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.

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.

A Smartphone App to Screen for HIV-Related Neurocognitive Impairment

PubMed Central

Robbins, Reuben N.; Brown, Henry; Ehlers, Andries; Joska, John A.; Thomas, Kevin G.F.; Burgess, Rhonda; Byrd, Desiree; Morgello, Susan

2014-01-01

Background Neurocognitive Impairment (NCI) is one of the most common complications of HIV-infection, and has serious medical and functional consequences. However, screening for it is not routine and NCI often goes undiagnosed. Screening for NCI in HIV disease faces numerous challenges, such as limited screening tests, the need for specialized equipment and apparatuses, and highly trained personnel to administer, score and interpret screening tests. To address these challenges, we developed a novel smartphone-based screening tool, NeuroScreen, to detect HIV-related NCI that includes an easy-to-use graphical user interface with ten highly automated neuropsychological tests. Aims To examine NeuroScreen’s: 1) acceptability among patients and different potential users; 2) test construct and criterion validity; and 3) sensitivity and specificity to detect NCI. Methods Fifty HIV+ individuals were administered a gold-standard neuropsychological test battery, designed to detect HIV-related NCI, and NeuroScreen. HIV+ test participants and eight potential provider-users of NeuroScreen were asked about its acceptability. Results There was a high level of acceptability of NeuroScreen by patients and potential provider-users. Moderate to high correlations between individual NeuroScreen tests and paper-and-pencil tests assessing the same cognitive domains were observed. NeuroScreen also demonstrated high sensitivity to detect NCI. Conclusion NeuroScreen, a highly automated, easy-to-use smartphone-based screening test to detect NCI among HIV patients and usable by a range of healthcare personnel could help make routine screening for HIV-related NCI feasible. While NeuroScreen demonstrated robust psychometric properties and acceptability, further testing with larger and less neurocognitively impaired samples is warranted. PMID:24860624

[Sensitivity and specificity of the breast screening program in the Isere region based on positive results between 1991 and 1999].

PubMed

Garnier, A; Poncet, F; Billette De Villemeur, A; Exbrayat, C; Bon, M F; Chevalier, A; Salicru, B; Tournegros, J M

2009-06-01

The screening program guidelines specify that the call back rate of women for additional imaging (positive mammogram) should not exceed 7% at initial screening, and 5% at subsequent screening. Materials and methods. Results in the Isere region (12%) have prompted a review of the correlation between the call back rate and indicators of quality (detection rate, sensitivity, specificity, positive predictive value) for the radiologists providing interpretations during that time period. Three groups of radiologists were identified: the group with call back rate of 10% achieved the best results (sensitivity: 92%, detection rate: 0.53%, specificity: 90%). The group with lowest call back rate (7.7%) showed insufficient sensitivity (58%). The last group with call back rate of 18.3%, showed no improvement in sensitivity (82%) and detection rate (0.53%), but showed reduced specificity (82%). The protocol update in 2001 does not resolve this problematic situation and national results continue to demonstrate a high percentage of positive screening mammograms. A significant increase in the number of positive screening examinations compared to recommended guidelines is not advantageous and leads to an overall decrease in the quality of the screening.

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

PubMed

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

2010-02-15

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

Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: experimental design.

PubMed

Malila, Nea; Oivanen, Tiina; Malminiemi, Outi; Hakama, Matti

2008-11-20

To report the sensitivities of the faecal occult blood test, screening episode, and screening programme for colorectal cancer and the benefits of applying a randomised design at the implementation phase of a new public health policy. Experimental design incorporated in public health evaluation using randomisation at individual level in the target population. 161 of the 431 Finnish municipalities in 2004-6. 106 000 adults randomised to screening or control arms. In total, 52 998 adults aged 60-64 in the screening arm received faecal occult blood test kits. Test, episode, and programme sensitivities estimated by the incidence method and corrected for selective attendance and overdiagnosis. The response for screening was high overall (70.8%), and significantly better in women (78.1%) than in men (63.3%). The incidence of cancer in the controls was somewhat higher in men than in women (103 v 93 per 100 000 person years), which was not true for interval cancers (42 v 49 per 100 000 person years). The sensitivity of the faecal occult blood test was 54.6%. Only a few interval cancers were detected among those with positive test results, hence the episode sensitivity of 51.3% was close to the test sensitivity. At the population level the sensitivity of the programme was 37.5%. Although relatively low, the sensitivity of screening for colorectal cancer with the faecal occult blood test in Finland was adequate. An experimental design is a prerequisite for evaluation of such a screening programme because the effectiveness of preventing deaths is likely to be small and results may otherwise remain inconclusive. Thus, screening for colorectal cancer using any primary test modality should be launched in a public health programme with randomisation of the target population at the implementation phase.

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

Sensitive high-throughput screening for the detection of reducing sugars.

PubMed

Mellitzer, Andrea; Glieder, Anton; Weis, Roland; Reisinger, Christoph; Flicker, Karlheinz

2012-01-01

The exploitation of renewable resources for the production of biofuels relies on efficient processes for the enzymatic hydrolysis of lignocellulosic materials. The development of enzymes and strains for these processes requires reliable and fast activity-based screening assays. Additionally, these assays are also required to operate on the microscale and on the high-throughput level. Herein, we report the development of a highly sensitive reducing-sugar assay in a 96-well microplate screening format. The assay is based on the formation of osazones from reducing sugars and para-hydroxybenzoic acid hydrazide. By using this sensitive assay, the enzyme loads and conversion times during lignocellulose hydrolysis can be reduced, thus allowing higher throughput. The assay is about five times more sensitive than the widely applied dinitrosalicylic acid based assay and can reliably detect reducing sugars down to 10 μM. The assay-specific variation over one microplate was determined for three different lignocellulolytic enzymes and ranges from 2 to 8%. Furthermore, the assay was combined with a microscale cultivation procedure for the activity-based screening of Pichia pastoris strains expressing functional Thermomyces lanuginosus xylanase A, Trichoderma reesei β-mannanase, or T. reesei cellobiohydrolase 2. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Display screen and method of manufacture therefor

NASA Technical Reports Server (NTRS)

Dubin, Matthew B. (Inventor); Larson, Brent D. (Inventor)

2002-01-01

A screen assembly that combines an angle re-distributing prescreen with a conventional diffusion screen. The prescreen minimizes or eliminates the sensitivity of the screen assembly to projector location. The diffusion screen provides other desirable screen characteristics. Compatible screen structures, along with methods for fabricating high resolution prescreens and methods and devices for maintaining the desired relationship between the prescreen and the diffusion screen are contemplated.

Quantitative estimates of the impact of sensitivity and specificity in mammographic screening in Germany.

PubMed Central

Warmerdam, P G; de Koning, H J; Boer, R; Beemsterboer, P M; Dierks, M L; Swart, E; Robra, B P

1997-01-01

STUDY OBJECTIVE: To estimate quantitatively the impact of the quality of mammographic screening (in terms of sensitivity and specificity) on the effects and costs of nationwide breast cancer screening. DESIGN: Three plausible "quality" scenarios for a biennial breast cancer screening programme for women aged 50-69 in Germany were analysed in terms of costs and effects using the Microsimulation Screening Analysis model on breast cancer screening and the natural history of breast cancer. Firstly, sensitivity and specificity in the expected situation (or "baseline" scenario) were estimated from a model based analysis of empirical data from 35,000 screening examinations in two German pilot projects. In the second "high quality" scenario, these properties were based on the more favourable diagnostic results from breast cancer screening projects and the nationwide programme in The Netherlands. Thirdly, a worst case, "low quality" hypothetical scenario with a 25% lower sensitivity than that experienced in The Netherlands was analysed. SETTING: The epidemiological and social situation in Germany in relation to mass screening for breast cancer. RESULTS: In the "baseline" scenario, an 11% reduction in breast cancer mortality was expected in the total German female population, ie 2100 breast cancer deaths would be prevented per year. It was estimated that the "high quality" scenario, based on Dutch experience, would lead to the prevention of an additional 200 deaths per year and would also cut the number of false positive biopsy results by half. The cost per life year gained varied from Deutsche mark (DM) 15,000 on the "high quality" scenario to DM 21,000 in the "low quality" setting. CONCLUSIONS: Up to 20% of the total costs of a screening programme can be spent on quality improvement in order to achieve a substantially higher reduction in mortality and reduce undesirable side effects while retaining the same cost effectiveness ratio as that estimated from the German data. PMID:9196649

[Primary cervical cancer screening].

PubMed

Vargas-Hernández, Víctor Manuel; Vargas-Aguilar, Víctor Manuel; Tovar-Rodríguez, José María

2015-01-01

Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

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.

Screening of depression in adolescents through the Internet : sensitivity and specificity of two screening questionnaires.

PubMed

Cuijpers, Pim; Boluijt, Petra; van Straten, Annemieke

2008-02-01

The Internet may offer new opportunities for treating depressed adolescents. However, before such treatments are possible, well-validated screening instruments are needed. In the current study, we validate two Internet-based screening instruments for depression among adolescents, the major depression inventory (MDI), and the Center for Epidemiological Studies-Depression scale (CES-D). A total of 1,392 adolescents, recruited through high schools and the Internet, filled in the online questionnaires. Of these, 243 (17%) were interviewed with the MINI diagnostic interview to assess the presence of a mood disorder. Cronbach's alpha was high for both the CES-D (0.93) and the MDI (0.88), and both correlated highly with each other (0.88; P < .001). The scores on both instruments were significantly increased in all subjects with a mood disorder, whether current or lifetime, except for lifetime minor depression. In the ROC analyses, high areas under the curve were found for the MDI (0.89) and CES-D (0.90). The best cut-off point for the MDI was 19 (sensitivity: 90.48; specificity: 71.53), and for the CES-D it was 22 (sensitivity: 90.48; specificity: 74.31). We conclude that the MDI and CES-D are reliable and valid instruments that can be used for this screening.

Screening for cognitive dysfunction in ALS: validation of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) using age and education adjusted normative data.

PubMed

Pinto-Grau, Marta; Burke, Tom; Lonergan, Katie; McHugh, Caroline; Mays, Iain; Madden, Caoifa; Vajda, Alice; Heverin, Mark; Elamin, Marwa; Hardiman, Orla; Pender, Niall

2017-02-01

Cognitive and behavioural changes are an important aspect in Amyotrophic Lateral Sclerosis (ALS). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) briefly assesses these changes in ALS. To validate the ECAS against a standardised neuropsychological battery and assess its sensitivity and specificity using age and education adjusted cut-off scores. 30 incident ALS cases were assessed on both, ECAS and neuropsychological battery. Age and education adjusted cut-off scores were created from a sample of 82 healthy controls. ECAS composite scores (Total, ALS Specific and Non-Specific) were highly correlated with battery composite scores. High correlations were also observed between ECAS and full battery cognitive domains and subtests. The ECAS Total, ALS Specific and Non-Specific scores were highly sensitive to cognitive impairment. ECAS ALS-Specific cognitive domains also evidenced high sensitivity. Individual subtest sensitivity was medium to low, suggesting that caution should be used when interpreting these scores. Low positive predictive values indicated the presence of false positives. Psychometric properties of the ECAS using age and education adjusted norms indicate that the ECAS, when used as an overall measure of cognitive decline, is highly sensitive. Further comprehensive assessment is required for patients that present as impaired on the ECAS.

An Escherichia coli Expression Assay and Screen for Human Immunodeficiency Virus Protease Variants with Decreased Susceptibility to Indinavir

PubMed Central

Melnick, Laurence; Yang, Shiow-Shong; Rossi, Rick; Zepp, Charlie; Heefner, Donald

1998-01-01

We have developed a recombinant Escherichia coli screening system for the rapid detection and identification of amino acid substitutions in the human immunodeficiency virus (HIV) protease associated with decreased susceptibility to the protease inhibitor indinavir (MK-639; Merck & Co.). The assay depends upon the correct processing of a segment of the HIV-1 HXB2 gag-pol polyprotein followed by detection of HIV reverse transcriptase activity by a highly sensitive, colorimetric enzyme-linked immunosorbent assay. The highly sensitive system detects the contributions of single substitutions such as I84V, L90M, and L63P. The combination of single substitutions further decreases the sensitivity to indinavir. We constructed a library of HIV protease variant genes containing dispersed mutations and, using the E. coli recombinant system, screened for mutants with decreased indinavir sensitivity. The discovered HIV protease variants contain amino acid substitutions commonly associated with indinavir resistance in clinical isolates, including the substitutions L90M, L63P, I64V, V82A, L24I, and I54T. One substitution, W6R, is also frequently found by the screen and has not been reported elsewhere. Of a total of 12,000 isolates that were screened, 12 protease variants with decreased sensitivity to indinavir were found. The L63P substitution, which is also associated with indinavir resistance, increases the stability of the isolated protease relative to that of the native HXB2 protease. The rapidity, sensitivity, and accuracy of this screen also make it useful for screening for novel inhibitors. We have found the approach described here to be useful for the detection of amino acid substitutions in HIV protease that have been associated with drug resistance as well as for the screening of novel compounds for inhibitory activity. PMID:9835523

Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis

PubMed Central

Phi, Xuan-Anh; Saadatmand, Sepideh; De Bock, Geertruida H; Warner, Ellen; Sardanelli, Francesco; Leach, Martin O; Riedl, Christopher C; Trop, Isabelle; Hooning, Maartje J; Mandel, Rodica; Santoro, Filippo; Kwan-Lim, Gek; Helbich, Thomas H; Tilanus-Linthorst, Madeleine MA; van den Heuvel, Edwin R; Houssami, Nehmat

2016-01-01

Background: We investigated the additional contribution of mammography to screening accuracy in BRCA1/2 mutation carriers screened with MRI at different ages using individual patient data from six high-risk screening trials. Methods: Sensitivity and specificity of MRI, mammography and the combination of these tests were compared stratified for BRCA mutation and age using generalised linear mixed models with random effect for studies. Number of screens needed (NSN) for additional mammography-only detected cancer was estimated. Results: In BRCA1/2 mutation carriers of all ages (BRCA1=1219 and BRCA2=732), adding mammography to MRI did not significantly increase screening sensitivity (increased by 3.9% in BRCA1 and 12.6% in BRCA2 mutation carriers, P>0.05). However, in women with BRCA2 mutation younger than 40 years, one-third of breast cancers were detected by mammography only. Number of screens needed for mammography to detect one breast cancer not detected by MRI was much higher for BRCA1 compared with BRCA2 mutation carriers at initial and repeat screening. Conclusions: Additional screening sensitivity from mammography above that from MRI is limited in BRCA1 mutation carriers, whereas mammography contributes to screening sensitivity in BRCA2 mutation carriers, especially those ⩽40 years. The evidence from our work highlights that a differential screening schedule by BRCA status is worth considering. PMID:26908327

Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis.

PubMed

Phi, Xuan-Anh; Saadatmand, Sepideh; De Bock, Geertruida H; Warner, Ellen; Sardanelli, Francesco; Leach, Martin O; Riedl, Christopher C; Trop, Isabelle; Hooning, Maartje J; Mandel, Rodica; Santoro, Filippo; Kwan-Lim, Gek; Helbich, Thomas H; Tilanus-Linthorst, Madeleine M A; van den Heuvel, Edwin R; Houssami, Nehmat

2016-03-15

We investigated the additional contribution of mammography to screening accuracy in BRCA1/2 mutation carriers screened with MRI at different ages using individual patient data from six high-risk screening trials. Sensitivity and specificity of MRI, mammography and the combination of these tests were compared stratified for BRCA mutation and age using generalised linear mixed models with random effect for studies. Number of screens needed (NSN) for additional mammography-only detected cancer was estimated. In BRCA1/2 mutation carriers of all ages (BRCA1 = 1,219 and BRCA2 = 732), adding mammography to MRI did not significantly increase screening sensitivity (increased by 3.9% in BRCA1 and 12.6% in BRCA2 mutation carriers, P > 0.05). However, in women with BRCA2 mutation younger than 40 years, one-third of breast cancers were detected by mammography only. Number of screens needed for mammography to detect one breast cancer not detected by MRI was much higher for BRCA1 compared with BRCA2 mutation carriers at initial and repeat screening. Additional screening sensitivity from mammography above that from MRI is limited in BRCA1 mutation carriers, whereas mammography contributes to screening sensitivity in BRCA2 mutation carriers, especially those ⩽ 40 years. The evidence from our work highlights that a differential screening schedule by BRCA status is worth considering.

An Efficient Variable Screening Method for Effective Surrogate Models for Reliability-Based Design Optimization

DTIC Science & Technology

2014-04-01

surrogate model generation is difficult for high -dimensional problems, due to the curse of dimensionality. Variable screening methods have been...a variable screening model was developed for the quasi-molecular treatment of ion-atom collision [16]. In engineering, a confidence interval of...for high -level radioactive waste [18]. Moreover, the design sensitivity method can be extended to the variable screening method because vital

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.

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.

Eliciting population preferences for mass colorectal cancer screening organization.

PubMed

Nayaradou, Maximilien; Berchi, Célia; Dejardin, Olivier; Launoy, Guy

2010-01-01

The implementation of mass colorectal cancer (CRC) screening is a public health priority. Population participation is fundamental for the success of CRC screening as for any cancer screening program. The preferences of the population may influence their likelihood of participation. The authors sought to elicit population preferences for CRC screening test characteristics to improve the design of CRC screening campaigns. A discrete choice experiment was used. Questionnaires were compiled with a set of pairs of hypothetical CRC screening scenarios. The survey was conducted by mail from June 2006 to October 2006 on a representative sample of 2000 inhabitants, aged 50 to 74 years from the northwest of France, who were randomly selected from electoral lists. Questionnaires were sent to 2000 individuals, each of whom made 3 or 4 discrete choices between hypothetical tests that differed in 7 attributes: how screening is offered, process, sensitivity, rate of unnecessary colonoscopy, expected mortality reduction, method of screening test result transmission, and cost. Complete responses were received from 656 individuals (32.8%). The attributes that influenced population preferences included expected mortality reduction, sensitivity, cost, and process. Participants from high social classes were particularly influenced by sensitivity. The results demonstrate that the discrete choice experiment provides information on patient preferences for CRC screening: improving screening program effectiveness, for instance, by improving test sensitivity (the most valued attribute) would increase satisfaction among the general population with regard to CRC screening programs. Additional studies are required to study how patient preferences actually affect adherence to regular screening programs.

Sesquiterpene lactone dermatitis in the young: is atopy a risk factor?

PubMed

Paulsen, Evy; Otkjaer, Aksel; Andersen, Klaus E

2008-07-01

Screening for Compositae contact allergy has documented fairly high prevalence in adults, and recent studies indicate that the allergy may be more common in children than previously believed. However, detailed information on sensitization in this age group is sparse. The objective of this study was to present another 2 cases in children and review the literature. Screening with sesquiterpene lactone (SL) mix has shown prevalence of 0.5% and 1.8% in 2 studies, while screening with 2 different Compositae mixes detected 4.2% and 2.6% positives among children and adolescents. All individual case reports describe sensitization in atopic children, and the largest screening study showed a prevalence of Compositae mix sensitization that was significantly higher in children with atopic dermatitis compared with non-atopics. Compositae sensitization should be considered in children with a family or personal history of atopy, summer-related, or -exacerbated dermatitis of any kind, and a history of plant exposure. Screening with SL mix is recommended but should be supplemented with plant extracts based on exposure history. Compositae weeds, especially dandelions, seem to be important sensitizers in children.

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

PubMed Central

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-01-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients. PMID:27653274

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

PubMed

Moczko, Ewa; Mirkes, Evgeny M; Cáceres, César; Gorban, Alexander N; Piletsky, Sergey

2016-09-22

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

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

NASA Astrophysics Data System (ADS)

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-09-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Cost effectiveness analysis of screening for sight threatening diabetic eye disease

PubMed Central

James, Marilyn; Turner, David A; Broadbent, Deborah M; Vora, Jiten; Harding, Simon P

2000-01-01

Objective To measure the cost effectiveness of systematic photographic screening for sight threatening diabetic eye disease compared with existing practice. Design Cost effectiveness analysis Setting Liverpool. Subjects A target population of 5000 diabetic patients invited for screening. Main outcome measures Cost effectiveness (cost per true positive) of systematic and opportunistic programmes; incremental cost effectiveness of replacing opportunistic with systematic screening. Results Baseline prevalence of sight threatening eye disease was 14.1%. The cost effectiveness of the systematic programme was £209 (sensitivity 89%, specificity 86%, compliance 80%, annual cost £104 996) and of the opportunistic programme was £289 (combined sensitivity 63%, specificity 92%, compliance 78%, annual cost £99 981). The incremental cost effectiveness of completely replacing the opportunistic programme was £32. Absolute values of cost effectiveness were highly sensitive to varying prevalence, sensitivity and specificity, compliance, and programme size. Conclusion Replacing existing programmes with systematic screening for diabetic eye disease is justified. PMID:10856062

Cost-effectiveness of WHO-Recommended Algorithms for TB Case Finding at Ethiopian HIV Clinics.

PubMed

Adelman, Max W; McFarland, Deborah A; Tsegaye, Mulugeta; Aseffa, Abraham; Kempker, Russell R; Blumberg, Henry M

2018-01-01

The World Health Organization (WHO) recommends active tuberculosis (TB) case finding and a rapid molecular diagnostic test (Xpert MTB/RIF) to detect TB among people living with HIV (PLHIV) in high-burden settings. Information on the cost-effectiveness of these recommended strategies is crucial for their implementation. We conducted a model-based cost-effectiveness analysis comparing 2 algorithms for TB screening and diagnosis at Ethiopian HIV clinics: (1) WHO-recommended symptom screen combined with Xpert for PLHIV with a positive symptom screen and (2) current recommended practice algorithm (CRPA; based on symptom screening, smear microscopy, and clinical TB diagnosis). Our primary outcome was US$ per disability-adjusted life-year (DALY) averted. Secondary outcomes were additional true-positive diagnoses, and false-negative and false-positive diagnoses averted. Compared with CRPA, combining a WHO-recommended symptom screen with Xpert was highly cost-effective (incremental cost of $5 per DALY averted). Among a cohort of 15 000 PLHIV with a TB prevalence of 6% (900 TB cases), this algorithm detected 8 more true-positive cases than CRPA, and averted 2045 false-positive and 8 false-negative diagnoses compared with CRPA. The WHO-recommended algorithm was marginally costlier ($240 000) than CRPA ($239 000). In sensitivity analysis, the symptom screen/Xpert algorithm was dominated at low Xpert sensitivity (66%). In this model-based analysis, combining a WHO-recommended symptom screen with Xpert for TB diagnosis among PLHIV was highly cost-effective ($5 per DALY averted) and more sensitive than CRPA in a high-burden, resource-limited setting.

Screening for anxiety disorders in patients with coronary artery disease.

PubMed

Bunevicius, Adomas; Staniute, Margarita; Brozaitiene, Julija; Pop, Victor J M; Neverauskas, Julius; Bunevicius, Robertas

2013-03-11

Anxiety disorders are prevalent and associated with poor prognosis in patients with coronary artery disease (CAD). However, studies examining screening of anxiety disorders in CAD patients are lacking. In the present study we evaluated the prevalence of anxiety disorders in patients with CAD and diagnostic utility of self-rating scales for screening of anxiety disorders. Five-hundred and twenty-three CAD patients not receiving psychotropic treatments at initiation of rehabilitation program completed self-rating scales (Hospital Anxiety and Depression Scale or HADS; Spielberger State-Anxiety Inventory or SSAI; and Spielberger Trait-Anxiety Inventory or STAI) and were interviewed for generalized anxiety disorder (GAD), social phobia, panic disorder and agoraphobia (Mini-International Neuropsychiatric Interview or MINI). Thirty-eight (7%) patients were diagnosed with anxiety disorder(s), including GAD (5%), social phobia (2%), agoraphobia (1%) and panic disorder (1%). Areas under the ROC curve of the HADS Anxiety subscale (HADS-A), STAI and SSAI for screening of any anxiety disorder were .81, .80 and .72, respectively. Optimal cut-off values for screening of any anxiety disorders were ≥ 8 for the HADS-A (sensitivity = 82%; specificity = 76%; and positive predictive value (PPV) = 21%); ≥ 45 for the STAI (sensitivity = 89%; specificity = 56%; and PPV = 14%); and ≥ 40 for the SSAI (sensitivity = 84%; specificity = 55%; PPV = 13%). In a subgroup of patients (n = 340) scoring below the optimal major depressive disorder screening cut-off value of HADS-Depression subscale (score <5), the HADS-A, STAI and SSAI had moderate-high sensitivity (range from 69% to 89%) and low PPVs (≤ 22%) for GAD and any anxiety disorders. Anxiety disorders are prevalent in CAD patients but can be reliably identified using self-rating scales. Anxiety self-rating scales had comparable sensitivities but the HADS-A had greater specificity and PPV when compared to the STAI and SSAI for screening of anxiety disorders. However, false positive rates were high, suggesting that patients with positive screening results should undergo psychiatric interview prior to initiating treatment for anxiety disorders and that routine use of anxiety self-rating scales for screening purposes can increase healthcare costs. Anxiety screening has incremental value to depression screening for identifying anxiety disorders.

High-throughput screening, predictive modeling and computational embryology - Abstract

EPA Science Inventory

High-throughput screening (HTS) studies are providing a rich source of data that can be applied to chemical profiling to address sensitivity and specificity of molecular targets, biological pathways, cellular and developmental processes. EPA’s ToxCast project is testing 960 uniq...

The role of oncogenic human papillomavirus determination for diagnosis of high-grade anal intraepithelial neoplasia in HIV-infected MSM.

PubMed

Burgos, Joaquin; Hernández-Losa, Javier; Landolfi, Stefania; Guelar, Ana; Dinares, MªCarmen; Villar, Judith; Navarro, Jordi; Ribera, Esteve; Falcó, Vicenç; Curran, Adria

2017-10-23

To assess the oncogenic human papillomavirus (HPV) determination and the cotesting HPV and anal cytology value to detect high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-MSM. Prospective study of HIV-infected MSM who underwent screening for anal dysplasia. Screening program includes anal cytology, HPV testing, and high-resolution anoscopy (HRA) at each visit. Histological samples were obtained if suspicious lesions were revealed by HRA. Sensitivity and specificity of the different tests were calculated by using histological results of HRA-guided biopsy as the reference test for HGAIN diagnosis. From May 2009 to August 2016, 692 HIV-infected MSM underwent 1827 anal cytologies, 1841 HRA examinations, and 1607 HPV testing. At first screening visit, anal cytology results were abnormal in 418 (60.4%) of 692 patients, and oncogenic HPV genotypes were found in 482 (79.5%) of 606 patients. Anal cytology showed a sensitivity of 89.2% [95% confidence interval (CI); 80.7-94.2] and a specificity of 44.2% (95% CI; 40.2-48.2) to detect HGAIN. Oncogenic HPV testing had 90.4% sensitivity (95% CI; 82-86.8) and 24.4% specificity (95% CI; 20.8-28.3). Cotesting showed a 97.4% sensitivity (95% CI; 91-99.3) and 14% specificity (95% CI; 11.2-17.3). In patients with atypical squamous cells of uncertain significance on cytology, oncogenic HPV testing had 91.3% sensitivity and 28.3% specificity to detect HGAIN. Abnormal cytology and oncogenic HPV determination showed similar sensitivity for detecting HGAIN. The two tests used together improved the sensitivity but with lowered specificity. In our opinion, HPV testing does not improve HGAIN detection and should not replace anal cytology as a standard screening test for HIV-infected MSM.

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

Comparative Evaluation of Preliminary Screening Methods for Colorectal Cancer in a Mass Program.

PubMed

Ye, Ding; Huang, Qiuchi; Li, Qilong; Jiang, Xiyi; Mamat, Mayila; Tang, Mengling; Wang, Jianbing; Chen, Kun

2017-09-01

The fecal immunochemical test (FIT) has been widely used in preliminary screening for colorectal cancer (CRC). The high-risk factor questionnaire (HRFQ) and quantitative risk-assessment method (QRAM) are recommended for estimating the risk of CRC qualitatively and quantitatively in China. We aimed to prospectively compare the diagnostic values of CRC preliminary screening methods to identify which method is preferable as a screening strategy. Individuals aged 40-74 years old were enrolled in a mass CRC screening program from January 1, 2007 to December 31, 2014, in Jiashan County, Zhejiang Province, China. FIT of two stool specimens at 1-week intervals was performed by laboratory personnel and face-to-face interviews were conducted by trained investigators. Screening data in the program were linked to a CRC surveillance and registry system, and CRC cases reported in the system were regarded as true patients. A total of 96,043 subjects were included. The sensitivity and specificity of FIT for detecting CRC cases were 75.49% (95% CI 69.84-80.39) and 90.36% (95% CI 90.17-90.54), respectively. QRAM was more sensitive (p < 0.001) and less specific (p < 0.001) than HRFQ. The sensitivity and specificity of FIT along with HRFQ were 86.56% (95% CI 81.81-90.22) and 81.37% (95% CI 81.12-81.62), and those of FIT along with QRAM were 88.93% (95% CI 84.47-92.23) and 73.95% (95% CI 73.67-74.23). Our findings suggest that CRC preliminary screening with FIT and QRAM in parallel has high sensitivity and satisfactory specificity, and is a useful strategy in mass screening programs.

Using the emergency department as a screening site for high blood pressure. A method for improving hypertension detection and appropriate referral.

PubMed

Mamon, J; Green, L; Levine, D M; Gibson, G; Gurley, H T

1987-08-01

This study describes the development and testing of a high blood pressure protocol for use in emergency departments (ED) to enhance detection of those patients appropriate for subsequent referral. The protocol involves two serial blood pressure measurements and a patient interview to determine: 1) previous history of high blood pressure (HBP), 2) treatment in past year for HBP, and 3) usual source of medical care. The accuracy of patient reporting was validated by comparison with the patients' hospital record (reflecting outpatient and inpatient visits). Results indicate that these self-reports have high levels of sensitivity (range 90-100%) and specificity (range 79-96%). Use of the additional patient information increased the sensitivity of the screening protocol in identifying when and where a patient should be referred. Use of this methodology indicates that the protocol is a simple and effective method for HBP screening. The findings also suggest that the ED is an ideal site for screening the "hard-to-reach" hypertensive population.

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

Alkylation sensitivity screens reveal a conserved cross-species functionome

PubMed Central

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

2013-01-01

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

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.

Contrast-enhanced spectral mammography (CESM) versus MRI in the high-risk screening setting: patient preferences and attitudes.

PubMed

Phillips, Jordana; Miller, Matthew M; Mehta, Tejas S; Fein-Zachary, Valerie; Nathanson, Audrey; Hori, Wendy; Monahan-Earley, Rita; Slanetz, Priscilla J

Our study evaluates patient preferences toward screening CESM versus MRI. As part of a prospective study, high-risk patients had breast MRI and CESM. Patients completed an anonymous survey to evaluate preferences regarding the two modalities. 88% of participants completed the survey. 79% preferred CESM over MRI if the exams had equal sensitivity. 89% would be comfortable receiving contrast as part of an annual screening test. High-risk populations may accept CESM as a screening exam and may prefer it over screening MRI if ongoing trials demonstrate screening CESM to be clinically non-inferior MRI. Copyright © 2016 Elsevier Inc. All rights reserved.

A systematic review of randomized trials assessing human papillomavirus testing in cervical cancer screening

PubMed Central

Patanwala, Insiyyah Y.; Bauer, Heidi M.; Miyamoto, Justin; Park, Ina U.; Huchko, Megan J.; Smith-McCune, Karen K.

2013-01-01

Our objective was to assess the sensitivity and specificity of human papillomavirus (HPV) testing for cervical cancer screening in randomized trials. We conducted a systematic literature search of the following databases: MEDLINE, CINAHL, EMBASE, and Cochrane. Eligible studies were randomized trials comparing HPV-based to cytology-based screening strategies, with disease status determined by colposcopy/biopsy for participants with positive results. Disease rates (cervical intraepithelial neoplasia [CIN]2 or greater and CIN3 or greater), sensitivity, and positive predictive value were abstracted or calculated from the articles. Six studies met inclusion criteria. Relative sensitivities for detecting CIN3 or greater of HPV testing-based strategies vs cytology ranged from 0.8 to 2.1. The main limitation of our study was that testing methodologies and screening/management protocols were highly variable across studies. Screening strategies in which a single initial HPV-positive test led to colposcopy were more sensitive than cytology but resulted in higher colposcopy rates. These results have implications for cotesting with HPV and cytology as recommended in the United States. PMID:23159693

Diagnostic accuracy of high-risk HPV genotyping in women with high-grade cervical lesions: evidence for improving the cervical cancer screening strategy in China.

PubMed

Xu, Huihui; Lin, Aifen; Shao, Xiujuan; Shi, Weiwu; Zhang, Yang; Yan, Weihua

2016-12-13

Currently, clinical data for primary HPV screening alone are lacking in China. Here, we evaluate cervical cancer screening with primary HPV genotyping, as well as possible future screening strategy. Overall, high-risk HPV (hrHPV) prevalence was 18.2% among hospital-based population in Taizhou area. For cervical intraepithelial neoplasia 2 or worse (CIN2+), the sensitivity of primary hrHPV genotyping strategy and current cervical cancer screening strategy were 93.5%, and 71.1%, respectively; whereas the specificity was 17.5%, and 62.4%, respectively. Current cervical screening strategy had slightly higher positive predictive values (28.4%) for CIN2+ than hrHPV genotyping strategy (21.9%), whereas primary hrHPV genotyping strategy demonstrated higher negative predictive values (94.7%) than current cervical screening strategy (91.1%). Compared to HPV35/39/45/51/56/59/66/68 genotypes, the odds ratios (OR) for CIN2+ in HPV16/18/31/33/52/58 infection women were 3.2 (95% confidence interval [CI] 2.3-4.1). Primary hrHPV genotyping strategy provides a better predictive value than HPV16/18 genotyping alone in guiding the clinical management of the current cervical cancer screening. HPV testing without adjunctive cytology may be sufficiently sensitive for primary cervical cancer screening.

Sensitivity of neuroprogenitor cells to chemical-induced apoptosis using a multiplexed assay suitable for high-throughput screening*

EPA Science Inventory

AbstractHigh-throughput methods are useful for rapidly screening large numbers of chemicals for biological activity, including the perturbation of pathways that may lead to adverse cellular effects. In vitro assays for the key events of neurodevelopment, including apoptosis, may ...

Composite scintillator screen

DOEpatents

Zeman, Herbert D.

1994-01-01

A scintillator screen for an X-ray system includes a substrate of low-Z material and bodies of a high-Z material embedded within the substrate. By preselecting the size of the bodies embedded within the substrate, the spacial separation of the bodies and the thickness of the screen, the sensitivity of the screen to X-rays within a predetermined energy range can be predicted.

A high-throughput screen of the GTPase activity of Escherichia coli EngA to find an inhibitor of bacterial ribosome biogenesis

PubMed Central

Bharat, Amrita; Blanchard, Jan E.; Brown, Eric D.

2014-01-01

The synthesis of ribosomes is an essential process, which is aided by a variety of transacting factors in bacteria. Among these is a group of GTPases essential for bacterial viability and emerging as promising targets for new antibacterial agents. Herein, we describe a robust high-throughput screening process for inhibitors of one such GTPase, the Escherichia coli EngA protein. The primary screen employed an assay of phosphate production in 384-well density. Reaction conditions were chosen to maximize sensitivity for the discovery of competitive inhibitors while maintaining a strong signal amplitude and low noise. In a pilot screen of 31,800 chemical compounds, 44 active compounds were identified. Further, we describe the elimination of non-specific inhibitors that were detergent-sensitive or reactive as well as those that interfered with the high-throughput phosphate assay. Four inhibitors survived these common counter-screens for non-specificity but these chemicals were also inhibitors of the unrelated enzyme dihydrofolate reductase, suggesting that they too were promiscuously active. The high-throughput screen of the EngA protein described here provides a meticulous pilot study in the search for specific inhibitors of GTPases involved in ribosome biogenesis. PMID:23606650

The Childhood Asperger Syndrome Test (CAST): Test-Retest Reliability in a High Scoring Sample

ERIC Educational Resources Information Center

Allison, Carrie; Williams, Jo; Scott, Fiona; Stott, Carol; Bolton, Patrick; Baron-Cohen, Simon; Brayne, Carol

2007-01-01

The Childhood Asperger Syndrome Test (CAST) is a 37-item parental self-completion questionnaire designed to screen for high-functioning autism spectrum conditions in epidemiological research. The CAST has previously demonstrated good accuracy for use as a screening test, with high sensitivity in studies with primary school aged children in…

The sensitivity and specificity of subjective memory complaints and the subjective memory rating scale, deterioration cognitive observee, mini-mental state examination, six-item screener and clock drawing test in dementia screening.

PubMed

Ramlall, S; Chipps, J; Bhigjee, A I; Pillay, B J

2013-01-01

The effectiveness of dementia screening depends on the availability of suitable screening tools with good sensitivity and specificity to confidently distinguish normal age-related cognitive decline from dementia. The aim of this study was to evaluate the discriminant validity of 7 screening measures for dementia. A sample of 140 participants aged ≥60 years living in a residential facility for the aged were assessed clinically and assigned caseness for dementia using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised diagnostic criteria. Sensitivity and specificity of a selection of the following screening measures were tested using receiver operating characteristic (ROC) analysis for individual and combined tests: the Mini-Mental State Examination (MMSE), Six-Item Screener (SIS), Subjective Memory Complaint, Subjective Memory Complaint Clinical (SMCC), Subjective Memory Rating Scale (SMRS), Deterioration Cognitive Observee (DECO) and the Clock Drawing Test (CDT). Using ROC analyses, the SMCC, MMSE and CDT were found to be 'moderately accurate' in screening for dementia with an area under the curve (AUC) >0.70. The AUCs for the SIS (0.526), SMRS (0.661) and DECO (0.687) classified these measures as being 'less accurate'. At recommended cutoff scores, the SMCC had a sensitivity of 90.9% and specificity of 45.7%; the MMSE had a sensitivity of 63.6% and a specificity of 76.0%, and the CDT had a sensitivity of 44.4% and a specificity of 88.9%. Combining the SMCC and MMSE did not improve their predictive power except for a modest increase when using the sequential rule. The SMCC is composed of valid screening questions that have high sensitivity, are simple to administer and ideal for administration at the community or primary health care level as a first level of 'rule-out' screening. The MMSE can be included at a second stage of screening at the general hospital level and the CDT in specialist clinical settings. Sequential use of the SMCC and MMSE will improve the specificity of the former and the sensitivity of the latter. Copyright © 2013 S. Karger AG, Basel.

Sensitivity and specificity of digital retinal imaging for screening diabetic retinopathy.

PubMed

Lopez-Bastida, J; Cabrera-Lopez, F; Serrano-Aguilar, P

2007-04-01

To assess the effectiveness of a non-mydriatic digital camera (45 degrees -30 degrees photographs) compared with the reference method for screening diabetic retinopathy. Type 1 and 2 diabetic patients (n = 773; 1546 eyes) underwent screening for diabetic retinopathy in a prospective observational study. Hospital-based non-mydriatic digital retinal imaging by a consultant specialist in retinal diseases was compared with slit-lamp biomicroscopy and indirect ophthalmoscopy through dilated pupils, as a gold standard, previously performed in a community health centre by another consultant specialist in retinal diseases. The main outcome measures were sensitivity and specificity of screening methods and prevalence of diabetic retinopathy. The prevalence of any form of diabetic retinopathy was 42.4% (n = 328); the prevalence of sight-threatening including macular oedema and proliferative retinopathy was 9.6% (n = 74). Sensitivity of detection of any diabetic retinopathy by digital imaging was 92% (95% confidence interval 90, 94). Specificity of detection of any diabetic retinopathy was 96% (95, 98). The predictive value of the negative tests was 94% and of a positive test 95%. For sight-threatening retinopathy digital imaging had a sensitivity of 100%. A high sensitivity and specificity are essential for an effective screening programme. These results confirm digital retinal imaging with a non-mydriatic camera as an effective option in community-based screening programmes for diabetic retinopathy.

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.

Classification and virtual screening of androgen receptor antagonists.

PubMed

Li, Jiazhong; Gramatica, Paola

2010-05-24

Computational tools, such as quantitative structure-activity relationship (QSAR), are highly useful as screening support for prioritization of substances of very high concern (SVHC). From the practical point of view, QSAR models should be effective to pick out more active rather than inactive compounds, expressed as sensitivity in classification works. This research investigates the classification of a big data set of endocrine-disrupting chemicals (EDCs)-androgen receptor (AR) antagonists, mainly aiming to improve the external sensitivity and to screen for potential AR binders. The kNN, lazy IB1, and ADTree methods and the consensus approach were used to build different models, which improve the sensitivity on external chemicals from 57.1% (literature) to 76.4%. Additionally, the models' predictive abilities were further validated on a blind collected data set (sensitivity: 85.7%). Then the proposed classifiers were used: (i) to distinguish a set of AR binders into antagonists and agonists; (ii) to screen a combined estrogen receptor binder database to find out possible chemicals that can bind to both AR and ER; and (iii) to virtually screen our in-house environmental chemical database. The in silico screening results suggest: (i) that some compounds can affect the normal endocrine system through a complex mechanism binding both to ER and AR; (ii) new EDCs, which are nonER binders, but can in silico bind to AR, are recognized; and (iii) about 20% of compounds in a big data set of environmental chemicals are predicted as new AR antagonists. The priority should be given to them to experimentally test the binding activities with AR.

Integrating Oral and General Health Screening at Senior Centers for Minority Elders

PubMed Central

Cheng, Bin; Northridge, Mary E.; Kunzel, Carol; Huang, Catherine; Lamster, Ira B.

2013-01-01

Racial/ethnic and socioeconomic disparities regarding untreated oral disease exist for older adults, and poor oral health diminishes quality of life. The ElderSmile program integrated screening for diabetes and hypertension into its community-based oral health activities at senior centers in northern Manhattan. The program found a willingness among minority seniors (aged ≥ 50 years) to be screened for primary care sensitive conditions by dental professionals and a high level of unrecognized disease (7.8% and 24.6% of ElderSmile participants had positive screening results for previously undiagnosed diabetes and hypertension, respectively). Dental professionals may screen for primary care–sensitive conditions and refer patients to health care providers for definitive diagnosis and treatment. The ElderSmile program is a replicable model for community-based oral and general health screening. PMID:23597378

[Effectiveness of human papillomavirus genotyping for detection of high-grade anal intraepithelial neoplasia compared to anal cytology].

PubMed

Padilla-España, Laura; Repiso-Jiménez, Juan Bosco; Fernández-Sánchez, Fernando; Pereda, Teresa; Rivas-Ruiz, Francisco; Fernández-Morano, Teresa; de la Torre-Lima, Javier; Palma, Fermín; Redondo, Maximino; de Troya-Martín, Magdalena

2016-01-01

The incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. This is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. Of the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. Anal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

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.

COMPARISON OF IN VIVO AND IN VITRO CHEMICAL SCREENING ASSAYS FOR ESTROGEN-RESPONSIVE PROTEIN BIOMARKER EXPRESSION IN THE SHEEPSHEAD MINNOW (CYPRINODON VARIEGATUS)

EPA Science Inventory

Animal welfare concerns and the high cost associated with in vivo chemical screening methods have prompted efforts to develop highly specific and sensitive in vitro techniques to evaluate chemicals for endocrine activity. Diagnostic biomarkers developed using in vitro methods sho...

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.

A randomized trial on screening for social determinants of health: the iScreen study.

PubMed

Gottlieb, Laura; Hessler, Danielle; Long, Dayna; Amaya, Anais; Adler, Nancy

2014-12-01

There is growing interest in clinical screening for pediatric social determinants of health, but little evidence on formats that maximize disclosure rates on a wide range of potentially sensitive topics. We designed a study to examine disclosure rates and hypothesized that there would be no difference in disclosure rates on face-to-face versus electronic screening formats for items other than highly sensitive items. We conducted a randomized trial of electronic versus face-to-face social screening formats in a pediatric emergency department. Consenting English-speaking and Spanish-speaking adult caregivers familiar with the presenting child's household were randomized to social screening via tablet computer (with option for audio assist) versus a face-to-face interview conducted by a fully bilingual/bicultural researcher. Almost all caregivers (96.8%) reported at least 1 social need, but rates of reporting on the more sensitive issues (household violence and substance abuse) were significantly higher in electronic format, and disclosure was marginally higher in electronic format for financial insecurity and neighborhood and school safety. There was a significant difference in the proportion of social needs items with higher endorsement in the computer-based group (70%) than the face-to-face group (30%). Pediatric clinical sites interested in incorporating caregiver-reported socioeconomic, environmental, and behavioral needs screening should consider electronic screening when feasible, particularly when assessing sensitive topics such as child safety and household member substance use. Copyright © 2014 by the American Academy of Pediatrics.

Pooled analysis of the accuracy of five cervical cancer screening tests assessed in eleven studies in Africa and India.

PubMed

Arbyn, Marc; Sankaranarayanan, Rengaswamy; Muwonge, Richard; Keita, Namory; Dolo, Amadou; Mbalawa, Charles Gombe; Nouhou, Hassan; Sakande, Boblewende; Wesley, Ramani; Somanathan, Thara; Sharma, Anjali; Shastri, Surendra; Basu, Parthasarathy

2008-07-01

Cervical cancer is the main cancer among women in sub-Saharan Africa, India and other parts of the developing world. Evaluation of screening performance of effective, feasible and affordable early detection and management methods is a public health priority. Five screening methods, naked eye visual inspection of the cervix uteri after application of diluted acetic acid (VIA), or Lugol's iodine (VILI) or with a magnifying device (VIAM), the Pap smear and human papillomavirus testing with the high-risk probe of the Hybrid Capture-2 assay (HC2), were evaluated in 11 studies in India and Africa. More than 58,000 women, aged 25-64 years, were tested with 2-5 screening tests and outcome verification was done on all women independent of the screen test results. The outcome was presence or absence of cervical intraepithelial neoplasia (CIN) of different degrees or invasive cervical cancer. Verification was based on colposcopy and histological interpretation of colposcopy-directed biopsies. Negative colposcopy was accepted as a truly negative outcome. VIA showed a sensitivity of 79% (95% CI 73-85%) and 83% (95% CI 77-89%), and a specificity of 85% (95% CI 81-89%) and 84% (95% CI 80-88%) for the outcomes CIN2+ or CIN3+, respectively. VILI was on average 10% more sensitive and equally specific. VIAM showed similar results as VIA. The Pap smear showed lowest sensitivity, even at the lowest cutoff of atypical squamous cells of undetermined significance (57%; 95% CI 38-76%) for CIN2+ but the specificity was rather high (93%; 95% CI 89-97%). The HC2-assay showed a sensitivity for CIN2+ of 62% (95% CI 56-68%) and a specificity of 94% (95% CI 92-95%). Substantial interstudy variation was observed in the accuracy of the visual screening methods. Accuracy of visual methods and cytology increased over time, whereas performance of HC2 was constant. Results of visual tests and colposcopy were highly correlated. This study was the largest ever done that evaluates the cross-sectional accuracy of screening tests for cervical cancer precursors in developing countries. The merit of the study was that all screened subjects were submitted to confirmatory investigations avoiding to verification bias. A major finding was the consistently higher sensitivity but equal specificity of VILI compared with VIA. Nevertheless, some caution is warranted in the interpretation of observed accuracy measures, since a certain degree of gold standard misclassification cannot be excluded. Because of the correlation between visual screening tests and colposcopy and a certain degree of over-diagnosis of apparent CIN2+ by study pathologists, it is possible that both sensitivity and specificity of VIA and VILI were overestimated. Gold standard verification error could also explain the surprisingly low sensitivity of HC2, which contrasts with findings from other studies. (c) 2008 Wiley-Liss, Inc.

Accuracy of screening women at familial risk of breast cancer without a known gene mutation: Individual patient data meta-analysis.

PubMed

Phi, Xuan-Anh; Houssami, Nehmat; Hooning, Maartje J; Riedl, Christopher C; Leach, Martin O; Sardanelli, Francesco; Warner, Ellen; Trop, Isabelle; Saadatmand, Sepideh; Tilanus-Linthorst, Madeleine M A; Helbich, Thomas H; van den Heuvel, Edwin R; de Koning, Harry J; Obdeijn, Inge-Marie; de Bock, Geertruida H

2017-11-01

Women with a strong family history of breast cancer (BC) and without a known gene mutation have an increased risk of developing BC. We aimed to investigate the accuracy of screening using annual mammography with or without magnetic resonance imaging (MRI) for these women outside the general population screening program. An individual patient data (IPD) meta-analysis was conducted using IPD from six prospective screening trials that had included women at increased risk for BC: only women with a strong familial risk for BC and without a known gene mutation were included in this analysis. A generalised linear mixed model was applied to estimate and compare screening accuracy (sensitivity, specificity and predictive values) for annual mammography with or without MRI. There were 2226 women (median age: 41 years, interquartile range 35-47) with 7478 woman-years of follow-up, with a BC rate of 12 (95% confidence interval 9.3-14) in 1000 woman-years. Mammography screening had a sensitivity of 55% (standard error of mean [SE] 7.0) and a specificity of 94% (SE 1.3). Screening with MRI alone had a sensitivity of 89% (SE 4.6) and a specificity of 83% (SE 2.8). Adding MRI to mammography increased sensitivity to 98% (SE 1.8, P < 0.01 compared to mammography alone) but lowered specificity to 79% (SE 2.7, P < 0.01 compared with mammography alone). In this population of women with strong familial BC risk but without a known gene mutation, in whom BC incidence was high both before and after age 50, adding MRI to mammography substantially increased screening sensitivity but also decreased its specificity. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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

PubMed Central

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

2016-01-01

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

Cervical screening in HPV-vaccinated populations.

PubMed

Canfell, K

2018-06-01

Cervical screening with cytology has been the basis for substantial reductions in cervical cancer incidence and mortality in most high-income countries over the last few decades. More recently, there have been two key, parallel developments which have prompted a major re-consideration of cervical screening. The first is the emergence of evidence on the improved sensitivity of human papillomavirus (HPV) DNA testing compared to cytology, and the second is the large-scale deployment of prophylactic vaccination against HPV. A key challenge to be overcome before HPV screening could be introduced into national cervical screening programs was the specificity of an infection, for detection of precancerous lesions. This has been done in three ways: (1) by considering the appropriate age for starting HPV screening (30 years in unvaccinated populations and 25 years in populations with mature vaccination programs and high vaccine uptake) and the appropriate screening interval; (2) via development of clinical HPV tests, which are (by design) not as sensitive to low viral loads; and (3) by introducing effective triaging for HPV-positive women, which further risk-stratifies women before referral for diagnostic evaluation. This review discusses these major developments and describes how the benefits of HPV screening are being optimized in both unvaccinated and vaccinated populations.

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.

The Beck Depression Inventory (BDI-II) and a single screening question as screening tools for depressive disorder in Dutch advanced cancer patients.

PubMed

Warmenhoven, Franca; van Rijswijk, Eric; Engels, Yvonne; Kan, Cornelis; Prins, Judith; van Weel, Chris; Vissers, Kris

2012-02-01

Depression is highly prevalent in advanced cancer patients, but the diagnosis of depressive disorder in patients with advanced cancer is difficult. Screening instruments could facilitate diagnosing depressive disorder in patients with advanced cancer. The aim of this study was to determine the validity of the Beck Depression Inventory (BDI-II) and a single screening question as screening tools for depressive disorder in advanced cancer patients. Patients with advanced metastatic disease, visiting the outpatient palliative care department, were asked to fill out a self-questionnaire containing the Beck Depression Inventory (BDI-II) and a single screening question "Are you feeling depressed?" The mood section of the PRIME-MD was used as a gold standard. Sixty-one patients with advanced metastatic disease were eligible to be included in the study. Complete data were obtained from 46 patients. The area under the curve of the receiver operating characteristics analysis of the BDI-II was 0.82. The optimal cut-off point of the BDI-II was 16 with a sensitivity of 90% and a specificity of 69%. The single screening question showed a sensitivity of 50% and a specificity of 94%. The BDI-II seems an adequate screening tool for a depressive disorder in advanced cancer patients. The sensitivity of a single screening question is poor.

Performance and comparison of self-reported STI symptoms among high-risk populations - MSM, sex workers, persons living with HIV/AIDS - in El Salvador.

PubMed

Shah, Neha S; Kim, Evelyn; de Maria Hernández Ayala, Flor; Guardado Escobar, Maria Elena; Nieto, Ana Isabel; Kim, Andrea A; Paz-Bailey, Gabriela

2014-12-01

Resource-limited countries have limited laboratory capability and rely on syndromic management to diagnose sexually transmitted infections (STIs). We aimed to estimate the sensitivity, specificity and positive predictive value (PPV) of STI syndromic management when used as a screening method within a study setting. Men who have sex with men (MSM), female sex workers (FSWs) and people living with HIV/AIDS (PLWHA) participated in a behavioural surveillance study. Data were obtained on demographics, sexual behaviours, STI history and service utilisation. Biological specimens were tested for genital inflammatory infections (Neisseria gonorrhoeae [GC], Chlamydia trachomatis [CT], Mycoplasma genitalium [MG], Trichomonas vaginalis [TV]) and genital ulcerative infection (syphilis and Herpes simplex virus-2). There was a high prevalence of Herpes simplex virus-2 (MSM 48.1%, FSW 82.0% and PLWHA 84.4%). Most participants reported no ulcerative symptoms and the majority of men reported no inflammatory symptoms. Sensitivity and PPV were poor for inflammatory infections among PLWHA and MSM. Sensitivity in FSWs for inflammatory infections was 75%. For ulcerative infections, sensitivity was poor, but specificity and PPV were high. Reliance on self-reported symptoms may not be an effective screening strategy for these populations. STI prevention studies should focus on symptom recognition and consider routine screening and referral for high-risk populations. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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.

Combined use of fasting plasma glucose and glycated hemoglobin A1c in the screening of diabetes and impaired glucose tolerance.

PubMed

Hu, Yaomin; Liu, Wei; Chen, Yawen; Zhang, Ming; Wang, Lihua; Zhou, Huan; Wu, Peihong; Teng, Xiangyu; Dong, Ying; Zhou, Jia wen; Xu, Hua; Zheng, Jun; Li, Shengxian; Tao, Tao; Hu, Yumei; Jia, Yun

2010-09-01

The aim of this study is to assess the validity of combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) as screening tests for diabetes and impaired glucose tolerance (IGT) in high-risk subjects. A total of 2,298 subjects were included. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and HbA1c measurement. Receiver operating characteristic curve (ROC curve) analysis was used to examine the sensitivity and specificity of FPG and HbA1c for detecting diabetes and IGT, which was defined according to the 1999 World Health Organization (WHO) criteria. (1) Based on the ROC curve, the optimal cut point of FPG related to diabetes diagnosed by OGTT was 6.1 mmol/l that was associated with a sensitivity and specificity of 81.5 and 81.0%, respectively; The optimal cut point of HbA1c related to diabetes diagnosed by OGTT was 6.1%, which was associated with a sensitivity and specificity of 81.0 and 81.0%, respectively; The screening model using FPG > or = 6.1 mmol/l or HbA1c > or = 6.1% had sensitivity of 96.5% for detecting undiagnosed diabetes; the screening model using FPG > or = 6.1 mmol/l and HbA1c > or = 6.1% had specificity of 96.3% for detecting undiagnosed diabetes. (2) Based on the ROC curve, the optimal cut point of FPG related to IGT diagnosed by OGTT was 5.6 mmol/l that was associated with a sensitivity and specificity of 64.1 and 65.4%, respectively; The optimal cut point of HbA1c related to IGT diagnosed by OGTT was 5.6%, which was associated with a sensitivity and specificity of 66.2 and 51.0%, respectively; The screening model using FPG > or = 5.6 mmol/l or HbA1c > or = 5.6% had sensitivity of 87.9% for detecting undiagnosed IGT; The screening model using FPG > or = 5.6 mmol/l and HbA1c > or = 5.6% had specificity of 82.4% for detecting undiagnosed IGT. Compared with FPG or HbA1c alone, the simultaneous measurement of FPG and HbA1c (FPG and/or HbA1C) might be a more sensitive and specific screening tool for identifying high-risk individuals with diabetes and IGT at an early stage.

Evaluation of high throughput gene expression platforms using a genomic biomarker signature for prediction of skin sensitization.

PubMed

Forreryd, Andy; Johansson, Henrik; Albrekt, Ann-Sofie; Lindstedt, Malin

2014-05-16

Allergic contact dermatitis (ACD) develops upon exposure to certain chemical compounds termed skin sensitizers. To reduce the occurrence of skin sensitizers, chemicals are regularly screened for their capacity to induce sensitization. The recently developed Genomic Allergen Rapid Detection (GARD) assay is an in vitro alternative to animal testing for identification of skin sensitizers, classifying chemicals by evaluating transcriptional levels of a genomic biomarker signature. During assay development and biomarker identification, genome-wide expression analysis was applied using microarrays covering approximately 30,000 transcripts. However, the microarray platform suffers from drawbacks in terms of low sample throughput, high cost per sample and time consuming protocols and is a limiting factor for adaption of GARD into a routine assay for screening of potential sensitizers. With the purpose to simplify assay procedures, improve technical parameters and increase sample throughput, we assessed the performance of three high throughput gene expression platforms--nCounter®, BioMark HD™ and OpenArray®--and correlated their performance metrics against our previously generated microarray data. We measured the levels of 30 transcripts from the GARD biomarker signature across 48 samples. Detection sensitivity, reproducibility, correlations and overall structure of gene expression measurements were compared across platforms. Gene expression data from all of the evaluated platforms could be used to classify most of the sensitizers from non-sensitizers in the GARD assay. Results also showed high data quality and acceptable reproducibility for all platforms but only medium to poor correlations of expression measurements across platforms. In addition, evaluated platforms were superior to the microarray platform in terms of cost efficiency, simplicity of protocols and sample throughput. We evaluated the performance of three non-array based platforms using a limited set of transcripts from the GARD biomarker signature. We demonstrated that it was possible to achieve acceptable discriminatory power in terms of separation between sensitizers and non-sensitizers in the GARD assay while reducing assay costs, simplify assay procedures and increase sample throughput by using an alternative platform, providing a first step towards the goal to prepare GARD for formal validation and adaption of the assay for industrial screening of potential sensitizers.

Assessment of the influence of test characteristics on the clinical and cost impacts of methicillin-resistant Staphylococcus aureus screening programs in US hospitals.

PubMed

Olchanski, Natalia; Mathews, Charles; Fusfeld, Lauren; Jarvis, William

2011-03-01

To compare the impacts of different methicillin-resistant Staphylococcus aureus (MRSA) screening test options (eg, polymerase chain reaction [PCR], rapid culture) and program characteristics on the clinical outcomes and budget of a typical US hospital. We developed an Excel-based decision-analytic model, using published literature to calculate and compare hospital costs and MRSA infection rates for PCR- or culture-based MRSA screening and then used multivariate sensitivity analysis to evaluate key variables. Same-day PCR testing for a representative 370-bed teaching hospital in the United States was assessed in different populations (high-risk patients, intensive care unit [ICU] patients, or all patients) and compared with other test options. Different screening program populations (all patients, high-risk patients, ICU patients, or patients with previous MRSA colonization or infection only) represented a potential savings of $12,158-$76,624 per month over no program ($188,618). Analysis of multiple test options in high-risk population screening indicated that same-day PCR testing of high-risk patients resulted in fewer infections over 1,720 patient-days (2.9, compared with 3.5 for culture on selective media and 3.8 for culture on nonselective media) and the lowest total cost ($112,012). The costs of other testing approaches ranged from $113,742 to $123,065. Sensitivity analysis revealed that variations in transmission rate, conversion to infection, prevalence increases, and hospital size are important to determine program impact. Among test characteristics, turnaround time is highly influential. All screening options showed reductions in infection rates and cost impact improvement over no screening program. Among the options, same-day PCR testing for high-risk patients slightly edges out the others in terms of fewest infections and greatest potential cost savings.

Reliability and Validity of Observational Risk Screening in Evaluating Dynamic Knee Valgus

PubMed Central

Ekegren, Christina L.; Miller, William C.; Celebrini, Richard G.; Eng, Janice J.; MacIntyre, Donna L.

2012-01-01

Study Design Nonexperimental methodological study. Objectives To determine the interrater and intrarater reliability and validity of using observational risk screening guidelines to evaluate dynamic knee valgus. Background A deficiency in the neuromuscular control of the hip has been identified as a key risk factor for non-contact anterior cruciate ligament (ACL) injury in post pubescent females. This deficiency can manifest itself as a valgus knee alignment during tasks involving hip and knee flexion. There are currently no scientifically tested methods to screen for dynamic knee valgus in the clinic or on the field. Methods Three physiotherapists used observational risk screening guidelines to rate 40 adolescent female soccer players according to their risk of ACL injury. The rating was based on the amount of dynamic knee valgus observed on a drop jump landing. Ratings were evaluated for intrarater and interrater agreement using kappa coefficients. Sensitivity and specificity of ratings were evaluated by comparing observational ratings with measurements obtained using 3-dimensional (3D) motion analysis. Results Kappa coefficients for intrarater and interrater agreement ranged from 0.75 to 0.85, indicating that ratings were reasonably consistent over time and between physiotherapists. Sensitivity values were inadequate, ranging from 67–87%. This indicated that raters failed to detect up to a third of “truly high risk” individuals. Specificity values ranged from 60–72% which was considered adequate for the purposes of the screen. Conclusion Observational risk screening is a practical and cost-effective method of screening for ACL injury risk. Rater agreement and specificity were acceptable for this method but sensitivity was not. To detect a greater proportion of individuals at risk of ACL injury, coaches and clinicians should ensure that they include additional tests for other high risk characteristics in their screening protocols. PMID:19721212

Comparison of Alcohol Use Disorder Screens During College Athlete Pre-Participation Evaluations.

PubMed

Majka, Erek; Graves, Travis; Diaz, Vanessa A; Player, Marty S; Dickerson, Lori M; Gavin, Jennifer K; Wessell, Andrea

2016-05-01

The US Preventive Services Task Force (USPSTF) recommends screening adults for alcohol misuse, a challenge among young adults who may not have regular primary care. The pre-participation evaluation (PPE) provides an opportunity for screening, but traditional screening tools require extra time in an already busy visit. The objective of this study was to compare the 10-item Alcohol Use Disorders Identification Test (AUDIT) with a single-question alcohol misuse screen in a population of college-aged athletes. This cross-sectional study was performed during an athletic PPE clinic at a college in the Southeastern United States among athletes ages 18 years and older. Written AUDIT and single-question screen "How many times in the past year have you had X or more drinks in a day?" (five for men, four for women) asked orally were administered to each participant. Sensitivity, specificity, and positive and negative predictive values for the single-question screen were compared to AUDIT. A total of 225 athletes were screened; 60% were female; 29% screened positive by AUDIT; 59% positive by single-question instrument. Males were more likely to screen positive by both methods. Compared to the AUDIT, the brief single-question screen had 92% sensitivity for alcohol misuse and 55% specificity. The negative predictive value of the single-question screen was 95% compared to AUDIT. A single-question screen for alcohol misuse in college-aged athletes had a high sensitivity and negative predictive value compared to the more extensive AUDIT screen. Ease of administration of this screening tool is ideal for use within the pre-participation physical among college-aged athletes who may not seek regular medical care.

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

USDA-ARS?s Scientific Manuscript database

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization integrated approaches combining different chemical, biological and in silico methods are recommended to r...

New technologies and advances in colposcopic assessment.

PubMed

Tan, Jeffrey H J; Wrede, C David H

2011-10-01

To have a good grasp of clinical colposcopy, it is necessary to understand the histopathologic structure of the normal and dysplastic cervical epithelium. Previous meta-analyses had indicated high overall sensitivity of colposcopy in detecting dysplastic lesions, but recent studies have suggested that the technique has much lower sensitivity in detecting high-grade intraepithelial neoplasia. The best practice in colposcopy relies on accurately taking a biopsy from the correct (i.e. most morphological abnormal) site, and by taking more than one biopsy, the sensitivity for detection of high-grade cervical intraepithelial neoplasia can be increased. Cytological screening programmes of proven and maintained high quality will enhance the predictive colposcopic accuracy for high-grade cervical intraepithelial neoplasia after referral. With the advent of computerised colposcopy and the Internet, digital imaging can be transmitted in real-time for instant viewing, facilitating distant consultation and education. This form of 'telemedicine' will allow family practice and remote areas to have access to colposcopy expertise. Of all the currently available technological adjuncts to colposcopy, spectroscopy devices have demonstrated relatively high sensitivities, and seem to have the best potential to become the technique of choice in future routine clinical practice in developed countries following the human papillomavirus vaccination. Other alternatives may need to be used in parts of the globe with high disease incidence and without organised screening or vaccination programmes. Opportunities remain for global collaboration in research, education and training to promote more effective and affordable cervical screening, and to enhance the skills of colposcopists worldwide. Copyright © 2011 Elsevier Ltd. All rights reserved.

Is breast compression associated with breast cancer detection and other early performance measures in a population-based breast cancer screening program?

PubMed

Moshina, Nataliia; Sebuødegård, Sofie; Hofvind, Solveig

2017-06-01

We aimed to investigate early performance measures in a population-based breast cancer screening program stratified by compression force and pressure at the time of mammographic screening examination. Early performance measures included recall rate, rates of screen-detected and interval breast cancers, positive predictive value of recall (PPV), sensitivity, specificity, and histopathologic characteristics of screen-detected and interval breast cancers. Information on 261,641 mammographic examinations from 93,444 subsequently screened women was used for analyses. The study period was 2007-2015. Compression force and pressure were categorized using tertiles as low, medium, or high. χ 2 test, t tests, and test for trend were used to examine differences between early performance measures across categories of compression force and pressure. We applied generalized estimating equations to identify the odds ratios (OR) of screen-detected or interval breast cancer associated with compression force and pressure, adjusting for fibroglandular and/or breast volume and age. The recall rate decreased, while PPV and specificity increased with increasing compression force (p for trend <0.05 for all). The recall rate increased, while rate of screen-detected cancer, PPV, sensitivity, and specificity decreased with increasing compression pressure (p for trend <0.05 for all). High compression pressure was associated with higher odds of interval breast cancer compared with low compression pressure (1.89; 95% CI 1.43-2.48). High compression force and low compression pressure were associated with more favorable early performance measures in the screening program.

Primary screening for cervical cancer based on high-risk human papillomavirus (HPV) detection and HPV 16 and HPV 18 genotyping, in comparison to cytology.

PubMed

Agorastos, Theodoros; Chatzistamatiou, Kimon; Katsamagkas, Taxiarchis; Koliopoulos, George; Daponte, Alexandros; Constantinidis, Theocharis; Constantinidis, Theodoros C

2015-01-01

The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. The study, conducted by the "HEllenic Real life Multicentric cErvical Screening" (HERMES) study group, involved the recruitment of 4,009 women, aged 25-55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25-29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.

Validation of the Arab Youth Mental Health scale as a screening tool for depression/anxiety in Lebanese children

PubMed Central

2011-01-01

Background Early detection of common mental disorders, such as depression and anxiety, among children and adolescents requires the use of validated, culturally sensitive, and developmentally appropriate screening instruments. The Arab region has a high proportion of youth, yet Arabic-language screening instruments for mental disorders among this age group are virtually absent. Methods We carried out construct and clinical validation on the recently-developed Arab Youth Mental Health (AYMH) scale as a screening tool for depression/anxiety. The scale was administered with 10-14 year old children attending a social service center in Beirut, Lebanon (N = 153). The clinical assessment was conducted by a child and adolescent clinical psychiatrist employing the DSM IV criteria. We tested the scale's sensitivity, specificity, and internal consistency. Results Scale scores were generally significantly associated with how participants responded to standard questions on health, mental health, and happiness, indicating good construct validity. The results revealed that the scale exhibited good internal consistency (Cronbach's alpha = 0.86) and specificity (79%). However, it exhibited moderate sensitivity for girls (71%) and poor sensitivity for boys (50%). Conclusions The AYMH scale is useful as a screening tool for general mental health states and a valid screening instrument for common mental disorders among girls. It is not a valid instrument for detecting depression and anxiety among boys in an Arab culture. PMID:21435213

A comparison of an immunological faecal occult blood test Fecatwin sensitive/FECA EIA with Haemoccult in population screening for colorectal cancer.

PubMed Central

Armitage, N.; Hardcastle, J. D.; Amar, S. S.; Balfour, T. W.; Haynes, J.; James, P. D.

1985-01-01

Two faecal occult blood tests, a simple chemical test Haemoccult and an immunological test, Fecatwin Sensitive/Feca EIA, were offered to 3,225 asymptomatic individuals as screening for colorectal cancer. One thousand three hundred and four (44%) completed and returned the tests and of these 126 (9.7%) were found to be positive - Haemoccult 40 (3%) and Feca EIA 106 (8.1%). Five cancers (4 Dukes' Stage A, 1 Dukes' Stage C) and 23 adenomas greater than 1 cm were detected - rates of 3.8 per 1000 persons screened and 17.7 per 1000 persons screened respectively. Of the five cancers identified 5 were Feca EIA positive and 3 were Haemoccult positive. Of the 23 adenomas greater than 1 cm diameter identified, J1 were Feca EIA positive and 20 were Haemoccult positive. Seventy-eight Feca EIA positive subjects were investigated and no neoplastic disease was identified. Whilst this sensitive immunological test increases the yield of carcinomas, the high false positive rate makes it unsuitable for population screening for colorectal cancer in its present form. PMID:4005139

Transforming Security Screening With Biometrics

DTIC Science & Technology

2003-04-09

prompted the Defense Advanced Research Projects Agency to experiment with facial recognition technology for identification of known terrorists. While DoD...screening of individuals. Facial recognition technology has been tested to some degree for accessing highly sensitive military areas, but not for...the military can implement facial recognition to screen personnel requesting access to bases and stations, DoD is not likely to use biometrics to

Anal cytology as a predictor of anal intraepithelial neoplasia in HIV-positive men and women.

PubMed

Betancourt, Eve M; Wahbah, Mary M; Been, Laura C; Chiao, Elizabeth Y; Citron, Deborah R; Laucirica, Rodolfo

2013-08-01

Human immunodeficiency virus (HIV)-infected individuals have increased risk of anal intraepithelial neoplasia (AIN) and squamous cell carcinoma (SCC). Cytologic screening is invaluable in the detection of cervical neoplasia, therefore many clinicians have adopted anal cytology as part of anal cancer screening in patients at high-risk for anal neoplasia. The purpose of this study is to determine whether anal cytology is a valuable screening test for identifying AIN in HIV+ patients. The cohort included 228 HIV+ patients who underwent anal cancer screening with collection of 318 anal cytology specimens between January 2006 and December 2009. Of this group, 74 (32.5%) patients had associated anal biopsies within a 6-month period, with a total of 89 comparison cases. The anal cytology samples were classified using the 2001 Bethesda System terminology. The sensitivity of anal cytology in detecting ASC-US, AIN 1-3 or SCC was 93%. Cytology was 88% sensitive for detecting low-grade AIN (AIN 1), but only 20% sensitive for detecting high-grade AIN (AIN 2-3) or SCC. Atypical squamous cells of undetermined significance cases were distributed evenly between low- and high-grade AIN, with two cases having normal histology. Only six cases had negative cytology, all of which were associated with AIN on biopsy, for a false negative rate of 7%. Anal cytology is a good predictor of AIN, as confirmed by the high degree of sensitivity. However, there is poor correlation between the cytological and histological grade of AIN. Cytology underestimates the grade of dysplasia compared to the corresponding biopsy. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Rapid assessment of Schistosoma mansoni: the validity, applicability and cost-effectiveness of the Lot Quality Assurance Sampling method in Uganda

PubMed Central

Brooker, Simon; Kabatereine, Narcis B.; Myatt, Mark; Stothard, J. Russell; Fenwick, Alan

2007-01-01

Summary Rapid and accurate identification of communities at highest risk of morbidity from schistosomiasis is key for sustainable control. Although school questionnaires can effectively and inexpensively identify communities with a high prevalence of Schistosoma haematobium, parasitological screening remains the preferred option for S. mansoni. To help reduce screening costs, we investigated the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools according categories of S. mansoni prevalence in Uganda, and explored its applicability and cost-effectiveness. First, we evaluated several sampling plans using computer simulation and then field tested one sampling plan in 34 schools in Uganda. Finally, cost-effectiveness of different screening and control strategies (including mass treatment without prior screening) was determined, and sensitivity analysis undertaken to assess the effect of infection levels and treatment costs. In identifying schools with prevalence ≥50%, computer simulations showed that LQAS had high levels of sensitivity and specificity (>90%) at sample sizes <20. The method also provides an ability to classify communities into three prevalence categories. Field testing showed that LQAS where 15 children were sampled had excellent diagnostic performance (sensitivity: 100%, specificity: 96.4%, positive predictive value: 85.7% and negative predictive value: 92.3%). Screening using LQAS was more cost-effective than mass treating all schools (US$ 218 vs. US$ 482 / high prevalence school treated). Threshold analysis indicated that parasitological screening and mass treatment would become equivalent for settings where prevalence exceeds 50% in 75% of schools and for treatment costs of US$ 0.19 per schoolchild. We conclude that, in Uganda, LQAS provides a rapid, valid, and cost-effective method for guiding decision makers in allocating finite resources for the control of schistosomiasis. PMID:15960703

Rapid assessment of Schistosoma mansoni: the validity, applicability and cost-effectiveness of the Lot Quality Assurance Sampling method in Uganda.

PubMed

Brooker, Simon; Kabatereine, Narcis B; Myatt, Mark; Russell Stothard, J; Fenwick, Alan

2005-07-01

Rapid and accurate identification of communities at highest risk of morbidity from schistosomiasis is key for sustainable control. Although school questionnaires can effectively and inexpensively identify communities with a high prevalence of Schistosoma haematobium, parasitological screening remains the preferred option for S. mansoni. To help reduce screening costs, we investigated the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools according to categories of S. mansoni prevalence in Uganda, and explored its applicability and cost-effectiveness. First, we evaluated several sampling plans using computer simulation and then field tested one sampling plan in 34 schools in Uganda. Finally, cost-effectiveness of different screening and control strategies (including mass treatment without prior screening) was determined, and sensitivity analysis undertaken to assess the effect of infection levels and treatment costs. In identifying schools with prevalences > or =50%, computer simulations showed that LQAS had high levels of sensitivity and specificity (>90%) at sample sizes <20. The method also provides an ability to classify communities into three prevalence categories. Field testing showed that LQAS where 15 children were sampled had excellent diagnostic performance (sensitivity: 100%, specificity: 96.4%, positive predictive value: 85.7% and negative predictive value: 92.3%). Screening using LQAS was more cost-effective than mass treating all schools (US$218 vs. US$482/high prevalence school treated). Threshold analysis indicated that parasitological screening and mass treatment would become equivalent for settings where prevalence > or =50% in 75% of schools and for treatment costs of US$0.19 per schoolchild. We conclude that, in Uganda, LQAS provides a rapid, valid and cost-effective method for guiding decision makers in allocating finite resources for the control of schistosomiasis.

Acute Brain Imaging in Children: Can MRI Replace CT as a Screening Tool?

PubMed

Wagner, Matthias W; Kontzialis, Marinos; Seeburg, Daniel; Stern, Steven E; Oshmyansky, Alexander; Poretti, Andrea; Huisman, Thierry A G M

2016-01-01

To determine if axial T2-weighted imaging can serve as screening tool for pediatric brain imaging. We retrospectively evaluated consecutive brain magnetic resonance imaging (MRI) data of 161 children (74 girls) with a mean age of 7.44 ± 5.71 years. Standard of reference was the final report of neuroradiology attendings. Three readers with different levels of experience were blinded for clinical diagnoses and study indications. First, readers studied only the axial T2-weighted screening sequence. Second, they studied all available anatomical and functional MRI sequences as performed per standard protocol for each clinical indication. The readings were classified as normal or abnormal. Sensitivity and specificity were measured. Axial T2 screening yielded a sensitivity of 77-88% and a specificity of 92%. The full studies/data sets had a sensitivity of 89-95% and a specificity of 86-93%. Nineteen of 167 studies were acquired for acute and 148 of 167 studies for nonacute clinical indication. Twenty-five false-negative diagnoses paneled in three groups were made by all readers together. Readers misread four of 19 studies with acute and 21 of 148 studies with nonacute clinical indication. Four of 21 misread studies with nonacute indications harbored unexpected findings needing management. Axial T2 screening can detect pediatric brain abnormalities with high sensitivity and specificity and can possibly replace CT as screening tool if the reading physician is aware of possible limitations/pitfalls. The level of experience influences sensitivity and specificity. Adding diffusion-weighted imaging and susceptibility-weighted imaging to a 3-dimensional T2-weighted sequence would most likely further increase sensitivity and specificity. Copyright © 2015 by the American Society of Neuroimaging.

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/.

Evaluation of Cervicography Screening for Cervical Cancer in a High Risk Population

DTIC Science & Technology

2000-02-16

Higher sensitivity was associated with younger age , premenopausal status, the presence of metaplasia. the absence of cervicovaginal atrophy, and improved...recommended for postmenopausal women and/or women ages 50 and older. iv EVALUATION OF CERVICOGRAPHY SCREENING FOR CERVICAL CANCER IN A HIGH-RISK POPULATION...Institute. The Guanacaste site was selected because of its consistently high age -adjusted rates of cervical cancer despite existing Papanicolaou

 The product of triglycerides and glucose as biomarker for screening simple steatosis and NASH in asymptomatic women.

PubMed

Simental-Mendía, Luis E; Simental-Mendía, Esteban; Rodríguez-Hernández, Heriberto; Rodríguez-Morán, Martha; Guerrero-Romero, Fernando

2016-01-01

 Introduction and aim. Given that early identification of non-alcoholic fatty liver disease (NAFLD) is an important issue for primary prevention of hepatic disease, the objectives of this study were to evaluate the efficacy of the product of triglyceride and glucose levels (TyG) for screening simple steatosis and non-alcoholic steatohepatitis (NASH) in asymptomatic women, and to compare its efficacy vs. other biomarkers for recognizing NAFLD. Asymptomatic women aged 20 to 65 years were enrolled into a cross-sectional study. The optimal values of TyG, for screening simple steatosis and NASH were established on a Receiver Operating Characteristic scatter plot; the sensitivity, specificity, and likelihood ratios of TyG index were estimated versus liver biopsy. According sensitivity and specificity, the efficacy of TyG was compared versus the well-known clinical biomarkers for recognizing NAFLD. A total of 50 asymptomatic women were enrolled. The best cutoff point of TyG for screening simple steatosis was 4.58 (sensitivity 0.94, specificity 0.69); in addition, the best cutoff point of TyG index for screening NASH was 4.59 (sensitivity 0.87, specificity 0.69). The positive and negative likelihood ratios were 3.03 and 0.08 for simple steatosis, and 2.80 and 0.18 for NASH. As compared versus SteatoTest, NashTest, Fatty liver index, and Algorithm, the TyG showed to be the best test for screening. TyG has high sensitivity and low negative likelihood ratio; as compared with other clinical biomarkers, the TyG showed to be the best test for screening simple steatosis and NASH.

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

PubMed

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

2015-01-01

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

School-Based Screening for Suicide Risk: Balancing Costs and Benefits

PubMed Central

Wilcox, Holly; Huo, Yanling; Turner, J. Blake; Fisher, Prudence; Shaffer, David

2010-01-01

Objectives. We examined the effects of a scoring algorithm change on the burden and sensitivity of a screen for adolescent suicide risk. Methods. The Columbia Suicide Screen was used to screen 641 high school students for high suicide risk (recent ideation or lifetime attempt and depression, or anxiety, or substance use), determined by subsequent blind assessment with the Diagnostic Interview Schedule for Children. We compared the accuracy of different screen algorithms in identifying high-risk cases. Results. A screen algorithm comprising recent ideation or lifetime attempt or depression, anxiety, or substance-use problems set at moderate-severity level classed 35% of students as positive and identified 96% of high-risk students. Increasing the algorithm's threshold reduced the proportion identified to 24% and identified 92% of high-risk cases. Asking only about recent suicidal ideation or lifetime suicide attempt identified 17% of the students and 89% of high-risk cases. The proportion of nonsuicidal diagnosis–bearing students found with the 3 algorithms was 62%, 34%, and 12%, respectively. Conclusions. The Columbia Suicide Screen threshold can be altered to reduce the screen-positive population, saving costs and time while identifying almost all students at high risk for suicide. PMID:20634467

Hearing Screening of High-Risk Newborns with Brainstem Auditory Evoked Potentials: A Follow-Up Study.

ERIC Educational Resources Information Center

Shannon, Dorothy A.; And Others

1984-01-01

The brainstem auditory evoked potential (BAEP) was evaluated as a hearing screening test in 168 high-risk newborns. The BAEP was found to be a sensitive procedure for the early identification of hearing-impaired newborns. However, the yield of significant hearing abnormalities was less than predicted in other studies using BAEP. (Author/CL)

An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer.

PubMed

Lu, Meng-Han; Hu, Ling-Yun; Du, Xin-Xin; Yang, Min; Zhang, Wei-Yi; Huang, Ke; Li, Li-An; Jiang, Shu-Fang; Li, Ya-Li

2015-01-01

High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People's liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable.

An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer

PubMed Central

Lu, Meng-Han; Hu, Ling-Yun; Du, Xin-Xin; Yang, Min; Zhang, Wei-Yi; Huang, Ke; Li, Li-An; Jiang, Shu-Fang; Li, Ya-Li

2015-01-01

High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People’s liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable. PMID:26221336

Improved sensitivity of vaginal self-collection and high-risk human papillomavirus testing.

PubMed

Belinson, Jerome L; Du, Hui; Yang, Bin; Wu, Ruifang; Belinson, Suzanne E; Qu, Xinfeng; Pretorius, Robert G; Yi, Xin; Castle, Philip E

2012-04-15

Self-collected vaginal specimens tested for high-risk human papillomavirus (HR-HPV) have been shown to be less sensitive for the detection of cervical intraepithelial neoplasia or cancer (≥CIN 3) than physician-collected endocervical specimens. To increase the sensitivity of self-collected specimens, we studied a self-sampling device designed to obtain a larger specimen from the upper vagina (POI/NIH self-sampler) and a more sensitive polymerase chain reaction (PCR)-based HR-HPV assay. Women (10,000) were screened with cervical cytology and HR-HPV testing of vaginal self-collected and endocervical physician-collected specimens. Women were randomly assigned to use either a novel self-collection device (POI/NIH self-sampler) or conical-shaped brush (Qiagen). The self-collected and clinician-collected specimens were assayed by Cervista (Hologic) and the research only PCR-based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Women with any abnormal screening test underwent colposcopy and biopsy. Women (8,556), mean age of 38.9, had complete data; 1.6% had ≥ CIN 3. For either HR-HPV assay, the sensitivity was similar for the two self-collection devices. Tested with Cervista, the sensitivity for ≥CIN 3 of self-collected specimens was 70.9% and for endocervical specimens was 95.0% (p = 0.0001). Tested with MALDI-TOF, the sensitivity for ≥CIN 3 of self-collected specimens was 94.3% and for endocervical specimens was also 94.3% (p = 1.0). A self-collected sample using a PCR-based assay with the capability of very high throughput has similar sensitivity as a direct endocervical specimen obtained by a physician. Large population-based screening "events" in low-resource settings could be achieved by promoting self-collection and centralized high-throughput, low-cost testing by PCR-based MALDI-TOF. Copyright © 2011 UICC.

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting.

PubMed

Ciatto, Stefano; Bonardi, Rita; Lombardi, Claudio; Zappa, Marco; Gervasi, Ginetta

2002-01-01

To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.

Self-rating inventory for posttraumatic stress disorder: review of the psychometric properties of a new brief Dutch screening instrument.

PubMed

Hovens, J E; Bramsen, I; van der Ploeg, H M

2002-06-01

The Self-rating Inventory for Posttraumatic Stress Disorder of 22 items was developed for use with populations without identified traumatic experiences. The inventory has been used extensively in survey research in The Netherlands. This paper examines the psychometric properties. In four different groups (trauma and psychiatric patients, elderly Dutch subjects, former peacekeepers, and medical students) internal consistency, test-retest reliability, concurrent and discriminant validity, and sensitivity and specificity are analyzed. The inventory showed good internal consistency, test-retest reliability, concurrent and discriminant validity, and high sensitivity and specificity. It appears to be valuable for survey research on posttraumatic stress in nonselected populations. As a screening device, high sensitivity for PTSD symptoms is evident even when the traumatic event has not been defined.

Home oximetry to screen for obstructive sleep apnoea in Down syndrome.

PubMed

Hill, Catherine M; Elphick, Heather E; Farquhar, Michael; Gringras, Paul; Pickering, Ruth M; Kingshott, Ruth N; Martin, Jane; Reynolds, Janine; Joyce, Anna; Gavlak, Johanna C; Evans, Hazel J

2018-05-14

Children with Down syndrome are at high risk of obstructive sleep apnoea (OSA) and screening is recommended. Diagnosis of OSA should be confirmed with multichannel sleep studies. We aimed to determine whether home pulse oximetry (HPO) discriminates children at high risk of OSA, who need further diagnostic multichannel sleep studies. Cross-sectional prospective study in a training sample recruited through three UK centres. Validation sample used single-centre retrospective analysis of clinical data. Children with Down syndrome aged 0.5-6 years. Diagnostic multichannel sleep study and HPO. Sensitivity and specificity of HPO to predict moderate-to-severe OSA. 161/202 children with Down syndrome met quality criteria for inclusion and 25 had OSA. In this training sample, the best HPO parameter predictors of OSA were the delta 12 s index >0.555 (sensitivity 92%, specificity 65%) and 3% oxyhaemoglobin (SpO 2 ) desaturation index (3% ODI)>6.15 dips/hour (sensitivity 92%, specificity 63%). Combining variables (delta 12 s index, 3% ODI, mean and minimum SpO 2 ) achieved sensitivity of 96% but reduced specificity to 52%. All predictors retained or improved sensitivity in a clinical validation sample of 50 children with variable loss of specificity, best overall was the delta 12 s index, a measure of baseline SpO 2 variability (sensitivity 92%; specificity 63%). HPO screening could halve the number of children with Down syndrome needing multichannel sleep studies and reduce the burden on children, families and health services alike. This approach offers a practical universal screening approach for OSA in Down syndrome that is accessible to the non-specialist paediatrician. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Psychometric properties and diagnostic value of 'lexical screening for aphasias'].

PubMed

Pena-Chavez, R; Martinez-Jimenez, L; Lopez-Espinoza, M

2014-09-16

INTRODUCTION. Language assessment in persons with brain injury makes it possible to know whether they require language rehabilitation or not. Given the importance of a precise evaluation, assessment instruments must be valid and reliable, so as to avoid mistaken and subjective diagnoses. AIM. To validate 'lexical screening for aphasias' in a sample of 58 Chilean individuals. SUBJECTS AND METHODS. A screening-type language test, lasting 20 minutes and based on the lexical processing model devised by Patterson and Shewell (1987), was constructed. The sample was made up of two groups containing 29 aphasic subjects and 29 control subjects from different health centres in the regions of Biobio and Maule, Chile. Their ages ranged between 24 and 79 years and had between 0 and 17 years' schooling. Tests were carried out to determine discriminating validity, concurrent validity with the aphasia disorder assessment battery, reliability, sensitivity and specificity. RESULTS. The statistical analysis showed a high discriminating validity (p < 0.001), an acceptable mean concurrent validity with aphasia disorder assessment battery (rs = 0.65), high mean reliability (alpha = 0.87), moderate mean sensitivity (69%) and high mean specificity (86%). CONCLUSION. 'Lexical screening for aphasias' is valid and reliable for assessing language in persons with aphasias; it is sensitive for detecting aphasic subjects and is specific for precluding language disorders in persons with normal language abilities.

Exploitation of the Apoptosis-Primed State of MYCN-Amplified Neuroblastoma to Develop a Potent and Specific Targeted Therapy Combination

PubMed Central

Ham, Jungoh; Costa, Carlotta; Sano, Renata; Lochmann, Timothy L.; Sennott, Erin M.; Patel, Neha U.; Dastur, Anahita; Gomez-Caraballo, Maria; Krytska, Kateryna; Hata, Aaron N.; Floros, Konstantinos V.; Hughes, Mark T.; Jakubik, Charles T.; Heisey, Daniel A.R.; Ferrell, Justin T.; Bristol, Molly L.; March, Ryan J.; Yates, Craig; Hicks, Mark A.; Nakajima, Wataru; Gowda, Madhu; Windle, Brad E.; Dozmorov, Mikhail G.; Garnett, Mathew J.; McDermott, Ultan; Harada, Hisashi; Taylor, Shirley M.; Morgan, Iain M.; Benes, Cyril H.; Engelman, Jeffrey A.; Mossé, Yael P.; Faber, Anthony C.

2016-01-01

Summary Fewer than half of children with high-risk neuroblastoma survive. Many of these tumors harbor high-level amplification of MYCN, which correlates with poor disease outcome. Using data from our large drug screen we predicted, and subsequently demonstrated, that MYCN-amplified neuroblastomas are sensitive to the BCL-2 inhibitor ABT-199. This sensitivity occurs in part through low anti-apoptotic BCL-xL expression, high pro-apoptotic NOXA expression, and paradoxical, MYCN-driven upregulation of NOXA. Screening for enhancers of ABT-199 sensitivity in MYCN-amplified neuroblastomas, we demonstrate that the Aurora Kinase A inhibitor MLN8237 combines with ABT-199 to induce widespread apoptosis. In diverse models of MYCN-amplified neuroblastoma, including a patient-derived xenograft model, this combination uniformly induced tumor shrinkage, and in multiple instances led to complete tumor regression. PMID:26859456

Revisiting the cost-effectiveness of universal cervical length screening: importance of progesterone efficacy.

PubMed

Jain, Siddharth; Kilgore, Meredith; Edwards, Rodney K; Owen, John

2016-07-01

Preterm birth (PTB) is a significant cause of neonatal morbidity and mortality. Studies have shown that vaginal progesterone therapy for women diagnosed with shortened cervical length can reduce the risk of PTB. However, published cost-effectiveness analyses of vaginal progesterone for short cervix have not considered an appropriate range of clinically important parameters. To evaluate the cost-effectiveness of universal cervical length screening in women without a history of spontaneous PTB, assuming that all women with shortened cervical length receive progesterone to reduce the likelihood of PTB. A decision analysis model was developed to compare universal screening and no-screening strategies. The primary outcome was the cost-effectiveness ratio of both the strategies, defined as the estimated patient cost per quality-adjusted life-year (QALY) realized by the children. One-way sensitivity analyses were performed by varying progesterone efficacy to prevent PTB. A probabilistic sensitivity analysis was performed to address uncertainties in model parameter estimates. In our base-case analysis, assuming that progesterone reduces the likelihood of PTB by 11%, the incremental cost-effectiveness ratio for screening was $158,000/QALY. Sensitivity analyses show that these results are highly sensitive to the presumed efficacy of progesterone to prevent PTB. In a 1-way sensitivity analysis, screening results in cost-saving if progesterone can reduce PTB by 36%. Additionally, for screening to be cost-effective at WTP=$60,000 in three clinical scenarios, progesterone therapy has to reduce PTB by 60%, 34% and 93%. Screening is never cost-saving in the worst-case scenario or when serial ultrasounds are employed, but could be cost-saving with a two-day hospitalization only if progesterone were 64% effective. Cervical length screening and treatment with progesterone is a not a dominant, cost-effective strategy unless progesterone is more effective than has been suggested by available data for US women. Until future trials demonstrate greater progesterone efficacy, and effectiveness studies confirm a benefit from screening and treatment, the cost-effectiveness of universal cervical length screening in the United States remains questionable. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Utility of screening ultrasound after first febrile UTI among patients with clinically significant vesicoureteral reflux.

PubMed

Massanyi, Eric Z; Preece, Janae; Gupta, Angela; Lin, Susan M; Wang, Ming-Hsien

2013-10-01

To assess the sensitivity and negative predictive value (NPV) of screening renal and bladder ultrasound (RBUS) after initial febrile urinary tract infection (UTI) among patients with clinically significant vesicoureteral reflux (VUR). A retrospective review was performed of all children <2 years of age who presented with a febrile UTI between 2004 and 2011. The sensitivity and NPV of initial RBUS was calculated among patients who were found to have high-grade (IV-V) VUR. Additionally, initial RBUS among patients with evidence of photopenia on dimercaptosuccinic acid (DMSA) scan or who underwent surgical intervention were reviewed. One hundred forty-four patients with febrile UTI were identified; available RBUS, voiding cystourethrogram (VCUG), and DMSA results for each kidney were reviewed. One hundred fifty-eight kidneys had evidence of VUR on VCUG, and initial RBUS demonstrated abnormality in 25 (sensitivity 0.17). Forty-five kidneys had high-grade VUR and RBUS revealed abnormality in 16 (sensitivity 0.36). One hundred seventy-eight kidneys had no evidence of abnormality on initial RBUS, and 136 (76%) were found to have VUR (NPV 0.24), of which 31 had high-grade VUR (NPV 0.83). Seven kidneys had scarring on DMSA and initial RBUS was normal in 4 (57%). Twelve of 19 patients (63%) who eventually underwent surgical intervention had a normal initial RBUS. RBUS has poor sensitivity and NPV for detecting high-grade VUR in patients <2 years who present with a febrile UTI. A significant number of patients who were diagnosed with high-grade VUR, renal scarring, or underwent surgical correction of VUR had a negative screening RBUS. Copyright © 2013 Elsevier Inc. All rights reserved.

Breast cancer screening effect across breast density strata: A case-control study.

PubMed

van der Waal, Daniëlle; Ripping, Theodora M; Verbeek, André L M; Broeders, Mireille J M

2017-01-01

Breast cancer screening is known to reduce breast cancer mortality. A high breast density may affect this reduction. We assessed the effect of screening on breast cancer mortality in women with dense and fatty breasts separately. Analyses were performed within the Nijmegen (Dutch) screening programme (1975-2008), which invites women (aged 50-74 years) biennially. Performance measures were determined. Furthermore, a case-control study was performed for women having dense and women having fatty breasts. Breast density was assessed visually with a dichotomized Wolfe scale. Breast density data were available for cases. The prevalence of dense breasts among controls was estimated with age-specific rates from the general population. Sensitivity analyses were performed on these estimates. Screening performance was better in the fatty than in the dense group (sensitivity 75.7% vs 57.8%). The mortality reduction appeared to be smaller for women with dense breasts, with an odds ratio (OR) of 0.87 (95% CI 0.52-1.45) in the dense and 0.59 (95% CI 0.44-0.79) in the fatty group. We can conclude that high density results in lower screening performance and appears to be associated with a smaller mortality reduction. Breast density is thus a likely candidate for risk-stratified screening. More research is needed on the association between density and screening harms. © 2016 UICC.

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.

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.

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

PubMed

Shankar, Manoharan; Priyadharshini, Ramachandran; Gunasekaran, Paramasamy

2009-08-01

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

A 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.

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

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.

Cost-effectiveness of screening for asymptomatic carotid atherosclerotic disease.

PubMed

Derdeyn, C P; Powers, W J

1996-11-01

The value of screening for asymptomatic carotid stenosis has become an important issue with the recently reported beneficial effect of endarterectomy. The purpose of this study is to evaluate the cost-effectiveness of using Doppler ultrasound as a screening tool to select subjects for arteriography and subsequent surgery. A computer model was developed to simulate the cost-effectiveness of screening a cohort of 1000 men during a 20-year period. The primary outcome measure was incremental present-value dollar expenditures for screening and treatment per incremental present-value quality-adjusted life-year (QALY) saved. Estimates of disease prevalence and arteriographic and surgical complication rates were obtained from the literature. Probabilities of stroke and death with surgical and medical treatment were obtained from published clinical trials. Doppler ultrasound sensitivity and specificity were obtained through review of local experience. Estimates of costs were obtained from local Medicare reimbursement data. A one-time screening program of a population with a high prevalence (20%) of > or = 60% stenosis cost $35130 per incremental QALY gained. Decreased surgical benefit or increased annual discount rate was detrimental, resulting in lost QALYs. Annual screening cost $457773 per incremental QALY gained. In a low-prevalence (4%) population, one-time screening cost $52588 per QALY gained, while annual screening was detrimental. The cost-effectiveness of a one-time screening program for an asymptomatic population with a high prevalence of carotid stenosis may be cost-effective. Annual screening is detrimental. The most sensitive variables in this simulation model were long-term stroke risk reduction after surgery and annual discount rate for accumulated costs and QALYs.

Validation of the 4P's Plus screen for substance use in pregnancy validation of the 4P's Plus.

PubMed

Chasnoff, I J; Wells, A M; McGourty, R F; Bailey, L K

2007-12-01

The purpose of this study is to validate the 4P's Plus screen for substance use in pregnancy. A total of 228 pregnant women enrolled in prenatal care underwent screening with the 4P's Plus and received a follow-up clinical assessment for substance use. Statistical analyses regarding reliability, sensitivity, specificity, and positive and negative predictive validity of the 4Ps Plus were conducted. The overall reliability for the five-item measure was 0.62. Seventy-four (32.5%) of the women had a positive screen. Sensitivity and specificity were very good, at 87 and 76%, respectively. Positive predictive validity was low (36%), but negative predictive validity was quite high (97%). Of the 31 women who had a positive clinical assessment, 45% were using less than 1 day per week. The 4P's Plus reliably and effectively screens pregnant women for risk of substance use, including those women typically missed by other perinatal screening methodologies.

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.

Sensitivity and specificity of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for detecting post-cardiac surgery delirium: A single-center study in Japan.

PubMed

Nishimura, Katsuji; Yokoyama, Kanako; Yamauchi, Noriko; Koizumi, Masako; Harasawa, Nozomi; Yasuda, Taeko; Mimura, Chizuru; Igita, Hazuki; Suzuki, Eriko; Uchiide, Yoko; Seino, Yusuke; Nomura, Minoru; Yamazaki, Kenji; Ishigooka, Jun

2016-01-01

To compare the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for detecting post-cardiac surgery delirium. These tools have not been tested in a specialized cardio-surgical ICU. Sensitivities and specificities of each tool were assessed in a cardio-surgical ICU in Japan by two trained nurses independently. Results were compared with delirium diagnosed by psychiatrists using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. There were 110 daily, paired assessments in 31 patients. The CAM-ICU showed 38% sensitivity and 100% specificity for both nurses. All 20 false-negative cases resulted from high scores in the auditory attention screening in CAM-ICU. The ICDSC showed 97% and 94% sensitivity, and 97% and 91% specificity for the two nurses (cutoff ≥4). In a Japanese cardio-surgical ICU, the ICDSC had a higher sensitivity than the CAM-ICU. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of RealStar Reverse Transcription–Polymerase Chain Reaction Kits for Filovirus Detection in the Laboratory and Field

PubMed Central

Rieger, Toni; Kerber, Romy; El Halas, Hussein; Pallasch, Elisa; Duraffour, Sophie; Günther, Stephan; Ölschläger, Stephan

2016-01-01

Background. Diagnosis of Ebola virus (EBOV) disease (EVD) requires laboratory testing. Methods. The RealStar Filovirus Screen reverse transcription–polymerase chain reaction (RT-PCR) kit and the derived RealStar Zaire Ebolavirus RT-PCR kit were validated using in vitro transcripts, supernatant of infected cell cultures, and clinical specimens from patients with EVD. Results. The Filovirus Screen kit detected EBOV, Sudan virus, Taï Forest virus, Bundibugyo virus, Reston virus, and Marburg virus and differentiated between the genera Ebolavirus and Marburgvirus. The amount of filovirus RNA that could be detected with a probability of 95% ranged from 11 to 67 RNA copies/reaction on a LightCycler 480 II. The Zaire Ebolavirus kit is based on the Filovirus Screen kit but was optimized for detection of EBOV. It has an improved signal-to-noise ratio at low EBOV RNA concentrations and is somewhat more sensitive than the Filovirus kit. Both kits show significantly lower analytical sensitivity on a SmartCycler II. Clinical evaluation revealed that the SmartCycler II, compared with other real-time PCR platforms, decreases the clinical sensitivity of the Filovirus Screen kit to diagnose EVD at an early stage. Conclusions. The Filovirus Screen kit detects all human-pathogenic filoviruses with good analytical sensitivity if performed on an appropriate real-time PCR platform. High analytical sensitivity is important for early diagnosis of EVD. PMID:27549586

Is computer aided detection (CAD) cost effective in screening mammography? A model based on the CADET II study

PubMed Central

2011-01-01

Background Single reading with computer aided detection (CAD) is an alternative to double reading for detecting cancer in screening mammograms. The aim of this study is to investigate whether the use of a single reader with CAD is more cost-effective than double reading. Methods Based on data from the CADET II study, the cost-effectiveness of single reading with CAD versus double reading was measured in terms of cost per cancer detected. Cost (Pound (£), year 2007/08) of single reading with CAD versus double reading was estimated assuming a health and social service perspective and a 7 year time horizon. As the equipment cost varies according to the unit size a separate analysis was conducted for high, average and low volume screening units. One-way sensitivity analyses were performed by varying the reading time, equipment and assessment cost, recall rate and reader qualification. Results CAD is cost increasing for all sizes of screening unit. The introduction of CAD is cost-increasing compared to double reading because the cost of CAD equipment, staff training and the higher assessment cost associated with CAD are greater than the saving in reading costs. The introduction of single reading with CAD, in place of double reading, would produce an additional cost of £227 and £253 per 1,000 women screened in high and average volume units respectively. In low volume screening units, the high cost of purchasing the equipment will results in an additional cost of £590 per 1,000 women screened. One-way sensitivity analysis showed that the factors having the greatest effect on the cost-effectiveness of CAD with single reading compared with double reading were the reading time and the reader's professional qualification (radiologist versus advanced practitioner). Conclusions Without improvements in CAD effectiveness (e.g. a decrease in the recall rate) CAD is unlikely to be a cost effective alternative to double reading for mammography screening in UK. This study provides updated estimates of CAD costs in a full-field digital system and assessment cost for women who are re-called after initial screening. However, the model is highly sensitive to various parameters e.g. reading time, reader qualification, and equipment cost. PMID:21241473

Laboratory audit as part of the quality assessment of a primary HPV-screening program.

PubMed

Hortlund, Maria; Sundström, Karin; Lamin, Helena; Hjerpe, Anders; Dillner, Joakim

2016-02-01

As primary HPV screening programs are rolled out, methods are needed for routine quality assurance of HPV laboratory analyzes. To explore the use of similar design for audit as currently used in cytology-based screening, to estimate the clinical sensitivity to identify women at risk for CIN 3 or worse (CIN3+). Population-based cohort study conducted within the cervical screening program in Stockholm, Sweden, in 2011-2012. All women with histopathologically confirmed CIN3+ in the following two years were identified by registry analysis. Primary HPV and cytology screening results were collected. For women who had not been HPV tested, biobanked cytology samples were HPV-tested. If the original HPV result had been negative, the sample and subsequent biopsies were analyzed with broad HPV typing (general primer PCR and Luminex). 154 women had a biobanked prediagnostic cytology sample taken up to 2 years before a histopathologically confirmed CIN3+. The high-risk HPV-positivity was 97% (148/154 women), whereas 143/154 (94%) women had had a cytological abnormality. Among the six HPV-negative samples, one sample was HPV 33 positive in repeat testing whereas the other five cases were HPV-negative also on repeat testing, but HPV-positive in the subsequent tumor tissue. A sensitivity of the HPV test that is higher than the sensitivity of cytology suggests adequate quality of the testing. Regular audits of clinical sensitivity, similar to those of cytology-based screening, should be used also in HPV-based screening programs, in order to continuously monitor the performance of the analyzes. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Impact of normalization methods on high-throughput screening data with high hit rates and drug testing with dose-response data.

PubMed

Mpindi, John-Patrick; Swapnil, Potdar; Dmitrii, Bychkov; Jani, Saarela; Saeed, Khalid; Wennerberg, Krister; Aittokallio, Tero; Östling, Päivi; Kallioniemi, Olli

2015-12-01

Most data analysis tools for high-throughput screening (HTS) seek to uncover interesting hits for further analysis. They typically assume a low hit rate per plate. Hit rates can be dramatically higher in secondary screening, RNAi screening and in drug sensitivity testing using biologically active drugs. In particular, drug sensitivity testing on primary cells is often based on dose-response experiments, which pose a more stringent requirement for data quality and for intra- and inter-plate variation. Here, we compared common plate normalization and noise-reduction methods, including the B-score and the Loess a local polynomial fit method under high hit-rate scenarios of drug sensitivity testing. We generated simulated 384-well plate HTS datasets, each with 71 plates having a range of 20 (5%) to 160 (42%) hits per plate, with controls placed either at the edge of the plates or in a scattered configuration. We identified 20% (77/384) as the critical hit-rate after which the normalizations started to perform poorly. Results from real drug testing experiments supported this estimation. In particular, the B-score resulted in incorrect normalization of high hit-rate plates, leading to poor data quality, which could be attributed to its dependency on the median polish algorithm. We conclude that a combination of a scattered layout of controls per plate and normalization using a polynomial least squares fit method, such as Loess helps to reduce column, row and edge effects in HTS experiments with high hit-rates and is optimal for generating accurate dose-response curves. john.mpindi@helsinki.fi. Supplementary information: R code and Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Gene expression analysis using a highly sensitive DNA microarray for colorectal cancer screening.

PubMed

Koga, Yoshikatsu; Yamazaki, Nobuyoshi; Takizawa, Satoko; Kawauchi, Junpei; Nomura, Osamu; Yamamoto, Seiichiro; Saito, Norio; Kakugawa, Yasuo; Otake, Yosuke; Matsumoto, Minori; Matsumura, Yasuhiro

2014-01-01

Half of all patients with small, right-sided, non-metastatic colorectal cancer (CRC) have negative results for the fecal occult blood test (FOBT). In the present study, the usefulness of CRC screening with a highly sensitive DNA microarray was evaluated in comparison with that by FOBT using fecal samples. A total of 53 patients with CRC and 61 healthy controls were divided into "training" and "validation sets". For the gene profiling, total RNA extracted from 0.5 g of feces was hybridized to a highly sensitive DNA chip. The expressions of 43 genes were significantly higher in the patients with CRC than in healthy controls (p<0.05). In the training set, the sensitivity and specificity of the DNA chip assay using six genes were 85.4% and 85.2%, respectively. On the other hand, in the validation set, the sensitivity and specificity of the DNA chip assay were 85.2% and 85.7%, respectively. The sensitivities of the DNA chip assay were higher than those of FOBT in cases of the small, right-sided, early-CRC, tumor invading up to the muscularis propria (i.e. surface tumor) subgroups. In particular, the sensitivities of the DNA chip assay in the surface tumor and early-CRC subgroups were significantly higher than those of FOBT (p=0.023 and 0.019, respectively.). Gene profiling assay using a highly sensitive DNA chip was more effective than FOBT at detecting patients with small, right-sided, surface tumor, and early-stage CRC.

Large-Area Cross-Aligned Silver Nanowire Electrodes for Flexible, Transparent, and Force-Sensitive Mechanochromic Touch Screens.

PubMed

Cho, Seungse; Kang, Saewon; Pandya, Ashish; Shanker, Ravi; Khan, Ziyauddin; Lee, Youngsu; Park, Jonghwa; Craig, Stephen L; Ko, Hyunhyub

2017-04-25

Silver nanowire (AgNW) networks are considered to be promising structures for use as flexible transparent electrodes for various optoelectronic devices. One important application of AgNW transparent electrodes is the flexible touch screens. However, the performances of flexible touch screens are still limited by the large surface roughness and low electrical to optical conductivity ratio of random network AgNW electrodes. In addition, although the perception of writing force on the touch screen enables a variety of different functions, the current technology still relies on the complicated capacitive force touch sensors. This paper demonstrates a simple and high-throughput bar-coating assembly technique for the fabrication of large-area (>20 × 20 cm 2 ), highly cross-aligned AgNW networks for transparent electrodes with the sheet resistance of 21.0 Ω sq -1 at 95.0% of optical transmittance, which compares favorably with that of random AgNW networks (sheet resistance of 21.0 Ω sq -1 at 90.4% of optical transmittance). As a proof of concept demonstration, we fabricate flexible, transparent, and force-sensitive touch screens using cross-aligned AgNW electrodes integrated with mechanochromic spiropyran-polydimethylsiloxane composite film. Our force-sensitive touch screens enable the precise monitoring of dynamic writings, tracing and drawing of underneath pictures, and perception of handwriting patterns with locally different writing forces. The suggested technique provides a robust and powerful platform for the controllable assembly of nanowires beyond the scale of conventional fabrication techniques, which can find diverse applications in multifunctional flexible electronic and optoelectronic devices.

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.

Anthropometric indicators of obesity as screening tools for high blood pressure in the elderly.

PubMed

Leal Neto, João de Souza; Coqueiro, Raildo da Silva; Freitas, Roberta Souza; Fernandes, Marcos Henrique; Oliveira, Daniela Sousa; Barbosa, Aline Rodrigues

2013-08-01

The study objectives were to investigate the indicators of obesity most associated with high blood pressure in community-dwelling elderly and identify among these which one best discriminates high blood pressure. This is an epidemiological, population, cross-sectional and home-based study of elderly people (≥ 60 years, n = 316) residing in northeastern Brazil. The results showed that the body mass index and the body adiposity index were the indicators more closely associated with high blood pressure in both sexes. Both in female and male genders, body mass index showed high values of specificity and low sensitivity values for discriminating high blood pressure, whereas the body adiposity index showed high sensitivity and moderate specificity values. In clinical practice and health surveillance, it is suggested that both indicators be used as screening tools for hypertension in the elderly. © 2013 Wiley Publishing Asia Pty Ltd.

Eight-Channel AC Magnetosusceptometer of Magnetic Nanoparticles for High-Throughput and Ultra-High-Sensitivity Immunoassay

PubMed Central

Chieh, Jen-Jie; Wei, Wen-Chun; Chen, Hsin-Hsein; Lee, Yen-Fu; Lin, Feng-Chun; Chiang, Ming-Hsien; Chiu, Ming-Jang; Horng, Herng-Er; Yang, Shieh-Yueh

2018-01-01

An alternating-current magnetosusceptometer of antibody-functionalized magnetic nanoparticles (MNPs) was developed for immunomagnetic reduction (IMR). A high-sensitivity, high-critical-temperature superconducting quantum interference device was used in the magnetosusceptometer. Minute levels of biomarkers of early-stage neurodegeneration diseases were detectable in serum, but measuring each biomarker required approximately 4 h. Hence, an eight-channel platform was developed in this study to fit minimal screening requirements for Alzheimer’s disease. Two consistent results were measured for three biomarkers, namely Aβ40, Aβ42, and tau protein, per human specimen. This paper presents the instrument configuration as well as critical characteristics, such as the low noise level variations among channels, a high signal-to-noise ratio, and the coefficient of variation for the biomarkers’ IMR values. The instrument’s ultrahigh sensitivity levels for the three biomarkers and the substantially shorter total measurement time in comparison with the previous single- and four-channels platforms were also demonstrated in this study. Thus, the eight-channel instrument may serve as a powerful tool for clinical high-throughput screening of Alzheimer’s disease. PMID:29601532

Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State Examination for diagnosing dementia in Parkinson's disease.

PubMed

Kaszás, B; Kovács, N; Balás, I; Kállai, J; Aschermann, Z; Kerekes, Z; Komoly, S; Nagy, F; Janszky, J; Lucza, T; Karádi, K

2012-06-01

Among the non-motor features of Parkinson's disease (PD), cognitive impairment is one of the most troublesome problems. Highly sensitive and specific screening instruments for detecting dementia in PD (PDD) are required in the clinical practice. In our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrooke's Cognitive Examination, ACE; Frontal Assessment Battery, FAB and Mattis Dementia Rating Scale, MDRS) in 73 Parkinson's disease patients without depression. By receiver operating characteristic curve analysis, these screening instruments were tested against the recently established clinical diagnostic criteria of PDD. Best cut-off score for ACE to identify PDD was 80 points (sensitivity = 74.0%, specificity = 78.1%). For FAB the most optimal cut-off value was 12 points (sensitivity = 66.3%, specificity = 72.2%); whereas for MDRS it was 125 points (sensitivity = 89.8%, specificity = 98.3%). Among the examined test batteries, MDRS had the best clinicometric profile for detecting PDD. Although the types of applied screening instruments might differ from movement disorder clinic to clinic within a country, determination of the most specific and sensitive test for the given population remains to be an important task. Our results demonstrated that the specificity and sensitivity of MDRS was better than those of ACE, FAB and MMSE in Hungary. However, further studies with larger sample size and more uniform criteria for participation are required to determine the most suitable screening instrument for cognitive impairment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of 3D-CPA, HR-HPV, and TCT joint detection on cervical disease screening.

PubMed

Liang, Hui; Fu, Min; Zhou, Jian; Song, Lei

2016-08-01

The application value of three-dimensional color power angiography (3D-CPA), high-risk human papillomavirus (HR-HPV), ThinPrep cytology test (TCT) joint detection on cervical disease screening was investigated. In total, 1,900 patients that were examined in Gynecological and Cervix Clinic of Maternal and Child Care Service Center of Xuzhou from June 2012 to March 2015 were enrolled in the present study. After admission, the patients underwent TCT, HR-HPV and 3D-CPA examinations, and vascular morphology and typing, vascularization index (VI) were recorded. Colposcopic biopsy was performed in patients with a positive outcome of any of the three indices. Pathological diagnosis was taken as the golden standard to assess the sensitivity, specificity, diagnostic rate, and Youden index of the three methods being used independently or jointly. Of the 1,900 patients, 276 cases (14.53%) were HR-HPV-positive, 214 cases (11.26%) were VI-positive and 164 cases (8.63%) were TCT-positive. A total of 418 cases were confirmed with a positive outcome of any of the three indices and a cervical biopsy was obtained. Of the 418 cases, 162 cases (38.75%) were diagnosed with chronic cervicitis, 146 cases with low-level cervical intraepithelial neoplasia (CIN) (34.93%), 104 cases (24.88%) with high level CIN, 6 cases (1.44%) with cervical cancer. Histology more than low level CIN was defined as positive: i) screening results when the three methods were used independently: HPV was confirmed with the highest sensitivity (90.63%), VI with the highest specificity (83.95%), and HPV with the highest diagnostic accuracy (83.73%); ii) screening results under HPV+TCT and HPV+TCT+VI: HPV+TCT+VI was confirmed with the highest sensitivity and specificity: sensitivity (94.53%), specificity (81.48%), diagnosis coincidence rate (89.47%) and the highest Youden index of 0.760; and iii) vascular morphology and grading were significantly different in the early stage cervical carcinoma, high level CIM, and cervicitis groups. In conclusion, the joint detection of 3D-CPA, HR-HPV, and TCT improved the sensitivity and accuracy of cervical disease screening. 3D-CPA technology may therefore be used as an auxiliary screening method for cervical cancer.

Sensitivity and specificity of Norwegian optometrists' evaluation of diabetic retinopathy in single-field retinal images - a cross-sectional experimental study.

PubMed

Sundling, Vibeke; Gulbrandsen, Pål; Straand, Jørund

2013-01-10

In the working age group, diabetic retinopathy is a leading cause of visual impairment. Regular eye examinations and early treatment of retinopathy can prevent visual loss, so screening for diabetic retinopathy is cost-effective. Dilated retinal digital photography with the additional use of ophthalmoscopy is the most effective and robust method of diabetic retinopathy screening. The aim of this study was to estimate the sensitivity and specificity of diabetic retinopathy screening when performed by Norwegian optometrists. This study employed a cross-sectional experimental design. Seventy-four optometrists working in private optometric practice were asked to screen 14 single-field retinal images for possible diabetic retinopathy. The screening was undertaken using a web-based visual identification and management of ophthalmological conditions (VIMOC) examination. The images used in the VIMOC examination were selected from a population survey and had been previously examined by two independent ophthalmologists. In order to establish a "gold standard", images were only chosen for use in the VIMOC examination if they had elicited diagnostic agreement between the two independent ophthalmologists. To reduce the possibility of falsely high specificity occurring by chance, half the presented images were of retinas that were not affected by diabetic retinopathy. Sensitivity and specificity for diabetic retinopathy was calculated with 95% confidence intervals (CIs). The mean (95%CI) sensitivity for identifying eyes with any diabetic retinopathy was 67% (62% to 72%). The mean (95%CI) specificity for identifying eyes without diabetic retinopathy was 84% (80% to 89%). The mean (95%CI) sensitivity for identifying eyes with mild non-proliferative diabetic retinopathy or moderate non-proliferative diabetes was 54% (47% to 61%) and 100%, respectively. Only four optometrists (5%) met the required standard of at least 80% sensitivity and 95% specificity that has been previously set for diabetic retinopathy screening programmes. The evaluation of retinal images for diabetic retinopathy by Norwegian optometrists does not meet the required screening standard of at least 80% sensitivity and 95% specificity. The introduction of measures to improve this situation could have implications for both formal optometric training and continuing optometric professional education.

Sensitivity and specificity of Norwegian optometrists’ evaluation of diabetic retinopathy in single-field retinal images – a cross-sectional experimental study

PubMed Central

2013-01-01

Background In the working age group, diabetic retinopathy is a leading cause of visual impairment. Regular eye examinations and early treatment of retinopathy can prevent visual loss, so screening for diabetic retinopathy is cost-effective. Dilated retinal digital photography with the additional use of ophthalmoscopy is the most effective and robust method of diabetic retinopathy screening. The aim of this study was to estimate the sensitivity and specificity of diabetic retinopathy screening when performed by Norwegian optometrists. Methods This study employed a cross-sectional experimental design. Seventy-four optometrists working in private optometric practice were asked to screen 14 single-field retinal images for possible diabetic retinopathy. The screening was undertaken using a web-based visual identification and management of ophthalmological conditions (VIMOC) examination. The images used in the VIMOC examination were selected from a population survey and had been previously examined by two independent ophthalmologists. In order to establish a “gold standard”, images were only chosen for use in the VIMOC examination if they had elicited diagnostic agreement between the two independent ophthalmologists. To reduce the possibility of falsely high specificity occurring by chance, half the presented images were of retinas that were not affected by diabetic retinopathy. Sensitivity and specificity for diabetic retinopathy was calculated with 95% confidence intervals (CIs). Results The mean (95%CI) sensitivity for identifying eyes with any diabetic retinopathy was 67% (62% to 72%). The mean (95%CI) specificity for identifying eyes without diabetic retinopathy was 84% (80% to 89%). The mean (95%CI) sensitivity for identifying eyes with mild non-proliferative diabetic retinopathy or moderate non-proliferative diabetes was 54% (47% to 61%) and 100%, respectively. Only four optometrists (5%) met the required standard of at least 80% sensitivity and 95% specificity that has been previously set for diabetic retinopathy screening programmes. Conclusions The evaluation of retinal images for diabetic retinopathy by Norwegian optometrists does not meet the required screening standard of at least 80% sensitivity and 95% specificity. The introduction of measures to improve this situation could have implications for both formal optometric training and continuing optometric professional education. PMID:23305337

Strategies to improve the accuracy of vision measurement by teachers in rural Chinese secondary schoolchildren: Xichang Pediatric Refractive Error Study (X-PRES) report no. 6.

PubMed

Sharma, Abhishek; Li, Liping; Song, Yue; Choi, Kai; Lam, Dennis S C; Zhang, Mingzhi; Zheng, Mingwei; Zhou, Zhongxia; Liu, Xiaojian; Wu, Bin; Congdon, Nathan

2008-10-01

To assess and improve the accuracy of lay screeners compared with vision professionals in detecting visual impairment in secondary schoolchildren in rural China. After brief training, 32 teachers and a team of vision professionals independently measured vision in 1892 children in Xichang. The children also underwent vision measurement by health technicians in a concurrent government screening program. Of 32 teachers, 28 (87.5%) believed that teacher screening was worthwhile. Sensitivity (93.5%) and specificity (91.2%) of teachers detecting uncorrected presenting visual acuity of 20/40 or less were better than for presenting visual acuity (sensitivity, 85.2%; specificity, 84.8%). Failure of teachers to identify children owning but not wearing glasses and teacher bias toward better vision in children wearing glasses explain the worse results for initial vision. Wearing glasses was the student factor most strongly predictive of inaccurate teacher screening (P < .001). The sensitivity and specificity of the government screening program detecting low presenting visual acuity were 86.7% and 28.7%, respectively. Teacher vision screening after brief training can achieve accurate results in this setting, and there is support among teachers for screening. Screening of uncorrected rather than presenting visual acuity is recommended in settings with a high prevalence of corrected and uncorrected refractive error. Low specificity in the government program renders it ineffective.

Toxicogenomic identification of biomarkers of acute respiratory exposure sensitizing agents

EPA Science Inventory

Allergy induction requires multiple exposures to an agent. Therefore the development of high-throughput or in vitro assays for effective screening of potential sensitizers will require the identification of biomarkers. The goal of this preliminary study was to identify potential ...

Toxicogenomic identification of biomarkers of acute respiratory expsoure to sensitizing agents

EPA Science Inventory

Allergy induction requires multiple exposures to an agent. Therefore the development of high-throughput or in vitro assays for effective screening of potential sensitizers will require the identification of biomarkers. The goal of this preliminary study was to identify potential ...

Electrocardiographic screening for emphysema: the frontal plane P axis.

PubMed

Baljepally, R; Spodick, D H

1999-03-01

Because the most characteristic and sensitive electrocardiographic (ECG) correlate of pulmonary emphysema in adults is verticalization of the frontal plane P-wave vector (P axis), we investigated its strength as a lone criterion to screen for obstructive pulmonary disease (OPD) in an adult hospital population. In all, 954 consecutive unselected ECGs were required to yield 100 with P axis > or = +70 degrees (unequivocally negative P in a VL during sinus rhythm) and pulmonary function tests. and 100 with P axis < or = +50 degrees (unequivocally positive P-aVL). Obstructive pulmonary disease by both pulmonary function test and clinical criteria was present in 89 of 100 patients with vertical P axes and 4 of 100 patients without OPD. The high sensitivity (89% for this series) and high specificity (96%) makes vertical P axis a useful screening criterion. Its at-a-glance simplicity makes it "user-friendly."

Cost-effectiveness of annual versus biennial screening mammography for women with high mammographic breast density.

PubMed

Pataky, Reka; Ismail, Zahra; Coldman, Andrew J; Elwood, Mark; Gelmon, Karen; Hedden, Lindsay; Hislop, Greg; Kan, Lisa; McCoy, Bonnie; Olivotto, Ivo A; Peacock, Stuart

2014-12-01

The sensitivity of screening mammography is much lower among women who have dense breast tissue, compared with women who have largely fatty breasts, and they are also at much higher risk of developing the disease. Increasing mammography screening frequency from biennially to annually has been suggested as a policy option to address the elevated risk in this population. The purpose of this study was to assess the cost-effectiveness of annual versus biennial screening mammography among women aged 50-79 with dense breast tissue. A Markov model was constructed based on screening, diagnostic, and treatment pathways for the population-based screening and cancer care programme in British Columbia, Canada. Model probabilities and screening costs were calculated from screening programme data. Costs for breast cancer treatment were calculated from treatment data, and utility values were obtained from the literature. Incremental cost-effectiveness was expressed as cost per quality adjusted life year (QALY), and probabilistic sensitivity analysis was conducted. Compared with biennial screening, annual screening generated an additional 0.0014 QALYs (95% CI: -0.0480-0.0359) at a cost of $819 ($ = Canadian dollars) per patient (95% CI: 506-1185), resulting in an incremental cost effectiveness ratio of $565,912/QALY. Annual screening had a 37.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000/QALY. There is considerable uncertainty about the incremental cost-effectiveness of annual mammography. Further research on the comparative effectiveness of screening strategies for women with high mammographic breast density is warranted, particularly as digital mammography and density measurement become more widespread, before cost-effectiveness can be reevaluated. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

[High-contrast resolution of film-screen systems in oral and maxillofacial radiology].

PubMed

Kaeppler, G; Reinert, S

2007-11-01

The aim was to determine differences in high-contrast resolution of film-screen systems used in dental panoramic and cephalometric radiography by calculating the modulation transfer function (MTF). The radiographs used to determine the MTF should be taken by the same x-ray units as those used for patient radiographs. The MTF was determined using a lead grid and according to DIN 6867-2 for 11 film-screen systems (speed 250, speed class 200 and 400) used in dental radiographic diagnostics. The optical density was measured using a microdensitometer developed by PTB. With 10% of the modulation transfer factor, newly developed film-screen systems (speed class 200 and 400) demonstrated a resolution of 4.9 to 6 line pairs per mm (panoramic radiography). In cephalometric radiography a film-screen system (speed class 400 and green-sensitive film) had a resolution of 4.2 line pairs per mm and surpassed two film-screen systems (speed class 400, resolution of 3 line pairs per mm, blue-sensitive films). The relevance of this study is underlined by the diagnostic reference doses defined in the German X-ray Ordinance (RöV) which are also intended for dentistry. Film-screen systems (speed 250, speed class 200) previously used in dental panoramic and cephalometric radiography can be replaced by newly developed film-screen systems (speed class 400). In dental radiography dose reductions are possible with film-screen systems (speed class 400) without impairing diagnostic accuracy. The introduction of newly developed film-screen systems (speed class 400) requires lower milliampere-seconds and therefore an adjustment of the x-ray units to lower milliampere settings.

Point-of-care urine tests for smoking status and isoniazid treatment monitoring in adult patients.

PubMed

Nicolau, Ioana; Tian, Lulu; Menzies, Dick; Ostiguy, Gaston; Pai, Madhukar

2012-01-01

Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs. 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment. IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference.

Point-of-Care Urine Tests for Smoking Status and Isoniazid Treatment Monitoring in Adult Patients

PubMed Central

Nicolau, Ioana; Tian, Lulu; Menzies, Dick; Ostiguy, Gaston; Pai, Madhukar

2012-01-01

Background Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs. Methodology/Principal Findings 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment. Conclusions IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference. PMID:23029310

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.

Development and Validation of a P-35S, T-nos, T-35S and P-FMV Tetraplex Real-time PCR Screening Method to Detect Regulatory Genes of Genetically Modified Organisms in Food.

PubMed

Eugster, Albert; Murmann, Petra; Kaenzig, Andre; Breitenmoser, Alda

2014-10-01

In routine analysis screening methods based on real-time PCR (polymerase chain reaction) are most commonly used for the detection of genetically modified (GM) plant material in food and feed. Screening tests are based on sequences frequently used for GM development, allowing the detection of a large number of GMOs (genetically modified organisms). Here, we describe the development and validation of a tetraplex real-time PCR screening assay comprising detection systems for the regulatory genes Cauliflower Mosaic Virus 35S promoter, Agrobacterium tumefaciens nos terminator, Cauliflower Mosaic Virus 35S terminator and Figwort Mosaic Virus 34S promoter. Three of the four primer and probe combinations have already been published elsewhere, whereas primers and probe for the 35S terminator have been developed in-house. Adjustment of primer and probe concentrations revealed a high PCR sensitivity with insignificant physical cross-talk between the four detection channels. The sensitivity of each PCR-system is sufficient to detect a GMO concentration as low as 0.05% of the containing respective element. The specificity of the described tetraplex is high when tested on DNA from GM maize, soy, rapeseed and tomato. We also demonstrate the robustness of the system by inter-laboratory tests. In conclusion, this method provides a sensitive and reliable screening procedure for the detection of the most frequently used regulatory elements present in GM crops either authorised or unauthorised for food.

Correspondence of the Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) clinical interview and the VA TBI screen.

PubMed

Fortier, Catherine Brawn; Amick, Melissa M; Kenna, Alexandra; Milberg, William P; McGlinchey, Regina E

2015-01-01

Mild traumatic brain injury is the signature injury of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND), yet its identification and diagnosis is controversial and fraught with challenges. In 2007, the Department of Veterans Affairs (VA) implemented a policy requiring traumatic brain injury (TBI) screening on all individuals returning from deployment in the OEF/OIF/OND theaters of operation that lead to the rapid and widespread use of the VA TBI screen. The Boston Assessment of TBI-Lifetime (BAT-L) is the first validated, postcombat semistructured clinical interview to characterize head injuries and diagnose TBIs throughout the life span, including prior to, during, and post-military service. Community-dwelling convenience sample of 179 OEF/OIF/OND veterans. BAT-L, VA TBI screen. Based on BAT-L diagnosis of military TBI, the VA TBI screen demonstrated similar sensitivity (0.85) and specificity (0.82) when administered by research staff. When BAT-L diagnosis was compared with historical clinician-administered VA TBI screen in a subset of participants, sensitivity was reduced. The specificity of the research-administered VA TBI screen was more than adequate. The sensitivity of the VA TBI screen, although relatively high, suggests that it does not oversample or "catch all" possible military TBIs. Traumatic brain injuries identified by the BAT-L, but not identified by the VA TBI screen, were predominantly noncombat military injuries. There is potential concern regarding the validity and reliability of the clinician administered VA TBI screen, as we found poor correspondence between it and the BAT-L, as well as low interrater reliability between the clinician-administered and research-administered screen.

Pilot study analyzing automated ECG screening of hypertrophic cardiomyopathy.

PubMed

Campbell, Matthew J; Zhou, Xuefu; Han, Chia; Abrishami, Hedayat; Webster, Gregory; Miyake, Christina Y; Sower, Christopher T; Anderson, Jeffrey B; Knilans, Timothy K; Czosek, Richard J

2017-06-01

Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death in athletes. However, preparticipation ECG screening has often been criticized for failing to meet cost-effectiveness thresholds, in part because of high false-positive rates and the cost of ECG screening itself. The purpose of this study was to assess the testing characteristics of an automated ECG algorithm designed to screen for HCM in a multi-institutional pediatric cohort. ECGs from patients with HCM aged 12 to 20 years from 3 pediatric institutions were screened for ECG criteria for HCM using a previously described automated computer algorithm developed specifically for HCM ECG screening. The results were compared to a known healthy pediatric cohort. The studies then were read by trained electrophysiologists using standard ECG criteria and compared to the results of automated screening. One hundred twenty-eight ECGs from unique patients with phenotypic HCM were obtained and compared with 256 studies from healthy control patients matched in 2:1 fashion. When presented with the ECGs, the non-voltage-based algorithm resulted in 81.2% sensitivity and 90.7% specificity. A trained electrophysiologist read the same data according to the Seattle Criteria, with 71% sensitivity with 95.7% specificity. The sensitivity of screening as well as the components of the ECG screening itself varied by institution. This pilot study demonstrates a potential for automated ECG screening algorithms to detect HCM with testing characteristics similar to that of a trained electrophysiologist. In addition, there appear to be differences in ECG characteristics between patient populations, which may account for the difficulties in universal screening. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Validation of Version 3.0 of the Breast Cancer Genetics Referral Screening Tool (B-RST™).

PubMed

Bellcross, Cecelia; Hermstad, April; Tallo, Christine; Stanislaw, Christine

2018-05-08

Despite increased awareness of hereditary breast and ovarian cancer among clinicians and the public, many BRCA1/2 mutation carriers remain unaware of their risk status. The Breast Cancer Genetics Referral Screening Tool (B-RST™) was created and validated to easily identify individuals at increased risk for hereditary breast and ovarian cancer for referral to cancer genetics services. The purpose of this study was to revise B-RST™ to maximize sensitivity against BRCA1/2 mutation status. We analyzed pedigrees of 277 individuals who had undergone BRCA1/2 testing to determine modifications to the B-RST™ 2.0 algorithm that would maximize sensitivity for mutations, while maintaining simplicity. We used McNemar's chi-square test to compare validation measures between the revised version (3.0) and the 2.0 version. Algorithmic changes made to B-RST™ 2.0 increased the sensitivity against BRCA1/2 mutation analysis from 71.1 to 94.0% (P < 0.0001). While specificity decreased, all screen-positive individuals were appropriate for cancer genetics referral, the primary purpose of the tool. Despite calls for BRCA1/2 population screening, there remains a critical need to identify those most at risk who should receive cancer genetics services. B-RST™ version 3.0 demonstrates high sensitivity for BRCA1/2 mutations, yet remains a simple and quick screening tool for at-risk individuals.

Modular, Antibody-free Time-Resolved LRET Kinase Assay Enabled by Quantum Dots and Tb3+-sensitizing Peptides

NASA Astrophysics Data System (ADS)

Cui, Wei; Parker, Laurie L.

2016-07-01

Fluorescent drug screening assays are essential for tyrosine kinase inhibitor discovery. Here we demonstrate a flexible, antibody-free TR-LRET kinase assay strategy that is enabled by the combination of streptavidin-coated quantum dot (QD) acceptors and biotinylated, Tb3+ sensitizing peptide donors. By exploiting the spectral features of Tb3+ and QD, and the high binding affinity of the streptavidin-biotin interaction, we achieved multiplexed detection of kinase activity in a modular fashion without requiring additional covalent labeling of each peptide substrate. This strategy is compatible with high-throughput screening, and should be adaptable to the rapidly changing workflows and targets involved in kinase inhibitor discovery.

Convenient, sensitive and high-throughput method for screening botanic origin.

PubMed

Yuan, Yuan; Jiang, Chao; Liu, Libing; Yu, Shulin; Cui, Zhanhu; Chen, Min; Lin, Shufang; Wang, Shu; Huang, Luqi

2014-06-23

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.

Mechanism behind Resistance against the Organophosphate Azamethiphos in Salmon Lice (Lepeophtheirus salmonis)

PubMed Central

Kaur, Kiranpreet; Helgesen, Kari Olli; Bakke, Marit Jørgensen; Horsberg, Tor Einar

2015-01-01

Acetylcholinesterase (AChE) is the primary target for organophosphates (OP). Several mutations have been reported in AChE to be associated with the reduced sensitivity against OP in various arthropods. However, to the best of our knowledge, no such reports are available for Lepeophtheirus salmonis. Hence, in the present study, we aimed to determine the association of AChE(s) gene(s) with resistance against OP. We screened the AChE genes (L. salmonis ace1a and ace1b) in two salmon lice populations: one sensitive (n=5) and the other resistant (n=5) for azamethiphos, a commonly used OP in salmon farming. The screening led to the identification of a missense mutation Phe362Tyr in L. salmonis ace1a, (corresponding to Phe331 in Torpedo californica AChE) in all the samples of the resistant population. We confirmed the potential role of the mutation, with reduced sensitivity against azamethiphos in L. salmonis, by screening for Phe362Tyr in 2 sensitive and 5 resistant strains. The significantly higher frequency of the mutant allele (362Tyr) in the resistant strains clearly indicated the possible association of Phe362Tyr mutation in L. salmonis ace1a with resistance towards azamethiphos. The 3D modelling, short term survival experiments and enzymatic assays further supported the imperative role of Phe362Tyr in reduced sensitivity of L. salmonis for azamethiphos. Based on all these observations, the present study, for the first time, presents the mechanism of resistance in L. salmonis against azamethiphos. In addition, we developed a rapid diagnostic tool for the high throughput screening of Phe362Tyr mutation using High Resolution Melt analysis. PMID:25893248

Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening.

PubMed

Tong, Zhi-Bin; Hogberg, Helena; Kuo, David; Sakamuru, Srilatha; Xia, Menghang; Smirnova, Lena; Hartung, Thomas; Gerhold, David

2017-02-01

More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

HIGHLY SENSITIVE ASSAY FOR ANTICHOLINESTERASE COMPOUNDS USING 96 WELL PLATE FORMAT

EPA Science Inventory

The rapid and sensitive detection of organophosphate insecticides using a 96 well plate format is reported. Several features of this assay make it attractive for development as a laboratory-based or field screening assay. Acetylcholinesterase (AChE) was stabilized in a gelati...

Laboratory screening markers in gastroenterology--state of the art.

PubMed

Kocna, Petr; Vanickova, Zdislava; Zima, Tomas

2013-06-01

Screening tests for gastrointestinal diseases acceptable for population with a high sensitivity and high specificity can now be offered by clinical laboratories. This paper summarizes major recent advances in this area of laboratory medicine. Relevant articles published within the last 5 years in the NLM (National Library of Medicine) PubMed - Medline database covering the three gastrointestinal diseases - colorectal cancer, coeliac disease, and atrophic gastritis were included for this overview. In Europe, colorectal cancer (CRCA) is the second most frequent malignant disease. Quantitative immunochemical analysis of the stool for haemoglobin provides the best screening test to date, with both sensitivity and specificity approaching 95%. Even though coeliac disease (CD) affects approximately 1% of the general population, it remains largely unrecognised. Recommended methods for screening currently involve the detection of IgA and IgG antibodies against tissue transglutaminase and deamidated gliadin peptide. Evaluations of screening are now discussed for other diseases of the gastrointestinal tract - such as chronic atrophic gastritis (CAG), and inflammatory bowel disease (IBD). Detection of infection by Helicobacter pylori and stomach-specific plasmatic biomarkers, especially pepsinogen I/II ratio, could help with the prevention of gastric carcinomas. The use of faecal calprotectin as a screening test could substantially reduce the number of invasive methods necessary for the diagnostic work-up of patients with IBD. Screening tests for CRCA and CD have been used worldwide for many years. Screening strategies for gastrointestinal diseases are suggested in the text, based on recent basic science, clinical papers as well as our own experience.

Point-of-care test for cervical cancer in LMICs.

PubMed

Mohammed, Sulma I; Ren, Wen; Flowers, Lisa; Rajwa, Bartek; Chibwesha, Carla J; Parham, Groesbeck P; Irudayaraj, Joseph M K

2016-04-05

Cervical cancer screening using Papanicolaou's smear test has been highly effective in reducing death from this disease. However, this test is unaffordable in low- and middle-income countries, and its complexity has limited wide-scale uptake. Alternative tests, such as visual inspection with acetic acid or Lugol's iodine and human papillomavirus DNA, are sub-optimal in terms of specificity and sensitivity, thus sensitive and affordable tests with high specificity for on-site reporting are needed. Using proteomics and bioinformatics, we have identified valosin-containing protein (VCP) as differentially expressed between normal specimens and those with cervical intra-epithelial neoplasia grade 2/3 (CIN2/CIN3+) or worse. VCP-specific immunohistochemical staining (validated by a point-of-care technology) provided sensitive (93%) and specific (88%) identification of CIN2/CIN3+ and may serve as a critical biomarker for cervical-cancer screening. Future efforts will focus on further refinements to enhance analytic sensitivity and specificity of our proposed test, as well as on prototype development.

Assessment of Uncertainty-Based Screening Volumes for NASA Robotic LEO and GEO Conjunction Risk Assessment

NASA Technical Reports Server (NTRS)

Narvet, Steven W.; Frigm, Ryan C.; Hejduk, Matthew D.

2011-01-01

Conjunction Assessment operations require screening assets against the space object catalog by placing a pre-determined spatial volume around each asset and predicting when another object will violate that volume. The selection of the screening volume used for each spacecraft is a trade-off between observing all conjunction events that may pose a potential risk to the primary spacecraft and the ability to analyze those predicted events. If the screening volumes are larger, then more conjunctions can be observed and therefore the probability of a missed detection of a high risk conjunction event is small; however, the amount of data which needs to be analyzed increases. This paper characterizes the sensitivity of screening volume size to capturing typical orbit uncertainties and the expected number of conjunction events observed. These sensitivities are quantified in the form of a trade space that allows for selection of appropriate screen-ing volumes to fit the desired concept of operations, system limitations, and tolerable analyst workloads. This analysis will specifically highlight the screening volume determination and selection process for use in the NASA Conjunction Assessment Risk Analysis process but will also provide a general framework for other Owner / Operators faced with similar decisions.

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program - A Markov Model.

PubMed

Perraudin, Clémence; Le Vaillant, Marc; Pelletier-Fleury, Nathalie

2013-01-01

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed. To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care. Markov decision model. Published data. Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS. The 5 years after initial evaluation for OSAS. Societal. Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening. Quality of life, survival and costs for each screening strategy. Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for "screening strategy with CP" was about 455€ per QALY gained. Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the "screening strategy with CP" was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases. CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.

Identification of Childhood Disability in Jamaica: The Ten Question Screen.

ERIC Educational Resources Information Center

Thorburn, Marigold; And Others

1992-01-01

This study evaluated use of the Ten Question Screen (TQ) to identify disability in a 2-stage population-based survey of 5,478 children aged 2-9 years in Clarendon, Jamaica. Findings indicated varied sensitivity by different subgroups (age, gender, and disability) and an unacceptably high false positive rate. (Author/DB)

75 FR 28619 - Meeting of the Advisory Committee on Blood Safety and Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... began prior to the availability of tests for HIV in early 1985. The deferral has existed in its current form since September 1985. This and other related FDA policies are designed to address the major... screened using highly sensitive tests, screening tests can be falsely negative during the ``window period...

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

Three dimensional graphene transistor for ultra-sensitive pH sensing directly in biological media.

PubMed

Ameri, Shideh Kabiri; Singh, Pramod K; Sonkusale, Sameer R

2016-08-31

In this work, pH sensing directly in biological media using three dimensional liquid gated graphene transistors is presented. The sensor is made of suspended network of graphene coated all around with thin layer of hafnium oxide (HfO2), showing high sensitivity and sensing beyond the Debye-screening limit. The performance of the pH sensor is validated by measuring the pH of isotonic buffered, Dulbecco's phosphate buffered saline (DPBS) solution, and of blood serum derived from Sprague-Dawley rat. The pH sensor shows high sensitivity of 71 ± 7 mV/pH even in high ionic strength media with molarities as high as 289 ± 1 mM. High sensitivity of this device is owing to suspension of three dimensional graphene in electrolyte which provides all around liquid gating of graphene, leading to higher electrostatic coupling efficiency of electrolyte to the channel and higher gating control of transistor channel by ions in the electrolyte. Coating graphene with hafnium oxide film (HfO2) provides binding sites for hydrogen ions, which results in higher sensitivity and sensing beyond the Debye-screening limit. The 3D graphene transistor offers the possibility of real-time pH measurement in biological media without the need for desaltation or sample preparation. Copyright © 2016 Elsevier B.V. All rights reserved.

A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans

PubMed Central

Lucanic, Mark; Garrett, Theo; Gill, Matthew S.; Lithgow, Gordon J.

2018-01-01

Caenorhabditis elegans is a useful organism for testing chemical effects on physiology. Whole organism small molecule screens offer significant advantages for identifying biologically active chemical structures that can modify complex phenotypes such as lifespan. Described here is a simple protocol for producing hundreds of 96-well culture plates with fairly consistent numbers of C. elegans in each well. Next, we specified how to use these cultures to screen thousands of chemicals for effects on the lifespan of the nematode C. elegans. This protocol makes use of temperature sensitive sterile strains, agar plate conditions, and simple animal handling to facilitate the rapid and high throughput production of synchronized animal cultures for screening. PMID:29630057

Sensitivity and specificity of the subcutaneous implantable cardioverter defibrillator pre-implant screening tool.

PubMed

Zeb, Mehmood; Curzen, Nick; Allavatam, Venugopal; Wilson, David; Yue, Arthur; Roberts, Paul; Morgan, John

2015-09-15

The sensitivity and specificity of the subcutaneous implantable cardioverter defibrillator (S-ICD) pre-implant screening tool required clinical evaluation. Bipolar vectors were derived from electrodes positioned at locations similar to those employed for S-ICD sensing and pre-implant screening electrodes, and recordings collected through 80-electrode PRIME®-ECGs, in six different postures, from 40 subjects (10 healthy controls, and 30 patients with complex congenital heart disease (CCHD); 10 with Tetralogy of Fallot (TOF), 10 with single ventricle physiology (SVP), and 10 with transposition of great arteries (TGA)). The resulting vectors were analysed using the S-ICD pre-implant screening tool (Boston Scientific) and processed through the sensing algorithm of S-ICD (Boston Scientific). The data were then evaluated using 2 × 2 contingency tables. Fisher exact and McNemar tests were used for a comparison of the different categories of CCHD, and p < 0.05 vs. controls considered to be statistically significant. 57% of patients were male, mean age of 36.3 years. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the S-ICD screening tool were 95%, 79%, 59% and 98%, respectively, for controls, and 84%, 79%, 76% and 86%, respectively, in patients with CCHD (p = 0.0001). The S-ICD screening tool was comparatively more sensitive in normal controls but less specific in both CCHD patients and controls; a possible explanation for the reported high incidence of inappropriate S-ICD shocks. Thus, we propose a pre-implant screening device using the S-ICD sensing algorithm to minimise false exclusion and selection, and hence minimise potentially inappropriate shocks. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Clinical Utility of Methicillin Resistant Staphylococcus aureus (MRSA) Nasal Screening to Rule Out MRSA Pneumonia: A Diagnostic Meta-analysis with Antimicrobial Stewardship Implications.

PubMed

Parente, Diane M; Cunha, Cheston B; Mylonakis, Eleftherios; Timbrook, Tristan T

2018-01-11

Recent literature has highlighted MRSA nasal screening as a possible antimicrobial stewardship program (ASP) tool for avoiding unnecessary empiric MRSA therapy for pneumonia, yet current guidelines recommend MRSA therapy based on risk factors. The objective of this meta-analysis was to evaluate the diagnostic value of MRSA nasal screening in MRSA pneumonia. Pubmed and EMBASE were searched from inception to November 2016 for English studies evaluating MRSA nasal screening and development of MRSA pneumonia. Data analysis was performed using a bivariate random-effects model to estimate pooled sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Twenty-two studies, comprising of 5,163 patients met our inclusion criteria. Pooled sensitivity and specificity of MRSA nares screen for all MRSA pneumonia types was 70.9% and 90.3%, respectively. With a 10% prevalence of potential MRSA pneumonia, the calculated PPV was 44.8% while the NPV was 96.5%. The pooled sensitivity and specificity for MRSA community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) were at 85% and 92.1%, respectively. For CAP and HCAP both the PPV and NPV increased to 56.8% and 98.1%, respectively. In comparison, for MRSA ventilated-associated pneumonia (VAP), the sensitivity, specificity, PPV, NPV was 40.3%, 93.7%, 35.7%, and 94.8%, respectively. Nares screening for MRSA had a high specificity and NPV for ruling out MRSA pneumonia, particularly in cases of CAP/HCAP. Based on the NPV, utilization of MRSA nares screening is a valuable tool for AMS to streamline empiric antibiotic therapy, especially among patients with pneu. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis.

PubMed

Yeh, Jennifer M; Hur, Chin; Ward, Zachary; Schrag, Deborah; Goldie, Sue J

2016-04-01

To estimate the cost-effectiveness of noncardia gastric adenocarcinoma (NCGA) screening strategies based on new biomarker and endoscopic technologies. Using an intestinal-type NCGA microsimulation model, we evaluated the following one-time screening strategies for US men: (1) serum pepsinogen to detect gastric atrophy (with endoscopic follow-up of positive screen results), (2) endoscopic screening to detect dysplasia and asymptomatic cancer (with endoscopic mucosal resection (EMR) treatment for detected lesions) and (3) Helicobacter pylori screening and treatment. Screening performance, treatment effectiveness, cancer and cost data were based on published literature and databases. Subgroups included current, former and never smokers. Outcomes included lifetime cancer risk and incremental cost-effectiveness ratios (ICERs), expressed as cost per quality-adjusted-life-year (QALY) gained. Screening the general population at age 50 years reduced the lifetime intestinal-type NCGA risk (0.24%) by 26.4% with serum pepsinogen screening, 21.2% with endoscopy and EMR and 0.2% with H. pylori screening/treatment. Targeting current smokers reduced the lifetime risk (0.35%) by 30.8%, 25.5%, and 0.1%, respectively. For all subgroups, serum pepsinogen screening was more effective and more cost-effective than all other strategies, although its ICER varied from $76,000/QALY (current smokers) to $105,400/QALY (general population). Results were sensitive to H. pylori prevalence, screen age and serum pepsinogen test sensitivity. Probabilistic sensitivity analysis found that at a $100,000/QALY willingness-to-pay threshold, the probability that serum pepsinogen screening was preferred was 0.97 for current smokers. Although not warranted for the general population, targeting high-risk smokers for serum pepsinogen screening may be a cost-effective strategy to reduce intestinal-type NCGA mortality. 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/

Impedimetric detection of cocaine by using an aptamer attached to a screen printed electrode modified with a dendrimer/silver nanoparticle nanocomposite.

PubMed

Roushani, Mahmoud; Shahdost-Fard, Faezeh

2018-03-12

The authors describe a highly sensitive method for the aptamer (Apt) based impedimetric determination of cocaine. The surface of a screen-printed electrode (SPE) was modified with a nanocomposite of dendrimer and silver nanoparticles (AgNPs). The cocaine-binding Apt was attached to a dendrimer/AgNP/SPE surface, forming a sensitive layer for the determination of cocaine. The incubation with the analyte resulted in the formation of a cocaine/Apt complex on the electrode surface. As a consequence, folding and conformational change in the aptamer structure was induced, this resulting in a change in the impedimetric signal. The aptaassay exhibits highly efficient sensing characteristics with a good linearity of 1 fmol L -1 to 100 nmol L -1 (with two linear ranges) and a limit of detection (LOD) of 333 amol L -1 . Its excellent specificity and high sensitivity suggest that this kind of aptamer-based assay may be applied to detect other targets in this field. Graphical Abstract Designing of an aptaassay via immobilization of a functionalized aptamer with silver nanoparticle (AgNPs-Apt) on the modified screen-printed electrode (SPE) with dendrimer/silver nanoparticle nanocomposite (Den-AgNPs) for impedimetric detection of cocaine.

The PHQ-PD as a Screening Tool for Panic Disorder in the Primary Care Setting in Spain

PubMed Central

Wood, Cristina Mae; Ruíz-Rodríguez, Paloma; Tomás-Tomás, Patricia; Gracia-Gracia, Irene; Dongil-Collado, Esperanza; Iruarrizaga, M. Iciar

2016-01-01

Introduction Panic disorder is a common anxiety disorder and is highly prevalent in Spanish primary care centres. The use of validated tools can improve the detection of panic disorder in primary care populations, thus enabling referral for specialized treatment. The aim of this study is to determine the accuracy of the Patient Health Questionnaire-Panic Disorder (PHQ-PD) as a screening and diagnostic tool for panic disorder in Spanish primary care centres. Method We compared the psychometric properties of the PHQ-PD to the reference standard, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interview. General practitioners referred 178 patients who completed the entire PHQ test, including the PHQ-PD, to undergo the SCID-I. The sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of the PHQ-PD were assessed. Results The operating characteristics of the PHQ-PD are moderate. The best cut-off score was 5 (sensitivity .77, specificity .72). Modifications to the questionnaire's algorithms improved test characteristics (sensitivity .77, specificity .72) compared to the original algorithm. The screening question alone yielded the highest sensitivity score (.83). Conclusion Although the modified algorithm of the PHQ-PD only yielded moderate results as a diagnostic test for panic disorder, it was better than the original. Using only the first question of the PHQ-PD showed the best psychometric properties (sensitivity). Based on these findings, we suggest the use of the screening questions for screening purposes and the modified algorithm for diagnostic purposes. PMID:27525977

Epi proColon® 2.0 CE: A Blood-Based Screening Test for Colorectal Cancer.

PubMed

Lamb, Yvette N; Dhillon, Sohita

2017-04-01

Epi proColon ® 2.0 CE is a blood-based test designed to aid in the early detection of colorectal cancer. The test comprises a qualitative assay for the polymerase chain reaction (PCR) detection of methylated Septin9 DNA, the presence of which is associated with colorectal cancer: however, positive results should be verified by colonoscopy or sigmoidoscopy. Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with high clinical sensitivity and specificity in pivotal case-control studies. The sensitivity of the test did not appear to be affected by the tumour location or by patient age or gender. In addition, limited data suggest that Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with higher sensitivity and generally similar specificity to that of the faecal immunochemical test, and with higher sensitivity and specificity to that of the guaiac-based faecal occult blood test (statistical data not available). In an observational study, most patients who refused colonoscopy for screening accepted a non-invasive test option as an alternative, and preferred Epi proColon ® 2.0 CE over a stool-based test. Large prospective trials of Epi proColon ® 2.0 CE in a screening setting will be required to further elucidate the cost-effectiveness of the test. Nevertheless, currently available data suggests that Epi proColon ® 2.0 CE has the potential to be a sensitive and convenient screening option for patients refusing screening by colonoscopy.

Determining when to conduct a violence risk assessment: Development and initial validation of the Fordham Risk Screening Tool (FRST).

PubMed

Rosenfeld, Barry; Foellmi, Melodie; Khadivi, Ali; Wijetunga, Charity; Howe, Jacqueline; Nijdam-Jones, Alicia; Grover, Shana; Rotter, Merrill

2017-08-01

Techniques to assess violence risk are increasingly common, but no systematic approach exists to help clinicians decide which psychiatric patients are most in need of a violence risk assessment. The Fordham Risk Screening Tool (FRST) was designed to fill this void, providing a structured, systematic approach to screening psychiatric patients and determining the need for further, more thorough violence risk assessment. The FRST was administered to a sample of 210 consecutive admissions to the civil psychiatric units of an urban medical center, 159 of whom were subsequently evaluated using the Historical Clinical Risk Management-20, version 3, to determine violence risk. The FRST showed a high degree of sensitivity (93%) in identifying patients subsequently deemed to be at high risk for violence (based on the Case Prioritization risk rating). The FRST also identified all of the patients (100%) rated high in potential for severe violence (based on the Serious Physical Harm Historical Clinical Risk Management-20, version 3, summary risk rating). Sensitivity was more modest when individuals rated as moderate risk were included as the criterion (rather than only those identified as high risk). Specificity was also moderate, screening out approximately half of all participants as not needing further risk assessment. A systematic approach to risk screening is clearly needed to prioritize psychiatric admissions for thorough risk assessment, and the FRST appears to be a potentially valuable step in that process. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Sensitivity and specificity of mammographic screening as practised in Vermont and Norway

PubMed Central

Hofvind, S; Geller, B M; Skelly, J; Vacek, P M

2012-01-01

Objective The aim of this study was to examine the sensitivity and specificity of screening mammography as performed in Vermont, USA, and Norway. Methods Incident screening data from 1997 to 2003 for female patients aged 50–69 years from the Vermont Breast Cancer Surveillance System (116 996 subsequent screening examinations) and the Norwegian Breast Cancer Screening Program (360 872 subsequent screening examinations) were compared. Sensitivity and specificity estimates for the initial (based on screening mammogram only) and final (screening mammogram plus any further diagnostic imaging) interpretations were directly adjusted for age using 5-year age intervals for the combined Vermont and Norway population, and computed for 1 and 2 years of follow-up, which ended at the time of the next screening mammogram. Results For the 1-year follow-up, sensitivities for initial assessments were 82.0%, 88.2% and 92.5% for 1-, 2- and >2-year screening intervals, respectively, in Vermont (p=0.022). For final assessments, the values were 73.6%, 83.3% and 81.2% (p=0.047), respectively. For Norway, sensitivities for initial assessments were 91.0% and 91.3% (p=0.529) for 2- and >2-year intervals, and 90.7% and 91.3%, respectively, for final assessments (p=0.630). Specificity was lower in Vermont than in Norway for each screening interval and for all screening intervals combined, for both initial (90.6% vs 97.8% for all intervals; p<0.001) and final (98.8% vs 99.5% for all intervals; p<0.001) assessments. Conclusion Our study showed higher sensitivity and specificity in a biennial screening programme with an independent double reading than in a predominantly annual screening program with a single reading. Advances in knowledge This study demonstrates that higher recall rates and lower specificity are not always associated with higher sensitivity of screening mammography. Differences in the screening processes in Norway and Vermont suggest potential areas for improvement in the latter. PMID:22993383

High-Throughput Screening of a Luciferase Reporter of Gene Silencing on the Inactive X Chromosome.

PubMed

Keegan, Alissa; Plath, Kathrin; Damoiseaux, Robert

2018-01-01

Assays of luciferase gene activity are a sensitive and quantitative reporter system suited to high-throughput screening. We adapted a luciferase assay to a screening strategy for identifying factors that reactivate epigenetically silenced genes. This epigenetic luciferase reporter is subject to endogenous gene silencing mechanisms on the inactive X chromosome (Xi) in primary mouse cells and thus captures the multilayered nature of chromatin silencing in development. Here, we describe the optimization of an Xi-linked luciferase reactivation assay in 384-well format and adaptation of the assay for high-throughput siRNA and chemical screening. Xi-luciferase reactivation screening has applications in stem cell biology and cancer therapy. We have used the approach described here to identify chromatin-modifying proteins and to identify drug combinations that enhance the gene reactivation activity of the DNA demethylating drug 5-aza-2'-deoxycytidine.

Monitoring well utility in a heterogeneous DNAPL source zone area: Insights from proximal multilevel sampler wells and sampling capture-zone modelling

NASA Astrophysics Data System (ADS)

McMillan, Lindsay A.; Rivett, Michael O.; Wealthall, Gary P.; Zeeb, Peter; Dumble, Peter

2018-03-01

Groundwater-quality assessment at contaminated sites often involves the use of short-screen (1.5 to 3 m) monitoring wells. However, even over these intervals considerable variation may occur in contaminant concentrations in groundwater adjacent to the well screen. This is especially true in heterogeneous dense non-aqueous phase liquid (DNAPL) source zones, where cm-scale contamination variability may call into question the effectiveness of monitoring wells to deliver representative data. The utility of monitoring wells in such settings is evaluated by reference to high-resolution multilevel sampler (MLS) wells located proximally to short-screen wells, together with sampling capture-zone modelling to explore controls upon well sample provenance and sensitivity to monitoring protocols. Field data are analysed from the highly instrumented SABRE research site that contained an old trichloroethene source zone within a shallow alluvial aquifer at a UK industrial facility. With increased purging, monitoring-well samples tend to a flow-weighted average concentration but may exhibit sensitivity to the implemented protocol and degree of purging. Formation heterogeneity adjacent to the well-screen particularly, alongside pump-intake position and water level, influence this sensitivity. Purging of low volumes is vulnerable to poor reproducibility arising from concentration variability predicted over the initial 1 to 2 screen volumes purged. Marked heterogeneity may also result in limited long-term sample concentration stabilization. Development of bespoke monitoring protocols, that consider screen volumes purged, alongside water-quality indicator parameter stabilization, is recommended to validate and reduce uncertainty when interpreting monitoring-well data within source zone areas. Generalised recommendations on monitoring well based protocols are also developed. A key monitoring well utility is their proportionately greater sample draw from permeable horizons constituting a significant contaminant flux pathway and hence representative fraction of source mass flux. Acquisition of complementary, high-resolution, site monitoring data, however, vitally underpins optimal interpretation of monitoring-well datasets and appropriate advancement of a site conceptual model and remedial implementation.

Validity of an interviewer-administered patient health questionnaire-9 to screen for depression in HIV-infected patients in Cameroon.

PubMed

Pence, Brian W; Gaynes, Bradley N; Atashili, Julius; O'Donnell, Julie K; Tayong, Gladys; Kats, Dmitry; Whetten, Rachel; Whetten, Kathryn; Njamnshi, Alfred K; Ndumbe, Peter M

2012-12-20

In high-income countries, depression is prevalent in HIV patients and is associated with lower medication adherence and clinical outcomes. Emerging evidence from low-income countries supports similar relationships. Yet little research has validated rapid depression screening tools integrated into routine HIV clinical care. Using qualitative methods, we adapted the Patient Health Questionnaire-9 (PHQ-9) depression screening instrument for use with Cameroonian patients. We then conducted a cross-sectional validity study comparing an interviewer-administered PHQ-9 to the reference standard Composite International Diagnostic Interview in 400 patients on antiretroviral therapy attending a regional HIV treatment center in Bamenda, Cameroon. The prevalence of major depressive disorder (MDD) in the past month was 3% (n=11 cases). Using a standard cutoff score of ≥10 as a positive depression screen, the PHQ-9 had estimated sensitivity of 27% (95% confidence interval: 6-61%) and specificity of 94% (91-96%), corresponding to positive and negative likelihood ratios of 4.5 and 0.8. There was little evidence of variation in specificity by gender, number of HIV symptoms, or result of a dementia screen. The low prevalence of MDD yielded very imprecise sensitivity estimates. Although the PHQ-9 was developed as a self-administered tool, we assessed an interviewer-administered version due to the literacy level of the target population. The PHQ-9 demonstrated high specificity but apparently low sensitivity for detecting MDD in this sample of HIV patients in Cameroon. Formative work to define the performance of proven screening tools in new settings remains important as research on mental health expands in low-income countries. Copyright © 2012 Elsevier B.V. All rights reserved.

Sensitivity and specificity of a two-question screening tool for depression in a specialist palliative care unit.

PubMed

Payne, Ann; Barry, Sandra; Creedon, Brian; Stone, Carol; Sweeney, Catherine; O' Brien, Tony; O' Sullivan, Kathleen

2007-04-01

The primary objective in this study is to determine the sensitivity and specificity of a two-item screening interview for depression versus the formal psychiatric interview, in the setting of a specialist palliative in-patient unit so that we may identify those individuals suffering from depressive disorder and therefore optimise their management in this often-complex population. A prospective sample of consecutive admissions (n = 167) consented to partake in the study, and the screening interview was asked separately to the formal psychiatric interview. The two-item questionnaire, achieved a sensitivity of 90.7% (95% CI 76.9-97.0) but a lower specificity of 67.7% (95% CI 58.7-75.7). The false positive rate was 32.3% (95% CI 24.3-41.3), but the false negative rate was found to be a low 9.3% (95% CI 3.0-23.1). A subgroup analysis of individuals with a past experience of depressive illness, (n = 95), revealed that a significant number screened positive for depression by the screening test, 55.2% (16/29) compared to those with no background history of depression, 33.3% (22/66) (P = 0.045). The high sensitivity and low false negative rate of the two-question screening tool will aid health professionals in identifying depression in the in-patient specialist palliative care unit. Individuals, who admit to a previous experience of depressive illness, are more likely to respond positively to the two-item questionnaire than those who report no prior history of depressive illness (P = 0.045).

Cervical Cancer Screening in Low-Resource Settings: A Cost-Effectiveness Framework for Valuing Tradeoffs between Test Performance and Program Coverage

PubMed Central

Campos, Nicole G.; Castle, Philip E.; Wright, Thomas C.; Kim, Jane J.

2016-01-01

As cervical cancer screening programs are implemented in low-resource settings, protocols are needed to maximize health benefits under operational constraints. Our objective was to develop a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage, and follow-up of screen-positive women, to help decision makers identify where program investments yield the greatest value. As an illustrative example, we used an individual-based Monte Carlo simulation model of the natural history of human papillomavirus (HPV) and cervical cancer calibrated to epidemiologic data from Uganda. We assumed once in a lifetime screening at age 35 with two-visit HPV DNA testing or one-visit visual inspection with acetic acid (VIA). We assessed the health and economic tradeoffs that arise between 1) test sensitivity and screening coverage; 2) test sensitivity and loss to follow-up (LTFU) of screen-positive women; and 3) test sensitivity, screening coverage, and LTFU simultaneously. The decline in health benefits associated with sacrificing HPV DNA test sensitivity by 20% (e.g., shifting from provider- to self-collection of specimens) could be offset by gains in coverage if coverage increased by at least 20%. When LTFU was 10%, two-visit HPV DNA testing with 80-90% sensitivity was more effective and more cost-effective than one-visit VIA with 40% sensitivity, and yielded greater health benefits than VIA even as VIA sensitivity increased to 60% and HPV test sensitivity declined to 70%. As LTFU increased, two-visit HPV DNA testing became more costly and less effective than one-visit VIA. Setting-specific data on achievable test sensitivity, coverage, follow-up rates, and programmatic costs are needed to guide programmatic decision making for cervical cancer screening. PMID:25943074

Usefulness of the volume-viscosity swallow test for screening dysphagia in subacute stroke patients in rehabilitation income.

PubMed

Guillén-Solà, Anna; Marco, Ester; Martínez-Orfila, Joan; Donaire Mejías, M Fernanda; Depolo Passalacqua, Marina; Duarte, Esther; Escalada, Ferran

2013-01-01

Swallowing disorders affect up to 35-85% of patients with stroke. Dysphagia complications can lead to malnutrition, dehydration, bronchoaspirative pneumonia and death, and have impact on health care costs. To evaluate the clinical screening capacity of the Volume Viscosity Swallow Test (V-VST) for oropharyngeal dysphagia and aspiration in a homogeneous stroke patient sample. Cohort study of 52 stroke patients in a subacute phase. Piecemeal deglutition and oropharyngeal residue were considered signs of impaired efficacy and cough, fall in oxygen saturation and voice changes, signs of impaired safety. Sensitivity, specificity, positive and negative predictive values, accuracy and likelihood ratios were calculated for V-VST results and compared with those of videofluoroscopy (VFS), the gold standard for studies on swallowing disorders. The V-VST is a highly sensitive and specific test to detect aspiration with sensitivity of 88.2% and specificity of 71.4%; negative predictive value was 92.6%; accuracy index was 0.74. Sensitivity and specificity for penetration were 34.3% and 70.6%, respectively; accuracy was 32%. The V-VST is low in cost, easy to use and very sensitive, meeting the requirements of oropharyngeal dysphagia and aspiration screening test in subacute stroke patients.

Identification of dysphagia using the Toronto Bedside Swallowing Screening Test (TOR-BSST©): are 10 teaspoons of water necessary?

PubMed

Martino, Rosemary; Maki, Ellen; Diamant, Nicholas

2014-06-01

Dysphagia screening often includes administration of water. This study assessed the accuracy in identifying dysphagia with each additional teaspoon of water. The original research of the TOR-BSST(©) permitted this assessment. Trained nurses from acute and rehabilitation facilities prospectively administered the TOR-BSST(©) to 311 eligible stroke inpatients. A sensitivity analysis was conducted for the water item using 10 teaspoons plus a sip as the standard. The proportion of positive screenings was 59.2% in acute and 38.5% in rehabilitation. Of all four items that form the TOR-BSST(©), the water swallow item contributed to the identification of dysphagia in 42.7% in acute and 29.0% in rehabilitation patients. Across all patients, dysphagia accuracy was that five teaspoons resulted in a sensitivity of 79% (95% confidence interval [CI] = 70-86), eight a sensitivity of 92% (95% CI = 85-96) and 10 a sensitivity of 96% (95% CI = 90-99). Although a primary contributor, the water swallow item alone does not identify all patients with dysphagia. For a water swallow to accurately identify dysphagia, it is critical to administer 10 teaspoons. The TOR-BSST(©) water swallow item contributes largely to the total TOR-BSST(©)'s screening score and in making the test highly accurate and reliable.

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.

Rapid screening for inflammatory neuropathies by standardized clinical criteria

PubMed Central

Tramontozzi, Louis A.

2016-01-01

Abstract Background: Delay in recognition and treatment of inflammatory neuropathies increases morbidity and mortality. We have developed and standardized 3 clinical screening criteria that rapidly detect inflammatory neuropathies. Methods: We reviewed all patients with definite large fiber neuropathy in 2 different patient populations: 1 from a private neurology clinic and the other from a tertiary care center. Patients were divided into 2 groups: those with an inflammatory neuropathy and those with a noninflammatory neuropathy. We specifically noted the 3 key neuropathy characteristics: onset, distribution, and associated systemic features (ODS). We studied the sensitivity and specificity of ODS in differentiating between inflammatory and noninflammatory neuropathies. Results: A total of 206 patients were included: 51 from the private clinic and 155 from the tertiary care center. The sensitivity of using ODS in detecting an inflammatory neuropathy was 96% and the specificity was 85%. The positive predictive value of ODS was 0.8 and negative predictive value was 0.97. Conclusions: Rapid screening for inflammatory neuropathies by ODS clinical criteria is highly sensitive and has a high negative predictive value for noninflammatory neuropathies. ODS uses simple clinical criteria to rapidly screen for patients with a potentially treatable form of neuropathy and accelerate their diagnostic evaluation. Classification of evidence: This study provides Class IV evidence that 3 neuropathy characteristics—onset, distribution, and associated systemic features—accurately identify patients with inflammatory neuropathies. PMID:29443273

Toward a generalized and high-throughput enzyme screening system based on artificial genetic circuits.

PubMed

Choi, Su-Lim; Rha, Eugene; Lee, Sang Jun; Kim, Haseong; Kwon, Kilkoang; Jeong, Young-Su; Rhee, Young Ha; Song, Jae Jun; Kim, Hak-Sung; Lee, Seung-Goo

2014-03-21

Large-scale screening of enzyme libraries is essential for the development of cost-effective biological processes, which will be indispensable for the production of sustainable biobased chemicals. Here, we introduce a genetic circuit termed the Genetic Enzyme Screening System that is highly useful for high-throughput enzyme screening from diverse microbial metagenomes. The circuit consists of two AND logics. The first AND logic, the two inputs of which are the target enzyme and its substrate, is responsible for the accumulation of a phenol compound in cell. Then, the phenol compound and its inducible transcription factor, whose activation turns on the expression of a reporter gene, interact in the other logic gate. We confirmed that an individual cell harboring this genetic circuit can present approximately a 100-fold higher cellular fluorescence than the negative control and can be easily quantified by flow cytometry depending on the amounts of phenolic derivatives. The high sensitivity of the genetic circuit enables the rapid discovery of novel enzymes from metagenomic libraries, even for genes that show marginal activities in a host system. The crucial feature of this approach is that this single system can be used to screen a variety of enzymes that produce a phenol compound from respective synthetic phenyl-substrates, including cellulase, lipase, alkaline phosphatase, tyrosine phenol-lyase, and methyl parathion hydrolase. Consequently, the highly sensitive and quantitative nature of this genetic circuit along with flow cytometry techniques could provide a widely applicable toolkit for discovering and engineering novel enzymes at a single cell level.

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

Study designs for determining and comparing sensitivities of disease screening tests.

PubMed

Prorok, Philip C; Kramer, Barnett S; Miller, Anthony B

2015-12-01

To investigate the capability of various study designs to determine the sensitivity of a disease screening test. Quantities that can be calculated from these designs were derived and examined for their relationship to true sensitivity (the ability to detect unrecognized disease that would surface clinically in the absence of screening) and overdiagnosis. To examine the sensitivity of one test, the single cohort design, in which all participants receive the test, is particularly weak, providing only an upper bound on the true sensitivity, and yields no information about overdiagnosis. A randomized design, with one control arm and participants tested in the other, that includes sufficient post-screening follow-up, allows calculation of bounds on, and an approximation to, true sensitivity and also determination of overdiagnosis. Without follow-up, bounds on the true sensitivity can be calculated. To compare two tests, the single cohort paired design in which all participants receive both tests is precarious. The three arm randomized design with post screening follow-up is preferred, yielding an approximation to the true sensitivity, bounds on the true sensitivity, and the extent of overdiagnosis of each test. Without post screening follow-up, bounds on the true sensitivities can be calculated. When an unscreened control arm is not possible, the two-arm randomized design is recommended. Individual test sensitivities cannot be determined, but with sufficient post-screening follow-up, an order relationship can be established, as can the difference in overdiagnosis between the two tests. © The Author(s) 2015.

Economic implications of three strategies for the control of taeniasis.

PubMed

Alexander, Anu; John, K R; Jayaraman, T; Oommen, Anna; Venkata Raghava, M; Dorny, Pierre; Rajshekhar, Vedantam

2011-11-01

To evaluate the cost-effectiveness of three strategies for the control of taeniasis in a community, in terms of cost per case treated. A study was conducted in South India to determine the prevalence of taeniasis by screening stool samples from 653 randomly chosen subjects, for coproantigens. The costs incurred in the project were used to estimate the cost per case screened and treated. A one-way sensitivity analysis was carried out for varying rates of taeniasis, different screening strategies and mass therapy. Further sensitivity analysis was carried out with different manpower and test costs. The rate of taeniasis as detected by ELISA for coproantigen was 3 per 1000 (2 of 653 samples). Our study showed that mass therapy without screening for taeniasis would be the most economical strategy in terms of cost per case treated if field workers are employed exclusively for either mass therapy or screening. For each strategy, costs per case treated are higher at low prevalence of taeniasis, with a sharp rise below 15%. In places that are endemic for taeniasis and neurocysticercosis, mass therapy or screening for taeniasis should be considered. Screening by stool microscopy is not cost-effective in terms of cost per case of taeniasis treated owing to its low sensitivity. Although the cost per case of taeniasis treated is high at low prevalence of taeniasis for all options, incorporating mass therapy into existing mass drug distribution programmes might prove to be the most cost-effective control strategy. © 2011 Blackwell Publishing Ltd.

Physiologic Screening Test for Eating Disorders/Disordered Eating Among Female Collegiate Athletes.

PubMed

Black, David R.; Larkin, Laurie J.S.; Coster, Daniel C.; Leverenz, Larry J.; Abood, Doris A.

2003-12-01

OBJECTIVE: To develop and evaluate a physiologic screening test specifically designed for collegiate female athletes engaged in athletic competition or highly athletic performances in order to detect eating disorders/disordered eating. No such physiologically based test currently exists. METHODS: Subjects included 148 (84.5%) of 175 volunteer, National Collegiate Athletic Association Division I (n = 92), club (n = 15), and dance team (n = 41) athletes 18 to 25 years old who attended a large, Midwestern university. Participants completed 4 tests: 2 normed for the general population (Eating Disorders Inventory-2 and Bulimia Test-Revised); a new physiologic test, developed and pilot tested by the investigators, called the Physiologic Screening Test; and the Eating Disorder Exam 12.0D, a structured, validated, diagnostic interview used for criterion validity. RESULTS: The 18-item Physiologic Screening Test produced the highest sensitivity (87%) and specificity (78%) and was superior to the Eating Disorders Inventory-2 (sensitivity = 62%, specificity = 74%) and Bulimia Test-Revised (sensitivity = 27%, specificity = 99%). A substantial number (n = 51, 35%) of athletes were classified as eating disordered/disordered eating. CONCLUSIONS: The Physiologic Screening Test should be considered for screening athletes for eating disorders/disordered eating. The Physiologic Screening Test seems to be a viable alternative to existing tests because it is specifically designed for female athletes, it is brief (4 measurements and 14 items), and validity is enhanced and response bias is lessened because the purpose is less obvious, especially when included as part of a mandatory preparticipation examination.

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.

The Abbott RealTime High Risk HPV test is a clinically validated human papillomavirus assay for triage in the referral population and use in primary cervical cancer screening in women 30 years and older: a review of validation studies.

PubMed

Poljak, Mario; Oštrbenk, Anja

2013-01-01

Human papillomavirus (HPV) testing has become an essential part of current clinical practice in the management of cervical cancer and precancerous lesions. We reviewed the most important validation studies of a next-generation real-time polymerase chain reaction-based assay, the RealTime High Risk HPV test (RealTime)(Abbott Molecular, Des Plaines, IL, USA), for triage in referral population settings and for use in primary cervical cancer screening in women 30 years and older published in peer-reviewed journals from 2009 to 2013. RealTime is designed to detect 14 high-risk HPV genotypes with concurrent distinction of HPV-16 and HPV-18 from 12 other HPV genotypes. The test was launched on the European market in January 2009 and is currently used in many laboratories worldwide for routine detection of HPV. We concisely reviewed validation studies of a next-generation real-time polymerase chain reaction (PCR)-based assay: the Abbott RealTime High Risk HPV test. Eight validation studies of RealTime in referral settings showed its consistently high absolute clinical sensitivity for both CIN2+ (range 88.3-100%) and CIN3+ (range 93.0-100%), as well as comparative clinical sensitivity relative to the currently most widely used HPV test: the Qiagen/Digene Hybrid Capture 2 HPV DNA Test (HC2). Due to the significantly different composition of the referral populations, RealTime absolute clinical specificity for CIN2+ and CIN3+ varied greatly across studies, but was comparable relative to HC2. Four validation studies of RealTime performance in cervical cancer screening settings showed its consistently high absolute clinical sensitivity for both CIN2+ and CIN3+, as well as comparative clinical sensitivity and specificity relative to HC2 and GP5+/6+ PCR. RealTime has been extensively evaluated in the last 4 years. RealTime can be considered clinically validated for triage in referral population settings and for use in primary cervical cancer screening in women 30 years and older.

A case study of haemoglobinopathy screening in the Netherlands: witnessing the past, lessons for the future

PubMed Central

Jans, Suze M.P.J.; van El, Carla G.; Houwaart, Eddy S.; Westerman, Marjan J.; Janssens, Rien J.P.A.; Lagro-Janssen, Antoinette L.M.; Plass, Anne Marie C.; Cornel, Martina C.

2011-01-01

Objectives. In 2007 neonatal screening (NNS) was expanded to include screening for sickle cell disease (SCD) and beta-thalassaemia. Up until that year no formal recommendations for haemoglobinopathy (carrier) screening existed in the Netherlands. Although it has been subject to debate in the past, preconceptional and prenatal haemoglobinopathy carrier screening are not part of routine healthcare in the Netherlands. This study aimed to explore the decision-making process of the past: why was the introduction of a screening programme for haemoglobinopathy considered to be untimely, and did ethnicity play a role given the history in other countries surrounding the introduction of haemoglobinopathy screening? Design. A witness seminar was organised, inviting key figures to discuss the decision-making process concerning haemoglobinopathy screening in the Netherlands, thereby adding new perspectives on past events. The transcript was content-analysed. Results. The subject of haemoglobinopathy screening first appeared in the 1970s. As opposed to a long history of neglect of African-American health in the United States, the heritage of the Second World War influenced the decision-making process in the Netherlands. As a consequence, registration of ethnicity surfaced as an impeding factor. However, overall, official Dutch screening policy was restrained regarding reproductive issues caused by fear of eugenics. In the 1990s haemoglobinopathy screening was found to be ‘not opportune’ due to low prevalence, lack of knowledge and fear of stigmatisation. Currently the registration of ethnicity remains on the political agenda, but still proves to be a sensitive subject. Discussion. Carrier screening in general never appeared high on the policy agenda. Registration of ethnicity remains sensitive caused by the current political climate. Complexities related to carrier screening are a challenge in Dutch healthcare. Whether carrier screening will be considered a valuable complementary strategy in the Netherlands, depends partly on participation of representatives of high-risk groups in policy making. PMID:21819310

Antibody screening by enzyme-linked immunosorbent assay using pooled soluble HLA in renal transplant candidates.

PubMed

Zaer, F; Metz, S; Scornik, J C

1997-01-15

The enzyme-linked immunosorbent assay (ELISA) using HLA class I molecules purified from pooled platelets has the potential to detect HLA antibodies with increased efficiency without sacrificing sensitivity or specificity. This test, which was originally developed in our institution, has been independently validated by recent studies and is now commercially available. We now present evidence of its usefulness as a routine HLA antibody screening test for renal transplant patients. A total of 515 patients were tested monthly by ELISA (13.9 tests/patient) and by antiglobulin-enhanced panel reactivity (6.3 tests/patient). In patients found to be unsensitized, the incidence of false-positive results was less for ELISA than for the panel studies. In patients who were highly sensitized, both tests performed equally well, whereas discordant results were registered mainly in cases of mild sensitization. Because 66% of our patients were not sensitized, the ELISA was effective in reducing the number of more involved tests aimed at characterizing the antibodies. These results provide a foundation to use the pooled platelet HLA ELISA on a routine basis for HLA antibody screening.

The local lymph node assay and skin sensitization: a cut-down screen to reduce animal requirements?

PubMed

Kimber, Ian; Dearman, Rebecca J; Betts, Catherine J; Gerberick, G Frank; Ryan, Cindy A; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A

2006-04-01

The local lymph node assay (LLNA), an alternative approach to skin-sensitizing testing, has made a significant contribution to animal welfare by permitting a reduction and refinement of animal use. Although there is clearly an aspiration to eliminate the use of animals in such tests, it is appropriate also to consider other opportunities for refinement and reduction of animal use. We have therefore explored the use of a modified version of the LLNA for screening purposes when there is a need to evaluate the sensitizing activity of a large number of chemicals, as will be the case under the auspices of registration, evaluation and authorization of chemicals (REACH). Using an existing LLNA database of 211 chemicals, we have examined whether a cut-down assay comprising a single high-dose group and a concurrent vehicle control would provide a realistic approach for screening chemicals for sensitizing potential. The analyses reported here suggest this is the case. We speculate that the animal welfare benefits may be enhanced further by reducing the number of animals per experimental group. However, a detailed evaluation will be necessary to provide reassurance that a reduction in group size would provide adequate sensitivity across a range of skin sensitization potencies.

Screening for attention-deficit/hyperactivity disorder in borderline personality disorder.

PubMed

Weibel, Sébastien; Nicastro, Rosetta; Prada, Paco; Cole, Pierre; Rüfenacht, Eva; Pham, Eléonore; Dayer, Alexandre; Perroud, Nader

2018-01-15

A valid screening instrument is needed to detect attention-deficit/hyperactivity disorder (ADHD) in treatment-seeking borderline personality disorder (BPD) patients. We aimed to test the performance of the widely-used Adult ADHD Self-Report Scale v1.1 screener (ASRS-v1.1). 317 BPD subjects were systematically assessed for comorbid ADHD and completed the ASRS-v1.1. 79 BPD patients also completed the Wender Utah Rating Scale (WURS-25). The prevalence of adult ADHD was of 32.4%. The overall positive predictive value of the ASRS-v1.1 was of 38.5%, the negative predictive value 77.0%, the sensitivity 72.8%, and the specificity 43.9%. Combining WURS-25 and ASRS-v1.1 improved sensitivity to 81.8% and specificity to 59.6%. Cross-sectional study on treatment-seeking patients. We found a high prevalence of ADHD using structured interviews. The ASRS-v1.1 was not a sensitive screener for identifying possible ADHD cases in a BPD population, with a high number of false positives. When combined with the WURS-25, it offered improved screening. Copyright © 2017 Elsevier B.V. All rights reserved.

Examining the Sensitivity and Specificity of 2 Screening Instruments: Odontogenic or Temporomandibular Disorder Pain?

PubMed

Fonseca Alonso, Barbara; Nixdorf, Donald R; Shueb, Sarah S; John, Mike T; Law, Alan S; Durham, Justin

2017-01-01

Two groups of patients with orofacial pains that are clinically important to distinguish from each other are patients with odontogenic pain and temporomandibular disorder (TMD) pain. The aim of this study was to determine the sensitivity and specificity of 2 screening instruments in distinguishing between patients with these types of pain. A convenience sample of patients seeking care at an endodontic clinic and an orofacial pain clinic were recruited. The 14-item dental pain questionnaire (DePaQ) was used to screen for odontogenic pain and the 6-item TMD screener was used to screen for TMD pain. Sensitivity and specificity calculations with 95% confidence intervals (CIs) were performed for both instruments, and thresholds/acceptability/performance was assessed using published guidelines. Thirty-four patients with odontogenic pain and 37 patients with TMD pain were included in this study. The sensitivity of the DePaQ was 0.85 (95% CI, 0.69-0.95), and specificity was 0.11 (95% CI, 0.03-0.25). The sensitivity of the TMD screener was 0.92 (95% CI, 0.78-0.98), and specificity was 0.59 (95% CI, 0.41-0.75). The point estimates, a single value used to estimate the population parameter, for both the DePaQ and TMD screener were "acceptable" in identifying patients who had the pain condition in question (ie, sensitivity), whereas the point estimate for appropriately identifying patients who did not have the pain condition when they did not have it (ie, specificity) was "nonacceptable" for both. The DePaQ and the TMD screener lack diagnostic accuracy for differentiating TMD from odontogenic tooth pain without adjunctive (clinical) investigation(s) or examination. However, the TMD screener has high sensitivity for identifying true positives (ie, TMD pain) and would therefore be useful as a screening instrument when one can definitively exclude odontogenic etiology for pain on clinical and radiographic grounds, for instance in endodontic practices. In this study, the negative predictive value was also high in the TMD screener, and, therefore, we can trust a negative result (ie, when the TMD screener is negative, we can be fairly certain the pain diagnosis is not TMD and rule out TMD). Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

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.

Specificity and Sensitivity Ratios of the Pediatric Language Acquisition Screening Tool for Early Referral-Revised.

ERIC Educational Resources Information Center

Sherman, Tracy; Shulman, Brian B.

1999-01-01

This study examined test characteristics of the Pediatric Language Acquisition Screening Tool for Early Referral-Revised (PLASTER-R), a set of developmental questionnaires for children 3 to 60 months of age. The PLASTER-R was moderately to highly successful in identifying children within normal limits for language development. Test-retest…

The DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure as a Screening Tool.

PubMed

Bastiaens, Leo; Galus, James

2018-03-01

The DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure was developed to aid clinicians with a dimensional assessment of psychopathology; however, this measure resembles a screening tool for several symptomatic domains. The objective of the current study was to examine the basic parameters of sensitivity, specificity, positive and negative predictive power of the measure as a screening tool. One hundred and fifty patients in a correctional community center filled out the measure prior to a psychiatric evaluation, including the Mini International Neuropsychiatric Interview screen. The above parameters were calculated for the domains of depression, mania, anxiety, and psychosis. The results showed that the sensitivity and positive predictive power of the studied domains was poor because of a high rate of false positive answers on the measure. However, when the lowest threshold on the Cross-Cutting Symptom Measure was used, the sensitivity of the anxiety and psychosis domains and the negative predictive values for mania, anxiety and psychosis were good. In conclusion, while it is foreseeable that some clinicians may use the DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure as a screening tool, it should not be relied on to identify positive findings. It functioned well in the negative prediction of mania, anxiety and psychosis symptoms.

Advantages and application of label-free detection assays in drug screening.

PubMed

Cunningham, Brian T; Laing, Lance G

2008-08-01

Adoption is accelerating for a new family of label-free optical biosensors incorporated into standard format microplates owing to their ability to enable highly sensitive detection of small molecules, proteins and cells for high-throughput drug discovery applications. Label-free approaches are displacing other detection technologies owing to their ability to provide simple assay procedures for hit finding/validation, accessing difficult target classes, screening the interaction of cells with drugs and analyzing the affinity of small molecule inhibitors to target proteins. This review describes several new drug discovery applications that are under development for microplate-based photonic crystal optical biosensors and the key issues that will drive adoption of the technology. Microplate-based optical biosensors are enabling a variety of cell-based assays, inhibition assays, protein-protein binding assays and protein-small molecule binding assays to be performed with high-throughput and high sensitivity.

Pulse Oximetry and Auscultation for Congenital Heart Disease Detection.

PubMed

Hu, Xiao-Jing; Ma, Xiao-Jing; Zhao, Qu-Ming; Yan, Wei-Li; Ge, Xiao-Ling; Jia, Bing; Liu, Fang; Wu, Lin; Ye, Ming; Liang, Xue-Cun; Zhang, Jing; Gao, Yan; Zhai, Xiao-Wen; Huang, Guo-Ying

2017-10-01

Pulse oximetry (POX) has been confirmed as a specific screening modality for critical congenital heart disease (CCHD), with moderate sensitivity. However, POX is not able to detect most serious and critical cardiac lesions (major congenital heart disease [CHD]) without hypoxemia. In this study, we investigated the accuracy and feasibility of the addition of cardiac auscultation to POX as a screening method for asymptomatic major CHD. A multicenter prospective observational screening study was conducted at 15 hospitals in Shanghai between July 1, 2012, and December 31, 2014. Newborns with either an abnormal POX or cardiac auscultation were defined as screen positive. All screen-positive newborns underwent further echocardiography. False-negative results were identified by clinical follow-up, parents' feedback, and telephone review. We assessed the accuracy of POX plus cardiac auscultation for the detection of major CHD. CHD screening was completed in all 15 hospitals, with a screening rate of 94.0% to 99.8%. In total, 167 190 consecutive asymptomatic newborn infants were screened, of which 203 had major CHD (44 critical and 159 serious). The sensitivity of POX plus cardiac auscultation was 95.5% (95% confidence interval 84.9%-98.7%) for CCHD and 92.1% (95% confidence interval 87.7%-95.1%) for major CHD. The false-positive rate was 1.2% for detecting CCHD and 1.1% for detecting major CHD. In our current study, we show that using POX plus cardiac auscultation significantly improved the detection rate of major CHD in the early neonatal stage, with high sensitivity and a reasonable false-positive rate. It provides strong evidence and a reliable method for neonatal CHD screening. Copyright © 2017 by the American Academy of Pediatrics.

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens.

PubMed

Morgens, David W; Wainberg, Michael; Boyle, Evan A; Ursu, Oana; Araya, Carlos L; Tsui, C Kimberly; Haney, Michael S; Hess, Gaelen T; Han, Kyuho; Jeng, Edwin E; Li, Amy; Snyder, Michael P; Greenleaf, William J; Kundaje, Anshul; Bassik, Michael C

2017-05-05

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens.

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens

PubMed Central

Morgens, David W.; Wainberg, Michael; Boyle, Evan A.; Ursu, Oana; Araya, Carlos L.; Tsui, C. Kimberly; Haney, Michael S.; Hess, Gaelen T.; Han, Kyuho; Jeng, Edwin E.; Li, Amy; Snyder, Michael P.; Greenleaf, William J.; Kundaje, Anshul; Bassik, Michael C.

2017-01-01

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens. PMID:28474669

Shifted Transversal Design smart-pooling for high coverage interactome mapping

PubMed Central

Xin, Xiaofeng; Rual, Jean-François; Hirozane-Kishikawa, Tomoko; Hill, David E.; Vidal, Marc; Boone, Charles; Thierry-Mieg, Nicolas

2009-01-01

“Smart-pooling,” in which test reagents are multiplexed in a highly redundant manner, is a promising strategy for achieving high efficiency, sensitivity, and specificity in systems-level projects. However, previous applications relied on low redundancy designs that do not leverage the full potential of smart-pooling, and more powerful theoretical constructions, such as the Shifted Transversal Design (STD), lack experimental validation. Here we evaluate STD smart-pooling in yeast two-hybrid (Y2H) interactome mapping. We employed two STD designs and two established methods to perform ORFeome-wide Y2H screens with 12 baits. We found that STD pooling achieves similar levels of sensitivity and specificity as one-on-one array-based Y2H, while the costs and workloads are divided by three. The screening-sequencing approach is the most cost- and labor-efficient, yet STD identifies about twofold more interactions. Screening-sequencing remains an appropriate method for quickly producing low-coverage interactomes, while STD pooling appears as the method of choice for obtaining maps with higher coverage. PMID:19447967

Sensitometric properties of Agfa Dentus OrthoLux, Agfa Dentus ST8G, and Kodak Ektavision panoramic radiographic film.

PubMed

Wakoh, M; Nishikawa, K; Kobayashi, N; Farman, A G; Kuroyanagi, K

2001-02-01

The purpose of this study was to compare the sensitometric properties of and visualization of anatomical structures with Agfa OrthoLux green-sensitive panoramic radiographic film, Agfa ST8G green sensitive panoramic radiographic film, and Kodak Ektavision green-sensitive panoramic radiographic film used in combination with an Agfa Ortho Regular 400 imaging screen, Kodak Ektavision imaging screen, and Kodak Lanex Regular imaging screen. The density response and resolution of panoramic radiographic film/intensifying screen combinations was evaluated by means of Hunter and Driffield curves, modulation transfer functions, and noise-equivalent number of quanta. Image clarity of selected anatomical structures was rated independently by 6 oral and maxillofacial radiologists. The ISO speed for the Agfa OrthoLux panoramic radiographic film combinations was the fastest, and the ISO speed for the Kodak Ektavision green-sensitive panoramic radiographic film combinations was the slowest. The average gradient for the Agfa ST8G systems was relatively steep in comparison with those for the other film/screen combinations. The modulation transfer functions for the Kodak Ektavision film were higher than those for the other films, irrespective of the screen combination used, and those for Agfa OrthoLux film were slightly higher than those for Agfa ST8G film. The noise-equivalent number of quanta for the Agfa ST8G film/screen combinations was lower than those for the other film/screen combinations. The noise-equivalent number of quanta for the Kodak Ektavision film/screen combinations was well within the high-frequency range, whereas Agfa OrthoLux combined with either the Kodak Ektavision imaging screen or the Kodak Lanex Regular imaging screen produced a noise-equivalent number of quanta similar to those of the Kodak Ektavision film/screen combinations in the low-frequency range. Agfa OrthoLux was perceived to provide clearer images of the selected anatomical details than Agfa ST8G, and the Agfa OrthoLux/Agfa Ortho Regular 400 combination was not significantly different from the Kodak Ektavision/Kodak Lanex Regular combination in terms of perceived image quality. Agfa OrthoLux is an improvement over Agfa ST8G in film speed, spatial resolution, granularity, and perceived diagnostic image quality. The Agfa OrthoLux/Agfa Ortho Regular 400 combination did not exceed the Kodak Ektavision film/Kodak Ektavision imaging screen combination in resolution, granularity, or perceived image quality.

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

PubMed

Hily, Jean-Michel; Liu, Zongrang

2009-03-01

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

A High-Sensitivity Potentiometric 65-nm CMOS ISFET Sensor for Rapid E. coli Screening.

PubMed

Jiang, Yu; Liu, Xu; Dang, Tran Chien; Huang, Xiwei; Feng, Hao; Zhang, Qing; Yu, Hao

2018-04-01

Foodborne bacteria, inducing outbreaks of infection or poisoning, have posed great threats to food safety. Potentiometric sensors can identify bacteria levels in food by measuring medium's pH changes. However, most of these sensors face the limitation of low sensitivity and high cost. In this paper, we developed a high-sensitivity ion-sensitive field-effect transistor sensor. It is small sized, cost-efficient, and can be massively fabricated in a standard 65-nm complementary metal-oxide-semiconductor process. A subthreshold pH-to-time-to-voltage conversion scheme was proposed to improve the sensitivity. Furthermore, design parameters, such as chemical sensing area, transistor size, and discharging time, were optimized to enhance the performance. The intrinsic sensitivity of passivation membrane was calculated as 33.2 mV/pH. It was amplified to 123.8 mV/pH with a 0.01-pH resolution, which greatly exceeded 6.3 mV/pH observed in a traditional source-follower based readout structure. The sensing system was applied to Escherichia coli (E. coli) detection with densities ranging from 14 to 140 cfu/mL. Compared to the conventional direct plate counting method (24 h), more efficient sixfold smaller screening time (4 h) was achieved to differentiate samples' E. coli levels. The demonstrated portable, time-saving, and low-cost prescreen system has great potential for food safety detection.

Looking ahead: a case for HPV testing of self-sampled vaginal specimens as a cervical cancer screening strategy

PubMed Central

Gravitt, Patti E.; Belinson, Jerome L.; Salmeron, Jorge; Shah, Keerti V.

2012-01-01

Even in the era of highly effective HPV prophylactic vaccines, substantial reduction in worldwide cervical cancer mortality will only be realized if effective early detection and treatment of the millions of women already infection and the millions who may not receive vaccination in the next decade can be broadly implemented through sustainable cervical cancer screening programs. Effective programs must meet three targets: 1) at least 70% of the targeted population should be screened at least once in a lifetime, 2) screening assays and diagnostic tests must be reproducible and sufficiently sensitive and specific for the detection of high-grade precursor lesions (i.e., CIN2+), and 3) effective treatment must be provided. We review the evidence that HPV DNA screening from swabs collected by the women in their home or village is sufficiently sound for consideration as a primary screening strategy in the developing world, with sensitivity and specificity for detection of CIN2+ as good or better than Pap smear cytology and VIA. A key feature of a self-collected HPV testing strategy (SC-HPV) is the move of the primary screening activities from the clinic to the community. Efforts to increase the affordability and availability of HPV DNA tests, community education and awareness, development of strong partnerships between community advocacy groups, health care centers and regional or local laboratories, and resource appropriate strategies to identify and treat screen-positive women should now be prioritized to ensure successful public health translation of the technologic advancements in cervical cancer prevention. PMID:21384341

Cost-effectiveness model for hepatitis C screening and treatment: Implications for Egypt and other countries with high prevalence

PubMed Central

Kim, David D.; Hutton, David W.; Raouf, Ahmed A.; Salama, Mohsen; Hablas, Ahmed; Seifeldin, Ibrahim A.; Soliman, Amr S.

2014-01-01

Hepatitis C Virus (HCV) infection is a major cause of cirrhosis and liver cancer, and many developing countries report intermediate-to-high prevalence. However, the economic impact of screening and treatment for HCV in high prevalence countries has not been well studied. Thus, we examined the cost-effectiveness of screening and treatment for HCV infection for asymptomatic, average-risk adults using a Markov decision analytic model. In our model, we collected age-specific prevalence, disease progression rates for Egyptians, and local cost estimates in Egypt, which has the highest prevalence of HCV infection (~15%) in the world. We estimated the incremental cost-effectiveness ratio (ICER) and conducted sensitivity analyses to determine how cost-effective HCV screening and treatment might be in other developing countries with high and intermediate prevalence. In Egypt, implementing a screening program using triple-therapy treatment (sofosbuvir with pegylated interferon and ribavirin) was dominant compared to no screening because it would have lower total costs and improve health outcomes. HCV screening and treatment would also be cost-effective in global settings with intermediate costs of drug treatment (~$8,000) and a higher sustained viral response rate (70–80%). PMID:25469976

Detection of phase I IgG antibodies to Coxiella burnetii with EIA as a screening test for blood donations.

PubMed

van der Hoek, W; Wielders, C C H; Schimmer, B; Wegdam-Blans, M C A; Meekelenkamp, J; Zaaijer, H L; Schneeberger, P M

2012-11-01

The presence of a high phase I IgG antibody titre may indicate chronic infection and a risk for the transmission of Coxiella burnetii through blood transfusion. The outbreak of Q fever in the Netherlands allowed for the comparison of an enzyme immunoassay (EIA) with the reference immunofluorescence assay (IFA) in a large group of individuals one year after acute Q fever. EIA is 100 % sensitive in detecting high (≥1:1,024) phase I IgG antibody titres. The cost of screening with EIA and confirming all EIA-positive results with IFA is much lower than screening all donations with IFA. This should be taken into account in cost-effectiveness analyses of screening programmes.

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

Burrage, Clare; Copeland, Edmund J.; Hinds, E.A., E-mail: Clare.Burrage@nottingham.ac.uk, E-mail: Edmund.Copeland@nottingham.ac.uk, E-mail: Ed.Hinds@imperial.ac.uk

Theories of dark energy require a screening mechanism to explain why the associated scalar fields do not mediate observable long range fifth forces. The archetype of this is the chameleon field. Here we show that individual atoms are too small to screen the chameleon field inside a large high-vacuum chamber, and therefore can detect the field with high sensitivity. We derive new limits on the chameleon parameters from existing experiments, and show that most of the remaining chameleon parameter space is readily accessible using atom interferometry.

Ultrasound as an Adjunct to Mammography for Breast Cancer Screening: A Health Technology Assessment

PubMed Central

Nikitovic-Jokic, Milica; Tu, Hong Anh; Palimaka, Stefan; Higgins, Caroline; Holubowich, Corinne

2016-01-01

Background Screening with mammography can detect breast cancer early, before clinical symptoms appear. Some cancers, however, are not captured with mammography screening alone. Ultrasound has been suggested as a safe adjunct screening tool that can detect breast cancers missed on mammography. We investigated the benefits, harms, cost-effectiveness, and cost burden of ultrasound as an adjunct to mammography compared with mammography alone for screening women at average risk and at high risk for breast cancer. Methods We searched Ovid MEDLINE, Ovid Embase, EBM Reviews, and the NHS Economic Evaluation Database, from January 1998 to June 2015, for evidence of effectiveness, harms, diagnostic accuracy, and cost-effectiveness. Only studies evaluating the use of ultrasound as an adjunct to mammography in the specified populations were included. We also conducted a cost analysis to estimate the costs in Ontario over the next 5 years to fund ultrasound as an adjunct to mammography in breast cancer screening for high-risk women who are contraindicated for MRI, the current standard of care to supplement mammography. Results No studies in average-risk women met the inclusion criteria of the clinical review. We included 5 prospective, paired cohort studies in high-risk women, 4 of which were relevant to the Ontario context. Adjunct ultrasound identified between 2.3 and 5.9 additional breast cancers per 1,000 screens. The average pooled sensitivity of mammography and ultrasound was 53%, a statistically significant increase relative to mammography alone (absolute increase 13%; P < .05). The average pooled specificity of the combined test was 96%, an absolute increase in the false-positive rate of 2% relative to mammography screening alone. The GRADE for this body of evidence was low. Additional annual costs of using breast ultrasound as an adjunct to mammography for high-risk women in Ontario contraindicated for MRI would range from $15,500 to $30,250 in the next 5 years. Conclusions We found no evidence that evaluated the comparative effectiveness or diagnostic accuracy of screening breast ultrasound as an adjunct to mammography among average-risk women aged 50 years and over. In women at high risk of developing breast cancer, there is low-quality evidence that screening with mammography and adjunct ultrasound detects additional cases of disease, with improved sensitivity compared to mammography alone. Screening with adjunct ultrasound also increases the number of false-positive findings and subsequent biopsy recommendations. It is unclear if the use of screening breast ultrasound as an adjunct to mammography will reduce breast cancer–related mortality among high-risk women. The annual cost burden of using adjunct ultrasound to screen high-risk women who cannot receive MRI in Ontario would be small. PMID:27468326

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

Assessment of circulating copy number variant detection for cancer screening.

PubMed

Molparia, Bhuvan; Nichani, Eshaan; Torkamani, Ali

2017-01-01

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

Cognitive Screening in Brain Tumors: Short but Sensitive Enough?

PubMed Central

Robinson, Gail A.; Biggs, Vivien; Walker, David G.

2015-01-01

Cognitive deficits in brain tumors are generally thought to be relatively mild and non-specific, although recent evidence challenges this notion. One possibility is that cognitive screening tools are being used to assess cognitive functions but their sensitivity to detect cognitive impairment may be limited. For improved sensitivity to recognize mild and/or focal cognitive deficits in brain tumors, neuropsychological evaluation tailored to detect specific impairments has been thought crucial. This study investigates the sensitivity of a cognitive screening tool, the Montreal Cognitive Assessment (MoCA), compared to a brief but tailored cognitive assessment (CA) for identifying cognitive deficits in an unselected primary brain tumor sample (i.e., low/high-grade gliomas, meningiomas). Performance is compared on broad measures of impairment: (a) number of patients impaired on the global screening measure or in any cognitive domain; and (b) number of cognitive domains impaired and specific analyses of MoCA-Intact and MoCA-Impaired patients on specific cognitive tests. The MoCA-Impaired group obtained lower naming and word fluency scores than the MoCA-Intact group, but otherwise performed comparably on cognitive tests. Overall, based on our results from patients with brain tumor, the MoCA has extremely poor sensitivity for detecting cognitive impairments and a brief but tailored CA is necessary. These findings will be discussed in relation to broader issues for clinical management and planning, as well as specific considerations for neuropsychological assessment of brain tumor patients. PMID:25815273

Global sensitivity analysis for urban water quality modelling: Terminology, convergence and comparison of different methods

NASA Astrophysics Data System (ADS)

Vanrolleghem, Peter A.; Mannina, Giorgio; Cosenza, Alida; Neumann, Marc B.

2015-03-01

Sensitivity analysis represents an important step in improving the understanding and use of environmental models. Indeed, by means of global sensitivity analysis (GSA), modellers may identify both important (factor prioritisation) and non-influential (factor fixing) model factors. No general rule has yet been defined for verifying the convergence of the GSA methods. In order to fill this gap this paper presents a convergence analysis of three widely used GSA methods (SRC, Extended FAST and Morris screening) for an urban drainage stormwater quality-quantity model. After the convergence was achieved the results of each method were compared. In particular, a discussion on peculiarities, applicability, and reliability of the three methods is presented. Moreover, a graphical Venn diagram based classification scheme and a precise terminology for better identifying important, interacting and non-influential factors for each method is proposed. In terms of convergence, it was shown that sensitivity indices related to factors of the quantity model achieve convergence faster. Results for the Morris screening method deviated considerably from the other methods. Factors related to the quality model require a much higher number of simulations than the number suggested in literature for achieving convergence with this method. In fact, the results have shown that the term "screening" is improperly used as the method may exclude important factors from further analysis. Moreover, for the presented application the convergence analysis shows more stable sensitivity coefficients for the Extended-FAST method compared to SRC and Morris screening. Substantial agreement in terms of factor fixing was found between the Morris screening and Extended FAST methods. In general, the water quality related factors exhibited more important interactions than factors related to water quantity. Furthermore, in contrast to water quantity model outputs, water quality model outputs were found to be characterised by high non-linearity.

Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology

PubMed Central

Constantinidis, Theocharis; Constantinidis, Theodoros C.

2015-01-01

Objectives The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. Methods The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Results Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). Conclusion HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women. PMID:25793281

Noninvasive Prenatal Screening for Genetic Diseases Using Massively Parallel Sequencing of Maternal Plasma DNA

PubMed Central

Chitty, Lyn S.; Lo, Y. M. Dennis

2015-01-01

The identification of cell-free fetal DNA (cffDNA) in maternal plasma in 1997 heralded the most significant change in obstetric care for decades, with the advent of safer screening and diagnosis based on analysis of maternal blood. Here, we describe how the technological advances offered by next-generation sequencing have allowed for the development of a highly sensitive screening test for aneuploidies as well as definitive prenatal molecular diagnosis for some monogenic disorders. PMID:26187875

Comparing sensitivity and specificity of screening mammography in the United States and Denmark

PubMed Central

Jacobsen, Katja Kemp; O'Meara, Ellen S.; Key, Dustin; Buist, Diana SM; Kerlikowske, Karla; Vejborg, Ilse; Sprague, Brian L.; Lynge, Elsebeth; von Euler-Chelpin, My

2015-01-01

Delivery of screening mammography differs substantially between the United States (US) and Denmark. We evaluate whether there are differences in screening sensitivity and specificity. We included screens from women screened at age 50-69 years during 1996-2008/2009 in the US Breast Cancer Surveillance Consortium (BCSC) (n=2,872,791), and from two population-based mammography screening programs in Denmark (Copenhagen, n=148,156 and Funen, n=275,553). Women were followed for one year. For initial screens, recall rate was significantly higher in BCSC (17.6%) than in Copenhagen (4.3%) and Funen (3.1%). Sensitivity was fairly similar in BCSC (91.8%) and Copenhagen (90.5%) and Funen (92.5%). At subsequent screens, recall rates were 8.8%, 1.8% and 1.4% in BCSC, Copenhagen and Funen, respectively. The BCSC sensitivity (82.3%) was lower compared to Copenhagen (88.9%) and Funen (86.9%), but when stratified by time since last screen, the sensitivity was similar. For both initial and subsequent screening, the specificity of screening in BCSC (83.2 and 91.6%) was significantly lower than in Copenhagen (96.6 and 98.8%) and Funen. (97.9 and 99.2%). Taking time since last screen into account, American and Danish women had the same probability of having their asymptomatic cancers detected at screening. However, the majority of women free of asymptomatic cancers experienced more harms in terms of false-positive findings in the US than in Denmark. PMID:25944711

Screening for prenatal substance use: development of the Substance Use Risk Profile-Pregnancy scale.

PubMed

Yonkers, Kimberly A; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B; Rounsaville, Bruce J

2010-10-01

To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. III.

Screening for Prenatal Substance Use

PubMed Central

Yonkers, Kimberly A.; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B.; Rounsaville, Bruce J.

2011-01-01

OBJECTIVE To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. METHODS Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into “training” (n=1,610) and “validation” (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. RESULTS The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike’s Information Criterion=579.75, Nagelkerke R2=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). CONCLUSION The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. PMID:20859145

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.

Highly broad-specific and sensitive enzyme-linked immunosorbent assay for screening sulfonamides: Assay optimization and application to milk samples

USDA-ARS?s Scientific Manuscript database

A broad-specific and sensitive immunoassay for the detection of sulfonamides was developed by optimizing the conditions of an enzyme-linked immunosorbent assay (ELISA) in regard to different monoclonal antibodies (MAbs), assay format, immunoreagents, and several physicochemical factors (pH, salt, de...

Single measure and gated screening approaches for identifying students at-risk for academic problems: Implications for sensitivity and specificity.

PubMed

Van Norman, Ethan R; Nelson, Peter M; Klingbeil, David A

2017-09-01

Educators need recommendations to improve screening practices without limiting students' instructional opportunities. Repurposing previous years' state test scores has shown promise in identifying at-risk students within multitiered systems of support. However, researchers have not directly compared the diagnostic accuracy of previous years' state test scores with data collected during fall screening periods to identify at-risk students. In addition, the benefit of using previous state test scores in conjunction with data from a separate measure to identify at-risk students has not been explored. The diagnostic accuracy of 3 types of screening approaches were tested to predict proficiency on end-of-year high-stakes assessments: state test data obtained during the previous year, data from a different measure administered in the fall, and both measures combined (i.e., a gated model). Extant reading and math data (N = 2,996) from 10 schools in the Midwest were analyzed. When used alone, both measures yielded similar sensitivity and specificity values. The gated model yielded superior specificity values compared with using either measure alone, at the expense of sensitivity. Implications, limitations, and ideas for future research are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

Effect of Antiretroviral Therapy on the Diagnostic Accuracy of Symptom Screening for Intensified Tuberculosis Case Finding in a South African HIV Clinic

PubMed Central

Rangaka, Molebogeng X.; Wilkinson, Robert J.; Glynn, Judith R.; Boulle, Andrew; van Cutsem, Gilles; Goliath, Rene; Mathee, Shaheed; Maartens, Gary

2012-01-01

Background. Current symptom screening algorithms for intensified tuberculosis case finding or prior to isoniazid preventive therapy (IPT) in patients infected with human immunodeficiency virus (HIV) were derived from antiretroviral-naive cohorts. There is a need to validate screening algorithms in patients on antiretroviral therapy (ART). Methods. We performed cross-sectional evaluation of the diagnostic accuracy of symptom screening, including the World Health Organization (WHO) algorithm, to rule out tuberculosis in HIV-infected individuals pre-ART and on ART undergoing screening prior to IPT. Results. A total of 1429 participants, 54% on ART, had symptom screening and a sputum culture result available. Culture-positive tuberculosis was diagnosed in 126 patients (8.8%, 95% confidence interval [CI], 7.4%–10.4%). The WHO symptom screen in the on-ART compared with the pre-ART group had a lower sensitivity (23.8% vs 47.6%), but higher specificity (94.4% vs 79.8%). The effect of ART was independent of CD4+ count in multivariable analyses. The posttest probability of tuberculosis following a negative WHO screen was 8.9% (95% CI, 7.4%–10.8%) and 4.4% (95% CI, 3.7%–5.2%) for the pre-ART and on-ART groups, respectively. Addition of body mass index to the WHO screen significantly improved discriminatory ability in both ART groups, which was further improved by adding CD4 count and ART duration. Conclusions. The WHO symptom screen has poor sensitivity, especially among patients on ART, in a clinic where regular tuberculosis screening is practiced. Consequently, a significant proportion of individuals with tuberculosis would inadvertently be placed on isoniazid monotherapy despite high negative predictive values. Until more sensitive methods of ruling out tuberculosis are established, it would be prudent to do a sputum culture prior to IPT where this is feasible. PMID:22955441

The Borderline Syndrome Index: a validation study using the personality assessment schedule.

PubMed

Marlowe, M J; O'Neill-Byrne, K; Lowe-Ponsford, F; Watson, J P

1996-01-01

This study examines the validity and screening properties of the Borderline Syndrome Index--BSI (developed in the USA) for categories of the Personality Assessment Schedule--PAS (developed in the UK). Patients were recruited by case control sampling. Chance corrected agreement between instruments and screening properties of the BSI were calculated. The BSI proved a moderately sensitive but non-specific screen. Questionnaire scores were highly correlated with symptom measures. The results do not support the validity of the BSI or its use as a screening instrument. BSI scores may be distorted by current symptoms.

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

PubMed

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

2017-07-01

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

Automatic detection of anomalies in screening mammograms

PubMed Central

2013-01-01

Background Diagnostic performance in breast screening programs may be influenced by the prior probability of disease. Since breast cancer incidence is roughly half a percent in the general population there is a large probability that the screening exam will be normal. That factor may contribute to false negatives. Screening programs typically exhibit about 83% sensitivity and 91% specificity. This investigation was undertaken to determine if a system could be developed to pre-sort screening-images into normal and suspicious bins based on their likelihood to contain disease. Wavelets were investigated as a method to parse the image data, potentially removing confounding information. The development of a classification system based on features extracted from wavelet transformed mammograms is reported. Methods In the multi-step procedure images were processed using 2D discrete wavelet transforms to create a set of maps at different size scales. Next, statistical features were computed from each map, and a subset of these features was the input for a concerted-effort set of naïve Bayesian classifiers. The classifier network was constructed to calculate the probability that the parent mammography image contained an abnormality. The abnormalities were not identified, nor were they regionalized. The algorithm was tested on two publicly available databases: the Digital Database for Screening Mammography (DDSM) and the Mammographic Images Analysis Society’s database (MIAS). These databases contain radiologist-verified images and feature common abnormalities including: spiculations, masses, geometric deformations and fibroid tissues. Results The classifier-network designs tested achieved sensitivities and specificities sufficient to be potentially useful in a clinical setting. This first series of tests identified networks with 100% sensitivity and up to 79% specificity for abnormalities. This performance significantly exceeds the mean sensitivity reported in literature for the unaided human expert. Conclusions Classifiers based on wavelet-derived features proved to be highly sensitive to a range of pathologies, as a result Type II errors were nearly eliminated. Pre-sorting the images changed the prior probability in the sorted database from 37% to 74%. PMID:24330643

Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis

PubMed Central

Beltrame, Anna; Guerriero, Massimo; Angheben, Andrea; Gobbi, Federico; Requena-Mendez, Ana; Zammarchi, Lorenzo; Formenti, Fabio; Perandin, Francesca; Bisoffi, Zeno

2017-01-01

Background Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting. Methodology/Principal findings A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone. Conclusions The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants. PMID:28582412

Prediction of permanent hearing loss in high-risk preterm infants at term age.

PubMed

Valkama, A M; Laitakari, K T; Tolonen, E U; Väyrynen, M R; Vainionpää, L K; Koivisto, M E

2000-06-01

The aim of this series was to assess hearing screenings; auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free field auditory responses (FF) for the prediction of permanent bilateral hearing loss in high-risk preterm infants at term post-conceptional age. A total of 51 preterm infants (gestational age < 34 weeks, birth weight < 1500 g) underwent examinations at term and hearing, speech and neurological development were followed up until a corrected age of 18 months. Significant hearing defects were verified by broader ABR examinations under sedation and by clinical ward observation including responsiveness to sounds and enhancement of hearing using an amplification device. Seven bilateral fails in ABR were found, together with nine bilateral fails in TEOAE and four fails in FF screening at term age. Six preterm infants were later confirmed to have a significant permanent bilateral hearing loss, four of whom had also cerebral palsy. Bilateral failure in ABR screening predicted hearing loss with a sensitivity of 100% and a specificity of 98%, TEOAE with a sensitivity of 50% and a specificity of 84% and in the FF examination at the levels of 50% and 98%, respectively. Transient evoked otoacoustic emissions alone seem not to be so applicable to the neonatal screening of hearing in high-risk preterm infants as shown earlier in full-term infants, possibly because a hearing defect may be due to retrocochlear damage. Consequently, auditory brainstem response screening seems to be more suitable for very low birth weight preterm infants.

An Independent Investigation of the Utility of the Learning Disability Screening Questionnaire (LDSQ) within a Community Learning Disability Team

ERIC Educational Resources Information Center

Stirk, Steven; Field, Bryony; Black, Jessica

2018-01-01

Background: The Learning Disability Screening Questionnaire (LDSQ) has been shown to have high sensitivity and specificity to identify those who are likely to meet intellectual disability diagnostic criteria (McKenzie, et al. [McKenzie K., 2015]). However, there is no independent research to date to support these findings. Materials and Methods:…

Diagnostic accuracy of high-risk HPV DNA genotyping for primary cervical cancer screening and triage of HPV-positive women, compared to cytology: preliminary results of the PIPAVIR study.

PubMed

Chatzistamatiou, Kimon; Moysiadis, Theodoros; Angelis, Eleftherios; Kaufmann, Andreas; Skenderi, Alkmini; Jansen-Duerr, Pidder; Lekka, Irini; Kilintzis, Vasilis; Angelidou, Stamatia; Katsiki, Evangelia; Hagemann, Ingke; Tsertanidou, Athena; Koch, Isabel; Boecher, Oliver; Soutschek, Erwin; Maglaveras, Nikolaos; Agorastos, Theodoros

2017-05-01

The purpose of the presented PIPAVIR (persistent infections with human papillomaviruses; http://www.pipavir.com ) subanalysis is to assess the performance of high-risk (hr) HPV-DNA genotyping as a method of primary cervical cancer screening and triage of HPV positive women to colposcopy compared to liquid-based cytology (LBC) in an urban female population. Women, aged 30-60, provided cervicovaginal samples at the Family-Planning Centre, Hippokratio Hospital of Thessaloniki, Greece, and the Department of Gynecology and Obstetrics in Mare Klinikum, Kiel, Germany. Cytology and HPV genotyping was performed using LBC and HPV Multiplex Genotyping (MPG), respectively. Women positive for cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] or hrHPV were referred for colposcopy. Among 1723/1762 women included in the final analysis, hrHPV and HPV16/18 prevalence was 17.7 and 9.6%, respectively. Cytology was ASCUS or worse in 7.6%. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 28 women (1.6%). Sensitivity of cytology (ASCUS or worse) and HPV DNA testing for the detection of CIN2+ was 50.0 and 100%, and specificity was 94.49 and 85.49%, respectively. The screening approach according to which only women positive for HPV16/18 and for hrHPV(non16/18) with ASCUS or worse were referred to colposcopy presented 78.57% sensitivity and 13.17% positive predictive value (PPV). HPV testing represents a more sensitive methodology for primary cervical cancer screening compared to cytology. For triage of HPV positive women to colposcopy, partial HPV genotyping offers better sensitivity than cytology, at the cost of higher number of colposcopies.

Hearing loss in the developing world: evaluating the iPhone mobile device as a screening tool.

PubMed

Peer, S; Fagan, J J

2015-01-01

Developing countries have the world's highest prevalence of hearing loss, and hearing screening programmes are scarce. Mobile devices such as smartphones have potential for audiometric testing. To evaluate the uHear app using an Apple iPhone as a possible hearing screening tool in the developing world, and to determine accuracy of certain hearing thresholds that could prove useful in early detection of hearing loss for high-risk populations in resource-poor communities. This was a quasi-experimental study design. Participants recruited from the Otolaryngology Clinic, Groote Schuur Hospital, Cape Town, South Africa, completed a uHear test in three settings--waiting room (WR), quiet roon (QR) and soundproof room (SR). Thresholds were compared with formal audiograms. Twenty-five patients were tested (50 ears). The uHear test detected moderate or worse hearing loss (pure-tone average (PTA) > 40 dB accurately with a sensitivity of 100% in all three environments. Specificity was 88% (SR), 73% (QR) and 68% (WR). Its was highly accurate in detecting high-frequency hearing loss (2 000, 4 000, 6 000 Hz) in the QR and SR with 'good' and 'very good' kappa values, showing statistical significance (p < 0.05). It was moderately accurate in low-frequency hearing loss (250, 500, 1 000 Hz) in the SR, and poor in the QR and WR. Using the iPhone, uHear is a feasible screening test to rule out significant hearing loss (PTA > 40 dB). It is highly sensitive for detecting threshold changes at high frequencies, making it reasonably well suited to detect presbycusis and ototoxic hearing loss from HIV, tuberculosis therapy and chemotherapy. Portability and ease of use make it appropriate to use in developing world communities that lack screening programmes.

A sensitive assay using a native protein substrate for screening HIV-1 maturation inhibitors targeting the protease cleavage site between the matrix and capsid.

PubMed

Lee, Sook-Kyung; Cheng, Nancy; Hull-Ryde, Emily; Potempa, Marc; Schiffer, Celia A; Janzen, William; Swanstrom, Ronald

2013-07-23

The matrix/capsid processing site in the HIV-1 Gag precursor is likely the most sensitive target to inhibit HIV-1 replication. We have previously shown that modest incomplete processing at the site leads to a complete loss of virion infectivity. In the study presented here, a sensitive assay based on fluorescence polarization that can monitor cleavage at the MA/CA site in the context of the folded protein substrate is described. The substrate, an MA/CA fusion protein, was labeled with the fluorescein-based FlAsH (fluorescein arsenical hairpin) reagent that binds to a tetracysteine motif (CCGPCC) that was introduced within the N-terminal domain of CA. By limiting the size of CA and increasing the size of MA (with an N-terminal GST fusion), we were able to measure significant differences in polarization values as a function of HIV-1 protease cleavage. The sensitivity of the assay was tested in the presence of increasing amounts of an HIV-1 protease inhibitor, which resulted in a gradual decrease in the fluorescence polarization values demonstrating that the assay is sensitive in discerning changes in protease processing. The high-throughput screening assay validation in 384-well plates showed that the assay is reproducible and robust with an average Z' value of 0.79 and average coefficient of variation values of <3%. The robustness and reproducibility of the assay were further validated using the LOPAC(1280) compound library, demonstrating that the assay provides a sensitive high-throughput screening platform that can be used with large compound libraries for identifying novel maturation inhibitors targeting the MA/CA site of the HIV-1 Gag polyprotein.

ADHD Is Highly Prevalent in Patients Seeking Treatment for Cannabis Use Disorders.

PubMed

Notzon, Daniel P; Pavlicova, Martina; Glass, Andrew; Mariani, John J; Mahony, Amy L; Brooks, Daniel J; Levin, Frances R

2016-03-31

To estimate the prevalence of ADHD and determine an effective screening test for ADHD in a population-seeking treatment for cannabis use disorders. The Conners Adult ADHD Diagnostic Interview forDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition(DSM-IV; CAADID) was used to generate sensitivity and specificity data for ADHD screening tests, which were then administered to 99 participants seeking treatment for cannabis use disorders to estimate ADHD prevalence. The prevalence estimated from the Wender Utah Rating Scale (WURS) was 45% (sensitivity = 0.88, sensitivity of 0.75), from the Conners Adult ADHD Rating Scale (CAARS) 34% (sensitivity = 0.80, specificity = 0.91), from the WURS + CAARS 36% (sensitivity = 0.71, specificity = 0.95), and from the Adult ADHD Self-Report Scale (ASRS) 46% (sensitivity = 0.61, specificity = 0.86). The prevalence of ADHD in adults seeking treatment for cannabis use disorders is estimated to be between 34% and 46%. The WURS paired with the CAARS provides excellent sensitivity and specificity for the diagnosis of ADHD in this population. © The Author(s) 2016.

Task shifting to clinical officer-led echocardiography screening for detecting rheumatic heart disease in Malawi, Africa.

PubMed

Sims Sanyahumbi, Amy; Sable, Craig A; Karlsten, Melissa; Hosseinipour, Mina C; Kazembe, Peter N; Minard, Charles G; Penny, Daniel J

2017-08-01

Echocardiographic screening for rheumatic heart disease in asymptomatic children may result in early diagnosis and prevent progression. Physician-led screening is not feasible in Malawi. Task shifting to mid-level providers such as clinical officers may enable more widespread screening. Hypothesis With short-course training, clinical officers can accurately screen for rheumatic heart disease using focussed echocardiography. A total of eight clinical officers completed three half-days of didactics and 2 days of hands-on echocardiography training. Clinical officers were evaluated by performing screening echocardiograms on 20 children with known rheumatic heart disease status. They indicated whether children should be referred for follow-up. Referral was indicated if mitral regurgitation measured more than 1.5 cm or there was any measurable aortic regurgitation. The κ statistic was calculated to measure referral agreement with a paediatric cardiologist. Sensitivity and specificity were estimated using a generalised linear mixed model, and were calculated on the basis of World Heart Federation diagnostic criteria. The mean κ statistic comparing clinical officer referrals with the paediatric cardiologist was 0.72 (95% confidence interval: 0.62, 0.82). The κ value ranged from a minimum of 0.57 to a maximum of 0.90. For rheumatic heart disease diagnosis, sensitivity was 0.91 (95% confidence interval: 0.86, 0.95) and specificity was 0.65 (95% confidence interval: 0.57, 0.72). There was substantial agreement between clinical officers and paediatric cardiologists on whether to refer. Clinical officers had a high sensitivity in detecting rheumatic heart disease. With short-course training, clinical officer-led echo screening for rheumatic heart disease is a viable alternative to physician-led screening in resource-limited settings.

Probing dark energy with atom interferometry

NASA Astrophysics Data System (ADS)

Burrage, Clare; Copeland, Edmund J.; Hinds, E. A.

2015-03-01

Theories of dark energy require a screening mechanism to explain why the associated scalar fields do not mediate observable long range fifth forces. The archetype of this is the chameleon field. Here we show that individual atoms are too small to screen the chameleon field inside a large high-vacuum chamber, and therefore can detect the field with high sensitivity. We derive new limits on the chameleon parameters from existing experiments, and show that most of the remaining chameleon parameter space is readily accessible using atom interferometry.

Colon Capsule Endoscopy compared to Conventional Colonoscopy under routine screening conditions

PubMed Central

2010-01-01

Background Colonoscopy (CSPY) for colorectal cancer screening has several limitations. Colon Capsule Endoscopy (PillCam Colon, CCE) was compared to CSPY under routine screening conditions. Methods We performed a prospective, single-center pilot study at a University Hospital. Data were obtained from November 2007 until May 2008. Patients underwent CCE on Day 1 and CSPY on Day 2. Outcomes were evaluated regarding sensitivity and specificity of polyp detection rate, with a significance level set at >5 mm. Results 59 individuals were included in this study, the results were evaluable in 56 patients (males 34, females 22; median age 59). CCE was complete in 36 subjects. Polyp detection rate for significant polyps was 11% on CSPY and 27% on CCE. 6/56 (11%) patients had polyps on CSPY not detected on CCE (miss rate). Overall sensitivity was 79% (95% confidence interval [CI], 61 to 90), specificity was 54% (95% CI, 35 to 70), positive predictive value (PPV) was 63% and negative predictive value (NPV) was 71%. Adjusted to significance of findings, sensitivity was 50% (95% CI, 19 to 81), specificity was 76% (95% CI, 63 to 86), PPV was 20% and NPV was 93%. Conclusion In comparison to the gold standard, the sensitivity of CCE for detection of relevant polyps is low, however, the high NPV supports its role as a possible screening tool. Trial Registration NCT00991003. PMID:20565828

A sensitive, rapid, and simple DR-EcoScreen bioassay for the determination of PCDD/Fs and dioxin-like PCBs in environmental and food samples.

PubMed

Kojima, Hiroyuki; Takeuchi, Shinji; Iida, Mitsuru; Nakayama, Shoji F; Shiozaki, Takuya

2018-03-01

In developing countries in Asia, such as China, Vietnam, and Thailand, there is a strong need for the development of relatively rapid and low-cost bioassays for the determination of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs) in environmental and food samples. These compounds are known to induce a variety of toxic and biological effects through their ligand-specific binding of the aryl hydrocarbon receptor (AhR). Indeed, several AhR-mediated reporter gene assays are widely used as prescreening tools for high-resolution gas chromatography/high-resolution mass spectrometry (HRGC-HRMS) analysis, which individually measures 17 PCDD/Fs and 12 DL-PCBs. In 2008, we have developed a new sensitive and rapid reporter gene assay using a genetically engineered stable cell line, designated DR-EcoScreen cells. The DR-EcoScreen assay using these cells has a number of great advantages of its sensitivity to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its simple procedure, which shows little variance in the data (within CV 10 %) compared to other reporter gene assays. In this review, we summarize the application of the DR-EcoScreen assay to the determination of PCDD/Fs and DL-PCBs in ambient air samples, in fish and shellfish samples, and in flue gas samples from incinerators and provide potential usefulness of this bioassay for the determination of PCDD/Fs and DL-PCBs in various matrices.

Screening disordered eating in a representative sample of the German population: Usefulness and psychometric properties of the German SCOFF questionnaire.

PubMed

Richter, Felicitas; Strauss, Bernhard; Braehler, Elmar; Adametz, Luise; Berger, Uwe

2017-04-01

The prevention of eating disorders and the identification of high-risk individuals are essential for the public health sector. There is need for sensitive and specific screening instruments of disordered eating that can be applied in universal samples as an initial step into disease prevention. The SCOFF is a screening instrument for disordered eating, frequently used in international and cross-cultural contexts to detect individuals at risk. The objective of this research is to evaluate whether the SCOFF can be used as a screening tool for disordered eating in universal samples. This is the first study which examined the psychometric properties of the German version of the SCOFF in a general population sample. A representative sample (N=2527) of the German population, aged 14-95years, was recruited. Psychometric properties were determined including reliability, concurrent and construct validity, and factor structure. The prevalence of disordered eating was assessed. The prevalence of disordered eating in the general population was 10%. Using the established cutoff point of ≥2, values for diagnostic accuracy were 26% (sensitivity), 97% (specificity), 80% (positive predictive value), and 74% (negative predictive value). Factorial analyses revealed an excellent model fit of a unidimensional model. Due to its low sensitivity and a high percentage of false negatives, there are limitations in using the German version of the SCOFF in general population samples with wide age ranges. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel assay for monoacylglycerol hydrolysis suitable for high-throughput screening.

PubMed

Brengdahl, Johan; Fowler, Christopher J

2006-12-01

A simple assay for monoacylglycerol hydrolysis suitable for high-throughput screening is described. The assay uses [(3)H]2-oleoylglycerol as substrate, with the tritium label in the glycerol part of the molecule and the use of phenyl sepharose gel to separate the hydrolyzed product ([(3)H]glycerol) from substrate. Using cytosolic fractions derived from rat cerebella as a source of hydrolytic activity, the assay gives the appropriate pH profile and sensitivity to inhibition with compounds known to inhibit hydrolysis of this substrate. The assay could also be adapted to a 96-well plate format, using C6 cells as the source of hydrolytic activity. Thus the assay is simple and appropriate for high-throughput screening of inhibitors of monoacylglycerol hydrolysis.

Detection of CIN by naked eye visualization after application of acetic acid.

PubMed

Londhe, M; George, S S; Seshadri, L

1997-06-01

A prospective study was undertaken to determine the sensitivity and specificity of acetic application to the cervix followed by naked eye visualization as a screening test for detection of cervical intraepithelial neoplasia. Three hundred and seventy two sexually active woman in the reproductive age group were studied. All the women underwent Papanicolaou test, acetic acid test and colposcopy. One hundred and seventy five woman were acetic acid test negative, 197 women were acetic acid test positive. The sensitivity of acetic acid test was 72.4%, specificity 54% and false negative rate 15.2%, as compared to papanicolaou test which had a sensitivity of 13.2%, specificity of 96.3% and false negative rate of 24.4%. The advantage of the acetic acid test lies in its easy technique, low cost and high sensitivity which are important factors for determining the efficacy of any screening programme in developing countries.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

PubMed

van der Have, Mike; Oldenburg, Bas; Fidder, Herma H; Belderbos, Tim D G; Siersema, Peter D; van Oijen, Martijn G H

2014-03-01

Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

Application of mass spectrometry technologies for the discovery of low-molecular weight modulators of enzymes and protein-protein interactions.

PubMed

Zehender, Hartmut; Mayr, Lorenz M

2007-10-01

In recent years, mass spectrometry has gained widespread use as an assay and screening technology in drug discovery because it enables sensitive, label-free detection of low-molecular weight modulators of biomolecules as well as sensitive and accurate detection of high-molecular weight modifications of biomolecules. Electrospray and matrix-assisted laser desorption ionization are the most widely used ionization techniques to identify chemical compounds interfering with enzymatic function, receptor-ligand binding or molecules modulating a protein-protein interaction of interest. Mass spectrometry based techniques are no longer restricted to screening in biochemical assay systems but have now become also applicable to imaging of biomolecules and chemical compounds in cell-based assay systems and even in highly complex tissue sections.

A Cost-Utility Analysis of Lung Cancer Screening and the Additional Benefits of Incorporating Smoking Cessation Interventions

PubMed Central

Villanti, Andrea C.; Jiang, Yiding; Abrams, David B.; Pyenson, Bruce S.

2013-01-01

Background A 2011 report from the National Lung Screening Trial indicates that three annual low-dose computed tomography (LDCT) screenings for lung cancer reduced lung cancer mortality by 20% compared to chest X-ray among older individuals at high risk for lung cancer. Discussion has shifted from clinical proof to financial feasibility. The goal of this study was to determine whether LDCT screening for lung cancer in a commercially-insured population (aged 50–64) at high risk for lung cancer is cost-effective and to quantify the additional benefits of incorporating smoking cessation interventions in a lung cancer screening program. Methods and Findings The current study builds upon a previous simulation model to estimate the cost-utility of annual, repeated LDCT screenings over 15 years in a high risk hypothetical cohort of 18 million adults between age 50 and 64 with 30+ pack-years of smoking history. In the base case, the lung cancer screening intervention cost $27.8 billion over 15 years and yielded 985,284 quality-adjusted life years (QALYs) gained for a cost-utility ratio of $28,240 per QALY gained. Adding smoking cessation to these annual screenings resulted in increases in both the costs and QALYs saved, reflected in cost-utility ratios ranging from $16,198 per QALY gained to $23,185 per QALY gained. Annual LDCT lung cancer screening in this high risk population remained cost-effective across all sensitivity analyses. Conclusions The findings of this study indicate that repeat annual lung cancer screening in a high risk cohort of adults aged 50–64 is highly cost-effective. Offering smoking cessation interventions with the annual screening program improved the cost-effectiveness of lung cancer screening between 20% and 45%. The cost-utility ratios estimated in this study were in line with other accepted cancer screening interventions and support inclusion of annual LDCT screening for lung cancer in a high risk population in clinical recommendations. PMID:23940744

The computerized adaptive diagnostic test for major depressive disorder (CAD-MDD): a screening tool for depression.

PubMed

Gibbons, Robert D; Hooker, Giles; Finkelman, Matthew D; Weiss, David J; Pilkonis, Paul A; Frank, Ellen; Moore, Tara; Kupfer, David J

2013-07-01

To develop a computerized adaptive diagnostic screening tool for depression that decreases patient and clinician burden and increases sensitivity and specificity for clinician-based DSM-IV diagnosis of major depressive disorder (MDD). 656 individuals with and without minor and major depression were recruited from a psychiatric clinic and a community mental health center and through public announcements (controls without depression). The focus of the study was the development of the Computerized Adaptive Diagnostic Test for Major Depressive Disorder (CAD-MDD) diagnostic screening tool based on a decision-theoretical approach (random forests and decision trees). The item bank consisted of 88 depression scale items drawn from 73 depression measures. Sensitivity and specificity for predicting clinician-based Structured Clinical Interview for DSM-IV Axis I Disorders diagnoses of MDD were the primary outcomes. Diagnostic screening accuracy was then compared to that of the Patient Health Questionnaire-9 (PHQ-9). An average of 4 items per participant was required (maximum of 6 items). Overall sensitivity and specificity were 0.95 and 0.87, respectively. For the PHQ-9, sensitivity was 0.70 and specificity was 0.91. High sensitivity and reasonable specificity for a clinician-based DSM-IV diagnosis of depression can be obtained using an average of 4 adaptively administered self-report items in less than 1 minute. Relative to the currently used PHQ-9, the CAD-MDD dramatically increased sensitivity while maintaining similar specificity. As such, the CAD-MDD will identify more true positives (lower false-negative rate) than the PHQ-9 using half the number of items. Inexpensive (relative to clinical assessment), efficient, and accurate screening of depression in the settings of primary care, psychiatric epidemiology, molecular genetics, and global health are all direct applications of the current system. © Copyright 2013 Physicians Postgraduate Press, Inc.

The psychometric properties, sensitivity and specificity of the geriatric anxiety inventory, hospital anxiety and depression scale, and rating anxiety in dementia scale in aged care residents.

PubMed

Creighton, Alexandra S; Davison, Tanya E; Kissane, David W

2018-02-22

Limited research has been conducted into the identification of a valid and reliable screening measure for anxiety in aged care settings, despite it being one of the most common psychological conditions. This study aimed to determine an appropriate anxiety screening tool for aged care by comparing the reliability and validity of three commonly used measures and identifying specific cut-offs for the identification of generalized anxiety disorder (GAD). One-hundred and eighty nursing home residents (M age = 85.39 years) completed the GAI, HADS-A, and RAID, along with a structured diagnostic interview. Twenty participants (11.1%) met DSM-5 criteria for GAD. All measures had good psychometric properties , although reliability estimates for the HADS-A were sub-optimal. Privileging sensitivity , the GAI cut-off score of 9 gave sensitivity of 90.0% and specificity of 86.3%; HADS-A cut-off of 6 gave sensitivity of 90.0% and specificity of 80.6%; and RAID cut-off of 11 gave sensitivity of 85.0% and specificity of 72.5%. While all three measures had adequate reliability, validity, and cut-scores with high levels of sensitivity and specificity to detect anxiety within aged care, the GAI was the most consistently reliable and valid measure for screening for GAD.

Cost-effectiveness of screening high-risk HIV-positive men who have sex with men (MSM) and HIV-positive women for anal cancer.

PubMed

Czoski-Murray, C; Karnon, J; Jones, R; Smith, K; Kinghorn, G

2010-11-01

Anal cancer is uncommon and predominantly a disease of the elderly. The human papillomavirus (HPV) has been implicated as a causal agent, and HPV infection is usually transmitted sexually. Individuals who are human immunodeficiency virus (HIV)-positive are particularly vulnerable to HPV infections, and increasing numbers from this population present with anal cancer. To estimate the cost-effectiveness of screening for anal cancer in the high-risk HIV-positive population [in particular, men who have sex with men (MSM), who have been identified as being at greater risk of the disease] by developing a model that incorporates the national screening guidelines criteria. A comprehensive literature search was undertaken in January 2006 (updated in November 2006). The following electronic bibliographic databases were searched: Applied Social Sciences Index and Abstracts (ASSIA), BIOSIS previews (Biological Abstracts), British Nursing Index (BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, NHS Database of Abstracts of Reviews of Effects (DARE), NHS Health Technology Assessment (HTA) Database, PsycINFO, Science Citation Index (SCI), and Social Sciences Citation Index (SSCI). Published literature identified by the search strategy was assessed by four reviewers. Papers that met the inclusion criteria contained the following: data on population incidence, effectiveness of screening, health outcomes or screening and/or treatment costs; defined suitable screening technologies; prospectively evaluated tests to detect anal cancer. Foreign-language papers were excluded. Searches identified 2102 potential papers; 1403 were rejected at title and a further 493 at abstract. From 206 papers retrieved, 81 met the inclusion criteria. A further treatment paper was added, giving a total of 82 papers included. Data from included studies were extracted into data extraction forms by the clinical effectiveness reviewer. To analyse the cost-effectiveness of screening, two decision-analytical models were developed and populated. The reference case cost-effectiveness model for MSM found that screening for anal cancer is very unlikely to be cost-effective. The negative aspects of screening included utility decrements associated with false-positive results and with treatment for high-grade anal intraepithelial neoplasia (HG-AIN). Sensitivity analyses showed that removing these utility decrements improved the cost-effectiveness of screening. However, combined with higher regression rates from low-grade anal intraepithelial neoplasia (LG-AIN), the lowest expected incremental cost-effectiveness ratio remained at over 44,000 pounds per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analysis showed that no screening retained over 50% probability of cost-effectiveness to a QALY value of 50,000 pounds. The screening model for HIV-positive women showed an even lower likelihood of cost-effectiveness, with the most favourable sensitivity analyses reporting an incremental cost per QALY of 88,000 pounds. Limited knowledge is available about the epidemiology and natural history of anal cancer, along with a paucity of good-quality evidence concerning the effectiveness of screening. Many of the criteria for assessing the need for a screening programme were not met and the cost-effectiveness analyses showed little likelihood that screening any of the identified high-risk groups would generate health improvements at a reasonable cost. Further studies could assess whether the screening model has underestimated the impact of anal cancer, the results of which may justify an evaluative study of the effects of treatment for HG-AIN.

A high-throughput colorimetric assay for glucose detection based on glucose oxidase-catalyzed enlargement of gold nanoparticles

NASA Astrophysics Data System (ADS)

Xiong, Yanmei; Zhang, Yuyan; Rong, Pengfei; Yang, Jie; Wang, Wei; Liu, Dingbin

2015-09-01

We developed a simple high-throughput colorimetric assay to detect glucose based on the glucose oxidase (GOx)-catalysed enlargement of gold nanoparticles (AuNPs). Compared with the currently available glucose kit method, the AuNP-based assay provides higher clinical sensitivity at lower cost, indicating its great potential to be a powerful tool for clinical screening of glucose.We developed a simple high-throughput colorimetric assay to detect glucose based on the glucose oxidase (GOx)-catalysed enlargement of gold nanoparticles (AuNPs). Compared with the currently available glucose kit method, the AuNP-based assay provides higher clinical sensitivity at lower cost, indicating its great potential to be a powerful tool for clinical screening of glucose. Electronic supplementary information (ESI) available: Experimental section and additional figures. See DOI: 10.1039/c5nr03758a

Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity.

PubMed

Kostenko, L; Kjer-Nielsen, L; Nicholson, I; Hudson, F; Lucas, A; Foley, B; Chen, K; Lynch, K; Nguyen, J; Wu, A H B; Tait, B D; Holdsworth, R; Mallal, S; Rossjohn, J; Bharadwaj, M; McCluskey, J

2011-07-01

HLA-B57 and HLA-B58 are major histocompatibility class (MHC)-I allotypes that are potentially predictive of important clinical immune phenotypes. HLA-B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from the antibiotic flucloxacillin and is a marker for slow progression of HIV AIDS. HLA-B*5801 is associated with hypersensitivity to allopurinol used to treat hyperuricaemia and recurrent gout. Here we describe a monoclonal antibody (mAb) specific for HLA-B57 and HLA-B58 that provides an inexpensive and sensitive screen for these MHC-I allotypes. The usefulness of HLA-B57 screening for prediction of abacavir hypersensitivity was shown in three independent laboratories, including confirmation of the mAb sensitivity and specificity in a cohort of patients enrolled in the PREDICT-1 trial. Our data show that patients who test negative by mAb screening comprise 90%-95% of all individuals in most human populations and require no further human leukocyte antigen (HLA) typing. Patients who test positive by mAb screening should proceed to high-resolution typing to ascertain the presence of HLA-B*5701 or HLA-B*5801. Hence, mAb screening provides a low-cost alternative to high-resolution typing of all patients and lends itself to point-of-care diagnostics and rapid ascertainment of low-risk patients who can begin immediate therapy with abacavir, flucloxacillin or allopurinol. © 2011 John Wiley & Sons A/S.

Computationally inexpensive identification of noninformative model parameters by sequential screening

NASA Astrophysics Data System (ADS)

Cuntz, Matthias; Mai, Juliane; Zink, Matthias; Thober, Stephan; Kumar, Rohini; Schäfer, David; Schrön, Martin; Craven, John; Rakovec, Oldrich; Spieler, Diana; Prykhodko, Vladyslav; Dalmasso, Giovanni; Musuuza, Jude; Langenberg, Ben; Attinger, Sabine; Samaniego, Luis

2015-08-01

Environmental models tend to require increasing computational time and resources as physical process descriptions are improved or new descriptions are incorporated. Many-query applications such as sensitivity analysis or model calibration usually require a large number of model evaluations leading to high computational demand. This often limits the feasibility of rigorous analyses. Here we present a fully automated sequential screening method that selects only informative parameters for a given model output. The method requires a number of model evaluations that is approximately 10 times the number of model parameters. It was tested using the mesoscale hydrologic model mHM in three hydrologically unique European river catchments. It identified around 20 informative parameters out of 52, with different informative parameters in each catchment. The screening method was evaluated with subsequent analyses using all 52 as well as only the informative parameters. Subsequent Sobol's global sensitivity analysis led to almost identical results yet required 40% fewer model evaluations after screening. mHM was calibrated with all and with only informative parameters in the three catchments. Model performances for daily discharge were equally high in both cases with Nash-Sutcliffe efficiencies above 0.82. Calibration using only the informative parameters needed just one third of the number of model evaluations. The universality of the sequential screening method was demonstrated using several general test functions from the literature. We therefore recommend the use of the computationally inexpensive sequential screening method prior to rigorous analyses on complex environmental models.

Computationally inexpensive identification of noninformative model parameters by sequential screening

NASA Astrophysics Data System (ADS)

Mai, Juliane; Cuntz, Matthias; Zink, Matthias; Thober, Stephan; Kumar, Rohini; Schäfer, David; Schrön, Martin; Craven, John; Rakovec, Oldrich; Spieler, Diana; Prykhodko, Vladyslav; Dalmasso, Giovanni; Musuuza, Jude; Langenberg, Ben; Attinger, Sabine; Samaniego, Luis

2016-04-01

Environmental models tend to require increasing computational time and resources as physical process descriptions are improved or new descriptions are incorporated. Many-query applications such as sensitivity analysis or model calibration usually require a large number of model evaluations leading to high computational demand. This often limits the feasibility of rigorous analyses. Here we present a fully automated sequential screening method that selects only informative parameters for a given model output. The method requires a number of model evaluations that is approximately 10 times the number of model parameters. It was tested using the mesoscale hydrologic model mHM in three hydrologically unique European river catchments. It identified around 20 informative parameters out of 52, with different informative parameters in each catchment. The screening method was evaluated with subsequent analyses using all 52 as well as only the informative parameters. Subsequent Sobol's global sensitivity analysis led to almost identical results yet required 40% fewer model evaluations after screening. mHM was calibrated with all and with only informative parameters in the three catchments. Model performances for daily discharge were equally high in both cases with Nash-Sutcliffe efficiencies above 0.82. Calibration using only the informative parameters needed just one third of the number of model evaluations. The universality of the sequential screening method was demonstrated using several general test functions from the literature. We therefore recommend the use of the computationally inexpensive sequential screening method prior to rigorous analyses on complex environmental models.

Screening for hypochondriasis with the Illness Attitude Scales.

PubMed

Weck, Florian; Bleichhardt, Gaby; Hiller, Wolfgang

2010-05-01

The Illness Attitude Scales (IAS; Kellner, 1986, 1987) may prove highly useful for the screening of hypochondriasis. We expected the IAS subscales to be equally as effective as the 7-item short version of the Whiteley Index (Whiteley-7; Fink et al., 1999), which has previously been shown to be useful in screening for somatoform disorders. We investigated participants of a German population (n = 1,575) and 61 patients with the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) diagnosis of hypochondriasis. The Bodily Preoccupations (BP) subscale showed high sensitivity (.92) and specificity (.90) as well as demonstrating convergent and discriminant validity. We found evidence for the superiority of the BP subscale over the Whiteley-7 in the screening of hypochondriasis.

Assessment of the efficacy of a hearing screening program for college students.

PubMed

Taylor, Emily J; Emanuel, Diana C

2013-01-01

The Towson University (TU) Speech-Language-Hearing Center (SLHC) conducts annual hearing screenings for college students entering education or health-care professions. Hearing is screened in therapy rooms, and students who fail the screening are rescreened in a sound-treated booth. Students who fail the rescreening are referred for a comprehensive audiological assessment, which is offered at no cost to students at the SLHC. The purpose of this study was to examine the efficacy of the hearing screening program, to report trends in hearing screening statistics for the college student population, and to make recommendations regarding ways universities can optimize hearing screening programs. The study included retrospective and prospective portions. Hearing screening records were reviewed from 1999 to 2011. The prospective study involved recruiting students to participate in diagnostic testing following the hearing screening and measuring background noise levels in the therapy rooms. Hearing screening records from 1999 to 2011 were reviewed. In addition, during the three-day fall 2011 hearing screenings, 80 students were selected to participate in diagnostic testing. Data from the retrospective review were used to determine positive predictive value (PPV) between screening and rescreening. Return rates were also examined. For the prospective study, pure tone threshold results were compared to screening results to determine sensitivity, specificity, and PPV. The retrospective file review indicated that the hearing screening in the therapy room had poor PPV compared with the rescreening in the sound booth. Specifically, if a student failed the screening, they had only a 49% chance of failing the rescreening. This may have been due to background noise, as the prospective study found noise levels were higher than allowed by American National Standards Institute (ANSI) standard. Only a third of students referred for diagnostic testing from 1999 to 2010 returned for recommended diagnostic testing. For the prospective study, specificity and sensitivity were good when considering hearing loss present at the same frequencies as those screened (1000, 2000, 4000 Hz) but poor in comparison to hearing loss overall. The screening missed many students with a high frequency notch, which was most prevalent at 6000 Hz. The prevalence of a high frequency notch was 21 and 51%, using two different criteria for establishing the presence of a notch. If college hearing screenings are conducted in rooms that are not sound treated, poor PPV should be expected; thus, an immediate second stage rescreening for failures should be conducted in a sound booth. Hearing screenings limited to 1000, 2000, and 4000 Hz will miss many cases of hearing loss in the college-age population. College hearing screening program directors should carefully consider the purpose of the screening and adjust screening protocol, such as adding 6000 Hz and a question about noise exposure, in order to identify early signs of noise-induced hearing loss in college students. Programs should focus on ways to promote high return for follow-up rates. Estimates of prevalence of a high-frequency audiometric notch are highly dependent on the criteria used to define a notch. American Academy of Audiology.

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.

Highly Sensitive Aluminium(III) Ion Sensor Based on a Self-assembled Monolayer on a Gold Nanoparticles Modified Screen-printed Carbon Electrode.

PubMed

See, Wong Pooi; Heng, Lee Yook; Nathan, Sheila

2015-01-01

A new approach for the development of a highly sensitive aluminium(III) ion sensor via the preconcentration of aluminium(III) ion with a self-assembled monolayer on a gold nanoparticles modified screen-printed carbon electrode and current mediation by potassium ferricyanide redox behavior during aluminium(III) ion binding has been attempted. A monolayer of mercaptosuccinic acid served as an effective complexation ligand for the preconcentration of trace aluminium; this led to an enhancement of aluminium(III) ion capture and thus improved the sensitivity of the sensor with a detection limit of down to the ppb level. Under the optimum experimental conditions, the sensor exhibited a wide linear dynamic range from 0.041 to 12.4 μM. The lower detection limit of the developed sensor was 0.037 μM (8.90 ppb) using a 10 min preconcentration time. The sensor showed excellent selectivity towards aluminium(III) ion over other interference ions.

[Methicillin resistance detection in Staphylococcus aureus: comparison between conventional methods and MRSA-Screen latex agglutination technique].

PubMed

Soloaga, R; Corso, A; Gagetti, P; Faccone, D; Galas, M

2004-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen that has emerged over the last four decades, causing both nosocomial and community-acquired infections. Rapid and accurate detection of methicillin resistance in S. aureus is important for the use of appropriate antimicrobial therapy and for the control of nosocomial spread of MRSA strains. We evaluated the efficiency of conventional methods for detection of methicillin resistance such as the disk diffusion, agar dilution, oxacillin agar screen test, and the latex agglutination test MRSA-Screen latex, in 100 isolates of S. aureus, 79 mecA positive and 21 mecA negative. The MRSA-Screen latex (Denka Seiken, Niigata, Japón), is a latex agglutination method that detects the presence of PLP-2a, product of mecA gene in S. aureus. The PCR of the mecA gene was used as the "gold standard" for the evaluation of the different methods tested. The percentages of sensitivity and specificity were as follows: disk difusión 97 and 100%, agar dilution 97 and 95%, oxacillin agar screen test 100 and 100%, and MRSA-Screen latex, 100 and 100 %. All methods presented high sensitivity and specificity, but MRSA-Screen latex had the advantage of giving a reliable result, equivalent to PCR, in only 15 minutes.

Phaeochromocytoma: diagnostic challenges for biochemical screening and diagnosis.

PubMed

Barron, Jeffrey

2010-08-01

The aim of this article is to provide knowledge of the origin of catecholamines and metabolites so that there can be an informed approach to the methods for biochemical screening for a possible phaeochromocytoma; The article includes a review of catecholamine and metadrenaline metabolism, with methods used in biochemical screening. In the adrenal medulla and a phaeochromocytoma, catecholamines continuously leak from chromaffin granules into the cytoplasm and are converted to metadrenalines. For a phaeochromocytoma to become biochemically detectable, metnoradrenaline secretion needs to rise fourfold, whereas noradrenaline secretion needs to rise 15-fold. The prevalence of a sporadic phaeochromocytoma is low; therefore false-positive results exceed true-positive results. Assay sensitivity is high because it is important not to miss a possible phaeochromocytoma. The use of urine or plasma fractionated metadrenalines as the first-line test has been recommended due to improved sensitivity. A negative result excludes a phaeochromocytoma. Only after a sporadic phaeochromocytoma has been diagnosed biochemically is it cost effective to request imaging. Sensitivities and specificities of the assays differ according to pre-test probabilities of the presence of a phaeochromocytoma, with hereditary and incidentalomas having a higher pre-test probability than sporadic phaeochromocytoma. In conclusion, in screening for a possible phaeochromocytoma, biochemical investigations should be completed first to exclude or establish the diagnosis. The preferred biochemical screening test is fractionated metadrenalines, including methoxytyramine so as not to miss dopamine-secreting tumours.

Usefulness of enzyme immunoassay (EIA) for screening of anti HIV antibodies in urinary specimens: A comparative analysis.

PubMed

Sahni, A K; Nagendra, A; Roy, Partha; Patrikar, S

2014-07-01

Standard HIV testing is done using serum or plasma. FDA approved ELISA to screen urine for IgG antibodies to HIV-1 in 1996. It is a simple, noninvasive test and is appropriate for developing countries where health care personnel may not be professionally trained or where clean needles for drawing blood may not always be available. 436 individuals with high-risk behavior and strong clinical suspicion of HIV infection were screened for IgG antibodies to HIV-1 in urine by ELISA. Urine HIV testing was performed by enzyme immunoassay, at the ongoing Voluntary Confidential Counseling and Testing Center (VCCTC) at a large tertiary care microbiology lab. The individuals enrolled for the study had high-risk exposure to the virus and majorities were from a state with a high incidence of HIV infection. In all individuals, both serum and urine were tested for IgG antibodies to HIV-1. Overall, 135 individuals (30.96%) were HIV-positive, of whom 96 (71%) had never previously tested positive; 87% of those who tested positive received their results, and most were referred for medical care. Sensitivity, specificity and predictive values of HIV-1 urine ELISA test kit were determined. Sensitivity was found to be 89.6%; 95% CI [82.9-94.0], specificity 97.3%; 95% CI [94.6-98.8], positive predictive value 93.8%; 95% CI [87.8-97.1] and negative predictive value 95.4%; 95% CI [92.3-97.4]. Efficiency, sensitivity, and specificity of the urine-based screening for HIV-1 test kits were excellent as compared to the reference test.

High content screening of patient-derived cell lines highlights the potential of non-standard chemotherapeutic agents for the treatment of glioblastoma.

PubMed

Yu, Kenny Kwok-Hei; Taylor, Jessica T; Pathmanaban, Omar N; Youshani, Amir Saam; Beyit, Deniz; Dutko-Gwozdz, Joanna; Benson, Roderick; Griffiths, Gareth; Peers, Ian; Cueppens, Peter; Telfer, Brian A; Williams, Kaye J; McBain, Catherine; Kamaly-Asl, Ian D; Bigger, Brian W

2018-01-01

Glioblastoma (GBM) is the most common primary brain malignancy in adults, yet survival outcomes remain poor. First line treatment is well established, however disease invariably recurs and improving prognosis is challenging. With the aim of personalizing therapy at recurrence, we have established a high content screening (HCS) platform to analyze the sensitivity profile of seven patient-derived cancer stem cell lines to 83 FDA-approved chemotherapy drugs, with and without irradiation. Seven cancer stem cell lines were derived from patients with GBM and, along with the established cell line U87-MG, each patient-derived line was cultured in tandem in serum-free conditions as adherent monolayers and three-dimensional neurospheres. Chemotherapeutics were screened at multiple concentrations and cells double-stained to observe their effect on both cell death and proliferation. Sensitivity was classified using high-throughput algorithmic image analysis. Cell line specific drug responses were observed across the seven patient-derived cell lines. Few agents were seen to have radio-sensitizing effects, yet some drug classes showed a marked difference in efficacy between monolayers and neurospheres. In vivo validation of six drugs suggested that cell death readout in a three-dimensional culture scenario is a more physiologically relevant screening model and could be used effectively to assess the chemosensitivity of patient-derived GBM lines. The study puts forward a number of non-standard chemotherapeutics that could be useful in the treatment of recurrent GBM, namely mitoxantrone, bortezomib and actinomycin D, whilst demonstrating the potential of HCS to be used for personalized treatment based on the chemosensitivity profile of patient tumor cells.

Plasmodium falciparum Transfected with Ultra Bright NanoLuc Luciferase Offers High Sensitivity Detection for the Screening of Growth and Cellular Trafficking Inhibitors

PubMed Central

Elsworth, Brendan; Charnaud, Sarah C.; Sanders, Paul R.; Crabb, Brendan S.; Gilson, Paul R.

2014-01-01

Drug discovery is a key part of malaria control and eradication strategies, and could benefit from sensitive and affordable assays to quantify parasite growth and to help identify the targets of potential anti-malarial compounds. Bioluminescence, achieved through expression of exogenous luciferases, is a powerful tool that has been applied in studies of several aspects of parasite biology and high throughput growth assays. We have expressed the new reporter NanoLuc (Nluc) luciferase in Plasmodium falciparum and showed it is at least 100 times brighter than the commonly used firefly luciferase. Nluc brightness was explored as a means to achieve a growth assay with higher sensitivity and lower cost. In addition we attempted to develop other screening assays that may help interrogate libraries of inhibitory compounds for their mechanism of action. To this end parasites were engineered to express Nluc in the cytoplasm, the parasitophorous vacuole that surrounds the intraerythrocytic parasite or exported to the red blood cell cytosol. As proof-of-concept, these parasites were used to develop functional screening assays for quantifying the effects of Brefeldin A, an inhibitor of protein secretion, and Furosemide, an inhibitor of new permeation pathways used by parasites to acquire plasma nutrients. PMID:25392998

Assessing sensitivity and specificity of the Manchester Triage System in the evaluation of acute coronary syndrome in adult patients in emergency care: a systematic review.

PubMed

Nishi, Fernanda Ayache; de Oliveira Motta Maia, Flávia; de Souza Santos, Itamar; de Almeida Lopes Monteiro da Cruz, Dina

2017-06-01

Triage is the first assessment and sorting process used to prioritize patients arriving in the emergency department (ED). As a triage tool, the Manchester Triage System (MTS) must have a high sensitivity to minimize the occurrence of under-triage, but must not compromise specificity to avoid the occurrence of overtriage. Sensitivity and specificity of the MTS can be calculated using the frequency of appropriately assigned clinical priority levels for patients presenting to the ED. However, although there are well established criteria for the prioritization of patients with suspected acute coronary syndrome (ACS), several studies have reported difficulties when evaluating patients with this condition. The objective of this review was to synthesize the best available evidence on assessing the sensitivity and specificity of the MTS for screening high-level priority adult patients presenting to the ED with ACS. The current review considered studies that evaluated the use of the MTS in the risk classification of adult patients in the ED. In this review, studies that investigated the priority level, as established by the MTS to screen patients under suspicion of ACS or the sensitivity and specificity of the MTS, for screening patients before the medical diagnosis of ACS were included. This review included both experimental and epidemiological study designs. The results were presented in a narrative synthesis. Six studies were appraised by the independent reviewers. All appraised studies enrolled a consecutive or random sample of patients and presented an overall moderate methodological quality, and all of them were included in this review. A total of 54,176 participants were included in the six studies. All studies were retrospective. Studies included in this review varied in content and data reporting. Only two studies reported sensitivity and specificity values or all the necessary data to calculate sensitivity and specificity. The remaining four studies presented either a sensitivity analysis or the number of true positives and false negatives. However, these four studies were conducted considering only data from patients diagnosed with ACS. Sensitivity values were relatively uniform among the studies: 0.70-0.80. A specificity of 0.59 was reported in the study including only patients with non-traumatic chest pain. On the other hand, in the study that included patients with any complaint, the specificity of MTS to screen patients with ACS was 0.97. The current review demonstrates that the MTS has a moderate sensitivity to evaluate patients with ACS. This may compromise time to treatment in the ED, an important variable in the prognosis of ACS. Atypical presentation of ACS, or high specificity, may also explain the moderate sensitivity demonstrated in this review. However, because of minimal data, it is not possible to confirm this hypothesis. It is difficult to determine the acceptable level of sensitivity or specificity to ensure that a certain triage system is safe.

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.

Cost-Effectiveness of Screening for Intermediate Age-Related Macular Degeneration during Diabetic Retinopathy Screening.

PubMed

Chan, Christina K W; Gangwani, Rita A; McGhee, Sarah M; Lian, JinXiao; Wong, David S H

2015-11-01

To determine whether screening for age-related macular degeneration (AMD) during a diabetic retinopathy (DR) screening program would be cost effective in Hong Kong. We compared and evaluated the impacts of screening, grading, and vitamin treatment for intermediate AMD compared with no screening using a Markov model. It was based on the natural history of AMD in a cohort with a mean age of 62 years, followed up until 100 years of age or death. Subjects attending a DR screening program were recruited. A cost-effectiveness analysis was undertaken from a public provider perspective. It included grading for AMD using the photographs obtained for DR screening and treatment with vitamin therapy for those with intermediate AMD. The measures of effectiveness were obtained largely from a local study, but the transition probabilities and utility values were from overseas data. Costs were all from local sources. The main assumptions and estimates were tested in sensitivity analyses. The outcome was cost per quality-adjusted life year (QALY) gained. Both costs and benefits were discounted at 3%. All costs are reported in United States dollars ($). The cost per QALY gained through screening for AMD and vitamin treatment for appropriate cases was $12,712 after discounting. This would be considered highly cost effective based on the World Health Organization's threshold of willingness to pay (WTP) for a QALY, that is, less than the annual per capita gross domestic product of $29,889. Because of uncertainty regarding the utility value for those with advanced AMD, we also tested an extreme, conservative value for utility under which screening remained cost effective. One-way sensitivity analyses revealed that, besides utility values, the cost per QALY was most sensitive to the progression rate from intermediate to advanced AMD. The cost-effectiveness acceptability curve showed a WTP for a QALY of $29,000 or more has a more than 86% probability of being cost effective compared with no screening. Our analysis demonstrated that AMD screening carried out simultaneously with DR screening for patients with diabetes would be cost effective in a Hong Kong public healthcare setting. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Radionuclide Methods and Instrumentation for Breast Cancer Detection and Diagnosis

PubMed Central

Surti, Suleman

2013-01-01

Breast cancer mammography is a well-acknowledged technique for patient screening due to its high sensitivity. However, in addition to its low specificity the sensitivity of mammography is limited when imaging patients with dense breasts. Radionuclide imaging techniques, such as coincidence photon-based positron emission tomography and single photon emission computed tomography or scintimammography, can play a role in assisting screening of such patients. Radionuclide techniques can also be useful in assessing treatment response of patients with breast cancer to therapy, and staging of patients to diagnose the disease extent. However, the performance of these imaging modalities is generally limited because of the poor spatial resolution and sensitivity of the commercially available multipurpose imaging systems. Here, we describe some of the dedicated imaging systems (positron emission mammography [PEM] and breast-specific gamma imaging [BSGI]) that have been developed both commercially and in research laboratories for radionuclide imaging of breast cancer. Clinical studies with dedicated PEM scanners show improved sensitivity to detecting cancer in patients when using PEM in conjunction with additional imaging modalities, such as magnetic resonance imaging or mammography or both, as well as improved disease staging that can have an effect on surgical planning. High-resolution BSGI systems are more widely available commercially and several clinical studies have shown very high sensitivity and specificity in detecting cancer in high-risk patients. Further development of dedicated PEM and BSGI systems is ongoing, promising further expansion of radionuclide imaging techniques in the realm of breast cancer detection and treatment. PMID:23725989

High sensitive and throughput screening of Aflatoxin using MALDI-TOF-TOF-PSD-MS/MS

USDA-ARS?s Scientific Manuscript database

We have achieved sensitive and efficient detection of aflatoxin B1(AFB1) through matrix-assisted laser desorption/ionization time-of-flight-time-of-flight mass spectrometry (MALDI-TOF-TOF) and post-source decay (PSD) tandem mass spectrometry (MS/MS) using an acetic acid – a-cyano-4-hydroxycinnamic a...

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

PubMed Central

2010-01-01

Background Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. Methods A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. Results The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). Conclusions This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials. PMID:20433705

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model.

PubMed

Furiak, Nicolas M; Klein, Robert W; Kahle-Wrobleski, Kristin; Siemers, Eric R; Sarpong, Eric; Klein, Timothy M

2010-04-30

Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age > or =55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

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

PubMed

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

2017-05-01

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

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.

Monitoring well utility in a heterogeneous DNAPL source zone area: Insights from proximal multilevel sampler wells and sampling capture-zone modelling.

PubMed

McMillan, Lindsay A; Rivett, Michael O; Wealthall, Gary P; Zeeb, Peter; Dumble, Peter

2018-03-01

Groundwater-quality assessment at contaminated sites often involves the use of short-screen (1.5 to 3 m) monitoring wells. However, even over these intervals considerable variation may occur in contaminant concentrations in groundwater adjacent to the well screen. This is especially true in heterogeneous dense non-aqueous phase liquid (DNAPL) source zones, where cm-scale contamination variability may call into question the effectiveness of monitoring wells to deliver representative data. The utility of monitoring wells in such settings is evaluated by reference to high-resolution multilevel sampler (MLS) wells located proximally to short-screen wells, together with sampling capture-zone modelling to explore controls upon well sample provenance and sensitivity to monitoring protocols. Field data are analysed from the highly instrumented SABRE research site that contained an old trichloroethene source zone within a shallow alluvial aquifer at a UK industrial facility. With increased purging, monitoring-well samples tend to a flow-weighted average concentration but may exhibit sensitivity to the implemented protocol and degree of purging. Formation heterogeneity adjacent to the well-screen particularly, alongside pump-intake position and water level, influence this sensitivity. Purging of low volumes is vulnerable to poor reproducibility arising from concentration variability predicted over the initial 1 to 2 screen volumes purged. Marked heterogeneity may also result in limited long-term sample concentration stabilization. Development of bespoke monitoring protocols, that consider screen volumes purged, alongside water-quality indicator parameter stabilization, is recommended to validate and reduce uncertainty when interpreting monitoring-well data within source zone areas. Generalised recommendations on monitoring well based protocols are also developed. A key monitoring well utility is their proportionately greater sample draw from permeable horizons constituting a significant contaminant flux pathway and hence representative fraction of source mass flux. Acquisition of complementary, high-resolution, site monitoring data, however, vitally underpins optimal interpretation of monitoring-well datasets and appropriate advancement of a site conceptual model and remedial implementation. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Effectiveness of the critical congenital heart disease screening program for early diagnosis of cardiac abnormalities in newborn infants.

PubMed

Almawazini, Abdulmajid M; Hanafi, Hamdi K; Madkhali, Hasan A; Majrashi, Noura B

2017-10-01

To evaluate the effectiveness of critical congenital heart disease (CCHD) screening program for early diagnosis of cardiac anomalies in newborn infants.  Methods: This is a hospital-based prospective cross-sectional study conducted in the Pediatric and Neonatology Department, King Fahad Hospital at  Albaha, Saudi Arabia, between February 2016 and February 2017. Results: We screened 2961 (95.4%) of 3103 patients in a nursery unit; 142 (4.6%) patients were not screened. The test was positive in 114 (3.9%) patients and negative in 2847 (96.1%). There were 94 (3.2%) false positives and 20 (0.7%) true positives. Critical cardiac defects were diagnosed in 7 (0.2%) patients of all screened infants, and severe pulmonary hypertension was diagnosed in 13 (0.4%) patients. True negative results were found in 2841(96%) patients, and no cardiac defect was diagnosed, whereas false negative results were seen in 6 (0.2%) patients diagnosed with ventricular septal defect. The sensitivity was 77%, and the specificity was very high at 97%, with a positive predictive value of 18%, and a negative predictive value of 99.8% (95% confidence interval 13.78-19.18, p=0.0001). Conclusion: Pulse oximetry was found to be easy, safe, sensitive, and highly specific for diagnosis of CCHD.

Preliminary Evaluation of a Brief Autism Screener for Young Children.

PubMed

Zahorodny, Walter; Shenouda, Josephine; Mehta, Uday; Yee, Emily; Garcia, Patricia; Rajan, Mangala; Goldfarb, Madeleine

2018-04-01

Our objective was to assess the operating characteristics of the Psychological Development Questionnaire-1 (PDQ-1), an autism screener for use with young children. In Phase 1, we evaluated the concordance of the PDQ-1 with established autism scales, determined test-retest reliability, and identified a risk threshold score. In Phase 2, a population of 1959 toddler-age children was prospectively screened through multiple pediatric practices in a diverse metropolitan region, using the new instrument. Screen-positive children were referred for diagnostic evaluation. Screened children received follow-up at age 4 years to identify autism cases missed by screening and to specify the scale's psychometric properties. By screening a diverse population of low risk children, age 18 to 36 months, with the PDQ-1, we detected individuals with autism who had not come to professional attention. Overall, the PDQ-1 showed a positive predictive value (PPV) of 88%, with a sensitivity of 85% and specificity of 99% in a low risk population. High specificity, good sensitivity, and PPV were observed across the 18 to 36 month age-range. The findings provide preliminary empirical support for this parent report-based indicator of toddler psychological development and suggest that the PDQ-1 may be a useful supplement to developmental surveillance of autism. Additional research is needed with high risk samples and large, unselected populations under real-world conditions.

Preliminary Evaluation of a Brief Autism Screener for Young Children

PubMed Central

Shenouda, Josephine; Mehta, Uday; Yee, Emily; Garcia, Patricia; Rajan, Mangala; Goldfarb, Madeleine

2018-01-01

ABSTRACT: Objective: Our objective was to assess the operating characteristics of the Psychological Development Questionnaire-1 (PDQ-1), an autism screener for use with young children. Methods: In Phase 1, we evaluated the concordance of the PDQ-1 with established autism scales, determined test-retest reliability, and identified a risk threshold score. In Phase 2, a population of 1959 toddler-age children was prospectively screened through multiple pediatric practices in a diverse metropolitan region, using the new instrument. Screen-positive children were referred for diagnostic evaluation. Screened children received follow-up at age 4 years to identify autism cases missed by screening and to specify the scale's psychometric properties. Results: By screening a diverse population of low risk children, age 18 to 36 months, with the PDQ-1, we detected individuals with autism who had not come to professional attention. Overall, the PDQ-1 showed a positive predictive value (PPV) of 88%, with a sensitivity of 85% and specificity of 99% in a low risk population. High specificity, good sensitivity, and PPV were observed across the 18 to 36 month age-range. Conclusion: The findings provide preliminary empirical support for this parent report–based indicator of toddler psychological development and suggest that the PDQ-1 may be a useful supplement to developmental surveillance of autism. Additional research is needed with high risk samples and large, unselected populations under real-world conditions. PMID:29300209

Colorimetry and SERS dual-mode detection of telomerase activity: combining rapid screening with high sensitivity.

PubMed

Zong, Shenfei; Wang, Zhuyuan; Chen, Hui; Hu, Guohua; Liu, Min; Chen, Peng; Cui, Yiping

2014-01-01

As an important biomarker and therapeutic target, telomerase has attracted considerable attention concerning its detection and monitoring. Here, we present a colorimetry and surface enhanced Raman scattering (SERS) dual-mode telomerase activity detection method, which has several distinctive advantages. First, colorimetric functionality allows rapid preliminary discrimination of telomerase activity by the naked eye. Second, the employment of SERS technique results in greatly improved detection sensitivity. Third, the combination of colorimetry and SERS into one detection system can ensure highly efficacious and sensitive screening of numerous samples. Besides, the avoidance of polymerase chain reaction (PCR) procedures further guarantees fine reliability and simplicity. Generally, the presented method is realized by an "elongate and capture" procedure. To be specific, gold nanoparticles modified with Raman molecules and telomeric repeat complementary oligonucleotide are employed as the colorimetric-SERS bifunctional reporting nanotag, while magnetic nanoparticles functionalized with telomerase substrate oligonucleotide are used as the capturing substrate. Telomerase can synthesize and elongate telomeric repeats onto the capturing substrate. The elongated telomeric repeats subsequently facilitate capturing of the reporting nanotag via hybridization between telomeric repeat and its complementary strand. The captured nanotags can cause a significant difference in the color and SERS intensity of the magnetically separated sediments. Thus both the color and SERS can be used as indicators of the telomerase activity. With fast screening ability and outstanding sensitivity, we anticipate that this method would greatly promote practical application of telomerase-based early-stage cancer diagnosis.

Improving multi-objective reservoir operation optimization with sensitivity-informed dimension reduction

NASA Astrophysics Data System (ADS)

Chu, J.; Zhang, C.; Fu, G.; Li, Y.; Zhou, H.

2015-08-01

This study investigates the effectiveness of a sensitivity-informed method for multi-objective operation of reservoir systems, which uses global sensitivity analysis as a screening tool to reduce computational demands. Sobol's method is used to screen insensitive decision variables and guide the formulation of the optimization problems with a significantly reduced number of decision variables. This sensitivity-informed method dramatically reduces the computational demands required for attaining high-quality approximations of optimal trade-off relationships between conflicting design objectives. The search results obtained from the reduced complexity multi-objective reservoir operation problems are then used to pre-condition the full search of the original optimization problem. In two case studies, the Dahuofang reservoir and the inter-basin multi-reservoir system in Liaoning province, China, sensitivity analysis results show that reservoir performance is strongly controlled by a small proportion of decision variables. Sensitivity-informed dimension reduction and pre-conditioning are evaluated in their ability to improve the efficiency and effectiveness of multi-objective evolutionary optimization. Overall, this study illustrates the efficiency and effectiveness of the sensitivity-informed method and the use of global sensitivity analysis to inform dimension reduction of optimization problems when solving complex multi-objective reservoir operation problems.

Improving multi-objective reservoir operation optimization with sensitivity-informed problem decomposition

NASA Astrophysics Data System (ADS)

Chu, J. G.; Zhang, C.; Fu, G. T.; Li, Y.; Zhou, H. C.

2015-04-01

This study investigates the effectiveness of a sensitivity-informed method for multi-objective operation of reservoir systems, which uses global sensitivity analysis as a screening tool to reduce the computational demands. Sobol's method is used to screen insensitive decision variables and guide the formulation of the optimization problems with a significantly reduced number of decision variables. This sensitivity-informed problem decomposition dramatically reduces the computational demands required for attaining high quality approximations of optimal tradeoff relationships between conflicting design objectives. The search results obtained from the reduced complexity multi-objective reservoir operation problems are then used to pre-condition the full search of the original optimization problem. In two case studies, the Dahuofang reservoir and the inter-basin multi-reservoir system in Liaoning province, China, sensitivity analysis results show that reservoir performance is strongly controlled by a small proportion of decision variables. Sensitivity-informed problem decomposition and pre-conditioning are evaluated in their ability to improve the efficiency and effectiveness of multi-objective evolutionary optimization. Overall, this study illustrates the efficiency and effectiveness of the sensitivity-informed method and the use of global sensitivity analysis to inform problem decomposition when solving the complex multi-objective reservoir operation problems.

Evaluation of an inpatient fall risk screening tool to identify the most critical fall risk factors in inpatients.

PubMed

Hou, Wen-Hsuan; Kang, Chun-Mei; Ho, Mu-Hsing; Kuo, Jessie Ming-Chuan; Chen, Hsiao-Lien; Chang, Wen-Yin

2017-03-01

To evaluate the accuracy of the inpatient fall risk screening tool and to identify the most critical fall risk factors in inpatients. Variations exist in several screening tools applied in acute care hospitals for examining risk factors for falls and identifying high-risk inpatients. Secondary data analysis. A subset of inpatient data for the period from June 2011-June 2014 was extracted from the nursing information system and adverse event reporting system of an 818-bed teaching medical centre in Taipei. Data were analysed using descriptive statistics, receiver operating characteristic curve analysis and logistic regression analysis. During the study period, 205 fallers and 37,232 nonfallers were identified. The results revealed that the inpatient fall risk screening tool (cut-off point of ≥3) had a low sensitivity level (60%), satisfactory specificity (87%), a positive predictive value of 2·0% and a negative predictive value of 99%. The receiver operating characteristic curve analysis revealed an area under the curve of 0·805 (sensitivity, 71·8%; specificity, 78%). To increase the sensitivity values, the Youden index suggests at least 1·5 points to be the most suitable cut-off point for the inpatient fall risk screening tool. Multivariate logistic regression analysis revealed a considerably increased fall risk in patients with impaired balance and impaired elimination. The fall risk factor was also significantly associated with days of hospital stay and with admission to surgical wards. The findings can raise awareness about the two most critical risk factors for falls among future clinical nurses and other healthcare professionals and thus facilitate the development of fall prevention interventions. This study highlights the needs for redefining the cut-off points of the inpatient fall risk screening tool to effectively identify inpatients at a high risk of falls. Furthermore, inpatients with impaired balance and impaired elimination should be closely monitored by nurses to prevent falling during hospitalisations. © 2016 John Wiley & Sons Ltd.

Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease, an Endemic Osteoarthritis, in China.

PubMed

Yu, Fang Fang; Ping, Zhi Guang; Yao, Chong; Wang, Zhi Wen; Wang, Fu Qi; Guo, Xiong

2017-02-01

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Screening for skin cancer.

PubMed

Helfand, M; Mahon, S M; Eden, K B; Frame, P S; Orleans, C T

2001-04-01

Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past 2 decades. Nonmelanoma skin cancer is seldom lethal, but, if advanced, can cause severe disfigurement and morbidity. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of nonmelanoma skin cancer might prevent major disfigurement and to a lesser extent prevent mortality. Current recommendations from professional societies regarding screening for skin cancer vary. To examine published data on the effectiveness of routine screening for skin cancer by a primary care provider, as part of an assessment for the U.S. Preventive Services Task Force. We searched the MEDLINE database for papers published between 1994 and June 1999, using search terms for screening, physical examination, morbidity, and skin neoplasms. For information on accuracy of screening tests, we used the search terms sensitivity and specificity. We identified the most important studies from before 1994 from the Guide to Clinical Preventive Services, second edition, and from high-quality reviews. We used reference lists and expert recommendations to locate additional articles. Two reviewers independently reviewed a subset of 500 abstracts. Once consistency was established, the remainder were reviewed by one reviewer. We included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost effectiveness. We abstracted the following descriptive information from full-text published studies of screening and recorded it in an electronic database: type of screening study, study design, setting, population, patient recruitment, screening test description, examiner, advertising targeted at high-risk groups or not targeted, reported risk factors of participants, and procedure for referrals. We also abstracted the yield of screening data including probabilities and numbers of referrals, types of suspected skin cancers, biopsies, confirmed skin cancers, and stages and thickness of skin cancers. For studies that reported test performance, we recorded the definition of a suspicious lesion, the "gold-standard" determination of disease, and the number of true positive, false positive, true negative, and false negative test results. When possible, positive predictive values, likelihood ratios, sensitivity, and specificity were recorded. No randomized or case-control studies have been done that demonstrate that routine screening for melanoma by primary care providers reduces morbidity or mortality. Basal cell carcinoma and squamous cell carcinoma are very common, but detection and treatment in the absence of formal screening are almost always curative. No controlled studies have shown that formal screening programs will improve this already high cure rate. While the efficacy of screening has not been established, the screening procedures themselves are noninvasive, and the follow-up test, skin biopsy, has low morbidity. Five studies from mass screening programs reported the accuracy of skin examination as a screening test. One of these, a prospective study, tracked patients with negative results to determine the number of patients with false-negative results. In this study, the sensitivity of screening for skin cancer was 94% and specificity was 98%. Several recent case-control studies confirm earlier evidence that risk of melanoma rises with the presence of atypical moles and/or many common moles. One well-done prospective study demonstrated that risk assessment by limited physical exam identified a relatively small (<10%) group of primary care patients for more thorough evaluation. The quality of the evidence addressing the accuracy of routine screening by primary care providers for early detection of melanoma or nonmelanoma skin cancer ranged from poor to fair. We found no studies that assessed the effectiveness of periodic skin examination by a clinician in reducing melanoma mortality. Both self-assessment of risk factors or clinician examination can classify a small proportion of patients as at highest risk for melanoma. Skin cancer screening, perhaps using a risk-assessment technique to identify high-risk patients who are seeing a physician for other reasons, merits additional study as a strategy to address the excess burden of disease in older adults.

The Autism Parent Screen for Infants: Predicting risk of autism spectrum disorder based on parent-reported behavior observed at 6-24 months of age.

PubMed

Sacrey, Lori-Ann R; Bryson, Susan; Zwaigenbaum, Lonnie; Brian, Jessica; Smith, Isabel M; Roberts, Wendy; Szatmari, Peter; Vaillancourt, Tracy; Roncadin, Caroline; Garon, Nancy

2018-04-01

This study examined whether a novel parent-report questionnaire, the Autism Parent Screen for Infants, could differentiate infants subsequently diagnosed with autism spectrum disorder from a high-risk cohort (siblings of children diagnosed with autism spectrum disorder (n = 66)) from high-risk and low-risk comparison infants (no family history of autism spectrum disorder) who did not develop autism spectrum disorder (n = 138 and 79, respectively). Participants were assessed prospectively at 6, 9, 12, 15, 18, and 24 months of age. At 36 months, a blind independent diagnostic assessment for autism spectrum disorder was completed. Parent report on the Autism Parent Screen for Infants was examined in relation to diagnostic outcome and risk status (i.e. high-risk sibling with autism spectrum disorder, high-risk sibling without autism spectrum disorder, and low-risk control). The results indicated that from 6 months of age, total score on the Autism Parent Screen for Infants differentiated between the siblings with autism spectrum disorder and the other two groups. The sensitivity, specificity, and positive and negative predictive validity of the Autism Parent Screen for Infants highlight its potential for the early screening of autism spectrum disorder in high-risk cohorts.

Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening

PubMed Central

Phillips, Michael; Bauer, Thomas L.; Cataneo, Renee N.; Lebauer, Cassie; Mundada, Mayur; Pass, Harvey I.; Ramakrishna, Naren; Rom, William N.; Vallières, Eric

2015-01-01

Background Breath volatile organic compounds (VOCs) have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening. Methods Model-building phase (unblinded): Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation): We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively). The algorithm predicted discriminant function (DF) values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B). Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening. Results Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88). In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel. Conclusions Breath VOC mass ion biomarkers identified lung cancer in a separate independent cohort, in a blinded replicated study. Combining breath biomarkers with chest CT could potentially improve the sensitivity and specificity of lung cancer screening. Trial Registration ClinicalTrials.gov NCT00639067 PMID:26698306

Global Sensitivity Analysis of Environmental Models: Convergence, Robustness and Validation

NASA Astrophysics Data System (ADS)

Sarrazin, Fanny; Pianosi, Francesca; Khorashadi Zadeh, Farkhondeh; Van Griensven, Ann; Wagener, Thorsten

2015-04-01

Global Sensitivity Analysis aims to characterize the impact that variations in model input factors (e.g. the parameters) have on the model output (e.g. simulated streamflow). In sampling-based Global Sensitivity Analysis, the sample size has to be chosen carefully in order to obtain reliable sensitivity estimates while spending computational resources efficiently. Furthermore, insensitive parameters are typically identified through the definition of a screening threshold: the theoretical value of their sensitivity index is zero but in a sampling-base framework they regularly take non-zero values. There is little guidance available for these two steps in environmental modelling though. The objective of the present study is to support modellers in making appropriate choices, regarding both sample size and screening threshold, so that a robust sensitivity analysis can be implemented. We performed sensitivity analysis for the parameters of three hydrological models with increasing level of complexity (Hymod, HBV and SWAT), and tested three widely used sensitivity analysis methods (Elementary Effect Test or method of Morris, Regional Sensitivity Analysis, and Variance-Based Sensitivity Analysis). We defined criteria based on a bootstrap approach to assess three different types of convergence: the convergence of the value of the sensitivity indices, of the ranking (the ordering among the parameters) and of the screening (the identification of the insensitive parameters). We investigated the screening threshold through the definition of a validation procedure. The results showed that full convergence of the value of the sensitivity indices is not necessarily needed to rank or to screen the model input factors. Furthermore, typical values of the sample sizes that are reported in the literature can be well below the sample sizes that actually ensure convergence of ranking and screening.

Reagent Strips as an Aid to Diagnosis of Neonatal Meningitis in a Resource-limited Setting.

PubMed

Burgoine, Kathy; Ikiror, Juliet; Naizuli, Ketty; Achom, Linda; Akol, Sylivia; Olupot-Olupot, Peter

2018-01-29

Without early recognition and treatment, neonatal meningitis (NM) has a high mortality and morbidity. Although some neonates have features of NM, many do not. In many low-resource settings, the laboratory support to diagnose NM is not available, and bedside diagnostics are needed. This retrospective study was conducted in a neonatal unit in Uganda. Clear cerebrospinal fluid samples were routinely screened for glucose, protein and leukocytes on a Combur®-10 urinalysis reagent strip. A definitive diagnosis was made using laboratory analysis. The results of the screening and definitive tests were compared. The reagent strip showed moderate sensitivity and high specificity for leukocytes ≥10×106 cells/l, high sensitivity for protein ≥100 mg/dl and high specificity for glucose <50 mg/dl. The use of reagent strips has the potential to improve and hasten the diagnosis of probable NM in settings where adequate or timely laboratory support is not available. © The Author(s) [2018]. Published by Oxford University Press.

High performance of a new PCR-based urine assay for HPV-DNA detection and genotyping.

PubMed

Tanzi, Elisabetta; Bianchi, Silvia; Fasolo, Maria Michela; Frati, Elena R; Mazza, Francesca; Martinelli, Marianna; Colzani, Daniela; Beretta, Rosangela; Zappa, Alessandra; Orlando, Giovanna

2013-01-01

Human papillomavirus (HPV) testing has been proposed as a means of replacing or supporting conventional cervical screening (Pap test). However, both methods require the collection of cervical samples. Urine sample is easier and more acceptable to collect and could be helpful in facilitating cervical cancer screening. The aim of this study was to evaluate the sensitivity and specificity of urine testing compared to conventional cervical smear testing using a PCR-based method with a new, designed specifically primer set. Paired cervical and first voided urine samples collected from 107 women infected with HIV were subjected to HPV-DNA detection and genotyping using a PCR-based assay and a restriction fragment length polymorphism method. Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated using the McNemar's test for differences. Concordance between tests was assessed using the Cohen's unweighted Kappa (k). HPV DNA was detected in 64.5% (95% CI: 55.1-73.1%) of both cytobrush and urine samples. High concordance rates of HPV-DNA detection (k = 0.96; 95% CI: 0.90-1.0) and of high risk-clade and low-risk genotyping in paired samples (k = 0.80; 95% CI: 0.67-0.92 and k = 0.74; 95% CI: 0.60-0.88, respectively) were observed. HPV-DNA detection in urine versus cervix testing revealed a sensitivity of 98.6% (95% CI: 93.1-99.9%) and a specificity of 97.4% (95% CI: 87.7-99.9%), with a very high NPV (97.4%; 95% CI: 87.7-99.9%). The PCR-based assay utilized in this study proved highly sensitive and specific for HPV-DNA detection and genotyping in urine samples. These data suggest that a urine-based assay would be a suitable and effective tool for epidemiological surveillance and, most of all, screening programs. Copyright © 2012 Wiley Periodicals, Inc.

One-stop microvascular screening service: an effective model for the early detection of diabetic peripheral neuropathy and the high-risk foot.

PubMed

Binns-Hall, O; Selvarajah, D; Sanger, D; Walker, J; Scott, A; Tesfaye, S

2018-04-02

To evaluate the feasibility of a one-stop microvascular screening service for the early diagnosis of diabetic distal symmetrical polyneuropathy, painful distal symmetrical polyneuropathy and the at-risk diabetic foot. People with diabetes attending retinal screening in hospital and community settings had their feet examined by a podiatrist. Assessment included: Toronto Clinical Neuropathy Score evaluation; a 10-g monofilament test; and two validated, objective and quick measures of neuropathy obtained using the point-of-care devices 'DPN-Check', a hand-held device that measures sural nerve conduction velocity and amplitude, and 'Sudoscan', a device that measures sudomotor function. The diagnostic utility of these devices was assessed against the Toronto Clinical Neuropathy Score as the 'gold standard'. A total of 236 consecutive people attending the retinal screening service, 18.9% of whom had never previously had their feet examined, were evaluated. The prevalence of distal symmetrical polyneuropathy, assessed using the Toronto Clinical Neuropathy Score, was 30.9%, and was underestimated by 10-g monofilament test (14.4%). The prevalence of distal symmetrical polyneuropathy using DPN-check was 51.5% (84.3% sensitivity, 68.3% specificity), 38.2% using Sudoscan foot electrochemical skin conductance (77.4% sensitivity, 68.3% specificity), and 61.9% using abnormality in either of the results (93.2% sensitivity, 52.8% specificity). The results of both devices correlated with Toronto Clinical Neuropathy Score (P<0.001). A new diagnosis of painful distal symmetrical polyneuropathy was made in 59 participants (25%), and 56.6% had moderate- or high-risk foot. Participants rated the service very highly. Combined, eye, foot and renal screening is feasible, has a high uptake, reduces clinic visits, and identifies painful distal symmetrical polyneuropathy and the at-risk foot. Combined large- and small-nerve-fibre assessment using non-invasive, quantitative and quick point-of-care devices may be an effective model for the early diagnosis of distal symmetrical polyneuropathy. © 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

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

PubMed

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

2016-03-15

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

The Ideal Strategy for Cervical Cancer Screening in Japan: Result from the Fukui Cervical Cancer Screening Study.

PubMed

Kurokawa, T; Onuma, T; Shinagawa, A; Chino, Y; Kobayashi, M; Yoshida, Y

2018-05-16

The aims of the Fukui Cervical Cancer Screening (FCCS) study are to determine the frequency of women with high-risk HPV (hrHPV), whether HPV16 or HPV18 (HPV16/18), in the Japanese cancer screening population for the first time and to identify the best strategy for cervical cancer screening in Japan. This study enrolled 7,584 women ≥25 years of age who were undergoing routine screening. All women underwent liquid-based cytology and cobas HPV tests. Women with abnormal cytology, whether hrHPV positive or negative; women with hrHPV positivity with either normal or abnormal cytology; and women randomly selected from women with normal cytology and negative hrHPV negative were referred for colposcopy. The prevalences of hrHPV positivity and HPV16/18 positivity were 6.8% and 1.7%, respectively. The baseline data from the FCCS study showed that the combination of HPV tests and cytology was more sensitive than cytology with respect to the detection of intraepithelial neoplasia grade 2 or worse. However, the specificity (94.1%) of the co-testing strategy that required all women with abnormal cytology or hrHPV positivity to be referred for colposcopy was much lower than that (97.8%) of cytology. The sensitivity and specificity of the co-testing strategy that required only women with abnormal cytology or HPV16/18 positivity to undergo colposcopy were 85.5% and 97.0%, respectively. The baseline data from the FCCS study suggest that a cervical cancer screening strategy in which only women with abnormal cytology or HPV16/18 positivity undergo colposcopy offers a more balanced sensitivity and specificity than other strategies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Field performance of clinical case definitions for influenza screening during the 2009 pandemic.

PubMed

Chen, Shey-Ying; Chen, Yee-Chun; Chiang, Wen-Chu; Kung, Hsiang-Chi; King, Chwan-Chuen; Lai, Mei-Shu; Chie, Wei-Chu; Chen, Shyr-Chyr; Chen, Wen-Jone; Chang, Shan-Chwen

2012-11-01

The aim of this study was to assess the performance of 3 different influenza-like illness (ILI) case definitions, adopted by the European (European-CDC), USA (USA-CDC), and Taiwan Centers for Disease Prevention and Control (Taiwan-CDC), as screening tools for influenza during the 2009 H1N1 pandemic. From August 15 to 30, 2009, all emergency department patients with clinical symptoms or at epidemiologic risk for influenza were enrolled in an observational cohort study. Influenza diagnosis was established by positive rapid influenza diagnostic test or virus isolation. Sensitivity, specificity, positive predictive value, and negative predictive value of the European-, USA, and Taiwan-CDC ILI case definitions for screening were determined. A total of 870 patients were screened during the study period. Rapid influenza diagnostic test was positive in 315 patients, 273 (85.6%) of whom had fever duration less than 72 hours. Virus isolation identified 4 more patients with influenza A initially negative by rapid influenza diagnostic test. The mean (SD) age of these 319 patients was 24.3 (18.1) years. Of the 870 screened patients, 670 (77.0%), 476 (54.7%), and 325 (37.4%) met the European-, USA-, and Taiwan-CDC ILI case definition, respectively. Screening sensitivity was 95%, 77.7%, and 57.7% and specificity was 33.4%, 58.6%, and 74.4%, respectively. Differences in sensitivity and specificity between any 2 of the 3 groups were statistically significant (P < .05). First-line physicians should recognize the advantage and limitation of different ILI case definitions in influenza screening, especially confronted by pandemic or highly pathogenic avian influenza in the future. Copyright © 2012 Elsevier Inc. All rights reserved.

Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

PubMed

Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

2009-06-01

It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

Ultra-sensitive high performance liquid chromatography-laser-induced fluorescence based proteomics for clinical applications.

PubMed

Patil, Ajeetkumar; Bhat, Sujatha; Pai, Keerthilatha M; Rai, Lavanya; Kartha, V B; Chidangil, Santhosh

2015-09-08

An ultra-sensitive high performance liquid chromatography-laser induced fluorescence (HPLC-LIF) based technique has been developed by our group at Manipal, for screening, early detection, and staging for various cancers, using protein profiling of clinical samples like, body fluids, cellular specimens, and biopsy-tissue. More than 300 protein profiles of different clinical samples (serum, saliva, cellular samples and tissue homogenates) from volunteers (normal, and different pre-malignant/malignant conditions) were recorded using this set-up. The protein profiles were analyzed using principal component analysis (PCA) to achieve objective detection and classification of malignant, premalignant and healthy conditions with high sensitivity and specificity. The HPLC-LIF protein profiling combined with PCA, as a routine method for screening, diagnosis, and staging of cervical cancer and oral cancer, is discussed in this paper. In recent years, proteomics techniques have advanced tremendously in life sciences and medical sciences for the detection and identification of proteins in body fluids, tissue homogenates and cellular samples to understand biochemical mechanisms leading to different diseases. Some of the methods include techniques like high performance liquid chromatography, 2D-gel electrophoresis, MALDI-TOF-MS, SELDI-TOF-MS, CE-MS and LC-MS techniques. We have developed an ultra-sensitive high performance liquid chromatography-laser induced fluorescence (HPLC-LIF) based technique, for screening, early detection, and staging for various cancers, using protein profiling of clinical samples like, body fluids, cellular specimens, and biopsy-tissue. More than 300 protein profiles of different clinical samples (serum, saliva, cellular samples and tissue homogenates) from healthy and volunteers with different malignant conditions were recorded by using this set-up. The protein profile data were analyzed using principal component analysis (PCA) for objective classification and detection of malignant, premalignant and healthy conditions. The method is extremely sensitive to detect proteins with limit of detection of the order of femto-moles. The HPLC-LIF combined with PCA as a potential proteomic method for the diagnosis of oral cancer and cervical cancer has been discussed in this paper. This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

Chlamydia screening is not cost-effective at low participation rates: evidence from a repeated register-based implementation study in The Netherlands.

PubMed

de Wit, G Ardine; Over, Eelco A B; Schmid, Boris V; van Bergen, Jan E A M; van den Broek, Ingrid V F; van der Sande, Marianne A B; Welte, Robert; Op de Coul, Eline L M; Kretzschmar, Mirjam E

2015-09-01

In three pilot regions of The Netherlands, all 16-29 year olds were invited to participate in three annual rounds of Chlamydia screening. The aim of the present study is to evaluate the cost-effectiveness of repeated Chlamydia screening, based on empirical data. A mathematical model was employed to estimate the influence of repeated screening on prevalence and incidence of Chlamydial infection. A model simulating the natural history of Chlamydia was combined with cost and utility data to estimate the number of major outcomes and quality-adjusted life-years (QALYs) associated with Chlamydia. Six screening scenarios (16-29 years annually; 16-24 years annually; women only; biennial screening; biennial screening women only; screening every five years) were compared with no screening in two sexual networks, representing both lower ('national network') and higher ('urban network') baseline prevalence. Incremental cost-effectiveness ratios (ICERs) for the different screening scenarios were estimated. Uncertainty and sensitivity analyses were performed. In all scenarios and networks, cost per major outcome averted are above €5000. Cost per QALY are at least €50,000. The default scenario as piloted in the Netherlands was least cost-effective, with ICERs of €232,000 in the national and €145,000 in the urban sexual network. Results were robust in sensitivity analyses. It is unlikely that repeated rounds of Chlamydia screening will be cost-effective. Only at high levels of willingness to pay for a QALY (>€50,000) screening may be more cost-effective than no screening. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Screening athletes with Down syndrome for ocular disease.

PubMed

Gutstein, Walter; Sinclair, Stephen H; North, Rachel V; Bekiroglu, N

2010-02-01

Persons with Down syndrome are well known to have a high prevalence of vision and eye health problems, many of which are undetected or untreated primarily because of infrequent ocular examinations. Public screening programs, directed toward the pediatric population, have become more popular and commonly use letter or symbol charts. This study compares 2 vision screening methods, the Lea Symbol chart and a newly developed interactive computer program, the Vimetrics Central Vision Analyzer (CVA), in their ability to identify ocular disease in the Down syndrome population. Athletes with Down syndrome participating in the European Special Olympics underwent an ocular screening including history, auto-refraction, colour vision assessment, stereopsis assessment, motility assessment, pupil reactivity, and tonometry testing, as well as anterior segment and fundus examinations to evaluate for ocular disease. Visual acuity was tested with the Lea chart and CVA to evaluate these as screening tests for detecting ocular disease as well as significant, uncorrected refractive errors. Among the 91 athletes that presented to the screening, 79 (158 eyes) were sufficiently cooperative for the examination to be completed. Mean age was 26 years +/-10.8 SD. Significant, uncorrected refractive errors (>/=1.00 spherical equivalent) were detected in 28 (18%) eyes and ocular pathology in 51 (32%) eyes. The Lea chart sensitivity and specificity were 43% and 74%, respectively, for detecting ocular pathology and 58% and 100% for detecting uncorrected refractive errors. The CVA sensitivity and specificity were 70% and 86% for detecting pathology and 71% and 100% for detecting uncorrected refractive errors. This study confirmed the findings of prior studies in identifying a significant presence of uncorrected refractive errors and ocular pathology in the Down syndrome population. Screening with the Lea symbol chart found borderline sufficient sensitivity and specificity for the test to be used for screening in this population. The better sensitivity and specificity of the CVA, if adjusted normative values are utilized, appear to make this test sufficient for testing Down syndrome children for identifying both refractive errors and ocular pathology. Copyright 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

32 CFR 651.29 - Determining when to use a CX (screening criteria).

Code of Federal Regulations, 2013 CFR

2013-07-01

...; areas of critical environmental concern; or other areas of high environmental sensitivity. (4) Cultural... agricultural lands; coastal zones; designated wilderness or wilderness study areas; wild and scenic rivers...

32 CFR 651.29 - Determining when to use a CX (screening criteria).

Code of Federal Regulations, 2014 CFR

2014-07-01

...; areas of critical environmental concern; or other areas of high environmental sensitivity. (4) Cultural... agricultural lands; coastal zones; designated wilderness or wilderness study areas; wild and scenic rivers...

32 CFR 651.29 - Determining when to use a CX (screening criteria).

Code of Federal Regulations, 2012 CFR

2012-07-01

...; areas of critical environmental concern; or other areas of high environmental sensitivity. (4) Cultural... agricultural lands; coastal zones; designated wilderness or wilderness study areas; wild and scenic rivers...

The malnutrition screening tool versus objective measures to detect malnutrition in hip fracture.

PubMed

Bell, J J; Bauer, J D; Capra, S

2013-12-01

The Malnutrition Screening Tool (MST) is the most commonly used screening tool in Australia. Poor screening tool sensitivity may lead to an under-diagnosis of malnutrition, with potential patient and economic ramifications. The present study aimed to determine whether the MST or anthropometric parameters adequately detect malnutrition in patients who were admitted to a hip fracture unit. Data were analysed for a prospective convenience sample (n = 100). MST screening was independently undertaken by nursing staff and a nutrition assistant. Mid upper arm circumference (MUAC) was measured by a trained nutrition assistant. Nutritional risk [MST score ≥ 2, body mass index (BMI) < 22 kg m(-2) , or MUAC < 25 cm] was compared with malnutrition diagnosed by accredited practicing dietitians using International Classification of Diseases version 10-Australian Modification (ICD10-AM) coding criteria. Malnutrition prevalence was 37.5% using ICD10-AM criteria. Delirium, dementia or preadmission cognitive impairment was present in 65% of patients. The BMI as a nutrition risk screen was the most valid predictor of malnutrition (sensitivity 75%; specificity 93%; positive predictive value 73%; negative predictive value 84%). Nursing MST screening was the least valid (sensitivity 73%; specificity 55%; positive predictive value 50%; negative predictive value 77%). There was only fair agreement between nursing and nutrition assistant screening using the MST (κ = 0.28). In this population with a high prevalence of delirium and dementia, further investigation is warranted into the performance of nutrition screening tools and anthropometric parameters such as BMI. All tools failed to predict a considerable number of patients with malnutrition. This may result in the under-diagnosis and treatment of malnutrition, leading to case-mix funding losses. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

Integrated Magneto-Electrochemical Sensor for Exosome Analysis.

PubMed

Jeong, Sangmoo; Park, Jongmin; Pathania, Divya; Castro, Cesar M; Weissleder, Ralph; Lee, Hakho

2016-02-23

Extracellular vesicles, including exosomes, are nanoscale membrane particles that carry molecular information on parental cells. They are being pursued as biomarkers of cancers that are difficult to detect or serially follow. Here we present a compact sensor technology for rapid, on-site exosome screening. The sensor is based on an integrated magneto-electrochemical assay: exosomes are immunomagnetically captured from patient samples and profiled through electrochemical reaction. By combining magnetic enrichment and enzymatic amplification, the approach enables (i) highly sensitive, cell-specific exosome detection and (ii) sensor miniaturization and scale-up for high-throughput measurements. As a proof-of-concept, we implemented a portable, eight-channel device and applied it to screen extracellular vesicles in plasma samples from ovarian cancer patients. The sensor allowed for the simultaneous profiling of multiple protein markers within an hour, outperforming conventional methods in assay sensitivity and speed.

Integrated Magneto-Electrochemical Sensor for Exosome Analysis

PubMed Central

Jeong, Sangmoo; Park, Jongmin; Pathania, Divya; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho

2016-01-01

Extracellular vesicles, including exosomes, are nanoscale vesicles that carry molecular information of parental cells. They are being pursued as biomarkers of cancers that are difficult to detect or serially follow. Here we present a compact sensor technology for rapid, on-site exosome screening. The sensor is based on an integrated magnetic-electrochemical assay: exosomes are immunomagnetically captured from patient samples, and profiled through electrochemical reaction. By combining magnetic enrichment and enzymatic amplification, the approach enables i) highly sensitive, cell-specific exosome detection, and ii) sensor miniaturization and scale-up for high throughput measurements. As a proof-of-concept, we implemented a portable, eight-channel device, and applied it to screen extracellular vesicles in plasma samples from ovarian cancer patients. The sensor allowed for the profiling of multiple protein markers simultaneously within an hour, outperforming conventional methods in assay sensitivity and speed. PMID:26808216

Protein-mimicking nanowire-inspired electro-catalytic biosensor for probing acetylcholinesterase activity and its inhibitors.

PubMed

Zhang, Qingqing; Hu, Yufang; Wu, Di; Ma, Shaohua; Wang, Jiao; Rao, Jiajia; Xu, Lihua; Xu, Huan; Shao, Huili; Guo, Zhiyong; Wang, Sui

2018-06-01

A highly sensitive electrochemical biosensor based on the synthetized L-Cysteine-Ag(I) coordination polymer (L-Cys-Ag(I) CP), which looks like a protein-mimicking nanowire, was constructed to detect acetylcholinesterase (AChE) activity and screen its inhibitors. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce hydrogen peroxide (H 2 O 2 ), thus L-Cys-Ag(I) CP possesses the electro-catalytic property to H 2 O 2 reduction. Herein, the protein-mimicking nanowire-based platform was capable of investigating successive of H 2 O 2 effectively by amperometric i-t (current-time) response, and was further applied for the turn-on electrochemical detection of AChE activity. The proposed sensor is highly sensitive (limit of detection is 0.0006 U/L) and is feasible for screening inhibitors of AChE. The model for AChE inhibition was further established and two traditional AChE inhibitors (donepezil and tacrine) were employed to verify the feasibility of the system. The IC 5 0 of donepezil and tacrine were estimated to be 1.4 nM and 3.5 nM, respectively. The developed protocol provides a new and promising platform for probing AChE activity and screening its inhibitors with low cost, high sensitivity and selectivity. Copyright © 2018 Elsevier B.V. All rights reserved.

Overview of online two-dimensional liquid chromatography based on cell membrane chromatography for screening target components from traditional Chinese medicines.

PubMed

Muhammad, Saqib; Han, Shengli; Xie, Xiaoyu; Wang, Sicen; Aziz, Muhammad Majid

2017-01-01

Cell membrane chromatography is a simple, specific, and time-saving technique for studying drug-receptor interactions, screening of active components from complex mixtures, and quality control of traditional Chinese medicines. However, the short column life, low sensitivity, low column efficiency (so cannot resolve satisfactorily mixture of compounds), low peak capacity, and inefficient in structure identification were bottleneck in its application. Combinations of cell membrane chromatography with multidimensional chromatography such as two-dimensional liquid chromatography and high sensitivity detectors like mass have significantly reduced many of the above-mentioned shortcomings. This paper provides an overview of the current advances in online two-dimensional-based cell membrane chromatography for screening target components from traditional Chinese medicines with particular emphasis on the instrumentation, preparation of cell membrane stationary phase, advantages, and disadvantages compared to alternative approaches. The last section of the review summarizes the applications of the online two-dimensional high-performance liquid chromatography based cell membrane chromatography reported since its emergence to date (2010-June 2016). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Posttraumatic stress disorder in veterans and military personnel: epidemiology, screening, and case recognition.

PubMed

Gates, Margaret A; Holowka, Darren W; Vasterling, Jennifer J; Keane, Terence M; Marx, Brian P; Rosen, Raymond C

2012-11-01

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that affects 7-8% of the general U.S. population at some point during their lifetime; however, the prevalence is much higher among certain subgroups, including active duty military personnel and veterans. In this article, we review the empirical literature on the epidemiology and screening of PTSD in military and veteran populations, including the availability of sensitive and reliable screening tools. Although estimates vary across studies, evidence suggests that the prevalence of PTSD in deployed U.S. military personnel may be as high as 14-16%. Prior studies have identified trauma characteristics and pre- and posttrauma factors that increase risk of PTSD among veterans and military personnel. This information may help to inform prevention and screening efforts, as screening programs could be targeted to high-risk populations. Large-scale screening efforts have recently been implemented by the U.S. Departments of Defense and Veterans Affairs. Given the prevalence and potential consequences of PTSD among veterans and active duty military personnel, development and continued evaluation of effective screening methods is an important public health need.

Comprehensive Mechanistic Analysis of Hits from High-Throughput and Docking Screens against β-Lactamase

PubMed Central

Babaoglu, Kerim; Simeonov, Anton; Irwin, John J.; Nelson, Michael E.; Feng, Brian; Thomas, Craig J.; Cancian, Laura; Costi, M. Paola; Maltby, David A.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.; Shoichet, Brian K.

2009-01-01

High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate “hit lists”; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against β-lactamase using quantitative HTS (qHTS). Of the 1274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting β-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 µM. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens. PMID:18333608

To Screen or Not to Screen? A Decision Analysis of the Utility of Screening for Developmental Dysplasia of the Hip

PubMed Central

Mahan, Susan T.; Katz, Jeffrey N.; Kim, Young-Jo

2009-01-01

Background: The United States Preventive Services Task Force recently determined that they could not recommend any screening strategies for developmental dysplasia of the hip. Disparate findings in the literature and treatment-related problems have led to confusion about whether or not to screen for this disorder. The purpose of the present study was to determine, with use of expected-value decision analysis, which of the following three strategies leads to the best chance of having a non-arthritic hip by the age of sixty years: (1) no screening for developmental dysplasia of the hip, (2) universal screening of newborns with both physical examination and ultrasonography, or (3) universal screening with physical examination but only selective use of ultrasonography for neonates considered to be at high risk. Methods: Developmental dysplasia of the hip, avascular necrosis, and the treatment algorithm were carefully defined. The outcome was determined as the probability of any neonate having a non-arthritic hip through the age of sixty years. A decision tree was then built with decision nodes as described above, and chance node probabilities were determined from a thorough review of the literature. Foldback analysis and sensitivity analyses were performed. Results: The expected value of a favorable hip outcome was 0.9590 for the strategy of screening all neonates with physical examination and selective use of ultrasonography, 0.9586 for screening all neonates with physical examination and ultrasonography, and 0.9578 for no screening. A lower expected value implies a greater risk for the development of osteoarthritis as a result of developmental dysplasia of the hip or avascular necrosis; thus, the optimum strategy was selective screening. This model was robust to sensitivity analysis, except when the rate of missed dysplasia rose as high as 4/1000 or the rate of treated hip subluxation/dislocation was the same; then, the optimum strategy was to screen all neonates with both physical examination and ultrasonography. Conclusions: Our decision analytic model indicated that the optimum strategy, associated with the highest probability of having a non-arthritic hip at the age of sixty years, was to screen all neonates for hip dysplasia with a physical examination and to use ultrasonography selectively for infants who are at high risk. Additional data on the costs and cost-effectiveness of these screening policies are needed to guide policy recommendations. Level of Evidence: Economic and decision analysis Level II. See Instructions to Authors for a complete description of levels of evidence. PMID:19571094

Are 2 Questions Enough to Screen for Depression and Anxiety in Patients With Chronic Low Back Pain?

PubMed Central

Lie, Stein Atle; Eriksen, Hege R.

2014-01-01

Study Design. Cross-sectional study. Objective. To examine the sensitivity of 2 single-item questions compared with 2 longer questionnaires for screening depression and anxiety among patients with chronic low back pain (CLBP). Summary of Background Data. Psychosocial factors are frequently identified as risk factors for developing CLBP and as predictors for treatment, and questionnaires are often used to screen for this. Shorter instruments may be easier to use in clinical practice settings. Methods. A total of 564 patients with 2 to 10 months of at least 50% sickness absence due to nonspecific low back pain were assessed for depression and anxiety with the Mini-International Neuropsychiatric Interview (MINI). Single-item questions for depression and anxiety from the Subjective Health Complaint Inventory and 2 longer questionnaires, the Hospital Anxiety and Depression Scale and Hopkins Symptom Checklist–25, were compared with MINI results, considered the “gold standard” in this study. Sensitivity and specificity of single-item and longer questionnaires and receiver operating characteristic curves were compared. Results. According to MINI, the prevalence of anxiety disorders was 12% whereas that of depressive disorders was 4%. The screening questions showed 95% sensitivity and 56% specificity for depressive disorders and 68% sensitivity and 85% specificity for anxiety disorders. The longer questionnaire, Hospital Anxiety and Depression Scale, showed 91% sensitivity and 85% specificity for depressive disorders and 58% sensitivity and 83% specificity for anxiety disorders. Hopkins Symptom Checklist–25 showed 86% sensitivity and 74% specificity for depressive disorders and 67% sensitivity and 87% specificity for anxiety disorders. For 3 of the anxiety disorders and 2 of the depressive disorders, a perfect sensitivity was found between the screening questions and MINI. Conclusions. A single-item screening question was sensitive for depression but less sensitive for anxiety. The screening questions further performed equal to 2 widely used questionnaires. Validation of these results in other populations and compared with other short-item screeners is needed. Level of Evidence: 3 PMID:24480946

The PlusoptiX Photoscreener and the Retinomax Autorefractor as Community-based Screening Devices for Preschool Children.

PubMed

Kinori, Michael; Molina, Iliana; Hernandez, Eric O; Robbins, Shira L; Granet, David B; Coleman, Anne L; Brown, Stuart I

2018-05-01

To compare the performance of the PlusoptiX S12 mobile photoscreener and the Retinomax K+3 Autorefractor as screening devices in preschool children. Children ranging from 3 to 5 years of age from 11 San Diego County preschools underwent vision screening in their schools where ambient light could not always be controlled using both the Retinomax and the PlusoptiX. Cycloplegic refraction on the consented children was subsequently performed on the UCSD EyeMobile for children on-site at the school locations. A total of 321 children were screened with the PlusoptiX and Retinomax. The PlusoptiX referred 22% of children, of whom 70% of the referrals were read as "unable". The Retinomax referred 13% and there were no "unables". Similar results occurred in the cycloplegic-refracted 182 consented children-64% of the PlusoptiX referrals were read as "unable" . Only one third of these "unables" required glasses. Both devices referred the four children with amblyopia and one case of strabismus. However, PlusoptiX's 3 false negatives had amblyopia risk factors (ARFs) while the one Retinomax's false negative did not have ARFs. The Retinomax screening had 95% sensitivity and 94% specificity. The PlusoptiX screening had 86% sensitivity and 84% specificity. In this preschool population and environment, the PlusoptiX referred 63% more than the Retinomax in addition to a lower specificity and sensitivity. Adjusting PlusoptiX referral criteria might not substantially improve the specificity of the PlusoptiX due to the high numbers of "unables".

The utility of the Edmonton Symptom Assessment System in screening for anxiety and depression.

PubMed

Bagha, S M; Macedo, A; Jacks, L M; Lo, C; Zimmermann, C; Rodin, G; Li, M

2013-01-01

The Edmonton Symptom Assessment System (ESAS) is a common screening tool in cancer, although its validity for distress screening is unproven. Here, screening performance of the ESAS anxiety (ESAS-A) and depression (ESAS-D) items were validated against the anxiety [Generalised Anxiety Disorder-7 (GAD-7)] and depression [Patient Health Questionnaire-9 (PHQ-9)] subscales of the PHQ. A total of 1215 cancer patients completed the Distress Assessment and Response Tool (DART), a computerised distress screening instrument. Spearman's rank correlation coefficients and receiver operating characteristic curve analyses were used to evaluate the ability of ESAS-A and ESAS-D to identify moderate distress (GAD-7/PHQ-9 ≥ 10). Spearman's rank correlation coefficients comparing ESAS-A and ESAS-D with GAD-7 and PHQ-9 were 0.74 and 0.72 respectively. Areas under the receiver operating characteristic curves were 0.89 and 0.88 for anxiety and depression respectively. A cut-off of ≥3 on ESAS-A demonstrated a sensitivity of 0.91, specificity of 0.68, positive predictive value of 0.34 and negative predictive value of 0.97. A cut-off of ≥2 on the ESAS-D demonstrated a sensitivity of 0.86, specificity of 0.72, positive predictive value of 0.46 and negative predictive value of 0.95. High sensitivities of ESAS-A and ESAS-D at certain cut-offs suggest they have use in ruling-out distress. However, their low specificities indicate secondary screening is needed to rule-in anxiety or depression for case-finding. © 2012 Blackwell Publishing Ltd.

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.

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.

The prevalence of depression and the accuracy of depression screening tools in migraine patients.

PubMed

Amoozegar, Farnaz; Patten, Scott B; Becker, Werner J; Bulloch, Andrew G M; Fiest, Kirsten M; Davenport, W Jeptha; Carroll, Christopher R; Jette, Nathalie

2017-09-01

Migraine and depression are common comorbid conditions. The purpose of this study was to assess how well the Patient Health Questionnaire (PHQ-9) and the Hospital Anxiety and Depression Scale (HADS) perform as depression screening tools in patients with migraine. Three hundred consecutive migraine patients were recruited from a large headache center. The PHQ-9 and HADS were self-administered and validated against the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV, a gold standard for the diagnosis of depression. Sensitivity, specificity, positive predictive value, negative predictive value and receiver-operator characteristic curves were calculated for the PHQ-9 and HADS. At the traditional cut-point of 10, the PHQ-9 demonstrated 82.0% sensitivity and 79.9% specificity. At a cut-point of 8, the HADS demonstrated 86.5% sensitivity and specificity. The PHQ-9 algorithm performed poorly (53.8% sensitivity, 94.9% specificity). The point prevalence of depression in this study was 25.0% (95% CI 19.0-31.0), and 17.0% of patients had untreated depression. In this study, the PHQ-9 and HADS performed well in migraine patients attending a headache clinic, but optimal cut-points to screen for depression vary depending on the goals of the assessment. Also, migraine patients attending a headache clinic have a high prevalence of depression and many are inadequately treated. Future studies are needed to confirm these findings and to evaluate the impact of depression screening. Copyright © 2017 Elsevier Inc. All rights reserved.

FiGHTS: a preliminary screening tool for adolescent firearms-carrying.

PubMed

Hayes, D Neil; Sege, Robert

2003-12-01

Adolescent firearms-carrying is a risk factor for serious injury and death. Clinical screening tools for firearms-carrying have not yet been developed. We present the development of a preliminary screening test for adolescent firearms-carrying based on the growing body of knowledge of firearms-related risk factors. A convenience sample of 15,000 high school students from the 1999 National Youth Risk Behavior Survey was analyzed for the purpose of model building. Known risk factors for firearms-carrying were candidates for 2 models predicting recent firearms-carrying. The "brief FiGHTS score" screening tool excluded terms related to sexual behavior, significant substance abuse, or criminal behavior (Fi=fighting, G=gender, H=hurt while fighting, T=threatened, S=smoker). An "extended FiGHTS score," which included 13 items, was developed for more precise estimates. The brief FiGHTS score had a sensitivity of 82%, a specificity of 71%, and an area under the receiver operating characteristic (ROC) curve of 0.84. The extended FiGHTS score had an area under the ROC curve of 0.90. Both models performed well in a validation data set of 55,000 students. The brief and extended FiGHTS scores have high sensitivity and specificity for predicting firearms-carrying and may be appropriate for clinical testing.

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

PubMed

Kindler, H

2010-10-01

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

Accuracy of a disability instrument to identify workers likely to develop upper extremity musculoskeletal disorders.

PubMed

Stover, Bert; Silverstein, Barbara; Wickizer, Thomas; Martin, Diane P; Kaufman, Joel

2007-06-01

Work related upper extremity musculoskeletal disorders (MSD) result in substantial disability, and expense. Identifying workers or jobs with high risk can trigger intervention before workers are injured or the condition worsens. We investigated a disability instrument, the QuickDASH, as a workplace screening tool to identify workers at high risk of developing upper extremity MSDs. Subjects included workers reporting recurring upper extremity MSD symptoms in the past 7 days (n = 559). The QuickDASH was reasonably accurate at baseline with sensitivity of 73% for MSD diagnosis, and 96% for symptom severity. Specificity was 56% for diagnosis, and 53% for symptom severity. At 1-year follow-up sensitivity and specificity for MSD diagnosis was 72% and 54%, respectively, as predicted by the baseline QuickDASH score. For symptom severity, sensitivity and specificity were 86% and 52%. An a priori target sensitivity of 70% and specificity of 50% was met by symptom severity, work pace and quality, and MSD diagnosis. The QuickDASH may be useful for identifying jobs or workers with increased risk for upper extremity MSDs. It may provide an efficient health surveillance screening tool useful for targeting early workplace intervention for prevention of upper extremity MSD problems.

New feature of the neutron color image intensifier

NASA Astrophysics Data System (ADS)

Nittoh, Koichi; Konagai, Chikara; Noji, Takashi; Miyabe, Keisuke

2009-06-01

We developed prototype neutron color image intensifiers with high-sensitivity, wide dynamic range and long-life characteristics. In the prototype intensifier (Gd-Type 1), a terbium-activated Gd 2O 2S is used as the input-screen phosphor. In the upgraded model (Gd-Type 2), Gd 2O 3 and CsI:Na are vacuum deposited to form the phosphor layer, which improved the sensitivity and the spatial uniformity. A europium-activated Y 2O 2S multi-color scintillator, emitting red, green and blue photons with different intensities, is utilized as the output screen of the intensifier. By combining this image intensifier with a suitably tuned high-sensitive color CCD camera, higher sensitivity and wider dynamic range could be simultaneously attained than that of the conventional P20-phosphor-type image intensifier. The results of experiments at the JRR-3M neutron radiography irradiation port (flux: 1.5×10 8 n/cm 2/s) showed that these neutron color image intensifiers can clearly image dynamic phenomena with a 30 frame/s video picture. It is expected that the color image intensifier will be used as a new two-dimensional neutron sensor in new application fields.

High-throughput Screening Identifies Aclacinomycin as a Radiosensitizer of EGFR-Mutant Non-Small Cell Lung Cancer1

PubMed Central

Bennett, Daniel C; Charest, Jonathan; Sebolt, Katrina; Lehrman, Mark; Rehemtulla, Alnawaz; Contessa, Joseph N

2013-01-01

The endoplasmic reticulum (ER) provides a specialized environment for the folding and modification of trans-membrane proteins, including receptor tyrosine kinases (RTKs), which are vital for the growth and survival of malignancies. To identify compounds which disrupt the function of the ER and thus could potentially impair cancer cell survival signaling, we adapted a set of glycosylation-sensitive luciferase reporters for the development and optimization of a cell-based high-throughput screen (HTS). Secondary screens for false-positive luciferase activation and tertiary lectin-based and biochemical analyses were also devised for compound triage. Through a pilot screen of 2802 compounds from the National Cancer Institute (NCI) chemical libraries, we identified aclacinomycin (Acm) as a compound that preferentially affects ER function. We report that Acm reduces plasma membrane expression of glycoproteins including epidermal growth factor receptor (EGFR) and Met but does not inhibit N-linked glycosylation or generalized protein translation. Fluorescence microscopy co-localization experiments were also performed and demonstrated Acm accumulation in the ER in further support of the overall HTS design. The consequences of Acm treatment on cell survival were analyzed through clonogenic survival analysis. Consistent with the reduction of EGFR levels, pretreatment with Acm sensitizes the EGFR-mutant non-small cell lung cancer (NSCLC) cell lines HCC827 and HCC2935 to ionizing radiation and did not affect the sensitivity of the RTK-independent and KRAS-mutant A549 NSCLC cell line. Thus, Acm and similar compounds targeting the ER may represent a novel approach for radiosensitizing tumor cells dependent on RTK function. PMID:23730419

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

PubMed

Blom, Johannes; Törnberg, Sven

2017-09-01

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

The diagnostic accuracy of screening questionnaires for the identification of adults with epilepsy: a systematic review.

PubMed

Keezer, Mark R; Bouma, Hanni K; Wolfson, Christina

2014-11-01

To describe the diagnostic accuracy of screening questionnaires to identify epilepsy in adults, we performed a systematic review of diagnostic studies that assessed the sensitivity and specificity of such screening questionnaires as compared to a physician's clinical assessment. We searched Ovid MEDLINE (1946 to present) and Ovid EMBASE (1947 to present) for studies that estimated the sensitivity and specificity of nonphysician administered screening questionnaires for adults with epilepsy. Both telephone and in-person administered questionnaires were included, whether applied to population or hospital/clinic-based cohorts. The risk of bias was assessed using the Quality Assessment of Diagnostic Studies-2 (QUADAS-2) tool. Our initial search strategy resulted in 917 records. We found nine studies eligible for inclusion. The estimated sensitivity and specificity of the questionnaires used to identify persons with a lifetime history of epilepsy ranged from 81.5% to 100% and 65.6% to 99.2%, respectively. The sensitivity and specificity of these questionnaires in identifying persons with active epilepsy ranged from 48.6% to 100% and 73.9% to 99.9%, respectively. Overall we found a high risk of bias in patient selection and study flow in the majority of studies. We identified nine validation studies of epilepsy screening questionnaires, summarized their study characteristics, presented their results, and performed a rigorous quality assessment. This review serves as a basis for future studies by providing a systematic review of existing work. Future research addressing previous limitations will ultimately allow us to more accurately estimate the burden and risk of epilepsy in the general population. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Testing the woman abuse screening tool to identify intimate partner violence in Indonesia.

PubMed

Iskandar, Livia; Braun, Kathryn L; Katz, Alan R

2015-04-01

Intimate Partner Violence (IPV) is a global public health problem. IPV prevalence in Indonesia has been estimated to be less than 1%, based on reported cases. It is likely that IPV prevalence is underreported in Indonesia, as it is in many other countries. Screening for IPV has been found to increase IPV identification, but no screening tools are in use in Indonesia. The aim of this study was to test the translated Woman Abuse Screening Tool (WAST) for detecting IPV in Indonesia. The WAST was tested against a diagnostic interview by a trained psychologist on 240 women attending two Primary Health Centers in Jakarta. IPV prevalence and the reliability, sensitivity, and specificity of the WAST were estimated. Prevalence of IPV by diagnostic interview was 36.3%, much higher than published estimates. The most common forms of IPV identified were psychological (85%) and physical abuse (24%). Internal reliability of the WAST was high (α = .801). A WAST score of 13 (out of 24) is the recommended cutoff for identifying IPV, but only 17% of the Indonesian sample scored 13 or higher. Test sensitivity of the WAST with a cutoff score of 13 was only 41.9%, with a specificity of 96.8%. With a cutoff score of 10, the sensitivity improved to 84.9%, while the specificity decreased to 61.0%. Use of the WAST with a cutoff score of 10 provides good sensitivity and reasonable specificity and would provide a much-needed screening tool for use in Indonesia. Although a lower cutoff would yield a greater proportion of false positives, most of the true cases would be identified, increasing the possibility that women experiencing abuse would receive needed assistance. © The Author(s) 2014.

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.

Crowdsourcing and Automated Retinal Image Analysis for Diabetic Retinopathy.

PubMed

Mudie, Lucy I; Wang, Xueyang; Friedman, David S; Brady, Christopher J

2017-09-23

As the number of people with diabetic retinopathy (DR) in the USA is expected to increase threefold by 2050, the need to reduce health care costs associated with screening for this treatable disease is ever present. Crowdsourcing and automated retinal image analysis (ARIA) are two areas where new technology has been applied to reduce costs in screening for DR. This paper reviews the current literature surrounding these new technologies. Crowdsourcing has high sensitivity for normal vs abnormal images; however, when multiple categories for severity of DR are added, specificity is reduced. ARIAs have higher sensitivity and specificity, and some commercial ARIA programs are already in use. Deep learning enhanced ARIAs appear to offer even more improvement in ARIA grading accuracy. The utilization of crowdsourcing and ARIAs may be a key to reducing the time and cost burden of processing images from DR screening.

Two-question depression-screeners - the solution to all problems?

PubMed

Albani, Cornelia; Bailer, Harald; Blaser, Gerd; Brähler, Elmar; Geyer, Michael; Grulke, Norbert

2006-04-01

Depression constitutes a considerable issue in medicine and it is anticipated that the amount of people suffering from affective disorders will increase significantly. It would be useful to have a simple, fast screening procedure which would help detect depression. In four recently published articles a two-question depression-screener is recommended. Sensitivity, specificity, likelihood ratios, negative and positive predictive values were compared. For four different clinical samples and one sample that was representative of the German population the prevalence for depression ranged from 6.9 % to 18.1 %. Sensitivity and specificity reached values from 72.6 % to 96.6 % and from 56.9 % to 90.0 % respectively. All negative predictive values were high (< 97 %) opposed to positive predictive values (17.8 % to 38.5 %). Overall, it seems that the two-question screenings are well suited for the exclusion of a major depression. It is possible that regular screening could further lower the percentage of undiagnosed cases.

Cost-Effectiveness of High-Risk Human Papillomavirus Testing With Messenger RNA Versus DNA Under United States Guidelines for Cervical Cancer Screening.

PubMed

Ting, Jie; Smith, Jennifer S; Myers, Evan R

2015-10-01

To compare the cost-effectiveness of high-risk human papillomavirus (hrHPV) testing using a hrHPV DNA and a hrHPV messenger RNA (mRNA) assay under current US cervical cancer screening guidelines. We constructed a Markov model for stochastic cost-effectiveness analysis using published data. We compared screening efficiency using DNA and mRNA testing for the following: (1) cotesting with cytology in women 30 to 65 years, and (2) triage of women with mild cervical cytological abnormalities (atypical squamous cells of undetermined significance [ASC-US]) in the United States. Screening end point is histologically confirmed high-grade lesions (cervical intraepithelial neoplasia grade 2, 3, or invasive cancer). Sensitivity and specificity estimates of DNA and mRNA testing to detect cervical intraepithelial neoplasia grade 2, 3, or invasive cancer were obtained from 2 published trials: the US Clinical Evaluation of APTIMA mRNA (CLEAR) study for ASC-US triage and the French APTIMA Screening Evaluation (FASE) study for cotesting. Costs of DNA and mRNA testing were assumed identical. Costs of screening, diagnosis, and treatment of cervical neoplasia and cancer were from previously published estimates, adjusted to 2012 US dollars. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity analysis. Model outcomes were costs per life-year saved for each strategy, discounted at 3% annually. For both cotesting and ASC-US triage, mRNA testing cost less than DNA testing, whereas life expectancies were widely overlapping. There was a 100% probability that DNA testing was not cost-effective at $100,000/life-year saved threshold for ASC-US triage and a 55% probability that DNA testing was not cost-effective at the same threshold for cotesting. Based on the available evidence, mRNA testing for cotesting or ASC-US triage is likely to be more efficient than DNA testing under current US cervical cancer screening guidelines.

Evaluation of a Screening Instrument for Autism Spectrum Disorders in Prisoners

PubMed Central

Robinson, Louise; Spencer, Michael D.; Thomson, Lindsay D. G.; Stanfield, Andrew C.; Owens, David G. C.; Hall, Jeremy; Johnstone, Eve C.

2012-01-01

There have been concerns that individuals with autism spectrum disorders (ASDs) are over-represented but not recognised in prison populations. A screening tool for ASDs in prisons has therefore been developed. Aims We aimed to evaluate this tool in Scottish prisoners by comparing scores with standard measures of autistic traits (Autism Quotient (AQ)), neurodevelopmental history (Asperger Syndrome (and High-Functioning Autism) Diagnostic Interview (ASDI)), and social cognition (Ekman 60 Faces test). Methods Prison officers across all 12 publicly-run closed prisons in Scotland assessed convicted prisoners using the screening tool. This sample included male and female prisoners and both adult and young offenders. Prisoners with high scores, along with an equal number of age and sex-matched controls, were invited to take part in interviews. Prisoners' relatives were contacted to complete a neurodevelopmental assessment. Results 2458 prisoners were screened using the tool, and 4% scored above the cut-off. 126 prisoners were further assessed using standardised measures. 7 of those 126 assessed scored 32 or above (cut-off) on the AQ. 44 interviews were completed with prisoners' relatives, no prisoner reached the cut-off score on the ASDI. Scores on the screening tool correlated significantly with AQ and ASDI scores, and not with the Ekman 60 Faces Test or IQ. Sensitivity was 28.6% and specificity 75.6%; AUC was 59.6%. Conclusions Although this screening tool measures autistic traits in this population, sensitivity for scores of 32 or above on the AQ is poor. We consider that this limits its usefulness and do not recommend that the tool is routinely used to screen for ASDs in prisons. PMID:22662113

Routine screening for α-thalassaemia using an immunochromatographic strip assay for haemoglobin Bart's.

PubMed

Prayalaw, Patcharawadee; Fucharoen, Goonnapa; Fucharoen, Supan

2014-09-01

To evaluate an immunochromatographic (IC) strip assay for Hb Bart's as a routine screening test for α-thalassaemia in area with a high prevalence of thalassaemia and haemoglobinopathies. A total of 300 adult screen positive blood specimens were collected at an ongoing thalassaemia screening programme in northeast Thailand. Routine screening was done using red blood cell indices, osmotic fragility, and dichlorophenolindophenol tests. The IC strip assay for haemoglobin Bart's was performed on all samples. The result was evaluated against thalassaemia genotypes determined using standard haemoglobin and DNA analyses. Of 300 subjects investigated, Hb and DNA analyses identified 32 with normal genotype. The remaining subjects carried thalassaemia with as many as 16 different genotypes. Hb Bart's was detected in all cases, with several α(0)-thalassaemia (SEA type) related disorders. Of cases with α(+)-thalassaemia, 86.1% showed a positive result; 100 out of 103 Hb E carriers, all homozygous Hb E and β-thalassaemia trait were negative. Nine out of 17 cases with β-thalassaemia/Hb E disease, and one case of double heterozygote for Hb Q-Thailand and Hb E returned positive results. The overall sensitivity and specificity of the IC strip assay for detecting α(0)-thalassaemia were 100% and 73.1%, respectively. The results showed a high sensitivity for screening for α(0)-thalassaemia using IC strip assay for Hb Bart's. This simple method, used in combination with conventional screening protocols, should lead to a significant reduction in the number of referral cases for DNA analysis. Cost effectiveness in each population should be taken into consideration. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer

PubMed Central

Azorsa, David O; Gonzales, Irma M; Basu, Gargi D; Choudhary, Ashish; Arora, Shilpi; Bisanz, Kristen M; Kiefer, Jeffrey A; Henderson, Meredith C; Trent, Jeffrey M; Von Hoff, Daniel D; Mousses, Spyro

2009-01-01

Background Pancreatic cancer retains a poor prognosis among the gastrointestinal cancers. It affects 230,000 individuals worldwide, has a very high mortality rate, and remains one of the most challenging malignancies to treat successfully. Treatment with gemcitabine, the most widely used chemotherapeutic against pancreatic cancer, is not curative and resistance may occur. Combinations of gemcitabine with other chemotherapeutic drugs or biological agents have resulted in limited improvement. Methods In order to improve gemcitabine response in pancreatic cancer cells, we utilized a synthetic lethal RNAi screen targeting 572 known kinases to identify genes that when silenced would sensitize pancreatic cancer cells to gemcitabine. Results Results from the RNAi screens identified several genes that, when silenced, potentiated the growth inhibitory effects of gemcitabine in pancreatic cancer cells. The greatest potentiation was shown by siRNA targeting checkpoint kinase 1 (CHK1). Validation of the screening results was performed in MIA PaCa-2 and BxPC3 pancreatic cancer cells by examining the dose response of gemcitabine treatment in the presence of either CHK1 or CHK2 siRNA. These results showed a three to ten-fold decrease in the EC50 for CHK1 siRNA-treated cells versus control siRNA-treated cells while treatment with CHK2 siRNA resulted in no change compared to controls. CHK1 was further targeted with specific small molecule inhibitors SB 218078 and PD 407824 in combination with gemcitabine. Results showed that treatment of MIA PaCa-2 cells with either of the CHK1 inhibitors SB 218078 or PD 407824 led to sensitization of the pancreatic cancer cells to gemcitabine. Conclusion These findings demonstrate the effectiveness of synthetic lethal RNAi screening as a tool for identifying sensitizing targets to chemotherapeutic agents. These results also indicate that CHK1 could serve as a putative therapeutic target for sensitizing pancreatic cancer cells to gemcitabine. PMID:19519883

[Screening strains for Trichoderma spp. for strong antagonism against ginseng root pathogens and study on their biological characters].

PubMed

Zhao, A-Na; Ding, Wan-Long; Zhu, Dian-Long

2006-10-01

To screen the Trichodenna spp. for strong antagonist against ginseng root pathogens. The biological characters of ten Trichoderma strains were compared by culturing on different media. And their antagonistic activity against Phytophthora cactorum, Cylindrocarpon destructans and Rhizoctonia solani were measured on PDA. Tv04-2 and Th3080 showed a good growth on soil solution medium and PDA, and also showed high inhibitory efficacy to the three pathogens. The two Trichoderma strains showed different growth rate under light conditions and pH. Trichoderma strains were sensitive to most fungicides used in ginseng root disease controlling, however Tv04-2 was not sensitive to the fungicide Junchong Jueba.

A novel hypothesis on the sensitivity of the fecal occult blood test: Results of a joint analysis of 3 randomized controlled trials.

PubMed

Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Boer, Rob; Zauber, Ann; Habbema, J Dik F

2009-06-01

Estimates of the fecal occult blood test (FOBT) (Hemoccult II) sensitivity differed widely between screening trials and led to divergent conclusions on the effects of FOBT screening. We used microsimulation modeling to estimate a preclinical colorectal cancer (CRC) duration and sensitivity for unrehydrated FOBT from the data of 3 randomized controlled trials of Minnesota, Nottingham, and Funen. In addition to 2 usual hypotheses on the sensitivity of FOBT, we tested a novel hypothesis where sensitivity is linked to the stage of clinical diagnosis in the situation without screening. We used the MISCAN-Colon microsimulation model to estimate sensitivity and duration, accounting for differences between the trials in demography, background incidence, and trial design. We tested 3 hypotheses for FOBT sensitivity: sensitivity is the same for all preclinical CRC stages, sensitivity increases with each stage, and sensitivity is higher for the stage in which the cancer would have been diagnosed in the absence of screening than for earlier stages. Goodness-of-fit was evaluated by comparing expected and observed rates of screen-detected and interval CRC. The hypothesis with a higher sensitivity in the stage of clinical diagnosis gave the best fit. Under this hypothesis, sensitivity of FOBT was 51% in the stage of clinical diagnosis and 19% in earlier stages. The average duration of preclinical CRC was estimated at 6.7 years. Our analysis corroborated a long duration of preclinical CRC, with FOBT most sensitive in the stage of clinical diagnosis. (c) 2009 American Cancer Society.

First day of life pulse oximetry screening to detect congenital heart defects.

PubMed

Meberg, Alf; Brügmann-Pieper, Sabine; Due, Reidar; Eskedal, Leif; Fagerli, Ingebjørg; Farstad, Teresa; Frøisland, Dag Helge; Sannes, Catharina Hovland; Johansen, Ole Jakob; Keljalic, Jasmina; Markestad, Trond; Nygaard, Egil Andre; Røsvik, Alet; Silberg, Inger Elisabeth

2008-06-01

To evaluate the efficacy of first day of life pulse oximetry screening to detect congenital heart defects (CHDs). We performed a population-based prospective multicenter study of postductal (foot) arterial oxygen saturation (SpO(2)) in apparently healthy newborns after transfer from the delivery suite to the nursery. SpO(2) < 95% led to further diagnostic evaluations. Of 57,959 live births, 50,008 (86%) were screened. In the screened population, 35 CHDs were [corrected] classified as critical (ductus dependent, cyanotic). CHDs were prospectively registered and diagnosed in 658/57,959 (1.1%) [corrected] Of the infants screened, 324 (0.6%) failed the test. Of these, 43 (13%) had CHDs (27 critical), and 134 (41%) had pulmonary diseases or other disorders. The remaining 147 infants (45%) were healthy with transitional circulation. The median age for babies with CHDs at failing the test was 6 hours (range, 1-21 hours). For identifying critical CHDs, the pulse oximetry screening had a sensitivity rate of 77.1% (95% CI, 59.4-89.0), specificity rate of 99.4% (95% CI, 99.3-99.5), and a false-positive rate of 0.6% (95% CI, 0.5-0.7). Early pulse oximetry screening promotes early detection of critical CHDs and other potentially severe diseases. The sensitivity rate for detecting critical CHDs is high, and the false-positive rate is low.

Transabdominal ultrasonography as a screening test for second-trimester placenta previa.

PubMed

Quant, Hayley S; Friedman, Alexander M; Wang, Eileen; Parry, Samuel; Schwartz, Nadav

2014-03-01

To determine the test characteristics of transabdominal ultrasonography as a screening test for second-trimester placenta previa. This secondary analysis of a prospective cohort study evaluated the distance from the placental edge to the internal os (placenta-cervix distance) through both transabdominal and transvaginal ultrasonography during the anatomic survey. Patients were recruited in the Maternal-Fetal Medicine Ultrasound Unit at the Hospital of the University of Pennsylvania, an urban tertiary care center. Transabdominal placenta-cervix distance cutoffs with high sensitivity for detection of previa and low-lying placenta were identified, and test characteristics were calculated. Follow-up ultrasound data, pregnancy, and delivery outcomes for those with second-trimester previa or low-lying placenta were obtained. One thousand two hundred fourteen women were included in the analysis. A transabdominal placenta-cervix distance cutoff of 4.2 cm was 93.3% sensitive and 76.7% specific for detection of previa with a 99.8% negative predictive value at a screen-positive rate of 25.0%. A cutoff of 2.8 cm was 86.7% sensitive and 90.5% specific with a 99.6% negative predictive value at a screen-positive rate of 11.4%. Only 9.8% (four of 41) of previas and low-lying placentas persisted through delivery. Transabdominal ultrasonography is an effective screening test for second-trimester placenta previa. At centers not performing universal transvaginal ultrasonography at the time of the anatomic survey, evidence-based transabdominal placenta-cervix distance cutoffs can optimize the identification of patients who require further surveillance for previa.

A tool for automated diabetic retinopathy pre-screening based on retinal image computer analysis.

PubMed

Gegundez-Arias, Manuel E; Marin, Diego; Ponte, Beatriz; Alvarez, Fatima; Garrido, Javier; Ortega, Carlos; Vasallo, Manuel J; Bravo, Jose M

2017-09-01

This paper presents a methodology and first results of an automatic detection system of first signs of Diabetic Retinopathy (DR) in fundus images, developed for the Health Ministry of the Andalusian Regional Government (Spain). The system detects the presence of microaneurysms and haemorrhages in retinography by means of techniques of digital image processing and supervised classification. Evaluation was conducted on 1058 images of 529 diabetic patients at risk of presenting evidence of DR (an image of each eye is provided). To this end, a ground-truth diagnosis was created based on gradations performed by 3 independent ophthalmology specialists. The comparison between the diagnosis provided by the system and the reference clinical diagnosis shows that the system can work at a level of sensitivity that is similar to that achieved by experts (0.9380 sensitivity per patient against 0.9416 sensitivity of several specialists). False negatives have proven to be mild cases. Moreover, while the specificity of the system is significantly lower than that of human graders (0.5098), it is high enough to screen more than half of the patients unaffected by the disease. Results are promising in integrating this system in DR screening programmes. At an early stage, the system could act as a pre-screening system, by screening healthy patients (with no obvious signs of DR) and identifying only those presenting signs of the disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of methods for in-house screening of HLA-B*57:01 to prevent abacavir hypersensitivity in HIV-1 care.

PubMed

De Spiegelaere, Ward; Philippé, Jan; Vervisch, Karen; Verhofstede, Chris; Malatinkova, Eva; Kiselinova, Maja; Trypsteen, Wim; Bonczkowski, Pawel; Vogelaers, Dirk; Callens, Steven; Ruelle, Jean; Kabeya, Kabamba; De Wit, Stephane; Van Acker, Petra; Van Sandt, Vicky; Emonds, Marie-Paule; Coucke, Paul; Sermijn, Erica; Vandekerckhove, Linos

2015-01-01

Abacavir is a nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy in HIV-1-infected patients. Because this drug can cause a hypersensitivity reaction that is correlated with the presence of the HLA-B*57:01 allotype, screening for the presence of HLA-B*57:01 is recommended before abacavir initiation. Different genetic assays have been developed for HLA-B*57:01 screening, each with specific sensitivity, turnaround time and assay costs. Here, a new real-time PCR (qPCR) based analysis is described and compared to sequence specific primer PCR with capillary electrophoresis (SSP PCR CE) on 149 patient-derived samples, using sequence specific oligonucleotide hybridization combined with high resolution SSP PCR as gold standard. In addition to these PCR based methods, a complementary approach was developed using flow cytometry with an HLA-B17 specific monoclonal antibody as a pre-screening assay to diminish the number of samples for genetic testing. All three assays had a maximum sensitivity of >99. However, differences in specificity were recorded, i.e. 84.3%, 97.2% and >99% for flow cytometry, qPCR and SSP PCR CE respectively. Our data indicate that the most specific and sensitive of the compared methods is the SSP PCR CE. Flow cytometry pre-screening can substantially decrease the number of genetic tests for HLA-B*57:01 typing in a clinical setting.

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.

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

Identification of Gambling Problems in Primary Care: Properties of the NODS-CLiP Screening Tool.

PubMed

Cowlishaw, Sean; McCambridge, Jim; Kessler, David

2018-06-25

There are several brief screening tools for gambling that possess promising psychometric properties, but have uncertain utility in generalist healthcare environments which prioritize prevention and brief interventions. This study describes an examination of the National Opinion Research Centre Diagnostic and Statistical Manual of Mental Disorders Screen for Gambling Problems (NODS-CLiP), in comparison with the Problem Gambling Severity Index (PGSI), when used to operationalize gambling problems across a spectrum of severity. Data were obtained from 1058 primary care attendees recruited from 11 practices in England who completed various measures including the NODS-CLiP and PGSI. The performance of the former was defined by estimates of sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs), when PGSI indicators of problem gambling (5+) and any gambling problems (1+), respectively, were reference standards. The NODS-CLiP demonstrated perfect sensitivity for problem gambling, along with high specificity and a NPV, but a low PPV. There was much lower sensitivity when the indicator of any gambling problems was the reference standard, with capture rates indicating only 20% of patients exhibiting low to moderate severity gambling problems (PGSI 1-4) were identified by the NODS-CLiP. The NODS-CLiP performs well when identifying severe cases of problem gambling, but lacks sensitivity for less severe problems and may be unsuitable for settings which prioritize prevention and brief interventions. There is a need for screening measures which are sensitive across the full spectrum of risk and severity, and can support initiatives for improving identification and responses to gambling problems in healthcare settings such as primary care.

Intracellular human papillomavirus E6, E7 mRNA quantification predicts CIN 2+ in cervical biopsies better than Papanicolaou screening for women regardless of age.

PubMed

Pierry, Deirdre; Weiss, Gerald; Lack, Benjamin; Chen, Victor; Fusco, Judy

2012-08-01

Cervical cancer screening in women younger than 30 years relies on cervical cytology because of the poor performance of human papillomavirus (HPV) DNA testing in this age group. To determine the performance of in-cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high-grade cervical intraepithelial neoplasia in women younger than 30 years. We analyzed 3133 cytology specimens from a screening population of women aged 19-75 years investigate HPV OncoTect as a triage/secondary screening test for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology in women younger than 30 years. Test results were compared to histology in 246 cases. The sensitivity of E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30 years and older. In women younger than 30 years, the sensitivity of E6, E7 mRNA for CIN 2+ lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology (≥ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women 30 years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+ in women younger than 30. The specificity of E6, E7 mRNA was >80% for CIN 2+ and CIN 3+ in both groups of women compared to a specificity of abnormal cytology of <10% for CIN 2+ and CIN 3+ in both groups. HPV OncoTect demonstrates a performance that would be effective for ASCUS/LSIL triage in women including those younger than 30 years.

Fully automated screening of immunocytochemically stained specimens for early cancer detection

NASA Astrophysics Data System (ADS)

Bell, André A.; Schneider, Timna E.; Müller-Frank, Dirk A. C.; Meyer-Ebrecht, Dietrich; Böcking, Alfred; Aach, Til

2007-03-01

Cytopathological cancer diagnoses can be obtained less invasive than histopathological investigations. Cells containing specimens can be obtained without pain or discomfort, bloody biopsies are avoided, and the diagnosis can, in some cases, even be made earlier. Since no tissue biopsies are necessary these methods can also be used in screening applications, e.g., for cervical cancer. Among the cytopathological methods a diagnosis based on the analysis of the amount of DNA in individual cells achieves high sensitivity and specificity. Yet this analysis is time consuming, which is prohibitive for a screening application. Hence, it will be advantageous to retain, by a preceding selection step, only a subset of suspicious specimens. This can be achieved using highly sensitive immunocytochemical markers like p16 ink4a for preselection of suspicious cells and specimens. We present a method to fully automatically acquire images at distinct positions at cytological specimens using a conventional computer controlled microscope and an autofocus algorithm. Based on the thus obtained images we automatically detect p16 ink4a-positive objects. This detection in turn is based on an analysis of the color distribution of the p16 ink4a marker in the Lab-colorspace. A Gaussian-mixture-model is used to describe this distribution and the method described in this paper so far achieves a sensitivity of up to 90%.

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.

PubMed

Wolf, Andrew M D; Fontham, Elizabeth T H; Church, Timothy R; Flowers, Christopher R; Guerra, Carmen E; LaMonte, Samuel J; Etzioni, Ruth; McKenna, Matthew T; Oeffinger, Kevin C; Shih, Ya-Chen Tina; Walter, Louise C; Andrews, Kimberly S; Brawley, Otis W; Brooks, Durado; Fedewa, Stacey A; Manassaram-Baptiste, Deana; Siegel, Rebecca L; Wender, Richard C; Smith, Robert A

2018-05-30

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;000:000-000. © 2018 American Cancer Society. © 2018 American Cancer Society.

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).

The sensitivity and specificity of the Middlesex Elderly Assessment of Mental State (MEAMS) for detecting cognitive impairment after stroke.

PubMed

Cartoni, A; Lincoln, N B

2005-03-01

The aim of the study was to assess the sensitivity and specificity of the MEAMS (Golding, 1989) for detecting cognitive impairment after stroke. Stroke patients admitted to hospital received a cognitive screening assessment, the MEAMS, and a detailed cognitive assessment. The information obtained from the detailed assessment was summarised in a structured written report. From the conclusions in these reports, patients were classified as "impaired" or "not impaired" in perception, memory, executive function and language. The sensitivity and specificity of the MEAMS subtests and the overall number of tests passed were determined in relation to the presence of impairment, as given in the overall conclusion of the written reports. There were 30 stroke patients, aged 58 to 92 (mean 75.80, SD 7.94) years. Of these, 17 were men and 13 were women. The sensitivity of the MEAMS subtests ranged from 11% to 100% and the specificity ranged from 69% to 100%. The sensitivity of the overall MEAMS score was 52% and the specificity was 100%, using a cut-off score of 3 or more fails to indicate impairment. Three subtests, Orientation, Naming and Unusual views had 81% sensitivity and 50% specificity for detecting problems in language, perception or memory. The MEAMS was not a sensitive screen for overall cognitive impairment or for memory, perceptual, language, or executive function problems after stroke, but it was specific. Although screening for cognitive impairment is important, the MEAMS is not recommended as the sole method, as it produces an unacceptably high false negative rate. Three subtests (Orientation, Naming and Unusual views) had 81% sensitivity and 50% specificity for detecting cognitive problems in language, perception or memory after stroke.

High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster.

PubMed

Filošević, Ana; Al-Samarai, Sabina; Andretić Waldowski, Rozi

2018-01-01

Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila . We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per) , Clock (Clk) , and cycle (cyc) . The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization to cocaine in individual Drosophila . Because of its high-throughput nature, FlyBong can be used in genetic screens or in selection experiments aimed at the unbiased identification of functional genes involved in acute or chronic effects of volatilized psychoactive substances.

High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster

PubMed Central

Filošević, Ana; Al-samarai, Sabina; Andretić Waldowski, Rozi

2018-01-01

Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila. We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per), Clock (Clk), and cycle (cyc). The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization to cocaine in individual Drosophila. Because of its high-throughput nature, FlyBong can be used in genetic screens or in selection experiments aimed at the unbiased identification of functional genes involved in acute or chronic effects of volatilized psychoactive substances. PMID:29459820

Prevalence of food sensitization and probable food allergy among adults in India: the EuroPrevall INCO study.

PubMed

Mahesh, P A; Wong, Gary W K; Ogorodova, L; Potts, J; Leung, T F; Fedorova, O; Holla, Amrutha D; Fernandez-Rivas, M; Clare Mills, E N; Kummeling, I; Versteeg, S A; van Ree, R; Yazdanbakhsh, M; Burney, P

2016-07-01

Data are lacking regarding the prevalence of food sensitization and probable food allergy among general population in India. We report the prevalence of sensitization and probable food allergy to 24 common foods among adults from general population in Karnataka, South India. The study was conducted in two stages: a screening study and a case-control study. A total of 11 791 adults in age group 20-54 were randomly sampled from general population in South India and answered a screening questionnaire. A total of 588 subjects (236 cases and 352 controls) participated in the case-control study involving a detailed questionnaire and specific IgE estimation for 24 common foods. A high level of sensitization (26.5%) was observed for most of the foods in the general population, higher than that observed among adults in Europe, except for those foods that cross-react with birch pollen. Most of the sensitization was observed in subjects who had total IgE above the median IgE level. A high level of cross-reactivity was observed among different pollens and foods and among foods. The prevalence of probable food allergy (self-reports of adverse symptoms after the consumption of food and specific IgE to the same food) was 1.2%, which was mainly accounted for cow's milk (0.5%) and apple (0.5%). Very high levels of sensitization were observed for most foods, including those not commonly consumed in the general population. For the levels of sensitization, the prevalence of probable food allergy was low. This disassociation needs to be further explored in future studies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differential antioxidative responses to dehydration-induced oxidative stress in core set of foxtail millet cultivars [Setaria italica (L.)].

PubMed

Lata, Charu; Jha, Sarita; Dixit, Vivek; Sreenivasulu, Nese; Prasad, Manoj

2011-10-01

Foxtail millet (Setaria italica L.) known as a relatively drought-tolerant crop across the world is grown in arid and semi-arid regions. To the best of our knowledge, no systematic study on drought tolerance screening of foxtail millet germplasm being a drought-tolerant crop has been reported so far. To explore genetic diversity of drought-induced oxidative stress tolerance in foxtail millet, we employed lipid peroxidation measure to assess membrane integrity under stress as biochemical marker to screen 107 cultivars and classified the genotypes as highly tolerant, tolerant, sensitive, and highly sensitive. From this comprehensive screening, four cultivars showing differential response to dehydration tolerance were selected to understand the physiological and biochemical basis of tolerance mechanisms. The dehydration-tolerant cultivars (IC-403579 and Prasad) showed considerably lower levels of lipid peroxidation and electrolyte leakage as compared with dehydration-sensitive cultivars (IC-480117 and Lepakshi), indicating better cell membrane integrity in tolerant cultivars. Correspondingly, tolerant genotypes maintained higher activity of catalase (EC 1.11.1.6), ascorbate peroxidase (APX; EC 1.11.1.11), and glutathione reductase (GR; EC 1.6.4.2) across different time-course period of polyethylene glycol (PEG) treatments in comparison to sensitive ones. The above biochemical results were further validated through quantitative real-time PCR analysis of APX and GR, whose transcripts were substantially induced by PEG treatments in tolerant cultivars. These results suggest that tolerant cultivars possess wider array of antioxidant machinery with efficient ascorbate-glutathione pathway to cope with drought-induced oxidative stress.

The Development of Novel Small Molecule Inhibitors of the Phosphoinositide-3-Kinase Pathway Through High-Throughput Cell-Based Screens

DTIC Science & Technology

2005-02-01

Akt in the P13K pathway. Given the emerging data for a positive feedback loop induced by mTOR inhibition, a bispecific 5 inhibitor might be attractive...cells relatively sensitive to rapamycin are also sensitive to thioridazine. PTEN null cells are known to be preferentially sensitized to mTOR ...a potent mTOR inhibitor, a downstream protein kinase in the Akt pathway. Rapamycin showed strong growth inhibitory effect in PTEN-null cells but 786

Noninvasive High-Throughput Single-Cell Analysis of HIV Protease Activity Using Ratiometric Flow Cytometry

PubMed Central

Gaber, Rok; Majerle, Andreja; Jerala, Roman; Benčina, Mojca

2013-01-01

To effectively fight against the human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) epidemic, ongoing development of novel HIV protease inhibitors is required. Inexpensive high-throughput screening assays are needed to quickly scan large sets of chemicals for potential inhibitors. We have developed a Förster resonance energy transfer (FRET)-based, HIV protease-sensitive sensor using a combination of a fluorescent protein pair, namely mCerulean and mCitrine. Through extensive in vitro characterization, we show that the FRET-HIV sensor can be used in HIV protease screening assays. Furthermore, we have used the FRET-HIV sensor for intracellular quantitative detection of HIV protease activity in living cells, which more closely resembles an actual viral infection than an in vitro assay. We have developed a high-throughput method that employs a ratiometric flow cytometry for analyzing large populations of cells that express the FRET-HIV sensor. The method enables FRET measurement of single cells with high sensitivity and speed and should be used when subpopulation-specific intracellular activity of HIV protease needs to be estimated. In addition, we have used a confocal microscopy sensitized emission FRET technique to evaluate the usefulness of the FRET-HIV sensor for spatiotemporal detection of intracellular HIV protease activity. PMID:24287545

Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis.

PubMed

Lefterova, Martina I; Shen, Peidong; Odegaard, Justin I; Fung, Eula; Chiang, Tsoyu; Peng, Gang; Davis, Ronald W; Wang, Wenyi; Kharrazi, Martin; Schrijver, Iris; Scharfe, Curt

2016-03-01

Newborn screening for cystic fibrosis enables early detection and management of this debilitating genetic disease. Implementing comprehensive CFTR analysis using Sanger sequencing as a component of confirmatory testing of all screen-positive newborns has remained impractical due to relatively lengthy turnaround times and high cost. Here, we describe CFseq, a highly sensitive, specific, rapid (<3 days), and cost-effective assay for comprehensive CFTR gene analysis from dried blood spots, the common newborn screening specimen. The unique design of CFseq integrates optimized dried blood spot sample processing, a novel multiplex amplification method from as little as 1 ng of genomic DNA, and multiplex next-generation sequencing of 96 samples in a single run to detect all relevant CFTR mutation types. Sequence data analysis utilizes publicly available software supplemented by an expert-curated compendium of >2000 CFTR variants. Validation studies across 190 dried blood spots demonstrated 100% sensitivity and a positive predictive value of 100% for single-nucleotide variants and insertions and deletions and complete concordance across the polymorphic poly-TG and consecutive poly-T tracts. Additionally, we accurately detected both a known exon 2,3 deletion and a previously undetected exon 22,23 deletion. CFseq is thus able to replace all existing CFTR molecular assays with a single robust, definitive assay at significant cost and time savings and could be adapted to high-throughput screening of other inherited conditions. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Screening for Trichomonas vaginalis in a Large High-Risk Population: Prevalence Among Men and Women Determined by Nucleic Acid Amplification Testing.

PubMed

Schwebke, Jane; Merriweather, Anthony; Massingale, Sharon; Scisney, Mary; Hill, Craig; Getman, Damon

2018-05-01

Men and women attending family planning and sexually transmitted disease clinics for sexually transmitted infection screening in 2012 to 2013 were tested for Trichomonas vaginalis (TV) using a sensitive nucleic acid amplification test. T. vaginalis prevalence in urogenital samples was 11.3% in 77,740 women and 6.1% in 12,604 men, and increased with age in both sexes.

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

Vaginal symptoms and bacterial vaginosis (BV): how useful is self-report? Development of a screening tool for predicting BV status.

PubMed

Nelson, D B; Bellamy, S; Odibo, A; Nachamkin, I; Ness, R B; Allen-Taylor, L

2007-11-01

Vaginal complaints compel an evaluation of bacterial vaginosis (BV), however, many cases of BV are asymptomatic. We evaluated the sensitivity and specificity of vaginal symptoms in the diagnosis of BV and examined the utility of creating a BV screening tool using clinical, behavioural and demographic characteristics. A total of 1916 pregnant women were included in this analysis. In total, 757 women screened positive for BV and over one third of BV-positive women presented without any lower genital tract symptoms (39.4%). African American race, abnormal vaginal odour, and smoking were independently related to BV positivity. A BV screening tool including these three factors was fairly predictive of BV status with the area under the ROC curve equal to 0.669. This three-item prediction rule may be useful in identifying high- risk pregnant women in need of BV screening and, given the high specificity, accurately identify the group of BV-negative pregnant women.

Comparison of Triage Strategies for HPV-Positive Women: Canadian Cervical Cancer Screening Trial Results.

PubMed

Isidean, Sandra D; Mayrand, Marie-Hélène; Ramanakumar, Agnihotram V; Rodrigues, Isabel; Ferenczy, Alex; Ratnam, Sam; Coutlée, François; Franco, Eduardo L

2017-06-01

Background: High-risk human papillomavirus (HR-HPV) testing has become a preferred cervical cancer screening strategy in some countries due to its superior sensitivity over cytology-based methods for identifying cervical intraepithelial neoplasia of grade 2 or worse (CIN2 + ). Improved sensitivity has been accompanied by reductions in specificity and concerns regarding overscreening and overtreatment of women with transient or nonprogressing HR-HPV infections. Triage of HR-HPV + women to colposcopy is, thus, warranted for appropriate management and treatment. Methods: Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we compared the performance of cytology and HR-HPV strategies to detect CIN2 + among HR-HPV + women (age, 30-69 years). Colposcopy referral rates and performance gains from adding other HR-HPV genotypes to HPV16/18 + triage were also evaluated. Results: A strategy referring all women HPV16/18 + and HPV16/18 - , but with atypical squamous cells of undetermined significance or worse cytology (ASC-US + ) had the highest sensitivity [82.5%; 95% confidence interval (CI), 70.9%-91.0%] but yielded the highest colposcopy referral rate. HPV16/18 + triage was the next most sensitive strategy (64.1%; 95% CI, 51.1%-75.7%). Low-grade squamous intraepithelial lesion or worse cytology (LSIL + ) triage yielded a low sensitivity (32.8%; 95% CI, 21.9%-45.4%) but had the most favorable specificity (93.6%; 95% CI, 91.0%-95.6%), positive predictive value (41.5%; 95% CI, 28.1%-55.9%), and colposcopy referral rate of strategies examined. HPV viral load triage strategies did not perform optimally overall. Inclusion of HR-HPV genotypes 31 and 52 to HPV16/18 + triage provided the highest sensitivities. Conclusion: Concerns surrounding HPV-based screening can be effectively mitigated via triage. Impact: Balancing the benefits of HPV-based primary cervical screening with informed management recommendations for HR-HPV + women may decide the success of its widening utilization. Cancer Epidemiol Biomarkers Prev; 26(6); 923-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Ovarian Cancer Screening Pilot Trial In High Risk Women — EDRN Public Portal

Cancer.gov

BACKGROUND: No proven ovarian cancer (OC) screening strategy exists for women who are at increased risk for the disease. A risk of ovarian cancer algorithm (ROCA) using serial CA125 values have previously shown greater positive predictive value (PPV) and sensitivity than a single CA125 in screening women at general population risk. We hypothesized that using ROCA would yield a reasonable PPV for ovarian cancer screening in a cohort at increased risk. METHODS: Between 7/2001 and 9/2006, 25 sites (14 CGN, 3 ovarian SPOREs, 1 EDRN, 7 others) prospectively enrolled patients. Inclusion criteria included: among self, 1st degree and 2nd degree relatives in same lineage either (i) BRCA 1/2 mutation, or (ii) two of OC or early onset (age 1% to ultrasound (US) and risk > 10% additionally to a gynecologic oncologist. Objectives included PPV for study indicated surgery, sensitivity, and compliance. Sample size was chosen to observe 8 OC endpoints with a power of 80% to rule out PPV < or = 10% if the true PPV = 20%.

Prevalence of asymptomatic bacteriuria among pregnant women in Benin City, Nigeria.

PubMed

Akerele, J; Abhulimen, P; Okonofua, F

2001-03-01

A semi-quantitative screening for asymptomatic bacteriuria was carried out in the first trimester of 500 consecutive pregnant women in Benin City. The purpose was to provide baseline data and rational therapy for asymptomatic bacteriuria in pregnant women. Of the 500 women screened, 433 clinical specimens showed significant bacteriuria, representing an incidence of 86.6%. Of this number, 38 (7.4%) were of mixed bacterial colonies while 395 (91%) were of single bacterial colonies. Staphylococcus aureus (29.8%), Escherichia coli (29.1%) and Klebsiella pneumoniae (21.5%) were the most frequently isolated pathogens. The high incidence of asymptomatic bacteriuria in pregnancy correlated significantly (P < 0.05) with the observed high proportion of pyuria. On average, sensitivity of the pathogens was ciprofloxacin 99.7%; ceftazidime 81.6%; co-trimoxazole 79.4%; augmentin 71.4%; nalidixic acid 61.7%; nitrofurantoin 61.%; gentamycin 56.9% and ampicillin 25.4%. S. aureus was most sensitive, while Proteus mirabilis was least sensitive among the pathogens. Rational therapy of asymptomatic bacteriuria in pregnant women may prevent associated risks such as pyelonephritis and pre-eclampsia.

High-Throughput, Motility-Based Sorter for Microswimmers and Gene Discovery Platform

NASA Astrophysics Data System (ADS)

Yuan, Jinzhou; Raizen, David; Bau, Haim

2015-11-01

Animal motility varies with genotype, disease progression, 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 was implemented in a simple microfluidic device capable of sorting many thousands of animals per hour per module, and is amenable to parallelism. The device successfully enriched for known C. elegans motility mutants. Furthermore, using this device, we isolated low-abundance mutants capable of suppressing the somnogenic effects of the flp-13 gene, which regulates sleep-like quiescence in C. elegans. Subsequent genomic sequencing led to the identification of a flp-13-suppressor gene. This research was supported, in part, by NIH NIA Grant 5R03AG042690-02.

A Sensitive in Vitro High-Throughput Screen To Identify Pan-filoviral Replication Inhibitors Targeting the VP35–NP Interface

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

Liu, Gai; Nash, Peter J.; Johnson, Britney

The 2014 Ebola outbreak in West Africa, the largest outbreak on record, highlighted the need for novel approaches to therapeutics targeting Ebola virus (EBOV). Within the EBOV replication complex, the interaction between polymerase cofactor, viral protein 35 (VP35), and nucleoprotein (NP) is critical for viral RNA synthesis. We recently identified a peptide at the N-terminus of VP35 (termed NPBP) that is sufficient for interaction with NP and suppresses EBOV replication, suggesting that the NPBP binding pocket can serve as a potential drug target. Here we describe the development and validation of a sensitive high-throughput screen (HTS) using a fluorescence polarizationmore » assay. Initial hits from this HTS include the FDA-approved compound tolcapone, whose potency against EBOV infection was validated in a nonfluorescent secondary assay. High conservation of the NP–VP35 interface among filoviruses suggests that this assay has the capacity to identify pan-filoviral inhibitors for development as antivirals.« less

Terbium-sensitized luminescence screening method for fluoroquinolones in beef serum

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

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

2017-05-15

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

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.

Age-related differences in recommended anthropometric cut-off point validity to identify cardiovascular risk factors in ostensibly healthy women

PubMed Central

Björkelund, Cecilia; Guo, Xinxin; Skoog, Ingmar; Bosaeus, Ingvar; Lissner, Lauren

2014-01-01

Aim: To investigate validity of widely recommended anthropometric and total fat percentage cut-off points in screening for cardiovascular risk factors in women of different ages. Methods: A population-based sample of 1002 Swedish women aged 38, 50, 75 (younger, middle-aged and elderly, respectively) underwent anthropometry, health examinations and blood tests. Total fat was estimated (bioimpedance) in 670 women. Sensitivity, specificity of body mass index (BMI; ≥25 and ≥30), waist circumference (WC; ≥80 cm and ≥88 cm) and total fat percentage (TF; ≥35%) cut-off points for cardiovascular risk factors (dyslipidaemias, hypertension and hyperglycaemia) were calculated for each age. Cut-off points yielding high sensitivity together with modest specificity were considered valid. Women reporting hospital admission for cardiovascular disease were excluded. Results: The sensitivity of WC ≥80 cm for one or more risk factors was ~60% in younger and middle-aged women, and 80% in elderly women. The specificity of WC ≥80 cm for one or more risk factors was 69%, 57% and 40% at the three ages (p < .05 for age trends). WC ≥80 cm yielded ~80% sensitivity for two or more risk factors across all ages. However, specificity decreased with increasing age (p < .0001), being 33% in elderly. WC ≥88 cm provided better specificity in elderly women. BMI and TF % cut-off points were not better than WC. Conclusions: Validity of recommended anthropometric cut-off points in screening asymptomatic women varies with age. In younger and middle-age, WC ≥80 cm yielded high sensitivity and modest specificity for two or more risk factors, however, sensitivity for one or more risk factor was less than optimal. WC ≥88 cm showed better validity than WC ≥80 cm in elderly. Our results support age-specific screening cut-off points for women. PMID:25294689

Age-related differences in recommended anthropometric cut-off point validity to identify cardiovascular risk factors in ostensibly healthy women.

PubMed

Subramoney, Sreevidya; Björkelund, Cecilia; Guo, Xinxin; Skoog, Ingmar; Bosaeus, Ingvar; Lissner, Lauren

2014-12-01

To investigate validity of widely recommended anthropometric and total fat percentage cut-off points in screening for cardiovascular risk factors in women of different ages. A population-based sample of 1002 Swedish women aged 38, 50, 75 (younger, middle-aged and elderly, respectively) underwent anthropometry, health examinations and blood tests. Total fat was estimated (bioimpedance) in 670 women. Sensitivity, specificity of body mass index (BMI; ≥25 and ≥30), waist circumference (WC; ≥80 cm and ≥88 cm) and total fat percentage (TF; ≥35%) cut-off points for cardiovascular risk factors (dyslipidaemias, hypertension and hyperglycaemia) were calculated for each age. Cut-off points yielding high sensitivity together with modest specificity were considered valid. Women reporting hospital admission for cardiovascular disease were excluded. The sensitivity of WC ≥80 cm for one or more risk factors was ~60% in younger and middle-aged women, and 80% in elderly women. The specificity of WC ≥80 cm for one or more risk factors was 69%, 57% and 40% at the three ages (p < .05 for age trends). WC ≥80 cm yielded ~80% sensitivity for two or more risk factors across all ages. However, specificity decreased with increasing age (p < .0001), being 33% in elderly. WC ≥88 cm provided better specificity in elderly women. BMI and TF % cut-off points were not better than WC. Validity of recommended anthropometric cut-off points in screening asymptomatic women varies with age. In younger and middle-age, WC ≥80 cm yielded high sensitivity and modest specificity for two or more risk factors, however, sensitivity for one or more risk factor was less than optimal. WC ≥88 cm showed better validity than WC ≥80 cm in elderly. Our results support age-specific screening cut-off points for women. © 2014 the Nordic Societies of Public Health.

Comparison of Three Different Commercial Kits for the Human Papilloma Virus Genotyping.

PubMed

Lim, Yong Kwan; Choi, Jee-Hye; Park, Serah; Kweon, Oh Joo; Park, Ae Ja

2016-11-01

High-risk type human papilloma virus (HPV) is the most important cause of cervical cancer. Recently, real-time polymerase chain reaction and reverse blot hybridization assay-based HPV DNA genotyping kits are developed. So, we compared the performances of different three HPV genotyping kits using different analytical principles and methods. Two hundred positive and 100 negative cervical swab specimens were used. DNA was extracted and all samples were tested by the MolecuTech REBA HPV-ID, Anyplex II HPV28 Detection, and HPVDNAChip. Direct sequencing was performed as a reference method for confirming high-risk HPV genotypes 16, 18, 45, 52, and 58. Although high-level agreement results were observed in negative samples, three kits showed decreased interassay agreement as screening setting in positive samples. Comparing the genotyping results, three assays showed acceptable sensitivity and specificity for the detection of HPV 16 and 18. Otherwise, various sensitivities showed in the detection of HPV 45, 52, and 58. The three assays had dissimilar performance of HPV screening capacity and exhibited moderate level of concordance in HPV genotyping. These discrepant results were unavoidable due to difference in type-specific analytical sensitivity and lack of standardization; therefore, we suggested that the efforts to standardization of HPV genotyping kits and adjusting analytical sensitivity would be important for the best clinical performance. © 2016 Wiley Periodicals, Inc.

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

PubMed

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

2012-11-01

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

Colonial legacy and the experience of First Nations women in cervical cancer screening: a Canadian multi-community study

PubMed Central

Wakewich, Pamela; Wood, Brianne; Davey, Crystal; Laframboise, Ashlie; Zehbe, Ingeborg

2016-01-01

Regular Papanicolaou (Pap) screening has dramatically reduced cervical cancer incidence in Canada since the 1950s. However, Indigenous women’s rates of cervical cancer remain disproportionately high, a factor which is not acknowledged in national media or in educational materials reporting Canada’s new cervical cancer screening guidelines. Here, we present findings from a cervical cancer screening initiative in Northwestern Ontario. Based on participatory action research, we worked with 10 First Nations communities in the Robinson Superior Treaty area to increase awareness of cervical cancer risk, develop culturally sensitive tools for screening and education and test the efficacy of human papillomavirus (HPV) self-sampling as an alternative to Pap cytology. We conducted 16 interviews with health care professionals and 9 focus groups with 69 women from the communities. A central theme for both health care providers (HCPs) and community members was the colonial legacy and its influence on women’s experiences of cervical cancer screening. This was evidenced by a strong sense of body shyness, including shame related to sexuality and sexually transmitted infections, concerns about confidentiality in clinical encounters and distrust or caution around HCPs. Reaffirming women’s traditional caregiving and educational roles, enhancing mother and daughter communication, improving cultural sensitivity in health care and education and adoption of HPV self-sampling to increase women’s privacy and control of the cervical cancer screening experience were endorsed. We argue that education and screening initiatives must reflect the cultural preferences of Indigenous women, empowering them to take control of their experiences of health and body in cervical cancer screening. PMID:27867262

The layer boundary effect on multi-layer mesoporous TiO 2 film based dye sensitized solar cells

DOE PAGES

Xu, Feng; Zhu, Kai; Zhao, Yixin

2016-10-10

Multi-layer mesoporous TiO 2 prepared by screen printing is widely used for fabrication of high-efficiency dye-sensitized solar cells (DSSCs). Here, we compare the three types of ~10 um thick mesoporous TiO 2 films, which were screen printed as 1-, 2- and 4-layers using the same TiO 2 nanocrystal paste. The layer boundary of the multi-layer mesoporous TiO 2 films was observed in the cross-section SEM. The existence of a layer boundary could reduce the photoelectron diffusion length with the increase of layer number. However, the photoelectron diffusion lengths of the Z907 dye sensitized solar cells based on these different layeredmore » mesoporous TiO 2 films are all longer than the film thickness. Consequently, the photovoltaic performance seems to have little dependence on the layer number of the multi-layer TiO 2 based DSSCs.« less

The layer boundary effect on multi-layer mesoporous TiO 2 film based dye sensitized solar cells

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

Xu, Feng; Zhu, Kai; Zhao, Yixin

Multi-layer mesoporous TiO 2 prepared by screen printing is widely used for fabrication of high-efficiency dye-sensitized solar cells (DSSCs). Here, we compare the three types of ~10 um thick mesoporous TiO 2 films, which were screen printed as 1-, 2- and 4-layers using the same TiO 2 nanocrystal paste. The layer boundary of the multi-layer mesoporous TiO 2 films was observed in the cross-section SEM. The existence of a layer boundary could reduce the photoelectron diffusion length with the increase of layer number. However, the photoelectron diffusion lengths of the Z907 dye sensitized solar cells based on these different layeredmore » mesoporous TiO 2 films are all longer than the film thickness. Consequently, the photovoltaic performance seems to have little dependence on the layer number of the multi-layer TiO 2 based DSSCs.« less

Sensitivity analysis and nonlinearity assessment of steam cracking furnace process

NASA Astrophysics Data System (ADS)

Rosli, M. N.; Sudibyo, Aziz, N.

2017-11-01

In this paper, sensitivity analysis and nonlinearity assessment of cracking furnace process are presented. For the sensitivity analysis, the fractional factorial design method is employed as a method to analyze the effect of input parameters, which consist of four manipulated variables and two disturbance variables, to the output variables and to identify the interaction between each parameter. The result of the factorial design method is used as a screening method to reduce the number of parameters, and subsequently, reducing the complexity of the model. It shows that out of six input parameters, four parameters are significant. After the screening is completed, step test is performed on the significant input parameters to assess the degree of nonlinearity of the system. The result shows that the system is highly nonlinear with respect to changes in an air-to-fuel ratio (AFR) and feed composition.

The development and initial validation of a sensitive bedside cognitive screening test.

PubMed

Faust, D; Fogel, B S

1989-01-01

Brief bedside cognitive examinations such as the Mini-Mental State Examination are designed to detect delirium and dementia but not more subtle or delineated cognitive deficits. Formal neuropsychological evaluation provides greater sensitivity and detects a wider range of cognitive deficits but is too lengthy for efficient use at the bedside or in epidemiological studies. The authors developed the High Sensitivity Cognitive Screen (HSCS), a 20-minute interview-based test, to identify patients who show disorder on formal neuropsychological evaluation. An initial study demonstrated satisfactory test-retest and interrater reliability. The HSCS was then administered to 60 psychiatric and neurological patients with suspected cognitive deficits but without gross impairment, who also completed formal neuropsychological testing. Results of both tests were independently classified as either normal, borderline, or abnormal. The HSCS correctly classified 93% of patients across the normal-abnormal dichotomy and showed promise for characterizing the extent and severity of cognitive dysfunction.

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

PubMed

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

2011-02-01

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

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.

Accuracy of Referring Provider and Endoscopist Impressions of Colonoscopy Indication.

PubMed

Naveed, Mariam; Clary, Meredith; Ahn, Chul; Kubiliun, Nisa; Agrawal, Deepak; Cryer, Byron; Murphy, Caitlin; Singal, Amit G

2017-07-01

Background: Referring provider and endoscopist impressions of colonoscopy indication are used for clinical care, reimbursement, and quality reporting decisions; however, the accuracy of these impressions is unknown. This study assessed the sensitivity, specificity, positive and negative predictive value, and overall accuracy of methods to classify colonoscopy indication, including referring provider impression, endoscopist impression, and administrative algorithm compared with gold standard chart review. Methods: We randomly sampled 400 patients undergoing a colonoscopy at a Veterans Affairs health system between January 2010 and December 2010. Referring provider and endoscopist impressions of colonoscopy indication were compared with gold-standard chart review. Indications were classified into 4 mutually exclusive categories: diagnostic, surveillance, high-risk screening, or average-risk screening. Results: Of 400 colonoscopies, 26% were performed for average-risk screening, 7% for high-risk screening, 26% for surveillance, and 41% for diagnostic indications. Accuracy of referring provider and endoscopist impressions of colonoscopy indication were 87% and 84%, respectively, which were significantly higher than that of the administrative algorithm (45%; P <.001 for both). There was substantial agreement between endoscopist and referring provider impressions (κ=0.76). All 3 methods showed high sensitivity (>90%) for determining screening (vs nonscreening) indication, but specificity of the administrative algorithm was lower (40.3%) compared with referring provider (93.7%) and endoscopist (84.0%) impressions. Accuracy of endoscopist, but not referring provider, impression was lower in patients with a family history of colon cancer than in those without (65% vs 84%; P =.001). Conclusions: Referring provider and endoscopist impressions of colonoscopy indication are both accurate and may be useful data to incorporate into algorithms classifying colonoscopy indication. Copyright © 2017 by the National Comprehensive Cancer Network.

Cost-Effectiveness Analysis of Screening for and Managing Identified Hypertension for Cardiovascular Disease Prevention in Vietnam

PubMed Central

Nguyen, Thi-Phuong-Lan; Wright, E. Pamela; Nguyen, Thanh-Trung; Schuiling-Veninga, C. C. M.; Bijlsma, M. J.; Nguyen, Thi-Bach-Yen; Postma, M. J.

2016-01-01

Objective To inform development of guidelines for hypertension management in Vietnam, we evaluated the cost-effectiveness of different strategies on screening for hypertension in preventing cardiovascular disease (CVD). Methods A decision tree was combined with a Markov model to measure incremental cost-effectiveness of different approaches to hypertension screening. Values used as input parameters for the model were taken from different sources. Various screening intervals (one-off, annually, biannually) and starting ages to screen (35, 45 or 55 years) and coverage of treatment were analysed. We ran both a ten-year and a lifetime horizon. Input parameters for the models were extracted from local and regional data. Probabilistic sensitivity analysis was used to evaluate parameter uncertainty. A threshold of three times GDP per capita was applied. Results Cost per quality adjusted life year (QALY) gained varied in different screening scenarios. In a ten-year horizon, the cost-effectiveness of screening for hypertension ranged from cost saving to Int$ 758,695 per QALY gained. For screening of men starting at 55 years, all screening scenarios gave a high probability of being cost-effective. For screening of females starting at 55 years, the probability of favourable cost-effectiveness was 90% with one-off screening. In a lifetime horizon, cost per QALY gained was lower than the threshold of Int$ 15,883 in all screening scenarios among males. Similar results were found in females when starting screening at 55 years. Starting screening in females at 45 years had a high probability of being cost-effective if screening biannually was combined with increasing coverage of treatment by 20% or even if sole biannual screening was considered. Conclusion From a health economic perspective, integrating screening for hypertension into routine medical examination and related coverage by health insurance could be recommended. Screening for hypertension has a high probability of being cost-effective in preventing CVD. An adequate screening strategy can best be selected based on age, sex and screening interval. PMID:27192051

Absolute charge calibration of scintillating screens for relativistic electron detection

NASA Astrophysics Data System (ADS)

Buck, A.; Zeil, K.; Popp, A.; Schmid, K.; Jochmann, A.; Kraft, S. D.; Hidding, B.; Kudyakov, T.; Sears, C. M. S.; Veisz, L.; Karsch, S.; Pawelke, J.; Sauerbrey, R.; Cowan, T.; Krausz, F.; Schramm, U.

2010-03-01

We report on new charge calibrations and linearity tests with high-dynamic range for eight different scintillating screens typically used for the detection of relativistic electrons from laser-plasma based acceleration schemes. The absolute charge calibration was done with picosecond electron bunches at the ELBE linear accelerator in Dresden. The lower detection limit in our setup for the most sensitive scintillating screen (KODAK Biomax MS) was 10 fC/mm2. The screens showed a linear photon-to-charge dependency over several orders of magnitude. An onset of saturation effects starting around 10-100 pC/mm2 was found for some of the screens. Additionally, a constant light source was employed as a luminosity reference to simplify the transfer of a one-time absolute calibration to different experimental setups.

MRI breast screening in high-risk women: cancer detection and survival analysis.

PubMed

Evans, D Gareth; Gareth, Evans D; Kesavan, Nisha; Nisha, Kesavan; Lim, Yit; Yit, Lim; Gadde, Soujanye; Soujanye, Gadde; Hurley, Emma; Emma, Hurley; Massat, Nathalie J; Maxwell, Anthony J; Ingham, Sarah; Sarah, Ingham; Eeles, Rosalind; Rosalind, Eeles; Leach, Martin O; Howell, Anthony; Anthony, Howell; Duffy, Stephen W; Stephen, Duffy

2014-06-01

Women with a genetic predisposition to breast cancer tend to develop the disease at a younger age with denser breasts making mammography screening less effective. The introduction of magnetic resonance imaging (MRI) for familial breast cancer screening programs in recent years was intended to improve outcomes in these women. We aimed to assess whether introduction of MRI surveillance improves 5- and 10-year survival of high-risk women and determine the accuracy of MRI breast cancer detection compared with mammography-only or no enhanced surveillance and compare size and pathology of cancers detected in women screened with MRI + mammography and mammography only. We used data from two prospective studies where asymptomatic women with a very high breast cancer risk were screened by either mammography alone or with MRI also compared with BRCA1/2 carriers with no intensive surveillance. 63 cancers were detected in women receiving MRI + mammography and 76 in women receiving mammography only. Sensitivity of MRI + mammography was 93 % with 63 % specificity. Fewer cancers detected on MRI were lymph node positive compared to mammography/no additional screening. There were no differences in 10-year survival between the MRI + mammography and mammography-only groups, but survival was significantly higher in the MRI-screened group (95.3 %) compared to no intensive screening (73.7 %; p = 0.002). There were no deaths among the 21 BRCA2 carriers receiving MRI. There appears to be benefit from screening with MRI, particularly in BRCA2 carriers. Extended follow-up of larger numbers of high-risk women is required to assess long-term survival.

Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and molecular methods.

PubMed

Gregg, R G; Simantel, A; Farrell, P M; Koscik, R; Kosorok, M R; Laxova, A; Laessig, R; Hoffman, G; Hassemer, D; Mischler, E H; Splaingard, M

1997-06-01

To evaluate neonatal screening for cystic fibrosis (CF), including study of the screening procedures and characteristics of false-positive infants, over the past 10 years in Wisconsin. An important objective evolving from the original design has been to compare use of a single-tier immunoreactive trypsinogen (IRT) screening method with that of a two-tier method using IRT and analyses of samples for the most common cystic fibrosis transmembrane regulator (CFTR) (DeltaF508) mutation. We also examined the benefit of including up to 10 additional CFTR mutations in the screening protocol. From 1985 to 1994, using either the IRT or IRT/DNA protocol, 220 862 and 104 308 neonates, respectively, were screened for CF. For the IRT protocol, neonates with an IRT >/=180 ng/mL were considered positive, and the standard sweat chloride test was administered to determine CF status. For the IRT/DNA protocol, samples from the original dried-blood specimen on the Guthrie card of neonates with an IRT >/=110 ng/mL were tested for the presence of the DeltaF508 CFTR allele, and if the DNA test revealed one or two DeltaF508 alleles, a sweat test was obtained. Both screening procedures had very high specificity. The sensitivity tended to be higher with the IRT/DNA protocol, but the differences were not statistically significant. The positive predictive value of the IRT/DNA screening protocol was 15.2% compared with 6.4% if the same samples had been screened by the IRT method. Assessment of the false-positive IRT/DNA population revealed that the two-tier method eliminates the disproportionate number of infants with low Apgar scores and also the high prevalence of African-Americans identified previously in our study of newborns with high IRT levels. We found that 55% of DNA-positive CF infants were homozygous for DeltaF508 and 40% had one DeltaF508 allele. Adding analyses for 10 more CFTR mutations has only a small effect on the sensitivity but is likely to add significantly to the cost of screening. Advantages of the IRT/DNA protocol over IRT analysis include improved positive predictive value, reduction of false-positive infants, and more rapid diagnosis with elimination of recall specimens.

Adenocarcinoma in situ of the cervix.

PubMed

Schoolland, Meike; Segal, Amanda; Allpress, Stephen; Miranda, Alina; Frost, Felicity A; Sterrett, Gregory F

2002-12-25

The current study examines 1) the sensitivity of detection and 2) sampling and screening/diagnostic error in the cytologic diagnosis of adenocarcinoma in situ (AIS) of the cervix. The data were taken from public and private sector screening laboratories reporting 25,000 and 80,000 smears, respectively, each year. The study group was comprised of women with a biopsy diagnosis of AIS or AIS combined with a high-grade squamous intraepithelial lesion (HSIL) who were accessioned by the Western Australian Cervical Cytology Registry (WACCR) between 1993-1998. Cervical smears reported by the Western Australia Centre for Pathology and Medical Research (PathCentre) or Western Diagnostic Pathology (WDP) in the 36 months before the index biopsy was obtained were retrieved. A true measure of the sensitivity of detection could not be determined because to the authors' knowledge the exact prevalence of disease is unknown at present. For the current study, sensitivity was defined as the percentage of smears reported as demonstrating a possible or definite high-grade epithelial abnormality (HGEA), either glandular or squamous. Sampling error was defined as the percentage of smears found to have no HGEA on review. Screening/diagnostic error was defined as the percentage of smears in which HGEA was not diagnosed initially but review demonstrated possible or definite HGEA. Sensitivity also was calculated for a randomly selected control group of biopsy proven cases of Grade 3 cervical intraepithelial neoplasia (CIN 3) accessioned at the WACCR in 1999. For biopsy findings of AIS alone, the diagnostic "sensitivity" of a single smear was 47.6% for the PathCentre and 54.3% for WDP. Nearly all the abnormalities were reported as glandular. The sampling and screening/diagnostic errors were 47.6% and 4.8%, respectively, for the PathCentre and 33.3% and 12.3%, respectively, for WDP. The results from the PathCentre were better for AIS plus HSIL than for AIS alone, but the results from WDP were similar for both groups. For the CIN 3 control cases, the "sensitivity" of a single smear was 42.5%. To the authors' knowledge epidemiologic studies published to date have not demonstrated a benefit from screening for precursors of cervical adenocarcinoma. However, in the study laboratories as in many others, reasonable expertise in diagnosing AIS has been acquired only within the last 10-15 years, which may be too short a period in which to demonstrate a significant effect. The results of the current study provide some encouraging baseline data regarding the sensitivity of the Papanicolaou smear in detecting AIS. Further improvements in sampling and cytodiagnosis may be possible. Copyright 2002 American Cancer Society.

Neuronal models for evaluation of proliferation in vitro using high content screening.

PubMed

Mundy, William R; Radio, Nicholas M; Freudenrich, Theresa M

2010-04-11

In vitro test methods can provide a rapid approach for the screening of large numbers of chemicals for their potential to produce toxicity (hazard identification). In order to identify potential developmental neurotoxicants, a battery of in vitro tests for neurodevelopmental processes such as cell proliferation, differentiation, growth, and synaptogenesis has been proposed. The development of in vitro approaches for toxicity testing will require choosing a model system that is appropriate to the endpoint of concern. This study compared several cell lines as models for neuronal proliferation. The sensitivities of neuronal cell lines derived from three species (PC12, rat; N1E-115, mouse; SH-SY5Y, human) to chemicals known to affect cell proliferation were assessed using a high content screening system. After optimizing conditions for cell growth in 96-well plates, proliferation was measured as the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into replicating DNA during S phase. BrdU-labeled cells were detected by immunocytochemistry and cell counts were obtained using automated image acquisition and analysis. The three cell lines showed approximately 30-40% of the population in S phase after a 4h pulse of BrdU. Exposure to the DNA polymerase inhibitor aphidicolin for 20 h prior to the 4h pulse of BrdU significantly decreased proliferation in all three cell lines. The sensitivities of the cell lines were compared by exposure to eight chemicals known to affect proliferation (positive controls) and determination of the concentration inhibiting proliferation by 50% of control (I(50)). PC12 cells were the most sensitive to chemicals; 6 out of 8 chemicals (aphidicolin, cadmium, cytosine arabinoside, dexamethasone, 5-fluorouracil, and methylmercury) inhibited proliferation at the concentrations tested. SH-SY5Y cells were somewhat less sensitive to chemical effects, with five out of eight chemicals inhibiting proliferation; dexamethasone had no effect, and cadmium inhibited proliferation only at concentrations that decreased cell viability. Data from the N1E-115 cell line was extremely variable between experiments, and only 4 out of 8 chemicals resulted in inhibition of proliferation. Chemicals that had not been previously shown to alter proliferation (negative controls) did not affect proliferation or cell viability in any cell line. The results show that high content screening can be used to rapidly assess chemical effects on proliferation. Three neuronal cell lines exhibited differential sensitivity to the effect of chemicals on this endpoint, with PC12 cells being the most sensitive to inhibition of proliferation. Published by Elsevier Ireland Ltd.

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis

PubMed Central

An, Jingna; Chen, Qixia; Liu, Qianqian; Rao, Chenli; Li, Dongdong; Wang, Tingting

2015-01-01

The resurgence of syphilis in recent years has become a serious threat to public health worldwide, and the serological detection of specific antibodies against Treponema pallidum remains the most reliable method for laboratory diagnosis of syphilis. This study examined the performance of the recently launched HISCL anti-Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high-volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis-positive samples, 704 fresh syphilis-negative samples, 48 preselected potentially interfering samples, and 30 “borderline” samples and was compared head to head with the commercially available Lumipulse G TP-N. In this study, the HISCL anti-TP assay was in perfect agreement with the applied testing algorithms with an overall agreement of 100%, comparable to that of Lumipulse G TP-N (99.63%). The sensitivity and specificity of the HISCL anti-TP assay were 100% (95% confidence interval [CI], 98.42% to 100%) and 100% (95% CI, 99.37% to 100%), respectively. Considering the excellent ease of use and automation, high throughput, and its favorable sensitivity and specificity, the HISCL anti-TP assay may represent a new choice for syphilis screening in high-volume laboratories. PMID:25972403

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis.

PubMed

An, Jingna; Chen, Qixia; Liu, Qianqian; Rao, Chenli; Li, Dongdong; Wang, Tingting; Tao, Chuanmin; Wang, Lanlan

2015-07-01

The resurgence of syphilis in recent years has become a serious threat to public health worldwide, and the serological detection of specific antibodies against Treponema pallidum remains the most reliable method for laboratory diagnosis of syphilis. This study examined the performance of the recently launched HISCL anti-Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high-volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis-positive samples, 704 fresh syphilis-negative samples, 48 preselected potentially interfering samples, and 30 "borderline" samples and was compared head to head with the commercially available Lumipulse G TP-N. In this study, the HISCL anti-TP assay was in perfect agreement with the applied testing algorithms with an overall agreement of 100%, comparable to that of Lumipulse G TP-N (99.63%). The sensitivity and specificity of the HISCL anti-TP assay were 100% (95% confidence interval [CI], 98.42% to 100%) and 100% (95% CI, 99.37% to 100%), respectively. Considering the excellent ease of use and automation, high throughput, and its favorable sensitivity and specificity, the HISCL anti-TP assay may represent a new choice for syphilis screening in high-volume laboratories. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A novel strategy for screening-out raw milk contaminated with Mycobacterium bovis on dairy farms by double-tagging PCR and electrochemical genosensing.

PubMed

Lermo, Anabel; Liébana, Susana; Campoy, Susana; Fabiano, Silvia; García, M Inés; Soutullo, Adriana; Zumárraga, Martín J; Alegret, Salvador; Pividori, M Isabel

2010-06-01

A highly sensitive assay for rapidly screening-out Mycobacterium bovis in contaminated samples was developed based on electrochemical genosensing. The assay consists of specific amplification and double-tagging of the IS6110 fragment, highly related to M. bovis, followed by electrochemical detection of the amplified product. PCR amplification was carried out using a labeled set of primers and resulted in a amplicon tagged at each terminus with both biotin and digoxigenin. Two different electrochemical platforms for the detection of the double-tagged amplicon were evaluated: (i) an avidin biocomposite (Av-GEB) and (ii) a magneto sensor (m-GEC) combined with streptavidin magnetic beads. In both cases, the double- tagged amplicon was immobilized through its biotinylated end and electrochemically detected, using an antiDig-HRP conjugate, through its digoxigenin end. The assay was determined to be highly sensitive, based on the detection of 620 and 10 fmol of PCR amplicon using the Av-GEB and m-GEC strategies, respectively. Moreover, the m-GEC assay showed promising features for the detection of M. bovis on dairy farms by screening for the presence of the bacterium's DNA in milk samples. The obtained results are discussed and compared with respect to those of inter-laboratory PCR assays and tuberculin skin testing.

TriGlycerides and high-density lipoprotein cholesterol ratio compared with homeostasis model assessment insulin resistance indexes in screening for metabolic syndrome in the chinese obese children: a cross section study.

PubMed

Liang, Jianfeng; Fu, Junfen; Jiang, Youyun; Dong, Guanping; Wang, Xiumin; Wu, Wei

2015-09-28

Metabolic Syndrome (MS) is prevalant in China, especially according to the pediatric obesity group. Based on the MS-CHN2012 definition for Chinese children and adolescents the need to explore and establish a convienent MS screening become imminent. This study aims to investigate the optimal cut-off values, compare the accuracy for the (TriGlycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C)) (TG/HDL-C) ratio and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) indexs to identify Metabolic Syndrome in obese pediatric population in China. A total sample of 976 children (female 286 male 690, BMI > = 95 percentile) aged from 6-16 years underwent a medical assessment including a physical examination and investigations of total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, insulin, glucose, and oral glucose tolerance test to identify the components of Metabolic Syndrome. The validity and accuracy between TG/HDL-C ratio and HOMA-IR were compared by Receiver Operating Characteristics analysis (ROC). TG/HDL-C ratio achieved a larger ROC Area under Curve (AUC = 0.843) than HOMA-IR indexes (0.640, 0.625 for HOMA1-IR, HOMA2-IR respectively) to screen for Metabolic Syndrome. The cut-off values for MS were: TG/HDL-C ratio > 1.25 (sensitivity: 80%; specificity: 75%), HOMA1-IR > 4.59 (sensitivity: 58.7%; specificity: 65.5%) and HOMA2-IR > 2.76 (sensitivity: 53.2%; specificity: 69.5%). The results kept robust after stratified by gender, age group and pubertal stage. TG/HDL-C ratio was a better indicator than the HOMA-IR to screen for a positive diagnosis for MS. Furthermore, the TG/HDL-C ratio was superior to the HOMA-IR indexes even after the control of possible confusions from the gender, age group and puberty stage. TG/HDL-C ratio proved a better index than HOMA-IR in screening for MS in obese children and adolescents. TG/HDL-C ratio has a discriminatory power in detecting potential MS in the Chinese obese pediatric population.

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.

Cost-effectiveness of Population Screening for BRCA Mutations in Ashkenazi Jewish Women Compared With Family History–Based Testing

PubMed Central

Manchanda, Ranjit; Legood, Rosa; Burnell, Matthew; McGuire, Alistair; Raikou, Maria; Loggenberg, Kelly; Wardle, Jane; Sanderson, Saskia; Gessler, Sue; Side, Lucy; Balogun, Nyala; Desai, Rakshit; Kumar, Ajith; Dorkins, Huw; Wallis, Yvonne; Chapman, Cyril; Taylor, Rohan; Jacobs, Chris; Tomlinson, Ian; Beller, Uziel; Menon, Usha

2015-01-01

Background: Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)–based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women. Methods: A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty. Results: Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days’ gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy. Conclusion: Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older. PMID:25435542

Validation of two screening instruments for PTSD in Dutch substance use disorder inpatients.

PubMed

Kok, Tim; de Haan, Hein A; van der Velden, Helena J W; van der Meer, Margreet; Najavits, Lisa M; de Jong, Cor A J

2013-03-01

Posttraumatic stress disorder (PTSD) is highly prevalent in substance use disorder (SUD) populations. Because resources for extensive and thorough diagnostic assessment are often limited, reliable screening instruments for PTSD are needed. The aim of the current study was to test two short PTSD measures for diagnostic efficiency in predicting PTSD compared to the Clinician-Administered PTSD Scale (CAPS). The sample consisted of 197 SUD patients receiving residential substance use treatment who completed questionnaires regarding substance use and trauma-related symptoms, all abstinent from substance for 4weeks. The PTSD section of the Mini International Neuropsychiatric Interview plus (MINIplus) and the Self-Report Inventory for PTSD (SRIP) are compared to the CAPS. Results showed low sensitivity (.58) and high specificity (.91) for the PTSD section of the MINIplus. The SRIP showed high sensitivity (.80) and moderately high specificity (.73) at a cut-off score of 48. The prevalence of PTSD as measured with the CAPS was 25.4% current and 46.2% lifetime. Results indicate that the MINIplus, a short clinical interview, has insufficient quality as a screener for PTSD. The SRIP, however, is a reliable instrument in detecting PTSD in a SUD inpatient population in The Netherlands. Screening for PTSD is time efficient and increases detection of PTSD in SUD treatment settings. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Mutation screening of the CDKL5 gene in cryptogenic infantile intractable epilepsy and review of clinical sensitivity.

PubMed

Intusoma, Utcharee; Hayeeduereh, Fadell; Plong-On, Oradawan; Sripo, Thanya; Vasiknanonte, Punnee; Janjindamai, Supachai; Lusawat, Apasri; Thammongkol, Sasipa; Visudtibhan, Anannit; Limprasert, Pornprot

2011-09-01

To perform CDKL5 mutation screening in Thai children with cryptogenic infantile intractable epilepsy and to determine the clinical sensitivity of CDKL5 screening when different inclusion criteria were applied. Children with cryptogenic infantile intractable epilepsy were screened for CDKL5 mutation using multiplex ligation-dependent probe amplification and DNA sequencing. The clinical sensitivity was reviewed by combining the results of studies using similar inclusion screening criteria. Thirty children (19 girls and 11 boys) with a median seizure onset of 7 months were screened. Almost a half had infantile spasms and one fifth had stereotypic hand movements. A novel c.2854C>T (p.R952X) was identified in an ambulatory girl who had severe mental retardation, multiple types of seizures without Rett-like features. Her mother had a mild intellectual disability, yet her grandmother and half sister were normal despite having the same genetic alteration (random X-inactivation patterns). The pathogenicity of p.R952X identified here was uncertain since healthy relatives and 6 female controls also harbor this alteration. The clinical sensitivity of CDKL5 mutation screening among females with Rett-like features and negative MECP2 screening was 7.8% while the clinical sensitivity among females having cryptogenic intractable seizures with an onset before the ages of 12, 6 and 3 months were 4.7, 11.6 and 14.3%, respectively. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The efficacy of using computer-aided detection (CAD) for detection of breast cancer in mammography screening: a systematic review.

PubMed

Henriksen, Emilie L; Carlsen, Jonathan F; Vejborg, Ilse Mm; Nielsen, Michael B; Lauridsen, Carsten A

2018-01-01

Background Early detection of breast cancer (BC) is crucial in lowering the mortality. Purpose To present an overview of studies concerning computer-aided detection (CAD) in screening mammography for early detection of BC and compare diagnostic accuracy and recall rates (RR) of single reading (SR) with SR + CAD and double reading (DR) with SR + CAD. Material and Methods PRISMA guidelines were used as a review protocol. Articles on clinical trials concerning CAD for detection of BC in a screening population were included. The literature search resulted in 1522 records. A total of 1491 records were excluded by abstract and 18 were excluded by full text reading. A total of 13 articles were included. Results All but two studies from the SR vs. SR + CAD group showed an increased sensitivity and/or cancer detection rate (CDR) when adding CAD. The DR vs. SR + CAD group showed no significant differences in sensitivity and CDR. Adding CAD to SR increased the RR and decreased the specificity in all but one study. For the DR vs. SR + CAD group only one study reported a significant difference in RR. Conclusion All but two studies showed an increase in RR, sensitivity and CDR when adding CAD to SR. Compared to DR no statistically significant differences in sensitivity or CDR were reported. Additional studies based on organized population-based screening programs, with longer follow-up time, high-volume readers, and digital mammography are needed to evaluate the efficacy of CAD.

Validity of the Patient Health Questionnaire-9 to screen for depression in a high-HIV burden primary healthcare clinic in Johannesburg, South Africa.

PubMed

Cholera, R; Gaynes, B N; Pence, B W; Bassett, J; Qangule, N; Macphail, C; Bernhardt, S; Pettifor, A; Miller, W C

2014-01-01

Integration of depression screening into primary care may increase access to mental health services in sub-Saharan Africa, but this approach requires validated screening instruments. We sought to validate the Patient Health Questionnaire-9 (PHQ-9) as a depression screening tool at a high HIV-burden primary care clinic in Johannesburg, South Africa. We conducted a validation study of an interviewer-administered PHQ-9 among 397 patients. Sensitivity and specificity of the PHQ-9 were calculated with the Mini International Neuropsychiatric Interview (MINI) as the reference standard; receiver operating characteristic (ROC) curve analyses were performed. The prevalence of depression was 11.8%. One-third of participants tested positive for HIV. HIV-infected patients were more likely to be depressed (15%) than uninfected patients (9%; p=0.08). Using the standard cutoff score of ≥10, the PHQ-9 had a sensitivity of 78.7% (95% CI: 64.3-89.3) and specificity of 83.4% (95% CI: 79.1-87.2). The area under the ROC curve was 0.88 (95% CI: 0.83-0.92). Test performance did not vary by HIV status or language. In sensitivity analyses, reference test bias associated with the MINI appeared unlikely. We were unable to conduct qualitative work to adapt the PHQ-9 to this cultural context. This is the first validation study of the PHQ-9 in a primary care clinic in sub-Saharan Africa. It highlights the potential for using primary care as an access point for identifying depressive symptoms during routine HIV testing. The PHQ-9 showed reasonable accuracy in classifying cases of depression, was easily implemented by lay health workers, and is a useful screening tool in this setting. Copyright © 2014 Elsevier B.V. All rights reserved.

An electrochemical immunoassay for the screening of celiac disease in saliva samples.

PubMed

Adornetto, Gianluca; Fabiani, Laura; Volpe, Giulia; De Stefano, Alessia; Martini, Sonia; Nenna, Raffaella; Lucantoni, Federica; Bonamico, Margherita; Tiberti, Claudio; Moscone, Danila

2015-09-01

A highly sensitive electrochemical immunoassay for the initial diagnosis of celiac disease (CD) in saliva samples that overcomes the problems related to its high viscosity and to the low concentration of anti-transglutaminase antigen (tTG) IgA in this medium has been developed for the first time. The system uses magnetic beads (MBs) covered with tTG, which reacts with the anti-tTG IgA antibodies present in positive saliva samples. An anti-human IgA, conjugated with alkaline phosphate (AP) enzyme, was used as the label and a strip of eight magnetized screen-printed electrodes as the electrochemical transducer. In particular, two different immunoassay approaches were optimized and blindly compared to analyze a large number of saliva samples, whose anti-tTG IgA levels were independently determined by the radioimmunoassay (RIA) method. The obtained results, expressed as Ab index, were used to perform a diagnostic test evaluation through the construction of receiver operating characteristic (ROC) curves. The approach, involving a pre-incubation between the anti-human IgA-AP and saliva samples prior to the addition of MBs-tTG, showed a cutoff of 0.022 with 95% clinical sensitivity and 96% clinical specificity. The area under the ROC curve is equal to 1, a result that classifies our test as "perfect." This study demonstrates that it is possible to perform the screening of CD with a rapid, simple, inexpensive, and sensitive method able to detect anti-tTG antibodies in saliva samples, which are easily obtained by non-invasive techniques. This aspect is of fundamental importance to screen a large number of subjects, especially in the pediatric age.

Tuberculosis Screening by Tuberculosis Skin Test or QuantiFERON®-TB Gold In-Tube Assay among an Immigrant Population with a High Prevalence of Tuberculosis and BCG Vaccination

PubMed Central

Painter, John A.; Graviss, Edward A.; Hai, Hoang Hoa; Nhung, Duong Thi Cam; Nga, Tran Thi Thanh; Ha, Ngan P.; Wall, Kirsten; Loan, Le Thien Huong; Parker, Matt; Manangan, Lilia; O’Brien, Rick; Maloney, Susan A.; Hoekstra, R. M.; Reves, Randall

2013-01-01

Rationale Each year 1 million persons acquire permanent U.S. residency visas after tuberculosis (TB) screening. Most applicants undergo a 2-stage screening with tuberculin skin test (TST) followed by CXR only if TST-positive at > 5 mm. Due to cross reaction with bacillus Calmette-Guérin (BCG), TST may yield false positive results in BCG-vaccinated persons. Interferon gamma release assays exclude antigens found in BCG. In Vietnam, like most high TB-prevalence countries, there is universal BCG vaccination at birth. Objectives 1. Compare the sensitivity of QuantiFERON ®-TB Gold In-Tube Assay (QFT) and TST for culture-positive pulmonary TB. 2. Compare the age-specific and overall prevalence of positive TST and QFT among applicants with normal and abnormal CXR. Methods We obtained TST and QFT results on 996 applicants with abnormal CXR, of whom 132 had TB, and 479 with normal CXR. Results The sensitivity for tuberculosis was 86.4% for QFT; 89.4%, 81.1%, and 52.3% for TST at 5, 10, and 15 mm. The estimated prevalence of positive results at age 15–19 years was 22% and 42% for QFT and TST at 10 mm, respectively. The prevalence increased thereafter by 0.7% year of age for TST and 2.1% for QFT, the latter being more consistent with the increase in TB among applicants. Conclusions During 2-stage screening, QFT is as sensitive as TST in detecting TB with fewer requiring CXR and being diagnosed with LTBI. These data support the use of QFT over TST in this population.  PMID:24367546

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.

A Novel Plasmid-Based Microarray Screen Identifies Suppressors of rrp6Δ in Saccharomyces cerevisiae▿†

PubMed Central

Abruzzi, Katharine; Denome, Sylvia; Olsen, Jens Raabjerg; Assenholt, Jannie; Haaning, Line Lindegaard; Jensen, Torben Heick; Rosbash, Michael

2007-01-01

Genetic screens in Saccharomyces cerevisiae provide novel information about interacting genes and pathways. We screened for high-copy-number suppressors of a strain with the gene encoding the nuclear exosome component Rrp6p deleted, with either a traditional plate screen for suppressors of rrp6Δ temperature sensitivity or a novel microarray enhancer/suppressor screening (MES) strategy. MES combines DNA microarray technology with high-copy-number plasmid expression in liquid media. The plate screen and MES identified overlapping, but also different, suppressor genes. Only MES identified the novel mRNP protein Nab6p and the tRNA transporter Los1p, which could not have been identified in a traditional plate screen; both genes are toxic when overexpressed in rrp6Δ strains at 37°C. Nab6p binds poly(A)+ RNA, and the functions of Nab6p and Los1p suggest that mRNA metabolism and/or protein synthesis are growth rate limiting in rrp6Δ strains. Microarray analyses of gene expression in rrp6Δ strains and a number of suppressor strains support this hypothesis. PMID:17101774

An UPLC-ESI-MS/MS Assay Using 6-Aminoquinolyl-N-Hydroxysuccinimidyl Carbamate Derivatization for Targeted Amino Acid Analysis: Application to Screening of Arabidopsis thaliana Mutants.

PubMed

Salazar, Carolina; Armenta, Jenny M; Shulaev, Vladimir

2012-07-06

In spite of the large arsenal of methodologies developed for amino acid assessment in complex matrices, their implementation in metabolomics studies involving wide-ranging mutant screening is hampered by their lack of high-throughput, sensitivity, reproducibility, and/or wide dynamic range. In response to the challenge of developing amino acid analysis methods that satisfy the criteria required for metabolomic studies, improved reverse-phase high-performance liquid chromatography-mass spectrometry (RPHPLC-MS) methods have been recently reported for large-scale screening of metabolic phenotypes. However, these methods focus on the direct analysis of underivatized amino acids and, therefore, problems associated with insufficient retention and resolution are observed due to the hydrophilic nature of amino acids. It is well known that derivatization methods render amino acids more amenable for reverse phase chromatographic analysis by introducing highly-hydrophobic tags in their carboxylic acid or amino functional group. Therefore, an analytical platform that combines the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) pre-column derivatization method with ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) is presented in this article. For numerous reasons typical amino acid derivatization methods would be inadequate for large scale metabolic projects. However, AQC derivatization is a simple, rapid and reproducible way of obtaining stable amino acid adducts amenable for UPLC-ESI-MS/MS and the applicability of the method for high-throughput metabolomic analysis in Arabidopsis thaliana is demonstrated in this study. Overall, the major advantages offered by this amino acid analysis method include high-throughput, enhanced sensitivity and selectivity; characteristics that showcase its utility for the rapid screening of the preselected plant metabolites without compromising the quality of the metabolic data. The presented method enabled thirty-eight metabolites (proteinogenic amino acids and related compounds) to be analyzed within 10 min with detection limits down to 1.02 × 10-11 M (i.e., atomole level on column), which represents an improved sensitivity of 1 to 5 orders of magnitude compared to existing methods. Our UPLC-ESI-MS/MS method is one of the seven analytical platforms used by the Arabidopsis Metabolomics Consortium. The amino acid dataset obtained by analysis of Arabidopsis T-DNA mutant stocks with our platform is captured and open to the public in the web portal PlantMetabolomics.org. The analytical platform herein described could find important applications in other studies where the rapid, high-throughput and sensitive assessment of low abundance amino acids in complex biosamples is necessary.

An UPLC-ESI-MS/MS Assay Using 6-Aminoquinolyl-N-Hydroxysuccinimidyl Carbamate Derivatization for Targeted Amino Acid Analysis: Application to Screening of Arabidopsis thaliana Mutants

PubMed Central

Salazar, Carolina; Armenta, Jenny M.; Shulaev, Vladimir

2012-01-01

In spite of the large arsenal of methodologies developed for amino acid assessment in complex matrices, their implementation in metabolomics studies involving wide-ranging mutant screening is hampered by their lack of high-throughput, sensitivity, reproducibility, and/or wide dynamic range. In response to the challenge of developing amino acid analysis methods that satisfy the criteria required for metabolomic studies, improved reverse-phase high-performance liquid chromatography-mass spectrometry (RPHPLC-MS) methods have been recently reported for large-scale screening of metabolic phenotypes. However, these methods focus on the direct analysis of underivatized amino acids and, therefore, problems associated with insufficient retention and resolution are observed due to the hydrophilic nature of amino acids. It is well known that derivatization methods render amino acids more amenable for reverse phase chromatographic analysis by introducing highly-hydrophobic tags in their carboxylic acid or amino functional group. Therefore, an analytical platform that combines the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) pre-column derivatization method with ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) is presented in this article. For numerous reasons typical amino acid derivatization methods would be inadequate for large scale metabolic projects. However, AQC derivatization is a simple, rapid and reproducible way of obtaining stable amino acid adducts amenable for UPLC-ESI-MS/MS and the applicability of the method for high-throughput metabolomic analysis in Arabidopsis thaliana is demonstrated in this study. Overall, the major advantages offered by this amino acid analysis method include high-throughput, enhanced sensitivity and selectivity; characteristics that showcase its utility for the rapid screening of the preselected plant metabolites without compromising the quality of the metabolic data. The presented method enabled thirty-eight metabolites (proteinogenic amino acids and related compounds) to be analyzed within 10 min with detection limits down to 1.02 × 10−11 M (i.e., atomole level on column), which represents an improved sensitivity of 1 to 5 orders of magnitude compared to existing methods. Our UPLC-ESI-MS/MS method is one of the seven analytical platforms used by the Arabidopsis Metabolomics Consortium. The amino acid dataset obtained by analysis of Arabidopsis T-DNA mutant stocks with our platform is captured and open to the public in the web portal PlantMetabolomics.org. The analytical platform herein described could find important applications in other studies where the rapid, high-throughput and sensitive assessment of low abundance amino acids in complex biosamples is necessary. PMID:24957640

The family context of low-income parents who restrict child screen time.

PubMed

Lampard, Amy M; Jurkowski, Janine M; Davison, Kirsten K

2013-10-01

The American Academy of Pediatrics recommends that parents restrict child screen time to two hours per day, but many preschool-aged children exceed this viewing recommendation. Modifying children's viewing habits will require collaborating with parents, but little is known about the factors that influence parents' capacity for effective screen-related parenting. This study aimed to identify the demographic, family and community contextual factors associated with low-income parents' restriction of child screen time. Parents (N=146) of children (age 2-5 years) attending Head Start centers in the United States completed a self-report survey in 2010 assessing parent and child screen use (television, DVD, video, video games, and leisure-time computer use), parent restriction of child screen time, and family (parent stress, social support, and life pressures) and community (neighborhood safety and social capital) factors. Children were more likely to meet the American Academy of Pediatrics screen time recommendation if their parent reported high restriction of child screen time. Parent and child demographic characteristics were not associated with parents' restriction of child screen time. In multivariate analysis, less parent screen time, fewer parent life pressures, and greater social support were associated with parents' high restriction of screen time. Family contextual factors may play an important role in enabling low-income parents to restrict their children's screen time. When counseling low-income parents about the importance of restricting child screen time, practitioners should be sensitive to family contextual factors that may influence parents' capacity to implement this behavior change.

The cost of implementation of the Clinical Laboratory Improvement Amendments of 1988--the example of pediatric office-based cholesterol screening.

PubMed

Tershakovec, A M; Brannon, S D; Bennett, M J; Shannon, B M

1995-08-01

To measure the additional costs of office-based laboratory testing due to the implementation of the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88), using cholesterol screening for children as an example. Four- to ten-year-old children who received their well child care at one of seven participating pediatric practices were screened for hypercholesterolemia. The average number of analyses per day and days per month were derived from the volume of testing completed by the practices. Nurses and technicians time in the screening process were measured and personnel costs were calculated based on salary and fringe benefit rates. Costs of supplies, analyzing control samples, instrument calibration, and instrument depreciation were included. Costs estimates of screening were then completed. CLIA '88 implementation costs were derived from appropriate proficiency testing and laboratory inspection programs. In six practices completing a low volume of testing, 2807 children (5 to 6 children per week) were screened during the observation period, while 414 (about 25 children per week) were screened in one high-volume practice implementing universal screening over a 4-month period. For the six low-volume practices, the cost of screening was $10.60 per child. This decreased to $5.47 for the high-volume practice. Estimated costs of CLIA '88 implementation, including additional proficiency testing and laboratory inspection, added $3.20 per test for the low-volume practices, and $0.71 per test for the high-volume testing. Implementation of CLIA adds significantly to the cost of office-based chemistry laboratory screening. Despite these additional expenses, the cost of testing is still within a reasonable charge for laboratory testing, and is highly sensitive to the volume of tests completed.

Quantum-Dot-Based Electrochemical Immunoassay for High-Throughput Screening of the Prostate-Specific Antigen

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

Wang, Jun; Liu, Guodong; Wu, Hong

2008-01-01

In this paper, we demonstrate an electrochemical high-throughput sensing platform for simple, sensitive detection of PSA based on QD labels. This sensing platform uses a microplate for immunoreactions and disposable screen-printed electrodes (SPE) for electrochemical stripping analysis of metal ions released from QD labels. With the 96-well microplate, capturing antibodies are conveniently immobilized to the well surface, and the process of immunoreaction is easily controlled. The formed sandwich complexes on the well surface are also easily isolated from reaction solutions. In particular, a microplate-based electrochemical assay can make it feasible to conduct a parallel analysis of several samples or multiplemore » protein markers. This assay offers a number of advantages including (1) simplicity, cost-effectiveness, (2) high sensitivity, (3) capability to sense multiple samples or targets in parallel, and (4) a potentially portable device with an SPE array implanted in the microplate. This PSA assay is sensitive because it uses two amplification processes: (1) QDs as a label for enhancing electrical signal since secondary antibodies are linked to QDs that contain a large number of metal atoms and (2) there is inherent signal amplification for electrochemical stripping analysis—preconcentration of metal ion onto the electrode surface for amplifying electrical signals. Therefore, the high sensitivity of this method, stemming from dual signal amplification via QD labels and pre-concentration, allows low concentration levels to be detected while using small sample volumes. Thus, this QD-based electrochemical detection approach offers a simple, rapid, cost-effective, and high throughput assay of PSA.« less

Visual Impairment Screening Assessment (VISA) tool: pilot validation.

PubMed

Rowe, Fiona J; Hepworth, Lauren R; Hanna, Kerry L; Howard, Claire

2018-03-06

To report and evaluate a new Vision Impairment Screening Assessment (VISA) tool intended for use by the stroke team to improve identification of visual impairment in stroke survivors. Prospective case cohort comparative study. Stroke units at two secondary care hospitals and one tertiary centre. 116 stroke survivors were screened, 62 by naïve and 54 by non-naïve screeners. Both the VISA screening tool and the comprehensive specialist vision assessment measured case history, visual acuity, eye alignment, eye movements, visual field and visual inattention. Full completion of VISA tool and specialist vision assessment was achieved for 89 stroke survivors. Missing data for one or more sections typically related to patient's inability to complete the assessment. Sensitivity and specificity of the VISA screening tool were 90.24% and 85.29%, respectively; the positive and negative predictive values were 93.67% and 78.36%, respectively. Overall agreement was significant; k=0.736. Lowest agreement was found for screening of eye movement and visual inattention deficits. This early validation of the VISA screening tool shows promise in improving detection accuracy for clinicians involved in stroke care who are not specialists in vision problems and lack formal eye training, with potential to lead to more prompt referral with fewer false positives and negatives. Pilot validation indicates acceptability of the VISA tool for screening of visual impairment in stroke survivors. Sensitivity and specificity were high indicating the potential accuracy of the VISA tool for screening purposes. Results of this study have guided the revision of the VISA screening tool ahead of full clinical validation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clarifying the debate on population-based screening for breast cancer with mammography

PubMed Central

Chen, Tony Hsiu-Hsi; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Gordon, Paula; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Hsu, Chen-Yang; Chang, King-Jen; Lee, Won-Chul; Yeoh, Khay Guan; Saito, Hiroshi; Promthet, Supannee; Hamashima, Chisato; Maidin, Alimin; Robinson, Fredie; Zhao, Li-Zhong

2017-01-01

Abstract Background: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality. Methods: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes. Results: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24–42%) and 13% (95% CI: 6–20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively. Conclusion: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives. PMID:28099330

Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial.

PubMed

Ronco, Guglielmo; Giorgi-Rossi, Paolo; Carozzi, Francesca; Dalla Palma, Paolo; Del Mistro, Annarosa; De Marco, Laura; De Lillo, Margherita; Naldoni, Carlo; Pierotti, Paola; Rizzolo, Raffaella; Segnan, Nereo; Schincaglia, Patrizia; Zorzi, Manuel; Confortini, Massimo; Cuzick, Jack

2006-07-01

Testing for human papillomavirus (HPV) DNA is more sensitive but less specific than cytological analysis. Loss in specificity is most relevant in women younger than 35 years because of increased HPV prevalence. We aimed to compare conventional screening with an experimental strategy in women aged 25-34 years, and investigate the effect of different criteria of referral to define the best methods of HPV screening. Women were randomly assigned to the conventional procedure (standard cytology, with referral to colposcopy if cytology showed atypical squamous cells of undetermined significance or more [ASCUS+]) or an experimental procedure (liquid-based cytology and testing for high-risk HPV types, with referral to colposcopy with ASCUS+ cytology). Women positive for HPV (cutoff > or = 1 pg/mL) but with normal cytology were retested after 1 year. The main endpoint was the presence of cervical intraepithelial neoplasia at grade 2 or more (CIN2+) in reviewed histology. The main analysis was by intention to screen. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN81678807. We randomly assigned 5808 women aged 25-34 years to the conventional group and 6002 to the experimental group. The experimental procedure was significantly more sensitive than the conventional procedure (55 vs 33 CIN2+ lesions detected; relative sensitivity 1.61 [95% CI 1.05-2.48]), but had a lower positive predictive value (PPV; relative PPV 0.55 [0.37-0.82]). HPV testing (> or = 1 pg/mL) with cytology triage was also more sensitive than conventional cytology (relative sensitivity 1.58 [1.03-2.44], relative PPV 0.78 [0.52-1.16]). Relative PPV could be improved, with minimum loss in sensitivity, by use of a 2 pg/mL cutoff for HPV testing. Compared with conventional cytology, liquid-based cytology had a relative sensitivity of 1.32 (0.84-2.06), relative PPV 0.58 [0.38-0.89]). HPV testing alone with cytology triage could be a feasible alternative to conventional cytology for screening women younger than 35 years. Follow-up will provide data on possible overdiagnosis and on the feasibility of extended intervals.

How to develop a business case to establish a neonatal pulse oximetry programme for screening of congenital heart defects.

PubMed

Ewer, Andrew K

2012-12-01

Pulse oximetry screening for critical congenital heart defects (CCHDs) is a highly specific, moderately sensitive test which is cost effective, acceptable to both clinical staff and parents and meets the criteria for universal screening. Pulse oximetry screening is gaining considerable worldwide support and last year was added to the recommended uniform screening panel in the USA following endorsement by the Health and Human Services Secretary. There is significant heterogeneity in published screening protocols and it is important to consider all available evidence and also take local factors into account when developing a screening programme, whether it is within an individual hospital, neonatal network or even at a national level. This paper presents available options based both on the published evidence and personal practice experience which will aid those considering the introduction of screening to make the right decisions both from a clinical and financial perspective. Copyright © 2012 Elsevier Ltd. All rights reserved.

Periodic Screening Pelvic Examination: Evidence Report and Systematic Review for the US Preventive Services Task Force.

PubMed

Guirguis-Blake, Janelle M; Henderson, Jillian T; Perdue, Leslie A

2017-03-07

Recent changes in the periodicity of cervical cancer screening have led to questions about the role of screening pelvic examinations among asymptomatic women. To systematically review literature on health benefits, accuracy, and harms of the screening pelvic examination for gynecologic conditions for the US Preventive Services Task Force (USPSTF). MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials for relevant English-language studies published through January 13, 2016, with surveillance through August 3, 2016. Two reviewers independently screened abstracts and studies. The search yielded 8678 unique citations; 316 full-text articles were reviewed, and 9 studies including 27 630 patients met inclusion criteria. Two reviewers rated study quality using USPSTF criteria. Morbidity; mortality; diagnostic accuracy for any gynecologic cancer or condition except cervical cancer, gonorrhea, and chlamydia, which are covered by other USPSTF screening recommendations; harms (false-positive rates, false-negative rates, surgery rates). No trials examined the effectiveness of the pelvic examination in reducing all-cause mortality, reducing cancer- and disease-specific morbidity and mortality, or improving quality of life. Eight studies reported accuracy for the screening pelvic examination: ovarian cancer (4 studies; n = 26 432), bacterial vaginosis (2 studies; n = 930), trichomoniasis (1 study; n = 779), and genital herpes (1 study; n = 779). In the 4 ovarian cancer screening studies, low prevalence of ovarian cancer consistently resulted in low positive predictive values (PPVs) and false-positive rates, with a lack of precision in accuracy estimates (sensitivity range, 0%-100%; specificity range, 91%-99%; PPV range, 0%-3.6%; negative predictive value [NPV] range, ≥99%). Each diagnostic accuracy study for bacterial vaginosis, trichomoniasis, and genital herpes was performed in a high-prevalence population with substantial proportions of symptomatic patients and reported accuracy characteristics for individual physical examination findings (bacterial vaginosis, homogeneous discharge: sensitivity range, 69%-79%; specificity range, 54%-97%; PPV range, 52%-95%; NPV range, 79%-80%; herpes simplex virus, vulvar ulcerations: sensitivity, 20%; specificity, 98%; PPV, 88%; NPV, 57%; trichomoniasis, colpitis macularis: sensitivity, 2%; specificity, 100%; PPV, 100%; NPV, 85%). Surgery rates resulting from an abnormal screening pelvic examination for ovarian cancer ranged from 5% to 36% at 1 year, with the largest study reporting an 11% surgery rate and 1% complication rate within 1 year of a screening pelvic examination with abnormal findings. No direct evidence was identified for overall benefits and harms of the pelvic examination as a 1-time or periodic screening test. Limited evidence was identified regarding the diagnostic accuracy and harms of routine screening pelvic examinations in asymptomatic primary care populations.

High-temperature-superconducting magnetic susceptibility bolometer

NASA Technical Reports Server (NTRS)

Brasunas, J.; Lakew, B.; Lee, C.

1992-01-01

An infrared detector called the magnetic susceptibility bolometer is introduced which is based on the tmperature dependence of the diamagnetic screening of a high-Tc superconductor film near Tc. Results are reported for the response of a prototype model to modulated blackbody radiation. Possible improvements are discussed as is the potential sensitivity of an improved device.

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

Development of a screening tool to predict malnutrition among children under two years old in Zambia

PubMed Central

Hasegawa, Junko; Ito, Yoichi M; Yamauchi, Taro

2017-01-01

ABSTRACT Background: Maternal and child undernutrition is an important issue, particularly in low- and middle-income countries. Children at high risk of malnutrition should be prioritized to receive necessary interventions to minimize such risk. Several risk factors have been proposed; however, until now, there has been no appropriate evaluation method to identify these children. In sub-Saharan Africa, children commonly receive regular check-ups from community health workers. A simple and easy nutrition assessment method is therefore needed for use by semi-professional health workers. Objectives: The aim of this study was to develop and test a practical screening tool for community use in predicting growth stunting in children under two years in rural Zambia. Methods: Field research was conducted from July to August 2014 in Southern Province, Zambia. Two hundred and sixty-four mother-child pairs participated in the study. Anthropometric measurements were performed on all children and mothers, and all mothers were interviewed. Risk factors for the screening test were estimated by using least absolute shrinkage and selection operator analysis. After re-evaluating all participants using the new screening tool, a receiver operating characteristic curve was drawn to set the cut-off value. Sensitivity and specificity were also calculated. Results: The screening tool included age, weight-for-age Z-score status, birth weight, feeding status, history of sibling death, multiple birth, and maternal education level. The total score ranged from 0 to 22, and the cut-off value was eight. Sensitivity and specificity were 0.963 and 0.697 respectively. Conclusions: A screening tool was developed to predict children at high risk of malnutrition living in Zambia. Further longitudinal studies are needed to confirm the test’s validity in detecting future stunting and to investigate the effectiveness of malnutrition treatment. PMID:28730929

Efficacy of functional movement screening for predicting injuries in coast guard cadets.

PubMed

Knapik, Joseph J; Cosio-Lima, Ludimila M; Reynolds, Katy L; Shumway, Richard S

2015-05-01

Functional movement screening (FMS) examines the ability of individuals to perform highly specific movements with the aim of identifying individuals who have functional limitations or asymmetries. It is assumed that individuals who can more effectively accomplish the required movements have a lower injury risk. This study determined the ability of FMS to predict injuries in the United States Coast Guard (USCG) cadets. Seven hundred seventy male and 275 female USCG freshman cadets were administered the 7 FMS tests before the physically intense 8-week Summer Warfare Annual Basic (SWAB) training. Physical training-related injuries were recorded during SWAB training. Cumulative injury incidence was calculated at various FMS cutpoint scores. The ability of the FMS total score to predict injuries was examined by calculating sensitivity and specificity. Determination of the FMS cutpoint that maximized specificity and sensitivity was determined from the Youden's index (sensitivity + specificity - 1). For men, FMS scores ≤ 12 were associated with higher injury risk than scores >12; for women, FMS scores ≤ 15 were associated with higher injury risk than scores >15. The Youden's Index indicated that the optimal FMS cutpoint was ≤ 11 for men (22% sensitivity, 87% specificity) and ≤ 14 for women (60% sensitivity, 61% specificity). Functional movement screening demonstrated moderate prognostic accuracy for determining injury risk among female Coast Guard cadets but relatively low accuracy among male cadets. Attempting to predict injury risk based on the FMS test seems to have some limited promise based on the present and past investigations.

[Symptoms of Celiac disease in childhood].

PubMed

Mouterde, O; Dumant, C; Mallet, E

2013-06-01

The knowledge regarding celiac disease has increased dramatically in recent years, due to the availability of accurate serologic markers. Mass screening studies have shown that the prevalence of sensitization can be as high as 1/80. The range of symptoms is wide, from the classic growth failure, denutrition and diarrhea in infancy to clinically and histologically asymptomatic sensitized subjects. The interest of a routine mass screening is debated. The classical celiac disease in infancy is well known. Atypical symptoms and potentially associated disease are more frequent and potentially confounding. Physicians should be aware of any clue for celiac disease in atypical cases in order to improve the diagnostic yield, and therefore avoiding short or long term consequences. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

In vitro methods for hazard assessment of industrial chemicals – opportunities and challenges

PubMed Central

Wong, Chin Lin; Ghassabian, Sussan; Smith, Maree T.; Lam, Ai-Leen

2015-01-01

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity immune reaction mediated by T-lymphocytes as a result of repeated exposure of an allergen primarily on skin. ACD accounts for up to 95% of occupational skin diseases, with epoxy resins implicated as one of the most common causes of ACD. Efficient high-throughput in vitro screening for accurate identification of compounds and materials that may pose hazardous risks in the workplace is crucial. At present, the murine local lymph node assay is the ‘method of choice’ for predicting the sensitizing potency of contact allergens. As the 3Rs principles of reduction, refinement, and replacement in animal testing has gained political and economic momentum, several in vitro screening methods have been developed for identifying potential contact allergens. To date, these latter methods have been utilized primarily to assess the skin sensitizing potential of the chemical components of cosmetic products with scant research attention as to the applicability of these methods to industrial chemicals, particularly epoxy resins. Herein we review the currently utilized in vitro methods and identify the knowledge gaps with regard to assessing the generalizability of in vitro screening methods for assessing the skin sensitizing potential of industrial chemicals. PMID:25999858

In vitro methods for hazard assessment of industrial chemicals - opportunities and challenges.

PubMed

Wong, Chin Lin; Ghassabian, Sussan; Smith, Maree T; Lam, Ai-Leen

2015-01-01

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity immune reaction mediated by T-lymphocytes as a result of repeated exposure of an allergen primarily on skin. ACD accounts for up to 95% of occupational skin diseases, with epoxy resins implicated as one of the most common causes of ACD. Efficient high-throughput in vitro screening for accurate identification of compounds and materials that may pose hazardous risks in the workplace is crucial. At present, the murine local lymph node assay is the 'method of choice' for predicting the sensitizing potency of contact allergens. As the 3Rs principles of reduction, refinement, and replacement in animal testing has gained political and economic momentum, several in vitro screening methods have been developed for identifying potential contact allergens. To date, these latter methods have been utilized primarily to assess the skin sensitizing potential of the chemical components of cosmetic products with scant research attention as to the applicability of these methods to industrial chemicals, particularly epoxy resins. Herein we review the currently utilized in vitro methods and identify the knowledge gaps with regard to assessing the generalizability of in vitro screening methods for assessing the skin sensitizing potential of industrial chemicals.

Electrocardiographic recognition of right ventricular hypertrophy.

PubMed

Nikus, Kjell; Pérez-Riera, Andrés Ricardo; Konttila, Kaari; Barbosa-Barros, Raimundo

The electrocardiogram (ECG) is a relatively insensitive tool for the detection of right ventricular hypertrophy (RVH), but some criteria have high specificity. The recommended ECG screening criteria for RVH are not sufficiently sensitive or specific for screening for mild RVH in adults without clinical cardiovascular disease. The greatest accuracy of the ECG is in congenital heart disease, with intermediate accuracy in acquired heart disease and primary pulmonary hypertension in adults. Copyright © 2017 Elsevier Inc. All rights reserved.

High density array screening to identify the genetic requirements for transition metal tolerance in Saccharomyces cerevisiae.

PubMed

Bleackley, Mark R; Young, Barry P; Loewen, Christopher J R; MacGillivray, Ross T A

2011-02-01

Biological systems have developed with a strong dependence on transition metals for accomplishing a number of biochemical reactions. Iron, copper, manganese and zinc are essential for virtually all forms of life with their unique chemistries contributing to a variety of physiological processes including oxygen transport, generation of cellular energy and protein structure and function. Properties of these metals (and to a lesser extent nickel and cobalt) that make them so essential to life also make them extremely cytotoxic in many cases through the formation of damaging oxygen radicals via Fenton chemistry. While life has evolved to exploit the chemistries of transition metals to drive physiological reactions, systems have concomitantly evolved to protect against the damaging effects of these same metals. Saccharomyces cerevisiae is a valuable tool for studying metal homeostasis with many of the genes identified thus far having homologs in higher eukaryotes including humans. Using high density arrays, we have screened a haploid S. cerevisiae deletion set containing 4786 non-essential gene deletions for strains sensitive to each of Fe, Cu, Mn, Ni, Zn and Co and then integrated the six screens using cluster analysis to identify pathways that are unique to individual metals and others with function shared between metals. Genes with no previous implication in metal homeostasis were found to contribute to sensitivity to each metal. Significant overlap was observed between the strains that were sensitive to Mn, Ni, Zn and Co with many of these strains lacking genes for the high affinity Fe transport pathway and genes involved in vacuolar transport and acidification. The results from six genome-wide metal tolerance screens show that there is some commonality between the cellular defenses against the toxicity of Mn, Ni, Zn and Co with Fe and Cu requiring different systems. Additionally, potential new factors been identified that function in tolerance to each of the six metals.

Falls risk assessment outcomes and factors associated with falls for older Indigenous Australians.

PubMed

Hill, Keith D; Flicker, Leon; LoGiudice, Dina; Smith, Kate; Atkinson, David; Hyde, Zoë; Fenner, Stephen; Skeaf, Linda; Malay, Roslyn; Boyle, Eileen

2016-12-01

To describe the prevalence of falls and associated risk factors in older Indigenous Australians, and compare the accuracy of validated falls risk screening and assessment tools in this population in classifying fall status. Cross-sectional study of 289 Indigenous Australians aged ≥45 years from the Kimberley region of Western Australia who had a detailed assessment including self-reported falls in the past year (n=289), the adapted Elderly Falls Screening Tool (EFST; n=255), and the Falls Risk for Older People-Community (FROP-Com) screening tool (3 items, n=74) and FROP-Com falls assessment tool (n=74). 32% of participants had ≥1 fall in the preceding year, and 37.3% were classified high falls risk using the EFST (cut-off ≥2). In contrast, for the 74 participants assessed with the FROP-Com, only 14.9% were rated high risk, 35.8% moderate risk, and 49.3% low risk. The FROP-Com screen and assessment tools had the highest classification accuracy for identifying fallers in the preceding year (area under curve >0.85), with sensitivity/specificity highest for the FROP-Com assessment (cut-off ≥12), sensitivity=0.84 and specificity=0.73. Falls are common in older Indigenous Australians. The FROP-Com falls risk assessment tool appears useful in this population, and this research suggests changes that may improve its utility further. © 2016 Public Health Association of Australia.

[Screening of parasitic diseases in the asymptomatic immigrant population].

PubMed

Goterris, Lidia; Bocanegra, Cristina; Serre-Delcor, Núria; Moure, Zaira; Treviño, Begoña; Zarzuela, Francesc; Espasa, Mateu; Sulleiro, Elena

2016-07-01

Parasitic diseases suppose an important health problem in people from high endemic areas, so these must be discarded properly. Usually, these infections develop asymptomatically but, in propitious situations, are likely to reactivate themselves and can cause clinical symptoms and/or complications in the receiving country. Moreover, in some cases it is possible local transmission. Early diagnosis of these parasitic diseases made by appropriate parasitological techniques and its specific treatment will benefit both, the individual and the community. These techniques must be selected according to geoepidemiological criteria, patient's origin, migration route or time spent outside the endemic area; but other factors must also be considered as its sensitivity and specificity, implementation experience and availability. Given the high prevalence of intestinal parasites on asymptomatic immigrants, it is recommended to conduct a study by coproparasitological techniques. Because of its potential severity, the screening of asymptomatic malaria with sensitive techniques such as PCR (polymerase chain reaction) is also advisable. Serological screening for Chagas disease should be performed on all Latin American immigrants, except for people from the Caribbean islands. Other important parasites, which should be excluded, are filariasis and urinary schistosomiasis, by using microscopic examination. The aim of this paper is to review the different techniques for the screening of parasitic diseases and its advices within the care protocols for asymptomatic immigrants. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Cross-national comparison of screening mammography accuracy measures in U.S., Norway, and Spain.

PubMed

Domingo, Laia; Hofvind, Solveig; Hubbard, Rebecca A; Román, Marta; Benkeser, David; Sala, Maria; Castells, Xavier

2016-08-01

To compare accuracy measures for mammographic screening in Norway, Spain, and the US. Information from women aged 50-69 years who underwent mammographic screening 1996-2009 in the US (898,418 women), Norway (527,464), and Spain (517,317) was included. Screen-detected cancer, interval cancer, and the false-positive rates, sensitivity, specificity, positive predictive value (PPV) for recalls (PPV-1), PPV for biopsies (PPV-2), 1/PPV-1 and 1/PPV-2 were computed for each country. Analyses were stratified by age, screening history, time since last screening, calendar year, and mammography modality. The rate of screen-detected cancers was 4.5, 5.5, and 4.0 per 1000 screening exams in the US, Norway, and Spain respectively. The highest sensitivity and lowest specificity were reported in the US (83.1 % and 91.3 %, respectively), followed by Spain (79.0 % and 96.2 %) and Norway (75.5 % and 97.1 %). In Norway, Spain and the US, PPV-1 was 16.4 %, 9.8 %, and 4.9 %, and PPV-2 was 39.4 %, 38.9 %, and 25.9 %, respectively. The number of women needed to recall to detect one cancer was 20.3, 6.1, and 10.2 in the US, Norway, and Spain, respectively. Differences were found across countries, suggesting that opportunistic screening may translate into higher sensitivity at the cost of lower specificity and PPV. • Positive predictive value is higher in population-based screening programmes in Spain and Norway. • Opportunistic mammography screening in the US has lower positive predictive value. • Screening settings in the US translate into higher sensitivity and lower specificity. • The clinical burden may be higher for women screened opportunistically.

Towards Risk-Based Test Protocols: Estimating the Contribution of Intensive Testing to the UK Bovine Tuberculosis Problem

PubMed Central

van Dijk, Jan

2013-01-01

Eradicating disease from livestock populations involves the balancing act of removing sufficient numbers of diseased animals without removing too many healthy individuals in the process. As ever more tests for bovine tuberculosis (BTB) are carried out on the UK cattle herd, and each positive herd test triggers more testing, the question arises whether ‘false positive’ results contribute significantly to the measured BTB prevalence. Here, this question is explored using simple probabilistic models of test behaviour. When the screening test is applied to the average UK herd, the estimated proportion of test-associated false positive new outbreaks is highly sensitive to small fluctuations in screening test specificity. Estimations of this parameter should be updated as a priority. Once outbreaks have been confirmed in screening-test positive herds, the following rounds of intensive testing with more sensitive, albeit less specific, tests are highly likely to remove large numbers of false positive animals from herds. Despite this, it is unlikely that significantly more truly infected animals are removed. BTB test protocols should become based on quantified risk in order to prevent the needless slaughter of large numbers of healthy animals. PMID:23717517

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

PubMed Central

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

2017-01-01

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

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.

Streamlining the Evaluation of Low Back Pain in Children

PubMed Central

Auerbach, Joshua D.; Ahn, Jaimo; Zgonis, Miltiadis H.; Reddy, Sudheer C.; Ecker, Malcolm L.

2008-01-01

The workup of low back pain in children often results in overimaging so as not to miss organic back pain. The primary goal of this study was to identify which combination of imaging modalities provides the most sensitive and specific screening protocol for children with low back pain. Medical records from 100 consecutive patients between 2 and 18 years of age presenting with low back pain, without night pain or constitutional symptoms, were evaluated. A hyperextension test combined with a radiograph showed a negative predictive value of 0.81 and sensitivity of 0.90. The addition of a bone scan was highly effective in achieving good negative predictive value and sensitivity. Bone scans had perfect negative predictive value and sensitivity when symptom duration was less than 6 weeks. We identified a set of factors that is highly predictive for distinguishing organic back pain from mechanical back pain. Painless hyperextension combined with negative anteroposterior, lateral, and oblique lumbar radiographs and magnetic resonance images predicts mechanical back pain. For patients with nonneurologic back pain of less than 6 weeks duration, bone scan is the most useful screening test because it is accurate, accessible, inexpensive, and unlikely to require sedation. Level of Evidence: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18553213

A novel immunochromatographic electrochemical biosensor for highly sensitive and selective detection of trichloropyridinol, a biomarker of exposure to chlorpyrifos.

PubMed

Wang, Limin; Lu, Donglai; Wang, Jun; Du, Dan; Zou, Zhexiang; Wang, Hua; Smith, Jordan N; Timchalk, Charles; Liu, Fengquan; Lin, Yuehe

2011-02-15

We present a novel portable immunochromatographic electrochemical biosensor (IEB) for simple, rapid, and sensitive biomonitoring of trichloropyridinol (TCP), a metabolite biomarker of exposure to organophosphorus insecticides. Our new approach takes the advantage of immunochromatographic test strip for a rapid competitive immunoreaction and a disposable screen-printed carbon electrode for a rapid and sensitive electrochemical analysis of captured HRP labeling. Several key experimental parameters (e.g. immunoreaction time, the amount of HRP labeled TCP, concentration of the substrate for electrochemical measurements, and the blocking agents for the nitrocellulose membrane) were optimized to achieve a high sensitivity, selectivity and stability. Under optimal conditions, the IEB has demonstrated a wide linear range (0.1-100 ng/ml) with a detection limit as low as 0.1 ng/ml TCP. Furthermore, the IEB has been successfully applied for biomonitoring of TCP in the rat plasma samples with in vivo exposure to organophosphorus insecticides like Chlorpyrifos-oxon (CPF-oxon). The IEB thus opens up new pathways for designing a simple, rapid, clinically accurate, and quantitative tool for TCP detection, as well as holds a great promise for in-field screening of metabolite biomarkers, e.g., TCP, for humans exposed to organophosphorus insecticides. Copyright © 2010 Elsevier B.V. All rights reserved.

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers.

PubMed

Avonto, Cristina; Chittiboyina, Amar G; Rua, Diego; Khan, Ikhlas A

2015-12-01

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, 'HTS-DCYA assay', is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. Copyright © 2015 Elsevier Inc. All rights reserved.

High-throughput cocrystal slurry screening by use of in situ Raman microscopy and multi-well plate.

PubMed

Kojima, Takashi; Tsutsumi, Shunichirou; Yamamoto, Katsuhiko; Ikeda, Yukihiro; Moriwaki, Toshiya

2010-10-31

Cocrystal has attracted much attention in order to improve poor physicochemical properties, since cocrystal former crystallize with the ionic drugs as well as nonionic drugs. Cocrystal screening was usually conducted by crystallization, slurry and co-grinding techniques, however sensitivity, cost and time for screening were limited because of issues such as dissociation of cocrystal during crystallization and cost and time required for slurry and co-grinding methods. To overcome these issues, novel high-throughput cocrystal slurry screening was developed by using in situ Raman microscope and a multi-well plate. Cocrystal screening of indomethacin was conducted with 46 cocrystal formers and potential cocrystals were prepared on a large scale for the characterization with powder X-ray diffractometry, thermal analysis, and Raman microscopy and (1)H NMR spectroscopy. Compared with the characterization of scale-up cocrystals, the cocrystal screening indicated that indomethacin structured novel cocrystals with D/L-mandelic acid, nicotinamide, lactamide and benzamide which was not obtained in the screening with crystallization technique previously reported. In addition, the screening provided not only information of cocrystal formation within a day but also information of equilibrium of cocrystal formation and polymorphic transformation in one screening. Information obtained in this screening allows effective solid form selection by saving cost and time for the development. Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Out-of-hospital stroke screen accuracy in a state with an emergency medical services protocol for routing patients to acute stroke centers.

PubMed

Asimos, Andrew W; Ward, Shana; Brice, Jane H; Rosamond, Wayne D; Goldstein, Larry B; Studnek, Jonathan

2014-11-01

Emergency medical services (EMS) protocols, which route patients with suspected stroke to stroke centers, rely on the use of accurate stroke screening criteria. Our goal is to conduct a statewide EMS agency evaluation of the accuracies of the Cincinnati Prehospital Stroke Scale (CPSS) and the Los Angeles Prehospital Stroke Screen (LAPSS) for identifying acute stroke patients. We conducted a retrospective study in North Carolina by linking a statewide EMS database to a hospital database, using validated deterministic matching. We compared EMS CPSS or LAPSS results (positive or negative) to the emergency department diagnosis International Classification of Diseases, Ninth Revision codes. We calculated sensitivity, specificity, and positive and negative likelihood ratios for the EMS diagnosis of stroke, using each screening tool. We included 1,217 CPSS patients and 1,225 LAPSS patients evaluated by 117 EMS agencies from 94 North Carolina counties. Most EMS agencies contributing data had high annual patient volumes and were governmental agencies with nonvolunteer, emergency medical technician-paramedic service level providers. The CPSS had a sensitivity of 80% (95% confidence interval [CI] 77% to 83%) versus 74% (95% CI 71% to 77%) for the LAPSS. Each had a specificity of 48% (CPSS 95% CI 44% to 52%; LAPSS 95% CI 43% to 53%). The CPSS and LAPSS had similar test characteristics, with each having only limited specificity. Development of stroke screening scales that optimize both sensitivity and specificity is required if these are to be used to determine transport diversion to acute stroke centers. Copyright © 2014. Published by Elsevier Inc.

Diagnostic accuracy of a two-item Drug Abuse Screening Test (DAST-2).

PubMed

Tiet, Quyen Q; Leyva, Yani E; Moos, Rudolf H; Smith, Brandy

2017-11-01

Drug use is prevalent and costly to society, but individuals with drug use disorders (DUDs) are under-diagnosed and under-treated, particularly in primary care (PC) settings. Drug screening instruments have been developed to identify patients with DUDs and facilitate treatment. The Drug Abuse Screening Test (DAST) is one of the most well-known drug screening instruments. However, similar to many such instruments, it is too long for routine use in busy PC settings. This study developed and validated a briefer and more practical DAST for busy PC settings. We recruited 1300 PC patients in two Department of Veterans Affairs (VA) clinics. Participants responded to a structured diagnostic interview. We randomly selected half of the sample to develop and the other half to validate the new instrument. We employed signal detection techniques to select the best DAST items to identify DUDs (based on the MINI) and negative consequences of drug use (measured by the Inventory of Drug Use Consequences). Performance indicators were calculated. The two-item DAST (DAST-2) was 97% sensitive and 91% specific for DUDs in the development sample and 95% sensitive and 89% specific in the validation sample. It was highly sensitive and specific for DUD and negative consequences of drug use in subgroups of patients, including gender, age, race/ethnicity, marital status, educational level, and posttraumatic stress disorder status. The DAST-2 is an appropriate drug screening instrument for routine use in PC settings in the VA and may be applicable in broader range of PC clinics. Published by Elsevier Ltd.

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

PubMed Central

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

2015-01-01

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

The need for supplemental breast cancer screening modalities: a perspective of population-based breast cancer screening programs in Japan.

PubMed

Uematsu, Takayoshi

2017-01-01

This article discusses possible supplemental breast cancer screening modalities for younger women with dense breasts from a perspective of population-based breast cancer screening program in Japan. Supplemental breast cancer screening modalities have been proposed to increase the sensitivity and detection rates of early stage breast cancer in women with dense breasts; however, there are no global guidelines that recommend the use of supplemental breast cancer screening modalities in such women. Also, no criterion standard exists for breast density assessment. Based on the current situation of breast imaging in Japan, the possible supplemental breast cancer screening modalities are ultrasonography, digital breast tomosynthesis, and breast magnetic resonance imaging. An appropriate population-based breast cancer screening program based on the balance between cost and benefit should be a high priority. Further research based on evidence-based medicine is encouraged. It is very important that the ethnicity, workforce, workflow, and resources for breast cancer screening in each country should be considered when considering supplemental breast cancer screening modalities for women with dense breasts.

A Novel Extraction Method Combining Plasma with a Whole-Blood Fraction Shows Excellent Sensitivity and Reproducibility for Patients at High Risk for Invasive Aspergillosis

PubMed Central

Springer, Jan; Schloßnagel, Hannes; Heinz, Werner; Doedt, Thomas; Soeller, Rainer; Einsele, Hermann

2012-01-01

Diagnosis of invasive aspergillosis (IA) is still a major problem in routine clinical practice. Early diagnosis is essential for a good patient prognosis. PCR is a highly sensitive method for the detection of nucleic acids and could play an important role in improving the diagnosis of fungal infections. Therefore, a novel DNA extraction method, ultraclean production (UCP), was developed allowing purification of both cellular and cell-free circulating fungal DNA. In this prospective study we evaluated the commercially available UCP extraction system and compared it to an in-house system. Sixty-three patients at high risk for IA were screened twice weekly, and DNA extracted by both methods was cross-analyzed, in triplicate, by two different real-time PCR assays. The negative predictive values were high for all methods (94.3 to 100%), qualifying them as screening methods, but the sensitivity and diagnostic odds ratios were higher using the UCP extraction method. Sensitivity ranged from 33.3 to 66.7% using the in-house extracts to 100% using the UCP extraction method. Most of the unclassified patients showed no positive PCR results; however, single-positive PCR replicates were observed in some cases. These can bear clinical relevance but should be interpreted with additional clinical and laboratory data. The PCR assays from the UCP extracts showed greater reproducibility than the in-house method for probable IA patients. The standardized UCP extraction method yielded superior results, with regard to sensitivity and reproducibility, than the in-house method. This was independent of the PCR assay used to detect fungal DNA in the sample extracts. PMID:22593600

Cost-effectiveness of screening and treatment for bacterial vaginosis in early pregnancy among women at low risk for preterm birth.

PubMed

Kekki, Minnamaija; Kurki, Tapio; Kotomäki, Teija; Sintonen, Harri; Paavonen, Jorma

2004-01-01

Bacterial vaginosis (BV) is an important risk factor for preterm birth. BV is detected in 10-30% of pregnant women and is often asymptomatic. Treatment of BV during pregnancy seems to reduce the risk of preterm delivery among high-risk women. We performed a cost-effectiveness analysis of screening and treatment for BV in early pregnancy among asymptomatic women at low risk for preterm delivery. A decision tree was built with two arms. For the screening (and treatment) arm the probabilities were derived from our earlier randomized trial on screening and treatment for BV, consisting of BV-positive women treated with intravaginal clindamycin cream or placebo and also of BV-negative pregnant women. The probabilities of outcomes among these women were collected from antenatal clinic records and hospital records, and for the no-screening arm mainly from the Finnish Perinatal Statistics. The outcomes considered were preterm delivery, mode of delivery, peripartum infections and postpartum complications. The unit costs associated with these outcomes were mainly based on disease-related groups (DRGs). No-screening was compared with two screening programs (one with clindamycin, the other with metronidazole treatment) and subjected to sensitivity analyses. There was no significant difference between screening and no-screening strategies in the costs and in the rate of preterm deliveries but the screening strategy produced significantly fewer peripartum infections and postpartum complications. Sensitivity analyses suggested that the screening strategy may become cost-saving if the rate of preterm deliveries exceeds 3%. Screening and treatment for BV in early pregnancy may not reduce costs compared to no-screening in a population at low risk for preterm birth but would produce, at the same cost, more health benefits in terms of fewer peripartum infections and postpartum complications. However, it may be cost-saving if the rate of preterm deliveries is higher than 3%.

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.

Screening for confabulations with the confabulation screen.

PubMed

Dalla Barba, Gianfranco; Brazzarola, Marta; Marangoni, Sara; La Corte, Valentina

2018-04-24

The objective of this work is to devise and validate a sensitive and specific test for confabulatory impairment. We conceived a screening test for confabulation, the Confabulation Screen (CS), a brief test using 10 questions of episodic memory (EM), where confabulators most frequently confabulate. It was postulated that the CS would predict confabulations not only in EM, but also in the other subordinate structures of personal temporality, namely the present and the future. Thirty confabulating amnesic patients of various aetiologies and 97 normal controls entered the study. Participants were administered the CS and the Confabulation Battery (Dalla Barba, G., & Decaix, C. (2009). "Do you remeber what you did on March 13 1985?" A case study of confabulatory hypermnesia. Cortex, 45(5), 566-574). Confabulations in the CS positively and significantly correlated with confabulations in personal temporality domains of the CB, namely EM, orientation in time and place and episodic plans. Conversely, as expected, they did not correlate with confabulations in impersonal temporality domains of the CB. Consistent with results of previous studies, the most frequently observed type of confabulation in the CS was Habits Confabulation. The CS had high construct validity and good discriminative validity in terms of sensitivity and specificity. Cut-off scores for clinical and research purposes are proposed. The CS provides efficient and valid screening for confabulatory impairment.

Cost-effectiveness of osteoporosis screening strategies for hip fracture prevention in older Chinese people: a decision tree modeling study in the Mr. OS and Ms. OS cohort in Hong Kong.

PubMed

Su, Y; Lai, F T T; Yip, B H K; Leung, J C S; Kwok, T C Y

2018-05-17

Despite the high costs of hip fracture, many governments provide limited support for osteoporosis screening. We demonstrated that osteoporosis screening by dual-energy X-ray absorptiometry (DXA) with or without pre-screening by Fracture Risk Assessment Tool (FRAX) or calcaneal ultrasound are more cost-effective than no screening in Chinese people aged 65 or over in Hong Kong. To examine the cost-effective potential osteoporosis screening strategies for hip fracture prevention in Hong Kong. Decision tree models were constructed to evaluate the cost per quality-adjusted life years (QALYs) of the different osteoporosis screening strategies followed by subsequent 5-year treatment with alendronate compared to no screening (but treat if a hip fracture occurs). The multiple osteoporosis screening strategies were composed of alternative tests and initiation age groups were evaluated with a 10-year horizon, and treatment were assigned if central dual-energy X-ray absorptiometry (DXA) T-score (at either the hip or spine) is - 2.5 or less. Strategies included DXA for all people and pre-screening with the Fracture Risk Assessment Tool (FRAX) at specific thresholds or by calcaneal quantitative ultrasonography (QUS) before taking DXA examination. All the model inputs were based on the Mr. OS and Ms. OS Hong Kong cohort; data are obtained from the Social Welfare Department or the published literature. All of the screening strategies, including the universal screening with DXA and the pre-screening with FRAX or QUS before DXA, were consistently more cost-effective than no screening for people aged 65 years old or over. One-way sensitivity analysis with a more optimistic assumption on treatment adherence or inclusion of other major osteoporotic fractures did not change the results materially. Probabilistic sensitivity analyses showed a dominant role of pre-screening with FRAX followed by subsequent osteoporosis drug treatment in people aged 70 years old or over in Hong Kong. Osteoporosis screening strategies based on DXA with or without pre-screening are more cost-effective compared to no screening for Chinese people aged 65 or over in Hong Kong.

Quadruplex MAPH: improvement of throughput in high-resolution copy number screening.

PubMed

Tyson, Jess; Majerus, Tamsin Mo; Walker, Susan; Armour, John Al

2009-09-28

Copy number variation (CNV) in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way. Multiplex Amplifiable Probe Hybridisation (MAPH) is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH") that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) samples. QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms.

Quadruplex MAPH: improvement of throughput in high-resolution copy number screening

PubMed Central

Tyson, Jess; Majerus, Tamsin MO; Walker, Susan; Armour, John AL

2009-01-01

Background Copy number variation (CNV) in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way. Results Multiplex Amplifiable Probe Hybridisation (MAPH) is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH") that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) samples. Conclusion QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms. PMID:19785739

Virtual Embryo: Systems Modeling in Developmental Toxicity

EPA Science Inventory

High-throughput screening (HTS) studies are providing a rich source of data that can be applied to chemical profiling to address sensitivity and specificity of molecular targets, biological pathways, cellular and developmental processes. EPA’s ToxCast project is testing 960 uniq...

High-Throughput Screening Using iPSC-Derived Neuronal Progenitors to Identify Compounds Counteracting Epigenetic Gene Silencing in Fragile X Syndrome.

PubMed

Kaufmann, Markus; Schuffenhauer, Ansgar; Fruh, Isabelle; Klein, Jessica; Thiemeyer, Anke; Rigo, Pierre; Gomez-Mancilla, Baltazar; Heidinger-Millot, Valerie; Bouwmeester, Tewis; Schopfer, Ulrich; Mueller, Matthias; Fodor, Barna D; Cobos-Correa, Amanda

2015-10-01

Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused in most of cases by epigenetic silencing of the Fmr1 gene. Today, no specific therapy exists for FXS, and current treatments are only directed to improve behavioral symptoms. Neuronal progenitors derived from FXS patient induced pluripotent stem cells (iPSCs) represent a unique model to study the disease and develop assays for large-scale drug discovery screens since they conserve the Fmr1 gene silenced within the disease context. We have established a high-content imaging assay to run a large-scale phenotypic screen aimed to identify compounds that reactivate the silenced Fmr1 gene. A set of 50,000 compounds was tested, including modulators of several epigenetic targets. We describe an integrated drug discovery model comprising iPSC generation, culture scale-up, and quality control and screening with a very sensitive high-content imaging assay assisted by single-cell image analysis and multiparametric data analysis based on machine learning algorithms. The screening identified several compounds that induced a weak expression of fragile X mental retardation protein (FMRP) and thus sets the basis for further large-scale screens to find candidate drugs or targets tackling the underlying mechanism of FXS with potential for therapeutic intervention. © 2015 Society for Laboratory Automation and Screening.

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.

Clinician Suspicion of an Alcohol Problem: An Observational Study From the AAFP National Research Network

PubMed Central

Vinson, Daniel C.; Turner, Barbara J.; MSED; Manning, Brian K.; Galliher, James M.

2013-01-01

PURPOSE In clinical practice, detection of alcohol problems often relies on clinician suspicion instead of using a screening instrument. We assessed the sensitivity, specificity, and predictive values of clinician suspicion compared with screening-detected alcohol problems in patients. METHODS We undertook a cross-sectional study of 94 primary care clinicians’ office visits. Brief questionnaires were completed separately after a visit by both clinicians and eligible patients. The patient’s anonymous exit questionnaire screened for hazardous drinking based on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and for harmful drinking (alcohol abuse or dependence) based on 2 questions from the Diagnostic and Statistical Manual of Mental Disorders. After the visit, clinicians responded to the question, “Does this patient have problems with alcohol?” with answer options including “yes, hazardous drinking” and “yes, alcohol abuse or dependence.” Analyses assessed the associations between patients’ responses to screening questions and clinician’s suspicions. RESULTS Of 2,518 patients with an office visit, 2,173 were eligible, and 1,699 (78%) completed the exit questionnaire. One hundred seventy-one (10.1%) patients had a positive screening test for hazardous drinking (an AUDIT-C score of 5 or greater) and 64 (3.8%) for harmful drinking. Clinicians suspected alcohol problems in 81 patients (hazardous drinking in 37, harmful drinking in 40, and both in 4). The sensitivity of clinician suspicion of either hazardous or harmful drinking was 27% and the specificity was 98%. Positive and negative predictive values were 62% and 92%, respectively. CONCLUSION Clinician suspicion of alcohol problems had poor sensitivity but high specificity for identifying patients who had a positive screening test for alcohol problems. These data support the routine use of a screening tool to supplement clinicians’ suspicions, which already provide reasonable positive predictive value. PMID:23319506

Colorimetry and SERS dual-mode detection of telomerase activity: combining rapid screening with high sensitivity

NASA Astrophysics Data System (ADS)

Zong, Shenfei; Wang, Zhuyuan; Chen, Hui; Hu, Guohua; Liu, Min; Chen, Peng; Cui, Yiping

2014-01-01

As an important biomarker and therapeutic target, telomerase has attracted considerable attention concerning its detection and monitoring. Here, we present a colorimetry and surface enhanced Raman scattering (SERS) dual-mode telomerase activity detection method, which has several distinctive advantages. First, colorimetric functionality allows rapid preliminary discrimination of telomerase activity by the naked eye. Second, the employment of SERS technique results in greatly improved detection sensitivity. Third, the combination of colorimetry and SERS into one detection system can ensure highly efficacious and sensitive screening of numerous samples. Besides, the avoidance of polymerase chain reaction (PCR) procedures further guarantees fine reliability and simplicity. Generally, the presented method is realized by an ``elongate and capture'' procedure. To be specific, gold nanoparticles modified with Raman molecules and telomeric repeat complementary oligonucleotide are employed as the colorimetric-SERS bifunctional reporting nanotag, while magnetic nanoparticles functionalized with telomerase substrate oligonucleotide are used as the capturing substrate. Telomerase can synthesize and elongate telomeric repeats onto the capturing substrate. The elongated telomeric repeats subsequently facilitate capturing of the reporting nanotag via hybridization between telomeric repeat and its complementary strand. The captured nanotags can cause a significant difference in the color and SERS intensity of the magnetically separated sediments. Thus both the color and SERS can be used as indicators of the telomerase activity. With fast screening ability and outstanding sensitivity, we anticipate that this method would greatly promote practical application of telomerase-based early-stage cancer diagnosis.As an important biomarker and therapeutic target, telomerase has attracted considerable attention concerning its detection and monitoring. Here, we present a colorimetry and surface enhanced Raman scattering (SERS) dual-mode telomerase activity detection method, which has several distinctive advantages. First, colorimetric functionality allows rapid preliminary discrimination of telomerase activity by the naked eye. Second, the employment of SERS technique results in greatly improved detection sensitivity. Third, the combination of colorimetry and SERS into one detection system can ensure highly efficacious and sensitive screening of numerous samples. Besides, the avoidance of polymerase chain reaction (PCR) procedures further guarantees fine reliability and simplicity. Generally, the presented method is realized by an ``elongate and capture'' procedure. To be specific, gold nanoparticles modified with Raman molecules and telomeric repeat complementary oligonucleotide are employed as the colorimetric-SERS bifunctional reporting nanotag, while magnetic nanoparticles functionalized with telomerase substrate oligonucleotide are used as the capturing substrate. Telomerase can synthesize and elongate telomeric repeats onto the capturing substrate. The elongated telomeric repeats subsequently facilitate capturing of the reporting nanotag via hybridization between telomeric repeat and its complementary strand. The captured nanotags can cause a significant difference in the color and SERS intensity of the magnetically separated sediments. Thus both the color and SERS can be used as indicators of the telomerase activity. With fast screening ability and outstanding sensitivity, we anticipate that this method would greatly promote practical application of telomerase-based early-stage cancer diagnosis. Electronic supplementary information (ESI) available: TEM images of individual MB@Au NPs, results of dynamic light scattering analysis and extinction spectrum obtained using colorimetry detection. See DOI: 10.1039/c3nr04942f

Coronary Computed Tomography Angiography for Screening in Patients with Diabetes: Can Enhanced Detection of Subclinical Coronary Atherosclerosis Improve Outcome?

PubMed

Muhlestein, Joseph Brent; Moreno, Fidela Ll

2016-11-01

It is well known that there is a very high risk of cardiovascular complications among diabetic patients. In spite of all efforts at aggressive control of diabetes and its complications, the incidence of cardiovascular morbidity and mortality remains high, including in patients with no prior symptoms, underscoring a possible advantage for appropriate screening of asymptomatic patients for the presence of obstructive coronary artery disease (CAD). In this article, we sought primarily to review the results of studies designed to evaluate a possible role of coronary computed tomography angiography (CCTA) in the screening of asymptomatic diabetic patients for possible obstructive CAD. Our review of current literature indicates that there is still no method of CAD screening identified that has been shown to reduce the cardiovascular risk of asymptomatic diabetic patients. Therefore, the utility and value of screening for CAD in asymptomatic diabetic patients remains controversial. CCTA screening has shown promise and has been demonstrated to predict future risk, but as yet has not demonstrated improvement in the outcomes of these high-risk patients. At our present state of knowledge, aggressive risk factor reduction appears to be the most important primary prevention strategy for all asymptomatic high-risk diabetic patients. However, there remains a great need for better and more sensitive and specific screening methods, as well as more effective treatments that may allow us to more accurately target diabetic patients who really are at high risk. Further large randomized and well-controlled clinical trials may be necessary to determine whether screening for CAD can reduce cardiovascular event rates in patients with diabetes.

Detection of BRAF mutation in Chinese tumor patients using a highly sensitive antibody immunohistochemistry assay

NASA Astrophysics Data System (ADS)

Qiu, Tian; Lu, Haizhen; Guo, Lei; Huang, Wenting; Ling, Yun; Shan, Ling; Li, Wenbin; Ying, Jianming; Lv, Ning

2015-03-01

BRAF mutations can be found in various solid tumors. But accurate and reliable screening for BRAF mutation that is compatible for clinical application is not yet available. In this study, we used an automated immunohistochemistry (IHC) staining coupled with mouse monoclonal anti-BRAF V600E (VE1) primary antibody to screen the BRAF V600E mutation in 779 tumor cases, including 611 colorectal carcinomas (CRC), 127 papillary thyroid carcinomas (PTC) and 41 malignant melanomas. Among the 779 cases, 150 cases were positive for BRAF (V600E) staining, including 38 (of 611, 6%) CRCs, 102 (of 127, 80%) PTCs and 10 (of 41, 24%) malignant melanomas. Sanger sequencing and real-time PCR confirmed the sensitivity and specificity of IHC staining for the V600E mutation are 100% and 99%, respectively. Therefore, our study demonstrates that the fully automated IHC is a reliable tool to determine BRAF mutation status in CRC, PTC and melanoma and can be used for routine clinical screen.

Screening for Binge Eating Disorders Using the Patient Health Questionnaire in a Community Sample

PubMed Central

Striegel-Moore, Ruth H.; Perrin, Nancy; DeBar, Lynn; Wilson, G. Terence; Rosselli, Francine; Kraemer, Helena C.

2009-01-01

Objective To examine the operating characteristics of the Patient Health Questionnaire eating disorder module (PHQ-ED) for identifying bulimia nervosa/binge eating disorder (BN/BED) or recurrent binge eating (RBE) in a community sample, and to compare true positive (TP) versus false positive (FP) cases on clinical validators. Method 259 screen positive individuals and a random sample of 89 screen negative cases completed a diagnostic interview. Sensitivity, specificity, and Positive Predictive Value (PPV) were calculated. TP and FP cases were compared using t-tests and Chi-Square tests. Results The PHQ-ED had high sensitivity (100%) and specificity (92%) for detecting BN/BED or RBE, but PPV was low (15% or 19%). TP and FP cases did not differ significantly on frequency of subjective bulimic episodes, objective overeating, restraint, on BMI, and on self-rated health. Conclusions The PHQ-ED is recommended for use in large populations only in conjunction with follow-up questions to rule out cases without objective bulimic episodes. PMID:19424976

Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus-related oropharyngeal cancer.

PubMed

Dahlstrom, Kristina R; Anderson, Karen S; Field, Matthew S; Chowell, Diego; Ning, Jing; Li, Nan; Wei, Qingyi; Li, Guojun; Sturgis, Erich M

2017-12-15

Because of the current epidemic of human papillomavirus (HPV)-related oropharyngeal cancer (OPC), a screening strategy is urgently needed. The presence of serum antibodies to HPV-16 early (E) antigens is associated with an increased risk for OPC. The purpose of this study was to evaluate the diagnostic accuracy of antibodies to a panel of HPV-16 E antigens in screening for OPC. This case-control study included 378 patients with OPC, 153 patients with nonoropharyngeal head and neck cancer (non-OPC), and 782 healthy control subjects. The tumor HPV status was determined with p16 immunohistochemistry and HPV in situ hybridization. HPV-16 E antibody levels in serum were identified with an enzyme-linked immunosorbent assay. A trained binary logistic regression model based on the combination of all E antigens was predefined and applied to the data set. The sensitivity and specificity of the assay for distinguishing HPV-related OPC from controls were calculated. Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals for the association of head and neck cancer with the antibody status. Of the 378 patients with OPC, 348 had p16-positive OPC. HPV-16 E antibody levels were significantly higher among patients with p16-positive OPC but not among patients with non-OPC or among controls. Serology showed high sensitivity and specificity for HPV-related OPC (binary classifier: 83% sensitivity and 99% specificity for p16-positive OPC). A trained binary classification algorithm that incorporates information about multiple E antibodies has high sensitivity and specificity and may be advantageous for risk stratification in future screening trials. Cancer 2017;123:4886-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

Optimizing multi-dimensional high throughput screening using zebrafish

PubMed Central

Truong, Lisa; Bugel, Sean M.; Chlebowski, Anna; Usenko, Crystal Y.; Simonich, Michael T.; Massey Simonich, Staci L.; Tanguay, Robert L.

2016-01-01

The use of zebrafish for high throughput screening (HTS) for chemical bioactivity assessments is becoming routine in the fields of drug discovery and toxicology. Here we report current recommendations from our experiences in zebrafish HTS. We compared the effects of different high throughput chemical delivery methods on nominal water concentration, chemical sorption to multi-well polystyrene plates, transcription responses, and resulting whole animal responses. We demonstrate that digital dispensing consistently yields higher data quality and reproducibility compared to standard plastic tip-based liquid handling. Additionally, we illustrate the challenges in using this sensitive model for chemical assessment when test chemicals have trace impurities. Adaptation of these better practices for zebrafish HTS should increase reproducibility across laboratories. PMID:27453428

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency.

PubMed

Cressman, Sonya; Peacock, Stuart J; Tammemägi, Martin C; Evans, William K; Leighl, Natasha B; Goffin, John R; Tremblay, Alain; Liu, Geoffrey; Manos, Daria; MacEachern, Paul; Bhatia, Rick; Puksa, Serge; Nicholas, Garth; McWilliams, Annette; Mayo, John R; Yee, John; English, John C; Pataky, Reka; McPherson, Emily; Atkar-Khattra, Sukhinder; Johnston, Michael R; Schmidt, Heidi; Shepherd, Frances A; Soghrati, Kam; Amjadi, Kayvan; Burrowes, Paul; Couture, Christian; Sekhon, Harmanjatinder S; Yasufuku, Kazuhiro; Goss, Glenwood; Ionescu, Diana N; Hwang, David M; Martel, Simon; Sin, Don D; Tan, Wan C; Urbanski, Stefan; Xu, Zhaolin; Tsao, Ming-Sound; Lam, Stephen

2017-08-01

Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited. Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency. Use of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non-lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention. Non-lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and screening may even offer cost savings if noncurative treatment costs continue to rise. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Efficient exploration of chemical space by fragment-based screening.

PubMed

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

2014-01-01

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

Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

PubMed

Camarata, Andrew S; Switchenko, Jeffrey M; Demidenko, Eugene; Flood, Ann B; Swartz, Harold M; Ali, Arif N

2016-04-01

Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.

Comparison of clinical and analytical performance of the Abbott Realtime High Risk HPV test to the performance of hybrid capture 2 in population-based cervical cancer screening.

PubMed

Poljak, Mario; Ostrbenk, Anja; Seme, Katja; Ucakar, Veronika; Hillemanns, Peter; Bokal, Eda Vrtacnik; Jancar, Nina; Klavs, Irena

2011-05-01

The clinical performance of the Abbott RealTime High Risk HPV (human papillomavirus) test (RealTime) and that of the Hybrid Capture 2 HPV DNA test (hc2) were prospectively compared in the population-based cervical cancer screening setting. In women >30 years old (n = 3,129), the clinical sensitivity of RealTime for detection of cervical intraepithelial neoplasia of grade 2 (CIN2) or worse (38 cases) and its clinical specificity for lesions of less than CIN2 (3,091 controls) were 100% and 93.3%, respectively, and those of hc2 were 97.4% and 91.8%, respectively. A noninferiority score test showed that the clinical specificity (P < 0.0001) and clinical sensitivity (P = 0.011) of RealTime were noninferior to those of hc2 at the recommended thresholds of 98% and 90%. In the total study population (women 20 to 64 years old; n = 4,432; 57 cases, 4,375 controls), the clinical sensitivity and specificity of RealTime were 98.2% and 89.5%, and those of hc2 were 94.7% and 87.7%, respectively. The analytical sensitivity and analytical specificity of RealTime in detecting targeted HPV types evaluated with the largest sample collection to date (4,479 samples) were 94.8% and 99.8%, and those of hc2 were 93.4% and 97.8%, respectively. Excellent analytical agreement between the two assays was obtained (kappa value, 0.84), while the analytical accuracy of RealTime was significantly higher than that of hc2. RealTime demonstrated high intralaboratory reproducibility and interlaboratory agreement with 500 samples retested 61 to 226 days after initial testing in two different laboratories. RealTime can be considered to be a reliable and robust HPV assay clinically comparable to hc2 for the detection of CIN2+ lesions in a population-based cervical cancer screening setting.

Comparison of the Microlife blood pressure monitor with the Omron blood pressure monitor for detecting atrial fibrillation.

PubMed

Wiesel, Joseph; Arbesfeld, Benjamin; Schechter, David

2014-10-01

Screening for atrial fibrillation (AF) by assessing the pulse is recommended in high-risk patients. Some clinical trials demonstrated that the Microlife blood pressure monitor (BPM) with AF detection is more accurate than pulse palpation. This led to a change in practice guidelines in the United Kingdom where AF screening with the Microlife device is recommended instead of pulse palpation. Many BPMs have irregular heart beat detection, but they have not been shown to detect AF reliably. Recently, one study, in a highly select population, suggested that the Omron BPM with irregular heart beat detection has a higher sensitivity for AF than the Microlife BPM. We compared the Microlife and Omron BPMs to electrocardiographic readings for AF detection in general cardiology patients. Inclusion criteria were age≥50 years without a pacemaker or defibrillator. A total of 199 subjects were enrolled, 30 with AF. Each subject had a 12-lead electrocardiography, 1 Omron BPM reading, and 3 Microlife BPM readings as per device instructions. The Omron device had a sensitivity of 30% (95% confidence interval [CI] 15.4% to 49.1%) with the sensitivity for the first Microlife reading of 97% (95% CI 81.4% to 100%) and the Microlife readings using the majority rule (AF positive if at least 2 of 3 individual readings were positive for AF) of 100% (95% CI 85.9% to 100%). Specificity for the Omron device was 97% (95% CI 92.5% to 99.2%) and for the first Microlife reading of 90% (95% CI 83.8% to 94.2%) and for the majority rule Microlife device of 92% (95% CI 86.2% to 95.7%; p<0.0001). The specificity of both devices is acceptable, but only the Microlife BPM has a sensitivity value that is high enough to be used for AF screening in clinical practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Low-background gamma spectroscopy at the Boulby Underground Laboratory

NASA Astrophysics Data System (ADS)

Scovell, P. R.; Meehan, E.; Araújo, H. M.; Dobson, J.; Ghag, C.; Kraus, H.; Kudryavtsev, V. A.; Liu, X.-. R.; Majewski, P.; Paling, S. M.; Preece, R. M.; Saakyan, R.; Tomás, A.; Toth, C.; Yeoman, L. M.

2018-01-01

The Boulby Underground Germanium Suite (BUGS) comprises three low-background, high-purity germanium detectors operating in the Boulby Underground Laboratory, located 1.1 km underground in the north-east of England, UK. BUGS utilises three types of detector to facilitate a high-sensitivity, high-throughput radio-assay programme to support the development of rare-event search experiments. A Broad Energy Germanium (BEGe) detector delivers sensitivity to low-energy gamma-rays such as those emitted by 210Pb and 234Th. A Small Anode Germanium (SAGe) well-type detector is employed for efficient screening of small samples. Finally, a standard p-type coaxial detector provides fast screening of standard samples. This paper presents the steps used to characterise the performance of these detectors for a variety of sample geometries, including the corrections applied to account for cascade summing effects. For low-density materials, BUGS is able to radio-assay to specific activities down to 3.6mBqkg-1 for 234Th and 6.6mBqkg-1 for 210Pb both of which have uncovered some significant equilibrium breaks in the 238U chain. In denser materials, where gamma-ray self-absorption increases, sensitivity is demonstrated to specific activities of 0.9mBqkg-1 for 226Ra, 1.1mBqkg-1 for 228Ra, 0.3mBqkg-1 for 224Ra, and 8.6mBqkg-1 for 40K with all upper limits at a 90% confidence level. These meet the requirements of most screening campaigns presently under way for rare-event search experiments, such as the LUX-ZEPLIN (LZ) dark matter experiment. We also highlight the ability of the BEGe detector to probe the X-ray fluorescence region which can be important to identify the presence of radioisotopes associated with neutron production; this is of particular relevance in experiments sensitive to nuclear recoils.

Evaluation of the GARD assay in a blind Cosmetics Europe study.

PubMed

Johansson, Henrik; Gradin, Robin; Forreryd, Andy; Agemark, Maria; Zeller, Kathrin; Johansson, Angelica; Larne, Olivia; van Vliet, Erwin; Borrebaeck, Carl; Lindstedt, Malin

2017-01-01

Chemical hypersensitivity is an immunological response towards foreign substances, commonly referred to as sensitizers, which gives rise primarily to the clinical symptoms known as allergic contact dermatitis. For the purpose of mitigating risks associated with consumer products, chemicals are screened for sensitizing effects. Historically, such predictive screenings have been performed using animal models. However, due to industrial and regulatory demand, animal models for the purpose of sensitization assessment are being replaced by non-animal testing methods, a global trend that is spreading across industries and market segments. To meet this demand, the Genomic Allergen Rapid Detection (GARD) assay was developed. GARD is a novel, cell-based assay that utilizes the innate recognition of xenobiotic substances by dendritic cells, as measured by a multivariate readout of genomic biomarkers. Following cellular stimulation, chemicals are classified as sensitizers or non-sensitizers based on induced transcriptional profiles. Recently, a number of non-animal methods were comparatively evaluated by Cosmetics Europe, using a coherent and blinded test panel of reference chemicals with human and local lymph node assay data, comprising a wide range of sensitizers and non-sensitizers. The outcome of the GARD assay is presented in this paper. It was demonstrated that GARD is a highly functional assay with a predictive performance of 83% in this Cosmetics Europe dataset. The average accumulated predictive accuracy of GARD across independent datasets was 86% for skin sensitization hazard.

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

PubMed Central

Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene; Braga, Rodolpho C.; Thornton, Thomas; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2016-01-01

Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin sensitization responses for a set of 135 unique chemicals was low (R = 28-43%), although several chemical classes had high concordance. We have succeeded to develop predictive QSAR models of all available human data with the external correct classification rate of 71%. A consensus model integrating concordant QSAR predictions and LLNA results afforded a higher CCR of 82% but at the expense of the reduced external dataset coverage (52%). We used the developed QSAR models for virtual screening of CosIng database and identified 1061 putative skin sensitizers; for seventeen of these compounds, we found published evidence of their skin sensitization effects. Models reported herein provide more accurate alternative to LLNA testing for human skin sensitization assessment across diverse chemical data. In addition, they can also be used to guide the structural optimization of toxic compounds to reduce their skin sensitization potential. PMID:28630595

Associations of reward sensitivity with food consumption, activity pattern, and BMI in children.

PubMed

De Decker, Annelies; Sioen, Isabelle; Verbeken, Sandra; Braet, Caroline; Michels, Nathalie; De Henauw, Stefaan

2016-05-01

In the current study, the associations of reward sensitivity with weight related behaviors and body mass index were investigated in a general population sample of 443 Flemish children (50.3% boys) aged 5.5-12 years. Cross-sectional data on palatable food consumption frequency, screen time, physical activity, parental education level and measured length and weight were collected. The Drive subscale of the 'Behavioral Inhibition Scale/Behavioral Activation Scale' was used as a short method to measure reward sensitivity. A significant positive association of reward sensitivity with the fast food and sweet drink consumption frequency was found. Furthermore, a significant positive association of reward sensitivity with the z-score of body mass index was demonstrated, which explained additional variance to the variance explained by palatable food consumption frequency, screen time, physical activity and parental education level. Hence, the assessment of reward sensitivity may have an added value to the assessment of weight-related behavior indicators when evaluating the determinants of overweight in a child. In sum, children high in reward sensitivity might be more attracted to fast food and sweet drinks, and hence, might be more vulnerable to develop unfavorable food habits and overweight. These findings suggest that considering inter-individual differences in reward sensitivity is of importance in future childhood obesity prevention campaigns. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age-specific performance of careHPV versus Papanicolaou and visual inspection of cervix with acetic acid testing in a primary cervical cancer screening.

PubMed

Labani, Satyanarayana; Asthana, Smita

2016-01-01

Human papillomavirus (HPV) is recommended as a primary screening tool for cervical screening. Assessment of age-specific performance of newer HPV careHPV DNA testing is important as risk of cervical intraepithelial neoplasia (CIN) varies at different ages. We aim to evaluate careHPV in comparison to Papanicolaou (Pap) test and visual inspection of the cervix with acetic acid (VIA) cervical screening tests for the detection of high-grade CIN. The cross sectional study was conducted in a rural population of North India. Ever-married women 30-59 years of age were invited for screening by careHPV (self-collected vaginal and physician-collected cervical samples), Pap test and VIA. Associations for trend in age for detecting histological-confirmed CINII+ and CINIII+ for each screening test were evaluated. Age-specific association with each screening test was evaluated. Of a total of 7761 women invited, 5032 were screened and analysis was performed on 4658 with all screen test results. No significant (p>0.05) association of age for any screening test in the detection of CINII+ or CINIII+ was observed. For the older age group, cervical HPV (CHPV) showed high sensitivity and specificity for CINII+ detection. Specificity of CHPV or vaginal HPV (VHPV) was equal or higher than Pap in all age groups. Cervical screening options of CHPV or VHPV, or Pap, performed equally in the younger age group while CHPV might be an option for all ages in the detection of high-grade CIN. 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/

Sensitivity and Specificity of 2 Autism Screeners Among Referred Children Between 16 and 48 Months of Age.

PubMed

Salisbury, Louisa A; Nyce, Jonathan D; Hannum, Charles D; Sheldrick, R Christopher; Perrin, Ellen C

2018-04-01

Autism screening is recommended by the American Academy of Pediatrics and the Centers for Disease Control and Prevention at ages 18 and 24 months. Popular screening tests have been validated for the age range of 16 to 30 months. However, only a minority of children with autism spectrum disorder (ASD) are identified by age 3 years, and many are not identified until after they enter school. Thus, we aimed to measure the sensitivity and specificity of 2 available screening tests for ASDs in children older than 30 months. We assessed the sensitivity and specificity of 2 ASD screening tools administered to parents of children who were referred to a developmental clinic between the ages of 16 and 48 months: the Modified Checklist for Autism in Toddlers (M-CHAT) and the Parent's Observations of Social Interactions (POSI), which is a component of a comprehensive screening instrument called, the Survey of Well-being of Young Children. Both the M-CHAT and the POSI had acceptable sensitivity (≥75%) among children across the age range studied. Their specificity was limited by the fact that the study was conducted in a developmental referral clinic. Two readily available screening tools, the POSI and the M-CHAT, have acceptable sensitivity in evaluating risk for autism in children at least to age 48 months. Further research should investigate their sensitivity and specificity when used in primary care settings.

Evaluation of the fluorescent gonococcal test-heated.

PubMed Central

Gaafar, H A

1976-01-01

In a 1-year evaluation of the indirect fluorescent antibody test for gonorrhea, 16,127 specimens from low-and high-risk groups were examined, and the results were compared with culture, history of exposure to a known patient, and clinical signs and symptoms. The results confirmed the usefulness of the indirect fluorescent antibody test for gonorrhea as a screening procedure, especially for women in the low-risk group. The test is more economic and probably more sensitive than culture for mass screening of asymptomatic women. PMID:791965

Multicolor fluorescent biosensor for multiplexed detection of DNA.

PubMed

Hu, Rong; Liu, Tao; Zhang, Xiao-Bing; Huan, Shuang-Yan; Wu, Cuichen; Fu, Ting; Tan, Weihong

2014-05-20

Development of efficient methods for highly sensitive and rapid screening of specific oligonucleotide sequences is essential to the early diagnosis of serious diseases. In this work, an aggregated cationic perylene diimide (PDI) derivative was found to efficiently quench the fluorescence emission of a variety of anionic oligonucleotide-labeled fluorophores that emit at wavelengths from the visible to NIR region. This broad-spectrum quencher was then adopted to develop a multicolor biosensor via a label-free approach for multiplexed fluorescent detection of DNA. The aggregated perylene derivative exhibits a very high quenching efficiency on all ssDNA-labeled dyes associated with biosensor detection, having efficiency values of 98.3 ± 0.9%, 97 ± 1.1%, and 98.2 ± 0.6% for FAM, TAMRA, and Cy5, respectively. An exonuclease-assisted autocatalytic target recycling amplification was also integrated into the sensing system. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity toward target DNA, resulting in a detection limit of 20 pM, which is about 50-fold lower than that of traditional unamplified homogeneous fluorescent assay methods. The quencher did not interfere with the catalytic activity of nuclease, and the biosensor could be manipulated in either preaddition or postaddition manner with similar sensitivity. Moreover, the proposed sensing system allows for simultaneous and multicolor analysis of several oligonucleotides in homogeneous solution, demonstrating its potential application in the rapid screening of multiple biotargets.

Nuclear morphology for the detection of alterations in bronchial cells from lung cancer: an attempt to improve sensitivity and specificity.

PubMed

Fafin-Lefevre, Mélanie; Morlais, Fabrice; Guittet, Lydia; Clin, Bénédicte; Launoy, Guy; Galateau-Sallé, Françoise; Plancoulaine, Benoît; Herlin, Paulette; Letourneux, Marc

2011-08-01

To identify which morphologic or densitometric parameters are modified in cell nuclei from bronchopulmonary cancer based on 18 parameters involving shape, intensity, chromatin, texture, and DNA content and develop a bronchopulmonary cancer screening method relying on analysis of sputum sample cell nuclei. A total of 25 sputum samples from controls and 22 bronchial aspiration samples from patients presenting with bronchopulmonary cancer who were professionally exposed to cancer were used. After Feulgen staining, 18 morphologic and DNA content parameters were measured on cell nuclei, via image cytom- etry. A method was developed for analyzing distribution quantiles, compared with simply interpreting mean values, to characterize morphologic modifications in cell nuclei. Distribution analysis of parameters enabled us to distinguish 13 of 18 parameters that demonstrated significant differences between controls and cancer cases. These parameters, used alone, enabled us to distinguish two population types, with both sensitivity and specificity > 70%. Three parameters offered 100% sensitivity and specificity. When mean values offered high sensitivity and specificity, comparable or higher sensitivity and specificity values were observed for at least one of the corresponding quantiles. Analysis of modification in morphologic parameters via distribution analysis proved promising for screening bronchopulmonary cancer from sputum.

An improvement of LLNA:DA to assess the skin sensitization potential of chemicals.

PubMed

Zhang, Hongwei; Shi, Ying; Wang, Chao; Zhao, Kangfeng; Zhang, Shaoping; Wei, Lan; Dong, Li; Gu, Wen; Xu, Yongjun; Ruan, Hongjie; Zhi, Hong; Yang, Xiaoyan

2017-01-01

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

Sensitivity and Specificity of a Five-Minute Cognitive Screening Test in Patients With Heart Failure.

PubMed

Cameron, Janette D; Gallagher, Robyn; Pressler, Susan J; McLennan, Skye N; Ski, Chantal F; Tofler, Geoffrey; Thompson, David R

2016-02-01

Cognitive impairment occurs in up to 80% of patients with heart failure (HF). The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) recommend a 5-minute cognitive screening protocol that has yet to be psychometrically evaluated in HF populations. The aim of this study was to conduct a secondary analysis of the sensitivity and specificity of the NINDS-CSN brief cognitive screening protocol in HF patients. The Montreal Cognitive Assessment (MoCA) was administered to 221 HF patients. The NINDS-CSN screen comprises 3 MoCA items, with lower scores indicating poorer cognitive function. Receiver operator characteristic (ROC) curves were constructed, determining the sensitivity, specificity and appropriate cutoff scores of the NINDS-CSN screen. In an HF population aged 76 ± 12 years, 136 (62%) were characterized with cognitive impairment (MoCA <26). Scores on the NINDS-CSN screen ranged from 3-11. The area under the receiver operating characteristic curve indicated good accuracy in screening for cognitive impairment (0.88; P < .01; 95% CI 0.83-0.92). A cutoff score of ≤9 provided 89% sensitivity and 71% specificity. The NINDS-CSN protocol offers clinicians a feasible telephone method to screen for cognitive impairment in patients with HF. Future studies should include a neuropsychologic battery to more comprehensively examine the diagnostic accuracy of brief cognitive screening protocols. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical Validity of hearScreen™ Smartphone Hearing Screening for School Children.

PubMed

Mahomed-Asmail, Faheema; Swanepoel, De Wet; Eikelboom, Robert H; Myburgh, Hermanus C; Hall, James

2016-01-01

The study aimed to determine the validity of a smartphone hearing screening technology (hearScreen™) compared with conventional screening audiometry in terms of (1) sensitivity and specificity, (2) referral rate, and (3) test time. One thousand and seventy school-age children in grades 1 to 3 (8 ± 1.1 average years) were recruited from five public schools. Children were screened twice, once using conventional audiometry and once with the smartphone hearing screening. Screening was conducted in a counterbalanced sequence, alternating initial screen between conventional or smartphone hearing screening. No statistically significant difference in performance between techniques was noted, with smartphone screening demonstrating equivalent sensitivity (75.0%) and specificity (98.5%) to conventional screening audiometry. While referral rates were lower with the smartphone screening (3.2 vs. 4.6%), it was not significantly different (p > 0.05). Smartphone screening (hearScreen™) was 12.3% faster than conventional screening. Smartphone hearing screening using the hearScreen™ application is accurate and time efficient.

Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

PubMed

Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

2015-10-01

To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

A Protein Microarray ELISA for the Detection of Botulinum neurotoxin A

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

Varnum, Susan M.

An enzyme-linked immunosorbent assay (ELISA) microarray was developed for the specific and sensitive detection of botulinum neurotoxin A (BoNT/A), using high-affinity recombinant monoclonal antibodies against the receptor binding domain of the heavy chain of BoNT/A. The ELISA microarray assay, because of its sensitivity, offers a screening test with detection limits comparable to the mouse bioassay, with results available in hours instead of days.

Cost-effectiveness of HPV vaccination in the context of high cervical cancer incidence and low screening coverage.

PubMed

Võrno, Triin; Lutsar, Katrin; Uusküla, Anneli; Padrik, Lee; Raud, Terje; Reile, Rainer; Nahkur, Oliver; Kiivet, Raul-Allan

2017-11-01

Estonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening. A Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN1-3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88years (up to 100years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%. Vaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367-21,711, €5142-21,800 and €4563-18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage. Vaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine used. Copyright © 2017 Elsevier Ltd. All rights reserved.

SFN-SIQ, SFNSL and skin biopsy of 55 cases with small fibre involvement.

PubMed

Sun, Bo; Li, Yifan; Liu, Lizhi; Chen, Zhaohui; Ling, Li; Yang, Fei; Liu, Jiexiao; Liu, Hong; Huang, Xusheng

2018-05-01

Purpose/aim of the study: To date, there are no validated screening scales for small fibre neuropathy. This study investigated the small-fibre neuropathy and the symptom inventory questionnaire as well as the small fibre neuropathy screening list for small fibre neuropathy diagnosis. Fifty-five patients were divided into small fibre neuropathy and mixed fibre damage groups. Relevant scales, nerve conduction studies and skin biopsies were performed. Relationships between the intraepidermal nerve fibre density and different scales as well as the diagnostic and cut-off values (score at which Youden's index is largest) were determined. Compared with healthy Chinese participants, 20 patients were diagnosed with small fibre neuropathy. Intraepidermal nerve fibre density was moderately and highly correlated with the small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list, respectively. The diagnostic values were moderate and high for the small fibre neuropathy-symptom inventory questionnaire (cut-off value = 5, sensitivity = 80%, specificity = 81.8%) and small fibre neuropathy screening list (cut-off value = 8, sensitivity = 94.1%, specificity = 90.9%), respectively. There were no significant differences in the visual analogue scale between the small fibre neuropathy group, mixed small and large fibre neuropathy group, pure large fibre neuropathy group and the normal group. Small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list represent potential small fibre neuropathy screening tools. Abbreviations EMG electromyography ENA anti-extractable nuclear antigens ESR erythrocyte sedimentation rate IENFD intraepidermal nerve fibre density IGT impaired glucose tolerance NCS nerve conduction studies NDS neuropathy disability score OGTT oral glucose tolerance test PGP protein gene product PN peripheral neuropathy ROC receiver operating characteristic curve ROC-AUC area under the ROC curve SFN small fibre neuropathy SFN-SIQ small-fibre neuropathy and symptom inventory questionnaire SFNSL small fibre neuropathy screening list VAS visual analogue scale WHO World Health Organization.

Identification of Patients with Sleep Disordered Breathing: Comparing the Four-Variable Screening Tool, STOP, STOP-Bang, and Epworth Sleepiness Scales

PubMed Central

Silva, Graciela E.; Vana, Kimberly D.; Goodwin, James L.; Sherrill, Duane L.; Quan, Stuart F.

2011-01-01

Study Objective: The Epworth Sleepiness Scale (ESS) has been used to detect patients with potential sleep disordered breathing (SDB). Recently, a 4-Variable screening tool was proposed to identify patients with SDB, in addition to the STOP and STOP-Bang questionnaires. This study evaluated the abilities of the 4-Variable screening tool, STOP, STOP-Bang, and ESS questionnaires in identifying subjects at risk for SDB. Methods: A total of 4,770 participants who completed polysomnograms in the baseline evaluation of the Sleep Heart Health Study (SHHS) were included. Subjects with RDIs ≥ 15 and ≥ 30 were considered to have moderate-to-severe or severe SDB, respectively. Variables were constructed to approximate those in the questionnaires. The risk of SDB was calculated by the 4-Variable screening tool according to Takegami et al. The STOP and STOP-Bang questionnaires were evaluated including variables for snoring, tiredness/sleepiness, observed apnea, blood pressure, body mass index, age, neck circumference, and gender. Sleepiness was evaluated using the ESS questionnaire and scores were dichotomized into < 11 and ≥ 11. Results: The STOP-Bang questionnaire had higher sensitivity to predict moderate-to-severe (87.0%) and severe (70.4%) SDB, while the 4-Variable screening tool had higher specificity to predict moderate-to-severe and severe SDB (93.2% for both). Conclusions: In community populations such as the SHHS, high specificities may be more useful in excluding low-risk patients, while avoiding false positives. However, sleep clinicians may prefer to use screening tools with high sensitivities, like the STOP-Bang, in order to avoid missing cases that may lead to adverse health consequences and increased healthcare costs. Citation: Silva GE; Vana KD; Goodwin JL; Sherrill DL; Quan SF. Identification of patients with sleep disordered breathing: comparing the Four-Variable screening tool, STOP, STOP-Bang, and Epworth Sleepiness Scales. J Clin Sleep Med 2011;7(5):467-472. PMID:22003341

Sensitivity and specificity enhanced enzyme-linked immunosorbent assay by rational hapten modification and heterogeneous antibody/coating antigen combinations for the detection of melamine in milk, milk powder and feed samples.

PubMed

Cao, Biyun; Yang, Hong; Song, Juan; Chang, Huafang; Li, Shuqun; Deng, Anping

2013-11-15

The adulteration of food products with melamine has led to an urgent requirement for sensitive, specific, rapid and reliable quantitative/screening methods. To enhance the sensitivity and specificity of the enzyme-linked immunosorbent assay (ELISA) for the detection of melamine in milk, milk powder and feed samples, rational hapten modification and heterogeneous antibody/coating antigen combinations were adopted. Three melamine derivatives with different length of carboxylic spacer at the end were synthesized and linked to carrier proteins for the production of immunogens and coating antigens. Monoclonal antibody against melamine was produced by hybridoma technology. Under optimal experimental conditions, the standard curves of the ELISAs for melamine were constructed in range of 0.1-100 ng mL(-1). The sensitivity was 10-300 times enhanced compared to those in the published literatures. The cross-reactivity values of the ELISAs also demonstrated the assays exhibited high specificity. Five samples were spiked with melamine at different concentrations and detected by the ELISA. The recovery rates of 72.8-123.0% and intra-assay coefficients of variation of 0.8-18.9% (n=3) were obtained. The ELISA for milk sample was confirmed by high-performance liquid chromatography with a high correlation coefficient of 0.9902 (n=6). The proposed ELISA was proven to be a feasible quantitative/screening method for melamine analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Deep-UV-sensitive high-frame-rate backside-illuminated CCD camera developments

NASA Astrophysics Data System (ADS)

Dawson, Robin M.; Andreas, Robert; Andrews, James T.; Bhaskaran, Mahalingham; Farkas, Robert; Furst, David; Gershstein, Sergey; Grygon, Mark S.; Levine, Peter A.; Meray, Grazyna M.; O'Neal, Michael; Perna, Steve N.; Proefrock, Donald; Reale, Michael; Soydan, Ramazan; Sudol, Thomas M.; Swain, Pradyumna K.; Tower, John R.; Zanzucchi, Pete

2002-04-01

New applications for ultra-violet imaging are emerging in the fields of drug discovery and industrial inspection. High throughput is critical for these applications where millions of drug combinations are analyzed in secondary screenings or high rate inspection of small feature sizes over large areas is required. Sarnoff demonstrated in1990 a back illuminated, 1024 X 1024, 18 um pixel, split-frame-transfer device running at > 150 frames per second with high sensitivity in the visible spectrum. Sarnoff designed, fabricated and delivered cameras based on these CCDs and is now extending this technology to devices with higher pixel counts and higher frame rates through CCD architectural enhancements. The high sensitivities obtained in the visible spectrum are being pushed into the deep UV to support these new medical and industrial inspection applications. Sarnoff has achieved measured quantum efficiencies > 55% at 193 nm, rising to 65% at 300 nm, and remaining almost constant out to 750 nm. Optimization of the sensitivity is being pursued to tailor the quantum efficiency for particular wavelengths. Characteristics of these high frame rate CCDs and cameras will be described and results will be presented demonstrating high UV sensitivity down to 150 nm.

High-throughput screening technologies for botulinum neurotoxins.

PubMed

Bompiani, Kristin M; Dickerson, Tobin J

2014-01-01

Botulinum neurotoxins (BoNTs) are a class of bacterial neurotoxins that are the most potent toxic compounds reported to date. Exposure to relatively low concentrations of the toxin protein can result in major muscle paralysis, which may result in death in severe cases. In addition to their role in natural human disease, BoNTs are currently under close scrutiny because of their potential to be used as biowarfare agents. Clinical treatment options for botulism are currently limited, and finite stockpiles of antitoxin exist. In light of current bioterrorist threats, researchers have focused on identifying new molecules that can be applied to either sensitive toxin detection or improved clinical treatment. High-throughput screening (HTS) is a laboratory technique commonly employed to screen large libraries of diverse compounds based on specific compound binding capabilities or function. Here we review existing HTS platforms that have been applied to identify novel BoNT diagnostic or therapeutic agents. HTS platforms for screening antibodies, peptides, small molecules, and aptamers are described, as well as the screening results and current progress of the identified compounds.

Sensitivity and specificity of a new automated system for the detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus nucleic acid in blood and plasma donations.

PubMed

Galel, Susan A; Simon, Toby L; Williamson, Phillip C; AuBuchon, James P; Waxman, Dan A; Erickson, Yasuko; Bertuzis, Rasa; Duncan, John R; Malhotra, Khushbeer; Vaks, Jeffrey; Huynh, Nancy; Pate, Lisa Lee

2018-03-01

Use of nucleic acid testing (NAT) in donor infectious disease screening improves transfusion safety. Advances in NAT technology include improvements in assay sensitivity and system automation, and real-time viral target discrimination in multiplex assays. This article describes the sensitivity and specificity of cobas MPX, a multiplex assay for detection of human immunodeficiency virus (HIV)-1 Group M, HIV-2 and HIV-1 Group O RNA, HCV RNA, and HBV DNA, for use on the cobas 6800/8800 Systems. The specificity of cobas MPX was evaluated in samples from donors of blood and source plasma in the United States. Analytic sensitivity was determined with reference standards. Infectious window periods (WPs) before NAT detectability were calculated for current donor screening assays. The specificity of cobas MPX was 99.946% (99.883%-99.980%) in 11,203 blood donor samples tested individually (IDT), 100% (99.994%-100%) in 63,012 donor samples tested in pools of 6, and 99.994% (99.988%-99.998%) in 108,306 source plasma donations tested in pools of 96. Seven HCV NAT-yield donations and one seronegative occult HBV infection were detected. Ninety-five percent and 50% detection limits in plasma (IU/mL) were 25.7 and 3.8 for HIV-1M, 7.0 and 1.3 for HCV, and 1.4 and 0.3 for HBV. The HBV WP was 1 to 4 days shorter than other donor screening assays by IDT. cobas MPX demonstrated high specificity in blood and source plasma donations tested individually and in pools. High sensitivity, in particular for HBV, shortens the WP and may enhance detection of occult HBV. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Diagnostic performance of short portable mental status questionnaire for screening dementia among patients attending cognitive assessment clinics in Singapore.

PubMed

Malhotra, Chetna; Chan, Angelique; Matchar, David; Seow, Dennis; Chuo, Adeline; Do, Young Kyung

2013-07-01

The Short Portable Mental Status Questionnaire (SPMSQ) is a brief cognitive screening instrument, which is easy to use by a healthcare worker with little training. However, the validity of this instrument has not been established in Singapore. Thus, the primary aim of this study was to determine the diagnostic performance of SPMSQ for screening dementia among patients attending outpatient cognitive assessment clinics and to assess whether the appropriate cut-off score varies by patient's age and education. A secondary aim of the study was to map the SPMSQ scores with Mini-Mental State Examination (MMSE) scores. SPMSQ and MMSE were administered by a trained interviewer to 127 patients visiting outpatient cognitive assessment clinics at the Singapore General Hospital, Changi General Hospital and Tan Tock Seng Hospital. The geriatricians at these clinics then diagnosed these patients with dementia or no dementia (reference standard). Sensitivity and specificity of SPMSQ with different cut-off points (number of errors) were calculated and compared to the reference standard using the Receiver Operator Characteristic (ROC) analysis. Correlation coefficient was also calculated between MMSE and SPMSQ scores. Based on the ROC analysis and a balance of sensitivity and specificity, the appropriate cut-off for SPMSQ was found to be 5 or more errors (sensitivity 78%, specificity 75%). The cut-off varied by education, but not by patient's age. There was a high correlation between SPMSQ and MMSE scores (r = 0.814, P <0.0001). Despite the advantage of being a brief screening instrument for dementia, the use of SPMSQ is limited by its low sensitivity and specificity, especially among patients with less than 6 years of education.

An evaluation of a rapid real time polymerase chain reaction assay for detection of group B streptococcus as part of a neonatal group B streptococcus prevention strategy.

PubMed

Money, Deborah; Dobson, Simon; Cole, Lesley; Karacabeyli, Eda; Blondel-Hill, Edith; Milner, Ruth; Thomas, Eva

2008-09-01

To evaluate the sensitivity, specificity, and feasibility of a rapid real-time polymerase chain reaction (PCR) test for group B streptococcus (GBS) completed during labour, compared with the standard culture test performed at 35 to 37 weeks' gestation. Women presenting to the maternity unit for term vaginal delivery had two vaginal/rectal samples collected. One swab was tested using a rapid PCR method (IDI-Strep B, Infectio Diagnostic [IDI] Inc., Sainte-Foy QC ), and the other was cultured after enrichment (intrapartum culture). Comparisons were made between these results and those of a culture-based screen at 35 to 37 weeks' gestation. Of the 190 women enrolled, 85% had results of the standard screen at 35 to 37 weeks available for comparison. The sensitivity and specificity of the standard 35- to 37-week screen were 84.3% (95% confidence interval [CI], 71.4-93.0) and 93.2% (95% CI 86.5-97.2) respectively, whereas the sensitivity and specificity of the rapid PCR were 90.7% (95% CI 79.7-96.9) and 97.6% (95% CI 93.1-99.5), respectively. The median reporting time for the rapid PCR test was 99 minutes (range 50-255). Results were available more than four hours before delivery in 81% of cases. In this Canadian centre, a rapid PCR test done at the time of labour (IDI-Strep B) demonstrated high sensitivity and specificity, comparable to the 35- to 37-week screen. The time to reporting results was acceptably short, allowing for timely administration of intrapartum prophylactic antibiotics.

Faecal immunochemical tests versus guaiac faecal occult blood tests: what clinicians and colorectal cancer screening programme organisers need to know.

PubMed

Tinmouth, Jill; Lansdorp-Vogelaar, Iris; Allison, James E

2015-08-01

Although colorectal cancer (CRC) is a common cause of cancer-related death, it is fortunately amenable to screening with faecal tests for occult blood and endoscopic tests. Despite the evidence for the efficacy of guaiac-based faecal occult blood tests (gFOBT), they have not been popular with primary care providers in many jurisdictions, in part because of poor sensitivity for advanced colorectal neoplasms (advanced adenomas and CRC). In order to address this issue, high sensitivity gFOBT have been recommended, however, these tests are limited by a reduction in specificity compared with the traditional gFOBT. Where colonoscopy is available, some providers have opted to recommend screening colonoscopy to their patients instead of faecal testing, as they believe it to be a better test. Newer methods for detecting occult human blood in faeces have been developed. These tests, called faecal immunochemical tests (FIT), are immunoassays specific for human haemoglobin. FIT hold considerable promise over the traditional guaiac methods including improved analytical and clinical sensitivity for CRC, better detection of advanced adenomas, and greater screenee participation. In addition, the quantitative FIT are more flexible than gFOBT as a numerical result is reported, allowing customisation of the positivity threshold. When compared with endoscopy, FIT are less sensitive for the detection of advanced colorectal neoplasms when only one time testing is applied to a screening population; however, this is offset by improved participation in a programme of annual or biennial screens and a better safety profile. This review will describe how gFOBT and FIT work and will present the evidence that supports the use of FIT over gFOBT, including the cost-effectiveness of FIT relative to gFOBT. Finally, specific issues related to FIT implementation will be discussed, particularly with respect to organised CRC screening programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Residential care/assisted living staff may detect undiagnosed dementia using the minimum data set cognition scale.

PubMed

Zimmerman, Sheryl; Sloane, Philip D; Williams, Christianna S; Dobbs, Debra; Ellajosyula, Ratnavalli; Braaten, Alyssa; Rupnow, Marcia F T; Kaufer, Daniel I

2007-09-01

To estimate the sensitivity, specificity, and reliability of the Minimum Data Set Cognition Scale (MDS-COGS) in screening for undetected dementia when completed by direct care staff in residential care/assisted living (RC/AL) facilities and secondarily to determine the prevalence of dementia in the sample. A cross-sectional study in which staff were trained to complete the MDS-COGS. Research interviewers and a neuropsychologist obtained information on each participant. Two neurologists reviewed the data and examined the participant, rendering a probable diagnosis of dementia/non-dementia diagnosis. MDS-COGS results were compared with the neurologists' determination. Fourteen RC/AL facilities in North Carolina. Data were collected from 50 staff on 166 residents without a diagnosis of dementia. In addition to the MDS-COGS, measures included a comprehensive neuropsychological battery. Depression and other neuropsychiatric symptoms were also assessed. Neurologists determined that 38% of participants had probable dementia. An MDS-COGS cutpoint of 2 was highly specific (0.97) but not very sensitive (0.49) for dementia. Test-retest and interrater agreement for a negative screen were high (88% and 93%, respectively). The MDS-COGS is a simple, brief screen that RC/AL staff can complete. It will identify with high specificity a subset of residents with undetected dementia, allowing rapid identification of those likely to need dementia care. Caution needs to be exercised in light of its low sensitivity, because some with milder dementia will not be detected. Further work is needed to determine whether staff can and will use the MDS-COGS as a trigger for more-thorough assessment and to guide care and improve outcomes.

Ultra-sensitive Sequencing Identifies High Prevalence of Clonal Hematopoiesis-Associated Mutations throughout Adult Life.

PubMed

Acuna-Hidalgo, Rocio; Sengul, Hilal; Steehouwer, Marloes; van de Vorst, Maartje; Vermeulen, Sita H; Kiemeney, Lambertus A L M; Veltman, Joris A; Gilissen, Christian; Hoischen, Alexander

2017-07-06

Clonal hematopoiesis results from somatic mutations in hematopoietic stem cells, which give an advantage to mutant cells, driving their clonal expansion and potentially leading to leukemia. The acquisition of clonal hematopoiesis-driver mutations (CHDMs) occurs with normal aging and these mutations have been detected in more than 10% of individuals ≥65 years. We aimed to examine the prevalence and characteristics of CHDMs throughout adult life. We developed a targeted re-sequencing assay combining high-throughput with ultra-high sensitivity based on single-molecule molecular inversion probes (smMIPs). Using smMIPs, we screened more than 100 loci for CHDMs in more than 2,000 blood DNA samples from population controls between 20 and 69 years of age. Loci screened included 40 regions known to drive clonal hematopoiesis when mutated and 64 novel candidate loci. We identified 224 somatic mutations throughout our cohort, of which 216 were coding mutations in known driver genes (DNMT3A, JAK2, GNAS, TET2, and ASXL1), including 196 point mutations and 20 indels. Our assay's improved sensitivity allowed us to detect mutations with variant allele frequencies as low as 0.001. CHDMs were identified in more than 20% of individuals 60 to 69 years of age and in 3% of individuals 20 to 29 years of age, approximately double the previously reported prevalence despite screening a limited set of loci. Our findings support the occurrence of clonal hematopoiesis-associated mutations as a widespread mechanism linked with aging, suggesting that mosaicism as a result of clonal evolution of cells harboring somatic mutations is a universal mechanism occurring at all ages in healthy humans. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Ab initio study of energy transfer rates and impact sensitivities of crystalline explosives.

PubMed

Bernstein, Jonathan

2018-02-28

Impact sensitivities of various crystalline explosives were predicted by means of plane wave-density functional theory calculations. Crystal structures and complete vibrational spectra of TATB, PETN, FOX7, TEX, 14DNI, and β-HMX molecular crystals were calculated. A correlation between the phonon-vibron coupling (which is proportionally related to the energy transfer rate between the phonon manifold and the intramolecular vibrational modes) and impact sensitivities of secondary explosives was found. We propose a method, based on ab initio calculations, for the evaluation of impact sensitivities, which consequently can assist in screening candidates for chemical synthesis of high energetic materials.

Ab initio study of energy transfer rates and impact sensitivities of crystalline explosives

NASA Astrophysics Data System (ADS)

Bernstein, Jonathan

2018-02-01

Impact sensitivities of various crystalline explosives were predicted by means of plane wave-density functional theory calculations. Crystal structures and complete vibrational spectra of TATB, PETN, FOX7, TEX, 14DNI, and β-HMX molecular crystals were calculated. A correlation between the phonon-vibron coupling (which is proportionally related to the energy transfer rate between the phonon manifold and the intramolecular vibrational modes) and impact sensitivities of secondary explosives was found. We propose a method, based on ab initio calculations, for the evaluation of impact sensitivities, which consequently can assist in screening candidates for chemical synthesis of high energetic materials.

Rapid screening for human-pathogenic Mucorales using rolling circle amplification.

PubMed

Dolatabadi, S; Najafzadeh, M J; de Hoog, G S

2014-12-01

Mucormycosis has emerged as a relatively common severe mycosis in patients with haematological and allogeneic stem cell transplantation. Source of transmission is from unidentified sources in the environment. Early diagnosis of infection and its source of contamination are paramount for rapid and appropriate therapy. In this study, rolling circle amplification (RCA) is introduced as a sensitive, specific and reproducible isothermal DNA amplification technique for rapid molecular identification of six of the most virulent species (Rhizopus microsporus, R. arrhizus var. arrhizus, R. arrhizus var. delemar, Mucor irregularis, Mucor circinelloides, Lichtheimia ramosa, Lichtheimia corymbifera). DNAs of target species were successfully amplified, with no cross reactivity between species. RCA can be considered as a rapid detection method with high specificity and sensitivity, suitable for large screening. © 2014 Blackwell Verlag GmbH.

Is prostate cancer screening cost-effective? A microsimulation model of prostate-specific antigen-based screening for British Columbia, Canada

PubMed Central

Pataky, Reka; Gulati, Roman; Etzioni, Ruth; Black, Peter; Chi, Kim N.; Coldman, Andrew J.; Pickles, Tom; Tyldesley, Scott; Peacock, Stuart

2015-01-01

Prostate-specific antigen (PSA) screening for prostate cancer may reduce mortality, but it incurs considerable risk of overdiagnosis and potential harm to quality of life. Our objective was to evaluate the cost-effectiveness of PSA screening, with and without adjustment for quality of life, for the British Columbia (BC) population. We adapted an existing natural history model using BC incidence, treatment, cost and mortality patterns. The modeled mortality benefit of screening derives from a stage-shift mechanism, assuming mortality reduction consistent with the European Study of Randomized Screening for Prostate Cancer. The model projected outcomes for 40 year-old men under 14 combinations of screening ages and frequencies. Cost and utility estimates were explored with deterministic sensitivity analysis. The incremental cost-effectiveness of regular screening ranged from $36,300/LYG, for screening every four years from ages 55-69, to $588,300/LYG, for screening every two years from ages 40-74. The marginal benefits of increasing screening frequency to two years or starting screening at age 40 were small and came at significant cost. After utility adjustment, all screening strategies resulted in a loss of QALYs; however, this result was very sensitive to utility estimates. Plausible outcomes under a range of screening strategies inform discussion of prostate cancer screening policy in BC and similar jurisdictions. Screening may be cost-effective but the sensitivity of results to utility values suggests individual preferences for quality versus quantity of life should be a key consideration. PMID:24443367

Serologic Screening for Genital Herpes: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

PubMed

Feltner, Cynthia; Grodensky, Catherine; Ebel, Charles; Middleton, Jennifer C; Harris, Russell P; Ashok, Mahima; Jonas, Daniel E

2016-12-20

Genital herpes simplex virus (HSV) infection is a prevalent sexually transmitted infection. Vertical transmission of HSV can lead to fetal morbidity and mortality. To assess the evidence on serologic screening and preventive interventions for genital HSV infection in asymptomatic adults and adolescents to support the US Preventive Services Task Force for an updated recommendation statement. MEDLINE, Cochrane Library, EMBASE, and trial registries through March 31, 2016. Surveillance for new evidence in targeted publications was conducted through October 31, 2016. English-language randomized clinical trials (RCTs) comparing screening with no screening in persons without past or current symptoms of genital herpes; studies evaluating accuracy and harms of serologic screening tests for HSV-2; RCTs assessing preventive interventions in asymptomatic persons seropositive for HSV-2. Dual review of abstracts, full-text articles, and study quality; pooled sensitivities and specificities of screening tests using a hierarchical summary receiver operating characteristic curve analysis when at least 3 similar studies were available. Accuracy of screening tests, benefits of screening, harms of screening, reduction in genital herpes outbreaks. A total of 17 studies (n = 9736 participants; range, 24-3290) in 19 publications were included. No RCTs compared screening with no screening. Most studies of the accuracy of screening tests were from populations with high HSV-2 prevalence (greater than 40% based on Western blot). Pooled estimates of sensitivity and specificity of the most commonly used test at the manufacturer's cutpoint were 99% (95% CI, 97%-100%) and 81% (95% CI, 68%-90%), respectively (10 studies; n = 6537). At higher cutpoints, pooled estimates were 95% (95% CI, 91%-97%) and 89% (95% CI, 82%-93%), respectively (7 studies; n = 5516). Use of this test at the manufacturer's cutpoint in a population of 100 000 with a prevalence of HSV-2 of 16% (the seroprevalence in US adults with unknown symptom status) would result in 15 840 true-positive results and 15 960 false-positive results (positive predictive value, 50%). Serologic screening for genital herpes was associated with psychosocial harms, including distress and anxiety related to positive test results. Four RCTs compared preventive medications with placebo, 2 in nonpregnant asymptomatic adults who were HSV-2 seropositive and 2 in HSV-2-serodiscordant couples. Results in both populations were heterogeneous and inconsistent. Serologic screening for genital herpes is associated with a high rate of false-positive test results and potential psychosocial harms. Evidence from RCTs does not establish whether preventive antiviral medication for asymptomatic HSV-2 infection has benefit.

Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

PubMed Central

Huang, Ya-kai; Yu, Jian-chun; Kang, Wei-ming; Ma, Zhi-qiang; Ye, Xin; Tian, Shu-bo; Yan, Chao

2015-01-01

Background Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection. Methods We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity. Results In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00). Conclusion SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future. PMID:26556485

Review of nutritional screening and assessment tools and clinical outcomes in heart failure.

PubMed

Lin, Hong; Zhang, Haifeng; Lin, Zheng; Li, Xinli; Kong, Xiangqin; Sun, Gouzhen

2016-09-01

Recent studies have suggested that undernutrition as defined using multidimensional nutritional evaluation tools may affect clinical outcomes in heart failure (HF). The evidence supporting this correlation is unclear. Therefore, we conducted this systematic review to critically appraise the use of multidimensional evaluation tools in the prediction of clinical outcomes in HF. We performed descriptive analyses of all identified articles involving qualitative analyses. We used STATA to conduct meta-analyses when at least three studies that tested the same type of nutritional assessment or screening tools and used the same outcome were identified. Sensitivity analyses were conducted to validate our positive results. We identified 17 articles with qualitative analyses and 11 with quantitative analysis after comprehensive literature searching and screening. We determined that the prevalence of malnutrition is high in HF (range 16-90 %), particularly in advanced and acute decompensated HF (approximate range 75-90 %). Undernutrition as identified by multidimensional evaluation tools may be significantly associated with hospitalization, length of stay and complications and is particularly strongly associated with high mortality. The meta-analysis revealed that compared with other tools, Mini Nutritional Assessment (MNA) scores were the strongest predictors of mortality in HF [HR (4.32, 95 % CI 2.30-8.11)]. Our results remained reliable after conducting sensitivity analyses. The prevalence of malnutrition is high in HF, particularly in advanced and acute decompensated HF. Moreover, undernutrition as identified by multidimensional evaluation tools is significantly associated with unfavourable prognoses and high mortality in HF.

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

PubMed

Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

2015-01-01

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.

Detection of Methylated Circulating DNA as Noninvasive Biomarkers for Breast Cancer Diagnosis

PubMed Central

Cheuk, Isabella Wai Yin; Shin, Vivian Yvonne

2017-01-01

Internationally, breast cancer is the most common female cancer, and is induced by a combination of environmental, genetic, and epigenetic risk factors. Despite the advancement of imaging techniques, invasive sampling of breast epithelial cells is the only definitive diagnostic procedure for patients with breast cancer. To date, molecular biomarkers with high sensitivity and specificity for the screening and early detection of breast cancer are lacking. Recent evidence suggests that the detection of methylated circulating cell-free DNA in the peripheral blood of patients with cancer may be a promising quantitative and noninvasive method for cancer diagnosis. Methylation detection based on a multi-gene panel, rather than on the methylation status of a single gene, may be used to increase the sensitivity and specificity of breast cancer screening. In this review, the results of 14 relevant studies, investigating the efficacy of cell-free DNA methylation screening for breast cancer diagnosis, have been summarized. The genetic risk factors for breast cancer, the methods used for breast cancer detection, and the techniques and limitations related to the detection of cell-free DNA methylation status, have also been reviewed and discussed. From this review, we conclude that the analysis of peripheral blood or other samples to detect differentially methylated cell-free DNA is a promising technique for use in clinical settings, and may improve the sensitivity of screening for both, early detection and disease relapse, and thus improve the future prognosis of patients with breast cancer. PMID:28382090

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines

PubMed Central

Yu, Channing; Mannan, Aristotle M.; Yvone, Griselda Metta; Ross, Kenneth N.; Zhang, Yan-Ling; Marton, Melissa A.; Taylor, Bradley R.; Crenshaw, Andrew; Gould, Joshua Z.; Tamayo, Pablo; Weir, Barbara A.; Tsherniak, Aviad; Wong, Bang; Garraway, Levi A.; Shamji, Alykhan F.; Palmer, Michelle A.; Foley, Michael A.; Winckler, Wendy; Schreiber, Stuart L.; Kung, Andrew L.; Golub, Todd R.

2016-01-01

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control1-4. Here, we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM displayed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo. PMID:26928769

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

PubMed

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

2009-01-01

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

Sensitivity and specificity of the gain short-screener for predicting substance use disorders in a large national sample of emerging adults.

PubMed

Smith, Douglas C; Bennett, Kyle M; Dennis, Michael L; Funk, Rodney R

2017-05-01

Emerging Adults (ages 18-25) have the highest prevalence of substance use disorders and rarely receive treatment from the specialty care system. Thus, it is important to have screening instruments specifically developed for emerging adults for use in Screening, Brief Intervention and Referral to Treatment (SBIRT) models. Optimal cutoffs for the widely-used GAIN Short-Screener's (GAIN-SS) Substance Disorder Screener (SDScrY) are not established specifically for emerging adults. Therefore, this study examined the sensitivity and specificity of the SDScrY in predicting emerging adult (ages 18-25) substance use disorders. We analyzed data from emerging adults in a large clinical sample (n=9,808) who completed both the five-item SDScrY (α=0.85) and the full criteria set for DSM-IV Substance Use Disorders. We estimated the sensitivity, specificity and area under the curve to determine optimal cutoffs. Analyses revealed a high correlation between the SDScrY screener and its longer parent scale (r=0.95, p<0.001). Sensitivity (83%) and specificity (95%) were highest at a cutoff score of two (AUC=94%) on the SDScrY for any past year substance use disorder. Sensitivity (85%) was also high at a cutoff score of two on the SDScrY for any past year alcohol disorder. The five-item Substance Use Disorder Screener is a sensitive and specific screener for emerging adults, and could be used to identify emerging adults who may benefit from SBIRT interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

A New Versatile Microarray-based Method for High Throughput Screening of Carbohydrate-active Enzymes*

PubMed Central

Vidal-Melgosa, Silvia; Pedersen, Henriette L.; Schückel, Julia; Arnal, Grégory; Dumon, Claire; Amby, Daniel B.; Monrad, Rune Nygaard; Westereng, Bjørge; Willats, William G. T.

2015-01-01

Carbohydrate-active enzymes have multiple biological roles and industrial applications. Advances in genome and transcriptome sequencing together with associated bioinformatics tools have identified vast numbers of putative carbohydrate-degrading and -modifying enzymes including glycoside hydrolases and lytic polysaccharide monooxygenases. However, there is a paucity of methods for rapidly screening the activities of these enzymes. By combining the multiplexing capacity of carbohydrate microarrays with the specificity of molecular probes, we have developed a sensitive, high throughput, and versatile semiquantitative enzyme screening technique that requires low amounts of enzyme and substrate. The method can be used to assess the activities of single enzymes, enzyme mixtures, and crude culture broths against single substrates, substrate mixtures, and biomass samples. Moreover, we show that the technique can be used to analyze both endo-acting and exo-acting glycoside hydrolases, polysaccharide lyases, carbohydrate esterases, and lytic polysaccharide monooxygenases. We demonstrate the potential of the technique by identifying the substrate specificities of purified uncharacterized enzymes and by screening enzyme activities from fungal culture broths. PMID:25657012

A systematic review of screening questionnaires for childhood lead poisoning.

PubMed

Ossiander, Eric M

2013-01-01

The Centers for Disease Control and Prevention encourages the use of risk factor questionnaires to screen children for lead poisoning. A majority of state health departments have formal lead screening guidelines that recommend health care providers use questionnaires. We conducted a systematic review to evaluate the ability of lead screening questionnaires to predict lead poisoning risk among children. Articles that reported the evaluation of a predesigned lead screening questionnaire were obtained by searching Medline/PubMed and by examining references of articles obtained through the online search. From each evaluation, we abstracted the number of children that were true positive, false positive, true negative, and false negative, according to the results of the screening questionnaire and the follow-up blood lead test. From these data, we calculated specificity and sensitivity of the questionnaire for each evaluation. Twenty articles met the inclusion criteria: these included 28 separate questionnaire evaluations. Among 17 evaluations of the 1991 Centers for Disease Control and Prevention questionnaire, sensitivity ranged from 0.25 to 0.87, specificity from 0.31 to 0.80, and accuracy (sum of sensitivity and specificity) from 0.74 to 1.39. The pooled mean estimates for this questionnaire were sensitivity 0.61 (95% confidence interval: 0.53-0.68); specificity 0.52 (0.45-0.60); accuracy 1.12 (1.06-1.18). Among 11 evaluations of all other questionnaires, sensitivity ranged from 0.43 to 0.90, specificity from 0.17 to 0.66, and accuracy from 0.94 to 1.27. For these questionnaires, the pooled mean estimates were sensitivity 0.76 (0.68-0.85), specificity 0.41 (0.33-0.49), and accuracy 1.12 (1.06-1.18). Lead screening questionnaires showed a wide range of sensitivity and specificity and performed little better than chance at predicting lead poisoning risk among children.

Screening strategies for atrial fibrillation: a systematic review and cost-effectiveness analysis.

PubMed

Welton, Nicky J; McAleenan, Alexandra; Thom, Howard Hz; Davies, Philippa; Hollingworth, Will; Higgins, Julian Pt; Okoli, George; Sterne, Jonathan Ac; Feder, Gene; Eaton, Diane; Hingorani, Aroon; Fawsitt, Christopher; Lobban, Trudie; Bryden, Peter; Richards, Alison; Sofat, Reecha

2017-05-01

Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of thromboembolic events. Anticoagulation therapy to prevent AF-related stroke has been shown to be cost-effective. A national screening programme for AF may prevent AF-related events, but would involve a substantial investment of NHS resources. To conduct a systematic review of the diagnostic test accuracy (DTA) of screening tests for AF, update a systematic review of comparative studies evaluating screening strategies for AF, develop an economic model to compare the cost-effectiveness of different screening strategies and review observational studies of AF screening to provide inputs to the model. Systematic review, meta-analysis and cost-effectiveness analysis. Primary care. Adults. Screening strategies, defined by screening test, age at initial and final screens, screening interval and format of screening {systematic opportunistic screening [individuals offered screening if they consult with their general practitioner (GP)] or systematic population screening (when all eligible individuals are invited to screening)}. Sensitivity, specificity and diagnostic odds ratios; the odds ratio of detecting new AF cases compared with no screening; and the mean incremental net benefit compared with no screening. Two reviewers screened the search results, extracted data and assessed the risk of bias. A DTA meta-analysis was perfomed, and a decision tree and Markov model was used to evaluate the cost-effectiveness of the screening strategies. Diagnostic test accuracy depended on the screening test and how it was interpreted. In general, the screening tests identified in our review had high sensitivity (> 0.9). Systematic population and systematic opportunistic screening strategies were found to be similarly effective, with an estimated 170 individuals needed to be screened to detect one additional AF case compared with no screening. Systematic opportunistic screening was more likely to be cost-effective than systematic population screening, as long as the uptake of opportunistic screening observed in randomised controlled trials translates to practice. Modified blood pressure monitors, photoplethysmography or nurse pulse palpation were more likely to be cost-effective than other screening tests. A screening strategy with an initial screening age of 65 years and repeated screens every 5 years until age 80 years was likely to be cost-effective, provided that compliance with treatment does not decline with increasing age. A national screening programme for AF is likely to represent a cost-effective use of resources. Systematic opportunistic screening is more likely to be cost-effective than systematic population screening. Nurse pulse palpation or modified blood pressure monitors would be appropriate screening tests, with confirmation by diagnostic 12-lead electrocardiography interpreted by a trained GP, with referral to a specialist in the case of an unclear diagnosis. Implementation strategies to operationalise uptake of systematic opportunistic screening in primary care should accompany any screening recommendations. Many inputs for the economic model relied on a single trial [the Screening for Atrial Fibrillation in the Elderly (SAFE) study] and DTA results were based on a few studies at high risk of bias/of low applicability. Comparative studies measuring long-term outcomes of screening strategies and DTA studies for new, emerging technologies and to replicate the results for photoplethysmography and GP interpretation of 12-lead electrocardiography in a screening population. This study is registered as PROSPERO CRD42014013739. The National Institute for Health Research Health Technology Assessment programme.

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

Digital Rectal Examination and Balloon Expulsion Test in the Study of Defecatory Disorders: Are They Suitable as Screening or Excluding Tests?

PubMed

Caetano, Ana C; Santa-Cruz, André; Rolanda, Carla

2016-01-01

Background . Rome III criteria add physiological criteria to symptom-based criteria of chronic constipation (CC) for the diagnosis of defecatory disorders (DD). However, a gold-standard test is still lacking and physiological examination is expensive and time-consuming. Aim . Evaluate the usefulness of two low-cost tests-digital rectal examination (DRE) and balloon expulsion test (BET)-as screening or excluding tests of DD. Methods . We performed a systematic search in PUBMED and MEDLINE. We selected studies where constipated patients were evaluated by DRE or BET. Heterogeneity was assessed and random effect models were used to calculate the sensitivity, specificity, and negative predictive value (NPV) of the DRE and the BET. Results . Thirteen studies evaluating BET and four studies evaluating DRE (2329 patients) were selected. High heterogeneity ( I 2 > 80%) among studies was demonstrated. The studies evaluating the BET showed a sensitivity and specificity of 67% and 80%, respectively. Regarding the DRE, a sensitivity of 80% and specificity of 84% were calculated. NPV of 72% for the BET and NPV of 64% for the DRE were estimated. The sensitivity and specificity were similar when we restrict the analysis to studies using Rome criteria to define CC. The BET seems to perform better when a cut-off time of 2 minutes is used and when it is compared with a combination of physiological tests. Considering the DRE, strict criteria seem to improve the sensitivity but not the specificity of the test. Conclusion . Neither of the low-cost tests seems suitable for screening or excluding DD.

Low-dose chest computed tomography for lung cancer screening among Hodgkin lymphoma survivors: a cost-effectiveness analysis.

PubMed

Wattson, Daniel A; Hunink, M G Myriam; DiPiro, Pamela J; Das, Prajnan; Hodgson, David C; Mauch, Peter M; Ng, Andrea K

2014-10-01

Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not for nonsmokers despite a small life expectancy benefit. Copyright © 2014 Elsevier Inc. All rights reserved.

Screening for Autism Spectrum Disorders in Children With Down Syndrome

PubMed Central

DiGuiseppi, Carolyn; Hepburn, Susan; Davis, Jonathan M.; Fidler, Deborah J.; Hartway, Sara; Lee, Nancy Raitano; Miller, Lisa; Ruttenber, Margaret; Robinson, Cordelia

2015-01-01

Objective We assessed the prevalence of autism spectrum disorders (ASD) and screening test characteristics in children with Down syndrome. Method Eligible children born in a defined geographic area between January 1, 1996, and December 31, 2003, were recruited through a population-based birth defects registry and community outreach, then screened with the modified checklist for autism in toddlers or social communication questionnaire, as appropriate. Screen-positive children and a random sample of screen-negative children underwent developmental evaluation. Results We screened 123 children (27.8% of the birth cohort). Mean age was 73.4 months (range, 31–142). Compared to screen-negative children, screen-positive children had similar sociodemo-graphic characteristics but a lower mean developmental quotient (mean difference: 11.0; 95% confidence interval: 4.8–17.3). Weighted prevalences of autistic disorder and total ASD were 6.4% (95% confidence interval [CI]: 2.6%–11.6%) and 18.2% (95% CI: 9.7%–26.8%), respectively. The estimated minimum ASD prevalence, accounting for unscreened children, is 5.1% (95% CI: 3.3%–7.4%). ASD prevalence increased with greater cognitive impairment. Screening test sensitivity was 87.5% (95% CI: 66.6%–97.7%); specificity was 49.9% (95% CI: 37.0%–61.4%). Conclusion The prevalence of ASD among children with Down syndrome aged 2 to 11 years is substantially higher than in the general population. The modified checklist for autism in toddlers and social communication questionnaire were highly sensitive in children with Down syndrome but could result in many false positive tests if universal screening were implemented using current algorithms. Research needs include development of specific ASD screening algorithms and improved diagnostic discrimination in children with Down syndrome. Timely identification of these co-occurring diagnoses is essential so appropriate interventions can be provided. PMID:20375732

Repeat Cytology and Human Papillomavirus Screening Strategies in Detecting Preinvasive Cervical Lesions

PubMed Central

Li, Kemin; Yin, Rutie

2015-01-01

Abstract The aim of the present study was to determine the value of human papillomavirus (HPV) testing in screening patients with preinvasive cervical lesions. Seven hundred thirty-four women diagnosed with atypical squamous cells of undetermined significance (ASCUS+) cervical cytology during routine screening had additional cytologic testing and HPV DNA testing within 6 months of their diagnosis, after which all women who tested positive were referred for colposcopy and biopsy. The test findings were then used to determine the screening value of HPV for diagnosing preinvasive cervical lesions. Cytology and HPV testing were compared by conventional cytology. The odds ratio (OR) of sensitivity using ASCUS+ or low-grade squamous intraepithelial neoplasia (LSIL+) as a cutoff for detecting cervical intraepithelial neoplasia (CIN) II+ was, respectively, 0.78 (0.72, 0.85) and 0.82 (0.70, 0.95) (P < 0.01). The cytology for triage and conventional cytology had different sensitivities using ASCUS+ or LSIL+ as the cutoff (P < 0.01). The cytology or HPV testing and conventional cytology had a difference in sensitivity using ASCUS+, LSIL+, or high-grade squamous intraepithelial neoplasia (HSIL+) as the cutoff (P < 0.01). Cytology and HPV testing were also compared with conventional cytology. The OR of specificity using ASCUS+ or LSIL+ as the cutoff for the detection of CIN II+ was 1.97 (1.68, 2.31) and 1.10 (1.02, 1.18), respectively (P < 0.01). The cytology for triage and conventional cytology had a difference in specificity when ASCUS+ or LSIL+ was used as the cutoff (P < 0.01). Finally, the cytology or HPV testing and conventional cytology had a difference in specificity when ASCUS+, LSIL+, or HSIL+ was used as the cutoff (P < 0.01). Cytology and HPV testing and cytology for triage improved the specificity of detecting CIN II+, but this did not improve the sensitivity. Additionally, cytology or HPV testing improved the sensitivity of detecting CIN II+ but not the specificity. PMID:25654377

Multiscale Systems Modeling of Male Reproductive Tract Defects: from Genes to Populations (SOT)

EPA Science Inventory

The reproductive tract is a complex, integrated organ system with diverse embryology and unique sensitivity to prenatal environmental exposures that disrupt morphoregulatory processes and endocrine signaling. U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB...

Adding retinal photography to screening for diabetic retinopathy: a prospective study in primary care.

PubMed

O'Hare, J P; Hopper, A; Madhaven, C; Charny, M; Purewell, T S; Harney, B; Griffiths, J

1996-03-16

To evaluate whether adding retinal photography improved community screening for diabetic retinopathy. Mobile screening unit at rural and urban general practices in south west England. 1010 diabetic patients from primary care. Prospective study; patients were examined by ophthalmoscopy by general practitioners or opticians without fundal photographs and again with photographs, and assessments were compared to those of an ophthalmologist. Whether fundal photography improved the sensitivity of detection of retinopathy and referrable diabetic retinopathy, and whether this sensitivity could be improved by including a review of the films by the specialist. Diabetic retinopathy was detected by the ophthalmologist in 205 patients (20.5%) and referrable retinopathy in 49 (4.9%). The sensitivity of the general practitioners and opticians for referrable retinopathy with ophthalmoscopy was 65%, and improved to 84% with retinal photographs. General practitioners' sensitivity in detecting background retinopathy improved with photographs from 22% to 65%; opticians' sensitivity in detecting background retinopathy improved from 43% to 71%. The sensitivity of detecting referrable retinopathy by general practitioners improved from 56% to 80% with photographs; for opticians it improved from 75% to 88%. Combining modalities of screening by providing photography with specialist review of all films in addition to direct ophthalmoscopy through dilated pupils improves assessment and referral for diabetic retinopathy by general practitioners and opticians. With further training and experience, primary care screeners should be able to achieve a sensitivity that will achieve an effective, acceptable, and economical community based screening programme for this condition.

A compact large-format streak tube for imaging lidar

NASA Astrophysics Data System (ADS)

Hui, Dandan; Luo, Duan; Tian, Liping; Lu, Yu; Chen, Ping; Wang, Junfeng; Sai, Xiaofeng; Wen, Wenlong; Wang, Xing; Xin, Liwei; Zhao, Wei; Tian, Jinshou

2018-04-01

The streak tubes with a large effective photocathode area, large effective phosphor screen area, and high photocathode radiant sensitivity are essential for improving the field of view, depth of field, and detectable range of the multiple-slit streak tube imaging lidar. In this paper, a high spatial resolution, large photocathode area, and compact meshless streak tube with a spherically curved cathode and screen is designed and tested. Its spatial resolution reaches 20 lp/mm over the entire Φ28 mm photocathode working area, and the simulated physical temporal resolution is better than 30 ps. The temporal distortion in our large-format streak tube, which is shown to be a non-negligible factor, has a minimum value as the radius of curvature of the photocathode varies. Furthermore, the photocathode radiant sensitivity and radiant power gain reach 41 mA/W and 18.4 at the wavelength of 550 nm, respectively. Most importantly, the external dimensions of our streak tube are no more than Φ60 mm × 110 mm.

Optimized ratiometric calcium sensors for functional in vivo imaging of neurons and T lymphocytes.

PubMed

Thestrup, Thomas; Litzlbauer, Julia; Bartholomäus, Ingo; Mues, Marsilius; Russo, Luigi; Dana, Hod; Kovalchuk, Yuri; Liang, Yajie; Kalamakis, Georgios; Laukat, Yvonne; Becker, Stefan; Witte, Gregor; Geiger, Anselm; Allen, Taylor; Rome, Lawrence C; Chen, Tsai-Wen; Kim, Douglas S; Garaschuk, Olga; Griesinger, Christian; Griesbeck, Oliver

2014-02-01

The quality of genetically encoded calcium indicators (GECIs) has improved dramatically in recent years, but high-performing ratiometric indicators are still rare. Here we describe a series of fluorescence resonance energy transfer (FRET)-based calcium biosensors with a reduced number of calcium binding sites per sensor. These 'Twitch' sensors are based on the C-terminal domain of Opsanus troponin C. Their FRET responses were optimized by a large-scale functional screen in bacterial colonies, refined by a secondary screen in rat hippocampal neuron cultures. We tested the in vivo performance of the most sensitive variants in the brain and lymph nodes of mice. The sensitivity of the Twitch sensors matched that of synthetic calcium dyes and allowed visualization of tonic action potential firing in neurons and high resolution functional tracking of T lymphocytes. Given their ratiometric readout, their brightness, large dynamic range and linear response properties, Twitch sensors represent versatile tools for neuroscience and immunology.

Performance of CHROMagar Selective Medium and Oxacillin Resistance Screening Agar Base for Identifying Staphylococcus aureus and Detecting Methicillin Resistance

PubMed Central

Kluytmans, Jan; Van Griethuysen, Arjanne; Willemse, Piet; Van Keulen, Peter

2002-01-01

Two new selective media, oxacillin resistance screening agar base (ORSAB) and CHROMagar Staph aureus (CSA), were evaluated for identification of Staphylococcus aureus and for screening of methicillin resistance by addition of antimicrobial agents to these media. A well-defined collection consisting of 1,140 staphylococci was used. A total of 624 were S. aureus, of which 358 were methicillin susceptible and 266 were methicillin resistant, and 516 were coagulase-negative staphylococci. The methicillin-resistant S. aureus (MRSA) strains were selected based on the results of phage typing; 247 different types were included in the analysis. For identification of S. aureus, both media performed better after 24 h than after 48 h. The sensitivities at 24 h were comparable (CSA, 98.6%; ORSAB, 97.1%), but the specificity of CSA was significantly higher (CSA, 97.1%; ORSAB, 92.1%). For screening of methicillin resistance, antibiotic supplements were added to both media. The sensitivity was lower after 24 h (CSA, 58.6%; ORSAB, 84.2%) and increased significantly after 48 h (CSA, 77.5%; ORSAB, 91.4%). At both time intervals ORSAB was significantly more sensitive than CSA. However, the specificities of both media were high after 24 h (CSA, 99.1%; ORSAB, 98.3%) and decreased significantly after 48 h of incubation (CSA, 94.7%; ORSAB, 95.5%). In conclusion, for identification of S. aureus, CSA is more accurate than ORSAB because of a significantly higher specificity. For screening of MRSA, ORSAB performs better than CSA, but the usefulness in clinical practice is limited because a significant number of strains are not detected. PMID:12089266