program at a shopping mall walk-in clinic. One hundred thirty-nine participants (37%) had desirable (less than 5.17 mmol/L [less than 200 mg/dL]), 135 (36%) had borderline (5.17 to 6.18 mmol/L [200 to 239 mg/dL]), and 101 (27%) had high (greater than 6.18 mmol/L [greater than 239 mg/dL]) cholesterol levels. Persons in the borderline and high categories were instructed to see their physicians within 2 months for confirmation of their levels. Of the 338 (90%) who responded to a follow-up questionnaire at 3 months, 8 (7%) in the desirable, 23 (22%) in the borderline, and 44 (50%) in the high group had been to see physicians concerning their cholesterol levels since the screening. In multiple logistic regression analyses only cholesterol category at time of screening, current use of antihypertensive drugs, history of coronary heart disease, and history of a high cholesterol level were associated with physician follow-up. Our results suggest that labeling persons as being at high rather than borderline risk results in greater physician follow-up.

Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic

International Nuclear Information System (INIS)

Morrison, B. F.; Aiken, W.; Mayhew, R.; Gordon, Y.; Reid, M.

2016-01-01

Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer-related deaths. Our aim was to evaluate the patterns of screening in the largest organized screening clinic in Jamaica at the Jamaica Cancer Society. A retrospective analysis of all men presenting for screening at the Jamaica Cancer Society from 1995 to 2005 was done. All patients had digital rectal examinations (DRE) and prostate specific antigen (PSA) tests done. Results of prostate biopsies were noted. 1117 men of mean age 59.9 ± 8.2 years presented for screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL). Most patients presented for only 1 screen. There was a gradual reduction in the mean age of presentation for screening over the period. Prostate biopsies were requested on 11% of screening visits; however, only 59% of these were done. 5.6% of all persons screened were found to have cancer. Of the cancers diagnosed, Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL (range 1.5-1059 ng/mL). Older men tend to screen for prostate cancer in Jamaica. However, compliance with regular maintenance visits and requests for confirmatory biopsies are poor. Screening needs intervention in the Jamaican population.

What are key factors influencing malnutrition screening in community-dwelling elderly populations by general practitioners? A large cross-sectional survey in two areas of France.

Science.gov (United States)

Gaboreau, Y; Imbert, P; Jacquet, J-P; Marchand, O; Couturier, P; Gavazzi, G

2013-11-01

Malnutrition is associated with a high morbi-mortality in elderly populations and their institutionalization at an early stage. The incidence is well known despite being often under-diagnosed in primary care. General practitioners (GPs) have a key role in home care. What are the factors affecting malnutrition-screening implementation by French GPs? We conducted a cross-sectional survey in two areas in the southeast of France (Savoie and Isère). In May 2008, an anonymized survey was sent by e-mail and/or post to all GPs with a large clinical practice. Two months later, reminder letters were sent. Potential barriers were measured by dichotomous scale. On GPs' characteristics (socio-demographic, medical training, geriatric practice and knowledge), multiple regression logistic was performed to identify others factors affecting malnutrition screening. In all, 493 GPs (26.85%) answered and 72.2% felt that malnutrition screening was useful although only 26.6% implemented it each year and 11.9% every 2-5 years. The main barriers to the implementation were patient selection (60.4%) and forgetting to screen (26.6%). Minor barriers were lack of knowledge (19.5%) or time (15%). New factors were identified: unsuitable working conditions (19.1%), insufficient motivation (6.8%) or technical support (7.2%). The quality of malnutrition information received was found to be the only promoter of annual screening (odds ratio=1.44 (1.087-1.919); P=0.011). This survey is the first in France to reveal GPs' factors affecting malnutrition implementation. New obstacles were identified in this survey. The hope of implementing regular malnutrition screening by GPs seems to lie with the quality of malnutrition information received.

Design of Web Questionnaires : A Test for Number of Items per Screen

NARCIS (Netherlands)

Toepoel, V.; Das, J.W.M.; van Soest, A.H.O.

2005-01-01

This paper presents results from an experimental manipulation of one versus multiple-items per screen format in a Web survey.The purpose of the experiment was to find out if a questionnaire s format influences how respondents provide answers in online questionnaires and if this is depending on

High-amplitude THz and GHz strain waves, generated by ultrafast screening of piezoelectric fields in InGaN/GaN multiple quantum wells

DEFF Research Database (Denmark)

Porte, Henrik; van Capel, P.J.S.; Turchinovich, Dmitry

2010-01-01

Screening of large built-in piezoelectric fields in InGaN/GaN quantum wells leads to high-amplitude acoustic emission. We will compare acoustic emission by quantum wells with different thicknesses with photoluminescence; indicating screening.......Screening of large built-in piezoelectric fields in InGaN/GaN quantum wells leads to high-amplitude acoustic emission. We will compare acoustic emission by quantum wells with different thicknesses with photoluminescence; indicating screening....

Feasibility study of the real-time IMRT dosimetry using a scintillation screen

Energy Technology Data Exchange (ETDEWEB)

Lim, Sang Wook; Yi, Byong Yong; Ko, Young Eun [Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of)] (and others)

2004-03-15

To study the feasibility of verifying real-time 2-D dose distribution measurement system with the scintillation screen for the quality assurance. The water phantom consisted of a scintillation screen (LANEX fast screen, Kodak, USA) that was axially located in the middle of an acrylic cylinder with a diameter of 25 cm. The charge-coupled device (CCD) camera was attached to the phantom in order to capture the visible light from the scintillation screen. To observe the dose distribution in real time, the intensity of the light from the scintillator was converted to a dosage. The isodose contours of the calculations from RTP and those of the measurements using the scintillation screen were compared for the arc therapy and the intensity modulated radiation therapy (IMRT). The kernel, expressed as a multiplication of two error functions, was obtained in order to correct the sensitivity of the CCD of the camera and the scintillation screen. When comparing the calculated isodose and measured isodose, a discrepancy of less than 8 mm in the high dose region was observed. Using the 2-D dosimetry system, the relationship between the light and the dosage could be found, and real-time verification of the dose distribution was feasible.

Feasibility study of the real-time IMRT dosimetry using a scintillation screen

International Nuclear Information System (INIS)

Lim, Sang Wook; Yi, Byong Yong; Ko, Young Eun

2004-01-01

To study the feasibility of verifying real-time 2-D dose distribution measurement system with the scintillation screen for the quality assurance. The water phantom consisted of a scintillation screen (LANEX fast screen, Kodak, USA) that was axially located in the middle of an acrylic cylinder with a diameter of 25 cm. The charge-coupled device (CCD) camera was attached to the phantom in order to capture the visible light from the scintillation screen. To observe the dose distribution in real time, the intensity of the light from the scintillator was converted to a dosage. The isodose contours of the calculations from RTP and those of the measurements using the scintillation screen were compared for the arc therapy and the intensity modulated radiation therapy (IMRT). The kernel, expressed as a multiplication of two error functions, was obtained in order to correct the sensitivity of the CCD of the camera and the scintillation screen. When comparing the calculated isodose and measured isodose, a discrepancy of less than 8 mm in the high dose region was observed. Using the 2-D dosimetry system, the relationship between the light and the dosage could be found, and real-time verification of the dose distribution was feasible

[Barriers to implementing screening, brief intervention and referral to treatment for substance use in HIV/AIDS health services in Peru].

Science.gov (United States)

Hoffman, Kim A; Beltrán, Jessica; Ponce, Javier; García-Fernandez, Lisset; Calderón, María; Muench, John; Benites, Carlos; Soto, Leslie; McCarty, Dennis; Fiestas, Fabián

2016-01-01

Screening and treatment for substance use among people living with HIV/AIDS (PLWHA) is highly recommended. Nevertheless, in Peru healthcare for PLWHA does not include a standardized or systematic assessment to identify substance use. The aim of this study was to assess the feasibility of implementing screening, brief intervention and referral to treatment (SBIRT) in healthcare settings attending people living with PLWHA. After providing training in SBIRT for PLWHA's healthcare personnel (including nurses and physicians) focus groups were conducted to explore knowledge, beliefs and perceived barriers to implementation and interviews were conducted to assess the barriers and facilitators of two tertiary hospitals in Lima, Peru. focus groups and interviews' thematic coding revealed three dimensions: 1) the unknown extent of substance use within PLWHA, 2) space and time limitations hinder completion of brief interventions during routine visits, and 3) insufficient access to substance use treatment appropriate for HIV patients. Multiple barriers, including lack of awareness of substance use problems, limited space and time of providers, and lack of specialized services to refer patients for treatment make it difficult to implement SBIRT in the Peruvian healthcare system.

A qualitative exploration of Malaysian cancer patients’ perceptions of cancer screening

Directory of Open Access Journals (Sweden)

Farooqui Maryam

2013-01-01

Full Text Available Abstract Background Despite the existence of different screening methods, the response to cancer screening is poor among Malaysians. The current study aims to examine cancer patients’ perceptions of cancer screening and early diagnosis. Methods A qualitative methodology was used to collect in-depth information from cancer patients. After obtaining institutional ethical approval, patients with different types and stages of cancer from the three major ethnic groups (Malay, Chinese and Indian were approached. Twenty semi-structured interviews were conducted. All interviews were audiotaped, transcribed verbatim, and translated into English for thematic content analysis. Results Thematic content analysis yielded four major themes: awareness of cancer screening, perceived benefits of cancer screening, perceived barriers to cancer screening, and cues to action. The majority of respondents had never heard of cancer screening before their diagnosis. Some participants reported hearing about mammogram and Pap smear tests but did not undergo screening due to a lack of belief in personal susceptibility. Those who had negative results from screening prior to diagnosis perceived such tests as untrustworthy. Lack of knowledge and financial constraints were reported as barriers to cancer screening. Finally, numerous suggestions were given to improve screening behaviour among healthy individuals, including the role of mass media in disseminating the message ‘prevention is better than cure’. Conclusions Patients’ narratives revealed some significant issues that were in line with the Health Belief Model which could explain negative health behaviour. The description of the personal experiences of people with cancer could provide many cues to action for those who have never encountered this potentially deadly disease, if incorporated into health promotion activities.

Cerebral metastases from multiple myeloma

International Nuclear Information System (INIS)

Norum, J.; Wist, E.; Dahl, I.M.; University Hospital, Tromsoe

1991-01-01

The authors report a patient with multiple intracerebral lesions from myeloma. The case also demonstrates that myeloma is a radiosensitive tumour and that radiotherapy is important to keep in mind when intracranial lesions are revealed. (orig.)

Screen time, weight status and the self-concept of physical attractiveness in adolescents.

Science.gov (United States)

Suchert, Vivien; Hanewinkel, Reiner; Isensee, Barbara

2016-04-01

Adolescents in modern societies spend about 3 h per day in front of small recreational screens. The present study aims at investigating the relationships between screen time and different indicators of overweight. In addition, associations with the self-concept of physical attractiveness and perceived weight status will be examined. In a total sample of 1228 students (47.5% girls) aged 12-17 years (M = 13.74, SD = 0.68) cross-sectional associations were determined by conducting multiple linear regression analyses. Screen time showed a significant positive dose-response relationship with body mass index percentile, waist circumference, body fat, waist-to-height-ratio, and a negative association with self-concept of physical attractiveness independent of age, gender and moderate to vigorous physical activity. Thus, screen time seems to be associated with adolescent overweight, abdominal obesity, and body dissatisfaction. Reducing adolescents' screen time could be a promising approach for primary prevention of obesity and for the promotion of a positive physical self-concept. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

"TV no longer commands our full attention": Effects of second-screen viewing and task relevance on cognitive load and learning from news

NARCIS (Netherlands)

Cauwenberge, A.M.R. van; Schaap, G.J.; Roy, R. van

2014-01-01

Second-screen viewing the use of smartphones, tablets, and laptops while watching television has increased dramatically in the last few years. Using multiple resource theory and threaded cognition theory, this study investigated the effects of second-screen viewing on cognitive load, factual recall

Automated Groundwater Screening

International Nuclear Information System (INIS)

Taylor, Glenn A.; Collard, Leonard B.

2005-01-01

The Automated Intruder Analysis has been extended to include an Automated Ground Water Screening option. This option screens 825 radionuclides while rigorously applying the National Council on Radiation Protection (NCRP) methodology. An extension to that methodology is presented to give a more realistic screening factor for those radionuclides which have significant daughters. The extension has the promise of reducing the number of radionuclides which must be tracked by the customer. By combining the Automated Intruder Analysis with the Automated Groundwater Screening a consistent set of assumptions and databases is used. A method is proposed to eliminate trigger values by performing rigorous calculation of the screening factor thereby reducing the number of radionuclides sent to further analysis. Using the same problem definitions as in previous groundwater screenings, the automated groundwater screening found one additional nuclide, Ge-68, which failed the screening. It also found that 18 of the 57 radionuclides contained in NCRP Table 3.1 failed the screening. This report describes the automated groundwater screening computer application

Cost-effectiveness of cervical-cancer screening in five developing countries.

Science.gov (United States)

Goldie, Sue J; Gaffikin, Lynne; Goldhaber-Fiebert, Jeremy D; Gordillo-Tobar, Amparo; Levin, Carol; Mahé, Cédric; Wright, Thomas C

2005-11-17

Cervical-cancer screening strategies that involve the use of conventional cytology and require multiple visits have been impractical in developing countries. We used computer-based models to assess the cost-effectiveness of a variety of cervical-cancer screening strategies in India, Kenya, Peru, South Africa, and Thailand. Primary data were combined with data from the literature to estimate age-specific incidence and mortality rates for cancer and the effectiveness of screening for and treatment of precancerous lesions. We assessed the direct medical, time, and program-related costs of strategies that differed according to screening test, targeted age and frequency, and number of clinic visits required. Single-visit strategies involved the assumption that screening and treatment could be provided in the same day. Outcomes included the lifetime risk of cancer, years of life saved, lifetime costs, and cost-effectiveness ratios (cost per year of life saved). The most cost-effective strategies were those that required the fewest visits, resulting in improved follow-up testing and treatment. Screening women once in their lifetime, at the age of 35 years, with a one-visit or two-visit screening strategy involving visual inspection of the cervix with acetic acid or DNA testing for human papillomavirus (HPV) in cervical cell samples, reduced the lifetime risk of cancer by approximately 25 to 36 percent, and cost less than 500 dollars per year of life saved. Relative cancer risk declined by an additional 40 percent with two screenings (at 35 and 40 years of age), resulting in a cost per year of life saved that was less than each country's per capita gross domestic product--a very cost-effective result, according to the Commission on Macroeconomics and Health. Cervical-cancer screening strategies incorporating visual inspection of the cervix with acetic acid or DNA testing for HPV in one or two clinical visits are cost-effective alternatives to conventional three

Preferred viewing distance and screen angle of electronic paper displays.

Science.gov (United States)

Shieh, Kong-King; Lee, Der-Song

2007-09-01

This study explored the viewing distance and screen angle for electronic paper (E-Paper) displays under various light sources, ambient illuminations, and character sizes. Data analysis showed that the mean viewing distance and screen angle were 495 mm and 123.7 degrees. The mean viewing distances for Kolin Chlorestic Liquid Crystal display was 500 mm, significantly longer than Sony electronic ink display, 491 mm. Screen angle for Kolin was 127.4 degrees, significantly greater than that of Sony, 120.0 degrees. Various light sources revealed no significant effect on viewing distances; nevertheless, they showed significant effect on screen angles. The screen angle for sunlight lamp (D65) was similar to that of fluorescent lamp (TL84), but greater than that of tungsten lamp (F). Ambient illumination and E-paper type had significant effects on viewing distance and screen angle. The higher the ambient illumination was, the longer the viewing distance and the lesser the screen angle. Character size had significant effect on viewing distances: the larger the character size, the longer the viewing distance. The results of this study indicated that the viewing distance for E-Paper was similar to that of visual display terminal (VDT) at around 500 mm, but greater than normal paper at about 360 mm. The mean screen angle was around 123.7 degrees, which in terms of viewing angle is 29.5 degrees below horizontal eye level. This result is similar to the general suggested viewing angle between 20 degrees and 50 degrees below the horizontal line of sight.

Cervical screening programme in Trabzon county

Directory of Open Access Journals (Sweden)

Şafak Ersöz

2010-03-01

Full Text Available AIM: Cytological evaluation carries a great significance for the early detection and treatment of invasive cervical carcinoma precursors. Pap-smear test are considered as a quite effective screening method for this purpose. This screening can be easily performed at the first step health care centers without causing an economic burden if only selected patients were referred to second and third step medical care centers. In this program we aimed to perform a cross-sectional survey for cervix cancer in Trabzon center and surrounding area using cervical smears obtained at first step health care centers. MATERIAL-METHOD: A total number of 3000 cases with an age range of 25-64 were screened between March and May of 2007. This program was supported by USIDER. Smears obtained with cytological brushes were prepared with conventional methods and stained with Papanicolaou dye. Pap smears were reviewed by two pathologists according to 2001 Bethesda classification. RESULTS: A great majority of the smears (93.3 % were found to be satisfactory, while only 6.7 were found to be insufficient. Analysis of satisfactory cervical smears revealed cervical epithelial cell anomalies in 73 cases (2.4%; of these cases 57 (1.9% had atypical squamous cell of undetermined significance (ASC-US, 11 (0.4 % had low grade squamous intra-epithelial lesion (LSIL, 3 (0.1% high grade squamous intra-epithelial lesion (HSIL, and 2 (0.07 % had squamous cell carcinoma. CONCLUSION: Smears obtained at the first step health care centers were found to be satisfactory in a major proportion of the cases. Screening programs play a great role in the declining of cancer incidence. These screening programs should be included in national health politics. First step health care centers might be used for this purpose concerning the health economics.

How information about overdetection changes breast cancer screening decisions: a mediation analysis within a randomised controlled trial.

Science.gov (United States)

Hersch, Jolyn; McGeechan, Kevin; Barratt, Alexandra; Jansen, Jesse; Irwig, Les; Jacklyn, Gemma; Houssami, Nehmat; Dhillon, Haryana; McCaffery, Kirsten

2017-10-06

In a randomised controlled trial, we found that informing women about overdetection changed their breast screening decisions. We now present a mediation analysis exploring the psychological pathways through which study participants who received the intervention processed information about overdetection and how this influenced their decision-making. We examined a series of potential mediators in the causal chain between exposure to overdetection information and women's subsequently reported breast screening intentions. Serial multiple mediation analysis within a randomised controlled trial. New South Wales, Australia. 811 women aged 48-50 years with no personal history of breast cancer. Two versions of a decision aid giving women information about breast cancer deaths averted and false positives from mammography screening, either with (intervention) or without (control) information on overdetection. Intentions to undergo breast cancer screening in the next 2-3 years. Knowledge about overdetection, worry about breast cancer, attitudes towards breast screening and anticipated regret. The effect of information about overdetection on women's breast screening intentions was mediated through multiple cognitive and affective processes. In particular, the information led to substantial improvements in women's understanding of overdetection, and it influenced-both directly and indirectly via its effect on knowledge-their attitudes towards having screening. Mediation analysis showed that the mechanisms involving knowledge and attitudes were particularly important in determining women's intentions about screening participation. Even in this emotive context, new information influenced women's decision-making by changing their understanding of possible consequences of screening and their attitudes towards undergoing it. These findings emphasise the need to provide good-quality information on screening outcomes and to communicate this information effectively, so that women can

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

Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

Energy Technology Data Exchange (ETDEWEB)

Tolosa, Laia [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Gómez-Lechón, M. José [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Jiménez, Nuria [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Hervás, David [Biostatistics Unit, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Jover, Ramiro [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Valencia 46010 (Spain); Donato, M. Teresa, E-mail: donato_mte@gva.es [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Valencia 46010 (Spain)

2016-07-01

Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.

Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

International Nuclear Information System (INIS)

Tolosa, Laia; Gómez-Lechón, M. José; Jiménez, Nuria; Hervás, David; Jover, Ramiro; Donato, M. Teresa

2016-01-01

Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.

Breast cancer screening

Science.gov (United States)

Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

Screening for carcinoma in situ in the contralateral testicle in patients with testicular cancer

DEFF Research Database (Denmark)

Kier, M G G; Lauritsen, Jakob; Almstrup, Kristian

2015-01-01

population-based screening programme for contralateral CIS in patients with testicular cancer showed no significant difference in the risk for metachronous GCC between a screened and an unscreened cohort. Single-site biopsy including modern immunohistochemistry does not identify all cases of CIS.......BACKGROUND: Screening programmes for contralateral carcinoma in situ (CIS) testis in patients with unilateral germ-cell cancer (GCC) have never been evaluated. We investigated the effect of screening for contralateral CIS in a large nation-wide, population-based study. PATIENTS AND METHODS...... years was 1.9% in the screened cohort and 3.1% in the unscreened cohort (P = 0.097), hazard ratio (HR) for the unscreened cohort: 1.59 (P = 0.144). Expert revision with contemporary methodology of CIS-negative biopsy samples from patients with metachronous cancer revealed CIS in 17 out of 45 (38%) cases...

Multiplicative properties of quantum channels

Science.gov (United States)

Rahaman, Mizanur

2017-08-01

In this paper, we study the multiplicative behaviour of quantum channels, mathematically described by trace preserving, completely positive maps on matrix algebras. It turns out that the multiplicative domain of a unital quantum channel has a close connection to its spectral properties. A structure theorem (theorem 2.5), which reveals the automorphic property of an arbitrary unital quantum channel on a subalgebra, is presented. Various classes of quantum channels (irreducible, primitive, etc) are then analysed in terms of this stabilising subalgebra. The notion of the multiplicative index of a unital quantum channel is introduced, which measures the number of times a unital channel needs to be composed with itself for the multiplicative algebra to stabilise. We show that the maps that have trivial multiplicative domains are dense in completely bounded norm topology in the set of all unital completely positive maps. Some applications in quantum information theory are discussed.

Prenatal screening for fetal aneuploidy in singleton pregnancies.

Science.gov (United States)

Chitayat, David; Langlois, Sylvie; Douglas Wilson, R

2011-07-01

studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. This guideline is intended to reduce the number of prenatal invasive procedures done when maternal age is the only indication. This will have the benefit of reducing the numbers of normal pregnancies lost because of complications of invasive procedures. Any screening test has an inherent false-positive rate, which may result in undue anxiety. It is not possible at this time to undertake a detailed cost-benefit analysis of the implementation of this guideline, since this would require health surveillance and research and health resources not presently available; however, these factors need to be evaluated in a prospective approach by provincial and territorial initiatives. RECOMMENDATIONS 1. All pregnant women in Canada, regardless of age, should be offered, through an informed counselling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies in addition to a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples. (I-A) 2. Counselling must be non-directive and must respect a woman's right to accept or decline any or all of the testing or options offered at any point in the process. (III-A) 3. Maternal age alone is a poor minimum standard for prenatal screening

RBC Antibody Screen

Science.gov (United States)

... C Cystic Fibrosis (CF) Gene Mutations Testing Cytomegalovirus (CMV) Tests D-dimer Dengue Fever Testing Des-gamma- ... Index of Screening Recommendations Not Listed? Not Listed? Newborn Screening Screening Tests for Infants Screening Tests for ...

Central nervous system remyelination in culture — A tool for multiple sclerosis research

Science.gov (United States)

Zhang, Hui; Jarjour, Andrew A.; Boyd, Amanda; Williams, Anna

2011-01-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. PMID:21515259

Reiki as a pain management adjunct in screening colonoscopy.

Science.gov (United States)

Bourque, Alda L; Sullivan, Mary E; Winter, Michael R

2012-09-01

The purpose of this study was to determine whether the use of Reiki decreases the amount of meperidine administered to patients undergoing screening colonoscopy. The literature review reveals limited studies to show whether Reiki has been able to decrease the amount of opioid the patient receives during screening colonoscopy. A chart review of 300 patients was conducted to obtain baseline average doses of meperidine patients received as the control. Following the chart review, 30 patients were recruited to the Reiki study. Twenty-five of the study arm patients received Reiki in conjunction with meperidine. Five randomly chosen study arm patients received placebo Reiki in conjunction with meperidine in an attempt to blind the clinicians to the treatment received by the patients. Results showed that there were no significant differences in meperidine administration between the patients in the chart review group (control) and the Reiki group. The study revealed that 16% who received Reiki, together with intravenous administration of conscious sedation, received less than 50 mg of meperidine. All the patients in the chart review group received more than 50 mg of meperidine. Results from this pilot study suggest that there may be a decrease in meperidine needed during screening colonoscopy when patients receive Reiki treatments before the procedure. A larger study powered to detect smaller medication differences is the next step in more accurately determining the effect of Reiki on pain management.

Analysis of Brassica oleracea early stage abiotic stress responses reveals tolerance in multiple crop types and for multiple sources of stress.

Science.gov (United States)

Beacham, Andrew M; Hand, Paul; Pink, David Ac; Monaghan, James M

2017-12-01

Brassica oleracea includes a number of important crop types such as cabbage, cauliflower, broccoli and kale. Current climate conditions and weather patterns are causing significant losses in these crops, meaning that new cultivars with improved tolerance of one or more abiotic stress types must be sought. In this study, genetically fixed B. oleracea lines belonging to a Diversity Fixed Foundation Set (DFFS) were assayed for their response to seedling stage-imposed drought, flood, salinity, heat and cold stress. Significant (P ≤ 0.05) variation in stress tolerance response was found for each stress, for each of four measured variables (relative fresh weight, relative dry weight, relative leaf number and relative plant height). Lines tolerant to multiple stresses were found to belong to several different crop types. There was no overall correlation between the responses to the different stresses. Abiotic stress tolerance was identified in multiple B. oleracea crop types, with some lines exhibiting resistance to multiple stresses. For each stress, no one crop type appeared significantly more or less tolerant than others. The results are promising for the development of more environmentally robust lines of different B. oleracea crops by identifying tolerant material and highlighting the relationship between responses to different stresses. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Multiple sclerosis on-screen: from disaster to coping.

Science.gov (United States)

Karenberg, Axel

2008-05-01

Fictional portrayals of multiple sclerosis (MS) in film and on television have remained largely unexamined to date. The aim of this review is consequently to catalog and analyse every available film with an MS motif. The author has identified relevant productions by means of international film databases and by handsearch. Each film is systematically evaluated along neurological and cinematic lines. Between 1941 and 2006 MS appeared as a theme in 23 films. Because screenplay writers often make use of medical knowledge, from a neurological perspective many films present a largely accurate picture of this disease's symptoms. The visual character of the medium and the effects of dramatic composition result in the prominence of certain symptoms. Ataxia, paralysis, blurred vision and fatigue are found in films with the same frequency as in epidemiological studies whereas sensory symptoms, eye movement disorders, incontinence and difficulties with sexual function were underrepresented. These films thematize the effects of MS on patients' self-image, the psychological adaptation process and their relations with proxy in a special way. Parallel with improvements in therapy and changing social attitudes toward the handicapped, these films have progressed from the earlier 'disaster' to modern 'coping' stories. The often life-like portrayal of MS distinguishes these films from the stereotypic representation of other neurological diseases. Because representations of MS in popular media have an immediate effect on an audience of millions, they deserve greater attention from professional neurology.

A study on software-based sensing technology for multiple object control in AR video.

Science.gov (United States)

Jung, Sungmo; Song, Jae-Gu; Hwang, Dae-Joon; Ahn, Jae Young; Kim, Seoksoo

2010-01-01

Researches on Augmented Reality (AR) have recently received attention. With these, the Machine-to-Machine (M2M) market has started to be active and there are numerous efforts to apply this to real life in all sectors of society. To date, the M2M market has applied the existing marker-based AR technology in entertainment, business and other industries. With the existing marker-based AR technology, a designated object can only be loaded on the screen from one marker and a marker has to be added to load on the screen the same object again. This situation creates a problem where the relevant marker'should be extracted and printed in screen so that loading of the multiple objects is enabled. However, since the distance between markers will not be measured in the process of detecting and copying markers, the markers can be overlapped and thus the objects would not be augmented. To solve this problem, a circle having the longest radius needs to be created from a focal point of a marker to be copied, so that no object is copied within the confines of the circle. In this paper, software-based sensing technology for multiple object detection and loading using PPHT has been developed and overlapping marker control according to multiple object control has been studied using the Bresenham and Mean Shift algorithms.

A Study on Software-based Sensing Technology for Multiple Object Control in AR Video

Directory of Open Access Journals (Sweden)

Seoksoo Kim

2010-11-01

Full Text Available Researches on Augmented Reality (AR have recently received attention. With these, the Machine-to-Machine (M2M market has started to be active and there are numerous efforts to apply this to real life in all sectors of society. To date, the M2M market has applied the existing marker-based AR technology in entertainment, business and other industries. With the existing marker-based AR technology, a designated object can only be loaded on the screen from one marker and a marker has to be added to load on the screen the same object again. This situation creates a problem where the relevant marker should be extracted and printed in screen so that loading of the multiple objects is enabled. However, since the distance between markers will not be measured in the process of detecting and copying markers, the markers can be overlapped and thus the objects would not be augmented. To solve this problem, a circle having the longest radius needs to be created from a focal point of a marker to be copied, so that no object is copied within the confines of the circle. In this paper, software-based sensing technology for multiple object detection and loading using PPHT has been developed and overlapping marker control according to multiple object control has been studied using the Bresenham and Mean Shift algorithms.

Complete genome-wide screening and subtractive genomic approach revealed new virulence factors, potential drug targets against bio-war pathogen Brucella melitensis 16M

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Pradeepkiran JA

2015-03-01

Full Text Available Jangampalli Adi Pradeepkiran,1* Sri Bhashyam Sainath,2,3* Konidala Kranthi Kumar,1 Matcha Bhaskar1 1Division of Animal Biotechnology, Department of Zoology, Sri Venkateswara University, Tirupati, India; 2CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Rua dos Bragas, Porto, Portugal, 3Department of Biotechnology, Vikrama Simhapuri University, Nellore, Andhra Pradesh, India *These authors contributed equally to this work Abstract: Brucella melitensis 16M is a Gram-negative coccobacillus that infects both animals and humans. It causes a disease known as brucellosis, which is characterized by acute febrile illness in humans and causes abortions in livestock. To prevent and control brucellosis, identification of putative drug targets is crucial. The present study aimed to identify drug targets in B. melitensis 16M by using a subtractive genomic approach. We used available database repositories (Database of Essential Genes, Kyoto Encyclopedia of Genes and Genomes Automatic Annotation Server, and Kyoto Encyclopedia of Genes and Genomes to identify putative genes that are nonhomologous to humans and essential for pathogen B. melitensis 16M. The results revealed that among 3 Mb genome size of pathogen, 53 putative characterized and 13 uncharacterized hypothetical genes were identified; further, from Basic Local Alignment Search Tool protein analysis, one hypothetical protein showed a close resemblance (50% to Silicibacter pomeroyi DUF1285 family protein (2RE3. A further homology model of the target was constructed using MODELLER 9.12 and optimized through variable target function method by molecular dynamics optimization with simulating annealing. The stereochemical quality of the restrained model was evaluated by PROCHECK, VERIFY-3D, ERRAT, and WHATIF servers. Furthermore, structure-based virtual screening was carried out against the predicted active site of the respective protein using the

Canonical correlation analysis of multiple sensory directed metabolomics data blocks reveals corresponding parts between data blocks.

NARCIS (Netherlands)

Doeswijk, T. G.; Hageman, J.A.; Westerhuis, J.A.; Tikunov, Y.; Bovy, A.; van Eeuwijk, F.A.

2011-01-01

Multiple analytical platforms are frequently used in metabolomics studies. The resulting multiple data blocks contain, in general, similar parts of information which can be disclosed by chemometric methods. The metabolites of interest, however, are usually just a minor part of the complete data

A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

Czech Academy of Sciences Publication Activity Database

Barreto, L.; Canadell, D.; Petrezsélyová, Silvia; Navarrete, C.; Marešová, Lydie; Peréz-Valle, J.; Herrera, R.; Olier, I.; Giraldo, J.; Sychrová, Hana; Yenush, L.; Ramos, J.; Ariňo, J.

2011-01-01

Roč. 10, č. 9 (2011), s. 1241-1250 ISSN 1535-9778 R&D Projects: GA MŠk(CZ) LC531; GA AV ČR(CZ) IAA500110801 Institutional research plan: CEZ:AV0Z50110509 Keywords : Potassium homeostasis * Saccharomyces cerevisiae * genomewide screen Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.604, year: 2011

Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts

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Koh, Kwang Joon; Park, Ha Na; Kim, Kyoung A [Dept. of Oral and Maxillofacial Radiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju (Korea, Republic of)

2016-12-15

Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome.

Three dimensional de novo micro bone marrow and its versatile application in drug screening and regenerative medicine.

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Li, Guanqun; Liu, Xujun; Du, Qian; Gao, Mei; An, Jing

2015-08-01

The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field. © 2015 by the Society for Experimental Biology and Medicine.

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

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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 directed RNAi screen based on larval growth arrest reveals new modifiers of C. elegans insulin signaling.

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Ola Billing

Full Text Available Genes regulating Caenorhabditis elegans insulin/IGF signaling (IIS have largely been identified on the basis of their involvement in dauer development or longevity. A third IIS phenotype is the first larval stage (L1 diapause, which is also influenced by asna-1, a regulator of DAF-28/insulin secretion. We reasoned that new regulators of IIS strength might be identified in screens based on the L1 diapause and the asna-1 phenotype. Eighty- six genes were selected for analysis by virtue of their predicted interaction with ASNA-1 and screened for asna-1-like larval arrest. ykt-6, mrps-2, mrps-10 and mrpl-43 were identified as genes which, when inactivated, caused larval arrest without any associated feeding defects. Several tests indicated that IIS strength was weaker and that insulin secretion was defective in these animals. This study highlights the role of the Golgi network and the mitochondria in insulin secretion and provides a new list of genes that modulate IIS in C. elegans.

A Network and Visual Quality Aware N-Screen Content Recommender System Using Joint Matrix Factorization

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Farman Ullah

2014-01-01

Full Text Available We propose a network and visual quality aware N-Screen content recommender system. N-Screen provides more ways than ever before to access multimedia content through multiple devices and heterogeneous access networks. The heterogeneity of devices and access networks present new questions of QoS (quality of service in the realm of user experience with content. We propose, a recommender system that ensures a better visual quality on user’s N-screen devices and the efficient utilization of available access network bandwidth with user preferences. The proposed system estimates the available bandwidth and visual quality on users N-Screen devices and integrates it with users preferences and contents genre information to personalize his N-Screen content. The objective is to recommend content that the user’s N-Screen device and access network are capable of displaying and streaming with the user preferences that have not been supported in existing systems. Furthermore, we suggest a joint matrix factorization approach to jointly factorize the users rating matrix with the users N-Screen device similarity and program genres similarity. Finally, the experimental results show that we also enhance the prediction and recommendation accuracy, sparsity, and cold start issues.

A network and visual quality aware N-screen content recommender system using joint matrix factorization.

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Ullah, Farman; Sarwar, Ghulam; Lee, Sungchang

2014-01-01

We propose a network and visual quality aware N-Screen content recommender system. N-Screen provides more ways than ever before to access multimedia content through multiple devices and heterogeneous access networks. The heterogeneity of devices and access networks present new questions of QoS (quality of service) in the realm of user experience with content. We propose, a recommender system that ensures a better visual quality on user's N-screen devices and the efficient utilization of available access network bandwidth with user preferences. The proposed system estimates the available bandwidth and visual quality on users N-Screen devices and integrates it with users preferences and contents genre information to personalize his N-Screen content. The objective is to recommend content that the user's N-Screen device and access network are capable of displaying and streaming with the user preferences that have not been supported in existing systems. Furthermore, we suggest a joint matrix factorization approach to jointly factorize the users rating matrix with the users N-Screen device similarity and program genres similarity. Finally, the experimental results show that we also enhance the prediction and recommendation accuracy, sparsity, and cold start issues.

Brief screening for co-occurring disorders among women entering substance abuse treatment

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Chernoff Miriam

2006-09-01

Full Text Available Abstract Background Despite the importance of identifying co-occurring psychiatric disorders in substance abuse treatment programs, there are few appropriate and validated instruments available to substance abuse treatment staff to conduct brief screen for these conditions. This paper describes the development, implementation and validation of a brief screening instrument for mental health diagnoses and trauma among a diverse sample of Black, Hispanic and White women in substance abuse treatment. With input from clinicians and consumers, we adapted longer existing validated instruments into a 14 question screen covering demographics, mental health symptoms and physical and sexual violence exposure. All women entering treatment (methadone, residential and out-patient at five treatment sites were screened at intake (N = 374. Results Eighty nine percent reported a history of interpersonal violence, and 70% reported a history of sexual assault. Eighty-eight percent reported mental health symptoms in the last 30 days. The screening questions administered to 88 female clients were validated against in-depth psychiatric diagnostic assessments by trained mental health clinicians. We estimated measures of predictive validity, including sensitivity, specificity and predictive values positive and negative. Screening items were examined multiple ways to assess utility. The screen is a useful and valid proxy for PTSD but not for other mental illness. Conclusion Substance abuse treatment programs should incorporate violence exposure questions into clinical use as a matter of policy. More work is needed to develop brief screening tools measures for front-line treatment staff to accurately assess other mental health needs of women entering substance abuse treatment

Screening of wild and cultivated Capsicum germplasm reveals new sources of Verticillium wilt resistance

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Verticillium wilt caused by Verticillium dahliae is an important soilborne disease of pepper (Capsicum species) worldwide. Most commercial pepper cultivars lack resistance to this pathogen. Our objective was to identify resistance to multiple V. dahliae isolates in wild and cultivated Capsicum acces...

Effect of deviation of nuchal translucency measurements on the performance of screening for trisomy 21.

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Kagan, K O; Wright, D; Etchegaray, A; Zhou, Y; Nicolaides, K H

2009-06-01

To examine the effect of deviations in median nuchal translucency thickness (NT) and the spread in measurements on the performance of screening for trisomy 21 by maternal age and fetal NT, and by maternal age, fetal NT and maternal serum biochemistry. We simulated the NT and multiples of the median values for pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) for 500 000 euploid and 500 000 trisomy 21 pregnancies at 12 weeks of gestation. Detection rates for trisomy 21 and false-positive rates were calculated without adjustments in NT and by adding or subtracting values ranging from 0.1 to 1.0 mm to each observed measurement. In addition, the effects of variation in the scatter of NT measurements were examined by applying a multiplicative factor ranging from 0.5 to 2 to the SD. The detection rate of trisomy 21 for a fixed false-positive rate of 3% in screening by maternal age and fetal NT was 72%, and in screening by maternal age, fetal NT and serum free beta-hCG and PAPP-A it was 86%. A consistent underestimate or overestimate in the measured NT reduced the detection rate of trisomy 21 for a fixed-false positive rate. At a fixed screen-positive cut-off an underestimate in fetal NT reduced the detection rate whereas an overestimate in NT increased the false-positive rate. A widening in the scatter of measurements had only a small impact on the detection rate but it caused a major increase in the false-positive rate. High performance of screening necessitates appropriate measurement of fetal NT. This paper demonstrates the effect of deviations in the median and SD of NT from the expected on the performance of screening and can form the basis of audit of results of individual sonographers. (c) 2009 ISUOG.

A comprehensive platform for highly multiplexed mammalian functional genetic screens

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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.

Holocarboxylase synthetase deficiency pre and post newborn screening

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Taraka R. Donti

2016-06-01

Full Text Available Holocarboxylase synthetase deficiency is an autosomal recessive disorder of biotin metabolism resulting in multiple carboxylase deficiency. The typical presentation described in the medical literature is of neonatal onset within hours to weeks of birth with emesis, hypotonia, lethargy, seizures, metabolic ketolactic acidosis, hyperammonemia, developmental delay, skin rash and alopecia. The condition is screened for by newborn screening (NBS tandem mass spectroscopy by elevated hydroxypentanoylcarnitine on dried blood spots. Urine organic acid profile may demonstrate elevated lactic, 3-OH isovaleric, 3-OH propionic, 3-MCC, methylcitric acids, and tiglylglycine consistent with loss of function of the above carboxylases. Here we describe a cohort of patients, 2 diagnosed pre-NBS and 3 post-NBS with broad differences in initial presentation and phenotype. In addition, prior to the advent of NBS, there are isolated reports of late-onset holocarboxylase synthetase deficiency in the medical literature, which describe patients diagnosed between 1 and 8 years of life, however to our knowledge there are no reports of late-onset HCLS being missed by NBS. Also we report two cases, each with novel pathogenic variants HCLS, diagnosed at age 3 years and 21 months respectively. The first patient had a normal newborn screen whilst the second had an abnormal newborn screen but was misdiagnosed as 3-methylcrotonylcarboxylase (3-MCC deficiency and subsequently lost to follow-up until they presented again with severe metabolic acidosis.

Screening mammography in Finland--1.5 million examinations with 97 percent specificity

International Nuclear Information System (INIS)

Dean, P.B.; Pamilo, M.

1999-01-01

A nationwide mammography screening program including women aged 50-59 years at the time of the first invitation and involving more than 100 radiologists was started in Finland in January, 1987. From 1987 through 1997, a total of 1,690,496 invitations to biennial two-view mammography screening was sent out. The compliance for screening was 88.5% with 1,495,744 screening examinations performed during this 11-year period. There were 49,020 recalls for further work-up studies and 9,689 women were referred for surgery. The total number of screening-detected breast cancers was 5,595, giving a detection rate of 3.7 cancers per 1000 screening studies. More than half of all surgical biopsies revealed breast cancer and 67.8% of the invasive cancers were at Stage I. The positive predictive value of referral to surgical biopsy increased from 33.2% in 1987 to 65.5% in 1997. and the ratio of malignant to benign biopsies more than tripled from the first to the fifth year of screening. The observed/expected ratio of invasive cancer detection was 2.44. Only 0.27% of all screening mammograms were followed by a benign biopsy, and 2.90% of all screening mammograms were followed by the women being recalled for further studies and not found to have breast cancer. This gave a specificity of recall after screening mammography greater than 97.0% and a specificity of referral to surgical biopsy greater than 99.7%. Measures of specificity improved considerably during the first three years of the screening program. The high specificity of screening mammography can be attributed to the nature of the screening process as well as to the opportunity for individual radiologists to attain a greater level of experience and competence. The decision to recall appears to have been crucial in determining the specificity

A Screening Mechanism Differentiating True from False Pain during Empathy.

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Sun, Ya-Bin; Lin, Xiao-Xiao; Ye, Wen; Wang, Ning; Wang, Jin-Yan; Luo, Fei

2017-09-13

Empathizing with another's suffering is important in social interactions. Empathic behavior is selectively elicited from genuine, meaningful pain but not from fake, meaningless scenarios. However, the brain's screening mechanism of false information from meaningful events and the time course for the screening process remains unclear. Using EEG combined with principle components analysis (PCA) techniques, here we compared temporal neurodynamics between the observation of pain and no-pain pictures as well as between true (painful expressions and needle-penetrated arms) and false (needle-penetrated faces with neutral expressions) pain pictures. The results revealed that pain vs. no-pain information is differentiated in the very early ERP components, i.e., the N1/P1 for the face and arm pictures categories and the VPP/N170 for the facial expression category while the mid-latency ERP components, N2 and P3, played key roles in differentiating true from false situations. The complex of N2 and P3 components may serve as a screening mechanism through which observers allocate their attentions to more important or relevant events and screen out false environmental information. This is the first study to describe and provide a time course of the screening process during pain empathy. These findings shed new light on the understanding of empathic processing.

Demographic, social cognitive and social ecological predictors of intention and participation in screening for colorectal cancer

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Duncan Amy

2011-01-01

Full Text Available Abstract Background Previous research points to differences between predictors of intention to screen for colorectal cancer (CRC and screening behavior, and suggests social ecological factors may influence screening behavior. The aim of this study was to compare the social cognitive and social ecological predictors of intention to screen with predictors of participation. Methods People aged 50 to 74 years recruited from the electoral roll completed a baseline survey (n = 376 and were subsequently invited to complete an immunochemical faecal occult blood test (iFOBT. Results Multivariate analyses revealed five predictors of intention to screen and two predictors of participation. Perceived barriers to CRC screening and perceived benefits of CRC screening were the only predictor of both outcomes. There was little support for social ecological factors, but measurement problems may have impacted this finding. Conclusions This study has confirmed that the predictors of intention to screen for CRC and screening behaviour, although overlapping, are not the same. Research should focus predominantly on those factors shown to predict participation. Perceptions about the barriers to screening and benefits of screening are key predictors of participation, and provide a focus for intervention programs.

Central nervous system remyelination in culture--a tool for multiple sclerosis research.

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Zhang, Hui; Jarjour, Andrew A; Boyd, Amanda; Williams, Anna

2011-07-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. Copyright © 2011 Elsevier Inc. All rights reserved.

Examining the Impact of Latino Nativity, Migration, and Acculturation Factors on Colonoscopy Screening.

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Costas-Muñiz, Rosario; Jandorf, Lina; Philip, Errol; Cohen, Noah; Villagra, Cristina; Sriphanlop, Pathu; Schofield, Elizabeth; DuHamel, Katherine

2016-10-01

Latinos are a diverse population comprised of multiple countries of origin with varying cultural profiles. This study examines differences in colonoscopy completion across place of birth and migration-related factors in a sample of predominantly Dominican and Puerto Rican Latinos living in New York City after receiving a recommendation for colonoscopy screening and navigation services. The sample included 702 Latinos recruited for two cancer screening projects targeting Latinos eligible for colonoscopy who seek healthcare in New York City. Participants completed a survey that included sociodemographic, health-related questions, psychosocial assessments and cancer screening practices, in Spanish or English. Migration, acculturation, and language factors were found to predict colonoscopy completion. The results indicated that Latinos born in the Dominican Republic and Central America were more likely to complete a screening colonoscopy than their counterparts born in the US. Further, those who emigrated at an older age, who have resided in the US for less than 20 years, preferred Spanish and those with lower US acculturation levels were also more likely to complete a screening colonoscopy. The findings suggest that Latinos who are less acculturated to the US are more likely to complete a screening colonoscopy after receiving a physician recommendation for colonoscopy screening. The results provide important information that can inform clinical practice and public health interventions. Continued attention to cultural and migration influences are important areas for cancer screening intervention development.

Virtual screening using combinatorial cyclic peptide libraries reveals protein interfaces readily targetable by cyclic peptides.

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Duffy, Fergal J; O'Donovan, Darragh; Devocelle, Marc; Moran, Niamh; O'Connell, David J; Shields, Denis C

2015-03-23

Protein-protein and protein-peptide interactions are responsible for the vast majority of biological functions in vivo, but targeting these interactions with small molecules has historically been difficult. What is required are efficient combined computational and experimental screening methods to choose among a number of potential protein interfaces worthy of targeting lead macrocyclic compounds for further investigation. To achieve this, we have generated combinatorial 3D virtual libraries of short disulfide-bonded peptides and compared them to pharmacophore models of important protein-protein and protein-peptide structures, including short linear motifs (SLiMs), protein-binding peptides, and turn structures at protein-protein interfaces, built from 3D models available in the Protein Data Bank. We prepared a total of 372 reference pharmacophores, which were matched against 108,659 multiconformer cyclic peptides. After normalization to exclude nonspecific cyclic peptides, the top hits notably are enriched for mimetics of turn structures, including a turn at the interaction surface of human α thrombin, and also feature several protein-binding peptides. The top cyclic peptide hits also cover the critical "hot spot" interaction sites predicted from the interaction crystal structure. We have validated our method by testing cyclic peptides predicted to inhibit thrombin, a key protein in the blood coagulation pathway of important therapeutic interest, identifying a cyclic peptide inhibitor with lead-like activity. We conclude that protein interfaces most readily targetable by cyclic peptides and related macrocyclic drugs may be identified computationally among a set of candidate interfaces, accelerating the choice of interfaces against which lead compounds may be screened.

Detection of Extramedullary Multiple Myeloma in Liver by FDG-PET/CT

International Nuclear Information System (INIS)

Kim, Daeweung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Choi, Keum Ha; Kim, Chang Guhn

2014-01-01

We present the case of a 42-year-old man with a painful mass lesion in the right shoulder that was detected by contrast-enhanced computed tomography (CT) and 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT. Excisional biopsy revealed infiltration of plasma cells with anaplastic features, consistent with solitary plasmacytoma (PC). Serum analysis showed elevation of serum free lambda light chain levels (27.78 mg/l), with an abnormally high kappa:lambda ratio (2.33) and high total proteins (10.4 g/dl). Serum protein electrophoresis revealed an M spike in the gamma-globulin region (56.1 %=5.8 g/dl). Subsequently, 18 F-FDG PET/CT revealed another hypermetabolic mass in the right lobe of the liver. CT-guided biopsy of the liver lesion revealed plasma cell myeloma, consistent with multiple myeloma. Multiple myeloma presenting as nodular liver masses is very rare in clinical practice. In a retrospective review of more than 2,000 patients, Talamo et al. reported only nine cases where there was nodular involvement of the liver by multiple myeloma. The organ most commonly involved was the liver, followed by pancreas, stomach, peritoneum with malignant ascites, colon, rectum, duodenum and ileum. Therefore, the literature published thus far has been limited to a few reports and case series. Among these reports, some had demonstrated the PET or PET/CT findings of nodular liver involvement of multiple myeloma. About 10 % of the solitary myelomas appeared as extramedullary PC or solitary PC of bone. In spite of the advances in therapy, the treatment of multiple myeloma is still palliative. However, solitary PC could be cured by resection or radiation therapy. Thus, differentiation between PC and multiple myeloma is essential in making a decision for the appropriate therapeutic regimen. 18 F-FDG PET/CT has the unique ability to detect and characterize malignant lesions in one single examination. Schirrmeister et al. reported that 18 F-FDG PET revealed

Does lack of resources impair access to breast and cervical cancer screening in Japan?

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Sano, Hiroshi; Goto, Rei; Hamashima, Chisato

2017-01-01

To assess the impact of the quantity of resources for breast and cervical cancer screening on the participation rates in screening in clinical settings in municipalities, as well as to clarify whether lack of resources impairs access to cancer screening in Japan. Of the 1,746 municipalities in 2010, 1,443 (82.6%) and 1,469 (84.1%) were included in the analyses for breast and cervical cancer screening, respectively. In order to estimate the effects of the number of mammography units and of gynecologists on the participation rates in breast and cervical cancer screening in clinical settings, multiple regression analyses were performed using the interaction term for urban municipalities. The average participation rate in screening in clinical settings was 6.01% for breast cancer, and was 8.93% for cervical cancer. The marginal effect of the number of mammography units per 1,000 women was significantly positive in urban municipalities (8.20 percent point). The marginal effect of the number of gynecologists per 1,000 women was significantly positive in all municipalities (2.54 percent point) and rural municipalities (3.68 percent point). Lack of mammography units in urban areas and of gynecologists particularly in rural areas impaired access to breast and cervical cancer screening. Strategies are required that quickly improve access for the residents and increase their participation rates in cancer screening.

Interesting images: Multiple coronary artery aneurysms.

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Howard, Jonathon M; Viswanath, Omar; Armas, Alfredo; Santana, Orlando; Rosen, Gerald P

2017-01-01

We present the case of a 65-year-old male who presented with stable angina and dyspnea on exertion. His initial workup yielded a positive treadmill stress test for reversible apical ischemia, and transthoracic echocardiogram demonstrated impaired systolic function. Cardiac catheterization was then performed, revealing severe atherosclerotic disease including multiple coronary artery aneurysms. As a result, the patient was advised to and subsequently underwent a coronary artery bypass graft. This case highlights the presence of multiple coronary artery aneurysms and the ability to appreciate these pathologic findings on multiple imaging modalities, including coronary angiogram, transesophageal echocardiography, and direct visualization through the surgical field.

Diffractive scattering on nuclei in multiple scattering theory with inelastic screening

International Nuclear Information System (INIS)

Zoller, V.R.

1988-01-01

The cross sections for the diffractive scattering of hadrons on nuclei are calculated in the two-channel approximation of multiple scattering theory. In contrast to the standard Glauber approach, it is not assumed that the nucleon scattering profile is a Gaussian or that the Regge radius of the hadron is small compared to the nuclear radius. The AGK Reggeon diagrammatic technique is used to calculate the topological cross sections and the cross sections for coherent and incoherent diffractive dissociation and quasielastic scattering. The features of hadron-nucleus scattering at superhigh energies are discussed

High-content screening of small compounds on human embryonic stem cells.

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Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

2010-08-01

Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

Multiple endocrine neoplasia type 2: achievements and current challenges

Directory of Open Access Journals (Sweden)

Andreas Machens

2012-01-01

Full Text Available Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations.

Human mast cell tryptase: Multiple cDNAs and genes reveal a multigene serine protease family

International Nuclear Information System (INIS)

Vanderslice, P.; Ballinger, S.M.; Tam, E.K.; Goldstein, S.M.; Craik, C.S.; Caughey, G.H.

1990-01-01

Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C-terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the ∼1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5' regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These findings provide genetic evidence that human mast cell tryptases are the products of a multigene family

Searching for Celiac Disease Screening-detected celiac disease in an HLA-genotyped birth cohort

OpenAIRE

Björck, Sara

2015-01-01

Objectives: Celiac disease is a common immune mediated enteropathy strongly associated with HLA-DQB1*02 (DQ2), *0302 (DQ8), or both and the presence of tissue transglutaminase autoantibodies (tTGA). Prevalence studies have revealed that most affected individuals go undetected because of subclinical signs or being asymptomatic rendering screening a method for identification. However, less is known about subclinical manifestations of screening-detected celiac disease during childhood and if the...

Multiple Realizability and Biological Laws

NARCIS (Netherlands)

Raerinne, Jani P.; Eronen, Markus I.

2012-01-01

We critically analyze Alexander Rosenberg's argument based on the multiple realizability of biological properties that there are no biological laws. The argument is intuitive and suggestive. Nevertheless, a closer analysis reveals that the argument rests on dubious assumptions about the nature of

Prenatal screening and genetics

DEFF Research Database (Denmark)

Alderson, P; Aro, A R; Dragonas, T

2001-01-01

Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

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Keiko Rausch

2017-01-01

Full Text Available Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition. Importantly, we identified nanchangmycin as a potent inhibitor of Zika virus entry across all cell types tested, including physiologically relevant primary cells. Nanchangmycin also was active against other medically relevant viruses, including West Nile, dengue, and chikungunya viruses that use a similar route of entry. This study provides a resource of small molecules to study Zika virus pathogenesis.

Products of cells from gliomas: VIII. Multiple-well immunoperoxidase assay of immunoreactivity of primary hybridoma supernatants with human glioma and brain tissue and cultured glioma cells.

Science.gov (United States)

McKeever, P E; Wahl, R L; Shakui, P; Jackson, G A; Letica, L H; Liebert, M; Taren, J A; Beierwaltes, W H; Hoff, J T

1990-06-01

To test the feasibility of primary screening of hybridoma supernatants against human glioma tissue, over 5000 combinations of hybridoma supernatants with glioma tissue, cultured glioma cells, and normal central neural tissue were screened with a new multiple-well (M-well) screening system. This is an immunoperoxidase assay system with visual endpoints for screening 20-30 hybridoma supernatants per single microscope slide. There were extensive differences between specificities to tissue and to cultured glioma cells when both were screened with M-wells and when cultured cells were screened with standard semi-automated fluorescence. Primary M-well screening with glioma tissue detected seven hybridoma supernatants that specifically identified parenchymal cells of glioma tissue and that were not detected with cultured cells. Immunoreactivities of individual supernatants for vascular components (nine supernatants), necrosis (five supernatants), and nuclei (three supernatants) were detected. Other supernatants bound multiple sites on glioma tissue and/or subpopulations of neurons and glia of normal tissue. The results show that primary screening with glioma tissue detects a number of different specificities of hybridoma supernatants to gliomas not detected by conventional screening with cultured cells. These are potentially applicable to diagnosis and therapy.

Multiple Intelligences and Perfectionism in Middle School Gifted Students

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Süleyman KAHRAMAN

2016-12-01

Full Text Available In this study, the perfectionism levels of 181 sixth, seventh, and eighth grade gifted students’ were investigated in terms of multiple intelligences. In the study a relational screening model, Survey of Positive and Negative Perfectionism, developed by Kırdök (2004, was used to assess the level of the students’ positive and negative perfectionism. The Multiple Intelligences Inventory, developed by Saban (2001, was used to determine the students’ multiple intelligences, and a personal information form was implemented to obtain socio-demographic data. The results of the study showed that [verbal-linguistic intelligence, mathematical-logical intelligence, and intrapersonal intelligence] [intrapersonal intelligence, mathematical-logical intelligence, and verbal-linguistic intelligence] predicted 34% of the students’ perfectionism levels (p<.001. The explanatory power of the scores in multiple intelligences over negative perfectionism was not found to be statistically significant for any of the sub-dimensions. In order to develop gifted students’ positive perfectionism qualifications, assuming that multiple intelligences can be used as a tool, some suggestions were presented for researchers, counselors, and teachers.

Developmental Screening Disparities for Languages Other than English and Spanish.

Science.gov (United States)

Knuti Rodrigues, Kristine; Hambidge, Simon J; Dickinson, Miriam; Richardson, Douglas B; Davidson, Arthur J

2016-01-01

Limited English proficiency (LEP) is a known barrier to preventive care. Children from families with LEP face socioeconomic circumstances associated with increased odds of developmental delays and decreased participation in early care and education programs. Little is known about developmental surveillance and screening for children from families who speak languages other than English and Spanish. We sought to compare developmental surveillance and screening at well-child visits (WCVs) by preferred parental language. Using a retrospective cohort (n = 15,320) of children aged 8 to 40 months with ≥2 WCVs from January 1, 2006, to July 1, 2010, in a community health system, 450 children from 3 language groups (150 English, 150 Spanish, and 150 non-English, non-Spanish) were randomly selected. Chart review assessed 2 primary outcomes, developmental surveillance at 100% of WCVs and screened with a standardized developmental screening tool, and also determined whether children were referred for diagnostic developmental evaluation. Bivariate and multiple logistic regression analyses were conducted. Compared to the English-speaking group, the non-English, non-Spanish group had lower odds of receiving developmental surveillance at 100% of WCVs (odds ratio, 0.3; 95% confidence interval, 0.2, 0.5) and of being screened with a standardized developmental screening tool (odds ratio, 0.1; 95% confidence interval, 0.1, 0.2). There were no differences between the English- and Spanish-speaking groups. Though underpowered, no differences were found for referral. Improved developmental surveillance and screening are needed for children from families who speak languages other than English and Spanish. Lack of statistically significant differences between English- and Spanish-speaking groups suggests that improved translation and interpretation resources may decrease disparities. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

A genetic screen reveals Arabidopsis stomatal and/or apoplastic defenses against Pseudomonas syringae pv. tomato DC3000.

Directory of Open Access Journals (Sweden)

Weiqing Zeng

2011-10-01

Full Text Available Bacterial infection of plants often begins with colonization of the plant surface, followed by entry into the plant through wounds and natural openings (such as stomata, multiplication in the intercellular space (apoplast of the infected tissues, and dissemination of bacteria to other plants. Historically, most studies assess bacterial infection based on final outcomes of disease and/or pathogen growth using whole infected tissues; few studies have genetically distinguished the contribution of different host cell types in response to an infection. The phytotoxin coronatine (COR is produced by several pathovars of Pseudomonas syringae. COR-deficient mutants of P. s. tomato (Pst DC3000 are severely compromised in virulence, especially when inoculated onto the plant surface. We report here a genetic screen to identify Arabidopsis mutants that could rescue the virulence of COR-deficient mutant bacteria. Among the susceptible to coronatine-deficient Pst DC3000 (scord mutants were two that were defective in stomatal closure response, two that were defective in apoplast defense, and four that were defective in both stomatal and apoplast defense. Isolation of these three classes of mutants suggests that stomatal and apoplastic defenses are integrated in plants, but are genetically separable, and that COR is important for Pst DC3000 to overcome both stomatal guard cell- and apoplastic mesophyll cell-based defenses. Of the six mutants defective in bacterium-triggered stomatal closure, three are defective in salicylic acid (SA-induced stomatal closure, but exhibit normal stomatal closure in response to abscisic acid (ABA, and scord7 is compromised in both SA- and ABA-induced stomatal closure. We have cloned SCORD3, which is required for salicylic acid (SA biosynthesis, and SCORD5, which encodes an ATP-binding cassette (ABC protein, AtGCN20/AtABCF3, predicted to be involved in stress-associated protein translation control. Identification of SCORD5 begins to

Breast cancer knowledge, attitudes and screening behaviors among Indian-Australian women.

Science.gov (United States)

Kwok, C; Tranberg, R; Lee, F C

2015-12-01

The aims of the study were to report breast cancer screening practices among Indian-Australian women and to examine the relationship between demographic characteristics, cultural beliefs and women's breast cancer screening (BCS) behaviors. A descriptive and cross-sectional method was used. Two hundred and forty two Indian-Australian women were recruited from several Indian organizations. English versions of the Breast Cancer Screening Beliefs Questionnaire (BCSBQ) were administered. The main research variables are BCS practices, demographic characteristics and total scores on each of the BCSBQ subscales. The majority of participants (72.7%-81.4%) had heard of breast awareness, clinical breast examination (CBE) and mammograms. Only 28.9% performed a BSE monthly and although 60% had practiced CBE, only 27.3% of women within the targeted age group had annual CBE. Only 23.6% of women within the targeted age group reported they had a mammogram biennial. Marital status and length of stay in Australia were positively associated with women's screening behaviors. In terms of BCSBQ score, women who had the three screening practices regularly as recommended obtained significantly higher scores on the "attitude towards general health check-ups" and "barriers to mammographic screening" subscales. There was a significant difference in the mean score of the "knowledge and perceptions about breast cancer" between women who did and who did not engage in breast awareness. Our study reveals that attitudes toward health check-ups and perceived barriers to mammographic screening were influential in determining compliance with breast cancer screening practices among Indian-Australian women. Copyright © 2015 Elsevier Ltd. All rights reserved.

Developing a novel fiber optic fluorescence device for multiplexed high-throughput cytotoxic screening.

Science.gov (United States)

Lee, Dennis; Barnes, Stephen

2010-01-01

The need for new pharmacological agents is unending. Yet the drug discovery process has changed substantially over the past decade and continues to evolve in response to new technologies. There is presently a high demand to reduce discovery time by improving specific lab disciplines and developing new technology platforms in the area of cell-based assay screening. Here we present the developmental concept and early stage testing of the Ab-Sniffer, a novel fiber optic fluorescence device for high-throughput cytotoxicity screening using an immobilized whole cell approach. The fused silica fibers are chemically functionalized with biotin to provide interaction with fluorescently labeled, streptavidin functionalized alginate-chitosan microspheres. The microspheres are also functionalized with Concanavalin A to facilitate binding to living cells. By using lymphoma cells and rituximab in an adaptation of a well-known cytotoxicity protocol we demonstrate the utility of the Ab-Sniffer for functional screening of potential drug compounds rather than indirect, non-functional screening via binding assay. The platform can be extended to any assay capable of being tied to a fluorescence response including multiple target cells in each well of a multi-well plate for high-throughput screening.

Automatic Generation of User Interface Layouts for Alternative Screen Orientations

OpenAIRE

Zeidler , Clemens; Weber , Gerald; Stuerzlinger , Wolfgang; Lutteroth , Christof

2017-01-01

Part 1: Adaptive Design and Mobile Applications; International audience; Creating multiple layout alternatives for graphical user interfaces to accommodate different screen orientations for mobile devices is labor intensive. Here, we investigate how such layout alternatives can be generated automatically from an initial layout. Providing good layout alternatives can inspire developers in their design work and support them to create adaptive layouts. We performed an analysis of layout alternat...

Rapid recombination mapping for high-throughput genetic screens in Drosophila.

Science.gov (United States)

Sapiro, Anne L; Ihry, Robert J; Buhr, Derek L; Konieczko, Kevin M; Ives, Sarah M; Engstrom, Anna K; Wleklinski, Nicholas P; Kopish, Kristin J; Bashirullah, Arash

2013-12-09

Mutagenesis screens are a staple of classical genetics. Chemical-induced mutations, however, are often difficult and time-consuming to identify. Here, we report that recombination analysis with pairs of dominant visible markers provides a rapid and reliable strategy to map mutations in Drosophila melanogaster. This method requires only two generations and a total of six crosses in vials to estimate the genetic map position of the responsible lesion with high accuracy. This genetic map position can then be reliably used to identify the mutated gene through complementation testing with an average of nine deficiencies and Sanger sequencing. We have used this approach to successfully map a collection of mutations from an ethyl methanesulfonate-based mutagenesis screen on the third chromosome. We propose that this method also may be used in conjunction with whole-genome sequencing, particularly when multiple independent alleles of the mutated locus are not available. By facilitating the rapid identification of mutated genes, our mapping strategy removes a primary obstacle to the widespread use of powerful chemical mutagenesis screens to understand fundamental biological phenomena.

The mediating role of the home environment in relation to parental educational level and preschool children's screen time: a cross-sectional study.

Science.gov (United States)

Määttä, Suvi; Kaukonen, Riikka; Vepsäläinen, Henna; Lehto, Elviira; Ylönen, Anna; Ray, Carola; Erkkola, Maijaliisa; Roos, Eva

2017-09-02

Previous studies suggest that preschoolers from low socioeconomic backgrounds engage in more screen time. Still, the factors in the social and physical home environment driving these differences in preschool children's screen time are poorly understood. This study examines potential home environment mediators in the associations between parental educational level and preschoolers' screen time. A total of 864 children aged 3-6 years and their parents participated in a cross-sectional DAGIS study in 2015-2016. Parents recorded their children's screen time in a diary (N = 823). For the analyses, the daily average screen time at home was calculated. Parental questionnaires (N = 808) assessed educational level and eight social and physical environment factors in the home (i.e., descriptive norm for children's screen time, parental screen use in front of children, parental importance for limiting children's screen time, parental attitude toward societal pressures for children's screen time, access to screens at home, parental self-efficacy for limiting children's screen time, satisfaction of children's screen time, and rules for limiting children's screen time). Parental education was grouped into low, middle, and high education. The associations were tested by conducting mediation analyses adjusted by season and children's sex and age. The significant mediators in the single-mediator models were included in the final multiple-mediator models. Of the potential eight mediators, the following four had a significant indirect association: descriptive norm for children's screen time, parental screen use in front of children, parental importance for limiting children's screen time, and parental attitude toward societal pressures for children's screen time. Parents with high education had lower descriptive norm and used fewer screens in front of children compared to parents with middle or low education, and in turn, these factors were associated with less screen time among

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

Analysis of previous screening examinations for patients with breast cancer

International Nuclear Information System (INIS)

Lee, Eun Hye; Cha, Joo Hee; Han, Dae Hee; Choi, Young Ho; Hwang, Ki Tae; Ryu, Dae Sik; Kwak, Jin Ho; Moon, Woo Kyung

2007-01-01

We wanted to improve the quality of subsequent screening by reviewing the previous screening of breast cancer patients. Twenty-four breast cancer patients who underwent previous screening were enrolled. All 24 took mammograms and 15 patients also took sonograms. We reviewed the screening retrospectively according to the BI-RADS criteria and we categorized the results into false negative, true negative, true positive and occult cancers. We also categorized the causes of false negative cancers into misperception, misinterpretation and technical factors and then we analyzed the attributing factors. Review of the previous screening revealed 66.7% (16/24) false negative, 25.0% (6/24) true negative, and 8.3% (2/24) true positive cancers. False negative cancers were caused by the mammogram in 56.3% (9/16) and by the sonogram in 43.7% (7/16). For the false negative cases, all of misperception were related with mammograms and this was attributed to dense breast, a lesion located at the edge of glandular tissue or the image, and findings seen on one view only. Almost all misinterpretations were related with sonograms and attributed to loose application of the final assessment. To improve the quality of breast screening, it is essential to overcome the main causes of false negative examinations, including misperception and misinterpretation. We need systematic education and strict application of final assessment categories of BI-RADS. For effective communication among physicians, it is also necessary to properly educate them about BI-RADS

Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

Science.gov (United States)

Rodriguez-Ruiz, A; Etxebarria, J; Boatti, L; Marigómez, I

2015-09-01

Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

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

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

Science.gov (United States)

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

2018-03-01

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

Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

Science.gov (United States)

Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

2017-03-01

In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mini Screening of Kinase Inhibitors Affecting Period-length of Mammalian Cellular Circadian Clock

International Nuclear Information System (INIS)

Yagita, Kazuhiro; Yamanaka, Iori; Koinuma, Satoshi; Shigeyoshi, Yasufumi; Uchiyama, Yasuo

2009-01-01

In mammalian circadian rhythms, the transcriptional-translational feedback loop (TTFL) consisting of a set of clock genes is believed to elicit the circadian clock oscillation. The TTFL model explains that the accumulation and degradation of mPER and mCRY proteins control the period-length (tau) of the circadian clock. Although recent studies revealed that the Casein Kinase Iεδ (CKIεδ) regurates the phosphorylation of mPER proteins and the circadian period-length, other kinases are also likely to contribute the phosphorylation of mPER. Here, we performed small scale screening using 84 chemical compounds known as kinase inhibitors to identify candidates possibly affecting the circadian period-length in mammalian cells. Screening by this high-throughput real-time bioluminescence monitoring system revealed that the several chemical compounds apparently lengthened the cellular circadian clock oscillation. These compounds are known as inhibitors against kinases such as Casein Kinase II (CKII), PI3-kinase (PI3K) and c-Jun N-terminal Kinase (JNK) in addition to CKIεδ. Although these kinase inhibitors may have some non-specific effects on other factors, our mini screening identified new candidates contributing to period-length control in mammalian cells

Carrier screening in the era of expanding genetic technology.

Science.gov (United States)

Arjunan, Aishwarya; Litwack, Karen; Collins, Nick; Charrow, Joel

2016-12-01

The Center for Jewish Genetics provides genetic education and carrier screening to individuals of Jewish descent. Carrier screening has traditionally been performed by targeted mutation analysis for founder mutations with an enzyme assay for Tay-Sachs carrier detection. The development of next-generation sequencing (NGS) allows for higher detection rates regardless of ethnicity. Here, we explore differences in carrier detection rates between genotyping and NGS in a primarily Jewish population. Peripheral blood samples or saliva samples were obtained from 506 individuals. All samples were analyzed by sequencing, targeted genotyping, triplet-repeat detection, and copy-number analysis; the analyses were carried out at Counsyl. Of 506 individuals screened, 288 were identified as carriers of at least 1 condition and 8 couples were carriers for the same disorder. A total of 434 pathogenic variants were identified. Three hundred twelve variants would have been detected via genotyping alone. Although no additional mutations were detected by NGS in diseases routinely screened for in the Ashkenazi Jewish population, 26.5% of carrier results and 2 carrier couples would have been missed without NGS in the larger panel. In a primarily Jewish population, NGS reveals a larger number of pathogenic variants and provides individuals with valuable information for family planning.Genet Med 18 12, 1214-1217.

Cancer screening guidelines.

Science.gov (United States)

Zoorob, R; Anderson, R; Cefalu, C; Sidani, M

2001-03-15

Numerous medical organizations have developed cancer screening guidelines. Faced with the broad, and sometimes conflicting, range of recommendations for cancer screening, family physicians must determine the most reasonable and up-to-date method of screening. Major medical organizations have generally achieved consensus on screening guidelines for breast, cervical and colorectal cancer. For breast cancer screening in women ages 50 to 70, clinical breast examination and mammography are generally recommended every one or two years, depending on the medical organization. For cervical cancer screening, most organizations recommend a Papanicolaou test and pelvic examination at least every three years in patients between 20 and 65 years of age. Annual fecal occult blood testing along with flexible sigmoidoscopy at five-year to 10-year intervals is the standard recommendation for colorectal cancer screening in patients older than 50 years. Screening for prostate cancer remains a matter of debate. Some organizations recommend digital rectal examination and a serum prostate-specific antigen test for men older than 50 years, while others do not. In the absence of compelling evidence to indicate a high risk of endometrial cancer, lung cancer, oral cancer and ovarian cancer, almost no medical organizations have developed cancer screening guidelines for these types of cancer.

Effect of providing risk information on undergoing cervical cancer screening: a randomized controlled trial.

Science.gov (United States)

Fujiwara, Hiroyuki; Shimoda, Akihiro; Ishikawa, Yoshiki; Taneichi, Akiyo; Ohashi, Mai; Takahashi, Yoshifumi; Koyanagi, Takahiro; Morisawa, Hiroyuki; Takahashi, Suzuyo; Sato, Naoto; Machida, Shizuo; Takei, Yuji; Saga, Yasushi; Suzuki, Mitsuaki

2015-01-01

In Japan, the cervical cancer screening rate is extremely low. Towards improving the cervical cancer screening rate, encouraging eligible people to make an informed choice, which is a decision-making process that relies on beliefs informed by adequate information about the possible benefits and risks of screening, has attracted increased attention in the public health domain. However, there is concern that providing information on possible risks of screening might prevent deter from participating. In total, 1,912 women aged 20-39 years who had not participated in screening in the fiscal year were selected from a Japanese urban community setting. Participants were randomly divided into 3 groups. Group A received a printed reminder with information about the possible benefits of screening, group B received a printed reminder with information about possible benefits and risks, and group C received a printed reminder with simple information only (control group). Out of 1,912 participants, 169 (8.8%) participated in cervical cancer screening. In the intervention groups, 137 (10.9%) participated in cervical cancer screening, compared to only 32 (4.9%) of the control group (p < 0.001). In addition, logistic regression analysis revealed that there was no significant difference in screening rate between group A and group B (p = 0.372). Providing information on the possible risks of screening may not prevent people from taking part in cervical cancer screening among a Japanese non-adherent population.

Heterointerface Screening Effects between Organic Monolayers and Monolayer Transition Metal Dichalcogenides

KAUST Repository

Zheng, Yu Jie; Huang, Yu Li; Chen, Yifeng; Zhao, Weijie; Eda, Goki; Spataru, Catalin D.; Zhang, Wenjing; Chang, Yung-Huang; Li, Lain-Jong; Chi, Dongzhi; Quek, Su Ying; Wee, Andrew Thye Shen

2016-01-01

© 2016 American Chemical Society. The nature and extent of electronic screening at heterointerfaces and their consequences on energy level alignment are of profound importance in numerous applications, such as solar cells, electronics etc. The increasing availability of two-dimensional (2D) transition metal dichalcogenides (TMDs) brings additional opportunities for them to be used as interlayers in "van der Waals (vdW) heterostructures" and organic/inorganic flexible devices. These innovations raise the question of the extent to which the 2D TMDs participate actively in dielectric screening at the interface. Here we study perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) monolayers adsorbed on single-layer tungsten diselenide (WSe2), bare graphite, and Au(111) surfaces, revealing a strong dependence of the PTCDA HOMO-LUMO gap on the electronic screening effects from the substrate. The monolayer WSe2 interlayer provides substantial, but not complete, screening at the organic/inorganic interface. Our results lay a foundation for the exploitation of the complex interfacial properties of hybrid systems based on TMD materials.

Do Physician Recommendations for Colorectal Cancer Screening Differ by Patient Age?

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Maida J Sewitch

2007-01-01

Full Text Available Colorectal cancer screening is underutilized, resulting in preventable morbidity and mortality. In the present study, age-related and other disparities associated with physicians’ delivery of colorectal cancer screening recommendations were examined. The present cross-sectional study included 43 physicians and 618 of their patients, aged 50 to 80 years, without past or present colorectal cancer. Of the 285 screen-eligible patients, 45% received a recommendation. Multivariate analyses revealed that, compared with younger nonde-pressed patients, older depressed patients were less likely to receive fecal occult blood test recommendations, compared with no recommendation (OR=0.31, 95% CI 0.09 to 1.02, as well as less likely to receive colonoscopy recommendations, compared with no recommendation (OR=0.14; 95% CI 0.03 to 0.66. Comorbidity and marital status were associated with delivery of fecal occult blood test and colonoscopy recommendations, respectively, compared with no recommendation. In summary, patient age and other characteristics appeared to influence physicians’ delivery of colorectal cancer screening and choice of modality.

Heterointerface Screening Effects between Organic Monolayers and Monolayer Transition Metal Dichalcogenides

KAUST Repository

Zheng, Yu Jie

2016-01-21

© 2016 American Chemical Society. The nature and extent of electronic screening at heterointerfaces and their consequences on energy level alignment are of profound importance in numerous applications, such as solar cells, electronics etc. The increasing availability of two-dimensional (2D) transition metal dichalcogenides (TMDs) brings additional opportunities for them to be used as interlayers in "van der Waals (vdW) heterostructures" and organic/inorganic flexible devices. These innovations raise the question of the extent to which the 2D TMDs participate actively in dielectric screening at the interface. Here we study perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) monolayers adsorbed on single-layer tungsten diselenide (WSe2), bare graphite, and Au(111) surfaces, revealing a strong dependence of the PTCDA HOMO-LUMO gap on the electronic screening effects from the substrate. The monolayer WSe2 interlayer provides substantial, but not complete, screening at the organic/inorganic interface. Our results lay a foundation for the exploitation of the complex interfacial properties of hybrid systems based on TMD materials.

Thyroid in pregnancy: From physiology to screening.

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Springer, Drahomira; Jiskra, Jan; Limanova, Zdenka; Zima, Tomas; Potlukova, Eliska

2017-03-01

Thyroid hormones are crucial for the growth and maturation of many target tissues, especially the brain and skeleton. During critical periods in the first trimester of pregnancy, maternal thyroxine is essential for fetal development as it supplies thyroid hormone-dependent tissues. The ontogeny of mature thyroid function involves organogenesis, and maturation of the hypothalamus, pituitary and the thyroid gland; and it is almost complete by the 12th-14th gestational week. In case of maternal hypothyroidism, substitution with levothyroxine must be started in early pregnancy. After the 14th gestational week, fetal brain development may already be irreversibly affected by lack of thyroid hormones. The prevalence of manifest hypothyroidism in pregnancy is about 0.3-0.5%. The prevalence of subclinical hypothyroidism varies between 4 and 17%, strongly depending on the definition of the upper TSH cutoff limit. Hyperthyroidism occurs in 0.1-1% of all pregnancies. Positivity for antibodies against thyroid peroxidase (TPOAb) is common in women of childbearing age with an incidence rate of 5.1-12.4%. TPOAb-positivity may be regarded as a manifestation of a general autoimmune state which may alter the fertilization and implantation processes or cause early missed abortions. Women positive for TPOAb are at a significant risk of developing hypothyroidism during pregnancy and postpartum. Laboratory diagnosis of thyroid dysfunction during pregnancy is based upon serum TSH concentration. TSH in pregnancy is physiologically lower than the non-pregnant population. Results of multiple international studies point toward creation of trimester-specific reference intervals for TSH in pregnancy. Screening for hypothyroidism in pregnancy is controversial and its implementation varies from country to country. Currently, the case-finding approach of screening high-risk women is preferred in most countries to universal screening. However, numerous studies have shown that one-third to one

Implementation of the first worldwide quality assurance program for cystic fibrosis multiple mutation detection in population-based screening.

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Earley, Marie C; Laxova, Anita; Farrell, Philip M; Driscoll-Dunn, Rena; Cordovado, Suzanne; Mogayzel, Peter J; Konstan, Michael W; Hannon, W Harry

2011-07-15

CDC's Newborn Screening Quality Assurance Program collaborated with several U.S. Cystic Fibrosis Care Centers to collect specimens for development of a molecular CFTR proficiency testing program using dried-blood spots for newborn screening laboratories. Adult and adolescent patients or carriers donated whole blood that was aliquoted onto filter paper cards. Five blind-coded specimens were sent to participating newborn screening laboratories quarterly. Proficiency testing results were evaluated based on presumptive clinical assessment. Individual evaluations and summary reports were sent to each participating laboratory and technical consultations were offered if incorrect assessments were reported. The current CDC repository contains specimens with 39 different CFTR mutations. Up to 45 laboratories have participated in the program. Three years of data showed that correct assessments were reported 97.7% of the time overall when both mutations could be determined. Incorrect assessments that could have lead to a missed case occurred 0.9% of the time, and no information was reported 1.1% of the time due to sample failure. Results show that laboratories using molecular assays to detect CFTR mutations are performing satisfactorily. The programmatic results presented demonstrate the importance and complexity of providing proficiency testing for DNA-based assays. Published by Elsevier B.V.

Screening sealed bottles for liquid explosives

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Kumar, Sankaran; McMichael, W. Casey; Kim, Y.-W.; Sheldon, Alan G.; Magnuson, Erik E.; Ficke, L.; Chhoa, T. K.; Moeller, C. R.; Barrall, Geoffrey A.; Burnett, Lowell J.; Czipott, Peter V.; Pence, J. S.; Skvoretz, David C.

1997-01-01

A particularly disturbing development affecting transportation safety and security is the increasing use of terrorist devices which avoid detection by conventional means through the use of liquid explosives and flammables. The hazardous materials are generally hidden in wine or liquor bottles that cannot be opened routinely for inspection. This problem was highlighted by the liquid explosives threat which disrupted air traffic between the US an the Far East for an extended period in 1995. Quantum Magnetics has developed a Liquid Explosives Screening systems capable of scanning unopened bottles for liquid explosives. The system can be operated to detect specific explosives directly or to verify the labeled or bar-coded contents of the container. In this system, magnetic resonance (MR) is used to interrogate the liquid. MR produces an extremely rich data set and many characteristics of the MR response can be determined simultaneously. As a result, multiple MR signatures can be defined for any given set of liquids, and the signature complexity then selected according to the level of threat. The Quantum Magnetics Liquid Explosives Screening System is currently operational. Following extensive laboratory testing, a field trial of the system was carried out at the Los Angeles International Airport.

Examining the Influence of Cost Concern and Awareness of Low-cost Health Care on Cancer Screening among the Medically Underserved.

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Best, Alicia L; Strane, Alcha; Christie, Omari; Bynum, Shalanda; Wiltshire, Jaqueline

2017-01-01

African Americans suffer a greater burden of mortality from breast, cervical, and colorectal cancers than other groups in the United States. Early detection through timely screening can improve survival outcomes; however, cost is frequently reported as a barrier to screening. Federally qualified health centers (FQHCs) provide preventive and primary care to underserved populations regardless of ability to pay, positioning them to improve cancer screening rates. The purpose of this study was to examine the influence of concern about health care cost (cost concern) and awareness of low-cost health care (awareness) on cancer screening among 236 African Americans within an FQHC service area using self-report surveys. Multiple logistic regression indicated that awareness was positively associated with cervical and colorectal cancer screening, while cost concern was negatively associated with mammography screening. Results indicate that improving awareness and understanding of low-cost health care could increase cancer screening among underserved African Americans.

"Is It Worth Knowing?" Focus Group Participants' Perceived Utility of Genomic Preconception Carrier Screening.

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Schneider, Jennifer L; Goddard, Katrina A B; Davis, James; Wilfond, Benjamin; Kauffman, Tia L; Reiss, Jacob A; Gilmore, Marian; Himes, Patricia; Lynch, Frances L; Leo, Michael C; McMullen, Carmit

2016-02-01

As genome sequencing technology advances, research is needed to guide decision-making about what results can or should be offered to patients in different clinical settings. We conducted three focus groups with individuals who had prior preconception genetic testing experience to explore perceived advantages and disadvantages of genome sequencing for preconception carrier screening, compared to usual care. Using a discussion guide, a trained qualitative moderator facilitated the audio-recorded focus groups. Sixteen individuals participated. Thematic analysis of transcripts started with a grounded approach and subsequently focused on participants' perceptions of the value of genetic information. Analysis uncovered two orientations toward genomic preconception carrier screening: "certain" individuals desiring all possible screening information; and "hesitant" individuals who were more cautious about its value. Participants revealed valuable information about barriers to screening: fear/anxiety about results; concerns about the method of returning results; concerns about screening necessity; and concerns about partner participation. All participants recommended offering choice to patients to enhance the value of screening and reduce barriers. Overall, two groups of likely users of genome sequencing for preconception carrier screening demonstrated different perceptions of the advantages or disadvantages of screening, suggesting tailored approaches to education, consent, and counseling may be warranted with each group.

Ductal carcinoma in a multiple fibroadenoma: Diagnostic inaccuracies

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Rao Shalinee

2010-01-01

Full Text Available We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.

Ductal carcinoma in a multiple fibroadenoma: diagnostic inaccuracies.

Science.gov (United States)

Rao, Shalinee; Latha, P Suvarna; Ravi, A; Thanka, J

2010-01-01

We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.

Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening.

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Abdelsattar, Zaid M; Wong, Sandra L; Regenbogen, Scott E; Jomaa, Diana M; Hardiman, Karin M; Hendren, Samantha

2016-03-15

Although colorectal cancer (CRC) screening guidelines recommend initiating screening at age 50 years, the percentage of cancer cases in younger patients is increasing. To the authors' knowledge, the national treatment patterns and outcomes of these patients are largely unknown. The current study was a population-based, retrospective cohort study of the nationally representative Surveillance, Epidemiology, and End Results registry for patients diagnosed with CRC from 1998 through 2011. Patients were categorized as being younger or older than the recommended screening age. Differences with regard to stage of disease at diagnosis, patterns of therapy, and disease-specific survival were compared between age groups using multinomial regression, multiple regression, Cox proportional hazards regression, and Weibull survival analysis. Of 258,024 patients with CRC, 37,847 (15%) were aged Cancer Society.

Screening of ten advanced chickpea lines for blight and wilt resistance

International Nuclear Information System (INIS)

Jamil, F.F.; Haq, I.; Sarwar, N.; Alam, S.S.; Khan, J.A.; Hanif, M.; Khan, I.A.; Sarwar, M.; Haq, M.A.

2002-01-01

Ten advanced chickpea lines developed at NIAB were screened for resistance to Ascochyta blight and Fusarium wilt diseases in different sets of experiments conducted under controlled environment. Inoculation of plants by spore suspension of virulent strains of Ascochyta rabiei revealed that one line (97313) was resistant tolerant, two lines (97305, 97392) were tolerant, six lines (97306, 97310, 97311, 97303, 97302, 97393) were tolerant/susceptible and one line (97301) was susceptible. Screening of the same lines against Fusarium wilt by water culture method showed that two lines (97301, 97313) were moderately resistant, four lines (97302, 97303, 97306, 97393) were tolerant and the remaining four lines were susceptible. Screening through phytotoxic culture filtrates revealed that two lines (97302, 97313) were less sensitive to culture filtrates of Ascochyta rabiei and Fusarium oxysporum than the resistant check (CM88). These lines were also analyzed spectrophotometrically for peroxidase enzyme activity. Maximum enzyme activity was detected after 48 hours of inoculation with A. rabiei in three lines (97305, 97311, 97313) and resistant check (CM88) while enzyme activity in the remaining lines reached its maximum after 72 hours of inoculation which was comparable to the susceptible check (Pb-1). These studies lead to the conclusion that one line (97313) exhibited resistance against both the diseases and can be used as a source of resistance for further improvement of chickpea germplasm. (author)

Small molecule screening platform for assessment of cardiovascular toxicity on adult zebrafish heart

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Kitambi Satish

2012-03-01

Full Text Available Abstract Background Cardiovascular toxicity is a major limiting factor in drug development and requires multiple cost-effective models to perform toxicological evaluation. Zebrafish is an excellent model for many developmental, toxicological and regenerative studies. Using approaches like morpholino knockdown and electrocardiogram, researchers have demonstrated physiological and functional similarities between zebrafish heart and human heart. The close resemblance of the genetic cascade governing heart development in zebrafish to that of humans has propelled the zebrafish system as a cost-effective model to conduct various genetic and pharmacological screens on developing embryos and larvae. The current report describes a methodology for rapid isolation of adult zebrafish heart, maintenance ex vivo, and a setup to perform quick small molecule throughput screening, including an in-house implemented analysis script. Results Adult zebrafish were anesthetized and after rapid decapitation the hearts were isolated. The short time required for isolation of hearts allows dissection of multiple fishes, thereby obtaining a large sample size. The simple protocol for ex vivo culture allowed maintaining the beating heart for several days. The in-house developed script and spectral analyses allowed the readouts to be presented either in time domain or in frequency domain. Taken together, the current report offers an efficient platform for performing cardiac drug testing and pharmacological screens. Conclusion The new methodology presents a fast, cost-effective, sensitive and reliable method for performing small molecule screening. The variety of readouts that can be obtained along with the in-house developed analyses script offers a powerful setup for performing cardiac toxicity evaluation by researchers from both academics and industry.

Screening of Danish traffic cases for synthetic cannabinoids in whole blood by LC-MS/MS

DEFF Research Database (Denmark)

Holm, Niels Bjerre; Pineda, Rebeca; Andersen, David Wederkinck

2013-01-01

A target screening method for the detection of 13 synthetic cannabinoids in whole blood was developed and validated. Samples underwent automated solid-phase extraction, and sample extracts were analyzed by liquid chromatography-positive electrospray ionization-tandem mass spectrometry using two...... transitions in multiple reaction monitoring mode. The limit of detection was between 0.1-2.5 ng/mL for the compounds except HU-210, and extraction recovery ranged from 59 to 78%. The method was used to screen 393 Danish traffic cases from 2012, where the driver was suspected of driving under the influence...

Data integration and warehousing: coordination between newborn screening and related public health programs.

Science.gov (United States)

Therrell, Bradford L

2003-01-01

At birth, patient demographic and health information begin to accumulate in varied databases. There are often multiple sources of the same or similar data. New public health programs are often created without considering data linkages. Recently, newborn hearing screening (NHS) programs and immunization programs have virtually ignored the existence of newborn dried blood spot (DBS) newborn screening databases containing similar demographic data, creating data duplication in their 'new' systems. Some progressive public health departments are developing data warehouses of basic, recurrent patient information, and linking these databases to other health program databases where programs and services can benefit from such linkages. Demographic data warehousing saves time (and money) by eliminating duplicative data entry and reducing the chances of data errors. While newborn screening data are usually the first data available, they should not be the only data source considered for early data linkage or for populating a data warehouse. Birth certificate information should also be considered along with other data sources for infants that may not have received newborn screening or who may have been born outside of the jurisdiction and not have birth certificate information locally available. This newborn screening serial number provides a convenient identification number for use in the DBS program and for linking with other systems. As a minimum, data linkages should exist between newborn dried blood spot screening, newborn hearing screening, immunizations, birth certificates and birth defect registries.

Self-reported screen time and cardiometabolic risk in obese Dutch adolescents.

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Teatske M Altenburg

Full Text Available BACKGROUND: It is not clear whether the association between sedentary time and cardiometabolic risk exists among obese adolescents. We examined the association between screen time (TV and computer time and cardiometabolic risk in obese Dutch adolescents. METHODS AND FINDINGS: For the current cross-sectional study, baseline data of 125 Dutch overweight and obese adolescents (12-18 years participating in the Go4it study were included. Self-reported screen time (Activity Questionnaire for Adolescents and Adults and clustered and individual cardiometabolic risk (i.e. body composition, systolic and diastolic blood pressure, low-density (LDL-C, high-density (HDL-C and total cholesterol (TC, triglycerides, glucose and insulin were assessed in all participants. Multiple linear regression analyses were used to assess the association between screen time and cardiometabolic risk, adjusting for age, gender, pubertal stage, ethnicity and moderate-to-vigorous physical activity. We found no significant relationship between self-reported total screen time and clustered cardiometabolic risk or individual risk factors in overweight and obese adolescents. Unexpectedly, self-reported computer time, but not TV time, was slightly but significantly inversely associated with TC (B = -0.002; CI = [-0.003;-0.000] and LDL-C (B = -0.002; CI = [-0.001;0.000]. CONCLUSIONS: In obese adolescents we could not confirm the hypothesised positive association between screen time and cardiometabolic risk. Future studies should consider computer use as a separate class of screen behaviour, thereby also discriminating between active video gaming and other computer activities.

Breast cancer screening (BCS) chart: a basic and preliminary model for making screening mammography more productive and efficient.

Science.gov (United States)

Poorolajal, Jalal; Akbari, Mohammad Esmaeil; Ziaee, Fatane; Karami, Manoochehr; Ghoncheh, Mahshid

2017-05-15

The breast cancer screening (BCS) chart is suggested as a basic and preliminary tool to improve efficiency of screening mammography. We conducted this case-control study in 2016 and enrolled 1422 women aged 30-75 years, including 506 women with breast cancer (cases) and 916 women without breast cancer (controls). We developed the BCS chart using a multiple logistic regression analysis. We combined the risks of breast cancer to predict the individual risk of breast cancer. Then, we stratified and colored the predicted risk probabilities as follows: green), 05-09% (yellow), 10-14% (orange), 15-19% (red), 20-24% (brown) and ≥25% (black). The BCS chart provides the risk probability of breast cancer, based on age, body mass index, late menopause, having a benign breast disease and a positive family history of breast cancer among the first-degree or the second/third-degree relatives. According to this chart, an individual can be classified in a category of low risk (green), medium risk (yellow and orange), high risk (red and brown) and very high risk (black) for breast cancer. This chart is a flexible and easy to use tool that can detect high-risk subjects and make the screening program more efficient and productive. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Syphilis: an atypical case of sepsis and multiple anogenital lesions in secondary syphilis

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Nichole Smith

2016-10-01

Full Text Available The incidence of syphilis has historically been cyclical in nature, often in relation to the rise and fall of public health initiatives directed toward eradication along with social attitudes toward sexual practices. The incidence of syphilis has increased by 15% in the last 6 years in the United States, with similar increases worldwide. Herein, we present an atypical case of syphilis presenting with severe septic shock and multiple anogenital lesions in an immunocompetent host. A 22-year-old male with no significant past medical history presented with fevers, chills, sore throat, diaphoresis, and diarrhea. He was febrile, tachycardic, hypotensive, and unresponsive to fluid resuscitation requiring short-term vasopressor support. Physical exam revealed diffuse lymphadenopathy; lower extremity macular rash involving the soles of the feet; papular non-pustular lesions on the scrotum; and a 0.5 cm non-tender irregular, healing lesion on the shaft of the penis. Laboratory analysis was significant for leukocytosis and elevated creatinine. Serum screening rapid plasma reagin was positive, and further testing revealed a titer of 1:32, with confirmation via fluorescent treponemal antibody absorption test. The patient was diagnosed with secondary syphilis, which was determined to be the underlying etiology of the sepsis as all other serological evaluations were negative. He was treated with penicillin G benzathine 2.4 million units intramuscular and supportive management, with improvement of symptoms. The patient engaged in high-risk sexual behaviors, including prior unprotected sexual contact with males. New research indicates that up to one-third of patients may present with atypical cutaneous manifestations, as demonstrated by this patient. It is important for physicians to familiarize themselves with the varied clinical presentations of syphilis, which include multiple anogenital lesions and tender primary lesions in primary or secondary syphilis.

Breast Cancer Screening Programmes across the WHO European Region: Differences among Countries Based on National Income Level.

Science.gov (United States)