Evaluation of the Utility of Screening Mammography for High-Risk Women Undergoing Screening Breast MR Imaging.

PubMed

Lo, Glen; Scaranelo, Anabel M; Aboras, Hana; Ghai, Sandeep; Kulkarni, Supriya; Fleming, Rachel; Bukhanov, Karina; Crystal, Pavel

2017-10-01

Purpose To evaluate the value of mammography in detecting breast cancer in high-risk women undergoing screening breast magnetic resonance (MR) imaging. Materials and Methods An ethics-approved, retrospective review of prospective databases was performed to identify outcomes of 3934 screening studies (1977 screening MR imaging examinations and 1957 screening mammograms) performed between January 2012 and July 2014 in 1249 high-risk women. Performance measures including recall and cancer detection rates, sensitivity, specificity, and positive predictive values were calculated for both mammography and MR imaging. Results A total of 45 cancers (33 invasive and 12 ductal carcinomas in situ) were diagnosed, 43 were seen with MR imaging and 14 with both mammography and MR imaging. Additional tests (further imaging and/or biopsy) were recommended in 461 screening MR imaging studies (recall rate, 23.3%; 95% confidence interval [CI]: 21.5%, 25.2%), and mammography recalled 217 (recall rate, 11.1%; 95% CI: 9.7%, 12.6%). The cancer detection rate for MR imaging was 21.8 cancers per 1000 examinations (95% CI: 15.78, 29.19) and that for mammography was 7.2 cancers per 1000 examinations (95% CI: 3.92, 11.97; P < .001). Sensitivity and specificity of MR imaging were 96% and 78% respectively, and those of mammography were 31% and 89%, respectively (P < .001). Positive predictive value for MR imaging recalls was 9.3% (95% CI: 6.83%, 12.36%) and that for mammography recalls was 6.5% (95% CI: 3.57%, 10.59%). Conclusion Contemporaneous screening mammography did not have added value in detection of breast cancer for women who undergo screening MR imaging. Routine use of screening mammography in women undergoing screening breast MR imaging warrants reconsideration. © RSNA, 2017 Online supplemental material is available for this article.

High-performance and flexible thermoelectric films by screen printing solution-processed nanoplate crystals.

PubMed

Varghese, Tony; Hollar, Courtney; Richardson, Joseph; Kempf, Nicholas; Han, Chao; Gamarachchi, Pasindu; Estrada, David; Mehta, Rutvik J; Zhang, Yanliang

2016-09-12

Screen printing allows for direct conversion of thermoelectric nanocrystals into flexible energy harvesters and coolers. However, obtaining flexible thermoelectric materials with high figure of merit ZT through printing is an exacting challenge due to the difficulties to synthesize high-performance thermoelectric inks and the poor density and electrical conductivity of the printed films. Here, we demonstrate high-performance flexible films and devices by screen printing bismuth telluride based nanocrystal inks synthesized using a microwave-stimulated wet-chemical method. Thermoelectric films of several tens of microns thickness were screen printed onto a flexible polyimide substrate followed by cold compaction and sintering. The n-type films demonstrate a peak ZT of 0.43 along with superior flexibility, which is among the highest reported ZT values in flexible thermoelectric materials. A flexible thermoelectric device fabricated using the printed films produces a high power density of 4.1 mW/cm(2) with 60 °C temperature difference between the hot side and cold side. The highly scalable and low cost process to fabricate flexible thermoelectric materials and devices demonstrated here opens up many opportunities to transform thermoelectric energy harvesting and cooling applications.

High-performance and flexible thermoelectric films by screen printing solution-processed nanoplate crystals

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

Varghese, Tony; Hollar, Courtney; Richardson, Joseph

Screen printing allows for direct conversion of thermoelectric nanocrystals into flexible energy harvesters and coolers. However, obtaining flexible thermoelectric materials with high figure of merit ZT through printing is an exacting challenge due to the difficulties to synthesize high-performance thermoelectric inks and the poor density and electrical conductivity of the printed films. Here, we demonstrate high-performance flexible films and devices by screen printing bismuth telluride based nanocrystal inks synthesized using a microwave-stimulated wet-chemical method. Thermoelectric films of several tens of microns thickness were screen printed onto a flexible polyimide substrate followed by cold compaction and sintering. The n-type films demonstratemore » a peak ZT of 0.43 along with superior flexibility, which is among the highest reported ZT values in flexible thermoelectric materials. A flexible thermoelectric device fabricated using the printed films produces a high power density of 4.1 mW/cm 2 with 60°C temperature difference between the hot side and cold side. In conclusion, the highly scalable and low cost process to fabricate flexible thermoelectric materials and devices demonstrated here opens up many opportunities to transform thermoelectric energy harvesting and cooling applications.« less

High-performance and flexible thermoelectric films by screen printing solution-processed nanoplate crystals

DOE PAGES

Varghese, Tony; Hollar, Courtney; Richardson, Joseph; ...

2016-09-12

Screen printing allows for direct conversion of thermoelectric nanocrystals into flexible energy harvesters and coolers. However, obtaining flexible thermoelectric materials with high figure of merit ZT through printing is an exacting challenge due to the difficulties to synthesize high-performance thermoelectric inks and the poor density and electrical conductivity of the printed films. Here, we demonstrate high-performance flexible films and devices by screen printing bismuth telluride based nanocrystal inks synthesized using a microwave-stimulated wet-chemical method. Thermoelectric films of several tens of microns thickness were screen printed onto a flexible polyimide substrate followed by cold compaction and sintering. The n-type films demonstratemore » a peak ZT of 0.43 along with superior flexibility, which is among the highest reported ZT values in flexible thermoelectric materials. A flexible thermoelectric device fabricated using the printed films produces a high power density of 4.1 mW/cm 2 with 60°C temperature difference between the hot side and cold side. In conclusion, the highly scalable and low cost process to fabricate flexible thermoelectric materials and devices demonstrated here opens up many opportunities to transform thermoelectric energy harvesting and cooling applications.« less

High-performance and flexible thermoelectric films by screen printing solution-processed nanoplate crystals

PubMed Central

Varghese, Tony; Hollar, Courtney; Richardson, Joseph; Kempf, Nicholas; Han, Chao; Gamarachchi, Pasindu; Estrada, David; Mehta, Rutvik J.; Zhang, Yanliang

2016-01-01

Screen printing allows for direct conversion of thermoelectric nanocrystals into flexible energy harvesters and coolers. However, obtaining flexible thermoelectric materials with high figure of merit ZT through printing is an exacting challenge due to the difficulties to synthesize high-performance thermoelectric inks and the poor density and electrical conductivity of the printed films. Here, we demonstrate high-performance flexible films and devices by screen printing bismuth telluride based nanocrystal inks synthesized using a microwave-stimulated wet-chemical method. Thermoelectric films of several tens of microns thickness were screen printed onto a flexible polyimide substrate followed by cold compaction and sintering. The n-type films demonstrate a peak ZT of 0.43 along with superior flexibility, which is among the highest reported ZT values in flexible thermoelectric materials. A flexible thermoelectric device fabricated using the printed films produces a high power density of 4.1 mW/cm2 with 60 °C temperature difference between the hot side and cold side. The highly scalable and low cost process to fabricate flexible thermoelectric materials and devices demonstrated here opens up many opportunities to transform thermoelectric energy harvesting and cooling applications. PMID:27615036

[Screening and confirmation of 24 hormones in cosmetics by ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry].

PubMed

Li, Zhaoyong; Wang, Fengmei; Niu, Zengyuan; Luo, Xin; Zhang, Gang; Chen, Junhui

2014-05-01

A method of ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UPLC-LTQ/Orbitrap MS) was established to screen and confirm 24 hormones in cosmetics. Various cosmetic samples were extracted with methanol. The extract was loaded onto a Waters ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 microm) using a gradient elution of acetonitrile/water containing 0.1% (v/v) formic acid for the separation. The accurate mass of quasi-molecular ion was acquired by full scanning of electrostatic field orbitrap. The rapid screening was carried out by the accurate mass of quasi-molecular ion. The confirmation analysis for targeted compounds was performed with the retention time and qualitative fragments obtained by data dependent scan mode. Under the optimal conditions, the 24 hormones were routinely detected with mass accuracy error below 3 x 10(-6) (3 ppm), and good linearities were obtained in their respective linear ranges with correlation coefficients higher than 0.99. The LODs (S/N = 3) of the 24 compounds were < or = 10 microg/kg, which can meet the requirements for the actual screening of cosmetic samples. The developed method was applied to screen the hormones in 50 cosmetic samples. The results demonstrate that the method is a useful tool for the rapid screening and identification of the hormones in cosmetics.

Quantitative description on structure-property relationships of Li-ion battery materials for high-throughput computations

NASA Astrophysics Data System (ADS)

Wang, Youwei; Zhang, Wenqing; Chen, Lidong; Shi, Siqi; Liu, Jianjun

2017-12-01

Li-ion batteries are a key technology for addressing the global challenge of clean renewable energy and environment pollution. Their contemporary applications, for portable electronic devices, electric vehicles, and large-scale power grids, stimulate the development of high-performance battery materials with high energy density, high power, good safety, and long lifetime. High-throughput calculations provide a practical strategy to discover new battery materials and optimize currently known material performances. Most cathode materials screened by the previous high-throughput calculations cannot meet the requirement of practical applications because only capacity, voltage and volume change of bulk were considered. It is important to include more structure-property relationships, such as point defects, surface and interface, doping and metal-mixture and nanosize effects, in high-throughput calculations. In this review, we established quantitative description of structure-property relationships in Li-ion battery materials by the intrinsic bulk parameters, which can be applied in future high-throughput calculations to screen Li-ion battery materials. Based on these parameterized structure-property relationships, a possible high-throughput computational screening flow path is proposed to obtain high-performance battery materials.

Quantitative description on structure-property relationships of Li-ion battery materials for high-throughput computations.

PubMed

Wang, Youwei; Zhang, Wenqing; Chen, Lidong; Shi, Siqi; Liu, Jianjun

2017-01-01

Li-ion batteries are a key technology for addressing the global challenge of clean renewable energy and environment pollution. Their contemporary applications, for portable electronic devices, electric vehicles, and large-scale power grids, stimulate the development of high-performance battery materials with high energy density, high power, good safety, and long lifetime. High-throughput calculations provide a practical strategy to discover new battery materials and optimize currently known material performances. Most cathode materials screened by the previous high-throughput calculations cannot meet the requirement of practical applications because only capacity, voltage and volume change of bulk were considered. It is important to include more structure-property relationships, such as point defects, surface and interface, doping and metal-mixture and nanosize effects, in high-throughput calculations. In this review, we established quantitative description of structure-property relationships in Li-ion battery materials by the intrinsic bulk parameters, which can be applied in future high-throughput calculations to screen Li-ion battery materials. Based on these parameterized structure-property relationships, a possible high-throughput computational screening flow path is proposed to obtain high-performance battery materials.

High-throughput measurements of biochemical responses using the plate::vision multimode 96 minilens array reader.

PubMed

Huang, Kuo-Sen; Mark, David; Gandenberger, Frank Ulrich

2006-01-01

The plate::vision is a high-throughput multimode reader capable of reading absorbance, fluorescence, fluorescence polarization, time-resolved fluorescence, and luminescence. Its performance has been shown to be quite comparable with other readers. When the reader is integrated into the plate::explorer, an ultrahigh-throughput screening system with event-driven software and parallel plate-handling devices, it becomes possible to run complicated assays with kinetic readouts in high-density microtiter plate formats for high-throughput screening. For the past 5 years, we have used the plate::vision and the plate::explorer to run screens and have generated more than 30 million data points. Their throughput, performance, and robustness have speeded up our drug discovery process greatly.

Contribution to the epidemiology of postnatal depression in Germany--implications for the utilization of treatment.

PubMed

v Ballestrem, C-L; Strauss, M; Kächele, H

2005-05-01

Using a longitudinal screening model, 772 mothers were screened for postnatal depression after delivery in Stuttgart (Germany). This model contained the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Depression Scale (HAMD). The first screening was 6-8 weeks after delivery with the EPDS. Mothers with high scores in the first screening had a second screening 9-12 weeks after delivery with the EPDS at least three weeks after the first. Mothers with high scores in both screenings were investigated with the Hamilton Depression Scale (HAMD). Classification was performed with the DSM-IV. After observation until the third month after delivery, 3.6% (N = 28) of the 772 mothers were diagnosed with postnatal depression. Various methods of therapy were offered to those mothers. 18% (N = 5) accepted one or more of these methods of treatment. The rest of the mothers with postnatal depression refused--mostly for attitudinal or practical reasons. 13.4% of the mothers showed high scores in the first screening but not in the second. For those mothers a longitudinal observation is currently being performed to distinguish between a depressive episode and a depression with oscillating symptoms.

A universal array-based multiplexed test for cystic fibrosis carrier screening.

PubMed

Amos, Jean A; Bridge-Cook, Philippa; Ponek, Victor; Jarvis, Michael R

2006-01-01

Cystic fibrosis is a multisystem autosomal recessive disorder with high carrier frequencies in caucasians and significant, but lower, carrier frequencies in other ethnicities. Based on technology that allows high detection of mutations in caucasians and significant detection in other ethnic groups, the American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG) have recommended pan-ethnic cystic fibrosis carrier screening for all reproductive couples. This paper discusses carrier screening using the Tag-It multiplex mutation platform and the Cystic Fibrosis Mutation Detection Kit. The Tag-It cystic fibrosis assay is a multiplexed genotyping assay that detects a panel of 40 cystic fibrosis transmembrane conductance regulator mutations including the 23 mutations recommended by the ACMG and ACOG for population screening. A total of 16 additional mutations detected by the Tag-It cystic fibrosis assay may also be common. The assay method is described in detail, and its performance in a genetics reference laboratory performing high-volume cystic fibrosis carrier screening is assessed.

Primary care practice and facility quality orientation: influence on breast and cervical cancer screening rates.

PubMed

Goldzweig, Caroline Lubick; Parkerton, Patricia H; Washington, Donna L; Lanto, Andrew B; Yano, Elizabeth M

2004-04-01

Despite the importance of early cancer detection, variation in screening rates among physicians is high. Insights into factors influencing variation can guide efforts to decrease variation and increase screening rates. To explore the association of primary care practice features and a facility's quality orientation with breast and cervical cancer screening rates. Cross-sectional study of screening rates among 144 Department of Veterans Affairs (VA) medical centers and for a national sample of women. We linked practice structure and quality improvement characteristics of individual VA medical centers from 2 national surveys (1 to primary care directors and 1 to a stratified random sample of employees) to breast and cervical cancer screening rates determined from a review of random medical records. We conducted bivariate analyses and multivariate logistic regression of primary care practice and facility features on cancer screening rates, above and below the median. While the national screening rates were high for breast (87%) and cervical cancer (90%), higher screening rates were more likely when primary care providers were consistently notified of specialty visits and when staff perceived a greater organizational commitment to quality and anticipated rewards and recognition for better performance. Organization and quality orientation of the primary care practice and its facility can enhance breast and cervical cancer screening rates. Internal recognition of quality performance and an overall commitment to quality improvement may foster improved prevention performance, with impact varying by clinical service.

The high throughput biomedicine unit at the institute for molecular medicine Finland: high throughput screening meets precision medicine.

PubMed

Pietiainen, Vilja; Saarela, Jani; von Schantz, Carina; Turunen, Laura; Ostling, Paivi; Wennerberg, Krister

2014-05-01

The High Throughput Biomedicine (HTB) unit at the Institute for Molecular Medicine Finland FIMM was established in 2010 to serve as a national and international academic screening unit providing access to state of the art instrumentation for chemical and RNAi-based high throughput screening. The initial focus of the unit was multiwell plate based chemical screening and high content microarray-based siRNA screening. However, over the first four years of operation, the unit has moved to a more flexible service platform where both chemical and siRNA screening is performed at different scales primarily in multiwell plate-based assays with a wide range of readout possibilities with a focus on ultraminiaturization to allow for affordable screening for the academic users. In addition to high throughput screening, the equipment of the unit is also used to support miniaturized, multiplexed and high throughput applications for other types of research such as genomics, sequencing and biobanking operations. Importantly, with the translational research goals at FIMM, an increasing part of the operations at the HTB unit is being focused on high throughput systems biological platforms for functional profiling of patient cells in personalized and precision medicine projects.

The FLIGHT Drosophila RNAi database

PubMed Central

Bursteinas, Borisas; Jain, Ekta; Gao, Qiong; Baum, Buzz; Zvelebil, Marketa

2010-01-01

FLIGHT (http://flight.icr.ac.uk/) is an online resource compiling data from high-throughput Drosophila in vivo and in vitro RNAi screens. FLIGHT includes details of RNAi reagents and their predicted off-target effects, alongside RNAi screen hits, scores and phenotypes, including images from high-content screens. The latest release of FLIGHT is designed to enable users to upload, analyze, integrate and share their own RNAi screens. Users can perform multiple normalizations, view quality control plots, detect and assign screen hits and compare hits from multiple screens using a variety of methods including hierarchical clustering. FLIGHT integrates RNAi screen data with microarray gene expression as well as genomic annotations and genetic/physical interaction datasets to provide a single interface for RNAi screen analysis and datamining in Drosophila. PMID:20855970

NCCN Guidelines as a Model of Extended Criteria for Lung Cancer Screening.

PubMed

McKee, Brady J; Regis, Shawn; Borondy-Kitts, Andrea K; Hashim, Jeffrey A; French, Robert J; Wald, Christoph; McKee, Andrea B

2018-04-01

Background: This review assessed the performance of patients in NCCN high-risk group 2 in a clinical CT lung screening (CTLS) program. Methods: We retrospectively reviewed screening results for all patients from our institution undergoing clinical CTLS from January 2012 through December 2016, with follow-up through June 2017. To qualify for screening, patients had to meet the NCCN Guidelines high-risk criteria for CTLS, have a physician order for screening, be asymptomatic, be lung cancer-free for 5 years, and have no known metastatic disease. We compared demographics and screening performance of NCCN high-risk groups 1 and 2 across >4 rounds of screening. Screening metrics assessed included rates of positive and suspicious examinations, significant incidental and infectious/inflammatory findings, false negatives, and cancer detection. We also compared cancer stage and histology detected in each NCCN high-risk group. Results: A total of 2,927 individuals underwent baseline screening, of which 698 (24%) were in NCCN group 2. On average, group 2 patients were younger (60.6 vs 63.1 years), smoked less (38.8 vs 50.8 pack-years), had quit longer (18.1 vs 6.3 years), and were more often former smokers (61.4% vs 44.2%). Positive and suspicious examination rates, false negatives, and rates of infectious/inflammatory findings were equivalent in groups 1 and 2 across all rounds of screening. An increased rate of cancer detection was observed in group 2 during the second annual (T2) screening round (2.7% vs 0.5%; P =.005), with no difference in the other screening rounds: baseline (T0; 2% vs 2.3%; P =.61), first annual (T1; 1.2% vs 1.7%; P =.41), and third annual and beyond (≥T3; 1.2% vs 1.1%; P =1.00). Conclusions: CTLS appears to be equally effective in both NCCN high-risk groups. Copyright © 2018 by the National Comprehensive Cancer Network.

Validation of a school-based amblyopia screening protocol in a kindergarten population.

PubMed

Casas-Llera, Pilar; Ortega, Paula; Rubio, Inmaculada; Santos, Verónica; Prieto, María J; Alio, Jorge L

2016-08-04

To validate a school-based amblyopia screening program model by comparing its outcomes to those of a state-of-the-art conventional ophthalmic clinic examination in a kindergarten population of children between the ages of 4 and 5 years. An amblyopia screening protocol, which consisted of visual acuity measurement using Lea charts, ocular alignment test, ocular motility assessment, and stereoacuity with TNO random-dot test, was performed at school in a pediatric 4- to 5-year-old population by qualified healthcare professionals. The outcomes were validated in a selected group by a conventional ophthalmologic examination performed in a fully equipped ophthalmologic center. The ophthalmologic evaluation was used to confirm whether or not children were correctly classified by the screening protocol. The sensitivity and specificity of the test model to detect amblyopia were established. A total of 18,587 4- to 5-year-old children were subjected to the amblyopia screening program during the 2010-2011 school year. A population of 100 children were selected for the ophthalmologic validation screening. A sensitivity of 89.3%, specificity of 93.1%, positive predictive value of 83.3%, negative predictive value of 95.7%, positive likelihood ratio of 12.86, and negative likelihood ratio of 0.12 was obtained for the amblyopia screening validation model. The amblyopia screening protocol model tested in this investigation shows high sensitivity and specificity in detecting high-risk cases of amblyopia compared to the standard ophthalmologic examination. This screening program may be highly relevant for amblyopia screening at schools.

Smart Screening System (S3) In Taconite Processing

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

Daryoush Allaei; Ryan Wartman; David Tarnowski

2006-03-01

The conventional screening machines used in processing plants have had undesirable high noise and vibration levels. They also have had unsatisfactorily low screening efficiency, high energy consumption, high maintenance cost, low productivity, and poor worker safety. These conventional vibrating machines have been used in almost every processing plant. Most of the current material separation technology uses heavy and inefficient electric motors with an unbalanced rotating mass to generate the shaking. In addition to being excessively noisy, inefficient, and high-maintenance, these vibrating machines are often the bottleneck in the entire process. Furthermore, these motors, along with the vibrating machines and supportingmore » structure, shake other machines and structures in the vicinity. The latter increases maintenance costs while reducing worker health and safety. The conventional vibrating fine screens at taconite processing plants have had the same problems as those listed above. This has resulted in lower screening efficiency, higher energy and maintenance cost, and lower productivity and workers safety concerns. The focus of this work is on the design of a high performance screening machine suitable for taconite processing plants. SmartScreens{trademark} technology uses miniaturized motors, based on smart materials, to generate the shaking. The underlying technologies are Energy Flow Control{trademark} and Vibration Control by Confinement{trademark}. These concepts are used to direct energy flow and confine energy efficiently and effectively to the screen function. The SmartScreens{trademark} technology addresses problems related to noise and vibration, screening efficiency, productivity, and maintenance cost and worker safety. Successful development of SmartScreens{trademark} technology will bring drastic changes to the screening and physical separation industry. The final designs for key components of the SmartScreens{trademark} have been developed. The key components include smart motor and associated electronics, resonators, and supporting structural elements. It is shown that the smart motors have an acceptable life and performance. Resonator (or motion amplifier) designs are selected based on the final system requirement and vibration characteristics. All the components for a fully functional prototype are fabricated. The development program is on schedule. The last semi-annual report described the completion of the design refinement phase. This phase resulted in a Smart Screen design that meets performance targets both in the dry condition and with taconite slurry flow using PZT motors. This system was successfully demonstrated for the DOE and partner companies at the Coleraine Mineral Research Laboratory in Coleraine, Minnesota. Since then, the fabrication of the dry application prototype (incorporating an electromagnetic drive mechanism and a new deblinding concept) has been completed and successfully tested at QRDC's lab.« less

Acceptability and validity of older driver screening with the DrivingHealth Inventory.

PubMed

Edwards, Jerri D; Leonard, Kathleen M; Lunsman, Melissa; Dodson, Joan; Bradley, Stacy; Myers, Charlsie A; Hubble, Bridgette

2008-05-01

Research has indicated that technology can be effectively used to identify high-risk older drivers. However, adaptation of such technology has been limited. Researchers debate whether older drivers represent a safety problem as well as whether they should be screened for driving fitness. The present study examined how drivers feel regarding technological screening and mandatory state testing. The validity and acceptability of a new technological screening battery for identifying high-risk drivers, the DrivingHealth Inventory (DHI), was also evaluated. In a sample of 258 Alabama drivers aged 18-87, older drivers performed significantly worse than younger drivers on sensory, cognitive, and physical subtests of the DHI, and older drivers with a crash history performed worse than older drivers without crashes. Regardless of age, 90% of participants supported states requiring screening for older drivers' license renewal. The majority of the participants (72%) supported use of technological screening batteries such as the DHI as a driver screening tool. Considering the acceptability and potential efficacy of the DHI, it may be a useful tool in evaluating driving fitness among older adults.

Enhanced piezoelectric operation of NiO/GaN heterojunction generator by suppressed internal carrier screening

NASA Astrophysics Data System (ADS)

Jeong, Dae Kyung; Kang, Jin-Ho; Ha, Jun-Seok; Ryu, Sang-Wan

2017-10-01

A NiO/GaN heterojunction piezoelectric generator was fabricated, and the improvement in device performance was analyzed. The electrical properties of NiO were varied by regulating the gas environment during sputtering. An optimized NiO layer was adopted for high piezoelectric voltage generation. Internal carrier screening was revealed to be the dominant mechanism degrading the piezoelectric performance, necessitating the suppression of carrier screening. The highly resistive NiO layer was advantageous in the suppression of carrier transport across the junction that screened the piezoelectric field. The maximum piezoelectric voltage and current density values obtained were 7.55 V and 1.14 µA cm-2, respectively. The power obtained was sufficient to operate a light-emitting diode combined with a charging circuit.

Thermal Testing and Analysis of an Efficient High-Temperature Multi-Screen Internal Insulation

NASA Technical Reports Server (NTRS)

Weiland, Stefan; Handrick, Karin; Daryabeigi, Kamran

2007-01-01

Conventional multi-layer insulations exhibit excellent insulation performance but they are limited to the temperature range to which their components reflective foils and spacer materials are compatible. For high temperature applications, the internal multi-screen insulation IMI has been developed that utilizes unique ceramic material technology to produce reflective screens with high temperature stability. For analytical insulation sizing a parametric material model is developed that includes the main contributors for heat flow which are radiation and conduction. The adaptation of model-parameters based on effective steady-state thermal conductivity measurements performed at NASA Langley Research Center (LaRC) allows for extrapolation to arbitrary stack configurations and temperature ranges beyond the ones that were covered in the conductivity measurements. Experimental validation of the parametric material model was performed during the thermal qualification test of the X-38 Chin-panel, where test results and predictions showed a good agreement.

Quantitative description on structure–property relationships of Li-ion battery materials for high-throughput computations

PubMed Central

Wang, Youwei; Zhang, Wenqing; Chen, Lidong; Shi, Siqi; Liu, Jianjun

2017-01-01

Abstract Li-ion batteries are a key technology for addressing the global challenge of clean renewable energy and environment pollution. Their contemporary applications, for portable electronic devices, electric vehicles, and large-scale power grids, stimulate the development of high-performance battery materials with high energy density, high power, good safety, and long lifetime. High-throughput calculations provide a practical strategy to discover new battery materials and optimize currently known material performances. Most cathode materials screened by the previous high-throughput calculations cannot meet the requirement of practical applications because only capacity, voltage and volume change of bulk were considered. It is important to include more structure–property relationships, such as point defects, surface and interface, doping and metal-mixture and nanosize effects, in high-throughput calculations. In this review, we established quantitative description of structure–property relationships in Li-ion battery materials by the intrinsic bulk parameters, which can be applied in future high-throughput calculations to screen Li-ion battery materials. Based on these parameterized structure–property relationships, a possible high-throughput computational screening flow path is proposed to obtain high-performance battery materials. PMID:28458737

A rapid echocardiographic screening protocol for rheumatic heart disease in Samoa: a high prevalence of advanced disease.

PubMed

Allen, Marvin; Allen, John; Naseri, Take; Gardner, Rebecca; Tolley, Dennis; Allen, Lori

2017-10-01

Echocardiography has been proposed as a method to screen children for rheumatic heart disease. The World Heart Federation has established guidelines for echocardiographic screening. In this study, we describe a rapid echocardiogram screening protocol according to the World Heart Federation guidelines in Samoa, endemic for rheumatic heart disease. We performed echocardiogram screening in schoolchildren in Samoa between 2013 and 2015. A brief screening echocardiogram was performed on all students. Children with predefined criteria suspicious for rheumatic hear diseases were referred for a more comprehensive echocardiogram. Complete echocardiograms were classified according to the World Heart Federation guidelines and severity of valve disease. Echocardiographic screening was performed on 11,434 children, with a mean age of 10.2 years; 51% of them were females. A total of 558 (4.8%) children underwent comprehensive echocardiography, including 49 students who were randomly selected as controls. Definite rheumatic heart disease was observed in 115 students (10.0 per 1000): 92 students were classified as borderline (8.0 per 1000) and 23 with CHD. Advanced disease was identified in 50 students (4.4 per 1000): 15 with severe mitral regurgitation, five with severe aortic regurgitation, 11 with mitral stenoses, and 19 with mitral and aortic valve disease. We successfully applied a rapid echocardiographic screening protocol to a large number of students over a short time period - 28 days of screening over a 3-year time period - to identify a high prevalence of rheumatic heart disease. We also reported a significantly higher rate of advanced disease compared with previously published echocardiographic screening programmes.

Screening Chemicals for Estrogen Receptor Bioactivity Using a Computational Model.

PubMed

Browne, Patience; Judson, Richard S; Casey, Warren M; Kleinstreuer, Nicole C; Thomas, Russell S

2015-07-21

The U.S. Environmental Protection Agency (EPA) is considering high-throughput and computational methods to evaluate the endocrine bioactivity of environmental chemicals. Here we describe a multistep, performance-based validation of new methods and demonstrate that these new tools are sufficiently robust to be used in the Endocrine Disruptor Screening Program (EDSP). Results from 18 estrogen receptor (ER) ToxCast high-throughput screening assays were integrated into a computational model that can discriminate bioactivity from assay-specific interference and cytotoxicity. Model scores range from 0 (no activity) to 1 (bioactivity of 17β-estradiol). ToxCast ER model performance was evaluated for reference chemicals, as well as results of EDSP Tier 1 screening assays in current practice. The ToxCast ER model accuracy was 86% to 93% when compared to reference chemicals and predicted results of EDSP Tier 1 guideline and other uterotrophic studies with 84% to 100% accuracy. The performance of high-throughput assays and ToxCast ER model predictions demonstrates that these methods correctly identify active and inactive reference chemicals, provide a measure of relative ER bioactivity, and rapidly identify chemicals with potential endocrine bioactivities for additional screening and testing. EPA is accepting ToxCast ER model data for 1812 chemicals as alternatives for EDSP Tier 1 ER binding, ER transactivation, and uterotrophic assays.

Automation in visual inspection tasks: X-ray luggage screening supported by a system of direct, indirect or adaptable cueing with low and high system reliability.

PubMed

Chavaillaz, Alain; Schwaninger, Adrian; Michel, Stefan; Sauer, Juergen

2018-05-25

The present study evaluated three automation modes for improving performance in an X-ray luggage screening task. 140 participants were asked to detect the presence of prohibited items in X-ray images of cabin luggage. Twenty participants conducted this task without automatic support (control group), whereas the others worked with either indirect cues (system indicated the target presence without specifying its location), or direct cues (system pointed out the exact target location) or adaptable automation (participants could freely choose between no cue, direct and indirect cues). Furthermore, automatic support reliability was manipulated (low vs. high). The results showed a clear advantage for direct cues regarding detection performance and response time. No benefits were observed for adaptable automation. Finally, high automation reliability led to better performance and higher operator trust. The findings overall confirmed that automatic support systems for luggage screening should be designed such that they provide direct, highly reliable cues.

High-Throughput Screening for a Moderately Halophilic Phenol-Degrading Strain and Its Salt Tolerance Response

PubMed Central

Lu, Zhi-Yan; Guo, Xiao-Jue; Li, Hui; Huang, Zhong-Zi; Lin, Kuang-Fei; Liu, Yong-Di

2015-01-01

A high-throughput screening system for moderately halophilic phenol-degrading bacteria from various habitats was developed to replace the conventional strain screening owing to its high efficiency. Bacterial enrichments were cultivated in 48 deep well microplates instead of shake flasks or tubes. Measurement of phenol concentrations was performed in 96-well microplates instead of using the conventional spectrophotometric method or high-performance liquid chromatography (HPLC). The high-throughput screening system was used to cultivate forty-three bacterial enrichments and gained a halophilic bacterial community E3 with the best phenol-degrading capability. Halomonas sp. strain 4-5 was isolated from the E3 community. Strain 4-5 was able to degrade more than 94% of the phenol (500 mg·L−1 starting concentration) over a range of 3%–10% NaCl. Additionally, the strain accumulated the compatible solute, ectoine, with increasing salt concentrations. PCR detection of the functional genes suggested that the largest subunit of multicomponent phenol hydroxylase (LmPH) and catechol 1,2-dioxygenase (C12O) were active in the phenol degradation process. PMID:26020478

CRISPR/Cas9-Directed Gene Editing for the Generation of Loss-of-Function Mutants in High-Throughput Zebrafish F0 Screens.

PubMed

Shankaran, Sunita S; Dahlem, Timothy J; Bisgrove, Brent W; Yost, H Joseph; Tristani-Firouzi, Martin

2017-07-05

The ability to perform reverse genetics in the zebrafish model organism has been greatly advanced with the advent of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated) system. The high level of efficiency in generating mutations when using the CRISPR/Cas9 system combined with the rapid generation time of the zebrafish model organism has made the possibility of performing F 0 screens in this organism a reality. This unit describes a detailed protocol for performing an F 0 screen using the CRISPR/Cas9 system in zebrafish starting with the design and production of custom CRISPR/Cas9 reagents for injection. Next, two approaches for determining the efficiency of mutation induction by the custom CRISPR/Cas9 reagents that are easily performed using standard molecular biology protocols are detailed. Finally, screening for F 0 induced phenotypes using the zebrafish flh gene as an example is discussed. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Droplet microfluidic technology for single-cell high-throughput screening.

PubMed

Brouzes, Eric; Medkova, Martina; Savenelli, Neal; Marran, Dave; Twardowski, Mariusz; Hutchison, J Brian; Rothberg, Jonathan M; Link, Darren R; Perrimon, Norbert; Samuels, Michael L

2009-08-25

We present a droplet-based microfluidic technology that enables high-throughput screening of single mammalian cells. This integrated platform allows for the encapsulation of single cells and reagents in independent aqueous microdroplets (1 pL to 10 nL volumes) dispersed in an immiscible carrier oil and enables the digital manipulation of these reactors at a very high-throughput. Here, we validate a full droplet screening workflow by conducting a droplet-based cytotoxicity screen. To perform this screen, we first developed a droplet viability assay that permits the quantitative scoring of cell viability and growth within intact droplets. Next, we demonstrated the high viability of encapsulated human monocytic U937 cells over a period of 4 days. Finally, we developed an optically-coded droplet library enabling the identification of the droplets composition during the assay read-out. Using the integrated droplet technology, we screened a drug library for its cytotoxic effect against U937 cells. Taken together our droplet microfluidic platform is modular, robust, uses no moving parts, and has a wide range of potential applications including high-throughput single-cell analyses, combinatorial screening, and facilitating small sample analyses.

Vibration characteristics of an inclined flip-flow screen panel in banana flip-flow screens

NASA Astrophysics Data System (ADS)

Xiong, Xiaoyan; Niu, Linkai; Gu, Chengxiang; Wang, Yinhua

2017-12-01

A banana flip-flow screen is an effective solution for the screening of high-viscosity, high-water and fine materials. As one of the key components, the vibration characteristics of the inclined flip-flow screen panel largely affects the screen performance and the processing capacity. In this paper, a mathematical model for the vibration characteristic of the inclined flip-flow screen panel is proposed based on Catenary theory. The reasonability of Catenary theory in analyzing the vibration characteristic of flip-flow screen panels is verified by a published experiment. Moreover, the effects of the rotation speed of exciters, the incline angle, the slack length and the characteristics of the screen on the vertical deflection, the vertical velocity and the vertical acceleration of the screen panel are investigated parametrically. The results show that the rotation speed of exciters, the incline angle, the slack length and the characteristics of the screen have significant effects on the vibrations of an inclined flip-flow screen panel, and these parameters should be optimized.

HTS techniques for patch clamp-based ion channel screening - advances and economy.

PubMed

Farre, Cecilia; Fertig, Niels

2012-06-01

Ten years ago, the first publication appeared showing patch clamp recordings performed on a planar glass chip instead of using a conventional patch clamp pipette. "Going planar" proved to revolutionize ion channel drug screening as we know it, by allowing high quality measurements of ion channels and their effectors at a higher throughput and at the same time de-skilling the highly laborious technique. Over the years, platforms evolved in response to user requirements regarding experimental features, data handling plus storage, and suitable target diversity. This article gives a snapshot image of patch clamp-based ion channel screening with focus on platforms developed to meet requirements of high-throughput screening environments. The commercially available platforms are described, along with their benefits and drawbacks in ion channel drug screening. Automated patch clamp (APC) platforms allow faster investigation of a larger number of ion channel active compounds or cell clones than previously possible. Since patch clamp is the only method allowing direct, real-time measurements of ion channel activity, APC holds the promise of picking up high quality leads, where they otherwise would have been overseen using indirect methods. In addition, drug candidate safety profiling can be performed earlier in the drug discovery process, avoiding late-phase compound withdrawal due to safety liability issues, which is highly costly and inefficient.

High-performance liquid chromatography coupled with post-column dual-bioactivity assay for simultaneous screening of xanthine oxidase inhibitors and free radical scavengers from complex mixture.

PubMed

Li, D Q; Zhao, J; Li, S P

2014-06-06

Xanthine oxidase (XO) can catalyze hypoxanthine and xanthine to generate uric acid and reactive oxygen species (ROS), including superoxide anion radical (O₂(•-)) and hydrogen peroxide. XO inhibitors and free radical scavengers are beneficial to the treatment of gout and many related diseases. In the present study, an on-line high-performance liquid chromatography (HPLC) coupled with post-column dual-bioactivity assay was established and successfully applied to simultaneously screening of XO inhibitors and free radical scavengers from a complex mixture, Oroxylum indicum extract. The integrated system of HPLC separation, bioactivity screening and mass spectrometry identification was proved to be simple and effective for rapid and sensitive screening of individual bioactive compounds in complex mixtures. Copyright © 2014 Elsevier B.V. All rights reserved.

Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency.

PubMed

Ho, Sirikit; Lukacs, Zoltan; Hoffmann, Georg F; Lindner, Martin; Wetter, Thomas

2007-07-01

In newborn screening with tandem mass spectrometry, multiple intermediary metabolites are quantified in a single analytical run for the diagnosis of fatty-acid oxidation disorders, organic acidurias, and aminoacidurias. Published diagnostic criteria for these disorders normally incorporate a primary metabolic marker combined with secondary markers, often analyte ratios, for which the markers have been chosen to reflect metabolic pathway deviations. We applied a procedure to extract new markers and diagnostic criteria for newborn screening to the data of newborns with confirmed medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and a control group from the newborn screening program, Heidelberg, Germany. We validated the results with external data of the screening center in Hamburg, Germany. We extracted new markers by performing a systematic search for analyte combinations (features) with high discriminatory performance for MCADD. To select feature thresholds, we applied automated procedures to separate controls and cases on the basis of the feature values. Finally, we built classifiers from these new markers to serve as diagnostic criteria in screening for MCADD. On the basis of chi(2) scores, we identified approximately 800 of >628,000 new analyte combinations with superior discriminatory performance compared with the best published combinations. Classifiers built with the new features achieved diagnostic sensitivities and specificities approaching 100%. Feature construction methods provide ways to disclose information hidden in the set of measured analytes. Other diagnostic tasks based on high-dimensional metabolic data might also profit from this approach.

Predicting the stage shift as a result of breast cancer screening in low- and middle-income countries: a proof of concept.

PubMed

Zelle, Sten G; Baltussen, Rob; Otten, Johannes D M; Heijnsdijk, Eveline A M; van Schoor, Guido; Broeders, Mireille J M

2015-03-01

To provide proof of concept for a simple model to estimate the stage shift as a result of breast cancer screening in low- and middle-income countries (LMICs). Stage shift is an essential early detection indicator and an important proxy for the performance and possible further impact of screening programmes. Our model could help LIMCs to choose appropriate control strategies. We assessed our model concept in three steps. First, we calculated the proportional performance rates (i.e. index number Z) based on 16 screening rounds of the Nijmegen Screening Program (384,884 screened women). Second, we used linear regression to assess the association between Z and the amount of stage shift observed in the programme. Third, we hypothesized how Z could be used to estimate the stage shift as a result of breast cancer screening in LMICs. Stage shifts can be estimated by the proportional performance rates (Zs) using linear regression. Zs calculated for each screening round are highly associated with the observed stage shifts in the Nijmegen Screening Program (Pearson's R: 0.798, R square: 0.637). Our model can predict the stage shifts in the Nijmegen Screening Program, and could be applied to settings with different characteristics, although it should not be straightforwardly used to estimate the impact on mortality. Further research should investigate the extrapolation of our model to other settings. As stage shift is an essential screening performance indicator, our model could provide important information on the performance of breast cancer screening programmes that LMICs consider implementing. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Breast cancer screening in Italy: evaluating key performance indicators for time trends and activity volumes.

PubMed

Giordano, Livia; Castagno, Roberta; Giorgi, Daniela; Piccinelli, Cristiano; Ventura, Leonardo; Segnan, Nereo; Zappa, Marco

2015-01-01

Together with the National centre for screening monitoring (ONS), GISMa supports annual collection of data on national breast screening activities. Aggregated data on implementation and performance are gathered through a standardized form to calculate process and impact indicators. Analyzed data belong to 153 local programmes in the period 2006-2011 (2006-2012 for participation rate only). During the whole period, Italian crude participation rate exceeded GISMa's acceptable standard (50%), even though a higher participation in northern and central Italy compared to southern Italy and Islands was observed. Time trend analysis of diagnostic indicators confirmed in 2011 an adequate quality of breast screening performance, especially at subsequent screening. Recall rate at initial screening did not reach the acceptable standard (<7%) and rose slightly over the period. On the contrary, a good performance was achieved at subsequent screening. The same trend was followed by the overall detection rate and positive predictive value. They both showed a progressive reduction (from 6.2‰ in 2006 to 4.5‰ in 2011 for DR and from 8.0% in 2006 to 5.2% in 2011 for PPV, respectively) at initial screening and a good, stable trend at subsequent screening. Activity volume analysis shows that in programmes with greater activity (test/year ≥10,000) RR at both initial and subsequent screening has a better performance. This is also true for DR and PPV where programmes with high volumes of activity do better, especially when compared with those that interpret fewer than 5,000 mammograms per year. In spite of a few limits, these results are reassuring, and they reward the efforts made by screening professionals. It is therefore important to continue to monitor screening indicators and suggest, test, and evaluate new strategies for continuous improvement.

COTS Ceramic Chip Capacitors: An Evaluation of the Parts and Assurance Methodologies

NASA Technical Reports Server (NTRS)

Brusse, Jay A.; Sampson, Michael J.

2004-01-01

Commercial-Off-The-Shelf (COTS) multilayer ceramic chip capacitors (MLCCs) are continually evolving to reduce physical size and increase volumetric efficiency. Designers of high reliability aerospace and military systems are attracted to these attributes of COTS MLCCs and would like to take advantage of them while maintaining the high standards for long-term reliable operation they are accustomed io when selecting military qualified established reliability (MIL-ER) MLCCs. However, MIL-ER MLCCs are not available in the full range of small chip sizes with high capacitance as found in today's COTS MLCCs. The objectives for this evaluation were to assess the long-term performance of small case size COTS MLCCs and to identify effective, lower-cost product assurance methodologies. Fifteen (15) lots of COTS X7R dielectric MLCCs from four (4) different manufacturers and two (2) MIL-ER BX dielectric MLCCs from two (2) of the same manufacturers were evaluated. Both 0805 and 0402 chip sizes were included. Several voltage ratings were tested ranging from a high of 50 volts to a low of 6.3 volts. The evaluation consisted of a comprehensive screening and qualification test program based upon MIL-PRF-55681 (i.e., voltage conditioning, thermal shock, moisture resistance, 2000-hour life test, etc.). In addition, several lot characterization tests were performed including Destructive Physical Analysis (DPA), Highly Accelerated Life Test (HALT) and Dielectric Voltage Breakdown Strength. The data analysis included a comparison of the 2000-hour life test results (used as a metric for long-term performance) relative to the screening and characterization test results. Results of this analysis indicate that the long-term life performance of COTS MLCCs is variable -- some lots perform well, some lots perform poorly. DPA and HALT were found to be promising lot characterization tests to identify substandard COTS MLCC lots prior to conducting more expensive screening and qualification tests. The results indicate that lot- specific screening and qualification are still recommended for high reliability applications. One significant and concerning observation is that MIL- type voltage conditioning (100 hours at twice rated voltage, 125 C) was not an effective screen in removing infant mortality parts for the particular lots of COTS MLCCs evaluated.

Hypothesis generation using network structures on community health center cancer-screening performance.

PubMed

Carney, Timothy Jay; Morgan, Geoffrey P; Jones, Josette; McDaniel, Anna M; Weaver, Michael T; Weiner, Bryan; Haggstrom, David A

2015-10-01

Nationally sponsored cancer-care quality-improvement efforts have been deployed in community health centers to increase breast, cervical, and colorectal cancer-screening rates among vulnerable populations. Despite several immediate and short-term gains, screening rates remain below national benchmark objectives. Overall improvement has been both difficult to sustain over time in some organizational settings and/or challenging to diffuse to other settings as repeatable best practices. Reasons for this include facility-level changes, which typically occur in dynamic organizational environments that are complex, adaptive, and unpredictable. This study seeks to understand the factors that shape community health center facility-level cancer-screening performance over time. This study applies a computational-modeling approach, combining principles of health-services research, health informatics, network theory, and systems science. To investigate the roles of knowledge acquisition, retention, and sharing within the setting of the community health center and to examine their effects on the relationship between clinical decision support capabilities and improvement in cancer-screening rate improvement, we employed Construct-TM to create simulated community health centers using previously collected point-in-time survey data. Construct-TM is a multi-agent model of network evolution. Because social, knowledge, and belief networks co-evolve, groups and organizations are treated as complex systems to capture the variability of human and organizational factors. In Construct-TM, individuals and groups interact by communicating, learning, and making decisions in a continuous cycle. Data from the survey was used to differentiate high-performing simulated community health centers from low-performing ones based on computer-based decision support usage and self-reported cancer-screening improvement. This virtual experiment revealed that patterns of overall network symmetry, agent cohesion, and connectedness varied by community health center performance level. Visual assessment of both the agent-to-agent knowledge sharing network and agent-to-resource knowledge use network diagrams demonstrated that community health centers labeled as high performers typically showed higher levels of collaboration and cohesiveness among agent classes, faster knowledge-absorption rates, and fewer agents that were unconnected to key knowledge resources. Conclusions and research implications: Using the point-in-time survey data outlining community health center cancer-screening practices, our computational model successfully distinguished between high and low performers. Results indicated that high-performance environments displayed distinctive network characteristics in patterns of interaction among agents, as well as in the access and utilization of key knowledge resources. Our study demonstrated how non-network-specific data obtained from a point-in-time survey can be employed to forecast community health center performance over time, thereby enhancing the sustainability of long-term strategic-improvement efforts. Our results revealed a strategic profile for community health center cancer-screening improvement via simulation over a projected 10-year period. The use of computational modeling allows additional inferential knowledge to be drawn from existing data when examining organizational performance in increasingly complex environments. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of a High-Throughput Gene Expression Screen for Modulators of RAS-MAPK Signaling in a Mutant RAS Cellular Context.

PubMed

Severyn, Bryan; Nguyen, Thi; Altman, Michael D; Li, Lixia; Nagashima, Kumiko; Naumov, George N; Sathyanarayanan, Sriram; Cook, Erica; Morris, Erick; Ferrer, Marc; Arthur, Bill; Benita, Yair; Watters, Jim; Loboda, Andrey; Hermes, Jeff; Gilliland, D Gary; Cleary, Michelle A; Carroll, Pamela M; Strack, Peter; Tudor, Matt; Andersen, Jannik N

2016-10-01

The RAS-MAPK pathway controls many cellular programs, including cell proliferation, differentiation, and apoptosis. In colorectal cancers, recurrent mutations in this pathway often lead to increased cell signaling that may contribute to the development of neoplasms, thereby making this pathway attractive for therapeutic intervention. To this end, we developed a 26-member gene signature of RAS-MAPK pathway activity utilizing the Affymetrix QuantiGene Plex 2.0 reagent system and performed both primary and confirmatory gene expression-based high-throughput screens (GE-HTSs) using KRAS mutant colon cancer cells (SW837) and leveraging a highly annotated chemical library. The screen achieved a hit rate of 1.4% and was able to enrich for hit compounds that target RAS-MAPK pathway members such as MEK and EGFR. Sensitivity and selectivity performance measurements were 0.84 and 1.00, respectively, indicating high true-positive and true-negative rates. Active compounds from the primary screen were confirmed in a dose-response GE-HTS assay, a GE-HTS assay using 14 additional cancer cell lines, and an in vitro colony formation assay. Altogether, our data suggest that this GE-HTS assay will be useful for larger unbiased chemical screens to identify novel compounds and mechanisms that may modulate the RAS-MAPK pathway. © 2016 Society for Laboratory Automation and Screening.

[Analysis on risk factors of screen time among Chinese primary and middle school students in 12 provinces].

PubMed

Wu, X Y; Tao, S M; Zhang, S C; Zhang, Y K; Huang, K; Tao, F B

2016-06-01

To investigate the characteristics of screen time and its risk factors in Chinese primary and middle school students. During April 2012 and June 2012, according to the geographical distribution, the stratified random cluster sampling method was used to select 4 provinces from eastern, central and western China, respectively. The convenience sampling method was used to select 2 primary and middle schools from urban, 2 primary and middle schools from rural in each province. In each school, all grades were included, and 2 classes were selected in each grade. A total of 51 866 students or parents were selected as study participants, and 43 771 questionnaires were valid. Information on demographics, academic performance, screen time (TV, computer and cellphone) at weekdays and weekends and the prevalence of the high screen time were compared, multivariate logistic regression was used to analyze the association between screen time >2 h/d and potential influential factors. The percentage of students with screen time >2 h/d at weekdays and weekends were 16.2% (7 082/43 771) and 41.5% (18 141/43 771) (χ(2)=6 280.14, P<0.001), respectively. The distribution of P50 (P25-P75) for screen time at weekdays and weekends were 0.9(0.4-1.6) and 1.8(1.0-3.0) (Z=-131.26, P<0.001), respectively. The results of multinomial logistic regression analysis showed that, at weekdays, subjects characterized as primary school students, boys, urban area, living in western area and sufficient vigorous physical activity ≤2 d/w had higher risk for screen time >2 h/d than those characterized as elementary school students, girls, rural area, living in eastern area and sufficient vigorous physical activity >3 d/w, odds ratio were 2.01, 1.54, 1.21, 1.09, and 1.07, respectively (P<0.05 for all); subjects characterized as a normal or worse self rating academic performance had higher risk for screen time >2 h/d than those characterized as a good self rating academic performance, odds ratioes were 1.24 and 1.73, respectively (P<0.05 for all); subjects characterized as paternal education level as elementary school, middle school, high school or secondary school had higher risk for screen time >2 h/d than those characterized as paternal education level as college school or high, odds ratioes were 1.41, 1.47 and 1.52, respectively (P<0.05 for all); subjects characterized as maternal education level as elementary school, middle school and high school or secondary school had higher risk for screen time >2 h/d than those characterized as maternal education level as college, odds ratioes were 1.40, 1.52 and 1.47, respectively (P<0.05 for all). At weekends, subjects characterized as primary school students, boys, urban area and sufficient vigorous physical activity ≤2 d/w had higher risk for screen time >2 h/d than those characterized as elementary school students, girls, rural area and sufficient vigorous physical activity >3 d/w, odds ratioes were 2.11, 1.51, 1.20 and 1.05, respectively (P<0.05 for all). At weekends, subjects characterized as a normal or worse self rating academic performance had higher risk for screen time >2 h/d than those characterized as a good self rating academic performance, odds ratioes were 1.09 and 1.26, respectively (P<0.05 for all); subjects characterized as paternal education level as elementary school, middle school, high school or secondary school had higher risk for screen time >2 h/d than those characterized as paternal education level as college school or high, odds ratioes were 1.29, 1.30 and 1.19, respectively (P<0.05 for all); subjects characterized as maternal education level as elementary school, middle school had higher risk for screen time >2 h/d than those characterized as maternal education level as college school or high, odds ratioes were 1.19 and 1.16 and, respectively (P<0.05 for all). The prevalence of screen time >2 h/d is high; screen time at weekdays is longer than weekends, and there are significant differences among different sexes, urban or rural areas, living areas, self rating academic performance, parents education levels and physical activity groups.

[Progresses in screening active compounds from herbal medicine by affinity chromatography].

PubMed

Feng, Ying-shu; Tong, Shan-shan; Xu, Xi-ming; Yu, Jiang-nan

2015-03-01

Affinity chromatography is a chromatographic method for separating molecules using the binding characteristics of the stationary phase with potential drug molecules. This method can be performed as a high throughput screening method and a chromatographic separation method to screen a variety of active drugs. This paper summarizes the history of affinity chromatography, screening technology of affinity chromatography, and application of affinity chromatography in screening bio-active compounds in herbal medicines, and then discusses its application prospects, in order to broaden applications of the affinity chromatography in drug screening.

Above-real-time training (ARTT) improves transfer to a simulated flight control task.

PubMed

Donderi, D C; Niall, Keith K; Fish, Karyn; Goldstein, Benjamin

2012-06-01

The aim of this study was to measure the effects of above-real-time-training (ARTT) speed and screen resolution on a simulated flight control task. ARTT has been shown to improve transfer to the criterion task in some military simulation experiments. We tested training speed and screen resolution in a project, sponsored by Defence Research and Development Canada, to develop components for prototype air mission simulators. For this study, 54 participants used a single-screen PC-based flight simulation program to learn to chase and catch an F-18A fighter jet with another F-18A while controlling the chase aircraft with a throttle and side-stick controller. Screen resolution was varied between participants, and training speed was varied factorially across two sessions within participants. Pretest and posttest trials were at high resolution and criterion (900 knots) speed. Posttest performance was best with high screen resolution training and when one ARTT training session was followed by a session of criterion speed training. ARTT followed by criterion training improves performance on a visual-motor coordination task. We think that ARTT influences known facilitators of transfer, including similarity to the criterion task and contextual interference. Use high-screen resolution, start with ARTT, and finish with criterion speed training when preparing a mission simulation.

Controlled carrier screening in p-n NiO/GaN piezoelectric generators by an Al2O3 insertion layer

NASA Astrophysics Data System (ADS)

Johar, Muhammad Ali; Jeong, Dae Kyung; Afifi Hassan, Mostafa; Kang, Jin-Ho; Ha, Jun-Seok; Key Lee, June; Ryu, Sang-Wan

2017-12-01

The performance of a piezoelectric generator (PG) depends significantly on the internal screening process inside the device. As piezoelectric charges appear on both ends of the piezoelectric crystal, internal screening starts to decrease the piezoelectric bias. Therefore, the piezoelectric energy generated by external stress is not fully utilized by external circuit, which is the most challenging aspect of high-efficiency PGs. In this work, the internal screening effect of a NiO/GaN p-n PG was analyzed and controlled with an Al2O3 insertion layer. Internal screening in the p-n diode PG was categorized into free-carrier screening in neutral regions and junction screening due to charge drift across the junction. It was observed that junction screening could be significantly suppressed by inserting an Al2O3 layer and that effect was dominant in a leaky diode PG. With this implementation, the piezoelectric bias of the NiO/GaN PG was improved by a factor of ~100 for high-leakage diodes and a factor of ~1.6 for low-leakage diodes. Consequently, NiO/Al2O3/GaN PGs under a stress of 5 MPa provided a piezoelectric bias of 12.1 V and a current density of 2.25 µA cm-2. The incorporation of a highly resistive Al2O3 layer between p-NiO and n-GaN layers in NiO/GaN heterojunctions provides an efficient means of improving the piezoelectric performance by controlling the internal screening of the piezoelectric field.

High Prevalence of Anal Human Papillomavirus-Associated Cancer Precursors in a Contemporary Cohort of Asymptomatic HIV-Infected Women.

PubMed

Heard, Isabelle; Etienney, Isabelle; Potard, Valérie; Poizot-Martin, Isabelle; Moore, Catherine; Lesage, Anne-Carole; Ressiot, Emmanuelle; Crenn-Hebert, Catherine; Fléjou, Jean-François; Cubie, Heather; Costagliola, Dominique; Darragh, Teresa M

2015-05-15

Although human immunodeficiency virus (HIV)-infected women are at high risk for anal cancer, few data have been published on prevalence of and risk factors for anal precancer and potential screening strategies in this risk group. A cross-sectional anal screening study was nested in a gynecological cohort of HIV-infected women. Anal swab specimens were collected for cytology and human papillomavirus (HPV) testing. High-resolution anoscopy, with biopsy when indicated, was systematically performed. Among the 171 enrolled women, median age was 47.3 years and 98% were receiving combination antiretroviral therapy. Median CD4(+) count was 655 cells/µL and HIV load was <50 copies/mL in 89% of subjects. High-grade anal intraepithelial neoplasia or worse (HG-AIN+) was diagnosed in 12.9% (n = 21). In multivariable analysis, a history of cervical squamous intraepithelial lesion (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.1-16.4) and anal HPV-16 infection (OR, 16.1; 95% CI, 5.4-48.3) was associated with increased risk of HG-AIN+. Abnormal anal cytology and HPV-16 infection performed best as a screening strategy for HG-AIN+ histology, with positive likelihood ratios of 3.4 (95% CI, 2.3-5.1) and 4.7 (95% CI, 2.5-8.7) and negative likelihood ratios of 0.2 (95% CI, .07-.8) and 0.4 (95% CI, .2-.9), respectively. HIV-infected women with a history of HPV-associated cervical disease are at increased risk for HG-AIN+ and should be offered anal cancer screening. Anal cytology and HPV-16 genotyping had the best screening performance. Anal cytology is easy to perform routinely; it may be the best candidate for screening for HG-AIN among HIV-infected women. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2004-11-01

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

Mathematical modeling of high and low temperature heat pipes

NASA Technical Reports Server (NTRS)

Chi, S. W.

1971-01-01

Following a review of heat and mass transfer theory relevant to heat pipe performance, math models are developed for calculating heat-transfer limitations of high-temperature heat pipes and heat-transfer limitations and temperature gradient of low temperature heat pipes. Calculated results are compared with the available experimental data from various sources to increase confidence in the present math models. Complete listings of two computer programs for high- and low-temperature heat pipes respectively are included. These programs enable the performance to be predicted of heat pipes with wrapped-screen, rectangular-groove, or screen-covered rectangular-groove wick.

Screening anti-tumor compounds from Ligusticum wallichii using cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry.

PubMed

Zhang, Tao; Ding, Yuanyuan; An, Hongli; Feng, Liuxin; Wang, Sicen

2015-07-14

Tyrosine 367 Cysteine-fibroblast growth factor receptor 4 cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry was developed. Tyrosine 367 Cysteine-HEK293 cells were used as cell membrane stationary phase. Specificity and reproducibility of the cell membrane chromatography was evaluated using 1-tert-butyl-3-{2-[4-(diethylamino)butylamino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl}urea, Nimodipine and dexamethasone acetate. Then, anti-tumor components acting on Tyrosine 367 Cysteine-fibroblast growth factor receptor 4 were screened and identified from extracts of Ligusticum wallichii. Components from the extract were retained on the cell membrane chromatographic column. The retained fraction was directly eluted into high-performance liquid chromatography with mass spectrometry system for separation and identification. Finally, Levistolide A was identified as an active component from Ligusticum wallichii extracts. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan colorimetric assay revealed that Levistolide A inhibits proliferation of overexpressing the mutated receptor cells with dose-dependent manner. Phosphorylation of fibroblast growth factor receptor 4 was also decrease under Levistolide A treatment. Flex dock simulation verified that Levistolide A could bind with the tyrosine kinase domain of fibroblast growth factor receptor 4. Therefore, Levistolide A screened by the cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry can arrest cell growth. In conclusion, the two-dimensional high-performance liquid chromatography method can screen and identify potential anti-tumor ingredients which specifically act on the tyrosine kinase domain of the mutated fibroblast growth factor receptor 4. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Fluorescence imaging technology (FI) for high-throughput screening of selenide-modified nano-TiO2 catalysts.

PubMed

Wang, Liping; Lee, Jianchao; Zhang, Meijuan; Duan, Qiannan; Zhang, Jiarui; Qi, Hailang

2016-02-18

A high-throughput screening (HTS) method based on fluorescence imaging (FI) was implemented to evaluate the catalytic performance of selenide-modified nano-TiO2. Chemical ink-jet printing (IJP) technology was reformed to fabricate a catalyst library comprising 1405 (Ni(a)Cu(b)Cd(c)Ce(d)In(e)Y(f))Se(x)/TiO2 (M6Se/Ti) composite photocatalysts. Nineteen M6Se/Tis were screened out from the 1405 candidates efficiently.

A strategy for screening antioxidants in Ginkgo biloba extract by comprehensive two-dimensional ultra high performance liquid chromatography.

PubMed

Guo, Ru-Zhou; Liu, Xin-Guang; Gao, Wen; Dong, Xin; Fanali, Salvatore; Li, Ping; Yang, Hua

2015-11-27

Recently, screening of bioactive compounds by on-line ultra-high performance liquid chromatography (UHPLC) draws increasing attentions for the advantages of rapidity and intuition. Nevertheless, most on-line methods were limited to the shortcoming like low resolution and peak capacity, which could interfere the active ingredient identification. Comprehensive two-dimensional UHPLC (LC×LC) has revealed to be a powerful tool to separate complex mixtures. Herein, a strategy based on LC×LC analysis coupled with pre-column 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was proposed to screen the antioxidants from the extract of Ginkgo biloba (EGB). A total of 61 compounds were identified in EGB, and 25 of them showed appreciable radical scavenging capacity. This work may offer pharmacodynamics base for further research about EGB, also the strategy is likelihood to be applied in screening antioxidant in other herbal medicine. Copyright © 2015 Elsevier B.V. All rights reserved.

Screening and identification of radical scavengers from Neo-Taraxacum siphonanthum by online rapid screening method and nuclear magnetic resonance experiments.

PubMed

Shi, Shu Yun; Zhang, Yu Ping; Zhou, Hong Hao; Huang, Ke Long; Jiang, Xin Yu

2010-01-01

An online rapid screening method, the high-performance liquid chromatography (HPLC)-diode array detector (DAD)-radical scavenging detection (RSD)-electrospray ionization (ESI)-mass spectroscopy (MS)/MS system, was developed for the screening and identification of radical scavengers from Neo-Taraxacum siphonanthum, a new species found in China in 1989. For further characterization, the target compounds were isolated by silica column chromatography, preparative high-performance liquid chromatography (HPLC), HSCCC, and Sephadex LH-20 column chromatography and elucidated on the basis of ultraviolet (UV), ESI-MS/MS, and nuclear magnetic resonance (NMR) spectroscopy, as well as the chemical analysis. Eighteen antioxidative polyphenols (5 caffeic acid derivatives and 13 flavonoid derivatives) were characterized from Neo-T. siphonanthum. The distribution of all compounds was discussed in a chemosystematic context, which suggested that the genera Neo-Taraxacum and Taraxacum might relate chemosystematically.

Posture and performance: sitting vs. standing for security screening.

PubMed

Drury, C G; Hsiao, Y L; Joseph, C; Joshi, S; Lapp, J; Pennathur, P R

2008-03-01

A classification of the literature on the effects of workplace posture on performance of different mental tasks showed few consistent patterns. A parallel classification of the complementary effect of performance on postural variables gave similar results. Because of a lack of data for signal detection tasks, an experiment was performed using 12 experienced security operators performing an X-ray baggage-screening task with three different workplace arrangements. The current workplace, sitting on a high chair viewing a screen placed on top of the X-ray machine, was compared to a standing workplace and a conventional desk-sitting workplace. No performance effects of workplace posture were found, although the experiment was able to measure performance effects of learning and body part discomfort effects of workplace posture. There are implications for the classification of posture and performance and for the justification of ergonomics improvements based on performance increases.

A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

PubMed

Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

2015-11-24

Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

ScreenMasker: An Open-source Gaze-contingent Screen Masking Environment.

PubMed

Orlov, Pavel A; Bednarik, Roman

2016-09-01

The moving-window paradigm, based on gazecontingent technic, traditionally used in a studies of the visual perceptual span. There is a strong demand for new environments that could be employed by non-technical researchers. We have developed an easy-to-use tool with a graphical user interface (GUI) allowing both execution and control of visual gaze-contingency studies. This work describes ScreenMasker, an environment that allows create gaze-contingent textured displays used together with stimuli presentation software. ScreenMasker has an architecture that meets the requirements of low-latency real-time eye-movement experiments. It also provides a variety of settings and functions. Effective rendering times and performance are ensured by means of GPU processing under CUDA technology. Performance tests show ScreenMasker's latency to be 67-74 ms on a typical office computer, and high-end 144-Hz screen latencies of about 25-28 ms. ScreenMasker is an open-source system distributed under the GNU Lesser General Public License and is available at https://github.com/PaulOrlov/ScreenMasker .

Ionic-liquid-based ultrasound-assisted extraction of isoflavones from Belamcanda chinensis and subsequent screening and isolation of potential α-glucosidase inhibitors by ultrafiltration and semipreparative high-performance liquid chromatography.

PubMed

Li, Senlin; Li, Sainan; Huang, Yu; Liu, Chunming; Chen, Lina; Zhang, Yuchi

2017-06-01

The separation of a compound of interest from its structurally similar homologues to produce high-purity natural products is a challenging problem. This work proposes a novel method for the separation of iristectorigenin A from its structurally similar homologues by ionic-liquid-based ultrasound-assisted extraction and the subsequent screening and isolation of potential α-glucosidase inhibitors via ultrafiltration and semipreparative high-performance liquid chromatography. Ionic-liquid-based ultrasound-assisted extraction was successfully applied to the extraction of tectorigenin, iristectorigenin A, irigenin, and irisflorentin from Belamcanda chinensis. The optimum conditions for the efficient extraction of isoflavones were determined as 1.0 M 1-ethyl-3-methylimidazolium tetrafluoroborate with extraction time of 30 min and a solvent to solid ratio of 30 mL/g. Ultrafiltration with liquid chromatography and mass spectrometry was applied to screen and identify α-glucosidase inhibitors from B. chinensis, followed by the application of semipreparative high-performance liquid chromatography to separate and isolate the active constituents. Four major compounds including tectorigenin, iristectorigenin A, irigenin, and irisflorentin were screened and identified as α-glucosidase inhibitors, and then the four active compounds abovementioned were subsequently isolated by semipreparative high-performance liquid chromatography (99.89, 88.97, 99.79, and 99.97% purity, respectively). The results demonstrate that ionic liquid extraction can be successfully applied to the extraction of isoflavones from B. chinensis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of feedback interventions for improving the quality assurance of cancer screening in Japan: study design and report of the baseline survey.

PubMed

Machii, Ryoko; Saika, Kumiko; Higashi, Takahiro; Aoki, Ayako; Hamashima, Chisato; Saito, Hiroshi

2012-02-01

The importance of quality assurance in cancer screening has recently gained increasing attention in Japan. To evaluate and improve quality, checklists and process indicators have been developed. To explore effective methods of enhancing quality in cancer screening, we started a randomized control study of the methods of evaluation and feedback for cancer control from 2009 to 2014. We randomly assigned 1270 municipal governments, equivalent to 71% of all Japanese municipal governments that performed screening programs, into three groups. The high-intensity intervention groups (n = 425) were individually evaluated using both checklist performance and process indicator values, while the low-intensity intervention groups (n= 421) were individually evaluated on the basis of only checklist performance. The control group (n = 424) received only a basic report that included the national average of checklist performance scores. We repeated the survey for each municipality's quality assurance activity performance using checklists and process indicators. In this paper, we report our study design and the result of the baseline survey. The checklist adherence rates were especially low in the checklist elements related to invitation of individuals, detailed monitoring of process indicators such as cancer detection rates according to screening histories and appropriate selection of screening facilities. Screening rate and percentage of examinees who underwent detailed examination tended to be lower for large cities when compared with smaller cities for all cancer sites. The performance of the Japanese cancer screening program in 2009 was identified for the first time.

Universal neonatal screening for sickle cell disease and other haemoglobinopathies in Ferrara, Italy

PubMed Central

Ballardini, Elisa; Tarocco, Anna; Marsella, Maria; Bernardoni, Roberto; Carandina, Gianni; Melandri, Claudia; Guerra, Giovanni; Patella, Alfredo; Zucchelli, Miranda; Ferlini, Alessandra; Bigoni, Stefania; Ravani, Anna; Garani, Giampaolo; Borgna-Pignatti, Caterina

2013-01-01

Background Sickle cell disease is the commonest haemoglobinopathy in Africa, the Middle East and India. In recent years, its incidence has increased dramatically also in Europe and North America because of the high rate of migration of people from endemic areas. From January 2009 to January 2010 the number of foreign residents in the province of Ferrara (Italy) increased by 12.2%: most of the immigrants were from countries at high risk of sickle cell disease. Since neonatal screening and prophylactic penicillin in early childhood could reduce mortality by 10 years of age to less than 2%, the aim of this study was to establish a neonatal screening programme for haemoglobinopathies in Ferrara. Materials and methods First we assessed how many pregnant women underwent haemoglobin analysis by high performance liquid chromatography before or during pregnancy and how many of them were carriers of haemoglobinopathies. Subsequently, we verified the feasibility of neonatal screening for sickle cell disease and other haemoglobinopathies, analysing cord blood by high performance liquid chromatography. Neonates found to be positive were managed by a multidisciplinary team to implement all the appropriate prophylactic and therapeutic measures. Results We found that 59% of women who delivered at the University Hospital of Ferrara, from 2007 to 2009, had undergone high performance liquid chromatography. Of the 41% who were not tested, many were from areas in which sickle cell disease is common. Between September 26th 2010 and January 31st 2012, 1992 neonatal tests were performed and 24 carriers of haemoglobinopathies were identified (16 with HbS, 4 with HbC, 2 with HbE, 1 with HbD Punjab and 1 with HbD-Ouled Rabah); 42.6% of the mothers of these 1,992 neonates had not undergone high performance liquid chromatography during pregnancy. Discussion Currently prevention of haemoglobinopathies in Italy is provided during the pre-conception period but only to patients with abnormal blood counts. Neonatal screening is useful and cost-effective to ensure early diagnosis and appropriate treatment for infants with sickle cell disease or other haemoglobinopathies. PMID:23058858

Universal neonatal screening for sickle cell disease and other haemoglobinopathies in Ferrara, Italy.

PubMed

Ballardini, Elisa; Tarocco, Anna; Marsella, Maria; Bernardoni, Roberto; Carandina, Gianni; Melandri, Claudia; Guerra, Giovanni; Patella, Alfredo; Zucchelli, Miranda; Ferlini, Alessandra; Bigoni, Stefania; Ravani, Anna; Garani, Giampaolo; Borgna-Pignatti, Caterina

2013-04-01

Sickle cell disease is the commonest haemoglobinopathy in Africa, the Middle East and India. In recent years, its incidence has increased dramatically also in Europe and North America because of the high rate of migration of people from endemic areas. From January 2009 to January 2010 the number of foreign residents in the province of Ferrara (Italy) increased by 12.2%: most of the immigrants were from countries at high risk of sickle cell disease. Since neonatal screening and prophylactic penicillin in early childhood could reduce mortality by 10 years of age to less than 2%, the aim of this study was to establish a neonatal screening programme for haemoglobinopathies in Ferrara. First we assessed how many pregnant women underwent haemoglobin analysis by high performance liquid chromatography before or during pregnancy and how many of them were carriers of haemoglobinopathies. Subsequently, we verified the feasibility of neonatal screening for sickle cell disease and other haemoglobinopathies, analysing cord blood by high performance liquid chromatography. Neonates found to be positive were managed by a multidisciplinary team to implement all the appropriate prophylactic and therapeutic measures. We found that 59% of women who delivered at the University Hospital of Ferrara, from 2007 to 2009, had undergone high performance liquid chromatography. Of the 41% who were not tested, many were from areas in which sickle cell disease is common. Between September 26th 2010 and January 31st 2012, 1992 neonatal tests were performed and 24 carriers of haemoglobinopathies were identified (16 with HbS, 4 with HbC, 2 with HbE, 1 with HbD Punjab and 1 with HbD-Ouled Rabah); 42.6% of the mothers of these 1,992 neonates had not undergone high performance liquid chromatography during pregnancy. Currently prevention of haemoglobinopathies in Italy is provided during the pre-conception period but only to patients with abnormal blood counts. Neonatal screening is useful and cost-effective to ensure early diagnosis and appropriate treatment for infants with sickle cell disease or other haemoglobinopathies.

Screening for diabetes and prediabetes should be cost-saving in patients at high risk.

PubMed

Chatterjee, Ranee; Narayan, K M Venkat; Lipscomb, Joseph; Jackson, Sandra L; Long, Qi; Zhu, Ming; Phillips, Lawrence S

2013-07-01

Although screening for diabetes and prediabetes is recommended, it is not clear how best or whom to screen. We therefore compared the economics of screening according to baseline risk. Five screening tests were performed in 1,573 adults without known diabetes--random plasma/capillary glucose, plasma/capillary glucose 1 h after 50-g oral glucose (any time, without previous fast, plasma glucose 1 h after a 50-g oral glucose challenge [GCTpl]/capillary glucose 1 h after a 50-g oral glucose challenge [GCTcap]), and A1C--and a definitive 75-g oral glucose tolerance test. Costs of screening included the following: costs of testing (screen plus oral glucose tolerance test, if screen is positive); costs for false-negative results; and costs of treatment of true-positive results with metformin, all over the course of 3 years. We compared costs for no screening, screening everyone for diabetes or high-risk prediabetes, and screening those with risk factors based on age, BMI, blood pressure, waist circumference, lipids, or family history of diabetes. Compared with no screening, cost-savings would be obtained largely from screening those at higher risk, including those with BMI >35 kg/m(2), systolic blood pressure ≥130 mmHg, or age >55 years, with differences of up to -46% of health system costs for screening for diabetes and -21% for screening for dysglycemia110, respectively (all P < 0.01). GCTpl would be the least expensive screening test for most high-risk groups for this population over the course of 3 years. From a health economics perspective, screening for diabetes and high-risk prediabetes should target patients at higher risk, particularly those with BMI >35 kg/m(2), systolic blood pressure ≥130 mmHg, or age >55 years, for whom screening can be most cost-saving. GCTpl is generally the least expensive test in high-risk groups and should be considered for routine use as an opportunistic screen in these groups.

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

PubMed

Shankar, Manoharan; Priyadharshini, Ramachandran; Gunasekaran, Paramasamy

2009-08-01

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

CrossCheck: an open-source web tool for high-throughput screen data analysis.

PubMed

Najafov, Jamil; Najafov, Ayaz

2017-07-19

Modern high-throughput screening methods allow researchers to generate large datasets that potentially contain important biological information. However, oftentimes, picking relevant hits from such screens and generating testable hypotheses requires training in bioinformatics and the skills to efficiently perform database mining. There are currently no tools available to general public that allow users to cross-reference their screen datasets with published screen datasets. To this end, we developed CrossCheck, an online platform for high-throughput screen data analysis. CrossCheck is a centralized database that allows effortless comparison of the user-entered list of gene symbols with 16,231 published datasets. These datasets include published data from genome-wide RNAi and CRISPR screens, interactome proteomics and phosphoproteomics screens, cancer mutation databases, low-throughput studies of major cell signaling mediators, such as kinases, E3 ubiquitin ligases and phosphatases, and gene ontological information. Moreover, CrossCheck includes a novel database of predicted protein kinase substrates, which was developed using proteome-wide consensus motif searches. CrossCheck dramatically simplifies high-throughput screen data analysis and enables researchers to dig deep into the published literature and streamline data-driven hypothesis generation. CrossCheck is freely accessible as a web-based application at http://proteinguru.com/crosscheck.

Rapid screening, separation, and detection of hydroxyl radical scavengers from total flavonoids of Ginkgo biloba leaves by chromatography combined with molecular devices.

PubMed

Wang, Jing; Zheng, Meizhu; Chen, Lina; Liu, Zhiqiang; Zhang, Yuchi; Liu, Chun-Ming; Liu, Shu

2016-11-01

Hydroxyl radicals are the most reactive free radical of human body, a strong contributor to tissue damage. In this study, liquid chromatography coupled to electrospray ionization mass spectrometry was applied to screen and identify hydroxyl radical scavengers from the total flavonoids of Ginkgo biloba leaves, and high-performance counter current chromatography was used to separate and isolate the active compounds. Furthermore, molecular devices were used to determine hydroxyl radical scavenging activities of the obtained hydroxyl radical scavengers and other flavonoids from G. biloba leaves. As a result, six compounds were screened as hydroxyl radical scavengers, but only three flavonoids, namely, rutin, cosmos glycosides and apigenin-7-O-Glu-4'-O-Rha, were isolated successfully from total flavonoids by high-performance counter current chromatography. The purities of the three obtained compounds were over 90%, respectively, as determined by liquid chromatography. Molecular devices with 96-well microplates evaluation indicated that the 50% scavenging concentration values of screened compounds were lower than that of other flavonoids, they performed greater hydroxyl radical scavenging activity, and the evaluation effects were consistent with the liquid chromatography with mass spectrometry screening results. Therefore, chromatography combined with molecular devices is a feasible and an efficient method for systematic screening, identification, isolation, and evaluation of bioactive components in mixture of botanical medicines. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Capillary flow of amorphous metal for high performance electrode

PubMed Central

Kim, Se Yun; Kim, Suk Jun; Jee, Sang Soo; Park, Jin Man; Park, Keum Hwan; Park, Sung Chan; Cho, Eun Ae; Lee, Jun Ho; Song, In Yong; Lee, Sang Mock; Han, In Taek; Lim, Ka Ram; Kim, Won Tae; Park, Ju Cheol; Eckert, Jürgen; Kim, Do Hyang; Lee, Eun-Sung

2013-01-01

Metallic glass (MG) assists electrical contact of screen-printed silver electrodes and leads to comparable electrode performance to that of electroplated electrodes. For high electrode performance, MG needs to be infiltrated into nanometer-scale cavities between Ag particles and reacts with them. Here, we show that the MG in the supercooled state can fill the gap between Ag particles within a remarkably short time due to capillary effect. The flow behavior of the MG is revealed by computational fluid dynamics and density funtional theory simulation. Also, we suggest the formation mechanism of the Ag electrodes, and demonstrate the criteria of MG for higher electrode performance. Consequently, when Al85Ni5Y8Co2 MG is added in the Ag electrodes, cell efficiency is enhanced up to 20.30% which is the highest efficiency reported so far for screen-printed interdigitated back contact solar cells. These results show the possibility for the replacement of electroplating process to screen-printing process. PMID:23851671

Performance Studies on Distributed Virtual Screening

PubMed Central

Krüger, Jens; de la Garza, Luis; Kohlbacher, Oliver; Nagel, Wolfgang E.

2014-01-01

Virtual high-throughput screening (vHTS) is an invaluable method in modern drug discovery. It permits screening large datasets or databases of chemical structures for those structures binding possibly to a drug target. Virtual screening is typically performed by docking code, which often runs sequentially. Processing of huge vHTS datasets can be parallelized by chunking the data because individual docking runs are independent of each other. The goal of this work is to find an optimal splitting maximizing the speedup while considering overhead and available cores on Distributed Computing Infrastructures (DCIs). We have conducted thorough performance studies accounting not only for the runtime of the docking itself, but also for structure preparation. Performance studies were conducted via the workflow-enabled science gateway MoSGrid (Molecular Simulation Grid). As input we used benchmark datasets for protein kinases. Our performance studies show that docking workflows can be made to scale almost linearly up to 500 concurrent processes distributed even over large DCIs, thus accelerating vHTS campaigns significantly. PMID:25032219

Diagnostic Validity of High-Density Barium Sulfate in Gastric Cancer Screening: Follow-up of Screenees by Record Linkage with the Osaka Cancer Registry

PubMed Central

Yamamoto, Kenyu; Yamazaki, Hideo; Kuroda, Chikazumi; Kubo, Tsugio; Oshima, Akira; Katsuda, Toshizo; Kuwano, Tadao; Takeda, Yoshihiro

2010-01-01

Background The use of high-density barium sulfate was recommended by the Japan Society of Gastroenterological Cancer Screening (JSGCS) in 2004. We evaluated the diagnostic validity of gastric cancer screening that used high-density barium sulfate. Methods The study subjects were 171 833 residents of Osaka, Japan who underwent gastric cancer screening tests at the Osaka Cancer Prevention and Detection Center during the period from 1 January 2000 through 31 December 2001. Screening was conducted using either high-density barium sulfate (n = 48 336) or moderate-density barium sulfate (n = 123 497). The subjects were followed up and their medical records were linked to those of the Osaka Cancer Registry through 31 December 2002. The results of follow-up during 1 year were defined as the gold standard, and test performance values were calculated. Results The sensitivity and specificity of the screening test using moderate-density barium sulfate were 92.3% and 91.0%, respectively, while the sensitivity and specificity of the high-density barium test were 91.8% and 91.4%, respectively. The results of area under receiver-operating-characteristic (ROC) curve analysis revealed no significant difference between the 2 screening tests. Conclusions Screening tests using high- and moderate-density barium sulfate had similar validity, as determined by sensitivity, specificity, and ROC curve analysis. PMID:20551581

A Systematic Review of Studies Evaluating the Cost Utility of Screening High-Risk Populations for Latent Tuberculosis Infection.

PubMed

Campbell, Jonathon R; Sasitharan, Thenuga; Marra, Fawziah

2015-08-01

As tuberculosis screening trends to targeting high-risk populations, knowing the cost effectiveness of such screening is vital to decision makers. The purpose of this review was to compile cost-utility analyses evaluating latent tuberculosis infection (LTBI) screening in high-risk populations that used quality-adjusted life-years (QALYs) as their measure of effectiveness. A literature search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Web of Knowledge, and PubMed was performed from database start to November 2014. Studies performed in populations at high risk of LTBI and subsequent reactivation that used the QALY as an effectiveness measure were included. Quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Data extracted included tuberculin skin test (TST) and/or interferon-gamma release assay (IGRA) use, economic, screening, treatment, health state, and epidemiologic parameters. Data were summarized in regard to consistency in model parameters and the incremental cost-effectiveness ratio (ICER), with costs adjusted to 2013 US dollars. Of 415 studies identified, ultimately eight studies were included in the review. Most took a societal perspective (n = 4), used lifetime time horizons (n = 6), and used Markov models (n = 8). Screening of adult immigrants was found to be cost effective with a TST in one study, but moderately cost effective with an IGRA in another study; screening immigrants arriving more than 5 years prior with an IGRA was moderately cost effective until 44 years of age (n = 1). Screening HIV-positive patients was highly cost effective with a TST (n = 1) and moderately cost effective with an IGRA (n = 1). Screening in those with renal diseases (n = 2) and diabetes (n = 1) was not cost effective. Very few studies used the QALY as their effectiveness measure. Parameter and study design inconsistencies limit the comparability of studies. With validity issues in terms of parameters and assumptions, any conclusion should be interpreted with caution. Despite this, some cautionary recommendations emerged: screening HIV patients with a TST is highly cost effective, while screening adult immigrants with an IGRA is moderately cost effective.

X ray screening at entry and systematic screening for the control of tuberculosis in a highly endemic prison.

PubMed

Sanchez, Alexandra; Massari, Veronique; Gerhardt, Germano; Espinola, Ana Beatriz; Siriwardana, Mahinda; Camacho, Luiz Antonio B; Larouzé, Bernard

2013-10-20

Tuberculosis (TB) is a major issue in prisons of low and middle income countries where TB incidence rates are much higher in prison populations as compared with the general population. In the Rio de Janeiro (RJ) State prison system, the TB control program is limited to passive case-finding and supervised short duration treatment. The aim of this study was to measure the impact of X-ray screening at entry associated with systematic screening on the prevalence and incidence of active TB. We followed up for 2 years a RJ State prison for adult males (1429 inmates at the beginning of the study) and performed, in addition to passive case-finding, 1) two "cross-sectional" X-ray systematic screenings: the first at the beginning of the study period and the second 13 months later; 2) X-ray screening of inmates entering the prison during the 2 year study period. Bacteriological examinations were performed in inmates presenting any pulmonary, pleural or mediastinal X-ray abnormality or spontaneously attending the prison clinic for symptoms suggestive of TB. Overall, 4326 X-rays were performed and 246 TB cases were identified. Prevalence among entering inmates remained similar during 1st and the 2nd year of the study: 2.8% (21/754) and 2.9% (28/954) respectively, whereas prevalence decreased from 6.0% (83/1374) to 2.8% (35/1244) between 1st and 2nd systematic screenings (p < 0.0001). Incidence rates of cases identified by passive case-finding decreased from 42 to 19 per 1000 person-years between the 1st and the 2nd year (p < 0.0001). Cases identified by screenings were less likely to be bacteriologically confirmed as compared with cases identified by passive-case finding. The strategy investigated, which seems highly effective, should be considered in highly endemic confined settings such as prisons.

Impact of Immediate Interpretation of Screening Tomosynthesis Mammography on Performance Metrics.

PubMed

Winkler, Nicole S; Freer, Phoebe; Anzai, Yoshimi; Hu, Nan; Stein, Matthew

2018-05-07

This study aimed to compare performance metrics for immediate and delayed batch interpretation of screening tomosynthesis mammograms. This HIPAA compliant study was approved by institutional review board with a waiver of consent. A retrospective analysis of screening performance metrics for tomosynthesis mammograms interpreted in 2015 when mammograms were read immediately was compared to historical controls from 2013 to 2014 when mammograms were batch interpreted after the patient had departed. A total of 5518 screening tomosynthesis mammograms (n = 1212 for batch interpretation and n = 4306 for immediate interpretation) were evaluated. The larger sample size for the latter group reflects a group practice shift to performing tomosynthesis for the majority of patients. Age, breast density, comparison examinations, and high-risk status were compared. An asymptotic proportion test and multivariable analysis were used to compare performance metrics. There was no statistically significant difference in recall or cancer detection rates for the batch interpretation group compared to immediate interpretation group with respective recall rate of 6.5% vs 5.3% = +1.2% (95% confidence interval -0.3 to 2.7%; P = .101) and cancer detection rate of 6.6 vs 7.2 per thousand = -0.6 (95% confidence interval -5.9 to 4.6; P = .825). There was no statistically significant difference in positive predictive values (PPVs) including PPV1 (screening recall), PPV2 (biopsy recommendation), or PPV 3 (biopsy performed) with batch interpretation (10.1%, 42.1%, and 40.0%, respectively) and immediate interpretation (13.6%, 39.2%, and 39.7%, respectively). After adjusting for age, breast density, high-risk status, and comparison mammogram, there was no difference in the odds of being recalled or cancer detection between the two groups. There is no statistically significant difference in interpretation performance metrics for screening tomosynthesis mammograms interpreted immediately compared to those interpreted in a delayed fashion. Copyright © 2018. Published by Elsevier Inc.

Next generation smart window display using transparent organic display and light blocking screen.

PubMed

Kim, Gyeong Woo; Lampande, Raju; Choe, Dong Cheol; Ko, Ik Jang; Park, Jin Hwan; Pode, Ramchandra; Kwon, Jang Hyuk

2018-04-02

Transparent organic light emitting diodes (TOLED) have widespread applications in the next-generation display devices particularly in the large size transparent window and interactive displays. Herein, we report high performance and stable attractive smart window displays using facile process. Advanced smart window display is realized by integrating the high performance light blocking screen and highly transparent white OLED panel. The full smart window display reveals a maximum transmittance as high as 64.2% at the wavelength of 600 nm and extremely good along with tunable ambient contrast ratio (171.94:1) compared to that of normal TOLED (4.54:1). Furthermore, the performance decisive light blocking screen has demonstrated an excellent optical and electrical characteristics such as i) high transmittance (85.56% at 562nm) at light-penetrating state, ii) superior absorbance (2.30 at 562nm) in light interrupting mode, iii) high optical contrast (85.50 at 562 nm), iv) high optical stability for more than 25,000 cycle of driving, v) fast switching time of 1.9 sec, and vi) low driving voltage of 1.7 V. The experimental results of smart window display are also validated using optical simulation. The proposed smart window display technology allows us to adjust the intensity of daylight entering the system quickly and conveniently.

[Cervical cancer screening: Is active recruitment worth the effort?].

PubMed

Morales Martínez, Ángeles; Blanco Rodríguez, Lorena; Morales Martínez, Cristina; Tejuca Somoano, Sonia

2015-12-01

To determine the percentage of women who have had a Pap smear in the last 5 years, and the place where it was carried out. To detect cytological abnormalities and precursors of cervical cancer in un-screened or inadequately screened women and the prevalence of HPV-positive determinations. Cross sectional study. Natahoyo Health Centre, Gijón (Spain). Women aged 40-50 years living in the area and assigned to the Health Centre. The information was collected from databases, telephone and home surveys. There was active recruitment of unscreened women or inadequately screened in Primary Care as well as offering to perform cytology and HPV determination. Of the 1420 women aged 40 to 50 years, 1236 (87%) had cytology in the last 5 years, and 184 women (13%) had no screening or it was inadequate. Of these 184 women, 108 (58.7%) agreed to have cytology and HPV test performed. No high-grade cervical dysplasia was diagnosed. The prevalence of HPV-positive was 8.3%. In our population there is a high coverage of opportunistic screening for cervical cancer. The active recruitment of women who were not in the screening program was not useful. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Fitness for duty: A 3 minute version of the Psychomotor Vigilance Test predicts fatigue related declines in luggage screening performance

PubMed Central

Basner, Mathias; Rubinstein, Joshua

2011-01-01

Objective To evaluate the ability of a 3-min Psychomotor Vigilance Test (PVT) to predict fatigue related performance decrements on a simulated luggage screening task (SLST). Methods Thirty-six healthy non-professional subjects (mean age 30.8 years, 20 female) participated in a 4 day laboratory protocol including a 34 hour period of total sleep deprivation with PVT and SLST testing every 2 hours. Results Eleven and 20 lapses (355 ms threshold) on the PVT optimally divided SLST performance into high, medium, and low performance bouts with significantly decreasing threat detection performance A′. Assignment to the different SLST performance groups replicated homeostatic and circadian patterns during total sleep deprivation. Conclusions The 3 min PVT was able to predict performance on a simulated luggage screening task. Fitness-for-duty feasibility should now be tested in professional screeners and operational environments. PMID:21912278

Fitness for duty: a 3-minute version of the Psychomotor Vigilance Test predicts fatigue-related declines in luggage-screening performance.

PubMed

Basner, Mathias; Rubinstein, Joshua

2011-10-01

To evaluate the ability of a 3-minute Psychomotor Vigilance Test (PVT) to predict fatigue-related performance decrements on a simulated luggage-screening task (SLST). Thirty-six healthy nonprofessional subjects (mean age = 30.8 years, 20 women) participated in a 4-day laboratory protocol including a 34-hour period of total sleep deprivation with PVT and SLST testing every 2 hours. Eleven and 20 lapses (355-ms threshold) on the PVT optimally divided SLST performance into high-, medium-, and low-performance bouts with significantly decreasing threat detection performance A'. Assignment to the different SLST performance groups replicated homeostatic and circadian patterns during total sleep deprivation. The 3-minute PVT was able to predict performance on a simulated luggage-screening task. Fitness-for-duty feasibility should now be tested in professional screeners and operational environments.

Development of a Rapid Fluorescence-Based High-Throughput Screening Assay to Identify Novel Kynurenine 3-Monooxygenase Inhibitor Scaffolds.

PubMed

Jacobs, K R; Guillemin, G J; Lovejoy, D B

2018-02-01

Kynurenine 3-monooxygenase (KMO) is a well-validated therapeutic target for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD) and Huntington's disease (HD). This work reports a facile fluorescence-based KMO assay optimized for high-throughput screening (HTS) that achieves a throughput approximately 20-fold higher than the fastest KMO assay currently reported. The screen was run with excellent performance (average Z' value of 0.80) from 110,000 compounds across 341 plates and exceeded all statistical parameters used to describe a robust HTS assay. A subset of molecules was selected for validation by ultra-high-performance liquid chromatography, resulting in the confirmation of a novel hit with an IC 50 comparable to that of the well-described KMO inhibitor Ro-61-8048. A medicinal chemistry program is currently underway to further develop our novel KMO inhibitor scaffolds.

Understanding and development of manufacturable screen-printed contacts on high sheet-resistance emitters for low-cost silicon solar cells

NASA Astrophysics Data System (ADS)

Hilali, Mohamed M.

2005-11-01

A simple cost-effective approach was proposed and successfully employed to fabricate high-quality screen-printed (SP) contacts to high sheet-resistance emitters (100 O/sq) to improve the Si solar cell efficiency. Device modeling was used to quantify the performance enhancement possible from the high sheet-resistance emitter for various cell designs. It was found that for performance enhancement from the high sheet-resistance emitter, certain cell design criteria must be satisfied. Model calculations showed that in order to achieve any performance enhancement over the conventional ˜40 O/sq emitter, the high sheet resistance emitter solar cell must have a reasonably good (<120,000 cm/s) or low front-surface recombination velocity (FSRV). Model calculations were also performed to establish requirements for high fill factors (FFs). The results showed that the series resistance should be less than 0.8 O-cm2, the shunt resistance should be greater than 1000 O-cm2, and the junction leakage current should be less than 25 nA/cm2. Analytical microscopy and surface analysis techniques were used to study the Ag-Si contact interface of different SP Ag pastes. Physical and electrical properties of SP Ag thick-film contacts were studied and correlated to understand and achieve good-quality ohmic contacts to high sheet-resistance emitters for solar cells. This information was then used to define the criteria for high-quality screen-printed contacts. The role of paste constituents and firing scheme on contact quality were investigated to tailor the high-quality screen-printed contact interface structure that results in high performance solar cells. Results indicated that small particle size, high glass transition temperature, rapid firing and less aggressive glass frit help in producing high-quality contacts. Based on these results high-quality SP contacts with high FFs > 0.78 on high sheet-resistance emitters were achieved for the first time using a simple single-step firing process. This technology was applied to different substrates (monocrystalline and multicrystalline) and surfaces (textured and planar). Cell efficiencies of ˜16.2% on low-cost EFG ribbon substrates were achieved on high sheet-resistance emitters with SP contacts. A record high-efficiency SP solar cell of 19% with textured high sheet-resistance emitter was also fabricated and modeled.

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

PubMed Central

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

2015-01-01

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

Developing the Biomolecular Screening Facility at the EPFL into the Chemical Biology Screening Platform for Switzerland.

PubMed

Turcatti, Gerardo

2014-05-01

The Biomolecular Screening Facility (BSF) is a multidisciplinary laboratory created in 2006 at the Ecole Polytechnique Federale de Lausanne (EPFL) to perform medium and high throughput screening in life sciences-related projects. The BSF was conceived and developed to meet the needs of a wide range of researchers, without privileging a particular biological discipline or therapeutic area. The facility has the necessary infrastructure, multidisciplinary expertise and flexibility to perform large screening programs using small interfering RNAs (siRNAs) and chemical collections in the areas of chemical biology, systems biology and drug discovery. In the framework of the National Centres of Competence in Research (NCCR) Chemical Biology, the BSF is hosting 'ACCESS', the Academic Chemical Screening Platform of Switzerland that provides the scientific community with chemical diversity, screening facilities and know-how in chemical genetics. In addition, the BSF started its own applied research axes that are driven by innovation in thematic areas related to preclinical drug discovery and discovery of bioactive probes.

Large-screen display technology assessment for military applications

NASA Astrophysics Data System (ADS)

Blaha, Richard J.

1990-08-01

Full-color, large screen display systems can enhance military applications that require group presentation, coordinated decisions, or interaction between decision makers. The technology already plays an important role in operations centers, simulation facilities, conference rooms, and training centers. Some applications display situational, status, or briefing information, while others portray instructional material for procedural training or depict realistic panoramic scenes that are used in simulators. While each specific application requires unique values of luminance, resolution, response time, reliability, and the video interface, suitable performance can be achieved with available commercial large screen displays. Advances in the technology of large screen displays are driven by the commercial applications because the military applications do not provide the significant market share enjoyed by high definition television (HDTV), entertainment, advertisement, training, and industrial applications. This paper reviews the status of full-color, large screen display technologies and includes the performance and cost metrics of available systems. For this discussion, performance data is based upon either measurements made by our personnel or extractions from vendors' data sheets.

Nutritional screening in hospitalized pediatric patients: a systematic review.

PubMed

Teixeira, Adriana Fonseca; Viana, Kátia Danielle Araújo Lourenço

2016-01-01

This systematic review aimed to verify the available scientific evidence on the clinical performance and diagnostic accuracy of nutritional screening tools in hospitalized pediatric patients. A search was performed in the Medline (National Library of Medicine United States), LILACS (Latin American and Caribbean Health Sciences), PubMed (US National Library of Medicine National Institutes of Health), in the SCIELO (Scientific Electronic Library Online), through CAPES portal (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), bases Scopus e Web of Science. The descriptors used in accordance with the Descriptors in Health Sciences (DeCS)/Medical Subject Headings (MeSH) list were "malnutrition", "screening", and "pediatrics", as well as the equivalent words in Portuguese. The authors identified 270 articles published between 2004 and 2014. After applying the selection criteria, 35 were analyzed in full and eight articles were included in the systematic review. We evaluated the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Five nutritional screening tools in pediatrics were identified. Among these, the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) showed high sensitivity, almost perfect inter-rater agreement and between the screening and the reference standard; the Screening Tool Risk on Nutritional Status and Growth (STRONGkids) showed high sensitivity, lower percentage of specificity, substantial intra-rater agreement, and ease of use in clinical practice. The studies included in this systematic review showed good performance of the nutritional screening tools in pediatrics, especially STRONGkids and STAMP. The authors emphasize the need to perform for more studies in this area. Only one tool was translated and adapted to the Brazilian pediatric population, and it is essential to carry out studies of tool adaptation and validation for this population. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file.

PubMed

Bell, Andrew S; Bradley, Joseph; Everett, Jeremy R; Knight, Michelle; Loesel, Jens; Mathias, John; McLoughlin, David; Mills, James; Sharp, Robert E; Williams, Christine; Wood, Terence P

2013-05-01

The screening files of many large companies, including Pfizer, have grown considerably due to internal chemistry efforts, company mergers and acquisitions, external contracted synthesis, or compound purchase schemes. In order to screen the targets of interest in a cost-effective fashion, we devised an easy-to-assemble, plate-based diversity subset (PBDS) that represents almost the entire computed chemical space of the screening file whilst comprising only a fraction of the plates in the collection. In order to create this file, we developed new design principles for the quality assessment of screening plates: the Rule of 40 (Ro40) and a plate selection process that insured excellent coverage of both library chemistry and legacy chemistry space. This paper describes the rationale, design, construction, and performance of the PBDS, that has evolved into the standard paradigm for singleton (one compound per well) high-throughput screening in Pfizer since its introduction in 2006.

Breast Cancer Screening Programmes across the WHO European Region: Differences among Countries Based on National Income Level.

PubMed

Altobelli, Emma; Rapacchietta, Leonardo; Angeletti, Paolo Matteo; Barbante, Luca; Profeta, Filippo Valerio; Fagnano, Roberto

2017-04-23

Breast cancer (BC) is the most frequent tumour affecting women all over the world. In low- and middle-income countries, where its incidence is expected to rise further, BC seems set to become a public health emergency. The aim of the present study is to provide a systematic review of current BC screening programmes in WHO European Region to identify possible patterns. Multiple correspondence analysis was performed to evaluate the association among: measures of occurrence; GNI level; type of BC screening programme; organization of public information and awareness campaigns regarding primary prevention of modifiable risk factors; type of BC screening services; year of screening institution; screening coverage and data quality. A key difference between High Income (HI) and Low and Middle Income (LMI) States, emerging from the present data, is that in the former screening programmes are well organized, with approved screening centres, the presence of mobile units to increase coverage, the offer of screening tests free of charge; the fairly high quality of occurrence data based on high-quality sources, and the adoption of accurate methods to estimate incidence and mortality. In conclusion, the governments of LMI countries should allocate sufficient resources to increase screening participation and they should improve the accuracy of incidence and mortality rates.

Electronic fitness function for screening semiconductors as thermoelectric materials

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

Xing, Guangzong; Sun, Jifeng; Li, Yuwei

Here, we introduce a simple but efficient electronic fitness function (EFF) that describes the electronic aspect of the thermoelectric performance. This EFF finds materials that overcome the inverse relationship between σ and S based on the complexity of the electronic structures regardless of specific origin (e.g., isosurface corrugation, valley degeneracy, heavy-light bands mixture, valley anisotropy or reduced dimensionality). This function is well suited for application in high throughput screening. We applied this function to 75 different thermoelectric and potential thermoelectric materials including full- and half-Heuslers, binary semiconductors, and Zintl phases. We find an efficient screening using this transport function. Themore » EFF identifies known high-performance p- and n-type Zintl phases and half-Heuslers. In addition, we find some previously unstudied phases with superior EFF.« less

Electronic fitness function for screening semiconductors as thermoelectric materials

DOE PAGES

Xing, Guangzong; Sun, Jifeng; Li, Yuwei; ...

2017-11-17

Here, we introduce a simple but efficient electronic fitness function (EFF) that describes the electronic aspect of the thermoelectric performance. This EFF finds materials that overcome the inverse relationship between σ and S based on the complexity of the electronic structures regardless of specific origin (e.g., isosurface corrugation, valley degeneracy, heavy-light bands mixture, valley anisotropy or reduced dimensionality). This function is well suited for application in high throughput screening. We applied this function to 75 different thermoelectric and potential thermoelectric materials including full- and half-Heuslers, binary semiconductors, and Zintl phases. We find an efficient screening using this transport function. Themore » EFF identifies known high-performance p- and n-type Zintl phases and half-Heuslers. In addition, we find some previously unstudied phases with superior EFF.« less

A strategy for screening of α-glucosidase inhibitors from Morus alba root bark based on the ligand fishing combined with high-performance liquid chromatography mass spectrometer and molecular docking.

PubMed

Wang, Zhen; Li, Xiaoqing; Chen, Menghan; Liu, Feiyan; Han, Chao; Kong, Lingyi; Luo, Jianguang

2018-04-01

A new method based on ligand fishing combined with high-performance liquid chromatography quadrupole-time-of-flight mass spectrometer and molecular docking was established to screen α-glucosidase inhibitors from a traditional Chinese medicine Morus alba root bark. α-Glucosidase was immobilized on magnetic nanoparticles, used as a solid support to incubate with crude extract. After ligand fishing, the eluates were analyzed by high-performance liquid chromatography quadrupole-time-of-flight mass spectrometer, obtaining eleven ligands (1-4, 6-12) eventually. In order to discriminate the non-specific binders and discover powerful enzyme inhibitors, molecular docking was further performed and three of the eleven ligands were optimized to be excellent α-glucosidase inhibitors by the confirmation of isolation and bioassay of individual compounds. These three ligands, sanggenons G (6), O (7) and sanggenol G (12) exhibited striking inhibitory activities with extremely low IC 50 values. The results suggest that established method will be applied to a wide range of target protein to screen potential bioactive constituents from herbal medicines. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-10-01

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

1-Adamantylamine a simple urine marker for screening for third generation adamantyl-type synthetic cannabinoids by ultra-performance liquid chromatography tandem mass spectrometry.

PubMed

Ford, Loretta T; Berg, Jonathan D

2016-11-01

Background Synthetic cannabinoids (NOIDS) are novel psychotropic drugs (NPS) currently freely sold in the United Kingdom as 'research chemicals'. Detection of NOIDS use is not available in current routine methods. Here we describe a marker which helps determine which patients have used these substances. Methods In a test case, ultra-performance liquid chromatography mass spectrometry (UPLC-Tof) was used to screen the legal high Herbal Haze II, the contents of hand-rolled cigarettes and five patient samples for NOIDS and their metabolites. Results Analysis of legal high Herbal Haze II and cigarettes identified the third generation adamantyl-type NOIDS N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), 5F-AKB-48 and N-adamantyl-1-fluoropentylindole-3-carboxamide (STS-135). Out of 18 potential metabolites, 1-adamantylamine (C 10 H 17 N) was detected in all five urine samples. This adamantyl-type NOID marker was incorporated into our routine LC-MS/MS urine screen. Out of 14,436 random urine samples screened over eight months, 296 (2.05%) tested positive for the adamantyl-type NOID marker. Conclusion We have discovered a urine marker for identifying patients smoking legal high products containing the third generation adamantyl-type NOIDS such as AKB-48 and its fluoropentyl analogue 5F-AKB-48, which are among the most popular NOIDS currently available in legal high products sold in UK. This marker can be incorporated into routine LC-MS/MS drug screening alongside classic drugs of abuse. Positive detection rates for this new legal high marker are greater than for established classic drugs that are routinely screened such as amphetamine. This work highlights the need for a flexible toxicology screening service capable of adapting to changes in drug use such as the growing popularity of legal highs/NPS.

Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening.

PubMed

Sestini, Stefano; Boeri, Mattia; Marchiano, Alfonso; Pelosi, Giuseppe; Galeone, Carlotta; Verri, Carla; Suatoni, Paola; Sverzellati, Nicola; La Vecchia, Carlo; Sozzi, Gabriella; Pastorino, Ugo

2015-10-20

Liquid biopsies can detect biomarkers carrying information on the development and progression of cancer. We demonstrated that a 24 plasma-based microRNA signature classifier (MSC) was capable of increasing the specificity of low dose computed tomography (LDCT) in a lung cancer screening trial. In the present study, we tested the prognostic performance of MSC, and its ability to monitor disease status recurrence in LDCT screening-detected lung cancers.Between 2000 and 2010, 3411 heavy smokers enrolled in two screening programmes, underwent annual or biennial LDCT. During the first five years of screening, 84 lung cancer patients were classified according to one of the three MSC levels of risk: high, intermediate or low. Kaplan-Meier survival analysis was performed according to MSC and clinico-pathological information. Follow-up MSC analysis was performed on longitudinal plasma samples (n = 100) collected from 31 patients before and after surgical resection.Five-year survival was 88.9% for low risk, 79.5% for intermediate risk and 40.1% for high risk MSC (p = 0.001). The prognostic power of MSC persisted after adjusting for tumor stage (p = 0.02) and when the analysis was restricted to LDCT-detected cases after exclusion of interval cancers (p < 0.001). The MSC risk level decreased after surgery in 76% of the 25 high-intermediate subjects who remained disease free, whereas in relapsing patients an increase of the MSC risk level was observed at the time of detection of second primary tumor or metastatic progression.These results encourage exploiting the MSC test for lung cancer monitoring in LDCT screening for lung cancer.

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

Improving compound-protein interaction prediction by building up highly credible negative samples.

PubMed

Liu, Hui; Sun, Jianjiang; Guan, Jihong; Zheng, Jie; Zhou, Shuigeng

2015-06-15

Computational prediction of compound-protein interactions (CPIs) is of great importance for drug design and development, as genome-scale experimental validation of CPIs is not only time-consuming but also prohibitively expensive. With the availability of an increasing number of validated interactions, the performance of computational prediction approaches is severely impended by the lack of reliable negative CPI samples. A systematic method of screening reliable negative sample becomes critical to improving the performance of in silico prediction methods. This article aims at building up a set of highly credible negative samples of CPIs via an in silico screening method. As most existing computational models assume that similar compounds are likely to interact with similar target proteins and achieve remarkable performance, it is rational to identify potential negative samples based on the converse negative proposition that the proteins dissimilar to every known/predicted target of a compound are not much likely to be targeted by the compound and vice versa. We integrated various resources, including chemical structures, chemical expression profiles and side effects of compounds, amino acid sequences, protein-protein interaction network and functional annotations of proteins, into a systematic screening framework. We first tested the screened negative samples on six classical classifiers, and all these classifiers achieved remarkably higher performance on our negative samples than on randomly generated negative samples for both human and Caenorhabditis elegans. We then verified the negative samples on three existing prediction models, including bipartite local model, Gaussian kernel profile and Bayesian matrix factorization, and found that the performances of these models are also significantly improved on the screened negative samples. Moreover, we validated the screened negative samples on a drug bioactivity dataset. Finally, we derived two sets of new interactions by training an support vector machine classifier on the positive interactions annotated in DrugBank and our screened negative interactions. The screened negative samples and the predicted interactions provide the research community with a useful resource for identifying new drug targets and a helpful supplement to the current curated compound-protein databases. Supplementary files are available at: http://admis.fudan.edu.cn/negative-cpi/. © The Author 2015. Published by Oxford University Press.

High-throughput screening of metal-porphyrin-like graphenes for selective capture of carbon dioxide

PubMed Central

Bae, Hyeonhu; Park, Minwoo; Jang, Byungryul; Kang, Yura; Park, Jinwoo; Lee, Hosik; Chung, Haegeun; Chung, ChiHye; Hong, Suklyun; Kwon, Yongkyung; Yakobson, Boris I.; Lee, Hoonkyung

2016-01-01

Nanostructured materials, such as zeolites and metal-organic frameworks, have been considered to capture CO2. However, their application has been limited largely because they exhibit poor selectivity for flue gases and low capture capacity under low pressures. We perform a high-throughput screening for selective CO2 capture from flue gases by using first principles thermodynamics. We find that elements with empty d orbitals selectively attract CO2 from gaseous mixtures under low CO2 pressures (~10−3 bar) at 300 K and release it at ~450 K. CO2 binding to elements involves hybridization of the metal d orbitals with the CO2 π orbitals and CO2-transition metal complexes were observed in experiments. This result allows us to perform high-throughput screening to discover novel promising CO2 capture materials with empty d orbitals (e.g., Sc– or V–porphyrin-like graphene) and predict their capture performance under various conditions. Moreover, these findings provide physical insights into selective CO2 capture and open a new path to explore CO2 capture materials. PMID:26902156

High-throughput screening of metal-porphyrin-like graphenes for selective capture of carbon dioxide.

PubMed

Bae, Hyeonhu; Park, Minwoo; Jang, Byungryul; Kang, Yura; Park, Jinwoo; Lee, Hosik; Chung, Haegeun; Chung, ChiHye; Hong, Suklyun; Kwon, Yongkyung; Yakobson, Boris I; Lee, Hoonkyung

2016-02-23

Nanostructured materials, such as zeolites and metal-organic frameworks, have been considered to capture CO2. However, their application has been limited largely because they exhibit poor selectivity for flue gases and low capture capacity under low pressures. We perform a high-throughput screening for selective CO2 capture from flue gases by using first principles thermodynamics. We find that elements with empty d orbitals selectively attract CO2 from gaseous mixtures under low CO2 pressures (~10(-3) bar) at 300 K and release it at ~450 K. CO2 binding to elements involves hybridization of the metal d orbitals with the CO2 π orbitals and CO2-transition metal complexes were observed in experiments. This result allows us to perform high-throughput screening to discover novel promising CO2 capture materials with empty d orbitals (e.g., Sc- or V-porphyrin-like graphene) and predict their capture performance under various conditions. Moreover, these findings provide physical insights into selective CO2 capture and open a new path to explore CO2 capture materials.

High-throughput screening of metal-porphyrin-like graphenes for selective capture of carbon dioxide

NASA Astrophysics Data System (ADS)

Bae, Hyeonhu; Park, Minwoo; Jang, Byungryul; Kang, Yura; Park, Jinwoo; Lee, Hosik; Chung, Haegeun; Chung, Chihye; Hong, Suklyun; Kwon, Yongkyung; Yakobson, Boris I.; Lee, Hoonkyung

2016-02-01

Nanostructured materials, such as zeolites and metal-organic frameworks, have been considered to capture CO2. However, their application has been limited largely because they exhibit poor selectivity for flue gases and low capture capacity under low pressures. We perform a high-throughput screening for selective CO2 capture from flue gases by using first principles thermodynamics. We find that elements with empty d orbitals selectively attract CO2 from gaseous mixtures under low CO2 pressures (~10-3 bar) at 300 K and release it at ~450 K. CO2 binding to elements involves hybridization of the metal d orbitals with the CO2 π orbitals and CO2-transition metal complexes were observed in experiments. This result allows us to perform high-throughput screening to discover novel promising CO2 capture materials with empty d orbitals (e.g., Sc- or V-porphyrin-like graphene) and predict their capture performance under various conditions. Moreover, these findings provide physical insights into selective CO2 capture and open a new path to explore CO2 capture materials.

Screen media usage, sleep time and academic performance in adolescents: clustering a self-organizing maps analysis.

PubMed

Peiró-Velert, Carmen; Valencia-Peris, Alexandra; González, Luis M; García-Massó, Xavier; Serra-Añó, Pilar; Devís-Devís, José

2014-01-01

Screen media usage, sleep time and socio-demographic features are related to adolescents' academic performance, but interrelations are little explored. This paper describes these interrelations and behavioral profiles clustered in low and high academic performance. A nationally representative sample of 3,095 Spanish adolescents, aged 12 to 18, was surveyed on 15 variables linked to the purpose of the study. A Self-Organizing Maps analysis established non-linear interrelationships among these variables and identified behavior patterns in subsequent cluster analyses. Topological interrelationships established from the 15 emerging maps indicated that boys used more passive videogames and computers for playing than girls, who tended to use mobile phones to communicate with others. Adolescents with the highest academic performance were the youngest. They slept more and spent less time using sedentary screen media when compared to those with the lowest performance, and they also showed topological relationships with higher socioeconomic status adolescents. Cluster 1 grouped boys who spent more than 5.5 hours daily using sedentary screen media. Their academic performance was low and they slept an average of 8 hours daily. Cluster 2 gathered girls with an excellent academic performance, who slept nearly 9 hours per day, and devoted less time daily to sedentary screen media. Academic performance was directly related to sleep time and socioeconomic status, but inversely related to overall sedentary screen media usage. Profiles from the two clusters were strongly differentiated by gender, age, sedentary screen media usage, sleep time and academic achievement. Girls with the highest academic results had a medium socioeconomic status in Cluster 2. Findings may contribute to establishing recommendations about the timing and duration of screen media usage in adolescents and appropriate sleep time needed to successfully meet the demands of school academics and to improve interventions targeting to affect behavioral change.

Screen Media Usage, Sleep Time and Academic Performance in Adolescents: Clustering a Self-Organizing Maps Analysis

PubMed Central

Peiró-Velert, Carmen; Valencia-Peris, Alexandra; González, Luis M.; García-Massó, Xavier; Serra-Añó, Pilar; Devís-Devís, José

2014-01-01

Screen media usage, sleep time and socio-demographic features are related to adolescents' academic performance, but interrelations are little explored. This paper describes these interrelations and behavioral profiles clustered in low and high academic performance. A nationally representative sample of 3,095 Spanish adolescents, aged 12 to 18, was surveyed on 15 variables linked to the purpose of the study. A Self-Organizing Maps analysis established non-linear interrelationships among these variables and identified behavior patterns in subsequent cluster analyses. Topological interrelationships established from the 15 emerging maps indicated that boys used more passive videogames and computers for playing than girls, who tended to use mobile phones to communicate with others. Adolescents with the highest academic performance were the youngest. They slept more and spent less time using sedentary screen media when compared to those with the lowest performance, and they also showed topological relationships with higher socioeconomic status adolescents. Cluster 1 grouped boys who spent more than 5.5 hours daily using sedentary screen media. Their academic performance was low and they slept an average of 8 hours daily. Cluster 2 gathered girls with an excellent academic performance, who slept nearly 9 hours per day, and devoted less time daily to sedentary screen media. Academic performance was directly related to sleep time and socioeconomic status, but inversely related to overall sedentary screen media usage. Profiles from the two clusters were strongly differentiated by gender, age, sedentary screen media usage, sleep time and academic achievement. Girls with the highest academic results had a medium socioeconomic status in Cluster 2. Findings may contribute to establishing recommendations about the timing and duration of screen media usage in adolescents and appropriate sleep time needed to successfully meet the demands of school academics and to improve interventions targeting to affect behavioral change. PMID:24941009

Accuracy of Nutritional Screening Tools in Assessing the Risk of Undernutrition in Hospitalized Children.

PubMed

Huysentruyt, Koen; Devreker, Thierry; Dejonckheere, Joachim; De Schepper, Jean; Vandenplas, Yvan; Cools, Filip

2015-08-01

The aim of the present study was to evaluate the predictive accuracy of screening tools for assessing nutritional risk in hospitalized children in developed countries. The study involved a systematic review of literature (MEDLINE, EMBASE, and Cochrane Central databases up to January 17, 2014) of studies on the diagnostic performance of pediatric nutritional screening tools. Methodological quality was assessed using a modified QUADAS tool. Sensitivity and specificity were calculated for each screening tool per validation method. A meta-analysis was performed to estimate the risk ratio of different screening result categories of being truly at nutritional risk. A total of 11 studies were included on ≥1 of the following screening tools: Pediatric Nutritional Risk Score, Screening Tool for the Assessment of Malnutrition in Paediatrics, Paediatric Yorkhill Malnutrition Score, and Screening Tool for Risk on Nutritional Status and Growth. Because of variation in reference standards, a direct comparison of the predictive accuracy of the screening tools was not possible. A meta-analysis was performed on 1629 children from 7 different studies. The risk ratio of being truly at nutritional risk was 0.349 (95% confidence interval [CI] 0.16-0.78) for children in the low versus moderate screening category and 0.292 (95% CI 0.19-0.44) in the moderate versus high screening category. There is insufficient evidence to choose 1 nutritional screening tool over another based on their predictive accuracy. The estimated risk of being at "true nutritional risk" increases with each category of screening test result. Each screening category should be linked to a specific course of action, although further research is needed.

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

PubMed

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

2014-12-23

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

A new large area scintillator screen for X-ray imaging

NASA Astrophysics Data System (ADS)

Nagarkar, V. V.; Miller, S. R.; Tipnis, S. V.; Lempicki, A.; Brecher, C.; Lingertat, H.

2004-01-01

We report on the development of a new, large area, powdered scintillator screen based on Lu 2O 3(Eu). As reported earlier, the transparent ceramic form of this material has a very high density of 9.4 g/cm 3, a high light output comparable to that of CsI(Tl), and emits in a narrow spectral band centered at about 610 nm. Research into fabrication of this ceramic scintillator in a large area format is currently underway, however the process is not yet practical for large scale production. Here we have explored fabrication of large area screens using precursor powders from which the ceramics are fabricated. To date we have produced up to 16 × 16 cm 2 area screens with thickness in the range of 18 mg/cm 2. This paper outlines the screen fabrication technique and presents its imaging performance in comparison with a commercial Gd 2O 2S:Tb (GOS) screen.

Random plasma glucose in serendipitous screening for glucose intolerance: screening for impaired glucose tolerance study 2.

PubMed

Ziemer, David C; Kolm, Paul; Foster, Jovonne K; Weintraub, William S; Vaccarino, Viola; Rhee, Mary K; Varughese, Rincy M; Tsui, Circe W; Koch, David D; Twombly, Jennifer G; Narayan, K M Venkat; Phillips, Lawrence S

2008-05-01

With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. This is a cross-sectional study. The participants of this study include a voluntary sample of 990 adults not known to have diabetes. RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose(110) (IFG(110); fasting glucose, 110-125 mg/dl, and 2 h glucose < 140 mg/dl). Screening performance was measured by area under receiver operating characteristic curves (AROC). Mean age was 48 years, and body mass index (BMI) was 30.4 kg/m(2); 66% were women, and 52% were black; 5.1% had previously unrecognized diabetes, and 24.0% had any "high-risk" glucose intolerance (diabetes or IGT or IFG(110)). The AROC was 0.80 (95% CI 0.74-0.86) for RPG to identify diabetes and 0.72 (0.68-0.75) to identify any glucose intolerance, both highly significant (p < 0.001). Screening performance was generally consistent at different times of the day, regardless of meal status, and across a range of risk factors such as age, BMI, high density lipoprotein cholesterol, triglycerides, and blood pressure. RPG values should be considered by health care providers to be an opportunistic initial screening test and used to prompt further evaluation of patients at risk of glucose intolerance. Such "serendipitous screening" could help to identify unrecognized diabetes and prediabetes.

Anal intraepithelial neoplasia: A review of diagnosis and management

PubMed Central

Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

2017-01-01

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations. PMID:28255426

Anal intraepithelial neoplasia: A review of diagnosis and management.

PubMed

Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

2017-02-15

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.

High-content screening in microfluidic devices.

PubMed

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2010-08-01

Miniaturization is the key to advancing the state of the art in high-content screening (HCS) in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. The advantages of this technology are discussed, including cost savings, high-throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration and scaling. The reader will understand the capabilities of anew microfluidics-based platform for HCS and the advantages it provides over conventional plate-based HCS. Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery.

The Association Between Primary Source of Healthcare Coverage and Colorectal Cancer Screening Among US Veterans.

PubMed

May, Folasade P; Yano, Elizabeth M; Provenzale, Dawn; Neil Steers, W; Washington, Donna L

2017-08-01

Colorectal cancer (CRC) is a deadly but largely preventable disease. Screening improves outcomes, but screening rates vary across healthcare coverage models. In the Veterans Health Administration (VA), screening rates are high; however, it is unknown how CRC screening rates compare for Veterans with other types of healthcare coverage. To determine whether Veterans with Veteran-status-related coverage (VA, military, TRICARE) have higher rates of CRC screening than Veterans with alternate sources of healthcare coverage. We conducted a cross-sectional analysis of Veterans 50-75 years from the 2014 Behavioral Risk Factor Surveillance System survey. We examined CRC screening rates and screening modalities. We performed multivariable logistic regression to identify the role of coverage type, demographics, and clinical factors on screening status. The cohort included 22,138 Veterans. Of these, 76.7% reported up-to-date screening. Colonoscopy was the most common screening modality (83.7%). Screening rates were highest among Veterans with Veteran-status-related coverage (82.3%), as was stool-based screening (10.8%). The adjusted odds of up-to-date screening among Veterans with Veteran-status-related coverage were 83% higher than among Veterans with private coverage (adjusted OR = 1.83, 95% CI = 1.52-2.22). Additional predictors of screening included older age, black race, high income, access to medical care, frequent medical visits, and employed or married status. CRC screening rates were highest among Veterans with Veteran-status-related coverage. High CRC screening rates among US Veterans may be related to system-level characteristics of VA and military care. Insight to these system-level characteristics may inform mechanisms to improve CRC screening in non-VA settings.

A high-sensitivity ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method for screening synthetic cannabinoids and other drugs of abuse in urine.

PubMed

Sundström, Mira; Pelander, Anna; Angerer, Verena; Hutter, Melanie; Kneisel, Stefan; Ojanperä, Ilkka

2013-10-01

The continuing emergence of designer drugs imposes high demands on the scope and sensitivity of toxicological drug screening procedures. An ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method was developed for screening and simultaneous confirmation of both designer drugs and other drugs of abuse in urine samples in a single run. The method covered selected synthetic cannabinoids and cathinones, amphetamines, natural cannabinoids, opioids, cocaine and other important drugs of abuse, together with their main urinary metabolites. The database consisted of 277 compounds with molecular formula and exact monoisotopic mass; retention time was included for 192 compounds, and primary and secondary qualifier ion exact mass for 191 and 95 compounds, respectively. Following a solid-phase extraction, separation was performed by UHPLC and mass analysis by HR-TOFMS. MS, and broad-band collision-induced dissociation data were acquired at m/z range 50-700. Compound identification was based on a reverse database search with acceptance criteria for retention time, precursor ion mass accuracy, isotopic pattern and abundance of qualifier ions. Mass resolving power in spiked urine samples was on average FWHM 23,500 and mass accuracy 0.3 mDa. The mean and median cut-off concentrations determined for 75 compounds were 4.2 and 1 ng/mL, respectively. The range of cut-off concentrations for synthetic cannabinoids was 0.2-60 ng/mL and for cathinones 0.7-15 ng/mL. The method proved to combine high sensitivity and a wide scope in a manner not previously reported in drugs of abuse screening. The method's feasibility was demonstrated with 50 authentic urine samples.

Screening breast magnetic resonance imaging in women with atypia or lobular carcinoma in situ.

PubMed

Schwartz, Theresa; Cyr, Amy; Margenthaler, Julie

2015-02-01

Atypical lesions and lobular carcinoma in situ (LCIS) are associated with an increased risk of breast malignancy. The utility of breast magnetic resonance imaging (MRI) screening in this cohort of women after excision of a high-risk lesion has not been previously established. The objective of this study was to investigate outcomes of breast MRI surveillance in this subgroup of high-risk patients. We performed a retrospective review of women who required excision of an atypical lesion or LCIS who underwent at least one screening breast MRI from April 2005-December 2011. We collected information on demographics, number of second-look imaging studies recommended, number of biopsies performed and pathologic outcomes. A total of 179 patients met the inclusion criteria, including 131 (73%) with atypical lesions and 48 (27%) with LCIS. Second-look imaging was recommended for 31 of 131 (23.7%) patients with atypical lesions and 8 of 48 (16.7%) with LCIS. Ten biopsies were performed in the atypical cohort (7.6%) with two revealing a malignancy (Positive Predictive Value [PPV] of 20%). In the LCIS cohort, five biopsies were performed (10.4%) with one revealing a malignancy (PPV of 20%). The benefit of breast MRI surveillance in patients after excision of atypical lesions or LCIS has not been clearly delineated previously. Our data demonstrate that the use of screening breast MRI in this cohort results in additional work-up in one-fifth of patients, but a PPV of only 20%. Large, prospective studies would be needed to determine whether breast cancer outcomes differ between patients undergoing conventional breast screening and those undergoing conventional breast screening plus breast MRI surveillance. Copyright © 2015 Elsevier Inc. All rights reserved.

Colorectal cancer screening in high-risk groups is increasing, although current smokers fall behind.

PubMed

Oluyemi, Aminat O; Welch, Amy R; Yoo, Lisa J; Lehman, Erik B; McGarrity, Thomas J; Chuang, Cynthia H

2014-07-15

There is limited information about colorectal cancer (CRC) screening trends in high-risk groups, including the black, obese, diabetic, and smoking populations. For this study, the authors evaluated national CRC screening trends in these high-risk groups to provide insights into whether screening resources are being appropriately used. This was a nationally representative, population-based study using the Behavioral Risk Factor Surveillance System from the Centers for Disease Control. Data analysis was performed using bivariate analyses with weighted logistic regression. In the general population, CRC screening increased significantly from 59% to 65% during the years 2006 to 2010. The screening prevalence in non-Hispanic blacks was 58% in 2006 and 65% in 2010. Among obese individuals, the prevalence of up-to-date CRC screening increased significantly from 59% in 2006 to 66% in 2010. Screening prevalence in individuals with diabetes was 63% in 2006 and 69% in 2010. The CRC screening prevalence in current smokers was 45% in 2006 and 50% in 2010. The odds of CRC screening in the non-Hispanic black population, the obese population, and the diabetic population were higher than in non-Hispanic whites, normal weight individuals, and the population without diabetes, respectively. Current smokers had significantly lower odds of CRC screening than never-smokers in the years studied (2006: odds ratio [OR], 0.71; 95% confidence interval [CI], 0.66-0.76; 2008: OR, 0.67; 95% CI, 0.63-0.71; 2010: OR, 0.69; 95% CI, 0.66-0.73). The prevalence of CRC screening in high-risk groups is trending upward. Despite this, current smokers have significantly lower odds of CRC screening compared with the general population. © 2014 American Cancer Society.

Visual ergonomic aspects of glare on computer displays: glossy screens and angular dependence

NASA Astrophysics Data System (ADS)

Brunnström, Kjell; Andrén, Börje; Konstantinides, Zacharias; Nordström, Lukas

2007-02-01

Recently flat panel computer displays and notebook computer are designed with a so called glare panel i.e. highly glossy screens, have emerged on the market. The shiny look of the display appeals to the costumers, also there are arguments that the contrast, colour saturation etc improves by using a glare panel. LCD displays suffer often from angular dependent picture quality. This has been even more pronounced by the introduction of Prism Light Guide plates into displays for notebook computers. The TCO label is the leading labelling system for computer displays. Currently about 50% of all computer displays on the market are certified according to the TCO requirements. The requirements are periodically updated to keep up with the technical development and the latest research in e.g. visual ergonomics. The gloss level of the screen and the angular dependence has recently been investigated by conducting user studies. A study of the effect of highly glossy screens compared to matt screens has been performed. The results show a slight advantage for the glossy screen when no disturbing reflexes are present, however the difference was not statistically significant. When disturbing reflexes are present the advantage is changed into a larger disadvantage and this difference is statistically significant. Another study of angular dependence has also been performed. The results indicates a linear relationship between the picture quality and the centre luminance of the screen.

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests

PubMed Central

2011-01-01

Background We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer. Methods 545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000- December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate- and low-risk) of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing. Results The median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingo-oophorectomy (BSO). Prophylactic BSO was performed in 138 women (25.3%). Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%. Conclusion No early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified. PMID:22112691

The Modified Checklist for Autism in Toddlers: A Follow-Up Study Investigating the Early Detection of Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kleinman, Jamie M.; Robins, Diana L.; Ventola, Pamela E.; Pandey, Juhi; Boorstein, Hilary C.; Esser, Emma L.; Wilson, Leandra B.; Rosenthal, Michael A.; Sutera, Saasha; Verbalis, Alyssa D.; Barton, Marianne; Hodgson, Sarah; Green, James; Dumont-Mathieu, Thyde; Volkmar, Fred; Chawarska, Katarzyna; Klin, Ami; Fein, Deborah

2008-01-01

Autism spectrum disorders (ASD) often go undetected in toddlers. The Modified Checklist for Autism in Toddlers (M-CHAT) was used to screen 3,793 children aged 16-30 months from low- and high-risk sources; screen positive cases were diagnostically evaluated. Re-screening was performed on 1,416 children aged 42-54 months. Time1 Positive Predictive…

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

PubMed

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

2015-02-01

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

Tailored breast cancer screening program with microdose mammography, US, and MR Imaging: short-term results of a pilot study in 40-49-year-old women.

PubMed

Venturini, Elena; Losio, Claudio; Panizza, Pietro; Rodighiero, Maria Grazia; Fedele, Isabella; Tacchini, Simona; Schiani, Elena; Ravelli, Silvia; Cristel, Giulia; Panzeri, Marta Maria; De Cobelli, Francesco; Del Maschio, Alessandro

2013-08-01

To evaluate the feasibility, performance, and cost of a breast cancer screening program aimed at 40-49-year-old women and tailored to their risk profile with supplemental ultrasonography (US) and magnetic resonance (MR) imaging. The institutional review board approved this study, and informed written consent was obtained. A total of 3017 40-49-year-old women were invited to participate. The screening program was tailored to lifetime risk (Gail test) and mammographic density (according to Breast Imaging Reporting and Data Systems [BI-RADS] criteria) with supplemental US or MR imaging and bilateral two-view microdose mammography. The indicators suggested by European guidelines, US incremental cancer detection rate (CDR), and estimated costs were evaluated. A total of 1666 women (67.5% participation rate) were recruited. The average lifetime risk of breast cancer was 11.6%, and nine women had a high risk of breast cancer; 917 women (55.0%) had a high density score (BI-RADS density category 3 or 4). The average glandular dose for screening examinations was 1.49 mGy. Screening US was performed in 835 study participants (50.1%), mostly due to high breast density (800 of 1666 women [48.0%]). Screening MR imaging was performed in nine women (0.5%) at high risk for breast cancer. Breast cancer was diagnosed in 14 women (8.4 cases per 1000 women). Twelve diagnoses were made with microdose mammography, and two were made with supplemental US in dense breasts (2.4 cases per 1000 women). All patients were submitted for surgery, and 10 underwent breast-conserving surgery. The sentinel lymph node was evaluated in 11 patients, resulting in negative findings in six. Pathologic analysis resulted in the diagnosis of four ductal carcinomas in situ and 10 invasive carcinomas (five at stage I). A tailored breast cancer screening program in 40-49-year-old women yielded a greater-than-expected number of cancers, most of which were low-stage disease.

High-throughput fabrication and screening improves gold nanoparticle chemiresistor sensor performance.

PubMed

Hubble, Lee J; Cooper, James S; Sosa-Pintos, Andrea; Kiiveri, Harri; Chow, Edith; Webster, Melissa S; Wieczorek, Lech; Raguse, Burkhard

2015-02-09

Chemiresistor sensor arrays are a promising technology to replace current laboratory-based analysis instrumentation, with the advantage of facile integration into portable, low-cost devices for in-field use. To increase the performance of chemiresistor sensor arrays a high-throughput fabrication and screening methodology was developed to assess different organothiol-functionalized gold nanoparticle chemiresistors. This high-throughput fabrication and testing methodology was implemented to screen a library consisting of 132 different organothiol compounds as capping agents for functionalized gold nanoparticle chemiresistor sensors. The methodology utilized an automated liquid handling workstation for the in situ functionalization of gold nanoparticle films and subsequent automated analyte testing of sensor arrays using a flow-injection analysis system. To test the methodology we focused on the discrimination and quantitation of benzene, toluene, ethylbenzene, p-xylene, and naphthalene (BTEXN) mixtures in water at low microgram per liter concentration levels. The high-throughput methodology identified a sensor array configuration consisting of a subset of organothiol-functionalized chemiresistors which in combination with random forests analysis was able to predict individual analyte concentrations with overall root-mean-square errors ranging between 8-17 μg/L for mixtures of BTEXN in water at the 100 μg/L concentration. The ability to use a simple sensor array system to quantitate BTEXN mixtures in water at the low μg/L concentration range has direct and significant implications to future environmental monitoring and reporting strategies. In addition, these results demonstrate the advantages of high-throughput screening to improve the performance of gold nanoparticle based chemiresistors for both new and existing applications.

Breast cancer screening (breast self-examination, clinical breast exam, and mammography) in women referred to health centers in Tabriz, Iran.

PubMed

Khalili, Azizeh Farshbaf; Shahnazi, Mahnaz

2010-04-01

Breast cancer is the most common cancer and the most common cause of death in Iranian women aged 35-55 years. Breast cancer screening comprises breast self-examination (BSE), clinical breast examination (CBE) and mammography. The study aimed to examine the performance of screening methods among women referring to health centers of Tabriz, Iran. This was a descriptive-analytical research carried out on 400 women aged 20-50 years. The samples were chosen through random multistage sampling among health centers of Tabriz then active records of women. A questionnaire and observational checklist was used to elicit socio-demographic information and performance of women towards breast cancer screening methods. Descriptive and inferential statistics (chi-square and Fisher's exact test) were used to analyze the data. Only 18.8% of women did breast self-examination, 19.1% had clinical breast examination and 3.3% had mammogram. Statistical test showed a significant relationship between performing BSE and educational level, employment, income, number of children, breastfeeding history, breastfeeding quality and family history of breast cancer. There was a significant correlation between performing CBE and history of breast tumor and also, between performing the mammography and family history of breast cancer and history of breast tumor (P < 0.05). The findings showed that the performance of breast cancer screening methods was not satisfactory. Performance in high risk women was very desirable than others. The presentation of imperative education about breast cancer screening methods through health staff especially in pregnancy, post-partum and even in pre marriage counseling periods seems necessary.

Comparison of the clinical performances of the AdvanSure HPV Screening Real-Time PCR, the Abbott Real-Time High-Risk HPV Test, and the Hybrid Capture High-Risk HPV DNA Test for Cervical Cancer Screening.

PubMed

Chung, Hae-Sun; Hahm, Chorong; Lee, Miae

2014-09-01

The clinical performance of three human papillomavirus (HPV) DNA commercial assays for cervical cancer screening was evaluated; the AdvanSure HPV Screening Real-Time PCR (AdvanSure PCR; LG Life Sciences) that was developed recently for the detection of both high-risk and low-risk genotypes, the Abbott RealTime High-Risk HPV Test (Abbott PCR; Abbott Molecular) and the Hybrid Capture High-Risk HPV DNA test (HC2; Qiagen). The three different HPV DNA tests were compared using cytology samples obtained from 619 women who underwent routine cervical cancer screening. The gold-standard assay was histopathological confirmation of cervical intraepithelial neoplasia of grade 2 or worse. The clinical sensitivities of the AdvanSure PCR, the Abbott PCR and the HC2 for the detection of cervical intraepithelial neoplasia of grade 2 or worse were 95.5%, 95.5% and 100%, respectively, while the clinical specificities were 61.6%, 86.4% and 83.3%, respectively. There were no significant differences in the clinical sensitivities of the Abbott PCR and the AdvanSure PCR compared to the HC2. The clinical specificities of the Abbott PCR and the AdvanSure PCR for the detection of HPV types 16/18 were 97.8% and 98.5%, respectively. For cervical cancer screening, all three tests showed relatively good clinical sensitivities, but the AdvanSure PCR had lower clinical specificity than the Abbott PCR and the HC2. The AdvanSure PCR and the Abbott PCR assays have the advantage of being automated and the ability to distinguish between HPV types 16/18 and other HPV types. The two real-time PCR assays could be useful tools in HPV testing for cervical cancer screening. Copyright © 2014 Elsevier B.V. All rights reserved.

Breast imaging. A practical look at its capabilities and its limitations.

PubMed

Clark, R; Nemec, L; Love, N

1992-10-01

The film-screen technique is evolving as the standard for mammography. Sonography is the only other method that currently has a defined role in breast imaging. Mammography should be performed at facilities that have received American College of Radiology accreditation or its equivalent, because technical quality assurance is an important part of mammographic practice. Interpretive quality may be assured by outcome audits performed by mammography facilities. Primary care physicians are best suited to encouraging eligible women to undergo screening studies and should consider these recommendations: Refer patients for screening mammography to accredited facilities according to established guidelines. Educate patients about the need for regular screening. Provide annual breast physical examination. Refresh your knowledge on breast health and the techniques of physical examination if necessary. Teach patients breast self-examination techniques. Demand low-cost, high-quality screening mammography; be aware of local variability of charges and quality.

Delivering colonoscopy screening for low-income populations in Suffolk County: strategies, outcomes, and benchmarks.

PubMed

Lane, Dorothy S; Messina, Catherine R; Cavanagh, Mary F; Anderson, Joseph C

2013-08-01

Current and pending legislation provides colorectal cancer screening reimbursement for previously uninsured populations. Colonoscopy is currently the screening method most frequently recommended by physicians for insured patients. The experience of the SCOPE (Suffolk County Preventive Endoscopy) demonstration project (Project SCOPE) at Stony Brook University Medical Center provides a model for delivering colonoscopy screening to low-income populations to meet anticipated increasing demands. Project SCOPE, based in the Department of Preventive Medicine, featured internal collaboration with the academic medical center's large gastroenterology practice and external collaboration with the Suffolk County Department of Health Services' network of community health centers. Colonoscopies were performed by faculty gastroenterologists or supervised fellows. Measures of colonoscopy performance were compared with quality indicators and differences between faculty and supervised fellows were identified. During a 40-month screening period, 800 initial colonoscopies were performed. Approximately 21% of women screened were found to have adenomatous polyps compared with 36% of men. Five cancers were detected. The majority of the population screened (70%) were members of minority populations. African American individuals had a higher percentage of proximally located adenomas (78%) compared with white individuals (65%) and Hispanics (49%), based on the location of the most advanced lesion. Hispanic individuals had a 36% lower risk of adenomas compared with white individuals. Performance measures including the percentage of procedures with adequate bowel preparation, cecum reached, scope withdrawal time, and adenoma detection rate met quality benchmarks when performed by either faculty or supervised fellows. Project SCOPE's operational strategies demonstrated a feasible method for an academic medical center to provide high-quality screening colonoscopy for low-income populations. © 2013 American Cancer Society.

Sensitivity and specificity of the Beck Depression Inventory in cardiologic inpatients: how useful is the conventional cut-off score?

PubMed

Forkmann, Thomas; Vehren, Thomas; Boecker, Maren; Norra, Christine; Wirtz, Markus; Gauggel, Siegfried

2009-10-01

The Beck Depression Inventory (BDI) is widely used for depression screening in various patient populations. However, there are still insufficient data about its sensitivity and specificity in nonpsychiatric patients. Furthermore, some research suggests that somatic BDI items heighten its sum score artificially in physically ill patients. The aim of the present study was to validate the conventional BDI cut-off score by examination of its sensitivity and specificity in a mixed sample of cardiac inpatients and compare it to a modified "cognitive-emotional" BDI (BDI(c/e)) after exclusion of somatic items. A total of 126 cardiologic inpatients were assessed. Receiver operating characteristic curves (ROC) were calculated for total BDI (BDI(t)) and BDI(c/e). Screening performance of cut-off scores was evaluated using the Youden Index (Y). With the application of the conventional BDI cut-off score, ROC analysis revealed a moderate overall screening performance with Y=52.6 and an area under the curve (AUC) of 0.83. In contrast, Y improved to 57.5 at a cut-off score of >9, but screening performance was still not optimal. BDI(c/e) showed also a moderate screening performance (AUC=.82); Y was maximized at a cut-off score of >8 (Y=0.53.5). Again, no cut-off score provided optimal screening performance. The BDI cannot be recommended as a formal screening instrument in cardiac inpatients since no cut-off score for either BDI(t) or BDI(c/e) combined both sufficiently high sensitivity and specificity. However, the shorter BDI(c/e) could be used as alternative to BDI(t) which may be confounded in physically ill patients. Generally, researchers should consider using alternative screening instruments (e.g., the Hospital Anxiety and Depression Scale) instead.

High-resolution microendoscopy for esophageal cancer screening in China: A cost-effectiveness analysis.

PubMed

Hur, Chin; Choi, Sung Eun; Kong, Chung Yin; Wang, Gui-Qi; Xu, Hong; Polydorides, Alexandros D; Xue, Li-Yan; Perzan, Katherine E; Tramontano, Angela C; Richards-Kortum, Rebecca R; Anandasabapathy, Sharmila

2015-05-14

To study the cost-effectiveness of high-resolution microendoscopy (HRME) in an esophageal squamous cell carcinoma (ESCC) screening program in China. A decision analytic Markov model of ESCC was developed. Separate model analyses were conducted for cohorts consisting of an average-risk population or a high-risk population in China. Hypothetical 50-year-old individuals were followed until age 80 or death. We compared three different strategies for both cohorts: (1) no screening; (2) standard endoscopic screening with Lugol's iodine staining; and (3) endoscopic screening with Lugol's iodine staining and an HRME. Model parameters were estimated from the literature as well as from GLOBOCAN, the Cancer Incidence and Mortality Worldwide cancer database. Health states in the model included non-neoplasia, mild dysplasia, moderate dysplasia, high-grade dysplasia, intramucosal carcinoma, operable cancer, inoperable cancer, and death. Separate ESCC incidence transition rates were generated for the average-risk and high-risk populations. Costs in Chinese currency were converted to international dollars (I$) and were adjusted to 2012 dollars using the Consumer Price Index. The main outcome measurements for this study were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). For the average-risk population, the HRME screening strategy produced 0.043 more QALYs than the no screening strategy at an additional cost of I$646, resulting in an ICER of I$11808 per QALY gained. Standard endoscopic screening was weakly dominated. Among the high-risk population, when the HRME screening strategy was compared with the standard screening strategy, the ICER was I$8173 per QALY. For both the high-risk and average-risk screening populations, the HRME screening strategy appeared to be the most cost-effective strategy, producing ICERs below the willingness-to-pay threshold, I$23500 per QALY. One-way sensitivity analysis showed that, for the average-risk population, higher specificity of Lugol's iodine (> 40%) and lower specificity of HRME (< 70%) could make Lugol's iodine screening cost-effective. For the high-risk population, the results of the model were not substantially affected by varying the follow-up rate after Lugol's iodine screening, Lugol's iodine test characteristics (sensitivity and specificity), or HRME specificity. The incorporation of HRME into an ESCC screening program could be cost-effective in China. Larger studies of HRME performance are needed to confirm these findings.

Components Necessary for High-Quality Lung Cancer Screening

PubMed Central

Powell, Charles A.; Arenberg, Douglas; Detterbeck, Frank; Gould, Michael K.; Jaklitsch, Michael T.; Jett, James; Naidich, David; Vachani, Anil; Wiener, Renda Soylemez; Silvestri, Gerard

2015-01-01

Lung cancer screening with a low-dose chest CT scan can result in more benefit than harm when performed in settings committed to developing and maintaining high-quality programs. This project aimed to identify the components of screening that should be a part of all lung cancer screening programs. To do so, committees with expertise in lung cancer screening were assembled by the Thoracic Oncology Network of the American College of Chest Physicians (CHEST) and the Thoracic Oncology Assembly of the American Thoracic Society (ATS). Lung cancer program components were derived from evidence-based reviews of lung cancer screening and supplemented by expert opinion. This statement was developed and modified based on iterative feedback of the committees. Nine essential components of a lung cancer screening program were identified. Within these components 21 Policy Statements were developed and translated into criteria that could be used to assess the qualification of a program as a screening facility. Two additional Policy Statements related to the need for multisociety governance of lung cancer screening were developed. High-quality lung cancer screening programs can be developed within the presented framework of nine essential program components outlined by our committees. The statement was developed, reviewed, and formally approved by the leadership of CHEST and the ATS. It was subsequently endorsed by the American Association of Throacic Surgery, American Cancer Society, and the American Society of Preventive Oncology. PMID:25356819

Screening bioactive quality control markers of QiShenYiQi dripping pills based on the relationship between the ultra-high performance liquid chromatography fingerprint and vascular protective activity.

PubMed

Zhuo, Limeng; Peng, Jingjing; Zhao, Yunli; Li, Dongxiang; Xie, Xiuman; Tong, Ling; Yu, Zhiguo

2017-10-01

Traditional Chinese medicine consists of complex phytochemical constituents. Selecting appropriate analytical markers of traditional Chinese medicine is a critical step in quality control. Currently, the combination of fingerprinting and efficacy evaluation is considered as a useful method for screening active ingredients in complex mixtures. This study was designed to develop an orthogonal partial least squares model for screening bioactive quality control markers of QishenYiqi dripping pills based on the fingerprint-efficacy relationship. First, the chemical fingerprints of 49 batches of QishenYiqi dripping pill samples were established by ultra-high performance liquid chromatography coupled with a photodiode array detector. Second, ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was exploited to systematically investigate the 36 copossessing fingerprint components in QishenYiqi dripping pills. The vascular protective activity of QishenYiqi dripping pills was determined by using a cell counting kit-8 assay. Finally, fingerprint-efficacy relationship was established by orthogonal partial least squares model. The results indicated that ten components exhibited strong correlation with vascular protective activity, and these were preliminarily screened as quality control markers. The present study provided a novel idea for the study of the pharmacodynamic material basis and quality evaluation of QishenYiqi dripping pills. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variable screening via quantile partial correlation

PubMed Central

Ma, Shujie; Tsai, Chih-Ling

2016-01-01

In quantile linear regression with ultra-high dimensional data, we propose an algorithm for screening all candidate variables and subsequently selecting relevant predictors. Specifically, we first employ quantile partial correlation for screening, and then we apply the extended Bayesian information criterion (EBIC) for best subset selection. Our proposed method can successfully select predictors when the variables are highly correlated, and it can also identify variables that make a contribution to the conditional quantiles but are marginally uncorrelated or weakly correlated with the response. Theoretical results show that the proposed algorithm can yield the sure screening set. By controlling the false selection rate, model selection consistency can be achieved theoretically. In practice, we proposed using EBIC for best subset selection so that the resulting model is screening consistent. Simulation studies demonstrate that the proposed algorithm performs well, and an empirical example is presented. PMID:28943683

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

PubMed

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

2015-11-01

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

Brief screening questionnaires to identify problem drinking during pregnancy: a systematic review.

PubMed

Burns, Ethel; Gray, Ron; Smith, Lesley A

2010-04-01

Although prenatal screening for problem drinking during pregnancy has been recommended, guidance on screening instruments is lacking. We investigated the sensitivity, specificity and predictive value of brief alcohol screening questionnaires to identify problem drinking in pregnant women. Electronic databases from their inception to June 2008 were searched, as well as reference lists of eligible papers and related review papers. We sought cohort or cross-sectional studies that compared one or more brief alcohol screening questionnaire(s) with reference criteria obtained using structured interviews to detect 'at-risk' drinking, alcohol abuse or dependency in pregnant women receiving prenatal care. Five studies (6724 participants) were included. In total, seven instruments were evaluated: TWEAK (Tolerance, Worried, Eye-opener, Amnesia, Kut down), T-ACE [Take (number of drinks), Annoyed, Cut down, Eye-opener], CAGE (Cut down, Annoyed, Guilt, Eye-opener], NET (Normal drinker, Eye-opener, Tolerance), AUDIT (Alcohol Use Disorder Identification Test), AUDIT-C (AUDIT-consumption) and SMAST (Short Michigan Alcohol Screening Test). Study quality was generally good, but lack of blinding was a common weakness. For risk drinking sensitivity was highest for T-ACE (69-88%), TWEAK (71-91%) and AUDIT-C (95%), with high specificity (71-89%, 73-83% and 85%, respectively). CAGE and SMAST performed poorly. Sensitivity of AUDIT-C at score >or=3 was high for past year alcohol dependence (100%) or alcohol use disorder (96%) with moderate specificity (71% each). For life-time alcohol dependency the AUDIT at score >or=8 performed poorly. T-ACE, TWEAK and AUDIT-C show promise for screening for risk drinking, and AUDIT-C may also be useful for identifying alcohol dependency or abuse. However, their performance as stand-alone tools is uncertain, and further evaluation of questionnaires for prenatal alcohol use is warranted.

To twist, roll, stroke or poke? A study of input devices for menu navigation in the cockpit.

PubMed

Stanton, Neville A; Harvey, Catherine; Plant, Katherine L; Bolton, Luke

2013-01-01

Modern interfaces within the aircraft cockpit integrate many flight management system (FMS) functions into a single system. The success of a user's interaction with an interface depends upon the optimisation between the input device, tasks and environment within which the system is used. In this study, four input devices were evaluated using a range of Human Factors methods, in order to assess aspects of usability including task interaction times, error rates, workload, subjective usability and physical discomfort. The performance of the four input devices was compared using a holistic approach and the findings showed that no single input device produced consistently high performance scores across all of the variables evaluated. The touch screen produced the highest number of 'best' scores; however, discomfort ratings for this device were high, suggesting that it is not an ideal solution as both physical and cognitive aspects of performance must be accounted for in design. This study evaluated four input devices for control of a screen-based flight management system. A holistic approach was used to evaluate both cognitive and physical performance. Performance varied across the dependent variables and between the devices; however, the touch screen produced the largest number of 'best' scores.

Parametric study on the thermal performance of beam screen samples of the High-Luminosity LHC upgrade

NASA Astrophysics Data System (ADS)

Borges de Sousa, P.; Morrone, M.; Hovenga, N.; Garion, C.; van Weelderen, R.; Koettig, T.; Bremer, J.

2017-12-01

The High-Luminosity upgrade of the Large Hadron Collider (HL-LHC) will increase the accelerator’s luminosity by a factor 10 beyond its original design value, giving rise to more collisions and generating an intense flow of debris. A new beam screen has been designed for the inner triplets that incorporates tungsten alloy blocks to shield the superconducting magnets and the 1.9 K superfluid helium bath from incoming radiation. These screens will operate between 60 K and 80 K and are designed to sustain a nominal head load of 15 Wm-1, over 10 times the nominal heat load for the original LHC design. Their overall new and more complex design requires them and their constituent parts to be characterised from a thermal performance standpoint. In this paper we describe the experimental parametric study carried out on two principal thermal components: a representative sample of the beam screen with a tungsten-based alloy block and thermal link and the supporting structure composed of an assembly of ceramic spheres and titanium springs. Results from both studies are shown and discussed regarding their impact on the baseline considerations for the thermal design of the beam screens.

Combinatorial electrochemical cell array for high throughput screening of micro-fuel-cells and metal/air batteries.

PubMed

Jiang, Rongzhong

2007-07-01

An electrochemical cell array was designed that contains a common air electrode and 16 microanodes for high throughput screening of both fuel cells (based on polymer electrolyte membrane) and metal/air batteries (based on liquid electrolyte). Electrode materials can easily be coated on the anodes of the electrochemical cell array and screened by switching a graphite probe from one cell to the others. The electrochemical cell array was used to study direct methanol fuel cells (DMFCs), including high throughput screening of electrode catalysts and determination of optimum operating conditions. For screening of DMFCs, there is about 6% relative standard deviation (percentage of standard deviation versus mean value) for discharge current from 10 to 20 mAcm(2). The electrochemical cell array was also used to study tin/air batteries. The effect of Cu content in the anode electrode on the discharge performance of the tin/air battery was investigated. The relative standard deviations for screening of metal/air battery (based on zinc/air) are 2.4%, 3.6%, and 5.1% for discharge current at 50, 100, and 150 mAcm(2), respectively.

Screening for obstructive sleep apnea syndrome in patients with type 2 diabetes mellitus: a prospective study on sensitivity of Berlin and STOP-Bang questionnaires.

PubMed

Westlake, Katerina; Plihalova, Andrea; Pretl, Martin; Lattova, Zuzana; Polak, Jan

2016-10-01

Obstructive sleep apnea (OSA) is highly prevalent in patients with Type 2 diabetes mellitus representing an additional risk factor for already increased cardiovascular mortality. As cardiovascular diseases are the main cause of death in this population, there is a need to identify patients with moderate to severe OSA indicated for treatment. We aimed to evaluate the performance of the Berlin, STOP, and STOP-Bang screening questionnaires in a population of patients with Type 2 diabetes mellitus. 294 consecutive patients with Type 2 diabetes mellitus filled in the questionnaires and underwent overnight home sleep monitoring using a type IV sleep monitor. Severe, moderate, and mild OSA was found in 31 (10%), 61 (21%), and 121 (41%) patients, respectively. The questionnaires showed a similar sensitivity and specificity for AHI ≥ 15: 0.69 and 0.50 for Berlin, 0.65 and 0.49 for STOP, and 0.59 and 0.68 for STOP-Bang. However, the performance of the STOP-Bang questionnaire was different in men vs. women, sensitivity being 0.74 vs. 0.29 (p < 0.05) and specificity 0.56 vs. 0.82 (p < 0.05). Even the best-performing Berlin questionnaire failed to identify 31% of patients with moderate to severe OSA as being at high risk of OSA, thus preventing them from receiving a correct diagnosis and treatment. Considering that patients with Type 2 diabetes mellitus are at high risk of cardiovascular mortality and also have a high prevalence of moderate to severe OSA, we find screening based on the questionnaires suboptimal and suggest that OSA screening should be performed using home sleep monitoring devices. Copyright © 2016 Elsevier B.V. All rights reserved.

Use of the Combined First-Trimester Screen in High- and Low-Risk Patient Populations After Introduction of Noninvasive Prenatal Testing.

PubMed

Larion, Sebastian; Warsof, Steven L; Romary, Letty; Mlynarczyk, Margaret; Peleg, David; Abuhamad, Alfred Z

2015-08-01

To report changes in the use of the combined first-trimester screen (FTS) in patients classified as high and low risk for fetal aneuploidy, including after introduction of noninvasive prenatal testing (NIPT). A prospectively collected database was reviewed to investigate changes in FTS use before and after American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 77 (Obstet Gynecol 2007; 109:217-227), which recommended that all patients be offered aneuploidy screening, and after NIPT introduction. High-risk patients were classified as 35 years or older at the estimated time of delivery or those with an abnormal prior screen, abnormal ultrasound findings, or family history of aneuploidy. Data were normalized per 100 morphologic ultrasound examinations to account for changes in patient number over time. Statistical significance was defined as P < .05. A total of 10,125 FTSs were recorded during the 88-month study period, including 2962 in high-risk patients and 7163 in low-risk patients. The total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No. 77 and significantly decreased after NIPT introduction. In high-risk patients, the total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No. 77 but significantly decreased after NIPT introduction. In contrast, in low-risk patients, the total number of FTSs performed per 100 morphologic ultrasound examinations significantly increased after ACOG Practice Bulletin No.77 but was not statistically different after NIPT introduction. American College of Obstetricians and Gynecologists Practice Bulletin No. 77 significantly increased patient use of FTS. The introduction of NIPT significantly decreased FTS use in the high-risk population but not in the low-risk population. © 2015 by the American Institute of Ultrasound in Medicine.

Screening for celiac disease in the general population and in high-risk groups

PubMed Central

Card, Timothy R; Kaukinen, Katri; Bai, Julio; Zingone, Fabiana; Sanders, David S; Murray, Joseph A

2015-01-01

Background Celiac disease (CD) occurs in approximately 1% of the Western population. It is a lifelong disorder that is associated with impaired quality of life (QOL) and an excessive risk of comorbidity and death. Objectives To review the literature on screening for CD in relation to the current World Health Organization (WHO) criteria for mass screening. Methods We performed a PubMed search to identify indexed papers on CD screening with a publication date from 1900 until 1 June 2014. When we deemed an abstract relevant, we read the corresponding paper in detail. Results CD fulfills several WHO criteria for mass screening (high prevalence, available treatment and difficult clinical detection), but it has not yet been established that treatment of asymptomatic CD may reduce the excessive risk of severe complications, leading to higher QOL nor that it is cost-effective. Conclusions Current evidence is not sufficient to support mass screening for CD, but active case-finding may be appropriate, as we recognize that most patients with CD will still be missed by this strategy. Although proof of benefit is still lacking, screening for CD may be appropriate in high-risk groups. PMID:25922671

Design and evaluation of thermodynamic vent/screen baffle cryogenic storage system. [for space shuttles, space tugs, and spacelab

NASA Technical Reports Server (NTRS)

Cady, E. C.

1975-01-01

A comprehensive analytical program was performed to compare an integrated thermodynamic vent/screen baffle orbital cryogenic propellant storage and transfer system with other concepts. The screen systems were found to be 20% to 29% lighter in weight than a propulsively accelerated Tug-scale LH2/LO2 resupply module. The screen systems were compared with small-scale supercritical storage systems for the space shuttle fuel cell reactant and life support system fluid supply and were lighter by up to 556 kg (1225 lb) for the extended 30-day mission. When compared with high-pressure gas storage for the spacelab atmosphere supply, the screen system saved 79% of the inert system weight for the 30-day mission. An experimental program found that heat flux rates up to 9,450 watts/sq m (3,000 Btu/hr-sq ft) degraded the LH2 bubble point performance of eight screens by a maximum of 12.5%. No effects of helium pressurant, screen material, or LH2 superheat were observed.

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

PubMed

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

2016-01-01

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

Mathematical modeling of high and low temperature heat pipes

NASA Technical Reports Server (NTRS)

Chi, S. W.

1971-01-01

Mathematical models are developed for calculating heat-transfer limitations of high-temperature heat pipes and heat-transfer limitations and temperature gradient of low temperature heat pipes. Calculated results are compared with the available experimental data from various sources to increase confidence in the present math models. Complete listings of two computer programs for high- and low-temperature heat pipes respectively are appended. These programs enable the performance of heat pipes with wrapped-screen, rectangular-groove or screen-covered rectangular-groove wick to be predicted.

Motion effects in multistatic millimeter-wave imaging systems

NASA Astrophysics Data System (ADS)

Schiessl, Andreas; Ahmed, Sherif Sayed; Schmidt, Lorenz-Peter

2013-10-01

At airport security checkpoints, authorities are demanding improved personnel screening devices for increased security. Active mm-wave imaging systems deliver the high quality images needed for reliable automatic detection of hidden threats. As mm-wave imaging systems assume static scenarios, motion effects caused by movement of persons during the screening procedure can degrade image quality, so very short measurement time is required. Multistatic imaging array designs and fully electronic scanning in combination with digital beamforming offer short measurement time together with high resolution and high image dynamic range, which are critical parameters for imaging systems used for passenger screening. In this paper, operational principles of such systems are explained, and the performance of the imaging systems with respect to motion within the scenarios is demonstrated using mm-wave images of different test objects and standing as well as moving persons. Electronic microwave imaging systems using multistatic sparse arrays are suitable for next generation screening systems, which will support on the move screening of passengers.

Association between physiological falls risk and physical performance tests among community-dwelling older adults.

PubMed

Singh, Devinder K A; Pillai, Sharmila G K; Tan, Sin Thien; Tai, Chu Chiau; Shahar, Suzana

2015-01-01

Physical performance and balance declines with aging and may lead to increased risk of falls. Physical performance tests may be useful for initial fall-risk screening test among community-dwelling older adults. Physiological profile assessment (PPA), a composite falls risk assessment tool is reported to have 75% accuracy to screen for physiological falls risk. PPA correlates with Timed Up and Go (TUG) test. However, the association between many other commonly used physical performance tests and PPA is not known. The aim of the present study was to examine the association between physiological falls risk measured using PPA and a battery of physical performance tests. One hundred and forty older adults from a senior citizens club in Kuala Lumpur, Malaysia (94 females, 46 males), aged 60 years and above (65.77±4.61), participated in this cross-sectional study. Participants were screened for falls risk using PPA. A battery of physical performance tests that include ten-step test (TST), short physical performance battery (SPPB), functional reach test (FRT), static balance test (SBT), TUG, dominant hand-grip strength (DHGS), and gait speed test (GST) were also performed. Spearman's rank correlation and binomial logistic regression were performed to examine the significantly associated independent variables (physical performance tests) with falls risk (dependent variable). Approximately 13% older adults were at high risk of falls categorized using PPA. Significant differences (P<0.05) were demonstrated for age, TST, SPPB, FRT, SBT, TUG between high and low falls risk group. A significant (P<0.01) weak correlation was found between PPA and TST (r=0.25), TUG (r=0.27), SBT (r=0.23), SPPB (r=-0.33), and FRT (r=-0.23). Binary logistic regression results demonstrated that SBT measuring postural sways objectively using a balance board was the only significant predictor of physiological falls risk (P<0.05, odds ratio of 2.12). The reference values of physical performance tests in our study may be used as a guide for initial falls screening to categorize high and low physiological falls risk among community-dwelling older adults. A more comprehensive assessment of falls risk can be performed thereafter for more specific intervention of underlying impairments.

Rapid and Accurate Machine Learning Recognition of High Performing Metal Organic Frameworks for CO2 Capture.

PubMed

Fernandez, Michael; Boyd, Peter G; Daff, Thomas D; Aghaji, Mohammad Zein; Woo, Tom K

2014-09-04

In this work, we have developed quantitative structure-property relationship (QSPR) models using advanced machine learning algorithms that can rapidly and accurately recognize high-performing metal organic framework (MOF) materials for CO2 capture. More specifically, QSPR classifiers have been developed that can, in a fraction of a section, identify candidate MOFs with enhanced CO2 adsorption capacity (>1 mmol/g at 0.15 bar and >4 mmol/g at 1 bar). The models were tested on a large set of 292 050 MOFs that were not part of the training set. The QSPR classifier could recover 945 of the top 1000 MOFs in the test set while flagging only 10% of the whole library for compute intensive screening. Thus, using the machine learning classifiers as part of a high-throughput screening protocol would result in an order of magnitude reduction in compute time and allow intractably large structure libraries and search spaces to be screened.

High resolution colonoscopy in a bowel cancer screening program improves polyp detection

PubMed Central

Banks, Matthew R; Haidry, Rehan; Butt, M Adil; Whitley, Lisa; Stein, Judith; Langmead, Louise; Bloom, Stuart L; O’Bichere, Austin; McCartney, Sara; Basherdas, Kalpesh; Rodriguez-Justo, Manuel; Lovat, Laurence B

2011-01-01

AIM: To compare high resolution colonoscopy (Olympus Lucera) with a megapixel high resolution system (Pentax HiLine) as an in-service evaluation. METHODS: Polyp detection rates and measures of performance were collected for 269 colonoscopy procedures. Five colonoscopists conducted the study over a three month period, as part of the United Kingdom bowel cancer screening program. RESULTS:There were no differences in procedure duration (χ2 P = 0.98), caecal intubation rates (χ2 P = 0.67), or depth of sedation (χ2 P = 0.64). Mild discomfort was more common in the Pentax group (χ2 P = 0.036). Adenoma detection rate was significantly higher in the Pentax group (χ2 test for trend P = 0.01). Most of the extra polyps detected were flat or sessile adenomas. CONCLUSION: Megapixel definition colonoscopes improve adenoma detection without compromising other measures of endoscope performance. Increased polyp detection rates may improve future outcomes in bowel cancer screening programs. PMID:22090787

Rapid screening, identification, and purification of neuraminidase inhibitors from Lithospermum erythrorhizon Sieb.et Zucc. by ultrafiltration with HPLC-ESI-TOF-MS combined with semipreparative HPLC.

PubMed

Zhang, Minmin; Zhao, Hengqiang; Zhao, Zhiguo; Yan, Huijiao; Lv, Ruimin; Cui, Li; Yuan, Jinpeng; Wang, Daijie; Geng, Yanling; Liu, Daicheng; Wang, Xiao

2016-06-01

We put forward an efficient strategy based on bioassay guidance for the rapid screening, identification, and purification of the neuraminidase inhibitors from traditional Chinese medicines, and apply to the discovery of anti-influenza components from Lithospermiun erythrorhizon Sieb.et Zucc. Ultrafiltration with high-performance liquid chromatography and electrospray ionization time-of-flight mass spectrometry was employed for the rapid screening and preliminarily identification of anti-influenza components from Zicao. Semipreparative high-performance liquid chromatography was used for the rapid separation and purification of the target compounds. NMR spectroscopy, mass spectrometry, and UV spectroscopy were used for further structural identification, and the activity of the compounds was verified by in vitro assay. Five compounds were found to have neuraminidase inhibitory activity by this method. Subsequently, the five compounds were separated by semipreparative high-performance liquid chromatography with the purity over 98% for all of them by high-performance liquid chromatography test. Combined with the NMR spectroscopy, mass spectrometry, and UV spectroscopy data, they were identified as alkannin, acetylalkannin, isobutyrylalkannin, β,β-dimethylacryloylalkannin and isovalerylalkannin. The in vitro assay showed that all five compounds had good neuraminidase inhibitory activities. These results suggested that the method is highly efficient, and it can provide platform and methodology supports for the rapid discovery of anti-influenza active ingredients from complex Chinese herbal medicines. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The cost-effectiveness of screening for colorectal cancer.

PubMed

Telford, Jennifer J; Levy, Adrian R; Sambrook, Jennifer C; Zou, Denise; Enns, Robert A

2010-09-07

Published decision analyses show that screening for colorectal cancer is cost-effective. However, because of the number of tests available, the optimal screening strategy in Canada is unknown. We estimated the incremental cost-effectiveness of 10 strategies for colorectal cancer screening, as well as no screening, incorporating quality of life, noncompliance and data on the costs and benefits of chemotherapy. We used a probabilistic Markov model to estimate the costs and quality-adjusted life expectancy of 50-year-old average-risk Canadians without screening and with screening by each test. We populated the model with data from the published literature. We calculated costs from the perspective of a third-party payer, with inflation to 2007 Canadian dollars. Of the 10 strategies considered, we focused on three tests currently being used for population screening in some Canadian provinces: low-sensitivity guaiac fecal occult blood test, performed annually; fecal immunochemical test, performed annually; and colonoscopy, performed every 10 years. These strategies reduced the incidence of colorectal cancer by 44%, 65% and 81%, and mortality by 55%, 74% and 83%, respectively, compared with no screening. These strategies generated incremental cost-effectiveness ratios of $9159, $611 and $6133 per quality-adjusted life year, respectively. The findings were robust to probabilistic sensitivity analysis. Colonoscopy every 10 years yielded the greatest net health benefit. Screening for colorectal cancer is cost-effective over conventional levels of willingness to pay. Annual high-sensitivity fecal occult blood testing, such as a fecal immunochemical test, or colonoscopy every 10 years offer the best value for the money in Canada.

Sensitivity and specificity of clinician administered screening instruments in detecting depression among HIV-positive individuals in Uganda.

PubMed

Akena, Dickens; Joska, John; Obuku, Ekwaro A; Stein, Dan J

2013-01-01

Depressive disorders are highly prevalent in Africa where diseases such as HIV/AIDS are common. The aim of this study was to assess the validity of commonly used depression screening instruments in a setting characterized by low literacy, where patients may not be able to self-administer depression scales. We explored the validity of the Patient Health Questionaire-9 (PHQ-9), Centre for Epidemiological Surveys for Depression (CES-D), and the Kessler-10 (K-10), using the Mini International Neuropsychiatric Instrument (MINI) as a gold standard in 368 persons living with HIV/AIDS (PLWHA) in Uganda. The shorter versions of the K-10 and PHQ-9 were extracted to assess their performance in comparison to the longer versions. We used STATA 11.2 to analyze the data. The prevalence of a MINI defined depression in this patient sample was 17.4%. The three instruments all performed well, with areas under the curve (AUC) ranging from 0.82 to 0.96. The PHQ-9 showed the best performance characteristics with an AUC of 0.96, a sensitivity of 91.6%, and specificity 81.2%. The extracted versions performed more modestly. All three instruments showed good properties as screening tools; the PHQ-9 has particularly high sensitivity and specificity, and so can be considered useful for screening HIV-positive patients for depression.

Integrated economic and experimental framework for screening of primary recovery technologies for high cell density CHO cultures

PubMed Central

Popova, Daria; Stonier, Adam; Pain, David; Titchener‐Hooker, Nigel J.

2016-01-01

Abstract Increases in mammalian cell culture titres and densities have placed significant demands on primary recovery operation performance. This article presents a methodology which aims to screen rapidly and evaluate primary recovery technologies for their scope for technically feasible and cost‐effective operation in the context of high cell density mammalian cell cultures. It was applied to assess the performance of current (centrifugation and depth filtration options) and alternative (tangential flow filtration (TFF)) primary recovery strategies. Cell culture test materials (CCTM) were generated to simulate the most demanding cell culture conditions selected as a screening challenge for the technologies. The performance of these technology options was assessed using lab scale and ultra scale‐down (USD) mimics requiring 25–110mL volumes for centrifugation and depth filtration and TFF screening experiments respectively. A centrifugation and depth filtration combination as well as both of the alternative technologies met the performance selection criteria. A detailed process economics evaluation was carried out at three scales of manufacturing (2,000L, 10,000L, 20,000L), where alternative primary recovery options were shown to potentially provide a more cost‐effective primary recovery process in the future. This assessment process and the study results can aid technology selection to identify the most effective option for a specific scenario. PMID:27067803

Multi-component identification and target cell-based screening of potential bioactive compounds in toad venom by UPLC coupled with high-resolution LTQ-Orbitrap MS and high-sensitivity Qtrap MS.

PubMed

Ren, Wei; Han, Lingyu; Luo, Mengyi; Bian, Baolin; Guan, Ming; Yang, Hui; Han, Chao; Li, Na; Li, Tuo; Li, Shilei; Zhang, Yangyang; Zhao, Zhenwen; Zhao, Haiyu

2018-04-28

Traditional Chinese medicines (TCMs) are undoubtedly treasured natural resources for discovering effective medicines in treating and preventing various diseases. However, it is still extremely difficult for screening the bioactive compounds due to the tremendous constituents in TCMs. In this work, the chemical composition of toad venom was comprehensively analyzed using ultra-high performance liquid chromatography (UPLC) coupled with high-resolution LTQ-Orbitrap mass spectrometry and 93 compounds were detected. Among them, 17 constituents were confirmed by standard substances and 8 constituents were detected in toad venom for the first time. Further, a compound database of toad venom containing the fullest compounds was further constructed using UPLC coupled with high-sensitivity Qtrap MS. Then a target cell-based approach for screening potential bioactive compounds from toad venom was developed by analyzing the target cell extracts. The reliability of this method was validated by negative controls and positive controls. In total, 17 components in toad venom were discovered to interact with the target cancer cells. Further, in vitro pharmacological trials were performed to confirm the anti-cancer activity of four of them. The results showed that the six bufogenins and seven bufotoxins detected in our research represented a promising resource to explore bufogenins/bufotoxins-based anticancer agents with low cardiotoxic effect. The target cell-based screening method coupled with the compound database of toad venom constructed by UPLC-Qtrap-MS with high sensitivity provide us a new strategy to rapidly screen and identify the potential bioactive constituents with low content in natural products, which was beneficial for drug discovery from other TCMs. ᅟ Graphical abstract.

Screening high-risk patients and assisting in diagnosing anxiety in primary care: the Patient Health Questionnaire evaluated

PubMed Central

2013-01-01

Background Questionnaires may help in detecting and diagnosing anxiety disorders in primary care. However, since utility of these questionnaires in target populations is rarely studied, the Patient Health Questionnaire anxiety modules (PHQ) were evaluated for use as: a) a screener in high-risk patients, and/or b) a case finder for general practitioners (GPs) to assist in diagnosing anxiety disorders. Methods A cross-sectional analysis was performed in 43 primary care practices in the Netherlands. The added value of the PHQ was assessed in two samples: 1) 170 patients at risk of anxiety disorders (or developing them) according to their electronic medical records (high-risk sample); 2) 141 patients identified as a possible ‘anxiety case’ by a GP (GP-identified sample). All patients completed the PHQ and were interviewed using the Mini International Neuropsychiatric interview to classify DSM-IV anxiety disorders. Psychometric properties were calculated, and a logistic regression analysis was performed to assess the diagnostic value of the PHQ. Results Using only the screening questions of the PHQ, the area under the curve was 83% in the high-risk sample. In GP-identified patients the official algorithm showed the best characteristics with an area under the curve of 77%. Positive screening questions significantly increased the odds of an anxiety disorder diagnosis in high-risk patients (odds ratio = 23.4; 95% confidence interval 6.9 to 78.8) as did a positive algorithm in GP-identified patients (odds ratio = 13.9; 95% confidence interval 3.8 to 50.6). Conclusions The PHQ screening questions can be used to screen for anxiety disorders in high-risk primary care patients. In GP-identified patients, the benefit of the PHQ is less evident. PMID:23865984

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

PubMed

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

2017-09-01

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

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

NASA Technical Reports Server (NTRS)

Newman, Lauri K.; Hejduk, Matthew D.

2015-01-01

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

Comparison of Colonoscopy Quality Measures Across Various Practice Settings and the Impact of Performance Scorecards.

PubMed

Inra, Jennifer A; Nayor, Jennifer; Rosenblatt, Margery; Mutinga, Muthoka; Reddy, Sarathchandra I; Syngal, Sapna; Kastrinos, Fay

2017-04-01

Quality performance measures for screening colonoscopy vary among endoscopists. The impact of practice setting is unknown. We aimed to (1) compare screening colonoscopy performance measures among three different US practice settings; (2) evaluate factors associated with adenoma detection; and (3) assess a scorecard intervention on performance metrics. This multi-center prospective study compared patient, endoscopist, and colonoscopy characteristics performed at a tertiary care hospital (TCH), community-based hospital (CBH), and private practice group (PPG). Withdrawal times (WT), cecal intubation, and adenoma detection rates (ADR) were compared by site at baseline and 12 weeks following scorecard distribution. Generalized linear mixed models identified factors associated with adenoma detection. Twenty-eight endoscopists performed colonoscopies on 1987 asymptomatic, average-risk individuals ≥50 years. Endoscopist and patient characteristics were similar across sites. The PPG screened more men (TCH: 42.8%, CBH: 45.0%, PPG: 54.2%; p < 0.0001). Preparation quality varied with good/excellent results in 70.6, 88.3, and 92% of TCH, CBH, and PPG cases, respectively (p < 0.0001). Male ADRs, cecal intubation, and WT exceeded recommended benchmarks despite variable results at each site; female ADRs were <15% at the PPG which screened the fewest females. Performance remained unchanged following scorecard distribution. Adenoma detection was associated with increasing patient age, male gender, WT, adequate preparation, but not practice setting. Each practice performed high-quality screening colonoscopy. Scorecards did not improve performance metrics. Preparation quality varies among practice settings and can be modified to improve adenoma detection.

Colorectal Cancer Screening Programme in Spain: Results of Key Performance Indicators After Five Rounds (2000-2012).

PubMed

Binefa, Gemma; Garcia, Montse; Milà, Núria; Fernández, Esteve; Rodríguez-Moranta, Francisco; Gonzalo, Núria; Benito, Llúcia; Clopés, Ana; Guardiola, Jordi; Moreno, Víctor

2016-01-20

Effective quality assurance is essential in any screening programme. This article provides a unique insight into key quality indicators of five rounds of the first population-based colorectal cancer screening programme implemented in Spain (2000-2012), providing the results according to the type of screening (prevalent or first screen and incident or subsequent screen) and test (guaiac or immunochemical). The total crude participation rate increased from 17.2% (11,011) in the first round to 35.9% (22,988) in the last one. Rescreening rate was very high (88.6% in the fifth round). Positivity rate was superior with the faecal immunochemical test (6.2%) than with the guaiac-based test (0.7%) (p < 0.0001) and detection rates were also better with the immunochemical test. The most significant rise in detection rate was observed for high risk adenoma in men (45.5 per 1,000 screened). Most cancers were diagnosed at an early stage (61.4%) and there was a statistically significant difference between those detected in first or subsequent screening (52.6% and 70.0% respectively; p = 0.024). The availability of these results substantially improves data comparisons and the exchange of experience between screening programmes.

High-speed spectral nanocytology for early cancer screening

PubMed Central

Subramanian, Hariharan; Maneval, Charles D.; White, Craig A.; Levenson, Richard M.; Backman, Vadim

2013-01-01

Abstract. High-throughput partial wave spectroscopy (HTPWS) is introduced as a high-speed spectral nanocytology technique that utilizes the field effect of carcinogenesis to perform minimally invasive cancer screening on at-risk populations. HTPWS uses fully automated hardware and an acousto-optic tunable filter to scan slides at low magnification, to select cells, and to rapidly acquire spectra at each spatial pixel in a cell between 450 and 700 nm, completing measurements of 30 cells in 40 min. Statistical quantitative analysis on the size and density of intracellular nanostructures extracted from the spectra at each pixel in a cell yields the diagnostic biomarker, disorder strength (Ld). Linear correlation between Ld and the length scale of nanostructures was measured in phantoms with R2=0.93. Diagnostic sensitivity was demonstrated by measuring significantly higher Ld from a human colon cancer cell line (HT29 control vector) than a less aggressive variant (epidermal growth factor receptor knockdown). Clinical diagnostic performance for lung cancer screening was tested on 23 patients, yielding a significant difference in Ld between smokers and cancer patients, p=0.02 and effect size=1.00. The high-throughput performance, nanoscale sensitivity, and diagnostic sensitivity make HTPWS a potentially clinically relevant modality for risk stratification of the large populations at risk of developing cancer. PMID:24193949

Independence screening for high dimensional nonlinear additive ODE models with applications to dynamic gene regulatory networks.

PubMed

Xue, Hongqi; Wu, Shuang; Wu, Yichao; Ramirez Idarraga, Juan C; Wu, Hulin

2018-05-02

Mechanism-driven low-dimensional ordinary differential equation (ODE) models are often used to model viral dynamics at cellular levels and epidemics of infectious diseases. However, low-dimensional mechanism-based ODE models are limited for modeling infectious diseases at molecular levels such as transcriptomic or proteomic levels, which is critical to understand pathogenesis of diseases. Although linear ODE models have been proposed for gene regulatory networks (GRNs), nonlinear regulations are common in GRNs. The reconstruction of large-scale nonlinear networks from time-course gene expression data remains an unresolved issue. Here, we use high-dimensional nonlinear additive ODEs to model GRNs and propose a 4-step procedure to efficiently perform variable selection for nonlinear ODEs. To tackle the challenge of high dimensionality, we couple the 2-stage smoothing-based estimation method for ODEs and a nonlinear independence screening method to perform variable selection for the nonlinear ODE models. We have shown that our method possesses the sure screening property and it can handle problems with non-polynomial dimensionality. Numerical performance of the proposed method is illustrated with simulated data and a real data example for identifying the dynamic GRN of Saccharomyces cerevisiae. Copyright © 2018 John Wiley & Sons, Ltd.

When and Why Threats Go Undetected: Impacts of Event Rate and Shift Length on Threat Detection Accuracy During Airport Baggage Screening.

PubMed

Meuter, Renata F I; Lacherez, Philippe F

2016-03-01

We aimed to assess the impact of task demands and individual characteristics on threat detection in baggage screeners. Airport security staff work under time constraints to ensure optimal threat detection. Understanding the impact of individual characteristics and task demands on performance is vital to ensure accurate threat detection. We examined threat detection in baggage screeners as a function of event rate (i.e., number of bags per minute) and time on task across 4 months. We measured performance in terms of the accuracy of detection of Fictitious Threat Items (FTIs) randomly superimposed on X-ray images of real passenger bags. Analyses of the percentage of correct FTI identifications (hits) show that longer shifts with high baggage throughput result in worse threat detection. Importantly, these significant performance decrements emerge within the first 10 min of these busy screening shifts only. Longer shift lengths, especially when combined with high baggage throughput, increase the likelihood that threats go undetected. Shorter shift rotations, although perhaps difficult to implement during busy screening periods, would ensure more consistently high vigilance in baggage screeners and, therefore, optimal threat detection and passenger safety. © 2015, Human Factors and Ergonomics Society.

An automated high throughput screening-compatible assay to identify regulators of stem cell neural differentiation.

PubMed

Casalino, Laura; Magnani, Dario; De Falco, Sandro; Filosa, Stefania; Minchiotti, Gabriella; Patriarca, Eduardo J; De Cesare, Dario

2012-03-01

The use of Embryonic Stem Cells (ESCs) holds considerable promise both for drug discovery programs and the treatment of degenerative disorders in regenerative medicine approaches. Nevertheless, the successful use of ESCs is still limited by the lack of efficient control of ESC self-renewal and differentiation capabilities. In this context, the possibility to modulate ESC biological properties and to obtain homogenous populations of correctly specified cells will help developing physiologically relevant screens, designed for the identification of stem cell modulators. Here, we developed a high throughput screening-suitable ESC neural differentiation assay by exploiting the Cell(maker) robotic platform and demonstrated that neural progenies can be generated from ESCs in complete automation, with high standards of accuracy and reliability. Moreover, we performed a pilot screening providing proof of concept that this assay allows the identification of regulators of ESC neural differentiation in full automation.

Nonlinear dimensionality reduction of CT histogram based feature space for predicting recurrence-free survival in non-small-cell lung cancer

NASA Astrophysics Data System (ADS)

Kawata, Y.; Niki, N.; Ohmatsu, H.; Aokage, K.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

2015-03-01

Advantages of CT scanners with high resolution have allowed the improved detection of lung cancers. In the recent release of positive results from the National Lung Screening Trial (NLST) in the US showing that CT screening does in fact have a positive impact on the reduction of lung cancer related mortality. While this study does show the efficacy of CT based screening, physicians often face the problems of deciding appropriate management strategies for maximizing patient survival and for preserving lung function. Several key manifold-learning approaches efficiently reveal intrinsic low-dimensional structures latent in high-dimensional data spaces. This study was performed to investigate whether the dimensionality reduction can identify embedded structures from the CT histogram feature of non-small-cell lung cancer (NSCLC) space to improve the performance in predicting the likelihood of RFS for patients with NSCLC.

Applying Risk Prediction Models to Optimize Lung Cancer Screening: Current Knowledge, Challenges, and Future Directions.

PubMed

Sakoda, Lori C; Henderson, Louise M; Caverly, Tanner J; Wernli, Karen J; Katki, Hormuzd A

2017-12-01

Risk prediction models may be useful for facilitating effective and high-quality decision-making at critical steps in the lung cancer screening process. This review provides a current overview of published lung cancer risk prediction models and their applications to lung cancer screening and highlights both challenges and strategies for improving their predictive performance and use in clinical practice. Since the 2011 publication of the National Lung Screening Trial results, numerous prediction models have been proposed to estimate the probability of developing or dying from lung cancer or the probability that a pulmonary nodule is malignant. Respective models appear to exhibit high discriminatory accuracy in identifying individuals at highest risk of lung cancer or differentiating malignant from benign pulmonary nodules. However, validation and critical comparison of the performance of these models in independent populations are limited. Little is also known about the extent to which risk prediction models are being applied in clinical practice and influencing decision-making processes and outcomes related to lung cancer screening. Current evidence is insufficient to determine which lung cancer risk prediction models are most clinically useful and how to best implement their use to optimize screening effectiveness and quality. To address these knowledge gaps, future research should be directed toward validating and enhancing existing risk prediction models for lung cancer and evaluating the application of model-based risk calculators and its corresponding impact on screening processes and outcomes.

Development of high-performance low-reflection rugged resistive touch screens for military displays

NASA Astrophysics Data System (ADS)

Wang, Raymond; Wang, Minshine; Thomas, John; Wang, Lawrence; Chang, Victor

2010-04-01

Just as iPhones with sophisticated touch interfaces have revolutionised the human interface for the ubiquitous cell phone, the Military is rapidly adopting touch-screens as a primary interface to their computers and vehicle systems. This paper describes the development of a true military touch interface solution from an existing industrial design. We will report on successful development of 10.4" and 15.4" high performance rugged resistive touch panels using IAD sputter coating. Low reflectance (specular < 1% and diffuse < 0.07%) was achieved with high impact, dust, and chemical resistant surface finishes. These touch panels were qualified over a wide operational temperature range, -51°C to +80°C specifically for military and rugged industrial applications.

Co-Percolating Graphene-Wrapped Silver Nanowire Network for High Performance, Highly Stable, Transparent Conducting Electrodes

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

Chen, Ruiyi; Das, Suprem R; Jeong, Changwook

Transparent conducting electrodes (TCEs) require high transparency and low sheet resistance for applications in photovoltaics, photodetectors, flat panel displays, touch screen devices, and imagers. Indium tin oxide (ITO), or other transparent conductive oxides, have been used, and provide a baseline sheet resistance (RS) vs. transparency (T) relationship. Several alternative material systems have been investigated. The development of high-performance hybrid structures provides a route towards robust, scalable and low-cost approaches for realizing high-performance TCE.

Preparticipation Screening for Sudden Cardiac Death in High School and College Athletes.

ERIC Educational Resources Information Center

Braden, David S.; Strong, William B.

1988-01-01

A properly performed screening history and cardiovascular examination can identify most young athletes at risk for sudden death from heart abnormalities. Warning signs and examiner response are discussed as well as appropriate use of echocardiography. Included is a sample preparticipation examination form recommended by the American Academy of…

Screening of cervical cancer in Catalonia 2006-2012.

PubMed

de Sanjosé, Silvia; Ibáñez, Raquel; Rodríguez-Salés, Vanesa; Peris, Mercè; Roura, Esther; Diaz, Mireia; Torné, Aureli; Costa, Dolors; Canet, Yolanda; Falguera, Gemma; Alejo, Maria; Espinàs, Josep Alfons; Bosch, F Xavier

2015-01-01

The early detection of intraepithelial lesions of the cervix, through the periodic examination of cervical cells, has been fundamental for the prevention of invasive cervical cancer and its related mortality. In this report, we summarise the cervical cancer screening activities carried out in Catalonia, Spain, within the National Health System during 2008-2011. The study population covers over two million women resident in the area. The evaluation includes 758,690 cervical cytologies performed on a total of 595,868 women. The three-year coverage of cervical cytology among women aged between 25 and 65 years was 40.8%. About 50% of first screened women with negative results had not returned to the second screening round. The introduction of high-risk human papillomavirus DNA (HPV) detection, as a primary screening cotest with cytology among women over age 40 with a poor screening history, significantly improved the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior to cytology alone. Cotesting did not improve the detection of CIN2+. The use of the HPV test for the triage of atypical squamous cell undetermined significance (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both cytology and HPV test) was largely performed by midwives (66.7%), followed by obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full use of online medical records. During the study period, educational activities for professionals and for women were carried out periodically. The organisation of screening as a population activity in which women are actively called to the screening visit and the introduction of HPV testing as a primary screening tool are strongly recommended to ensure the maximum population impact in the reduction of the cervical cancer burden.

Screening of cervical cancer in Catalonia 2006–2012

PubMed Central

de Sanjosé, Silvia; Ibáñez, Raquel; Rodríguez-Salés, Vanesa; Peris, Mercè; Roura, Esther; Diaz, Mireia; Torné, Aureli; Costa, Dolors; Canet, Yolanda; Falguera, Gemma; Alejo, Maria; Espinàs, Josep Alfons; Bosch, F. Xavier

2015-01-01

The early detection of intraepithelial lesions of the cervix, through the periodic examination of cervical cells, has been fundamental for the prevention of invasive cervical cancer and its related mortality. In this report, we summarise the cervical cancer screening activities carried out in Catalonia, Spain, within the National Health System during 2008–2011. The study population covers over two million women resident in the area. The evaluation includes 758,690 cervical cytologies performed on a total of 595,868 women. The three-year coverage of cervical cytology among women aged between 25 and 65 years was 40.8%. About 50% of first screened women with negative results had not returned to the second screening round. The introduction of high-risk human papillomavirus DNA (HPV) detection, as a primary screening cotest with cytology among women over age 40 with a poor screening history, significantly improved the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior to cytology alone. Cotesting did not improve the detection of CIN2+. The use of the HPV test for the triage of atypical squamous cell undetermined significance (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both cytology and HPV test) was largely performed by midwives (66.7%), followed by obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full use of online medical records. During the study period, educational activities for professionals and for women were carried out periodically. The organisation of screening as a population activity in which women are actively called to the screening visit and the introduction of HPV testing as a primary screening tool are strongly recommended to ensure the maximum population impact in the reduction of the cervical cancer burden. PMID:25987901

Fully Screen-Printed, Large-Area, and Flexible Active-Matrix Electrochromic Displays Using Carbon Nanotube Thin-Film Transistors.

PubMed

Cao, Xuan; Lau, Christian; Liu, Yihang; Wu, Fanqi; Gui, Hui; Liu, Qingzhou; Ma, Yuqiang; Wan, Haochuan; Amer, Moh R; Zhou, Chongwu

2016-11-22

Semiconducting single-wall carbon nanotubes are ideal semiconductors for printed electronics due to their advantageous electrical and mechanical properties, intrinsic printability in solution, and desirable stability in air. However, fully printed, large-area, high-performance, and flexible carbon nanotube active-matrix backplanes are still difficult to realize for future displays and sensing applications. Here, we report fully screen-printed active-matrix electrochromic displays employing carbon nanotube thin-film transistors. Our fully printed backplane shows high electrical performance with mobility of 3.92 ± 1.08 cm 2 V -1 s -1 , on-off current ratio I on /I off ∼ 10 4 , and good uniformity. The printed backplane was then monolithically integrated with an array of printed electrochromic pixels, resulting in an entirely screen-printed active-matrix electrochromic display (AMECD) with good switching characteristics, facile manufacturing, and long-term stability. Overall, our fully screen-printed AMECD is promising for the mass production of large-area and low-cost flexible displays for applications such as disposable tags, medical electronics, and smart home appliances.

Bias in discriminating very mild dementia for older adults with different levels of education in Hong Kong.

PubMed

Chang, Jianfang; Tse, Chi-Shing; Leung, Grace Tak Yu; Fung, Ada Wai Tung; Hau, Kit-Tai; Chiu, Helen Fung Kum; Lam, Linda Chiu Wa

2014-06-01

Education has a profound effect on older adults' cognitive performance. In Hong Kong, some dementia screening tasks were originally designed for developed population with, on average, higher education. We compared the screening power of these tasks for Chinese older adults with different levels of education. Community-dwelling older adults who were healthy (N = 383) and with very mild dementia (N = 405) performed the following tasks: Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive subscales, Verbal Fluency, Abstract Thinking, and Visual/Digit Span. Logistic regression was used to examine the power of these tasks to predict Clinical Dementia Rating (CDR 0.5 vs. 0). Logistic regression analysis showed that while the screening power of the total scores in all tasks was similar for high and low education groups, there were education biases in some items of these tasks. The differential screening power in high and low education groups was not identical across items in some tasks. Thus, in cognitive assessments, we should exercise great caution when using these potentially biased items for older adults with limited education.

Use of the Analysis of the Volatile Faecal Metabolome in Screening for Colorectal Cancer

PubMed Central

2015-01-01

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT. PMID:26086914

[Comparison of the sensibility and specificity between single-stranded conformation polymorphism and denaturing high-performance liquid chromatography in screening hMSH2 and hMLH1 gene mutations in hereditary non-polyposis colorectal cancer].

PubMed

Wei, Guang-hui; Zhao, Bo; Wang, Zhen-jun

2008-09-01

To compare the sensibility and specificity between single-stranded conformation polymorphism (SSCP) and denaturing high-performance liquid chromatography (DHPLC) in screening hMSH2 and hMLH1 gene mutations for the diagnosis of hereditary non-polyposis colorectal cancer (HNPCC). Seven Chinese HNPCC kindreds were collected. PCR-SSCP and DHPLC were used to screen the coding regions of hMSH2 and hMLH1 genes and the abnormal profiles were sequenced by a 377 DNA sequencer. Seven gene sequence variations of hMSH2 or hMLH1 were found. Among them, 4 variations were not found by SSCP, but by DHPLC. The sensibility of SSCP and DHPLC were 51.6% and 100% respectively, and the specificity were 66.6% and 93.3% respectively. DHPLC has better sensibility and specificity in screening hMSH2 and hMLH1 gene mutation as compared to SSCP. DHPLC is an ideal method in the diagnosis of HNPCC.

Screening for Pancreatic Cancer

PubMed Central

Brand, Randall E.

2007-01-01

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

Screening for Fall Risks in the Emergency Department: A Novel Nursing-Driven Program.

PubMed

Huded, Jill M; Dresden, Scott M; Gravenor, Stephanie J; Rowe, Theresa; Lindquist, Lee A

2015-12-01

Seniors represent the fasting growing population in the U.S., accounting for 20.3 million visits to emergency departments (EDs) annually. The ED visit can provide an opportunity for identifying seniors at high risk of falls. We sought to incorporate the Timed Up & Go Test (TUGT), a commonly used falls screening tool, into the ED encounter to identify seniors at high fall risk and prompt interventions through a geriatric nurse liaison (GNL) model. Patients aged 65 and older presenting to an urban ED were evaluated by a team of ED nurses trained in care coordination and geriatric assessment skills. They performed fall risk screening with the TUGT. Patients with abnormal TUGT results could then be referred to physical therapy (PT), social work or home health as determined by the GNL. Gait assessment with the TUGT was performed on 443 elderly patients between 4/1/13 and 5/31/14. A prior fall was reported in 37% of patients in the previous six months. Of those screened with the TUGT, 368 patients experienced a positive result. Interventions for positive results included ED-based PT (n=63, 17.1%), outpatient PT referrals (n=56, 12.2%) and social work consultation (n=162, 44%). The ED visit may provide an opportunity for older adults to be screened for fall risk. Our results show ED nurses can conduct the TUGT, a validated and time efficient screen, and place appropriate referrals based on assessment results. Identifying and intervening on high fall risk patients who visit the ED has the potential to improve the trajectory of functional decline in our elderly population.

Nontargeted Screening Method for Illegal Additives Based on Ultrahigh-Performance Liquid Chromatography-High-Resolution Mass Spectrometry.

PubMed

Fu, Yanqing; Zhou, Zhihui; Kong, Hongwei; Lu, Xin; Zhao, Xinjie; Chen, Yihui; Chen, Jia; Wu, Zeming; Xu, Zhiliang; Zhao, Chunxia; Xu, Guowang

2016-09-06

Identification of illegal additives in complex matrixes is important in the food safety field. In this study a nontargeted screening strategy was developed to find illegal additives based on ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). First, an analytical method for possible illegal additives in complex matrixes was established including fast sample pretreatment, accurate UHPLC separation, and HRMS detection. Second, efficient data processing and differential analysis workflow were suggested and applied to find potential risk compounds. Third, structure elucidation of risk compounds was performed by (1) searching online databases [Metlin and the Human Metabolome Database (HMDB)] and an in-house database which was established at the above-defined conditions of UHPLC-HRMS analysis and contains information on retention time, mass spectra (MS), and tandem mass spectra (MS/MS) of 475 illegal additives, (2) analyzing fragment ions, and (3) referring to fragmentation rules. Fish was taken as an example to show the usefulness of the nontargeted screening strategy, and six additives were found in suspected fish samples. Quantitative analysis was further carried out to determine the contents of these compounds. The satisfactory application of this strategy in fish samples means that it can also be used in the screening of illegal additives in other kinds of food samples.

Incidence of elbow injuries in adolescent baseball players: screening by a low field magnetic resonance imaging system specialized for small joints.

PubMed

Okamoto, Yoshikazu; Maehara, Kiyoshi; Kanahori, Tetsuya; Hiyama, Takashi; Kawamura, Takashi; Minami, Manabu

2016-04-01

The aim of this preliminary study was to examine the capability of screening for elbow injuries induced by baseball using a low field small joint MRI system. Sixty-two players in the 4th-6th elementary school grades, with ages ranging from 9 to 12 years, participated in this study. Screening for elbow injuries was performed using a low-magnetic-field (0.2-T) magnetic resonance imaging (MRI) system designed for examinations of small joints of the extremities. Gradient-echo coronal, sagittal, and short-tau inversion recovery (STIR) coronal images of the dominant arm used for pitching were obtained to identify medial collateral ligament (MCL) injuries with or without avulsion fracture and osteochondritis dissecans. All 62 examinations were performed successfully, with 26 players (41.9 %) showing positive findings, all being confined to the MCL. No child showed bone damage. All criteria in the MRI evaluation of injuries showed high agreement rates and kappa values between two radiologists. Screening for early detection of elbow injuries in junior Japanese baseball players can be successfully performed using a low-field MRI system specialized for small joints. The percentage of MCL injury without avulsion fracture was unexpectedly high (41.9 %).

Validity of data in the Danish Colorectal Cancer Screening Database.

PubMed

Thomsen, Mette Kielsholm; Njor, Sisse Helle; Rasmussen, Morten; Linnemann, Dorte; Andersen, Berit; Baatrup, Gunnar; Friis-Hansen, Lennart Jan; Jørgensen, Jens Christian Riis; Mikkelsen, Ellen Margrethe

2017-01-01

In Denmark, a nationwide screening program for colorectal cancer was implemented in March 2014. Along with this, a clinical database for program monitoring and research purposes was established. The aim of this study was to estimate the agreement and validity of diagnosis and procedure codes in the Danish Colorectal Cancer Screening Database (DCCSD). All individuals with a positive immunochemical fecal occult blood test (iFOBT) result who were invited to screening in the first 3 months since program initiation were identified. From these, a sample of 150 individuals was selected using stratified random sampling by age, gender and region of residence. Data from the DCCSD were compared with data from hospital records, which were used as the reference. Agreement, sensitivity, specificity and positive and negative predictive values were estimated for categories of codes "clean colon", "colonoscopy performed", "overall completeness of colonoscopy", "incomplete colonoscopy", "polypectomy", "tumor tissue left behind", "number of polyps", "lost polyps", "risk group of polyps" and "colorectal cancer and polyps/benign tumor". Hospital records were available for 136 individuals. Agreement was highest for "colorectal cancer" (97.1%) and lowest for "lost polyps" (88.2%). Sensitivity varied between moderate and high, with 60.0% for "incomplete colonoscopy" and 98.5% for "colonoscopy performed". Specificity was 92.7% or above, except for the categories "colonoscopy performed" and "overall completeness of colonoscopy", where the specificity was low; however, the estimates were imprecise. A high level of agreement between categories of codes in DCCSD and hospital records indicates that DCCSD reflects the hospital records well. Further, the validity of the categories of codes varied from moderate to high. Thus, the DCCSD may be a valuable data source for future research on colorectal cancer screening.

High content screening in microfluidic devices

PubMed Central

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2011-01-01

Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

Laser-Induced Fluorescence Detection in High-Throughput Screening of Heterogeneous Catalysts and Single Cells Analysis

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

Su, Hui

2001-01-01

Laser-induced fluorescence detection is one of the most sensitive detection techniques and it has found enormous applications in various areas. The purpose of this research was to develop detection approaches based on laser-induced fluorescence detection in two different areas, heterogeneous catalysts screening and single cell study. First, we introduced laser-induced imaging (LIFI) as a high-throughput screening technique for heterogeneous catalysts to explore the use of this high-throughput screening technique in discovery and study of various heterogeneous catalyst systems. This scheme is based on the fact that the creation or the destruction of chemical bonds alters the fluorescence properties of suitablymore » designed molecules. By irradiating the region immediately above the catalytic surface with a laser, the fluorescence intensity of a selected product or reactant can be imaged by a charge-coupled device (CCD) camera to follow the catalytic activity as a function of time and space. By screening the catalytic activity of vanadium pentoxide catalysts in oxidation of naphthalene, we demonstrated LIFI has good detection performance and the spatial and temporal resolution needed for high-throughput screening of heterogeneous catalysts. The sample packing density can reach up to 250 x 250 subunits/cm 2 for 40-μm wells. This experimental set-up also can screen solid catalysts via near infrared thermography detection.« less

Who should swing the stethoscope? An audit of baseline physical examination and blood monitoring on new patients accepted by an early intervention in psychosis team.

PubMed

Crabb, Jim; McAllister, Mark; Blair, Alison

2009-11-01

It has been established that patients with severe mental illness are at increased risk of physical illness and that physical health screening should be performed when an individual experiences a first episode of psychosis. The aim of the audit was to examine how physical health screening was achieved in the real world of an early intervention in psychosis (EIP) service in Scotland. Of particular interest was considering if primary or secondary care were more effective in providing specific physical health assessment for those presenting to the service. A case note audit was performed. The audit shows that physical examination and blood tests were being completed in the majority of service users under the care of the Esteem service. However, an unacceptably high number were not undergoing sufficient initial screening for metabolic syndrome or having baseline monitoring prior to commencing antipsychotic medication. Our results suggest that relying on primary care to provide physical health screening was not an effective approach in a population experiencing first-episode psychosis. Having a psychiatrist motivated to perform physical health screening within the EIP team may help to improve the uptake of physical health screening. Strategies to improve physical health screening in EIP services are discussed. © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Asia Pty Ltd.

Full Implementation of Screening for Nutritional Risk and Dysphagia in an Acute Stroke Unit: A Clinical Audit.

PubMed

Kampman, Margitta T; Eltoft, Agnethe; Karaliute, Migle; Børvik, Margrethe T; Nilssen, Hugo; Rasmussen, Ida; Johnsen, Stein H

2015-10-01

In patients with acute stroke, undernutrition and aspiration pneumonia are associated with increased mortality and length of hospital stay. Formal screening for nutritional risk and dysphagia helps to ensure optimal nutritional management in all patients with stroke and to reduce the risk of aspiration in patients with dysphagia. We developed a national guideline for nutritional and dysphagia screening in acute stroke, which was introduced in our stroke unit on June 1, 2012. The primary objective was to audit adherence to the guideline and to achieve full implementation. Second, we assessed the prevalence of nutritional risk and dysphagia. We performed a chart review to assess performance of screening for nutritional risk and dysphagia in all patients with stroke hospitalized for ≥48 hours between June 1, 2012, and May 31, 2013. Next we applied a "clinical microsystems approach" with rapid improvement cycles and audits over a 6-month period to achieve full implementation. The chart review showed that nutritional risk screening was performed in 65% and swallow testing in 91% of eligible patients (n = 185). Proactive implementation resulted in >95% patients screened (n = 79). The overall prevalence of nutritional risk was 29%, and 23% of the patients failed the initial swallow test. Proactive implementation is required to obtain high screening rates for nutritional risk and swallowing difficulties using validated screening tools. The proportion of patients at nutritional risk and the prevalence of dysphagia at initial swallow test were in the lower range of previous reports.

Comparison of mental health screening tools for detecting antenatal depression and anxiety disorders in South African women

PubMed Central

Honikman, Simone; Tomlinson, Mark; Field, Sally; Myer, Landon

2018-01-01

Background Antenatal depression and anxiety disorders are highly prevalent in low and middle-income countries. Screening of pregnant women in primary care antenatal settings provides an opportunity for entry to care, but data are needed on the performance of different screening tools. We compared five widely-used questionnaires in a sample of pregnant women in urban South Africa. Method Pregnant women attending a primary care antenatal clinic were administered five tools by trained research assistants: the Edinburgh Postnatal Depression Scale (EPDS), the Patient Health Questionnaire (PHQ-9), the Kessler Psychological Distress scale (K10) and a shortened 6-item version (K6), the Whooley questions and the two-item Generalised Anxiety Disorder scale (GAD-2). Following this, a registered mental health counsellor administered the MINI Plus, a structured clinical diagnostic interview. The Area Under the Curve (AUC) from Receiver Operator Characteristic curve analysis was used to summarise screening test performance and Cronbach’s α used to assess internal consistency. Results Of 376 participants, 32% were diagnosed with either MDE and/or anxiety disorders. All five questionnaires demonstrated moderate to high performance (AUC = 0.78–0.85). The EPDS was the best performing instrument for detecting MDE and the K10 and K6 for anxiety disorder. For MDE and/or anxiety disorders, the EPDS had the highest AUC (0.83). Of the short instruments, the K10 (AUC = 0.85) and the K6 (AUC = 0.85) performed the best, with the K6 showing good balance between sensitivity (74%) and specificity (85%) and a good positive predictive value (70%). The Whooley questions (AUC = 0.81) were the best performing ultra-short instrument. Internal consistency ranged from good to acceptable (α = 0.89–0.71). However, the PPV of the questionnaires compared with the diagnostic interview, ranged from 54% to 71% at the optimal cut-off scores. Conclusions Universal screening for case identification of antenatal depression and anxiety disorders in low-resource settings can be conducted with a number of commonly used screening instruments. Short and ultra-short screening instruments such as the K6 and the Whooley questions may be feasible and acceptable for use in these settings. PMID:29668725

High throughput screening of active pharmaceutical ingredients by UPLC.

PubMed

Al-Sayah, Mohammad A; Rizos, Panagiota; Antonucci, Vincent; Wu, Naijun

2008-07-01

Ultra performance LC (UPLC) was evaluated as an efficient screening approach to facilitate method development for drug candidates. Three stationary phases were screened: C-18, phenyl, and Shield RP 18 with column dimensions of 150 mm x 2.1 mm, 1.7 microm, which should theoretically generate 35,000 plates or 175% of the typical column plate count of a conventional 250 mm x 4.6 mm, 5 microm particle column. Thirteen different active pharmaceutical ingredients (APIs) were screened using this column set with a standardized mobile-phase gradient. The UPLC method selectivity results were compared to those obtained for these compounds via methods developed through laborious trial and error screening experiments using numerous conventional HPLC mobile and stationary phases. Peak capacity was compared for columns packed with 5 microm particles and columns packed with 1.7 microm particles. The impurities screened by UPLC were confirmed by LC/MS. The results demonstrate that simple, high efficiency UPLC gradients are a feasible and productive alternative to more conventional multiparametric chromatographic screening approaches for many compounds in the early stages of drug development.

Screening antiallergic components from Carthamus tinctorius using rat basophilic leukemia 2H3 cell membrane chromatography combined with high-performance liquid chromatography and tandem mass spectrometry.

PubMed

Han, Shengli; Huang, Jing; Cui, Ronghua; Zhang, Tao

2015-02-01

Carthamus tinctorius, used in traditional Chinese medicine, has many pharmacological effects, such as anticoagulant effects, antioxidant effects, antiaging effects, regulation of gene expression, and antitumor effects. However, there is no report on the antiallergic effects of the components in C. tinctorius. In the present study, we investigated the antiallergic components of C. tinctorius and its mechanism of action. A rat basophilic leukemia 2H3/cell membrane chromatography coupled online with high-performance liquid chromatography and tandem mass spectrometry method was developed to screen antiallergic components from C. tinctorius. The screening results showed that Hydroxysafflor yellow A, from C. tinctorius, was the targeted component that retained on the rat basophilic leukemia 2H3/cell membrane chromatography column. We measured the amount of β-hexosaminidase and histamine released in mast cells and the key markers of degranulation. The release assays showed that Hydroxysafflor yellow A could attenuate the immunoglobulin E induced release of allergic cytokines without affecting cell viability from 1.0 to 50.0 μM. In conclusion, the established rat basophilic leukemia 2H3 cell membrane chromatography coupled with online high-performance liquid chromatography and tandem mass spectrometry method successfully screened and identified Hydroxysafflor yellow A from C. tinctorius as a potential antiallergic component. Pharmacological analysis elucidated that Hydroxysafflor yellow A is an effective natural component for inhibiting immunoglobulin E-antigen-mediated degranulation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A High Content Screening (HCS) Assay for the Identification of Chemical Inducers of PML Oncogenic Domains (PODs)

PubMed Central

Yip, Kenneth W.; Cuddy, Michael; Pinilla, Clemencia; Giulanotti, Marc; Heynen-Genel, Susanne; Matsuzawa, Shu-ichi; Reed, John C.

2014-01-01

PML is a tumor suppressor that promotes apoptosis through both p53-dependent and - independent mechanisms, participates in Rb-mediated cell cycle arrest, inhibits neoangiogenesis, and contributes to maintenance of genomic stability. PML also plays a role in host defense against viruses, conferring antiviral activity. When active, PML localizes to subnuclear structures named PML oncogenic domains (PODs) or PML nuclear bodies (PML-NBs), whereas inactive PML is located diffusely throughout the nucleus of cells, thus providing a morphological indicator. Known activators of PML include arsenicals and interferons, however, these agents induce a plethora of toxic effects, limiting their effectiveness. The objective of the current study was to develop a high content screening (HCS) assay for the identification of chemical activators of PML. We describe methods for automated analysis of POD formation using high throughput microscopy (HTM) to localize PML immunofluorescence in conjunction with image analysis software for POD quantification. Using this HCS assay in 384 well format, we performed pilot screens of a small synthetic chemical library and mixture-based combinatorial libraries, demonstrating the robust performance of the assay. HCS counter-screening assays were also developed for hit characterization, based on immunofluorescence analyses of the subcellular location of phosphorylated H2AX or phosphorylated CHK1, which increase in a punctate nuclear pattern in response to DNA damage. Thus, the HCS assay devised here represents a high throughput screen that can be utilized to discover POD-inducing compounds that may restore the tumor suppressor activity of PML in cancers or possibly promote anti-viral states. PMID:21233309

Conjunction Assessment Screening Volume Sizing and Event Filtering in Light of Natural Conjunction Event Development Behaviors

NASA Technical Reports Server (NTRS)

Hejduk, M. D.; Pachura, D. A.

2017-01-01

Conjunction Assessment screening volumes used in the protection of NASA satellites are constructed as geometric volumes about these satellites, of a size expected to capture a certain percentage of the serious conjunction events by a certain time before closest approach. However, the analyses that established these sizes were grounded on covariance-based projections rather than empirical screening results, did not tailor the volume sizes to ensure operational actionability of those results, and did not consider the adjunct ability to produce data that could provide prevenient assistance for maneuver planning. The present study effort seeks to reconsider these questions based on a six-month dataset of empirical screening results using an extremely large screening volume. The results, pursued here for a highly-populated orbit regime near 700 km altitude, identify theoretical limits of screening volume performance, explore volume configuration to facilitate both maneuver remediation planning as well as basic asset protection, and recommend sizing principles that maximize volume performance while minimizing the capture of "chaff" conjunctions that are unlikely ever to become serious events.

Application of chemical arrays in screening elastase inhibitors.

PubMed

Gao, Feng; Du, Guan-Hua

2006-06-01

Protein chip technology provides a new and useful tool for high-throughput screening of drugs because of its high performance and low sample consumption. In order to screen elastase inhibitors on a large scale, we designed a composite microarray integrating enzyme chip containing chemical arrays on glass slides to screen for enzymatic inhibitors. The composite microarray includes an active proteinase film, screened chemical arrays distributed on the film, and substrate microarrays to demonstrate change of color. The detection principle is that elastase hydrolyzes synthetic colorless substrates and turns them into yellow products. Because yellow is difficult to detect, bromochlorophenol blue (BPB) was added into substrate solutions to facilitate the detection process. After the enzyme had catalyzed reactions for 2 h, effects of samples on enzymatic activity could be determined by detecting color change of the spots. When chemical samples inhibited enzymatic activity, substrates were blue instead of yellow products. If the enzyme retained its activity, the yellow color of the products combined with blue of BPB to make the spots green. Chromogenic differences demonstrated whether chemicals inhibited enzymatic activity or not. In this assay, 11,680 compounds were screened, and two valuable chemical hits were identified, which demonstrates that this assay is effective, sensitive and applicable for high-throughput screening (HTS).

Feasibility of telemammography as biomedical application for breast imaging

NASA Astrophysics Data System (ADS)

Beckerman, Barbara G.; Batsell, Stephen G.; MacIntyre, Lawrence P.; Sarraf, Hamed S.; Gleason, Shaun S.; Schnall, Mitchell D.

1999-07-01

Mammographic screening is an important tool in the early detection of breast cancer. The migration of mammography from the current mode of x-ray mammography using a film screen image detector and display to a digital technology provides an opportunity to improve access and performance of breast cancer screening. The sheer size and volume of the typical screening exam, the need to have previous screening data readily available, and the need to view other breast imaging data together to provide a common consensus and to plan treatment, make telemammography an ideal application for breast imaging. For telemammography to be a viable option, it must overcome the technical challenges related to transmission, archiving, management, processing and retrieval of large data sets. Researchers from the University of Pennsylvania, the University of Chicago and Lockheed Martin Energy Systems/Oak Ridge National Laboratory have developed a framework for transmission of large-scale medical images over high-speed networks, leveraged existing high-speed networks between research and medical facilities; tested the feasibility of point-to-point transmission of mammographic images in a near-real time environment; evaluated network performance and transmission scenarios; and investigated the impact of image preprocessing on an experimental computer-aided diagnosis system. Results of the initial study are reported here.

Challenges for Detecting Valproic Acid in a Nontargeted Urine Drug Screening Method.

PubMed

Pope, Jeffrey D; Black, Marion J; Drummer, Olaf H; Schneider, Hans G

2017-08-01

Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. As such, it should be included in any nontargeted urine drug screening method. In many published liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) methods, VPA is usually measured using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a simple ultra-high-performance liquid chromatography-quadrupole time-of-flight (QTof) approach to detect the presence of VPA with more confidence. Three commercially sourced VPA metabolites were characterized and added to a nontargeted high-resolution MS urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization mode. The mass detector was operated in MS mode, and data were processed with UNIFI software. Sixty-eight patient urine samples, which were previously identified by a well-established gas chromatography-MS method as containing VPA, were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach. VPA metabolite standards were characterized, and their detection data were added to the broad drug screening library. VPA metabolites were readily detectable in the urine of patients taking VPA. The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.

Cytotechnologist performance for screening microfollicular atypia in indeterminate thyroid fine-needle aspirates.

PubMed

VandenBussche, Christopher J; Olson, Matthew T; Adams, Christina; Ali, Syed Z

2014-01-01

We previously identified a high level of accuracy among our cytotechnologists (CTs) for identifying nuclear atypia in thyroid fine-needle aspiration (FNA) specimens. Herewith, we present our CT performance at screening for microfollicular atypia. 8,814 thyroid FNA specimens were identified in our archives, all screened by 1 of 11 CTs and signed out by a cytopathologist. A subsample of cases was categorized either as atypia of uncertain significance (AUS) with microfollicular proliferation (AUS-F) or suspicious for a follicular neoplasm (SFN). The agreement rate was low between CTs and cytopathologists for SFN and AUS-F. Only 55.8% of SFN screening diagnoses were upheld; 27.9% were downgraded to AUS, 10.4% were downgraded to benign, and 5% were upgraded. Of AUS-F screening diagnoses, 35.5% were upheld, 33.7% were downgraded to benign, and 20.2% were upgraded to SFN. Among all cases, two-step discrepancies were uncommon. Most disagreements were one-category discrepancies between AUS-F and SFN. The evaluation of microfollicular atypia is challenging given that certain follicular lesions cannot be definitively diagnosed on cytology, a high level of subjectivity is involved in the interpretation of such lesions, and the presence of nuclear or Hurthle cell atypia may complicate the diagnosis. © 2014 S. Karger AG, Basel.

Application of Titration-Based Screening for the Rapid Pilot Testing of High-Throughput Assays.

PubMed

Zhang, Ji-Hu; Kang, Zhao B; Ardayfio, Ophelia; Ho, Pei-i; Smith, Thomas; Wallace, Iain; Bowes, Scott; Hill, W Adam; Auld, Douglas S

2014-06-01

Pilot testing of an assay intended for high-throughput screening (HTS) with small compound sets is a necessary but often time-consuming step in the validation of an assay protocol. When the initial testing concentration is less than optimal, this can involve iterative testing at different concentrations to further evaluate the pilot outcome, which can be even more time-consuming. Quantitative HTS (qHTS) enables flexible and rapid collection of assay performance statistics, hits at different concentrations, and concentration-response curves in a single experiment. Here we describe the qHTS process for pilot testing in which eight-point concentration-response curves are produced using an interplate asymmetric dilution protocol in which the first four concentrations are used to represent the range of typical HTS screening concentrations and the last four concentrations are added for robust curve fitting to determine potency/efficacy values. We also describe how these data can be analyzed to predict the frequency of false-positives, false-negatives, hit rates, and confirmation rates for the HTS process as a function of screening concentration. By taking into account the compound pharmacology, this pilot-testing paradigm enables rapid assessment of the assay performance and choosing the optimal concentration for the large-scale HTS in one experiment. © 2013 Society for Laboratory Automation and Screening.

Isotonic Regression Based-Method in Quantitative High-Throughput Screenings for Genotoxicity

PubMed Central

Fujii, Yosuke; Narita, Takeo; Tice, Raymond Richard; Takeda, Shunich

2015-01-01

Quantitative high-throughput screenings (qHTSs) for genotoxicity are conducted as part of comprehensive toxicology screening projects. The most widely used method is to compare the dose-response data of a wild-type and DNA repair gene knockout mutants, using model-fitting to the Hill equation (HE). However, this method performs poorly when the observed viability does not fit the equation well, as frequently happens in qHTS. More capable methods must be developed for qHTS where large data variations are unavoidable. In this study, we applied an isotonic regression (IR) method and compared its performance with HE under multiple data conditions. When dose-response data were suitable to draw HE curves with upper and lower asymptotes and experimental random errors were small, HE was better than IR, but when random errors were big, there was no difference between HE and IR. However, when the drawn curves did not have two asymptotes, IR showed better performance (p < 0.05, exact paired Wilcoxon test) with higher specificity (65% in HE vs. 96% in IR). In summary, IR performed similarly to HE when dose-response data were optimal, whereas IR clearly performed better in suboptimal conditions. These findings indicate that IR would be useful in qHTS for comparing dose-response data. PMID:26673567

Performance index: An expeditious tool to screen for improved drought resistance in the Lathyrus genus.

PubMed

Silvestre, Susana; Araújo, Susana de Sousa; Vaz Patto, Maria Carlota; Marques da Silva, Jorge

2014-07-01

Some species of the Lathyrus genus are among the most promising crops for marginal lands, with high resilience to drought, flood, and fungal diseases, combined with high yields and seed nutritional value. However, lack of knowledge on the mechanisms underlying its outstanding performance and methodologies to identify elite genotypes has hampered its proper use in breeding. Chlorophyll a fast fluorescence transient (JIP test), was used to evaluate water deficit (WD) resistance in Lathyrus genus. Our results reveal unaltered photochemical values for all studied genotypes showing resistance to mild WD. Under severe WD, two Lathyrus sativus genotypes showed remarkable resilience maintaining the photochemical efficiency, contrary to other genotypes studied. Performance index (PIABS) is the best parameter to screen genotypes with improved performance and grain production under WD. Moreover, we found that JIP indices are good indicators of genotypic grain production under WD. Quantum yield of electron transport (ϕEo) and efficiency with which trapped excitons can move electrons further than QA (ψ0) revealed as important traits related to improved photosynthetic performance and should be exploited in future Lathyrus germplasm improvements. The JIP test herein described showed to be an expeditious tool to screen and to identify elite genotypes with improved drought resistance.

A Screen Space GPGPU Surface LIC Algorithm for Distributed Memory Data Parallel Sort Last Rendering Infrastructures

NASA Astrophysics Data System (ADS)

Loring, B.; Karimabadi, H.; Rortershteyn, V.

2015-10-01

The surface line integral convolution(LIC) visualization technique produces dense visualization of vector fields on arbitrary surfaces. We present a screen space surface LIC algorithm for use in distributed memory data parallel sort last rendering infrastructures. The motivations for our work are to support analysis of datasets that are too large to fit in the main memory of a single computer and compatibility with prevalent parallel scientific visualization tools such as ParaView and VisIt. By working in screen space using OpenGL we can leverage the computational power of GPUs when they are available and run without them when they are not. We address efficiency and performance issues that arise from the transformation of data from physical to screen space by selecting an alternate screen space domain decomposition. We analyze the algorithm's scaling behavior with and without GPUs on two high performance computing systems using data from turbulent plasma simulations.

A Screen Space GPGPU Surface LIC Algorithm for Distributed Memory Data Parallel Sort Last Rendering Infrastructures

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

Loring, Burlen; Karimabadi, Homa; Rortershteyn, Vadim

2014-07-01

The surface line integral convolution(LIC) visualization technique produces dense visualization of vector fields on arbitrary surfaces. We present a screen space surface LIC algorithm for use in distributed memory data parallel sort last rendering infrastructures. The motivations for our work are to support analysis of datasets that are too large to fit in the main memory of a single computer and compatibility with prevalent parallel scientific visualization tools such as ParaView and VisIt. By working in screen space using OpenGL we can leverage the computational power of GPUs when they are available and run without them when they are not.more » We address efficiency and performance issues that arise from the transformation of data from physical to screen space by selecting an alternate screen space domain decomposition. We analyze the algorithm's scaling behavior with and without GPUs on two high performance computing systems using data from turbulent plasma simulations.« less

Using screen-based simulation to improve performance during pediatric resuscitation.

PubMed

Biese, Kevin J; Moro-Sutherland, Donna; Furberg, Robert D; Downing, Brian; Glickman, Larry; Murphy, Alison; Jackson, Cheryl L; Snyder, Graham; Hobgood, Cherri

2009-12-01

To assess the ability of a screen-based simulation-training program to improve emergency medicine and pediatric resident performance in critical pediatric resuscitation knowledge, confidence, and skills. A pre-post, interventional design was used. Three measures of performance were created and assessed before and after intervention: a written pre-course knowledge examination, a self-efficacy confidence score, and a skills-based high-fidelity simulation code scenario. For the high-fidelity skills assessment, independent physician raters recorded and reviewed subject performance. The intervention consisted of eight screen-based pediatric resuscitation scenarios that subjects had 4 weeks to complete. Upon completion of the scenarios, all three measures were repeated. For the confidence assessment, summary pre- and post-test summary confidence scores were compared using a t-test, and for the skills assessment, pre-scores were compared with post-test measures for each individual using McNemar's chi-square test for paired samples. Twenty-six of 35 (71.3%) enrolled subjects completed the institutional review board-approved study. Increases were observed in written test scores, confidence, and some critical interventions in high-fidelity simulation. The mean improvement in cumulative confidence scores for all residents was 10.1 (SD +/-4.9; range 0-19; p < 0.001), with no resident feeling less confident after the intervention. Although overall performance in simulated codes did not change significantly, with average scores of 6.65 (+/-1.76) to 7.04 (+/-1.37) out of 9 possible points (p = 0.58), improvement was seen in the administering of appropriate amounts of IV fluids (59-89%, p = 0.03). In this study, improvements in resident knowledge, confidence, and performance of certain skills in simulated pediatric cardiac arrest scenarios suggest that screen-based simulations may be an effective way to enhance resuscitation skills of pediatric providers. These results should be confirmed using a randomized design with an appropriate control group. (c) 2009 by the Society for Academic Emergency Medicine.

E-beam-pumped semiconductor lasers

NASA Astrophysics Data System (ADS)

Rice, Robert R.; Shanley, James F.; Ruggieri, Neil F.

1995-04-01

The collapse of the Soviet Union opened many areas of laser technology to the West. E-beam- pumped semiconductor lasers (EBSL) were pursued for 25 years in several Soviet Institutes. Thin single crystal screens of II-VI alloys (ZnxCd1-xSe, CdSxSe1-x) were incorporated in laser CRTs to produce scanned visible laser beams at average powers greater than 10 W. Resolutions of 2500 lines were demonstrated. MDA-W is conducting a program for ARPA/ESTO to assess EBSL technology for high brightness, high resolution RGB laser projection application. Transfer of II-VI crystal growth and screen processing technology is underway, and initial results will be reported. Various techniques (cathodoluminescence, one- and two-photon laser pumping, etc.) have been used to assess material quality and screen processing damage. High voltage (75 kV) video electronics were procured in the U.S. to operate test EBSL tubes. Laser performance was documented as a function of screen temperature, beam voltage and current. The beam divergence, spectrum, efficiency and other characteristics of the laser output are being measured. An evaluation of the effect of laser operating conditions upon the degradation rate is being carried out by a design-of-experiments method. An initial assessment of the projected image quality will be performed.

Screening studies of advanced control concepts for airbreathing engines

NASA Technical Reports Server (NTRS)

Ouzts, Peter J.; Lorenzo, Carl F.; Merrill, Walter C.

1993-01-01

The application of advanced control concepts to airbreathing engines may yield significant improvements in aircraft/engine performance and operability. Accordingly, the NASA Lewis Research Center has conducted screening studies of advanced control concepts for airbreathing engines to determine their potential impact on turbine engine performance and operability. The purpose of the studies was to identify concepts which offered high potential yet may incur high research and development risk. A target suite of proposed concepts was formulated by NASA and industry. These concepts were evaluated in a two phase study to quantify each concept's impact on desired engine characteristics. To aid in the evaluation, three target aircraft/engine combinations were considered: a military high performance fighter mission, a high speed civil transport mission, and a civil tiltrotor mission. Each of the advanced control concepts considered in the study were defined and described. The concept's potential impact on engine performance was determined. Relevant figures of merit on which to evaluate the concepts were also determined. Finally, the concepts were ranked with respect to the target aircraft/engine missions.

Comparison of the Substance Use Brief Screen (SUBS) to the AUDIT-C and ASSIST for detecting unhealthy alcohol and drug use in a population of hospitalized smokers.

PubMed

Han, Benjamin H; Sherman, Scott E; Link, Alissa R; Wang, Binhuan; McNeely, Jennifer

2017-08-01

Hospitalized patients have high rates of unhealthy substance use, which has important impacts on health both during and after hospitalization, but is infrequently identified in the absence of screening. The Substance Use Brief Screen (SUBS) was developed as a brief, self-administered instrument to identify use of tobacco, alcohol, illicit drugs, and non-medical use of prescription drugs, and was previously validated in primary care patients. This study assessed the diagnostic accuracy of the SUBS in comparison to longer screening instruments to identify unhealthy and high-risk alcohol and drug use in hospitalized current smokers. Participants were 439 patients, aged 18 and older, who were admitted to either two urban safety-net hospitals in New York City and enrolled in a smoking cessation trial. We measured the performance of the SUBS for identifying illicit drug and non-medical use of prescription drugs in comparison to a modified Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and its performance for identifying excessive alcohol use in comparison to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). At the standard cutoff (response other than 'never' indicates a positive screen), the SUBS had a sensitivity of 98% (95% CI 95-100%) and specificity of 61% (95% CI 55-67%) for unhealthy alcohol use, a sensitivity of 85% (95% CI 80-90%) and specificity of 75% (95% CI 78-87%) for illicit drug use, and a sensitivity of 73% (95% CI 61-83%) and specificity of 83% (95% CI 78-87%) for prescription drug non-medical use. For identifying high-risk use, a higher cutoff (response of '3 or more days' of use indicates a positive screen), the SUBS retained high sensitivity (77-90%), and specificity was 62-88%. The SUBS can be considered as an alternative to longer screening instruments, which may fit more easily into busy inpatient settings. Further study is needed to evaluate its validity using gold standard measures in hospitalized populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Surface plasmon resonance as a tool for ligand-binding assay reagent characterization in bioanalysis of biotherapeutics.

PubMed

Duo, Jia; Bruno, JoAnne; Kozhich, Alexander; David-Brown, Donata; Luo, Linlin; Kwok, Suk; Santockyte, Rasa; Haulenbeek, Jonathan; Liu, Rong; Hamuro, Lora; Peterson, Jon E; Piccoli, Steven; DeSilva, Binodh; Pillutla, Renuka; Zhang, Yan J

2018-04-01

Ligand-binding assay (LBA) performance depends on quality reagents. Strategic reagent screening and characterization is critical to LBA development, optimization and validation. Application of advanced technologies expedites the reagent screening and assay development process. By evaluating surface plasmon resonance technology that offers high-throughput kinetic information, this article aims to provide perspectives on applying the surface plasmon resonance technology to strategic LBA critical reagent screening and characterization supported by a number of case studies from multiple biotherapeutic programs.

Tuberculin reactivity in bacille Calmette-Guérin vaccinated populations: a compilation of international data.

PubMed

Joos, T J; Miller, W C; Murdoch, D M

2006-08-01

The effect of previously administered bacille Calmette-Guérin (BCG) vaccine on subsequent tuberculin skin tests (TSTs) complicates screening for latent tuberculosis infection (LTBI) in foreign-born persons. To determine the usefulness of the TST as a screening test for LTBI in foreign-born persons. A literature search was performed of published studies that compared tuberculin reactivity amongst BCG-vaccinated and non-vaccinated groups. The percentages of positive reactors in the two groups were then used to calculate a prevalence ratio. The prevalence ratio varied with the age of the groups tested and the incidence of TB in their countries of origin. The TST performed poorly in vaccinated persons of all ages from countries of low TB incidence, but was a useful screen for LTBI in vaccinated adults from countries of high and intermediate incidence. The test performed poorly as a screening method for vaccinated children under 2 years of age. Its usefulness in vaccinated children aged 2-14 years varied considerably. The usefulness of the TST as a screening method for LTBI depends on the age of the patient and the incidence of TB in their country of origin.

Screening for Language Delay: Growth Trajectories of Language Ability in Low- and High-Performing Children

ERIC Educational Resources Information Center

Klem, Marianne; Hagtvet, Bente; Hulme, Charles; Gustafsson, Jan-Eric

2016-01-01

Purpose: This study investigated the stability and growth of preschool language skills and explores latent class analysis as an approach for identifying children at risk of language impairment. Method: The authors present data from a large-scale 2-year longitudinal study, in which 600 children were assessed with a language-screening tool…

A method for screening active components from Chinese herbs by cell membrane chromatography-offline-high performance liquid chromatography/mass spectrometry and an online statistical tool for data processing.

PubMed

Cao, Yan; Wang, Shaozhan; Li, Yinghua; Chen, Xiaofei; Chen, Langdong; Wang, Dongyao; Zhu, Zhenyu; Yuan, Yongfang; Lv, Diya

2018-03-09

Cell membrane chromatography (CMC) has been successfully applied to screen bioactive compounds from Chinese herbs for many years, and some offline and online two-dimensional (2D) CMC-high performance liquid chromatography (HPLC) hyphenated systems have been established to perform screening assays. However, the requirement of sample preparation steps for the second-dimensional analysis in offline systems and the need for an interface device and technical expertise in the online system limit their extensive use. In the present study, an offline 2D CMC-HPLC analysis combined with the XCMS (various forms of chromatography coupled to mass spectrometry) Online statistical tool for data processing was established. First, our previously reported online 2D screening system was used to analyze three Chinese herbs that were reported to have potential anti-inflammatory effects, and two binding components were identified. By contrast, the proposed offline 2D screening method with XCMS Online analysis was applied, and three more ingredients were discovered in addition to the two compounds revealed by the online system. Then, cross-validation of the three compounds was performed, and they were confirmed to be included in the online data as well, but were not identified there because of their low concentrations and lack of credible statistical approaches. Last, pharmacological experiments showed that these five ingredients could inhibit IL-6 release and IL-6 gene expression on LPS-induced RAW cells in a dose-dependent manner. Compared with previous 2D CMC screening systems, this newly developed offline 2D method needs no sample preparation steps for the second-dimensional analysis, and it is sensitive, efficient, and convenient. It will be applicable in identifying active components from Chinese herbs and practical in discovery of lead compounds derived from herbs. Copyright © 2018 Elsevier B.V. All rights reserved.

High-content screening of small compounds on human embryonic stem cells.

PubMed

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.

IETM Usability: Using Empirical Studies to Improve Performance Aiding

DTIC Science & Technology

2001-05-14

is highly graphical . An example screen is shown in Figure 3. Following is a description of the design solutions incorporated in Interface B to...in enabling lesser skilled U.S. Navy maintainers to perform their jobs. This empirical study about the design and effectiveness of high level IETMs...novice preferences and performance were documented to inform future adaptive interface design efforts. The maintainers who participated were

Engineering 'cell robots' for parallel and highly sensitive screening of biomolecules under in vivo conditions.

PubMed

Song, Lifu; Zeng, An-Ping

2017-11-09

Cells are capable of rapid replication and performing tasks adaptively and ultra-sensitively and can be considered as cheap "biological-robots". Here we propose to engineer cells for screening biomolecules in parallel and with high sensitivity. Specifically, we place the biomolecule variants (library) on the bacterial phage M13. We then design cells to screen the library based on cell-phage interactions mediated by a specific intracellular signal change caused by the biomolecule of interest. For proof of concept, we used intracellular lysine concentration in E. coli as a signal to successfully screen variants of functional aspartate kinase III (AK-III) under in vivo conditions, a key enzyme in L-lysine biosynthesis which is strictly inhibited by L-lysine. Comparative studies with flow cytometry method failed to distinguish the wild-type from lysine resistance variants of AK-III, confirming a higher sensitivity of the method. It opens up a new and effective way of in vivo high-throughput screening for functional molecules and can be easily implemented at low costs.

HTS-Net: An integrated regulome-interactome approach for establishing network regulation models in high-throughput screenings

PubMed Central

Rioualen, Claire; Da Costa, Quentin; Chetrit, Bernard; Charafe-Jauffret, Emmanuelle; Ginestier, Christophe

2017-01-01

High-throughput RNAi screenings (HTS) allow quantifying the impact of the deletion of each gene in any particular function, from virus-host interactions to cell differentiation. However, there has been less development for functional analysis tools dedicated to RNAi analyses. HTS-Net, a network-based analysis program, was developed to identify gene regulatory modules impacted in high-throughput screenings, by integrating transcription factors-target genes interaction data (regulome) and protein-protein interaction networks (interactome) on top of screening z-scores. HTS-Net produces exhaustive HTML reports for results navigation and exploration. HTS-Net is a new pipeline for RNA interference screening analyses that proves better performance than simple gene rankings by z-scores, by re-prioritizing genes and replacing them in their biological context, as shown by the three studies that we reanalyzed. Formatted input data for the three studied datasets, source code and web site for testing the system are available from the companion web site at http://htsnet.marseille.inserm.fr/. We also compared our program with existing algorithms (CARD and hotnet2). PMID:28949986

A high-performance, flexible and robust metal nanotrough-embedded transparent conducting film for wearable touch screen panels.

PubMed

Im, Hyeon-Gyun; An, Byeong Wan; Jin, Jungho; Jang, Junho; Park, Young-Geun; Park, Jang-Ung; Bae, Byeong-Soo

2016-02-21

We report a high-performance, flexible and robust metal nanotrough-embedded transparent conducting hybrid film (metal nanotrough-GFRHybrimer). Using an electro-spun polymer nanofiber web as a template and vacuum-deposited gold as a conductor, a junction resistance-free continuous metal nanotrough network is formed. Subsequently, the metal nanotrough is embedded on the surface of a glass-fabric reinforced composite substrate (GFRHybrimer). The monolithic composite structure of our transparent conducting film allows simultaneously high thermal stability (24 h at 250 °C in air), a smooth surface topography (Rrms < 1 nm) and excellent opto-electrical properties. A flexible touch screen panel (TSP) is fabricated using the transparent conducting films. The flexible TSP device stably operates on the back of a human hand and on a wristband.

Advanced controls for airbreathing engines, volume 3: Allison gas turbine

NASA Technical Reports Server (NTRS)

Bough, R. M.

1993-01-01

The application of advanced control concepts to airbreathing engines may yield significant improvements in aircraft/engine performance and operability. Screening studies of advanced control concepts for airbreathing engines were conducted by three major domestic aircraft engine manufacturers to determine the potential impact of concepts on turbine engine performance and operability. The purpose of the studies was to identify concepts which offered high potential yet may incur high research and development risk. A target suite of proposed advanced control concepts was formulated and evaluated in a two-phase study to quantify each concept's impact on desired engine characteristics. To aid in the evaluation specific aircraft/engine combinations were considered: a Military High Performance Fighter mission, a High Speed Civil Transport mission, and a Civil Tiltrotor mission. Each of the advanced control concepts considered in the study are defined and described. The concept potential impact on engine performance was determined. Relevant figures of merit on which to evaluate the concepts are determined. Finally, the concepts are ranked with respect to the target aircraft/engine missions. A final report describing the screening studies was prepared by each engine manufacturer. Volume 3 of these reports describes the studies performed by the Allison Gas Turbine Division.

Advanced control for airbreathing engines, volume 1: Pratt and Whitney

NASA Technical Reports Server (NTRS)

Ralph, J. A.

1993-01-01

The application of advanced control concepts to air breathing engines may yield significant improvements in aircraft/engine performance and operability. Screening studies of advanced control concepts for air breathing engines were conducted by three major domestic aircraft engine manufacturers to determine the potential impact of concepts on turbine engine performance and operability. The purpose of the studies was to identify concepts which offered high potential yet may incur high research and development risk. A target suite of proposed advanced control concepts was formulated and evaluated in a two phase study to quantify each concept's impact on desired engine characteristics. To aid in the evaluation specific aircraft/engine combinations were considered: a Military High Performance Fighter mission, a High Speed Civil Transport mission, and a Civil Tiltrotor mission. Each of the advanced control concepts considered in the study are defined and described. The concept potential impact on engine performance was determined. Relevant figures of merit on which to evaluate the concepts are determined. Finally, the concepts are ranked with respect to the target aircraft/engine missions. A final report describing the screening studies was prepared by each engine manufacturer. Volume 1 of these reports describes the studies performed by Pratt & Whitney.

Advanced control for airbreathing engines, volume 2: General Electric aircraft engines

NASA Technical Reports Server (NTRS)

Bansal, Indar

1993-01-01

The application of advanced control concepts to air breathing engines may yield significant improvements in aircraft/engine performance and operability. Screening studies of advanced control concepts for air breathing engines were conducted by three major domestic aircraft engine manufacturers to determine the potential impact of concepts on turbine engine performance and operability. The purpose of the studies was to identify concepts which offered high potential yet may incur high research and development risk. A target suite of proposed advanced control concepts was formulated and evaluated in a two phase study to quantify each concept's impact on desired engine characteristics. To aid in the evaluation specific aircraft/engine combinations were considered: a Military High Performance Fighter mission, a High Speed Civil Transport mission, and a Civil Tiltrotor mission. Each of the advanced control concepts considered in the study are defined and described. The concept potential impact on engine performance was determined. Relevant figures of merit on which to evaluate the concepts are determined. Finally, the concepts are ranked with respect to the target aircraft/engine missions. A final report describing the screening studies was prepared by each engine manufacturer. Volume 2 of these reports describes the studies performed by GE Aircraft Engines.

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

PubMed

Liu, Min; Zhang, Chunsun; Liu, Feifei

2015-09-03

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

Performance of a quantitative fecal immunochemical test in a colorectal cancer screening pilot program: a prospective cohort study.

PubMed

Telford, Jennifer; Gentile, Laura; Gondara, Lovedeep; McGahan, Colleen; Coldman, Andrew

2016-01-01

British Columbia undertook a colorectal cancer screening pilot program in 3 communities. Our objective was to assess the performance of 2-specimen fecal immunochemical testing in the detection of colorectal neoplasms in this population-based screening program. A prospective cohort of asymptomatic, average-risk people aged 50 to 74 years completed 2 quantitative fecal immunochemical tests every 2 years, with follow-up colonoscopy if the result of either test was positive. Participant demographics, fecal immunochemical test results, colonoscopy quality indicators and pathology results were recorded. Non-screen-detected colorectal cancer that developed in program participants was identified through review of data from the BC Cancer Registry. A total of 16 234 people completed a first round of fecal immunochemical testing, with a positivity rate of 8.6%; 5378 (86.0% of eligible participants) completed a second round before the end of the pilot program, with a positivity rate of 6.7%. Of the 1756 who had a positive test result, 1555 (88.6%) underwent colonoscopy. The detection rate of colorectal cancer was 3.5 per 1000 participants. The positive predictive value of the fecal immunochemical test was 4.9% (95% confidence interval [CI] 3.8%-6.0%) for colorectal cancer, 35.0% (95% CI 32.5%-37.2%) for high-risk polyps and 62.0% (95% CI 59.6%-64.4%) for all neoplasms. The number needed to screen was 283 to detect 1 cancer, 40 to detect 1 high-risk polyp and 22 to detect any neoplasm. Screening every 2 years with a 2-specimen fecal immunochemical test surpassed the current benchmark for colorectal cancer detection in population-based screening. This study has implications for other jurisdictions planning colorectal cancer screening programs.

Augmented reality 3D display using head-mounted projectors and transparent retro-reflective screen

NASA Astrophysics Data System (ADS)

Soomro, Shoaib R.; Urey, Hakan

2017-02-01

A 3D augmented reality display is proposed that can provide glass-free stereo parallax using a highly transparent projection screen. The proposed display is based on a transparent retro-reflective screen and a pair of laser pico projectors placed close to the viewer's head. The retro-reflective screen directs incident light towards its source with little scattering so that each of the viewer's eyes only perceives the content projected by the associated projector. Each projector displays one of the two components (left or right channel) of stereo content. The retro-reflective nature of screen provides high brightness compared to the regular diffused screens. The partially patterned retro-reflective material on clear substrate introduces optical transparency and facilitates the viewer to see the real-world scene on the other side of screen. The working principle and design of the proposed see-through 3D display are presented. A tabletop prototype consisting of an in-house fabricated 60×40cm2 see-through retro-reflective screen and a pair of 30 lumen pico-projectors with custom 3D printed housings is demonstrated. Geometric calibration between projectors and optimal viewing conditions (eye box size, eye-to-projector distance) are discussed. The display performance is evaluated by measuring the brightness and crosstalk for each eye. The screen provides high brightness (up to 300 cd/m2 per eye) using 30 lumens mobile projectors while maintaining the 75% screen transparency. The crosstalk between left and right views is measured as <10% at the optimum distance of 125-175 cm, which is within acceptable range.

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

PubMed

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

2014-03-01

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

Conventional and right-sided screening for subcutaneous ICD in a population with congenital heart disease at high risk of sudden cardiac death.

PubMed

Alonso, Pau; Osca, Joaquín; Rueda, Joaquín; Cano, Oscar; Pimenta, Pedro; Andres, Ana; Sancho, María José; Martinez, Luis

2017-11-01

Information regarding suitability for subcutaneous defibrillator (sICD) implantation in tetralogy of Fallot (ToF) and systemic right ventricle is scarce and needs to be further explored. The main objective of our study was to determine the proportion of patients with ToF and systemic right ventricle eligible for sICD with both, standard and right-sided screening methods. Secondary objectives were: (i) to study sICD eligibility specifically in patients at high risk of sudden cardiac death, (ii) to identify independent predictors for sICD eligibility, and (iii) to compare the proportion of eligible patients in a nonselected ICD population. We recruited 102 patients with ToF, 33 with systemic right ventricle, and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left-arm and right-arm electrodes 1 cm right lateral of the xiphoid midline. The Boston Scientific ECG screening tool was utilized. In high-risk patients with ToF, eligibility was higher with right-sided screening in comparison with standard screening (61% vs. 44%; p = .018). Eligibility in high-risk right ventricle population was identical with both screening methods (77%, p = ns). The only independent predictor for sICD eligibility was QRS duration. In high-risk patients with ToF, right-sided implantation of the sICD could be an alternative to a conventional ICD. In patients with a systemic right ventricle, implantation of a sICD is an alternative to a conventional sICD. © 2017 Wiley Periodicals, Inc.

A high-throughput screen for single gene activities: isolation of apoptosis inducers.

PubMed

Albayrak, Timur; Grimm, Stefan

2003-05-16

We describe a novel genetic screen that is performed by transfecting every individual clone of an expression library into a separate population of cells in a high-throughput mode. The screen allows one to achieve a hitherto unattained sensitivity in expression cloning which was exploited in a first read-out to clone apoptosis-inducing genes. This led to the isolation of several genes whose proteins induce distinct phenotypes of apoptosis in 293T cells. One of the isolated genes is the tumor suppressor cytochrome b(L) (cybL), a component of the respiratory chain complex II, that diminishes the activity of this complex for apoptosis induction. This gene is more efficient and specific for causing cell death than a drug with the same activity. These results suggest further applications, both of the isolated genes and the screen.

Association between physiological falls risk and physical performance tests among community-dwelling older adults

PubMed Central

Singh, Devinder KA; Pillai, Sharmila GK; Tan, Sin Thien; Tai, Chu Chiau; Shahar, Suzana

2015-01-01

Background Physical performance and balance declines with aging and may lead to increased risk of falls. Physical performance tests may be useful for initial fall-risk screening test among community-dwelling older adults. Physiological profile assessment (PPA), a composite falls risk assessment tool is reported to have 75% accuracy to screen for physiological falls risk. PPA correlates with Timed Up and Go (TUG) test. However, the association between many other commonly used physical performance tests and PPA is not known. The aim of the present study was to examine the association between physiological falls risk measured using PPA and a battery of physical performance tests. Methods One hundred and forty older adults from a senior citizens club in Kuala Lumpur, Malaysia (94 females, 46 males), aged 60 years and above (65.77±4.61), participated in this cross-sectional study. Participants were screened for falls risk using PPA. A battery of physical performance tests that include ten-step test (TST), short physical performance battery (SPPB), functional reach test (FRT), static balance test (SBT), TUG, dominant hand-grip strength (DHGS), and gait speed test (GST) were also performed. Spearman’s rank correlation and binomial logistic regression were performed to examine the significantly associated independent variables (physical performance tests) with falls risk (dependent variable). Results Approximately 13% older adults were at high risk of falls categorized using PPA. Significant differences (P<0.05) were demonstrated for age, TST, SPPB, FRT, SBT, TUG between high and low falls risk group. A significant (P<0.01) weak correlation was found between PPA and TST (r=0.25), TUG (r=0.27), SBT (r=0.23), SPPB (r=−0.33), and FRT (r=−0.23). Binary logistic regression results demonstrated that SBT measuring postural sways objectively using a balance board was the only significant predictor of physiological falls risk (P<0.05, odds ratio of 2.12). Conclusion The reference values of physical performance tests in our study may be used as a guide for initial falls screening to categorize high and low physiological falls risk among community-dwelling older adults. A more comprehensive assessment of falls risk can be performed thereafter for more specific intervention of underlying impairments. PMID:26316727

Evidence of Stage Shift in Women Diagnosed With Ovarian Cancer During Phase II of the United Kingdom Familial Ovarian Cancer Screening Study.

PubMed

Rosenthal, Adam N; Fraser, Lindsay S M; Philpott, Susan; Manchanda, Ranjit; Burnell, Matthew; Badman, Philip; Hadwin, Richard; Rizzuto, Ivana; Benjamin, Elizabeth; Singh, Naveena; Evans, D Gareth; Eccles, Diana M; Ryan, Andy; Liston, Robert; Dawnay, Anne; Ford, Jeremy; Gunu, Richard; Mackay, James; Skates, Steven J; Menon, Usha; Jacobs, Ian J

2017-05-01

Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). Patients and Methods Women whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO. Results Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical complexity, P = .16) (CI, 74.0% to 99.9%) compared with 13 (72.2%) of 18 cancers subsequently diagnosed (CI, 46.5% to 90.3%; P = .09). Conclusion ROCA-based screening is an option for women at high risk of OC/FTC who defer or decline RRSO, given its high sensitivity and significant stage shift. However, it remains unknown whether this strategy would improve survival in screened high-risk women.

Evidence of Stage Shift in Women Diagnosed With Ovarian Cancer During Phase II of the United Kingdom Familial Ovarian Cancer Screening Study

PubMed Central

Rosenthal, Adam N.; Fraser, Lindsay S.M.; Philpott, Susan; Manchanda, Ranjit; Burnell, Matthew; Badman, Philip; Hadwin, Richard; Rizzuto, Ivana; Benjamin, Elizabeth; Singh, Naveena; Evans, D. Gareth; Eccles, Diana M.; Ryan, Andy; Liston, Robert; Dawnay, Anne; Ford, Jeremy; Gunu, Richard; Mackay, James; Skates, Steven J.; Menon, Usha; Jacobs, Ian J.

2017-01-01

Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). Patients and Methods Women whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO. Results Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical complexity, P = .16) (CI, 74.0% to 99.9%) compared with 13 (72.2%) of 18 cancers subsequently diagnosed (CI, 46.5% to 90.3%; P = .09). Conclusion ROCA-based screening is an option for women at high risk of OC/FTC who defer or decline RRSO, given its high sensitivity and significant stage shift. However, it remains unknown whether this strategy would improve survival in screened high-risk women. PMID:28240969

A Stochastic Spiking Neural Network for Virtual Screening.

PubMed

Morro, A; Canals, V; Oliver, A; Alomar, M L; Galan-Prado, F; Ballester, P J; Rossello, J L

2018-04-01

Virtual screening (VS) has become a key computational tool in early drug design and screening performance is of high relevance due to the large volume of data that must be processed to identify molecules with the sought activity-related pattern. At the same time, the hardware implementations of spiking neural networks (SNNs) arise as an emerging computing technique that can be applied to parallelize processes that normally present a high cost in terms of computing time and power. Consequently, SNN represents an attractive alternative to perform time-consuming processing tasks, such as VS. In this brief, we present a smart stochastic spiking neural architecture that implements the ultrafast shape recognition (USR) algorithm achieving two order of magnitude of speed improvement with respect to USR software implementations. The neural system is implemented in hardware using field-programmable gate arrays allowing a highly parallelized USR implementation. The results show that, due to the high parallelization of the system, millions of compounds can be checked in reasonable times. From these results, we can state that the proposed architecture arises as a feasible methodology to efficiently enhance time-consuming data-mining processes such as 3-D molecular similarity search.

Performance of screening questionnaires for obstructive sleep apnea during pregnancy: A systematic review and meta-analysis.

PubMed

Tantrakul, Visasiri; Numthavaj, Pawin; Guilleminault, Christian; McEvoy, Mark; Panburana, Panyu; Khaing, Win; Attia, John; Thakkinstian, Ammarin

2017-12-01

This review aims to evaluate the performance of obstructive sleep apnea (OSA) screening questionnaires during pregnancy. A systematic review and meta-analysis was performed using MEDLINE Scopus, CINAHL, and the Cochrane library. A bivariate meta-analysis was applied for pooling of diagnostic parameters. Six of the total 4719 articles met the inclusion criteria. The Berlin questionnaire (BQ, N = 604) and Epworth sleepiness scale (ESS, N = 420) were the most frequently used screening tools during pregnancy. The pooled prevalence of OSA during pregnancy was 26.7% (95%CI: 16.9%, 34.4%, I 2  = 83.15%). BQ performance was poor to fair with pooled sensitivity and specificity of 0.66 (95%CI: 0.45, 0.83; I 2  = 78.65%) and 0.62 (95%CI: 0.48, 0.75; I 2  = 81.55%), respectively. BQ performance was heterogeneous depending on type of reference test and pregnancy. Sensitivity increased if diagnosis was based on polysomnography (0.90), and respiratory disturbance index (0.90). However, sensitivity decreased if screening was performed in early pregnancy (≤20 weeks gestation: 0.47), and high-risk pregnancy (0.44). Performance of ESS was poor with pooled sensitivity and specificity of 0.44 (95%CI: 0.33, 0.56; I 2  = 32.8%) and 0.62 (95%CI: 0.48, 0.75; I 2  = 81.55%), respectively. In conclusion, BQ and ESS showed poor performance during pregnancy, hence a new OSA screening questionnaire is needed. Registration: PROSPERO registration CRD42015025848. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Generic Degraded Congiguration Probability Analysis for DOE Codisposal Waste Package

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

S.F.A. Deng; M. Saglam; L.J. Gratton

2001-05-23

In accordance with the technical work plan, ''Technical Work Plan For: Department of Energy Spent Nuclear Fuel Work Packages'' (CRWMS M&O 2000c), this Analysis/Model Report (AMR) is developed for the purpose of screening out degraded configurations for U.S. Department of Energy (DOE) spent nuclear fuel (SNF) types. It performs the degraded configuration parameter and probability evaluations of the overall methodology specified in the ''Disposal Criticality Analysis Methodology Topical Report'' (YMP 2000, Section 3) to qualifying configurations. Degradation analyses are performed to assess realizable parameter ranges and physical regimes for configurations. Probability calculations are then performed for configurations characterized by k{submore » eff} in excess of the Critical Limit (CL). The scope of this document is to develop a generic set of screening criteria or models to screen out degraded configurations having potential for exceeding a criticality limit. The developed screening criteria include arguments based on physical/chemical processes and probability calculations and apply to DOE SNF types when codisposed with the high-level waste (HLW) glass inside a waste package. The degradation takes place inside the waste package and is long after repository licensing has expired. The emphasis of this AMR is on degraded configuration screening and the probability analysis is one of the approaches used for screening. The intended use of the model is to apply the developed screening criteria to each DOE SNF type following the completion of the degraded mode criticality analysis internal to the waste package.« less

Dementia Screening Accuracy is Robust to Premorbid IQ Variation: Evidence from the Addenbrooke's Cognitive Examination-III and the Test of Premorbid Function.

PubMed

Stott, Joshua; Scior, Katrina; Mandy, William; Charlesworth, Georgina

2017-01-01

Scores on cognitive screening tools for dementia are associated with premorbid IQ. It has been suggested that screening scores should be adjusted accordingly. However, no study has examined whether premorbid IQ variation affects screening accuracy. To investigate whether the screening accuracy of a widely used cognitive screening tool for dementia, the Addenbrooke's cognitive examination-III (ACE-III), is improved by adjusting for premorbid IQ. 171 UK based adults (96 memory service attendees diagnosed with dementia and 75 healthy volunteers over the age of 65 without subjective memory impairments) completed the ACE-III and the Test of Premorbid Function (TOPF). The difference in screening performance between the ACE-III alone and the ACE-III adjusted for TOPF was assessed against a reference standard; the presence or absence of a diagnosis of dementia (Alzheimer's disease, vascular dementia, or others). Logistic regression and receiver operating curve analyses indicated that the ACE-III has excellent screening accuracy (93% sensitivity, 94% specificity) in distinguishing those with and without a dementia diagnosis. Although ACE-III scores were associated with TOPF scores, TOPF scores may be affected by having dementia and screening accuracy was not improved by accounting for premorbid IQ, age, or years of education. ACE-III screening accuracy is high and screening performance is robust to variation in premorbid IQ, age, and years of education. Adjustment of ACE-III cut-offs for premorbid IQ is not recommended in clinical practice. The analytic strategy used here may be useful to assess the impact of premorbid IQ on other screening tools.

HPV self-sampling in CIN2+ detection: sensitivity and specificity of different RLU cut-off of HC2 in specimens from 786 women.

PubMed

Bottari, F; Igidbashian, S; Boveri, S; Tricca, A; Gulmini, C; Sesia, M; Spolti, N; Sideri, M; Landoni, F; Sandri, M T

2017-04-01

Mortality for cervical cancer varies between the different regions of the world, with high rates in low-income countries where screening programmes are not present and organised. However, increasing screening coverage is still a priority in all countries: one way to do that is to base screening on self-sampled screening. The success of a self-sampling screening strategy depends on capacity to recruit unscreened women, on the performance and acceptability of the device and on the clinical performance of the high-risk human papillomavirus (HPV) test. This study based on 786 enrolled women investigates the best cut-off value of Hybrid Capture 2 HPV test (HC2) for self-sampled specimens in terms of sensitivity and specificity. In this population, we found that the sensitivity and the specificity for cervical intraepithelial neoplasia grade 2 or more detection of HC2 performed on self-sampled specimens were 82.5% and 82.8%, respectively considering the relative light units (RLU) cut-off value of 1. Increasing the cut-off value the sensitivity decreases and the specificity raises and the best area under the curve for the RLU cut-off value is 1. Our results confirm that the cut-off value of 1 suggested by Qiagen for PreservCyt specimen is the best cut-off value also for self-sampled specimens. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Multiplex newborn screening for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases using a digital microfluidic platform.

PubMed

Sista, Ramakrishna S; Wang, Tong; Wu, Ning; Graham, Carrie; Eckhardt, Allen; Winger, Theodore; Srinivasan, Vijay; Bali, Deeksha; Millington, David S; Pamula, Vamsee K

2013-09-23

New therapies for lysosomal storage diseases (LSDs) have generated interest in screening newborns for these conditions. We present performance validation data on a digital microfluidic platform that performs multiplex enzymatic assays for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases. We developed an investigational disposable digital microfluidic cartridge that uses a single dried blood spot (DBS) punch for performing a 5-plex fluorometric enzymatic assay on up to 44 DBS samples. Precision and linearity of the assays were determined by analyzing quality control DBS samples; clinical performance was determined by analyzing 600 presumed normal and known affected samples (12 for Pompe, 7 for Fabry and 10 each for Hunter, Gaucher and Hurler). Overall coefficient of variation (CV) values between cartridges, days, instruments, and operators ranged from 2 to 21%; linearity correlation coefficients were ≥0.98 for all assays. The multiplex enzymatic assay performed from a single DBS punch was able to discriminate presumed normal from known affected samples for 5 LSDs. Digital microfluidic technology shows potential for rapid, high-throughput screening for 5 LSDs in a newborn screening laboratory environment. Sample preparation to enzymatic activity on each cartridge is less than 3h. Copyright © 2013 Elsevier B.V. All rights reserved.

Academic Performance and Lifestyle Behaviors in Australian School Children: A Cluster Analysis

ERIC Educational Resources Information Center

Dumuid, Dorothea; Olds, Timothy; Martín-Fernández, Josep-Antoni; Lewis, Lucy K.; Cassidy, Leah; Maher, Carol

2017-01-01

Poor academic performance has been linked with particular lifestyle behaviors, such as unhealthy diet, short sleep duration, high screen time, and low physical activity. However, little is known about how lifestyle behavior patterns (or combinations of behaviors) contribute to children's academic performance. We aimed to compare academic…

How to identify students for school-based depression intervention: can school record review be substituted for universal depression screening?

PubMed

Kuo, Elena S; Vander Stoep, Ann; Herting, Jerald R; Grupp, Katherine; McCauley, Elizabeth

2013-02-01

Early identification and intervention are critical for reducing the adverse effects of depression on academic and occupational performance. Cost-effective approaches are needed for identifying adolescents at high depression risk. This study evaluated the utility of school record review versus universal school-based depression screening for determining eligibility for an indicated depression intervention program implemented in the middle school setting. Algorithms derived from grades, attendance, suspensions, and basic demographic information were evaluated with regard to their ability to predict students' depression screening scores. The school information-based algorithms proved poor proxies for individual students' depression screening results. However, school records showed promise for identifying low, medium, and high-yield subgroups on the basis of which efficient screening targeting decisions could be made. Study results will help to guide school nurses who coordinate indicated depression intervention programs in school settings as they evaluate options of approaches for determining which students are eligible for participation. © 2012 Wiley Periodicals, Inc.

An automatic on-line 2,2-diphenyl-1-picrylhydrazyl-high performance liquid chromatography method for high-throughput screening of antioxidants from natural products.

PubMed

Lu, Yanzhen; Wu, Nan; Fang, Yingtong; Shaheen, Nusrat; Wei, Yun

2017-10-27

Many natural products are rich in antioxidants which play an important role in preventing or postponing a variety of diseases, such as cardiovascular and inflammatory disease, diabetes as well as breast cancer. In this paper, an automatic on-line 2,2-diphenyl-1-picrylhydrazyl-high performance liquid chromatography (DPPH-HPLC) method was established for antioxidants screening with nine standards including organic acids (4-hydroxyphenylacetic acid, p-coumaric acid, ferulic acid, and benzoic acid), alkaloids (coptisine and berberine), and flavonoids (quercitrin, astragalin, and quercetin). The optimal concentration of DPPH was determined, and six potential antioxidants including 4-hydroxyphenylacetic acid, p-coumaric acid, ferulic acid, quercitrin, astragalin, and quercetin, and three non-antioxidants including benzoic acid, coptisine, and berberine, were successfully screened out and validated by conventional DPPH radical scavenging activity assay. The established method has been applied to the crude samples of Saccharum officinarum rinds, Coptis chinensis powders, and Malus pumila leaves, consecutively. Two potential antioxidant compounds from Saccharum officinarum rinds and five potential antioxidant compounds from Malus pumila eaves were rapidly screened out. Then these seven potential antioxidants were purified and identified as p-coumaric acid, ferulic acid, phloridzin, isoquercitrin, quercetin-3-xyloside, quercetin-3-arabinoside, and quercetin-3-rhamnoside using countercurrent chromatography combined with mass spectrometry and their antioxidant activities were further evaluated by conventional DPPH radical scavenging assay. The activity result was in accordance with that of the established method. This established method is cheap and automatic, and could be used as an efficient tool for high-throughput antioxidant screening from various complex natural products. Copyright © 2017 Elsevier B.V. All rights reserved.

High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells.

PubMed

Karmaus, Agnes L; Toole, Colleen M; Filer, Dayne L; Lewis, Kenneth C; Martin, Matthew T

2016-04-01

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells

PubMed Central

Toole, Colleen M.; Filer, Dayne L.; Lewis, Kenneth C.; Martin, Matthew T.

2016-01-01

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. PMID:26781511

Feasibility of nonselective testing for hemoglobinopathies in early pregnancy in The Netherlands.

PubMed

Kaufmann, Judith O; Demirel-Güngör, Gönül; Selles, Anke; Hudig, Cisca; Steen, Gerard; Ponjee, Gabrielle; Holleboom, Cas; Freeman, Liv M; Hendiks, Joris; Wijermans, Pierre; Giordano, Piero C; Kerkhoffs, Jean-Louis

2011-12-01

To examine the feasibility of standardized hemoglobinopathy (HBP) carrier testing for pregnant women in The Netherlands in addition to the standard anemia screening. We assessed the prevalence of HBP in women at the time of the first pregnancy visit using both a prospective cohort (N = 703) and a retrospective series of women selected at random (N = 588). For the purpose of analysis, the population was divided into a high risk and a low risk group for HBP based on maternal ethnicity. Screening for HBP utilized standard screening tests for anemia, with additional high performance liquid chromatography (Variant II); molecular analysis was performed by Gap-polymerase chain reaction (Gap-PCR) and if necessary, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Family history was reported or collected from the medical records. β-Globin defects were found in 3.9% of the total population (50/1291). The frequency in the high risk population was 5.6% (37/656), compared with 1.2% (6/501) in the low risk group. In the prospective study we found 30 HBP carriers, leading to testing of 16 partners and identification of two couples at risk. One affected child was born. Mean gestational age at the screening was 11.3 weeks with a standard deviation (SD) of 5.8. We found that the prevalence of HBP carriers is high enough in our population to warrant HBP testing for the entire multiethnic population in early pregnancy at the time of anemia screening. This is feasible as most women had their booking early in their first trimester. Copyright © 2011 John Wiley & Sons, Ltd.

Screening Coccidioides Serology in Kidney Transplant Recipients: A 10-Year Cross-Sectional Analysis.

PubMed

Phonphok, Korntip; Beaird, Omer; Duong, Tin; Datta, Nakul; Schaenman, Joanna; Bunnapradist, Suphamai

2018-05-29

Kidney transplant recipients (KTRs) are at risk for reactivation and complicated infection due to Coccidioides. Pre-transplant serological screening should provide benefit for patients from endemic areas. We evaluated Coccidioides seroprevalence by area of residence in KTRs at a major transplant program in Los Angeles. We performed cross-sectional analyses of adult KTRs who underwent transplantation at UCLA between 2007-2016. Patients with Coccidioides serology by Enzyme Immunoassay (EIA) before or within 14 days from transplantation were included. Patients were classified as living in highly, established, suspected, or not endemic areas by their residential zip code. Overall prevalence of Coccidioides IgG and IgM were 1.4% and 2.8%, respectively. Of patients with positive serology, 31.4% had isolated IgG and 66.3% isolated IgM. Patients from established and highly endemic areas had IgG seropositivity of 3.7% versus 1.3% for patients living in suspected endemic areas(p<0.01). Rates of IgM seropositivity were 3.7% compared to 2.8% respectively(p=0.28). No patients from non-endemic areas had positive screening serology. Pre-transplant serological screening for Coccidioides is recommended in kidney transplant candidates from endemic areas. We observed high seroprevalence among patients from highly and established endemic areas, for whom universal prophylaxis is recommended. For residents from less well-established areas of endemicity, serological screening showed benefit in identifying patients at risk. In patients with isolated EIA IgM, performing repeat and confirmatory tests is recommended. Patients from non-endemic areas had low risk of infection, however a thorough social history is necessary to evaluate risk. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Sensitivity of nested-PCR for plasmodium detection in pooled whole blood samples and its usefulness to blood donor screening in endemic areas.

PubMed

de Freitas, Daniel Roberto Coradi; Gomes, Luciano Teixeira; Fontes, Cor Jesus F; Tauil, Pedro Luiz; Pang, Lorrin W; Duarte, Elisabeth Carmen

2014-04-01

Transfusion-transmitted malaria is a severe disease with high fatality rate. Most Brazilian blood banks in the Amazon region perform malaria screening using microscopic examination (thick smears). Since low parasite concentrations are expected in asymptomatic blood donors a high sensitivity test should be used for donor screening. This study determined the sensitivity of a nested-PCR for plasmodium detection in pooled samples. We performed a one-stage criterion validation study with 21 positive samples pooled with samples from ten negative volunteer until three different concentrations were reached (0.33; 0.25; 0.20 parasites/μL - p/μL). Nested PCR was performed as described by Snounou et al. (1993). Sensitivities (and confidence intervals) were determined by stratum of final parasite concentration on the pooled samples. All samples with parasitemia values of 0.33 and 0.25 p/μL had 100% sensitivity (95%CI=86.3-100). One negative result was obtained from a sample with 0.20 p/μL sensitivity=95.2% (95%CI=76.2-99.9). Compared to parasitemia detectable under ideal conditions of thick smear, this nested-PCR in pooled sample was able to detect 40 times more parasites per microliter. Nested-PCR in pooled samples should be considered as a high sensitive alternative to thick smear for donor screening in blood banks at endemic regions. Local authorities need to assess cost:benefit advantages of this method compared to alternatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

Coformer screening using thermal analysis based on binary phase diagrams.

PubMed

Yamashita, Hiroyuki; Hirakura, Yutaka; Yuda, Masamichi; Terada, Katsuhide

2014-08-01

The advent of cocrystals has demonstrated a growing need for efficient and comprehensive coformer screening in search of better development forms, including salt forms. Here, we investigated a coformer screening system for salts and cocrystals based on binary phase diagrams using thermal analysis and examined the effectiveness of the method. Indomethacin and tenoxicam were used as models of active pharmaceutical ingredients (APIs). Physical mixtures of an API and 42 kinds of coformers were analyzed using Differential Scanning Calorimetry (DSC) and X-ray DSC. We also conducted coformer screening using a conventional slurry method and compared these results with those from the thermal analysis method and previous studies. Compared with the slurry method, the thermal analysis method was a high-performance screening system, particularly for APIs with low solubility and/or propensity to form solvates. However, this method faced hurdles for screening coformers combined with an API in the presence of kinetic hindrance for salt or cocrystal formation during heating or if there is degradation near the metastable eutectic temperature. The thermal analysis and slurry methods are considered complementary to each other for coformer screening. Feasibility of the thermal analysis method in drug discovery practice is ensured given its small scale and high throughput.

Colorectal cancer screening programme by faecal occult blood test in Tuscany: first round results.

PubMed

Grazzini, G; Castiglione, G; Ciabattoni, C; Franceschini, F; Giorgi, D; Gozzi, S; Mantellini, P; Lopane, P; Perco, M; Rubeca, T; Salvadori, P; Visioli, C B; Zappa, M

2004-02-01

Screening with faecal occult blood test (FOBT) has been shown to be effective in reducing mortality from colorectal cancer. Tuscany was the first region in Italy in which a screening programme for colorectal cancer by FOBT was initiated region-wide. The aim of the paper was to describe organizational aspects, a quality control model and the results of this experience. From June 2000 to December 2001, 192583 subjects aged 50-70 were invited to undergo a 1-day immunochemical test without any dietary restriction. A total of 78505 subjects (41%) performed the screening test, of whom 4537 responders had a positive test result (5.8%). Among them, 1122 refused any form of assessment or underwent a colonoscopy outside the screening referral centres, with an overall assessment compliance of 75.3%. Malignancies were found in 193 patients and at least a high-risk adenomatous polyp in 692 patients. In about a quarter of the positive subjects who underwent assessment, cancer or high-risk adenoma was detected. In conclusion, data from this experience supported the feasibility of biennial colorectal screening programme by FOBT, particularly regarding invitation compliance and positivity rate. Further efforts are necessary to implement screening extension and to improve data collection.

Population Screening for Chronic Q-Fever Seven Years after a Major Outbreak

PubMed Central

Morroy, Gabriëlla; van der Hoek, Wim; Albers, Jelle; Coutinho, Roel A.; Bleeker-Rovers, Chantal P.; Schneeberger, Peter M.

2015-01-01

Introduction From 2007 through 2010, the Netherlands experienced a large Q-fever epidemic, with 4,107 notifications. The most serious complication of Q-fever is chronic Q-fever. Method In 2014, we contacted all 2,161 adult inhabitants of the first village in the Netherlands affected by the Q-fever epidemic and offered to test for antibodies against Coxiella burnetii using immunofluorescence assay (IFA) to screen for chronic infections and assess whether large-scale population screening elsewhere is warranted. Results Of the 1,517 participants, 33.8% were IFA-positive. Six IFA-positive participants had an IgG phase I titer ≥1:512. Two of these six participants were previously diagnosed with chronic Q-fever. Chronic infection was diagnosed in one of the other four participants after clinical examination. Conclusions Seven years after the initial outbreak, seroprevalence remains high, but the yield of screening the general population for chronic Q-fever is low. A policy of screening known high-risk groups for chronic Q-fever in outbreak areas directly following an outbreak might be more efficient than population screening. A cost-effectiveness analysis should also be performed before initiating a population screening program for chronic Q-fever. PMID:26132155

An automated compound screening for anti-aging effects on the function of C. elegans sensory neurons.

PubMed

Bazopoulou, Daphne; Chaudhury, Amrita R; Pantazis, Alexandros; Chronis, Nikos

2017-08-24

Discovery of molecular targets or compounds that alter neuronal function can lead to therapeutic advances that ameliorate age-related neurodegenerative pathologies. Currently, there is a lack of in vivo screening technologies for the discovery of compounds that affect the age-dependent neuronal physiology. Here, we present a high-throughput, microfluidic-based assay for automated manipulation and on-chip monitoring and analysis of stimulus-evoked calcium responses of intact C. elegans at various life stages. First, we successfully applied our technology to quantify the effects of aging and age-related genetic and chemical factors in the calcium transients of the ASH sensory neuron. We then performed a large-scale screen of a library of 107 FDA-approved compounds to identify hits that prevented the age-dependent functional deterioration of ASH. The robust performance of our assay makes it a valuable tool for future high-throughput applications based on in vivo functional imaging.

Rapid screening and identification of multi-class substances of very high concern in textiles using liquid chromatography-hybrid linear ion trap orbitrap mass spectrometry.

PubMed

Zhang, Li; Luo, Xin; Niu, Zengyuan; Ye, Xiwen; Tang, Zhixu; Yao, Peng

2015-03-20

A new analytical method was established and validated for the analysis of 19 substances of very high concern (SVHCs) in textiles, including phthalic acid esters (PAEs), organotins (OTs), perfluorochemicals (PFCs) and flame retardants (FRs). After ultrasonic extraction in methanol, the textile samples were analyzed by high performance liquid chromatography-hybrid linear ion trap Orbitrap high resolution mass spectrometry (HPLC-LTQ/Orbitrap). The values of LOQ were in the range of 2-200mg/kg. Recoveries at two levels (at the LOQ and at half the limit of regulation) ranged from 68% to 120%, and the repeatability was lower than 13%. This method was successfully applied to the screening of SVHCs in commercial textile samples and is useful for the fast screening of various SVHCs. Copyright © 2015 Elsevier B.V. All rights reserved.

Screening via CT angiogram after traumatic cervical spine fractures: narrowing imaging to improve cost effectiveness. Experience of a Level I trauma center

PubMed Central

Lockwood, Megan M.; Smith, Gabriel A.; Tanenbaum, Joseph; Lubelski, Daniel; Seicean, Andreea; Pace, Jonathan; Benzel, Edward C.; Mroz, Thomas E.; Steinmetz, Michael P.

2017-01-01

OBJECT Screening for vertebral artery injury (VAI) following cervical spine fractures is routinely performed across trauma centers in North America. From 2002 to 2007, the total number of neck CT angiography (CTA) studies performed in the Medicare population after trauma increased from 9796 to 115,021. In the era of cost-effective medical care, the authors aimed to evaluate the utility of CTA screening in detecting VAI and reduce chances of posterior circulation strokes after traumatic cervical spine fractures. METHODS A retrospective review of all patients presenting with cervical spine fractures to Northeast Ohio’s Level I trauma institution from 2002 to 2012 was performed. RESULTS There was a total of 1717 cervical spine fractures in patients presenting to Northeast Ohio’s Level I trauma institution between 2002 and 2012. CTA screening was performed in 732 patients, and 51 patients (0.7%) were found to have a VAI. Fracture patterns with increased odds of VAI were C-1 and C-2 combined fractures, transverse foramen fractures, and subluxation of adjacent vertebral levels. Ten posterior circulation strokes were identified in this patient population (0.6%) and found in only 4 of 51 cases of VAI (7.8%). High-risk fractures defined by Denver Criteria, VAI, and antiplatelet treatment of VAI were not independent predictors of stroke. CONCLUSIONS Cost-effective screening must be reevaluated in the setting of blunt cervical spine fractures on a case-by-case basis. Further prospective studies must be performed to elucidate the utility of screening for VAI and posterior circulation stroke prevention, if identified. PMID:26613284

Development of a high risk pancreatic screening clinic using 3.0 T MRI.

PubMed

Barnes, Chad A; Krzywda, Elizabeth; Lahiff, Shannon; McDowell, Dena; Christians, Kathleen K; Knechtges, Paul; Tolat, Parag; Hohenwalter, Mark; Dua, Kulwinder; Khan, Abdul H; Evans, Douglas B; Geurts, Jennifer; Tsai, Susan

2018-01-01

Selective screening for pancreatic cancer (PC) has been proposed. We describe the establishment of a comprehensive multidisciplinary screening program using 3.0 T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic ultrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peutz-Jeghers (1). A family history of PC was present in ≥ 2 FDR in 12 (16%) pts, 1 FDR and 1 SDR in 5 (7) pts, and ≥ 3 ADR in 16 (21%) pts. Of the 65 pts who received screening MRI, 28 (43%) pts had pancreatic cystic lesions identified, including 1 (1%) patient in whom a cholangiocarcinoma was diagnosed as well. No patient underwent surgical resection. Using a 3.0 T MRI to screen patients at high risk for developing PC identified radiographic abnormalities in 43% of patients, which were stable on subsequent surveillance. Specific guidelines for the frequency of surveillance and indications for surgery remain areas of active investigation as the global experience with high risk screening continues to mature.

Disparity between Clinical and Ultrasound Examinations in Neonatal Hip Screening.

PubMed

Kyung, Bong Soo; Lee, Soon Hyuck; Jeong, Woong Kyo; Park, Si Young

2016-06-01

For early detection of developmental dysplasia of the hip (DDH), neonatal hip screening using clinical examination and/or ultrasound has been recommended. Although there have been many studies on the reliability of both screening techniques, there is still controversy in the screening strategies; clinical vs. selective or universal ultrasound screening. To determine the screening strategy, we assessed the agreement among the methods; clinical examination by an experienced pediatric orthopedic surgeon, sonographic morphology, and sonographic stability. From January 2004 to June 2009, a single experienced pediatric orthopedic surgeon performed clinical hip screenings for 2,686 infants in the neonatal unit and 43 infants who were referred due to impressions of hip dysplasia before 3 months of age. Among them, 156 clinically unstable or high-risk babies selectively received bilateral hip ultrasound examinations performed by the same surgeon using the modified Graf method. The results were analyzed statistically to detect any correlations between the clinical and sonographic findings. Although a single experienced orthopedic surgeon conducted all examinations, we detected only a limited relationship between the results of clinical and ultrasound examinations. Ninety-three percent of the clinically subluxatable hips were normal or immature based on static ultrasound examination, and 74% of dislocating hips and 67% of limited abduction hips presented with the morphology below Graf IIa. A total of 80% of clinically subluxatable, 42% of dislocating and 67% of limited abduction hips appeared stable or exhibited minor instability on dynamic ultrasound examination. About 7% of clinically normal hips were abnormal upon ultrasound examination; 5% showed major instability and 3% showed dysplasia above Graf IIc. Clinical stability had small coefficients between ultrasound examinations; 0.39 for sonographic stability and 0.37 for sonographic morphology. Between sonographic stability and morphology, although 71% of hips with major instability showed normal or immature morphology according to static ultrasound examination, the coefficient was as high as 0.64. Discrepancies between clinical and ultrasound examinations were present even if almost all of the exams were performed by a single experienced pediatric orthopedic surgeon. In relation to screening for DDH, it is recommended that both sonographic morphology and stability be checked in addition to clinical examination.

A comparison of the performance of modern screen-film and digital mammography systems.

PubMed

Monnin, P; Gutierrez, D; Bulling, S; Lepori, D; Valley, J-F; Verdun, F R

2005-06-07

This work compares the detector performance and image quality of the new Kodak Min-R EV mammography screen-film system with the Fuji CR Profect detector and with other current mammography screen-film systems from Agfa, Fuji and Kodak. Basic image quality parameters (MTF, NPS, NEQ and DQE) were evaluated for a 28 kV Mo/Mo (HVL = 0.646 mm Al) beam using different mAs exposure settings. Compared with other screen-film systems, the new Kodak Min-R EV detector has the highest contrast and a low intrinsic noise level, giving better NEQ and DQE results, especially at high optical density. Thus, the properties of the new mammography film approach those of a fine mammography detector, especially at low frequency range. Screen-film systems provide the best resolution. The presampling MTF of the digital detector has a value of 15% at the Nyquist frequency and, due to the spread size of the laser beam, the use of a smaller pixel size would not permit a significant improvement of the detector resolution. The dual collection reading technology increases significantly the low frequency DQE of the Fuji CR system that can at present compete with the most efficient mammography screen-film systems.

Hypertrophic Cardiomyopathy in Youth Athletes

PubMed Central

Fox, J. Christian; Lahham, Shadi; Maldonado, Graciela; Klaus, Suzi; Aish, Bassil; Sylwanowicz, Lauren V.; Yanuck, Justin; Wilson, Sean P.; Shieh, Mason; Anderson, Craig L.; English, Carter; Mayer, Ryan; Mohan, Uthara R.

2018-01-01

Objectives Hypertrophic cardiomyopathy (HCM) is a life-threatening genetic cardiovascular disease that often goes undetected in young athletes. Neither history nor physical examination are reliable to identify those at risk. The objective of this study is to determine whether minimally trained medical student volunteers can use ultrasound to screen for HCM. Methods This was a prospective enrollment of young athletes performed at 12 area high schools and three area colleges, between May 2012 and August 2013. All participants underwent point-of-care ultrasound performed screening for HCM by trained medical students and reviewed by a pediatric cardiologist. An interventricular septum to left ventricular posterior wall ratio greater than 1.25 was considered to be abnormal (positive screen). Results A total of 2332 participants were enrolled. There were 137 (5.8%) with a positive screening for HCM, of which 7 (5.1%) were confirmed to have HCM by a pediatric cardiologist. In a small cohort with positive screen for HCM, there was a 100% sensitivity (95% confidence interval, 59.04 to 100%) and 4.86% (95% confidence interval, 1.98 to 9.76%) positive predictive value of for having HCM. Conclusions Volunteer medical students, using point-of-care ultrasound, were able to effectively screen for HCM in young athletes. PMID:28258593

Hypertrophic Cardiomyopathy in Youth Athletes: Successful Screening With Point-of-Care Ultrasound by Medical Students.

PubMed

Fox, J Christian; Lahham, Shadi; Maldonado, Graciela; Klaus, Suzi; Aish, Bassil; Sylwanowicz, Lauren V; Yanuck, Justin; Wilson, Sean P; Shieh, Mason; Anderson, Craig L; English, Carter; Mayer, Ryan; Mohan, Uthara R

2017-06-01

Hypertrophic cardiomyopathy (HCM) is a life-threatening genetic cardiovascular disease that often goes undetected in young athletes. Neither history nor physical examination are reliable to identify those at risk. The objective of this study is to determine whether minimally trained medical student volunteers can use ultrasound to screen for HCM. This was a prospective enrollment of young athletes performed at 12 area high schools and three area colleges, between May 2012 and August 2013. All participants underwent point-of-care ultrasound performed screening for HCM by trained medical students and reviewed by a pediatric cardiologist. An interventricular septum to left ventricular posterior wall ratio greater than 1.25 was considered to be abnormal (positive screen). A total of 2332 participants were enrolled. There were 137 (5.8%) with a positive screening for HCM, of which 7 (5.1%) were confirmed to have HCM by a pediatric cardiologist. In a small cohort with positive screen for HCM, there was a 100% sensitivity (95% confidence interval, 59.04 to 100%) and 4.86% (95% confidence interval, 1.98 to 9.76%) positive predictive value of for having HCM. Volunteer medical students, using point-of-care ultrasound, were able to effectively screen for HCM in young athletes. © 2017 by the American Institute of Ultrasound in Medicine.

Development of On-Line High Performance Liquid Chromatography (HPLC)-Biochemical Detection Methods as Tools in the Identification of Bioactives

PubMed Central

Malherbe, Christiaan J.; de Beer, Dalene; Joubert, Elizabeth

2012-01-01

Biochemical detection (BCD) methods are commonly used to screen plant extracts for specific biological activities in batch assays. Traditionally, bioactives in the most active extracts were identified through time-consuming bio-assay guided fractionation until single active compounds could be isolated. Not only are isolation procedures often tedious, but they could also lead to artifact formation. On-line coupling of BCD assays to high performance liquid chromatography (HPLC) is gaining ground as a high resolution screening technique to overcome problems associated with pre-isolation by measuring the effects of compounds post-column directly after separation. To date, several on-line HPLC-BCD assays, applied to whole plant extracts and mixtures, have been published. In this review the focus will fall on enzyme-based, receptor-based and antioxidant assays. PMID:22489144

Pinning down high-performance Cu-chalcogenides as thin-film solar cell absorbers: A successive screening approach

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

Zhang, Yubo; Zhang, Wenqing, E-mail: wqzhang@mail.sic.ac.cn, E-mail: pzhang3@buffalo.edu; State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050

2016-05-21

Photovoltaic performances of Cu-chalcogenides solar cells are strongly correlated with the absorber fundamental properties such as optimal bandgap, desired band alignment with window material, and high photon absorption ability. According to these criteria, we carry out a successive screening for 90 Cu-chalcogenides using efficient theoretical approaches. Besides the well-recognized CuInSe{sub 2} and Cu{sub 2}ZnSnSe{sub 4} materials, several novel candidates are identified to have optimal bandgaps of around 1.0–1.5 eV, spike-like band alignments with CdS window layer, sharp photon absorption edges, and high absorption coefficients. These new systems have great potential to be superior absorbers for photovolatic applications if their carrriermore » transport and defect properties are properly optimized.« less

Artificial intelligence for breast cancer screening: Opportunity or hype?

PubMed

Houssami, Nehmat; Lee, Christoph I; Buist, Diana S M; Tao, Dacheng

2017-12-01

Interpretation of mammography for breast cancer (BC) screening can confer a mortality benefit through early BC detection, can miss a cancer that is present or fast growing, or can result in false-positives. Efforts to improve screening outcomes have mostly focused on intensifying imaging practices (double instead of single-reading, more frequent screens, or supplemental imaging) that may add substantial resource expenditures and harms associated with population screening. Less attention has been given to making mammography screening practice 'smarter' or more efficient. Artificial intelligence (AI) is capable of advanced learning using large complex datasets and has the potential to perform tasks such as image interpretation. With both highly-specific capabilities, and also possible un-intended (and poorly understood) consequences, this viewpoint considers the promise and current reality of AI in BC detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Results of Annual Screening in Phase I of the United Kingdom Familial Ovarian Cancer Screening Study Highlight the Need for Strict Adherence to Screening Schedule

PubMed Central

Rosenthal, Adam N.; Fraser, Lindsay; Manchanda, Ranjit; Badman, Philip; Philpott, Susan; Mozersky, Jessica; Hadwin, Richard; Cafferty, Fay H.; Benjamin, Elizabeth; Singh, Naveena; Evans, D. Gareth; Eccles, Diana M.; Skates, Steven J.; Mackay, James; Menon, Usha; Jacobs, Ian J.

2013-01-01

Purpose To establish the performance characteristics of annual transvaginal ultrasound and serum CA125 screening for women at high risk of ovarian/fallopian tube cancer (OC/FTC) and to investigate the impact of delayed screening interval and surgical intervention. Patients and Methods Between May 6, 2002, and January 5, 2008, 3,563 women at an estimated ≥ 10% lifetime risk of OC/FTC were recruited and screened by 37 centers in the United Kingdom. Participants were observed prospectively by centers, questionnaire, and national cancer registries. Results Sensitivity for detection of incident OC/FTC at 1 year after last annual screen was 81.3% (95% CI, 54.3% to 96.0%) if occult cancers were classified as false negatives and 87.5% (95% CI, 61.7% to 98.5%) if they were classified as true positives. Positive and negative predictive values of incident screening were 25.5% (95% CI, 14.3 to 40.0) and 99.9% (95% CI, 99.8 to 100) respectively. Four (30.8%) of 13 incident screen-detected OC/FTCs were stage I or II. Compared with women screened in the year before diagnosis, those not screened in the year before diagnosis were more likely to have ≥ stage IIIc disease (85.7% v 26.1%; P = .009). Screening interval was delayed by a median of 88 days before detection of incident OC/FTC. Median interval from detection screen to surgical intervention was 79 days in prevalent and incident OC/FTC. Conclusion These results in the high-risk population highlight the need for strict adherence to screening schedule. Screening more frequently than annually with prompt surgical intervention seems to offer a better chance of early-stage detection. PMID:23213100

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

PubMed

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

2016-02-01

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

High-throughput screening of chemical effects on steroidogenesis using H295R human adrenocortical carcinoma cells

EPA Pesticide Factsheets

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ? 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 00b5M forskolin for 48??h to induce steroidogenesis followed by chemical treatment for 48??h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 1703b2-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mec

Depression screening with patient-targeted feedback in cardiology: The cost-effectiveness of DEPSCREEN-INFO.

PubMed

Brettschneider, Christian; Kohlmann, Sebastian; Gierk, Benjamin; Löwe, Bernd; König, Hans-Helmut

2017-01-01

Although depression is common in patients with heart disease, screening for depression is much debated. DEPSCREEN-INFO showed that a patient-targeted feedback in addition to screening results in lower depression level six months after screening. The purpose of this analysis was to perform a cost-effectiveness analysis of DEPSCREEN-INFO. Patients with coronary heart disease or arterial hypertension were included. Participants in both groups were screened for depression. Participants in the intervention group additionally received a patient-targeted feedback of their result and recommended treatment options. A cost-utility analysis using quality-adjusted life years (QALY) based on the EQ-5D was performed. The time horizon was 6 months. Resource utilization was assessed by a telephone interview. Multiple imputation using chained equations was used. Net-benefit regressions controlled for prognostic variables at baseline were performed to construct cost-effectiveness acceptability curves. Different sensitivity analyses were performed. 375 participants (intervention group: 155; control group: 220) were included at baseline. After 6 months, in the intervention group adjusted total costs were lower (-€2,098; SE: €1,717) and more QALY were gained (0.0067; SD: 0.0133); yet differences were not statistically significant. The probability of cost-effectiveness was around 80% independent of the willingness-to-pay (range: €0/QALY-€130,000/QALY). The results were robust. A patient-targeted feedback in addition to depression screening in cardiology is cost-effective with a high probability. This underpins the use of the patient-targeted feedbacks and the PHQ-9 that are both freely available and easy to implement in routine care.

Functionality screen of streptavidin mutants by non-denaturing SDS-PAGE using biotin-4-fluorescein.

PubMed

Humbert, Nicolas; Ward, Thomas R

2008-01-01

Site-directed mutagenesis or directed evolution of proteins often leads to the production of inactive mutants. For streptavidin and related proteins, mutations may lead to the loss of their biotin-binding properties. With high-throughput screening methodologies in mind, it is imperative to detect, prior to the high-density protein production, the bacteria that produce non-functional streptavidin isoforms. Based on the incorporation of biotin-4-fluorescein in streptavidin mutants present in Escherichia coli bacterial extracts, we detail a functional screen that allows the identification of biotin-binding streptavidin variants. Bacteria are cultivated in a small volume, followed by a rapid treatment of the cells; biotin-4-fluorescein is added to the bacterial extract and loaded on an Sodium Dodecyl Sulfate Poly-Acrylamide Gel Electrophoresis (SDS-PAGE) under non-denaturing conditions. Revealing is performed using a UV transilluminator. This screen is thus easy to implement, cheap and requires only readily available equipment.

Can Touch Screen Tablets be Used to Assess Cognitive and Motor Skills in Early Years Primary School Children? A Cross-Cultural Study.

PubMed

Pitchford, Nicola J; Outhwaite, Laura A

2016-01-01

Assessment of cognitive and motor functions is fundamental for developmental and neuropsychological profiling. Assessments are usually conducted on an individual basis, with a trained examiner, using standardized paper and pencil tests, and can take up to an hour or more to complete, depending on the nature of the test. This makes traditional standardized assessments of child development largely unsuitable for use in low-income countries. Touch screen tablets afford the opportunity to assess cognitive functions in groups of participants, with untrained administrators, with precision recording of responses, thus automating the assessment process. In turn, this enables cognitive profiling to be conducted in contexts where access to qualified examiners and standardized assessments are rarely available. As such, touch screen assessments could provide a means of assessing child development in both low- and high-income countries, which would afford cross-cultural comparisons to be made with the same assessment tool. However, before touch screen tablet assessments can be used for cognitive profiling in low-to-high-income countries they need to be shown to provide reliable and valid measures of performance. We report the development of a new touch screen tablet assessment of basic cognitive and motor functions for use with early years primary school children in low- and high-income countries. Measures of spatial intelligence, visual attention, short-term memory, working memory, manual processing speed, and manual coordination are included as well as mathematical knowledge. To investigate if this new touch screen assessment tool can be used for cross-cultural comparisons we administered it to a sample of children ( N = 283) spanning standards 1-3 in a low-income country, Malawi, and a smaller sample of children ( N = 70) from first year of formal schooling from a high-income country, the UK. Split-half reliability, test-retest reliability, face validity, convergent construct validity, predictive criterion validity, and concurrent criterion validity were investigated. Results demonstrate "proof of concept" that touch screen tablet technology can provide reliable and valid psychometric measures of performance in the early years, highlighting its potential to be used in cross-cultural comparisons and research.

Current practice, accuracy, effectiveness and cost-effectiveness of the school entry hearing screen.

PubMed

Bamford, J; Fortnum, H; Bristow, K; Smith, J; Vamvakas, G; Davies, L; Taylor, R; Watkin, P; Fonseca, S; Davis, A; Hind, S

2007-08-01

To describe and analyse in detail current practice of school entry hearing screening (SES) in the UK. Main electronic databases were searched up to May 2005. A national postal questionnaire survey was addressed to all leads for SES in the UK, considering current practice in terms of implementation, protocols, target population and performance data. Primary data from cohort studies in one area of London were examined. A systematic review of alternative SES tests, test performance and impact on outcomes was carried out. Finally, a review of published studies on costs, plus economic modelling of current and alternative programmes was prepared. The survey suggested that SES is used in most of England, Wales and Scotland; just over 10% of respondents have abandoned the screen; others are awaiting national guidance. Coverage of SES is variable, but is often over 90% for children in state schools. Referral rates are variable, with a median of about 8%. The test used for the screen is the pure tone sweep test but with wide variation in implementation, with differing frequencies, pass criteria and retest protocols; written examples of protocols were often poor and ambiguous. There is no national approach to data collection, audit and quality assurance, and there are variable approaches at local level. The screen is performed in less than ideal test conditions and resources are often limited, which has an impact on the quality of the screen. The primary cohort studies show that the prevalence of permanent childhood hearing loss continues to increase through infancy. Of the 3.47 in 1000 children with a permanent hearing loss at school screen age, 1.89 in 1000 required identification after the newborn screen. Newborn hearing screening is likely to reduce significantly the yield of SES for permanent bilateral and unilateral hearing impairments; yield had fallen from about 1.11 in 1000 before newborn screening to about 0.34 in 1000 for cohorts that had had newborn screening, of which only 0.07 in 1000 were unilateral impairments. Just under 20% of permanent moderate or greater bilateral, mild bilateral and unilateral impairments, known to services as 6-year-olds or older, remained to be identified around the time of school entry. No good-quality published comparative trials of alternative screens or tests for SES were identified and studies concerned with the relative accuracy of alternative tests are difficult to compare and often flawed by differing referral criteria and case definitions; with full pure tone audiometry as the reference test, the pure tone sweep test appears to have high sensitivity and high specificity for minimal, mild and greater hearing impairments, better than alternative tests for which evidence was identified. There is insufficient evidence regarding possible harm of the screen. There were no published studies identified that examined the possible effects of SES on longer term outcomes. No good-quality published economic evaluations of SES were identified and a universal SES based on pure tone sweep tests was associated with higher costs and slightly higher quality-adjusted life-years (QALYs) compared with no screen and other screen alternatives; the incremental cost-effectiveness ratio for such a screen is around 2500 pounds per QALY gained; the range of expected costs, QALYs and net benefits was broad, indicating a considerable degree of uncertainty. Targeted screening could be more cost-effective than universal school entry screening; however, the lack of primary data and the wide limits for variables in the modelling mean that any conclusions must be considered indicative and exploratory only. A national screening programme for permanent hearing impairment at school entry meets all but three of the criteria for a screening programme, but at least six criteria are not met for screening for temporary hearing impairment. The lack of good-quality evidence in this area remains a serious problem. Services should improve quality and audit screen performance for identification of previously unknown permanent hearing impairment, pending evidence-based policy decisions based on the research recommendations. Further research is needed into a number of important areas including the evaluation of an agreed national protocol for services delivering SES to make future studies and audits of screen performance more directly comparable.

Fixed-facility workplace screening mammography.

PubMed

Reynolds, H E; Larkin, G N; Jackson, V P; Hawes, D R

1997-02-01

Potential barriers to compliance with screening mammography guidelines include the cost and inconvenience involved with undergoing the procedure. Workplace screening with mobile mammography is one possible approach to the convenience barrier. However, fixed-facility workplace screening is a viable alternative for any company with a large workforce in one location. This paper describes our initial experience with one such fixed facility. The facility was a cooperative venture by a large pharmaceutical company and an academic radiology department to provide convenient, no-cost (to the patient) screening mammography to employees, dependents, and retirees more than 40 years old. The pharmaceutical company built the facility within its corporate headquarters and the academic radiology department provided the equipment and personnel. The company was billed a fixed cost per examination. In the first 22 months of operation, 4210 (of 4559 scheduled) screening mammograms were obtained. The mean age of the population was 53 years old. Ninety percent of the screening mammograms were interpreted as negative or benign; 10% required additional workup. Of the screened population, 62 biopsies were recommended and 60 were performed. Of these, 42 were benign and 18 malignant. The cancer detection rate was 4.3 per 1000 (0.43%). At the time of diagnosis, six patients were stage 0, 10 patients were stage I, one patient was stage II, and one patient was stage III. Eleven of the 18 patients had minimal cancers. Of the patients who completed a satisfaction survey, 97% percent expressed a high degree of satisfaction with the screening process and stated they would use the facility in the future. A fixed facility for workplace screening mammography is a viable way to provide nearly barrier-free access to high-quality mammography. Patient acceptance is high.

Rural physicians' perspectives on cervical and breast cancer screening: a gender-based analysis.

PubMed

Ahmad, F; Stewart, D E; Cameron, J I; Hyman, I

2001-03-01

Several studies highlight the role of physicians in determining cervical and breast cancer screening rates, and some urban studies report higher screening rates by female physicians. Rural women in North America remain underscreened for breast and cervical cancers. This survey was conducted to determine if there were significant gender differences in practices and perceptions of barriers to breast and cervical cancer screening among rural family physicians in Ontario, Canada. One hundred ninety-one family physicians (response rate 53.1%) who practiced in rural areas, small towns, or small cities completed a mail questionnaire. The physicians' mean age was 44.4 years (SD 9.9), and mean number of years in practice was 16.6 years (SD 10.3). Over 90% of physicians reported that they were very likely to conduct a Pap test and clinical breast examination (CBE) during a periodic health examination, and they had high levels of confidence and comfort in performing these procedures. Male (68%) and female (32%) physicians were similar in their likelihood to conduct screening, levels of confidence and comfort, and knowledge of breast and cervical cancer screening guidelines. However, the self-reported screening rates for Pap tests and CBE performed during last year were higher for female than male physicians (p < 0.01). Male physicians reported they were asked more frequently by patients for a referral to another physician to perform Pap tests and CBE (p < 0.001). Also, male physicians perceived patients' embarrassment as a stronger barrier to performing Pap tests (p < 0.05) and CBE (p < 0.01) than female physicians. No gender differences were observed in screening rates or related barriers to mammography referrals. These findings suggest that physicians' gender plays a role in sex-sensitive examination, such as Pap tests and CBE. There is a need to facilitate physician-patient interactions for sex-sensitive cancer screening examinations by health education initiatives targeting male physicians and women themselves. The feasibility of providing sex-sensitive cancer screening examinations by a same-sex health provider should also be explored.

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

PubMed

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

2007-01-01

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

One-Time Password Tokens | High-Performance Computing | NREL

Science.gov Websites

One-Time Password Tokens One-Time Password Tokens For connecting to NREL's high-performance computing (HPC) systems, learn how to set up a one-time password (OTP) token for remote and privileged a one-time pass code from the HPC Operations team. At the sign-in screen Enter your HPC Username in

High-throughput metabolic stability studies in drug discovery by orthogonal acceleration time-of-flight (OATOF) with analogue-to-digital signal capture (ADC).

PubMed

Temesi, David G; Martin, Scott; Smith, Robin; Jones, Christopher; Middleton, Brian

2010-06-30

Screening assays capable of performing quantitative analysis on hundreds of compounds per week are used to measure metabolic stability during early drug discovery. Modern orthogonal acceleration time-of-flight (OATOF) mass spectrometers equipped with analogue-to-digital signal capture (ADC) now offer performance levels suitable for many applications normally supported by triple quadruple instruments operated in multiple reaction monitoring (MRM) mode. Herein the merits of MRM and OATOF with ADC detection are compared for more than 1000 compounds screened in rat and/or cryopreserved human hepatocytes over a period of 3 months. Statistical comparison of a structurally diverse subset indicated good agreement for the two detection methods. The overall success rate was higher using OATOF detection and data acquisition time was reduced by around 20%. Targeted metabolites of diazepam were detected in samples from a CLint determination performed at 1 microM. Data acquisition by positive and negative ion mode switching can be achieved on high-performance liquid chromatography (HPLC) peak widths as narrow as 0.2 min (at base), thus enabling a more comprehensive first pass analysis with fast HPLC gradients. Unfortunately, most existing OATOF instruments lack the software tools necessary to rapidly convert the huge amounts of raw data into quantified results. Software with functionality similar to open access triple quadrupole systems is needed for OATOF to truly compete in a high-throughput screening environment. Copyright 2010 John Wiley & Sons, Ltd.

Brief assessment of food insecurity accurately identifies high-risk US adults.

PubMed

Gundersen, Craig; Engelhard, Emily E; Crumbaugh, Amy S; Seligman, Hilary K

2017-06-01

To facilitate the introduction of food insecurity screening into clinical settings, we examined the test performance of two-item screening questions for food insecurity against the US Department of Agriculture's Core Food Security Module. We examined sensitivity, specificity and accuracy of various two-item combinations of questions assessing food insecurity in the general population and high-risk population subgroups. 2013 Current Population Survey December Supplement, a population-based US survey. All survey participants from the general population and high-risk subgroups. The test characteristics of multiple two-item combinations of questions assessing food insecurity had adequate sensitivity (>97 %) and specificity (>70 %) for widespread adoption as clinical screening measures. We recommend two specific items for clinical screening programmes based on their widespread current use and high sensitivity for detecting food insecurity. These items query how often the household 'worried whether food would run out before we got money to buy more' and how often 'the food that we bought just didn't last and we didn't have money to get more'. The recommended items have sensitivity across high-risk population subgroups of ≥97 % and a specificity of ≥74 % for food insecurity.

High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3 ) in Urine Collected on Filter Paper.

PubMed

Auray-Blais, Christiane; Lavoie, Pamela; Boutin, Michel; Abaoui, Mona

2017-04-06

Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000. Its complexity lies in the marked genotypic and phenotypic heterogeneity. Despite the fact that it is an X-linked disease, more than 600 mutations affect both males and females. In fact, some females may be affected as severely as males. The purpose of this protocol is to focus on the high-risk screening of patients who might have Fabry disease using a simple, rapid, non-invasive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for urinary globotriaosylceramide (Gb 3 ) analysis. Urine filter paper samples are easily collected at home by patients and sent by regular mail. This method has been successfully used for high-risk screening of patients with ophthalmologic manifestations and in an on-going study for high-risk screening of Fabry disease in patients with chronic kidney diseases. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Drug screening in medical examiner casework by high-resolution mass spectrometry (UPLC-MSE-TOF).

PubMed

Rosano, Thomas G; Wood, Michelle; Ihenetu, Kenneth; Swift, Thomas A

2013-10-01

Postmortem drug findings yield important analytical evidence in medical examiner casework, and chromatography coupled with nominal mass spectrometry (MS) serves as the predominant general unknown screening approach. We report screening by ultra performance liquid chromatography (UPLC) coupled with hybrid quadrupole time-of-flight mass spectrometer (MS(E)-TOF), with comparison to previously validated nominal mass UPLC-MS and UPLC-MS-MS methods. UPLC-MS(E)-TOF screening for over 950 toxicologically relevant drugs and metabolites was performed in a full-spectrum (m/z 50-1,000) mode using an MS(E) acquisition of both molecular and fragment ion data at low (6 eV) and ramped (10-40 eV) collision energies. Mass error averaged 1.27 ppm for a large panel of reference drugs and metabolites. The limit of detection by UPLC-MS(E)-TOF ranges from 0.5 to 100 ng/mL and compares closely with UPLC-MS-MS. The influence of column recovery and matrix effect on the limit of detection was demonstrated with ion suppression by matrix components correlating closely with early and late eluting reference analytes. Drug and metabolite findings by UPLC-MS(E)-TOF were compared with UPLC-MS and UPLC-MS-MS analyses of postmortem blood in 300 medical examiner cases. Positive findings by all methods totaled 1,528, with a detection rate of 57% by UPLC-MS, 72% by UPLC-MS-MS and 80% by combined UPLC-MS and UPLC-MS-MS screening. Compared with nominal mass screening methods, UPLC-MS(E)-TOF screening resulted in a 99% detection rate and, in addition, offered the potential for the detection of nontargeted analytes via high-resolution acquisition of molecular and fragment ion data.

[Evaluation of diabetic retinopathy screening using non-mydriatic fundus camera performed by physicians' assistants in the endocrinology service].

PubMed

Barcatali, M-G; Denion, E; Miocque, S; Reznik, Y; Joubert, M; Morera, J; Rod, A; Mouriaux, F

2015-04-01

Since 2010, the High Authority for health (HAS) recommends the use of non-mydriatic fundus camera for diabetic retinopathy screening. The purpose of this study is to evaluate the results of screening for diabetic retinopathy using the non-mydriatic retinal camera by a physician's assistant in the endocrinology service. This is a retrospective study of all diabetic patients hospitalized in the endocrinology department between May 2013 and November 2013. For each endocrinology patient requiring screening, a previously trained physician's assistant performed fundus photos. The ophthalmologist then provided a written interpretation of the photos on a consultant's sheet. Of the 120 patients screened, 40 (33.3%) patients had uninterpretable photos. Among the 80 interpretable photos, 64 (53.4%) patients had no diabetic retinopathy, and 16 (13.3%) had diabetic retinopathy. No patient had diabetic maculopathy. Specific quality criteria were established by the HAS for screening for diabetic retinopathy using the non-mydriatic retinal camera in order to ensure sufficient sensitivity and specificity. In our study, the two quality criteria were not achieved: the rates of uninterpretable photos and the total number of photos analyzed in a given period. In our center, we discontinued this method of diabetic retinopathy screening due to the high rate of uninterpretable photos. Due to the logistic impossibility of the ophthalmologists taking all the fundus photos, we proposed that the ophthalmic nurses take the photos. They are better trained in the use of the equipment, and can confer directly with an ophthalmologist in questionable cases and to obtain pupil dilation as necessary. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Standing wave performance test of IDT-SAW transducer prepared by silk-screen printing

NASA Astrophysics Data System (ADS)

Wang, Ziping; Jiang, Zhengxuan; Chen, Liangbin; Li, Yefei; Li, Meixia; Wang, Shaohan

2018-05-01

With the advantages of high performance and low loss, interdigital surface acoustic wave (IDT-SAW) transducers are widely used in the fields of nondestructive testing, communication and broadcasting. The production, performance and application of surface acoustic wave (SAW) actuators has become a research hotspot. Based on the basic principle of SAW, an IDT-SAW transducer is designed and fabricated using silk-screen printing in this work. The experiment results show that in terms of SAW performance, the fabricated IDT-SAW transducer can generate standing wave fields comparable to those generated using traditional fabrication methods. The resonant frequency response of the IDT-SAW transducer and SAW attenuation coefficient were obtained by experiments. It has provided a method to test the transducer sensing performance by using fabricated IDT-SAW transducer.

A brief measure of high nicotine dependence for busy clinicians and large epidemiological surveys.

PubMed

Diaz, Francisco J; Jané, Mireia; Saltó, Esteve; Pardell, Hélios; Salleras, Lluís; Pinet, Cristina; de Leon, Jose

2005-03-01

It is important to perform a routine screening of nicotine dependence in psychiatric patients. The Fagerstrom Test for Nicotine Dependence (FTND) is a widely used six-item questionnaire. The Heavy Smoking Index (HSI) is a briefer measure including only two FTND items (time to first cigarette of day and number of daily cigarettes). In a prior study comparing HSI with FTND, a high HSI (score > or = 4) was a good and briefer alternative for detecting high nicotine dependence. The goals of this study were: (i) to compare the effectiveness of the HSI with the effectiveness of Items 1 and 4 alone for the screening of high nicotine dependence; (ii) to investigate the optimality of 4 as a cut-off score for the HSI so that the HSI can be used as a binary indicator of high nicotine dependence; and (iii) to compare the sensitivity and specificity of four indexes of high nicotine dependence, namely 'High HSI', 'Very Early Smoking', 'Heavy Smoking' and 'High in Either Item'. The FTND was administered to 819 current daily smokers from a general population survey. As in a prior study, an FTND score > or = 6 was considered the reference or 'gold standard' test for detecting high nicotine dependence. Receiver-operating characteristic analyses were performed. This new study using more sophisticated statistical methodology verified that a cut-off of 4 for the HSI is appropriate and that the 'high' HSI has good sensitivity and specificity even across different population subclassifications. With four questions (smoking, daily smoking, time to first cigarette of day and number of daily cigarettes) and minimal calculations, it may be possible to screen whether a smoker has high nicotine dependence. If other studies in other populations and settings verify this finding, this brief measure might be an ideal screening instrument for busy clinicians, epidemiologists developing questionnaires for health surveys and psychiatric researchers.

A comparison of the imaging characteristics of the new Kodak Hyper Speed G film with the current T-MAT G/RA film and the CR 9000 system.

PubMed

Monnin, P; Gutierrez, D; Bulling, S; Lepori, D; Verdun, F R

2005-10-07

Three standard radiation qualities (RQA 3, RQA 5 and RQA 9) and two screens, Kodak Lanex Regular and Insight Skeletal, were used to compare the imaging performance and dose requirements of the new Kodak Hyper Speed G and the current Kodak T-MAT G/RA medical x-ray films. The noise equivalent quanta (NEQ) and detective quantum efficiencies (DQE) of the four screen-film combinations were measured at three gross optical densities and compared with the characteristics for the Kodak CR 9000 system with GP (general purpose) and HR (high resolution) phosphor plates. The new Hyper Speed G film has double the intrinsic sensitivity of the T-MAT G/RA film and a higher contrast in the high optical density range for comparable exposure latitude. By providing both high sensitivity and high spatial resolution, the new film significantly improves the compromise between dose and image quality. As expected, the new film has a higher noise level and a lower signal-to-noise ratio than the standard film, although in the high frequency range this is compensated for by a better resolution, giving better DQE results--especially at high optical density. Both screen-film systems outperform the phosphor plates in terms of MTF and DQE for standard imaging conditions (Regular screen at RQA 5 and RQA 9 beam qualities). At low energy (RQA 3), the CR system has a comparable low-frequency DQE to screen-film systems when used with a fine screen at low and middle optical densities, and a superior low-frequency DQE at high optical density.

Detecting and removing multiplicative spatial bias in high-throughput screening technologies.

PubMed

Caraus, Iurie; Mazoure, Bogdan; Nadon, Robert; Makarenkov, Vladimir

2017-10-15

Considerable attention has been paid recently to improve data quality in high-throughput screening (HTS) and high-content screening (HCS) technologies widely used in drug development and chemical toxicity research. However, several environmentally- and procedurally-induced spatial biases in experimental HTS and HCS screens decrease measurement accuracy, leading to increased numbers of false positives and false negatives in hit selection. Although effective bias correction methods and software have been developed over the past decades, almost all of these tools have been designed to reduce the effect of additive bias only. Here, we address the case of multiplicative spatial bias. We introduce three new statistical methods meant to reduce multiplicative spatial bias in screening technologies. We assess the performance of the methods with synthetic and real data affected by multiplicative spatial bias, including comparisons with current bias correction methods. We also describe a wider data correction protocol that integrates methods for removing both assay and plate-specific spatial biases, which can be either additive or multiplicative. The methods for removing multiplicative spatial bias and the data correction protocol are effective in detecting and cleaning experimental data generated by screening technologies. As our protocol is of a general nature, it can be used by researchers analyzing current or next-generation high-throughput screens. The AssayCorrector program, implemented in R, is available on CRAN. makarenkov.vladimir@uqam.ca. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Screening large-scale association study data: exploiting interactions using random forests.

PubMed

Lunetta, Kathryn L; Hayward, L Brooke; Segal, Jonathan; Van Eerdewegh, Paul

2004-12-10

Genome-wide association studies for complex diseases will produce genotypes on hundreds of thousands of single nucleotide polymorphisms (SNPs). A logical first approach to dealing with massive numbers of SNPs is to use some test to screen the SNPs, retaining only those that meet some criterion for further study. For example, SNPs can be ranked by p-value, and those with the lowest p-values retained. When SNPs have large interaction effects but small marginal effects in a population, they are unlikely to be retained when univariate tests are used for screening. However, model-based screens that pre-specify interactions are impractical for data sets with thousands of SNPs. Random forest analysis is an alternative method that produces a single measure of importance for each predictor variable that takes into account interactions among variables without requiring model specification. Interactions increase the importance for the individual interacting variables, making them more likely to be given high importance relative to other variables. We test the performance of random forests as a screening procedure to identify small numbers of risk-associated SNPs from among large numbers of unassociated SNPs using complex disease models with up to 32 loci, incorporating both genetic heterogeneity and multi-locus interaction. Keeping other factors constant, if risk SNPs interact, the random forest importance measure significantly outperforms the Fisher Exact test as a screening tool. As the number of interacting SNPs increases, the improvement in performance of random forest analysis relative to Fisher Exact test for screening also increases. Random forests perform similarly to the univariate Fisher Exact test as a screening tool when SNPs in the analysis do not interact. In the context of large-scale genetic association studies where unknown interactions exist among true risk-associated SNPs or SNPs and environmental covariates, screening SNPs using random forest analyses can significantly reduce the number of SNPs that need to be retained for further study compared to standard univariate screening methods.

Cardiac Screening Prior to Stimulant Treatment of ADHD: A Survey of US-Based Pediatricians

PubMed Central

Rodday, Angie Mae; Saunders, Tully S.; Cohen, Joshua T.; Wong, John B.; Parsons, Susan K.

2012-01-01

OBJECTIVES: To determine pediatricians’ attitudes, barriers, and practices regarding cardiac screening before initiating treatment with stimulants for attention-deficit/hyperactivity disorder. METHODS: A survey of 1600 randomly selected, practicing US pediatricians with American Academy of Pediatrics membership was conducted. Multivariate models were created for 3 screening practices: (1) performing an in-depth cardiac history and physical (H & P) examination, (2) discussing potential stimulant-related cardiac risks, and (3) ordering an electrocardiogram (ECG). RESULTS: Of 817 respondents (51%), 525 (64%) met eligibility criteria. Regarding attitudes, pediatricians agreed that both the risk for sudden cardiac death (SCD) (24%) and legal liability (30%) were sufficiently high to warrant cardiac assessment; 75% agreed that physicians were responsible for informing families about SCD risk. When identifying cardiac disorders, few (18%) recognized performing an in-depth cardiac H & P as a barrier; in contrast, 71% recognized interpreting a pediatric ECG as a barrier. When asked about cardiac screening practices before initiating stimulant treatment for a recent patient, 93% completed a routine H & P, 48% completed an in-depth cardiac H & P, and 15% ordered an ECG. Almost half (46%) reported discussing stimulant-related cardiac risks. Multivariate modeling indicated that ≥1 of these screening practices were associated with physicians’ attitudes about SCD risk, legal liability, their responsibility to inform about risk, their ability to perform an in-depth cardiac H & P, and family concerns about risk. CONCLUSIONS: Variable pediatrician attitudes and cardiac screening practices reflect the limited evidence base and conflicting guidelines regarding cardiac screening. Barriers to identifying cardiac disorders influence practice. PMID:22250023

A High-Content Live-Cell Viability Assay and Its Validation on a Diverse 12K Compound Screen.

PubMed

Chiaravalli, Jeanne; Glickman, J Fraser

2017-08-01

We have developed a new high-content cytotoxicity assay using live cells, called "ImageTOX." We used a high-throughput fluorescence microscope system, image segmentation software, and the combination of Hoechst 33342 and SYTO 17 to simultaneously score the relative size and the intensity of the nuclei, the nuclear membrane permeability, and the cell number in a 384-well microplate format. We then performed a screen of 12,668 diverse compounds and compared the results to a standard cytotoxicity assay. The ImageTOX assay identified similar sets of compounds to the standard cytotoxicity assay, while identifying more compounds having adverse effects on cell structure, earlier in treatment time. The ImageTOX assay uses inexpensive commercially available reagents and facilitates the use of live cells in toxicity screens. Furthermore, we show that we can measure the kinetic profile of compound toxicity in a high-content, high-throughput format, following the same set of cells over an extended period of time.

Automated microscopy for high-content RNAi screening

PubMed Central

2010-01-01

Fluorescence microscopy is one of the most powerful tools to investigate complex cellular processes such as cell division, cell motility, or intracellular trafficking. The availability of RNA interference (RNAi) technology and automated microscopy has opened the possibility to perform cellular imaging in functional genomics and other large-scale applications. Although imaging often dramatically increases the content of a screening assay, it poses new challenges to achieve accurate quantitative annotation and therefore needs to be carefully adjusted to the specific needs of individual screening applications. In this review, we discuss principles of assay design, large-scale RNAi, microscope automation, and computational data analysis. We highlight strategies for imaging-based RNAi screening adapted to different library and assay designs. PMID:20176920

Screening for illicit and medicinal drugs in whole blood using fully automated SPE and ultra-high-performance liquid chromatography with TOF-MS with data-independent acquisition.

PubMed

Pedersen, Anders Just; Dalsgaard, Petur Weihe; Rode, Andrej Jaroslav; Rasmussen, Brian Schou; Müller, Irene Breum; Johansen, Sys Stybe; Linnet, Kristian

2013-07-01

A broad forensic screening method for 256 analytes in whole blood based on a fully automated SPE robotic extraction and ultra-high-performance liquid chromatography (UHPLC) with TOF-MS with data-independent acquisition has been developed. The limit of identification was evaluated for all 256 compounds and 95 of these compounds were validated with regard to matrix effects, extraction recovery, and process efficiency. The limit of identification ranged from 0.001 to 0.1 mg/kg, and the process efficiency exceeded 50% for 73 of the 95 analytes. As an example of application, 1335 forensic traffic cases were analyzed with the presented screening method. Of these, 992 cases (74%) were positive for one or more traffic-relevant drugs above the Danish legal limits. Commonly abused drugs such as amphetamine, cocaine, and frequent types of benzodiazepines were the major findings. Nineteen less frequently encountered drugs were detected e.g. buprenorphine, butylone, cathine, fentanyl, lysergic acid diethylamide, m-chlorophenylpiperazine, 3,4-methylenedioxypyrovalerone, mephedrone, 4-methylamphetamine, p-fluoroamphetamine, and p-methoxy-N-methylamphetamine. In conclusion, using UHPLC-TOF-MS screening with data-independent acquisition resulted in the detection of common drugs of abuse as well as new designer drugs and more rarely occurring drugs. Thus, TOF-MS screening of blood samples constitutes a practical way for screening traffic cases, with the exception of δ-9-tetrahydrocannabinol, which should be handled in a separate method. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of Urine Drug Testing in the Current Opioid Epidemic.

PubMed

Mahajan, Gagan

2017-12-01

While the evidence for urine drug testing for patients on chronic opioid therapy is weak, the guidelines created by numerous medical societies and state and federal regulatory agencies recommend that it be included as one of the tools used to monitor patients for compliance with chronic opioid therapy. To get the most comprehensive results, clinicians should order both an immunoassay screen and confirmatory urine drug test. The immunoassay screen, which can be performed as an in-office point-of-care test or as a laboratory-based test, is a cheap and convenient study to order. Limitations of an immunoassay screen, however, include having a high threshold of detectability and only providing qualitative information about a select number of drug classes. Because of these restrictions, clinicians should understand that immunoassay screens have high false-positive and false-negative rates. Despite these limitations, though, the results can assist the clinician with making preliminary treatment decisions. In comparison, a confirmatory urine drug test, which can only be performed as a laboratory-based test, has a lower threshold of detectability and provides both qualitative and quantitative information. A urine drug test's greater degree of specificity allows for a relatively low false-negative and false-positive rate in contrast to an immunoassay screen. Like any other diagnostic test, an immunoassay screen and a confirmatory urine drug test both possess limitations. Clinicians must keep this in mind when interpreting an unexpected test result and consult with their laboratory when in doubt about the meaning of the test result to avoid making erroneous decisions that negatively impact both the patient and clinician.

A Computable Definition of Sepsis Facilitates Screening and Performance Improvement Tracking.

PubMed

Alessi, Lauren J; Warmus, Holly R; Schaffner, Erin K; Kantawala, Sajel; Carcillo, Joseph; Rosen, Johanna; Horvat, Christopher M

2018-03-01

Sepsis kills almost 5,000 children annually, accounting for 16% of pediatric health care spending in the United States. We sought to identify sepsis within the Electronic Health Record (EHR) of a quaternary children's hospital to characterize disease incidence, improve recognition and response, and track performance metrics. Methods are organized in a plan-do-study-act cycle. During the "plan" phase, electronic definitions of sepsis (blood culture and antibiotic within 24 hours) and septic shock (sepsis plus vasoactive medication) were created to establish benchmark data and track progress with statistical process control. The performance of a screening tool was evaluated in the emergency department. During the "do" phase, a novel inpatient workflow is being piloted, which involves regular sepsis screening by nurses using the tool, and a regimented response to high risk patients. Screening tool use in the emergency department reduced time to antibiotics (Fig. 1). Of the 6,159 admissions, EHR definitions identified 1,433 (23.3%) between July and December 2016 with sepsis, of which 159 (11.1%) had septic shock. Hospital mortality for all sepsis patients was 2.2% and 15.7% for septic shock (Table 1). These findings approximate epidemiologic studies of sepsis and severe sepsis, which report a prevalence range of 0.45-8.2% and mortality range of 8.2-25% (Table 2). 1-5 . Implementation of a sepsis screening tool is associated with improved performance. The prevalence of sepsis conditions identified with electronic definitions approximates the epidemiologic landscape characterized by other point-prevalence and administrative studies, providing face validity to this approach, and proving useful for tracking performance improvement.

High performance in silico virtual drug screening on many-core processors.

PubMed

McIntosh-Smith, Simon; Price, James; Sessions, Richard B; Ibarra, Amaurys A

2015-05-01

Drug screening is an important part of the drug development pipeline for the pharmaceutical industry. Traditional, lab-based methods are increasingly being augmented with computational methods, ranging from simple molecular similarity searches through more complex pharmacophore matching to more computationally intensive approaches, such as molecular docking. The latter simulates the binding of drug molecules to their targets, typically protein molecules. In this work, we describe BUDE, the Bristol University Docking Engine, which has been ported to the OpenCL industry standard parallel programming language in order to exploit the performance of modern many-core processors. Our highly optimized OpenCL implementation of BUDE sustains 1.43 TFLOP/s on a single Nvidia GTX 680 GPU, or 46% of peak performance. BUDE also exploits OpenCL to deliver effective performance portability across a broad spectrum of different computer architectures from different vendors, including GPUs from Nvidia and AMD, Intel's Xeon Phi and multi-core CPUs with SIMD instruction sets.

High performance in silico virtual drug screening on many-core processors

PubMed Central

Price, James; Sessions, Richard B; Ibarra, Amaurys A

2015-01-01

Drug screening is an important part of the drug development pipeline for the pharmaceutical industry. Traditional, lab-based methods are increasingly being augmented with computational methods, ranging from simple molecular similarity searches through more complex pharmacophore matching to more computationally intensive approaches, such as molecular docking. The latter simulates the binding of drug molecules to their targets, typically protein molecules. In this work, we describe BUDE, the Bristol University Docking Engine, which has been ported to the OpenCL industry standard parallel programming language in order to exploit the performance of modern many-core processors. Our highly optimized OpenCL implementation of BUDE sustains 1.43 TFLOP/s on a single Nvidia GTX 680 GPU, or 46% of peak performance. BUDE also exploits OpenCL to deliver effective performance portability across a broad spectrum of different computer architectures from different vendors, including GPUs from Nvidia and AMD, Intel’s Xeon Phi and multi-core CPUs with SIMD instruction sets. PMID:25972727

DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0.

PubMed

Jiang, Xiaohui; Kumar, Kamal; Hu, Xin; Wallqvist, Anders; Reifman, Jaques

2008-09-08

Small-molecule docking is an important tool in studying receptor-ligand interactions and in identifying potential drug candidates. Previously, we developed a software tool (DOVIS) to perform large-scale virtual screening of small molecules in parallel on Linux clusters, using AutoDock 3.05 as the docking engine. DOVIS enables the seamless screening of millions of compounds on high-performance computing platforms. In this paper, we report significant advances in the software implementation of DOVIS 2.0, including enhanced screening capability, improved file system efficiency, and extended usability. To keep DOVIS up-to-date, we upgraded the software's docking engine to the more accurate AutoDock 4.0 code. We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs. We also implemented an algorithm to output docked ligands in an industry standard format, sd-file format, which can be easily interfaced with other modeling programs. Finally, we constructed a wrapper-script interface to enable automatic rescoring of docked ligands by arbitrarily selected third-party scoring programs. The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability. The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands. The new DOVIS 2.0 package is freely available to the public under the GNU General Public License.

A comparison of human papillomavirus testing of clinician-collected and self-collected samples during follow-up after screen-and-treat.

PubMed

Taylor, Sylvia; Wang, Chunhui; Wright, Thomas C; Denny, Lynette; Kuhn, Louise

2011-08-15

Screen-and-treat cervical cancer prevention programs based on high-risk human papillomavirus (HPV) testing and cryotherapy have been shown to be effective in resource-limited settings. However, because cryotherapy is not 100% effective, follow-up is needed after treatment to detect post-treatment failures. We compared the test performances of high-risk HPV testing (Hybrid Capture 2) using self-collected and clinician-collected samples as well as cervical cytology for identifying cervical intraepithelial neoplasia grades 2 or 3 or invasive cervical cancer (CIN2+) among women who did (n=812) and did not (n=1858) undergo cryotherapy in a South African screen-and-treat trial. At 6 months after enrolment (and after cryotherapy, if performed), women were tested using all three screening methods and then underwent colposcopy/biopsy. A predefined subset of women (n=1,455) had extended follow-up with colposcopy/biopsy at 12 months. A total of 33 and 91 cases of CIN2+ were detected among treated and untreated women, respectively. The sensitivity of HPV testing using clinician-collected samples and cervical cytology did not differ by treatment status. HPV testing of clinician-collected samples detected the most cases of CIN2+ among both treated (85%) and untreated (91%) women (p=0.31). Cytology (at a cutoff of atypical squamous cells of undetermined significance or greater) detected 76% of cases among both treated and untreated women. However, the sensitivity of HPV testing using self-collected samples was significantly lower among treated versus untreated women (55% vs. 78%, p=0.01). HPV testing using self-collected vaginal specimens may be useful in primary screening but performs poorly for detecting post-treatment failures. Copyright © 2010 UICC.

Associations among Screen Time and Unhealthy Behaviors, Academic Performance, and Well-Being in Chinese Adolescents.

PubMed

Yan, Hanyi; Zhang, Rui; Oniffrey, Theresa M; Chen, Guoxun; Wang, Yueqiao; Wu, Yingru; Zhang, Xinge; Wang, Quan; Ma, Lu; Li, Rui; Moore, Justin B

2017-06-04

Screen time is negatively associated with markers of health in western youth, but very little is known about these relationships in Chinese youth. Middle-school and high-school students ( n = 2625) in Wuhan, China, completed questionnaires assessing demographics, health behaviors, and self-perceptions in spring/summer 2016. Linear and logistic regression analyses were conducted to determine whether, after adjustment for covariates, screen time was associated with body mass index (BMI), eating behaviors, average nightly hours of sleep, physical activity (PA), academic performance, and psychological states. Watching television on school days was negatively associated with academic performance, PA, anxiety, and life satisfaction. Television viewing on non-school days was positively associated with sleep duration. Playing electronic games was positively associated with snacking at night and less frequently eating breakfast, and negatively associated with sleep duration and self-esteem. Receiving electronic news and study materials on non-school days was negatively associated with PA, but on school days, was positively associated with anxiety. Using social networking sites was negatively associated with academic performance, but positively associated with BMI z-score, PA and anxiety. Screen time in adolescents is associated with unhealthy behaviors and undesirable psychological states that can contribute to poor quality of life.

Associations among Screen Time and Unhealthy Behaviors, Academic Performance, and Well-Being in Chinese Adolescents

PubMed Central

Yan, Hanyi; Zhang, Rui; Oniffrey, Theresa M.; Chen, Guoxun; Wang, Yueqiao; Wu, Yingru; Zhang, Xinge; Wang, Quan; Ma, Lu; Li, Rui; Moore, Justin B.

2017-01-01

Screen time is negatively associated with markers of health in western youth, but very little is known about these relationships in Chinese youth. Middle-school and high-school students (n = 2625) in Wuhan, China, completed questionnaires assessing demographics, health behaviors, and self-perceptions in spring/summer 2016. Linear and logistic regression analyses were conducted to determine whether, after adjustment for covariates, screen time was associated with body mass index (BMI), eating behaviors, average nightly hours of sleep, physical activity (PA), academic performance, and psychological states. Watching television on school days was negatively associated with academic performance, PA, anxiety, and life satisfaction. Television viewing on non-school days was positively associated with sleep duration. Playing electronic games was positively associated with snacking at night and less frequently eating breakfast, and negatively associated with sleep duration and self-esteem. Receiving electronic news and study materials on non-school days was negatively associated with PA, but on school days, was positively associated with anxiety. Using social networking sites was negatively associated with academic performance, but positively associated with BMI z-score, PA and anxiety. Screen time in adolescents is associated with unhealthy behaviors and undesirable psychological states that can contribute to poor quality of life. PMID:28587225

SCREENING FOR PERSONALITY DISORDERS

PubMed Central

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

Comparing Universal Lynch Syndrome Tumor Screening Programs to Evaluate Associations Between Implementation Strategies and Patient Follow-through

PubMed Central

Cragun, Deborah; DeBate, Rita D.; Vadaparampil, Susan T.; Baldwin, Julie; Hampel, Heather; Pal, Tuya

2014-01-01

Purpose Universal tumor screening (UTS) for all colorectal cancer (CRC) patients can improve the identification of Lynch syndrome, the most common cause of hereditary CRC. This multiple-case study explored how variability in UTS procedures influence patient follow-through (PF) with germline testing after a screen-positive result. Methods Data were obtained through web-based surveys and telephone interviews with institutional informants. Institutions were categorized as Low-PF (≤10% underwent germline testing), Medium-PF (11–40%), or High-PF (>40%). To identify implementation procedures (i.e., conditions) unique High-PF institutions, qualitative comparative analysis was performed. Results Twenty-one informants from fifteen institutions completed surveys and/or interviews. Conditions present among all five High-PF institutions included: 1) disclosure of screen-positive results to patients by genetic counselors (GCs); and 2) GCs either facilitate physician referrals to genetics or eliminated the need for referrals. Although both of these High-PF conditions were present among two Medium-PF institutions, automatic reflex testing was lacking and difficulty contacting screen-positive patients was a barrier. The three remaining Medium-PF and five Low-PF institutions lacked High-PF conditions. Conclusion Methods for streamlining UTS procedures, incorporating a high level of involvement of GCs in results tracking and communication, and reducing barriers to patient contact are reviewed within a broader discussion on maximizing the effectiveness and public health impact of UTS. PMID:24651603

Thalassaemia screening and confirmation of carriers in parents.

PubMed

Barrett, Angela N; Saminathan, Ramasamy; Choolani, Mahesh

2017-02-01

Haemoglobinopathies are among the most common inherited monogenic disorders worldwide. Thalassaemia screening for carrier status is recommended for adults of reproductive age if suspected of being at risk. Conventional laboratory methods for screening include the assessment of haematological indices, and high-performance liquid chromatography, capillary electrophoresis or isoelectric focusing to measure the levels of HbA 2 and HbF, and to identify haemoglobin variants. Each screening method has its advantages and disadvantages, the main disadvantage being that none can fully resolve all variants. The complex nature of the genetics of haemoglobinopathies necessitates expertise in the interpretation of screening results to evaluate the most likely genotypes, which must then be confirmed using the DNA diagnosis. This review highlights the limits and pitfalls of each screening technique, and outlines a rational combination of different methods to overcome issues in thalassaemia carrier detection. Copyright © 2016. Published by Elsevier Ltd.

Clinical Validation of Anyplex II HPV HR Detection Test for Cervical Cancer Screening in Korea.

PubMed

Jung, Sunkyung; Lee, Byungdoo; Lee, Kap No; Kim, Yonggoo; Oh, Eun-Jee

2016-03-01

The Anyplex II HPV HR detection kit (Seegene Inc, Seoul, Korea) is a new, multiplex, real-time polymerase chain reaction assay to detect individual 14 high-risk (HR) human papillomavirus (HPV) types in a single tube. To evaluate the clinical performance of the HPV HR kit in predicting high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse in cervical cancer screening. We analyzed 1137 cervical samples in Huro Path medium (CelltraZone, Seoul, Korea) from Korean women. The clinical performance of the HPV HR kit was compared with Hybrid Capture 2 (Qiagen, Valencia, California) using the noninferiority score test in a routine cervical cancer screening setting. The intralaboratory and interlaboratory agreements of HPV HR were also evaluated. Overall agreement between the 2 assays was 92.4% (1051 of 1137) with a κ value of 0.787. Clinical sensitivity of HPV HR for high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse was 94.4% (95% confidence interval [CI], 89.2-99.7) and 92.5% (95% CI, 84.3-100.0), respectively. The respective values for Hybrid Capture 2 were 93.1% (95% CI, 87.2-98.9) and 87.5% (95% CI, 77.3-99.7). Clinical sensitivity and specificity of HPV HR were not inferior to those of Hybrid Capture 2 (P = .005 and P = .04, respectively). The HPV HR showed good intralaboratory and interlaboratory reproducibility at 98.0% (κ = 0.953) and 97.4% (κ = 0.940), respectively. The HPV HR demonstrates comparable performance to the Hybrid Capture 2 test and can be useful for HPV-based cervical cancer screening testing.

A suite of MATLAB-based computational tools for automated analysis of COPAS Biosort data

PubMed Central

Morton, Elizabeth; Lamitina, Todd

2010-01-01

Complex Object Parametric Analyzer and Sorter (COPAS) devices are large-object, fluorescence-capable flow cytometers used for high-throughput analysis of live model organisms, including Drosophila melanogaster, Caenorhabditis elegans, and zebrafish. The COPAS is especially useful in C. elegans high-throughput genome-wide RNA interference (RNAi) screens that utilize fluorescent reporters. However, analysis of data from such screens is relatively labor-intensive and time-consuming. Currently, there are no computational tools available to facilitate high-throughput analysis of COPAS data. We used MATLAB to develop algorithms (COPAquant, COPAmulti, and COPAcompare) to analyze different types of COPAS data. COPAquant reads single-sample files, filters and extracts values and value ratios for each file, and then returns a summary of the data. COPAmulti reads 96-well autosampling files generated with the ReFLX adapter, performs sample filtering, graphs features across both wells and plates, performs some common statistical measures for hit identification, and outputs results in graphical formats. COPAcompare performs a correlation analysis between replicate 96-well plates. For many parameters, thresholds may be defined through a simple graphical user interface (GUI), allowing our algorithms to meet a variety of screening applications. In a screen for regulators of stress-inducible GFP expression, COPAquant dramatically accelerated data analysis and allowed us to rapidly move from raw data to hit identification. Because the COPAS file structure is standardized and our MATLAB code is freely available, our algorithms should be extremely useful for analysis of COPAS data from multiple platforms and organisms. The MATLAB code is freely available at our web site (www.med.upenn.edu/lamitinalab/downloads.shtml). PMID:20569218

Use and imaging performance of CMOS flat panel imager with LiF/ZnS(Ag) and Gadox scintillation screens for neutron radiography

NASA Astrophysics Data System (ADS)

Cha, B. K.; kim, J. Y.; Kim, T. J.; Sim, C.; Cho, G.; Lee, D. H.; Seo, C.-W.; Jeon, S.; Huh, Y.

2011-01-01

In digital neutron radiography system, a thermal neutron imaging detector based on neutron-sensitive scintillating screens with CMOS(complementary metal oxide semiconductor) flat panel imager is introduced for non-destructive testing (NDT) application. Recently, large area CMOS APS (active-pixel sensor) in conjunction with scintillation films has been widely used in many digital X-ray imaging applications. Instead of typical imaging detectors such as image plates, cooled-CCD cameras and amorphous silicon flat panel detectors in combination with scintillation screens, we tried to apply a scintillator-based CMOS APS to neutron imaging detection systems for high resolution neutron radiography. In this work, two major Gd2O2S:Tb and 6LiF/ZnS:Ag scintillation screens with various thickness were fabricated by a screen printing method. These neutron converter screens consist of a dispersion of Gd2O2S:Tb and 6LiF/ZnS:Ag scintillating particles in acrylic binder. These scintillating screens coupled-CMOS flat panel imager with 25x50mm2 active area and 48μm pixel pitch was used for neutron radiography. Thermal neutron flux with 6x106n/cm2/s was utilized at the NRF facility of HANARO in KAERI. The neutron imaging characterization of the used detector was investigated in terms of relative light output, linearity and spatial resolution in detail. The experimental results of scintillating screen-based CMOS flat panel detectors demonstrate possibility of high sensitive and high spatial resolution imaging in neutron radiography system.

A Multiplexed Serum Biomarker Immunoassay Panel Discriminates Clinical Lung Cancer Patients from High-Risk Individuals Found to be Cancer-Free by CT Screening

PubMed Central

Bigbee, William L.; Gopalakrishnan, Vanathi; Weissfeld, Joel L.; Wilson, David O.; Dacic, Sanja; Lokshin, Anna E.; Siegfried, Jill M.

2012-01-01

Introduction Clinical decision-making in the setting of CT screening could benefit from accessible biomarkers that help predict the level of lung cancer risk in high-risk individuals with indeterminate pulmonary nodules. Methods To identify candidate serum biomarkers, we measured 70 cancer-related proteins by Luminex xMAP® multiplexed immunoassays in a training set of sera from 56 patients with biopsy-proven primary non small cell lung cancer and 56 age-, sex- and smoking-matched CT-screened controls. Results We identified a panel of 10 serum biomarkers – prolactin, transthyretin, thrombospondin-1, E-selectin, C-C motif chemokine 5, macrophage migration inhibitory factor, plasminogen activator inhibitor, receptor tyrosine-protein kinase, Cyfra 21.1, and serum amyloid A – that distinguished lung cancer from controls with an estimated balanced accuracy (average of sensitivity and specificity) of 76.0%±3.8% from 20-fold internal cross-validation. We then iteratively evaluated this model in independent test and verification case/control studies confirming the initial classification performance of the panel. The classification performance of the 10-biomarker panel was also analytically validated using ELISAs in a second independent case/control population further validating the robustness of the panel. Conclusions The performance of this 10-biomarker panel based model was 77.1% sensitivity/76.2% specificity in cross-validation in the expanded training set, 73.3% sensitivity/93.3% specificity (balanced accuracy 83.3%) in the blinded verification set with the best discriminative performance in Stage I/II cases: 85% sensitivity (balanced accuracy 89.2%). Importantly, the rate of misclassification of CT-screened controls was not different in most control subgroups with or without airflow obstruction or emphysema or pulmonary nodules. These biomarkers have potential to aid in the early detection of lung cancer and more accurate interpretation of indeterminate pulmonary nodules detected by screening CT. PMID:22425918

A pilot study of community-based self-sampling for HPV testing among non-attenders of cervical cancer screening programs in El Salvador.

PubMed

Laskow, Bari; Figueroa, Ruben; Alfaro, Karla M; Scarinci, Isabel C; Conlisk, Elizabeth; Maza, Mauricio; Chang, Judy C; Cremer, Miriam

2017-08-01

To establish the feasibility and acceptability of home-based HPV self-sampling among women who did not attend screening appointments in rural El Salvador. In a cross-sectional study, data were collected from May 2015 to January 2016 among 60 women aged 30-59 years who were not pregnant, provided informed consent, had not been screened in 2 years, had no history of pre-cancer treatment, and did not attend a scheduled HPV screening. Participants completed questionnaires and received educational information before being given an opportunity to self-sample with the Hybrid Capture 2 High Risk HPV DNA Test. Self-sampling was accepted by 41 (68%) participants. Almost all women chose to self-sample because the process was easy (40/41, 98%), could be performed at home (40/41, 98%), and saved time (38/41, 93%), and because they felt less embarrassed (33/41, 80%). The most common reason for declining the test was not wanting to be screened (8/19, 42%). The prevalence of high-risk HPV types among women who accepted self-sampling was 17% (7/41). For most women, community-based self-sampling was an acceptable way to participate in a cervical cancer screening program. In low-resource countries, incorporating community-based self-sampling into screening programs might improve coverage of high-risk women. © 2017 International Federation of Gynecology and Obstetrics.

Exploiting PubChem for Virtual Screening

PubMed Central

Xie, Xiang-Qun

2011-01-01

Importance of the field PubChem is a public molecular information repository, a scientific showcase of the NIH Roadmap Initiative. The PubChem database holds over 27 million records of unique chemical structures of compounds (CID) derived from nearly 70 million substance depositions (SID), and contains more than 449,000 bioassay records with over thousands of in vitro biochemical and cell-based screening bioassays established, with targeting more than 7000 proteins and genes linking to over 1.8 million of substances. Areas covered in this review This review builds on recent PubChem-related computational chemistry research reported by other authors while providing readers with an overview of the PubChem database, focusing on its increasing role in cheminformatics, virtual screening and toxicity prediction modeling. What the reader will gain These publicly available datasets in PubChem provide great opportunities for scientists to perform cheminformatics and virtual screening research for computer-aided drug design. However, the high volume and complexity of the datasets, in particular the bioassay-associated false positives/negatives and highly imbalanced datasets in PubChem, also creates major challenges. Several approaches regarding the modeling of PubChem datasets and development of virtual screening models for bioactivity and toxicity predictions are also reviewed. Take home message Novel data-mining cheminformatics tools and virtual screening algorithms are being developed and used to retrieve, annotate and analyze the large-scale and highly complex PubChem biological screening data for drug design. PMID:21691435

Detection of protein-small molecule binding using a self-referencing external cavity laser biosensor.

PubMed

Meng Zhang; Peh, Jessie; Hergenrother, Paul J; Cunningham, Brian T

2014-01-01

High throughput screening of protein-small molecule binding interactions using label-free optical biosensors is challenging, as the detected signals are often similar in magnitude to experimental noise. Here, we describe a novel self-referencing external cavity laser (ECL) biosensor approach that achieves high resolution and high sensitivity, while eliminating thermal noise with sub-picometer wavelength accuracy. Using the self-referencing ECL biosensor, we demonstrate detection of binding between small molecules and a variety of immobilized protein targets with binding affinities or inhibition constants in the sub-nanomolar to low micromolar range. The demonstrated ability to perform detection in the presence of several interfering compounds opens the potential for increasing the throughput of the approach. As an example application, we performed a "needle-in-the-haystack" screen for inhibitors against carbonic anhydrase isozyme II (CA II), in which known inhibitors are clearly differentiated from inactive molecules within a compound library.

Identifying congenital hearing impairment. Personal experience based on selective hearing screening.

PubMed

Molini, E; Ricci, G; Baroni, S; Ciorba, A; Bellocci, A; Simoncelli, C

2004-06-01

If all degrees of permanent uni- or bilateral hypoacusis are taken into consideration, hearing impairment is the most common congenital disease. Early detection of permanent infantile hearing impairment has become extremely important in preventive medicine, since steps can be taken with hearing aids and rehabilitation to ensure better development of language and higher cognitive functions. Aim of this study is to provide a critical review of the time of diagnosis of hypoacusis at our audiology laboratory, where two methods were used to screen hearing of children with/without risk indicators. Results of approximately 10 years' work were re-examined during which time outpatient screening was conducted on children referred by colleagues in neonatology and paediatrics. All were carriers of congenital risk indicators associated with sensorineural and/or conductive hearing loss, based on the Joint Committee on Infant Hearing findings, or were suspected of being hypoacusic even if they had no known congenital risk factors. Hearing screening was conducted in hospital on newborns with no risk factors, within the first few days of birth. Results of the present study showed that when selective hearing screening was performed, the mean age of high-risk patients diagnosed with hypoacusis was slightly higher than that in international guidelines. Moreover, these patients represent approximately half the hypoacusic population identified in the study period. The other half of congenital hypoacusic subjects identified had no risk indicators and there was a significant delay in diagnosis due to later manifestation of symptoms indicating hypoacusis, and thus, in turn, delayed referral for hearing tests. In contrast, subjects without risk indicators who underwent in-hospital hearing screening and proved to be hypoacusic, were diagnosed early. In our experience, however, universal screening has considerable disadvantages, such as difficulty in covering the entire population, difficulty in follow-up after discharge from hospital, and last, but by no means least, significant organisational and professional commitments, making it impossible to perform in all hospitals. In order to ensure effective hearing screening for congenital hearing loss and, thus permit prompt identification of hypoacusic children, use of hearing aids and rehabilitation screening should incorporate two aspects. First, selection should be compulsory, thereby reducing waiting time between collecting case histories and performing outpatient tests; second, hospital screening of children without risk factors should be performed whenever possible. Integrating these two aspects would make it possible to approach the "utopia" of universal hearing screening.

Outcomes of transient evoked otoacoustic emission testing in 6-year-old school children: a comparison with pure tone screening and tympanometry.

PubMed

Driscoll, C; Kei, J; McPherson, B

2001-01-01

(1) To establish test performance measures for Transient Evoked Otoacoustic Emission testing of 6-year-old children in a school setting; (2) To investigate whether Transient Evoked Otoacoustic Emission testing provides a more accurate and effective alternative to a pure tone screening plus tympanometry protocol. Pure tone screening, tympanometry and transient evoked otoacoustic emission data were collected from 940 subjects (1880 ears), with a mean age of 6.2 years. Subjects were tested in non-sound-treated rooms within 22 schools. Receiver operating characteristics curves along with specificity, sensitivity, accuracy and efficiency values were determined for a variety of transient evoked otoacoustic emission/pure tone screening/tympanometry comparisons. The Transient Evoked Otoacoustic Emission failure rate for the group was 20.3%. The failure rate for pure tone screening was found to be 8.9%, whilst 18.6% of subjects failed a protocol consisting of combined pure tone screening and tympanometry results. In essence, findings from the comparison of overall Transient Evoked Otoacoustic Emission pass/fail with overall pure tone screening pass/fail suggested that use of a modified Rhode Island Hearing Assessment Project criterion would result in a very high probability that a child with a pass result has normal hearing (true negative). However, the hit rate was only moderate. Selection of a signal-to-noise ratio (SNR) criterion set at > or =1 dB appeared to provide the best test performance measures for the range of SNR values investigated. Test performance measures generally declined when tympanometry results were included, with the exception of lower false alarm rates and higher positive predictive values. The exclusion of low frequency data from the Transient Evoked Otoacoustic Emission SNR versus pure tone screening analysis resulted in improved performance measures. The present study poses several implications for the clinical implementation of Transient Evoked Otoacoustic Emission screening for entry level school children. Transient Evoked Otoacoustic Emission pass/fail criteria will require revision. The findings of the current investigation offer support to the possible replacement of pure tone screening with Transient Evoked Otoacoustic Emission testing for 6-year-old children. However, they do not suggest the replacement of the pure tone screening plus tympanometry battery.

The effectiveness and cost-effectiveness of screening for active tuberculosis among migrants in the EU/EEA: a systematic review.

PubMed

Greenaway, Christina; Pareek, Manish; Abou Chakra, Claire-Nour; Walji, Moneeza; Makarenko, Iuliia; Alabdulkarim, Balqis; Hogan, Catherine; McConnell, Ted; Scarfo, Brittany; Christensen, Robin; Tran, Anh; Rowbotham, Nick; Noori, Teymur; van der Werf, Marieke J; Pottie, Kevin; Matteelli, Alberto; Zenner, Dominik; Morton, Rachael L

2018-04-01

The foreign-born population make up an increasing and large proportion of tuberculosis (TB) cases in European Union/European Economic Area (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods : We conducted a systematic review to determine effectiveness (yield and performance of chest radiography (CXR) to detect active TB, treatment outcomes and acceptance of screening) and a second systematic review on cost-effectiveness of screening for active TB among migrants living in the EU/EEA. Results : We identified six systematic reviews, one report and three individual studies that addressed our aims. CXR was highly sensitive (98%) but only moderately specific (75%). The yield of detecting active TB with CXR screening among migrants was 350 per 100,000 population overall but ranged widely by host country (110-2,340), migrant type (170-1,192), TB incidence in source country (19-336) and screening setting (220-1,720). The CXR yield was lower (19.6 vs 336/100,000) and the numbers needed to screen were higher (5,076 vs 298) among migrants from source countries with lower TB incidence (≤ 50 compared with ≥ 350/100,000). Cost-effectiveness was highest among migrants originating from high (> 120/100,000) TB incidence countries. The foreign-born had similar or better TB treatment outcomes than those born in the EU/EEA. Acceptance of CXR screening was high (85%) among migrants. Discussion : Screening programmes for active TB are most efficient when targeting migrants from higher TB incidence countries. The limited number of studies identified and the heterogeneous evidence highlight the need for further data to inform screening programmes for migrants in the EU/EEA.

Relationships Between Performance on Assessments of Executive Function and Fall Risk Screening Measures in Community-Dwelling Older Adults.

PubMed

Blackwood, Jennifer; Shubert, Tiffany; Forgarty, Kieran; Chase, Carla

2016-01-01

Fall-related injuries are a leading cause of institutionalization and morbidity in older adults. Limitations in cognition, including deficits in higher cognitive processes, like executive function (EF), contribute to a higher risk of falling in older adults. Specifically, declines in EF have been associated with changes in gait, limited mobility, and an increased frequency of falling. It is unknown whether associations between performance on commonly used clinical assessments of EF and performance on commonly used physical performance measures of fall risk are present. The purpose of this study was to examine the relationship between a clinical measure of EF, the Trail Making Test Part B (TMT-B), and 3 physical performance measures of fall risk: the Timed Up and Go (TUG) test, gait speed, and the Five Times Sit to Stand (FTSTS) test, in a group of community-dwelling older adults. Forty-seven community-dwelling older adults met the inclusion/exclusion criteria. Demographic information was obtained and measures of fall risk and cognition were performed. Correlations and linear regression analyses to assess relationships between measures were completed. To account for the high prevalence of mild cognitive impairment (MCI) in this population, the sample was screened and stratified for MCI in post hoc analyses. The EF performance was not significantly correlated with performance on the FTSTS test (ρ = 0.26, P > .05) but was significantly correlated with the TUG test (ρ = 0.31, P < .05) and gait speed (r = -0.36, P < .05). These relationships remained after adjusting for age and education in multivariate models. Results from post hoc analyses demonstrated that only those with MCI had significant relationships between EF and physical performance measures. TMT-B scores in the MCI group were significantly correlated with gait speed (ρ = -0.51, P < .05) and TUG test (ρ = 0.58, P < .05). A significant relationship exists between performance on clinical assessments of EF and fall risk assessments that integrate a mobility task for those individuals who screen positive for MCI. For those who screened negative, no significant relationship exists. Given the large prevalence of undiagnosed MCI in community-dwelling older adults, this finding could be used as an indication to screen older adults for MCI. Screening tools that require cognitive resources such as gait speed appear to have significant relationships with performance of EF for those who screen positive for MCI. This information could be used clinically to identify older adults with cognitive limitations, which could put them at higher risk for falling.

High test positivity and low positive predictive value for colorectal cancer of continued faecal occult blood test screening after negative colonoscopy.

PubMed

Brown, Jeremy P; Wooldrage, Kate; Wright, Suzanne; Nickerson, Claire; Cross, Amanda J; Atkin, Wendy S

2018-06-01

Objectives The English Bowel Cancer Screening Programme offers biennial guaiac faecal occult blood test (gFOBT) screening to 60-74-year-olds. Participants with positive results are referred for follow-up, but many do not have significant findings. If they remain age eligible, these individuals are reinvited for gFOBT screening. We evaluated the performance of repeat screening in this group. Methods We analysed data on programme participants reinvited to gFOBT screening after either previous negative gFOBT ( n = 327,542), or positive gFOBT followed by a diagnostic investigation negative for colorectal cancer (CRC) or adenomas requiring surveillance ( n = 42,280). Outcomes calculated were uptake, test positivity, yield of CRC, and positive predictive value (PPV) of gFOBT for CRC. Results For participants with a previous negative gFOBT, uptake in the subsequent screening round was 87.5%, positivity was 1.3%, yield of CRC was 0.112% of those adequately screened, and the PPV of gFOBT for CRC was 9.1%. After a positive gFOBT and a negative diagnostic investigation, uptake in the repeat screening round was 82.6%, positivity was 11.3%, CRC yield was 0.172% of participants adequately screened, and the PPV of gFOBT for CRC was 1.7%. Conclusion With high positivity and low PPV for CRC, the suitability of routine repeat gFOBT screening in two years among individuals with a previous positive test and a negative diagnostic examination needs to be carefully considered.

Is it worth screening for vancomycin-resistant Enterococcus faecium colonization?: Financial burden of screening in a developing country.

PubMed

Ulu-Kilic, Aysegul; Özhan, Esra; Altun, Dilek; Perçin, Duygu; Güneş, Tamer; Alp, Emine

2016-04-01

The screening of critically ill patients at high risk of vancomycin resistant enterococci (VRE) colonization, to detect and isolate colonized patients, is recommended to prevent and control the transmission of VRE. Screening asymptomatic carriers brings financial burden for institutions. In this study, we performed risk analysis for VRE colonization and determined the financial burden of screening in a middle-income country, Turkey. We retrospectively analyzed the VRE surveillance data from a pediatric hospital between 2010 and 2014. A case-control study was conducted to identify the risk factors of colonization. Total cost of VRE screening and additional costs for a VRE colonized patient (including active surveillance cultures and contact isolation) were calculated. During the 4-year period, 6,372 patients were screened for perirectal VRE colonization. The rate of culture-positive specimens among all patients screened was 239 (3.75%). The rate of VRE infection was 0.04% (n = 3) among all patients screened. Length of hospital stay, malignancy, and being transferred from another institution were independently associated risk factors for colonization. Annual estimated costs for the laboratory were projected as $19,074 (76,295/4) for all patients screened. Cost of contact isolation for each patient colonized in a ward and an intensive care unit was $270 and $718, respectively. In developing countries, institutions should identify their own high-risk patients; screening priorities should be based on prevalence of infection and hospital financial resources. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

20180312 - Uncertainty and Variability in High-Throughput Toxicokinetics for Risk Prioritization (SOT)

EPA Science Inventory

Streamlined approaches that use in vitro experimental data to predict chemical toxicokinetics (TK) are increasingly being used to perform risk-based prioritization based upon dosimetric adjustment of high-throughput screening (HTS) data across thousands of chemicals. However, ass...

Performance of an automated electronic acute lung injury screening system in intensive care unit patients.

PubMed

Koenig, Helen C; Finkel, Barbara B; Khalsa, Satjeet S; Lanken, Paul N; Prasad, Meeta; Urbani, Richard; Fuchs, Barry D

2011-01-01

Lung protective ventilation reduces mortality in patients with acute lung injury, but underrecognition of acute lung injury has limited its use. We recently validated an automated electronic acute lung injury surveillance system in patients with major trauma in a single intensive care unit. In this study, we assessed the system's performance as a prospective acute lung injury screening tool in a diverse population of intensive care unit patients. Patients were screened prospectively for acute lung injury over 21 wks by the automated system and by an experienced research coordinator who manually screened subjects for enrollment in Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSNet) trials. Performance of the automated system was assessed by comparing its results with the manual screening process. Discordant results were adjudicated blindly by two physician reviewers. In addition, a sensitivity analysis using a range of assumptions was conducted to better estimate the system's performance. The Hospital of the University of Pennsylvania, an academic medical center and ARDSNet center (1994-2006). Intubated patients in medical and surgical intensive care units. None. Of 1270 patients screened, 84 were identified with acute lung injury (incidence of 6.6%). The automated screening system had a sensitivity of 97.6% (95% confidence interval, 96.8-98.4%) and a specificity of 97.6% (95% confidence interval, 96.8-98.4%). The manual screening algorithm had a sensitivity of 57.1% (95% confidence interval, 54.5-59.8%) and a specificity of 99.7% (95% confidence interval, 99.4-100%). Sensitivity analysis demonstrated a range for sensitivity of 75.0-97.6% of the automated system under varying assumptions. Under all assumptions, the automated system demonstrated higher sensitivity than and comparable specificity to the manual screening method. An automated electronic system identified patients with acute lung injury with high sensitivity and specificity in diverse intensive care units of a large academic medical center. Further studies are needed to evaluate the effect of automated prompts that such a system can initiate on the use of lung protective ventilation in patients with acute lung injury.

Field-expedient screening and injury risk algorithm categories as predictors of noncontact lower extremity injury.

PubMed

Lehr, M E; Plisky, P J; Butler, R J; Fink, M L; Kiesel, K B; Underwood, F B

2013-08-01

In athletics, efficient screening tools are sought to curb the rising number of noncontact injuries and associated health care costs. The authors hypothesized that an injury prediction algorithm that incorporates movement screening performance, demographic information, and injury history can accurately categorize risk of noncontact lower extremity (LE) injury. One hundred eighty-three collegiate athletes were screened during the preseason. The test scores and demographic information were entered into an injury prediction algorithm that weighted the evidence-based risk factors. Athletes were then prospectively followed for noncontact LE injury. Subsequent analysis collapsed the groupings into two risk categories: Low (normal and slight) and High (moderate and substantial). Using these groups and noncontact LE injuries, relative risk (RR), sensitivity, specificity, and likelihood ratios were calculated. Forty-two subjects sustained a noncontact LE injury over the course of the study. Athletes identified as High Risk (n = 63) were at a greater risk of noncontact LE injury (27/63) during the season [RR: 3.4 95% confidence interval 2.0 to 6.0]. These results suggest that an injury prediction algorithm composed of performance on efficient, low-cost, field-ready tests can help identify individuals at elevated risk of noncontact LE injury. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Assessment of HPV detection assays for use in cervical cancer screening programs].

PubMed

Cañadas, M Paz; Lloveras, Belén; Lorincz, Attila; Ejarque, Maijo; Font, Rebeca; Bosch, F Xavier; de Sanjosé, Silvia

2006-01-01

Detection of high-risk human papillomavirus types (HPV) infection is an important tool in the screening of cervical cancer and triage of cytological abnormalities. The different techniques for detection of this cancer need to be contrasted and validated for use in population screening. Cervical cell samples were collected from 166 women attending a dermatology clinic in Oviedo (Spain). We evaluated the performance of three different assays for VPH detection. The methods utilized were 1) In-house PCR-EIA using LI consensus primers MY09/ MY11, 2) A PCR-reverse line blot hybridization (PCR-LBH) that uses LI consensus PGMY primers. 3) Hybrid Capture 2. All assays were performed blinded. The kappa statistic was used to test for global agreement between assay pairs. HPV DNA was detected in 24,7%, 25,3% and 29,5% of the women, respective to the assay. The overall agreement between the in-house PCR, PCR-LBH and HC2 was (73.5%) with all kappa values between assay pairs exceeding 0.56 (p<0.001). The three HPV assays were equally accurate in estimating high-risk HPV prevalence and HPV-related lesions. The method for HPV detection must be decided depending on the goals of the search (screening, follow-up or molecular studies).

Development of a language screening instrument for Swedish 4-year-olds.

PubMed

Lavesson, Ann; Lövdén, Martin; Hansson, Kristina

2018-05-01

The Swedish Program for health surveillance of preschool children includes screening of language and communication abilities. One important language screening is carried out at age 4 years as part of a general screening conducted by health nurses at child health centres. The instruments presently in use for this screening mainly focus on expressive phonology. This may result in both over-referral of children with phonological difficulties and under-referral of children with language disorders (LDs), involving difficulties with vocabulary, grammar and/or language comprehension. Previous research has proposed non-word repetition as a clinical marker for LD. It has also been found that higher predictive power is achieved when non-word repetition is combined with the assessment of lexical/semantic skills. Taking these findings into account, the construction of a language screening instrument may yield more adequate referrals to speech-language therapists (SLTs). To construct a new standardized language screening instrument for 4-year-olds and to test its properties. An instrument was developed and revised after piloting. A population of 352 children was screened at the regular 4-year check-up by 11 health nurses. The final sample consisted of 328 children aged 46-53 months (23% multilingual). Children performing below a preliminary cut-off were referred to an SLT (n = 52). Five SLTs carried out an assessment on average within 5 weeks using a gold standard language test battery. Children who screened negatively were followed up with a parent questionnaire at age 5;6. Thirty-one true-positives and 11 false-positives were identified after SLT assessment. A further six children were identified as false-negatives (two through referral to an SLT and four through parent questionnaire at age 5;6). A receiver-operating characteristics curve with a C statistic of .94 was calculated. Based on optimal cut-off, the sensitivity of the screening instrument was found to be .84, and specificity was .96. Multilingual children performed similar to monolingual children; boys performed significantly lower than girls; and children with a family history of language-related problems performed lower than those without. Interrater reliability was high, as was Cronbach's alpha. The screening instrument seems sufficiently valid for its purpose to identify children who need further assessment by an SLT. A follow-up study including SLT assessment for all children to check for false-negatives would be interesting in future, as would studies comparing results from the 4-year screening with those from earlier screens. © 2018 Royal College of Speech and Language Therapists.

Automated high-performance cIMT measurement techniques using patented AtheroEdge™: a screening and home monitoring system.

PubMed

Molinari, Filippo; Meiburger, Kristen M; Suri, Jasjit

2011-01-01

The evaluation of the carotid artery wall is fundamental for the assessment of cardiovascular risk. This paper presents the general architecture of an automatic strategy, which segments the lumen-intima and media-adventitia borders, classified under a class of Patented AtheroEdge™ systems (Global Biomedical Technologies, Inc, CA, USA). Guidelines to produce accurate and repeatable measurements of the intima-media thickness are provided and the problem of the different distance metrics one can adopt is confronted. We compared the results of a completely automatic algorithm that we developed with those of a semi-automatic algorithm, and showed final segmentation results for both techniques. The overall rationale is to provide user-independent high-performance techniques suitable for screening and remote monitoring.

Health-related quality of life, anxiety and depression related to mammography screening in Norway.

PubMed

Hafslund, Bjorg; Espehaug, Birgitte; Nortvedt, Monica Wammen

2012-11-01

To measure health-related quality of life, anxiety and depression ahead of mammography screening and to assess any differences in health-related quality of life compared to reference population. The study of health-related quality of life among attendees prior to mammography screening has received little attention, and increased knowledge is needed to better understand the overall health benefits of participation. A two-group cross-sectional comparative study was performed. The samples comprised 4,249 attendees to mammography screening and a comparison group of 943 women. We used the SF-36 Health Survey to assess health-related quality of life. Linear regression was used to study any differences between the groups with adjustment for age, level of education, occupation, having children and smoking status. Other normative data were also used. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Attendees scored statistically significant higher on the SF-36 than the comparison group but were in line with normative data. Attendees had anxiety mean 4·1 and depression mean 2·6. The majority of the attendees have a high health-related quality of life, low anxiety and depression ahead of screening. Anxiety and depression were less than shown in normative data from Norway. Despite a high health-related quality of life, low anxiety and depression among the majority, healthcare workers should pay special attention to the few women who are anxious and depressed, and have a lower health-related quality of life. Omitted from mammography screening may be women who are unemployed, have lower socioeconomic status, are anxious and are depressed. Further research should be performed with non-attendees and subgroups to improve the screening programme. It is important to identify which patients have the greatest need for support and caring in an organised mammography screening and who may be overlooked. © 2012 Blackwell Publishing Ltd.

Patient navigation for lung cancer screening among current smokers in community health centers a randomized controlled trial.

PubMed

Percac-Lima, Sanja; Ashburner, Jeffrey M; Rigotti, Nancy A; Park, Elyse R; Chang, Yuchiao; Kuchukhidze, Salome; Atlas, Steven J

2018-03-01

Annual chest computed tomography (CT) can decrease lung cancer mortality in high-risk individuals. Patient navigation improves cancer screening rates in underserved populations. Randomized controlled trial was conducted from February 2016 to January 2017 to evaluate the impact of a patient navigation program on lung cancer screening (LCS) among current smokers in five community health centers (CHCs) affiliated with an academic primary care network. We randomized 1200 smokers aged 55-77 years to intervention (n = 400) or usual care (n = 800). Navigators contacted patients to determine LCS eligibility, introduce shared decision making about screening, schedule appointments with primary care physicians (PCPs), and help overcome barriers to obtaining screening and follow-up. Control patients received usual care. The main outcome was the proportion of patients who had any chest CT. Secondary outcomes were the proportion of patients contacted, proportion receiving LCS CTs, screening results and number of lung cancers diagnosed. Of the 400 intervention patients, 335 were contacted and 76 refused participation. Of the 259 participants, 124 (48%) were ineligible for screening; 119 had smoked <30 pack-years, and five had competing comorbidities. Among the 135 eligible participants in the intervention group, 124 (92%) had any chest CT performed. In intention-to-treat analyses, 124 intervention patients (31%) had any chest CT versus 138 control patients (17.3%, P < 0.001). LCS CTs were performed in 94 intervention patients (23.5%) versus 69 controls (8.6%, P < 0.001). A total of 20% of screened patients required follow-up. Lung cancer was diagnosed in eight intervention (2%) and four control (0.5%) patients. A patient navigation program implemented in CHCs significantly increased LCS among high-risk current smokers. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Ultrathin disposable gastroscope for screening and surveillance of gastroesophageal varices in patients with liver cirrhosis: a prospective comparative study.

PubMed

Huynh, Dep K; Toscano, Leanne; Phan, Vinh-An; Ow, Tsai-Wing; Schoeman, Mark; Nguyen, Nam Q

2017-06-01

This study aims to evaluate the role of unsedated, ultrathin disposable gastroscopy (TDG) against conventional gastroscopy (CG) in the screening and surveillance of gastroesophageal varices (GEVs) in patients with liver cirrhosis. Forty-eight patients (56.4 ± 1.3 years; 38 male, 10 female) with liver cirrhosis referred for screening (n = 12) or surveillance (n = 36) of GEVs were prospectively enrolled. Unsedated gastroscopy was initially performed with TDG, followed by CG with conscious sedation. The 2 gastroscopies were performed by different endoscopists blinded to the results of the previous examination. Video recordings of both gastroscopies were validated by an independent investigator in a random, blinded fashion. Endpoints were accuracy and interobserver agreement of detecting GEVs, safety, and potential cost saving. CG identified GEVs in 26 (54%) patients, 10 of whom (21%) had high-risk esophageal varices (HREV). Compared with CG, TDG had an accuracy of 92% for the detection of all GEVs, which increased to 100% for high-risk GEVs. The interobserver agreement for detecting all GEVs on TDG was 88% (κ = 0.74). This increased to 94% (κ = 0.82) for high-risk GEVs. There were no serious adverse events. Unsedated TDG is safe and has high diagnostic accuracy and interobserver reliability for the detection of GEVs. The use of clinic-based TDG would allow immediate determination of a follow-up plan, making it attractive for variceal screening and surveillance programs. (Clinical trial (ANZCTR) registration number: ACTRN12616001103459.). Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Performance Characteristics of the Reverse Syphilis Screening Algorithm in a Population With a Moderately High Prevalence of Syphilis.

PubMed

Rourk, Angela R; Nolte, Frederick S; Litwin, Christine M

2016-11-01

With the recent introduction of automated treponemal tests, a new reverse syphilis algorithm has been proposed and now used by many clinical laboratories. We analyzed the impact of instituting the reverse screening syphilis algorithm in a laboratory that serves a geographic area with a moderately high prevalence of syphilis infection. Serum samples sent for syphilis testing were tested using a treponemal enzyme immunoassay (EIA) as the screening assay. EIA reactive samples were tested by rapid plasma reagin (RPR) and titered to end point if reactive. RPR nonreactive samples were analyzed by the Treponema pallidum particle agglutination test (TP-PA). Pertinent medical records were reviewed for false-reactive screens and samples with evidence of past syphilis infection. Among 10,060 patients tested, 502 (5%) were reactive on the initial EIA screen. The RPR was reactive in 150 (1.5%). TP-PA testing determined that 103 (1.0%) were falsely reactive on initial EIA screen. The reverse screening algorithm, however, identified 242 (2.4%) with evidence of latent, secondary, or past syphilis, 21 of whom had no or unknown prior treatment with antibiotics. Despite a 1.0% false-reactive rate, the reverse syphilis algorithm detected 21 patients with possible latent syphilis that may have gone undetected by traditional syphilis screening. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Oral cancer screening and socioeconomic status.

PubMed

Johnson, Stephanie; McDonald, J Ted; Corsten, Martin

2012-04-01

To determine if awareness of oral cancer screening correlates with socioeconomic status (SES) and to determine if screening for oral cancer correlates with SES. Data were obtained from the 2008 American National Health Interview Survey (NHIS). Our primary measure of SES was education; additional measures for SES included income, race, health insurance, and immigration status. We performed a logistic regression analysis, controlling for important demographic characteristics. Awareness of oral cancer screening increases with higher education levels (< grade 9 OR 0.37 [CI 0.29-0.48], grade 9-12 OR 0.53 [CI 0.44-0.65], high school OR 0.68 [CI 0.59-0.77], higher degree OR 1.13 [CI 0.96-1.34]). Similarly, screening for oral cancer increases with higher education levels (< grade 9 OR 0.31 [CI 0.23-0.42], grade 9-12 OR 0.34 [CI 0.26-0.43], high school OR 0.60 [CI 0.52-0.68], higher degree OR 1.41 [CI 1.18-1.67]). We found that race, income, immigration, and health insurance status were statistically significant correlates with oral cancer awareness and screening. Higher SES individuals are more likely to be aware of and screened for oral cancer. This is problematic because oral cancers are more prevalent in low SES groups. Future awareness and screening campaigns should be directed at vulnerable low SES populations.

Whole organism high content screening identifies stimulators of pancreatic beta-cell proliferation.

PubMed

Tsuji, Naoki; Ninov, Nikolay; Delawary, Mina; Osman, Sahar; Roh, Alex S; Gut, Philipp; Stainier, Didier Y R

2014-01-01

Inducing beta-cell mass expansion in diabetic patients with the aim to restore glucose homeostasis is a promising therapeutic strategy. Although several in vitro studies have been carried out to identify modulators of beta-cell mass expansion, restoring endogenous beta-cell mass in vivo has yet to be achieved. To identify potential stimulators of beta-cell replication in vivo, we established transgenic zebrafish lines that monitor and allow the quantification of cell proliferation by using the fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology. Using these new reagents, we performed an unbiased chemical screen, and identified 20 small molecules that markedly increased beta-cell proliferation in vivo. Importantly, these structurally distinct molecules, which include clinically-approved drugs, modulate three specific signaling pathways: serotonin, retinoic acid and glucocorticoids, showing the high sensitivity and robustness of our screen. Notably, two drug classes, retinoic acid and glucocorticoids, also promoted beta-cell regeneration after beta-cell ablation. Thus, this study establishes a proof of principle for a high-throughput small molecule-screen for beta-cell proliferation in vivo, and identified compounds that stimulate beta-cell proliferation and regeneration.

High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

PubMed

Czerniecki, Stefan M; Cruz, Nelly M; Harder, Jennifer L; Menon, Rajasree; Annis, James; Otto, Edgar A; Gulieva, Ramila E; Islas, Laura V; Kim, Yong Kyun; Tran, Linh M; Martins, Timothy J; Pippin, Jeffrey W; Fu, Hongxia; Kretzler, Matthias; Shankland, Stuart J; Himmelfarb, Jonathan; Moon, Randall T; Paragas, Neal; Freedman, Benjamin S

2018-05-15

Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening. Copyright © 2018 Elsevier Inc. All rights reserved.

Depression screening with patient-targeted feedback in cardiology: The cost-effectiveness of DEPSCREEN-INFO

PubMed Central

Kohlmann, Sebastian; Gierk, Benjamin

2017-01-01

Background Although depression is common in patients with heart disease, screening for depression is much debated. DEPSCREEN-INFO showed that a patient-targeted feedback in addition to screening results in lower depression level six months after screening. The purpose of this analysis was to perform a cost-effectiveness analysis of DEPSCREEN-INFO. Methods Patients with coronary heart disease or arterial hypertension were included. Participants in both groups were screened for depression. Participants in the intervention group additionally received a patient-targeted feedback of their result and recommended treatment options. A cost-utility analysis using quality-adjusted life years (QALY) based on the EQ-5D was performed. The time horizon was 6 months. Resource utilization was assessed by a telephone interview. Multiple imputation using chained equations was used. Net-benefit regressions controlled for prognostic variables at baseline were performed to construct cost-effectiveness acceptability curves. Different sensitivity analyses were performed. Results 375 participants (intervention group: 155; control group: 220) were included at baseline. After 6 months, in the intervention group adjusted total costs were lower (-€2,098; SE: €1,717) and more QALY were gained (0.0067; SD: 0.0133); yet differences were not statistically significant. The probability of cost-effectiveness was around 80% independent of the willingness-to-pay (range: €0/QALY–€130,000/QALY). The results were robust. Conclusions A patient-targeted feedback in addition to depression screening in cardiology is cost-effective with a high probability. This underpins the use of the patient-targeted feedbacks and the PHQ-9 that are both freely available and easy to implement in routine care. PMID:28806775

Sensitivity and specificity of the Distress Thermometer and a two-item depression screen (Patient Health Questionnaire-2) with a 'help' question for psychological distress and psychiatric morbidity in patients with advanced cancer.

PubMed

Ryan, Dermot Anthony; Gallagher, Pamela; Wright, Shelagh; Cassidy, Eugene M

2012-12-01

Brief screening tools may help clinicians in busy settings detect patients who are experiencing severe psychological distress. This study examined the performance of the Distress Thermometer (DT) and a two-item depression screen [the Patient Health Questionnaire-2 (PHQ-2)] with a 'help' question in screening for distress and psychiatric morbidity among patients with advanced cancer. Two hundred and five patients with advanced cancer completed the DT, the PHQ-2 and 'help' question and the Hospital Anxiety and Depression Scale and were interviewed using the Structured Clinical Interview for DSM-IV (SCID). The performance of the screening tools was examined against the Hospital Anxiety and Depression Scale and the SCID. Overall, discrimination levels were comparable for the DT [area under the curve (AUC) 0.80-0.81] and the PHQ-2 (AUC 0.73-0.85). The DT performed best in detecting cases of distress and mood, anxiety or adjustment disorders (sensitivity 100%), but it had poor specificity (49-60%). The best performance in terms of combined sensitivity and specificity was the PHQ depression item versus the SCID (sensitivity 88%, specificity 73%). The inclusion of the 'help' question with the PHQ-2 resulted in high levels of specificity (≥89%), but there was a significant drop in sensitivity (≤54%). Ultra-brief screening tools offer an efficient means of identifying patients with advanced cancer with severe distress or psychiatric morbidity but are less effective at identifying non-distressed individuals. Used in conjunction with a 'help' question, these tools can help clinicians identify patients who are both distressed and likely to accept professional support. Copyright © 2011 John Wiley & Sons, Ltd.

Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen

PubMed Central

Adissu, Hibret A.; Estabel, Jeanne; Sunter, David; Tuck, Elizabeth; Hooks, Yvette; Carragher, Damian M.; Clarke, Kay; Karp, Natasha A.; Project, Sanger Mouse Genetics; Newbigging, Susan; Jones, Nora; Morikawa, Lily; White, Jacqueline K.; McKerlie, Colin

2014-01-01

The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice. PMID:24652767

[Rapid screening and identification of 22 allergenic disperse dyes in ecological textiles by high performance liquid chromatography-linear ion trap/orbitrap mass spectrometry].

PubMed

Niu, Zengyuan; Luo, Xin; Ye, Xiwen; Xiu, Xiaoli; Zhang, Li; Wang, Xin; Chen, Jing

2015-10-01

A rapid screening method based on high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry (HPLC-LTQ/Orbitrap MS) for 22 disperse dyes in ecological textiles has been established. The target compounds were extracted by pyridine/water (1:1, v/v) by shaking extraction in 90 degrees C water bath. The extracts were then separated by a CAPCELL PAK C18 column (100 mm x 2.0 mm, 5 μm) using gradient elution with acetonitrile-5 mmol/L ammonium acetate containing 0.01% (v/v) formic acid as mobile phases, and finally analyzed by HPLC-LTQ/Orbitrap in positive and negative ESI modes. The retention time and accurate mass of parent ion were used for fast screening of 22 disperse dyes, while the confirmatory analysis was obtained by fragments generated by collision-induced dissociation (CID) MS/MS. Target analysis exhibited high mass accuracy (< 5 x 10(-6)). Each target showed a good linearity in its own concentration range and the correlation coefficient was higher than 0.99. The LOQs were 0.125-2.5 mg/kg. Except for Disperse Yellow 49, the average recoveries of most disperse dyes at three spiked levels were 65%-120%, and the relative standard deviations (n = 6) were less than 15%. The method was applied for screening 40 different kinds of textiles, and Disperse Orange 37/76 was detected in one of them. With high selectivity and strong anti-jamming ability, this method is simple, rapid, accurate, and it can be used for the inspection of disperse dyes in textiles.

Gas pressure assisted microliquid-liquid extraction coupled online to direct infusion mass spectrometry: a new automated screening platform for bioanalysis.

PubMed

Raterink, Robert-Jan; Witkam, Yoeri; Vreeken, Rob J; Ramautar, Rawi; Hankemeier, Thomas

2014-10-21

In the field of bioanalysis, there is an increasing demand for miniaturized, automated, robust sample pretreatment procedures that can be easily connected to direct-infusion mass spectrometry (DI-MS) in order to allow the high-throughput screening of drugs and/or their metabolites in complex body fluids like plasma. Liquid-Liquid extraction (LLE) is a common sample pretreatment technique often used for complex aqueous samples in bioanalysis. Despite significant developments that have been made in automated and miniaturized LLE procedures, fully automated LLE techniques allowing high-throughput bioanalytical studies on small-volume samples using direct infusion mass spectrometry, have not been matured yet. Here, we introduce a new fully automated micro-LLE technique based on gas-pressure assisted mixing followed by passive phase separation, coupled online to nanoelectrospray-DI-MS. Our method was characterized by varying the gas flow and its duration through the solvent mixture. For evaluation of the analytical performance, four drugs were spiked to human plasma, resulting in highly acceptable precision (RSD down to 9%) and linearity (R(2) ranging from 0.990 to 0.998). We demonstrate that our new method does not only allow the reliable extraction of analytes from small sample volumes of a few microliters in an automated and high-throughput manner, but also performs comparable or better than conventional offline LLE, in which the handling of small volumes remains challenging. Finally, we demonstrate the applicability of our method for drug screening on dried blood spots showing excellent linearity (R(2) of 0.998) and precision (RSD of 9%). In conclusion, we present the proof of principe of a new high-throughput screening platform for bioanalysis based on a new automated microLLE method, coupled online to a commercially available nano-ESI-DI-MS.

T-SPOT.TB Interferon-γ Release Assay Performance in Healthcare Worker Screening at Nineteen U.S. Hospitals.

PubMed

King, Thomas C; Upfal, Mark; Gottlieb, Andrew; Adamo, Philip; Bernacki, Edward; Kadlecek, Chris P; Jones, Jeffrey G; Humphrey-Carothers, Frances; Rielly, Albert F; Drewry, Pamela; Murray, Kathy; DeWitt, Marcie; Matsubara, Janet; O'Dea, Louis; Balser, John; Wrighton-Smith, Peter

2015-08-01

Interferon-γ release assays have significant advantages over tuberculin skin testing in many clinical situations. However, recent studies have called into question their reliability in serial testing of healthcare workers because of reportedly high rates of positivity and high conversion/reversion rates on retesting. To define the performance characteristics of the T-SPOT.TB test, an interferon-γ release assay, during serial screening programs of healthcare workers at 19 U.S. hospitals. A total of 42,155 T-SPOT.TB test results from healthcare workers at 19 geographically diverse hospitals obtained for routine tuberculosis screening programs were analyzed to determine the rates of positivity, reversion, and conversion in serial testing data. In 19,630 evaluable serial pairs from 16,076 healthcare workers, the mean test positivity rate was 2.3% (range, 0.0-27.4%). The mean conversion rate was 0.8% (range, 0.0-2.5%), and the mean reversion rate was 17.6%. Positivity and conversion rates correlated with known tuberculosis risk factors including age and sex. The observed specificity of the T-SPOT.TB test was at least 98.6%. The high concordance and test completion rates in this study suggest that the T-SPOT.TB test is a reliable tool for healthcare worker serial screening. As expected, the observed positivity rates were lower compared with the tuberculin skin test, likely reflecting the higher specificity of this test. Furthermore, the observed rates of conversion were low and significantly correlated with the geographic incidence of tuberculosis. Our findings suggest that the T-SPOT.TB test is an accurate and reliable way to screen healthcare workers.

Microgravity Passive Phase Separator

NASA Technical Reports Server (NTRS)

Paragano, Matthew; Indoe, William; Darmetko, Jeffrey

2012-01-01

A new invention disclosure discusses a structure and process for separating gas from liquids in microgravity. The Microgravity Passive Phase Separator consists of two concentric, pleated, woven stainless- steel screens (25-micrometer nominal pore) with an axial inlet, and an annular outlet between both screens (see figure). Water enters at one end of the center screen at high velocity, eventually passing through the inner screen and out through the annular exit. As gas is introduced into the flow stream, the drag force exerted on the bubble pushes it downstream until flow stagnation or until it reaches an equilibrium point between the surface tension holding bubble to the screen and the drag force. Gas bubbles of a given size will form a front that is moved further down the length of the inner screen with increasing velocity. As more bubbles are added, the front location will remain fixed, but additional bubbles will move to the end of the unit, eventually coming to rest in the large cavity between the unit housing and the outer screen (storage area). Owing to the small size of the pores and the hydrophilic nature of the screen material, gas does not pass through the screen and is retained within the unit for emptying during ground processing. If debris is picked up on the screen, the area closest to the inlet will become clogged, so high-velocity flow will persist farther down the length of the center screen, pushing the bubble front further from the inlet of the inner screen. It is desired to keep the velocity high enough so that, for any bubble size, an area of clean screen exists between the bubbles and the debris. The primary benefits of this innovation are the lack of any need for additional power, strip gas, or location for venting the separated gas. As the unit contains no membrane, the transport fluid will not be lost due to evaporation in the process of gas separation. Separation is performed with relatively low pressure drop based on the large surface area of the separating screen. Additionally, there are no moving parts, and there are no failure modes that involve fluid loss. A patent application has been filed.

Performance of a subsidised mammographic screening programme in Malaysia, a middle-income Asian country.

PubMed

Lee, Marianne; Mariapun, Shivaani; Rajaram, Nadia; Teo, Soo-Hwang; Yip, Cheng-Har

2017-01-28

The incidence of breast cancer in Asia is increasing because of urbanization and lifestyle changes. In the developing countries in Asia, women present at late stages, and mortality is high. Mammographic screening is the only evidence-based screening modality that reduces breast cancer mortality. To date, only opportunistic screening is offered in the majority of Asian countries because of the lack of justification and funding. Nevertheless, there have been few reports on the effectiveness of such programmes. In this study, we describe the cancer detection rate and challenges experienced in an opportunistic mammographic screening programme in Malaysia. From October 2011 to June 2015, 1,778 asymptomatic women, aged 40-74 years, underwent subsidised mammographic screening. All patients had a clinical breast examination before mammographic screening, and women with mammographic abnormalities were referred to a surgeon. The cancer detection rate and variables associated with a recommendation for adjunct ultrasonography were determined. The mean age for screening was 50.8 years and seven cancers (0.39%) were detected. The detection rate was 0.64% in women aged 50 years and above, and 0.12% in women below 50 years old. Adjunct ultrasonography was recommended in 30.7% of women, and was significantly associated with age, menopausal status, mammographic density and radiologist's experience. The main reasons cited for recommendation of an adjunct ultrasound was dense breasts and mammographic abnormalities. The cancer detection rate is similar to population-based screening mammography programmes in high-income Asian countries. Unlike population-based screening programmes in Caucasian populations where the adjunct ultrasonography rate is 2-4%, we report that 3 out of 10 women attending screening mammography were recommended for adjunct ultrasonography. This could be because Asian women attending screening are likely premenopausal and hence have denser breasts. Radiologists who reported more than 360 mammograms were more confident in reporting a mammogram as normal without adjunct ultrasonography compared to those who reported less than 180 mammograms. Our subsidised opportunistic mammographic screening programme is able to provide equivalent cancer detection rates but the high recall for adjunct ultrasonography would make screening less cost-effective.

Physical phenomena in mercury ion thrusters

NASA Technical Reports Server (NTRS)

Wilbur, P. J.

1979-01-01

Experimental tests results demonstrating that reductions in screen grid thickness enhance the performance of ion thruster grids are presented. Shaping of the screen hole cross section is shown on the other hand not to affect performance substantially. The effect of the magnetic field in the vicinity of the hollow cathode on cathode performance is studied and test results are presented that show reductions in keeper voltages of a few volts can be realized by judicious applications of fields on the order of 100 gauss. The plasma downstream of a SERT 2 thruster operating without high voltage is studied. A model describing electron escape from the thruster under these conditions is discussed. A model defining the performance of the baffle aperture of an ion thruster is refined and experimental verification of the model is undertaken.

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

PubMed Central

Ramasamy, Sakthivel; Bennet, Devasier; Kim, Sanghyo

2014-01-01

This review will present a brief discussion on the recent advancements of bioelectrical impedance cell-based biosensors, especially the electric cell-substrate impedance sensing (ECIS) system for screening of various bioactive molecules. The different technical integrations of various chip types, working principles, measurement systems, and applications for drug targeting of molecules in cells are highlighted in this paper. Screening of bioactive molecules based on electric cell-substrate impedance sensing is a trial-and-error process toward the development of therapeutically active agents for drug discovery and therapeutics. In general, bioactive molecule screening can be used to identify active molecular targets for various diseases and toxicity at the cellular level with nanoscale resolution. In the innovation and screening of new drugs or bioactive molecules, the activeness, the efficacy of the compound, and safety in biological systems are the main concerns on which determination of drug candidates is based. Further, drug discovery and screening of compounds are often performed in cell-based test systems in order to reduce costs and save time. Moreover, this system can provide more relevant results in in vivo studies, as well as high-throughput drug screening for various diseases during the early stages of drug discovery. Recently, MEMS technologies and integration with image detection techniques have been employed successfully. These new technologies and their possible ongoing transformations are addressed. Select reports are outlined, and not all the work that has been performed in the field of drug screening and development is covered. PMID:25525360

The cost-effectiveness of training US primary care physicians to conduct colorectal cancer screening in family medicine residency programs.

PubMed

Edwardson, Nicholas; Bolin, Jane N; McClellan, David A; Nash, Philip P; Helduser, Janet W

2016-04-01

Demand for a wide array of colorectal cancer screening strategies continues to outpace supply. One strategy to reduce this deficit is to dramatically increase the number of primary care physicians who are trained and supportive of performing office-based colonoscopies or flexible sigmoidoscopies. This study evaluates the clinical and economic implications of training primary care physicians via family medicine residency programs to offer colorectal cancer screening services as an in-office procedure. Using previously established clinical and economic assumptions from existing literature and budget data from a local grant (2013), incremental cost-effectiveness ratios are calculated that incorporate the costs of a proposed national training program and subsequent improvements in patient compliance. Sensitivity analyses are also conducted. Baseline assumptions suggest that the intervention would produce 2394 newly trained residents who could perform 71,820 additional colonoscopies or 119,700 additional flexible sigmoidoscopies after ten years. Despite high costs associated with the national training program, incremental cost-effectiveness ratios remain well below standard willingness-to-pay thresholds under base case assumptions. Interestingly, the status quo hierarchy of preferred screening strategies is disrupted by the proposed intervention. A national overhaul of family medicine residency programs offering training for colorectal cancer screening yields satisfactory incremental cost-effectiveness ratios. However, the model places high expectations on primary care physicians to improve current compliance levels in the US. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-10-18

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

Prospective Study of Combined Colon and Endometrial Cancer Screening in Women With Lynch Syndrome: A Patient-Centered Approach

PubMed Central

Huang, Marilyn; Sun, Charlotte; Boyd-Rogers, Stephanie; Burzawa, Jennifer; Milbourne, Andrea; Keeler, Elizabeth; Yzquierdo, Rebecca; Lynch, Patrick; Peterson, Susan K.; Lu, Karen

2011-01-01

Background: Endometrial and colorectal cancers are the most common cancers in Lynch syndrome. Consensus guidelines recommend annual endometrial biopsy (EMB) and regular colonoscopies. We assessed the feasibility of concurrently performing EMB and colonoscopy and evaluated women's perception of pain, satisfaction, and acceptability. Methods: From July 2002 to December 2009, women who had a gene mutation for Lynch syndrome, met the Amsterdam II criteria, or had a high-risk situation that required screening were prospectively enrolled. After conscious sedation, the procedures were sequentially performed. Patients completed pre- and postprocedure questionnaires assessing pain, level of satisfaction, and acceptability. The Wilcoxon rank test and Mann-Whitney test were used to compare pain scores. Results: Forty-two women completed the study. Median age was 37 years (range, 25 to 73). Nineteen had previously had an EMB in the office setting. Women reported significantly lower median levels of pain in the combined procedure compared with previous office setting biopsies (P < .001). Regardless of parity, women reported significantly less pain for an EMB as part of the combined screen compared with an office EMB (parous, P = .003; nulliparous, P = .026). Women also reported a high level of satisfaction and more convenience in the combined procedure. All participants preferred combined to separately scheduled procedures and would recommend the combined procedure to their relatives. Conclusion: Combined colon and endometrial cancer screening is a patient-centered approach that is feasible, acceptable, and may improve adherence to Lynch syndrome screening recommendations. PMID:21532810

Standardized assessment of infrared thermographic fever screening system performance

NASA Astrophysics Data System (ADS)

Ghassemi, Pejhman; Pfefer, Joshua; Casamento, Jon; Wang, Quanzeng

2017-03-01

Thermal modalities represent the only currently viable mass fever screening approach for outbreaks of infectious disease pandemics such as Ebola and SARS. Non-contact infrared thermometers (NCITs) and infrared thermographs (IRTs) have been previously used for mass fever screening in transportation hubs such as airports to reduce the spread of disease. While NCITs remain a more popular choice for fever screening in the field and at fixed locations, there has been increasing evidence in the literature that IRTs can provide greater accuracy in estimating core body temperature if appropriate measurement practices are applied - including the use of technically suitable thermographs. Therefore, the purpose of this study was to develop a battery of evaluation test methods for standardized, objective and quantitative assessment of thermograph performance characteristics critical to assessing suitability for clinical use. These factors include stability, drift, uniformity, minimum resolvable temperature difference, and accuracy. Two commercial IRT models were characterized. An external temperature reference source with high temperature accuracy was utilized as part of the screening thermograph. Results showed that both IRTs are relatively accurate and stable (<1% error of reading with stability of +/-0.05°C). Overall, results of this study may facilitate development of standardized consensus test methods to enable consistent and accurate use of IRTs for fever screening.

Improving newborn screening for cystic fibrosis using next-generation sequencing technology: a technical feasibility study.

PubMed

Baker, Mei W; Atkins, Anne E; Cordovado, Suzanne K; Hendrix, Miyono; Earley, Marie C; Farrell, Philip M

2016-03-01

Many regions have implemented newborn screening (NBS) for cystic fibrosis (CF) using a limited panel of cystic fibrosis transmembrane regulator (CFTR) mutations after immunoreactive trypsinogen (IRT) analysis. We sought to assess the feasibility of further improving the screening using next-generation sequencing (NGS) technology. An NGS assay was used to detect 162 CFTR mutations/variants characterized by the CFTR2 project. We used 67 dried blood spots (DBSs) containing 48 distinct CFTR mutations to validate the assay. NGS assay was retrospectively performed on 165 CF screen-positive samples with one CFTR mutation. The NGS assay was successfully performed using DNA isolated from DBSs, and it correctly detected all CFTR mutations in the validation. Among 165 screen-positive infants with one CFTR mutation, no additional disease-causing mutation was identified in 151 samples consistent with normal sweat tests. Five infants had a CF-causing mutation that was not included in this panel, and nine with two CF-causing mutations were identified. The NGS assay was 100% concordant with traditional methods. Retrospective analysis results indicate an IRT/NGS screening algorithm would enable high sensitivity, better specificity and positive predictive value (PPV). This study lays the foundation for prospective studies and for introducing NGS in NBS laboratories.

Pilot production and testing of high efficiency wraparound contact solar cells

NASA Technical Reports Server (NTRS)

Gillanders, M.

1981-01-01

Modifications were made to the process sequence until a device capable of high performance and satisfactory processing yields could be fabricated on a production line. Pilot production resulted in a 2 x 4 cm screen printed dielectric wraparound contact solar cell with average 28 C, Air Mass Zero (AMO) conversion efficiencies of 14.2% and reasonable process yields. This high performance was obtained with two different back contact configurations, making the device acceptable for many applications.

A survey of attitudes, behaviors, and needs of team dentists.

PubMed

McGovern, Lesley A; Spolarich, Ann Eshenaur; Keim, Robert

2015-01-01

Elite athletes strive to attain superior levels of health and fitness; however, many have high levels of oral disease. Oral screenings detect disease and need for treatment and identify opportunities for preventive interventions. Many dentists volunteer their time with sports organizations, but their scope of practice and needs are unknown. The purposes of this study were to gather baseline data about attitudes, practice behaviors, and needs of team dentists and to assess dental services provided, including the type and frequency of oral screenings conducted on athletes and any associated barriers to those screenings. This descriptive study utilized an original online survey, comprising 37 supplied-response questions, that was pilot tested for face and content validity. All dentist members of the Academy for Sports Dentistry were invited to participate (n = 491), and 150 responded, yielding a 31% response rate. The survey format allowed respondents to skip questions, and some respondents chose not to answer some questions. Quantitative data collected included level of athletes, league affiliation, scope of services provided, and types of oral screening performed. Dentists' attitudes regarding athletes' treatment and preventive needs, practice behaviors, and self-identified needs were assessed. Descriptive statistics were used to analyze the data. Results revealed that 116 of 146 respondents (80%) had a league affiliation. Among 112 dentists who reported providing services to athletes, the most frequently provided services were emergency treatment (96%), mouthguards (96%), restorative treatment (79%), oral hygiene instruction (63%), prophylaxis (61%), periodontal charting (61%), and dental charting (60%). Most team dentists (80%; n = 90/112) performed oral screenings for the athletes. Among 87 respondents who performed screenings and reported the type of screening they provided, 36 (41%) screened all athletes prior to the season and then provided individualized follow-up examinations as needed. The most commonly cited barrier to screenings was lack of awareness of the importance of oral health. Additional education for athletes, coaches, owners, schools, and leagues is needed to increase the value placed on oral health.

Score Reliability and Construct Validity of the Flinn Performance Screening Tool for Adults With Symptoms of Carpal Tunnel Syndrome

PubMed Central

Flinn, Sharon R.; Pease, William S.; Freimer, Miriam L.

2013-01-01

OBJECTIVE We investigated the psychometric properties of the Flinn Performance Screening Tool (FPST) for people referred with symptoms of carpal tunnel syndrome (CTS). METHOD An occupational therapist collected data from 46 participants who completed the Functional Status Scale (FSS) and FPST after the participants’ nerve conduction velocity study to test convergent and contrasted-group validity. RESULTS Seventy-four percent of the participants had abnormal nerve conduction studies. Cronbach’s α coefficients for subscale and total scores of the FPST ranged from .96 to .98. Intrarater reliability for six shared items of the FSS and the FPST was supported by high agreement (71%) and a fair κ statistic (.36). Strong to moderate positive relationships were found between the FSS and FPST scores. Functional status differed significantly among severe, mild, and negative CTS severity groups. CONCLUSION The FPST shows adequate psychometric properties as a client-centered screening tool for occupational performance of people referred for symptoms of CTS. PMID:22549598

Factors associated with decisions to attend cervical cancer screening among women aged 30-60 years in Chatapadung Contracting Medical Unit, Thailand.

PubMed

Budkaew, Jiratha; Chumworathayi, Bandit

2014-01-01

This study aimed to identify factors associated with women's decisions to attend cervical cancer screening and to explore those linked with intention to attend in the coming year and to continue regular screening. A community based case-control study was conducted among woman 30-60 years of age in catchment area of Chatapadung Contracting Medical Unit (CCMU), networking of Khon Kaen Center Hospital, Thailand. Self-administered questionnaires were used to collect data, and in-depth interviews were then performed to explore in greater detail. There were 195 participants. Only one third (32.3 %) had been screened for cervical cancer within the past 5 years. Some 67.7% reported that they had not been screened because they had no abnormal symptoms, single marital status, and no children. Only 10.6% of those never had screening intent to be screened within the next 12 months. High family income (adjusted OR=2.16, 95%CI=1.13-4.14), good attitude towards a Pap test (OR=1.87, 95%CI=1.09-4.23), and having received a recommendation from health care providers were important factors associated with decisions to attend cervical cancer screening (OR=1.73, 95%CI=1.01-4.63). From in-depth interviews, there were five reasons of their decisions to attend cervical cancer screening including yearly check-up, postpartum check-up, having abnormal symptom, encouragement by health care providers, and request from workplace. High family income, good attitude towards a Pap test, and receiving proper recommendation by health care providers, were important factors associated with decision to have cervical cancer screening among women 30-60 years old. Trying to enhance these factors and reduce barriers regarding screening, may increase the coverage rate for cervical cancer screening in Thailand.

Fecal Immunochemical Test (FIT) for Colon Cancer Screening: Variable Performance with Ambient Temperature

PubMed Central

Doubeni, Chyke A.; Jensen, Christopher D.; Fedewa, Stacey A.; Quinn, Virginia P.; Zauber, Ann G.; Schottinger, Joanne E.; Corley, Douglas A.; Levin, Theodore R.

2017-01-01

Introduction Fecal immunochemical tests (FITs) are widely used in colorectal cancer (CRC) screening, but hemoglobin degradation, due to exposure of the collected sample to high temperatures, could reduce test sensitivity. We examined the relation of ambient temperature exposure with FIT positivity rate and sensitivity. Methods This was a retrospective cohort study of patients 50 to 75 years in Kaiser Permanente Northern California’s CRC screening program, which began mailing FIT kits annually to screen-eligible members in 2007. Primary outcomes were FIT positivity rate and sensitivity to detect CRC. Predictors were month, season, and daily ambient temperatures of test result dates based on US National Oceanic and Atmospheric Administration data. Results Patients (n =472,542) completed 1,141,162 FITs. Weekly test positivity rate ranged from 2.6% to 8.0% (median, 4.4%) and varied significantly by month (June/July vs December/January rate ratio [RR] =0.79, 95% confidence interval [CI], 0.76 to 0.83) and season. FIT sensitivity was lower in June/July (74.5%; 95% CI, 72.5 to 76.6) than January/December (78.9%; 95% CI, 77.0 to 80.7). Conclusions FITs completed during high ambient temperatures had lower positivity rates and lower sensitivity. Changing kit design, specimen transportation practices, or avoiding periods of high ambient temperatures may help optimize FIT performance, but may also increase testing complexity and reduce patient adherence, requiring careful study. PMID:28076249

Low cost automated whole smear microscopy screening system for detection of acid fast bacilli.

PubMed

Law, Yan Nei; Jian, Hanbin; Lo, Norman W S; Ip, Margaret; Chan, Mia Mei Yuk; Kam, Kai Man; Wu, Xiaohua

2018-01-01

In countries with high tuberculosis (TB) burden, there is urgent need for rapid, large-scale screening to detect smear-positive patients. We developed a computer-aided whole smear screening system that focuses in real-time, captures images and provides diagnostic grading, for both bright-field and fluorescence microscopy for detection of acid-fast-bacilli (AFB) from respiratory specimens. To evaluate the performance of dual-mode screening system in AFB diagnostic algorithms on concentrated smears with auramine O (AO) staining, as well as direct smears with AO and Ziehl-Neelsen (ZN) staining, using mycobacterial culture results as gold standard. Adult patient sputum samples requesting for M. tuberculosis cultures were divided into three batches for staining: direct AO-stained, direct ZN-stained and concentrated smears AO-stained. All slides were graded by an experienced microscopist, in parallel with the automated whole smear screening system. Sensitivity and specificity of a TB diagnostic algorithm in using the screening system alone, and in combination with a microscopist, were evaluated. Of 488 direct AO-stained smears, 228 were culture positive. These yielded a sensitivity of 81.6% and specificity of 74.2%. Of 334 direct smears with ZN staining, 142 were culture positive, which gave a sensitivity of 70.4% and specificity of 76.6%. Of 505 concentrated smears with AO staining, 250 were culture positive, giving a sensitivity of 86.4% and specificity of 71.0%. To further improve performance, machine grading was confirmed by manual smear grading when the number of AFBs detected fell within an uncertainty range. These combined results gave significant improvement in specificity (AO-direct:85.4%; ZN-direct:85.4%; AO-concentrated:92.5%) and slight improvement in sensitivity while requiring only limited manual workload. Our system achieved high sensitivity without substantially compromising specificity when compared to culture results. Significant improvement in specificity was obtained when uncertain results were confirmed by manual smear grading. This approach had potential to substantially reduce workload of microscopists in high burden countries.

Generalizing Screen Inferiority--Does the Medium, Screen versus Paper, Affect Performance Even with Brief Tasks?

ERIC Educational Resources Information Center

Sidi, Yael; Ophir, Yael; Ackerman, Rakefet

2016-01-01

Screen inferiority in performance and metacognitive processes has been repeatedly found with text learning. Common explanations for screen inferiority relate to technological and physiological disadvantages associated with extensive reading on screen. However, recent studies point to lesser recruitment of mental effort on screen than on paper.…

Tailored community cancer education programs: Pawsox and prostates.

PubMed

Glicksman, Arvin S; Meyer, Andrea; Dipiero, Maureen

2010-06-01

To assess the prostate cancer screening practices in Rhode Island, we designed a questionnaire which was sent to 150 primary care physicians. A population-based survey was distributed to 194 men over 40 asking about screening history and risk factors. Eighty-five percent of primary care physicians reported performing annual prostate-specific antigen tests (PSAs) and digital rectal exams, 63% recognized family history as a risk factor, and 14% identified African Americans as a high-risk population. The survey found that 48% of men recognized family history as a risk factor and 6% understood that African Americans were at high risk. Each year, 200 men, primarily SED, are invited to a PawSox baseball game where physicians provide information on prostate cancer risk, treatment options, and outcomes. Free PSAs are provided. The questionnaire and survey demonstrate a need for more public education regarding prostate cancer in high-risk populations. Tailored community-based interventions, such as the Pawsox & Prostate program, can be effective professional and public education strategies to increase screening in high-risk populations.

Novel method for high-throughput colony PCR screening in nanoliter-reactors

PubMed Central

Walser, Marcel; Pellaux, Rene; Meyer, Andreas; Bechtold, Matthias; Vanderschuren, Herve; Reinhardt, Richard; Magyar, Joseph; Panke, Sven; Held, Martin

2009-01-01

We introduce a technology for the rapid identification and sequencing of conserved DNA elements employing a novel suspension array based on nanoliter (nl)-reactors made from alginate. The reactors have a volume of 35 nl and serve as reaction compartments during monoseptic growth of microbial library clones, colony lysis, thermocycling and screening for sequence motifs via semi-quantitative fluorescence analyses. nl-Reactors were kept in suspension during all high-throughput steps which allowed performing the protocol in a highly space-effective fashion and at negligible expenses of consumables and reagents. As a first application, 11 high-quality microsatellites for polymorphism studies in cassava were isolated and sequenced out of a library of 20 000 clones in 2 days. The technology is widely scalable and we envision that throughputs for nl-reactor based screenings can be increased up to 100 000 and more samples per day thereby efficiently complementing protocols based on established deep-sequencing technologies. PMID:19282448

A rapid enzymatic assay for high-throughput screening of adenosine-producing strains

PubMed Central

Dong, Huina; Zu, Xin; Zheng, Ping; Zhang, Dawei

2015-01-01

Adenosine is a major local regulator of tissue function and industrially useful as precursor for the production of medicinal nucleoside substances. High-throughput screening of adenosine overproducers is important for industrial microorganism breeding. An enzymatic assay of adenosine was developed by combined adenosine deaminase (ADA) with indophenol method. The ADA catalyzes the cleavage of adenosine to inosine and NH3, the latter can be accurately determined by indophenol method. The assay system was optimized to deliver a good performance and could tolerate the addition of inorganic salts and many nutrition components to the assay mixtures. Adenosine could be accurately determined by this assay using 96-well microplates. Spike and recovery tests showed that this assay can accurately and reproducibly determine increases in adenosine in fermentation broth without any pretreatment to remove proteins and potentially interfering low-molecular-weight molecules. This assay was also applied to high-throughput screening for high adenosine-producing strains. The high selectivity and accuracy of the ADA assay provides rapid and high-throughput analysis of adenosine in large numbers of samples. PMID:25580842

Performance of prenatal screening using maternal serum and ultrasound markers for Down syndrome in Chinese women: a systematic review and meta-analysis.

PubMed

Tu, S; Rosenthal, M; Wang, D; Huang, J; Chen, Y

2016-09-01

Controversies about the performance of conventional prenatal screening using maternal serum and ultrasound markers (PSMSUM) in detecting Down syndrome (DS) have been raised as a result of a recently available noninvasive prenatal test based on cell-free fetal DNA sequencing. To evaluate the screening performance of PSMSUM in detecting DS in Chinese women. An exhaustive literature search of MEDLINE, Embase, the Cochrane Library, ISI Web of Science and China BioMedical Disc. Primary studies, published from January 2004 to November 2014, which examined the screening accuracy of PSMSUM in pregnant Chinese women, compared with a reference standard, either chromosomal verification or inspection of the newborn. Data were extracted as screening positive/negative results for Down and non-Down syndrome pregnancies, allowing estimation of sensitivities and specificities. Risks of bias within and across studies were assessed. Screening accuracy measures were pooled using a bivariate random effects regression model. Seventy-eight studies, involving six categories of PSMSUM, were included. Second-trimester double serum [pooled sensitivity (SEN) = 0.80, pooled specificity (SPE) = 0.95] and triple-serum (pooled SEN = 0.79, pooled SPE = 0.96) screening were the predominant PSMSUM methods. The screening performances of these methods achieved the national standard but varied enormously across studies. First-trimester combined screening (pooled SEN = 0.92, pooled SPE = 0.93) and second-trimester quadruple serum screening (median SEN = 0.86, median SPE = 0.96) performed better, but were rarely used. Second-trimester maternal serum screening has the potential to achieve satisfactory screening performance in middle- and low-income countries. The reported enormous range in screening performance of second-trimester PSMSUM calls for urgent implementation of methods for performance optimization. Meta-analysis results show good accuracy of maternal serum and ultrasound screening for trisomy 21 in Chinese women. © 2016 Royal College of Obstetricians and Gynaecologists.

A prospective clinical trial to compare the performance of dried blood spots prenatal screening for Down's syndrome with conventional non-invasive testing technology.

PubMed

Hu, Huiying; Jiang, Yulin; Zhang, Minghui; Liu, Shanying; Hao, Na; Zhou, Jing; Liu, Juntao; Zhang, Xiaojin; Ma, Liangkun

2017-03-01

To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down's syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down's syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down's syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down's syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a "before and after" two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation. Impact statement Children born with Down's syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down's syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down's syndrome and to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. Results demonstrate that fetal cfDNA can significantly reduce false-positive rate close to none while distinguishing all true positives. Thus, we recommend that fetal cfDNA analysis to be utilized as a secondary screening tool atop of the primary blood protein screening to further minimize the capacity of undesirable invasive diagnostic operations.

Laser-Induced Fluorescence Detection in High-Throughput Screening of Heterogeneous Catalysts and Single Cells Analysis

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

Su, Hui

2001-01-01

Laser-induced fluorescence detection is one of the most sensitive detection techniques and it has found enormous applications in various areas. The purpose of this research was to develop detection approaches based on laser-induced fluorescence detection in two different areas, heterogeneous catalysts screening and single cell study. First, the author introduced laser-induced imaging (LIFI) as a high-throughput screening technique for heterogeneous catalysts to explore the use of this high-throughput screening technique in discovery and study of various heterogeneous catalyst systems. This scheme is based on the fact that the creation or the destruction of chemical bonds alters the fluorescence properties ofmore » suitably designed molecules. By irradiating the region immediately above the catalytic surface with a laser, the fluorescence intensity of a selected product or reactant can be imaged by a charge-coupled device (CCD) camera to follow the catalytic activity as a function of time and space. By screening the catalytic activity of vanadium pentoxide catalysts in oxidation of naphthalene, they demonstrated LIFI has good detection performance and the spatial and temporal resolution needed for high-throughput screening of heterogeneous catalysts. The sample packing density can reach up to 250 x 250 subunits/cm 2 for 40-μm wells. This experimental set-up also can screen solid catalysts via near infrared thermography detection. In the second part of this dissertation, the author used laser-induced native fluorescence coupled with capillary electrophoresis (LINF-CE) and microscope imaging to study the single cell degranulation. On the basis of good temporal correlation with events observed through an optical microscope, they have identified individual peaks in the fluorescence electropherograms as serotonin released from the granular core on contact with the surrounding fluid.« less

Proposed biopsy performance benchmarks for MRI based on an audit of a large academic center.

PubMed

Sedora Román, Neda I; Mehta, Tejas S; Sharpe, Richard E; Slanetz, Priscilla J; Venkataraman, Shambhavi; Fein-Zachary, Valerie; Dialani, Vandana

2018-05-01

Performance benchmarks exist for mammography (MG); however, performance benchmarks for magnetic resonance imaging (MRI) are not yet fully developed. The purpose of our study was to perform an MRI audit based on established MG and screening MRI benchmarks and to review whether these benchmarks can be applied to an MRI practice. An IRB approved retrospective review of breast MRIs was performed at our center from 1/1/2011 through 12/31/13. For patients with biopsy recommendation, core biopsy and surgical pathology results were reviewed. The data were used to derive mean performance parameter values, including abnormal interpretation rate (AIR), positive predictive value (PPV), cancer detection rate (CDR), percentage of minimal cancers and axillary node negative cancers and compared with MG and screening MRI benchmarks. MRIs were also divided by screening and diagnostic indications to assess for differences in performance benchmarks amongst these two groups. Of the 2455 MRIs performed over 3-years, 1563 were performed for screening indications and 892 for diagnostic indications. With the exception of PPV2 for screening breast MRIs from 2011 to 2013, PPVs were met for our screening and diagnostic populations when compared to the MRI screening benchmarks established by the Breast Imaging Reporting and Data System (BI-RADS) 5 Atlas ® . AIR and CDR were lower for screening indications as compared to diagnostic indications. New MRI screening benchmarks can be used for screening MRI audits while the American College of Radiology (ACR) desirable goals for diagnostic MG can be used for diagnostic MRI audits. Our study corroborates established findings regarding differences in AIR and CDR amongst screening versus diagnostic indications. © 2017 Wiley Periodicals, Inc.

The evolving role of new imaging methods in breast screening.

PubMed

Houssami, Nehmat; Ciatto, Stefano

2011-09-01

The potential to avert breast cancer deaths through screening means that efforts continue to identify methods which may enhance early detection. While the role of most new imaging technologies remains in adjunct screening or in the work-up of mammography-detected abnormalities, some of the new breast imaging tests (such as MRI) have roles in screening groups of women defined by increased cancer risk. This paper highlights the evidence and the current role of new breast imaging technologies in screening, focusing on those that have broader application in population screening, including digital mammography, breast ultrasound in women with dense breasts, and computer-aided detection. It highlights that evidence on new imaging in screening comes mostly from non-randomised studies that have quantified test detection capability as adjunct to mammography, or have compared measures of screening performance for new technologies with that of conventional mammography. Two RCTs have provided high-quality evidence on the equivalence of digital and conventional mammography and on outcomes of screen-reading complemented by CAD. Many of these imaging technologies enhance cancer detection but also increase recall and false positives in screening. Copyright © 2011 Elsevier Inc. All rights reserved.

Mammography performance in Oman: Review of factors influencing cancer yield and positive predictive value.

PubMed

Taif, Sawsan; Tufail, Fatma; Alnuaimi, Ahmed Sameer

2016-06-01

The aim of this study is to assess mammography performance in Oman by estimating the breast cancer rate and the positive predictive value (PPV) with the influence of some variables. This cross-sectional study was conducted on mammograms done in one of the three main breast imaging centers in Oman between January 2008 and July 2012. Diagnostic and screening groups were identified and assessed separately. Rate of abnormal mammograms, rate of breast cancer and the PPV were estimated according to Breast Imaging Reporting and Data System (BIRADS) score, presence of breast lump and patient's age. Total of 653 mammograms were included, 254 diagnostic and 399 screening. Abnormal mammograms (BIRADS 4 and 5) form 31.9% of the diagnostic examinations compared with 6.8% of screening examinations. Breast cancer was present in 17.9% of the diagnostic compared with 1.0% of the screening group. The PPV of BIRADS 5 was 94.1%, and for BIRADS 4 was 37.1 and 26.7% for diagnostic and screening studies. Overall PPV for abnormal mammograms was 65.2% in the diagnostic and 26.7% in the screening group. Mammography PPV shows positive association with age (P = 0.039) while presence of breast lump has no significant effect on the PPV (P = 0.38). BIRADS 5 score was found to have a high cancer yield making it a strong predictor of cancer. Different results were obtained in the diagnostic compared with screening mammography with higher rates of abnormal mammograms and breast cancer. Mammography performance should be better in the older women. © 2014 Wiley Publishing Asia Pty Ltd.

Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study.

PubMed

Yang, Zhihong; Lin, James; Zhang, John; Fong, Wai Ieng; Li, Pei; Zhao, Rong; Liu, Xiaohong; Podevin, William; Kuang, Yanping; Liu, Jiaen

2015-06-23

Recent advances in next-generation sequencing (NGS) have provided new methods for preimplantation genetic screening (PGS) of human embryos from in vitro fertilization (IVF) cycles. However, there is still limited information about clinical applications of NGS in IVF and PGS (IVF-PGS) treatments. The present study aimed to investigate the effects of NGS screening on clinical pregnancy and implantation outcomes for PGS patients in comparison to array comparative genomic hybridization (aCGH) screening. This study was performed in two phases. Phase I study evaluated the accuracy of NGS for aneuploidy screening in comparison to aCGH. Whole-genome amplification (WGA) products (n = 164) derived from previous IVF-PGS cycles (n = 38) were retrospectively analyzed with NGS. The NGS results were then compared with those of aCGH. Phase II study further compared clinical pregnancy and implantation outcomes between NGS and aCGH for IVF-PGS patients. A total of 172 patients at mean age 35.2 ± 3.5 years were randomized into two groups: 1) NGS (Group A): patients (n = 86) had embryos screened with NGS and 2) aCGH (Group B): patients (n = 86) had embryos screened with aCGH. For both groups, blastocysts were vitrified after trophectoderm biopsy. One to two euploid blastocysts were thawed and transferred to individual patients primarily based on the PGS results. Ongoing pregnancy and implantation rates were compared between the two study groups. NGS detected all types of aneuploidies of human blastocysts accurately and provided a 100 % 24-chromosome diagnosis consistency with the highly validated aCGH method. Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05). The observed implantation rates were also comparable between the NGS and aCGH groups (70.5 % vs. 66.2 %, respectively, p >0.05). While NGS screening has been recently introduced to assist IVF patients, this is the first randomized clinical study on the efficiency of NGS for preimplantation genetic screening in comparison to aCGH. With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.

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

PubMed

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.

Exploring avenues for best use of cytotechnologists in non-gynaecological cytology: Double screening or independent sign-out.

PubMed

Fischer, G; Haddad, M; Cormier, K

2018-02-01

Cytotechnologist (CT) screening workload has been decreasing due to the falling number of Papanicolaou tests. This continuing trend has prompted exploration of ways to best employ the CT skillset. One potential way of more effective use is by having two CTs double screen non-gynaecological (NGC) cases to assess whether this improves screening quality and concordance with pathologists. Another is evaluating the CT's performance on low-complexity negative NGC cases for a potential independent CT sign-out without pathologist review. In total, 1119 NGC cases were reviewed; 577 screened by two CTs and 542 screened by one CT. All cases were signed out by a pathologist and all CT interpretations were compared to the pathologist final diagnoses. The disagreements were classified based on degree of discrepancy. The extra workload by adding the second screener was assessed. The agreement rate between the CT's screening interpretation and pathologist's interpretation did not improve by adding a second CT compared to a single screener (91.5% vs 92.9%, respectively). CT to pathologist concordance was very high on low complexity NGC cases (voided urine, fluid, sputum) whether screened and interpreted as negative by one CT (97.3%) or two CTs (99.3%). Double screening of NGC cases by two cytotechnologists prior to pathologist sign-out does not improve screening quality and is not cost-effective. The high concordance between the CTs and pathologists in this limited group of low complexity negative cases suggests that such cases could be signed out independently by cytotechnologists. © 2017 John Wiley & Sons Ltd.

DOVIS: an implementation for high-throughput virtual screening using AutoDock.

PubMed

Zhang, Shuxing; Kumar, Kamal; Jiang, Xiaohui; Wallqvist, Anders; Reifman, Jaques

2008-02-27

Molecular-docking-based virtual screening is an important tool in drug discovery that is used to significantly reduce the number of possible chemical compounds to be investigated. In addition to the selection of a sound docking strategy with appropriate scoring functions, another technical challenge is to in silico screen millions of compounds in a reasonable time. To meet this challenge, it is necessary to use high performance computing (HPC) platforms and techniques. However, the development of an integrated HPC system that makes efficient use of its elements is not trivial. We have developed an application termed DOVIS that uses AutoDock (version 3) as the docking engine and runs in parallel on a Linux cluster. DOVIS can efficiently dock large numbers (millions) of small molecules (ligands) to a receptor, screening 500 to 1,000 compounds per processor per day. Furthermore, in DOVIS, the docking session is fully integrated and automated in that the inputs are specified via a graphical user interface, the calculations are fully integrated with a Linux cluster queuing system for parallel processing, and the results can be visualized and queried. DOVIS removes most of the complexities and organizational problems associated with large-scale high-throughput virtual screening, and provides a convenient and efficient solution for AutoDock users to use this software in a Linux cluster platform.

Polarization-mediated Debye-screening of surface potential fluctuations in dual-channel AlN/GaN high electron mobility transistors

NASA Astrophysics Data System (ADS)

Deen, David A.; Miller, Ross A.; Osinsky, Andrei V.; Downey, Brian P.; Storm, David F.; Meyer, David J.; Scott Katzer, D.; Nepal, Neeraj

2016-12-01

A dual-channel AlN/GaN/AlN/GaN high electron mobility transistor (HEMT) architecture is proposed, simulated, and demonstrated that suppresses gate lag due to surface-originated trapped charge. Dual two-dimensional electron gas (2DEG) channels are utilized such that the top 2DEG serves as an equipotential that screens potential fluctuations resulting from surface trapped charge. The bottom channel serves as the transistor's modulated channel. Two device modeling approaches have been performed as a means to guide the device design and to elucidate the relationship between the design and performance metrics. The modeling efforts include a self-consistent Poisson-Schrodinger solution for electrostatic simulation as well as hydrodynamic three-dimensional device modeling for three-dimensional electrostatics, steady-state, and transient simulations. Experimental results validated the HEMT design whereby homo-epitaxial growth on free-standing GaN substrates and fabrication of the same-wafer dual-channel and recessed-gate AlN/GaN HEMTs have been demonstrated. Notable pulsed-gate performance has been achieved by the fabricated HEMTs through a gate lag ratio of 0.86 with minimal drain current collapse while maintaining high levels of dc and rf performance.

Broad screening and identification of β-agonists in feed and animal body fluid and tissues using ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry combined with spectra library search.

PubMed

Li, Tingting; Cao, Jingjing; Li, Zhen; Wang, Xian; He, Pingli

2016-02-01

Broad screening and identification of β-agonists in feed, serum, urine, muscle and liver samples was achieved in a quick and highly sensitive manner using ultra high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) combined with a spectra library search. Solid-phase extraction technology was employed for sample purification and enrichment. After extraction and purification, the samples were analyzed using a Q-Orbitrap high-resolution mass spectrometer under full-scan and data-dependent MS/MS mode. The acquired mass spectra were compared with an in-house library (compound library and MS/MS mass spectral library) built with TraceFinder Software which contained the M/Z of the precursor ion, chemical formula, retention time, character fragment ions and the entire MS/MS spectra of 32 β-agonist standards. Screening was achieved by comparing 5 key mass spectral results and positive matches were marked. Using the developed method, the identification results from 10 spiked samples and 238 actual samples indicated that only 2% of acquired mass spectra produced false identities. The method validation results showed that the limit of detection ranged from 0.021-3.854 μg kg(-1)and 0.015-1.198 ng mL(-1) for solid and liquid samples, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

High-performance thin-layer chromatography screening of multi class antibiotics in animal food by bioluminescent bioautography and electrospray ionization mass spectrometry.

PubMed

Chen, Yisheng; Schwack, Wolfgang

2014-08-22

The world-wide usage and partly abuse of veterinary antibiotics resulted in a pressing need to control residues in animal-derived foods. Large-scale screening for residues of antibiotics is typically performed by microbial agar diffusion tests. This work employing high-performance thin-layer chromatography (HPTLC) combined with bioautography and electrospray ionization mass spectrometry introduces a rapid and efficient method for a multi-class screening of antibiotic residues. The viability of the bioluminescent bacterium Aliivibrio fischeri to the studied antibiotics (16 species of 5 groups) was optimized on amino plates, enabling detection sensitivity down to the strictest maximum residue limits. The HPTLC method was developed not to separate the individual antibiotics, but for cleanup of sample extracts. The studied antibiotics either remained at the start zones (tetracyclines, aminoglycosides, fluoroquinolones, and macrolides) or migrated into the front (amphenicols), while interfering co-extracted matrix compounds were dispersed at hRf 20-80. Only after a few hours, the multi-sample plate image clearly revealed the presence or absence of antibiotic residues. Moreover, molecular information as to the suspected findings was rapidly achieved by HPTLC-mass spectrometry. Showing remarkable sensitivity and matrix-tolerance, the established method was successfully applied to milk and kidney samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Assessment of wheelchair driving performance in a virtual reality-based simulator

PubMed Central

Mahajan, Harshal P.; Dicianno, Brad E.; Cooper, Rory A.; Ding, Dan

2013-01-01

Objective To develop a virtual reality (VR)-based simulator that can assist clinicians in performing standardized wheelchair driving assessments. Design A completely within-subjects repeated measures design. Methods Participants drove their wheelchairs along a virtual driving circuit modeled after the Power Mobility Road Test (PMRT) and in a hallway with decreasing width. The virtual simulator was displayed on computer screen and VR screens and participants interacted with it using a set of instrumented rollers and a wheelchair joystick. Driving performances of participants were estimated and compared using quantitative metrics from the simulator. Qualitative ratings from two experienced clinicians were used to estimate intra- and inter-rater reliability. Results Ten regular wheelchair users (seven men, three women; mean age ± SD, 39.5 ± 15.39 years) participated. The virtual PMRT scores from the two clinicians show high inter-rater reliability (78–90%) and high intra-rater reliability (71–90%) for all test conditions. More research is required to explore user preferences and effectiveness of the two control methods (rollers and mathematical model) and the display screens. Conclusions The virtual driving simulator seems to be a promising tool for wheelchair driving assessment that clinicians can use to supplement their real-world evaluations. PMID:23820148

Determination of Ochratoxin A in Rye and Rye-Based Products by Fluorescence Polarization Immunoassay

PubMed Central

Lippolis, Vincenzo; Porricelli, Anna C. R.; Cortese, Marina; Zanardi, Sandro; Pascale, Michelangelo

2017-01-01

A rapid fluorescence polarization immunoassay (FPIA) was optimized and validated for the determination of ochratoxin A (OTA) in rye and rye crispbread. Samples were extracted with a mixture of acetonitrile/water (60:40, v/v) and purified by SPE-aminopropyl column clean-up before performing the FPIA. Overall mean recoveries were 86 and 95% for spiked rye and rye crispbread with relative standard deviations lower than 6%. Limits of detection (LOD) of the optimized FPIA was 0.6 μg/kg for rye and rye crispbread, respectively. Good correlations (r > 0.977) were observed between OTA contents in contaminated samples obtained by FPIA and high-performance liquid chromatography (HPLC) with immunoaffinity cleanup used as reference method. Furthermore, single laboratory validation and small-scale collaborative trials were carried out for the determination of OTA in rye according to Regulation 519/2014/EU laying down procedures for the validation of screening methods. The precision profile of the method, cut-off level and rate of false suspect results confirm the satisfactory analytical performances of assay as a screening method. These findings show that the optimized FPIA is suitable for high-throughput screening, and permits reliable quantitative determination of OTA in rye and rye crispbread at levels that fall below the EU regulatory limits. PMID:28954398

Screening US in patients with mammographically dense breasts: initial experience with Connecticut Public Act 09-41.

PubMed

Hooley, Regina J; Greenberg, Kathryn L; Stackhouse, Rebecca M; Geisel, Jaime L; Butler, Reni S; Philpotts, Liane E

2012-10-01

To determine performance and utilization of screening breast ultrasonography (US) in women with dense breast tissue who underwent additional screening breast US in the 1st year since implementation of Connecticut Public Act 09-41 requiring radiologists to inform patients with heterogeneous or extremely dense breasts at mammography that they may benefit from such examination. Informed consent was waived for this institutional review board-approved, HIPAA-compliant retrospective review of 935 women with dense breasts at mammography who subsequently underwent handheld screening and whole-breast US from October 1, 2009, through September 30, 2010. Of 935 women, 614 (65.7%) were at low risk, 149 (15.9%) were at intermediate risk, and 87 (9.3%) were at high risk for breast cancer. Of the screening breast US examinations, in 701 (75.0%), results were classified as Breast Imaging Reporting and Data System (BI-RADS) category 1 or 2; in 187 (20.0%), results were classified as BI-RADS category 3; and in 47 (5.0%), results were classified as BI-RADS category 4. Of 63 aspirations or biopsies recommended and performed in 53 patients, in nine, lesions were BI-RADS category 3, and in 54, lesions were BI-RADS category 4. Among 63 biopsies and aspirations, three lesions were malignant (all BI-RADS category 4, diagnosed with biopsy). All three cancers were smaller than 1 cm, were found in postmenopausal patients, and were solid masses. One cancer was found in each risk group. In 44 of 935 (4.7%) patients, examination results were false-positive. Overall positive predictive value (PPV) for biopsy or aspirations performed in patients with BI-RADS category 4 masses was 6.5% (three of 46; 95% confidence interval [CI]: 1.7%, 19%). Overall cancer detection rate was 3.2 cancers per 1000 women screened (three of 935; 95% CI: 0.8 cancers per 1000 women screened, 10 cancers per 1000 women screened). Technologist-performed handheld screening breast US offered to women in the general population with dense breasts can aid detection of small mammographically occult breast cancers (cancer detection rate, 0.8-10 cancers per 1000 women screened), although the overall PPV is low. © RSNA, 2012.

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

PubMed Central

Moberg, Andreas; Hansson, Eva; Boyd, Helen

2014-01-01

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

Evaluation of an enhanced gravity-based fine-coal circuit for high-sulfur coal

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

Mohanty, M.K.; Samal, A.R.; Palit, A.

One of the main objectives of this study was to evaluate a fine-coal cleaning circuit using an enhanced gravity separator specifically for a high sulfur coal application. The evaluation not only included testing of individual unit operations used for fine-coal classification, cleaning and dewatering, but also included testing of the complete circuit simultaneously. At a scale of nearly 2 t/h, two alternative circuits were evaluated to clean a minus 0.6-mm coal stream utilizing a 150-mm-diameter classifying cyclone, a linear screen having a projected surface area of 0.5 m{sup 2}, an enhanced gravity separator having a bowl diameter of 250 mmmore » and a screen-bowl centrifuge having a bowl diameter of 500 mm. The cleaning and dewatering components of both circuits were the same; however, one circuit used a classifying cyclone whereas the other used a linear screen as the classification device. An industrial size coal spiral was used to clean the 2- x 0.6-mm coal size fraction for each circuit to estimate the performance of a complete fine-coal circuit cleaning a minus 2-mm particle size coal stream. The 'linear screen + enhanced gravity separator + screen-bowl circuit' provided superior sulfur and ash-cleaning performance to the alternative circuit that used a classifying cyclone in place of the linear screen. Based on these test data, it was estimated that the use of the recommended circuit to treat 50 t/h of minus 2-mm size coal having feed ash and sulfur contents of 33.9% and 3.28%, respectively, may produce nearly 28.3 t/h of clean coal with product ash and sulfur contents of 9.15% and 1.61 %, respectively.« less

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

PubMed

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

2018-04-11

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

A Computable Definition of Sepsis Facilitates Screening and Performance Improvement Tracking

PubMed Central

Warmus, Holly R.; Schaffner, Erin K.; Kantawala, Sajel; Carcillo, Joseph; Rosen, Johanna; Horvat, Christopher M.

2018-01-01

Background: Sepsis kills almost 5,000 children annually, accounting for 16% of pediatric health care spending in the United States. Objectives: We sought to identify sepsis within the Electronic Health Record (EHR) of a quaternary children’s hospital to characterize disease incidence, improve recognition and response, and track performance metrics. Methods: Methods are organized in a plan-do-study-act cycle. During the “plan” phase, electronic definitions of sepsis (blood culture and antibiotic within 24 hours) and septic shock (sepsis plus vasoactive medication) were created to establish benchmark data and track progress with statistical process control. The performance of a screening tool was evaluated in the emergency department. During the “do” phase, a novel inpatient workflow is being piloted, which involves regular sepsis screening by nurses using the tool, and a regimented response to high risk patients. Results: Screening tool use in the emergency department reduced time to antibiotics (Fig. 1). Of the 6,159 admissions, EHR definitions identified 1,433 (23.3%) between July and December 2016 with sepsis, of which 159 (11.1%) had septic shock. Hospital mortality for all sepsis patients was 2.2% and 15.7% for septic shock (Table 1). These findings approximate epidemiologic studies of sepsis and severe sepsis, which report a prevalence range of 0.45–8.2% and mortality range of 8.2–25% (Table 2).1–5 Conclusions/Implications: Implementation of a sepsis screening tool is associated with improved performance. The prevalence of sepsis conditions identified with electronic definitions approximates the epidemiologic landscape characterized by other point-prevalence and administrative studies, providing face validity to this approach, and proving useful for tracking performance improvement. PMID:29732457

Metabolomics as a Functional Tool in Screening Gastro Intestinal Diseases: Where are we in High Throughput Screening?

PubMed

Gundamaraju, Rohit; Vemuri, Ravichandra; Eri, Rajaraman; Ishiki, Hamilton M; Coy-Barrera, Ericsson; Yarla, Nagendra Sastry; Dos Santos, Sócrates Golzio; Alves, Mateus Feitosa; Barbosa Filho, José Maria; Diniz, Margareth F F M; Scotti, Marcus T; Scotti, Luciana

2017-01-01

Identifying novel bio markers in gastro intestinal disease is a promising method where a comprehensive analysis of the metabolome is performed. Metabolomics has evolved enormously in the past decade, paving a path in gastro intestinal disease research, especially diseases which lead to high morbidity and mortality. Metabolomics involves identifying metabolites such as anti-oxidants, and amino acids etc., which are screened in the urine, feces and tissue samples. Certain cases employ advanced tools like GC-MS, 1HNMR and GC-MS/SPME which reveal valuable information concerning disease severity and differentiation. In light of escalating health care costs and risky invasive procedures, metabolomics can be chosen as a safe yet precise method for screening diseases like ulcerative colitis, Crohns' disease, celiac disease, and gastro intestinal cancers. The present review focuses on major advancements in gastro intestinal metabolomics, giving attention to which parameters are assessed, and to recent changes in metabolite analysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efficient Modeling and Active Learning Discovery of Biological Responses

PubMed Central

Naik, Armaghan W.; Kangas, Joshua D.; Langmead, Christopher J.; Murphy, Robert F.

2013-01-01

High throughput and high content screening involve determination of the effect of many compounds on a given target. As currently practiced, screening for each new target typically makes little use of information from screens of prior targets. Further, choices of compounds to advance to drug development are made without significant screening against off-target effects. The overall drug development process could be made more effective, as well as less expensive and time consuming, if potential effects of all compounds on all possible targets could be considered, yet the cost of such full experimentation would be prohibitive. In this paper, we describe a potential solution: probabilistic models that can be used to predict results for unmeasured combinations, and active learning algorithms for efficiently selecting which experiments to perform in order to build those models and determining when to stop. Using simulated and experimental data, we show that our approaches can produce powerful predictive models without exhaustive experimentation and can learn them much faster than by selecting experiments at random. PMID:24358322

Screen Color and Reading Performance on Closed-Circuit Television.

ERIC Educational Resources Information Center

Jacobs, R. J.

1990-01-01

To investigate whether screen color is an important variable in the prescription of closed circuit television (CCTV) systems, 16 adults with low vision were assessed on reading performance on white, green, and amber screens. When the screen luminance and contrast were equated for each CCTV, subjects' reading performance was unaffected by screen…

Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand

PubMed Central

Khunamornpong, Surapan; Settakorn, Jongkolnee; Sukpan, Kornkanok; Suprasert, Prapaporn; Srisomboon, Jatupol; Intaraphet, Suthida; Siriaunkgul, Sumalee

2016-01-01

Background Testing for high-risk human papillomavirus DNA (HPV test) has gained increasing acceptance as an alternative method to cytology in cervical cancer screening. Compared to cytology, HPV test has a higher sensitivity for the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), but this could lead to a large colposcopy burden. Genotyping for HPV16/18 has been recommended in triaging HPV-positive women. This study was aimed to evaluate the screening performance of HPV testing and the role of genotyping triage in Northern Thailand. Methods A population-based cervical screening program was performed in Chiang Mai (Northern Thailand) using cytology (conventional Pap test) and HPV test (Hybrid Capture 2). Women who had abnormal cytology or were HPV-positive were referred for colposcopy. Cervical samples from these women were genotyped using the Linear Array assay. Results Of 5,456 women, 2.0% had abnormal Pap test results and 6.5% tested positive with Hybrid Capture 2. Of 5,433 women eligible for analysis, 355 with any positive test had histologic confirmation and 57 of these had histologic HSIL+. The sensitivity for histologic HSIL+ detection was 64.9% for Pap test and 100% for Hybrid Capture 2, but the ratio of colposcopy per detection of each HSIL+ was more than two-fold higher with Hybrid Capture 2 than Pap test (5.9 versus 2.8). Genotyping results were available in 316 samples. HPV52, HPV16, and HPV58 were the three most common genotypes among women with histologic HSIL+. Performance of genotyping triage using HPV16/18/52/58 was superior to that of HPV16/18, with a higher sensitivity (85.7% versus 28.6%) and negative predictive value (94.2% versus 83.9%). Conclusions In Northern Thailand, HPV testing with genotyping triage shows better screening performance than cervical cytology alone. In this region, the addition of genotyping for HPV52/58 to HPV16/18 is deemed necessary in triaging women with positive HPV test. PMID:27336913

The accuracy of Patient Health Questionnaire-9 in detecting depression and measuring depression severity in high-risk groups in primary care.

PubMed

Wittkampf, Karin; van Ravesteijn, Hiske; Baas, Kim; van de Hoogen, Henk; Schene, Aart; Bindels, Patrick; Lucassen, Peter; van de Lisdonk, Eloy; van Weert, Henk

2009-01-01

Only half of patients with depressive disorder are diagnosed by their family physicians. Screening in high-risk groups might reduce this hidden morbidity. This study aims to determine the accuracy of the Patient Health Questionnaire-9 (PHQ-9) in (a) screening for depressive disorder, (b) diagnosing depressive disorder and (c) measuring the severity of depressive disorder in groups that are at high risk for depressive disorder. We compared the performance of the PHQ-9 as a screening instrument and as a diagnostic instrument to that of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interview, which we used as reference standard. Three high-risk groups of patients were selected: (a) frequent attenders, (b) patients with mental health problems and (c) patients with unexplained complaints. Patients completed the PHQ-9. Next, patients who were at risk for depression (based on PHQ scores) and a random sample of 20% of patients who were not at risk were selected for a second PHQ-9 and the reference standard (SCID-I). We assessed the adequacy of the PHQ-9 as a tool for severity measurement by comparing PHQ-9 scores with scores on the 17-item Hamilton Depression Rating Scale (HDRS-17) in patients diagnosed with a depressive disorder. Among 440 patients, both PHQ-9 and SCID-I were analyzed. The test characteristics for screening were sensitivity=0.93 and specificity=0.85; those for diagnosing were sensitivity=0.68 and specificity=0.95. The positive likelihood ratio for diagnosing was 14.2. The HDRS-17 was administered in 49 patients with depressive disorder. The Pearson correlation coefficient of the PHQ-9 to the HDRS-17 was r=.52 (P<.01). The PHQ-9 performs well as a screening instrument, but in diagnosing depressive disorder, a formal diagnostic process following the PHQ-9 remains imperative. The PHQ-9 does not seem adequate for measuring severity.

Ultrasensitive Single Fluorescence-Labeled Probe-Mediated Single Universal Primer-Multiplex-Droplet Digital Polymerase Chain Reaction for High-Throughput Genetically Modified Organism Screening.

PubMed

Niu, Chenqi; Xu, Yuancong; Zhang, Chao; Zhu, Pengyu; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

2018-05-01

As genetically modified (GM) technology develops and genetically modified organisms (GMOs) become more available, GMOs face increasing regulations and pressure to adhere to strict labeling guidelines. A singleplex detection method cannot perform the high-throughput analysis necessary for optimal GMO detection. Combining the advantages of multiplex detection and droplet digital polymerase chain reaction (ddPCR), a single universal primer-multiplex-ddPCR (SUP-M-ddPCR) strategy was proposed for accurate broad-spectrum screening and quantification. The SUP increases efficiency of the primers in PCR and plays an important role in establishing a high-throughput, multiplex detection method. Emerging ddPCR technology has been used for accurate quantification of nucleic acid molecules without a standard curve. Using maize as a reference point, four heterologous sequences ( 35S, NOS, NPTII, and PAT) were selected to evaluate the feasibility and applicability of this strategy. Surprisingly, these four genes cover more than 93% of the transgenic maize lines and serve as preliminary screening sequences. All screening probes were labeled with FAM fluorescence, which allows the signals from the samples with GMO content and those without to be easily differentiated. This fiveplex screening method is a new development in GMO screening. Utilizing an optimal amplification assay, the specificity, limit of detection (LOD), and limit of quantitation (LOQ) were validated. The LOD and LOQ of this GMO screening method were 0.1% and 0.01%, respectively, with a relative standard deviation (RSD) < 25%. This method could serve as an important tool for the detection of GM maize from different processed, commercially available products. Further, this screening method could be applied to other fields that require reliable and sensitive detection of DNA targets.

Frequency and Determinants of a Short-Interval Follow-up Recommendation After an Abnormal Screening Mammogram.

PubMed

Pelletier, Eric; Daigle, Jean-Marc; Defay, Fannie; Major, Diane; Guertin, Marie-Hélène; Brisson, Jacques

2016-11-01

After imaging assessment of an abnormal screening mammogram, a follow-up examination 6 months later is recommended to some women. Our aim was to identify which characteristics of lesions, women, and physicians are associated to such short-interval follow-up recommendation in the Quebec Breast Cancer Screening Program. Between 1998 and 2008, 1,839,396 screening mammograms were performed and a total of 114,781 abnormal screens were assessed by imaging only. Multivariate analysis was done with multilevel Poisson regression models with robust variance and generalized linear mixed models. A short-interval follow-up was recommended in 26.7% of assessments with imaging only, representing 2.3% of all screens. Case-mix adjusted proportion of short-interval follow-up recommendations varied substantially across physicians (range: 4%-64%). Radiologists with high recall rates (≥15%) had a high proportion of short-interval follow-up recommendation (risk ratio: 1.82; 95% confidence interval: 1.35-2.45) compared to radiologists with low recall rates (<5%). The adjusted proportion of short-interval follow-up was high (22.8%) even when a previous mammogram was usually available. Short-interval follow-up recommendation at assessment is frequent in this Canadian screening program, even when a previous mammogram is available. Characteristics related to radiologists appear to be key determinants of short-interval follow-up recommendation, rather than characteristics of lesions or patient mix. Given that it can cause anxiety to women and adds pressure on the health system, it appears important to record and report short-interval follow-up and to identify ways to reduce its frequency. Short-interval follow-up recommendations should be considered when assessing the burden of mammography screening. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

High performance flexible heat pipes

NASA Technical Reports Server (NTRS)

Shaubach, R. M.; Gernert, N. J.

1985-01-01

A Phase I SBIR NASA program for developing and demonstrating high-performance flexible heat pipes for use in the thermal management of spacecraft is examined. The program combines several technologies such as flexible screen arteries and high-performance circumferential distribution wicks within an envelope which is flexible in the adiabatic heat transport zone. The first six months of work during which the Phase I contract goal were met, are described. Consideration is given to the heat-pipe performance requirements. A preliminary evaluation shows that the power requirement for Phase II of the program is 30.5 kilowatt meters at an operating temperature from 0 to 100 C.

Otoacoustic Emissions in Rural Nicaragua: Cost Analysis and Implications for Newborn Hearing Screening.

PubMed

Wong, Lye-Yeng; Espinoza, Francisca; Alvarez, Karen Mojica; Molter, Dave; Saunders, James E

2017-05-01

Objective (1) Determine the incidence and risk factors for congenital hearing loss. (2) Perform cost analysis of screening programs. Study Design Proportionally distributed cross-sectional survey. Setting Jinotega, Nicaragua. Subjects and Methods Otoacoustic emissions (OAEs) were used to screen 640 infants <6 months of age from neonatal intensive care unit, institutional, and home birth settings. Data on 15 risk factors were analyzed. Cost of 4 implementation strategies was studied: universal screening, screening at the regional health center (RHC), targeted screening, and screening at the RHC plus targeted screening. Cost-effectiveness analysis over 10 years was based on disability-adjusted life year estimates, with the World Health Organization standard of cost-effectiveness ratio (CER) / gross domestic product (GDP) <3, with GDP set at $4884.15. Results Thirty-eight infants failed the initial OAE (5.94%). In terms of births, 325 (50.8%) were in the RHC, 69 (10.8%) in the neonatal intensive care unit, and 29 (4.5%) at home. Family history and birth defect were significant in univariate analysis; birth defect was significant in multivariate analysis. Cost-effectiveness analysis demonstrated that OAE screening is cost-effective without treatment (CER/GDP = 0.06-2.00) and with treatment (CER/GDP = 0.58-2.52). Conclusions Our rate of OAE failures was comparable to those of developed countries and lower than hearing loss rates noted among Nicaraguan schoolchildren, suggesting acquired or progressive etiology in the latter. Birth defects and familial hearing loss correlated with OAE failure. OAE screening of infants is feasible and cost-effective in rural Nicaragua, although highly influenced by estimated hearing loss severity in identified infants and the high travel costs incurred in a targeted screening strategy.

Washington Phase II Fish Diversion Screen Evaluations in the Yakima and Touchet River Basins, 2005-2006 Annual Reports.

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

Chamness, Mickie; Abernethy, C.; Tunnicliffe, Cherylyn

2006-02-01

In 2005, Pacific Northwest National Laboratory (PNNL) researchers evaluated 25 Phase II fish screen sites in the Yakima and Touchet river basins. Pacific Northwest National Laboratory performs these evaluations for Bonneville Power Administration (BPA) to determine whether the fish screening devices meet National Marine Fisheries Service (NMFS) criteria to promote safe and timely fish passage. Evaluations consist of measuring velocities in front of the screens, using an underwater camera to look at the condition and environment in front of the screens, and noting the general condition and operation of the sites. Results of the evaluations in 2005 include the following:more » (1) Most approach velocities met the NMFS criterion of less than or equal to 0.4 fps. Less than 13% of all approach measurements exceeded the criterion, and these occurred at 10 of the sites. Flat-plate screens had more problems than drum screens with high approach velocities. (2) Bypass velocities generally were greater than sweep velocities, but sweep velocities often did not increase toward the bypass. The latter condition could slow migration of fish through the facility. (3) Screen and seal materials generally were in good condition. (4) Automated cleaning brushes generally functioned properly; chains and other moving parts were typically well-greased and operative. (5) Washington Department of Fish and Wildlife (WDFW) and U.S. Bureau of Reclamation (USBR) generally operate and maintain fish screen facilities in a way that provides safe passage for juvenile fish. (6) In some instances, irrigators responsible for specific maintenance at their sites (e.g., debris removal) are not performing their tasks in a way that provides optimum operation of the fish screen facility. New ways need to be found to encourage them to maintain their facilities properly. (7) We recommend placing datasheets providing up-to-date operating criteria and design flows in each sites logbox. The datasheet should include bypass design flows and a table showing depths of water over the weir and corresponding bypass flow. This information is available at some of the sites but may be outdated. These data are used to determine if the site is running within design criteria. (8) Modifying use of debris control plates at Gleed helped minimize the extreme fluctuations in flow, but approach velocities are still too high. Other ways to reduce the approach velocities need to be tried, possibly including redesign of the site. (9) Alternatives to a screen site at Taylor should be considered. A lot of effort was spent trying to increase water to the site, but it still was unable to operate within NMFS criteria for most of the year and may be a hazard to juvenile salmonids. We conclude that the conditions at most of the Phase II fish screen facilities we evaluated in 2005 would be expected to provide safe passage for juvenile fish. For those sites where conditions are not always optimum for safe fish passage, PNNL researchers will try to coordinate with the WDFW and USBR in 2006 to find solutions to the problems. Some of those problems are consistently high approach velocities at specific sites, including Congdon, Naches-Selah, Union Gap, and Yakima-Tieton. We would like to be able to monitor changes in velocities as soon as operations and maintenance personnel adjust the louvers or porosity boards at these sites. This will give them immediate feedback on the results of their modifications and allow additional adjustments as necessary until the conditions meet NMFS criteria. Pacific Northwest National Laboratory has performed evaluations at many of these sites over the past 8 years, providing information WDFW and USBR personnel can use to perform their operations and maintenance more effectively. Consequently, overall effectiveness of the screens facilities has improved over time.« less

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

PubMed

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.

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

PubMed

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

2009-11-01

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

A high-performance, flexible and robust metal nanotrough-embedded transparent conducting film for wearable touch screen panels

NASA Astrophysics Data System (ADS)

Im, Hyeon-Gyun; An, Byeong Wan; Jin, Jungho; Jang, Junho; Park, Young-Geun; Park, Jang-Ung; Bae, Byeong-Soo

2016-02-01

We report a high-performance, flexible and robust metal nanotrough-embedded transparent conducting hybrid film (metal nanotrough-GFRHybrimer). Using an electro-spun polymer nanofiber web as a template and vacuum-deposited gold as a conductor, a junction resistance-free continuous metal nanotrough network is formed. Subsequently, the metal nanotrough is embedded on the surface of a glass-fabric reinforced composite substrate (GFRHybrimer). The monolithic composite structure of our transparent conducting film allows simultaneously high thermal stability (24 h at 250 °C in air), a smooth surface topography (Rrms < 1 nm) and excellent opto-electrical properties. A flexible touch screen panel (TSP) is fabricated using the transparent conducting films. The flexible TSP device stably operates on the back of a human hand and on a wristband.We report a high-performance, flexible and robust metal nanotrough-embedded transparent conducting hybrid film (metal nanotrough-GFRHybrimer). Using an electro-spun polymer nanofiber web as a template and vacuum-deposited gold as a conductor, a junction resistance-free continuous metal nanotrough network is formed. Subsequently, the metal nanotrough is embedded on the surface of a glass-fabric reinforced composite substrate (GFRHybrimer). The monolithic composite structure of our transparent conducting film allows simultaneously high thermal stability (24 h at 250 °C in air), a smooth surface topography (Rrms < 1 nm) and excellent opto-electrical properties. A flexible touch screen panel (TSP) is fabricated using the transparent conducting films. The flexible TSP device stably operates on the back of a human hand and on a wristband. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07657a

A High-Throughput Screening Approach to Discovering Good Forms of Biologically Inspired Visual Representation

PubMed Central

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

2009-01-01

While many models of biological object recognition share a common set of “broad-stroke” properties, the performance of any one model depends strongly on the choice of parameters in a particular instantiation of that model—e.g., the number of units per layer, the size of pooling kernels, exponents in normalization operations, etc. Since the number of such parameters (explicit or implicit) is typically large and the computational cost of evaluating one particular parameter set is high, the space of possible model instantiations goes largely unexplored. Thus, when a model fails to approach the abilities of biological visual systems, we are left uncertain whether this failure is because we are missing a fundamental idea or because the correct “parts” have not been tuned correctly, assembled at sufficient scale, or provided with enough training. Here, we present a high-throughput approach to the exploration of such parameter sets, leveraging recent advances in stream processing hardware (high-end NVIDIA graphic cards and the PlayStation 3's IBM Cell Processor). In analogy to high-throughput screening approaches in molecular biology and genetics, we explored thousands of potential network architectures and parameter instantiations, screening those that show promising object recognition performance for further analysis. We show that this approach can yield significant, reproducible gains in performance across an array of basic object recognition tasks, consistently outperforming a variety of state-of-the-art purpose-built vision systems from the literature. As the scale of available computational power continues to expand, we argue that this approach has the potential to greatly accelerate progress in both artificial vision and our understanding of the computational underpinning of biological vision. PMID:19956750

Combinatorial high-throughput optical screening of high performance Pd alloy cathode for hybrid Li-air battery.

PubMed

Jun, Young Jin; Park, Sung Hyeon; Woo, Seong Ihl

2014-12-08

Combinatorial high-throughput optical screening method was developed to find the optimum composition of highly active Pd-based catalysts at the cathode of the hybrid Li-air battery. Pd alone, which is one-third the cost of Pt, has difficulty in replacing Pt; therefore, the integration of other metals was investigated to improve its performance toward oxygen reduction reaction (ORR). Among the binary Pd-based catalysts, the composition of Pd-Ir derived catalysts had higher performance toward ORR compared to other Pd-based binary combinations. The composition at 88:12 at. % (Pd: Ir) showed the highest activity toward ORR at the cathode of the hybrid Li-air battery. The prepared Pd(88)Ir(12)/C catalyst showed a current density of -2.58 mA cm(-2) at 0.8 V (vs RHE), which was around 30% higher compared to that of Pd/C (-1.97 mA cm(-2)). When the prepared Pd(88)Ir(12)/C catalyst was applied to the hybrid Li-air battery, the polarization of the cell was reduced and the energy efficiency of the cell was about 30% higher than that of the cell with Pd/C.

Molecular markers for colorectal cancer screening

PubMed Central

Dickinson, Brandon T.; Kisiel, John; Ahlquist, David A.; Grady, William M.

2016-01-01

Colorectal cancer (CRC), although a significant cause of morbidity and mortality worldwide, has seen a declining incidence and mortality in countries with programmatic screening. Fecal occult blood testing (FOBT) and endoscopic approaches are the predominant screening methods currently. The discovery of the adenoma→carcinoma sequence and a greater understanding of the genetic and epigenetic changes that drive the formation of CRC have contributed to innovative research to identify molecular markers for highly accurate, non-invasive screening tests for CRC. DNA, proteins, messenger RNA, and micro-RNA have all been evaluated. The observation of tumor cell exfoliation into the mucocellular layer of the colonic epithelium and proven stability of DNA in a harsh stool environment make stool DNA a particularly promising marker. The development of a clinically useful stool DNA test has required numerous technical advances, including optimization in DNA stabilization, the development of assays with high analytical sensitivity, and the identification of specific and broadly informative molecular markers. A multi-target stool DNA (MT-sDNA) test, which combines both mutant and methylated DNA markers and a fecal immunochemical test (FIT), recently performed favorably in a large cross-sectional validation study and has been approved by the US Food and Drug Administration (FDA) for the screening of asymptomatic, average risk individuals. The ultimate way in which molecular marker screening assays will be used in clinical practice will require additional studies to determine optimal screening intervals, factors affecting compliance, management of false positive results, and the use of these assays in high-risk populations, as well as other considerations. PMID:25994221

The cost and yield of photoscreening: impact of photoscreening on overall pediatric ophthalmic costs.

PubMed

Arnold, Robert W; Armitage, M Diane; Gionet, Elisha G; Balinger, Adam; Kovtoun, Tatiana A; Machida, Christy; Coon, Lynn J

2005-01-01

Approximately 5% of preschool-age children suffer from amblyopia. Many of them have high or unequal hyperopia. Amblyogenic risk factors frequently can be detected by photoscreening. Free photoscreening was offered to Alaskan children ages 1 to 5 from urban and rural screening hubs. Screened images were mailed to the Alaska Blind Child Discovery coordinating center for physician photoscreen interpretation, specifically seeking latent or anisometropic hyperopia. Parents and screeners then were mailed results and information about amblyopia. Follow-up examination data were tallied, and a cost-consequence analysis was developed for various vision screening paradigms and eye care. From 1996 through 2003, a total of 13,255 screenings were performed with a positive interpretation rate of 4.7%. Penetrance of screening was 22% in urban and 44% in rural communities. Positive predictive value was estimated to be more than 90%. Average cost to screen and inform an Alaskan preschooler was approximately 10.67 dollars, and cost to detect amblyogenic risk factors by photoscreening in an Alaskan was approximately 206 dollars. Compared to American Academy of Pediatrics (AAP) 1995 guidelines, implementing photoscreening added 9%, while mandating complete prekindergarten examination added 49% to overall eye care. MTI photoscreening achieved high community penetrance and high positive predictive value for latent hyperopia and other amblyogenic factors. When follow-up costs are considered, adding photoscreening to current AAP guidelines may add 112 dollars per child over 10 years, but probably would assist in the reduction of amblyopia. Penetrance of urban photoscreening likely will remain low unless pediatric vision screening guidelines and reimbursement are revised.

[Opinion from physicians on the need for dyslipidemia screening in cardiovascular risk. Similarities and differences between primary care and other specialties. The DIANA study].

PubMed

Serrano, Adalberto; Pascual, Vicente

2017-10-01

The clinical inertia in the screening and treatment of patients at high or very high cardiovascular risk leads to the failure to achieve LDLc targets in this population. The aim of the DIANA study was to determine the opinion of doctors about the screening for dyslipidaemia, the usual practice, and the differences between Primary Care physicians and other specialties. A questionnaire, using the modified Delphi method, included four blocks on dyslipidemic patients with impaired glucose metabolism. Of the 497 participating experts, 58% were Primary Care physicians. There was agreement on the need for dyslipidemia screening in patients with diabetes, ischaemic heart disease or hypertension, although to a lesser extent among Primary Care physicians. Greater significant differences were found in situations such as pre-diabetes or family history of premature cardiovascular disease (86.2% and 88.6% in Primary Care physicians versus 96.1% and 97.6% in other specialties, respectively). There was no agreement on the need for screening in the presence of xanthomas, xanthelasmas or corneal arcus in people under the age of 45 years, with statistically significant differences in the latter. Dyslipidaemia screening is mainly performed on patients with cardiovascular disease or any major cardiovascular risk factor, and cutaneous lesions of familial hypercholesterolaemia are underestimated. The need for accurate screening and treatment of dyslipidemia in subjects at high cardiovascular risk must be stressed. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of Radiologists’ Diagnostic Work-up Volume on Interpretive Performance

PubMed Central

Anderson, Melissa L.; Smith, Robert A.; Carney, Patricia A.; Miglioretti, Diana L.; Monsees, Barbara S.; Sickles, Edward A.; Taplin, Stephen H.; Geller, Berta M.; Yankaskas, Bonnie C.; Onega, Tracy L.

2014-01-01

Purpose To examine radiologists’ screening performance in relation to the number of diagnostic work-ups performed after abnormal findings are discovered at screening mammography by the same radiologist or by different radiologists. Materials and Methods In an institutional review board–approved HIPAA-compliant study, the authors linked 651 671 screening mammograms interpreted from 2002 to 2006 by 96 radiologists in the Breast Cancer Surveillance Consortium to cancer registries (standard of reference) to evaluate the performance of screening mammography (sensitivity, false-positive rate [FPRfalse-positive rate], and cancer detection rate [CDRcancer detection rate]). Logistic regression was used to assess the association between the volume of recalled screening mammograms (“own” mammograms, where the radiologist who interpreted the diagnostic image was the same radiologist who had interpreted the screening image, and “any” mammograms, where the radiologist who interpreted the diagnostic image may or may not have been the radiologist who interpreted the screening image) and screening performance and whether the association between total annual volume and performance differed according to the volume of diagnostic work-up. Results Annually, 38% of radiologists performed the diagnostic work-up for 25 or fewer of their own recalled screening mammograms, 24% performed the work-up for 0–50, and 39% performed the work-up for more than 50. For the work-up of recalled screening mammograms from any radiologist, 24% of radiologists performed the work-up for 0–50 mammograms, 32% performed the work-up for 51–125, and 44% performed the work-up for more than 125. With increasing numbers of radiologist work-ups for their own recalled mammograms, the sensitivity (P = .039), FPRfalse-positive rate (P = .004), and CDRcancer detection rate (P < .001) of screening mammography increased, yielding a stepped increase in women recalled per cancer detected from 17.4 for 25 or fewer mammograms to 24.6 for more than 50 mammograms. Increases in work-ups for any radiologist yielded significant increases in FPRfalse-positive rate (P = .011) and CDRcancer detection rate (P = .001) and a nonsignificant increase in sensitivity (P = .15). Radiologists with a lower annual volume of any work-ups had consistently lower FPRfalse-positive rate, sensitivity, and CDRcancer detection rate at all annual interpretive volumes. Conclusion These findings support the hypothesis that radiologists may improve their screening performance by performing the diagnostic work-up for their own recalled screening mammograms and directly receiving feedback afforded by means of the outcomes associated with their initial decision to recall. Arranging for radiologists to work up a minimum number of their own recalled cases could improve screening performance but would need systems to facilitate this workflow. © RSNA, 2014 Online supplemental material is available for this article. PMID:24960110

Effect of radiologists' diagnostic work-up volume on interpretive performance.

PubMed

Buist, Diana S M; Anderson, Melissa L; Smith, Robert A; Carney, Patricia A; Miglioretti, Diana L; Monsees, Barbara S; Sickles, Edward A; Taplin, Stephen H; Geller, Berta M; Yankaskas, Bonnie C; Onega, Tracy L

2014-11-01

To examine radiologists' screening performance in relation to the number of diagnostic work-ups performed after abnormal findings are discovered at screening mammography by the same radiologist or by different radiologists. In an institutional review board-approved HIPAA-compliant study, the authors linked 651 671 screening mammograms interpreted from 2002 to 2006 by 96 radiologists in the Breast Cancer Surveillance Consortium to cancer registries (standard of reference) to evaluate the performance of screening mammography (sensitivity, false-positive rate [ FPR false-positive rate ], and cancer detection rate [ CDR cancer detection rate ]). Logistic regression was used to assess the association between the volume of recalled screening mammograms ("own" mammograms, where the radiologist who interpreted the diagnostic image was the same radiologist who had interpreted the screening image, and "any" mammograms, where the radiologist who interpreted the diagnostic image may or may not have been the radiologist who interpreted the screening image) and screening performance and whether the association between total annual volume and performance differed according to the volume of diagnostic work-up. Annually, 38% of radiologists performed the diagnostic work-up for 25 or fewer of their own recalled screening mammograms, 24% performed the work-up for 0-50, and 39% performed the work-up for more than 50. For the work-up of recalled screening mammograms from any radiologist, 24% of radiologists performed the work-up for 0-50 mammograms, 32% performed the work-up for 51-125, and 44% performed the work-up for more than 125. With increasing numbers of radiologist work-ups for their own recalled mammograms, the sensitivity (P = .039), FPR false-positive rate (P = .004), and CDR cancer detection rate (P < .001) of screening mammography increased, yielding a stepped increase in women recalled per cancer detected from 17.4 for 25 or fewer mammograms to 24.6 for more than 50 mammograms. Increases in work-ups for any radiologist yielded significant increases in FPR false-positive rate (P = .011) and CDR cancer detection rate (P = .001) and a nonsignificant increase in sensitivity (P = .15). Radiologists with a lower annual volume of any work-ups had consistently lower FPR false-positive rate , sensitivity, and CDR cancer detection rate at all annual interpretive volumes. These findings support the hypothesis that radiologists may improve their screening performance by performing the diagnostic work-up for their own recalled screening mammograms and directly receiving feedback afforded by means of the outcomes associated with their initial decision to recall. Arranging for radiologists to work up a minimum number of their own recalled cases could improve screening performance but would need systems to facilitate this workflow.

Development of biosensors and their application in metabolic engineering.

PubMed

Zhang, Jie; Jensen, Michael K; Keasling, Jay D

2015-10-01

In a sustainable bioeconomy, many commodities and high value chemicals, including pharmaceuticals, will be manufactured using microbial cell factories from renewable feedstocks. These cell factories can be efficiently generated by constructing libraries of diversified genomes followed by screening for the desired phenotypes. However, methods available for microbial genome diversification far exceed our ability to screen and select for those variants with optimal performance. Genetically encoded biosensors have shown the potential to address this gap, given their ability to respond to small molecule binding and ease of implementation with high-throughput analysis. Here we describe recent progress in biosensor development and their applications in a metabolic engineering context. We also highlight examples of how biosensors can be integrated with synthetic circuits to exert feedback regulation on the metabolism for improved performance of cell factories. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Evaluation of the national epidemiological program of breast cancer screening in the Grand Duchy of Luxembourg, 1999-2002].

PubMed

Scharpantgen, Astrid; Lux, Christiane; Wagnon, Marie-Christine; Shannoun, Ferid; Schank, Jean-Marie; Back, Carlo; Brochmann, Chantal; Hansen-Koenig, Danielle

2004-01-01

In 1992 a national breast cancer screening programme was launched in Luxembourg with following characteristics; invitation at 2-yearly interval, 2 views, double reading for women aged between 50 and 64 and since 2001, those aged 65-69 are as well included. From the beginning on, one of the main concern was to respect a rigorous methodology, in accordance with the recommendations of the European Commission. This paper presents the early performance indicators of the years 1999-2002 of the "Programme Mammographie". Almost all histopathological results were obtained, because only one national pathology laboratory exists in Luxembourg, where also the national tumor's register is located. In ten years, a total of 91.432 mammograms were performed. The results of the early performance indicators are in agreement with the European Recommendations. A 36% detection rate of small size cancers, < or = 10 mm, and since 2000, more then 70% of node negative cancers are observed among women aged 50-64 attending the Programme. The cancer rate with a good prognostic factor for the patients is high. Despite good results, the rate of interval cancers is still too high, and two conclusions can be drown: the women's participation at screening has to be steady in time without trespassing a two years intervals, and after the detection of small cancer a high quality assessment should be followed by an adequate treatment, leading to a reduction of mortality and also to a decrease of morbidity by treatment.

Influence relevance voting: an accurate and interpretable virtual high throughput screening method.

PubMed

Swamidass, S Joshua; Azencott, Chloé-Agathe; Lin, Ting-Wan; Gramajo, Hugo; Tsai, Shiou-Chuan; Baldi, Pierre

2009-04-01

Given activity training data from high-throughput screening (HTS) experiments, virtual high-throughput screening (vHTS) methods aim to predict in silico the activity of untested chemicals. We present a novel method, the Influence Relevance Voter (IRV), specifically tailored for the vHTS task. The IRV is a low-parameter neural network which refines a k-nearest neighbor classifier by nonlinearly combining the influences of a chemical's neighbors in the training set. Influences are decomposed, also nonlinearly, into a relevance component and a vote component. The IRV is benchmarked using the data and rules of two large, open, competitions, and its performance compared to the performance of other participating methods, as well as of an in-house support vector machine (SVM) method. On these benchmark data sets, IRV achieves state-of-the-art results, comparable to the SVM in one case, and significantly better than the SVM in the other, retrieving three times as many actives in the top 1% of its prediction-sorted list. The IRV presents several other important advantages over SVMs and other methods: (1) the output predictions have a probabilistic semantic; (2) the underlying inferences are interpretable; (3) the training time is very short, on the order of minutes even for very large data sets; (4) the risk of overfitting is minimal, due to the small number of free parameters; and (5) additional information can easily be incorporated into the IRV architecture. Combined with its performance, these qualities make the IRV particularly well suited for vHTS.

A quartz-based micro catalytic methane sensor by high resolution screen printing

NASA Astrophysics Data System (ADS)

Lu, Wenshuai; Jing, Gaoshan; Bian, Xiaomeng; Yu, Hongyan; Cui, Tianhong

2016-02-01

A micro catalytic methane sensor was proposed and fabricated on a bulk fused quartz substrate using a high resolution screen printing technique for the first time, with reduced power consumption and optimized sensitivity. The sensor was designed by the finite element method and quartz was chosen as the substrate material and alumina support with optimized dimensions. Fabrication of the sensor consisted of two MEMS processes, lift-off and high resolution screen printing, with the advantages of high yield and uniformity. When the sensor’s regional working temperature changes from 250 °C to 470 °C, its sensitivity increases, as well as the power consumption. The highest sensitivity can reach 1.52 mV/% CH4. A temperature of 300 °C was chosen as the optimized working temperature, and the sensor’s sensitivity, power consumption, nonlinearity and response time are 0.77 mV/% CH4, 415 mW, 2.6%, and 35 s, respectively. This simple, but highly uniform fabrication process and the reliable performance of this sensor may lead to wide applications for methane detection.

High-resolution anoscopy: Unchartered territory for gastroenterologists?

PubMed

Albuquerque, Andreia

2015-09-25

High-resolution anoscopy (HRA) is a procedure where patients with an increased risk of anal cancer, like men who have sex with men, human immunodeficiency virus infected individuals, transplant patients and women with a history of lower genital tract neoplasia, with abnormal anal cytology results, are submitted to anal and perianal visualization under magnification. This will allow for a better detection of anal high-grade lesions that can be treated, in an effort to prevent anal cancer. Anal cancer screening follows the same principles that cervical cancer screening. During this procedure, an anoscope is inserted and a colposcope is used to examine systematically the squamocolumnar junction, the transformation zone and the perianal skin. Initially the observation is done with no staining and then with the application of acetic acid and Lugol's iodine solution, allowing for better lesion identification and characterization. Any suspicious lesion seen should be carefully evaluated and biopsied. Without HRA only a small percentage of suspicious lesions are identified. High-grade lesions that are detected can be ablated under HRA. This is a challenging exam to perform, with a long learning curve and the number of clinicians performing it is limited, although the growing number of patients that need to been screened. Specific equipment is required, with these patients ideally been followed by a multidisciplinary team, in a reference centre. HRA remains unfamiliar for many gastroenterologists.

Insights into Inpatients with Poor Vision: A High Value Proposition

PubMed Central

Press, Valerie G.; Matthiesen, Madeleine I.; Ranadive, Alisha; Hariprasad, Seenu M.; Meltzer, David O.; Arora, Vineet M.

2015-01-01

Background Vision impairment is an under-recognized risk factor for adverse events among hospitalized patients, yet vision is neither routinely tested nor documented for inpatients. Low-cost ($8 and up) non-prescription ‘readers’ may be a simple, high-value intervention to improve inpatients’ vision. We aimed to study initial feasibility and efficacy of screening and correcting inpatients’ vision. Methods From June 2012 through January 2014 we began testing whether participants’ vision corrected with non-prescription lenses for eligible participants failing a vision screen (Snellen chart) performed by research assistants (RAs). Descriptive statistics and tests of comparison, including t-tests and chi-squared tests, were used when appropriate. All analyses were performed using Stata version 12 (StataCorps, College Station, TX). Results Over 800 participants’ vision was screened (n=853). Older (≥65 years; 56%) participants were more likely to have insufficient vision than younger (<65 years; 28%; p<0.001). Non-prescription readers corrected the majority of eligible participants’ vision (82%, 95/116). Discussion Among an easily identified sub-group of inpatients with poor vision, low-cost ‘readers’ successfully corrected most participants’ vision. Hospitalists and other clinicians working in the inpatient setting can play an important role in identifying opportunities to provide high-value care related to patients’ vision. PMID:25755206

Cost-effectiveness analysis of different types of human papillomavirus vaccination combined with a cervical cancer screening program in mainland China.

PubMed

Mo, Xiuting; Gai Tobe, Ruoyan; Wang, Lijie; Liu, Xianchen; Wu, Bin; Luo, Huiwen; Nagata, Chie; Mori, Rintaro; Nakayama, Takeo

2017-07-18

China has a high prevalence of human papillomavirus (HPV) and a consequently high burden of disease with respect to cervical cancer. The HPV vaccine has proved to be effective in preventing cervical cancer and is now a part of routine immunization programs worldwide. It has also proved to be cost effective. This study aimed to assess the cost-effectiveness of 2-, 4-, and 9-valent HPV vaccines (hereafter, HPV2, 4 or 9) combined with current screening strategies in China. A Markov model was developed for a cohort of 100,000 HPV-free girls to simulate the natural history to HPV infection. Three recommended screening methods (1. liquid-based cytology test + HPV DNA test; 2. pap smear cytology test + HPV DNA test; 3. visual inspection with acetic acid) and three types of HPV vaccination program (HPV2/4/9) were incorporated into 15 intervention options, and the incremental cost-effectiveness ratio (ICER) was calculated to determine the dominant strategies. Costs, transition probabilities and utilities were obtained from a review of the literature and national databases. One-way sensitivity analyses and threshold analyses were performed for key variables in different vaccination scenarios. HPV9 combined with screening showed the highest health impact in terms of reducing HPV-related diseases and increasing the number of quality-adjusted life years (QALYs). Under the current thresholds of willingness to pay (WTP, 3 times the per capita GDP or USD$ 23,880), HPV4/9 proved highly cost effective, while HPV2 combined with screening cost more and was less cost effective. Only when screening coverage increased to 60% ~ 70% did the HPV2 and screening combination strategy become economically feasible. The combination of the HPV4/9 vaccine with current screening strategies for adolescent girls was highly cost-effective and had a significant impact on reducing the HPV infection-related disease burden in Mainland China.

Screening for colorectal cancer in Tianhe, Guangzhou: results of combining fecal immunochemical tests and risk factors for selecting patients requiring colonoscopy.

PubMed

Liao, Yi; Li, Senmao; Chen, Chunyu; He, Xuan; Lin, Feng; Wang, Jianping; Yang, Zuli; Lan, Ping

2018-05-01

To explore the performance of a protocol combining fecal immunochemical test (FIT) and a high-risk factor questionnaire (HRFQ) for selecting patients requiring colonoscopy as part of a population-based colorectal cancer (CRC) screening program in China. From 2015 to 2016, we conducted a CRC screening program for all residents aged 45 years or older in Tianhe District, Guangzhou City, China. Participants underwent an FIT and received an HRFQ as part of primary screening. Those with positive FIT and/or HRFQ results were considered to be at high risk and were recommended to undergo colonoscopy. A total of 10 074 subjects were recruited and enrolled in the screening program. In the enrolled population, 17.5% had positive FIT results and 19.4% had positive HRFQ results. Of those recommended to undergo diagnostic colonoscopy, 773 did so. The screening method's overall positive predictive value (PPV) was 4.9% for non-adenomatous polyps, 11.4% for low-risk adenomas (LRAs), 15.9% for high-risk adenomas (HRAs) and 1.6% for CRC. The PPVs of positive FIT results for non-adenomatous polyps, LRAs, HRAs and CRC were 5.2%, 15.9%, 22.5% and 2.5%, respectively. The PPVs of positive HRFQ results for non-adenomatous polyps, LRA, HRA and CRC were 4.1%, 10.2%, 14.3% and 1.4%, respectively. The PPVs associated with combined positive FIT and HRFQ results for non-adenomatous polyps, LRAs, HRAs and CRC were 4.5%, 16.4%, 23.7% and 2.8%, respectively. Our results suggest that this two-step CRC screening strategy, involving a combination of FIT and HRFQ followed by colonoscopy, is useful to identify early-stage CRC. The high detection rates and PPVs for CRC and adenomas encourage this strategy's use in ongoing screening programs.

Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density

PubMed Central

Edwards, D. L.; Saleh, A. A.; Greenspan, S. L.

2015-01-01

Summary We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90 % at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. Introduction The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. Methods Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. Results One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89 % (95%CI 82–96 %) and 41 % (95%CI 23–59 %), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88 % (95%CI 79–97 %) and 55 % (95%CI 42–68 %), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90 % but always with a trade-off of relatively low specificity. Conclusions Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90 % for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. PMID:25644147

SPOT-ligand 2: improving structure-based virtual screening by binding-homology search on an expanded structural template library.

PubMed

Litfin, Thomas; Zhou, Yaoqi; Yang, Yuedong

2017-04-15

The high cost of drug discovery motivates the development of accurate virtual screening tools. Binding-homology, which takes advantage of known protein-ligand binding pairs, has emerged as a powerful discrimination technique. In order to exploit all available binding data, modelled structures of ligand-binding sequences may be used to create an expanded structural binding template library. SPOT-Ligand 2 has demonstrated significantly improved screening performance over its previous version by expanding the template library 15 times over the previous one. It also performed better than or similar to other binding-homology approaches on the DUD and DUD-E benchmarks. The server is available online at http://sparks-lab.org . yaoqi.zhou@griffith.edu.au or yuedong.yang@griffith.edu.au. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Screening Children for Family Violence: A Review of the Evidence for the US Preventive Services Task Force

PubMed Central

Nygren, Peggy; Nelson, Heidi D.; Klein, Jonathan

2004-01-01

BACKGROUND We wanted to evaluate the benefits and harms of screening children in primary health care settings for abuse and neglect resulting from family violence by examining the evidence on the performance of screening instruments and the effectiveness of interventions. METHODS We searched for relevant studies in MEDLINE, PsycINFO, CINAHL, ERIC, Cochrane Controlled Trials Register, and reference lists. English language abstracts with original data about family violence against children focusing on screening and interventions initiated or based in health care settings were included. We extracted selected information about study design, patient populations and settings, methods of assessment or intervention, and outcome measures, and applied a set of criteria to evaluate study quality. RESULTS All instruments designed to screen for child abuse and neglect were directed to parents, particularly pregnant women. These instruments had fairly high sensitivity but low specificity when administered in high-risk study populations and have not been widely tested in other populations. Randomized controlled trials of frequent nurse home visitation programs beginning during pregnancy that address behavioral and psychological factors indicated improved abuse measures and outcomes. No studies were identified about interventions in older children or harms associated with screening and intervention. CONCLUSIONS No trials of the effectiveness of screening in a health care setting have been published. Clinician referrals to nurse home visitation during pregnancy and in early childhood may reduce abuse in selected populations. There are no studies about harms of screening and interventions. PMID:15083858

1001 Ways to run AutoDock Vina for virtual screening

NASA Astrophysics Data System (ADS)

Jaghoori, Mohammad Mahdi; Bleijlevens, Boris; Olabarriaga, Silvia D.

2016-03-01

Large-scale computing technologies have enabled high-throughput virtual screening involving thousands to millions of drug candidates. It is not trivial, however, for biochemical scientists to evaluate the technical alternatives and their implications for running such large experiments. Besides experience with the molecular docking tool itself, the scientist needs to learn how to run it on high-performance computing (HPC) infrastructures, and understand the impact of the choices made. Here, we review such considerations for a specific tool, AutoDock Vina, and use experimental data to illustrate the following points: (1) an additional level of parallelization increases virtual screening throughput on a multi-core machine; (2) capturing of the random seed is not enough (though necessary) for reproducibility on heterogeneous distributed computing systems; (3) the overall time spent on the screening of a ligand library can be improved by analysis of factors affecting execution time per ligand, including number of active torsions, heavy atoms and exhaustiveness. We also illustrate differences among four common HPC infrastructures: grid, Hadoop, small cluster and multi-core (virtual machine on the cloud). Our analysis shows that these platforms are suitable for screening experiments of different sizes. These considerations can guide scientists when choosing the best computing platform and set-up for their future large virtual screening experiments.

1001 Ways to run AutoDock Vina for virtual screening.

PubMed

Jaghoori, Mohammad Mahdi; Bleijlevens, Boris; Olabarriaga, Silvia D

2016-03-01

Large-scale computing technologies have enabled high-throughput virtual screening involving thousands to millions of drug candidates. It is not trivial, however, for biochemical scientists to evaluate the technical alternatives and their implications for running such large experiments. Besides experience with the molecular docking tool itself, the scientist needs to learn how to run it on high-performance computing (HPC) infrastructures, and understand the impact of the choices made. Here, we review such considerations for a specific tool, AutoDock Vina, and use experimental data to illustrate the following points: (1) an additional level of parallelization increases virtual screening throughput on a multi-core machine; (2) capturing of the random seed is not enough (though necessary) for reproducibility on heterogeneous distributed computing systems; (3) the overall time spent on the screening of a ligand library can be improved by analysis of factors affecting execution time per ligand, including number of active torsions, heavy atoms and exhaustiveness. We also illustrate differences among four common HPC infrastructures: grid, Hadoop, small cluster and multi-core (virtual machine on the cloud). Our analysis shows that these platforms are suitable for screening experiments of different sizes. These considerations can guide scientists when choosing the best computing platform and set-up for their future large virtual screening experiments.

[Screening of the risk of functional decline performed by an inpatient geriatric consultation team in a general hospital].

PubMed

Benoît, F; Bertiaux, M; Schouterden, R; Huard, E; Segers, K; Decorte, L; Robberecht, J; Simonetti, C; Surquin, M

2013-01-01

The Mobile Geriatric Team (MGT) is part of the Geriatric Care Program and aims to provide interdisciplinary geriatric expertise to other professionals for old patients hospitalized outside geriatric department. Our hospital has a MGT since 2008. Our objective is to retrospectively describe the population of patients of 75 years and older hospitalized outside the geriatric ward and screened for the risk of functional decline by the MGT between 1 October 2009 and 30 September 2011. We recorded the risk of functional decline, as indicated by the Identification of Senior At Risk score (ISAR) performed within 48 h after admission, place of living, discharge destination, Mini Mental State Examination (MMSE) and Geriatric Depression Scale (GDS) scores. In two years, 1.568 patients > or = 75 Y were screened with the ISAR score (mean age 82.5 Y, 60.7% of women). We identified 833 patients with a high-risk of functional decline (ISAR > or = 3). The majority of high-risk subjects (78%) were living at home before hospitalization and 58.7% returned home after discharge. Depression and cognitive impairment were identified among respectively 41% and 59% of high-risk subjects. Only 128 patients were admitted for fall. Most of the faller patients were living at home prior hospitalization and had an ISAR score > or = 3. The MGT allowed identifying many patients > or = 75 Y living at home and presenting with high-risk of functional decline and geriatric syndromes, confirming that good screening procedures are necessary to optimize management of hospitalized olders. Most of faller patients have an ISAR score > or = 3 and should benefit a comprehensive geriatric assessment.

ENERCA clinical recommendations for disease management and prevention of complications of sickle cell disease in children.

PubMed

de Montalembert, Mariane; Ferster, Alina; Colombatti, Raffaella; Rees, David C; Gulbis, Beatrice

2011-01-01

Universal neonatal screening is performed in the United States, England, the Netherlands, and several cities in Belgium, with selective screening targeted on "high-risk" population in France (globally, one quarter of all the babies born in France are screened). Newborns diagnosed with a major sickle cell syndrome (SCD) should be referred to a designated pediatric sickle cell centre, and the parents are informed that their child has SCD; this may be in the sickle cell centre by an expert physician or in the community by an experienced nurse counsellor. The pediatric sickle cell centre should organize the care of the baby.

Influencing factors on cervical cancer screening from the Kurdish women's perspective: A qualitative study.

PubMed

Rasul, V H; Cheraghi, M A; Behboodi Moqadam, Z

2015-01-01

Aim: This study was aimed to explore and describe the Kurdish women's perception of cervical cancer screening. Methods: A qualitative design based on a conventional content analysis approach. Purposive sampling was applied to 19 women chosen, who had a Pap smear or refused to have one. The study was performed in the Kurdistan Region, Iraq. Semi-structure din-depth individual interviews were carried out to collect data. Results: Four main themes including conflict, belief, and awareness about cervical cancer screening and socio-cultural factors emerged during data analysis Conclusions: Cervical cancer has a high mortality rate in the developing countries. However, only a few Kurdish women participated in the cervical cancer screening in the Kurdistan Region, Iraq. Understanding the factors associated with the women's perception of cervical cancer could guide future educational planning and clinical interventions improve the cervical cancer screening.

Influencing factors on cervical cancer screening from the Kurdish women’s perspective: A qualitative study

PubMed Central

Rasul, VH; Cheraghi, MA; Behboodi Moqadam, Z

2015-01-01

Aim:This study was aimed to explore and describe the Kurdish women’s perception of cervical cancer screening. Methods: A qualitative design based on a conventional content analysis approach. Purposive sampling was applied to 19 women chosen, who had a Pap smear or refused to have one. The study was performed in the Kurdistan Region, Iraq. Semi-structure din-depth individual interviews were carried out to collect data. Results: Four main themes including conflict, belief, and awareness about cervical cancer screening and socio-cultural factors emerged during data analysis Conclusions: Cervical cancer has a high mortality rate in the developing countries. However, only a few Kurdish women participated in the cervical cancer screening in the Kurdistan Region, Iraq. Understanding the factors associated with the women’s perception of cervical cancer could guide future educational planning and clinical interventions improve the cervical cancer screening. PMID:28255397

Detection of other inborn errors of metabolism in hyperphenylalaninemic babies picked up on narrow-spectrum screening programs.

PubMed

Unal, Ozlem; Oztürk-Hişmi, Burcu; Coşkun, Turgay; Tokatlı, Ayşegül; Dursun, Ali; Sivri, Hatice Serap

2012-01-01

In many countries, neonatal screening programs have been unable to expand and have been limited to a few diseases. We highlight herein the opportunity available for the early detection of some inborn errors of metabolism (IEMs) in those countries in which newborn screening programs are limited. All the newborns that are referred to us for hyperphenylalaninemia are examined physically and their blood samples are checked by both high-performance liquid chromatography (HPLC) for blood phenylalanine levels and by amino acid analyzer for the measurement of blood amino acid concentrations. Seven patients who had been referred to our unit for hyperphenylalaninemia were eventually diagnosed with another IEM. A careful physical examination of the babies sent for positive screening test result combined with the utilization of low expense screening techniques at the experienced referring centers might facilitate otherwise missed opportunities for the early detection of some IEMs.

Modality dependence and intermodal transfer in the Corsi Spatial Sequence Task: Screen vs. Floor.

PubMed

Röser, Andrea; Hardiess, Gregor; Mallot, Hanspeter A

2016-07-01

Four versions of the Corsi Spatial Sequence Task (CSST) were tested in a complete within-subject design, investigating whether participants' performance depends on the modality of task presentation and reproduction that put different demands on spatial processing. Presentation of the sequence (encoding phase) and the reproduction (recall phase) were each carried out either on a computer screen or on the floor of a room, involving actual walking in the recall phase. Combinations of the two different encoding and recall procedures result in the modality conditions Screen-Screen, Screen-Floor, Floor-Screen, and Floor-Floor. Results show the expected decrease in performance with increasing sequence length, which is likely due to processing limitations of working memory. We also found differences in performance between the modality conditions indicating different involvements of spatial working memory processes. Participants performed best in the Screen-Screen modality condition. Floor-Screen and Floor-Floor modality conditions require additional working memory resources for reference frame transformation and spatial updating, respectively; the resulting impairment of the performance was about the same in these two conditions. Finally, the Screen-Floor modality condition requires both types of additional spatial demands and led to the poorest performance. Therefore, we suggest that besides the well-known spatial requirements of CSST, additional working memory resources are demanded in walking CSST supporting processes such as spatial updating, mental rotation, reference frame transformation, and the control of walking itself.

A high-throughput platform for population reformatting and mammalian expression of phage display libraries to enable functional screening as full-length IgG.

PubMed

Xiao, Xiaodong; Douthwaite, Julie A; Chen, Yan; Kemp, Ben; Kidd, Sara; Percival-Alwyn, Jennifer; Smith, Alison; Goode, Kate; Swerdlow, Bonnie; Lowe, David; Wu, Herren; Dall'Acqua, William F; Chowdhury, Partha S

Phage display antibody libraries are a rich resource for discovery of potential therapeutic antibodies. Single-chain variable fragment (scFv) libraries are the most common format due to the efficient display of scFv by phage particles and the ease by which soluble scFv antibodies can be expressed for high-throughput screening. Typically, a cascade of screening and triaging activities are performed, beginning with the assessment of large numbers of E. coli-expressed scFv, and progressing through additional assays with individual reformatting of the most promising scFv to full-length IgG. However, use of high-throughput screening of scFv for the discovery of full-length IgG is not ideal because of the differences between these molecules. Furthermore, the reformatting step represents a bottle neck in the process because each antibody has to be handled individually to preserve the unique VH and VL pairing. These problems could be resolved if populations of scFv could be reformatted to full-length IgG before screening without disrupting the variable region pairing. Here, we describe a novel strategy that allows the reformatting of diverse populations of scFv from phage selections to full-length IgG in a batch format. The reformatting process maintains the diversity and variable region pairing with high fidelity, and the resulted IgG pool enables high-throughput expression of IgG in mammalian cells and cell-based functional screening. The improved process led to the discovery of potent candidates that are comparable or better than those obtained by traditional methods. This strategy should also be readily applicable to Fab-based phage libraries. Our approach, Screening in Product Format (SiPF), represents a substantial improvement in the field of antibody discovery using phage display.

Screening tools to identify patients with complex health needs at risk of high use of health care services: A scoping review.

PubMed

Marcoux, Valérie; Chouinard, Maud-Christine; Diadiou, Fatoumata; Dufour, Isabelle; Hudon, Catherine

2017-01-01

Many people with chronic conditions have complex health needs often due to multiple chronic conditions, psychiatric comorbidities, psychosocial issues, or a combination of these factors. They are at high risk of frequent use of healthcare services. To offer these patients interventions adapted to their needs, it is crucial to be able to identify them early. The aim of this study was to find all existing screening tools that identify patients with complex health needs at risk of frequent use of healthcare services, and to highlight their principal characteristics. Our purpose was to find a short, valid screening tool to identify adult patients of all ages. A scoping review was performed on articles published between 1985 and July 2016, retrieved through a comprehensive search of the Scopus and CINAHL databases, following the methodological framework developed by Arksey and O'Malley (2005), and completed by Levac et al. (2010). Of the 3,818 articles identified, 30 were included, presenting 14 different screening tools. Seven tools were self-reported. Five targeted adult patients, and nine geriatric patients. Two tools were designed for specific populations. Four can be completed in 15 minutes or less. Most screening tools target elderly persons. The INTERMED self-assessment (IM-SA) targets adults of all ages and can be completed in less than 15 minutes. Future research could evaluate its usefulness as a screening tool for identifying patients with complex needs at risk of becoming high users of healthcare services.

Effectiveness of Diabetes Foot Screening in Primary Care in Preventing Lower Extremity Amputations.

PubMed

Ang, Gary Y; Yap, Chun Wei; Saxena, Nakul

2017-11-01

The risk of lower extremity amputations (LEAs) in diabetics is 20 times higher than in non-diabetics. Clinical practice guidelines recommend that all diabetics should receive an annual foot examination to identify high-risk foot conditions. Despite this recommendation, there is little evidence in the literature to show its effectiveness in preventing LEA. This study aims to evaluate the effectiveness of diabetes foot screening in primary care in preventing LEA and to identify LEA risk factors. This is a retrospective cohort study of diabetic patients who visited the National Healthcare Group Polyclinics for the first time from 1 January 2008 to 31 December 2012. The intervention of interest was foot screening performed at least once during 2 years of follow-up, and the outcome of interest was LEA (major and/or minor) performed during 2 years of follow-up. Patients who did foot screening (n=8150) were compared to a propensity score matched control group (n=8150) who did not do foot screening. Logistics regression was done to identify factors associated with LEA. Among those who underwent foot screening, there were 2 (0.02%) major amputations and 15 (0.18%) minor amputations compared with 42 (0.52%) and 52 (0.64%) among those who did not ( P <0.001). Lack of diabetes foot screening, lower socioeconomic status, hip fracture, Malay ethnicity, chronic kidney disease, poorer glycaemic control, longer diabetes duration and male gender have been found to be associated with a higher risk of LEA.

Adaptive Gaussian mixture models for pre-screening in GPR data

NASA Astrophysics Data System (ADS)

Torrione, Peter; Morton, Kenneth, Jr.; Besaw, Lance E.

2011-06-01

Due to the large amount of data generated by vehicle-mounted ground penetrating radar (GPR) antennae arrays, advanced feature extraction and classification can only be performed on a small subset of data during real-time operation. As a result, most GPR based landmine detection systems implement "pre-screening" algorithms to processes all of the data generated by the antennae array and identify locations with anomalous signatures for more advanced processing. These pre-screening algorithms must be computationally efficient and obtain high probability of detection, but can permit a false alarm rate which might be higher than the total system requirements. Many approaches to prescreening have previously been proposed, including linear prediction coefficients, the LMS algorithm, and CFAR-based approaches. Similar pre-screening techniques have also been developed in the field of video processing to identify anomalous behavior or anomalous objects. One such algorithm, an online k-means approximation to an adaptive Gaussian mixture model (GMM), is particularly well-suited to application for pre-screening in GPR data due to its computational efficiency, non-linear nature, and relevance of the logic underlying the algorithm to GPR processing. In this work we explore the application of an adaptive GMM-based approach for anomaly detection from the video processing literature to pre-screening in GPR data. Results with the ARA Nemesis landmine detection system demonstrate significant pre-screening performance improvements compared to alternative approaches, and indicate that the proposed algorithm is a complimentary technique to existing methods.

Performance of screening tools in detecting major depressive disorder among patients with coronary heart disease: a systematic review.

PubMed

Ren, Yanping; Yang, Hui; Browning, Colette; Thomas, Shane; Liu, Meiyan

2015-03-01

Eligible studies published before 31 Dec 2013 were identified from the following databases: Ovid Medline, EMBASE, PsycINFO, Scopus, Cochrane Library, CINAHL Plus, and Web of Science. Eligible studies published before 31, Dec 2013 were identified from the following databases: Ovid Medline, EMBASE, psycINFO, Scopus, Cochrane Library, CINAHL Plus, and Web of Science. Eight studies aiming to identify MDD in CHD patients were included, and there were 10 self-reporting questionnaires (such as PHQ-2, PHQ-9, PHQ categorical algorithm, HADS-D, BDI, BDI-II, BDI-II-cog, CES-D, SCL-90, 2 simple yes/no items) and 1 observer rating scale (Ham-D). For MDD alone, the sensitivity and specificity of various screening tools at the validity and optimal cut-off point varied from 0.34 [0.19, 0.52] to 0.96 [0.78, 1.00] and 0.69 [0.65, 0.73] to 0.97 [0.93, 0.99]. Results showed PHQ-9 (≥10), BDI-II (³14 or ≥16), and HADS-D (≥5 or ≥4) were widely used for screening MDD in CHD patients. There is no consensus on the optimal screening tool for MDD in CHD patients. When evaluating the performance of a screening tool, balancing the high sensitivity and negative predictive value (NPV) between specificity and positive predictive value (PPV) for screening or diagnostic purpose should be considered. After screening, further diagnosis, appropriate management, and necessary referral may also improve cardiovascular outcomes.

[Screening for diabetes in France: data from the 2000-2001 cohort of the national medical insurance system].

PubMed

Hirtzlin, I; Fagot-Campagna, A; Girard-Le Gallo, I; Vallier, N; Poutignat, N; Weill, A; Le Laidier, S

2004-04-01

Type 2 diabetes mellitus may go undiagnosed for several Years while complications are silently developing. In France, from 2 to 3.7% of adults aged 35-65 are unaware they have diabetes. Nevertheless fasting serum glucose is a simple diagnostic test. We described people who underwent opportunist diabetes screening (serum glucose) within 2 Years (2000-2001). We used the administrative EPAS cohort from the employee National Health Insurance System which covers 70% of the total population in France. The data are based on reimbursements of glucose testing and hospitalization among people who did not received reimbursements of treatment for diabetes but used medical services during the 2 Years. The opportunistic screening rate within 2 Years was 48.6% overall and increased with age. Among those 45 Years old or older, it was 71.2%. The screening rate was higher among women than men. Opportunistic screening for diabetes is commonly practised in France, despite the lack of official guidelines. Several hypotheses may explain the discrepancy between common opportunist screening and high prevalence of undiagnosed diabetes: 1). undiagnosed diabetes is mostly present in people who do not use medical services; 2). opportunistic screening is not performed among the most at-risk population; 3). testing is not performed on fasting samples or results are neglected; 4). results of testing are overlooked by doctors/patients; 5). epidemiological studies based on self-report of diagnosis and only one testing overestimate undiagnosed diabetes.

Comparison of immunohistochemistry and polymerase chain reaction for detection of West Nile virus in naturally infected dead birds.

PubMed

Sandhu, Tejbir; Sidhu, Dalbinder; Dhillon, Major; Fang, Ying

2010-10-04

Credible vector-borne disease surveillance programs, especially in developing countries with limited resources, must include diagnostic tests that are efficient, inexpensive and simple and safe to administer while maintaining high levels of sensitivity and specificity. Since immunohistochemistry (IHC) includes most of these features, its sensitivity, specificity, predictive positive value (PPV) and predictive negative value (PNV) for West Nile virus (WNv) screening were compared to those of the gold standard, RT-PCR testing of kidney tissue in dead birds. IHC and RT-PCR were performed for WNv antigen on 41 dead birds (belonging to five orders) collected from the northwest region of the Riverside County of California. Fixed tissue sections were screened by IHC using polyclonal antibodies, and frozen kidney tissues were tested with RT-PCR. Kidney screening with IHC showed sensitivity, specificity, PPV and NPV of 95.45%, 73.68%, 80.77% and 93.33%, respectively. Based on WNv screening of kidney tissue, IHC and RT-PCR were in agreement with 95.45% (21/22) for positive dead birds and were in 100% (22/22) agreement when multi-organ screening by IHC was performed. The present study showed that IHC is as equally effective as RT-PCR in screening for WNv in dead birds. Therefore, IHC can effectively serve as a competent screening technique for those disease surveillance agencies that lack expensive RT-PCR technology while promoting safer biohazardous conditions, except at the initial stage of tissue collection.

Community validation of the IDEA study cognitive screen in rural Tanzania.

PubMed

Gray, William K; Paddick, Stella Maria; Collingwood, Cecilia; Kisoli, Aloyce; Mbowe, Godfrey; Mkenda, Sarah; Lissu, Carolyn; Rogathi, Jane; Kissima, John; Walker, Richard W; Mushi, Declare; Chaote, Paul; Ogunniyi, Adesola; Dotchin, Catherine L

2016-11-01

The dementia diagnosis gap in sub-Saharan Africa (SSA) is large, partly because of difficulties in screening for cognitive impairment in the community. As part of the Identification and Intervention for Dementia in Elderly Africans (IDEA) study, we aimed to validate the IDEA cognitive screen in a community-based sample in rural Tanzania METHODS: Study participants were recruited from people who attended screening days held in villages within the rural Hai district of Tanzania. Criterion validity was assessed against the gold standard clinical dementia diagnosis using DSM-IV criteria. Construct validity was assessed against, age, education, sex and grip strength and instrumental activities of daily living (IADLs). Internal consistency and floor and ceiling effects were also examined. During community screening, the IDEA cognitive screen had high criterion validity, with an area under the receiver operating characteristic curve of 0.855 (95% CI 0.794 to 0.915). Higher scores on the screen were significantly correlated with lower age, male sex, having attended school, better grip strength and improved performance in activities of daily living. Factor analysis revealed a single factor with an eigenvalue greater than one, although internal consistency was only moderate (Cronbach's alpha = 0.534). The IDEA cognitive screen had high criterion and construct validity and is suitable for use as a cognitive screening instrument in a community setting in SSA. Only moderate internal consistency may partly reflect the multi-domain nature of dementia as diagnosed clinically. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Rheology of cellulose nanofibrils/silver nanowires suspension for the production of transparent and conductive electrodes by screen printing

NASA Astrophysics Data System (ADS)

Hoeng, Fanny; Denneulin, Aurore; Reverdy-Bruas, Nadège; Krosnicki, Guillaume; Bras, Julien

2017-02-01

With the aim of processing silver nanowires-based electrodes using screen printing process, this study proposes to evaluate the suitability of cellulose nanofibrils (CNF) as a thickening agent for providing a high viscosity silver nanowires screen printing ink. Rheology of CNF suspension has been specifically investigated according to screen printing process requirements using both rotational and oscillating rheology. It has been found that CNF indeed act as a thickener and stabilizer for the silver nanowires suspension. However, the solid dominant visco-elastic behavior of the CNF suspension was not suitable for screen printing and leads to defects within the printed film. CNF visco-elastic properties were modified by adding hydroxypropylmethyl cellulose (HPMC) to the suspension. Homogeneous transparent conductive layers have been obtained when using CNF-HPMC as a matrix for silver nanowires. The screen printed layers were characterized and performances of Rsh = 12 ± 5 Ω□-1 and T%500nm = 74,8% were achieved without any additional post-treatment to the film.

[Screening for malnutrition among hospitalized patients in a Colombian University Hospital].

PubMed

Cruz, Viviana; Bernal, Laura; Buitrago, Giancarlo; Ruiz, Álvaro J

2017-04-01

On admission, 30 to 50% of hospitalized patients have some degree of malnutrition, which is associated with longer length of stay, higher rates of complications, mortality and greater costs. To determine the frequency of screening for risk of malnutrition in medical records and assess the usefulness of the Malnutrition Screening Tool (MST). In a cross-sectional study, we searched for malnutrition screening in medical records, and we applied the MST tool to hospitalized patients at the Internal Medicine Wards of San Ignacio University Hospital. Of 295 patients included, none had been screened for malnutrition since hospital admission. Sixty one percent were at nutritional risk, with a higher prevalence among patients with HIV (85.7%), cancer (77.5%) and pneumonia. A positive MST result was associated with a 3.2 days increase in length of hospital stay (p = 0.024). The prevalence of malnutrition risk in hospitalized patients is high, but its screening is inadequate and it is underdiagnosed. The MST tool is simple, fast, low-cost, and has a good diagnostic performance.

Predictive validity of the UKCAT for medical school undergraduate performance: a national prospective cohort study.

PubMed

Tiffin, Paul A; Mwandigha, Lazaro M; Paton, Lewis W; Hesselgreaves, H; McLachlan, John C; Finn, Gabrielle M; Kasim, Adetayo S

2016-09-26

The UK Clinical Aptitude Test (UKCAT) has been shown to have a modest but statistically significant ability to predict aspects of academic performance throughout medical school. Previously, this ability has been shown to be incremental to conventional measures of educational performance for the first year of medical school. This study evaluates whether this predictive ability extends throughout the whole of undergraduate medical study and explores the potential impact of using the test as a selection screening tool. This was an observational prospective study, linking UKCAT scores, prior educational attainment and sociodemographic variables with subsequent academic outcomes during the 5 years of UK medical undergraduate training. The participants were 6812 entrants to UK medical schools in 2007-8 using the UKCAT. The main outcome was academic performance at each year of medical school. A receiver operating characteristic (ROC) curve analysis was also conducted, treating the UKCAT as a screening test for a negative academic outcome (failing at least 1 year at first attempt). All four of the UKCAT scale scores significantly predicted performance in theory- and skills-based exams. After adjustment for prior educational achievement, the UKCAT scale scores remained significantly predictive for most years. Findings from the ROC analysis suggested that, if used as a sole screening test, with the mean applicant UKCAT score as the cut-off, the test could be used to reject candidates at high risk of failing at least 1 year at first attempt. However, the 'number needed to reject' value would be high (at 1.18), with roughly one candidate who would have been likely to pass all years at first sitting being rejected for every higher risk candidate potentially declined entry on this basis. The UKCAT scores demonstrate a statistically significant but modest degree of incremental predictive validity throughout undergraduate training. Whilst the UKCAT could be considered a fairly crude screening tool for future academic performance, it may offer added value when used in conjunction with other selection measures. Future work should focus on the optimum role of such tests within the selection process and the prediction of post-graduate performance.

Characterization of screen-printed electrodes for dielectric elastomer (DE) membranes: influence of screen dimensions and electrode thickness on actuator performance

NASA Astrophysics Data System (ADS)

Fasolt, Bettina; Hodgins, Micah; Seelecke, Stefan

2016-04-01

Screen printing is used as a method for printing electrodes on silicone thin films for the fabrication of dielectric elastomer transducers (DET). This method can be used to manufacture a multitude of patternable designs for actuator and sensor applications, implementing the same method for prototyping as well as large-scale production. The fabrication of DETs does not only require the development of a flexible, highly conductive electrode material, which adheres to a stretched and unstretched silicone film, but also calls for a thorough understanding of the effects of the different printing parameters. This work studies the influence of screen dimensions (open area, mesh thickness) as well as the influence of multiple-layer- printing on the electrode stiffness, electrical resistance and capacitance as well as actuator performance. The investigation was conducted in a custom-built testing device, which enabled an electro-mechanical characterization of the DET, simultaneously measuring parameters such as strain, voltage, current, force, sheet resistance, capacitance and membrane thickness. Magnified pictures of the electrodes will additionally illustrate the effects of the different printing parameters.

The cost-effectiveness of Welcome to Medicare visual acuity screening and a possible alternative welcome to medicare eye evaluation among persons without diagnosed diabetes mellitus.

PubMed

Rein, David B; Wittenborn, John S; Zhang, Xinzhi; Hoerger, Thomas J; Zhang, Ping; Klein, Barbara Eden Kobrin; Lee, Kris E; Klein, Ronald; Saaddine, Jinan B

2012-05-01

To estimate the cost-effectiveness of visual acuity screening performed in primary care settings and of dilated eye evaluations performed by an eye care professional among new Medicare enrollees with no diagnosed eye disorders. Medicare currently reimburses visual acuity screening for new enrollees during their initial preventive primary care health check, but dilated eye evaluations may be a more cost-effective policy. Monte Carlo cost-effectiveness simulation model with a total of 50 000 simulated patients with demographic characteristics matched to persons 65 years of age in the US population. Compared with no screening policy, dilated eye evaluations increased quality-adjusted life-years(QALYs) by 0.008 (95% credible interval [CrI], 0.005-0.011) and increased costs by $94 (95% CrI, −$35 to$222). A visual acuity screening increased QALYs in less than 95% of the simulations (0.001 [95% CrI, −0.002 to 0.004) and increased total costs by $32 (95% CrI, −$97 to $159) per person. The incremental cost-effectiveness ratio of a visual acuity screening and an eye examination compared with no screening were $29 000 and$12 000 per QALY gained, respectively. At a willingness-to-pay value of $15 000 or more per QALY gained, a dilated eye evaluation was the policy option most likely to be cost-effective. The currently recommended visual acuity screening showed limited efficacy and cost-effectiveness compared with no screening. In contrast, anew policy of reimbursement for Welcome to Medicare dilated eye evaluations was highly cost-effective.

The Cost-effectiveness of Welcome to Medicare Visual Acuity Screening and a Possible Alternative Welcome to Medicare Eye Evaluation Among Persons Without Diagnosed Diabetes Mellitus

PubMed Central

Rein, David B.; Wittenborn, John S.; Zhang, Xinzhi; Hoerger, Thomas J.; Zhang, Ping; Klein, Barbara Eden Kobrin; Lee, Kris E.; Klein, Ronald; Saaddine, Jinan B.

2013-01-01

Objective To estimate the cost-effectiveness of visual acuity screening performed in primary care settings and of dilated eye evaluations performed by an eye care professional among new Medicare enrollees with no diagnosed eye disorders. Medicare currently reimburses visual acuity screening for new enrollees during their initial preventive primary care health check, but dilated eye evaluations may be a more cost-effective policy. Design Monte Carlo cost-effectiveness simulation model with a total of 50 000 simulated patients with demographic characteristics matched to persons 65 years of age in the US population. Results Compared with no screening policy, dilated eye evaluations increased quality-adjusted life-years (QALYs) by 0.008 (95% credible interval [CrI], 0.005–0.011) and increased costs by $94 (95% CrI, −$35 to $222). A visual acuity screening increased QALYs in less than 95% of the simulations (0.001 [95% CrI, −0.002 to 0.004) and increased total costs by $32 (95% CrI, −$97 to $159) per person. The incremental cost-effectiveness ratio of a visual acuity screening and an eye examination compared with no screening were $29 000 and $12 000 per QALY gained, respectively. At a willingness-to-pay value of $15 000 or more per QALY gained, a dilated eye evaluation was the policy option most likely to be cost-effective. Conclusions The currently recommended visual acuity screening showed limited efficacy and cost-effectiveness compared with no screening. In contrast, a new policy of reimbursement for Welcome to Medicare dilated eye evaluations was highly cost-effective. PMID:22232367

Screening, separation, and evaluation of xanthine oxidase inhibitors from Paeonia lactiflora using chromatography combined with a multi-mode microplate reader.

PubMed

Wang, Jing; Shi, Dongfang; Zheng, Meizhu; Ma, Bing; Cui, Jing; Liu, Chunming; Liu, Chengyu

2017-11-01

Natural products have become one of the most important resources for discovering novel xanthine oxidase inhibitors, which are commonly employed in the treatment of hyperuricemia and gout. However, to date, few reports exist regarding the use of monoterpene glycosides as xanthine oxidase inhibitors. Thus, we herein report the use of ultrafiltration coupled with liquid chromatography in the screening of monoterpene glycoside xanthine oxidase inhibitors from the extract of Paeonia lactiflora (P. lactiflora), and both high-performance counter-current chromatography and medium-pressure liquid chromatography were employed to separate the main constituents. Furthermore, the xanthine oxidase inhibitory activities and the mechanisms of inhibition of the isolated compounds were evaluated using a multi-mode microplate reader by Molecular Devices. As a result, three monoterpene glycosides were separated by combined high-performance counter-current chromatography and medium-pressure liquid chromatography in purities of 90.4, 98.0, and 86.3%, as determined by liquid chromatography. These three compounds were identified as albiflorin, paeoniflorin, and 1-O-β-ᴅ-glucopyranosyl-8-O-benzoylpaeonisuffrone by electrospray ionization tandem mass spectrometry, and albiflorin and paeoniflorin were screened as potential xanthine oxidase inhibitors by ultrafiltration with liquid chromatography. The evaluation results of xanthine oxidase inhibitory activity corresponded with the screening results, as only albiflorin and paeoniflorin exhibited xanthine oxidase inhibitory activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The use of presurgical psychological screening to predict the outcome of spine surgery.

PubMed

Block, A R; Ohnmeiss, D D; Guyer, R D; Rashbaum, R F; Hochschuler, S H

2001-01-01

Several previous studies have shown that psychosocial factors can influence the outcome of elective spine surgery. The purpose of the current study was to determine how well a presurgical screening instrument could predict surgical outcome. The study was conducted by staff of a psychologist's office. They performed preoperative screening for spine surgery candidates and collected the follow-up data. Presurgical screening and follow-up data collection was performed on 204 patients who underwent laminectomy/discectomy (n=118) or fusion (n=86) of the lumbar spine. The outcome measures used in the study were visual analog pain scales, the Oswestry Disability Questionnaire, and medication use. A semi-structured interview and psychometric testing were used to identify specific, quantifiable psychological, and "medical" risk factors for poor surgical outcome. A presurgical psychological screening (PPS) scorecard was completed for each patient, assessing whether the patient had a high or low level of risk on these psychological and medical dimensions. Based on the scorecard, an overall surgical prognosis of "good," "fair," or "poor" was generated. Results showed spine surgery led to significant overall improvements in pain, functional ability, and medication use. Medical and psychological risk levels were significantly related to outcome, with the poorest results obtained by patients having both high psychological and medical risk. Further, the accuracy of PPS surgical prognosis in predicting overall outcome was 82%. Only 9 of 53 patients predicted to have poor outcome achieved fair or good results from spine surgery. These findings suggest that PPS should become a more routine part of the evaluation of chronic pain patients in whom spine surgery is being considered.

Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer.

PubMed

Siraj, Abdul K; Prabhakaran, Sarita; Bavi, Prashant; Bu, Rong; Beg, Shaham; Hazmi, Mohsen Al; Al-Rasheed, Maha; Al-Assiri, Mohammed; Sairafi, Rami; Al-Dayel, Fouad; Al-Sanea, Nasser; Uddin, Shahab; Al-Kuraya, Khawla S

2015-06-01

Lynch syndrome (LS; hereditary nonpolyposis colorectal cancer) is a common cause of hereditary colorectal cancer (CRC). CRC is the most common cancer diagnosed among males in Saudi Arabia but to the authors' knowledge there is a lack of data regarding the prevalence of LS in patients with CRC. There currently are no clear guidelines for the selection criteria for these patients to screen for LS. A comprehensive molecular characterization was performed in a cohort of 807 CRC cases by immunohistochemical and microsatellite analysis using polymerase chain reaction. BRAF mutation screening, high CpG island methylator phenotype, and analysis for germline mutations were performed in 425 CRC samples. These were all high microsatellite instability (MSI-H) samples (91 cases), all low MSI samples (143 cases), and selected cases from the microsatellite stable group (191 cases) that met revised Bethesda guidelines. Polymerase chain reaction identified 91 MSI-H cases (11.3%) and sequencing revealed mismatch repair germline mutations in 8 CRC cases only. Of the total of 807 CRC cases, these 8 cases (0.99%) were MSI-H, met the revised Bethesda guidelines, and did not harbor BRAF mutations. The results of the current study confirmed cases of LS in approximately 1.0% of CRC samples and reflects the efficacy of screening among MSI-H cases that lack BRAF mutations. This comprehensive study from Saudi Arabia will help in implementing a universal screening/reflex testing strategy in a clinical setting in Saudi Arabia and in conducting a national screening program that benefits both patients and their relatives. © 2015 American Cancer Society.

A utility/cost analysis of breast cancer risk prediction algorithms

NASA Astrophysics Data System (ADS)

Abbey, Craig K.; Wu, Yirong; Burnside, Elizabeth S.; Wunderlich, Adam; Samuelson, Frank W.; Boone, John M.

2016-03-01

Breast cancer risk prediction algorithms are used to identify subpopulations that are at increased risk for developing breast cancer. They can be based on many different sources of data such as demographics, relatives with cancer, gene expression, and various phenotypic features such as breast density. Women who are identified as high risk may undergo a more extensive (and expensive) screening process that includes MRI or ultrasound imaging in addition to the standard full-field digital mammography (FFDM) exam. Given that there are many ways that risk prediction may be accomplished, it is of interest to evaluate them in terms of expected cost, which includes the costs of diagnostic outcomes. In this work we perform an expected-cost analysis of risk prediction algorithms that is based on a published model that includes the costs associated with diagnostic outcomes (true-positive, false-positive, etc.). We assume the existence of a standard screening method and an enhanced screening method with higher scan cost, higher sensitivity, and lower specificity. We then assess expected cost of using a risk prediction algorithm to determine who gets the enhanced screening method under the strong assumption that risk and diagnostic performance are independent. We find that if risk prediction leads to a high enough positive predictive value, it will be cost-effective regardless of the size of the subpopulation. Furthermore, in terms of the hit-rate and false-alarm rate of the of the risk prediction algorithm, iso-cost contours are lines with slope determined by properties of the available diagnostic systems for screening.

Mass spectrometry for fragment screening.

PubMed

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

2017-11-08

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

Who should be screened for chromosomal abnormalities before ICSI treatment?

PubMed

Dul, E C; van Ravenswaaij-Arts, C M A; Groen, H; van Echten-Arends, J; Land, J A

2010-11-01

Guidelines on karyotyping infertile men before ICSI treatment are not consistent. Most guidelines recommend chromosomal screening in azoospermic and severe oligozoospermic men, because they are assumed to have the highest risk of abnormalities. We performed a retrospective cohort study in azoospermic men and men eligible for ICSI. We determined the prevalence of chromosomal abnormalities in relation to sperm concentration and compared our data to studies in the literature. A high prevalence of chromosomal abnormalities in azoospermic men was found, but no difference in the prevalence of abnormalities was seen between different sperm concentration categories in non-azoospermic men. This raises the question of who should be screened for chromosomal abnormalities before ICSI treatment. Considering the costs and benefits, we would propose limiting screening to infertile couples with non-obstructive azoospermia.

Performance indicators evaluation of the population-based breast cancer screening programme in Northern Portugal using the European Guidelines.

PubMed

Bento, Maria José; Gonçalves, Guilherme; Aguiar, Ana; Castro, Clara; Veloso, Vitor; Rodrigues, Vítor

2015-10-01

To evaluate the first 10 years of operation of the population-based breast cancer screening programme implemented in the Northern Region of Portugal, using selected recommended standard performance indicators. Data from women aged 50-69 screened with two-view mammography, biennially, in the period 2000-2009, were included. Main performance indicators were compared with the recommended levels of the European Guidelines. A total of 202,039 screening examinations were performed, 71,731 (35.5%) in the initial screening and 130,308 (64.5%) in the subsequent screening. Coverage rate by examination reached 74.3% of the target population, in the last period evaluated. Recall rates were 8.1% and 2.4% and cancer detection rates were 4.4/1000 and 2.9/1000 respectively, for initial and subsequent screenings. The breast cancer detection rate, expressed as a multiple of the background expected incidence was 3.1 in initial screen and 2.2 in subsequent screen. The incidence of invasive interval cancers met the desirable recommended levels both the first and second years since last screening examination, in the initial and subsequent screenings. Invasive tumours <15mm were 50.4% and 53.8% of the invasive cancers detected in initial and subsequent screenings. Less favourable size, grading and biomarkers expression were found in interval cancers compared to screen-detected cancers. Breast cancer screening programme in the Northern Region of Portugal was well accepted by the population. Most of the performance indicators were consistent with the desirable levels of the European Guidelines, which indicate an effective screening programme. Future research should verify the consistency of some of these results by using updated information from a larger population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Congestion game scheduling for virtual drug screening optimization

NASA Astrophysics Data System (ADS)

Nikitina, Natalia; Ivashko, Evgeny; Tchernykh, Andrei

2018-02-01

In virtual drug screening, the chemical diversity of hits is an important factor, along with their predicted activity. Moreover, interim results are of interest for directing the further research, and their diversity is also desirable. In this paper, we consider a problem of obtaining a diverse set of virtual screening hits in a short time. To this end, we propose a mathematical model of task scheduling for virtual drug screening in high-performance computational systems as a congestion game between computational nodes to find the equilibrium solutions for best balancing the number of interim hits with their chemical diversity. The model considers the heterogeneous environment with workload uncertainty, processing time uncertainty, and limited knowledge about the input dataset structure. We perform computational experiments and evaluate the performance of the developed approach considering organic molecules database GDB-9. The used set of molecules is rich enough to demonstrate the feasibility and practicability of proposed solutions. We compare the algorithm with two known heuristics used in practice and observe that game-based scheduling outperforms them by the hit discovery rate and chemical diversity at earlier steps. Based on these results, we use a social utility metric for assessing the efficiency of our equilibrium solutions and show that they reach greatest values.

Clinical and economic impact of various strategies for varicella immunity screening and vaccination of health care personnel.

PubMed

Baracco, G J; Eisert, S; Saavedra, S; Hirsch, P; Marin, M; Ortega-Sanchez, I R

2015-10-01

Exposure to patients with varicella or herpes zoster causes considerable disruption to a health care facility's operations and has a significant health and economic impact. However, practices related to screening for immunity and immunization of health care personnel (HCP) for varicella vary widely. A decision tree model was built to evaluate the cost-effectiveness of 8 different strategies of screening and vaccinating HCP for varicella. The outcomes are presented as probability of acquiring varicella, economic impact of varicella per employee per year, and cost to prevent additional cases of varicella. Monte Carlo simulations and 1-way sensitivity analyses were performed to address the uncertainties inherent to the model. Alternative epidemiologic and technologic scenarios were also analyzed. Performing a clinical screening followed by serologic testing of HCP with negative history diminished the cost impact of varicella by >99% compared with not having a program. Vaccinating HCP with negative screen cost approximately $50,000 per case of varicella prevented at the current level of U.S. population immunity, but was projected to be cost-saving at 92% or lower immunity prevalence. Improving vaccine acceptance rates and using highly sensitive assays also optimize cost-effectiveness. Strategies relying on screening and vaccinating HCP for varicella on employment were shown to be cost-effective for health care facilities and are consistent with current national guidelines for varicella prevention. Published by Elsevier Inc.

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

PubMed

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

2014-01-24

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

Developments in SPR Fragment Screening.

PubMed

Chavanieu, Alain; Pugnière, Martine

2016-01-01

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

High-Throughput Screening to Identify Regulators of Meiosis-Specific Gene Expression in Saccharomyces cerevisiae.

PubMed

Kassir, Yona

2017-01-01

Meiosis and gamete formation are processes that are essential for sexual reproduction in all eukaryotic organisms. Multiple intracellular and extracellular signals feed into pathways that converge on transcription factors that induce the expression of meiosis-specific genes. Once triggered the meiosis-specific gene expression program proceeds in a cascade that drives progress through the events of meiosis and gamete formation. Meiosis-specific gene expression is tightly controlled by a balance of positive and negative regulatory factors that respond to a plethora of signaling pathways. The budding yeast Saccharomyces cerevisiae has proven to be an outstanding model for the dissection of gametogenesis owing to the sophisticated genetic manipulations that can be performed with the cells. It is possible to use a variety selection and screening methods to identify genes and their functions. High-throughput screening technology has been developed to allow an array of all viable yeast gene deletion mutants to be screened for phenotypes and for regulators of gene expression. This chapter describes a protocol that has been used to screen a library of homozygous diploid yeast deletion strains to identify regulators of the meiosis-specific IME1 gene.

The Incidence of Oral and Oropharyngeal Cancers in Betel Quid-Chewing Populations in South Myanmar Rural Areas.

PubMed

Mizukawa, Nobuyoshi; Swe Swe Win; Zaw Moe Thein; Moe Thida Htwe; Yoshioka, Yohsuke; Kimata, Yoshihiro; Iida, Seiji; Myo Khin; Okada, Shigeru; Than Sein

2017-12-01

Oral cancer is a very common disease in South and Southeast Asia. Betel quid (BQ)- chewing and tobaccosmoking habits are etiological factors for oral cancer patients in these regions. We conducted an oral cancer screening in BQ-chewing endemic rural areas in South Myanmar for the early detection of oral cancer in BQ-chewing and smoking individuals. We examined 105 subjects who were at high risk of oral cancer due to their oral habits (BQ users and/or smokers). Three carcinoma cases were detected, and there were 8 dysplasia cases. The carcinoma detection rate was 2.9%, and the carcinoma and precancerous lesion detection rate was 10.5%. In Myanmar, oral cancer screening has been conducted sporadically on a voluntary basis, and nationwide surveys have never been performed. There are also few reports of oral cancer screening for high-risk groups among the general population in Myanmar. Our present findings highlight the need for further screening and surveys. Education on betel quid chewing- and tobacco- related oral diseases and screening for the early detection of oral cancer are of the utmost importance in the control and prevention of oral cancer.

Identifying Novel Molecular Structures for Advanced Melanoma by Ligand-Based Virtual Screening

PubMed Central

Wang, Zhao; Lu, Yan; Seibel, William; Miller, Duane D.; Li, Wei

2009-01-01

We recently discovered a new class of thiazole analogs that are highly potent against melanoma cells. To expand the structure-activity relationship study and to explore potential new molecular scaffolds, we performed extensive ligand-based virtual screening against a compound library containing 342,910 small molecules. Two different approaches of virtual screening were carried out using the structure of our lead molecule: 1) connectivity-based search using Scitegic Pipeline Pilot from Accelerys and 2) molecular shape similarity search using Schrodinger software. Using a testing compound library, both approaches can rank similar compounds very high and rank dissimilar compounds very low, thus validating our screening methods. Structures identified from these searches were analyzed, and selected compounds were tested in vitro to assess their activity against melanoma cancer cell lines. Several molecules showed good anticancer activity. While none of the identified compounds showed better activity than our lead compound, they provided important insight into structural modifications for our lead compound and also provided novel platforms on which we can optimize new classes of anticancer compounds. One of the newly synthesized analogs based on this virtual screening has improved potency and selectivity against melanoma. PMID:19445498

Computed tomography screening for lung cancer: results of ten years of annual screening and validation of cosmos prediction model.

PubMed

Veronesi, G; Maisonneuve, P; Rampinelli, C; Bertolotti, R; Petrella, F; Spaggiari, L; Bellomi, M

2013-12-01

It is unclear how long low-dose computed tomographic (LDCT) screening should continue in populations at high risk of lung cancer. We assessed outcomes and the predictive ability of the COSMOS prediction model in volunteers screened for 10 years. Smokers and former smokers (>20 pack-years), >50 years, were enrolled over one year (2000-2001), receiving annual LDCT for 10 years. The frequency of screening-detected lung cancers was compared with COSMOS and Bach risk model estimates. Among 1035 recruited volunteers (71% men, mean age 58 years) compliance was 65% at study end. Seventy-one (6.95%) lung cancers were diagnosed, 12 at baseline. Disease stage was: IA in 48 (66.6%); IB in 6; IIA in 5; IIB in 2; IIIA in 5; IIIB in 1; IV in 5; and limited small cell cancer in 3. Five- and ten-year survival were 64% and 57%, respectively, 84% and 65% for stage I. Ten (12.1%) received surgery for a benign lesion. The number of lung cancers detected during the first two screening rounds was close to that predicted by the COSMOS model, while the Bach model accurately predicted frequency from the third year on. Neither cancer frequency nor proportion at stage I decreased over 10 years, indicating that screening should not be discontinued. Most cancers were early stage, and overall survival was high. Only a limited number of invasive procedures for benign disease were performed. The Bach model - designed to predict symptomatic cancers - accurately predicted cancer frequency from the third year, suggesting that overdiagnosis is a minor problem in lung cancer screening. The COSMOS model - designed to estimate screening-detected lung cancers - accurately predicted cancer frequency at baseline and second screening round. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Multi-residue determination of seventeen sulfonamides and five tetracyclines in fish tissue using a multi-stage LC-ESI-MS/MS approach based on advanced mass spectrometric techniques.

PubMed

Dasenaki, Marilena E; Thomaidis, Nikolaos S

2010-07-05

A strategy was newly developed to rapidly screen seventeen sulfonamides and five tetracyclines in a single run from fish tissues using ultra-high performance liquid chromatography (UHPLC) coupled with comprehensive mass spectrometric approaches, including precursor-ion scan and data dependent scan. The product ions for precursor-ion scanning were selected by studying the MS/MS fragmentation of the analytes. All sulfonamides share the same diagnostic product ion at m/z 156 in positive MS/MS scan, while for tetracycline antibiotics the diagnostic product ion was proved to be at m/z 153.8. Further characterization of each compound was performed using a data dependent scan. Separation was performed on a Zorbax Eclipse Plus C18 column with a gradient elution using acetonitrile - 0.1% formic acid mobile phase at a flow rate of 0.1 mL min(-1). This approach has proven to be a powerful, highly selective, and sensitive tool for rapid screening and detection of non-targeted components in fish tissue and requires a minimum sample preparation such as one generic extraction step with MeOH:ACN 50:50 (v/v) acidified with 0.05% formic acid. The method has also been applied successfully to porcine and poultry meat. The validation of such a screening method was performed for the first time according to Commission Decision 2002/657/EC and satisfactory method performance characteristics were achieved. Copyright 2010 Elsevier B.V. All rights reserved.

Screening strategies for tubal factor subfertility.

PubMed

den Hartog, J E; Lardenoije, C M J G; Severens, J L; Land, J A; Evers, J L H; Kessels, A G H

2008-08-01

Different screening strategies exist to estimate the risk of tubal factor subfertility, preceding laparoscopy. Three screening strategies, comprising Chlamydia trachomatis IgG antibody testing (CAT), high-sensitivity C-reactive protein (hs-CRP) testing and hysterosalpingography (HSG), were explored using laparoscopy as reference standard and the occurrence of a spontaneous pregnancy as a surrogate marker for the absence of tubal pathology. In this observational study, 642 subfertile women, who underwent tubal testing, participated. Data on serological testing, HSG, laparoscopy and interval conception were collected. Multiple imputations were used to compensate for missing data. Strategy A (HSG) has limited value in estimating the risk of tubal pathology. Strategy B (CAT-->HSG) shows that CAT significantly discerns patients with a high versus low risk of tubal pathology, whereas HSG following CAT has no additional value. Strategy C (CAT-->hs-CRP-->HSG) demonstrates that hs-CRP may be valuable in CAT-positive patients only and HSG has no additional value. CAT is proposed as first screening test for tubal factor subfertility. In CAT-negative women, HSG may be performed because of its high specificity and fertility-enhancing effect. In CAT-positive women, hs-CRP seems promising, whereas HSG has no additional value. The position and timing of laparoscopy deserves critical reappraisal.

Screening for Natural Inhibitors of Topoisomerases I from Rhamnus davurica by Affinity Ultrafiltration and High-Performance Liquid Chromatography–Mass Spectrometry

PubMed Central

Chen, Guilin; Guo, Mingquan

2017-01-01

Topoisomerase I (Topo I) catalyzes topological interconversion of duplex DNA during DNA replication and transcription, and has been deemed as important antineoplastic targets. In this study, the fraction R.d-60 from ethyl acetate extracts of Rhamnus davurica showed higher inhibitory rates against SGC-7901 and HT-29 compared with the R.d-30 fraction in vitro. However, the specific active components of R.d-60 fraction remain elusive. To this end, a method based on bio-affinity ultrafiltration and high performance liquid chromatography/electrospray mass spectrometry (HPLC- ESI-MS/MS) was developed to rapidly screen and identify the Topo I inhibitors in this fraction. The enrichment factors (EFs) were calculated to evaluate the binding affinities between the bioactive constituents and Topo I. As a result, eight ligands were identified and six of which with higher EFs showed more potential antitumor activity. Furthermore, antiproliferative assays in vitro (IC50 values) with two representative candidates (apigenin, quercetin) against SGC-7901, HT-29 and Hep G2 cells were conducted and further validated. Finally, the structure-activity relationships revealed that flavones contain a C2-C3 double bond of C ring exhibited higher bio-affinities to Topo I than those without it. This integrated method combining Topo I ultrafiltration with HPLC-MS/MS proved to be very efficient in rapid screening and identification of potential Topo I inhibitors from the complex extracts of medicinal plants, and could be further explored as a valuable high-throughput screening platform in the early drug discovery stage. PMID:28919906

Evaluation of the King-Devick test as a concussion screening tool in high school football players.

PubMed

Seidman, Daniel H; Burlingame, Jennifer; Yousif, Lina R; Donahue, Xinh P; Krier, Joshua; Rayes, Lydia J; Young, Rachel; Lilla, Muareen; Mazurek, Rochelle; Hittle, Kristie; McCloskey, Charles; Misra, Saroj; Shaw, Michael K

2015-09-15

Concussion is the most common type of traumatic brain injury, and results from impact or impulsive forces to the head, neck or face. Due to the variability and subtlety of symptoms, concussions may go unrecognized or be ignored, especially with the pressure placed on athletes to return to competition. The King-Devick (KD) test, an oculomotor test originally designed for reading evaluation, was recently validated as a concussion screening tool in collegiate athletes. A prospective study was performed using high school football players in an attempt to study the KD as a concussion screening tool in this younger population. 343 athletes from four local high school football teams were recruited to participate. These athletes were given baseline KD tests prior to competition. Individual demographic information was collected on the subjects. Standard team protocol was employed to determine if a concussion had occurred during competition. Immediately after diagnosis, the KD test was re-administered to the concussed athlete for comparison to baseline. Post-season testing was also performed in non-concussed individuals. Of the 343 athletes, nine were diagnosed with concussions. In all concussed players, cumulative read times for the KD test were significantly increased (p<0.001). Post-season testing of non-concussed athletes revealed minimal change in read times relative to baseline. Univariate analysis revealed that history of concussion was the only demographic factor predictive of concussion in this cohort. The KD test is an accurate and easily administered sideline screening tool for concussion in adolescent football players. Copyright © 2015 Elsevier B.V. All rights reserved.

When does mass screening for open neural tube defects in low-risk pregnancies result in cost savings?

PubMed Central

Tosi, L L; Detsky, A S; Roye, D P; Morden, M L

1987-01-01

Using a decision analysis model, we estimated the savings that might be derived from a mass prenatal screening program aimed at detecting open neural tube defects (NTDs) in low-risk pregnancies. Our baseline analysis showed that screening v. no screening could be expected to save approximately $8 per pregnancy given a cost of $7.50 for the maternal serum alpha-feto-protein (MSAFP) test and a cost of $42,507 for hospital and rehabilitation services for the first 10 years of life for a child with spina bifida. When a more liberal estimate of the costs of caring for such a child was used, the savings with the screening program were more substantial. We performed extensive sensitivity analyses, which showed that the savings were somewhat sensitive to the cost of the MSAFP test and highly sensitive to the specificity (but not the sensitivity) of the test. A screening program for NTDs in low-risk pregnancies may result in substantial savings in direct health care costs if the screening protocol is followed rigorously and efficiently. PMID:2433011

Using constitutive activity to define appropriate high-throughput screening assays for orphan g protein-coupled receptors.

PubMed

Ngo, Tony; Coleman, James L J; Smith, Nicola J

2015-01-01

Orphan G protein-coupled receptors represent an underexploited resource for drug discovery but pose a considerable challenge for assay development because their cognate G protein signaling pathways are often unknown. In this methodological chapter, we describe the use of constitutive activity, that is, the inherent ability of receptors to couple to their cognate G proteins in the absence of ligand, to inform the development of high-throughput screening assays for a particular orphan receptor. We specifically focus on a two-step process, whereby constitutive G protein coupling is first determined using yeast Gpa1/human G protein chimeras linked to growth and β-galactosidase generation. Coupling selectivity is then confirmed in mammalian cells expressing endogenous G proteins and driving accumulation of transcription factor-fused luciferase reporters specific to each of the classes of G protein. Based on these findings, high-throughput screening campaigns can be performed on the already miniaturized mammalian reporter system.

Combinatorial Screening for Transgenic Yeasts with High Cellulase Activities in Combination with a Tunable Expression System

PubMed Central

Ito, Yoichiro; Yamanishi, Mamoru; Ikeuchi, Akinori; Imamura, Chie; Matsuyama, Takashi

2015-01-01

Combinatorial screening used together with a broad library of gene expression cassettes is expected to produce a powerful tool for the optimization of the simultaneous expression of multiple enzymes. Recently, we proposed a highly tunable protein expression system that utilized multiple genome-integrated target genes to fine-tune enzyme expression in yeast cells. This tunable system included a library of expression cassettes each composed of three gene-expression control elements that in different combinations produced a wide range of protein expression levels. In this study, four gene expression cassettes with graded protein expression levels were applied to the expression of three cellulases: cellobiohydrolase 1, cellobiohydrolase 2, and endoglucanase 2. After combinatorial screening for transgenic yeasts simultaneously secreting these three cellulases, we obtained strains with higher cellulase expressions than a strain harboring three cellulase-expression constructs within one high-performance gene expression cassette. These results show that our method will be of broad use throughout the field of metabolic engineering. PMID:26692026

Cost effectiveness of fecal DNA screening for colorectal cancer: a systematic review and quality appraisal of the literature.

PubMed

Skally, Mairead; Hanly, Paul; Sharp, Linda

2013-06-01

Fecal DNA (fDNA) testing is a noninvasive potential alternative to current colorectal cancer screening tests. We conducted a systematic review and quality assessment of studies of cost-effectiveness of fDNA as a colorectal cancer screening tool (compared with no screening and other screening modalities), and identified key variables that impinged on cost-effectiveness. We searched MEDLINE, Embase, and the Centre for Reviews and Dissemination for cost-effectiveness studies of fDNA-based screening, published in English by September 2011. Studies that undertook an economic evaluation of fDNA, using either a cost-effectiveness or cost-utility analysis, compared with other relevant screening modalities and/or no screening were included. Additional inclusion criteria related to the presentation of data pertaining to model variables including time horizon, costs, fDNA performance characteristics, screening uptake, and comparators. A total of 369 articles were initially identified for review. After removing duplicates and applying inclusion and exclusion criteria, seven articles were included in the final review. Data was abstracted on key descriptor variables including screening scenarios, time horizon, costs, test performance characteristics, screening uptake, comparators, and incremental cost-effectiveness ratios. Quality assessment was undertaken using a standard checklist for economic evaluations. Studies cited by cost-effectiveness articles as the source of data on fDNA test performance characteristics were also reviewed. Seven cost-effectiveness studies were included, from the USA (4), Canada (1), Israel (1), and Taiwan (1). Markov models (5), a partially observable Markov decision process model (1) and MISCAN and SimCRC (1) microsimulation models were used. All studies took a third-party payer perspective and one included, in addition, a societal perspective. Comparator screening tests, screening intervals, and specific fDNA tests varied between studies. fDNA sensitivity and specificity parameters were derived from 12 research studies and one meta-analysis. Outcomes assessed were life-years gained and quality-adjusted life-years gained. fDNA was cost-effective when compared with no screening in six studies. Compared with other screening modalities, fDNA was not considered cost-effective in any of the base-case analyses: in five studies it was dominated by all alternatives considered. Sensitivity analyses identified cost, compliance, and test parameters as key influential parameters. In general, poor presentation of "study design" and "data collection" details lowered the quality of included articles. Although the literature searches were designed for high sensitivity, the possibility cannot be excluded that some eligible studies may have been missed. Reports (such as Health Technology Assessments produced by government agencies) and other forms of grey literature were excluded because they are difficult to identify systematically and/or may not report methods and results in sufficient detail for assessment. On the basis of the available (albeit limited) evidence, while fDNA is cost-effective when compared with no screening, it is currently dominated by most of the other available screening options. Cost and test performance appear to be the main influences on cost-effectiveness.

CT Scan Screening for Lung Cancer: Risk Factors for Nodules and Malignancy in a High-Risk Urban Cohort

PubMed Central

Greenberg, Alissa K.; Lu, Feng; Goldberg, Judith D.; Eylers, Ellen; Tsay, Jun-Chieh; Yie, Ting-An; Naidich, David; McGuinness, Georgeann; Pass, Harvey; Tchou-Wong, Kam-Meng; Addrizzo-Harris, Doreen; Chachoua, Abraham; Crawford, Bernard; Rom, William N.

2012-01-01

Background Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24–50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant. Methods We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128). Results The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas. Conclusions NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases. PMID:22768300

In use performance of catalytic converters on properly maintained high mileage vehicles

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

Sabourin, M.A.; Larson, R.E.; Donahue, K.S.

1986-01-01

A test program to evaluate the performance of catalytic converters from fifty-six 1981 and 1982 model year high mileage properly maintained in-use vehicles (from 21 engine families) was performed by the Certification Division of the Office of Mobile Sources (EPA). The program is called the Catalyst Change Program. All program vehicles were screened for proper maintenance and for mileages that ranged from 35,000 to 60,000 miles. Among vehicles belonging to 21 high sales volume and high technology engine and emission control system designs tested, poor catalyst performance was determined to be a significant contributor to emissions failure of properly-maintained vehiclesmore » at or near their warranted useful life mileage.« less

Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

PubMed

2012-04-06

Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn screening laboratories. The recommended practices address the benefits of using a quality management system approach, factors to consider before introducing new tests, establishment and verification of test performance specifications, the total laboratory testing process (which consists of the preanalytic, analytic, and postanalytic phases), confidentiality of patient information and test results, and personnel qualifications and responsibilities for laboratory testing for inherited metabolic diseases. These recommendations are intended for laboratories that perform biochemical genetic testing to improve the quality of laboratory services and for newborn screening laboratories to ensure the quality of laboratory practices for inherited metabolic disorders. These recommendations also are intended as a resource for medical and public health professionals who evaluate laboratory practices, for users of laboratory services to facilitate their collaboration with newborn screening systems and use of biochemical genetic tests, and for standard-setting organizations and professional societies in developing future laboratory quality standards and practice recommendations. This report complements Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions (CDC. Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR 2009;58 [No. RR-6]) to provide guidance for ensuring and improving the quality of genetic laboratory services and public health outcomes. Future recommendations for additional areas of genetic testing will be considered on the basis of continued monitoring and evaluation of laboratory practices, technology advancements, and the development of laboratory standards and guidelines.

A High-Throughput Screen Reveals New Small-Molecule Activators and Inhibitors of Pantothenate Kinases

PubMed Central

2016-01-01

Pantothenate kinase (PanK) is a regulatory enzyme that controls coenzyme A (CoA) biosynthesis. The association of PanK with neurodegeneration and diabetes suggests that chemical modifiers of PanK activity may be useful therapeutics. We performed a high throughput screen of >520000 compounds from the St. Jude compound library and identified new potent PanK inhibitors and activators with chemically tractable scaffolds. The HTS identified PanK inhibitors exemplified by the detailed characterization of a tricyclic compound (7) and a preliminary SAR. Biophysical studies reveal that the PanK inhibitor acts by binding to the ATP–enzyme complex. PMID:25569308

Convenient, Sensitive and High-Throughput Method for Screening Botanic Origin

NASA Astrophysics Data System (ADS)

Yuan, Yuan; Jiang, Chao; Liu, Libing; Yu, Shulin; Cui, Zhanhu; Chen, Min; Lin, Shufang; Wang, Shu; Huang, Luqi

2014-06-01

In this work, a rapid (within 4-5 h), sensitive and visible new method for assessing botanic origin is developed by combining loop-mediated isothermal amplification with cationic conjugated polymers. The two Chinese medicinal materials (Jin-Yin-Hua and Shan-Yin-Hua) with similar morphology and chemical composition were clearly distinguished by gene SNP genotyping assays. The identification of plant species in Patented Chinese drugs containing Lonicera buds is successfully performed using this detection system. The method is also robust enough to be used in high-throughput screening. This new method is very helpful to identify herbal materials, and is beneficial for detecting safety and quality of botanic products.

Targeted screening and treatment for latent tuberculosis infection using QuantiFERON-TB Gold is cost-effective in Mexico.

PubMed

Burgos, J L; Kahn, J G; Strathdee, S A; Valencia-Mendoza, A; Bautista-Arredondo, S; Laniado-Laborin, R; Castañeda, R; Deiss, R; Garfein, R S

2009-08-01

To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective.

Targeted screening and treatment for latent tuberculosis infection using QuantiFERON®-TB Gold is cost-effective in Mexico

PubMed Central

Burgos, J. L.; Kahn, J. G.; Strathdee, S. A.; Valencia-Mendoza, A.; Bautista-Arredondo, S.; Laniado-Laborin, R.; Castañeda, R.; Deiss, R.; Garfein, R. S.

2009-01-01

SUMMARY OBJECTIVE To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. DESIGN We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON®-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. RESULTS Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. CONCLUSIONS In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective. PMID:19723375

Introduction of a hydrolysis probe PCR assay for high-throughput screening of methicillin-resistant Staphylococcus aureus with the ability to include or exclude detection of Staphylococcus argenteus.

PubMed

Bogestam, Katja; Vondracek, Martin; Karlsson, Mattias; Fang, Hong; Giske, Christian G

2018-01-01

Many countries using sensitive screening methods for detection of carriage of methicillin-resistant Staphylococcus aureus (MRSA) have a sustained low incidence of MRSA infections. For diagnostic laboratories with high sample volumes, MRSA screening requires stability, low maintenance and high performance at a low cost. Herein we designed oligonucleotides for a new nuc targeted hydrolysis probe PCR to replace the standard in-house nuc SybrGreen PCR assay. This new, more time-efficient, PCR assay resulted in a 40% increase in daily sample capacity, with maintained high specificity and sensitivity. The assay was also able to detect Staphylococcus aureus clonal cluster 75 (CC75) lineage strains, recently re-classified as Staphylococcus argenteus, with a sensitivity considerably increased compared to our previous assay. While awaiting consensus if the CC75 lineage of S. aureus should be considered as S. argenteus, and whether methicillin-resistant S. argenteus should be included in the MRSA definition, many diagnostic laboratories need to update their MRSA assay sensitivity/specificity towards this lineage/species. The MRSA screening assay presented in this manuscript is comprised of nuc oligonucleotides separately targeting S. aureus and CC75 lineage strains/S. argenteus, thus providing high user flexibility for the detection of CC75 lineage strains/S. argenteus.

AutoClickChem: click chemistry in silico.

PubMed

Durrant, Jacob D; McCammon, J Andrew

2012-01-01

Academic researchers and many in industry often lack the financial resources available to scientists working in "big pharma." High costs include those associated with high-throughput screening and chemical synthesis. In order to address these challenges, many researchers have in part turned to alternate methodologies. Virtual screening, for example, often substitutes for high-throughput screening, and click chemistry ensures that chemical synthesis is fast, cheap, and comparatively easy. Though both in silico screening and click chemistry seek to make drug discovery more feasible, it is not yet routine to couple these two methodologies. We here present a novel computer algorithm, called AutoClickChem, capable of performing many click-chemistry reactions in silico. AutoClickChem can be used to produce large combinatorial libraries of compound models for use in virtual screens. As the compounds of these libraries are constructed according to the reactions of click chemistry, they can be easily synthesized for subsequent testing in biochemical assays. Additionally, in silico modeling of click-chemistry products may prove useful in rational drug design and drug optimization. AutoClickChem is based on the pymolecule toolbox, a framework that may facilitate the development of future python-based programs that require the manipulation of molecular models. Both the pymolecule toolbox and AutoClickChem are released under the GNU General Public License version 3 and are available for download from http://autoclickchem.ucsd.edu.

AutoClickChem: Click Chemistry in Silico

PubMed Central

Durrant, Jacob D.; McCammon, J. Andrew

2012-01-01

Academic researchers and many in industry often lack the financial resources available to scientists working in “big pharma.” High costs include those associated with high-throughput screening and chemical synthesis. In order to address these challenges, many researchers have in part turned to alternate methodologies. Virtual screening, for example, often substitutes for high-throughput screening, and click chemistry ensures that chemical synthesis is fast, cheap, and comparatively easy. Though both in silico screening and click chemistry seek to make drug discovery more feasible, it is not yet routine to couple these two methodologies. We here present a novel computer algorithm, called AutoClickChem, capable of performing many click-chemistry reactions in silico. AutoClickChem can be used to produce large combinatorial libraries of compound models for use in virtual screens. As the compounds of these libraries are constructed according to the reactions of click chemistry, they can be easily synthesized for subsequent testing in biochemical assays. Additionally, in silico modeling of click-chemistry products may prove useful in rational drug design and drug optimization. AutoClickChem is based on the pymolecule toolbox, a framework that may facilitate the development of future python-based programs that require the manipulation of molecular models. Both the pymolecule toolbox and AutoClickChem are released under the GNU General Public License version 3 and are available for download from http://autoclickchem.ucsd.edu. PMID:22438795

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification

PubMed Central

Ballester, Pedro J.; Mangold, Martina; Howard, Nigel I.; Robinson, Richard L. Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B. O.

2012-01-01

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated Ki ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification. PMID:22933186

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification.

PubMed

Ballester, Pedro J; Mangold, Martina; Howard, Nigel I; Robinson, Richard L Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B O

2012-12-07

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated K(i) ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.

Predicting School Performance with the Early Screening Inventory.

ERIC Educational Resources Information Center

Meisels, Samuel J.; And Others

1984-01-01

Proposes criteria for defining and selecting preschool developmental screening instruments and describes the Early Screening Inventory (ESI), a developmental screening instrument designed to satisfy these criteria. Presents results of several studies demonstrating that the ESI predicts school performance with moderate to excellent accuracy through…

Hollow fiber based affinity selection combined with high performance liquid chromatography-mass spectroscopy for rapid screening lipase inhibitors from lotus leaf.

PubMed

Tao, Yi; Zhang, Yufeng; Wang, Yi; Cheng, Yiyu

2013-06-27

A novel kind of immobilized enzyme affinity selection strategy based on hollow fibers has been developed for screening inhibitors from extracts of medicinal plants. Lipases from porcine pancreas were adsorbed onto the surface of polypropylene hollow fibers to form a stable matrix for ligand fishing, which was called hollow fibers based affinity selection (HF-AS). A variety of factors related to binding capability, including enzyme concentration, incubation time, temperature, buffer pH and ion strength, were optimized using a known lipase inhibitor hesperidin. The proposed approach was applied in screening potential lipase bound ligands from extracts of lotus leaf, followed by rapid characterization of active compounds using high performance liquid chromatography-mass spectrometry. Three flavonoids including quercetin-3-O-β-D-arabinopyranosyl-(1→2)-β-D-galactopyranoside, quercetin-3-O-β-D-glucuronide and kaempferol-3-O-β-d-glucuronide were identified as lipase inhibitors by the proposed HF-AS approach. Our findings suggested that the hollow fiber-based affinity selection could be a rapid and convenient approach for drug discovery from natural products resources. Copyright © 2013 Elsevier B.V. All rights reserved.

Screening and analysis of the multiple absorbed bioactive components and metabolites in rat plasma after oral administration of Jitai tablets by high-performance liquid chromatography/diode-array detection coupled with electrospray ionization tandem mass spectrometry.

PubMed

Wang, Shu-Ping; Liu, Lei; Wang, Ling-Ling; Jiang, Peng; Zhang, Ji-Quan; Zhang, Wei-Dong; Liu, Run-Hui

2010-06-15

Based on the serum pharmacochemistry technique and high-performance liquid chromatography/diode-array detection (HPLC/DAD) coupled with electrospray tandem mass spectrometry (HPLC/ESI-MS/MS), a method for screening and analysis of the multiple absorbed bioactive components and metabolites of Jitai tablets (JTT) in orally dosed rat plasma was developed. Plasma was treated by methanol precipitation prior to liquid chromatography, and the separation was carried out on a Symmetry C(18) column, with a linear gradient (0.1% formic acid/water/acetonitrile). Mass spectra were acquired in negative and positive ion modes, respectively. As a result, 26 bioactive components originated from JTT and 5 metabolites were tentatively identified in orally dosed rat plasma by comparing their retention times and MS spectra with those of authentic standards and literature data. It is concluded that an effective and reliable analytical method was set up for screening the bioactive components of Chinese herbal medicine, which provided a meaningful basis for further pharmacology and active mechanism research of JTT. Copyright (c) 2010 John Wiley & Sons, Ltd.

New antibody and immunoassay pretreatment strategy to screen polychlorinated biphenyls in Korean transformer oil.

PubMed

Terakado, Shingo; Ohmura, Naoya; Park, Seok-Un; Lee, Seung-Min; Glass, Thomas R

2013-01-01

Development and modifications are described that expand the application of an immunoassay from the detection of Kanechlors (Japanese technical PCBs mixtures) to the detection of Aroclors (U. S. technical PCB mixtures, used in Korea) in contaminated Korean transformer oil. The first necessary modification was the development of a new antibody with a reactivity profile favorable for Aroclors. The second modification was the addition of a second column to the solid-phase extraction method to reduce assay interference caused by the Korean oil matrix. The matrix interference is suspected to be caused by the presence of synthetic oils (or similar materials) present as contaminants. The modified assay was validated by comparison to high-resolution gas chromatography/high-resolution mass spectrometry analysis, and was shown to be tolerant of up to 10% of several common synthetic insulating oils. Finally the screening performance of the modified assay was evaluated using 500 used transformer oil samples of Korean origin, and was shown to have good performance in terms of false positive and false negative rates. This report provides evidence for the first establishment of immunoassay screening for Aroclor based PCB contamination in Korean transformer oil.

A network pharmacology-integrated metabolomics strategy for clarifying the difference between effective compounds of raw and processed Farfarae flos by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry.

PubMed

Ding, Mingya; Li, Zhen; Yu, Xie-An; Zhang, Dong; Li, Jin; Wang, Hui; He, Jun; Gao, Xiu-Mei; Chang, Yan-Xu

2018-07-15

This study aimed to clarify the difference between the effective compounds of raw and processed Farfarae flos using a network pharmacology-integrated metabolomics strategy. First, metabolomics data were obtained by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS). Then, metabolomics analysis was developed to screen for the influential compounds that were different between raw and processed Farfarae flos. Finally, a network pharmacology approach was applied to verify the activity of the screened compounds. As a result, 4 compounds (chlorogenic acid, caffeic acid, rutin and isoquercitrin) were successfully screened, identified, quantified and verified as the most influential effective compounds. They may synergistically inhibit the p38, JNK and ERK-mediated pathways, which would induce the inhibition of the expression of the IFA virus. The results revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful tool for discovering the effective compounds that were responsible for the difference between raw and processed Chinese herbs. Copyright © 2018 Elsevier B.V. All rights reserved.

Searching for “Defect-Tolerant” Photovoltaic Materials: Combined Theoretical and Experimental Screening

DOE PAGES

Brandt, Riley E.; Poindexter, Jeremy R.; Gorai, Prashun; ...

2017-05-09

Recently, we and others have proposed screening criteria for 'defect-tolerant' photovoltaic (PV) absorbers, identifying several classes of semiconducting compounds with electronic structures similar to those of hybrid lead-halide perovskites. In this work, we reflect on the accuracy and prospects of these new design criteria through a combined experimental and theoretical approach. We construct a model to extract photoluminescence lifetimes of six of these candidate PV absorbers, including four (InI, SbSI, SbSeI, and BiOI) for which time-resolved photoluminescence has not been previously reported. The lifetimes of all six candidate materials exceed 1 ns, a threshold for promising early stage PV devicemore » performance. However, there are variations between these materials, and none achieve lifetimes as high as those of the hybrid lead-halide perovskites, suggesting that the heuristics for defect-tolerant semiconductors are incomplete. Here, we explore this through first-principles point defect calculations and Shockley-Read-Hall recombination models to describe the variation between the measured materials. In light of these insights, we discuss the evolution of screening criteria for defect tolerance and high-performance PV materials.« less

Audit feedback on reading performance of screening mammograms: An international comparison.

PubMed

Hofvind, S; Bennett, R L; Brisson, J; Lee, W; Pelletier, E; Flugelman, A; Geller, B

2016-09-01

Providing feedback to mammography radiologists and facilities may improve interpretive performance. We conducted a web-based survey to investigate how and why such feedback is undertaken and used in mammographic screening programmes. The survey was sent to representatives in 30 International Cancer Screening Network member countries where mammographic screening is offered. Seventeen programmes in 14 countries responded to the survey. Audit feedback was aimed at readers in 14 programmes, and facilities in 12 programmes. Monitoring quality assurance was the most common purpose of audit feedback. Screening volume, recall rate, and rate of screen-detected cancers were typically reported performance measures. Audit reports were commonly provided annually, but more frequently when target guidelines were not reached. The purpose, target audience, performance measures included, form and frequency of the audit feedback varied amongst mammographic screening programmes. These variations may provide a basis for those developing and improving such programmes. © The Author(s) 2016.

Use of probability analysis to establish routine bioassay screening levels

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

Carbaugh, E.H.; Sula, M.J.; McFadden, K.M.

1990-09-01

Probability analysis was used by the Hanford Internal Dosimetry Program to establish bioassay screening levels for tritium and uranium in urine. Background environmental levels of these two radionuclides are generally detectable by the highly sensitive urine analysis procedures routinely used at Hanford. Establishing screening levels requires balancing the impact of false detection with the consequence of potentially undetectable occupation dose. To establish the screening levels, tritium and uranium analyses were performed on urine samples collected from workers exposed only to environmental sources. All samples were collected at home using a simulated 12-hour protocol for tritium and a simulated 24-hour collectionmore » protocol for uranium. Results of the analyses of these samples were ranked according to tritium concentration or total sample uranium. The cumulative percentile was calculated and plotted using log-probability coordinates. Geometric means and screening levels corresponding to various percentiles were estimated by graphical interpolation and standard calculations. The potentially annual internal dose associated with a screening level was calculated. Screening levels were selected corresponding to the 99.9 percentile, implying that, on the average, 1 out of 1000 samples collected from an unexposed worker population would be expected to exceed the screening level. 4 refs., 2 figs.« less

Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening.

PubMed

Wolf, Barry

2017-04-01

We began screening newborns for biotinidase deficiency disorder in 1984, and now all states in the United States and many countries perform this screening. The purpose of this study was to determine the outcomes of older adolescent and adult individuals with the disorder identified by newborn screening. We located and surveyed, by questionnaire and telephone interviews, 44 individuals with profound biotinidase deficiency identified by newborn screening with a mean age of 23.1 years. All individuals had successfully completed high school, and many were attending or had completed college or graduate school. Compliance in using biotin has been excellent. Several individuals developed a variety of symptoms when they discontinued biotin for days or weeks. These features readily resolved when biotin was resumed. In addition, five treated women had nine uneventful pregnancies and deliveries. Newborn screening for profound biotinidase deficiency and early treatment with biotin result in excellent outcomes for older adolescents and adults with the disorder. In addition, mothers with profound biotinidase deficiency who were treated with biotin had pregnancies with good outcomes. These outcome results indicate that newborn screening for biotinidase deficiency is one of the most successful newborn screening programs.Genet Med 19 4, 396-402.

Effect of transient liquid flow on retention characteristics of screen acquisition systems. [design of Space Shuttle feed system

NASA Technical Reports Server (NTRS)

Cady, E. C.

1977-01-01

A design analysis, is developed based on experimental data, to predict the effects of transient flow and pressure surges (caused either by valve or pump operation, or by boiling of liquids in warm lines) on the retention performance of screen acquisition systems. A survey of screen liquid acquisition system applications was performed to determine appropriate system environment and classification. A screen model was developed which assumed that the screen device was a uniformly distributed composite orthotropic structure, and which accounted for liquid inflow/outflow, gas ingestion quality, screen stress, and liquid spill. A series of 177 tests using 13 specimens (5 screen meshes, 4 screen device construction/backup methods, and 2 orientations) with three test fluids (isopropyl alcohol, Freon 114, and LH2) provided data which verified important features of the screen model and resulted in a design tool which could accurately predict the transient startup performance acquisition devices.

Graphitized Porous Carbon for Rapid Screening of Angiotensin-Converting Enzyme Inhibitory Peptide GAMVVH from Silkworm Pupa Protein and Molecular Insight into Inhibition Mechanism.

PubMed

Tao, Mengliang; Sun, Huaju; Liu, Long; Luo, Xuan; Lin, Guoyou; Li, Renbo; Zhao, Zhenxia; Zhao, Zhongxing

2017-10-04

A novel hydrophobic hexapeptide with high angiotensin-converting enzyme (ACE) inhibitory activity was screened from silkworm pupa protein (SPP) hydrolysate via graphitized porous carbon and reverse-phase high-performance liquid chromatography methods. Graphitized porous carbon derived from dopamine, possessing high surface area and high graphitic carbon, was used to rapidly screen and enrich hydrophobic peptides from SPP hydrolysate. The ACE inhibition pattern and mechanism of the purified peptide were also systematically studied by the classic Lineweaver-Burk model and by molecular docking/dynamic simulation. The novel hydrophobic hexapeptide was identified as Gly-Ala-Met-Val-Val-His (GAMVVH, IC 50 = 19.39 ± 0.21 μM) with good thermal/antidigestive stabilities. Lineweaver-Burk plots revealed that GAMVVH behaved as a competitive ACE inhibitor. It formed hydrogen bonds with S1 and S2 pockets of ACE and established competitive coordination with Zn(II) of ACE. The synergy of hydrogen bonds with active pockets and Zn(II) coordination efficiently changed the three-dimensional structure of ACE and thus inhibited bioactivity of ACE.

High-Content Microscopy Analysis of Subcellular Structures: Assay Development and Application to Focal Adhesion Quantification.

PubMed

Kroll, Torsten; Schmidt, David; Schwanitz, Georg; Ahmad, Mubashir; Hamann, Jana; Schlosser, Corinne; Lin, Yu-Chieh; Böhm, Konrad J; Tuckermann, Jan; Ploubidou, Aspasia

2016-07-01

High-content analysis (HCA) converts raw light microscopy images to quantitative data through the automated extraction, multiparametric analysis, and classification of the relevant information content. Combined with automated high-throughput image acquisition, HCA applied to the screening of chemicals or RNAi-reagents is termed high-content screening (HCS). Its power in quantifying cell phenotypes makes HCA applicable also to routine microscopy. However, developing effective HCA and bioinformatic analysis pipelines for acquisition of biologically meaningful data in HCS is challenging. Here, the step-by-step development of an HCA assay protocol and an HCS bioinformatics analysis pipeline are described. The protocol's power is demonstrated by application to focal adhesion (FA) detection, quantitative analysis of multiple FA features, and functional annotation of signaling pathways regulating FA size, using primary data of a published RNAi screen. The assay and the underlying strategy are aimed at researchers performing microscopy-based quantitative analysis of subcellular features, on a small scale or in large HCS experiments. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Do subjective memory complaints predict senile Alzheimer dementia?

PubMed

Jungwirth, Susanne; Zehetmayer, Sonja; Weissgram, Silvia; Weber, Germain; Tragl, Karl Heinz; Fischer, Peter

2008-01-01

Many elderly complain about their memory and undergo dementia screening by the Mini-Mental State Examination (MMSE). While objective memory impairment always precedes Alzheimer dementia (AD) it is unclear whether subjective memory complaints are predicting AD. We tried to answer this question in a prospective cohort study. The 75-years old non-demented inhabitants of Vienna-Transdanube were investigated for conversion to AD after 30 months. The predictive value of subjective memory complaints was analysed in two groups: subjects with high MMSE-score (28-30) and subjects with low MMSE-score (23-27). Only in subjects with high MMSE univariate analyses showed an association between subjective memory complaints and incident AD. In both groups the verbal memory test was the main predictor of AD in multivariate analyses. We suggest to perform memory testing in subjects complaining about memory irrespective of their performance in a screening procedure like the MMSE.

Origin of long lifetime of band-edge charge carriers in organic–inorganic lead iodide perovskites

PubMed Central

Chen, Tianran; Chen, Wei-Liang; Foley, Benjamin J.; Lee, Jooseop; Ruff, Jacob P. C.; Ko, J. Y. Peter; Brown, Craig M.; Harriger, Leland W.; Zhang, Depei; Park, Changwon; Yoon, Mina; Chang, Yu-Ming; Choi, Joshua J.; Lee, Seung-Hun

2017-01-01

Long carrier lifetime is what makes hybrid organic–inorganic perovskites high-performance photovoltaic materials. Several microscopic mechanisms behind the unusually long carrier lifetime have been proposed, such as formation of large polarons, Rashba effect, ferroelectric domains, and photon recycling. Here, we show that the screening of band-edge charge carriers by rotation of organic cation molecules can be a major contribution to the prolonged carrier lifetime. Our results reveal that the band-edge carrier lifetime increases when the system enters from a phase with lower rotational entropy to another phase with higher entropy. These results imply that the recombination of the photoexcited electrons and holes is suppressed by the screening, leading to the formation of polarons and thereby extending the lifetime. Thus, searching for organic–inorganic perovskites with high rotational entropy over a wide range of temperature may be a key to achieve superior solar cell performance. PMID:28673975

Origin of long lifetime of band-edge charge carriers in organic-inorganic lead iodide perovskites.

PubMed

Chen, Tianran; Chen, Wei-Liang; Foley, Benjamin J; Lee, Jooseop; Ruff, Jacob P C; Ko, J Y Peter; Brown, Craig M; Harriger, Leland W; Zhang, Depei; Park, Changwon; Yoon, Mina; Chang, Yu-Ming; Choi, Joshua J; Lee, Seung-Hun

2017-07-18

Long carrier lifetime is what makes hybrid organic-inorganic perovskites high-performance photovoltaic materials. Several microscopic mechanisms behind the unusually long carrier lifetime have been proposed, such as formation of large polarons, Rashba effect, ferroelectric domains, and photon recycling. Here, we show that the screening of band-edge charge carriers by rotation of organic cation molecules can be a major contribution to the prolonged carrier lifetime. Our results reveal that the band-edge carrier lifetime increases when the system enters from a phase with lower rotational entropy to another phase with higher entropy. These results imply that the recombination of the photoexcited electrons and holes is suppressed by the screening, leading to the formation of polarons and thereby extending the lifetime. Thus, searching for organic-inorganic perovskites with high rotational entropy over a wide range of temperature may be a key to achieve superior solar cell performance.

Selecting the Best and Brightest: A Structured Approach to Orthopedic Resident Selection.

PubMed

Schenker, Mara L; Baldwin, Keith D; Israelite, Craig L; Levin, L Scott; Mehta, Samir; Ahn, Jaimo

2016-01-01

Resident selection is integral to the graduate medical educational process and the future of our profession. There is no consensus among residency directors as to how to systematically and consistently screen and select applicants who would perform well as residents. The purpose of this study was to introduce and assess a high volume application screening tool and semistructured interview process. This study took place in an academic orthopedic surgery department over 2 years (2013-2014). Overall, 1382 applications were screened in 7 categories, with a maximum score of 100. A total of 14 faculty reviewed applications; 218 interviews were offered; 165 applicants accepted the interview. Overall, 4 interview domains (cognitive, affective, activities, and theme), and an impression score were ranked from 1 (Exceptional) to 6 (Concern). Each room had an assigned "theme" (ethics, affective, cognitive, research, and "fit") with standardized questions. A summary score was generated of all scores to determine the preliminary rank list; the final rank list was determined after group discussion. Correlation between preliminary rank, final rank, and screening scores were assessed. The average screening score was 62.5 (range: 0-100, median = 64). The average interview score was 69.5 (range: 32.24-95.0). Final rank lists correlated most highly with initial rank (0.912, p < 0.001), impression (0.847, p < 0.001), and affective domain (0.834, p < 0.001). Cognitive domain (0.628, p < 0.001) and screening scores (0.264, p < 0.001) less highly correlated with final rank position. A systematic approach was used to screen and evaluate a large number of orthopedic surgery applicants. Our system demonstrated excellent feasibility, reliability, and predictability for the final rank list. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Low Voltage, Low Power Organic Light Emitting Transistors for AMOLED Displays

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

McCarthy, M. A.; Liu, B.; Donoghue, E. P.

2011-01-01

Low voltage, low power dissipation, high aperture ratio organic light emitting transistors are demonstrated. The high level of performance is enabled by a carbon nanotube source electrode that permits integration of the drive transistor and the organic light emitting diode into an efficient single stacked device. Given the demonstrated performance, this technology could break the technical logjam holding back widespread deployment of active matrix organic light emitting displays at flat panel screen sizes.

A strategy for clone selection under different production conditions.

PubMed

Legmann, Rachel; Benoit, Brian; Fedechko, Ronald W; Deppeler, Cynthia L; Srinivasan, Sriram; Robins, Russell H; McCormick, Ellen L; Ferrick, David A; Rodgers, Seth T; Russo, A Peter

2011-01-01

Top performing clones have failed at the manufacturing scale while the true best performer may have been rejected early in the screening process. Therefore, the ability to screen multiple clones in complex fed-batch processes using multiple process variations can be used to assess robustness and to identify critical factors. This dynamic ranking of clones' strategy requires the execution of many parallel experiments than traditional approaches. Therefore, this approach is best suited for micro-bioreactor models which can perform hundreds of experiments quickly and efficiently. In this study, a fully monitored and controlled small scale platform was used to screen eight CHO clones producing a recombinant monoclonal antibody across several process variations, including different feeding strategies, temperature shifts and pH control profiles. The first screen utilized 240 micro-bioreactors were run for two weeks for this assessment of the scale-down model as a high-throughput tool for clone evaluation. The richness of the outcome data enable to clearly identify the best and worst clone as well as process in term of maximum monoclonal antibody titer. The follow-up comparison study utilized 180 micro-bioreactors in a full factorial design and a subset of 12 clone/process combinations was selected to be run parallel in duplicate shake flasks. Good correlation between the micro-bioreactor predictions and those made in shake flasks with a Pearson correlation value of 0.94. The results also demonstrate that this micro-scale system can perform clone screening and process optimization for gaining significant titer improvements simultaneously. This dynamic ranking strategy can support better choices of production clones. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

Setup of a Protocol of Molecular Diagnosis of β-Thalassemia Mutations in Tunisia using Denaturing High-Performance Liquid Chromatography (DHPLC).

PubMed

Sahli, Chaima Abdelhafidh; Ben Salem, Ikbel; Jouini, Latifa; Laouini, Naouel; Dabboubi, Rym; Hadj Fredj, Sondes; Siala, Hajer; Othmeni, Rym; Dakhlaoui, Boutheina; Fattoum, Slaheddine; Bibi, Amina; Messaoud, Taieb

2016-09-01

β-Thalassemia is one of the most prevalent worldwide autosomal recessive disorders. It presents a great molecular heterogeneity resulting from more than 200 causative mutations in the β-globin gene. In Tunisia, β-thalassemia represents the most prevalent monogenic hemoglobin disorder with 2.21% of carriers. Efficient and reliable mutation-screening methods are essential in order to establish appropriate prevention programs for at risk couples. The aim of the present study is to develop an efficient method based on the denaturing high-performance liquid chromatography (DHPLC) in which the whole β-globin gene (HBB) is screened for mutations covering about 90% of the spectrum. We have performed the validation of a DHPLC assay for direct genotyping of 11 known β-thalassemia mutations in the Tunisian population. DHPLC assay was established based on the analysis of 62 archival β-thalassemia samples previously genotyped then validated with full concordance on 50 tests with blind randomized samples previously genotyped with DNA sequencing and with 96% of consistency on 40 samples as a prospective study. Compared to other genotyping techniques, the DHPLC method can meet the requirements of direct genotyping of known β-thalassemia mutations in Tunisia and to be applied as a powerful tool for the genetic screening of prenatal and postnatal individuals. © 2016 Wiley Periodicals, Inc.

Development of small scale cell culture models for screening poloxamer 188 lot-to-lot variation.

PubMed

Peng, Haofan; Hall, Kaitlyn M; Clayton, Blake; Wiltberger, Kelly; Hu, Weiwei; Hughes, Erik; Kane, John; Ney, Rachel; Ryll, Thomas

2014-01-01

Shear protectants such as poloxamer 188 play a critical role in protecting cells during cell culture bioprocessing. Lot-to-lot variation of poloxamer 188 was experienced during a routine technology transfer across sites of similar scale and equipment. Cell culture medium containing a specific poloxamer 188 lot resulted in an unusual drop in cell growth, viability, and titer during manufacturing runs. After switching poloxamer lots, culture performance returned to the expected level. In order to control the quality of poloxamer 188 and thus maintain better consistency in manufacturing, multiple small scale screening models were developed. Initially, a 5L bioreactor model was established to evaluate cell damage by high sparge rates with different poloxamer 188 lots. Subsequently, a more robust, simple, and efficient baffled shake flask model was developed. The baffled shake flask model can be performed in a high throughput manner to investigate the cell damage in a bubbling environment. The main cause of the poor performance was the loss of protection, rather than toxicity. It was also suggested that suspicious lots can be identified using different cell line and media. The screening methods provide easy, yet remarkable models for understanding and controlling cell damage due to raw material lot variation as well as studying the interaction between poloxamer 188 and cells. © 2014 American Institute of Chemical Engineers.

Miniaturizing 3D assay for high-throughput drug and genetic screens for small patient-derived tumor samples (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rotem, Asaf; Garraway, Levi; Su, Mei-Ju; Basu, Anindita; Regev, Aviv; Struhl, Kevin

2017-02-01

Three-dimensional growth conditions reflect the natural environment of cancer cells and are crucial to be performed at drug screens. We developed a 3D assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the 50-year old benchmark assay-soft agar. Using GILA, we performed high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. This phenotypic approach is complementary to our genetic approach that utilizes single-cell RNA-sequencing of a patient sample to identify putative oncogenes that confer sensitivity to drugs designed to specifically inhibit the identified oncoprotein. Currently, we are dealing with a big challenge in our field- the limited number of cells that might be extracted from a biopsy. Small patient-derived samples are hard to test in the traditional multiwell plate and it will be helpful to minimize the culture area and the experimental system. We managed to design a suitable microfluidic device for limited number of cells and perform the assay using image analysis. We aim to test drugs on tumor cells, outside of the patient body- and recommend on the ideal treatment that is tailored to the individual. This device will help to minimize biopsy-sampling volumes and minimize interventions in the patient's tumor.

High-Throughput, Motility-Based Sorter for Microswimmers such as C. elegans

PubMed Central

Yuan, Jinzhou; Zhou, Jessie; Raizen, David M.; Bau, Haim H.

2015-01-01

Animal motility varies with genotype, disease, aging, and environmental conditions. In many studies, it is desirable to carry out high throughput motility-based sorting to isolate rare animals for, among other things, forward genetic screens to identify genetic pathways that regulate phenotypes of interest. Many commonly used screening processes are labor-intensive, lack sensitivity, and require extensive investigator training. Here, we describe a sensitive, high throughput, automated, motility-based method for sorting nematodes. Our method is implemented in a simple microfluidic device capable of sorting thousands of animals per hour per module, and is amenable to parallelism. The device successfully enriches for known C. elegans motility mutants. Furthermore, using this device, we isolate low-abundance mutants capable of suppressing the somnogenic effects of the flp-13 gene, which regulates C. elegans sleep. By performing genetic complementation tests, we demonstrate that our motility-based sorting device efficiently isolates mutants for the same gene identified by tedious visual inspection of behavior on an agar surface. Therefore, our motility-based sorter is capable of performing high throughput gene discovery approaches to investigate fundamental biological processes. PMID:26008643

Estimation of the costs of cervical cancer screening, diagnosis and treatment in rural Shanxi Province, China: a micro-costing study

PubMed Central

2012-01-01

Background Cost estimation is a central feature of health economic analyses. The aim of this study was to use a micro-costing approach and a societal perspective to estimate aggregated costs associated with cervical cancer screening, diagnosis and treatment in rural China. Methods We assumed that future screening programs will be organized at a county level (population ~250,000), and related treatments will be performed at county or prefecture hospitals; therefore, this study was conducted in a county and a prefecture hospital in Shanxi during 2008–9. Direct medical costs were estimated by gathering information on quantities and prices of drugs, supplies, equipment and labour. Direct non-medical costs were estimated via structured patient interviews and expert opinion. Results Under the base case assumption of a high-volume screening initiative (11,475 women screened annually per county), the aggregated direct medical costs of visual inspection, self-sampled careHPV (Qiagen USA) screening, clinician-sampled careHPV, colposcopy and biopsy were estimated as US$2.64,$7.49,$7.95,$3.90 and $5.76, respectively. Screening costs were robust to screening volume (<5% variation if 2,000 women screened annually), but costs of colposcopy/biopsy tripled at the lower volume. Direct medical costs of Loop Excision, Cold-Knife Conization and Simple and Radical Hysterectomy varied from $61–544, depending on the procedure and whether conducted at county or prefecture level. Direct non-medical expenditure varied from $0.68–$3.09 for screening/diagnosis and $83–$494 for pre-cancer/cancer treatment. Conclusions Diagnostic costs were comparable to screening costs for high-volume screening but were greatly increased in lower-volume situations, which is a key consideration for the scale-up phase of new programs. The study’s findings will facilitate cost-effectiveness evaluation and budget planning for cervical cancer prevention initiatives in China. PMID:22624619

Screening of 23 β-lactams in foodstuffs by LC-MS/MS using an alkaline QuEChERS-like extraction.

PubMed

Bessaire, Thomas; Mujahid, Claudia; Beck, Andrea; Tarres, Adrienne; Savoy, Marie-Claude; Woo, Pei-Mun; Mottier, Pascal; Desmarchelier, Aurélien

2018-04-01

A fast and robust high performance LC-MS/MS screening method was developed for the analysis of β-lactam antibiotics in foods of animal origin: eggs, raw milk, processed dairy ingredients, infant formula, and meat- and fish-based products including baby foods. QuEChERS extraction with some adaptations enabled 23 drugs to be simultaneously monitored. Screening target concentrations were set at levels adequate to ensure compliance with current European, Chinese, US and Canadian regulations. The method was fully validated according to the European Community Reference Laboratories Residues Guidelines using 93 food samples of different composition. False-negative and false-positive rates were below 5% for all analytes. The method is adequate for use in high-routine laboratories. A 1-year study was additionally conducted to assess the stability of the 23 analytes in the working standard solution.

High efficiency ion beam accelerator system

NASA Technical Reports Server (NTRS)

Aston, G.

1981-01-01

An ion accelerator system that successfully combines geometrical and electrostatic focusing principles is presented. This accelerator system uses thin, concave, multiple-hole, closely spaced graphite screen and focusing grids which are coupled to single slot accelerator and decelerator grids to provide high ion extraction efficiency and good focusing. Tests with the system showed a substantial improvement in ion beam current density and collimation as compared with a Pierce electrode configuration. Durability of the thin graphite screen and focusing grids has been proven, and tests are being performed to determine the minimum screen and focusing grid spacing and thickness required to extract the maximum reliable beam current density. Compared with present neutral beam injector accelerator systems, this one has more efficient ion extraction, easier grid alignment, easier fabrication, a less cumbersome design, and the capacity to be constructed in a modular fashion. Conceptual neutral beam injector designs using this modular approach have electrostatic beam deflection plates downstream of each module.

Improving the photostability of bright monomeric orange and red fluorescent proteins.

PubMed

Shaner, Nathan C; Lin, Michael Z; McKeown, Michael R; Steinbach, Paul A; Hazelwood, Kristin L; Davidson, Michael W; Tsien, Roger Y

2008-06-01

All organic fluorophores undergo irreversible photobleaching during prolonged illumination. Although fluorescent proteins typically bleach at a substantially slower rate than many small-molecule dyes, in many cases the lack of sufficient photostability remains an important limiting factor for experiments requiring large numbers of images of single cells. Screening methods focusing solely on brightness or wavelength are highly effective in optimizing both properties, but the absence of selective pressure for photostability in such screens leads to unpredictable photobleaching behavior in the resulting fluorescent proteins. Here we describe an assay for screening libraries of fluorescent proteins for enhanced photostability. With this assay, we developed highly photostable variants of mOrange (a wavelength-shifted monomeric derivative of DsRed from Discosoma sp.) and TagRFP (a monomeric derivative of eqFP578 from Entacmaea quadricolor) that maintain most of the beneficial qualities of the original proteins and perform as reliably as Aequorea victoria GFP derivatives in fusion constructs.

Longitudinal Rates of Colon Cancer Screening Use in Winnipeg, Canada: The Experience of a Universal Health-Care System with an Organized Colon Screening Program.

PubMed

Decker, Kathleen M; Demers, Alain A; Nugent, Zoann; Biswanger, Natalie; Singh, Harminder

2015-12-01

We examined trends in colorectal cancer (CRC) screening (fecal occult blood test (FOBT), colonoscopy, and flexible sigmoidoscopy (FS)) and differences in CRC screening by income in a population with an organized CRC screening program and universal health-care coverage. Individuals who had an FOBT, colonoscopy, or FS were identified from the provincial Physician Claims database and the population-based colon cancer screening registry. Trends in age-standardized rates were determined. Logistic regression was performed to explore the association between CRC screening and income quintiles by year. Up-to-date CRC screening (FOBT, colonoscopy, or FS) increased over time for men and women, all age groups, and all income quintiles. Up-to-date CRC screening was very high among 65- to 69- and 70- to 74-year-olds (70% and 73%, respectively). There was a shift toward the use of an FOBT for CRC screening for individuals in the lower income quintiles. The disparity in colonoscopy/FS coverage by income quintile was greater in 2012 than in 1995. Overall, there was no reduction in disparities by income in up-to-date CRC screening nor did the rate of increase in up-to-date CRC screening or FOBT use change after the introduction of the organized provincial CRC screening program. CRC screening is increasing over time for both men and women and all age groups. However, a disparity in up-to-date CRC screening by income persisted even with an organized CRC screening program in a universal health-care setting.

"Plate cherry picking": a novel semi-sequential screening paradigm for cheaper, faster, information-rich compound selection.

PubMed

Crisman, Thomas J; Jenkins, Jeremy L; Parker, Christian N; Hill, W Adam G; Bender, Andreas; Deng, Zhan; Nettles, James H; Davies, John W; Glick, Meir

2007-04-01

This work describes a novel semi-sequential technique for in silico enhancement of high-throughput screening (HTS) experiments now employed at Novartis. It is used in situations in which the size of the screen is limited by the readout (e.g., high-content screens) or the amount of reagents or tools (proteins or cells) available. By performing computational chemical diversity selection on a per plate basis (instead of a per compound basis), 25% of the 1,000,000-compound screening was optimized for general initial HTS. Statistical models are then generated from target-specific primary results (percentage inhibition data) to drive the cherry picking and testing from the entire collection. Using retrospective analysis of 11 HTS campaigns, the authors show that this method would have captured on average two thirds of the active compounds (IC(50) < 10 microM) and three fourths of the active Murcko scaffolds while decreasing screening expenditure by nearly 75%. This result is true for a wide variety of targets, including G-protein-coupled receptors, chemokine receptors, kinases, metalloproteinases, pathway screens, and protein-protein interactions. Unlike time-consuming "classic" sequential approaches that require multiple iterations of cherry picking, testing, and building statistical models, here individual compounds are cherry picked just once, based directly on primary screening data. Strikingly, the authors demonstrate that models built from primary data are as robust as models built from IC(50) data. This is true for all HTS campaigns analyzed, which represent a wide variety of target classes and assay types.

Compatibility of Automatic Exposure Control with New Screen Phosphors in Diagnostic Roentgenography.

NASA Astrophysics Data System (ADS)

Mulvaney, James Arthur

1982-03-01

Automatic exposure control systems are used in diagnostic roentgenography to obtain proper film density for a variety of patient examinations and roentgenographic techniques. Most automatic exposure control systems have been designed for use with par speed, calcium tungstate intensifying screens. The use of screens with faster speeds and new phosphor materials has put extreme demands on present systems. The performance of a representative automatic exposure control system is investigated to determine its ability to maintain constant film density over a wide range of x-ray tube voltages and acrylic phantom thicknesses with four different intensifying screen phosphors. The effects of x-ray energy dependence, generator switching time and stored change are investigated. The system is able to maintain film density to within plus or minus 0.2 optical density units for techniques representing adult patients. A single nonadjustable tube voltage compensation circuit is adequate for the four different screen phosphors for x-ray tube voltages above sixty peak kilovolts. For techniques representing pediatric patients at high x-ray tube voltages, excess film density occurs due to stored charge in the transformer and high-voltage cables. An anticipation circuit in the automatic exposure control circuit can be modified to correct for stored charge effects. In a separate experiment the energy dependence of three different ionization chamber detectors used in automatic exposure control systems is compared directly with the energy dependence of three different screen phosphors. The data on detector sensitivity and screen speed are combined to predict the best tube voltage compensation for each combination of screen and detector.

Exploratory factor analysis of the functional movement screen in elite athletes.

PubMed

Li, Yongming; Wang, Xiong; Chen, Xiaoping; Dai, Boyi

2015-01-01

The functional movement screen is developed to examine individuals' movement patterns through 7 functional tasks. The purpose of this study was to identify the internal consistency and factor structure of the 7 tasks of the functional movement screen in elite athletes; 290 elite athletes from a variety of Chinese national teams were assessed using the functional movement screen. Cronbach's alpha was calculated for the scores of the 7 tasks. Exploratory factor analysis was performed to explore the factor structure of the functional movement screen. The mean and standard deviation of the sum score were 15.2 ± 3.0. A low Cronbach's alpha (0.58) was found for the scores of the 7 tasks. Exploratory factor analysis extracted 2 factors with eigenvalues greater than 1, and these 2 factors explained 47.3% of the total variance. The first factor had a high loading on the rotatory stability (loading = 0.99) and low loadings on the other 6 tasks (loading range: 0.04-0.34). The second factor had high loadings on the deep squat, hurdle step and inline lunge (loading range: 0.46-0.61) and low loadings on the other 3 tasks (loading range: 0.12-0.32). The 7 tasks of the functional movement screen had low internal consistency and were not indicators of a single factor. Evidence for unidimensionality was not found for the functional movement screen in elite athletes. More attention should be paid to the score of each task rather than the sum score when we interpret the functional movement screen scores.

Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia.

PubMed

Sarafoglou, Kyriakie; Banks, Kathryn; Gaviglio, Amy; Hietala, Amy; McCann, Mark; Thomas, William

2012-11-01

Newborn screening (NBS) for the classic forms of congenital adrenal hyperplasia (CAH) is mandated in all states in the United States. Compared with other NBS disorders, the false-positive rate (FPR) of CAH screening remains high and has not been significantly improved by adjusting 17α-hydroxyprogesterone cutoff values for birth weight and/or gestational age. Minnesota was the first state to initiate, and only 1 of 4 states currently performing, second-tier steroid profiling for CAH. False-negative rates (FNRs) for CAH are not well known. This is a population-based study of all Minnesota infants (769,834) born 1999-2009, grouped by screening protocol (one-tier with repeat screen, January 1999 to May 2004; two-tier with second-tier steroid profiling, June 2004 to December 2009). FPR, FNR, and positive predictive value (PPV) were calculated per infant, rather than per sample, and compared between protocols. Overall, 15 false-negatives (4 salt-wasting, 11 simple-virilizing) and 45 true-positives were identified from 1999 to 2009. With two-tier screening, FNR was 32%, FPR increased to 0.065%, and PPV decreased to 8%, but these changes were not statistically significant. Second-tier steroid profiling obviated repeat screens of borderline results (355 per year average). In comparing the 2 screening protocols, the FPR of CAH NBS remains high, the PPV remains low, and false-negatives occur more frequently than has been reported. Physicians should be cautioned that a negative NBS does not necessarily rule out classic CAH; therefore, any patient for whom there is clinical concern for CAH should receive immediate diagnostic testing.

Screen or not to screen for peripheral arterial disease: guidance from a decision model.

PubMed

Vaidya, Anil; Joore, Manuela A; Ten Cate-Hoek, Arina J; Ten Cate, Hugo; Severens, Johan L

2014-01-29

Asymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling. A probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5% and 4% for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters. For the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Years, 28,052 Euros), these results indicate that PAD screening and treatment is a dominant strategy. The cost effectiveness acceptability curves show 88% probability of PAD screening being cost effective at the Willingness To Pay (WTP) threshold of 40000 Euros. In a scenario analysis using clopidogrel as an alternative anti-platelet drug, PAD screening strategy remained dominant. This decision analysis suggests that targeted ABI screening and consequent secondary prevention of cardiovascular events using low dose aspirin or clopidogrel in the identified patients is a cost-effective strategy. Implementation of targeted PAD screening and subsequent treatment in primary care practices and in public health programs is likely to improve the societal health and to save health care costs by reducing catastrophic cardiovascular events.

[SCREENING OF NUTRITIONAL STATUS AMONG ELDERLY PEOPLE AT FAMILY MEDICINE].

PubMed

Račić, M; Ivković, N; Kusmuk, S

2015-11-01

The prevalence of malnutrition in elderly is high. Malnutrition or risk of malnutrition can be detected by use of nutritional screening or assessment tools. This systematic review aimed to identify tools that would be reliable, valid, sensitive and specific for nutritional status screening in patients older than 65 at family medicine. The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were retrieved using MEDLINE (via Ovid), PubMed and Cochrane Library electronic databases and by manual searching of relevant articles listed in reference list of key publications. The electronic databases were searched using defined key words adapted to each database and using MESH terms. Manual revision of reviews and original articles was performed using Electronic Journals Library. Included studies involved development and validation of screening tools in the community-dwelling elderly population. The tools, subjected to validity and reliability testing for use in the community-dwelling elderly population were Mini Nutritional Assessment (MNA), Mini Nutritional Assessment-Short Form (MNA-SF), Nutrition Screening Initiative (NSI), which includes DETERMINE list, Level I and II Screen, Seniors in the Community: Risk Evaluation for Eating, and Nutrition (SCREEN I and SCREEN II), Subjective Global Assessment (SGA), Nutritional Risk Index (NRI), and Malaysian and South African tool. MNA and MNA-SF appear to have highest reliability and validity for screening of community-dwelling elderly, while the reliability and validity of SCREEN II are good. The authors conclude that whilst several tools have been developed, most have not undergone extensive testing to demonstrate their ability to identify nutritional risk. MNA and MNA-SF have the highest reliability and validity for screening of nutritional status in the community-dwelling elderly, and the reliability and validity of SCREEN II are satisfactory. These instruments also contain all three nutritional status indicators and are practical for use in family medicine. However, the gold standard for screening cannot be set because testing of reliability and continuous validation in the study with a higher level of evidence need to be conducted in family medicine.

Random plasma glucose in early pregnancy is a better predictor of gestational diabetes diagnosis than maternal obesity.

PubMed

Meek, Claire L; Murphy, Helen R; Simmons, David

2016-03-01

Asymptomatic pregnant women are screened for gestational diabetes (GDM) at 24-28 weeks' gestation. Recent guidelines also recommend screening early in gestation to identify undiagnosed pre-existing overt diabetes. We assessed the performance of random plasma glucose (RPG) testing at antenatal booking in predicting GDM diagnosis later in pregnancy. Data from 25,543 consecutive singleton pregnancies at the Rosie Hospital in Cambridge (UK) were obtained from hospital electronic records as a service evaluation. All women were invited for an antenatal RPG (12-16 weeks) and a 50 g glucose challenge test (GCT; 24-28 weeks) with a 75 g OGTT if GCT >7.7 mmol/l (139 mg/dl). At booking, 17,736 women had an RPG that was able to predict GDM (receiver operating characteristic AUC 0.8) according to various diagnostic criteria in common use. A cut-off point of ≥7.5 mmol/l (135 mg/dl) gave a sensitivity of 0.70 and a specificity of 0.90 for GDM diagnosis. Theoretically, using this screening policy, 13.2% of women would have been categorised at high risk (26.3% had GDM) and 86.8% of women at low risk (1.7% had GDM). RPG performed better than maternal age (AUC 0.60) or BMI (AUC 0.65) at predicting GDM diagnosis. RPG at booking has reasonable performance as a screening test and is better than maternal age or BMI for identifying women at high risk of GDM. RPG cannot replace OGTT for diagnosis but it may be useful to exclude women who do not need further investigation for GDM and to identify women who could be prioritised for early diagnosis or lifestyle interventions.

Validation of an ELISA Synthetic Cannabinoids Urine Assay.

PubMed

Barnes, Allan J; Spinelli, Eliani; Young, Sheena; Martin, Thomas M; Kleete, Kevin L; Huestis, Marilyn A

2015-10-01

Synthetic cannabinoids are touted as legal alternatives to cannabis, at least when first released, and routine urine cannabinoid screening methods do not detect these novel psychoactive substances. Synthetic cannabinoids are widely available, are a major public health and safety problem, and a difficult challenge for drug-testing laboratories. We evaluated performance of the National Medical Services (NMS) JWH-018 direct enzyme-linked immunosorbent assay (ELISA) kit to sensitively, selectively, and rapidly screen urinary synthetic cannabinoids. The NMS ELISA kit targeting the JWH-018 N-(5-hydroxypentyl) metabolite was used to screen 2492 urine samples with 5 and 10 mcg/L cutoffs. A fully validated liquid chromatography-tandem mass spectrometry method for 29 synthetic cannabinoids markers confirmed all presumptive positive and negative results. Performance challenges at ±25% and ±50% of cutoffs determined intraplate and interplate imprecision around proposed cutoffs. The immunoassay was linear from 1 to 500 mcg/L with intraplate and interplate imprecision of ≤8.2% and <14.0%, respectively. No interferences were present from 93 common drugs of abuse, metabolites, coadministered drugs, over-the-counter medications, or structurally similar compounds, and 19 of 73 individual synthetic cannabinoids (26%) exhibited moderate to high cross-reactivity to JWH-018 N-(5-hydroxypentyl) metabolite. Sensitivity, specificity, and efficiency results were 83.7%, 99.4%, and 97.6%, as well as 71.6%, 99.7%, and 96.4% with the 5 and 10 mcg/L urine cutoffs, respectively. This high throughput immunoassay exhibited good diagnostic efficiency and documented that the NMS JWH-018 direct ELISA is a viable method for screening synthetic cannabinoids in urine targeting the JWH-018 N-(5-hydroxypentyl) and related analytes. Optimal performance was achieved with a matrix-matched 5 mcg/L urine cutoff.

Validation of an ELISA Synthetic Cannabinoids Urine Assay

PubMed Central

Barnes, Allan J.; Spinelli, Eliani; Young, Sheena; Martin, Thomas M.; Klette, Kevin L.; Huestis, Marilyn A.

2015-01-01

Background Synthetic cannabinoids are touted as legal alternatives to cannabis, at least when first released, and routine urine cannabinoid screening methods do not detect these novel psychoactive substances. Synthetic cannabinoids are widely available, are a major public health and safety problem, and a difficult challenge for drug testing laboratories. We evaluated performance of the NMS JWH-018 direct ELISA kit to sensitively, selectively, and rapidly screen urinary synthetic cannabinoids. Materials/ Methods The NMS ELISA kit targeting the JWH-018 N-(5-hydroxypentyl) metabolite was utilized to screen 2492 urine samples with 5 and 10µg/L cutoffs. A fully validated LC-MS/MS method for 29 synthetic cannabinoids markers confirmed all presumptive positive and negative results. Performance challenges at ±25 and ±50% of cutoffs determined intra- and inter-plate imprecision around proposed cutoffs. Result The immunoassay was linear from 1–500µg/L with intra- and inter-plate imprecision of ≤8.2% and <14.0%, respectively. No interferences were present from 93 common drugs of abuse, metabolites, co-administered drugs, over-the-counter medications or structurally similar compounds, and 19 of 73 individual, synthetic cannabinoids (26%) exhibited moderate to high cross-reactivity to JWH-018 N-(5-hydroxypentyl) metabolite. Sensitivity, specificity, and efficiency results were 83.7%, 99.4% and 97.6% and 71.6%, 99.7% and 96.4%, with the 5 and 10µg/L urine cutoffs, respectively. Conclusion This high throughput immunoassay exhibited good diagnostic efficiency and documented that the NMS JWH-018 direct ELISA is a viable method for screening synthetic cannabinoids in urine targeting the JWH-018 N-(5-hydroxypentyl) and related analytes. Optimal performance was achieved with a matrix-matched 5µg/L urine cutoff. PMID:25706046

An Arrayed Genome-Scale Lentiviral-Enabled Short Hairpin RNA Screen Identifies Lethal and Rescuer Gene Candidates

PubMed Central

Bhinder, Bhavneet; Antczak, Christophe; Ramirez, Christina N.; Shum, David; Liu-Sullivan, Nancy; Radu, Constantin; Frattini, Mark G.

2013-01-01

Abstract RNA interference technology is becoming an integral tool for target discovery and validation.; With perhaps the exception of only few studies published using arrayed short hairpin RNA (shRNA) libraries, most of the reports have been either against pooled siRNA or shRNA, or arrayed siRNA libraries. For this purpose, we have developed a workflow and performed an arrayed genome-scale shRNA lethality screen against the TRC1 library in HeLa cells. The resulting targets would be a valuable resource of candidates toward a better understanding of cellular homeostasis. Using a high-stringency hit nomination method encompassing criteria of at least three active hairpins per gene and filtered for potential off-target effects (OTEs), referred to as the Bhinder–Djaballah analysis method, we identified 1,252 lethal and 6 rescuer gene candidates, knockdown of which resulted in severe cell death or enhanced growth, respectively. Cross referencing individual hairpins with the TRC1 validated clone database, 239 of the 1,252 candidates were deemed independently validated with at least three validated clones. Through our systematic OTE analysis, we have identified 31 microRNAs (miRNAs) in lethal and 2 in rescuer genes; all having a seed heptamer mimic in the corresponding shRNA hairpins and likely cause of the OTE observed in our screen, perhaps unraveling a previously unknown plausible essentiality of these miRNAs in cellular viability. Taken together, we report on a methodology for performing large-scale arrayed shRNA screens, a comprehensive analysis method to nominate high-confidence hits, and a performance assessment of the TRC1 library highlighting the intracellular inefficiencies of shRNA processing in general. PMID:23198867

Bias-corrected diagnostic performance of the naked-eye single-tube red-cell osmotic fragility test (NESTROFT): an effective screening tool for beta-thalassemia.

PubMed

Mamtani, Manju; Jawahirani, Anil; Das, Kishor; Rughwani, Vinky; Kulkarni, Hemant

2006-08-01

It is being increasingly recognized that a majority of the countries in the thalassemia-belt need a cost-effective screening program as the first step towards control of thalassemia. Although the naked eye single tube red cell osmotic fragility test (NESTROFT) has been considered to be a very effective screening tool for beta-thalassemia trait, assessment of its diagnostic performance has been affected with the reference test- and verification-bias. Here, we set out to provide estimates of sensitivity and specificity of NESTROFT corrected for these potential biases. We conducted a cross-sectional diagnostic test evaluation study using data from 1563 subjects from Central India with a high prevalence of beta-thalassemia. We used latent class modelling after ensuring its validity to account for the reference test bias and global sensitivity analysis to control the verification bias. We also compared the results of latent class modelling with those of five discriminant indexes. We observed that across a range of cut-offs for the mean corpuscular volume (MCV) and the hemoglobin A2 (HbA2) concentration the average sensitivity and specificity of NESTROFT obtained from latent class modelling was 99.8 and 83.7%, respectively. These estimates were comparable to those characterizing the diagnostic performance of HbA2, which is considered by many as the reference test to detect beta-thalassemia. After correction for the verification bias these estimates were 93.4 and 97.2%, respectively. Combined with the inexpensive and quick disposition of NESTROFT, these results strongly support its candidature as a screening tool-especially in the resource-poor and high-prevalence settings.

Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations.

PubMed

D'Andrea, Elvira; Marzuillo, Carolina; De Vito, Corrado; Di Marco, Marco; Pitini, Erica; Vacchio, Maria Rosaria; Villari, Paolo

2016-12-01

There is considerable evidence regarding the efficacy and effectiveness of BRCA genetic testing programs, but whether they represent good use of financial resources is not clear. Therefore, we aimed to identify the main health-care programs for BRCA testing and to evaluate their cost-effectiveness. We performed a systematic review of full economic evaluations of health-care programs involving BRCA testing. Nine economic evaluations were included, and four main categories of BRCA testing programs were identified: (i) population-based genetic screening of individuals without cancer, either comprehensive or targeted based on ancestry; (ii) family history (FH)-based genetic screening, i.e., testing individuals without cancer but with FH suggestive of BRCA mutation; (iii) familial mutation (FM)-based genetic screening, i.e., testing individuals without cancer but with known familial BRCA mutation; and (iv) cancer-based genetic screening, i.e., testing individuals with BRCA-related cancers. Currently BRCA1/2 population-based screening represents good value for the money among Ashkenazi Jews only. FH-based screening is potentially very cost-effective, although further studies that include costs of identifying high-risk women are needed. There is no evidence of cost-effectiveness for BRCA screening of all newly diagnosed cases of breast/ovarian cancers followed by cascade testing of relatives, but programs that include tools for identifying affected women at higher risk for inherited forms are promising. Cost-effectiveness is highly sensitive to the cost of BRCA1/2 testing.Genet Med 18 12, 1171-1180.

No advanced retinopathy of prematurity stages 4 or 5 in a large high-risk German cohort.

PubMed

Muether, Philipp S; Kribs, Angela; Hahn, Moritz; Schumacher, Jasmin; Eifinger, Frank; Kirchhof, Bernd; Roth, Bernhard; Fauser, Sascha

2012-03-01

Retinopathy of prematurity (ROP) remains a major cause of juvenile blindness. As screening recommendations are refined, decreasing gestational age (GA) and birth weight (BW) constitute an increasing risk for ROP. This retrospective case series reviews the screening results of a very immature cohort in Germany. We conducted ROP screening according to the German guidelines of 1999: all preterm infants with a GA of < 32 weeks and/or a BW of < 1501 g, or with GA ≥ 32 weeks and postnatal oxygen treatment for > 3 days, were assigned for screening. Dense laser coagulation was performed according to the current treatment criteria. All 767 consecutive inborn (patients born at the Department of Neonatology, University Hospital of Cologne, Germany) preterm infants of a tertiary medical centre of maximum care underwent complete screening from 2001 to 2009. The treatment incidence was 7.0%. No preterm infant developed stage 4/5 ROP. Mean GA and BW of untreated/treated preterm infants were 28.4/24.6 weeks and 1109/635 g, respectively. Increasing treatment incidence was associated with lower GA, but not with lower BW in logistic regression analysis. In this very immature high-risk cohort, advanced stages 4 and 5 were avoided throughout 9 years of screening. We suggest three factors that contributed to this outcome: (1) strict adherence to current ROP screening and treatment guidelines; (2) prompt and very dense laser coagulation if necessary; and (3) a specialised neonatal intensive care unit with experience of very immature babies.

Vasa previa screening strategies: a decision and cost-effectiveness analysis.

PubMed

Sinkey, R G; Odibo, A O

2018-05-22

The aim of this study is to perform a decision and cost-effectiveness analysis comparing four screening strategies for the antenatal diagnosis of vasa previa among singleton pregnancies. A decision-analytic model was constructed comparing vasa previa screening strategies. Published probabilities and costs were applied to four transvaginal screening scenarios which occurred at the time of mid-trimester ultrasound: no screening, ultrasound-indicated screening, screening pregnancies conceived by in vitro fertilization (IVF), and universal screening. Ultrasound-indicated screening was defined as performing a transvaginal ultrasound at the time of routine anatomy ultrasound in response to one of the following sonographic findings associated with an increased risk of vasa previa: low-lying placenta, marginal or velamentous cord insertion, or bilobed or succenturiate lobed placenta. The primary outcome was cost per quality adjusted life years (QALY) in U.S. dollars. The analysis was from a healthcare system perspective with a willingness to pay (WTP) threshold of $100,000 per QALY selected. One-way and multivariate sensitivity analyses (Monte-Carlo simulation) were performed. This decision-analytic model demonstrated that screening pregnancies conceived by IVF was the most cost-effective strategy with an incremental cost effectiveness ratio (ICER) of $29,186.50 / QALY. Ultrasound-indicated screening was the second most cost-effective with an ICER of $56,096.77 / QALY. These data were robust to all one-way and multivariate sensitivity analyses performed. Within our baseline assumptions, transvaginal ultrasound screening for vasa previa appears to be most cost-effective when performed among IVF pregnancies. However, both IVF and ultrasound-indicated screening strategies fall within contemporary willingness-to-pay thresholds, suggesting that both strategies may be appropriate to apply in clinical practice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The administrative project of Helicobacter pylori infection screening among junior high school students in an area of Japan with a high incidence of gastric cancer.

PubMed

Kusano, Chika; Gotoda, Takuji; Ishikawa, Hideki; Moriyama, Mitsuhiko

2017-03-01

Helicobacter pylori infection is a common chronic infection that is closely associated with gastric cancer, known to be decreasing worldwide. We set up an administrative project of screening examination for H. pylori infection in junior high school students in Akita Prefecture to investigate the current prevalence of H. pylori infection in childhood in an area where the incidence of gastric cancer is particularly high. All students in their second or third year of junior high school (13 to 15 years old) in two cities in Akita Prefecture were recruited. First, a urine-based enzyme-linked immunosorbent assay for detection of H. pylori antibody was performed. Then, a 13 C-urea breath test ( 13 C-UBT) was carried out in students who tested positive on the urinary test. Written informed consent was obtained from all participants and their parents. A total of 1813 students were recruited in this study; 1765 (97.3%) students agreed to participate in this project and underwent a screening examination. Among 96 students (5.4%) testing positive for H. pylori on the initial screening examination, 90 (93.7%, 90/96) underwent a subsequent 13 C-UBT, and 85 (4.8%, 85/1765) were diagnosed as positive for H. pylori. The current prevalence of H. pylori infection among students was low even in an area of Japan with a high incidence of gastric cancer.

Design, development, and validation of a high-throughput drug-screening assay for targeting of human leukemia

PubMed Central

Karjalainen, Katja; Pasqualini, Renata; Cortes, Jorge E.; Kornblau, Steven M.; Lichtiger, Benjamin; O'Brien, Susan; Kantarjian, Hagop M.; Sidman, Richard L.; Arap, Wadih; Koivunen, Erkki

2015-01-01

Background We introduce an ex vivo methodology to perform drug library screening against human leukemia. Method Our strategy relies on human blood or bone marrow cultures under hypoxia; under these conditions, leukemia cells deplete oxygen faster than normal cells, causing a hemoglobin oxygenation shift. We demonstrate several advantages: (I) partial recapitulation of the leukemia microenvironment, (ii) use of native hemoglobin oxygenation as real-time sensor/reporter, (iii) cost-effectiveness, (iv) species-specificity, and (v) format that enables high-throughput screening. Results As a proof-of-concept, we screened a chemical library (size ∼20,000) against human leukemia cells. We identified 70 compounds (“hit” rate=0.35%; Z-factor=0.71) with activity; we examined 20 to find 18 true-positives (90%). Finally, we show that carbonohydraxonic diamide group-containing compounds are potent anti-leukemia agents that induce cell death in leukemia cells and patient-derived samples. Conclusions This unique functional assay can identify novel drug candidates as well as find future applications in personalized drug selection for leukemia patients. PMID:24496871

Radon and lung cancer: a cost-effectiveness analysis.

PubMed Central

Ford, E S; Kelly, A E; Teutsch, S M; Thacker, S B; Garbe, P L

1999-01-01

OBJECTIVES: This study examined the cost-effectiveness of general and targeted strategies for residential radon testing and mitigation in the United States. METHODS: A decision-tree model was used to perform a cost-effectiveness analysis of preventing radon-associated deaths from lung cancer. RESULTS: For a radon threshold of 4 pCi/L, the estimated costs to prevent 1 lung cancer death are about $3 million (154 lung cancer deaths prevented), or $480,000 per life-year saved, based on universal radon screening and mitigation, and about $2 million (104 lung cancer deaths prevented), or $330,000 per life-year saved, if testing and mitigation are confined to geographic areas at high risk for radon exposure. For mitigation undertaken after a single screening test and after a second confirmatory test, the estimated costs are about $920,000 and $520,000, respectively, to prevent a lung cancer death with universal screening and $130,000 and $80,000 per life-year for high risk screening. The numbers of preventable lung cancer deaths are 811 and 527 for universal and targeted approaches, respectively. CONCLUSIONS: These data suggest possible alternatives to current recommendations. PMID:10076484

Modeling Test and Treatment Strategies for Presymptomatic Alzheimer Disease

PubMed Central

Burke, James F.; Langa, Kenneth M.; Hayward, Rodney A.; Albin, Roger L.

2014-01-01

Objectives In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. Methods Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. Findings In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. Conclusions Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment. PMID:25474698

Producibility of Vertically Integrated Photodiode (VIP)tm scanning focal plane arrays

NASA Astrophysics Data System (ADS)

Turner, Arthur M.; Teherani, Towfik; Ehmke, John C.; Pettitt, Cindy; Conlon, Peggy; Beck, Jeffrey D.; McCormack, Kent; Colombo, Luigi; Lahutsky, Tom; Murphy, Terry; Williams, Robert L.

1994-07-01

Vertically integrated photodiode, VIPTM, technology is now being used to produce second generation infrared focal plane arrays with high yields and performance. The VIPTM process employs planar, ion implanted, n on p diodes in HgCdTe which is epoxy hybridized directly to the read out integrated circuits on 100 mm Si wafers. The process parameters that are critical for high performance and yield include: HgCdTe dislocation density and thickness, backside passivation, frontside passivation, and junction formation. Producibility of infrared focal plane arrays (IRFPAs) is also significantly enhanced by read out integrated circuits (ROICs) which have the ability to deselect defective pixels. Cold probe screening before lab dewar assembly reduces costs and improves cycle times. The 240 X 1 and 240 X 2 scanning array formats are used to demonstrate the effect of process optimization, deselect, and cold probe screening on yield and cycle time. The versatility of the VIPTM technology and its extension to large area arrays is demonstrated using 240/288 X 4 and 480 X 5 TDI formats. Finally, the high performance of VIPTM IRFPAs is demonstrated by comparing data from a 480 X 5 to the SADA-II specification.

Lysergic acid amide as chemical marker for the total ergot alkaloids in rye flour - Determination by high-performance thin-layer chromatography-fluorescence detection.

PubMed

Oellig, Claudia

2017-07-21

Ergot alkaloids are generally determined by high-performance liquid chromatography (HPLC) coupled to fluorescence detection (FLD) or mass selective detection, analyzing the individual compounds. However, fast and easy screening methods for the determination of the total ergot alkaloid content are more suitable, since for monitoring only the sum of the alkaloids is relevant. The herein presented screening uses lysergic acid amide (LSA) as chemical marker, formed from ergopeptine alkaloids, and ergometrine for the determination of the total ergot alkaloids in rye with high-performance thin-layer chromatography-fluorescence detection (HPTLC-FLD). An ammonium acetate buffered extraction step was followed by liquid-liquid partition for clean-up before the ergopeptine alkaloids were selectively transformed to LSA and analyzed by HPTLC-FLD on silica gel with isopropyl acetate/methanol/water/25% ammonium hydroxide solution (80:10:3.8:1.1, v/v/v/v) as the mobile phase. The enhanced native fluorescence of LSA and unaffected ergometrine was used for quantitation without any interfering matrix. Limits of detection and quantitation were 8 and 26μg LSA/kg rye, which enables the determination of the total ergot alkaloids far below the applied quality criterion limit for rye. Close to 100% recoveries for different rye flours at relevant spiking levels were obtained. Thus, reliable results were guaranteed, and the fast and efficient screening for the total ergot alkaloids in rye offers a rapid alternative to the HPLC analysis of the individual compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

Performance of Emergency Department Screening Criteria for an Early ECG to Identify ST-Segment Elevation Myocardial Infarction.

PubMed

Yiadom, Maame Yaa A B; Baugh, Christopher W; McWade, Conor M; Liu, Xulei; Song, Kyoung Jun; Patterson, Brian W; Jenkins, Cathy A; Tanski, Mary; Mills, Angela M; Salazar, Gilberto; Wang, Thomas J; Dittus, Robert S; Liu, Dandan; Storrow, Alan B

2017-02-23

Timely diagnosis of ST-segment elevation myocardial infarction (STEMI) in the emergency department (ED) is made solely by ECG. Obtaining this test within 10 minutes of ED arrival is critical to achieving the best outcomes. We investigated variability in the timely identification of STEMI across institutions and whether performance variation was associated with the ED characteristics, the comprehensiveness of screening criteria, and the STEMI screening processes. We examined STEMI screening performance in 7 EDs, with the missed case rate (MCR) as our primary end point. The MCR is the proportion of primarily screened ED patients diagnosed with STEMI who did not receive an ECG within 15 minutes of ED arrival. STEMI was defined by hospital discharge diagnosis. Relationships between the MCR and ED characteristics, screening criteria, and STEMI screening processes were assessed, along with differences in door-to-ECG times for captured versus missed patients. The overall MCR for all 7 EDs was 12.8%. The lowest and highest MCRs were 3.4% and 32.6%, respectively. The mean difference in door-to-ECG times for captured and missed patients was 31 minutes, with a range of 14 to 80 minutes of additional myocardial ischemia time for missed cases. The prevalence of primarily screened ED STEMIs was 0.09%. EDs with the greatest informedness (sensitivity+specificity-1) demonstrated superior performance across all other screening measures. The 29.2% difference in MCRs between the highest and lowest performing EDs demonstrates room for improving timely STEMI identification among primarily screened ED patients. The MCR and informedness can be used to compare screening across EDs and to understand variable performance. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Cytology and human papillomavirus testing 6 to 12 months after ASCUS or LSIL cytology in organized screening to predict high-grade cervical neoplasia between screening rounds.

PubMed

Tropé, Ameli; Sjøborg, Katrine D; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G Cecilie; Jonassen, Christine M

2012-06-01

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting.

Providing data for serrated polyp detection rate benchmarks: an analysis of the New Hampshire Colonoscopy Registry.

PubMed

Anderson, Joseph C; Butterly, Lynn F; Weiss, Julia E; Robinson, Christina M

2017-06-01

Similar to achieving adenoma detection rate (ADR) benchmarks to prevent colorectal cancer (CRC), achieving adequate serrated polyp detection rates (SDRs) may be essential to the prevention of CRC associated with the serrated pathway. Previous studies have been based on data from high-volume endoscopists at single academic centers. Based on a hypothesis that ADR is correlated with SDR, we stratified a large, diverse group of endoscopists (n = 77 practicing at 28 centers) into high performers and low performers, based on ADR, to provide data for corresponding target SDR benchmarks. By using colonoscopies in adults aged ≥50 years (4/09-12/14), we stratified endoscopists by high and low ADRs (<15%, 15%-<25%, 25%-<35%, ≥35%) to determine corresponding SDRs by using 2 SDR measures, for screening and surveillance colonoscopies separately: (1) Clinically significant SDR (CSSDR), meaning colonoscopies with any sessile serrated adenoma/polyp (SSA/P), traditional serrated adenoma (TSA), or hyperplastic polyp (HP) >1 cm anywhere in the colon or HP >5 mm in the proximal colon only divided by the total number of screening and surveillance colonoscopies, respectively. (2) Proximal SDR (PSDR) meaning colonoscopies with any serrated polyp (SSA/P, HP, TSA) of any size proximal to the sigmoid colon divided by the total number of screening and surveillance colonoscopies, respectively. A total of 45,996 (29,960 screening) colonoscopies by 77 endoscopists (28 facilities) were included. Moderately strong positive correlation coefficients were observed for screening ADR/CSSDR (P = .69) and ADR/PSDR (P = .79) and a strong positive correlation (P = .82) for CSSDR/PSDR (P < .0001 for all) was observed. For ADR ≥25%, endoscopists' median (interquartile range) screening CSSDR was 6.8% (4.3%-8.6%) and PSDR was 10.8% (8.6%-16.1%). Derived from ADR, the primary colonoscopy quality indicator, our results suggest potential SDR benchmarks (CSSDR = 7% and PSDR = 11%) that may guide adequate serrated polyp detection. Because CSSDR and PSDR are strongly correlated, endoscopists could use the simpler PSDR calculation to assess quality. Published by Elsevier Inc.

Validation of screening tools for depression and anxiety disorders in a primary care population with high HIV prevalence in Zimbabwe.

PubMed

Chibanda, Dixon; Verhey, Ruth; Gibson, Lorna J; Munetsi, Epiphania; Machando, Debra; Rusakaniko, Simbarashe; Munjoma, Ronald; Araya, Ricardo; Weiss, Helen A; Abas, Melanie

2016-07-01

In low income countries in Sub-Saharan Africa there are few validated tools to screen for common disabling mental disorders such as depression and general anxiety disorder (GAD). We validated three screening tools: the Shona Symptom Questionnaire for common mental disorders (SSQ-14), the Patient Health Questionnaire for depression (PHQ-9), and the Generalized Anxiety Disorder questionnaire (GAD-7). The study participants were attendees at a primary health care clinic in Harare, Zimbabwe. Consecutive adults aged 18 and above attending the clinic were enrolled over a two-week period in September 2013. Trained research assistants administered the screening tools to eligible participants after obtaining written consent. Participants were then interviewed by one of four psychiatrists using the Structured Clinical Interview of the DSM-IV (SCID). Performance characteristics were calculated for each tool, against the SCID as the gold standard. A total of 264 participants were enrolled, of whom 52 (20%) met the SCID criteria for depression alone, 97 (37%) for mixed depression and anxiety and 9 (3%) for anxiety alone. Of the 237 where HIV status was known, 165 (70%) were HIV positive. With the optimal cutoff of ≥9, the sensitivity and specificity for the SSQ-14 against a diagnosis of either depression and/or general anxiety were 84% (95%CI:78-89%) and 73% (95%CI:63-81%) respectively. Internal reliability was high (Cronbach α=0.74). The optimal cutoff for PHQ-9 was ≥11, which provided a sensitivity of 85% (95%CI:78-90%) and specificity of 69% (95%CI:59-77%) against a SCID diagnosis of depression (Cronbach α=0.86). The GAD-7 (optimal cutoff ≥10) had sensitivity and specificity of 89% (95%CI:81-94%) and 73% (95%CI:65-80%) respectively against a SCID diagnosis of GAD (Cronbach α=0.87). Screening tools for depression and GAD had good performance characteristics in a primary health care population in Zimbabwe with a high prevalence of HIV. These can be used for research and also in clinical care to screen patients who may benefit from treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

PubMed Central

Sjøborg, Katrine D.; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G. Cecilie; Jonassen, Christine M.

2012-01-01

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting. PMID:22518869

Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs.

PubMed

Lörincz, Attila T; Richart, Ralph M

2003-08-01

Our objective was to review current large studies of human papillomavirus (HPV) DNA testing as an adjunct to the Papanicolaou test for cervical cancer screening programs. We analyzed 10 large screening studies that used the Hybrid Capture 2 test and 3 studies that used the polymerase chain reaction test in a manner that enabled reliable estimates of accuracy for detecting or predicting high-grade cervical intraepithelial neoplasia (CIN). Most studies allowed comparison of HPV DNA and Papanicolaou testing and estimates of the performance of Papanicolaou and HPV DNA as combined tests. The studies were selected on the basis of a sufficient number of cases of high-grade CIN and cancer to provide meaningful statistical values. Investigators had to demonstrate the ability to generate reasonably reliable Hybrid Capture 2 or polymerase chain reaction data that were either minimally biased by nature of study design or that permitted analytical techniques for addressing issues of study bias to be applied. Studies had to provide data for the calculation of test sensitivity, specificity, predictive values, odds ratios, relative risks, confidence intervals, and other relevant measures. Final data were abstracted directly from published articles or estimated from descriptive statistics presented in the articles. In some studies, new analyses were performed from raw data supplied by the principal investigators. We concluded that HPV DNA testing was a more sensitive indicator for prevalent high-grade CIN than either conventional or liquid cytology. A combination of HPV DNA and Papanicolaou testing had almost 100% sensitivity and negative predictive value. The specificity of the combined tests was slightly lower than the specificity of the Papanicolaou test alone, but this decrease could potentially be offset by greater protection from neoplastic progression and cost savings available from extended screening intervals. One "double-negative" HPV DNA and Papanicolaou test indicated better prognostic assurance against risk of future CIN 3 than 3 subsequent negative conventional Papanicolaou tests and may safely allow 3-year screening intervals for such low-risk women.