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PubMed2001

Characterization of a minimal screening set of 172 microsatellite markers for genome-wide screens of the canine genome.

We have characterized a subset of 172 microsatellite markers from the canine map, termed 'Minimal Screening Set 1' (Canine MSS-1), which we propose be used for initial genome-wide genetic linkage studies. Three hierarchical criteria were used to select markers from the current meiotic linkage and radiation hybrid maps for MSS-1. Markers were selected that (1) provided as complete coverage as possible of the canine genome, (2) were highly informative, and (3) have been ordered in linkage groups with a high degree of statistical support. This resulting screening set spans all reported meiotic linkage and RH groups, leaving only 10 known gaps > or = 20 cM. The average polymorphic information content (PIC) value of markers tested is 0.74. Coverage estimates suggest 42% of the genome is within 5 cM of at least one marker in the minimal screening set, 77% of the genome is within 10 cM. This minimal mapping set therefore provides an efficient and cost effective way to begin screening pedigrees of interest for genetic linkage.

Animals↗

PubMed2001

Comparison of point-of-collection screening of drugs of abuse in oral fluid with a laboratory-based urine screen.

Oral fluid is becoming increasingly useful for the detection of drugs, since it is a non-invasive specimen to collect and, because collection is directly observed, it is difficult to adulterate. A point-of-collection (POCT) oral fluid drug analysis kit has been developed for use in many drug testing situations. This paper summarizes the results of field evaluations of the ORALscreen System for screening of drugs in oral fluid. The ORALscreen System consists of an oral fluid collection device and a test device containing a lateral flow membrane immunoassay system. Paired samples (oral fluid and urine) were collected from drug users and the results from the ORALscreen POCT system were compared to urine screening results conducted in a licensed laboratory. The results demonstrate that the ORALscreen System has excellent percent agreement with the laboratory-based urine screening test results for the detection of cocaine and opiates through 2.5-3 days following drug use, respectively. Tetrahydrocannabinol (THC) was detected by ORALscreen on the day of use and 1 day after use. Good correlation between urine and oral fluid screening results was observed for the methamphetamine positive samples; however, the number of days following drug use was not determined.

Clinical Laboratory Techniques↗

PubMedDate not supplied

The reduced graph descriptor in virtual screening and data-driven clustering of high-throughput screening data.

Virtual screening and high-throughput screening are two major components of lead discovery within the pharmaceutical industry. In this paper we describe improvements to previously published methods for similarity searching with reduced graphs, with a particular focus on ligand-based virtual screening, and describe a novel use of reduced graphs in the clustering of high-throughput screening data. Literature methods for reduced graph similarity searching encode the reduced graphs as binary fingerprints, which has a number of issues. In this paper we extend the definition of the reduced graph to include positively and negatively ionizable groups and introduce a new method for measuring the similarity of reduced graphs based on a weighted edit distance. Moving beyond simple similarity searching, we show how more flexible queries can be built using reduced graphs and describe a database system that allows iterative querying with multiple representations. Reduced graphs capture many important features of ligand-receptor interactions and, in conjunction with other whole molecule descriptors, provide an informative way to review HTS data. We describe a novel use of reduced graphs in this context, introducing a method we have termed data-driven clustering, that identifies clusters of molecules represented by a particular whole molecule descriptor and enriched in active compounds.

Journal Article↗

PubMedDate not supplied

Noise reduction method for molecular interaction energy: application to in silico drug screening and in silico target protein screening.

We developed a new method to improve the accuracy of molecular interaction data using a molecular interaction matrix. This method was applied to enhance the database enrichment of in silico drug screening and in silico target protein screening using a protein-compound affinity matrix calculated by a protein-compound docking software. Our assumption was that the protein-compound binding free energy of a compound could be improved by a linear combination of its docking scores with many different proteins. We proposed two approaches to determine the coefficients of the linear combination. The first approach is based on similarity among the proteins, and the second is a machine-learning approach based on the known active compounds. These methods were applied to in silico screening of the active compounds of several target proteins and in silico target protein screening.

Pharmaceutical Preparations↗

PubMed2002

The application of computer touch-screen technology in screening for psychosocial distress in an ambulatory oncology setting.

The objective of the study was to evaluate the acceptability and feasibility of computer touch-screen technology as a method for patients to report psychosocial functioning in an ambulatory cancer clinic. Patients participating in a randomized trial evaluating the use of self-reported psychosocial information in the clinical encounter were surveyed. The patients completed the Cancer Needs Questionnaire (CNQ), European Organization for the Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the Beck Depression Inventory - Short Form (BDI) using a touch-screen computer. The time taken to complete the questionnaires was recorded electronically. Patients completed a seven-item pen and paper survey to assess acceptability of the process. Of the 450 patients, 244 (54%) were 60 years or older. Although over half the patients had no prior computer experience, nearly all found the touch screen easy to use and the instructions easy to understand. Each question was answered by at least 447 (99.3%) patients. The average time to complete the CNQ was 9.1 min, EORTC QLQ-C30 4.0 min and BDI 3.1 min. Factors influencing time to completion were prior use of computers, physical condition, education and overall level of needs. The study found that the use of computer touch-screen technology is an acceptable and efficient method for obtaining self-reported information on quality of life, cancer needs and psychological distress.

Adaptation, Psychological↗

PubMed1999

Predictive validity of the BRASS index in screening patients with post-discharge problems. Blaylock Risk Assessment Screening Score.

RATIONALE: Discharge planning is a nursing intervention that aims to ensure continuity of care; it consists of several steps of which selecting patients in need of it is the first one. The Blaylock Risk Assessment Screening Score (BRASS) index is a risk screening instrument which can be used early after admission to identify those patients in need of discharge planning. AIM: To test the predictive validity of the BRASS index in screening patients with post-discharge problems. DESIGN: Prospective longitudinal design with prediction instrument measured at admission, and outcomes measured at discharge and 7 and 30 days after discharge. OUTCOME MEASURES: length of stay, discharge destination, status after discharge. INSTRUMENTS: BRASS index, Problems after discharge Questionnaire, Nottingham Health Profile, COOP/WONCA charts. RESEARCH METHOD: 503 elderly patients were screened at admission with the BRASS index. Length of stay and discharge destination were measured at discharge in these same patients. Outcomes after discharge were gathered only in patients who were discharged home and with length of stay of more than 3 days (n=226); outcomes were measured by postal questionnaires at day 7 and day 30 after discharge. RESULTS: patients identified by the BRASS index as high risk are frequently not discharged home and have a longer length of stay. The BRASS scores correlate significantly with the outcome scores after discharge: the higher the BRASS score, the higher the difficulty score after discharge on all domains. However, the sensitivity of the BRASS index is rather low. CONCLUSION: This study demonstrates that the BRASS index is a good predictor instrument for indicating patients who are not discharged home, that the BRASS scores correlate significantly with problems experienced after discharge and that it has high specificity to predict patients with problems after discharge. Clinical use, however, is limited due to the low sensitivity. The BRASS index is a promising case-finding instrument for discharge planning, but needs further development.

Aged↗

PubMed2006

Influence of the exchange screening parameter on the performance of screened hybrid functionals.

This work reexamines the effect of the exchange screening parameter omega on the performance of the Heyd-Scuseria-Ernzerhof (HSE) screened hybrid functional. We show that variation of the screening parameter influences solid band gaps the most. Other properties such as molecular thermochemistry or lattice constants of solids change little with omega. We recommend a new version of HSE with the screening parameter omega=0.11 bohr(-1) for further use. Compared to the original implementation, the new parametrization yields better thermochemical results and preserves the good accuracy for band gaps and lattice constants in solids.

Journal Article↗

PubMed1994

Nature screen: an efficient method for screening natural populations of Drosophila for targeted P-element insertions.

The efficiency of molecular techniques is making it increasingly necessary to rely on reverse genetics to understand the function of genes. Tissue-specific libraries allow one to identify numerous genes that can be cloned, sequenced, and mapped and whose temporal and tissue-specific pattern of expression are well characterized but whose function remains unknown. In such cases, it is desirable to generate targeted mutations to examine the phenotype of loss-of-function lesions. Here we describe a method for identifying naturally occurring variants of Drosophila melanogaster with specific genes tagged by a nearby P element. Imprecise P-element excision can then be used to generate a series of small deletions in or near the gene. In the method described here, large numbers of wild-caught males were crossed to balancer females, and inserts were identified in pooled samples by the polymerase chain reaction with one primer from each target gene and one primer from the P-element terminal repeat. We present the calculations for the probability of successfully tagging a gene and show that it is greatly improved by simultaneously screening inserts into several genes. If a large natural population is available, a nature screen is faster and easier than inducing P-element transposition in the laboratory, but the resulting lines, being genetically heterogeneous, may require more subsequent work to isolate. Using this method to screen the genomes of approximately 10,400 males, we found P-element inserts in close proximity to 3 of 10 genes that were screened.

Animals↗

PubMed2002

A high throughput screening assay to screen for CYP2E1 metabolism and inhibition using a fluorogenic vivid p450 substrate.

Large-scale screening of multiple compound libraries and combinatorial libraries for pharmacological activity is one of the novel approaches of the modern drug discovery process. The application of isozyme-specific high-throughput screening (HTS) assays for characterizing the interactions of potential drug candidates with major human drug-metabolizing cytochrome p450 enzymes (p450s) is newly becoming an essential part of this process. Fluorescence-based HTS assays have been successfully employed for in vitro assessment of drug-drug interactions and enzyme inhibition with several p450 isoforms, including CYP3A4, CYP2D6, CYP2C9, and CYP2C19. Here we describe a fluorescence-based HTS assay for detecting drug metabolism and inhibition with human CYP2E1. CYP2E1 plays an important role in the metabolism of several drugs, many solvents, and toxins and therefore has been repeatedly linked to numerous pathologies, including cancer, liver and kidney toxicity, diabetes, and alcoholism. The assay is based on the ability of a drug to compete with the fluorogenic Vivid CYP2E1 Blue Substrate for CYP2E1 metabolism and thus enables rapid screening of lead molecules for their inhibitory potential. We have used this assay to screen a panel of drugs and compounds for their effects on CYP2E1 metabolism and inhibition. Our results demonstrate the assay's usefulness in identifying CYP2E1 substrates and inhibitors and in enabling in-depth characterization of their interactions with the CYP2E1 isozyme. We also present detailed characteristics of the assay, including its dynamic range and Z'-factor values, which indicate that this robust assay is well suited for kinetic and inhibition studies in HTS formats.

Baculoviridae↗

PubMed2005

The development of a brief screening instrument for depression and suicidal ideation for elderly: the Depression and Suicide Screen.

The early detection of depression and suicidal ideation is essential for the prevention of suicide in the community. This study therefore aimed to develop a brief screen for depression and suicidal ideation that can be easily administered in primary-care settings. The Self-rating Depression Scale (SDS), the Hospital Anxiety and Depression Scale (HADS) and a modified version of the Composite International Diagnostic Interview (CIDI) were administered by 353 residents of a single community aged 64 years and over. A five-item screen was derived from SDS and HADS, using CIDI as the external criterion (study 1). The scale was modified so that it was more appropriate for our use, and was labeled the Depression and Suicide Screen (DSS). Its validity and reliability were examined among a further 382 residents of the same community aged 64 years and over, using the Short-Form Geriatric Depression Scale (GDS-S) as the external criterion (study 2). The DSS was internally consistent (Cronbach's alpha=0.62). Its reliability in detecting depression (defined as >or= 6 in GDS-S) and suicidal ideation (screened out by the inquiry by our trained staff) was 0.768 and 0.721, respectively. For depression, the sensitivity was 0.705; specificity, 0.729; positive predictive value (PPV), 0.446; negative predictive value (NPV), 0.888; and the overall diagnostic power, 0.723. For suicidal ideation, its sensitivity was 0.698; specificity, 0.693; PPV, 0.317; NPV, 0.926; and overall diagnostic power, 0.694. The DSS demonstrated a reasonable level of sensitivity and specificity in identifying both depression and suicidal ideation among the elderly within a community.

Aged↗

PubMed1977

General health screening of four-year-olds in a Swedish country. V. A strategy for improving the effectiveness and the cost efficiency of the psychological screening program.

Data presented in a previous paper pointed to the necessity for improving the overall sensitivity of the psychological screening program. The present report indicates possibilities for such an improvement without changing the screening methods. A comparison of the primary data of the true positives, the false positives and all the negatives (non-referred) revealed the necessity of more stringent referral criteria. It is predicted that the systematic application these criteria would result in an increase in the rate of true positives form 2.8 to 4.8% of the screened population. In addition a strategy aiming at a reduction of the costs without deteriorating the effectiveness and based on a differential application of the various elements of the screening program is presented.

Child Behavior Disorders↗

PubMed2003

Rapid screening of multiple beta-globin gene mutations by real-time PCR on the LightCycler: application to carrier screening and prenatal diagnosis of thalassemia syndromes.

BACKGROUND: Hemoglobinopathies are priority genetic diseases for prevention programs. Rapid genotype characterization is fundamental in the diagnostic laboratory, especially when offering prenatal diagnosis for carrier couples. METHODS: As a model, we designed a protocol based on the LightCycler technology to screen for a spectrum of beta-globin gene mutations in the Greek population. Design was facilitated by dual fluorochrome detection and close proximity of many mutations. Three probe sets were capable of screening 95% of beta-globin gene mutations in the Greek population, including IVSII-745C-->G, HbS, Cd5-CT, Cd6-A, Cd8-AA, IVSI-1G-->A, IVSI-5G-->A, IVSI-6T-->C, IVSI-110G-->A, and Cd39 C-->T. RESULTS: The protocol, standardized by analysis of 100 beta-thalassemia heterozygotes with known mutations, was 100% reliable in distinguishing wild-type from mutant alleles. Subsequent screening of 100 Greek beta-thalassemia heterozygotes with unknown mutations found 96 of 100 samples heterozygous for 1 of the 10 mutations, although melting curves were indistinguishable for mutations HbS/Cd6 and IVSI-5/IVSI-1, indicating a need of alternative methods for definitive diagnosis. One sample demonstrating a unique melting curve was characterized by sequencing as Cd8/9+G. Three samples carried mutations outside the gene region covered by the probes. The protocol was 100% accurate in 25 prenatal diagnosis samples, with 14 different genotype combinations diagnosed. The protocol was also flexible, detecting five beta-globin gene mutations from other population groups (IVSI-1G-->T, IVSI-5G-->C, IVSI-116T-->G, Cd37 TGG-->TGA, and Cd41/42 -TCTT). CONCLUSIONS: The described LightCycler system protocol can rapidly screen for many beta-globin gene mutations. It is appropriate for use in many populations for directing definitive mutation diagnosis and is suited for rapid prenatal diagnosis with low cost per assay.

DNA Mutational Analysis↗

PubMed1999

The Iowa Personality Disorder Screen: development and preliminary validation of a brief screening interview.

The length and expense of comprehensive personality disorder interviews makes them unwieldy for routine use. A brief but sensitive screen could eliminate administration of longer instruments in many instances. We describe the development of the Iowa Personality Disorder Screen (IPDS)--a mini-structured interview which can be completed in less than 5 minutes. Retrospective analyses using 1,203 SIDP-R interviews suggested that the IPDS items should provide good sensitivity and specificity. We present results from a prospective validation study, using a mixed group of 52 nonpsychotic inpatients and outpatients who were diagnosed using the SIDP-IV. Blind administration of the IPDS yielded excellent sensitivity (92%) and good specificity (79%), using a subset of five screening items. Addition of two more items leads to an estimated sensitivity of 79% and specificity of 86%. The IPDS shows promise as a quick personality disorder screen for use in research settings or standard clinical interviews.

Adult↗

PubMed2000

Screening adolescents for problem drinking: performance of brief screens against DSM-IV alcohol diagnoses.

OBJECTIVE: The performance of three brief screens, the CAGE, TWEAK and Alcohol Use Disorders Identification Test (AUDIT), was evaluated against a DSM-IV diagnosis of alcohol abuse or dependence in an adolescent sample. METHOD: Adolescents (13-19 years old) who presented to an emergency department for treatment of an injury, and who tested negative for blood alcohol concentration at time of admission, were administered a structured diagnostic interview and modified versions of the CAGE, TWEAK and AUDIT. RESULTS: Of the 415 adolescents for whom complete data were available, 18% met criteria for a DSM-IV alcohol use disorder according to the Diagnostic Interview Schedule for Children (version 2.3). Teens who reported alcohol use in the last year (n = 261, 58% male, 71% white) were included in analyses that compared the performance of the three screening instruments. Receiver Operating Characteristic analysis indicated that the AUDIT demonstrated the best performance across the range of its cut-scores, with optimal performance at a cut-score of 4. The TWEAK performed optimally at a cut-score of 2 and the CAGE at a cut-score of 1. CONCLUSIONS: Routine alcohol screening among adolescents seen in a hospital setting is indicated. Two important directions for future research include the identification of adolescent-specific alcohol screening items, and the validation of an adolescent-specific definition of problem drinking that addresses limitations of DSM-IV alcohol diagnoses when applied to adolescents.

Adolescent↗

PubMed1985

Epidemiologic evaluation of screening for risk factors: application to genetic screening.

To assess the usefulness of screening for risk factors, we derived arithmetic relationships between screening parameters (sensitivity, specificity, and positive predictive value PPV) and risk factor frequency, disease frequency and relative risk. We evaluated these relationships in the special case of genetic markers and disease susceptibility. It can be shown that even in the face of very large relative risks, sensitivity and positive predictive value are affected by the relative magnitude of disease and genetic marker frequencies. When the genetic marker is less frequent than the disease, PPV increases with increasing relative risk but sensitivity remains low. When the genetic marker is more frequent than the disease, sensitivity increases with increasing relative risk but PPV remains low. When marker and disease frequencies are equal, both PPV and sensitivity increase with increasing relative risks, but very high relative risks (greater than 100) have to be obtained for rare diseases. Depending on the goals of the screening program, these relationships can be used to predict the relative magnitudes of false positives (low PPV) and false negatives (low sensitivity). This approach can be generalized to evaluate nongenetic risk factors in screening programs as well.

Epidemiologic Methods↗

PubMed1995

Maternal serum alpha-fetoprotein screening for neural tube defects. Report of a program with more than 30000 screened pregnancies.

Maternal serum alphafetoprotein (MSAFP) screening has been set up in Asturias, in the north of Spain, in 1987 in order to make possible the prenatal diagnosis of neural tube defects (NTD) to overall pregnancy population. This large study shows the high sensitivity and specificity of MSAFP screening when it is done with absolute control of all variables such as gestational age, pregnant woman's weight, diabetes, etc. On the other hand, this study also shows a poor sensitivity second level ultrasound for the early diagnosis of NTD in the presence of spina bifidas with no bulge. We have also observed that the incidence of NTD in Asturias remained constant in the last six years, around 1.5-1.6 per 1000 pregnancies. However, due to MSAFP screening, there has been a decline in the prevalence of children born with these defects. We conclude that MSAFP screening is the best tool to identify and reduce NTD in our Region (Spain).

Female↗

PubMed2002

To screen or not to screen--that is the question in perinatal depression.

Significant perinatal distress and depression affects 14% of women, producing short and long term consequences for the family. This suggests that measures for early detection are important, and non-identification of these women may exacerbate difficulties. Screening provides an opportunity to access large numbers of women and facilitate pathways to best-practice care. A valid, reliable, economical screening tool (the Edinburgh Postnatal Depression Scale, EPDS) is available. Arguments against screening pertain largely to lack of evidence about the acceptability of routine use of the EPDS during pregnancy and the postnatal period, and inadequate evidence regarding outcomes and cost-effectiveness. To address these concerns, the National Postnatal Depression Prevention and Early Intervention Program will evaluate outcomes of screening in terms of acceptability, cost-effectiveness, access and satisfaction with management in up to 100 000 women.

Australia↗

PubMed1999

Biomolecular-chemical screening: a novel screening approach for the discovery of biologically active secondary metabolites. II. Application studies with pure metabolites.

The novel screening strategy called "biomolecular-chemical screening" combines the advantages of the chemical screening approach--the analysis of the chromatographic and chemical behaviour of secondary metabolites on TLC plates--with binding studies of these molecules with bio-macromolecules like DNA. This approach was advantageously used to detect the interaction of pure compounds with DNA. In order to prove the reliability of the biomolecular-chemical screening and to examine DNA-binding properties, 470 pure secondary metabolites were analysed by this method. Besides the confirmation of already known binders with the TLC-based method, for a number of natural products DNA-binding properties were discovered for the first time. In consequence, binding of pure compounds can be measured by 1D TLC in a reliable and easy manner, in which DNA is applied together with the test compound at the starting spot. Analysis is performed via differences in Rf-values in comparison to a reference chromatogram without DNA.

Bacteria↗