Relationship between echocardiographic LV mass and ECG based left ventricular voltages in an adolescent population: related or random?

PubMed

Czosek, Richard J; Cnota, James F; Knilans, Timothy K; Pratt, Jesse; Guerrier, Karine; Anderson, Jeffrey B

2014-09-01

In attempts to detect diseases that may place adolescents at risk for sudden death, some have advocated for population-based screening. Controversy exists over electrocardiography (ECG) screening due to the lack of specificity, cost, and detrimental effects of false positive or extraneous outcomes. Analyze the relationship between precordial lead voltage on ECG and left ventricle (LV) mass by echocardiogram in adolescent athletes. Retrospective cohort analysis of a prospectively obtained population of self-identified adolescent athletes during sports screening with ECG and echocardiogram. Correlation between ECG LV voltages (R wave in V6 [RV6] and S wave in lead V1 [SV1]) was compared to echocardiogram-based measurements of left ventricular mass. Potential effects on ECG voltages by body anthropometrics, including weight, body mass index (BMI), and body surface area were analyzed, and ECG voltages indexed to BMI were compared to LV mass indices to analyze for improved correlation. A total of 659 adolescents enrolled in this study (64% male). The mean age was 15.4 years (14-18). The correlations between LV mass and RV6, SV1, and RV6 + SV1 were all less than 0.20. The false positive rate for abnormal voltages was relatively high (5.5%) but improved if abnormal voltages in both RV6 and SV1 were mandated simultaneously (0%). Indexing ECG voltages to BMI significantly improved correlation to LV mass, though false positive findings were increased (12.9%). There is poor correlation between ECG precordial voltages and echocardiographic LV mass. This relationship is modified by BMI. This finding may contribute to the poor ECG screening characteristics. ©2014 Wiley Periodicals, Inc.

Parents of Elementary School Students Weigh in on Height, Weight, and Body Mass Index Screening at School

ERIC Educational Resources Information Center

Kubik, Martha Y.; Fulkerson, Jayne A.; Story, Mary; Rieland, Gayle

2006-01-01

School-based body mass index (BMI) screening and parent notification programs have been recommended as a childhood overweight prevention strategy. However, there are little empirical data available to guide decision making about the acceptability and safety of programs. A pilot study was conducted using a quasiexperimental research design. In fall…

Computer-aided diagnosis workstation and network system for chest diagnosis based on multislice CT images

NASA Astrophysics Data System (ADS)

Satoh, Hitoshi; Niki, Noboru; Eguchi, Kenji; Moriyama, Noriyuki; Ohmatsu, Hironobu; Masuda, Hideo; Machida, Suguru

2008-03-01

Mass screening based on multi-helical CT images requires a considerable number of images to be read. It is this time-consuming step that makes the use of helical CT for mass screening impractical at present. To overcome this problem, we have provided diagnostic assistance methods to medical screening specialists by developing a lung cancer screening algorithm that automatically detects suspected lung cancers in helical CT images, a coronary artery calcification screening algorithm that automatically detects suspected coronary artery calcification and a vertebra body analysis algorithm for quantitative evaluation of osteoporosis likelihood by using helical CT scanner for the lung cancer mass screening. The function to observe suspicious shadow in detail are provided in computer-aided diagnosis workstation with these screening algorithms. We also have developed the telemedicine network by using Web medical image conference system with the security improvement of images transmission, Biometric fingerprint authentication system and Biometric face authentication system. Biometric face authentication used on site of telemedicine makes "Encryption of file" and Success in login" effective. As a result, patients' private information is protected. Based on these diagnostic assistance methods, we have developed a new computer-aided workstation and a new telemedicine network that can display suspected lesions three-dimensionally in a short time. The results of this study indicate that our radiological information system without film by using computer-aided diagnosis workstation and our telemedicine network system can increase diagnostic speed, diagnostic accuracy and security improvement of medical information.

Development of a fully automatic scheme for detection of masses in whole breast ultrasound images.

PubMed

Ikedo, Yuji; Fukuoka, Daisuke; Hara, Takeshi; Fujita, Hiroshi; Takada, Etsuo; Endo, Tokiko; Morita, Takako

2007-11-01

Ultrasonography has been used for breast cancer screening in Japan. Screening using a conventional hand-held probe is operator dependent and thus it is possible that some areas of the breast may not be scanned. To overcome such problems, a mechanical whole breast ultrasound (US) scanner has been proposed and developed for screening purposes. However, another issue is that radiologists might tire while interpreting all images in a large-volume screening; this increases the likelihood that masses may remain undetected. Therefore, the aim of this study is to develop a fully automatic scheme for the detection of masses in whole breast US images in order to assist the interpretations of radiologists and potentially improve the screening accuracy. The authors database comprised 109 whole breast US imagoes, which include 36 masses (16 malignant masses, 5 fibroadenomas, and 15 cysts). A whole breast US image with 84 slice images (interval between two slice images: 2 mm) was obtained by the ASU-1004 US scanner (ALOKA Co., Ltd., Japan). The feature based on the edge directions in each slice and a method for subtracting between the slice images were used for the detection of masses in the authors proposed scheme. The Canny edge detector was applied to detect edges in US images; these edges were classified as near-vertical edges or near-horizontal edges using a morphological method. The positions of mass candidates were located using the near-vertical edges as a cue. Then, the located positions were segmented by the watershed algorithm and mass candidate regions were detected using the segmented regions and the low-density regions extracted by the slice subtraction method. For the removal of false positives (FPs), rule-based schemes and a quadratic discriminant analysis were applied for the distribution between masses and FPs. As a result, the sensitivity of the authors scheme for the detection of masses was 80.6% (29/36) with 3.8 FPs per whole breast image. The authors scheme for a computer-aided detection may be useful in improving the screening performance and efficiency.

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

PubMed

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

2017-07-15

A screening concept for residues in complex matrices based on liquid chromatography coupled to ion mobility high-resolution mass spectrometry LC/IMS-HRMS is presented. The comprehensive four-dimensional data (chromatographic retention time, drift time, mass-to-charge and ion abundance) obtained in data-independent acquisition (DIA) mode was used for data mining. An in silico fragmenter utilizing a molecular structure database was used for suspect screening, instead of targeted screening with reference substances. The utilized data-independent acquisition mode relies on the MS E concept; where two constantly alternating HRMS scans (low and high fragmentation energy) are acquired. Peak deconvolution and drift time alignment of ions from the low (precursor ion) and high (product ion) energy scan result in relatively clean product ion spectra. A bond dissociation in silico fragmenter (MassFragment) supplied with mol files of compounds of interest was used to explain the observed product ions of each extracted candidate component (chromatographic peak). Two complex matrices (fish and bovine liver extract) were fortified with 98 veterinary drugs. Out of 98 screened compounds 94 could be detected with the in silico based screening approach. The high correlation among drift time and m/z value of equally charged ions was utilized for an orthogonal filtration (ranking). Such an orthogonal ion mobility based filter removes multiply charged ions (e.g. peptides and proteins from the matrix) as well as noise and artefacts. Most significantly, this filtration dramatically reduces false positive findings but hardly increases false negative findings. The proposed screening approach may offer new possibilities for applications where reference compounds are hardly or not at all commercially available. Such areas may be the analysis of metabolites of drugs, pyrrolizidine alkaloids, marine toxins, derivatives of sildenafil or novel designer drugs (new psychoactive substances). Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

High impact technologies for natural products screening.

PubMed

Koehn, Frank E

2008-01-01

Natural products have historically been a rich source of lead molecules in drug discovery. However, natural products have been de-emphasized as high throughput screening resources in the recent past, in part because of difficulties in obtaining high quality natural products screening libraries, or in applying modern screening assays to these libraries. In addition, natural products programs based on screening of extract libraries, bioassay-guided isolation, structure elucidation and subsequent production scale-up are challenged to meet the rapid cycle times that are characteristic of the modern HTS approach. Fortunately, new technologies in mass spectrometry, NMR and other spectroscopic techniques can greatly facilitate the first components of the process - namely the efficient creation of high-quality natural products libraries, bimolecular target or cell-based screening, and early hit characterization. The success of any high throughput screening campaign is dependent on the quality of the chemical library. The construction and maintenance of a high quality natural products library, whether based on microbial, plant, marine or other sources is a costly endeavor. The library itself may be composed of samples that are themselves mixtures - such as crude extracts, semi-pure mixtures or single purified natural products. Each of these library designs carries with it distinctive advantages and disadvantages. Crude extract libraries have lower resource requirements for sample preparation, but high requirements for identification of the bioactive constituents. Pre-fractionated libraries can be an effective strategy to alleviate interferences encountered with crude libraries, and may shorten the time needed to identify the active principle. Purified natural product libraries require substantial resources for preparation, but offer the advantage that the hit detection process is reduced to that of synthetic single component libraries. Whether the natural products library consists of crude or partially fractionated mixtures, the library contents should be profiled to identify the known components present - a process known as dereplication. The use of mass spectrometry and HPLC-mass spectrometry together with spectral databases is a powerful tool in the chemometric profiling of bio-sources for natural product production. High throughput, high sensitivity flow NMR is an emerging tool in this area as well. Whether by cell based or biomolecular target based assays, screening of natural product extract libraries continues to furnish novel lead molecules for further drug development, despite challenges in the analysis and prioritization of natural products hits. Spectroscopic techniques are now being used to directly screen natural product and synthetic libraries. Mass spectrometry in the form of methods such as ESI-ICRFTMS, and FACS-MS as well as NMR methods such as SAR by NMR and STD-NMR have been utilized to effectively screen molecular libraries. Overall, emerging advances in mass spectrometry, NMR and other technologies are making it possible to overcome the challenges encountered in screening natural products libraries in today's drug discovery environment. As we apply these technologies and develop them even further, we can look forward to increased impact of natural products in the HTS based drug discovery.

Computer-aided diagnosis workstation and telemedicine network system for chest diagnosis based on multislice CT images

NASA Astrophysics Data System (ADS)

Satoh, Hitoshi; Niki, Noboru; Eguchi, Kenji; Ohmatsu, Hironobu; Kakinuma, Ryutaru; Moriyama, Noriyuki

2009-02-01

Mass screening based on multi-helical CT images requires a considerable number of images to be read. It is this time-consuming step that makes the use of helical CT for mass screening impractical at present. Moreover, the doctor who diagnoses a medical image is insufficient in Japan. To overcome these problems, we have provided diagnostic assistance methods to medical screening specialists by developing a lung cancer screening algorithm that automatically detects suspected lung cancers in helical CT images, a coronary artery calcification screening algorithm that automatically detects suspected coronary artery calcification and a vertebra body analysis algorithm for quantitative evaluation of osteoporosis likelihood by using helical CT scanner for the lung cancer mass screening. The functions to observe suspicious shadow in detail are provided in computer-aided diagnosis workstation with these screening algorithms. We also have developed the telemedicine network by using Web medical image conference system with the security improvement of images transmission, Biometric fingerprint authentication system and Biometric face authentication system. Biometric face authentication used on site of telemedicine makes "Encryption of file" and "Success in login" effective. As a result, patients' private information is protected. We can share the screen of Web medical image conference system from two or more web conference terminals at the same time. An opinion can be exchanged mutually by using a camera and a microphone that are connected with workstation. Based on these diagnostic assistance methods, we have developed a new computer-aided workstation and a new telemedicine network that can display suspected lesions three-dimensionally in a short time. The results of this study indicate that our radiological information system without film by using computer-aided diagnosis workstation and our telemedicine network system can increase diagnostic speed, diagnostic accuracy and security improvement of medical information.

Mass spectrometric screening of ligands with lower off-rate from a clicked-based pooled library.

PubMed

Arai, Satoshi; Hirosawa, Shota; Oguchi, Yusuke; Suzuki, Madoka; Murata, Atsushi; Ishiwata, Shin'ichi; Takeoka, Shinji

2012-08-13

This paper describes a convenient screening method using ion trap electrospray ionization mass spectrometry to classify ligands to a target molecule in terms of kinetic parameters. We demonstrate this method in the screening of ligands to a hexahistidine tag from a pooled library synthesized by click chemistry. The ion trap mass spectrometry analysis revealed that higher stabilities of ligand-target complexes in the gas phase were related to lower dissociation rate constants, i.e., off-rates in solution. Finally, we prepared a fluorescent probe utilizing the ligand with lowest off-rate and succeeded in performing single molecule observations of hexahistidine-tagged myosin V walking on actin filaments.

A Comprehensive Review of School-Based Body Mass Index Screening Programs and Their Implications for School Health: Do the Controversies Accurately Reflect the Research?

ERIC Educational Resources Information Center

Ruggieri, Dominique G.; Bass, Sarah B.

2015-01-01

Background: Whereas legislation for body mass index (BMI) surveillance and screening programs has passed in 25 states, the programs are often subject to ethical debates about confidentiality and privacy, school-to-parent communication, and safety and self-esteem issues for students. Despite this debate, no comprehensive analysis has been completed…

Breast cancer biology varies by method of detection and may contribute to overdiagnosis.

PubMed

Hayse, Brandon; Hooley, Regina J; Killelea, Brigid K; Horowitz, Nina R; Chagpar, Anees B; Lannin, Donald R

2016-08-01

Recently, it has been suggested that screening mammography may result in some degree of overdiagnosis (ie, detection of breast cancers that would never become clinically important within the lifespan of the patient). The extent and biology of these overdiagnosed cancers, however, is not well understood, and the effect of newer screening modalities on overdiagnosis is unknown. We performed a retrospective review of a prospectively collected database of breast cancers diagnosed at the Yale Breast Center from 2004-2014. The mode of initial presentation was categorized into 5 groups: screening mammogram, screening magnetic resonance imaging, screening ultrasonography, self-detected masses, and physician-detected masses. Compared with cancers presenting with masses, cancers detected by image-based screening were more likely to present with ductal carcinoma-in-situ or T1 cancers (P < .001). In addition to a simple stage shift, however, cancers detected by image-based screening were also more likely to be luminal and low-grade cancers; symptomatic cancers were more likely high-grade and triple-negative (P < .001, respectively). On a multivariate analysis, adjusting for age, race, and tumor size, cancers detected by mammogram, US, and magnetic resonance imaging had greater odds of being luminal (odds ratio 1.8, 95% confidence interval, 1.5-2.3; odds ratio 2.2, 95% confidence interval, 1.1-4.7; and odds ratio 4.7, 95% confidence interval, 2.1-10.6, respectively), and low-grade (odds ratio 2.2, 95% confidence interval, 1.6-2.9; odds ratio 4.9, 95% confidence interval, 2.7-8.9; and odds ratio 4.6, 95% confidence interval, 2.6-8.1, respectively) compared with cancers presenting with self-detected masses. Screening detects cancers with more indolent biology, potentially contributing to the observed rate of overdiagnosis. With magnetic resonance imaging and US being used more commonly for screening, the rate of overdiagnosis may increase further. Copyright © 2016. Published by Elsevier Inc.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2016-09-06

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

Real-time detection method and system for identifying individual aerosol particles

DOEpatents

Gard, Eric E [San Francisco, CA; Coffee, Keith R [Patterson, CA; Frank, Matthias [Oakland, CA; Tobias, Herbert J [Kensington, CA; Fergenson, David P [Alamo, CA; Madden, Norm [Livermore, CA; Riot, Vincent J [Berkeley, CA; Steele, Paul T [Livermore, CA; Woods, Bruce W [Livermore, CA

2007-08-21

An improved method and system of identifying individual aerosol particles in real time. Sample aerosol particles are collimated, tracked, and screened to determine which ones qualify for mass spectrometric analysis based on predetermined qualification or selection criteria. Screening techniques include one or more of determining particle size, shape, symmetry, and fluorescence. Only qualifying particles passing all screening criteria are subject to desorption/ionization and single particle mass spectrometry to produce corresponding test spectra, which is used to determine the identities of each of the qualifying aerosol particles by comparing the test spectra against predetermined spectra for known particle types. In this manner, activation cycling of a particle ablation laser of a single particle mass spectrometer is reduced.

[Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience].

PubMed

Bozkowa, K; Cabalska, B; Radomyska, B; Ołtarzewski, M; Lenartowska, I

1999-01-01

The results and the significance of neonatal mass-screening programmes for inborn errors of metabolism, conducted by the National Research Institute of Mother and Child (NRIMC), are discussed. As the first in Poland, in 1964, mass-screening for phenylketonuria (PKU) was introduced. The BIA-Guthrie test was used. Other Guthrie tests (GBIA) were applied in homocystinuria, tyrosinemia, histidinemia and leucinosis (Maple Syrup Urine Disease-MSUD). In the middle of the 60. the Beutler and Baluda test was introduced for galactosaemia, as well as the Efron urine test in infant screening for different inborn errors of metabolism. In the middle of the 70., neonatal mass-screening for cystic fibrosis (CF, mucoviscidosis) was started. Meconium tests and the sweat test with ion selective chloride electrode were used. Apart from inborn errors of metabolism, we also introduced a screening programme for neuroblastoma in which vaniline mandelic acid (VMA) in urine was estimated and for congenital hypothyroidism were TSH level was assessed. The results of screening are shown in the tables and in the figures. In our opinion the best clinical results are obtained with screening for congenital hypothyroidism and for PKU, since very early detection and treatment in these diseases prevents severe mental retardation. We therefore consider that both these screening programmes should be treated as obligatory examinations in all neonates. Taking into consideration the fact that there are different types of hyperhenylalaninemias, the principles of differential diagnosis are discussed. Molecular genetic investigations, carried out in the NRIMC Department of Genetics proved to be a very important procedure in the verification of diagnosis of different mutations. The authors also discuss the problem of dietary treatment duration in PKU. In our opinion the hypophenyloalanine diet regimen in girls, should not be discontinued during adolescence, since there is the problem of maternal PKU and the possibility of foetal damage. The results of our own investigations of maternal PKU are discussed. The significance of mass-screening for galactosemia is still under discussion. In our opinion, mass-screening for galactosemia is not useful and we have discontinued it. Selective screening has been started combined with molecular genetic studies in high risk families. In the future, we plan to prepare guidelines on the principles of diagnosis and treatment of galactosemia in children and women in the reproductive age. Mass-screening for cystic fibrosis is also still under discussion. The results of the early screening programmes were not satisfactory and the tests were discontinued. In 1998, after reorganisation of the whole system, CF screening, using tripsin-radioimmune assays, was started again. The new screening programme is combined with molecular genetic investigation of different mutations. It is still too early to assess the importance and success of this CF mass-screening programme. We decided to discontinue the screening for homocystinuria, histidinemia, tyrosinemia, leucinosis and for neuroblastoma, since these programmes did not comply with criteria of mass-screening. In 1997, major reorganisation of screening programmes for inborn errors of metabolism, at NRIMC, was undertaken. The Guthrie test for PKU was changed to a quantitative colorimetric method. The immuno-luminometric method is used for TSH estimation. The whole system is based on complete computer control of all the steps of screening, from blood sampling on filter paper until the final diagnosis. The advantages of this modern system of organisation of the screening programme are discussed.

Continuous flow immobilized enzyme reactor-tandem mass spectrometry for screening of AChE inhibitors in complex mixtures.

PubMed

Forsberg, Erica M; Green, James R A; Brennan, John D

2011-07-01

A method is described for identifying bioactive compounds in complex mixtures based on the use of capillary-scale monolithic enzyme-reactor columns for rapid screening of enzyme activity. A two-channel nanoLC system was used to continuously infuse substrate coupled with automated injections of substrate/small molecule mixtures, optionally containing the chromogenic Ellman reagent, through sol-gel derived acetylcholinesterase (AChE) doped monolithic columns. This is the first report of AChE encapsulated in monolithic silica for use as an immobilized enzyme reactor (IMER), and the first use of such IMERs for mixture screening. AChE IMER columns were optimized to allow rapid functional screening of compound mixtures based on changes in the product absorbance or the ratio of mass spectrometric peaks for product and substrate ions in the eluent. The assay had robust performance and produced a Z' factor of 0.77 in the presence of 2% (v/v) DMSO. A series of 52 mixtures consisting of 1040 compounds from the Canadian Compound Collection of bioactives was screened and two known inhibitors, physostigmine and 9-aminoacridine, were identified from active mixtures by manual deconvolution. The activity of the compounds was confirmed using the enzyme reactor format, which allowed determination of both IC(50) and K(I) values. Screening results were found to correlate well with a recently published fluorescence-based microarray screening assay for AChE inhibitors.

Immobilized magnetic beads-based multi-target affinity selection coupled with HPLC-MS for screening active compounds from traditional Chinese medicine and natural products.

PubMed

Chen, Yaqi; Chen, Zhui; Wang, Yi

2015-01-01

Screening and identifying active compounds from traditional Chinese medicine (TCM) and other natural products plays an important role in drug discovery. Here, we describe a magnetic beads-based multi-target affinity selection-mass spectrometry approach for screening bioactive compounds from natural products. Key steps and parameters including activation of magnetic beads, enzyme/protein immobilization, characterization of functional magnetic beads, screening and identifying active compounds from a complex mixture by LC/MS, are illustrated. The proposed approach is rapid and efficient in screening and identification of bioactive compounds from complex natural products.

Multifactorial Analysis of Mortality in Screening Detected Lung Cancer.

PubMed

Digumarthy, Subba R; De Man, Ruben; Canellas, Rodrigo; Otrakji, Alexi; Wang, Ge; Kalra, Mannudeep K

2018-01-01

We hypothesized that severity of coronary artery calcification (CAC), emphysema, muscle mass, and fat attenuation can help predict mortality in patients with lung cancer participating in the National Lung Screening Trial (NLST). Following regulatory approval from the Cancer Data Access System (CDAS), all patients diagnosed with lung cancer at the time of the screening study were identified. These subjects were classified into two groups: survivors and nonsurvivors at the conclusion of the NLST trial. These groups were matched based on their age, gender, body mass index (BMI), smoking history, lung cancer stage, and survival time. CAC, emphysema, muscle mass, and subcutaneous fat attenuation were quantified on baseline low-dose chest CT (LDCT) for all patients in both groups. Nonsurvivor group had significantly greater CAC, decreased muscle mass, and higher fat attenuation compared to the survivor group ( p < 0.01). No significant difference in severity of emphysema was noted between the two groups ( p > 0.1). We thus conclude that it is possible to create a quantitative prediction model for lung cancer mortality for subjects with lung cancer detected on screening low-dose CT (LDCT).

Direct mass spectrometric screening of antibiotics from bacterial surfaces using liquid extraction surface analysis.

PubMed

Kai, Marco; González, Ignacio; Genilloud, Olga; Singh, Sheo B; Svatoš, Aleš

2012-10-30

There is a need to find new antibiotic agents to fight resistant pathogenic bacteria. To search successfully for novel antibiotics from bacteria cultivated under diverse conditions, we need a fast and cost-effective screening method. A combination of Liquid Extraction Surface Analysis (LESA), automated chip-based nanoelectrospray ionization, and high-resolution mass or tandem mass spectrometry using an Orbitrap XL was tested as the screening platform. Actinobacteria, known to produce well-recognized thiazolyl peptide antibiotics, were cultivated on a plate of solid medium and the antibiotics were extracted by organic solvent mixtures from the surface of colonies grown on the plate and analyzed using mass spectrometry (MS). LESA combined with high-resolution MS is a powerful tool with which to extract and detect thiazolyl peptide antibiotics from different Actinobacteria. Known antibiotics were correctly detected with high mass accuracy (<4 ppm) and structurally characterized using tandem mass spectra. Our method is the first step toward the development of a novel high-throughput extraction and identification tool for antibiotics in particular and natural products in general. The method described in this paper is suitable for (1) screening the natural products produced by bacterial colonies on cultivation plates within the first 2 min following extraction and (2) detecting antibiotics at high mass accuracy; the cost is around 2 Euro per sample. Copyright © 2012 John Wiley & Sons, Ltd.

Validation of a nutrition risk screening tool for children and adolescents with cystic fibrosis ages 2-20 years.

PubMed

McDonald, Catherine M

2008-04-01

According to the 2002 Cystic Fibrosis (CF) Foundation nutrition consensus report, children with CF should grow normally. Cross-sectional data from the foundation's patient registry concluded that a body mass index at or greater than the 50th percentile is associated with better lung function. A consistent, evidence-based screening process can identify those individuals with CF having nutrition risk factors associated with a decrease in pulmonary function, target early intervention, and prevent further decline. A tool for screening nutrition risk is described to identify those children with CF who would benefit from more extensive nutrition intervention. The proposed screening tool is a risk-based classification system with 3 categories: weight gain, height velocity, and body mass index. The CF Foundation recommendations regarding these parameters are incorporated, with risk points assigned when minimum body mass index, weight gain, and/or height gain standards are unmet. An interrater measure of agreement determined a satisfactory level of reliability (kappa = 0.85). Patient records (n = 85) were reviewed to determine nutrition status category (no risk or at risk) of this tool compared with the CF Foundation 2002 Nutrition Consensus, yielding sensitivity and specificity at 84% and 75%, respectively. A second comparison was made with combined, independent nutrition risk factors not included in the screening tool. The sensitivity and specificity of the screening tool compared with the combined risk factors were 86% and 78%, respectively. This tool for screening nutrition risk for CF is reliable and valid, with consistent, reproducible results, free from subject or observer bias.

Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Hvastkovs, Eli, G.; Schenkman, John B.; Rusling, James, F.

2012-07-01

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography-mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates.

Development and Validation of a Qualitative Method for Target Screening of 448 Pesticide Residues in Fruits and Vegetables Using UHPLC/ESI Q-Orbitrap Based on Data-Independent Acquisition and Compound Database.

PubMed

Wang, Jian; Chow, Willis; Chang, James; Wong, Jon W

2017-01-18

A semiautomated qualitative method for target screening of 448 pesticide residues in fruits and vegetables was developed and validated using ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC/ESI Q-Orbitrap). The Q-Orbitrap Full MS/dd-MS 2 (data dependent acquisition) was used to acquire product-ion spectra of individual pesticides to build a compound database or an MS library, while its Full MS/DIA (data independent acquisition) was utilized for sample data acquisition from fruit and vegetable matrices fortified with pesticides at 10 and 100 μg/kg for target screening purpose. Accurate mass, retention time and response threshold were three key parameters in a compound database that were used to detect incurred pesticide residues in samples. The concepts and practical aspects of in-spectrum mass correction or solvent background lock-mass correction, retention time alignment and response threshold adjustment are discussed while building a functional and working compound database for target screening. The validated target screening method is capable of screening at least 94% and 99% of 448 pesticides at 10 and 100 μg/kg, respectively, in fruits and vegetables without having to evaluate every compound manually during data processing, which significantly reduced the workload in routine practice.

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.

Nontarget approach for environmental monitoring by GC × GC-HRTOFMS in the Tokyo Bay basin.

PubMed

Zushi, Yasuyuki; Hashimoto, Shunji; Tanabe, Kiyoshi

2016-08-01

In this study, we developed an approach for sequential nontarget and target screening for the rapid and efficient analysis of multiple samples as an environmental monitoring using a comprehensive two-dimensional gas chromatograph coupled to a high resolution time-of-flight mass spectrometer (GC × GC-HRTOFMS). A key feature of the approach was the construction of an accurate mass spectral database learned from the sample via nontarget screening. To enhance the detection power in the nontarget screening, a global spectral deconvolution procedure based on non-negative matrix factorization was applied. The approach was applied to the monitoring of rivers in the Tokyo Bay basin. The majority of the compounds detected by the nontarget screening were alkyl chain-based compounds (55%). In the quantitative target screening based on the output from the nontarget screening, particularly high levels of organophosphorus flame retardants (median concentrations of 31, 116 and 141 ng l(-1) for TDCPP, TCIPP and TBEP, respectively) were observed among the target compounds. Flame retardants used for household furniture and building materials were detected in river basins where buildings and arterial traffic were dominated. The developed GC × GC-HRTOFMS approach was efficient and effective for environmental monitoring and provided valuable new information on various aspects of monitoring in the context of environmental management. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sedentary Behavior Is Independently Related to Fat Mass among Children and Adolescents in South China.

PubMed

Xue, Hongmei; Tian, Guo; Duan, Ruonan; Quan, Liming; Zhao, Li; Yang, Min; Libuda, Lars; Muckelbauer, Rebecca; Cheng, Guo

2016-10-25

We aim to explore the independent associations of sedentary behaviors (SB) with body mass distribution among Chinese children. Data on the screen-based sedentary time (television viewing and computer use) and doing homework, physical activities and dietary intake of 1586 Chinese children (50.3% girls) aged 7-15 years were obtained through validated questionnaires. Skin-fold thickness, body height, and weight were measured to calculate percent body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI). Parental characteristics were collected by questionnaires. Among girls, time of SB (screen time or doing homework) was positively related to %BF, FMI, and FFMI ( p < 0.03) after adjusting for maternal overweight, the average annual income of family, moderate-to-vigorous physical activity energy expenditure, and energy intake: Girls in the highest tertile of screen time/homework had 16.7%/23.3% higher relative FMI and 2.9%/2.9% higher relative FFMI than girls in the lowest tertile. Among boys, screen time was positively associated with FFMI ( p < 0.003), but not related to %BF and FMI ( p > 0.09), while time of doing homework was positively related to %BF and FMI ( p = 0.03). Sedentary behaviors might be positively and independently related to fat mass among Chinese children, and were more pronounced in girls.

Laser desorption mass spectrometry for molecular diagnosis

NASA Astrophysics Data System (ADS)

Chen, C. H. Winston; Taranenko, N. I.; Zhu, Y. F.; Allman, S. L.; Tang, K.; Matteson, K. J.; Chang, L. Y.; Chung, C. N.; Martin, Steve; Haff, Lawrence

1996-04-01

Laser desorption mass spectrometry has been used for molecular diagnosis of cystic fibrosis. Both 3-base deletion and single-base point mutation have been successfully detected by clinical samples. This new detection method can possibly speed up the diagnosis by one order of magnitude in the future. It may become a new biotechnology technique for population screening of genetic disease.

Lung Cancer Risk Models for Screening (R package: lcrisks)

Cancer.gov

In both the absence and presence of screening, the R package lcrisks, calculates individual risks of lung cancer and lung cancer death based on covariates: age, education, sex, race, smoking intensity/duration/quit-years, Body Mass Index, family history of lung-cancer, and self-reported emphysema. In the presence of CT screening akin to the NLST (3 yearly screens, 5 years of follow-up), it uses the covariates to estimate risk of false-positive CT screen as well as the reduction in risk of lung cancer death and increase in risk of lung cancer screening.

Cost-effectiveness of organized versus opportunistic cervical cytology screening in Hong Kong.

PubMed

Kim, Jane J; Leung, Gabriel M; Woo, Pauline P S; Goldie, Sue J

2004-06-01

To assess the cost-effectiveness of alternative cervical cancer screening strategies to inform the design and implementation of a government-sponsored population-based screening programme in Hong Kong. Cost-effectiveness analysis using a computer-based model of cervical carcinogenesis was performed. Strategies included no screening, opportunistic screening (status quo), organized screening using either conventional or liquid-based cytology conducted at different frequencies. The main outcome measures were cancer incidence reduction, years of life saved (YLS), lifetime costs and incremental cost-effectiveness ratios. Data were from local hospitals and laboratories, clinical trials, prospective studies and other published literature. Compared with no screening, a simulation of the current situation of opportunistic screening using cervical cytology produced a nearly 40 per cent reduction in the lifetime risk of cervical cancer. However, with organized screening every 3, 4 and 5 years, corresponding reductions with conventional (and liquid-based) cytology were 90.4 (92.9), 86.8 (90.2) and 83.2 per cent (87.3 per cent) compared with no screening. For all cytology-based screening strategies, opportunistic screening was more costly and less effective than an organized programme of screening every 3, 4 and 5 years. Every 3-, 4- and 5-year screening cost $12,300, $7100 and $800 per YLS, each compared with the next best alternative. Compared with the status quo of opportunistic screening, adopting a policy of organized, mass cervical screening in Hong Kong can substantially increase benefits and reduce costs.

The Report Card on BMI Report Cards.

PubMed

Thompson, Hannah R; Madsen, Kristine A

2017-06-01

Half of states in the USA have legislation requiring that schools conduct body mass index (BMI) screening among students; just under half of these states report results to parents. The effectiveness of school-based BMI screening and reporting in reducing childhood obesity is not established and the practice has raised concerns about the potential for increased weight-based stigmatization. Recent experimental studies of BMI screening and reporting have not demonstrated a positive impact on students' weight status. However, the language and formatting of BMI reports used in studies to date have been suboptimal and have likely limited the potential effectiveness of the practice. This article reviews the recent literature on school-based BMI screening and reporting and highlights important areas for future inquiry. The present review suggests that evidence to date is not sufficient to support definitive conclusions about the value of school-based BMI screening and reporting as a childhood obesity prevention tool.

Sedentary Screen Time and Left Ventricular Structure and Function: the CARDIA Study

PubMed Central

Gibbs, Bethany Barone; Reis, Jared P.; Schelbert, Erik B.; Craft, Lynette L.; Sidney, Steve; Lima, Joao; Lewis, Cora E.

2013-01-01

Sedentary screen time (watching TV or using a computer) predicts cardiovascular outcomes independently from moderate and vigorous physical activity and could impact left ventricular structure and function through the adverse consequences of sedentary behavior. Purpose To determine whether sedentary screen time is associated with measures of left ventricular structure and function. Methods The Coronary Artery Risk Development in Young Adults (CARDIA) Study measured screen time by questionnaire and left ventricular structure and function by echocardiography in 2,854 black and white participants, aged 43–55 years, in 2010–2011. Generalized linear models evaluated cross-sectional trends for echocardiography measures across higher categories of screen time and adjusting for demographics, smoking, alcohol, and physical activity. Further models adjusted for potential intermediate factors (blood pressure, antihypertensive medication use, diabetes, and body mass index (BMI). Results The relationship between screen time and left ventricular mass(LVM) differed in blacks vs. whites. Among whites, higher screen time was associated with larger LVM (P<0.001), after adjustment for height, demographics, and lifestyle variables. Associations between screen time and LVM persisted when adjusting for blood pressure, antihypertensive medication use, and diabetes (P=0.008) but not with additional adjustment for BMI (P=0.503). Similar relationships were observed for screen time with LVM indexed to height2.7, relative wall thickness, and mass-to-volume ratio. Screen time was not associated with left ventricular structure among blacks or left ventricular function in either race group. Conclusions Sedentary screen time is associated with greater LVM in white adults and this relationship was largely explained by higher overall adiposity. The lack of association in blacks supports a potential qualitative difference in the cardiovascular consequences of sedentary screen-based behavior. PMID:23863618

Comprehensive Urine Drug Screen by Gas Chromatography/Mass Spectrometry (GC/MS).

PubMed

Ramoo, Bheemraj; Funke, Melissa; Frazee, Clint; Garg, Uttam

2016-01-01

Drug screening is an essential component of clinical toxicology laboratory service. Some laboratories use only automated chemistry analyzers for limited screening of drugs of abuse and few other drugs. Other laboratories use a combination of various techniques such as immunoassays, colorimetric tests, and mass spectrometry to provide more detailed comprehensive drug screening. Mass spectrometry, gas or liquid, can screen for hundreds of drugs and is often considered the gold standard for comprehensive drug screening. We describe an efficient and rapid gas chromatography/mass spectrometry (GC/MS) method for comprehensive drug screening in urine which utilizes a liquid-liquid extraction, sample concentration, and analysis by GC/MS.

LC-MS/MS profiling-based secondary metabolite screening of Myxococcus xanthus.

PubMed

Kim, Jiyoung; Choi, Jung Nam; Kim, Pil; Sok, Dai-Eun; Nam, Soo-Wan; Lee, Choong Hwan

2009-01-01

Myxobacteria, Gram-negative soil bacteria, are a well-known producer of bioactive secondary metabolites. Therefore, this study presents a methodological approach for the high-throughput screening of secondary metabolites from 4 wild-type Myxococcus xanthus strains. First, electrospray ionization mass spectrometry (ESI-MS) was performed using extracellular crude extracts. As a result, 22 metabolite peaks were detected, and the metabolite profiling was then conducted using the m/z value, retention time, and MS/MS fragmentation pattern analyses. Among the peaks, one unknown compound peak was identified as analogous to the myxalamid A, B, and C series. An analysis of the tandem mass spectrometric fragmentation patterns and HR-MS identified myxalamid K as a new compound derived from M. xanthus. In conclusion, LC-MS/MS-based chemical screening of diverse secondary metabolites would appear to be an effective approach for discovering unknown microbial secondary metabolites.

Screening for trace explosives by AccuTOF™-DART®: an in-depth validation study.

PubMed

Sisco, Edward; Dake, Jeffrey; Bridge, Candice

2013-10-10

Ambient ionization mass spectrometry is finding increasing utility as a rapid analysis technique in a number of fields. In forensic science specifically, analysis of many types of samples, including drugs, explosives, inks, bank dye, and lotions, has been shown to be possible using these techniques [1]. This paper focuses on one type of ambient ionization mass spectrometry, Direct Analysis in Real Time Mass Spectrometry (DART-MS or DART), and its viability as a screening tool for trace explosives analysis. In order to assess viability, a validation study was completed which focused on the analysis of trace amounts of nitro and peroxide based explosives. Topics which were studied, and are discussed, include method optimization, reproducibility, sensitivity, development of a search library, discrimination of mixtures, and blind sampling. Advantages and disadvantages of this technique over other similar screening techniques are also discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography–Mass Spectrometry

PubMed Central

Hvastkovs, Eli G.; Schenkman, John B.; Rusling, James F.

2012-01-01

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography–mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates. PMID:22482786

Mammographic findings of women recalled for diagnostic work-up in digital versus screen-film mammography in a population-based screening program.

PubMed

Lipasti, Seppo; Anttila, Ahti; Pamilo, Martti

2010-06-01

Limited information is available concerning differences in the radiological findings of women recalled for diagnostic work-up in digital mammography (DM) versus screen-film mammography (SFM) screening. To compare the radiological findings, their positive predictive values (PPVs) for cancer and other process indicators of DM screening performed by computed radiography (CR) technology and SFM screening in a population-based program. The material consisted of women, 50-59 years of age, who were invited for screening: 30 153 women with DM in 2007-2008 and 32 939 women with SFM in 1999-2000. The attendance rate was 77.7% (23 440) in the DM arm and 83.8% (27 593) in the SFM arm. In the DM arm, 1.71% of those screened (401) and in the SFM arm 1.59% (438) were recalled for further work-up. The images resulting in the recall were classified as: 1) tumor-like mass, 2) parenchymal distortion/asymmetry, 3) calcifications, and 4) combination of mass and calcifications. The distributions of the various radiological findings and their PPVs for cancer were compared in both study groups. The recall rates, cancer detection rates, test specificities, and PPVs of the DM and SFM groups were also compared. Women were recalled for diagnostic work-up most often due to tumor-like mass. It was more common in SFM (1.08% per woman screened) than in DM (0.93%). The second most common finding was parenchymal distortion and asymmetry, more often in DM (0.58%) than in SFM (0.37%). Calcifications were the third most common finding. DM exposed calcifications more often (0.49%) than SFM (0.26%). The PPVs for cancer of the recalls were higher in DM than in SFM in all subgroups of radiological findings. The test specificities were similar (DM 98.9%, SFM 98.8%). Significantly more cancers were detected by DM (cancer detection rate 0.623% per woman screened, n=146) than by SFM (cancer detection rate 0.406% per woman screened, n=112). The PPVs for cancer of all recalls for diagnostic work-up were significantly higher in DM (36%) than in SFM (26%). In DM women were recalled for diagnostic work-up more often for calcifications, parenchymal distortions, and asymmetries than in SFM. In the case of tumor-like masses, more women were recalled in SFM. DM detected more cancers than SFM, and the PPVs for cancer were higher in DM than in SFM in all subgroups of radiological findings.

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.

Sedentary Behavior Is Independently Related to Fat Mass among Children and Adolescents in South China

PubMed Central

Xue, Hongmei; Tian, Guo; Duan, Ruonan; Quan, Liming; Zhao, Li; Yang, Min; Libuda, Lars; Muckelbauer, Rebecca; Cheng, Guo

2016-01-01

We aim to explore the independent associations of sedentary behaviors (SB) with body mass distribution among Chinese children. Data on the screen-based sedentary time (television viewing and computer use) and doing homework, physical activities and dietary intake of 1586 Chinese children (50.3% girls) aged 7–15 years were obtained through validated questionnaires. Skin-fold thickness, body height, and weight were measured to calculate percent body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI). Parental characteristics were collected by questionnaires. Among girls, time of SB (screen time or doing homework) was positively related to %BF, FMI, and FFMI (p < 0.03) after adjusting for maternal overweight, the average annual income of family, moderate-to-vigorous physical activity energy expenditure, and energy intake: Girls in the highest tertile of screen time/homework had 16.7%/23.3% higher relative FMI and 2.9%/2.9% higher relative FFMI than girls in the lowest tertile. Among boys, screen time was positively associated with FFMI (p < 0.003), but not related to %BF and FMI (p > 0.09), while time of doing homework was positively related to %BF and FMI (p = 0.03). Sedentary behaviors might be positively and independently related to fat mass among Chinese children, and were more pronounced in girls. PMID:27792134

Immobilized enzyme reactors in HPLC and its application in inhibitor screening: A review

PubMed Central

Fang, Si-Meng; Wang, Hai-Na; Zhao, Zhong-Xi; Wang, Wei-Hong

2011-01-01

This paper sets out to summarize the literatures based on immobilized enzyme bio-chromatography and its application in inhibitors screening in the last decade. In order to screen enzyme inhibitors from a mass of compounds in preliminary screening, multi-pore materials with good biocompatibility are used for the supports of immobilizing enzymes, and then the immobilized enzyme reactor applied as the immobilized enzyme stationary phase in HPLC. Therefore, a technology platform of high throughput screening is gradually established to screen the enzyme inhibitors as new anti-tumor drugs. Here, we briefly summarize the selective methods of supports, immobilization techniques, co-immobilized enzymes system and the screening model. PMID:29403726

Recent advances of liquid chromatography-(tandem) mass spectrometry in clinical and forensic toxicology.

PubMed

Peters, Frank T

2011-01-01

Liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) has become increasingly important in clinical and forensic toxicology as well as doping control and is now a robust and reliable technique for routine analysis in these fields. In recent years, methods for LC-MS(/MS)-based systematic toxicological analysis using triple quadrupole or ion trap instruments have been considerably improved and a new screening approach based on high-resolution MS analysis using benchtop time-of-flight MS instruments has been developed. Moreover, many applications for so-called multi-target screening and/or quantification of drugs, poisons, and or their metabolites in various biomatrices have been published. The present paper will provide an overview and discuss these recent developments focusing on the literature published after 2006. Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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.

Screening of HIV-1 Protease Using a Combination of an Ultra-High-Throughput Fluorescent-Based Assay and RapidFire Mass Spectrometry.

PubMed

Meng, Juncai; Lai, Ming-Tain; Munshi, Vandna; Grobler, Jay; McCauley, John; Zuck, Paul; Johnson, Eric N; Uebele, Victor N; Hermes, Jeffrey D; Adam, Gregory C

2015-06-01

HIV-1 protease (PR) represents one of the primary targets for developing antiviral agents for the treatment of HIV-infected patients. To identify novel PR inhibitors, a label-free, high-throughput mass spectrometry (HTMS) assay was developed using the RapidFire platform and applied as an orthogonal assay to confirm hits identified in a fluorescence resonance energy transfer (FRET)-based primary screen of > 1 million compounds. For substrate selection, a panel of peptide substrates derived from natural processing sites for PR was evaluated on the RapidFire platform. As a result, KVSLNFPIL, a new substrate measured to have a ~ 20- and 60-fold improvement in k cat/K m over the frequently used sequences SQNYPIVQ and SQNYPIV, respectively, was identified for the HTMS screen. About 17% of hits from the FRET-based primary screen were confirmed in the HTMS confirmatory assay including all 304 known PR inhibitors in the set, demonstrating that the HTMS assay is effective at triaging false-positives while capturing true hits. Hence, with a sampling rate of ~7 s per well, the RapidFire HTMS assay enables the high-throughput evaluation of peptide substrates and functions as an efficient tool for hits triage in the discovery of novel PR inhibitors. © 2015 Society for Laboratory Automation and Screening.

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.

Laser mass spectrometry for DNA sequencing, disease diagnosis, and fingerprinting

NASA Astrophysics Data System (ADS)

Chen, C. H. Winston; Taranenko, N. I.; Zhu, Y. F.; Chung, C. N.; Allman, S. L.

1997-05-01

Since laser mass spectrometry has the potential for achieving very fast DNA analysis, we recently applied it to DNA sequencing, DNA typing for fingerprinting, and DNA screening for disease diagnosis. Two different approaches for sequencing DNA have been successfully demonstrated. One is to sequence DNA with DNA ladders produced from Sanger's enzymatic method. The other is to do direct sequencing without DNA ladders. The need for quick DNA typing for identification purposes is critical for forensic application. Our preliminary results indicate laser mass spectrometry can possible be used for rapid DNA fingerprinting applications at a much lower cost than gel electrophoresis. Population screening for certain genetic disease can be a very efficient step to reducing medical costs through prevention. Since laser mass spectrometry can provide very fast DNA analysis, we applied laser mass spectrometry to disease diagnosis. Clinical samples with both base deletion and point mutation have been tested with complete success.

Hidden aconite poisoning: identification of yunaconitine and related aconitum alkaloids in urine by liquid chromatography-tandem mass spectrometry.

PubMed

Lai, Chi-Kong; Poon, Wing-Tat; Chan, Yan-Wo

2006-09-01

Poisoning from aconite occurs worldwide as a result of misuse of the potent plant. Laboratory investigation into suspected intoxication cases is challenging because the content of toxic aconitum alkaloids varies depending on the plant source, market processing, dosing protocol, hydrolytic degradation, and metabolic transformation. Using a triple-quadrupole tandem mass spectrometer, a group screening method was developed based on the mass-fragmentographic scheme of common aconitum alkaloids. The precursor-ion scans of m/z 105 and 135 permitted selective profiling of 14-O-benzoyl-norditerpenoids and the 14-O-anisoyl-norditerpenoids, respectively. Gradient reversed-phase liquid chromatography minimized coelution of isobaric compounds. The screening protocol was applied to a clinical investigation of suspected herbal poisoning. In total, 15 urine samples were thus screened positive for aconitum alkaloid over 5 years. The diagnoses of aconite poisoning in 11 patients were firmly established based on the known prescription history and the positive urine finding. In four patients, without aconitum herbs being listed in the herbal prescriptions, contamination of the herbal remedies by aconite was suspected to be the hidden cause of their acute poisoning. Yunaconitne, a highly toxic aconitum alkaloid, was thus identified in human urine for the first time. The group screening method of aconitum alkaloids in urine is an important diagnostic aid for acute poisoning by aconites of an unclear origin.

Characteristics of invasive breast cancer and overall survival of patients eligible for mass breast cancer screening in Guadeloupe compared to those of the preceding age group.

PubMed

Kadhel, Philippe; Borja De Mozota, Daphné; Gaumond, Stéphanie; Deloumeaux, Jacqueline

2017-10-01

Mass breast cancer screening is offered to French women between the ages of 50 and 74. In the French overseas department of Guadeloupe, where the population is of mostly African ancestry, a low age at diagnosis of breast cancer has been reported, as for African-Americans. This raises the question of whether breast cancer is more aggressive in the age group preceding that eligible for mass screening (40-49) in Guadeloupe. We compared the tumor-related prognostic factors, first line therapy and overall survival rates of breast cancer cases diagnosed between the 40-49 and 50-74 age groups, based on reports of the cancer registry of Guadeloupe for the period 2008-2013. The characteristics studied, risk of death after breast cancer (HR 0.84 [95% CI: 0.58-1.22] and overall survival, did not differ significantly between the two groups, except for higher tumor size (28.8 vs 24.0; p=0.004) in the younger group. These results do not show a pattern of more aggressive breast cancer in the age group preceding that eligible for mass screening in Guadeloupe. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mass Media Campaign Improves Cervical Screening across All Socio-Economic Groups

ERIC Educational Resources Information Center

Anderson, Jenny O.; Mullins, Robyn M.; Siahpush, Mohammad; Spittal, Matthew J.; Wakefield, Melanie

2009-01-01

Low socio-economic status (SES) has been associated with lower cervical screening rates. Mass media is one known strategy that can increase cervical screening participation. This study sought to determine whether a mass media campaign conducted in Victoria, Australia, in 2005 was effective in encouraging women across all SES groups to screen. Data…

An integrated high resolution mass spectrometric data acquisition method for rapid screening of saponins in Panax notoginseng (Sanqi).

PubMed

Lai, Chang-Jiang-Sheng; Tan, Ting; Zeng, Su-Ling; Qi, Lian-Wen; Liu, Xin-Guang; Dong, Xin; Li, Ping; Liu, E-Hu

2015-05-10

The aim of this study was to develop a convenient method without pretreatments for nontarget discovery of interested compounds. The segment and exposure strategy, coupled with two mass spectrometer data acquisition methods was firstly proposed for screening the saponins in extract of Panax notoginseng (Sanqi) via high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-QTOF/MS). By gradually removing certain major or moderate interference compounds, the developed segment and exposure strategy could significantly improve the detection efficiency for trace compounds. Moreover, the newly developed five-point screening approach based on a modified mass defect filter strategy and the visual isotopic ion technique was verified to be efficient and reliable in picking out the interested precursor ions. In total, 234 ginsenosides including 67 potential new ones were characterized or tentatively identified from the extract of Sanqi. Particularly, some unusual compounds containing the branched glycosyl group or new substituted acyl groups were firstly reported. The proposed integrated strategy held a strong promise for analyses of the complex mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

The effects of gray scale image processing on digital mammography interpretation performance.

PubMed

Cole, Elodia B; Pisano, Etta D; Zeng, Donglin; Muller, Keith; Aylward, Stephen R; Park, Sungwook; Kuzmiak, Cherie; Koomen, Marcia; Pavic, Dag; Walsh, Ruth; Baker, Jay; Gimenez, Edgardo I; Freimanis, Rita

2005-05-01

To determine the effects of three image-processing algorithms on diagnostic accuracy of digital mammography in comparison with conventional screen-film mammography. A total of 201 cases consisting of nonprocessed soft copy versions of the digital mammograms acquired from GE, Fischer, and Trex digital mammography systems (1997-1999) and conventional screen-film mammograms of the same patients were interpreted by nine radiologists. The raw digital data were processed with each of three different image-processing algorithms creating three presentations-manufacturer's default (applied and laser printed to film by each of the manufacturers), MUSICA, and PLAHE-were presented in soft copy display. There were three radiologists per presentation. Area under the receiver operating characteristic curve for GE digital mass cases was worse than screen-film for all digital presentations. The area under the receiver operating characteristic for Trex digital mass cases was better, but only with images processed with the manufacturer's default algorithm. Sensitivity for GE digital mass cases was worse than screen film for all digital presentations. Specificity for Fischer digital calcifications cases was worse than screen film for images processed in default and PLAHE algorithms. Specificity for Trex digital calcifications cases was worse than screen film for images processed with MUSICA. Specific image-processing algorithms may be necessary for optimal presentation for interpretation based on machine and lesion type.

Recent developments and new applications of tandem mass spectrometry in newborn screening.

PubMed

Rinaldo, Piero; Tortorelli, Silvia; Matern, Dietrich

2004-08-01

To summarize recent developments in the field of newborn screening related to the use of tandem mass spectrometry as an analytic platform. Novel inborn errors of metabolism with informative amino acid and/or acylcarnitine profiles have been characterized, increasing the complexity of the differential diagnosis of abnormal results. In addition, methods have been developed for the analysis in dried blood spots of steroids and lysosomal enzymes. Previously unrecognized genotype/phenotype correlations have been found among cohorts of patients whose conditions were diagnosed by screening rather than clinically. Several government entities and professional organizations have issued position statements on newborn screening, and worldwide outcome studies continue to underscore the clinical and financial benefits of expanded newborn screening. Although it is done inconsistently, newborn screening in the United States is undergoing a rapid expansion driven by the introduction of tandem mass spectrometry in at least 34 state programs. This technology is also used to detect disease markers beyond acylcarnitines and amino acids, as both primary and second-tier tests. In addition to analytic improvements, there is a trend toward the development of joint programs not limited to contiguous geographic areas, often based upon public-private partnerships. This review will summarize several new developments in the field that have occurred since early 2003 and will mention others likely to occur in the near future.

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

PubMed

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

2018-04-01

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

Systematic screening and characterization of flavonoid glycosides in Carthamus tinctorius L. by liquid chromatography/UV diode-array detection/electrospray ionization tandem mass spectrometry.

PubMed

Jin, Yu; Xiao, Yuan-sheng; Zhang, Fei-fang; Xue, Xing-ya; Xu, Qing; Liang, Xin-miao

2008-02-13

The traditional Chinese medicine (TCM) is a complex system, which always consists of numerous compounds with significant difference in the content and physical and chemical properties. In this paper, a screening method based on target molecular weights was developed to characterize the flavonoid glycosides in the flower of Carthamus tinctorius L. The screening tables of aglycone and glycan were designed, respectively, in order to select and combine freely. The multiple reaction monitoring (MRM) scan mode with higher sensitivity and selectivity was adopted in the screening, which benefit the characterization for the minor components. Seventy-seven flavonoid glycosides were screened out finally, and their structures were characterized by tandem mass spectrometric method in both positive and negative ion modes. The glycosylation mode, aglycone, sequence and/or the interglycosidic linkages of the glycan portion and glycosylation position were elucidated by the fragmentation rule in the MS. Numerous compounds screened out with this method showed the structure variety in secondary plant metabolites, and the purposeful screening systemically and subsequent structure characterization offered more information about the chemical constitutions of TCM.

Screening of lysosomal storage disorders: application of the online trapping-and-cleanup liquid chromatography/mass spectrometry method for mucopolysaccharidosis I.

PubMed

Ombrone, Daniela; Malvagia, Sabrina; Funghini, Silvia; Giocaliere, Elisa; Della Bona, Maria Luisa; Forni, Giulia; De Luca, Alessio; Villanelli, Fabio; Casetta, Bruno; Guerrini, Renzo; la Marca, Giancarlo

2013-01-01

In recent years, new treatments have become available to treat some lysosomal storage disorders (LSDs) and many studies suggest that there is a benefit with starting therapy early. Newborn screening should detect diseases early enough for prompt treatment. Some countries include additional conditions, such as some LSDs, into their newborn screening panels. Mucopolysaccharidosis Type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase (IDUA) activity. Currently, enzyme replacement therapy (ERT) or bone marrow transplantation is available and this has raised a growing interest for the development of a newborn screening test. In 2009, we reported a new fast and simplified tandem mass spectrometry-based method for quantifying five enzyme activities on dried blood spots. Here, we describe the inclusion of IDUA activity determination for the simultaneous detection of six lysosomal storage diseases. We have defined reference normal ranges by testing 680 healthy newborns and 240 adults. The assay was checked through three confirmed MPS I patients whose IDUA activity was below the normal range. Reproducibility of the assays has been established by assessing the intra-day and inter-day assay imprecisions. This quick assay has been devised to be implemented in newborn screening by liquid chromatography tandem mass spectrometry.

Effect of implementation of the mass breast cancer screening programme in older women in the Netherlands: population based study.

PubMed

de Glas, Nienke A; de Craen, Anton J M; Bastiaannet, Esther; Op 't Land, Ester G; Kiderlen, Mandy; van de Water, Willemien; Siesling, Sabine; Portielje, Johanneke E A; Schuttevaer, Herman M; de Bock, Geertruida Truuske H; van de Velde, Cornelis J H; Liefers, Gerrit-Jan

2014-09-14

To assess the incidence of early stage and advanced stage breast cancer before and after the implementation of mass screening in women aged 70-75 years in the Netherlands in 1998. Prospective nationwide population based study. National cancer registry, the Netherlands. Patients aged 70-75 years with a diagnosis of invasive or ductal carcinoma in situ breast cancer between 1995 and 2011 (n=25,414). Incidence rates were calculated using population data from Statistics Netherlands. Incidence rates of early stage (I, II, or ductal carcinoma in situ) and advanced stage (III and IV) breast cancer before and after implementation of screening. Hypotheses were formulated before data collection. The incidence of early stage tumours significantly increased after the extension for implementation of screening (248.7 cases per 100,000 women before screening up to 362.9 cases per 100,000 women after implementation of screening, incidence rate ratio 1.46, 95% confidence interval 1.40 to 1.52, P<0.001). However, the incidence of advanced stage breast cancers decreased to a far lesser extent (58.6 cases per 100,000 women before screening to 51.8 cases per 100,000 women after implementation of screening, incidence rate ratio 0.88, 0.81 to 0.97, P<0.001). The extension of the upper age limit to 75 years has only led to a small decrease in incidence of advanced stage breast cancer, while that of early stage tumours has strongly increased. © de Glas et al 2014.

A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus.

PubMed

Melo, Carlos Fernando Odir Rodrigues; Navarro, Luiz Claudio; de Oliveira, Diogo Noin; Guerreiro, Tatiane Melina; Lima, Estela de Oliveira; Delafiori, Jeany; Dabaja, Mohamed Ziad; Ribeiro, Marta da Silva; de Menezes, Maico; Rodrigues, Rafael Gustavo Martins; Morishita, Karen Noda; Esteves, Cibele Zanardi; de Amorim, Aline Lopes Lucas; Aoyagui, Caroline Tiemi; Parise, Pierina Lorencini; Milanez, Guilherme Paier; do Nascimento, Gabriela Mansano; Ribas Freitas, André Ricardo; Angerami, Rodrigo; Costa, Fábio Trindade Maranhão; Arns, Clarice Weis; Resende, Mariangela Ribeiro; Amaral, Eliana; Junior, Renato Passini; Ribeiro-do-Valle, Carolina C; Milanez, Helaine; Moretti, Maria Luiza; Proenca-Modena, Jose Luiz; Avila, Sandra; Rocha, Anderson; Catharino, Rodrigo Ramos

2018-01-01

Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus) identification. Reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a "fingerprint" for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening-faster and more accurate-with improved cost-effectiveness when compared to existing technologies.

Allele-specific HLA-DR typing by mass spectrometry: an alternative to hybridization-based typing methods.

PubMed

Worrall, T A; Schmeckpeper, B J; Corvera, J S; Cotter, R J

2000-11-01

The primer oligomer base extension (PROBE) reaction, combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, is used to characterize HLA-DR2 polymorphism. Alleles are distinguished rapidly and accurately by measuring the mass of primer extension products at every known variable region of HLA-DR2 alleles. Since differentiation of alleles by PROBE relies on measuring differences in extension product mass rather than differences in hybridization properties, mistyped alleles resulting from nonspecific hybridization are absent. The method shows considerable potential for high-throughput screening of HLA-DR polymorphism in a chip-based format, including rapid tissue typing of unrelated volunteer donors.

Rapid screening of illicit additives in weight loss dietary supplements with desorption corona beam ionisation (DCBI) mass spectrometry.

PubMed

Wang, H; Wu, Y; Zhao, Y; Sun, W; Ding, L; Guo, B; Chen, B

2012-08-01

Desorption corona beam ionisation (DCBI), the relatively novel ambient mass spectrometry (MS) technique, was utilised to screen for illicit additives in weight-loss food. The five usually abused chemicals - fenfluramine, N-di-desmethyl sibutramine, N-mono-desmethyl sibutramine, sibutramine and phenolphthalein - were detected with the proposed DCBI-MS method. Fast single-sample and high-throughput analysis was demonstrated. Semi-quantification was accomplished based on peak areas in the ion chromatograms. Four illicit additives were identified and semi-quantified in commercial samples. As there was no tedious sample pre-treatment compared with conventional HPLC methods, high-throughput analysis was achieved with DCBI. The results proved that DCBI-MS is a powerful tool for the rapid screening of illicit additives in weight-loss dietary supplements.

Mapping HL7 CDA R2 Formatted Mass Screening Data to OpenEHR Archetypes.

PubMed

Kobayashi, Shinji; Kume, Naoto; Yoshihara, Hiroyuki

2017-01-01

Mass screening of adults was performed to manage employee healthcare. The screening service defined the data collection format as HL7 Clinical Document Architecture (CDA) R2. To capture mass screening data for nationwide electronic health records (her), we programmed a model within the CDA format and mapped the data items to the ISO13606/openEHR archetype for semantic interoperabiilty.

Bidirectional associations between activity-related parenting practices, and child physical activity, sedentary screen-based behavior and body mass index: a longitudinal analysis.

PubMed

Sleddens, Ester F C; Gubbels, Jessica S; Kremers, Stef P J; van der Plas, Eline; Thijs, Carel

2017-07-06

It has been generally assumed that activity-related parenting practices influence children's activity behavior and weight status. However, vice versa parents may also change their parenting behaviors in response to their perceptions of their child's activity behavior and weight status. This study examined the bidirectional relationships between activity-related parenting practices, and physical activity, sedentary screen-based behavior, and body mass index (BMI) between children's age of 5 and 7 years. Three scales of the Activity-related Parenting Questionnaire (i.e. 'restriction of sedentary behavior', 'stimulation of physical activity', and 'monitoring of physical activity') were completed by 1694 parents of the Dutch KOALA Birth Cohort Study at the child's age of around 5 and again around age 7. Physical activity, sedentary screen-based behavior and BMI were measured at both ages as well. Linear regression models were used to estimate the bidirectional associations between each parenting practice and the child's physical activity levels, sedentary screen-based behavior and BMI z-scores. Several parenting practices at age 5 predicted child physical activity, sedentary screen-based behavior, and BMI z-scores at age 7. Restriction of sedentary behavior positively predicted child BMI and sedentary screen-based behavior, whereas this practice negatively predicted child physical activity. In addition, stimulation of physical activity at age 5 was significantly associated with higher levels of child physical activity at age 7. The following child factors at age 5 predicted parenting practices at age 7: Child physical activity positively predicted parental stimulation of physical activity and monitoring activities. Sedentary screen-based behavior was associated with lower parental stimulation to be active. Findings generally revealed that parents and children mutually influence each other's behavior. A reinforcing feedback loop was present between parental stimulation of physical activity and child physical activity. Bidirectional parent-child interaction should be considered in future research in order to properly inform parenting-related intervention programs aimed at preventing or treating childhood overweight or obesity. System dynamic methods to explore the existence of reinforcing or balancing loops are needed in this regard.

Hollow fiber based affinity selection combined with high performance liquid chromatography-mass spectroscopy for rapid screening lipase inhibitors from lotus leaf.

PubMed

Tao, Yi; Zhang, Yufeng; Wang, Yi; Cheng, Yiyu

2013-06-27

A novel kind of immobilized enzyme affinity selection strategy based on hollow fibers has been developed for screening inhibitors from extracts of medicinal plants. Lipases from porcine pancreas were adsorbed onto the surface of polypropylene hollow fibers to form a stable matrix for ligand fishing, which was called hollow fibers based affinity selection (HF-AS). A variety of factors related to binding capability, including enzyme concentration, incubation time, temperature, buffer pH and ion strength, were optimized using a known lipase inhibitor hesperidin. The proposed approach was applied in screening potential lipase bound ligands from extracts of lotus leaf, followed by rapid characterization of active compounds using high performance liquid chromatography-mass spectrometry. Three flavonoids including quercetin-3-O-β-D-arabinopyranosyl-(1→2)-β-D-galactopyranoside, quercetin-3-O-β-D-glucuronide and kaempferol-3-O-β-d-glucuronide were identified as lipase inhibitors by the proposed HF-AS approach. Our findings suggested that the hollow fiber-based affinity selection could be a rapid and convenient approach for drug discovery from natural products resources. Copyright © 2013 Elsevier B.V. All rights reserved.

Non-invasive prenatal testing for fetal chromosome abnormalities: review of clinical and ethical issues

PubMed Central

Gekas, Jean; Langlois, Sylvie; Ravitsky, Vardit; Audibert, François; van den Berg, David Gradus; Haidar, Hazar; Rousseau, François

2016-01-01

Genomics-based non-invasive prenatal screening using cell-free DNA (cfDNA screening) was proposed to reduce the number of invasive procedures in current prenatal diagnosis for fetal aneuploidies. We review here the clinical and ethical issues of cfDNA screening. To date, it is not clear how cfDNA screening is going to impact the performances of clinical prenatal diagnosis and how it could be incorporated in real life. The direct marketing to users may have facilitated the early introduction of cfDNA screening into clinical practice despite limited evidence-based independent research data supporting this rapid shift. There is a need to address the most important ethical, legal, and social issues before its implementation in a mass setting. Its introduction might worsen current tendencies to neglect the reproductive autonomy of pregnant women. PMID:26893576

Non-invasive prenatal testing for fetal chromosome abnormalities: review of clinical and ethical issues.

PubMed

Gekas, Jean; Langlois, Sylvie; Ravitsky, Vardit; Audibert, François; van den Berg, David Gradus; Haidar, Hazar; Rousseau, François

2016-01-01

Genomics-based non-invasive prenatal screening using cell-free DNA (cfDNA screening) was proposed to reduce the number of invasive procedures in current prenatal diagnosis for fetal aneuploidies. We review here the clinical and ethical issues of cfDNA screening. To date, it is not clear how cfDNA screening is going to impact the performances of clinical prenatal diagnosis and how it could be incorporated in real life. The direct marketing to users may have facilitated the early introduction of cfDNA screening into clinical practice despite limited evidence-based independent research data supporting this rapid shift. There is a need to address the most important ethical, legal, and social issues before its implementation in a mass setting. Its introduction might worsen current tendencies to neglect the reproductive autonomy of pregnant women.

Radiologists' preferences for digital mammographic display. The International Digital Mammography Development Group.

PubMed

Pisano, E D; Cole, E B; Major, S; Zong, S; Hemminger, B M; Muller, K E; Johnston, R E; Walsh, R; Conant, E; Fajardo, L L; Feig, S A; Nishikawa, R M; Yaffe, M J; Williams, M B; Aylward, S R

2000-09-01

To determine the preferences of radiologists among eight different image processing algorithms applied to digital mammograms obtained for screening and diagnostic imaging tasks. Twenty-eight images representing histologically proved masses or calcifications were obtained by using three clinically available digital mammographic units. Images were processed and printed on film by using manual intensity windowing, histogram-based intensity windowing, mixture model intensity windowing, peripheral equalization, multiscale image contrast amplification (MUSICA), contrast-limited adaptive histogram equalization, Trex processing, and unsharp masking. Twelve radiologists compared the processed digital images with screen-film mammograms obtained in the same patient for breast cancer screening and breast lesion diagnosis. For the screening task, screen-film mammograms were preferred to all digital presentations, but the acceptability of images processed with Trex and MUSICA algorithms were not significantly different. All printed digital images were preferred to screen-film radiographs in the diagnosis of masses; mammograms processed with unsharp masking were significantly preferred. For the diagnosis of calcifications, no processed digital mammogram was preferred to screen-film mammograms. When digital mammograms were preferred to screen-film mammograms, radiologists selected different digital processing algorithms for each of three mammographic reading tasks and for different lesion types. Soft-copy display will eventually allow radiologists to select among these options more easily.

An Analysis of Mass Screening Strategies Using a Mathematical Model: Comparison of Breast Cancer Screening in Japan and the United States

PubMed Central

Tsunematsu, Miwako; Kakehashi, Masayuki

2015-01-01

Background Although the United States Preventive Services Task Force (USPSTF) downgraded their recommendation for breast cancer screening for women aged 40–49 years in 2009, Japanese women in their 40s have been encouraged to attend breast cancer screenings since 2004. The aim of this study is to examine whether these different mass-screening strategies are justifiable by the different situations of these countries and to provide evidence for suitable judgment. Methods Performance of screening strategies (annual/biennial intervals; initiating/terminating ages) was evaluated using a mathematical model based on the natural history of breast cancer and the transition between its stages. Benefits (reduced number of deaths and extended average life expectancy) and harm (false-positives) associated with these strategies were calculated. Results Additional average life expectancy by including women in their 40s as participants were 13 days (26%) and 25 days (22%) in Japan and the United States, respectively, under the biennial screening condition; however, the respective increases in numbers of false-positive cases were 65% and 53% in Japan and the United States. Moreover, the number of screenings needed to detect one diagnosis or to avert one death was smaller when participants were limited to women of age 50 or over than when women in their 40s were included. The validity of including women in their 40s in Japan could not be determined without specifying the weight of harms compared to benefits. Conclusions Whether screening of women in their 40s in Japan is justifiable must be carefully determined based the quantitative balance of benefits and harms. PMID:25483105

[Model project for updating neonatal screening in Bavaria: concept and initial results].

PubMed

Liebl, B; Fingerhut, R; Röschinger, W; Muntau, A; Knerr, I; Olgemöller, B; Zapf, A; Roscher, A A

2000-04-01

The newborn screening programme in Bavaria was confronted with several problems. Number of disorders and process quality no longer complied with screening guidelines. Mixed financing, distributed between the state (PKU, galactosaemia) and health insurances (hypothyroidism) had promoted an increasing dissipation of the system. Notified participation rates had dropped to < 80%. Increasing need for a second screening due to early discharge was an additional challenge. To overcome these problems, and considering the availability of improved screening methodology (tandem mass spectrometry) the programme was reorganised. The project, which started on Jan 1, 1999, is based on a cooperation model between laboratory (logistics, analysis), universities (treatment, scientific evaluation), and public health services (coordination, tracking). Time of blood sampling was predated to the third day of life. Screening was extended to biotinidase deficiency, congenital adrenal hyperplasia (CAH) and by introduction of tandem mass spectrometry for screening of many other disorders (besides PKU). Insurances now finance complete laboratory analysis which was transferred to the private sector. To enable all newborn to participate, the names of screened children are matched against birth lists by public health services on a regional basis. Recalls and conspicuous results are consistently followed up until disorders are either excluded or confirmed. Two clinical hotlines were established in the children's hospitals of the universities in Munich (Southern Bavaria) and in Erlangen (Northern Bavaria). Written consent is required for participation in the programme. Participation in the new programme could be continually increased; coverage is > 95% since April. In several cases screening was made up for not tested children by contacting their parents. Omitted screening was mostly due to misunderstandings regarding testing responsibility or lost samples. Altogether 52 cases of disorder were found in the 87,000 newborn screened until August 1999. Hence, the detection rate of children affected by inborn errors of metabolism was about twice as high than before changes. Among the newly screened diseases CAH was detected most often (11 cases). In 22 cases diagnosis was based on the use of tandem mass spectrometry. Among these (besides PKU, 9 cases) MCAD deficiency (6 cases) was detected most frequently. Whereas recall rates of most disorders were < 0.1%, screening for CAH still revealed a high recall rate, particularly in premature births. Second screening due to early discharge (< 48 h) was required in 1.3%. About 20% of pending recalls required contacting birth hospitals, doctors, midwives or parents. So far all affected children could be brought to treatment in time.

Long term effects of community-based STI screening and mass media HIV prevention messages on sexual risk behaviors of African American adolescents.

PubMed

Sznitman, Sharon; Stanton, Bonita F; Vanable, Peter A; Carey, Michael P; Valois, Robert F; Brown, Larry K; DiClemente, Ralph; Hennessy, Michael; Salazar, Laura F; Romer, Daniel

2011-11-01

We examined the long-term effects of two interventions designed to reduce sexual risk behavior among African American adolescents. African American adolescents (N = 1383, ages 14-17) were recruited from community-based organizations over a period of 16 months in two northeastern and two southeastern mid-sized U.S. cities with high rates of sexually transmitted infection (STI). Participants were screened for three STIs (gonorrhea, chlamydia, and trichomoniasis) and completed an audio computer-assisted attitude, intention, and behavior self-interview. Youth who tested positive for an STI (8.3%) received treatment and risk reduction counseling. In addition, television and radio HIV-prevention messages were delivered during the recruitment period and 18 months of follow-up in one randomly selected city in each region. Analyses determined effects of the media program for those receiving a positive versus negative STI test result on number of sexual partners and occurrence of unprotected sex. Adolescents who tested STI-positive reduced their number of vaginal sex partners and the probability of unprotected sex over the first 6 months. However, in the absence of the mass media program, adolescents returned to their previously high levels of sexual risk behavior after 6 months. Adolescents who tested STI-positive and received the mass media program showed more stable reductions in unprotected sex. Community-based STI treatment and counseling can achieve significant, but short-lived reductions in sexual risk behavior among STI-positive youth. A culturally sensitive mass media program has the potential to achieve more stable reductions in sexual risk behavior and can help to optimize the effects of community-based STI screening.

Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring

EPA Science Inventory

There is a growing need in the field of exposure science for monitoring methods that rapidly screen environmental media for suspect contaminants. Measurement and analysis platforms, based on high resolution mass spectrometry (HRMS), now exist to meet this need. Here we describe r...

Wide-range screening of psychoactive substances by FIA-HRMS: identification strategies.

PubMed

Alechaga, Élida; Moyano, Encarnación; Galceran, Maria Teresa

2015-06-01

Recreational drugs (illicit drugs, human and veterinary medicines, legal highs, etc.) often contain lacing agents and adulterants which are not related to the main active ingredient. Serious side effects and even the death of the consumer have been related to the consumption of mixtures of psychoactive substances and/or adulterants, so it is important to know the actual composition of recreational drugs. In this work, a method based on flow injection analysis (FIA) coupled with high-resolution mass spectrometry (HRMS) is proposed for the fast identification of psychoactive substances in recreational drugs and legal highs. The FIA and HRMS working conditions were optimized in order to detect a wide range of psychoactive compounds. As most of the psychoactive substances are acid-base compounds, methanol-0.1 % aqueous formic acid (1:1 v/v) as a carrier solvent and electrospray in both positive ion mode and negative ion mode were used. Two data acquisition modes, full scan at high mass resolution (HRMS) and data-dependent tandem mass spectrometry (ddMS/HRMS) with a quadrupole-Orbitrap mass analyzer were used, resulting in sufficient selectivity for identification of the components of the samples. A custom-made database containing over 450 substances, including psychoactive compounds and common adulterants, was built to perform a high-throughput target and suspect screening. Moreover, online accurate mass databases and mass fragmenter software were used to identify unknowns. Some examples, selected among the analyzed samples of recreational drugs and legal highs using the FIA-HRMS(ddMS/HRMS) method developed, are discussed to illustrate the screening strategy used in this study. The results showed that many of the analyzed samples were adulterated, and in some cases the sample composition did not match that of the supposed marketed substance.

Mass Detection in Mammographic Images Using Wavelet Processing and Adaptive Threshold Technique.

PubMed

Vikhe, P S; Thool, V R

2016-04-01

Detection of mass in mammogram for early diagnosis of breast cancer is a significant assignment in the reduction of the mortality rate. However, in some cases, screening of mass is difficult task for radiologist, due to variation in contrast, fuzzy edges and noisy mammograms. Masses and micro-calcifications are the distinctive signs for diagnosis of breast cancer. This paper presents, a method for mass enhancement using piecewise linear operator in combination with wavelet processing from mammographic images. The method includes, artifact suppression and pectoral muscle removal based on morphological operations. Finally, mass segmentation for detection using adaptive threshold technique is carried out to separate the mass from background. The proposed method has been tested on 130 (45 + 85) images with 90.9 and 91 % True Positive Fraction (TPF) at 2.35 and 2.1 average False Positive Per Image(FP/I) from two different databases, namely Mammographic Image Analysis Society (MIAS) and Digital Database for Screening Mammography (DDSM). The obtained results show that, the proposed technique gives improved diagnosis in the early breast cancer detection.

A data-independent acquisition workflow for qualitative screening of new psychoactive substances in biological samples.

PubMed

Kinyua, Juliet; Negreira, Noelia; Ibáñez, María; Bijlsma, Lubertus; Hernández, Félix; Covaci, Adrian; van Nuijs, Alexander L N

2015-11-01

Identification of new psychoactive substances (NPS) is challenging. Developing targeted methods for their analysis can be difficult and costly due to their impermanence on the drug scene. Accurate-mass mass spectrometry (AMMS) using a quadrupole time-of-flight (QTOF) analyzer can be useful for wide-scope screening since it provides sensitive, full-spectrum MS data. Our article presents a qualitative screening workflow based on data-independent acquisition mode (all-ions MS/MS) on liquid chromatography (LC) coupled to QTOFMS for the detection and identification of NPS in biological matrices. The workflow combines and structures fundamentals of target and suspect screening data processing techniques in a structured algorithm. This allows the detection and tentative identification of NPS and their metabolites. We have applied the workflow to two actual case studies involving drug intoxications where we detected and confirmed the parent compounds ketamine, 25B-NBOMe, 25C-NBOMe, and several predicted phase I and II metabolites not previously reported in urine and serum samples. The screening workflow demonstrates the added value for the detection and identification of NPS in biological matrices.

Probing nanoparticles and nanoparticle-conjugated biomolecules using time-of-flight secondary ion mass spectrometry.

PubMed

Kim, Young-Pil; Shon, Hyun Kyong; Shin, Seung Koo; Lee, Tae Geol

2015-01-01

Bio-conjugated nanoparticles have emerged as novel molecular probes in nano-biotechnology and nanomedicine and chemical analyses of their surfaces have become challenges. The time-of-flight (TOF) secondary ion mass spectrometry (SIMS) has been one of the most powerful surface characterization techniques for both nanoparticles and biomolecules. When combined with various nanoparticle-based signal enhancing strategies, TOF-SIMS can probe the functionalization of nanoparticles as well as their locations and interactions in biological systems. Especially, nanoparticle-based SIMS is an attractive approach for label-free drug screening because signal-enhancing nanoparticles can be designed to directly measure the enzyme activity. The chemical-specific imaging analysis using SIMS is also well suited to screen nanoparticles and nanoparticle-biomolecule conjugates in complex environments. This review presents some recent applications of nanoparticle-based TOF-SIMS to the chemical analysis of complex biological systems. © 2014 Wiley Periodicals, Inc.

Breast Mass Detection in Digital Mammogram Based on Gestalt Psychology

PubMed Central

Bu, Qirong; Liu, Feihong; Zhang, Min; Ren, Yu; Lv, Yi

2018-01-01

Inspired by gestalt psychology, we combine human cognitive characteristics with knowledge of radiologists in medical image analysis. In this paper, a novel framework is proposed to detect breast masses in digitized mammograms. It can be divided into three modules: sensation integration, semantic integration, and verification. After analyzing the progress of radiologist's mammography screening, a series of visual rules based on the morphological characteristics of breast masses are presented and quantified by mathematical methods. The framework can be seen as an effective trade-off between bottom-up sensation and top-down recognition methods. This is a new exploratory method for the automatic detection of lesions. The experiments are performed on Mammographic Image Analysis Society (MIAS) and Digital Database for Screening Mammography (DDSM) data sets. The sensitivity reached to 92% at 1.94 false positive per image (FPI) on MIAS and 93.84% at 2.21 FPI on DDSM. Our framework has achieved a better performance compared with other algorithms. PMID:29854359

Anatomy of the magnetic catalysis by renormalization-group method

NASA Astrophysics Data System (ADS)

Hattori, Koichi; Itakura, Kazunori; Ozaki, Sho

2017-12-01

We first examine the scaling argument for a renormalization-group (RG) analysis applied to a system subject to the dimensional reduction in strong magnetic fields, and discuss the fact that a four-Fermi operator of the low-energy excitations is marginal irrespective of the strength of the coupling constant in underlying theories. We then construct a scale-dependent effective four-Fermi interaction as a result of screened photon exchanges at weak coupling, and establish the RG method appropriately including the screening effect, in which the RG evolution from ultraviolet to infrared scales is separated into two stages by the screening-mass scale. Based on a precise agreement between the dynamical mass gaps obtained from the solutions of the RG and Schwinger-Dyson equations, we discuss an equivalence between these two approaches. Focusing on QED and Nambu-Jona-Lasinio model, we clarify how the properties of the interactions manifest themselves in the mass gap, and point out an importance of respecting the intrinsic energy-scale dependences in underlying theories for the determination of the mass gap. These studies are expected to be useful for a diagnosis of the magnetic catalysis in QCD.

Newborn screening by matrix-assisted laser desorption/ionization mass spectrometry based on parylene-matrix chip.

PubMed

Kim, Jo-Il; Noh, Joo-Yoon; Kim, Mira; Park, Jong-Min; Song, Hyun-Woo; Kang, Min-Jung; Pyun, Jae-Chul

2017-08-01

Newborn screening for diagnosis of phenylketonuria, homocystinuria, and maple syrup urine disease have been conducted by analyzing the concentration of target amino acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) based on parylene-matrix chip. Parylene-matrix chip was applied to MALDI-ToF MS analysis reducing the matrix peaks significantly at low mass-to-charge ratio range (m/z < 500). Reproducibility of inter-spot and intra-spot analyses of amino acids was less than 10%. Methanol extraction was adopted for simple and rapid sample preparation of serum before mass spectrometric analysis showing 13.3 to 45% of extraction efficiency. Calibration curves for diagnosis of neonatal metabolic disorders were obtained by analyzing methanol-extracted serum spiked with target amino acids using MALDI-ToF MS. They showed good linearity (R 2  > 0.98) and the LODs were ranging from 9.0 to 22.9 μg/mL. Effect of proteins in serum was estimated by comparing MALDI-ToF mass spectra of amino acids-spiked serum before and after the methanol extraction. Interference of other amino acids on analysis of target analyte was determined to be insignificant. From these results, MALDI-ToF MS based on parylene-matrix chip could be applicable to medical diagnosis of neonatal metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

What the neurosurgeon should know about hemangioblastoma, both sporadic and in Von Hippel-Lindau disease: A literature review

PubMed Central

Bamps, Sven; Calenbergh, Frank Van; Vleeschouwer, Steven De; Loon, Johannes Van; Sciot, Raf; Legius, Eric; Goffin, Jan

2013-01-01

Background: Hemangioblastomas are associated with Von Hippel-Lindau disease (VHLD) in 10-40% of cases. Based upon a literature review we state the core features the neurosurgeon should be aware of. Methods: We performed a selective literature (Cochrane and Medline) search for hemangioblastoma, both sporadic and VHL associated. We reviewed general characteristics (epidemiology, symptomatology, diagnosis, and management) and focused on follow-up as well as screening modalities for sporadic and VHL associated lesions. Results: Based upon our literature search, we established guidelines for screening and follow-up in both sporadic and VHL associated hemangioblastoma patients. Conclusions: Screening for retinal angiomas, abdominal masses, and pheochromocytomas as well as genetic analysis is recommended for every patient with a newly diagnosed hemangioblastoma. Follow-up is by magnetic resonance imaging (MRI) of the clinical neuronal region at 6 and at 12-24 months postoperatively. For VHL-associated hemangioblastomas yearly investigation for craniospinal hemangioblastoma by MRI and yearly screening and follow-up for retinal angiomas is recommended. Annual abdominal ultrasound with triennial computed tomography (CT) imaging for abdominal masses is postulated. Annual audiometry is to be performed for possible endolymphatic sac tumor, detailed radiographic imaging of the skull base should be performed upon abnormality in auditory testing. Investigations for cystadenomas of the epidydimis and broad ligament only are mandatory on indication. Annual investigation for pheochromocytoma is recommended. PMID:24340227

Suspected-target pesticide screening using gas chromatography-quadrupole time-of-flight mass spectrometry with high resolution deconvolution and retention index/mass spectrum library.

PubMed

Zhang, Fang; Wang, Haoyang; Zhang, Li; Zhang, Jing; Fan, Ruojing; Yu, Chongtian; Wang, Wenwen; Guo, Yinlong

2014-10-01

A strategy for suspected-target screening of pesticide residues in complicated matrices was exploited using gas chromatography in combination with hybrid quadrupole time-of-flight mass spectrometry (GC-QTOF MS). The screening workflow followed three key steps of, initial detection, preliminary identification, and final confirmation. The initial detection of components in a matrix was done by a high resolution mass spectrum deconvolution; the preliminary identification of suspected pesticides was based on a special retention index/mass spectrum (RI/MS) library that contained both the first-stage mass spectra (MS(1) spectra) and retention indices; and the final confirmation was accomplished by accurate mass measurements of representative ions with their response ratios from the MS(1) spectra or representative product ions from the second-stage mass spectra (MS(2) spectra). To evaluate the applicability of the workflow in real samples, three matrices of apple, spinach, and scallion, each spiked with 165 test pesticides in a set of concentrations, were selected as the models. The results showed that the use of high-resolution TOF enabled effective extractions of spectra from noisy chromatograms, which was based on a narrow mass window (5 mDa) and suspected-target compounds identified by the similarity match of deconvoluted full mass spectra and filtering of linear RIs. On average, over 74% of pesticides at 50 ng/mL could be identified using deconvolution and the RI/MS library. Over 80% of pesticides at 5 ng/mL or lower concentrations could be confirmed in each matrix using at least two representative ions with their response ratios from the MS(1) spectra. In addition, the application of product ion spectra was capable of confirming suspected pesticides with specificity for some pesticides in complicated matrices. In conclusion, GC-QTOF MS combined with the RI/MS library seems to be one of the most efficient tools for the analysis of suspected-target pesticide residues in complicated matrices. Copyright © 2014 Elsevier B.V. All rights reserved.

Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a cost-effectiveness analysis.

PubMed

Pfeil, Johannes; Listl, Stefan; Hoffmann, Georg F; Kölker, Stefan; Lindner, Martin; Burgard, Peter

2013-10-17

Glutaric aciduria type I (GA-I) is a rare metabolic disorder caused by inherited deficiency of glutaryl-CoA dehydrogenase. Despite high prognostic relevance of early diagnosis and start of metabolic treatment as well as an additional cost saving potential later in life, only a limited number of countries recommend newborn screening for GA-I. So far only limited data is available enabling health care decision makers to evaluate whether investing into GA-I screening represents value for money. The aim of our study was therefore to assess the cost-effectiveness of newborn screening for GA-I by tandem mass spectrometry (MS/MS) compared to a scenario where GA-I is not included in the MS/MS screening panel. We assessed the cost-effectiveness of newborn screening for GA-I against the alternative of not including GA-I in MS/MS screening. A Markov model was developed simulating the clinical course of screened and unscreened newborns within different time horizons of 20 and 70 years. Monte Carlo simulation based probabilistic sensitivity analysis was used to determine the probability of GA-I screening representing a cost-effective therapeutic strategy. Within a 20 year time horizon, GA-I screening averts approximately 3.7 DALYs (95% CI 2.9 - 4.5) and about one life year is gained (95% CI 0.7 - 1.4) per 100,000 neonates screened initially . Moreover, the screening programme saves a total of around 30,682 Euro (95% CI 14,343 to 49,176 Euro) per 100,000 screened neonates over a 20 year time horizon. Within the limitations of the present study, extending pre-existing MS/MS newborn screening programmes by GA-I represents a highly cost-effective diagnostic strategy when assessed under conditions comparable to the German health care system.

Photovoltaic and Impedance Spectroscopy Study of Screen-Printed TiO₂ Based CdS Quantum Dot Sensitized Solar Cells.

PubMed

Atif, M; Farooq, W A; Fatehmulla, Amanullah; Aslam, M; Ali, Syed Mansoor

2015-01-19

Cadmium sulphide (CdS) quantum dot sensitized solar cells (QDSSCs) based on screen-printed TiO₂ were assembled using a screen-printing technique. The CdS quantum dots (QDs) were grown by using the Successive Ionic Layer Adsorption and Reaction (SILAR) method. The optical properties were studied by UV-Vis absorbance spectroscopy. Photovoltaic characteristics and impedance spectroscopic measurements of CdS QDSSCs were carried out under air mass 1.5 illuminations. The experimental results of capacitance against voltage indicate a trend from positive to negative capacitance because of the injection of electrons from the Fluorine doped tin oxide (FTO) electrode into TiO₂.

Association between Functional Capacity Decline and Nutritional Status Based on the Nutrition Screening Initiative Checklist: A 2-Year Cohort Study of Japanese Community-Dwelling Elderly.

PubMed

Sugiura, Yumiko; Tanimoto, Yoshimi; Imbe, Ayumi; Inaba, Yuiko; Sakai, Satoshi; Shishikura, Kanako; Tanimoto, Keiji; Hanafusa, Toshiaki

2016-01-01

To assess whether nutritional status based on the Nutrition Screening Initiative Checklist is useful for predicting functional capacity decline in community-dwelling Japanese elderly. This two-year observational cohort study included 536 community-dwelling Japanese (65 years and older at baseline) who were independent in both activities and instrumental activities of daily living. Demographic attributes, chronic illness, lifestyle-related habits, nutritional status, functional capacity, and anthropometric measurements were assessed, with decline in functional capacity used as the outcome measure. Subjects were classified into three groups as follows based on the Nutrition Screening Initiative Checklist: low (59.5%), moderate (23.7%), and high (16.8%) nutritional risk. Significant differences were found between nutritional status and the following four baseline variables: age, hypertension, cerebrovascular diseases, and current smoking. However, no significant differences were evident between nutritional status and sex, body mass index, diabetes, drinking habit, or exercise habit. Logistic regression analysis adjusted for age, sex, body mass index, hypertension, cerebrovascular diseases and smoking habit showed that the high nutritional risk group was significantly associated with a decline in both activities of daily living (odds ratio: 4.96; 95% confidence interval (CI): 1.59-15.50) and instrumental activities of daily living (OR: 2.58; 95% CI: 1.31-5.06) compared with the low nutritional risk group. Poor nutritional status based on the Nutrition Screening Initiative Checklist was associated with a decline in functional capacity over a 2-year period in community-dwelling Japanese elderly. These results suggest that the Nutrition Screening Initiative Checklist is a suitable tool for predicting functional capacity decline in community-dwelling elderly.

Parents of elementary school students weigh in on height, weight, and body mass index screening at school.

PubMed

Kubik, Martha Y; Fulkerson, Jayne A; Story, Mary; Rieland, Gayle

2006-12-01

School-based body mass index (BMI) screening and parent notification programs have been recommended as a childhood overweight prevention strategy. However, there are little empirical data available to guide decision making about the acceptability and safety of programs. A pilot study was conducted using a quasiexperimental research design. In fall 2004, children in 4 suburban elementary schools (kindergarten to sixth grade) in the St Paul/Minneapolis, MN, metropolitan area completed height/weight screening. The following spring, parents in 2 schools received letters containing height/weight and BMI results. A self-administered post-only survey examined parents' opinions and beliefs regarding school-based BMI screening and parent notification programs (response rate: 790/1133 = 70%). The chi2 test of significance was used to examine differences in program support by treatment condition, child's weight status, and sociodemographic characteristics. Among all parents, 78% believed it was important for schools to assess student's height/weight annually and wanted to receive height, weight, and BMI information yearly. Among parents receiving the letter, 95% read most/all of the letter. Most parents (80%) and children (83%) reported comfort with the information in the letter. Parents of overweight children were more likely to report parental discomfort as well as child discomfort with letter content. There was considerable parental support for school-based BMI screening and parent notification programs. Programs may be a useful overweight prevention tool for children. However, continued attention to how best to support parents and children affected by overweight is required.

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

PubMed

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

2016-10-01

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

Multi-modality image registration for effective thermographic fever screening

NASA Astrophysics Data System (ADS)

Dwith, C. Y. N.; Ghassemi, Pejhman; Pfefer, Joshua; Casamento, Jon; Wang, Quanzeng

2017-02-01

Fever screening based on infrared thermographs (IRTs) is a viable mass screening approach during infectious disease pandemics, such as Ebola and Severe Acute Respiratory Syndrome (SARS), for temperature monitoring in public places like hospitals and airports. IRTs have been found to be powerful, quick and non-invasive methods for detecting elevated temperatures. Moreover, regions medially adjacent to the inner canthi (called the canthi regions in this paper) are preferred sites for fever screening. Accurate localization of the canthi regions can be achieved through multi-modality registration of infrared (IR) and white-light images. Here we propose a registration method through a coarse-fine registration strategy using different registration models based on landmarks and edge detection on eye contours. We have evaluated the registration accuracy to be within +/- 2.7 mm, which enables accurate localization of the canthi regions.

Structure-based manual screening and automatic networking for systematically exploring sansanmycin analogues using high performance liquid chromatography tandem mass spectroscopy.

PubMed

Jiang, Zhi-Bo; Ren, Wei-Cong; Shi, Yuan-Yuan; Li, Xing-Xing; Lei, Xuan; Fan, Jia-Hui; Zhang, Cong; Gu, Ren-Jie; Wang, Li-Fei; Xie, Yun-Ying; Hong, Bin

2018-05-18

Sansanmycins (SS), one of several known uridyl peptide antibiotics (UPAs) possessing a unique chemical scaffold, showed a good inhibitory effect on the highly refractory pathogens Pseudomonas aeruginosa and Mycobacterium tuberculosis, especially on the multi-drug resistant M. tuberculosis. This study employed high performance liquid chromatography-mass spectrometry detector (HPLC-MSD) ion trap and LTQ orbitrap tandem mass spectrometry (MS/MS) to explore sansanmycin analogues manually and automatically by re-analysis of the Streptomyces sp. SS fermentation broth. The structure-based manual screening method, based on analysis of the fragmentation pathway of known UPAs and on comparisons of the MS/MS spectra with that of sansanmycin A (SS-A), resulted in identifying twenty sansanmycin analogues, including twelve new structures (1-12). Furthermore, to deeply explore sansanmycin analogues, we utilized a GNPS based molecular networking workflow to re-analyze the HPLC-MS/MS data automatically. As a result, eight more new sansanmycins (13-20) were discovered. Compound 1 was discovered to lose two amino acids of residue 1 (AA 1 ) and (2S, 3S)-N 3 -methyl-2,3-diamino butyric acid (DABA) from the N-terminus, and compounds 6, 11 and 12 were found to contain a 2',3'-dehydrated 4',5'-enamine-3'-deoxyuridyl moiety, which have not been reported before. Interestingly, three trace components with novel 5,6-dihydro-5'-aminouridyl group (16-18) were detected for the first time in the sansanmycin-producing strain. Their structures were primarily determined by detail analysis of the data from MS/MS. Compounds 8 and 10 were further confirmed by nuclear magnetic resonance (NMR) data, which proved the efficiency and accuracy of the method of HPLC-MS/MS for exploration of novel UPAs. Comparing to manual screening, the networking method can provide systematic visualization results. Manual screening and networking method may complement with each other to facilitate the mining of novel UPAs. Copyright © 2018 Elsevier B.V. All rights reserved.

Extraction and Refinement Strategy for Detection of Autism in 18-Month-Olds: A Guarantee of Higher Sensitivity and Specificity in the Process of Mass Screening

ERIC Educational Resources Information Center

Honda, Hideo; Shimizu, Yasuo; Nitto, Yukari; Imai, Miho; Ozawa, Takeshi; Iwasa, Mitsuaki; Shiga, Keiko; Hira, Tomoko

2009-01-01

Background: For early detection of autism, it is difficult to maintain an efficient level of sensitivity and specificity based on observational data from a single screening. The Extraction and Refinement (E&R) Strategy utilizes a public children's health surveillance program to produce maximum efficacy in early detection of autism. In the…

Navy Fuel Composition and Screening Tool (FCAST) v2.8

DTIC Science & Technology

2016-05-10

allowed us to develop partial least squares (PLS) models based on gas chromatography–mass spectrometry (GC-MS) data that predict fuel properties. The...Chemometric property modeling Partial least squares PLS Compositional profiler Naval Air Systems Command Air-4.4.5 Patuxent River Naval Air Station Patuxent...Cumulative predicted residual error sum of squares DiEGME Diethylene glycol monomethyl ether FCAST Fuel Composition and Screening Tool FFP Fit for

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. II: Confirmatory analysis.

PubMed

Badoud, F; Grata, E; Perrenoud, L; Saugy, M; Rudaz, S; Veuthey, J-L

2010-06-18

For doping control, analyses of samples are generally achieved in two steps: a rapid screening and, in the case of a positive result, a confirmatory analysis. A two-step methodology based on ultra-high-pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was developed to screen and confirm 103 doping agents from various classes (e.g., beta-blockers, stimulants, diuretics, and narcotics). The screening method was presented in a previous article as part I (i.e., Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. Part I: screening analysis). For the confirmatory method, basic, neutral and acidic compounds were extracted by a dedicated solid-phase extraction (SPE) in a 96-well plate format and detected by MS in the tandem mode to obtain precursor and characteristic product ions. The mass accuracy and the elemental composition of precursor and product ions were used for compound identification. After validation including matrix effect determination, the method was considered reliable to confirm suspect results without ambiguity according to the positivity criteria established by the World Anti-Doping Agency (WADA). Moreover, an isocratic method was developed to separate ephedrine from its isomer pseudoephedrine and cathine from phenylpropanolamine in a single run, what allowed their direct quantification in urine. Copyright (c) 2010 Elsevier B.V. All rights reserved.

[Application of precursor ion scanning method in rapid screening of illegally added phosphodiesterase-5 inhibitors and their unknown derivatives in Chinese traditional patent medicines and health foods].

PubMed

Sun, Jing; Cao, Ling; Feng, Youlong; Tan, Li

2014-11-01

The compounds with similar structure often have similar pharmacological activities. So it is a trend for illegal addition that new derivatives of effective drugs are synthesized to avoid the statutory test. This bring challenges to crack down on illegal addition behavior, however, modified derivatives usually have similar product ions, which allow for precursor ion scanning. In this work, precursor ion scanning mode of a triple quadrupole mass spectrometer was first applied to screen illegally added drugs in complex matrix such as Chinese traditional patent medicines and healthy foods. Phosphodiesterase-5 inhibitors were used as experimental examples. Through the analysis of the structure and mass spectrum characteristics of the compounds, phosphodiesterase-5 inhibitors were classified, and their common product ions were screened by full scan of product ions of typical compounds. Then high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method with precursor ion scanning mode was established based on the optimization of MS parameters. The effect of mass parameters and the choice of fragment ions were also studied. The method was applied to determine actual samples and further refined. The results demonstrated that this method can meet the need of rapid screening of unknown derivatives of phosphodiesterase-5 inhibitors in complex matrix, and prevent unknown derivatives undetected. This method shows advantages in sensitivity, specificity and efficiency, and is worth to be further investigated.

Advances in fragment-based drug discovery platforms.

PubMed

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

Preventive doping control screening analysis of prohibited substances in human urine using rapid-resolution liquid chromatography/high-resolution time-of-flight mass spectrometry.

PubMed

Vonaparti, A; Lyris, E; Angelis, Y S; Panderi, I; Koupparis, M; Tsantili-Kakoulidou, A; Peters, R J B; Nielen, M W F; Georgakopoulos, C

2010-06-15

Unification of the screening protocols for a wide range of doping agents has become an important issue for doping control laboratories. This study presents the development and validation of a generic liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) screening method of 241 small molecule analytes from various categories of prohibited substances (stimulants, narcotics, diuretics, beta(2)-agonists, beta-blockers, hormone antagonists and modulators, glucocorticosteroids and anabolic agents). It is based on a single-step liquid-liquid extraction of hydrolyzed urine and the use of a rapid-resolution liquid chromatography/high-resolution time-of-flight mass spectrometric system acquiring continuous full scan data. Electrospray ionization in the positive mode was used. Validation parameters consisted of identification capability, limit of detection, specificity, ion suppression, extraction recovery, repeatability and mass accuracy. Detection criteria were established on the basis of retention time reproducibility and mass accuracy. The suitability of the methodology for doping control was demonstrated with positive urine samples. The preventive role of the method was proved by the case where full scan acquisition with accurate mass measurement allowed the retrospective reprocessing of acquired data from past doping control samples for the detection of a designer drug, the stimulant 4-methyl-2-hexanamine, which resulted in re-reporting a number of stored samples as positives for this particular substance, when, initially, they had been reported as negatives. Copyright (c) 2010 John Wiley & Sons, Ltd.

Early Detection and Mass Screening For Cancer

PubMed Central

Miller, A. B.

1972-01-01

The author reviews the evidence for the efficacy of early detection and mass screening programs in reducing morbidity and mortality from cancer. In cancer of the cervix, although screening reduces morbidity, we still do not have evidence for reduction in mortality. In cancer of the breast, one study suggests a reduction in mortality in the 50-59 year age group following screening by clinical examination and mammography. In other sites, especially lung, there is no evidence at present to support the adoption of mass screening programs. It is important that such programs should be carefully evaluated in the population, preferably in controlled studies. PMID:20468806

Regional Differences as Barriers to Body Mass Index Screening Described by Ohio School Nurses

ERIC Educational Resources Information Center

Stalter, Ann M.; Chaudry, Rosemary V.; Polivka, Barbara J.

2011-01-01

Background: Body mass index (BMI) screening is advocated by the National Association of School Nurses (NASN). Research identifying barriers to BMI screening in public elementary school settings has been sparse. The purpose of the study was to identify barriers and facilitating factors of BMI screening practices among Ohio school nurses working in…

Dual-Energy Contrast-Enhanced Spectral Mammography: Enhancement Analysis on BI-RADS 4 Non-Mass Microcalcifications in Screened Women.

PubMed

Cheung, Yun-Chung; Juan, Yu-Hsiang; Lin, Yu-Ching; Lo, Yung-Feng; Tsai, Hsiu-Pei; Ueng, Shir-Hwa; Chen, Shin-Cheh

2016-01-01

Mammography screening is a cost-efficient modality with high sensitivity for detecting impalpable cancer with microcalcifications, and results in reduced mortality rates. However, the probability of finding microcalcifications without associated cancerous masses varies. We retrospectively evaluated the diagnosis and cancer probability of the non-mass screened microcalcifications by dual-energy contrast-enhanced spectral mammography (DE-CESM). With ethical approval from our hospital, we enrolled the cases of DE-CESM for analysis under the following inclusion criteria: (1) referrals due to screened BI-RADS 4 microcalcifications; (2) having DE-CESM prior to stereotactic biopsy; (3) no associated mass found by sonography and physical examination; and (4) pathology-based diagnosis using stereotactic vacuum-assisted breast biopsy. We analyzed the added value of post-contrast enhancement on DE-CESM. A total of 94 biopsed lesions were available for analysis in our 87 women, yielding 27 cancers [19 ductal carcinoma in situ (DCIS), and 8 invasive ductal carcinoma (IDC)], 32 pre-malignant and 35 benign lesions. Of these 94 lesions, 33 showed associated enhancement in DE-CESM while the other 61 did not. All 8 IDC (100%) and 16 of 19 DCIS (84.21%) showed enhancement, but the other 3 DCIS (15.79%) did not. Overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 88.89%, 86.56%, 72.72%, 95.08% and 87.24%, respectively. The performances of DE-CESM on both amorphous and pleomorphic microcalcifications were satisfactory (AUC 0.8 and 0.92, respectively). The pleomorphous microcalcifications with enhancement showed higher positive predictive value (90.00% vs 46.15%, p = 0.013) and higher cancer probability than the amorphous microcalcifications (46.3% VS 15.1%). The Odds Ratio was 4.85 (95% CI: 1.84-12.82). DE-CESM might provide added value in assessing the non-mass screened breast microcalcification, with enhancement favorable to the diagnosis of cancers or lack of enhancement virtually diagnostic for non-malignant lesions or noninvasive subgroup cancers.

Anthropometric Variables Accurately Predict Dual Energy X-Ray Absorptiometric-Derived Body Composition and Can Be Used to Screen for Diabetes

PubMed Central

Yavari, Reza; McEntee, Erin; McEntee, Michael; Brines, Michael

2011-01-01

The current world-wide epidemic of obesity has stimulated interest in developing simple screening methods to identify individuals with undiagnosed diabetes mellitus type 2 (DM2) or metabolic syndrome (MS). Prior work utilizing body composition obtained by sophisticated technology has shown that the ratio of abdominal fat to total fat is a good predictor for DM2 or MS. The goals of this study were to determine how well simple anthropometric variables predict the fat mass distribution as determined by dual energy x-ray absorptometry (DXA), and whether these are useful to screen for DM2 or MS within a population. To accomplish this, the body composition of 341 females spanning a wide range of body mass indices and with a 23% prevalence of DM2 and MS was determined using DXA. Stepwise linear regression models incorporating age, weight, height, waistline, and hipline predicted DXA body composition (i.e., fat mass, trunk fat, fat free mass, and total mass) with good accuracy. Using body composition as independent variables, nominal logistic regression was then performed to estimate the probability of DM2. The results show good discrimination with the receiver operating characteristic (ROC) having an area under the curve (AUC) of 0.78. The anthropometrically-derived body composition equations derived from the full DXA study group were then applied to a group of 1153 female patients selected from a general endocrinology practice. Similar to the smaller study group, the ROC from logistical regression using body composition had an AUC of 0.81 for the detection of DM2. These results are superior to screening based on questionnaires and compare favorably with published data derived from invasive testing, e.g., hemoglobin A1c. This anthropometric approach offers promise for the development of simple, inexpensive, non-invasive screening to identify individuals with metabolic dysfunction within large populations. PMID:21915276

Who attends a UK diabetes screening programme? Findings from the ADDITION-Cambridge study.

PubMed

Sargeant, L A; Simmons, R K; Barling, R S; Butler, R; Williams, K M; Prevost, A T; Kinmonth, A L; Wareham, N J; Griffin, S J

2010-09-01

One of the factors influencing the cost-effectiveness of population screening for Type 2 diabetes may be uptake. We examined attendance and practice- and individual-level factors influencing uptake at each stage of a diabetes screening programme in general practice. A stepwise screening programme was undertaken among 135, 825 people aged 40-69 years without known diabetes in 49 general practices in East England. The programme included a score based on routinely available data (age, sex, body mass index and prescribed medication) to identify those at high risk, who were offered random capillary blood glucose (RBG) and glycosylated haemoglobin tests. Those screening positive were offered fasting capillary blood glucose (FBG) and confirmatory oral glucose tolerance tests (OGTT). There were 33 539 high-risk individuals invited for a RBG screening test; 24 654 (74%) attended. Ninety-four per cent attended the follow-up FBG test and 82% the diagnostic OGTT. Seventy per cent of individuals completed the screening programme. Practices with higher general practitioner staff complements and those located in more deprived areas had lower uptake for RBG and FBG tests. Male sex and a higher body mass index were associated with lower attendance for RBG testing. Older age, prescription of antihypertensive medication and a higher risk score were associated with higher attendance for FBG and RBG tests. High attendance rates can be achieved by targeted stepwise screening of individuals assessed as high risk by data routinely available in general practice. Different strategies may be required to increase initial attendance, ensure completion of the screening programme, and reduce the risk that screening increases health inequalities.

Material characterisation and preliminary mechanical design for the HL-LHC shielded beam screens operating at cryogenic temperatures.

NASA Astrophysics Data System (ADS)

Garion, C.; Dufay-Chanat, L.; Koettig, T.; Machiocha, W.; Morrone, M.

2015-12-01

The High Luminosity LHC project (HL-LHC) aims at increasing the luminosity (rate of collisions) in the Large Hadron Collider (LHC) experiments by a factor of 10 beyond the original design value (from 300 to 3000 fb-1). It relies on new superconducting magnets, installed close to the interaction points, equipped with new beam screen. This component has to ensure the vacuum performance together with shielding the cold mass from physics debris and screening the cold bore cryogenic system from beam induced heating. The beam screen operates in the range 40-60 K whereas the magnet cold bore temperature is 1.9 K. A tungsten-based material is used to absorb the energy of particles. In this paper, measurements of the mechanical and physical properties of such tungsten material are shown at room and cryogenic temperature. In addition, the design and the thermal mechanical behaviour of the beam screen assembly are presented also. They include the heat transfer from the tungsten absorbers to the cooling pipes and the supporting system that has to minimise the heat inleak into the cold mass. The behaviour during a magnet quench is also presented.

Optimization of information content in a mass spectrometry based flow-chemistry system by investigating different ionization approaches.

PubMed

Martha, Cornelius T; Hoogendoorn, Jan-Carel; Irth, Hubertus; Niessen, Wilfried M A

2011-05-15

Current development in catalyst discovery includes combinatorial synthesis methods for the rapid generation of compound libraries combined with high-throughput performance-screening methods to determine the associated activities. Of these novel methodologies, mass spectrometry (MS) based flow chemistry methods are especially attractive due to the ability to combine sensitive detection of the formed reaction product with identification of introduced catalyst complexes. Recently, such a mass spectrometry based continuous-flow reaction detection system was utilized to screen silver-adducted ferrocenyl bidentate catalyst complexes for activity in a multicomponent synthesis of a substituted 2-imidazoline. Here, we determine the merits of different ionization approaches by studying the combination of sensitive detection of product formation in the continuous-flow system with the ability to simultaneous characterize the introduced [ferrocenyl bidentate+Ag](+) catalyst complexes. To this end, we study the ionization characteristics of electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), no-discharge APCI, dual ESI/APCI, and dual APCI/no-discharge APCI. Finally, we investigated the application potential of the different ionization approaches by the investigation of ferrocenyl bidentate catalyst complex responses in different solvents. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-04-01

Evidence suggests sitting time is independently associated with a range of health issues in adults, yet the relationship between sedentary behavior and health indicators in young people is less clear. Age-related increases in sedentary behavior are well-documented; the behavioral patterns of adolescent girls are of particular concern. More than one third of adolescent girls' sedentary behavior time is accumulated through use of recreational screen-based behaviors. The objective of this review was to investigate the association between recreational screen-based sedentary behavior and the physical, behavioral, and psychosocial health indicators for adolescent girls. A secondary objective was to identify studies that have adjusted sedentary behavior indicators for physical activity. A structured electronic search of all publication years (through December 2011) was conducted to identify studies in: CINAHL, Communications and Mass Media Complete, ERIC, MEDLINE with Full Text, PsycINFO, and SPORTDiscus with Full Text. Included publications were observational and interventional studies involving adolescent girls (12-18 years) that examined associations between screen-based, sedentary behavior and health indicators (physical, psychosocial, and/or behavioral). The search identified 33 studies that evaluated health indicators of screen-based sedentary behaviors among adolescent girls. Strong evidence for a positive association between screen-based sedentary behavior and weight status was found. A positive association was observed between screen-time and sleep problems, musculoskeletal pain and depression. Negative associations were identified between screen time and physical activity/fitness, screen time and psychological well-being, and screen time and social support. The relationship between screen-based sedentary behavior and diet quality was inconclusive. Less than half of the studies adjusted sedentary behavior indicators for physical activity. Screen-based sedentary behavior is associated with a range of adverse health consequences, but additional longitudinal studies are needed to better understand the health impacts. In addition, screen-time guidelines for youth should be regularly revised and updated to reflect rapid technological changes. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Cosmic web and environmental dependence of screening: Vainshtein vs. chameleon

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

Falck, Bridget; Koyama, Kazuya; Zhao, Gong-Bo, E-mail: bridget.falck@port.ac.uk, E-mail: kazuya.koyama@port.ac.uk, E-mail: gong-bo.zhao@port.ac.uk

Theories which modify general relativity to explain the accelerated expansion of the Universe often use screening mechanisms to satisfy constraints on Solar System scales. We investigate the effects of the cosmic web and the local environmental density of dark matter halos on the screening properties of the Vainshtein and chameleon screening mechanisms. We compare the cosmic web morphology of dark matter particles, mass functions of dark matter halos, mass and radial dependence of screening, velocity dispersions and peculiar velocities, and environmental dependence of screening mechanisms in f(R) and nDGP models. Using the ORIGAMI cosmic web identification routine we find thatmore » the Vainshtein mechanism depends on the cosmic web morphology of dark matter particles, since these are defined according to the dimensionality of their collapse, while the chameleon mechanism shows no morphology dependence. The chameleon screening of halos and their velocity dispersions depend on halo mass, and small halos and subhalos can be environmentally screened in the chameleon mechanism. On the other hand, the screening of halos in the Vainshtein mechanism does not depend on mass nor environment, and their velocity dispersions are suppressed. The peculiar velocities of halos in the Vainshtein mechanism are enhanced because screened objects can still feel the fifth force generated by external fields, while peculiar velocities of chameleon halos are suppressed when the halo centers are screened.« less

Screening College Students for Hypercholesterolemia.

ERIC Educational Resources Information Center

Faigel, Harris C.

1992-01-01

Describes one college's mandatory mass cholesterol screening for new students. Each year, over 30 beginning students with unknown hypercholesterolemia were detected. The program suggests that mass screening efficiently and economically identifies students who would benefit from cholesterol reduction, a modifiable risk in coronary artery disease.…

Component analysis and target cell-based neuroactivity screening of Panax ginseng by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

PubMed

Yuan, Jinbin; Chen, Yang; Liang, Jian; Wang, Chong-Zhi; Liu, Xiaofei; Yan, Zhihong; Tang, Yi; Li, Jiankang; Yuan, Chun-Su

2016-12-01

Ginseng is one of the most widely used natural medicines in the world. Recent studies have suggested Panax ginseng has a wide range of beneficial effects on aging, central nervous system disorders, and neurodegenerative diseases. However, knowledge about the specific bioactive components of ginseng is still limited. This work aimed to screen for the bioactive components in Panax ginseng that act against neurodegenerative diseases, using the target cell-based bioactivity screening method. Firstly, component analysis of Panax ginseng extracts was performed by UPLC-QTOF-MS, and a total of 54 compounds in white ginseng were characterized and identified according to the retention behaviors, accurate MW, MS characteristics, parent nucleus, aglycones, side chains, and literature data. Then target cell-based bioactivity screening method was developed to predict the candidate compounds in ginseng with SH-SY5Y cells. Four ginsenosides, Rg 2 , Rh 1 , Ro, and Rd, were observed to be active. The target cell-based bioactivity screening method coupled with UPLC-QTOF-MS technique has suitable sensitivity and it can be used as a screening tool for low content bioactive constituents in natural products. Copyright © 2016 Elsevier B.V. All rights reserved.

Newborn screening for sickling and other haemoglobin disorders using tandem mass spectrometry: A pilot study of methodology in laboratories in England.

PubMed

Daniel, Yvonne A; Henthorn, Joan

2016-12-01

To determine (i) if electrospray mass spectrometry-mass spectrometry with the SpOtOn Diagnostics Ltd reagent kit for sickle cell screening could be integrated into the English newborn screening programme, under routine screening conditions, and provide mass spectrometry-mass spectrometry results which match existing methods, and (ii) if common action values could be set for all manufacturers in the study, for all assessed haemoglobins, to indicate which samples require further investigation. Anonymised residual blood spots were analysed using the SpOtOn reagent kit as per manufacturer's instructions, in parallel with existing techniques at four laboratories. Mass spectrometry-mass spectrometry instrumentation at Laboratories A and B was AB Sciex (Warrington, UK) AP4000, and at Laboratories C and D, Waters Micromass (Manchester, UK), Xevo TQMS and Premier, respectively. There were 23,898 results accepted from the four laboratories. Excellent specificity at 100% sensitivity was observed for haemoglobin S, haemoglobin C, haemoglobin E and haemoglobin O Arab . A common action value was not possible for Hb C, but action values were set by manufacturer. The two haemoglobin D Punjab cases at Laboratory D were not detected using the common action value. Conversely, false-positive results with haemoglobin D Punjab were a problem at the remaining three laboratories. This multicentre study demonstrates that it is possible to implement mass spectrometry-mass spectrometry into an established screening programme while maintaining consistency with existing methods for haemoglobinopathy screening. However, one of the instruments investigated cannot be recommended for use with this application. © The Author(s) 2016.

Achieving accurate compound concentration in cell-based screening: validation of acoustic droplet ejection technology.

PubMed

Grant, Richard John; Roberts, Karen; Pointon, Carly; Hodgson, Clare; Womersley, Lynsey; Jones, Darren Craig; Tang, Eric

2009-06-01

Compound handling is a fundamental and critical step in compound screening throughout the drug discovery process. Although most compound-handling processes within compound management facilities use 100% DMSO solvent, conventional methods of manual or robotic liquid-handling systems in screening workflows often perform dilutions in aqueous solutions to maintain solvent tolerance of the biological assay. However, the use of aqueous media in these applications can lead to suboptimal data quality due to compound carryover or precipitation during the dilution steps. In cell-based assays, this effect is worsened by the unpredictable physical characteristics of compounds and the low DMSO tolerance within the assay. In some cases, the conventional approaches using manual or automated liquid handling resulted in variable IC(50) dose responses. This study examines the cause of this variability and evaluates the accuracy of screening data in these case studies. A number of liquid-handling options have been explored to address the issues and establish a generic compound-handling workflow to support cell-based screening across our screening functions. The authors discuss the validation of the Labcyte Echo reformatter as an effective noncontact solution for generic compound-handling applications against diverse compound classes using triple-quad liquid chromatography/mass spectrometry. The successful validation and implementation challenges of this technology for direct dosing onto cells in cell-based screening is discussed.

Microfluidic microscopy-assisted label-free approach for cancer screening: automated microfluidic cytology for cancer screening.

PubMed

Jagannadh, Veerendra Kalyan; Gopakumar, G; Subrahmanyam, Gorthi R K Sai; Gorthi, Sai Siva

2017-05-01

Each year, about 7-8 million deaths occur due to cancer around the world. More than half of the cancer-related deaths occur in the less-developed parts of the world. Cancer mortality rate can be reduced with early detection and subsequent treatment of the disease. In this paper, we introduce a microfluidic microscopy-based cost-effective and label-free approach for identification of cancerous cells. We outline a diagnostic framework for the same and detail an instrumentation layout. We have employed classical computer vision techniques such as 2D principal component analysis-based cell type representation followed by support vector machine-based classification. Analogous to criminal face recognition systems implemented with help of surveillance cameras, a signature-based approach for cancerous cell identification using microfluidic microscopy surveillance is demonstrated. Such a platform would facilitate affordable mass screening camps in the developing countries and therefore help decrease cancer mortality rate.

Using In Silico Fragmentation to Improve Routine Residue Screening in Complex Matrices.

PubMed

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

2017-12-01

Targeted residue screening requires the use of reference substances in order to identify potential residues. This becomes a difficult issue when using multi-residue methods capable of analyzing several hundreds of analytes. Therefore, the capability of in silico fragmentation based on a structure database ("suspect screening") instead of physical reference substances for routine targeted residue screening was investigated. The detection of fragment ions that can be predicted or explained by in silico software was utilized to reduce the number of false positives. These "proof of principle" experiments were done with a tool that is integrated into a commercial MS vendor instrument operating software (UNIFI) as well as with a platform-independent MS tool (Mass Frontier). A total of 97 analytes belonging to different chemical families were separated by reversed phase liquid chromatography and detected in a data-independent acquisition (DIA) mode using ion mobility hyphenated with quadrupole time of flight mass spectrometry. The instrument was operated in the MS E mode with alternating low and high energy traces. The fragments observed from product ion spectra were investigated using a "chopping" bond disconnection algorithm and a rule-based algorithm. The bond disconnection algorithm clearly explained more analyte product ions and a greater percentage of the spectral abundance than the rule-based software (92 out of the 97 compounds produced ≥1 explainable fragment ions). On the other hand, tests with a complex blank matrix (bovine liver extract) indicated that the chopping algorithm reports significantly more false positive fragments than the rule based software. Graphical Abstract.

Using In Silico Fragmentation to Improve Routine Residue Screening in Complex Matrices

NASA Astrophysics Data System (ADS)

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

2017-12-01

Targeted residue screening requires the use of reference substances in order to identify potential residues. This becomes a difficult issue when using multi-residue methods capable of analyzing several hundreds of analytes. Therefore, the capability of in silico fragmentation based on a structure database ("suspect screening") instead of physical reference substances for routine targeted residue screening was investigated. The detection of fragment ions that can be predicted or explained by in silico software was utilized to reduce the number of false positives. These "proof of principle" experiments were done with a tool that is integrated into a commercial MS vendor instrument operating software (UNIFI) as well as with a platform-independent MS tool (Mass Frontier). A total of 97 analytes belonging to different chemical families were separated by reversed phase liquid chromatography and detected in a data-independent acquisition (DIA) mode using ion mobility hyphenated with quadrupole time of flight mass spectrometry. The instrument was operated in the MSE mode with alternating low and high energy traces. The fragments observed from product ion spectra were investigated using a "chopping" bond disconnection algorithm and a rule-based algorithm. The bond disconnection algorithm clearly explained more analyte product ions and a greater percentage of the spectral abundance than the rule-based software (92 out of the 97 compounds produced ≥1 explainable fragment ions). On the other hand, tests with a complex blank matrix (bovine liver extract) indicated that the chopping algorithm reports significantly more false positive fragments than the rule based software. [Figure not available: see fulltext.

Mass media campaign improves cervical screening across all socio-economic groups.

PubMed

Anderson, Jenny O; Mullins, Robyn M; Siahpush, Mohammad; Spittal, Matthew J; Wakefield, Melanie

2009-10-01

Low socio-economic status (SES) has been associated with lower cervical screening rates. Mass media is one known strategy that can increase cervical screening participation. This study sought to determine whether a mass media campaign conducted in Victoria, Australia, in 2005 was effective in encouraging women across all SES groups to screen. Data were obtained from the Victorian Cervical Cytology Registry for each Pap test registered during 2005 and categorized into SES quintiles using the Index of Socio-Economic Advantage/Disadvantage. Negative binomial regression was used to determine the impact of the campaign on the weekly number of Pap tests and whether the media campaign had a differential effect by SES, after adjusting for the number of workdays per week, age group and time since previous test. Cervical screening increased 27% during the campaign period and was equally effective in encouraging screening across all SES groups, including low-SES women. Mass media campaigns can prompt increased rates of cervical screening among all women, not just those from more advantaged areas. Combining media with additional strategies targeted at low-SES women may help lessen the underlying differences in screening rates across SES.

Monitoring compliance to therapy during addiction treatments by means of hair analysis for drugs and drug metabolites using capillary zone electrophoresis coupled to time-of-flight mass spectrometry.

PubMed

Gottardo, Rossella; Fanigliulo, Ameriga; Sorio, Daniela; Liotta, Eloisa; Bortolotti, Federica; Tagliaro, Franco

2012-03-10

Capillary electrophoresis coupled to time-of-flight mass spectrometry was used in the present work for the determination of therapeutic and abused drugs and their metabolites in the hair of subjects undergoing addiction treatments, in order to monitor their compliance to therapy. For this purpose a rapid, qualitative drug screening method was adopted based on capillary electrophoresis hyphenated with time-of-flight mass spectrometry, which had earlier been developed and validated for the forensic-toxicological analysis of hair, limitedly to illicit/abused drugs [1]. Sampling of hair was carried out in order to refer to a time window of about two months from the date of sampling (i.e. 2cm ca. from cortex). A single extraction procedure was applied, allowing the determination in the hair matrix of "drugs of abuse" referred to the past abuses, and therapeutic drugs prescribed in the detoxification program as well as their metabolites. Analyte identification was based on accurate mass measurements and comparison of isotope patterns, providing the most likely matching between accurate mass value and elemental formula. Small molecules (<500Da) of forensic and toxicological interest could be identified unambiguously using mass spectrometric conditions tailored to meet a mass accuracy ≤5ppm. In the present study, the proposed approach proved suitable for the rapid broad spectrum screening of hair samples, although needing further confirmation of results by using fragmentation mass spectrometry. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The view from the trenches: part 2-technical considerations for EPR screening.

PubMed

Nicolalde, Roberto J; Gougelet, Robert M; Rea, Michael; Williams, Benjamin B; Dong, Ruhong; Kmiec, Maciej M; Lesniewski, Piotr N; Swartz, Harold M

2010-02-01

There is growing awareness of the need for methodologies that can be used retrospectively to provide the biodosimetry needed to carry out screening and triage immediately after an event in which large numbers of people have potentially received clinically significant doses of ionizing radiation. The general approach to developing such methodologies has been a technology centric one, often ignoring the system integrations considerations that are key to their effective use. In this study an integrative approach for the evaluation and development of a physical biodosimetry technology was applied based on in vivo electron paramagnetic resonance (EPR) dosimetry. The EPR measurements are based on physical changes in tissues whose magnitudes are not affected by the factors that can confound biologically-based assessments. In this study the use of a pilot simulation exercise to evaluate an experimental EPR system and gather stakeholders' feedback early on in the development process is described. The exercise involved: ten non-irradiated participants, representatives from a local fire department; Department of Homeland Security certified exercise evaluators, EPR experts, physicians; and a human factors engineer. Stakeholders were in agreement that the EPR technology in its current state of development could be deployed for the screening of mass casualties. Furthermore, stakeholders' recommendations will be prioritized and incorporated in future developments of the EPR technique. While the results of this exercise were aimed specifically at providing feedback for the development of EPR dosimetry for screening mass casualties, the methods and lessons learned are likely to be applicable to other biodosimetric methods.

Development of an Automated Modality-Independent Elastographic Image Analysis System for Tumor Screening

DTIC Science & Technology

2006-02-01

further develop modality-independent elastography as a system that is able to reproducibly detect regions of increased stiffness within the breast based...tested on a tissue-like polymer phantom. elastography , breast cancer screening, image processing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...is a map of the breast (or other tissue of interest) that reflects material inhomogeneity, such as in the case of a tumor mass that disrupts the

Lead discovery for mammalian elongation of long chain fatty acids family 6 using a combination of high-throughput fluorescent-based assay and RapidFire mass spectrometry assay

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

Takamiya, Mari; Discovery Technology Laboratories, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Kawagishi, Toda-shi, Saitama; Sakurai, Masaaki

A high-throughput RapidFire mass spectrometry assay is described for elongation of very long-chain fatty acids family 6 (Elovl6). Elovl6 is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids. Elovl6 may be a new therapeutic target for fat metabolism disorders such as obesity, type 2 diabetes, and nonalcoholic steatohepatitis. To identify new Elovl6 inhibitors, we developed a high-throughput fluorescence screening assay in 1536-well format. However, a number of false positives caused by fluorescent interference have been identified. To pick up the real active compounds among the primary hits from the fluorescence assay, we developed amore » RapidFire mass spectrometry assay and a conventional radioisotope assay. These assays have the advantage of detecting the main products directly without using fluorescent-labeled substrates. As a result, 276 compounds (30%) of the primary hits (921 compounds) in a fluorescence ultra-high-throughput screening method were identified as common active compounds in these two assays. It is concluded that both methods are very effective to eliminate false positives. Compared with the radioisotope method using an expensive {sup 14}C-labeled substrate, the RapidFire mass spectrometry method using unlabeled substrates is a high-accuracy, high-throughput method. In addition, some of the hit compounds selected from the screening inhibited cellular fatty acid elongation in HEK293 cells expressing Elovl6 transiently. This result suggests that these compounds may be promising lead candidates for therapeutic drugs. Ultra-high-throughput fluorescence screening followed by a RapidFire mass spectrometry assay was a suitable strategy for lead discovery against Elovl6. - Highlights: • A novel assay for elongation of very-long-chain fatty acids 6 (Elovl6) is proposed. • RapidFire mass spectrometry (RF-MS) assay is useful to select real screening hits. • RF-MS assay is proved to be beneficial because of its high-throughput and accuracy. • A combination of fluorescent and RF-MS assays is effective for Elovl6 inhibitors.« less

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.

Qualitative screening for new psychoactive substances in wastewater collected during a city festival using liquid chromatography coupled to high-resolution mass spectrometry.

PubMed

Causanilles, Ana; Kinyua, Juliet; Ruttkies, Christoph; van Nuijs, Alexander L N; Emke, Erik; Covaci, Adrian; de Voogt, Pim

2017-10-01

The inclusion of new psychoactive substances (NPS) in the wastewater-based epidemiology approach presents challenges, such as the reduced number of users that translates into low concentrations of residues and the limited pharmacokinetics information available, which renders the choice of target biomarker difficult. The sampling during special social settings, the analysis with improved analytical techniques, and data processing with specific workflow to narrow the search, are required approaches for a successful monitoring. This work presents the application of a qualitative screening technique to wastewater samples collected during a city festival, where likely users of recreational substances gather and consequently higher residual concentrations of used NPS are expected. The analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. Data were processed using an algorithm that involves the extraction of accurate masses (calculated based on molecular formula) of expected m/z from an in-house database containing about 2,000 entries, including NPS and transformation products. We positively identified eight NPS belonging to the classes of synthetic cathinones, phenethylamines and opioids. In addition, the presence of benzodiazepine analogues, classical drugs and other licit substances with potential for abuse was confirmed. The screening workflow based on a database search was useful in the identification of NPS biomarkers in wastewater. The findings highlight the specific classical drugs and low NPS use in the Netherlands. Additionally, meta-chlorophenylpiperazine (mCPP), 2,5-dimethoxy-4-bromophenethylamine (2C-B), and 4-fluoroamphetamine (FA) were identified in wastewater for the first time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rapid screening of bioactive compounds from natural products by integrating 5-channel parallel chromatography coupled with on-line mass spectrometry and microplate based assays.

PubMed

Zhang, Yufeng; Xiao, Shun; Sun, Lijuan; Ge, Zhiwei; Fang, Fengkai; Zhang, Wen; Wang, Yi; Cheng, Yiyu

2013-05-13

A high throughput method was developed for rapid screening and identification of bioactive compounds from traditional Chinese medicine, marine products and other natural products. The system, integrated with five-channel chromatographic separation and dual UV-MS detection, is compatible with in vitro 96-well microplate based bioassays. The stability and applicability of the proposed method was validated by testing radical scavenging capability of a mixture of seven known compounds (rutin, dihydroquercetin, salvianolic acid A, salvianolic acid B, glycyrrhizic acid, rubescensin A and tangeretin). Moreover, the proposed method was successfully applied to the crude extracts of traditional Chinese medicine and a marine sponge from which 12 bioactive compounds were screened and characterized based on their anti-oxidative or anti-tumor activities. In particular, two diterpenoid derivatives, agelasine B and (-)-agelasine D, were identified for the first time as anti-tumor compounds from the sponge Agelas mauritiana, showing a considerable activity toward MCF-7 cells (IC50 values of 7.84±0.65 and 10.48±0.84 μM, respectively). Our findings suggested that the integrated system of 5-channel parallel chromatography coupled with on-line mass spectrometry and microplate based assays can be a versatile and high efficient approach for the discovery of active compounds from natural products. Copyright © 2013 Elsevier B.V. All rights reserved.

Screening for Natural Chemoprevention Agents that Modify Human Keap1

PubMed Central

Hu, Chenqi; Nikolic, Dejan; Eggler, Aimee L.; Mesecar, Andrew D.; van Breemen, Richard B.

2012-01-01

Upregulation of cytoprotective enzymes by therapeutic agents to prevent damage by reactive oxygen species and xenobiotic electrophiles is a strategy for cancer chemoprevention. The Kelch-like ECH-associated protein 1 (Keap1) and its binding partner, transcription factor NF-E2-related factor-2 (Nrf2), are chemoprevention targets because of their role in regulating the antioxidant response element (ARE) in response to oxidative stress and exposure to electrophiles. Modification of the sensor protein Keap1 by electrophiles such as the isothiocyanate sulforaphane can direct Nrf2 accumulation in the nucleus and subsequent ARE activation. Since our previous matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS)-based screening method to discover natural products that modify Keap1 does not detect covalent modification of Keap1 by some highly reversible agents such as sulforaphane, a more sensitive screening assay was developed. In this new assay, electrophiles that have reversibly modified Keap1 can be released, trapped and detected as β-mercaptoethanol adducts by mass spectrometry. Isoliquiritigenin and sulforaphane, known ARE activators that target Keap1, were used to validate the assay. To determine the ability of the assay to identify electrophiles in complex matrixes that modify Keap1, sulforaphane was spiked into a cocoa extract, and LC-MS/MS using high resolution mass spectrometry with accurate mass measurement was used to identify β-mercaptoethanol adducts of sulforaphane that had been released from Keap1. This screening assay permits identification of potential chemoprevention agents in complex natural product mixtures that reversibly modify Keap1 but cannot be detected using MALDI-TOF MS. PMID:22074792

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

PubMed

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

2014-10-21

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

MIPHENO: Data normalization for high throughput metabolic analysis.

EPA Science Inventory

High throughput methodologies such as microarrays, mass spectrometry and plate-based small molecule screens are increasingly used to facilitate discoveries from gene function to drug candidate identification. These large-scale experiments are typically carried out over the course...

Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a cost-effectiveness analysis

PubMed Central

2013-01-01

Background Glutaric aciduria type I (GA-I) is a rare metabolic disorder caused by inherited deficiency of glutaryl-CoA dehydrogenase. Despite high prognostic relevance of early diagnosis and start of metabolic treatment as well as an additional cost saving potential later in life, only a limited number of countries recommend newborn screening for GA-I. So far only limited data is available enabling health care decision makers to evaluate whether investing into GA-I screening represents value for money. The aim of our study was therefore to assess the cost-effectiveness of newborn screening for GA-I by tandem mass spectrometry (MS/MS) compared to a scenario where GA-I is not included in the MS/MS screening panel. Methods We assessed the cost-effectiveness of newborn screening for GA-I against the alternative of not including GA-I in MS/MS screening. A Markov model was developed simulating the clinical course of screened and unscreened newborns within different time horizons of 20 and 70 years. Monte Carlo simulation based probabilistic sensitivity analysis was used to determine the probability of GA-I screening representing a cost-effective therapeutic strategy. Results Within a 20 year time horizon, GA-I screening averts approximately 3.7 DALYs (95% CI 2.9 – 4.5) and about one life year is gained (95% CI 0.7 – 1.4) per 100,000 neonates screened initially . Moreover, the screening programme saves a total of around 30,682 Euro (95% CI 14,343 to 49,176 Euro) per 100,000 screened neonates over a 20 year time horizon. Conclusion Within the limitations of the present study, extending pre-existing MS/MS newborn screening programmes by GA-I represents a highly cost-effective diagnostic strategy when assessed under conditions comparable to the German health care system. PMID:24135440

Personality and Body-Mass-Index in School-Age Children: An Exploration of Mediating and Moderating Variables

PubMed Central

Allen, Mark S.; Vella, Stewart A.

2016-01-01

This study explored longitudinal associations between personality and body-mass-index (BMI) in school-age children, including the potential mediating role of screen time and physical activity, and the potential moderating roles of child demographics and neighbourhood socioeconomic position. Participants were the parents (and teachers) of 3857 ten-year-old children, who completed questionnaires at baseline with a two-year follow-up. After controlling for child demographics (e.g., sex, pubertal status), we found that personality was unimportant for concurrent BMI, but was important for subsequent BMI and change in BMI over two years. Low levels of introversion and persistence at baseline, and decreases in persistence over time, were associated with a higher BMI at follow-up and a greater increase in BMI over time. Moderator analyses showed that introversion was more strongly related to subsequent BMI for children listed as aboriginal or Torres Strait Islander. The relationship between personality and change in BMI was mediated by screen time, but not by physical activity. To conclude, findings demonstrate that personality is important for change in body mass in Australian children (particularly indigenous children), and that screen-based sedentary behaviour features an important role in this association. PMID:27486752

Personality and Body-Mass-Index in School-Age Children: An Exploration of Mediating and Moderating Variables.

PubMed

Allen, Mark S; Vella, Stewart A

2016-01-01

This study explored longitudinal associations between personality and body-mass-index (BMI) in school-age children, including the potential mediating role of screen time and physical activity, and the potential moderating roles of child demographics and neighbourhood socioeconomic position. Participants were the parents (and teachers) of 3857 ten-year-old children, who completed questionnaires at baseline with a two-year follow-up. After controlling for child demographics (e.g., sex, pubertal status), we found that personality was unimportant for concurrent BMI, but was important for subsequent BMI and change in BMI over two years. Low levels of introversion and persistence at baseline, and decreases in persistence over time, were associated with a higher BMI at follow-up and a greater increase in BMI over time. Moderator analyses showed that introversion was more strongly related to subsequent BMI for children listed as aboriginal or Torres Strait Islander. The relationship between personality and change in BMI was mediated by screen time, but not by physical activity. To conclude, findings demonstrate that personality is important for change in body mass in Australian children (particularly indigenous children), and that screen-based sedentary behaviour features an important role in this association.

Screening and analysis of the multiple absorbed bioactive components and metabolites in rat plasma after oral administration of Jitai tablets by high-performance liquid chromatography/diode-array detection coupled with electrospray ionization tandem mass spectrometry.

PubMed

Wang, Shu-Ping; Liu, Lei; Wang, Ling-Ling; Jiang, Peng; Zhang, Ji-Quan; Zhang, Wei-Dong; Liu, Run-Hui

2010-06-15

Based on the serum pharmacochemistry technique and high-performance liquid chromatography/diode-array detection (HPLC/DAD) coupled with electrospray tandem mass spectrometry (HPLC/ESI-MS/MS), a method for screening and analysis of the multiple absorbed bioactive components and metabolites of Jitai tablets (JTT) in orally dosed rat plasma was developed. Plasma was treated by methanol precipitation prior to liquid chromatography, and the separation was carried out on a Symmetry C(18) column, with a linear gradient (0.1% formic acid/water/acetonitrile). Mass spectra were acquired in negative and positive ion modes, respectively. As a result, 26 bioactive components originated from JTT and 5 metabolites were tentatively identified in orally dosed rat plasma by comparing their retention times and MS spectra with those of authentic standards and literature data. It is concluded that an effective and reliable analytical method was set up for screening the bioactive components of Chinese herbal medicine, which provided a meaningful basis for further pharmacology and active mechanism research of JTT. Copyright (c) 2010 John Wiley & Sons, Ltd.

Direct screening and confirmation of priority volatile organic pollutants in drinking water.

PubMed

Caro, J; Serrano, A; Gallego, M

2007-01-05

A screening tool was proposed for the rapid detection of eight priority volatile organic pollutants according to European standards in drinking water. The method is based on the direct coupling of a headspace sampler with a mass spectrometer, using a chromatographic column heated to 175 degrees C as an interface. The water sample was subjected to the headspace extraction process and the volatile fraction was introduced directly into the mass spectrometer, without prior chromatographic separation, achieving low detection limits (0.6-1.2 ng/ml) for all compounds. The mass spectrum resulting from the simultaneous ionization and fragmentation of the mixture of molecules constitutes the volatile profile of each sample. An appropriate chemometric treatment of these signals permitted them to be classified, on the basis of their volatile composition, as contaminated or uncontaminated with respect to the legally established concentration levels for these compounds in drinking water, and providing no false negatives. A conventional confirmation method was carried out to analyze positive water samples by using the same instrumental setup as in the screening method, but using an appropriate temperature program in the chromatographic column to separate, identify and quantify each analyte.

Screening a fragment cocktail library using ultrafiltration

PubMed Central

Shibata, Sayaka; Zhang, Zhongsheng; Korotkov, Konstantin V.; Delarosa, Jaclyn; Napuli, Alberto; Kelley, Angela M.; Mueller, Natasha; Ross, Jennifer; Zucker, Frank H.; Buckner, Frederick S.; Merritt, Ethan A.; Verlinde, Christophe L. M. J.; Van Voorhis, Wesley C.; Hol, Wim G. J.; Fan, Erkang

2011-01-01

Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar Kd, the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins. PMID:21750879

Recent applications of gas chromatography with high-resolution mass spectrometry.

PubMed

Špánik, Ivan; Machyňáková, Andrea

2018-01-01

Gas chromatography coupled to high-resolution mass spectrometry is a powerful analytical method that combines excellent separation power of gas chromatography with improved identification based on an accurate mass measurement. These features designate gas chromatography with high-resolution mass spectrometry as the first choice for identification and structure elucidation of unknown volatile and semi-volatile organic compounds. Gas chromatography with high-resolution mass spectrometry quantitative analyses was previously focused on the determination of dioxins and related compounds using magnetic sector type analyzers, a standing requirement of many international standards. The introduction of a quadrupole high-resolution time-of-flight mass analyzer broadened interest in this method and novel applications were developed, especially for multi-target screening purposes. This review is focused on the development and the most interesting applications of gas chromatography coupled to high-resolution mass spectrometry towards analysis of environmental matrices, biological fluids, and food safety since 2010. The main attention is paid to various approaches and applications of gas chromatography coupled to high-resolution mass spectrometry for non-target screening to identify contaminants and to characterize the chemical composition of environmental, food, and biological samples. The most interesting quantitative applications, where a significant contribution of gas chromatography with high-resolution mass spectrometry over the currently used methods is expected, will be discussed as well. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Searching for microbial protein over-expression in a complex matrix using automated high throughput MS-based proteomics tools.

PubMed

Akeroyd, Michiel; Olsthoorn, Maurien; Gerritsma, Jort; Gutker-Vermaas, Diana; Ekkelkamp, Laurens; van Rij, Tjeerd; Klaassen, Paul; Plugge, Wim; Smit, Ed; Strupat, Kerstin; Wenzel, Thibaut; van Tilborg, Marcel; van der Hoeven, Rob

2013-03-10

In the discovery of new enzymes genomic and cDNA expression libraries containing thousands of differential clones are generated to obtain biodiversity. These libraries need to be screened for the activity of interest. Removing so-called empty and redundant clones significantly reduces the size of these expression libraries and therefore speeds up new enzyme discovery. Here, we present a sensitive, generic workflow for high throughput screening of successful microbial protein over-expression in microtiter plates containing a complex matrix based on mass spectrometry techniques. MALDI-LTQ-Orbitrap screening followed by principal component analysis and peptide mass fingerprinting was developed to obtain a throughput of ∼12,000 samples per week. Alternatively, a UHPLC-MS(2) approach including MS(2) protein identification was developed for microorganisms with a complex protein secretome with a throughput of ∼2000 samples per week. TCA-induced protein precipitation enhanced by addition of bovine serum albumin is used for protein purification prior to MS detection. We show that this generic workflow can effectively reduce large expression libraries from fungi and bacteria to their minimal size by detection of successful protein over-expression using MS. Copyright © 2012 Elsevier B.V. All rights reserved.

Nanoparticle-assisted laser desorption/ionization mass spectrometry: Novel sample preparation methods and nanoparticle screening for plant metabolite imaging

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

Yagnik, Gargey B.

The main goal of the presented research is development of nanoparticle based matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). This dissertation includes the application of previously developed data acquisition methods, development of novel sample preparation methods, application and comparison of novel nanoparticle matrices, and comparison of two nanoparticle matrix application methods for MALDI-MS and MALDI-MS imaging.

A New Method for Determining Permethrin Level on Military Uniform Fabrics

DTIC Science & Technology

2017-06-01

new desorption- gas chromatography–mass spectrometry based screening tool for permethrin content in military fabrics was developed. The method allows...SUBJECT TERMS permethrin, Army Combat Uniform, ACU, camouflage, desorption- gas chromatography-mass spectrometry, D-GC-MS 16. SECURITY CLASSIFICATION OF...and the permethrin contained in the specimens is extracted with solvent with a recovery rate of at least 95%. Samples are analyzed using a gas

Fostering Informed Decisions: Impact of a Decision Aid Among Men Registered to Undergo Mass Screening for Prostate Cancer in a Randomized Controlled Trial

PubMed Central

Williams, Randi M.; Davis, Kimberly M.; Luta, George; Edmond, Sara N.; Dorfman, Caroline S.; Schwartz, Marc D.; Lynch, John; Ahaghotu, Chiledum; Taylor, Kathryn L.

2013-01-01

Objective Screening asymptomatic men for prostate cancer is controversial and informed decision making is recommended. Within two prostate cancer screening programs, we evaluated the impact of a print-based decision aid (DA) on decision-making outcomes. Methods Men (N=543) were 54.9 (SD=8.1) years old and 61% were African-American. The 2 (booklet type: DA vs. usual care (UC)) × 2 (delivery mode: Home vs. Clinic) randomized controlled trial assessed decisional and screening outcomes at baseline, two-months, and 13-months. Results Intention-to-treat linear regression analyses using generalized estimating equations revealed that DA participants reported improved knowledge relative to UC (B=.41, p<.05). For decisional conflict, per-protocol analyses revealed a group by time interaction (B = −.69, p<.05), indicating that DA participants were less likely to report decisional conflict at two-months compared to UC participants (OR=.49, 95% CI: .26–.91, p<.05). Conclusion This is the first randomized trial to evaluate a DA in the context of free mass screening, a challenging setting in which to make an informed decision. The DA was highly utilized by participants, improved knowledge and reduced decisional conflict. Practice implications These results are valuable in understanding ways to improve the decisions of men who seek screening and can be easily implemented within many settings. PMID:23357414

An Evaluation of Mass Screening Using Fecal Occult Blood Test for Colorectal Cancer in Japan: A Case‐Control Study

PubMed Central

Hiwatashi, Nobuo; Morimoto, Tomizo; Fukao, Akira; Sato, Hirofusa; Sugahara, Nobuyuki; Hisamichi, Shigeru; Toyota, Takayoshi

1993-01-01

There is as yet no firm evidence showing that mass screening for colorectal cancer using fecal occult blood tests (FOBTs) reduces the mortality from this cancer. Therefore we evaluated the effectiveness of the screening by a case‐control study in Miyagi Prefecture, Japan. The study included as case subjects 28 individuals who had died from colorectal cancer and had had an opportunity to participate in the mass screening before the date of diagnosis as colorectal cancer, and 3 controls for each case subject randomly selected from residents who were alive on the date of death of case subjects and matched by sex, age (within 3 years) and living area using residential files. For each set, i.e., a case subject and 3 controls, screening histories before the date of the diagnosis of the case as colorectal cancer were examined. Both the case subjects and the controls who had participated in the screening at least once within 3 years before the date of diagnosis of the case were classified as “screened.” The 28 case subjects consisted of 12 males and 16 females (average age: 60.8 years). The odds ratio of death from colorectal cancer for the screened versus the non‐screened persons was 0.24 (95% confidence interval = 0.08–0.76) by the Mantel‐Haenszel method. The present study suggests that mass screening using FOBTs for colorectal cancer significantly reduces the mortality from this cancer epidemiologically. PMID:8276715

Factors affecting reproducibility between genome-scale siRNA-based screens

PubMed Central

Barrows, Nicholas J.; Le Sommer, Caroline; Garcia-Blanco, Mariano A.; Pearson, James L.

2011-01-01

RNA interference-based screening is a powerful new genomic technology which addresses gene function en masse. To evaluate factors influencing hit list composition and reproducibility, we performed two identically designed small interfering RNA (siRNA)-based, whole genome screens for host factors supporting yellow fever virus infection. These screens represent two separate experiments completed five months apart and allow the direct assessment of the reproducibility of a given siRNA technology when performed in the same environment. Candidate hit lists generated by sum rank, median absolute deviation, z-score, and strictly standardized mean difference were compared within and between whole genome screens. Application of these analysis methodologies within a single screening dataset using a fixed threshold equivalent to a p-value ≤ 0.001 resulted in hit lists ranging from 82 to 1,140 members and highlighted the tremendous impact analysis methodology has on hit list composition. Intra- and inter-screen reproducibility was significantly influenced by the analysis methodology and ranged from 32% to 99%. This study also highlighted the power of testing at least two independent siRNAs for each gene product in primary screens. To facilitate validation we conclude by suggesting methods to reduce false discovery at the primary screening stage. In this study we present the first comprehensive comparison of multiple analysis strategies, and demonstrate the impact of the analysis methodology on the composition of the “hit list”. Therefore, we propose that the entire dataset derived from functional genome-scale screens, especially if publicly funded, should be made available as is done with data derived from gene expression and genome-wide association studies. PMID:20625183

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 cost-effectiveness of 10 antenatal syphilis screening and treatment approaches in Peru, Tanzania, and Zambia.

PubMed

Terris-Prestholt, Fern; Vickerman, Peter; Torres-Rueda, Sergio; Santesso, Nancy; Sweeney, Sedona; Mallma, Patricia; Shelley, Katharine D; Garcia, Patricia J; Bronzan, Rachel; Gill, Michelle M; Broutet, Nathalie; Wi, Teodora; Watts, Charlotte; Mabey, David; Peeling, Rosanna W; Newman, Lori

2015-06-01

Rapid plasma reagin (RPR) is frequently used to test women for maternal syphilis. Rapid syphilis immunochromatographic strip tests detecting only Treponema pallidum antibodies (single RSTs) or both treponemal and non-treponemal antibodies (dual RSTs) are now available. This study assessed the cost-effectiveness of algorithms using these tests to screen pregnant women. Observed costs of maternal syphilis screening and treatment using clinic-based RPR and single RSTs in 20 clinics across Peru, Tanzania, and Zambia were used to model the cost-effectiveness of algorithms using combinations of RPR, single, and dual RSTs, and no and mass treatment. Sensitivity analyses determined drivers of key results. Although this analysis found screening using RPR to be relatively cheap, most (>70%) true cases went untreated. Algorithms using single RSTs were the most cost-effective in all observed settings, followed by dual RSTs, which became the most cost-effective if dual RST costs were halved. Single test algorithms dominated most sequential testing algorithms, although sequential algorithms reduced overtreatment. Mass treatment was relatively cheap and effective in the absence of screening supplies, though treated many uninfected women. This analysis highlights the advantages of introducing RSTs in three diverse settings. The results should be applicable to other similar settings. Copyright © 2015 International Federation of Gynecology and Obstetrics. All rights reserved.

The cost-effectiveness of 10 antenatal syphilis screening and treatment approaches in Peru, Tanzania, and Zambia

PubMed Central

Terris-Prestholt, Fern; Vickerman, Peter; Torres-Rueda, Sergio; Santesso, Nancy; Sweeney, Sedona; Mallma, Patricia; Shelley, Katharine D.; Garcia, Patricia J.; Bronzan, Rachel; Gill, Michelle M.; Broutet, Nathalie; Wi, Teodora; Watts, Charlotte; Mabey, David; Peeling, Rosanna W.; Newman, Lori

2015-01-01

Objective Rapid plasma reagin (RPR) is frequently used to test women for maternal syphilis. Rapid syphilis immunochromatographic strip tests detecting only Treponema pallidum antibodies (single RSTs) or both treponemal and non-treponemal antibodies (dual RSTs) are now available. This study assessed the cost-effectiveness of algorithms using these tests to screen pregnant women. Methods Observed costs of maternal syphilis screening and treatment using clinic-based RPR and single RSTs in 20 clinics across Peru, Tanzania, and Zambia were used to model the cost-effectiveness of algorithms using combinations of RPR, single, and dual RSTs, and no and mass treatment. Sensitivity analyses determined drivers of key results. Results Although this analysis found screening using RPR to be relatively cheap, most (> 70%) true cases went untreated. Algorithms using single RSTs were the most cost-effective in all observed settings, followed by dual RSTs, which became the most cost-effective if dual RST costs were halved. Single test algorithms dominated most sequential testing algorithms, although sequential algorithms reduced overtreatment. Mass treatment was relatively cheap and effective in the absence of screening supplies, though treated many uninfected women. Conclusion This analysis highlights the advantages of introducing RSTs in three diverse settings. The results should be applicable to other similar settings. PMID:25963907

Influence of magnetic fields on the color screening masses

NASA Astrophysics Data System (ADS)

Bonati, Claudio; D'Elia, Massimo; Mesiti, Michele; Negro, Francesco; Rucci, Andrea; Sanfilippo, Francesco

2018-03-01

We present some recent results obtained in the study of the color magnetic and electric screening masses in the QCD plasma. In particular, we discuss how the masses get modified by strong external fields which are expected to be created in physical situations such as heavy-ion collisions.

A pre-classification strategy based on UPLC-Triple-TOF/MS for metabolic screening and identification of Radix glehniae in rats.

PubMed

Wang, Shuang; Qi, Pengcheng; Zhou, Na; Zhao, Minmin; Ding, Weijing; Li, Song; Liu, Minyan; Wang, Qiao; Jin, Shumin

2016-10-01

Traditional Chinese Medicines (TCMs) have gained increasing popularity in modern society. However, the profiles of TCMs in vivo are still unclear owing to their complexity and low level in vivo. In this study, UPLC-Triple-TOF techniques were employed for data acquiring, and a novel pre-classification strategy was developed to rapidly and systematically screen and identify the absorbed constituents and metabolites of TCMs in vivo using Radix glehniae as the research object. In this strategy, pre-classification for absorbed constituents was first performed according to the similarity of their structures. Then representative constituents were elected from every class and analyzed separately to screen non-target absorbed constituents and metabolites in biosamples. This pre-classification strategy is basing on target (known) constituents to screen non-target (unknown) constituents from the massive data acquired by mass spectrometry. Finally, the screened candidate compounds were interpreted and identified based on a predicted metabolic pathway, well - studied fragmentation rules, a predicted metabolic pathway, polarity and retention time of the compounds, and some related literature. With this method, a total of 111 absorbed constituents and metabolites of Radix glehniae in rats' urine, plasma, and bile samples were screened and identified or tentatively characterized successfully. This strategy provides an idea for the screening and identification of the metabolites of other TCMs.

Smart material screening machines using smart materials and controls

NASA Astrophysics Data System (ADS)

Allaei, Daryoush; Corradi, Gary; Waigand, Al

2002-07-01

The objective of this product is to address the specific need for improvements in the efficiency and effectiveness in physical separation technologies in the screening areas. Currently, the mining industry uses approximately 33 billion kW-hr per year, costing 1.65 billion dollars at 0.05 cents per kW-hr, of electrical energy for physical separations. Even though screening and size separations are not the single most energy intensive process in the mining industry, they are often the major bottleneck in the whole process. Improvements to this area offer tremendous potential in both energy savings and production improvements. Additionally, the vibrating screens used in the mining processing plants are the most costly areas from maintenance and worker health and safety point of views. The goal of this product is to reduce energy use in the screening and total processing areas. This goal is accomplished by developing an innovative screening machine based on smart materials and smart actuators, namely smart screen that uses advanced sensory system to continuously monitor the screening process and make appropriate adjustments to improve production. The theory behind the development of Smart Screen technology is based on two key technologies, namely smart actuators and smart Energy Flow ControlT (EFCT) strategies, developed initially for military applications. Smart Screen technology controls the flow of vibration energy and confines it to the screen rather than shaking much of the mass that makes up the conventional vibratory screening machine. Consequently, Smart Screens eliminates and downsizes many of the structural components associated with conventional vibratory screening machines. As a result, the surface area of the screen increases for a given envelope. This increase in usable screening surface area extends the life of the screens, reduces required maintenance by reducing the frequency of screen change-outs and improves throughput or productivity.

Development of a metabolomic approach based on liquid chromatography-high resolution mass spectrometry to screen for clenbuterol abuse in calves.

PubMed

Courant, Frédérique; Pinel, Gaud; Bichon, Emmanuelle; Monteau, Fabrice; Antignac, Jean-Philippe; Le Bizec, Bruno

2009-08-01

Beta-agonist compounds can be misused in food-producing animals for growth promoting purposes. Efficient methods based on mass spectrometry detection have been developed to ensure the control of such veterinary drug residues. Nevertheless, the use of "cocktails" composed of mixtures of low amounts of several substances as well as the synthesis of new compounds of unknown structure prevent efficient prevention. To circumvent those problems, new analytical tools able to detect such abuse are today mandatory. In this context, metabolomics may represent a new emerging strategy for investigating the global physiological effects associated to a family of substances and therefore, to suspect the administration of beta-agonists (either "cocktails" or unknown compounds). As a first demonstration of feasibility, an untargeted metabolomic approach based on liquid chromatography coupled to high resolution mass spectrometry measurements was developed and made it possible to highlight metabolic modifications in urine consecutively to a clenbuterol administration. By the means of chemometrics, those metabolic differences were used to build predictive models able to suspect clenbuterol administration in calves. This new approach may be considered of valuable interest to overcome current limitations in the control of growth promoters' abuse, with promising perspectives in terms of screening.

THE VIEW FROM THE TRENCHES: PART 2–TECHNICAL CONSIDERATIONS FOR EPR SCREENING

PubMed Central

Nicolalde, Roberto J.; Gougelet, Robert M.; Rea, Michael; Williams, Benjamin B.; Dong, Ruhong; Kmiec, Maciej M.; Lesniewski, Piotr N.; Swartz, Harold M.

2014-01-01

There is growing awareness of the need for methodologies that can be used retrospectively to provide the biodosimetry needed to carry out screening and triage immediately after an event in which large numbers of people have potentially received clinically significant doses of ionizing radiation. The general approach to developing such methodologies has been a technology centric one, often ignoring the system integrations considerations that are key to their effective use. In this study an integrative approach for the evaluation and development of a physical biodosimetry technology was applied based on in vivo electron paramagnetic resonance (EPR) dosimetry. The EPR measurements are based on physical changes in tissues whose magnitudes are not affected by the factors that can confound biologically-based assessments. In this study the use of a pilot simulation exercise to evaluate an experimental EPR system and gather stakeholders’ feedback early on in the development process is described. The exercise involved: ten non-irradiated participants, representatives from a local fire department; Department of Homeland Security certified exercise evaluators, EPR experts, physicians; and a human factors engineer. Stakeholders were in agreement that the EPR technology in its current state of development could be deployed for the screening of mass casualties. Furthermore, stakeholders’ recommendations will be prioritized and incorporated in future developments of the EPR technique. While the results of this exercise were aimed specifically at providing feedback for the development of EPR dosimetry for screening mass casualties, the methods and lessons learned are likely to be applicable to other biodosimetric methods. PMID:20065674

Steroid profiling for congenital adrenal hyperplasia by tandem mass spectrometry as a second-tier test reduces follow-up burdens in a tertiary care hospital: a retrospective and prospective evaluation.

PubMed

Seo, Ja Young; Park, Hyung-Doo; Kim, Jong Won; Oh, Hyeon Ju; Yang, Jeong Soo; Chang, Yun Sil; Park, Won Soon; Lee, Soo-Youn

2014-01-01

Newborn screening for congenital adrenal hyperplasia (CAH) based on measuring 17-hydroxyprogesterone (17-OHP) by immunoassay generates a number of false-positive results, especially in preterm neonates. We applied steroid profiling by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a second-tier test in newborns with positive CAH screening and evaluated its clinical utility in a tertiary care hospital setting. By performing a 4-year retrospective data review, we were able to test 121 dried blood spots from newborns with positive CAH screening for 17-OHP, androstenedione and cortisol levels by LC-MS/MS. We prospectively evaluated the clinical utility of steroid profiling after the implementation of steroid profiling as a second-tier test in our routine clinical practice. During the 2-year prospective study period, 104 cases with positive initial screening by FIA were tested by LC-MS/MS. Clinical and laboratory follow-up were performed for at least 6 months. The preterm neonates accounted for 50.7% (76/150) and 70.4% (88/125) of screening-positive cases in retrospective and prospective cohorts, respectively. By applying steroid profiling as a second-tier test for positive CAH screening, we eliminated all false-positive results and decreased the median follow-up time from 75 to 8 days. Our data showed that steroid profiling reduced the burden of follow-up exams by improving the positive predictive value of the CAH screening program. The use of steroid profiling as a second-tier test for positive CAH screening will improve clinical practice particularly in a tertiary care hospital setting where positive CAH screening from preterm neonates is frequently encountered.

Gravitational lensing by a smoothly variable three-dimensional mass distribution

NASA Technical Reports Server (NTRS)

Lee, Man Hoi; Paczynski, Bohdan

1990-01-01

A smooth three-dimensional mass distribution is approximated by a model with multiple thin screens, with surface mass density varying smoothly on each screen. It is found that 16 screens are sufficient for a good approximation of the three-dimensional distribution of matter. It is also found that in this multiscreen model the distribution of amplifications of single images is dominated by the convergence due to matter within the beam. The shear caused by matter outside the beam has no significant effect. This finding considerably simplifies the modeling of lensing by a smooth three-dimensional mass distribution by effectively reducing the problem to one dimension, as it is sufficient to know the mass distribution along a straight light ray.

Dual-Energy Contrast-Enhanced Spectral Mammography: Enhancement Analysis on BI-RADS 4 Non-Mass Microcalcifications in Screened Women

PubMed Central

Cheung, Yun-Chung; Juan, Yu-Hsiang; Lin, Yu-Ching; Lo, Yung-Feng; Tsai, Hsiu-Pei; Ueng, Shir-Hwa; Chen, Shin-Cheh

2016-01-01

Background Mammography screening is a cost-efficient modality with high sensitivity for detecting impalpable cancer with microcalcifications, and results in reduced mortality rates. However, the probability of finding microcalcifications without associated cancerous masses varies. We retrospectively evaluated the diagnosis and cancer probability of the non-mass screened microcalcifications by dual-energy contrast-enhanced spectral mammography (DE-CESM). Patients and Methods With ethical approval from our hospital, we enrolled the cases of DE-CESM for analysis under the following inclusion criteria: (1) referrals due to screened BI-RADS 4 microcalcifications; (2) having DE-CESM prior to stereotactic biopsy; (3) no associated mass found by sonography and physical examination; and (4) pathology-based diagnosis using stereotactic vacuum-assisted breast biopsy. We analyzed the added value of post-contrast enhancement on DE-CESM. Results A total of 94 biopsed lesions were available for analysis in our 87 women, yielding 27 cancers [19 ductal carcinoma in situ (DCIS), and 8 invasive ductal carcinoma (IDC)], 32 pre-malignant and 35 benign lesions. Of these 94 lesions, 33 showed associated enhancement in DE-CESM while the other 61 did not. All 8 IDC (100%) and 16 of 19 DCIS (84.21%) showed enhancement, but the other 3 DCIS (15.79%) did not. Overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 88.89%, 86.56%, 72.72%, 95.08% and 87.24%, respectively. The performances of DE-CESM on both amorphous and pleomorphic microcalcifications were satisfactory (AUC 0.8 and 0.92, respectively). The pleomorphous microcalcifications with enhancement showed higher positive predictive value (90.00% vs 46.15%, p = 0.013) and higher cancer probability than the amorphous microcalcifications (46.3% VS 15.1%). The Odds Ratio was 4.85 (95% CI: 1.84–12.82). Conclusion DE-CESM might provide added value in assessing the non-mass screened breast microcalcification, with enhancement favorable to the diagnosis of cancers or lack of enhancement virtually diagnostic for non-malignant lesions or noninvasive subgroup cancers. PMID:27611215

21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Code of Federal Regulations, 2012 CFR

2012-04-01

... mass spectrometry is a device that consists of stable isotope internal standards, control materials..., free carnitine, and acylcarnitines using tandem mass spectrometry. 862.1055 Section 862.1055 Food and... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a...

21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Code of Federal Regulations, 2014 CFR

2014-04-01

... mass spectrometry is a device that consists of stable isotope internal standards, control materials..., free carnitine, and acylcarnitines using tandem mass spectrometry. 862.1055 Section 862.1055 Food and... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a...

Unlocking nature’s treasure-chest: screening for oleaginous algae

PubMed Central

Slocombe, Stephen P.; Zhang, QianYi; Ross, Michael; Anderson, Avril; Thomas, Naomi J.; Lapresa, Ángela; Rad-Menéndez, Cecilia; Campbell, Christine N.; Black, Kenneth D.; Stanley, Michele S.; Day, John G.

2015-01-01

Micro-algae synthesize high levels of lipids, carbohydrates and proteins photoautotrophically, thus attracting considerable interest for the biotechnological production of fuels, environmental remediation, functional foods and nutraceuticals. Currently, only a few micro-algae species are grown commercially at large-scale, primarily for “health-foods” and pigments. For a range of potential products (fuel to pharma), high lipid productivity strains are required to mitigate the economic costs of mass culture. Here we present a screen concentrating on marine micro-algal strains, which if suitable for scale-up would minimise competition with agriculture for water. Mass-Spectrophotometric analysis (MS) of nitrogen (N) and carbon (C) was subsequently validated by measurement of total fatty acids (TFA) by Gas-Chromatography (GC). This identified a rapid and accurate screening strategy based on elemental analysis. The screen identified Nannochloropsis oceanica CCAP 849/10 and a marine isolate of Chlorella vulgaris CCAP 211/21A as the best lipid producers. Analysis of C, N, protein, carbohydrate and Fatty Acid (FA) composition identified a suite of strains for further biotechnological applications e.g. Dunaliella polymorpha CCAP 19/14, significantly the most productive for carbohydrates, and Cyclotella cryptica CCAP 1070/2, with utility for EPA production and N-assimilation. PMID:26202369

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

PubMed

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

2007-01-01

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

Barriers to asymptomatic screening and other STD services for adolescents and young adults: focus group discussions

PubMed Central

Tilson, Elizabeth C; Sanchez, Victoria; Ford, Chandra L; Smurzynski, Marlene; Leone, Peter A; Fox, Kimberley K; Irwin, Kathleen; Miller, William C

2004-01-01

Background Sexually transmitted diseases (STDs) are a major public health problem among young people and can lead to the spread of HIV. Previous studies have primarily addressed barriers to STD care for symptomatic patients. The purpose of our study was to identify perceptions about existing barriers to and ideal services for STDs, especially asymptomatic screening, among young people in a southeastern community. Methods Eight focus group discussions including 53 White, African American, and Latino youth (age 14–24) were conducted. Results Perceived barriers to care included lack of knowledge of STDs and available services, cost, shame associated with seeking services, long clinic waiting times, discrimination, and urethral specimen collection methods. Perceived features of ideal STD services included locations close to familiar places, extended hours, and urine-based screening. Television was perceived as the most effective route of disseminating STD information. Conclusions Further research is warranted to evaluate improving convenience, efficiency, and privacy of existing services; adding urine-based screening and new services closer to neighborhoods; and using mass media to disseminate STD information as strategies to increase STD screening. PMID:15189565

Digital Image Processing Technique for Breast Cancer Detection

NASA Astrophysics Data System (ADS)

Guzmán-Cabrera, R.; Guzmán-Sepúlveda, J. R.; Torres-Cisneros, M.; May-Arrioja, D. A.; Ruiz-Pinales, J.; Ibarra-Manzano, O. G.; Aviña-Cervantes, G.; Parada, A. González

2013-09-01

Breast cancer is the most common cause of death in women and the second leading cause of cancer deaths worldwide. Primary prevention in the early stages of the disease becomes complex as the causes remain almost unknown. However, some typical signatures of this disease, such as masses and microcalcifications appearing on mammograms, can be used to improve early diagnostic techniques, which is critical for women’s quality of life. X-ray mammography is the main test used for screening and early diagnosis, and its analysis and processing are the keys to improving breast cancer prognosis. As masses and benign glandular tissue typically appear with low contrast and often very blurred, several computer-aided diagnosis schemes have been developed to support radiologists and internists in their diagnosis. In this article, an approach is proposed to effectively analyze digital mammograms based on texture segmentation for the detection of early stage tumors. The proposed algorithm was tested over several images taken from the digital database for screening mammography for cancer research and diagnosis, and it was found to be absolutely suitable to distinguish masses and microcalcifications from the background tissue using morphological operators and then extract them through machine learning techniques and a clustering algorithm for intensity-based segmentation.

Proteomics meets blue biotechnology: a wealth of novelties and opportunities.

PubMed

Hartmann, Erica M; Durighello, Emie; Pible, Olivier; Nogales, Balbina; Beltrametti, Fabrizio; Bosch, Rafael; Christie-Oleza, Joseph A; Armengaud, Jean

2014-10-01

Blue biotechnology, in which aquatic environments provide the inspiration for various products such as food additives, aquaculture, biosensors, green chemistry, bioenergy, and pharmaceuticals, holds enormous promise. Large-scale efforts to sequence aquatic genomes and metagenomes, as well as campaigns to isolate new organisms and culture-based screenings, are helping to push the boundaries of known organisms. Mass spectrometry-based proteomics can complement 16S gene sequencing in the effort to discover new organisms of potential relevance to blue biotechnology by facilitating the rapid screening of microbial isolates and by providing in depth profiles of the proteomes and metaproteomes of marine organisms, both model cultivable isolates and, more recently, exotic non-cultivable species and communities. Proteomics has already contributed to blue biotechnology by identifying aquatic proteins with potential applications to food fermentation, the textile industry, and biomedical drug development. In this review, we discuss historical developments in blue biotechnology, the current limitations to the known marine biosphere, and the ways in which mass spectrometry can expand that knowledge. We further speculate about directions that research in blue biotechnology will take given current and near-future technological advancements in mass spectrometry. Copyright © 2014 Elsevier B.V. All rights reserved.

Gauge-invariant screening masses and static quark free energies in Nf=2 +1 QCD at nonzero baryon density

NASA Astrophysics Data System (ADS)

Andreoli, Michele; Bonati, Claudio; D'Elia, Massimo; Mesiti, Michele; Negro, Francesco; Rucci, Andrea; Sanfilippo, Francesco

2018-03-01

We discuss the extension of gauge-invariant electric and magnetic screening masses in the quark-gluon plasma to the case of a finite baryon density, defining them in terms of a matrix of Polyakov loop correlators. We present lattice results for Nf=2 +1 QCD with physical quark masses, obtained using the imaginary chemical potential approach, which indicate that the screening masses increase as a function of μB. A separate analysis is carried out for the theoretically interesting case μB/T =3 i π , where charge conjugation is not explicitly broken and the usual definition of the screening masses can be used for temperatures below the Roberge-Weiss transition. Finally, we investigate the dependence of the static quark free energy on the baryon chemical potential, showing that it is a decreasing function of μB, which displays a peculiar behavior as the pseudocritical transition temperature at μB=0 is approached.

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

PubMed

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

2015-10-01

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

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

PubMed

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

2013-10-01

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

Television viewing and other screen-based entertainment in relation to multiple socioeconomic status indicators and area deprivation: the Scottish Health Survey 2003.

PubMed

Stamatakis, E; Hillsdon, M; Mishra, G; Hamer, M; Marmot, M

2009-09-01

Sedentary behaviour (sitting) is detrimental to health, independently of participation in physical activity. Socioeconomic position (SEP) is known to relate strongly to physical activity participation but we know very little about how SEP relates to sedentary behaviour. This study aimed to assess the relationships between SEP, neighbourhood deprivation and an index of sedentary time. Cross-sectional study of a representative sample of 7940 Scottish adults who participated in the 2003 Scottish Health Survey, which collected information on SEP (household income, social class and education), neighbourhood deprivation (Scottish Index of Multiple Deprivation), television and other screen-based entertainment time, and physical activity. The three indicators of SEP and deprivation index were independently of each other associated with daily times of television and other screen-based entertainment, even after adjustment for occupational and leisure-time physical activity, health status, smoking, alcohol drinking, car ownership and body mass index: income p = 0.002; social class p<0.001; education p<0.001, deprivation p<0.001. Also, there was a strong cumulative effect of SEP (a composite scale where 0 = lowest, 9 = highest SEP position) with those in the lowest SEP spending an additional 109 minutes each day on screen-based entertainment compared to those in the highest socioeconomic position (p<0.001 for linear trend). Adverse socioeconomic position is associated with a cumulative increase in the time spent on screen-based entertainment. Reducing inequalities would be expected to reduce exposure to sedentary behaviours, such as excessive screen-based entertainment times, and therefore reduce the risk of chronic disease.

High-resolution chromatography/time-of-flight MSE with in silico data mining is an information-rich approach to reactive metabolite screening.

PubMed

Barbara, Joanna E; Castro-Perez, Jose M

2011-10-30

Electrophilic reactive metabolite screening by liquid chromatography/mass spectrometry (LC/MS) is commonly performed during drug discovery and early-stage drug development. Accurate mass spectrometry has excellent utility in this application, but sophisticated data processing strategies are essential to extract useful information. Herein, a unified approach to glutathione (GSH) trapped reactive metabolite screening with high-resolution LC/TOF MS(E) analysis and drug-conjugate-specific in silico data processing was applied to rapid analysis of test compounds without the need for stable- or radio-isotope-labeled trapping agents. Accurate mass defect filtering (MDF) with a C-heteroatom dealkylation algorithm dynamic with mass range was compared to linear MDF and shown to minimize false positive results. MS(E) data-filtering, time-alignment and data mining post-acquisition enabled detection of 53 GSH conjugates overall formed from 5 drugs. Automated comparison of sample and control data in conjunction with the mass defect filter enabled detection of several conjugates that were not evident with mass defect filtering alone. High- and low-energy MS(E) data were time-aligned to generate in silico product ion spectra which were successfully applied to structural elucidation of detected GSH conjugates. Pseudo neutral loss and precursor ion chromatograms derived post-acquisition demonstrated 50.9% potential coverage, at best, of the detected conjugates by any individual precursor or neutral loss scan type. In contrast with commonly applied neutral loss and precursor-based techniques, the unified method has the advantage of applicability across different classes of GSH conjugates. The unified method was also successfully applied to cyanide trapping analysis and has potential for application to alternate trapping agents. Copyright © 2011 John Wiley & Sons, Ltd.

Mass spectrometric screening and identification of acidic metabolites in fulvic acid fractions of contaminated groundwater.

PubMed

Jobelius, Carsten; Frimmel, Fritz H; Zwiener, Christian

2014-05-01

The anaerobic microbial degradation of aromatic and heterocyclic compounds is a prevalent process in contaminated groundwater systems. The introduction of functional groups into the contaminant molecules often results in aromatic and heterocyclic and succinic acids. These metabolites can be used as indicators for prevailing degradation processes. Therefore, there is a strong interest in developing analytical methods for screening and identification of these metabolites. In this study, neutral loss scans (NLS) by liquid chromatography-electrospray ionization/tandem mass spectrometry with losses of CO2 (NL ∆m/z = 44) and C2H4(CO2)2 (NL ∆m/z = 116) were applied for the first time successfully to screen selectively for acidic and succinic metabolites of aromatic and heterocyclic contaminants in two fulvic acid fractions from a contaminated site and a downstream region of a tar oil-polluted groundwater. Identification of these preselected signals was performed by high-resolution mass spectrometry with a liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry instrument. High-resolution mass and mass fragmentation data were then compared with a list of known metabolites from a literature search or matched with chemical databases supported with in silico fragmentation. Based on authentic analytical standards, several compounds from NLS were identified (e.g., 4-hydroxy-3-methylbenzoic acid, benzylsuccinic acid, naphthyl-2-methylsuccinic acid, 2-carboxyindane, and 2-carboxybenzothiophene) and tentatively identified (e.g., benzofuranmethylsuccinic acid and dihydrocarboxybenzothiophene) as aromatic, phenolic, heterocyclic, and succinic acids. The acidic metabolites were found exclusively in the contaminated region of the aquifer which indicates active biodegradation processes and no relevant occurrence of acidic metabolites in the downstream region.

Critical evaluation of a simple retention time predictor based on LogKow as a complementary tool in the identification of emerging contaminants in water.

PubMed

Bade, Richard; Bijlsma, Lubertus; Sancho, Juan V; Hernández, Felix

2015-07-01

There has been great interest in environmental analytical chemistry in developing screening methods based on liquid chromatography-high resolution mass spectrometry (LC-HRMS) for emerging contaminants. Using HRMS, compound identification relies on the high mass resolving power and mass accuracy attainable by these analyzers. When dealing with wide-scope screening, retention time prediction can be a complementary tool for the identification of compounds, and can also reduce tedious data processing when several peaks appear in the extracted ion chromatograms. There are many in silico, Quantitative Structure-Retention Relationship methods available for the prediction of retention time for LC. However, most of these methods use commercial software to predict retention time based on various molecular descriptors. This paper explores the applicability and makes a critical discussion on a far simpler and cheaper approach to predict retention times by using LogKow. The predictor was based on a database of 595 compounds, their respective LogKow values and a chromatographic run time of 18min. Approximately 95% of the compounds were found within 4.0min of their actual retention times, and 70% within 2.0min. A predictor based purely on pesticides was also made, enabling 80% of these compounds to be found within 2.0min of their actual retention times. To demonstrate the utility of the predictors, they were successfully used as an additional tool in the identification of 30 commonly found emerging contaminants in water. Furthermore, a comparison was made by using different mass extraction windows to minimize the number of false positives obtained. Copyright © 2015 Elsevier B.V. All rights reserved.

[Interval cancers and episode sensitivity in population-based screening programmes for colorectal cancer: a systematic review].

PubMed

Domènech, Xènia; Garcia, Montse; Benito, Llúcia; Binefa, Gemma; Vidal, Carmen; Milà, Núria; Moreno, Víctor

2015-01-01

To describe interval cancers (IC) and the sensitivity of colorectal cancer (CRC) screening programmes. A systematic review of the literature was conducted through a MEDLINE (PubMed) search. The search strategy combined the terms 'interval cancer', 'false negative', 'mass screening', 'screening' 'early detection of cancer', 'colorectal cancer' and 'bowel cancer'. Inclusion criteria consisted of population-based screening programmes, original articles written in English or Spanish and publication dates between 1999/01/01 and 2015/02/28. A narrative synthesis of the included articles was performed detailing the characteristics of the screening programmes, the IC rate, and the information sources used in each study. Thirteen articles were included. The episode sensitivity of CRC screening programmes ranged from 42.2% to 65.3% in programmes using the guaiac test and between 59.1% and 87.0% with the immunochemical test. We found a higher proportion of women who were diagnosed with IC and these lesions were mainly located in the proximal colon. There is wide variability in the IC rate in CRC programmes. To ensure comparability between programmes, there is a need for consensus on the working definition of IC and the methods used for their identification and quantification. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

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

PubMed

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

2014-05-01

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

Mass spectrometry-based phytochemical screening for hypoglycemic activity of Fagioli di Sarconi beans (Phaseolus vulgaris L.).

PubMed

Pascale, Raffaella; Bianco, Giuliana; Cataldi, Tommaso R I; Kopplin, Philippe-Schmitt; Bosco, Federica; Vignola, Lisiana; Uhl, Jenny; Lucio, Marianna; Milella, Luigi

2018-03-01

The present study deals with the evaluation of antidiabetic activities of Fagioli di Sarconi beans (Phaseolus vulgaris), including 21 ecotypes protected by the European Union with the mark PGI (i.e., Protected Geographical Indication), and cultivated in Basilicata (southern Italy). For this purpose, α-glucosidase and α-amylase assays were assessed; among all bean ecotypes, the tight green seed colour of Verdolino extracts exhibited the highest α-glucosidase and α-amylase inhibitory activity with IC 50 =1.1±0.1μg/ml and IC 50 =19.3±1.1μg/ml, respectively. Phytochemical compound screening of all Fagioli di Sarconi beans performed by flow injection-electrospray ionization-ultrahigh resolution mass spectrometry (uHRMS) and based on the calculation of elemental formulas from accurate m/z values, was helpful to annotate specific compounds, such as alkaloids, saponins, flavonoids, and terpenoids, which are most likely responsible for their biological activity. Copyright © 2017. Published by Elsevier Ltd.

Technical aspects of neonatal screening using tandem mass spectrometry. Report from the 4th meeting of the International Society for Neonatal Screening.

PubMed

Simonsen, H; Jensen, U G

1999-12-01

Quantitative analysis of amino acids (AA) and acylcarnitines using tandem mass spectrometry is an emerging technology used to screen neonatal dried blood spot samples for disorders in the metabolism of AA, organic acids and fatty acids. This paper provides a brief review of some of the technically oriented issues which emerged at the 4th meeting of the International Society for Neonatal Screening in Stockholm, 1999. The information covers sample preparation, instrumentation, data acquistion modes, internal standards, interpretation, confounding factors and practical screening experience.

A SIMPLE AND RAPID MATRIX-ASSISTED LASER DESORPTION/IONIZATION TIME OF FLIGHT MASS SPECTROMETRY METHOD TO SCREEN FISH PLASMA SAMPLES FOR ESTROGEN-RESPONSIVE BIOMARKERS

EPA Science Inventory

In this study, we describe and evaluate the performance of a simple and rapid mass spectral method for screening fish plasma for estrogen-responsive biomarkers using matrix assisted laster desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) couopled with a short...

In Vitro Androgen Bioassays as a Detection Method for Designer Androgens

PubMed Central

Cooper, Elliot R.; McGrath, Kristine C. Y.; Heather, Alison K.

2013-01-01

Androgens are the class of sex steroids responsible for male sexual characteristics, including increased muscle mass and decreased fat mass. Illicit use of androgen doping can be an attractive option for those looking to enhance sporting performance and/or physical appearance. The use of in vitro bioassays to detect androgens, especially designer or proandrogens, is becoming increasingly important in combating androgen doping associated with nutritional supplements. The nutritional sports supplement market has grown rapidly throughout the past decade. Many of these supplements contain androgens, designer androgens or proandrogens. Many designer or proandrogens cannot be detected by the standard highly-sensitive screening methods such as gas chromatography-mass spectrometry because their chemical structure is unknown. However, in vitro androgen bioassays can detect designer and proandrogens as these assays are not reliant on knowing the chemical structure but instead are based on androgen receptor activation. For these reasons, it may be advantageous to use routine androgen bioassay screening of nutraceutical samples to help curb the increasing problem of androgen doping. PMID:23389345

Simultaneous screening for 238 drugs in blood by liquid chromatography-ion spray tandem mass spectrometry with multiple-reaction monitoring.

PubMed

Gergov, M; Ojanperä, I; Vuori, E

2003-09-25

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method is presented for the qualitative screening for 238 drugs in blood samples, which is considerably more than in previous methods. After a two-step liquid-liquid extraction and C(18) chromatography, the compounds were introduced into a triple quadrupole mass spectrometer equipped with a turbo ion spray ion source operating in the positive ionization mode. Identification was based on the compound's absolute retention time, protonated molecular ion, and one representative fragment ion obtained by multiple reaction monitoring (MRM) at an individually selected collision energy of 20, 35, or 50 eV. The limit of detection (LOD) for the majority of the compounds (80%) was < or = 0.05 mg/l, ranging from 0.002 mg/l (e.g., antihistamines) to 5 mg/l (acidic compounds), and for malathion it was 10 mg/l. The LOD values were sufficiently low to allow the majority of compounds to be detected at therapeutic concentrations in the blood.

Clinical Variability in Cardiovascular Disease Risk Factor Screening and Management in Adolescent and Young Adult Women with Polycystic Ovary Syndrome.

PubMed

Baer, Tamara E; Milliren, Carly E; Walls, Courtney; DiVasta, Amy D

2015-10-01

To review the clinical presentation, evaluation, and management of normal-weight (NW), overweight (OW), and obese (OB) adolescent and young adult women with polycystic ovary syndrome (PCOS) during a 2-year follow-up. Retrospective chart review. One hundred seventy-three adolescent and young adult women, aged 12-22 years, diagnosed with PCOS. Demographic, health data, and laboratory measures were abstracted from 3 clinic visits: baseline and 1- and 2-year follow-up. Subjects were classified as NW, OW, or OB. Longitudinal data were analyzed using repeated-measures analysis of variance. Body mass index, self-reported concerns, and lifestyle changes. Most patients (73%) were OW or OB. Family history of type 2 diabetes was greater in OW (38%) and OB (53%) patients compared with NW (22%) patients (P = .002). Acanthosis nigricans was identified in OW (62%) and OB (21%) patients but not in NW patients (0%; P < .001). OW and OB patients had higher fasting insulin (P < .001) and lower high-density lipoprotein cholesterol (P = .005) levels than NW patients, although screening rates were low. Body mass index Z-scores decreased in both OW and OB patients over time (0.07 unit/yr, P < .001). Most patients with PCOS were OW or OB. Substantial clinical variability existed in cardiovascular disease (CVD) screening; among those screened, OW and OB patients had greater CVD risk factors. Despite self-reported concerns about weight and diabetes risk among OW and OB patients, no clinically significant change in body mass index percentile occurred. Evidence-based interventions and recommendations for screening tests are needed to address CVD risk in adolescents and young adults with PCOS. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Screen-based entertainment time, all-cause mortality, and cardiovascular events: population-based study with ongoing mortality and hospital events follow-up.

PubMed

Stamatakis, Emmanuel; Hamer, Mark; Dunstan, David W

2011-01-18

The aim of this study was to examine the independent relationships of television viewing or other screen-based entertainment ("screen time") with all-cause mortality and clinically confirmed cardiovascular disease (CVD) events. A secondary objective was to examine the extent to which metabolic (body mass index, high-density lipoprotein and total cholesterol) and inflammatory (C-reactive protein) markers mediate the relationship between screen time and CVD events. Although some evidence suggests that prolonged sitting is linked to CVD risk factor development regardless of physical activity participation, studies with hard outcomes are scarce. A population sample of 4,512 (1,945 men) Scottish Health Survey 2003 respondents (≥35 years) were followed up to 2007 for all-cause mortality and CVD events (fatal and nonfatal combined). Main exposures were interviewer-assessed screen time (<2 h/day; 2 to <4 h/day; and ≥4 h/day) and moderate to vigorous intensity physical activity. Two hundred fifteen CVD events and 325 any-cause deaths occurred during 19,364 follow-up person-years. The covariable (age, sex, ethnicity, obesity, smoking, social class, long-standing illness, marital status, diabetes, hypertension)-adjusted hazard ratio (HR) for all-cause mortality was 1.52 (95% confidence interval [CI]: 1.06 to 2.16) and for CVD events was 2.30 (95% CI: 1.33 to 3.96) for participants engaging in ≥4 h/day of screen time relative to <2 h/day. Adjusting for physical activity attenuated these associations only slightly (all-cause mortality: HR: 1.48, 95% CI: 1.04 to 2.13; CVD events: HR: 2.25, 95% CI: 1.30 to 3.89). Exclusion of participants with CVD events in the first 2 years of follow-up and previous cancer registrations did not change these results appreciably. Approximately 25% of the association between screen time and CVD events was explained collectively by C-reactive protein, body mass index, and high-density lipoprotein cholesterol. Recreational sitting, as reflected by television/screen viewing time, is related to raised mortality and CVD risk regardless of physical activity participation. Inflammatory and metabolic risk factors partly explain this relationship. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Outcomes from a mass media campaign to promote cervical screening in NSW, Australia.

PubMed

Morrell, Stephen; Perez, Donna A; Hardy, Margaret; Cotter, Trish; Bishop, James F

2010-09-01

Despite the decline in the incidence of cervical cancer in Australia as a result of population screening, a substantial proportion of women in NSW screen less regularly than the recommended two-yearly interval or do not screen. With higher rates of cervical cancer in unscreened and underscreened women, and despite the introduction of the human papillomavirus vaccine, there remains a need to continue to remind women to screen. The mass media has been shown to be effective at improving participation in cervical screening. A 2007 television advertising campaign to promote cervical screening in New South Wales (NSW) was examined. Data from the NSW Papanicolaou (Pap) Test Register were used to compare weekly numbers of Pap tests for NSW overall and in metropolitan local government areas with low screening rates by age group and by time since the last Pap test. Time series regression analysis incorporating seasonal effects was used to estimate the strength of the association between screening and the media campaign. Overall during the advertising campaign, 15% more screens (16 700) occurred than expected for 2007 without the advertising campaign. Increases were evident among unscreened and underscreened women, with little overscreening occurring. Women living in low screening areas also showed a significant increase in mean weekly screens of 21% (388) over that expected in the absence of the media campaign. Despite the ecological nature of this study, the mass media campaign appears to have been successful in increasing screening in unscreened and underscreened women in NSW.

Large Subpectoral Lipoma on Screening Mammography

PubMed Central

Su, Andres; Margolies, Laurie

2017-01-01

A 61 year-old woman presenting for bilateral screening mammogram was found to have an oval fat-density mass in the posterior right breast, partially visualized, with anterior displacement and thinning of the pectoralis major muscle. This mass was found on CT and MRI correlation to represent a large fat-containing mass, likely a lipoma, deep to the pectoralis major. On subsequent screening mammograms, the visualized portion of the mass remained stable. Subpectoral lipomas and intramuscular lipomas within the pectoralis major are rare, and their appearance on mammography may not be familiar to most radiologists. A review of the literature and a discussion of their appearance on multiple imaging modalities is provided. PMID:29299106

Cost-effectiveness simulation and analysis of colorectal cancer screening in Hong Kong Chinese population: comparison amongst colonoscopy, guaiac and immunologic fecal occult blood testing.

PubMed

Wong, Carlos K H; Lam, Cindy L K; Wan, Y F; Fong, Daniel Y T

2015-10-15

The aim of this study was to evaluate the cost-effectiveness of CRC screening strategies from the healthcare service provider perspective based on Chinese population. A Markov model was constructed to compare the cost-effectiveness of recommended screening strategies including annual/biennial guaiac fecal occult blood testing (G-FOBT), annual/biennial immunologic FOBT (I-FOBT), and colonoscopy every 10 years in Chinese aged 50 year over a 25-year period. External validity of model was tested against data retrieved from published randomized controlled trials of G-FOBT. Recourse use data collected from Chinese subjects among staging of colorectal neoplasm were combined with published unit cost data ($USD in 2009 price values) to estimate a stage-specific cost per patient. Quality-adjusted life-years (QALYs) were quantified based on the stage duration and SF-6D preference-based value of each stage. The cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) represented by costs per life-years (LY) and costs per QALYs gained. In base-case scenario, the non-dominated strategies were annual and biennial I-FOBT. Compared with no screening, the ICER presented $20,542/LYs and $3155/QALYs gained for annual I-FOBT, and $19,838/LYs gained and $2976/QALYs gained for biennial I-FOBT. The optimal screening strategy was annual I-FOBT that attained the highest ICER at the threshold of $50,000 per LYs or QALYs gained. The Markov model informed the health policymakers that I-FOBT every year may be the most effective and cost-effective CRC screening strategy among recommended screening strategies, depending on the willingness-to-pay of mass screening for Chinese population. ClinicalTrials.gov Identifier NCT02038283.

Functionalized graphene quantum dots loaded with free radicals combined with liquid chromatography and tandem mass spectrometry to screen radical scavenging natural antioxidants from Licorice and Scutellariae.

PubMed

Wang, Guoying; Niu, XiuLi; Shi, Gaofeng; Chen, Xuefu; Yao, Ruixing; Chen, Fuwen

2014-12-01

A novel screening method was developed for the detection and identification of radical scavenging natural antioxidants based on a free radical reaction combined with liquid chromatography with tandem mass spectrometry. Functionalized graphene quantum dots were prepared for loading free radicals in the complex screening system. The detection was performed with and without a preliminary exposure of the samples to specific free radicals on the functionalized graphene quantum dots, which can facilitate charge transfer between free radicals and antioxidants. The difference in chromatographic peak areas was used to identify potential antioxidants. This is a novel approach to simultaneously evaluate the antioxidant power of a component versus a free radical, and to identify it in a vegetal matrix. The structures of the antioxidants in the samples were identified using tandem mass spectrometry and comparison with standards. Fourteen compounds were found to possess potential antioxidant activity, and their free radical scavenging capacities were investigated. The order of scavenging capacity of 14 compounds was compared according to their free radical scavenging rate. 4',5,6,7-Tetrahydroxyflavone (radical scavenging rate: 0.05253 mL mg(-1) s(-1) ) showed the strongest capability for scavenging free radicals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differential response to targeted recruitment strategies to fitness promotion research by African-American women of varying body mass index.

PubMed

Yancey, A K; Miles, O L; McCarthy, W J; Sandoval, G; Hill, J; Leslie, J J; Harrison, G G

2001-01-01

To assess patterns of recruitment into a community-based NCI-funded physical activity and dietary lifestyle change program targeting African-American women. Acquisition of a convenience sample to be screened for participation in a randomized, controlled prevention intervention. African-American-owned and -operated health club located in an area of Los Angeles in which African Americans are concentrated. 893 African-American women. RECRUITMENT STRATEGIES: Social networking/word-of-mouth, staff presentations, mass and targeted media, and physician referral. Completion of screening questionnaire indicating a desire to enroll in the study. Screening questionnaire domains included self-reported height and weight, recent participation in organized weight loss programs, ability to walk one mile unassisted, current medication use, smoking status, personal medical history of cancer, sociodemographic variables, and recruitment source. Sociodemographic and anthropometric characteristics distinguished between respondents obtained through different recruitment strategies. In particular, women with a higher body mass index (BMI) were more likely than those with lower BMIs (P = .014) to be recruited through more personalized methods (eg, social networking). Culturally tailored recruitment strategies are critical in securing the participation of members of "hard-to-reach" populations, who are both under-represented in health promotion research and at high risk for chronic diseases.

The Fit Study: Design and rationale for a cluster randomized trial of school-based BMI screening and reporting.

PubMed

Madsen, Kristine A; Linchey, Jennifer; Ritchie, Lorrene; Thompson, Hannah R

2017-07-01

In the U.S., 25 states conduct body mass index (BMI) screening in schools, just under half of which report results to parents. While some experts recommend the practice, evidence demonstrating its efficacy to reduce obesity is lacking, and concerns about weight-related stigma have been raised. The Fit Study is a 3-arm cluster-randomized trial assessing the effectiveness of school-based BMI screening and reporting in reducing pediatric obesity and identifying unintended consequences. Seventy-nine elementary and middle schools across California were randomized to 1 of 3 Arms: 1) BMI screening and reporting; 2) BMI screening only; or 3) no BMI screening or reporting. In Arm 1 schools, students were further randomized to receive reports with BMI results alone or both BMI and fitness test results. Over 3 consecutive years, staff in schools in Arms 1 and 2 will measure students' BMI (grades 3-8) and additional aspects of fitness (grades 5-8), and students in grades 4-8 in all Arms will complete surveys to assess weight-based stigmatization. Change in BMI z-score will be compared between Arm 1 and Arm 2 to determine the impact of BMI reporting on weight status, with sub-analyses stratified by report type (BMI results alone versus BMI plus fitness results) and by race/ethnicity. The potential for BMI reports to lead to weight-based stigma will be assessed by comparing student survey results among the 3 study Arms. This study will provide evidence on both the benefit and potential unintended harms of school-based BMI screening and reporting. Copyright © 2017. Published by Elsevier Inc.

A new mass screening method for methylmercury poisoning using mercury-volatilizing bacteria from Minamata Bay.

PubMed

Nakamura, K; Naruse, I; Takizawa, Y

1999-09-01

A simplified mass screening method for methylmercury exposure was developed using methylmercury-volatilizing bacteria from Minamata Bay. Some bacteria can transform methylmercury into mercury vapor. Most mercury in the hair is methylmercury, which is readily extracted with HCl solution. Black spots are formed on X-ray film due to the reduction of Ag(+) emulsion with mercury vapor produced by methylmercury-volatilizing bacteria. By exploiting these characteristics, a screening method was developed, whereby the fur of rats injected with methylmercury chloride formed clear black spots on X-ray film, whereas the fur of rats injected with saline did not. Subsequently, 50 human hair samples were examined using this mass screening method. The method identified people who had high mercury concentration, over 20 microg/g. A few thousand hair samples may be screened in a day using this method because it is rapid, simple, and economical. This method, therefore, enables screening of persons with methylmercury poisoning in mercury-polluted areas. Copyright 1999 Academic Press.

A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus

PubMed Central

Melo, Carlos Fernando Odir Rodrigues; Navarro, Luiz Claudio; de Oliveira, Diogo Noin; Guerreiro, Tatiane Melina; Lima, Estela de Oliveira; Delafiori, Jeany; Dabaja, Mohamed Ziad; Ribeiro, Marta da Silva; de Menezes, Maico; Rodrigues, Rafael Gustavo Martins; Morishita, Karen Noda; Esteves, Cibele Zanardi; de Amorim, Aline Lopes Lucas; Aoyagui, Caroline Tiemi; Parise, Pierina Lorencini; Milanez, Guilherme Paier; do Nascimento, Gabriela Mansano; Ribas Freitas, André Ricardo; Angerami, Rodrigo; Costa, Fábio Trindade Maranhão; Arns, Clarice Weis; Resende, Mariangela Ribeiro; Amaral, Eliana; Junior, Renato Passini; Ribeiro-do-Valle, Carolina C.; Milanez, Helaine; Moretti, Maria Luiza; Proenca-Modena, Jose Luiz; Avila, Sandra; Rocha, Anderson; Catharino, Rodrigo Ramos

2018-01-01

Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus) identification. Reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a “fingerprint” for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening—faster and more accurate—with improved cost-effectiveness when compared to existing technologies. PMID:29696139

Label-free measurement of histone lysine methyltransferases activity by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

PubMed

Guitot, Karine; Scarabelli, Silvia; Drujon, Thierry; Bolbach, Gérard; Amoura, Mehdi; Burlina, Fabienne; Jeltsch, Albert; Sagan, Sandrine; Guianvarc'h, Dominique

2014-07-01

Histone lysine methyltransferases (HKMTs) are enzymes that play an essential role in epigenetic regulation. Thus, identification of inhibitors specifically targeting these enzymes represents a challenge for the development of new antitumor therapeutics. Several methods for measuring HKMT activity are already available. Most of them use indirect measurement of the enzymatic reaction through radioactive labeling or antibody-recognized products or coupled enzymatic assays. Mass spectrometry (MS) represents an interesting alternative approach because it allows direct detection and quantification of enzymatic reactions and can be used to determine kinetics and to screen small molecules as potential inhibitors. Application of mass spectrometry to the study of HKMTs has not been fully explored yet. We describe here the development of a simple reliable label-free MALDI-TOF MS-based assay for the detection and quantification of peptide methylation, using SET7/9 as a model enzyme. Importantly, the use of expensive internal standard often required in mass spectrometry quantitative analysis is not necessary in this assay. This MS assay allowed us to determine enzyme kinetic parameters as well as IC50 for a known inhibitor of this enzyme. Furthermore, a comparative study with an antibody-based immunosorbent assay showed that the MS assay is more reliable and suitable for the screening of inhibitors. Copyright © 2014 Elsevier Inc. All rights reserved.

Screening for tuberculosis and testing for human immunodeficiency virus in Zambian prisons

PubMed Central

Maggard, Katie R; Hatwiinda, Sisa; Harris, Jennifer B; Phiri, Winifreda; Krüüner, Annika; Kaunda, Kaunda; Topp, Stephanie M; Kapata, Nathan; Ayles, Helen; Chileshe, Chisela; Henostroza, German

2015-01-01

Abstract Objective To improve the Zambia Prisons Service’s implementation of tuberculosis screening and human immunodeficiency virus (HIV) testing. Methods For both tuberculosis and HIV, we implemented mass screening of inmates and community-based screening of those residing in encampments adjacent to prisons. We also established routine systems – with inmates as peer educators – for the screening of newly entered or symptomatic inmates. We improved infection control measures, increased diagnostic capacity and promoted awareness of tuberculosis in Zambia’s prisons. Findings In a period of 9 months, we screened 7638 individuals and diagnosed 409 new patients with tuberculosis. We tested 4879 individuals for HIV and diagnosed 564 cases of infection. An additional 625 individuals had previously been found to be HIV-positive. Including those already on tuberculosis treatment at the time of screening, the prevalence of tuberculosis recorded in the prisons and adjacent encampments – 6.4% (6428/100 000) – is 18 times the national prevalence estimate of 0.35%. Overall, 22.9% of the inmates and 13.8% of the encampment residents were HIV-positive. Conclusion Both tuberculosis and HIV infection are common within Zambian prisons. We enhanced tuberculosis screening and improved the detection of tuberculosis and HIV in this setting. Our observations should be useful in the development of prison-based programmes for tuberculosis and HIV elsewhere. PMID:25883402

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

PubMed

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

2014-08-01

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

Determinants of non-participation in a mass screening program for colorectal cancer in Finland.

PubMed

Artama, M; Heinävaara, S; Sarkeala, T; Prättälä, R; Pukkala, E; Malila, N

2016-07-01

For an effective colorectal cancer (CRC) screening program, high participation rate is essential. However, non-participation in CRC screening program has increased in Finland. The study was based on a population-based nationwide cohort of persons invited for CRC screening in 2004-2011. Information on the first round of the CRC screening participation and related background factors was obtained from the Finnish Cancer Registry, and information about health behavior factors from the Health Behavior Survey (HBS) in 1978-1999. Non-participation in CRC screening was analyzed with Poisson regression as incidence rate ratios (IRR) with 95% confidence intervals (95% CI). Of all persons invited for CRC screening (79 871 men and 80 891 women) 35% of men and 21% of women refused. Of those invited for screening, 2456 men (3.1%) and 2507 women (3.1%) were also invited to the HBS. Persons, who declined HBS, were also more likely to refuse CRC screening (men IRR 1.40, 95% CI 1.26-1.56, women 1.75, 1.52-2.02) compared to HBS participants. Never married persons had about a 75% higher risk for refusing than married ones. The youngest age group (60 years) was more likely to refuse screening than the older age groups (62 or >64 years). Smoking was associated with non-participation in screening (current smokers, men: IRR 1.32, 95% CI 1.05-1.67, women: 2.10, 1.61-2.73). Participation in CRC screening was affected by gender, age, and marital status. Persons, who refused the HBS, were also more likely to refuse CRC screening. Smoking was a risk factor for non-participation in CRC screening.

Metabolomic tools for secondary metabolite discovery from marine microbial symbionts.

PubMed

Macintyre, Lynsey; Zhang, Tong; Viegelmann, Christina; Martinez, Ignacio Juarez; Cheng, Cheng; Dowdells, Catherine; Abdelmohsen, Usama Ramadam; Gernert, Christine; Hentschel, Ute; Edrada-Ebel, RuAngelie

2014-06-05

Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR 1H and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening.

Imaging and Screening of Cancer of the Small Bowel.

PubMed

Kim, Jin Sil; Park, Seong Ho; Hansel, Stephanie; Fletcher, Joel G

2017-11-01

Delayed diagnosis of small bowel cancers frequently occurs and may arise because of many factors, including low incidence of disease, difficult endoscopic access, lack of mucosal mass or abnormality, subtle radiologic features, and low index of clinical suspicion. As small bowel cancers are rare and their causes are largely unknown, routine population-based screening of asymptomatic patients to find precursor lesions or early cancers is ineffective. However, targeted screening/surveillance strategies are used in specific at-risk and symptomatic patient populations. This article reviews issues regarding early diagnosis of small bowel cancers, with focus on state-of-the-art cross-sectional imaging techniques. Copyright © 2017 Elsevier Inc. All rights reserved.

Screening and confirmation capabilities of liquid chromatography-time-of-flight mass spectrometry for the determination of 200 multiclass sport drugs in urine.

PubMed

Domínguez-Romero, Juan C; García-Reyes, Juan F; Lara-Ortega, Felipe J; Molina-Díaz, Antonio

2015-03-01

In this article, a screening method for the determination of 200 sport drugs in human urine has been developed using liquid-chromatography electrospray time-of-flight mass spectrometry (LC-TOFMS). The chromatographic separation of the targeted doping agents was carried out by fast liquid chromatography using a C18 column (4.6×50 mm) with 1.8 μm particle size. Accurate mass measurements of the selected ion (typically [M+H](+) and [M-H](-)) along with retention time matching was used for the screening and detection of the targeted species. The proposed methodology comprised also a simple sample treatment stage based on solid-phase extraction (SPE) with polymeric cartridges. The SPE method displayed satisfactory recoveries rates (between 70 and 120%) for the majority of the compounds at both concentration levels tested (2.5 and 25 μg L(-1)). The overall performance of the method was satisfactory with all 200 compounds fulfilling WADA minimum required performance levels (MRPLs), with limits of quantitation lower than 1 μg L(-1) for 80% of the compounds, and showing an appropriate linearity (r(2)>0.99) in most cases. Additionally, the ability of "in-source" collision induced dissociation (CID) for confirmatory purposes was examined using as criterion the presence of two high-resolution ions with relevant abundances for unambiguous confirmation. This stringent criterion was fulfilled for 75% of the species using in-source CID fragmentation. The use of an improved approach based on CID performed on a dedicated collision cell without precursor ion selection (using a Q-TOF) provided at least two ions in all cases with the exception of 2-aminoheptane. Finally, based on the use of diagnostic fragment ions, a workflow for the comprehensive screening and identification of non-targeted compounds (viz. compounds with no primary standards or retention time information available, such as metabolites) has been also examined using rat urine samples. The proposed screening method has proved to be effective for the analysis of targeted compounds, and also for the identification of metabolites, expanding easily the search for doping agents not only limited to specific banned parent compounds but also to derivate compounds with similar structure as well as metabolites. Copyright © 2014 Elsevier B.V. All rights reserved.

Multi-pathway exposure modelling of chemicals in cosmetics with application to shampoo

EPA Science Inventory

We present a novel multi-pathway, mass balance based, fate and exposure model compatible with life cycle and high-throughput screening assessments of chemicals in cosmetic products. The exposures through product use as well as post-use emissions and environmental media were quant...

Generic sample preparation combined with high-resolution liquid chromatography-time-of-flight mass spectrometry for unification of urine screening in doping-control laboratories.

PubMed

Peters, R J B; Oosterink, J E; Stolker, A A M; Georgakopoulos, C; Nielen, M W F

2010-04-01

A unification of doping-control screening procedures of prohibited small molecule substances--including stimulants, narcotics, steroids, beta2-agonists and diuretics--is highly urgent in order to free resources for new classes such as banned proteins. Conceptually this may be achieved by the use of a combination of one gas chromatography-time-of-flight mass spectrometry method and one liquid chromatography-time-of-flight mass spectrometry method. In this work a quantitative screening method using high-resolution liquid chromatography in combination with accurate-mass time-of-flight mass spectrometry was developed and validated for determination of glucocorticosteroids, beta2-agonists, thiazide diuretics, and narcotics and stimulants in urine. To enable the simultaneous isolation of all the compounds of interest and the necessary purification of the resulting extracts, a generic extraction and hydrolysis procedure was combined with a solid-phase extraction modified for these groups of compounds. All 56 compounds are determined using positive electrospray ionisation with the exception of the thiazide diuretics for which the best sensitivity was obtained by using negative electrospray ionisation. The results show that, with the exception of clenhexyl, procaterol, and reproterol, all compounds can be detected below the respective minimum required performance level and the results for linearity, repeatability, within-lab reproducibility, and accuracy show that the method can be used for quantitative screening. If qualitative screening is sufficient the instrumental analysis may be limited to positive ionisation, because all analytes including the thiazides can be detected at the respective minimum required levels in the positive mode. The results show that the application of accurate-mass time-of-flight mass spectrometry in combination with generic extraction and purification procedures is suitable for unification and expansion of the window of screening methods of doping laboratories. Moreover, the full-scan accurate-mass data sets obtained still allow retrospective examination for emerging doping agents, without re-analyzing the samples.

A new retrospective, multi-evidence veterinary drug screening method using drift tube ion mobility mass spectrometry.

PubMed

Xu, Zhenzhen; Li, Jianzhong; Chen, Ailiang; Ma, Xin; Yang, Shuming

2018-05-03

The retrospectivity (the ability to retrospect to a previously unknown compound in raw data) is very meaningful for food safety and risk assessment when facing new emerging drugs. Accurate mass and retention time based screening may lead false positive and false negative results so new retrospective, reliable platform is desirable. Different concentration levels of standards with and without matrix were analyzed using ion mobility (IM)-quadrupole-time-of-flight (Q-TOF) for collecting retrospective accurate mass, retention time, drift time and tandem MS evidence for identification in a single experiment. The isomer separation ability of IM and the four-dimensional (4D) feature abundance quantification abilities were evaluated for veterinary drugs for the first time. The sensitivity of the IM-Q-TOF workflow was obviously higher than that of the traditional database searching algorithm [find by formula (FbF) function] for Q-TOF. In addition, the IM-Q-TOF workflow contained most of the results from FbF and removed the false positive results. Some isomers were separated by IM and the 4D feature abundance quantitation removed interference with similar accurate mass and showed good linearity. A new retrospective, multi-evidence platform was built for veterinary drug screening in a single experiment. The sensitivity was significantly improved and the data can be used for quantification. The platform showed its potential to be used for food safety and risk assessment. This article is protected by copyright. All rights reserved.

Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH): A randomized controlled trial study protocol

PubMed Central

2011-01-01

Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33%) do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family oriented intervention to reduce sedentary screen time on children's body composition, sedentary behavior, physical activity, and diet. Methods/Design The study design is a pragmatic two-arm parallel randomized controlled trial. Two hundred and seventy overweight children aged 9-12 years and primary caregivers are being recruited. Participants are randomized to intervention (family-based screen time intervention) or control (no change). At the end of the study, the control group is offered the intervention content. Data collection is undertaken at baseline and 24 weeks. The primary trial outcome is child body mass index (BMI) and standardized body mass index (zBMI). Secondary outcomes are change from baseline to 24 weeks in child percentage body fat; waist circumference; self-reported average daily time spent in physical and sedentary activities; dietary intake; and enjoyment of physical activity and sedentary behavior. Secondary outcomes for the primary caregiver include change in BMI and self-reported physical activity. Discussion This study provides an excellent example of a theory-based, pragmatic, community-based trial targeting sedentary behavior in overweight children. The study has been specifically designed to allow for estimation of the consistency of effects on body composition for Māori (indigenous), Pacific and non-Māori/non-Pacific ethnic groups. If effective, this intervention is imminently scalable and could be integrated within existing weight management programs. Trial Registration ACTRN12611000164998 PMID:21718543

Weak cation exchange magnetic beads coupled with matrix-assisted laser desorption ionization-time of flight-mass spectrometry in screening serum protein markers in osteopenia.

PubMed

He, Wei-Tao; Liang, Bo-Cheng; Shi, Zhen-Yu; Li, Xu-Yun; Li, Chun-Wen; Shi, Xiao-Lin

2016-01-01

The present study aimed at investigating the weak cation magnetic separation technology and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) in screening serum protein markers of osteopenia from ten postmenopausal women and ten postmenopausal women without osteopenia as control group, to find a new method for screening biomarkers and establishing a diagnostic model for primary type I osteoporosis. Serum samples were collected from postmenopausal women with osteopenia and postmenopausal women with normal bone mass. Proteins were extracted from serum samples by weak cation exchange magnetic beads technology, and mass spectra acquisition was done by MALDI-TOF-MS. The visualization and comparison of data sets, statistical peak evaluation, model recognition, and discovery of biomarker candidates were handled by the proteinchip data analysis system software(ZJU-PDAS). The diagnostic models were established using genetic arithmetic based support vector machine (SVM). The SVM result with the highest Youden Index was selected as the model. Combinatorial Peaks having the highest accuracy in distinguishing different samples were selected as potential biomarker. From the two group serum samples, a total of 133 differential features were selected. Ten features with significant intensity differences were screened. In the pair-wise comparisons, processing of MALDI-TOF spectra resulted in the identification of ten differential features between postmenopausal women with osteopenia and postmenopausal women with normal bone mass. The difference of features by Youden index showed that the highest features had a mass to charge ratio of 1699 and 3038 Da. A diagnosis model was established with these two peaks as the candidate marker, and the specificity of the model is 100 %, the sensitivity was 90 % by leave-one-out cross validation test. The two groups of specimens in SVM results on the scatter plot could be clearly distinguished. The peak with m/z 3038 in the SVM model was suggested as Secretin by TagIdent tool. To provide further validation, the secretin levels in serum were analyzed using enzyme-linked immunosorbent assays that is a competitive inhibition enzyme immunoassay technique for the in vitro quantitative measurement of secretin in human serum.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry I. Screening analysis.

PubMed

Badoud, F; Grata, E; Perrenoud, L; Avois, L; Saugy, M; Rudaz, S; Veuthey, J-L

2009-05-15

The general strategy to perform anti-doping analyses of urine samples starts with the screening for a wide range of compounds. This step should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. The experiments presented in this work were based on ultra-high-pressure liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry. Thanks to the high sensitivity of the method, urine samples could be diluted 2-fold prior to injection. One hundred and three forbidden substances from various classes (such as stimulants, diuretics, narcotics, anti-estrogens) were analysed on a C(18) reversed-phase column in two gradients of 9min (including two 3min equilibration periods) for positive and negative electrospray ionisation and detected in the MS full scan mode. The automatic identification of analytes was based on retention time and mass accuracy, with an automated tool for peak picking. The method was validated according to the International Standard for Laboratories described in the World Anti-Doping Code and was selective enough to comply with the World Anti-Doping Agency recommendations. In addition, the matrix effect on MS response was measured on all investigated analytes spiked in urine samples. The limits of detection ranged from 1 to 500ng/mL, allowing the identification of all tested compounds in urine. When a sample was reported positive during the screening, a fast additional pre-confirmatory step was performed to reduce the number of confirmatory analyses.

Fast mass spectrometry-based enantiomeric excess determination of proteinogenic amino acids.

PubMed

Fleischer, Heidi; Thurow, Kerstin

2013-03-01

A rapid determination of the enantiomeric excess of proteinogenic amino acids is of great importance in various fields of chemical and biologic research and industries. Owing to their different biologic effects, enantiomers are interesting research subjects in drug development for the design of new and more efficient pharmaceuticals. Usually, the enantiomeric composition of amino acids is determined by conventional analytical methods such as liquid or gas chromatography or capillary electrophoresis. These analytical techniques do not fulfill the requirements of high-throughput screening due to their relative long analysis times. The method presented allows a fast analysis of chiral amino acids without previous time consuming chromatographic separation. The analytical measurements base on parallel kinetic resolution with pseudoenantiomeric mass tagged auxiliaries and were carried out by mass spectrometry with electrospray ionization. All 19 chiral proteinogenic amino acids were tested and Pro, Ser, Trp, His, and Glu were selected as model substrates for verification measurements. The enantiomeric excesses of amino acids with non-polar and aliphatic side chains as well as Trp and Phe (aromatic side chains) were determined with maximum deviations of the expected value less than or equal to 10ee%. Ser, Cys, His, Glu, and Asp were determined with deviations lower or equal to 14ee% and the enantiomeric excess of Tyr were calculated with 17ee% deviation. The total screening process is fully automated from the sample pretreatment to the data processing. The method presented enables fast measurement times about 1.38 min per sample and is applicable in the scope of high-throughput screenings.

Screening Methods for Metal-Containing Nanoparticles in Water

EPA Science Inventory

Screening-level analysis of water for metal-containing nanoparticles is achieved with single particle-inductively coupled plasma mass spectrometry (SP-ICPMS). This method measures both the concentration of nanoparticles containing an analyte metal and the mass of the metal in eac...

Guidelines for diagnosis and treatment of 21-hydroxylase deficiency (2014 revision)

PubMed Central

Ishii, Tomohiro; Anzo, Makoto; Adachi, Masanori; Onigata, Kazumichi; Kusuda, Satoshi; Nagasaki, Keisuke; Harada, Shohei; Horikawa, Reiko; Minagawa, Masanori; Minamitani, Kanshi; Mizuno, Haruo; Yamakami, Yuji; Fukushi, Masaru; Tajima, Toshihiro

2015-01-01

Purpose of developing the guidelines: The first guidelines for diagnosis and treatment of 21-hydroxylase deficiency (21-OHD) were published as a diagnostic handbook in Japan in 1989, with a focus on patients with severe disease. The “Guidelines for Treatment of Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) Found in Neonatal Mass Screening (1999 revision)” published in 1999 were revised to include 21-OHD patients with very mild or no clinical symptoms. Accumulation of cases and experience has subsequently improved diagnosis and treatment of the disease. Based on these findings, the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology further revised the guidelines for diagnosis and treatment. Target disease/conditions: 21-hydroxylase deficiency. Users of the guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, referring pediatric practitioners, general physicians; and patients. PMID:26594092

Simultaneous detection and classification of breast masses in digital mammograms via a deep learning YOLO-based CAD system.

PubMed

Al-Masni, Mohammed A; Al-Antari, Mugahed A; Park, Jeong-Min; Gi, Geon; Kim, Tae-Yeon; Rivera, Patricio; Valarezo, Edwin; Choi, Mun-Taek; Han, Seung-Moo; Kim, Tae-Seong

2018-04-01

Automatic detection and classification of the masses in mammograms are still a big challenge and play a crucial role to assist radiologists for accurate diagnosis. In this paper, we propose a novel Computer-Aided Diagnosis (CAD) system based on one of the regional deep learning techniques, a ROI-based Convolutional Neural Network (CNN) which is called You Only Look Once (YOLO). Although most previous studies only deal with classification of masses, our proposed YOLO-based CAD system can handle detection and classification simultaneously in one framework. The proposed CAD system contains four main stages: preprocessing of mammograms, feature extraction utilizing deep convolutional networks, mass detection with confidence, and finally mass classification using Fully Connected Neural Networks (FC-NNs). In this study, we utilized original 600 mammograms from Digital Database for Screening Mammography (DDSM) and their augmented mammograms of 2,400 with the information of the masses and their types in training and testing our CAD. The trained YOLO-based CAD system detects the masses and then classifies their types into benign or malignant. Our results with five-fold cross validation tests show that the proposed CAD system detects the mass location with an overall accuracy of 99.7%. The system also distinguishes between benign and malignant lesions with an overall accuracy of 97%. Our proposed system even works on some challenging breast cancer cases where the masses exist over the pectoral muscles or dense regions. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation of Microkernel-Based Mesoporous (SiO2-CdTe-SiO2)@SiO2 Fluorescent Nanoparticles for Imaging Screening and Enrichment of Heat Shock Protein 90 Inhibitors from Tripterygium Wilfordii.

PubMed

Hu, Yue; Miao, Zhao-Yi; Zhang, Xiao-Jing; Yang, Xiao-Tong; Tang, Ying-Ying; Yu, Sheng; Shan, Chen-Xiao; Wen, Hong-Mei; Zhu, Dong

2018-05-01

The currently utilized ligand fishing for bioactive molecular screening from complex matrixes cannot perform imaging screening. Here, we developed a new solid-phase ligand fishing coupled with an in situ imaging protocol for the specific enrichment and identification of heat shock protein 90 (Hsp 90) inhibitors from Tripterygium wilfordii, utilizing a multiple-layer and microkernel-based mesoporous nanostructure composed of a protective silica coating CdTe quantum dot (QD) core and a mesoporous silica shell, i.e., microkernel-based mesoporous (SiO 2 -CdTe-SiO 2 )@SiO 2 fluorescent nanoparticles (MMFNPs) as extracting carries and fluorescent probes. The prepared MMFNPs showed a highly uniform spherical morphology, retention of fluorescence emission, and great chemical stability. The fished ligands by Hsp 90α-MMFNPs were evaluated via the preliminary bioactivity based on real-time cellular morphology imaging by confocal laser scanning microscopy (CLSM) and then identified by mass spectrometry (MS). Celastrol was successfully isolated as an Hsp 90 inhibitor, and two other specific components screened by Hsp 90α-MMFNPs, i.e., demecolcine and wilforine, were preliminarily identified as potential Hsp 90 inhibitors through the verification of strong affinity to Hsp 90 and antitumor bioactivity. The approach based on the MMFNPs provides a strong platform for imaging screening and discovery of plant-derived biologically active molecules with high efficiency and selectivity.

Webinar Presentation: Suspect Screening of Environmental Organic Acids in Human Serum Using High-resolution Mass Spectrometry (HRMS)

EPA Pesticide Factsheets

This presentation, Suspect Screening of Environmental Organic Acids in Human Serum Using High-resolution Mass Spectrometry (HRMS), was given at the NIEHS/EPA Children's Centers 2016 Webinar Series: Exposome held on May 11, 2016.

Multiclass screening of >200 pharmaceutical and other residues in aquatic foods by ultrahigh-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry.

PubMed

Kong, Cong; Wang, Yang; Huang, Yuanfei; Yu, Huijuan

2018-05-11

A quick screening method of more than 200 pharmaceutical and other residues in aquatic foods based on ultrahigh-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UHPLC-Q/Orbitrap MS) was established. In this method, after the addition of 200 μL of 1 M EDTA-Na 2 , 2 g of each sample homogenate was extracted successively with 10 mL of acetonitrile and 10 mL of ethyl acetate. The extracts were combined, dried under nitrogen flow, and redissolved in 0.1% formic acid in acetonitrile/water (4:6, v/v) for analysis. The prepared samples were analyzed by UHPLC- Q/Orbitrap MS system in Full MS/ddMS 2 (full-scan data-dependent MS/MS) mode. Compound identification was performed through comparison of the sample data with the database for standard chemicals, including the retention time, precursor ion, product ions, and isotope pattern for all 206 compounds. Five different aquatic food matrices (carp, shrimp, crab, eel, and mussel) spiked with the analytes at 1, 10, and 50 ng/g were evaluated to assess recoveries, precision, matrix effects, stability, and detection limits using the method. UHPLC analyses required 25 min, and 178-200 analytes met identification criteria at 50 ng/g depending on the matrix. Furthermore, practical application of this method for real samples displayed strong screening capability. Graphical abstract A quick screening method of >200 pharmaceutical and other residues in aquatic foods based on ultrahighperformance liquid chromatography-quadrupole-Orbitrap mass spectrometer was established. Fivedifferent aquatic food matrices, including carp, shrimp, crab, eel and mussel, were studied to evaluatescreen limit at 1, 10 and 50 μg·kg-1 level. Results suggest the high reliability, high time-efficiency and goodsimplicity of the method.

Automated detection of masses on whole breast volume ultrasound scanner: false positive reduction using deep convolutional neural network

NASA Astrophysics Data System (ADS)

Hiramatsu, Yuya; Muramatsu, Chisako; Kobayashi, Hironobu; Hara, Takeshi; Fujita, Hiroshi

2017-03-01

Breast cancer screening with mammography and ultrasonography is expected to improve sensitivity compared with mammography alone, especially for women with dense breast. An automated breast volume scanner (ABVS) provides the operator-independent whole breast data which facilitate double reading and comparison with past exams, contralateral breast, and multimodality images. However, large volumetric data in screening practice increase radiologists' workload. Therefore, our goal is to develop a computer-aided detection scheme of breast masses in ABVS data for assisting radiologists' diagnosis and comparison with mammographic findings. In this study, false positive (FP) reduction scheme using deep convolutional neural network (DCNN) was investigated. For training DCNN, true positive and FP samples were obtained from the result of our initial mass detection scheme using the vector convergence filter. Regions of interest including the detected regions were extracted from the multiplanar reconstraction slices. We investigated methods to select effective FP samples for training the DCNN. Based on the free response receiver operating characteristic analysis, simple random sampling from the entire candidates was most effective in this study. Using DCNN, the number of FPs could be reduced by 60%, while retaining 90% of true masses. The result indicates the potential usefulness of DCNN for FP reduction in automated mass detection on ABVS images.

Detection and identification of drugs and toxicants in human body fluids by liquid chromatography-tandem mass spectrometry under data-dependent acquisition control and automated database search.

PubMed

Oberacher, Herbert; Schubert, Birthe; Libiseller, Kathrin; Schweissgut, Anna

2013-04-03

Systematic toxicological analysis (STA) is aimed at detecting and identifying all substances of toxicological relevance (i.e. drugs, drugs of abuse, poisons and/or their metabolites) in biological material. Particularly, gas chromatography-mass spectrometry (GC/MS) represents a competent and commonly applied screening and confirmation tool. Herein, we present an untargeted liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay aimed to complement existing GC/MS screening for the detection and identification of drugs in blood, plasma and urine samples. Solid-phase extraction was accomplished on mixed-mode cartridges. LC was based on gradient elution in a miniaturized C18 column. High resolution electrospray ionization-MS/MS in positive ion mode with data-dependent acquisition control was used to generate tandem mass spectral information that enabled compound identification via automated library search in the "Wiley Registry of Tandem Mass Spectral Data, MSforID". Fitness of the developed LC/MS/MS method for application in STA in terms of selectivity, detection capability and reliability of identification (sensitivity/specificity) was demonstrated with blank samples, certified reference materials, proficiency test samples, and authentic casework samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Newborn screening of metabolic disorders: recent progress and future developments.

PubMed

Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

2008-01-01

Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation.

[Rapid screening of acidity regulators in dairy by ion chromatography-high resolution mass spectrometry].

PubMed

Yun, Huan; Liu, Xin; Cui, Jie; Yang, Jing; Liu, Ying

2017-08-08

A method for screening of acidity regulators in dairy based on ion chromatography-high resolution mass spectrometry technology (IC-HRMS) was set up. The dairy samples were extracted by KOH (pH 7-8) and Oasis MAX SPE column, and separated by a Dionex IonPac AS11-HC column (250 mm×4 mm). All the acidity regulators were detected by Orbitrap full scan mode. Taking six organic acids as an example, the calibration curves showed good linearities in the range of 0.05-5.00 mg/L, and the correlation coefficients ( r ) were higher than 0.99. By detecting the spiked samples, the recoveries were in the range of 74.3%-115.5% with the relative standard deviations (RSDs) between 0.64% and 4.81%. Malic acid, citric acid, lactic acid, succinic acid and adipic acid could be detected by IC-HRMS in the commercial dairy samples. The results indicate that the method is simple, rapid and suitable for the qualitative screening of acidity regulators in dairy products.

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

Screen time and adiposity in adolescents in Mexico

PubMed Central

Lajous, Martín; Chavarro, Jorge; Peterson, Karen E; Hernández-Prado, Bernardo; Cruz-Valdéz, Aurelio; Hernández-Ávila, Mauricio; Lazcano-Ponce, Eduardo

2014-01-01

Objective To assess the association of time spent viewing television, videos and videogames with measures of fat mass [body mass index (BMI)] and distribution [triceps and subscapular skin folds (TSF, SSF)]. Design Cross-sectional validated survey, self-administered to students to assess screen time (TV, videos and videogames) and lifestyle variables. Trained personnel obtained anthropometry. The association of screen time with fat mass and distribution, stratified by sex, was modeled with multivariable linear regression, adjusting for potential confounders and correlation of observations within schools. Subjects and setting 3519 males and 5613 females aged 11 to 18 years attending urban and rural schools in the State of Morelos, Mexico Results In males, ≥5 hr/day compared with < 2 hr/day of screen time, was significantly associated with a 0.13 (95%CI 0.04, 0.23) higher BMI z score, 0.73 mm (95% CI 0.24, 1.22) higher SSF and 1.08 mm (95% CI 0.36, 1.81) higher TSF. The positive association of screen time with SSF was strongest in males 11–12 yr. Sexual maturity appeared to modify the association in females; a positive between screen time and SSF was observed in those who had not undergone menarche (p-trend 0.04) but not among sexually mature females (p-trend 0.75). Conclusion Screen time is associated with fat mass and distribution among adolescent males in Mexico. Maturational tempo appears to affect the relationship of screen time with adiposity in boys and girls. Findings suggest obesity preventive interventions in the Mexican context should explore strategies to reduce screen time among youth in early adolescence. PMID:19232154

Flow Cytometry: Impact on Early Drug Discovery.

PubMed

Edwards, Bruce S; Sklar, Larry A

2015-07-01

Modern flow cytometers can make optical measurements of 10 or more parameters per cell at tens of thousands of cells per second and more than five orders of magnitude dynamic range. Although flow cytometry is used in most drug discovery stages, "sip-and-spit" sampling technology has restricted it to low-sample-throughput applications. The advent of HyperCyt sampling technology has recently made possible primary screening applications in which tens of thousands of compounds are analyzed per day. Target-multiplexing methodologies in combination with extended multiparameter analyses enable profiling of lead candidates early in the discovery process, when the greatest numbers of candidates are available for evaluation. The ability to sample small volumes with negligible waste reduces reagent costs, compound usage, and consumption of cells. Improved compound library formatting strategies can further extend primary screening opportunities when samples are scarce. Dozens of targets have been screened in 384- and 1536-well assay formats, predominantly in academic screening lab settings. In concert with commercial platform evolution and trending drug discovery strategies, HyperCyt-based systems are now finding their way into mainstream screening labs. Recent advances in flow-based imaging, mass spectrometry, and parallel sample processing promise dramatically expanded single-cell profiling capabilities to bolster systems-level approaches to drug discovery. © 2015 Society for Laboratory Automation and Screening.

The suitability of matrix assisted laser desorption/ionization time of flight mass spectrometry in a laboratory developed test using cystic fibrosis carrier screening as a model.

PubMed

Farkas, Daniel H; Miltgen, Nicholas E; Stoerker, Jay; van den Boom, Dirk; Highsmith, W Edward; Cagasan, Lesley; McCullough, Ron; Mueller, Reinhold; Tang, Lin; Tynan, John; Tate, Courtney; Bombard, Allan

2010-09-01

We designed a laboratory developed test (LDT) by using an open platform for mutation/polymorphism detection. Using a 108-member (mutation plus variant) cystic fibrosis carrier screening panel as a model, we completed the last phase of LDT validation by using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Panel customization was accomplished via specific amplification primer and extension probe design. Amplified genomic DNA was subjected to allele specific, single base extension endpoint analysis by mass spectrometry for inspection of the cystic fibrosis transmembrane regulator gene (NM_000492.3). The panel of mutations and variants was tested against 386 blinded samples supplied by "authority" laboratories highly experienced in cystic fibrosis transmembrane regulator genotyping; >98% concordance was observed. All discrepant and discordant results were resolved satisfactorily. Taken together, these results describe the concluding portion of the LDT validation process and the use of mass spectrometry to detect a large number of complex reactions within a single run as well as its suitability as a platform appropriate for interrogation of scores to hundreds of targets.

Electrostatic analogy for symmetron gravity

NASA Astrophysics Data System (ADS)

Ogden, Lillie; Brown, Katherine; Mathur, Harsh; Rovelli, Kevin

2017-12-01

The symmetron model is a scalar-tensor theory of gravity with a screening mechanism that suppresses the effect of the symmetron field at high densities characteristic of the Solar System and laboratory scales but allows it to act with gravitational strength at low density on the cosmological scale. We elucidate the screening mechanism by showing that in the quasistatic Newtonian limit there are precise analogies between symmetron gravity and electrostatics for both strong and weak screening. For strong screening we find that large dense bodies behave in a manner analogous to perfect conductors in electrostatics. Based on this analogy we find that the symmetron field exhibits a lightning rod effect wherein the field gradients are enhanced near the ends of pointed or elongated objects. An ellipsoid placed in a uniform symmetron gradient is shown to experience a torque. By symmetry there is no gravitational torque in this case. Hence this effect unmasks the symmetron and might serve as the basis for future laboratory experiments. The symmetron force between a point mass and a large dense body includes a component corresponding to the interaction of the point mass with its image in the larger body. None of these effects have counterparts in the Newtonian limit of Einstein gravity. We discuss the similarities between symmetron gravity and the chameleon model as well as the differences between the two.

Facilitating high resolution mass spectrometry data processing for screening of environmental water samples: An evaluation of two deconvolution tools.

PubMed

Bade, Richard; Causanilles, Ana; Emke, Erik; Bijlsma, Lubertus; Sancho, Juan V; Hernandez, Felix; de Voogt, Pim

2016-11-01

A screening approach was applied to influent and effluent wastewater samples. After injection in a LC-LTQ-Orbitrap, data analysis was performed using two deconvolution tools, MsXelerator (modules MPeaks and MS Compare) and Sieve 2.1. The outputs were searched incorporating an in-house database of >200 pharmaceuticals and illicit drugs or ChemSpider. This hidden target screening approach led to the detection of numerous compounds including the illicit drug cocaine and its metabolite benzoylecgonine and the pharmaceuticals carbamazepine, gemfibrozil and losartan. The compounds found using both approaches were combined, and isotopic pattern and retention time prediction were used to filter out false positives. The remaining potential positives were reanalysed in MS/MS mode and their product ions were compared with literature and/or mass spectral libraries. The inclusion of the chemical database ChemSpider led to the tentative identification of several metabolites, including paraxanthine, theobromine, theophylline and carboxylosartan, as well as the pharmaceutical phenazone. The first three of these compounds are isomers and they were subsequently distinguished based on their product ions and predicted retention times. This work has shown that the use deconvolution tools facilitates non-target screening and enables the identification of a higher number of compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Mass spectrometry-driven drug discovery for development of herbal medicine.

PubMed

Zhang, Aihua; Sun, Hui; Wang, Xijun

2018-05-01

Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.

Screening and prioritization of micropollutants in wastewaters from on-site sewage treatment facilities.

PubMed

Gros, Meritxell; Blum, Kristin M; Jernstedt, Henrik; Renman, Gunno; Rodríguez-Mozaz, Sara; Haglund, Peter; Andersson, Patrik L; Wiberg, Karin; Ahrens, Lutz

2017-04-15

A comprehensive screening of micropollutants was performed in wastewaters from on-site sewage treatment facilities (OSSFs) and urban wastewater treatment plants (WWTPs) in Sweden. A suspect screening approach, using high resolution mass spectrometry, was developed and used in combination with target analysis. With this strategy, a total number of 79 micropollutants were successfully identified, which belong to the groups of per- and polyfluoroalkyl substances (PFASs), pesticides, phosphorus-containing flame retardants (PFRs) and pharmaceuticals and personal care products (PPCPs). Results from this screening indicate that concentrations of micropollutants are similar in influents and effluents of OSSFs and WWTPs, respectively. Removal efficiencies of micropollutants were assessed in the OSSFs and compared with those observed in WWTPs. In general, removal of PFASs and PFRs was higher in package treatment OSSFs, which are based on biological treatments, while removal of PPCPs was more efficient in soil bed OSSFs. A novel comprehensive prioritization strategy was then developed to identify OSSF specific chemicals of environmental relevance. The strategy was based on the compound concentrations in the wastewater, removal efficiency, frequency of detection in OSSFs and on in silico based data for toxicity, persistency and bioaccumulation potential. Copyright © 2016 Elsevier B.V. All rights reserved.

Instant screening and verification of carbapenemase activity in Bacteroides fragilis in positive blood culture, using matrix-assisted laser desorption ionization--time of flight mass spectrometry.

PubMed

Johansson, Åsa; Nagy, Elisabeth; Sóki, József

2014-08-01

Rapid identification of isolates in positive blood cultures are of great importance to secure correct treatment of septicaemic patients. As antimicrobial resistance is increasing, rapid detection of resistance is crucial. Carbapenem resistance in Bacteroides fragilis associated with cfiA-encoded class B metallo-beta-lactamase is emerging. In our study we spiked blood culture bottles with 26 B. fragilis strains with various cfiA-status and ertapenem MICs. By using main spectra specific for cfiA-positive and cfiA-negative B. fragilis strains, isolates could be screened for resistance. To verify strains that were positive in the screening, a carbapenemase assay was performed where the specific peaks of intact and hydrolysed ertapenem were analysed with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). We show here that it is possible to correctly identify B. fragilis and to screen for enzymic carbapenem resistance directly from the pellet of positive blood cultures. The carbapenemase assay to verify the presence of the enzyme was successfully performed on the pellet from the direct identification despite the presence of blood components. The result of the procedure was achieved in 3 h. Also the Bruker mass spectrometric β-lactamase assay (MSBL assay) prototype software was proven not only to be based on an algorithm that correlated with the manual inspection of the spectra, but also to improve the interpretation by showing the variation in the dataset. © 2014 The Authors.

Applying a new unequally weighted feature fusion method to improve CAD performance of classifying breast lesions

NASA Astrophysics Data System (ADS)

Zargari Khuzani, Abolfazl; Danala, Gopichandh; Heidari, Morteza; Du, Yue; Mashhadi, Najmeh; Qiu, Yuchen; Zheng, Bin

2018-02-01

Higher recall rates are a major challenge in mammography screening. Thus, developing computer-aided diagnosis (CAD) scheme to classify between malignant and benign breast lesions can play an important role to improve efficacy of mammography screening. Objective of this study is to develop and test a unique image feature fusion framework to improve performance in classifying suspicious mass-like breast lesions depicting on mammograms. The image dataset consists of 302 suspicious masses detected on both craniocaudal and mediolateral-oblique view images. Amongst them, 151 were malignant and 151 were benign. The study consists of following 3 image processing and feature analysis steps. First, an adaptive region growing segmentation algorithm was used to automatically segment mass regions. Second, a set of 70 image features related to spatial and frequency characteristics of mass regions were initially computed. Third, a generalized linear regression model (GLM) based machine learning classifier combined with a bat optimization algorithm was used to optimally fuse the selected image features based on predefined assessment performance index. An area under ROC curve (AUC) with was used as a performance assessment index. Applying CAD scheme to the testing dataset, AUC was 0.75+/-0.04, which was significantly higher than using a single best feature (AUC=0.69+/-0.05) or the classifier with equally weighted features (AUC=0.73+/-0.05). This study demonstrated that comparing to the conventional equal-weighted approach, using an unequal-weighted feature fusion approach had potential to significantly improve accuracy in classifying between malignant and benign breast masses.

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

PubMed Central

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

2015-01-01

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

Revisiting Abell 2744: a powerful synergy of GLASS spectroscopy and HFF photometry

NASA Astrophysics Data System (ADS)

Wang, Xin; Wang

We present new emission line identifications and improve the lensing reconstruction of the mass distribution of galaxy cluster Abell 2744 using the Grism Lens-Amplified Survey from Space (GLASS) spectroscopy and the Hubble Frontier Fields (HFF) imaging. We performed blind and targeted searches for faint line emitters on all objects, including the arc sample, within the field of view (FoV) of GLASS prime pointings. We report 55 high quality spectroscopic redshifts, 5 of which are for arc images. We also present an extensive analysis based on the HFF photometry, measuring the colors and photometric redshifts of all objects within the FoV, and comparing the spectroscopic and photometric redshift estimates. In order to improve the lens model of Abell 2744, we develop a rigorous algorithm to screen arc images, based on their colors and morphology, and selecting the most reliable ones to use. As a result, 25 systems (corresponding to 72 images) pass the screening process and are used to reconstruct the gravitational potential of the cluster pixellated on an adaptive mesh. The resulting total mass distribution is compared with a stellar mass map obtained from the Spitzer Frontier Fields data in order to study the relative distribution of stars and dark matter in the cluster.

Recent trends in analytical procedures in forensic toxicology.

PubMed

Van Bocxlaer, Jan F

2005-12-01

Forensic toxicology is a very demanding discipline,heavily dependent on good analytical techniques. That is why new trends appear continuously. In the past years. LC-MS has revolutionized target compound analysis and has become the trend, also in toxicology. In LC-MS screening analysis, things are less straightforward and several approaches exist. One promising approach based on accurate LC-MSTOF mass measurements and elemental formula based library searches is discussed. This way of screening has already proven its applicability but at the same time it became obvious that a single accurate mass measurement lacks some specificity when using large compound libraries. CE too is a reemerging approach. The increasingly polar and ionic molecules encountered make it a worthwhile addition to e.g. LC, as illustrated for the analysis of GHB. A third recent trend is the use of MALDI mass spectrometry for small molecules. It is promising for its ease-of-use and high throughput. Unfortunately, re-ports of disappointment but also accomplishment, e.g. the quantitative analysis of LSD as discussed here, alternate, and it remains to be seen whether MALDI really will establish itself. Indeed, not all new trends will prove themselves but the mere fact that many appear in the world of analytical toxicology nowadays is, in itself, encouraging for the future of (forensic) toxicology.

The distribution of ductal carcinoma in situ (DCIS) grade in 4232 women and its impact on overdiagnosis in breast cancer screening.

PubMed

van Luijt, P A; Heijnsdijk, E A M; Fracheboud, J; Overbeek, L I H; Broeders, M J M; Wesseling, J; den Heeten, G J; de Koning, H J

2016-05-10

The incidence of ductal carcinoma in situ (DCIS) has rapidly increased over time. The malignant potential of DCIS is dependent on its differentiation grade. Our aim is to determine the distribution of different grades of DCIS among women screened in the mass screening programme, and women not screened in the mass screening programme, and to estimate the amount of overdiagnosis by grade of DCIS. We retrospectively included a population-based sample of 4232 women with a diagnosis of DCIS in the years 2007-2009 from the Nationwide network and registry of histopathology and cytopathology in the Netherlands. Excluded were women with concurrent invasive breast cancer, lobular carcinoma in situ and no DCIS, women recently treated for invasive breast cancer, no grade mentioned in the record, inconclusive record on invasion, and prevalent DCIS. The screening status was obtained via the screening organisations. The distribution of grades was incorporated in the well-established and validated microsimulation model MISCAN. Overall, 17.7 % of DCIS were low grade, 31.4 % intermediate grade, and 50.9 % high grade. This distribution did not differ by screening status, but did vary by age. Older women were more likely to have low-grade DCIS than younger women. Overdiagnosis as a proportion of all cancers in women of the screening age was 61 % for low-grade, 57 % for intermediate-grade, 45 % for high-grade DCIS. For women age 50-60 years with a high-grade DCIS this overdiagnosis rate was 21-29 %, compared to 50-66 % in women age 60-75 years with high-grade DCIS. Amongst the rapidly increasing numbers of DCIS diagnosed each year is a significant number of overdiagnosed cases. Tailoring treatment to the probability of progression is the next step to preventing overtreatment. The basis of this tailoring could be DCIS grade and age.

School-based BMI and body composition screening and parent notification in California: methods and messages.

PubMed

Madsen, Kristine A; Linchey, Jennifer

2012-06-01

School-based body mass index (BMI) or body composition screening is increasing, but little is known about the process of parent notification. Since 2001, California has required annual screening of body composition via the FITNESSGRAM, with optional notification. This study sought to identify the prevalence of parental notification when screening is required but notification is optional, and the methods and messages used. Researchers conducted phone interviews with 851 school districts (89%) in California and reviewed notification materials from 54 districts. As of 2008, 53% of California districts notified parents of screening results. Many districts (24%) did not know the reason for their notification policy. Most districts notified parents via a letter mailed home (70%) or sent home with the child (18%). Whereas 79% of sample letters provided students' BMI, only 12% provided an explanation of BMI, and only half provided tips on what parents should do if concerned about their child's results. In California, where body composition screening is required but parent notification is not, approximately half of school districts elect to notify parents of results, most commonly via letter. Most letters do not explain BMI or percent body fat scores, nor do they suggest what parents should do for a child identified as at-risk. Further research to identify interpretable and actionable notification messages for parents will be critical if school-based BMI and body composition screening and notification is to reduce childhood obesity. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Development of a high-throughput screening assay for stearoyl-CoA desaturase using rat liver microsomes, deuterium labeled stearoyl-CoA and mass spectrometry.

PubMed

Soulard, Patricia; McLaughlin, Meg; Stevens, Jessica; Connolly, Brendan; Coli, Rocco; Wang, Leyu; Moore, Jennifer; Kuo, Ming-Shang T; LaMarr, William A; Ozbal, Can C; Bhat, B Ganesh

2008-10-03

Several recent reports suggest that stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis, plays an important role in regulating lipid homeostasis and lipid oxidation in metabolically active tissues. As several manifestations of type 2 diabetes and related metabolic disorders are associated with alterations in intracellular lipid partitioning, pharmacological manipulation of SCD1 activity might be of benefit in the treatment of these disease states. In an effort to identify small molecule inhibitors of SCD1, we have developed a mass spectrometry based high-throughput screening (HTS) assay using deuterium labeled stearoyl-CoA substrate and induced rat liver microsomes. The methodology developed allows the use of a nonradioactive substrate which avoids interference by the endogenous SCD1 substrate and/or product that exist in the non-purified enzyme source. Throughput of the assay was up to twenty 384-well assay plates per day. The assay was linear with protein concentration and time, and was saturable for stearoyl-CoA substrate (K(m)=10.5 microM). The assay was highly reproducible with an average Z' value=0.6. Conjugated linoleic acid and sterculic acid, known inhibitors of SCD1, exhibited IC(50) values of 0.88 and 0.12 microM, respectively. High-throughput mass spectrometry screening of over 1.7 million compounds in compressed format demonstrated that the enzyme target is druggable. A total of 2515 hits were identified (0.1% hit rate), and 346 were confirmed active (>40% inhibition of total SCD activity at 20 microM--14% conformation rate). Of the confirmed hits 172 had IC(50) values of <10 microM, including 111 <1 microM and 48 <100 nM. A large number of potent drug-like (MW<450) hits representing six different chemical series were identified. The application of mass spectrometry to high-throughput screening permitted the development of a high-quality screening protocol for an otherwise intractable target, SCD1. Further medicinal chemistry and characterization of SCD inhibitors should lead to the development of reagents to treat metabolic disorders.

Rapid Screening of Ergot Alkaloids in Sclerotia by MALDI-TOF Mass Spectrometry.

PubMed

Sivagnanam, Kumaran; Komatsu, Emy; Patrick, Susan; Rampitsch, Christoph; Perreault, Hélène; Gräfenhan, Tom

2016-07-01

Ergot is a common disease of wheat and other cereal grains that is predominantly caused by Claviceps purpurea in the field, often affecting crop yield in addition to the environment. Infected grain can be contaminated with dark sclerotia, which contain fungal metabolites such as ergot alkaloids. The occurrence of ergot alkaloids in cereal grain is a major health concern for humans and livestock. Effective and rapid screening of these mycotoxins is crucial for producers, processors, and consumers of cereal-based food and feed grain. Established methods of ergot alkaloid screening based on LC-MS or GC-MS require laborious processes. A novel method using matrix-assisted laser desorption ionization (MALDI)-time-of-flight (TOF) MS was developed to identify four ergot alkaloids. Using dihydroxybenzoic acid as the matrix, ergosine, ergocornine, ergocryptine, and ergocristine were readily detected in individual sclerotia of C. purpurea. The accuracy of the identified ergot alkaloids was further confirmed by tandem MS analysis. MALDI-TOF MS is suitable for high-throughput screening of ergot alkaloids because it permits rapid and accurate identification, simple sample preparation, and no derivatization or chromatographic separation.

A simultaneous screening and quantitative method for the multiresidue analysis of pesticides in spices using ultra-high performance liquid chromatography-high resolution (Orbitrap) mass spectrometry.

PubMed

Goon, Arnab; Khan, Zareen; Oulkar, Dasharath; Shinde, Raviraj; Gaikwad, Suresh; Banerjee, Kaushik

2018-01-12

A novel screening and quantitation method is reported for non-target multiresidue analysis of pesticides using ultra-HPLC-quadrupole-Orbitrap mass spectrometry in spice matrices, including black pepper, cardamom, chili, coriander, cumin, and turmeric. The method involved sequential full-scan (resolution = 70,000), and variable data independent acquisition (vDIA) with nine consecutive fragmentation events (resolution = 17,500). Samples were extracted by the QuEChERS method. The introduction of an SPE-based clean-up step through hydrophilic-lipophilic-balance (HLB) cartridges proved advantageous in minimizing the false negatives. For coriander, cumin, chili, and cardamom, the screening detection limit was largely at 2 ng/g, while it was 5 ng/g for black pepper, and turmeric. When the method was quantitatively validated for 199 pesticides, the limit of quantification (LOQ) was mostly at 10 ng/g (excluding black pepper, and turmeric with LOQ = 20 ng/g) with recoveries within 70-120%, and precision-RSDs <20%. Furthermore, the method allowed the identification of suspected non-target analytes through retrospective search of the accurate mass of the compound-specific precursor and product ions. Compared to LC-MS/MS, the quantitative performance of this Orbitrap-MS method had agreements in residue values between 78-100%. Copyright © 2017 Elsevier B.V. All rights reserved.

Fast screening of short-chain chlorinated paraffins in indoor dust samples by graphene-assisted laser desorption/ionization mass spectrometry.

PubMed

Huang, Xiu; Liu, Qian; Gao, Wei; Wang, Yawei; Nie, Zhou; Yao, Shouzhuo; Jiang, Guibin

2018-03-01

As an important class of emerging chemical contaminants, short-chain chlorinated paraffins (SCCPs) are considered as one of the most challenging groups of compounds to analyze. In this paper, we report a new method for fast screening of SCCPs based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with graphene as a matrix and 2,5,6,9-tetrachlorodecane as an internal standard. We found that the use of graphene as MALDI matrix generated high peak intensities for SCCPs while producing few background noises. The ion fragmentation mechanisms of SCCPs in MALDI are discussed in detail. Under the optimized conditions, much lower detection limits of SCCP congeners (0.1-5ng/mL) than those reported previously were obtained. Other distinct advantages such as short analysis time and simplified sample preparation procedures are also demonstrated. The method was successfully applied in fast screening of SCCPs in indoor dust samples and monitoring of human exposure levels to SCCPs, and the results were verified by gas chromatography coupled to negative chemical ionization quadrupole time-of-flight high-resolution mass spectrometry. This work not only offers a new promising tool for SCCP studies, but also further demonstrates the promise of graphene as a new generation of MALDI matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a suspect and non-target screening approach to detect veterinary antibiotic residues in a complex biological matrix using liquid chromatography/high-resolution mass spectrometry.

PubMed

Solliec, Morgan; Roy-Lachapelle, Audrey; Sauvé, Sébastien

2015-12-30

Swine manure can contain a wide range of veterinary antibiotics, which could enter the environment via manure spreading on agricultural fields. A suspect and non-target screening method was applied to swine manure samples to attempt to identify veterinary antibiotics and pharmaceutical compounds for a future targeted analysis method. A combination of suspect and non-target screening method was developed to identify various veterinary antibiotic families using liquid chromatography coupled with high-resolution mass spectrometry (LC/HRMS). The sample preparation was based on the physicochemical parameters of antibiotics for the wide scope extraction of polar compounds prior to LC/HRMS analysis. The amount of data produced was processed by applying restrictive thresholds and filters to significantly reduce the number of compounds found and eliminate matrix components. The suspect and non-target screening was applied on swine manure samples and revealed the presence of seven common veterinary antibiotics and some of their relative metabolites, including tetracyclines, β-lactams, sulfonamides and lincosamides. However, one steroid and one analgesic were also identified. The occurrence of the identified compounds was validated by comparing their retention times, isotopic abundance patterns and fragmentation patterns with certified standards. This identification method could be very useful as an initial step to screen for and identify emerging contaminants such as veterinary antibiotics and pharmaceuticals in environmental and biological matrices prior to quantification. Copyright © 2015 John Wiley & Sons, Ltd.

Analyzing Screening Policies for Childhood Obesity

PubMed Central

Yang, Yan; Goldhaber-Fiebert, Jeremy D.; Wein, Lawrence M.

2013-01-01

Due to the health and economic costs of childhood obesity, coupled with studies suggesting the benefits of comprehensive (dietary, physical activity and behavioral counseling) intervention, the United States Preventive Services Task Force recently recommended childhood screening and intervention for obesity beginning at age six. Using a longitudinal data set consisting of the body mass index of 3164 children up to age 18 and another longitudinal data set containing the body mass index at ages 18 and 40 and the presence or absence of disease (hypertension and diabetes) at age 40 for 747 people, we formulate and numerically solve – separately for boys and girls – a dynamic programming problem for the optimal biennial (i.e., at ages 2, 4, …, 16) obesity screening thresholds. Unlike most screening problem formulations, we take a societal viewpoint, where the state of the system at each age is the population-wide probability density function of the body mass index. Compared to the biennial version of the task force’s recommendation, the screening thresholds derived from the dynamic program achieve a relative reduction in disease prevalence of 3% at the same screening (and treatment) cost, or – due to the flatness of the disease vs. screening tradeoff curve – achieves the same disease prevalence at a 28% relative reduction in cost. Compared to the task force’s policy, which uses the 95th percentile of body mass index (from cross-sectional growth charts tabulated by the Centers for Disease Control and Prevention) as the screening threshold for each age, the dynamic programming policy treats mostly 16 year olds (including many who are not obese) and very few males under 14 years old. While our results suggest that adult hypertension and diabetes are minimized by focusing childhood obesity screening and treatment on older adolescents, the shortcomings in the available data and the narrowness of the medical outcomes considered prevent us from making a recommendation about childhood obesity screening policies. PMID:23956465

Inexpensive and fast pathogenic bacteria screening using field-effect transistors.

PubMed

Formisano, Nello; Bhalla, Nikhil; Heeran, Mel; Reyes Martinez, Juana; Sarkar, Amrita; Laabei, Maisem; Jolly, Pawan; Bowen, Chris R; Taylor, John T; Flitsch, Sabine; Estrela, Pedro

2016-11-15

While pathogenic bacteria contribute to a large number of globally important diseases and infections, current clinical diagnosis is based on processes that often involve culturing which can be time-consuming. Therefore, innovative, simple, rapid and low-cost solutions to effectively reduce the burden of bacterial infections are urgently needed. Here we demonstrate a label-free sensor for fast bacterial detection based on metal-oxide-semiconductor field-effect transistors (MOSFETs). The electric charge of bacteria binding to the glycosylated gates of a MOSFET enables quantification in a straightforward manner. We show that the limit of quantitation is 1.9×10(5) CFU/mL with this simple device, which is more than 10,000-times lower than is achieved with electrochemical impedance spectroscopy (EIS) and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-ToF) on the same modified surfaces. Moreover, the measurements are extremely fast and the sensor can be mass produced at trivial cost as a tool for initial screening of pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

High-performance liquid chromatography-mass spectrometry-based acetylcholinesterase assay for the screening of inhibitors in natural extracts.

PubMed

de Jong, Camiel F; Derks, Rico J E; Bruyneel, Ben; Niessen, Wilfried; Irth, Hubertus

2006-04-21

The present paper describes a High-performance liquid chromatography-mass spectrometry (LC-MS) methodology for the screening of acetylcholinesterase (AChE) inhibitors in natural extracts. AChE activity of sample components is monitored by a post-column biochemical assay that is based on the separate, sequential mixing of AChE and acetylcholine, respectively, with the HPLC eluate. AChE inhibitors are detected by measuring a decrease of product formation using electrospray MS. Ammonium bicarbonate was used as buffer in order to achieve optimum compatibility between biochemical assay and MS detection conditions. The assay is robust and stable for over 13 h and compares favourably with other AChE assays in terms of stability and sensitivity. IC(50) values of 9-aminoacridine, galanthamine, gallamine, (-)-huperzine A and thioflavin T were determined to be 0.12, 0.38, 6.4, 0.46 and 3.2 microM, respectively. The assay was used to effectively identify an AChE inhibitor present in a crude extract of Narcissus c.v. "Bridal Crown".

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.

Mass detection in digital breast tomosynthesis data using convolutional neural networks and multiple instance learning.

PubMed

Yousefi, Mina; Krzyżak, Adam; Suen, Ching Y

2018-05-01

Digital breast tomosynthesis (DBT) was developed in the field of breast cancer screening as a new tomographic technique to minimize the limitations of conventional digital mammography breast screening methods. A computer-aided detection (CAD) framework for mass detection in DBT has been developed and is described in this paper. The proposed framework operates on a set of two-dimensional (2D) slices. With plane-to-plane analysis on corresponding 2D slices from each DBT, it automatically learns complex patterns of 2D slices through a deep convolutional neural network (DCNN). It then applies multiple instance learning (MIL) with a randomized trees approach to classify DBT images based on extracted information from 2D slices. This CAD framework was developed and evaluated using 5040 2D image slices derived from 87 DBT volumes. The empirical results demonstrate that this proposed CAD framework achieves much better performance than CAD systems that use hand-crafted features and deep cardinality-restricted Bolzmann machines to detect masses in DBTs. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Pet dogs and child physical activity: the role of child-dog attachment.

PubMed

Gadomski, A M; Scribani, M B; Krupa, N; Jenkins, P

2017-10-01

Dog ownership has been associated with increased physical activity in children which in turn may mitigate childhood obesity. To measure the association between child-dog attachment and child physical activity and screen time. Cross-sectional study including 370 children (ages 4-10) who had pet dogs in the home. Parents completed the DartScreen, a web-based screener, before a well-child visit. Screener domains included child body mass index (BMI), physical activity, screen time and dog-related questions. The Companion Animal Bonding Scale (CABS) was used to measure child attachment to the dog. Clinic nurses weighed and measured the children. Associations between CABS, BMI z-score, screen time and physical activity were estimated. CABS was strongly associated with time spent being active with the dog (F = 22.81, p < 0.0001), but not with BMI z-score or screen time. A higher level of child attachment to a pet dog is associated with increased child physical activity. © 2016 World Obesity Federation.

Development of carbon plasma-coated multiwell plates for high-throughput mass spectrometric analysis of highly lipophilic fermentation products.

PubMed

Heinig, Uwe; Scholz, Susanne; Dahm, Pia; Grabowy, Udo; Jennewein, Stefan

2010-08-01

Classical approaches to strain improvement and metabolic engineering rely on rapid qualitative and quantitative analyses of the metabolites of interest. As an analytical tool, mass spectrometry (MS) has proven to be efficient and nearly universally applicable for timely screening of metabolites. Furthermore, gas chromatography (GC)/MS- and liquid chromatography (LC)/MS-based metabolite screens can often be adapted to high-throughput formats. We recently engineered a Saccharomyces cerevisiae strain to produce taxa-4(5),11(12)-diene, the first pathway-committing biosynthetic intermediate for the anticancer drug Taxol, through the heterologous and homologous expression of several genes related to isoprenoid biosynthesis. To date, GC/MS- and LC/MS-based high-throughput methods have been inherently difficult to adapt to the screening of isoprenoid-producing microbial strains due to the need for extensive sample preparation of these often highly lipophilic compounds. In the current work, we examined different approaches to the high-throughput analysis of taxa-4(5),11(12)-diene biosynthesizing yeast strains in a 96-deep-well format. Carbon plasma coating of standard 96-deep-well polypropylene plates allowed us to circumvent the inherent solvent instability of commonly used deep-well plates. In addition, efficient adsorption of the target isoprenoid product by the coated plates allowed rapid and simple qualitative and quantitative analyses of the individual cultures. Copyright 2010 Elsevier Inc. All rights reserved.

Direct and rapid mass spectral fingerprinting of maternal urine for the detection of Down syndrome pregnancy.

PubMed

Iles, Ray K; Shahpari, Maryam E; Cuckle, Howard; Butler, Stephen A

2015-01-01

The established methods of antenatal screening for Down syndrome are based on immunoassay for a panel of maternal serum biomarkers together with ultrasound measures. Recently, genetic analysis of maternal plasma cell free (cf) DNA has begun to be used but has a number of limitations including excessive turn-around time and cost. We aimed to develop an alternative method based on urinalysis that is simple, affordable and accurate. 101 maternal urine samples sampled at 12-17 weeks gestation were taken from an archival collection of 2567 spot urines collected from women attending a prenatal screening clinic. 18 pregnancies in this set subsequently proved to be Down pregnancies. Samples were either neat urine or diluted between 10 to 1000 fold in dH2O and subjected to matrix assisted laser desorption ionization (MALDI), time of flight (ToF) mass spectrometry (MS). Data profiles were examined in the region 6,000 to 14,000 m/z. Spectral data was normalised and quantitative characteristics of the profile were compared between Down and controls. In Down cases there were additional spectral profile peaks at 11,000-12,000 m/z and a corresponding reduction in intensity at 6,000-8,000 m/z. The ratio of the normalised values at these two ranges completely separated the 8 Down syndrome from the 39 controls at 12-14 weeks. Discrimination was poorer at 15-17 weeks where 3 of the 10 Down syndrome cases had values within the normal range. Direct MALDI ToF mass spectral profiling of maternal urinary has the potential for an affordable, simple, accurate and rapid alternative to current Down syndrome screening protocols.

Supplement to MTI study on selective passenger screening in the mass transit rail environment.

DOT National Transportation Integrated Search

2010-01-01

This supplement updates and adds to MTIs 2007 report on Selective Screening of Rail Passengers (Jenkins and Butterworth MTI 06-07: Selective Screening of Rail Passengers). The report reviews current screening programs implemented (or planned) by n...

Synthesis and screening of one-bead-one-compound cyclic peptide libraries.

PubMed

Qian, Ziqing; Upadhyaya, Punit; Pei, Dehua

2015-01-01

Cyclic peptides have been a rich source of biologically active molecules. Herein we present a method for the combinatorial synthesis and screening of large one-bead-one-compound (OBOC) libraries of cyclic peptides against biological targets such as proteins. Up to ten million different cyclic peptides are rapidly synthesized on TentaGel microbeads by the split-and-pool synthesis method and subjected to a multistage screening protocol which includes magnetic sorting, on-bead enzyme-linked and fluorescence-based assays, and in-solution binding analysis of cyclic peptides selectively released from single beads by fluorescence anisotropy. Finally, the most active hit(s) is identified by the partial Edman degradation-mass spectrometry (PED-MS) method. This method allows a single researcher to synthesize and screen up to ten million cyclic peptides and identify the most active ligand(s) in ~1 month, without the time-consuming and expensive hit resynthesis or the use of any special equipment.

Pilot trial on separation conditions for diaper recycling.

PubMed

Kim, Kyung-Shin; Cho, Hee-Sun

2017-09-01

By utilizing laboratory-scale tests, the optimal separation conditions for diaper recycling were identified, and then, these conditions were validated by a pilot trial. In this research, we determined the mass balances derived during various processing steps and identified the most feasible procedures to use for separating each material in the output flow. The results showed that drum screening was not able to remove all the fiber and super absorbent particles (SAP) in the plastic-rich fraction and that cellulose enzyme treatment can be a good solution. To achieve better separation of fibers and SAP, slot screening followed by a cleaner is a potential option. A feasible diaper recycling process was recommended based on these results. This process involves screening and enzymatic treatment for the plastic fraction, and screening, cleaning, and thickening for the fiber fraction. Treatment procedures were also proposed for the SAP fraction and rejected materials. Copyright © 2017. Published by Elsevier Ltd.

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

Advantages of Molecular Weight Identification during Native MS Screening.

PubMed

Khan, Ahad; Bresnick, Anne; Cahill, Sean; Girvin, Mark; Almo, Steve; Quinn, Ronald

2018-05-09

Native mass spectrometry detection of ligand-protein complexes allowed rapid detection of natural product binders of apo and calcium-bound S100A4 (a member of the metal binding protein S100 family), T cell/transmembrane, immunoglobulin (Ig), and mucin protein 3, and T cell immunoreceptor with Ig and ITIM (immunoreceptor tyrosine-based inhibitory motif) domains precursor protein from extracts and fractions. Based on molecular weight common hits were detected binding to all four proteins. Seven common hits were identified as apigenin 6- C - β - D -glucoside 8- C - α - L -arabinoside, sweroside, 4',5-dihydroxy-7-methoxyflavanone-6- C -rutinoside, loganin acid, 6- C -glucosylnaringenin, biochanin A 7- O -rutinoside and quercetin 3- O -rutinoside. Mass guided isolation and NMR identification of hits confirmed the mass accuracy of the ligand in the ligand-protein MS complexes. Thus, molecular weight ID from ligand-protein complexes by electrospray ionization Fourier transform mass spectrometry allowed rapid dereplication. Native mass spectrometry using electrospray ionization Fourier transform mass spectrometry is a tool for dereplication and metabolomics analysis. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of information-theoretic similarity measures for content-based retrieval and detection of masses in mammograms.

PubMed

Tourassi, Georgia D; Harrawood, Brian; Singh, Swatee; Lo, Joseph Y; Floyd, Carey E

2007-01-01

The purpose of this study was to evaluate image similarity measures employed in an information-theoretic computer-assisted detection (IT-CAD) scheme. The scheme was developed for content-based retrieval and detection of masses in screening mammograms. The study is aimed toward an interactive clinical paradigm where physicians query the proposed IT-CAD scheme on mammographic locations that are either visually suspicious or indicated as suspicious by other cuing CAD systems. The IT-CAD scheme provides an evidence-based, second opinion for query mammographic locations using a knowledge database of mass and normal cases. In this study, eight entropy-based similarity measures were compared with respect to retrieval precision and detection accuracy using a database of 1820 mammographic regions of interest. The IT-CAD scheme was then validated on a separate database for false positive reduction of progressively more challenging visual cues generated by an existing, in-house mass detection system. The study showed that the image similarity measures fall into one of two categories; one category is better suited to the retrieval of semantically similar cases while the second is more effective with knowledge-based decisions regarding the presence of a true mass in the query location. In addition, the IT-CAD scheme yielded a substantial reduction in false-positive detections while maintaining high detection rate for malignant masses.

Evaluation of information-theoretic similarity measures for content-based retrieval and detection of masses in mammograms

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

Tourassi, Georgia D.; Harrawood, Brian; Singh, Swatee

The purpose of this study was to evaluate image similarity measures employed in an information-theoretic computer-assisted detection (IT-CAD) scheme. The scheme was developed for content-based retrieval and detection of masses in screening mammograms. The study is aimed toward an interactive clinical paradigm where physicians query the proposed IT-CAD scheme on mammographic locations that are either visually suspicious or indicated as suspicious by other cuing CAD systems. The IT-CAD scheme provides an evidence-based, second opinion for query mammographic locations using a knowledge database of mass and normal cases. In this study, eight entropy-based similarity measures were compared with respect to retrievalmore » precision and detection accuracy using a database of 1820 mammographic regions of interest. The IT-CAD scheme was then validated on a separate database for false positive reduction of progressively more challenging visual cues generated by an existing, in-house mass detection system. The study showed that the image similarity measures fall into one of two categories; one category is better suited to the retrieval of semantically similar cases while the second is more effective with knowledge-based decisions regarding the presence of a true mass in the query location. In addition, the IT-CAD scheme yielded a substantial reduction in false-positive detections while maintaining high detection rate for malignant masses.« less

One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists.

PubMed

Schiebel, Johannes; Radeva, Nedyalka; Köster, Helene; Metz, Alexander; Krotzky, Timo; Kuhnert, Maren; Diederich, Wibke E; Heine, Andreas; Neumann, Lars; Atmanene, Cedric; Roecklin, Dominique; Vivat-Hannah, Valérie; Renaud, Jean-Paul; Meinecke, Robert; Schlinck, Nina; Sitte, Astrid; Popp, Franziska; Zeeb, Markus; Klebe, Gerhard

2015-09-01

Fragment-based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit-to-lead-to-drug optimization, the screening process should distinguish reliably between binders and non-binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease-relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361-entry library by using a reporter-displacement assay, saturation-transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stepwise strategy to improve Cervical Cancer Screening Adherence (SCAN-CC): automated text messages, phone calls and face-to-face interviews: protocol of a population-based randomised controlled trial.

PubMed

Firmino-Machado, João; Mendes, Romeu; Moreira, Amélia; Lunet, Nuno

2017-10-05

Screening is highly effective for cervical cancer prevention and control. Population-based screening programmes are widely implemented in high-income countries, although adherence is often low. In Portugal, just over half of the women adhere to cervical cancer screening, contributing for greater mortality rates than in other European countries. The most effective adherence raising strategies are based on patient reminders, small/mass media and face-to-face educational programmes, but sequential interventions targeting the general population have seldom been evaluated. The aim of this study is to assess the effectiveness of a stepwise approach, with increasing complexity and cost, to improve adherence to organised cervical cancer screening: step 1a-customised text message invitation; step 1b-customised automated phone call invitation; step 2-secretary phone call; step 3-family health professional phone call and face-to-face appointment. A population-based randomised controlled trial will be implemented in Portuguese urban and rural areas. Women eligible for cervical cancer screening will be randomised (1:1) to intervention and control. In the intervention group, women will be invited for screening through text messages, automated phone calls, manual phone calls and health professional appointments, to be applied sequentially to participants remaining non-adherent after each step. Control will be the standard of care (written letter). The primary outcome is the proportion of women adherent to screening after step 1 or sequences of steps from 1 to 3. The secondary outcomes are: proportion of women screened after each step (1a, 2 and 3); proportion of text messages/phone calls delivered; proportion of women previously screened in a private health institution who change to organised screening. The intervention and control groups will be compared based on intention-to-treat and per-protocol analyses. The study was approved by the Ethics Committee of the Northern Health Region Administration and National Data Protection Committee. Results will be disseminated through communications in scientific meetings and peer-reviewed journals. NCT03122275. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Television screen time, but not computer use and reading time, is associated with cardio-metabolic biomarkers in a multiethnic Asian population: a cross-sectional study.

PubMed

Nang, Ei Ei Khaing; Salim, Agus; Wu, Yi; Tai, E Shyong; Lee, Jeannette; Van Dam, Rob M

2013-05-30

Recent evidence shows that sedentary behaviour may be an independent risk factor for cardiovascular diseases, diabetes, cancers and all-cause mortality. However, results are not consistent and different types of sedentary behaviour might have different effects on health. Thus the aim of this study was to evaluate the association between television screen time, computer/reading time and cardio-metabolic biomarkers in a multiethnic urban Asian population. We also sought to understand the potential mediators of this association. The Singapore Prospective Study Program (2004-2007), was a cross-sectional population-based study in a multiethnic population in Singapore. We studied 3305 Singaporean adults of Chinese, Malay and Indian ethnicity who did not have pre-existing diseases and conditions that could affect their physical activity. Multiple linear regression analysis was used to assess the association of television screen time and computer/reading time with cardio-metabolic biomarkers [blood pressure, lipids, glucose, adiponectin, C reactive protein and homeostasis model assessment of insulin resistance (HOMA-IR)]. Path analysis was used to examine the role of mediators of the observed association. Longer television screen time was significantly associated with higher systolic blood pressure, total cholesterol, triglycerides, C reactive protein, HOMA-IR, and lower adiponectin after adjustment for potential socio-demographic and lifestyle confounders. Dietary factors and body mass index, but not physical activity, were potential mediators that explained most of these associations between television screen time and cardio-metabolic biomarkers. The associations of television screen time with triglycerides and HOMA-IR were only partly explained by dietary factors and body mass index. No association was observed between computer/ reading time and worse levels of cardio-metabolic biomarkers. In this urban Asian population, television screen time was associated with worse levels of various cardio-metabolic risk factors. This may reflect detrimental effects of television screen time on dietary habits rather than replacement of physical activity.

Application of mass spectrometry based electronic nose and chemometrics for fingerprinting radiation treatment

NASA Astrophysics Data System (ADS)

Gupta, Sumit; Variyar, Prasad S.; Sharma, Arun

2015-01-01

Volatile compounds were isolated from apples and grapes employing solid phase micro extraction (SPME) and subsequently analyzed by GC/MS equipped with a transfer line without stationary phase. Single peak obtained was integrated to obtain total mass spectrum of the volatile fraction of samples. A data matrix having relative abundance of all mass-to-charge ratios was subjected to principal component analysis (PCA) and linear discriminant analysis (LDA) to identify radiation treatment. PCA results suggested that there is sufficient variability between control and irradiated samples to build classification models based on supervised techniques. LDA successfully aided in segregating control from irradiated samples at all doses (0.1, 0.25, 0.5, 1.0, 1.5, 2.0 kGy). SPME-MS with chemometrics was successfully demonstrated as simple screening method for radiation treatment.

Mass Screening for Celiac Disease Among School-aged Children: Toward Exploring Celiac Iceberg in Saudi Arabia.

PubMed

Al-Hussaini, Abdulrahman; Troncone, Riccardo; Khormi, Musa; AlTuraiki, Muath; Alkhamis, Wahid; Alrajhi, Mona; Halal, Thana; Fagih, Mosa; Alharbi, Sahar; Bashir, Muhammed Salman; Chentoufi, Aziz Alami

2017-12-01

We conducted this mass screening study to determine the prevalence of celiac disease (CD) and characterize the celiac iceberg among Saudi pediatric population in Riyadh, the capital city of Saudi Arabia. During the study period (January 2014-June 2016), we have conducted a cross-sectional, mass screening, immunoglobulin A-tissue transglutaminase (TTG-IgA)-based study on 7930 Saudi students from primary and intermediate schools in Riyadh. Students with positive TTG-IgA (>20 U/L) were called in the hospital to undergo a repeat of TTG-IgA; in those with borderline positive TTG-IgA (20-60 U/L), IgA-endomyseal antibody (EMA-IgA) test was performed. Children with TTG-IgA >60 U/L and children with borderline positive TTG-IgA and positive EMA-IgA were advised to undergo upper endoscopy and intestinal biopsies. We identified 221 students with positive TTG-IgA (2.8%). CD was diagnosed in 119 cases (1.5%, 1:67 Saudi children) (mean age 11.5 ± 2.62 years; girls 81 [68%]). Another 51 children had persistently borderline positive TTG-IgA but negative EMA (0.64%) and the remaining 51 had transiently positive TTG-IgA. We have identified 3 clinical patterns in the screening-identified cases with CD: a silent form (37%), a mild symptomatic form characterized by gastrointestinal symptoms in presence of normal growth or overweight/obesity (48%), and gastrointestinal symptoms associated with impaired growth in 15%. Our study provided evidence of a high prevalence of CD among Saudi children (1.5%), a rate that is at least twice the average prevalence rate in Europe and North America.

[Screening and identification of apolipoprotein A-I as a potential marker for hepatoblastoma in children].

PubMed

Guo, Li-Hua; Zhao, Wei; Zhang, Jun-Jie; Zhang, Qian; Fan, Ying-Zhong; Wang, Jia-Xiang

2016-12-01

To screen and identify serum biomarkers for childhood hepatoblastoma (HB). The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins. After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group. Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.

LC-MS/MS screening strategy for unknown adducts to N-terminal valine in hemoglobin applied to smokers and nonsmokers.

PubMed

Carlsson, Henrik; von Stedingk, Hans; Nilsson, Ulrika; Törnqvist, Margareta

2014-12-15

Electrophilically reactive compounds have the ability to form adducts with nucleophilic sites in DNA and proteins, constituting a risk for toxic effects. Mass spectrometric detection of adducts to N-terminal valine in hemoglobin (Hb) after detachment by modified Edman degradation procedures is one approach for in vivo monitoring of exposure to electrophilic compounds/metabolites. So far, applications have been limited to one or a few selected reactive species, such as acrylamide and its metabolite glycidamide. This article presents a novel screening strategy for unknown Hb adducts to be used as a basis for an adductomic approach. The method is based on a modified Edman procedure, FIRE, specifically developed for LC-MS/MS analysis of N-terminal valine adducts in Hb detached as fluorescein thiohydantoin (FTH) derivatives. The aim is to detect and identify a priori unknown Hb adducts in human blood samples. Screening of valine adducts was performed by stepwise scanning of precursor ions in small mass increments, monitoring four fragments common for the FTH derivative of valine with different N-substitutions in the multiple-reaction mode, covering a mass range of 135 Da (m/z 503-638). Samples from six smokers and six nonsmokers were analyzed. Control experiments were performed to compare these results with known adducts and to check for artifactual formation of adducts. In all samples of smokers and nonsmokers, seven adducts were identified, of which six have previously been studied. Nineteen unknown adducts were observed, and 14 of those exhibited fragmentation patterns similar to earlier studied FTH derivatives of adducts to valine. Identification of the unknown adducts will be the focus of future work. The presented methodology is a promising screening tool using Hb adducts to indicate exposure to potentially toxic electrophilic compounds and metabolites.

Combine body mass index and body fat percentage measures to improve the accuracy of obesity screening in young adults.

PubMed

Hung, Shang-Ping; Chen, Ching-Yu; Guo, Fei-Ran; Chang, Ching-I; Jan, Chyi-Feng

Obesity screening among young adult groups is meaningful. Body mass index (BMI) is limited to discriminate between fat and lean mass. Asian young adult group tends to have lower BMI and higher body fat percentage (BFP) than other ethnic groups. Accuracy of obesity screening by commonly used BMI criteria is unclear in young Taiwanese population. A total of 894 young adults (447 males and 447 females) aged 20-26 were recruited. BMI, regional fat percentage and BFP determined by bioelectrical impedance analysis (BIA) were measured. BMI cutoff points were based on the criteria adopted by the Ministry of Health and Welfare in Taiwan. Cutoff points of low or high BFP were defined as 24% in men and 31.4% in women. Prevalence of BFP defining obesity was 14.8% in young men and 27.3% in young women. 23.2% of young men and only 8.3% of young women were classified to overweight or obesity categories according to the BMI criteria. Disagreement was noticed mainly among overweight males and normal weight females. 68.7% of BMI defining overweight young men had low BFP; however, 29.7% of young women of BMI defining normal group had high BFP. Up to 69.7% of young women with high BFP would be missed by BMI category only. Disagreement between BMI and BFP was significant among young adults, especially young women. We suggest combining BMI and BIA for obesity and overweight screening in Asian young adults. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Heterogeneous Antibody-Based Activity Assay for Lysine Specific Demethylase 1 (LSD1) on a Histone Peptide Substrate.

PubMed

Schmitt, Martin L; Ladwein, Kathrin I; Carlino, Luca; Schulz-Fincke, Johannes; Willmann, Dominica; Metzger, Eric; Schilcher, Pierre; Imhof, Axel; Schüle, Roland; Sippl, Wolfgang; Jung, Manfred

2014-07-01

Posttranslational modifications of histone tails are very important for epigenetic gene regulation. The lysine-specific demethylase LSD1 (KDM1A/AOF2) demethylates in vitro predominantly mono- and dimethylated lysine 4 on histone 3 (H3K4) and is a promising target for drug discovery. We report a heterogeneous antibody-based assay, using dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) for the detection of LSD1 activity. We used a biotinylated histone 3 peptide (amino acids 1-21) with monomethylated lysine 4 (H3K4me) as the substrate for the detection of LSD1 activity with antibody-mediated quantitation of the demethylated product. We have successfully used the assay to measure the potency of reference inhibitors. The advantage of the heterogeneous format is shown with cumarin-based LSD1 inhibitor candidates that we have identified using virtual screening. They had shown good potency in an established LSD1 screening assay. The new heterogeneous assay identified them as false positives, which was verified using mass spectrometry. © 2014 Society for Laboratory Automation and Screening.

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.

Risk communication considerations to facilitate the screening of mass populations for potential contamination with radioactive material.

PubMed

Emery, R J; Sprau, D D; Morecook, R C

2008-11-01

Experience gained during a field training exercise with a Medical Reserve Corps unit on the screening of large groups of individuals for possible contamination with radioactive material revealed that while exercise participants were generally attentive to the proper use of protective equipment and detectors, they tended to overlook important basic risk communications aspects. For example, drill participants did not actively communicate with the persons waiting in line for screening, a step which would provide re-assurance, possibly minimize apprehension, and would clarify expectations. When questioned on this issue of risk communication, drill participants were often able to craft ad hoc messages, but the messages were inconsistent and likely would not have significantly helped diminish anxiety and maintain crowd control. Similar difficulties were encountered regarding messaging for persons determined to be contaminated, those departing the screening center, and those to be delivered to the media. Based on these experiences, the need for a suggested list of risk communication points was identified. To address this need, a set of risk communication templates were developed that focused on the issues likely to be encountered in a mass screening event. The points include issues such as the importance of remaining calm, steps for minimizing possible intake or uptake, considerations for those exhibiting acute injuries, expected screening wait times, the process to be followed and the information to be collected, the process to be undertaken for those exhibiting contamination, and symptoms to watch for after departure. Drill participants indicated in follow-up discussions that such pre-established risk communication templates would serve to enhance their ability to assist in times of emergency and noted the potential broader applicably of the approach for use in responses for other disasters types as well.

Regional differences as barriers to body mass index screening described by Ohio school nurses.

PubMed

Stalter, Ann M; Chaudry, Rosemary V; Polivka, Barbara J

2011-08-01

Body mass index (BMI) screening is advocated by the National Association of School Nurses (NASN). Research identifying barriers to BMI screening in public elementary school settings has been sparse. The purpose of the study was to identify barriers and facilitating factors of BMI screening practices among Ohio school nurses working in suburban, rural, and urban public elementary schools. This descriptive study used focus groups with 25 school nurses in 3 geographic regions of Ohio. An adapted Healthy People 2010 model guided the development of semistructured focus group questions. Nine regional themes related to BMI screening emerged specific to suburban, rural, and/or urban school nurses' experiences with BMI screening practice, policy, school physical environment, school social environment, school risk/protection, and access to quality health care. Key facilitating factors to BMI screening varied by region. Key barriers to BMI screening were a lack of privacy, time, policy, and workload of school nurses. Regionally specific facilitating factors to BMI screening in schools provide opportunities for schools to accentuate the positive and to promote school health. © 2011, American School Health Association.

Screening of oil sources by using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry and multivariate statistical analysis.

PubMed

Zhang, Wanfeng; Zhu, Shukui; He, Sheng; Wang, Yanxin

2015-02-06

Using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOFMS), volatile and semi-volatile organic compounds in crude oil samples from different reservoirs or regions were analyzed for the development of a molecular fingerprint database. Based on the GC×GC/TOFMS fingerprints of crude oils, principal component analysis (PCA) and cluster analysis were used to distinguish the oil sources and find biomarkers. As a supervised technique, the geological characteristics of crude oils, including thermal maturity, sedimentary environment etc., are assigned to the principal components. The results show that tri-aromatic steroid (TAS) series are the suitable marker compounds in crude oils for the oil screening, and the relative abundances of individual TAS compounds have excellent correlation with oil sources. In order to correct the effects of some other external factors except oil sources, the variables were defined as the content ratio of some target compounds and 13 parameters were proposed for the screening of oil sources. With the developed model, the crude oils were easily discriminated, and the result is in good agreement with the practical geological setting. Copyright © 2014 Elsevier B.V. All rights reserved.

Flow Cytometry: Impact On Early Drug Discovery

PubMed Central

Edwards, Bruce S.; Sklar, Larry A.

2015-01-01

Summary Modern flow cytometers can make optical measurements of 10 or more parameters per cell at tens-of-thousands of cells per second and over five orders of magnitude dynamic range. Although flow cytometry is used in most drug discovery stages, “sip-and-spit” sampling technology has restricted it to low sample throughput applications. The advent of HyperCyt sampling technology has recently made possible primary screening applications in which tens-of-thousands of compounds are analyzed per day. Target-multiplexing methodologies in combination with extended multi-parameter analyses enable profiling of lead candidates early in the discovery process, when the greatest numbers of candidates are available for evaluation. The ability to sample small volumes with negligible waste reduces reagent costs, compound usage and consumption of cells. Improved compound library formatting strategies can further extend primary screening opportunities when samples are scarce. Dozens of targets have been screened in 384- and 1536-well assay formats, predominantly in academic screening lab settings. In concert with commercial platform evolution and trending drug discovery strategies, HyperCyt-based systems are now finding their way into mainstream screening labs. Recent advances in flow-based imaging, mass spectrometry and parallel sample processing promise dramatically expanded single cell profiling capabilities to bolster systems level approaches to drug discovery. PMID:25805180

Screening of missing proteins in the human liver proteome by improved MRM-approach-based targeted proteomics.

PubMed

Chen, Chen; Liu, Xiaohui; Zheng, Weimin; Zhang, Lei; Yao, Jun; Yang, Pengyuan

2014-04-04

To completely annotate the human genome, the task of identifying and characterizing proteins that currently lack mass spectrometry (MS) evidence is inevitable and urgent. In this study, as the first effort to screen missing proteins in large scale, we developed an approach based on SDS-PAGE followed by liquid chromatography-multiple reaction monitoring (LC-MRM), for screening of those missing proteins with only a single peptide hit in the previous liver proteome data set. Proteins extracted from normal human liver were separated in SDS-PAGE and digested in split gel slice, and the resulting digests were then subjected to LC-schedule MRM analysis. The MRM assays were developed through synthesized crude peptides for target peptides. In total, the expressions of 57 target proteins were confirmed from 185 MRM assays in normal human liver tissues. Among the proved 57 one-hit wonders, 50 proteins are of the minimally redundant set in the PeptideAtlas database, 7 proteins even have none MS-based information previously in various biological processes. We conclude that our SDS-PAGE-MRM workflow can be a powerful approach to screen missing or poorly characterized proteins in different samples and to provide their quantity if detected. The MRM raw data have been uploaded to ISB/SRM Atlas/PASSEL (PXD000648).

Pharmacological screening technologies for venom peptide discovery.

PubMed

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

2017-12-01

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

Non-Target Screening of Veterinary Drugs Using Tandem Mass Spectrometry on SmartMass

NASA Astrophysics Data System (ADS)

Xia, Bing; Liu, Xin; Gu, Yu-Cheng; Zhang, Zhao-Hui; Wang, Hai-Yan; Ding, Li-Sheng; Zhou, Yan

2013-05-01

Non-target screening of veterinary drugs using tandem mass spectrometric data was performed on the SmartMass platform. This newly developed software uses the characteristic fragmentation patterns (CFP) to identify chemicals, especially those containing particular substructures. A mixture of 17 sulfonamides was separated by ultra performance liquid chromatography (UPLC), and SmartMass was used to process the tandem mass spectrometry (MS/MS) data acquired on an Orbitrap mass spectrometer. The data were automatically extracted, and each sulfonamide was recognized and analyzed with a prebuilt analysis rule. By using this software, over 98 % of the false candidate structures were eliminated, and all the correct structures were found within the top 10 of the ranking lists. Furthermore, SmartMass could also be used to identify slightly modified contraband drugs and metabolites with simple prebuilt rules. [Figure not available: see fulltext.

Cathode material for lithium ion accumulators prepared by screen printing for Smart Textile applications

NASA Astrophysics Data System (ADS)

Syrový, T.; Kazda, T.; Syrová, L.; Vondrák, J.; Kubáč, L.; Sedlaříková, M.

2016-03-01

The presented study is focused on the development of LiFePO4 based cathode for thin and flexible screen printed secondary lithium based accumulators. An ink formulation was developed for the screen printing technique, which enabled mass production of accumulator's cathode for Smart Label and Smart Textile applications. The screen printed cathode was compared with an electrode prepared by the bar coating technique using an ink formulation based on the standard approach of ink composition. Obtained LiFePO4 cathode layers were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) and galvanostatic charge/discharge measurements at different loads. The discharge capacity, capacity retention and stability at a high C rate of the LiFePO4 cathode were improved when Super P and PVDF were replaced by conductive polymers PEDOT:PSS. The achieved capacity during cycling at various C rates was approximately the same at the beginning and at the end, and it was about 151 mAh/g for cycling under 1C. The obtained results of this novelty electrode layer exceed the parameters of several electrode layers based on LiFePO4 published in literature in terms of capacity, cycling stability and overcomes them in terms of simplicity/industrial process ability of cathode layer fabrication and electrode material preparation.

Current use of high-resolution mass spectrometry in drug screening relevant to clinical and forensic toxicology and doping control.

PubMed

Ojanperä, Ilkka; Kolmonen, Marjo; Pelander, Anna

2012-05-01

Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists. Combined chromatography-mass spectrometry techniques with standardised reference libraries have been most commonly used for the purpose. In the last ten years, the focus has shifted from gas chromatography-mass spectrometry to liquid chromatography-mass spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new relevant substances. High-resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power, has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation. The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier-transform mass spectrometry. Both techniques enable a range of different drug-screening strategies that essentially rely on measuring a compound's or a fragment's mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review discusses recent applications of HRMS in analytical toxicology.

Mass spectrometry as a quantitative tool in plant metabolomics

PubMed Central

Jorge, Tiago F.; Mata, Ana T.

2016-01-01

Metabolomics is a research field used to acquire comprehensive information on the composition of a metabolite pool to provide a functional screen of the cellular state. Studies of the plant metabolome include the analysis of a wide range of chemical species with very diverse physico-chemical properties, and therefore powerful analytical tools are required for the separation, characterization and quantification of this vast compound diversity present in plant matrices. In this review, challenges in the use of mass spectrometry (MS) as a quantitative tool in plant metabolomics experiments are discussed, and important criteria for the development and validation of MS-based analytical methods provided. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644967

Making the Case for Objective Performance Metrics in Newborn Screening by Tandem Mass Spectrometry

ERIC Educational Resources Information Center

Rinaldo, Piero; Zafari, Saba; Tortorelli, Silvia; Matern, Dietrich

2006-01-01

The expansion of newborn screening programs to include multiplex testing by tandem mass spectrometry requires understanding and close monitoring of performance metrics. This is not done consistently because of lack of defined targets, and interlaboratory comparison is almost nonexistent. Between July 2004 and April 2006 (N = 176,185 cases), the…

Rapid profiling of polymeric phenolic acids in Salvia miltiorrhiza by hybrid data-dependent/targeted multistage mass spectrometry acquisition based on expected compounds prediction and fragment ion searching.

PubMed

Shen, Yao; Feng, Zijin; Yang, Min; Zhou, Zhe; Han, Sumei; Hou, Jinjun; Li, Zhenwei; Wu, Wanying; Guo, De-An

2018-04-01

Phenolic acids are the major water-soluble components in Salvia miltiorrhiza (>5%). According to previous studies, many of them contribute to the cardiovascular effects and antioxidant effects of S. miltiorrhiza. Polymeric phenolic acids can be considered as the tanshinol derived metabolites, e.g., dimmers, trimers, and tetramers. A strategy combined with tanshinol-based expected compounds prediction, total ion chromatogram filtering, fragment ion searching, and parent list-based multistage mass spectrometry acquisition by linear trap quadropole-orbitrap Velos mass spectrometry was proposed to rapid profile polymeric phenolic acids in S. miltiorrhiza. More than 480 potential polymeric phenolic acids could be screened out by this strategy. Based on the fragment information obtained by parent list-activated data dependent multistage mass spectrometry acquisition, 190 polymeric phenolic acids were characterized by comparing their mass information with literature data, and 18 of them were firstly detected from S. miltiorrhiza. Seven potential compounds were tentatively characterized as new polymeric phenolic acids from S. miltiorrhiza. This strategy facilitates identification of polymeric phenolic acids in complex matrix with both selectivity and sensitivity, which could be expanded for rapid discovery and identification of compounds from complex matrix. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Challenges to be overcome using population-based sampling methods to recruit veterans for a study of post-traumatic stress disorder and traumatic brain injury.

PubMed

Bayley, Peter J; Kong, Jennifer Y; Helmer, Drew A; Schneiderman, Aaron; Roselli, Lauren A; Rosse, Stephanie M; Jackson, Jordan A; Baldwin, Janet; Isaac, Linda; Nolasco, Michael; Blackman, Marc R; Reinhard, Matthew J; Ashford, John Wesson; Chapman, Julie C

2014-04-08

Many investigators are interested in recruiting veterans from recent conflicts in Afghanistan and Iraq with Traumatic Brain Injury (TBI) and/or Post Traumatic Stress Disorder (PTSD). Researchers pursuing such studies may experience problems in recruiting sufficient numbers unless effective strategies are used. Currently, there is very little information on recruitment strategies for individuals with TBI and/or PTSD. It is known that groups of patients with medical conditions may be less likely to volunteer for clinical research. This study investigated the feasibility of recruiting veterans returning from recent military conflicts--Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF)--using a population-based sampling method. Individuals were sampled from a previous epidemiological study. Three study sites focused on recruiting survey respondents (n = 445) who lived within a 60 mile radius of one of the sites. Overall, the successful recruitment of veterans using a population-based sampling method was dependent on the ability to contact potential participants following mass mailing. Study enrollment of participants with probable TBI and/or PTSD had a recruitment yield (enrolled/total identified) of 5.4%. We were able to contact 146 individuals, representing a contact rate of 33%. Sixty-six of the individuals contacted were screened. The major reasons for not screening included a stated lack of interest in the study (n = 37), a failure to answer screening calls after initial contact (n = 30), and an unwillingness or inability to travel to a study site (n = 10). Based on the phone screening, 36 veterans were eligible for the study. Twenty-four veterans were enrolled, (recruitment yield = 5.4%) and twelve were not enrolled for a variety of reasons. Our experience with a population-based sampling method for recruitment of recent combat veterans illustrates the challenges encountered, particularly contacting and screening potential participants. The screening and enrollment data will help guide recruitment for future studies using population-based methods.

Adherence to cervical cancer screening guidelines for U.S. women aged 25-64: data from the 2005 Health Information National Trends Survey (HINTS).

PubMed

Nelson, Wendy; Moser, Richard P; Gaffey, Allison; Waldron, William

2009-11-01

Although it is widely accepted that Papanicolaou (Pap) screening can reduce cervical cancer mortality, many women still do not maintain regular cervical cancer screenings. To describe the prevalence of cervical cancer screening and the demographic, behavioral, psychological, and cancer-related knowledge factors associated with adherence to U.S. Preventive Services Task Force (USPSTF) cervical cancer screening guidelines among women in the United States. Data for women aged 25-64 were obtained from the National Cancer Institute's (NCI) 2005 Health Information National Trends Survey (HINTS). Women were considered adherent to screening guidelines if they had two consecutive, on-schedule screenings and planned to have another within the next 3 years. The sample comprised 2070 women. Ninety-eight percent of women reported ever having a Pap smear, 90% reported having had a recent Pap smear (within 3 years), and 84% were adherent to USPSTF screening guidelines. Maintaining regular cervical cancer screening was significantly associated with having health insurance, normal body mass index (BMI), smoking status (nonsmoker), mood (absence of a mood disturbance), and being knowledgeable about cervical cancer screening and human papillomavirus (HPV) infection. Based on the observation that women who were current smokers, obese, or experiencing a substantial degree of psychological distress were significantly less likely to adhere to recommended screening guidelines, we suggest that healthcare providers pay particular attention to the screening needs of these more vulnerable women.

Screening of 485 Pesticide Residues in Fruits and Vegetables by Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry Based on TOF Accurate Mass Database and QTOF Spectrum Library.

PubMed

Pang, Guo-Fang; Fan, Chun-Lin; Chang, Qiao-Ying; Li, Jian-Xun; Kang, Jian; Lu, Mei-Ling

2018-03-22

This paper uses the LC-quadrupole-time-of-flight MS technique to evaluate the behavioral characteristics of MSof 485 pesticides under different conditions and has developed an accurate mass database and spectra library. A high-throughput screening and confirmation method has been developed for the 485 pesticides in fruits and vegetables. Through the optimization of parameters such as accurate mass number, time of retention window, ionization forms, etc., the method has improved the accuracy of pesticide screening, thus avoiding the occurrence of false-positive and false-negative results. The method features a full scan of fragments, with 80% of pesticide qualitative points over 10, which helps increase pesticide qualitative accuracy. The abundant differences of fragment categories help realize the effective separation and qualitative identification of isomer pesticides. Four different fruits and vegetables-apples, grapes, celery, and tomatoes-were chosen to evaluate the efficiency of the method at three fortification levels of 5, 10, and 20 μg/kg, and satisfactory results were obtained. With this method, a national survey of pesticide residues was conducted between 2012 and 2015 for 12 551 samples of 146 different fruits and vegetables collected from 638 sampling points in 284 counties across 31 provincial capitals/cities directly under the central government, which provided scientific data backup for ensuring pesticide residue safety of the fruits and vegetables consumed daily by the public. Meanwhile, the big data statistical analysis of the new technique also further proves it to be of high speed, high throughput, high accuracy, high reliability, and high informatization.

Integrated strategy for identifying minor components in complex samples combining mass defect, diagnostic ions and neutral loss information based on ultra-performance liquid chromatography-high resolution mass spectrometry platform: Folium Artemisiae Argyi as a case study.

PubMed

Ren, Dabing; Ran, Lu; Yang, Chong; Xu, Meilin; Yi, Lunzhao

2018-05-18

Ultra-performance liquid chromatography coupled to high-resolution mass spectrometry (UPLC-HRMS) has been used as a powerful tool to profile chemicals in traditional Chinese medicines. However, identification of potentially bioactive compounds is still a challenging work because of the large amount of information contained in the raw UPLC-HRMS data. Especially the ubiquitous matrix interference makes it more difficult to characterize the minor components. Therefore, rapid recognition and efficient extraction of the corresponding parent ions is critically important for identifying the attractive compounds in complex samples. Herein, we propose an integrated filtering strategy to remove un-related or interference MS 1 ions from the raw UPLC-HRMS data, which helps to retain the MS features of the target components and expose the compounds of interest as effective as possible. The proposed strategy is based on the use of a combination of different filtering methods, including nitrogen rule, mass defect, and neutral loss/diagnostic fragment ions filtering. The strategy was validated by rapid screening and identification of 16 methoxylated flavonoids and 55 chlorogenic acids analogues from the raw UPLC-HRMS dataset of Folium Artemisiae Argyi. Particularly, successful detection of several minor components indicated that the integrated strategy has obvious advantages over individual filtering methods, and it can be used as a promising method for screening and identifying compounds from complex samples, such as herbal medicines. Copyright © 2018 Elsevier B.V. All rights reserved.

Surveillance of chronic obstructive pulmonary disease in high-risk individuals by using regional lung cancer mass screening.

PubMed

Sekine, Yasuo; Yanagibori, Ryoko; Suzuki, Kiminori; Sugiyama, Sonomi; Yamaji, Haruko; Ishibashi, Michiko; Fujisawa, Takehiko

2014-01-01

Patients with chronic obstructive pulmonary disease (COPD) are at risk for lung cancer; the diseases have common etiologies, including cigarette smoking. We aimed to clarify the effectiveness of COPD detection using a regional mass-screening program for lung cancer. A total of 7,067 residents of Togane, Chiba, Japan received lung cancer screening between May and July, 2011. We defined four groups of possible COPD candidates: group A (n=358), positive smoking history, positive chronic respiratory symptoms; group B (n=766), positive smoking history, positive lifestyle-related disease; group C (n=75), passive smoking history, positive chronic respiratory symptoms; and group D (n=301), passive smoking history, positive lifestyle-related disease. Candidates underwent on-site pulmonary function testing (PFT). The criteria for COPD candidates were fulfilled in 1,686 of 7,067 individuals (23.9%); 1,500 participants underwent PFT (89%), and 171 (11.4%) were diagnosed with COPD. The overall COPD detection rate was 2.4%. The frequency of COPD was significantly higher in groups A and B than in groups C and D (P=0.048); however, the distribution of COPD grades was similar among the groups (P=0.372). Multiple logistic regression analysis identified male sex, age 60 years or greater, and positive smoking history as risk factors for COPD. COPD screening using a community-based lung cancer-screening program may be effective for disease detection. Individuals who are 60 years of age or older with a positive smoking history should undergo PFT to detect COPD.

Rapid methodology to screen flame retardants in upholstered furniture for compliance with new California labeling law (SB 1019).

PubMed

Petreas, Myrto; Gill, Ranjit; Takaku-Pugh, Sayaka; Lytle, Eric; Parry, Emily; Wang, Miaomiao; Quinn, John; Park, June-Soo

2016-06-01

In response to concerns regarding the widespread use of flame retardants, the California Legislature passed a law (SB1019) requiring labels on furniture products to indicate whether they do or do not contain flame retardants. To support the enforcement of the new law, our laboratory developed a step-wise, screening approach to test for brominated (BFR) and phosphorus-based flame retardants (OPFRs) in several types of furniture components (foam, fabric, batting, plumage, etc.). We used X-Ray Fluorescence (XRF) to screen for the presence of Br (and other elements) and Inductively Coupled Plasma - Optical Emission Spectrometry (ICP-OES) to identify and measure the concentration of P (and other elements). The same samples were also extracted by dichloromethane using sonication and analyzed by a single injection into a Gas Chromatograph - Tandem Mass Spectrometer to obtain concentrations of specific BFRs and OPFRs. Our approach showed excellent screening potential for Br and Sb by XRF and for P by ICP-OES, with both tests having predictive values of a negative equal to 1. To explore and screen for flame retardants in products not included in our current list of target chemicals, we used Liquid Chromatography/Time-of-Flight Mass Spectrometry operated with electrospray ionization, to identify additional flame retardants to be incorporated in quantitative methods. We are making all our methodologies public to facilitate simple and low cost methods that can help manufacturers and suppliers have their products tested and correctly labeled, ultimately benefitting the consumer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Imaging and Screening of Cancer of the Gallbladder and Bile Ducts.

PubMed

Sandrasegaran, Kumar; Menias, Christine O

2017-11-01

Biliary cancers include gallbladder cancer (GBC) and cholangiocarcinoma (CCA). GBC may appear as a mass replacing the gallbladder, thickened gallbladder wall, or polypoid lesion in the gallbladder. Gallbladder polyps with low risk of GBC (eg, 6- to 10-mm polyps without other risk factors) are screened with sonography. In general, polyps smaller than 5 mm are ignored and those larger than 10 mm require surgical consideration. Screening for CCA is less well-established. On imaging, CCA may be divided into mass-forming, periductal infiltrating, and intraductal types. This review discusses the current state of screening and diagnosis of GBC and CCA. Copyright © 2017 Elsevier Inc. All rights reserved.

Cost-Effectiveness between Double and Single Fecal Immunochemical Test(s) in a Mass Colorectal Cancer Screening.

PubMed

Cai, Shan-Rong; Zhu, Hong-Hong; Huang, Yan-Qin; Li, Qi-Long; Ma, Xin-Yuan; Zhang, Su-Zhan; Zheng, Shu

2016-01-01

This study investigated the cost-effectiveness between double and single Fecal Immunochemical Test(s) (FIT) in a mass CRC screening. A two-stage sequential screening was conducted. FIT was used as a primary screening test and recommended twice by an interval of one week at the first screening stage. We defined the first-time FIT as FIT1 and the second-time FIT as FIT2. If either FIT1 or FIT2 was positive (+), then a colonoscopy was recommended at the second stage. Costs were recorded and analyzed. A total of 24,419 participants completed either FIT1 or FIT2. The detection rate of advanced neoplasm was 19.2% among both FIT1+ and FIT2+, especially high among men with age ≥55 (27.4%). About 15.4% CRC, 18.9% advanced neoplasm, and 29.9% adenoma missed by FIT1 were detected by FIT2 alone. Average cost was $2,935 for double FITs and $2,121 for FIT1 to detect each CRC and $901 for double FITs and $680 for FIT1 to detect each advanced neoplasm. Double FITs are overall more cost-effective, having significantly higher positive and detection rates with an acceptable higher cost, than single FIT. Double FITs should be encouraged for the first screening in a mass CRC screening, especially in economically and medically underserved populations/areas/countries.

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

PubMed

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

2016-06-01

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

Planar chromatography mediated screening of tetracycline and fluoroquinolone antibiotics in milk by fluorescence and mass selective detection.

PubMed

Chen, Yisheng; Schwack, Wolfgang

2013-10-18

A rapid and efficient method for preliminary screening of four tetracyclines (tetracycline, chlortetracycline, oxytetracycline, doxycline) and three fluoroquinolones (enrofloxacin, ciprofloxacin, marbofloxacin), mostly detected in milk, by high-performance thin-layer chromatography-fluorescence detection and electrospray ionization mass spectrometry (HPTLC-FLD-ESI/MS) is highlighted. The optimized separation of the target antibiotics on ethylenediamine tetraacetic acid modified silica gel plates showed marked benefits for screening purposes. Besides, selective and sensitive densitometry in fluorescence mode was established with excitation at 366nm for the tetracyclines, 300nm for enrofloxacin and ciprofloxacin, and 280nm for marbofloxacin. Limits of detection (LOD) and quantitation (LOQ) with 95% confidence were in the range of 12-25 and 45-95μg/kg, respectively, in milk samples. Recoveries of target antibiotics from milk samples spiked at three critical levels (50, 100 and 150μg/kg) ranged from 76% to 105%. More importantly, a mass selective detection (MSD) was established as additional tool for confirmatory purposes. Using the elution-head based TLC-MS interface, the optimized elution flow consisting of acetonitrile/ammonium formate buffer (9/1, v/v) at a rate of 0.3mL/min enabled time-dependent resolution of analytes from the major interfering compounds, thus circumventing serious ion suppression effects. The established MSD assay also offered high sensitivity (25μg/kg) for confirmation, meeting Commission Regulation (EU) No. 37/2010. Copyright © 2013 Elsevier B.V. All rights reserved.

Body Mass Index and Cancer Screening in Older American Indian and Alaska Native Men

ERIC Educational Resources Information Center

Muus, Kyle J.; Baker-Demaray, Twyla; McDonald, Leander R.; Ludtke, Richard L.; Allery, Alan J.; Bogart, T. Andy; Goldberg, Jack; Ramsey, Scott D.; Buchwald, Dedra S.

2009-01-01

Context: Regular screenings are important for reducing cancer morbidity and mortality. There are several barriers to receiving timely cancer screening, including overweight/obesity. No study has examined the relationship between overweight/obesity and cancer screening among American Indian/Alaska Natives (AI/ANs). Purpose: To describe the…

Evaluation of Candidate Measures for Home-Based Screening of Sleep Disordered Breathing in Taiwanese Bus Drivers

PubMed Central

Ting, Hua; Huang, Ren-Jing; Lai, Ching-Hsiang; Chang, Shen-Wen; Chung, Ai-Hui; Kuo, Teng-Yao; Chang, Ching-Haur; Shih, Tung-Sheng; Lee, Shin-Da

2014-01-01

Background: Sleepiness-at-the-wheel has been identified as a major cause of highway accidents. The aim of our study is identifying the candidate measures for home-based screening of sleep disordered breathing in Taiwanese bus drivers, instead of polysomnography. Methods: Overnight polysomnography accompanied with simultaneous measurements of alternative screening devices (pulse oximetry, ApneaLink, and Actigraphy), heart rate variability, wake-up systolic blood pressure and questionnaires were completed by 151 eligible participants who were long-haul bus drivers with a duty period of more than 12 h a day and duty shifting. Results: 63.6% of professional bus drivers were diagnosed as having sleep disordered breathing and had a higher body mass index, neck circumference, systolic blood pressure, arousal index and desaturation index than those professional bus drivers without evidence of sleep disordered breathing. Simple home-based candidate measures: (1) Pulse oximetry, oxygen-desaturation indices by ≥3% and 4% (r = 0.87∼0.92); (2) Pulse oximetry, pulse-rising indices by ≥7% and 8% from a baseline (r = 0.61∼0.89); and (3) ApneaLink airflow detection, apnea-hypopnea indices (r = 0.70∼0.70), based on recording-time or Actigraphy-corrected total sleep time were all significantly correlated with, and had high agreement with, corresponding polysomnographic apnea-hypopnea indices [(1) 94.5%∼96.6%, (2) 93.8%∼97.2%, (3) 91.1%∼91.3%, respectively]. Conversely, no validities of SDB screening were found in the multi-variables apnea prediction questionnaire, Epworth Sleepiness Scale, night-sleep heart rate variability, wake-up systolic blood pressure and anthropometric variables. Conclusions: The indices of pulse oximetry and apnea flow detection are eligible criteria for home-based screening of sleep disordered breathing, specifically for professional drivers. PMID:24803198

Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening: A Case-Control Study.

PubMed

Bosch, Linda J W; de Wit, Meike; Pham, Thang V; Coupé, Veerle M H; Hiemstra, Annemieke C; Piersma, Sander R; Oudgenoeg, Gideon; Scheffer, George L; Mongera, Sandra; Sive Droste, Jochim Terhaar; Oort, Frank A; van Turenhout, Sietze T; Larbi, Ilhame Ben; Louwagie, Joost; van Criekinge, Wim; van der Hulst, Rene W M; Mulder, Chris J J; Carvalho, Beatriz; Fijneman, Remond J A; Jimenez, Connie R; Meijer, Gerrit A

2017-12-19

The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. Case-control study. Colonoscopy-controlled referral population from several centers. 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001). Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples. Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening. Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.

A strategy for screening and identifying mycotoxins in herbal medicine using ultra-performance liquid chromatography with tandem quadrupole time-of-flight mass spectrometry.

PubMed

Fang, Lian-xiang; Xiong, Ai-zhen; Wang, Rui; Ji, Shen; Yang, Li; Wang, Zheng-tao

2013-09-01

The objective of this study was to develop an effective strategy for screening and identifying mycotoxins in herbal medicine (HM). Here, Imperatae Rhizoma, a commonly used Chinese herb, was selected as a model HM. A crude drug contaminated with fungi was analyzed by comparing with uncontaminated ones. Ultra-performance LC coupled to tandem quadrupole TOF-MS (UPLC-Q-TOF-MS) with collision energy function was applied to analyze different samples from Imperatae Rhizoma. Then, MarkerLynx(TM) software was employed to screen the excess components in analytes, compared with control samples, and those selected markers were likely to be the metabolites of fungi. Furthermore, each of the accurate masses of the markers obtained from MarkerLynx(TM) was then searched in a mycotoxins/fungal metabolites database established in advance. The molecular formulas with relative mass error between the measured and theoretical mass within 5 ppm were chosen and then applied to MassFragment(TM) analysis for further confirmation of their structures. With the use of this approach, five mycotoxins that have never been reported in HM were identified in contaminated Imperatae Rhizoma. The results demonstrate the potential of UPLC-Q-TOF-MS coupled with the MarkerLynx(TM) software and MassFragment(TM) tool as an efficient and convenient method to screen and identify mycotoxins in herbal materials and aid in the quality control of HM. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PTR-ToF-MS Coupled with an Automated Sampling System and Tailored Data Analysis for Food Studies: Bioprocess Monitoring, Screening and Nose-space Analysis.

PubMed

Capozzi, Vittorio; Yener, Sine; Khomenko, Iuliia; Farneti, Brian; Cappellin, Luca; Gasperi, Flavia; Scampicchio, Matteo; Biasioli, Franco

2017-05-11

Proton Transfer Reaction (PTR), combined with a Time-of-Flight (ToF) Mass Spectrometer (MS) is an analytical approach based on chemical ionization that belongs to the Direct-Injection Mass Spectrometric (DIMS) technologies. These techniques allow the rapid determination of volatile organic compounds (VOCs), assuring high sensitivity and accuracy. In general, PTR-MS requires neither sample preparation nor sample destruction, allowing real time and non-invasive analysis of samples. PTR-MS are exploited in many fields, from environmental and atmospheric chemistry to medical and biological sciences. More recently, we developed a methodology based on coupling PTR-ToF-MS with an automated sampler and tailored data analysis tools, to increase the degree of automation and, consequently, to enhance the potential of the technique. This approach allowed us to monitor bioprocesses (e.g. enzymatic oxidation, alcoholic fermentation), to screen large sample sets (e.g. different origins, entire germoplasms) and to analyze several experimental modes (e.g. different concentrations of a given ingredient, different intensities of a specific technological parameter) in terms of VOC content. Here, we report the experimental protocols exemplifying different possible applications of our methodology: i.e. the detection of VOCs released during lactic acid fermentation of yogurt (on-line bioprocess monitoring), the monitoring of VOCs associated with different apple cultivars (large-scale screening), and the in vivo study of retronasal VOC release during coffee drinking (nosespace analysis).

What factors influence uptake into family-based obesity treatment after weight screening?

PubMed

Taylor, Rachael W; Williams, Sheila M; Dawson, Anna M; Taylor, Barry J; Meredith-Jones, Kim; Brown, Deirdre

2013-12-01

To determine what factors drive participation in a family-based weight management program for 4- to 8-year-old children following screening for overweight or obesity. Children (n = 1093) attended a comprehensive screening appointment where parents completed questionnaires on demographics, motivation for healthy lifestyles, feeding practices, and beliefs about child size, prior to feedback about the child's weight. Parents of overweight or obese children (body mass index ≥85th percentile) attended a follow-up interview to assess reactions to feedback and willingness to participate in a 2-year intervention. A total of 271 (24.8%) children were overweight or obese with 197 (72.7%) agreeing to the intervention. Socioeconomic status differed in intervention participants (n = 197) compared with non-participants (n = 74), whereas no differences were observed in parental feeding practices, ineffective parenting practices, or self-determined forms of motivation. However, fewer non-participating parents believed their child to be overweight (23% vs 49%, P < .001) or were concerned about it (16% vs 43%, P < .001), despite children having an average body mass index approximating the 95th percentile. Non-participating parents did not expect their child to be overweight (P = .002) and rated receiving this information as less useful (P = .008) than participating parents. Preconceptions about child weight and reactions to feedback determined intervention uptake more than parenting or motivation for health. Many parents agreed to participate in the intervention despite not viewing their child as overweight. Copyright © 2013 Mosby, Inc. All rights reserved.

UHPLC-Q-TOF-MS/MS Method Based on Four-Step Strategy for Metabolism Study of Fisetin in Vitro and in Vivo.

PubMed

Zhang, Xia; Yin, Jintuo; Liang, Caijuan; Sun, Yupeng; Zhang, Lantong

2017-12-20

Fisetin has been identified as an anticancer agent with antiangiogenic properties in mice. However, its metabolism in vitro (rat liver microsomes) and in vivo (rats) is presently not characterized. In this study, ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was employed for data acquiring, and a four-step analytical strategy was developed to screen and identify metabolites. First, full-scan was applied, which was dependent on a multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS). Then PeakView 1.2 and Metabolitepilot 1.5 software were used to load data to seek possible metabolites. Finally, metabolites were identified according to mass measurement and retention time. Moreover, isomers were distinguished based on Clog P parameter. Based on the proposed method, 53 metabolites in vivo and 14 metabolites in vitro were characterized. Moreover, metabolic pathways mainly included oxidation, reduction, hydrogenation, methylation, sulfation, and glucuronidation.

Mass spectrometry-based metabolomics: applications to biomarker and metabolic pathway research.

PubMed

Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun

2016-01-01

Mass spectrometry-based metabolomics has become increasingly popular in molecular medicine. High-definition mass spectrometry (MS), coupled with pattern recognition methods, have been carried out to obtain comprehensive metabolite profiling and metabolic pathway of large biological datasets. This sets the scene for a new and powerful diagnostic approach. Analysis of the key metabolites in body fluids has become an important part of improving disease diagnosis. With technological advances in analytical techniques, the ability to measure low-molecular-weight metabolites in bio-samples provides a powerful platform for identifying metabolites that are uniquely correlated with a specific human disease. MS-based metabolomics can lead to enhanced understanding of disease mechanisms and to new diagnostic markers and has a strong potential to contribute to improving early diagnosis of diseases. This review will highlight the importance and benefit with certain characteristic examples of MS-metabolomics for identifying metabolic pathways and metabolites that accurately screen for potential diagnostic biomarkers of diseases. Copyright © 2015 John Wiley & Sons, Ltd.

Headspace screening of fluid obtained from the gut during colonoscopy and breath analysis by proton transfer reaction-mass spectrometry: A novel approach in the diagnosis of gastro-intestinal diseases

NASA Astrophysics Data System (ADS)

Lechner, M.; Colvin, H. P.; Ginzel, C.; Lirk, P.; Rieder, J.; Tilg, H.

2005-05-01

Background: The diagnosis of many gastro-intestinal diseases is difficult and can often be confirmed only by using invasive diagnostic means. In contrast, the headspace screening of fluid obtained from the gut during colonoscopy and the analysis of exhaled air may be a novel approach for the diagnosis of these diseases.Materials and methods: The screening was performed by using proton transfer reaction-mass spectrometry (PTR-MS) which allows rapid and sensitive measurement. Fluid samples obtained from the gut during colonoscopy were collected from 76 and breath samples from 70 subjects. Mass spectra of healthy controls were created. Afterwards these spectra were compared with those of patients suffering from inflammatory bowel diseases (IBD; Crohn's disease and ulcerative colitis; n = 10) and irritable bowel syndrome (IBS; n = 7).Results: Significant differences in the mass spectra could be observed both in the headspace of the fluid and in the exhaled air comparing patients with healthy controls.Conclusions: This study is the first describing headspace screening of fluid obtained from the gut during colonoscopy, possibly presenting a novel diagnostic tool in the differential diagnosis of gastro-intestinal diseases.

Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review.

PubMed

Pasin, Daniel; Cawley, Adam; Bidny, Sergei; Fu, Shanlin

2017-10-01

The proliferation of new psychoactive substances (NPS) in recent years has resulted in the development of numerous analytical methods for the detection and identification of known and unknown NPS derivatives. High-resolution mass spectrometry (HRMS) has been identified as the method of choice for broad screening of NPS in a wide range of analytical contexts because of its ability to measure accurate masses using data-independent acquisition (DIA) techniques. Additionally, it has shown promise for non-targeted screening strategies that have been developed in order to detect and identify novel analogues without the need for certified reference materials (CRMs) or comprehensive mass spectral libraries. This paper reviews the applications of HRMS for the analysis of NPS in forensic drug chemistry and analytical toxicology. It provides an overview of the sample preparation procedures in addition to data acquisition, instrumental analysis, and data processing techniques. Furthermore, it gives an overview of the current state of non-targeted screening strategies with discussion on future directions and perspectives of this technique. Graphical Abstract Missing the bullseye - a graphical respresentation of non-targeted screening. Image courtesy of Christian Alonzo.

Uncommon presentation of a rare tumour - incidental finding in an asymptomatic patient: case report and comprehensive review of the literature on intrapericardial solitary fibrous tumours.

PubMed

Czimbalmos, Csilla; Csecs, Ibolya; Polos, Miklos; Bartha, Elektra; Szucs, Nikolette; Toth, Attila; Maurovich-Horvat, Pal; Becker, David; Sapi, Zoltan; Szabolcs, Zoltan; Merkely, Bela; Vago, Hajnalka

2017-09-02

A solitary fibrous tumour is a rare, mainly benign spindle cell mesenchymal tumour most commonly originating from the pleura. An intrapericardial location of a solitary fibrous tumour is extremely unusual. We present a case of an asymptomatic patient with a slow-growing massive benign cardiac solitary fibrous tumour. A 37-year-old asymptomatic female patient was referred to our hospital with an enlarged cardiac silhouette found on her screening chest X-ray. The echocardiographic examination revealed pericardial effusion and an inhomogeneous mobile mass located in the pericardial sac around the left ventricle. Cardiac magnetic resonance (MRI) examination showed an intrapericardial, semilunar-shaped mass attached to the pulmonary trunk with an intermediate signal intensity on proton density-weighted images and high signal intensity on T2-weighted spectral fat saturation inversion recovery images. First-pass perfusion and early and late gadolinium-enhanced images showed a vascularized mass with septated, patchy, inhomogeneous late enhancement. Coronary computed tomography angiography revealed no invasion of the coronaries. Based on the retrospectively analysed screening chest X-rays, the mass had started to form at least 7 years earlier. Complete resection of the tumour with partial resection of the pulmonary trunk was performed. Histological evaluation of the septated, cystic mass revealed tumour cells forming an irregular patternless pattern; immunohistochemically, the cells tested positive for vimentin, CD34, CD99 and STAT6 but negative for keratin (AE1-AE3), CD31 and S100. Thus, the diagnosis of an intrapericardial solitary fibrous tumour was established. There has been no recurrence for 3 years based on the regular MRI follow-up. Intrapericardial SFTs, showing slow growth dynamics, can present with massive extent even in completely asymptomatic patients. MRI is exceedingly useful for characterizing intrapericardial masses, allowing precise surgical planning, and is reliable for long-term follow up.

Dissecting plasmodesmata molecular composition by mass spectrometry-based proteomics.

PubMed

Salmon, Magali S; Bayer, Emmanuelle M F

2012-01-01

In plants, the intercellular communication through the membranous channels called plasmodesmata (PD; singular plasmodesma) plays pivotal roles in the orchestration of development, defence responses, and viral propagation. PD are dynamic structures embedded in the plant cell wall that are defined by specialized domains of the endoplasmic reticulum (ER) and the plasma membrane (PM). PD structure and unique functions are guaranteed by their particular molecular composition. Yet, up to recent years and despite numerous approaches such as mutant screens, immunolocalization, or screening of random cDNAs, only few PD proteins had been conclusively identified and characterized. A clear breakthrough in the search of PD constituents came from mass-spectrometry-based proteomic approaches coupled with subcellular fractionation strategies. Due to their position, firmly anchored in the extracellular matrix, PD are notoriously difficult to isolate for biochemical analysis. Proteomic-based approaches have therefore first relied on the use of cell wall fractions containing embedded PD then on "free" PD fractions whereby PD membranes were released from the walls by enzymatic degradation. To discriminate between likely contaminants and PD protein candidates, bioinformatics tools have often been used in combination with proteomic approaches. GFP fusion proteins of selected candidates have confirmed the PD association of several protein families. Here we review the accomplishments and limitations of the proteomic-based strategies to unravel the functional and structural complexity of PD. We also discuss the role of the identified PD-associated proteins.

Development of liquid chromatography/mass spectrometry based screening assay for PfTrxR inhibitors using relative quantitation of intact thioredoxin.

PubMed

Munigunti, Ranjith; Calderón, Angela I

2012-09-15

Plasmodium falciparum (Pf) thioredoxin reductase (TrxR) catalyzes the reduction of thioredoxin disulfide (Trx-S(2)) to thioredoxin dithiol (Trx-(SH)(2)) that is essential for antioxidant defense mechanism and DNA synthesis in the parasite and is a validated drug target for new antimalarial agents. In this study, we have developed a liquid chromatography/mass spectrometry (LC/MS)-based functional assay to identify inhibitors of PfTrxR by quantifying the product formed (Trx-(SH)(2)) in the enzymatic reaction. Relative quantitation of the reaction product (intact Trx-(SH)(2)) was carried out using an Agilent 6520 QTOF mass spectrometer equipped with a positive mode electrospray ionization (ESI) source. The calibration curve prepared for Trx-(SH)(2) at concentrations ranging from 1.8 to 116.5 µg/mL was linear (R(2) >0.998). The limit of detection (LOD) and limit of quantification (LOQ) of Trx-(SH)(2) were at 0.45 and 1.8 µg/mL respectively. To validate the developed functional assay we have screened reference compounds 1, 2 and 3 for their PfTrxR inhibitory activity and ten natural compounds (at 10 μM) which were earlier identified as ligands of PfTrxR by a UF-LC/MS based binding assay. The developed LC/MS-based functional assay for identification of inhibitors of PfTrxR is a sensitive and reliable method that is also amendable for high-throughput format. This is the first representation of a relative quantitation of intact Trx-(SH)(2) using LC/MS. Copyright © 2012 John Wiley & Sons, Ltd.

Rapid Catalyst Screening by a Continuous-Flow Microreactor Interfaced with Ultra High Pressure Liquid Chromatography

PubMed Central

Fang, Hui; Xiao, Qing; Wu, Fanghui; Floreancig, Paul E.; Weber, Stephen G.

2010-01-01

A high-throughput screening system for homogeneous catalyst discovery has been developed by integrating a continuous-flow capillary-based microreactor with ultra-high pressure liquid chromatography (UHPLC) for fast online analysis. Reactions are conducted in distinct and stable zones in a flow stream that allows for time and temperature regulation. UHPLC detection at high temperature allows high throughput online determination of substrate, product, and byproduct concentrations. We evaluated the efficacies of a series of soluble acid catalysts for an intramolecular Friedel-Crafts addition into an acyliminium ion intermediate within one day and with minimal material investment. The effects of catalyst loading, reaction time, and reaction temperature were also screened. This system exhibited high reproducibility for high-throughput catalyst screening and allowed several acid catalysts for the reaction to be identified. Major side products from the reactions were determined through off-line mass spectrometric detection. Er(OTf)3, the catalyst that showed optimal efficiency in the screening, was shown to be effective at promoting the cyclization reaction on a preparative scale. PMID:20666502

Assessing psychosocial variables: a tool for diabetes educators.

PubMed

Fisher, Kelly L

2006-01-01

The purpose of this article is to share an educational strategy or tool that is relevant for use in patient and professional diabetes education. The tool offers an opportunity for diabetes educators to screen for psychosocial variables such as depression or emotional distress. A systematic review of the literature was conducted to identify psychological variables that have an impact on individuals living with diabetes and their ability to self-manage their disease. The literature revealed that both depression and emotional distress related to diabetes was experienced by individuals with diabetes along with those individuals who were unable to self-management their disease. The Accu-Check Interview is a computer software program that may assist diabetes educators to provide diabetes education. Use of the Accu-Check Interview software program has been implemented at various sites including the Joslin Clinic (Boston, Mass), Baystate Medical Center (Springfield, Mass), and Emerson Hospital (Concord, Mass). The Diabetes Self Care Profile is a Web-based version of the Accu-Check Interview and can be accessed as a demonstration in English and Spanish. These tools allow diabetes educators to screen for psychosocial variables and address issues with individuals while using a motivational interviewing approach.

Non-gassing nickel-cadmium battery electrodes and cells

NASA Technical Reports Server (NTRS)

Luksha, E.; Gordy, D. J.

1972-01-01

The concept of a negative limited nongassing nickel-cadmium battery was demonstrated by constructing and testing practical size experimental cells of approximately 25 Ah capacity. These batteries operated in a gas-free manner and had measured energy densities of 10-11 Wh/lb. Thirty cells were constructed for extensive testing. Some small cells were tested for over 200 cycles at 100% depth. For example, a small cell with an electrodeposited cadmium active mass on a silver screen still had 55% of its theoretical capacity (initial efficiency was 85%). There was no evidence of deterioration of gassing properties with cycling of the nickel electrodes. The charge temperature was observed to be the most critical variable governing nickel electrode gassing. This variable was shown to be age dependent. Four types of cadmium electrodes were tested: an electrodeposited cadmium active mass on a cadmium or silver substrate, a porous sintered silver substrate based electrode, and a Teflon bonded pressed cadmium electrode. The electrodeposited cadmium mass on a silver screen was found to be the best all-around electrode from a performance point of view and from the point of view of manufacturing them in a size required for a 25 Ah size battery.

Screening of environmental contaminants in honey bee wax comb using gas chromatography-high-resolution time-of-flight mass spectrometry.

PubMed

Gómez-Ramos, M M; García-Valcárcel, A I; Tadeo, J L; Fernández-Alba, A R; Hernando, M D

2016-03-01

This study reports an analytical approach intended to be used for investigation of non-targeted environmental contaminants and to characterize the organic pollution pattern of bee wax comb samples. The method comprises a generic extraction followed by detection with gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC-TOF-MS), operated in electron impact ionization (EI) mode. The screening approach for the investigation of non-targeted contaminants consisted of initial peak detection by deconvolution and matching the first-stage mass spectra EI-MS(1) with a nominal mass spectral library. To gain further confidence in the structural characterization of the contaminants under investigation, the molecular formula of representative ions (molecular ion when present in the EI spectrum) and, for at least other two fragment ions, was provided for those with an accurate mass scoring (mass error < 5 ppm). This methodology was applied for screening environmental contaminants in 50 samples of bee wax comb. This approach has allowed the tentative identification of some GC-amenable contaminants belonging to different chemical groups, among them, phthalates and polycyclic aromatic hydrocarbons (PAHs), along with residues of veterinary treatments used in apiculture.

Screening for Behavioral Health Issues in Children Enrolled in Massachusetts Medicaid

PubMed Central

Penfold, Robert; Arsenault, Lisa; Zhang, Fang; Murphy, Michael; Wissow, Larry

2014-01-01

OBJECTIVES: To understand mandated behavioral health (BH) screening in Massachusetts Medicaid including characteristics of screened children, predictors of positive screens, and whether screening identifies children without a previous BH history. METHODS: Massachusetts mandated BH screening in particularly among underidentified groups. 2008. Providers used a billing code and modifier to indicate a completed screen and whether a BH need was identified. Using MassHealth claims data, children with ≥300 days of eligibility in fiscal year (FY) 2009 were identified and categorized into groups based on first use of the modifier, screening code, or claim. Bivariate analyses were conducted to determine differences among groups. BH history was examined by limiting the sample to those continuously enrolled in FY 2008 and 2009. Multivariate logistic regression was used to determine predictors of positive screens. RESULTS: Of 355 490 eligible children, 46% had evidence of screening. Of those with modifiers, 12% were positive. Among continuously enrolled children (FY 2008 and FY 2009) with evidence of screening, 43% with positive modifiers had no BH history. This “newly identified” group were more likely to be female, younger, minority, and from rural residences (P < .0001). Among children with modifiers; gender (male), age (5–7), being in foster care, recent BH history, and Hispanic ethnicity predicted having a positive modifier. CONCLUSIONS: The high rate of newly identified Medicaid children with a BH need suggests that screening is performing well, particularly among underidentified groups. To better assess screening value, future work on cost-effectiveness and the impact on subsequent mental health treatment is needed. PMID:24298005

ColoNav: patient navigation for colorectal cancer screening in deprived areas - Study protocol.

PubMed

Allary, C; Bourmaud, A; Tinquaut, F; Oriol, M; Kalecinski, J; Dutertre, V; Lechopier, N; Pommier, M; Benoist, Y; Rousseau, S; Regnier, V; Buthion, V; Chauvin, F

2016-07-07

The mass colorectal cancer screening program was implemented in 2008 in France, targeting 16 million French people aged between 50 and 74. The current adhesion is insufficient and the participation rate is even lower among the underserved population, increasing health inequalities within our health care system. Patient Navigation programs have proved their efficiency to promote the access to cancer screening and diagnosis. The purpose of the study is to assess the implementation of a patient navigation intervention that has been described in another cultural environment and another health care system. The main objective of the program is to increase the colorectal cancer screening participation rate among the deprived population through the intervention of a navigator to promote the Fecal Occult Blood Test (FOBT) and complementary exams. We performed a multisite cluster randomized controlled trial, with three groups (one experimental group and two control groups) for 18 months. The study attempts to give a better understanding of the adhesion barriers to colorectal cancer screening among underserved populations. If this project is cost-effective, it could create a dynamic based on peer approaches that could be developed for other cancer screening programs and other chronic diseases. NCT02369757.

[Rapid screening the alkaloids of poppy shell in hot pot condiment, beef noodle soup and seasoning by direct analysis in real time-tandem mass spectrometry].

PubMed

Zhang, Baile; Gao, Lihong; Xie, Yingshuang; Zhou, Wei; Chen, Xiaofeng; Lei, Chunni; Zhang, Huan

2017-07-08

A direct analysis in real time tandem mass spectrometry (DART-MS/MS) method was established for quickly screening five illegally added alkaloids of poppy shell from the hot pot condiment, beef noodle soup and seasoning. The samples were extracted and purified by acetonitrile, and then injected under the conditions of ionization temperature of 300℃, grid electrode voltage of 150 V and sampling rate of 0.8 mm/s using DART in the positive ion mode. The determination was conducted by tandem mass spectrometry in positive ESI mode under multiple reaction monitoring (MRM) mode. The method is simple and rapid, and can meet the requirement of rapid screening and analysis of large quantities of samples.

A Healthy Lifestyle Intervention Delivered by Aspiring Physical Education Teachers to Children from Social Disadvantage: Study Protocol and Preliminary Findings

ERIC Educational Resources Information Center

Breslin, Gavin; Brennan, Deirdre

2012-01-01

We describe the design of a school-based healthy lifestyle intervention for eight-year-old to nine-year-old school children from lower socio-economic backgrounds, intended to increase physical activity, decrease sedentary behaviours, reduce screen-time behaviours, encourage healthy attitudes and behaviours to nutrition, and reduce body mass index.…

Tracing the metabolism of HT-2 toxin and T-2 toxin in barley by isotope-assisted untargeted screening and quantitative LC-HRMS analysis

USDA-ARS?s Scientific Manuscript database

An extensive study of the metabolism of the type-A trichothecene mycotoxins HT-2 toxin and T-2 toxin in barley using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) is reported. A recently developed untargeted approach based on stable isotopic labelling, LC-Orbitrap-MS a...

A magnetic bead-based ligand binding assay to facilitate human kynurenine 3-monooxygenase drug discovery.

PubMed

Wilson, Kris; Mole, Damian J; Homer, Natalie Z M; Iredale, John P; Auer, Manfred; Webster, Scott P

2015-02-01

Human kynurenine 3-monooxygenase (KMO) is emerging as an important drug target enzyme in a number of inflammatory and neurodegenerative disease states. Recombinant protein production of KMO, and therefore discovery of KMO ligands, is challenging due to a large membrane targeting domain at the C-terminus of the enzyme that causes stability, solubility, and purification difficulties. The purpose of our investigation was to develop a suitable screening method for targeting human KMO and other similarly challenging drug targets. Here, we report the development of a magnetic bead-based binding assay using mass spectrometry detection for human KMO protein. The assay incorporates isolation of FLAG-tagged KMO enzyme on protein A magnetic beads. The protein-bound beads are incubated with potential binding compounds before specific cleavage of the protein-compound complexes from the beads. Mass spectrometry analysis is used to identify the compounds that demonstrate specific binding affinity for the target protein. The technique was validated using known inhibitors of KMO. This assay is a robust alternative to traditional ligand-binding assays for challenging protein targets, and it overcomes specific difficulties associated with isolating human KMO. © 2014 Society for Laboratory Automation and Screening.

Exciton binding energy in a pyramidal quantum dot

NASA Astrophysics Data System (ADS)

Anitha, A.; Arulmozhi, M.

2018-05-01

The effects of spatially dependent effective mass, non-parabolicity of the conduction band and dielectric screening function on exciton binding energy in a pyramid-shaped quantum dot of GaAs have been investigated by variational method as a function of base width of the pyramid. We have assumed that the pyramid has a square base with area a× a and height of the pyramid H=a/2. The trial wave function of the exciton has been chosen according to the even mirror boundary condition, i.e. the wave function of the exciton at the boundary could be non-zero. The results show that (i) the non-parabolicity of the conduction band affects the light hole (lh) and heavy hole (hh) excitons to be more bound than that with parabolicity of the conduction band, (ii) the dielectric screening function (DSF) affects the lh and hh excitons to be more bound than that without the DSF and (iii) the spatially dependent effective mass (SDEM) affects the lh and hh excitons to be less bound than that without the SDEM. The combined effects of DSF and SDEM on exciton binding energy have also been calculated. The results are compared with those available in the literature.

The clinical impact of a false-positive urine cocaine screening result on a patient's pain management.

PubMed

Kim, James A; Ptolemy, Adam S; Melanson, Stacy E F; Janfaza, David R; Ross, Edgar L

2015-06-01

The urine of a patient admitted for chest and epigastric pain tested positive for cocaine using an immunoassay-based drug screening method (positive/negative cutoff concentration 150 ng/mL). Despite the patient's denial of recent cocaine use, this positive cocaine screening result in conjunction with a remote history of drug misuse impacted the patient's recommended pain therapy. Specifically, these factors prompted the clinical team to question the appropriateness of opioids and other potentially addictive therapeutics during the treatment of cancer pain from previously undetected advanced pancreatic carcinoma. After pain management and clinical pathology consultation, it was decided that the positive cocaine screening result should be confirmed by gas chromatography-mass spectrometry (GC-MS) testing. This more sensitive and specific analytical technique revealed that both cocaine and its primary metabolite benzoylecgonine were undetectable (i.e., less than the assay detection limit of 50 ng/mL), thus indicating that the positive urine screening result was falsely positive. With this confirmation, the pain management service team was reassured in offering intrathecal pump (ITP) therapy for pain control. ITP implantation was well tolerated, and the patient eventually achieved excellent pain relief. However, ITP therapy most likely would not have been utilized without the GC-MS confirmation testing unless alternative options failed and extensive vigilant monitoring was initiated. As exemplified in this case, confirmatory drug testing should be performed on specimens with unexpected immunoassay-based drug screening results. To our knowledge, this is the first report of a false-positive urine cocaine screening result and its impact on patient management. Wiley Periodicals, Inc.

Advances in biosensor development for the screening of antibiotic residues in food products of animal origin - A comprehensive review.

PubMed

Gaudin, Valérie

2017-04-15

Antibiotic residues may be found in food of animal origin, since veterinary drugs are used for preventive and curative purposes to treat animals. The control of veterinary drug residues in food is necessary to ensure consumer safety. Screening methods are the first step in the control of antibiotic residues in food of animal origin. Conventional screening methods are based on different technologies, microbiological methods, immunological methods or physico-chemical methods (e.g. thin-layer chromatography, HPLC, LC-MS/MS). Screening methods should be simple, quick, inexpensive and specific, with low detection limits and high sample throughput. Biosensors can meet some of these requirements. Therefore, the development of biosensors for the screening of antibiotic residues has been increasing since the 1980s. The present review provides extensive and up-to-date findings on biosensors for the screening of antibiotic residues in food products of animal origin. Biosensors are constituted of a bioreceptor and a transducer. In the detection of antibiotic residues, even though antibodies were the first bioreceptors to be used, new kinds of bioreceptors are being developed more and more (enzymes, aptamers, MIPs); their advantages and drawbacks are discussed in this review. The different categories of transducers (electrochemical, mass-based biosensors, optical and thermal) and their potential applications for the screening of antibiotic residues in food are presented. Moreover, the advantages and drawbacks of the different types of transducers are discussed. Lastly, outlook and the future development of biosensors for the control of antibiotic residues in food are highlighted. Copyright © 2016. Published by Elsevier B.V.

Screening diabetes in tuberculosis patients in eastern rural China: a community-based cross-sectional study.

PubMed

Zhao, Q; Xiao, X; Lu, W; Qiu, L-X; Zhou, C-M; Jiang, W-L; Xu, B; Diwan, V

2016-10-01

To understand the prevalence of diabetes mellitus (DM) and tuberculosis (TB) comorbidity in rural China and to identify factors associated with TB-DM comorbidity and screening efficacy. A community-based cross-sectional study was carried out in four counties in eastern rural China. All TB patients newly registered from April 2013 to March 2014 were screened for DM using fasting blood glucose (FBG). Screening-positive patients were further examined using glycosylated haemoglobin A1C (HbA1c). Ninety-seven (7.7%) of the 1252 recruited TB patients had DM, 44 (45.4%) of whom were newly diagnosed. The DM-TB patients were significantly older than non-diabetics (mean age 57 ± 13 years vs. 49 ± 19 years, P < 0.001). The risk of DM-TB was higher in patients aged >40 years (OR 3.039) and in overweight patients (OR 2.595). The number needed to screen (NNS) among TB patients to identify one case of DM was 12.97. The NNS to identify one new DM patient (27.4) was lower in participants aged >40 years (20.5), those who were illiterate (19.9), those with a family history of DM (9.3), those with missing bacille Calmette-Guérin vaccination (11.3), current smokers (14.2) and those with body mass index >24 (11.4). Regular DM screening in TB patients is practical in rural China. Better efficacy of DM-TB detection could be obtained by screening high-risk populations, such as overweight TB patients or those with a family history of DM.

Epidemiology and control of enterobiasis in a developmental center

PubMed Central

Lohiya, Ghan-Shyam; Tan-Figueroa, Lilia; Crinella, Francis M; Lohiya, Sonia

2000-01-01

Objective To determine if enterobiasis could be controlled in a developmental center. Design Population-based study. Annual screening of all residents by perianal swabs for enterobiasis and on admission or discharge. Treatment of infected residents and their contacts with mebendazole, 100 mg orally, with two doses given 14 days apart. Main outcome measures The number of residents with enterobiasis and the cost of the program. Results The prevalence of enterobiasis fell rapidly and progressively, from 21% before mass medication to 1% after 3 years. Conclusion Mass medication of residents with enterobiasis and their contacts was beneficial, harmless, and cost effective. PMID:10832422

An Evidence-Based Case Study of Unilateral Shin Splints: Do Red Flags Function in Paediatric Osteosarcoma?

PubMed

Rankin, Anne

2015-01-01

Physiotherapists use red flags to screen for serious pathology. Paediatric osteosarcoma is a rare disease, occurring predominantly in the area of the knee and shoulder, and it is not always included by physiotherapists on a differential diagnosis list. Traditional red flags do not always correspond to the initial signs and symptoms of osteosarcoma. Physiotherapists should routinely palpate along the length of the bone to detect a potential mass. The detection of a mass or symptoms that do not follow the expected course indicates the need for reassessment and possibly referral for further investigation.

Performance characterization of a combined material identification and screening algorithm

NASA Astrophysics Data System (ADS)

Green, Robert L.; Hargreaves, Michael D.; Gardner, Craig M.

2013-05-01

Portable analytical devices based on a gamut of technologies (Infrared, Raman, X-Ray Fluorescence, Mass Spectrometry, etc.) are now widely available. These tools have seen increasing adoption for field-based assessment by diverse users including military, emergency response, and law enforcement. Frequently, end-users of portable devices are non-scientists who rely on embedded software and the associated algorithms to convert collected data into actionable information. Two classes of problems commonly encountered in field applications are identification and screening. Identification algorithms are designed to scour a library of known materials and determine whether the unknown measurement is consistent with a stored response (or combination of stored responses). Such algorithms can be used to identify a material from many thousands of possible candidates. Screening algorithms evaluate whether at least a subset of features in an unknown measurement correspond to one or more specific substances of interest and are typically configured to detect from a small list potential target analytes. Thus, screening algorithms are much less broadly applicable than identification algorithms; however, they typically provide higher detection rates which makes them attractive for specific applications such as chemical warfare agent or narcotics detection. This paper will present an overview and performance characterization of a combined identification/screening algorithm that has recently been developed. It will be shown that the combined algorithm provides enhanced detection capability more typical of screening algorithms while maintaining a broad identification capability. Additionally, we will highlight how this approach can enable users to incorporate situational awareness during a response.

21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Recruitment methods employed in the prostate, lung, colorectal, and ovarian cancer screening trial

PubMed Central

Gren, Lisa; Broski, Karen; Childs, Jeffery; Cordes, Jill; Engelhard, Deborah; Gahagan, Betsy; Gamito, Eduard; Gardner, Vivien; Geisser, Mindy; Higgins, Darlene; Jenkins, Victoria; Lamerato, Lois; Lappe, Karen; Lowery, Heidi; McGuire, Colleen; Miedzinski, Mollie; Ogden, Sheryl; Tenorio, Sally; Watt, Gavin; Wohlers, Bonita; Marcus, Pamela

2015-01-01

Background The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) is a US National Cancer Institute (NCI)-funded randomized controlled trial designed to evaluate whether certain screening tests reduce mortality from prostate, lung, colorectal, and ovarian cancer. To obtain adequate statistical power, it was necessary to enroll over 150,000 healthy volunteers. Recruitment began in 1993 and ended in 2001. Purpose Our goal is to evaluate the success of recruitment methods employed by the 10 PLCO screening centers. We also provide estimates of recruitment yield and cost for our most successful strategy, direct mail. Methods Each screening center selected its own methods of recruitment. Methods changed throughout the recruitment period as needed. For this manuscript, representatives from each screening center provided information on methods utilized and their success. Results In the United States between 1993 and 2001, ten screening centers enrolled 154,934 study participants. Based on participant self-report, an estimated 95% of individuals were recruited by direct mail. Overall, enrollment yield for direct mail was 1.0%. Individual center enrollment yield ranged from 0.7% to 3.8%. Cost per enrolled participant was $9.64–35.38 for direct mail, excluding personnel costs. Limitations Numeric data on recruitment processes were not kept consistently at individual screening centers. Numeric data in this manuscript are based on the experiences of 5 of the 10 centers. Conclusions Direct mail, using rosters of names and addresses from profit and not-for-profit (including government) organizations, was the most successful and most often used recruitment method. Other recruitment strategies, such as community outreach and use of mass media, can be an important adjunct to direct mail in recruiting minority populations. PMID:19254935

[Cost effectiveness of mass orthoptic screening in kindergarten for early detection of developmental vision disorders].

PubMed

König, H H; Barry, J C; Leidl, R; Zrenner, E

2000-04-01

Orthoptic screening in the kindergarten is one option to improve early detection of amblyopia in children aged 3 years. The purpose of this study was to analyse the cost-effectiveness of such a screening programme in Germany. Based on data from the literature and own experience gained from orthoptic screening in kindergarten a decision-analytic model was developed. According to the model, all children in kindergarten, aged 3 years, who had not been treated for amblyopia before, were subjected to an orthoptic examination. Non-cooperative children were reexamined in kindergarten after one year. Children with positive test results were examined by an ophthalmologist for diagnosis. Effects were measured by the number of newly diagnosed cases of amblyopia, non-obvious strabismus and amblyogenic refractive errors. Direct costs were estimated from a third-party payer perspective. The influence of uncertain model parameters was tested by sensitivity analysis. In the base analysis the cost per orthoptic screening test was DM 15.39. Examination by an ophthalmologist cost DM 71.20. The total cost of the screening programme in all German kindergartens was DM 6.1 million. With a 1.5% age-specific prevalence of undiagnosed cases, a sensitivity of 95% and a specificity of 98%, a total of 4,261 new cases would be detected. The cost-effectiveness ratio was DM 1,421 per case detected. Sensitivity analysis showed considerable influence of prevalence and specificity on the cost-effectiveness ratio. It was more cost-effective to re-screen non-cooperative children in kindergarten than to have them examined by an ophthalmologist straight-away. The decision-analytic model showed stable results which may serve as a basis for discussion on the implementation of orthoptic screening and for planning a field study.

Cost and Efficacy Assessment of an Alternative Medication Compliance Urine Drug Testing Strategy.

PubMed

Doyle, Kelly; Strathmann, Frederick G

2017-02-01

This study investigates the frequency at which quantitative results provide additional clinical benefit compared to qualitative results alone. A comparison between alternative urine drug screens and conventional screens including the assessment of cost-to-payer differences, accuracy of prescription compliance or polypharmacy/substance abuse was also included. In a reference laboratory evaluation of urine specimens from across the United States, 213 urine specimens with provided prescription medication information (302 prescriptions) were analyzed by two testing algorithms: 1) conventional immunoassay screen with subsequent reflexive testing of positive results by quantitative mass spectrometry; and 2) a combined immunoassay/qualitative mass-spectrometry screen that substantially reduced the need for subsequent testing. The qualitative screen was superior to immunoassay with reflex to mass spectrometry in confirming compliance per prescription (226/302 vs 205/302), and identifying non-prescription abuse (97 vs 71). Pharmaceutical impurities and inconsistent drug metabolite patterns were detected in only 3.8% of specimens, suggesting that quantitative results have limited benefit. The percentage difference between the conventional testing algorithm and the alternative screen was projected to be 55%, and a 2-year evaluation of test utilization as a measure of test order volume follows an exponential trend for alternative screen test orders over conventional immunoassay screens that require subsequent confirmation testing. Alternative, qualitative urine drug screens provide a less expensive, faster, and more comprehensive evaluation of patient medication compliance and drug abuse. The vast majority of results were interpretable with qualitative results alone indicating a reduced need to automatically reflex to quantitation or provide quantitation for the majority of patients. This strategy highlights a successful approach using an alternative strategy for both the laboratory and physician to align clinical needs while being mindful of costs.

With the Advent of Tomosynthesis in the Workup of Mammographic Abnormality, is Spot Compression Mammography Now Obsolete? An Initial Clinical Experience.

PubMed

Ni Mhuircheartaigh, Neasa; Coffey, Louise; Fleming, Hannah; O' Doherty, Ann; McNally, Sorcha

2017-09-01

To determine if the routine use of spot compression mammography is now obsolete in the assessment of screen detected masses, asymmetries and architectural distortion since the availability of digital breast tomosynthesis. We introduced breast tomosynthesis in the workup of screen detected abnormalities in our screening center in January 2015. During an initial learning period with tomosynthesis standard spot compression views were also performed. Three consultant breast radiologists retrospectively reviewed all screening mammograms recalled for assessment over the first 6-month period. We assessed retrospectively whether there was any additional diagnostic information obtained from spot compression views not already apparent on tomography. All cases were also reviewed for any additional lesions detected by tomosynthesis, not detected on routine 2-view screening mammography. 548 women screened with standard 2-view digital screening mammography were recalled for assessment in the selected period and a total of 565 lesions were assessed. 341 lesions were assessed by both tomosynthesis and routine spot compression mammography. The spot compression view was considered more helpful than tomosynthesis in only one patient. This was because the breast was inadequately positioned for tomosynthesis and the area in question was not adequately imaged. Apart from this technical error there was no asymmetry, distortion or mass where spot compression provided more diagnostic information than tomosynthesis alone. We detected three additional cancers on tomosynthesis, not detected by routine screening mammography. From our initial experience with tomosynthesis we conclude that spot compression mammography is now obsolete in the assessment of screen detected masses, asymmetries and distortions where tomosynthesis is available. © 2017 Wiley Periodicals, Inc.

Pathology consultation on urine compliance testing and drug abuse screening.

PubMed

Ward, Michael B; Hackenmueller, Sarah A; Strathmann, Frederick G

2014-11-01

Compliance testing in pain management requires a distinct approach compared with classic clinical toxicology testing. Differences in the patient populations and clinical expectations require modifications to established reporting cutoffs, assay performance expectations, and critical review of how best to apply the available testing methods. Although other approaches to testing are emerging, immunoassay screening followed by mass spectrometry confirmation remains the most common testing workflow for pain management compliance and drug abuse testing. A case-based approach was used to illustrate the complexities inherent to and uniqueness of pain management compliance testing for both clinicians and laboratories. A basic understanding of the inherent strengths and weaknesses of immunoassays and mass spectrometry provides the clinician a better understanding of how best to approach pain management compliance testing. Pain management compliance testing is a textbook example of an emerging field requiring open communication between physician and performing laboratory to fully optimize patient care. Copyright© by the American Society for Clinical Pathology.

Assessing rare earth elements in quartz rich geological samples.

PubMed

Santoro, A; Thoss, V; Ribeiro Guevara, S; Urgast, D; Raab, A; Mastrolitti, S; Feldmann, J

2016-01-01

Sodium peroxide (Na2O2) fusion coupled to Inductively Coupled Plasma Tandem Mass Spectrometry (ICP-MS/MS) measurements was used to rapidly screen quartz-rich geological samples for rare earth element (REE) content. The method accuracy was checked with a geological reference material and Instrumental Neutron Activation Analysis (INAA) measurements. The used mass-mode combinations presented accurate results (only exception being (157)Gd in He gas mode) with recovery of the geological reference material QLO-1 between 80% and 98% (lower values for Lu, Nd and Sm) and in general comparable to INAA measurements. Low limits of detection for all elements were achieved, generally below 10 pg g(-1), as well as measurement repeatability below 15%. Overall, the Na2O2/ICP-MS/MS method proved to be a suitable lab-based method to quickly and accurately screen rock samples originating from quartz-rich geological areas for rare earth element content; particularly useful if checking commercial viability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interventions to enhance informed choices among invitees of screening programmes-a systematic review.

PubMed

van Agt, Heleen M E; Korfage, Ida J; Essink-Bot, Marie-Louise

2014-10-01

Informed decision making about participation has become an explicit purpose in invitations for screening programmes in western countries. An informed choice is commonly defined as based on: (i) adequate levels of knowledge of the screening and (ii) agreement between the invitee's values towards own screening participation and actual (intention to) participation. We systematically reviewed published studies that empirically evaluated the effects of interventions aiming at enhancing informed decision making in screening programmes targeted at the general population. We focused on prenatal screening and neonatal screening for diseases of the foetus/new-born and screening for breast cancer, cervical cancer and colorectal cancer. The Medline, EMBASE and Cochrane databases were searched for studies published till April 2012, using the terms 'informed choice', 'decision making' and 'mass screening' separately and in combination and terms referring to the specific screening programmes. Of the 2238 titles identified, 15 studies were included, which evaluated decision aids (DAs), information leaflets, film, video, counselling and a specific screening visit for informed decision making in prenatal screening, breast and colorectal cancer screening. Most of the included studies evaluated DAs and showed improved knowledge and informed decision making. Due to the limited number of studies the results could not be synthesized. The empirical evidence regarding interventions to improve informed decision making in screening is limited. It is unknown which strategies to enhance informed decision making are most effective, although DAs are promising. Systematic development of interventions to enhance informed choices in screening deserves priority, especially in disadvantaged groups. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Multi-constituent cardiovascular pills (MCCP)--challenges and promises of population-based prophylactic drug therapy for prevention of heart attack.

PubMed

Jamieson, Michael J; Naghavi, Morteza

2007-01-01

Risk factors for atherosclerotic cardiovascular disease (CVD) are highly co-prevalent but poorly identified and treated. The Screening for Heart Attack Prevention and Education (SHAPE) Task Force from the Association for Eradication of Heart Attack (AEHA) has recently proposed a new strategy that recommends screening for subclinical atherosclerosis and implementing aggressive treatment of "vulnerable patients". The Task Force has also envisioned future developments that may shift mass screening strategies to mass prophylactic therapy. The "Polypill" concept, introduced by Wald and Law suggests a combination of statin, low-dose antihypertensives, aspirin and folic acid, in a single pill, taken prophylactically by high risk population can cut CVD event rates by as much as 80%. In this communication, we review the challenges and promises of such a strategy. "Polypill" is but one of an astronomical number of possible multiconstituent pills (MCCP). Attractive as the MCCP concept is, it lacks evidence from randomized controlled trials, and begs numerous questions about the credibility of the concept, the design and synthesis of such complex pills, pharmacokinetics, pharmacodynamics, bioequivalence, "class" vs. unique properties, interactions, evidence of clinical efficacy and safety, regulatory approval, post-marketing surveillance, prescription vs. over-the-counter use, responsibility for initiating and monitoring therapy, patient education, counterfeiting and importation, reimbursement, advertisement, patent protection, commercial viability, etc. If these issues are favorably addressed, MCCP stand to dramatically change the manner in which CVD is prevented particularly in developing societies. Notwithstanding, assuming low commercial interests, realizing the promises of MCCP will demand serious attention from national public health policymakers. The clinical and regulatory implications of population-based secondary prevention (which rely on a different evidence base, and in which entirely different risk-benefit and cost-effectiveness considerations apply) remain issues for active debate.

Value of screening endoscopy in evaluation of esophageal, gastric and colon cancers

PubMed Central

Ro, Tae H; Mathew, Michelle A; Misra, Subhasis

2015-01-01

Esophageal, gastric, and colorectal cancers are deadly diseases that continue to plague our world today. The value of screening endoscopy in evaluating these types of cancers is a critical area of discussion due to a potential reduction in morbidity and mortality. This article describes how to identify a good screening test and explains what are important criteria in the field of screening endoscopy. Furthermore, the current status and progress of screening endoscopy for esophageal, gastric, and colorectal cancer will be evaluated and discussed. Mass screening programs have not been implemented for esophageal and gastric carcinomas in those with average or low risk populations. However, studies of high-risk populations have found value and a cost-benefit in conducting screening endoscopy. Colorectal cancer, on the other hand, has had mass screening programs in place for many years due to the clear evidence of improved outcomes. As the role of endoscopy as a screening tool has continued to develop, newer technology and techniques have emerged to improve its utility. Many new image enhancement techniques and computer processing programs have shown promise and may have a significant role in the future of endoscopic screening. These developments are paving the way for improving the diagnostic and therapeutic capability of endoscopy in the field of gastroenterology. PMID:26361416

Value of screening endoscopy in evaluation of esophageal, gastric and colon cancers.

PubMed

Ro, Tae H; Mathew, Michelle A; Misra, Subhasis

2015-09-07

Esophageal, gastric, and colorectal cancers are deadly diseases that continue to plague our world today. The value of screening endoscopy in evaluating these types of cancers is a critical area of discussion due to a potential reduction in morbidity and mortality. This article describes how to identify a good screening test and explains what are important criteria in the field of screening endoscopy. Furthermore, the current status and progress of screening endoscopy for esophageal, gastric, and colorectal cancer will be evaluated and discussed. Mass screening programs have not been implemented for esophageal and gastric carcinomas in those with average or low risk populations. However, studies of high-risk populations have found value and a cost-benefit in conducting screening endoscopy. Colorectal cancer, on the other hand, has had mass screening programs in place for many years due to the clear evidence of improved outcomes. As the role of endoscopy as a screening tool has continued to develop, newer technology and techniques have emerged to improve its utility. Many new image enhancement techniques and computer processing programs have shown promise and may have a significant role in the future of endoscopic screening. These developments are paving the way for improving the diagnostic and therapeutic capability of endoscopy in the field of gastroenterology.

Direct determination of trace phthalate esters in alcoholic spirits by spray-inlet microwave plasma torch ionization tandem mass spectrometry.

PubMed

Miao, Meng; Zhao, Gaosheng; Xu, Li; Dong, Junguo; Cheng, Ping

2018-03-01

A direct analytical method based on spray-inlet microwave plasma torch tandem mass spectrometry was applied to simultaneously determine 4 phthalate esters (PAEs), namely, benzyl butyl phthalate, diethyl phthalate, dipentyl phthalate, and dodecyl phthalate with extremely high sensitivity in spirits without sample treatment. Among the 4 brands of spirit products, 3 kinds of PAE compounds were directly determined at very low concentrations from 1.30 to 114 ng·g -1 . Compared with other online and off-line methods, the spray-inlet microwave plasma torch tandem mass spectrometry technique is extremely simple, rapid, sensitive, and high efficient, providing an ideal screening tool for PAEs in spirits. Copyright © 2017 John Wiley & Sons, Ltd.

Accurate mass screening and identification of emerging contaminants in environmental samples by liquid chromatography-hybrid linear ion trap Orbitrap mass spectrometry.

PubMed

Hogenboom, A C; van Leerdam, J A; de Voogt, P

2009-01-16

The European Reach legislation will possibly drive producers to develop newly designed chemicals that will be less persistent, bioaccumulative or toxic. If this innovation leads to an increased use of more hydrophilic chemicals it may result in higher mobilities of chemicals in the aqueous environment. As a result, the drinking water companies may face stronger demands on removal processes as the hydrophilic compounds inherently are more difficult to remove. Monitoring efforts will also experience a shift in focus to more water-soluble compounds. Screening source waters on the presence of (emerging) contaminants is an essential step in the control of the water cycle from source to tap water. In this article, some of our experiences are presented with the hybrid linear ion trap (LTQ) FT Orbitrap mass spectrometer, in the area of chemical water analysis. A two-pronged strategy in mass spectrometric research was employed: (i) exploring effluent, surface, ground- and drinking-water samples searching for accurate masses corresponding to target compounds (and their product ions) known from, e.g. priority lists or the scientific literature and (ii) full-scan screening of water samples in search of 'unknown' or unexpected masses, followed by MS(n) experiments to elucidate the structure of the unknowns. Applications of both approaches to emerging water contaminants are presented and discussed. Results are presented for target analysis search for pharmaceuticals, benzotriazoles, illicit drugs and for the identification of unknown compounds in a groundwater sample and in a polar extract of a landfill soil sample (a toxicity identification evaluation bioassay sample). The applications of accurate mass screening and identification described in this article demonstrate that the LC-LTQ FT Orbitrap MS is well equipped to meet the challenges posed by newly emerging polar contaminants.

Screening of the binding of small molecules to proteins by desorption electrospray ionization mass spectrometry combined with protein microarray.

PubMed

Yao, Chenxi; Wang, Tao; Zhang, Buqing; He, Dacheng; Na, Na; Ouyang, Jin

2015-11-01

The interaction between bioactive small molecule ligands and proteins is one of the important research areas in proteomics. Herein, a simple and rapid method is established to screen small ligands that bind to proteins. We designed an agarose slide to immobilize different proteins. The protein microarrays were allowed to interact with different small ligands, and after washing, the microarrays were screened by desorption electrospray ionization mass spectrometry (DESI MS). This method can be applied to screen specific protein binding ligands and was shown for seven proteins and 34 known ligands for these proteins. In addition, a high-throughput screening was achieved, with the analysis requiring approximately 4 s for one sample spot. We then applied this method to determine the binding between the important protein matrix metalloproteinase-9 (MMP-9) and 88 small compounds. The molecular docking results confirmed the MS results, demonstrating that this method is suitable for the rapid and accurate screening of ligands binding to proteins. Graphical Abstract ᅟ.

Predicting the risk for colorectal cancer with personal characteristics and fecal immunochemical test.

PubMed

Li, Wen; Zhao, Li-Zhong; Ma, Dong-Wang; Wang, De-Zheng; Shi, Lei; Wang, Hong-Lei; Dong, Mo; Zhang, Shu-Yi; Cao, Lei; Zhang, Wei-Hua; Zhang, Xi-Peng; Zhang, Qing-Huai; Yu, Lin; Qin, Hai; Wang, Xi-Mo; Chen, Sam Li-Sheng

2018-05-01

We aimed to predict colorectal cancer (CRC) based on the demographic features and clinical correlates of personal symptoms and signs from Tianjin community-based CRC screening data.A total of 891,199 residents who were aged 60 to 74 and were screened in 2012 were enrolled. The Lasso logistic regression model was used to identify the predictors for CRC. Predictive validity was assessed by the receiver operating characteristic (ROC) curve. Bootstrapping method was also performed to validate this prediction model.CRC was best predicted by a model that included age, sex, education level, occupations, diarrhea, constipation, colon mucosa and bleeding, gallbladder disease, a stressful life event, family history of CRC, and a positive fecal immunochemical test (FIT). The area under curve (AUC) for the questionnaire with a FIT was 84% (95% CI: 82%-86%), followed by 76% (95% CI: 74%-79%) for a FIT alone, and 73% (95% CI: 71%-76%) for the questionnaire alone. With 500 bootstrap replications, the estimated optimism (<0.005) shows good discrimination in validation of prediction model.A risk prediction model for CRC based on a series of symptoms and signs related to enteric diseases in combination with a FIT was developed from first round of screening. The results of the current study are useful for increasing the awareness of high-risk subjects and for individual-risk-guided invitations or strategies to achieve mass screening for CRC.

Multiplatform Mass Spectrometry-Based Approach Identifies Extracellular Glycolipids of the Yeast Rhodotorula babjevae UCDFST 04-877.

PubMed

Cajka, Tomas; Garay, Luis A; Sitepu, Irnayuli R; Boundy-Mills, Kyria L; Fiehn, Oliver

2016-10-28

A multiplatform mass spectrometry-based approach was used for elucidating extracellular lipids with biosurfactant properties produced by the oleaginous yeast Rhodotorula babjevae UCDFST 04-877. This strain secreted 8.6 ± 0.1 g/L extracellular lipids when grown in a benchtop bioreactor fed with 100 g/L glucose in medium without addition of hydrophobic substrate, such as oleic acid. Untargeted reversed-phase liquid chromatography-quadrupole/time-of-flight mass spectrometry (QTOFMS) detected native glycolipid molecules with masses of 574-716 Da. After hydrolysis into the fatty acid and sugar components and hydrophilic interaction chromatography-QTOFMS analysis, the extracellular lipids were found to consist of hydroxy fatty acids and sugar alcohols. Derivatization and chiral separation gas chromatography-mass spectrometry (GC-MS) identified these components as d-arabitol, d-mannitol, (R)-3-hydroxymyristate, (R)-3-hydroxypalmitate, and (R)-3-hydroxystearate. In order to assemble these substructures back into intact glycolipids that were detected in the initial screen, potential structures were in-silico acetylated to match the observed molar masses and subsequently characterized by matching predicted and observed MS/MS fragmentation using the Mass Frontier software program. Eleven species of acetylated sugar alcohol esters of hydroxy fatty acids were characterized for this yeast strain.

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

Microplate assay for screening the antibacterial activity of Schiff bases derived from substituted benzopyran-4-one.

PubMed

Amin, Rehab M; Abdel-Kader, Nora S; El-Ansary, Aida L

2012-09-01

Schiff bases (SB(1)-SB(3)) were synthesized from the condensation of 6-formyl-7-hydroxy-5-methoxy-2-methylbenzopyran-4-one with 2-aminopyridine (SB(1)), p-phenylenediamine (SB(2)) and o-phenylenediamine (SB(3)), while Schiff bases (SB(4)-SB(6)) were synthesized by condensation of 5,7-dihydroxy-6-formyl-2-methylbenzopyran-4-one with 2-aminopyridine (SB(4)), p-phenylenediamine (SB(5)) and o-phenylenediamine (SB(6)). Schiff bases were characterized using elemental analysis, IR, UV-Vis, (1)H NMR, (13)C NMR and mass spectroscopy. These compounds were screened for antibacterial activities by micro-plate assay technique. Escherichia coli and Staphylococcus capitis were exposed to different concentrations of the Schiff bases. Results showed that the antibacterial effect of these Schiff bases on Gram-negative bacteria were higher than that on Gram-positive bacteria moreover, the Schiff bases containing substituent OCH(3) on position five have higher antibacterial activity than that containing hydroxy group on the same position. Copyright © 2012 Elsevier B.V. All rights reserved.

Target discovery of cytotoxic withanolides from Physalis angulata var. villosa via reactivity-based screening.

PubMed

Zhang, Yi; Chen, Chen; Zhang, Ya-Long; Kong, Ling-Yi; Luo, Jian-Guang

2018-03-20

The reactivity-based screening (RBS) was developed for directed discovery of cytotoxic withanolides. In this study, a thiol probe, 4-chlorobenzenethiol, was used to selectively attack cytotoxic withanolides containing potential pharmacophore, 2(3)-en-1-one in ring A (AEO) and 5β,6β-epoxy in ring B (BE), from the plant extract of Physalis angulata var. villosa. The screening was performed based on the potential mechanism of 4-chlorobenzenethiol nucleophilic addition to AEO, followed by detection of adducts using liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS). Guided by RBS, eleven target withanolides, including five new compounds, physagulides R-V (10-14) and six known ones (2, 7-9, 15, 16) were discovered. All of them exhibited cytotoxicity against the both tested cell lines, especially, compounds 2, 7, 8 and 14 showed potent activities with IC 50 values of 1.57-6.29 μM. The results suggested that RBS was efficient and accurate for rapid identification of cytotoxic withanolides and could guide isolation of target components from the complex medicinal plant extract. Copyright © 2018 Elsevier B.V. All rights reserved.

Online versus paper-based screening for depression and anxiety in adults with cystic fibrosis in Ireland: a cross-sectional exploratory study.

PubMed

Cronly, Jennifer; Duff, Alistair J; Riekert, Kristin A; Perry, Ivan J; Fitzgerald, Anthony P; Horgan, Aine; Lehane, Elaine; Howe, Barbara; Ni Chroinin, Muireann; Savage, Eileen

2018-01-21

To compare online and paper-based screening for depression and anxiety in adults with cystic fibrosis (CF). Cross-sectional study in CF clinics in Ireland and through the Cystic Fibrosis Ireland online community. 160 adult patients aged 18 or above were recruited. Of these, 147 were included in the analysis; 83 online and 64 paper-based. The remaining 13 were excluded because of incomplete data. Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Data on pulmonary function (forced expiratory volume in 1 s %) and body mass index were self-reported based on clinical assessments. Sociodemographic data were collected. Compared with the paper-based participants, the online participants were more likely to be female (61.7% vs 48.4%), older (mean 32.2 vs 28.2 years) and were more likely to be married (32.5% vs 15.6%), living with their spouse or partner (42.5% vs 22.6%) and working either full time (33.7% vs 15.9%) or part time (30.1%vs 17.5%). The prevalence rates of elevated anxiety and depression were not significantly different (P=0.71 and P=0.56). HADS anxiety and depression scores were not statistically different between online (P=0.83) and paper-based (P=0.92) participants based on Mann-Whitney U test. A significant negative correlation was found between depression and pulmonary function (r=-0.39, P=0.01) and anxiety and pulmonary function (r=-0.36, P=0.02). Based on Cronbach's alpha, there were no statistically significant differences between the online and paper-based participants on the internal consistency of the HADS anxiety (P=0.073) and depression (P=0.378) scales. Our findings suggest that online and paper-based screening for depression and anxiety in adult patients with CF yield comparable findings on prevalence rates and scores, associations with health and internal consistency of subscales. This study highlights that online screening offers an alternative method to paper-based screening. Further research with a larger sample and assessment of measurement equivalence between online and paper based screening is needed to confirm our results. © 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.

A Hadoop-based Molecular Docking System

NASA Astrophysics Data System (ADS)

Dong, Yueli; Guo, Quan; Sun, Bin

2017-10-01

Molecular docking always faces the challenge of managing tens of TB datasets. It is necessary to improve the efficiency of the storage and docking. We proposed the molecular docking platform based on Hadoop for virtual screening, it provides the preprocessing of ligand datasets and the analysis function of the docking results. A molecular cloud database that supports mass data management is constructed. Through this platform, the docking time is reduced, the data storage is efficient, and the management of the ligand datasets is convenient.

Development and validation of risk models to select ever-smokers for CT lung-cancer screening

PubMed Central

Katki, Hormuzd A.; Kovalchik, Stephanie A.; Berg, Christine D.; Cheung, Li C.; Chaturvedi, Anil K.

2016-01-01

Importance The US Preventive Services Task Force (USPSTF) recommends computed-tomography (CT) lung-cancer screening for ever-smokers ages 55-80 years who smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung-cancer risk calculations may be more effective and efficient than current USPSTF recommendations. Objective Comparison of modeled outcomes from risk-based CT lung-screening strategies versus USPSTF recommendations. Design/Setting/Participants Empirical risk models for lung-cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age, education, sex, race, smoking intensity/duration/quit-years, Body Mass Index, family history of lung-cancer, and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the US. Models applied to US ever-smokers ages 50-80 (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung-screening, assuming screening for all ever-smokers yields the percent changes in lung-cancer detection and death observed in the NLST. Exposure Annual CT lung-screening for 3 years. Main Outcomes and Measures Model validity: calibration (number of model-predicted cases divided by number of observed cases (Estimated/Observed)) and discrimination (Area-Under-Curve (AUC)). Modeled screening outcomes: estimated number of screen-avertable lung-cancer deaths, estimated screening effectiveness (number needed to screen (NNS) to prevent 1 lung-cancer death). Results Lung-cancer incidence and death risk models were well-calibrated in PLCO and NLST. The lung-cancer death model calibrated and discriminated well for US ever-smokers ages 50-80 (NHIS 1997-2001: Estimated/Observed=0.94, 95%CI=0.84-1.05; AUC=0.78, 95%CI=0.76-0.80). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung-cancer screening and 46,488 (95%CI=43,924-49,053) lung-cancer deaths were estimated as screen-avertable over 5 years (estimated NNS=194, 95%CI=187-201). In contrast, risk-based selection screening the same number of ever-smokers (9.0 million) at highest 5-year lung-cancer risk (≥1.9%), was estimated to avert 20% more deaths (55,717; 95%CI=53,033-58,400) and was estimated to reduce the estimated NNS by 17% (NNS=162, 95%CI=157-166). Conclusions and Relevance Among a cohort of US ever-smokers age 50-80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung-cancer deaths prevented over 5 years along with a lower NNS to prevent 1 lung-cancer death. PMID:27179989

Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening.

PubMed

Katki, Hormuzd A; Kovalchik, Stephanie A; Berg, Christine D; Cheung, Li C; Chaturvedi, Anil K

2016-06-07

The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations. Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations. Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST. Annual CT lung screening for 3 years beginning at age 50 years. For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death). Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US ever-smokers aged 50 to 80 years (NHIS 1997-2001: estimated/observed = 0.94 [95%CI, 0.84-1.05]; AUC, 0.78 [95%CI, 0.76-0.80]). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung cancer screening and 46,488 (95% CI, 43,924-49,053) lung cancer deaths were estimated as screen-avertable over 5 years (estimated NNS, 194 [95% CI, 187-201]). In contrast, risk-based selection screening of the same number of ever-smokers (9.0 million) at highest 5-year lung cancer risk (≥1.9%) was estimated to avert 20% more deaths (55,717 [95% CI, 53,033-58,400]) and was estimated to reduce the estimated NNS by 17% (NNS, 162 [95% CI, 157-166]). Among a cohort of US ever-smokers aged 50 to 80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung cancer deaths prevented over 5 years, along with a lower NNS to prevent 1 lung cancer death.

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.

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.

Integrated quantification and identification of aldehydes and ketones in biological samples.

PubMed

Siegel, David; Meinema, Anne C; Permentier, Hjalmar; Hopfgartner, Gérard; Bischoff, Rainer

2014-05-20

The identification of unknown compounds remains to be a bottleneck of mass spectrometry (MS)-based metabolomics screening experiments. Here, we present a novel approach which facilitates the identification and quantification of analytes containing aldehyde and ketone groups in biological samples by adding chemical information to MS data. Our strategy is based on rapid autosampler-in-needle-derivatization with p-toluenesulfonylhydrazine (TSH). The resulting TSH-hydrazones are separated by ultrahigh-performance liquid chromatography (UHPLC) and detected by electrospray ionization-quadrupole-time-of-flight (ESI-QqTOF) mass spectrometry using a SWATH (Sequential Window Acquisition of all Theoretical Fragment-Ion Spectra) data-independent high-resolution mass spectrometry (HR-MS) approach. Derivatization makes small, poorly ionizable or retained analytes amenable to reversed phase chromatography and electrospray ionization in both polarities. Negatively charged TSH-hydrazone ions furthermore show a simple and predictable fragmentation pattern upon collision induced dissociation, which enables the chemo-selective screening for unknown aldehydes and ketones via a signature fragment ion (m/z 155.0172). By means of SWATH, targeted and nontargeted application scenarios of the suggested derivatization route are enabled in the frame of a single UHPLC-ESI-QqTOF-HR-MS workflow. The method's ability to simultaneously quantify and identify molecules containing aldehyde and ketone groups is demonstrated using 61 target analytes from various compound classes and a (13)C labeled yeast matrix. The identification of unknowns in biological samples is detailed using the example of indole-3-acetaldehyde.

Simple and rapid screening procedure for 143 new psychoactive substances by liquid chromatography-tandem mass spectrometry.

PubMed

Adamowicz, Piotr; Tokarczyk, Bogdan

2016-07-01

In recent years, many new psychoactive substances (NPS) from several drug classes have appeared on the drug market. These substances, also known as 'legal highs', belong to different chemical classes. Despite the increasing number of NPS, there are few comprehensive screening methods for their detection in biological specimens. In this context, the purpose of this study was to develop a fast and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening procedure for NPS in blood. The elaborated method allows the simultaneous screening of 143 compounds from different groups (number of compounds): cathinones (36), phenethylamines (26), tryptamines (18), piperazines (9), piperidines (2), synthetic cannabinoids (34), arylalkylamines (7), arylcyclohexylamines (3), aminoindanes (2), and other drugs (6). Blood samples (0.2 mL) were precipitated with acetonitrile (0.6 mL). The separation was achieved with gradient mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water in 14 min. Detection of all compounds was based on multiple reaction monitoring (MRM) transitions. The total number of transitions monitored in dynamic mode was 432. The whole procedure was rapid and simple. The limits of detection (LODs) estimated for 104 compounds were in the range 0.01-3.09 ng/mL. The extraction recoveries determined for 32 compounds were from 1.8 to 133%. The procedure was successfully applied to the analysis of forensic blood samples in routine casework. The developed method should have wide applicability for rapid screening of new drugs of abuse in forensic or clinical samples. The procedure can be easily expanded for more substances. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of the LTQ-Orbitrap mass spectrometer for the analysis of polymerase chain reaction products.

PubMed

Manduzio, Hélène; Ezan, Eric; Fenaille, François

2010-12-30

We have investigated the potential and robustness of the off-line coupling of polymerase chain reaction (PCR) with electrospray ionization mass spectrometry (ESI-MS), for further applications in the screening of single-nucleotide polymorphisms (SNPs). This was based on recently reported data demonstrating that anion-exchange solid-phase extraction was the most efficient technique for efficiently desalting PCR products, with a recovery of ∼70%. Results showed that this purification approach efficiently removes almost all the chemicals commonly added to PCR buffers. ESI-MS analysis of a model 114-bp PCR product performed on the LTQ-Orbitrap instrument demonstrated that detection limits in the nM range along with an average mass measurement uncertainty of 9.15 ± 7.11 ppm can be routinely obtained using an external calibration. The PCR/ESI-MS platform was able to detect just a few copies of a targeted oligonucleotide. However, it was shown that if two PCR products are present in a mixture in a ratio higher than 10 to 1, the lower abundance one might not be reproducibly detected. Applications to SNPs demonstrated that an LTQ-Orbitrap with a resolution of 30 000 (at m/z 400) easily identified a single (A ↔ G) switch, i.e. a 16 Da difference, in binary mixtures of ∼ 35 kDa PCR products. Complementary experiments also showed that the combination of endonucleases and ESI-MS could be used to confirm base composition and sequence, and thus to screen for unknown polymorphisms in specific sequences. For example, a single (T ↔ A) switch (9 Da mass difference) was successfully identified in a 114-bp PCR product. Copyright © 2010 John Wiley & Sons, Ltd.

Development of Fluorescent Substrates and Assays for the Key Autophagy-Related Cysteine Protease Enzyme, ATG4B

PubMed Central

Nguyen, Thanh G.; Honson, Nicolette S.; Arns, Steven; Davis, Tara L.; Dhe-Paganon, Sirano; Kovacic, Suzana; Kumar, Nag S.; Pfeifer, Tom A.

2014-01-01

Abstract The cysteine protease ATG4B plays a role in key steps of the autophagy process and is of interest as a potential therapeutic target. At an early step, ATG4B cleaves proLC3 isoforms to form LC3-I for subsequent lipidation to form LC3-II and autophagosome membrane insertion. ATG4B also cleaves phosphatidylethanolamine (PE) from LC3-II to regenerate LC3-I, enabling its recycling for further membrane biogenesis. Here, we report several novel assays for monitoring the enzymatic activity of ATG4B. An assay based on mass spectrometric analysis and quantification of cleavage of the substrate protein LC3-B was developed and, while useful for mechanistic studies, was not suitable for high throughput screening (HTS). A doubly fluorescent fluorescence resonance energy transfer (FRET) ligand YFP-LC3B-EmGFP (FRET-LC3) was constructed and shown to be an excellent substrate for ATG4B with rates of cleavage similar to that for LC3B itself. A HTS assay to identify candidate inhibitors of ATG4B utilizing FRET-LC3 as a substrate was developed and validated with a satisfactory Z′ factor and high signal-to-noise ratio suitable for screening small molecule libraries. Pilot screens of the 1,280-member library of pharmacologically active compounds (LOPAC™) and a 3,481-member library of known drugs (KD2) gave hit rates of 0.6% and 0.5% respectively, and subsequent titrations confirmed ATG4B inhibitory activity for three compounds, both in the FRET and mass spectrometry assays. The FRET- and mass spectrometry–based assays we have developed will allow for both HTS for inhibitors of ATG4B and mechanistic approaches to study inhibition of a major component of the autophagy pathway. PMID:24735444

High-throughput tandem mass spectrometry multiplex analysis for newborn urinary screening of creatine synthesis and transport disorders, Triple H syndrome and OTC deficiency.

PubMed

Auray-Blais, Christiane; Maranda, Bruno; Lavoie, Pamela

2014-09-25

Creatine synthesis and transport disorders, Triple H syndrome and ornithine transcarbamylase deficiency are treatable inborn errors of metabolism. Early screening of patients was found to be beneficial. Mass spectrometry analysis of specific urinary biomarkers might lead to early detection and treatment in the neonatal period. We developed a high-throughput mass spectrometry methodology applicable to newborn screening using dried urine on filter paper for these aforementioned diseases. A high-throughput methodology was devised for the simultaneous analysis of creatine, guanidineacetic acid, orotic acid, uracil, creatinine and respective internal standards, using both positive and negative electrospray ionization modes, depending on the compound. The precision and accuracy varied by <15%. Stability during storage at different temperatures was confirmed for three weeks. The limits of detection and quantification for each biomarker varied from 0.3 to 6.3 μmol/l and from 1.0 to 20.9 μmol/l, respectively. Analyses of urine specimens from affected patients revealed abnormal results. Targeted biomarkers in urine were detected in the first weeks of life. This rapid, simple and robust liquid chromatography/tandem mass spectrometry methodology is an efficient tool applicable to urine screening for inherited disorders by biochemical laboratories. Copyright © 2014 Elsevier B.V. All rights reserved.

A Dereplication and Bioguided Discovery Approach to Reveal New Compounds from a Marine-Derived Fungus Stilbella fimetaria

PubMed Central

Kildgaard, Sara; Subko, Karolina; Phillips, Emma; Goidts, Violaine; de la Cruz, Mercedes; Díaz, Caridad; Gotfredsen, Charlotte H.; Frisvad, Jens C.; Nielsen, Kristian F.; Larsen, Thomas O.

2017-01-01

A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds. Prefractionation before bioassay screening proved to be a great aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues, hydroxyl-ilicicolin H and ilicicolin I, and their antifungal activity was evaluated. PMID:28805711

Type 2 diabetes mellitus in Navajo adolescents.

PubMed Central

Kim, C; McHugh, C; Kwok, Y; Smith, A

1999-01-01

Diabetes mellitus afflicts over one-fifth of the Navajo population aged over 20 years, but the prevalence of diabetes in Navajo adolescents is unclear. We conducted voluntary testing for diabetes mellitus at two high schools on the Navajo reservation to clarify the prevalence as well as to assess the utility of a high-school based screening program. Body mass index measurements (BMI), oral glucose tolerance tests, and hemoglobin A1C measurements were obtained in consenting high school students. Of the 276 students that participated, 234 were Navajo. Only one Navajo student (0.4%) had diabetes mellitus, although eight (3%) had impaired glucose tolerance or impaired fasting glucose. Participant BMI did not differ significantly from nonparticipant BMI. No correlation existed between BMI or impaired glucose handling, and significant overlap existed between the hemoglobin A1C values of students with impaired glucose handling and students without impaired glucose handling. Increased participation in screening programs may reveal higher disease prevalence, but high school-based screening is not justified by this study, despite the high rates of diabetes mellitus in the Navajo population. PMID:10344174

Development of a Bile Acid-Based Newborn Screen for Niemann-Pick C Disease

PubMed Central

Jiang, Xuntian; Sidhu, Rohini; Mydock, Laurel; Hsu, Fong-Fu; Covey, Douglas F.; Scherrer, David E.; Earley, Brian; Gale, Sarah E.; Farhat, Nicole Y.; Porter, Forbes D.; Dietzen, Dennis J.; Orsini, Joseph J.; Berry-Kravis, Elizabeth; Zhang, Xiaokui; Reunert, Janice; Marquardt, Thorsten; Runz, Heiko; Giugliani, Roberto; Schaffer, Jean E.; Ory, Daniel S.

2017-01-01

Niemann-Pick disease type C (NPC) is a fatal, neurodegenerative, cholesterol storage disorder. With new therapeutics in clinical trials, it is imperative to improve diagnostics and facilitate early intervention. We used metabolomic profiling to identify potential markers and discovered three unknown bile acids that were increased in plasma from NPC but not control subjects. The bile acids most elevated in the NPC subjects were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, both of which were shown to be metabolites of cholestane-3β,5α,6β-triol, an oxysterol elevated in NPC. A high-throughput, mass spectrometry-based method was developed and validated to measure the glycine-conjugated bile acid in dried blood spots. Analysis of dried blood spots from 4992 controls, 134 NPC carriers, and 44 NPC subjects provided 100% sensitivity and specificity in the study samples. Quantification of the bile acid in dried blood spots, therefore, provides the basis for a newborn screen for NPC that is ready for piloting in newborn screening programs. PMID:27147587

Ultrasensitive Immunochromatographic Strip for Fast Screening of 27 Sulfonamides in Honey and Pork Liver Samples Based on a Monoclonal Antibody.

PubMed

Chen, Yanni; Guo, Lingling; Liu, Liqiang; Song, Shanshan; Kuang, Hua; Xu, Chuanlai

2017-09-20

Group-specific monoclonal antibodies (Mabs) with selectivity for 27 sulfonamides were developed based on new combinations of immunogen and coating antigen. The Mab was able to recognize 27 sulfonamides with 50% inhibition concentration (IC 50 ) values ranging from 0.15 to 15.38 μg/L. In particular, the IC 50 values for five sulfonamides (sulfamethazine, sulfaquinoxaline, sulfamonomethoxine, sulfadimethoxine, and sulfamethoxazole) were 0.51, 0.15, 0.56, 0.54, and 2.14 μg/L, respectively. On the basis of the Mab, an immunochromatographic lateral flow strip test was established for rapid screening of sulfonamides in honey samples. The visual limit of detection of the strip test for most sulfonamides in spiked honey samples was below 10 μg/kg, satisfying the requirements of authorities. Positive honey and pork liver samples, which had been confirmed by high-performance liquid chromatography/mass spectrometry, were used to validate the reliability of the proposed strip test. The immunochromatographic lateral flow strip test provides a rapid and convenient method for fast screening of sulfonamides in honey samples.

Hawking radiation from the holographic screen

NASA Astrophysics Data System (ADS)

Zhao, Ying-Jie

2017-10-01

In this paper, we generalize the Parikh-Wilczek scheme to a holographic screen in the framework of the ultraviolet self-complete quantum gravity. We calculate that the tunneling probability depends on the energy of the particle and the mass of the holographic screen. The radiating temperature has not been the standard Hawking temperature.

EVALUATION OF GROUNDWATER FLOW PATTERNS AROUND A DUAL-SCREENED GROUNDWATER CIRCULATION WELL

EPA Science Inventory

Dual-screened groundwater circulation wells (GCWs) can be used to remove contaminant mass and to mix reagents in situ. GCWs are so named because they force water in a circular pattern between injection and extraction screens. The radial extent, flux and direction of the effective...

Facilitating Factors and Barriers to BMI Screening in Schools

ERIC Educational Resources Information Center

Stalter, Ann M.; Chaudry, Rosemary V.; Polivka, Barbara J.

2010-01-01

The National Association of School Nurses advocates for body mass index (BMI) screening. Little research describes school nurse practice of BMI screening. In this descriptive study, 25 Ohio school nurses participated in three focus groups. An adapted "Healthy People 2010" Determinants of Health Model guided the research questions. School…

Ammonificins C and D, Hydroxyethylamine Chromene Derivatives from a Cultured Marine Hydrothermal Vent Bacterium, Thermovibrio ammonificans

PubMed Central

Andrianasolo, Eric H.; Haramaty, Liti; Rosario-Passapera, Richard; Vetriani, Costantino; Falkowski, Paul; White, Eileen; Lutz, Richard

2012-01-01

Chemical and biological investigation of the cultured marine hydrothermal vent bacterium, Thermovibrio ammonifican led to the isolation of two hydroxyethylamine chromene derivatives, ammonificins C and D. Their structures were elucidated using combination of NMR and mass spectrometry. Absolute stereochemistry was ascertained by comparison of experimental and calculated CD spectra. Biological evaluation and assessment were determined using the patented ApopScreen cell-based screen for apoptosis-induction. Ammonificins C and D induce apoptosis in micromolar concentrations. To our knowledge, this finding is the first report of chemical compounds that induce apoptosis from the cultured deep-sea marine organism, hydrothermal vent bacterium, Thermovibrio ammonificans. PMID:23170085

Accurate inclusion mass screening: a bridge from unbiased discovery to targeted assay development for biomarker verification.

PubMed

Jaffe, Jacob D; Keshishian, Hasmik; Chang, Betty; Addona, Theresa A; Gillette, Michael A; Carr, Steven A

2008-10-01

Verification of candidate biomarker proteins in blood is typically done using multiple reaction monitoring (MRM) of peptides by LC-MS/MS on triple quadrupole MS systems. MRM assay development for each protein requires significant time and cost, much of which is likely to be of little value if the candidate biomarker is below the detection limit in blood or a false positive in the original discovery data. Here we present a new technology, accurate inclusion mass screening (AIMS), designed to provide a bridge from unbiased discovery to MS-based targeted assay development. Masses on the software inclusion list are monitored in each scan on the Orbitrap MS system, and MS/MS spectra for sequence confirmation are acquired only when a peptide from the list is detected with both the correct accurate mass and charge state. The AIMS experiment confirms that a given peptide (and thus the protein from which it is derived) is present in the plasma. Throughput of the method is sufficient to qualify up to a hundred proteins/week. The sensitivity of AIMS is similar to MRM on a triple quadrupole MS system using optimized sample preparation methods (low tens of ng/ml in plasma), and MS/MS data from the AIMS experiments on the Orbitrap can be directly used to configure MRM assays. The method was shown to be at least 4-fold more efficient at detecting peptides of interest than undirected LC-MS/MS experiments using the same instrumentation, and relative quantitation information can be obtained by AIMS in case versus control experiments. Detection by AIMS ensures that a quantitative MRM-based assay can be configured for that protein. The method has the potential to qualify large number of biomarker candidates based on their detection in plasma prior to committing to the time- and resource-intensive steps of establishing a quantitative assay.

Calculation of the capnographic index based on expiratory molar mass-volume-curves--a suitable tool to screen for cystic fibrosis lung disease.

PubMed

Fuchs, Susanne I; Junge, Sibylle; Ellemunter, Helmut; Ballmann, Manfred; Gappa, Monika

2013-05-01

Volumetric capnography reflecting the course of CO2-exhalation is used to assess ventilation inhomogeneity. Calculation of the slope of expiratory phase 3 and the capnographic index (KPIv) from expirograms allows quantification of extent and severity of small airway impairment. However, technical limitations have hampered more widespread use of this technique. Using expiratory molar mass-volume-curves sampled with a handheld ultrasonic flow sensor during tidal breathing is a novel approach to extract similar information from expirograms in a simpler manner possibly qualifying as a screening tool for clinical routine. The aim of the present study was to evaluate calculation of the KPIv based on molar mass-volume-curves sampled with an ultrasonic flow sensor in patients with CF and controls by assessing feasibility, reproducibility and comparability with the Lung Clearance Index (LCI) derived from multiple breath washout (MBW) used as the reference method. Measurements were performed in patients with CF and healthy controls during a single test occasion using the EasyOne Pro, MBW Module (ndd Medical Technologies, Switzerland). Capnography and MBW were performed in 87/96 patients with CF and 38/42 controls, with a success rate of 90.6% for capnography. Mean age (range) was 12.1 (4-25) years. Mean (SD) KPIv was 6.94 (3.08) in CF and 5.10 (2.06) in controls (p=0.001). Mean LCI (SD) was 8.0 (1.4) in CF and 6.2 (0.4) in controls (p=<0.001) and correlated significantly with the KPIv (p=<0.001). Calculation of the KPIv based on molar mass-volume-curves is feasible. KPIv is significantly different between patients with CF and controls and correlates with the LCI. However, individual data revealed a relevant overlap between patients and controls requiring further evaluation, before this method can be recommended for clinical use. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Packaging strategy for maximizing the performance of a screen printed piezoelectric energy harvester

NASA Astrophysics Data System (ADS)

Zhang, Z.; Zhu, D.; Tudor, M. J.; Beeby, S. P.

2013-12-01

This paper reports the extended design and simulation of a screen printed piezoelectric energy harvester. The proposed design was based on a previous credit card sized smart tag sensor node, and packages the power conditioning circuit in the free space above the tungsten proof mass layer. This approach enables electronic components to be mounted onto the cantilever beam, which provides additional weight at the tip of the cantilever structure. The design structure contains a T-shape cantilever beam with size of 47 mm × 30 mm × 0.85 mm which is fabricated using screen printing. ANSYS simulation results predict the revised architecture can generate 421.9 μW approximately twice of the RMS power produced by the original design along with a higher open-circuit RMS Voltage of 8.0 V while the resonant frequency is dropped to 53.4 Hz.

Screening and characterization of novel bacteriocins from lactic acid bacteria.

PubMed

Zendo, Takeshi

2013-01-01

Bacteriocins produced by lactic acid bacteria (LAB) are expected to be safe antimicrobial agents. While the best studied LAB bacteriocin, nisin A, is widely utilized as a food preservative, various novel ones are required to control undesirable bacteria more effectively. To discover novel bacteriocins at the early step of the screening process, we developed a rapid screening system that evaluates bacteriocins produced by newly isolated LAB based on their antibacterial spectra and molecular masses. By means of this system, various novel bacteriocins were identified, including a nisin variant, nisin Q, a two-peptide bacteriocin, lactococcin Q, a leaderless bacteriocin, lacticin Q, and a circular bacteriocin, lactocyclicin Q. Moreover, some LAB isolates were found to produce multiple bacteriocins. They were characterized as to their structures, mechanisms of action, and biosynthetic mechanisms. Novel LAB bacteriocins and their biosynthetic mechanisms are expected for applications such as food preservation and peptide engineering.

Obstructive sleep apnea in North American commercial drivers.

PubMed

Kales, Stefanos N; Straubel, Madeleine G

2014-01-01

The most common medical cause of excessive daytime sleepiness (EDS) is obstructive sleep apnea (OSA). Specifically, among an estimated 14 million US commercial drivers, 17-28% or 2.4 to 3.9 million are expected to have OSA. Based on existing epidemiologic evidence, most of these drivers are undiagnosed and not adequately treated. Untreated OSA increases the risk of vehicular crashes as documented in multiple independent studies and by meta-analysis. Therefore, identifying commercial drivers with OSA and having them effectively treated should decrease crash-related fatalities and injuries. Several strategies are available for screening and identifying drivers with OSA. The simplest and most effective objective strategies use body mass index (BMI) cutoffs for obesity. Functional screens are promising adjuncts to other objective tests. The most effective approach will likely be a combination of a good questionnaire; BMI measures; and a careful physician-obtained history complemented by a functional screen.

Optimization of three- and four-component reactions for polysubstituted piperidines: application to the synthesis and preliminary biological screening of a prototype library.

PubMed

Ulaczyk-Lesanko, Agnieszka; Pelletier, Eric; Lee, Maria; Prinz, Heino; Waldmann, Herbert; Hall, Dennis G

2007-01-01

Several solid- and solution-phase strategies were evaluated for the preparation of libraries of polysubstituted piperidines of type 7 using the tandem aza[4+2]cycloaddition/allylboration multicomponent reaction between 1-aza-4-boronobutadienes, maleimides, and aldehydes. A novel four-component variant of this chemistry was developed in solution phase, and it circumvents the need for pre-forming the azabutadiene component. A parallel synthesis coupled with compound purification by HPLC with mass-based fraction collection allowed the preparation of a library of 944 polysubstituted piperidines in a high degree of purity suitable for biological screening. A representative subset of 244 compounds was screened against a panel of phosphatase enzymes, and despite the modest levels of activity obtained, this study demonstrated that piperidines of type 7 display the right physical properties (e.g., solubility) to be assayed effectively in high-throughput enzymatic tests.

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.

Detection of weapons of mass destruction

NASA Astrophysics Data System (ADS)

Bjorkholm, Paul J.

2003-07-01

High Energy X-ray cargo screening is a mature technology that has proven its value in the detection of contraband material hidden within cargo including fully loaded sea containers. To date high energy screening has been largely applied to manifest verification and to drug detection. However, the dramatic change in world terrorism has altered the application. Now it is essential that weapons of mass destruction (WMD"s) be interdicted with incredibly high accuracy. The implication of a missed detection has gone from loss of revenue or the lowering of the street price of drugs to potentially stopping, at least for some significant time, most world commerce. Screening containers with high energy x-rays (~250+ mm of steel penetration) is capable of detecting all nuclear threats at a fraction of the strategically important mass. The screening operation can be automated so that no human decisions are required with very low false alarms. Finally, the goal of 100% inspection of cargo inbound to the United States from the twenty largest international ports is an achievable goal with hardware costs in the area of that already spent on airport security.

[Evaluation of mass screening activity for cardiovascular disease risk factors in a rural environment].

PubMed

Boudreau, F

2001-01-01

The aim of this study was to evaluate the immediate and short-term impacts of a cardiovascular mass screening activity in a rural environment. A posttest-only control group design was used. Concerning the immediate impact, the results showed that the participants of the experimental group had, compared to the participants in the control group, a higher intention to participate regularly in physical activities and a higher intention to reduce their fat consumption. The participants' intention to stop smoking was not modified by the screening activity. After four months, the results revealed an increase in participation in physical activities and a decrease in fat consumption. The proportion of participants who smoked did not decrease. In conclusion, it is suggested that a cardiovascular mass screening activity such as the one performed in this study could be effective in motivating a population to adopt heart health-related behaviours. Others studies are necessary however to confirm the short-term impact of this type of activity on behaviour modification with regard to cardiovascular health.

Triglyceride-based screening tests fail to recognize cardiometabolic disease in African immigrant and African-American men.

PubMed

Yu, Sophia S K; Ramsey, Natalie L M; Castillo, Darleen C; Ricks, Madia; Sumner, Anne E

2013-02-01

The prevalence of cardiometabolic disease in Africa now rivals that of Western nations. Therefore, screening programs that lead to effective prevention of cardiometabolic disease in Africans is imperative. Most screening tests for cardiometabolic disease use triglyceride (TG) levels as a criterion. However, the failure rate of TG-based screening tests in African Americans is high. In Africans, the efficacy of TG-based screening tests is unknown. Our goal was to determine the association between hypertriglyceridemia (TG ≥150 mg/dL) and cardiometabolic disease in African and African-American men. This was a cross-sectional study of 155 men (80 African immigrants, 75 African Americans) [age, 35±9 years, mean±standard deviation (SD), body mass index (BMI) 28.5±5.2 kg/m(2)] who self-identified as healthy. Lipid profiles were performed. Glucose tolerance and insulin resistance was determined by oral glucose tolerance tests (OGTT) and the insulin sensitivity index (S(I)), respectively. Cardiometabolic disease was defined by four possible subtypes--prediabetes, diabetes, insulin resistance, or metabolic triad [hyperinsulinemia, hyperapolipoprotein B, small low-density lipoprotein (LDL) particles]. TG levels were higher in men with cardiometabolic disease than without (88±43 versus 61±26 mg/dL, P<0.01). However, <10% of men with cardiometabolic disease had TG ≥150 mg/dL. Even within each cardiometabolic disease subtype, the prevalence of TG ≥150 mg/dL was <10%. Furthermore, TG levels in the 5% of men identified by OGTT as diabetic were ≤100 mg/dL (mean 71±24, range 45-100 mg/dL). Hypertriglyceridemia is a poor marker of cardiometabolic disease in men of African descent. Therefore TG-based screening tests fail to identify both African immigrants and African-American men with cardiometabolic disease. As a consequence, the opportunity for early intervention and prevention is lost.

Added value of shear-wave elastography for evaluation of breast masses detected with screening US imaging.

PubMed

Lee, Su Hyun; Chang, Jung Min; Kim, Won Hwa; Bae, Min Sun; Seo, Mirinae; Koo, Hye Ryoung; Chu, A Jung; Gweon, Hye Mi; Cho, Nariya; Moon, Woo Kyung

2014-10-01

To evaluate the additional value of shear-wave elastography (SWE) to B-mode ultrasonography (US) and to determine an appropriate guideline for the combined assessment of screening US-detected breast masses. This study was conducted with institutional review board approval, and written informed consent was obtained. From March 2010 to February 2012, B-mode US and SWE were performed in 159 US-detected breast masses before biopsy. For each lesion, Breast Imaging Reporting and Data System (BI-RADS) category on B-mode US images and the maximum stiffness color and elasticity values on SWE images were assessed. A guideline for adding SWE data to B-mode US was developed with the retrospective cohort to improve diagnostic performance in sensitivity and specificity and was validated in a distinct prospective cohort of 207 women prior to biopsy. Twenty-one of 159 masses in the development cohort and 12 of 207 breast masses in the validation cohort were malignant. In the development cohort, when BI-RADS category 4a masses showing a dark blue color or a maximum elasticity value of 30 kPa or less on SWE images were downgraded to category 3, specificity increased from 9.4% (13 of 138) to 59.4% (82 of 138) and 57.2% (79 of 138) (P < .001), respectively, without loss in sensitivity (100% [21 of 21]). In the validation cohort, specificity increased from 17.4% (34 of 195) to 62.1% (121 of 195) and 53.3% (104 of 195) (P < .001) respectively, without loss in sensitivity (91.7% [11 of 12]). The addition of SWE to B-mode US improved diagnostic performance with increased specificity for screening US-detected breast masses. BI-RADS category 4a masses detected at US screening that showed a dark blue color or a maximum elasticity value of 30 kPa or less on SWE images can be safely followed up instead of performing biopsy. © RSNA, 2014.

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

PubMed

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

2014-01-24

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

Body burden of pesticides and wastewater-derived pollutants on freshwater invertebrates: Method development and application in the Danube River.

PubMed

Inostroza, Pedro A; Wicht, Anna-Jorina; Huber, Thomas; Nagy, Claudia; Brack, Werner; Krauss, Martin

2016-07-01

While environmental risk assessment is typically based on toxicant concentrations in water and/or sediment, awareness is increasing that internal concentrations or body burdens are the key to understand adverse effects in organisms. In order to link environmental micropollutants as causes of observed effects, there is an increasing demand for methods to analyse these chemicals in organisms. Here, a multi-target screening method based on pulverised liquid extraction (PuLE) and a modified QuEChERS approach with an additional hexane phase was developed. It is capable to extract and quantify organic micropollutants of diverse chemical classes in freshwater invertebrates. The method was tested on gammarids from the Danube River (within the Joint Danube Survey 3) and target compounds were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, a non-target screening using high resolution-tandem mass spectrometry (LC-HRMS/MS) was conducted. A total of 17 pollutants were detected and/or quantified in gammarids at low concentrations. Pesticide concentrations ranged from 0.1 to 6.52 ng g(-1) (wet weight), those of wastewater-derived pollutants from 0.1 to 2.83 ng g(-1) (wet weight). The presence of wastewater-derived pollutants was prominent at all spots sampled. Using non-target screening, we could successfully identify several chlorinated compounds. These results demonstrate for the first time the presence of pesticides and wastewater-derived pollutants in invertebrates of the Danube River. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rapid screening and identification of ACE inhibitors in snake venoms using at-line nanofractionation LC-MS.

PubMed

Mladic, Marija; de Waal, Tessa; Burggraaff, Lindsey; Slagboom, Julien; Somsen, Govert W; Niessen, Wilfried M A; Manjunatha Kini, R; Kool, Jeroen

2017-10-01

This study presents an analytical method for the screening of snake venoms for inhibitors of the angiotensin-converting enzyme (ACE) and a strategy for their rapid identification. The method is based on an at-line nanofractionation approach, which combines liquid chromatography (LC), mass spectrometry (MS), and pharmacology in one platform. After initial LC separation of a crude venom, a post-column flow split is introduced enabling parallel MS identification and high-resolution fractionation onto 384-well plates. The plates are subsequently freeze-dried and used in a fluorescence-based ACE activity assay to determine the ability of the nanofractions to inhibit ACE activity. Once the bioactive wells are identified, the parallel MS data reveals the masses corresponding to the activities found. Narrowing down of possible bioactive candidates is provided by comparison of bioactivity profiles after reversed-phase liquid chromatography (RPLC) and after hydrophilic interaction chromatography (HILIC) of a crude venom. Additional nanoLC-MS/MS analysis is performed on the content of the bioactive nanofractions to determine peptide sequences. The method described was optimized, evaluated, and successfully applied for screening of 30 snake venoms for the presence of ACE inhibitors. As a result, two new bioactive peptides were identified: pELWPRPHVPP in Crotalus viridis viridis venom with IC 50  = 1.1 μM and pEWPPWPPRPPIPP in Cerastes cerastes cerastes venom with IC 50  = 3.5 μM. The identified peptides possess a high sequence similarity to other bradykinin-potentiating peptides (BPPs), which are known ACE inhibitors found in snake venoms.

Development of a new screening method for the detection of antibiotic residues in muscle tissues using liquid chromatography and high resolution mass spectrometry with a LC-LTQ-Orbitrap instrument.

PubMed

Hurtaud-Pessel, D; Jagadeshwar-Reddy, T; Verdon, E

2011-10-01

A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed for screening meat for a wide range of antibiotics used in veterinary medicine. Full-scan mode under high resolution mass spectral conditions using an LTQ-Orbitrap mass spectrometer with resolving power 60,000 full width at half maximum (FWHM) was applied for analysis of the samples. Samples were prepared using two extraction protocols prior to LC-HRMS analysis. The scope of the method focuses on screening the following main families of antibacterial veterinary drugs: penicillins, cephalosporins, sulfonamides, macrolides, tetracyclines, aminoglucosides and quinolones. Compounds were successfully identified in spiked samples from their accurate mass and LC retention times from the acquired full-scan chromatogram. Automated data processing using ToxId software allowed rapid treatment of the data. Analyses of muscle tissues from real samples collected from antibiotic-treated animals was carried out using the above methodology and antibiotic residues were identified unambiguously. Further analysis of the data for real samples allowed the identification of the targeted antibiotic residues but also non-targeted compounds, such as some of their metabolites.

Broad screening of illicit ingredients in cosmetics using ultra-high-performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometry with customized accurate-mass database and mass spectral library.

PubMed

Meng, Xianshuang; Bai, Hua; Guo, Teng; Niu, Zengyuan; Ma, Qiang

2017-12-15

Comprehensive identification and quantitation of 100 multi-class regulated ingredients in cosmetics was achieved using ultra-high-performance liquid chromatography (UHPLC) coupled with hybrid quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS). A simple, efficient, and inexpensive sample pretreatment protocol was developed using ultrasound-assisted extraction (UAE), followed by dispersive solid-phase extraction (dSPE). The cosmetic samples were analyzed by UHPLC-Q-Orbitrap HRMS under synchronous full-scan MS and data-dependent MS/MS (full-scan MS 1 /dd-MS 2 ) acquisition mode. The mass resolution was set to 70,000 FWHM (full width at half maximum) for full-scan MS 1 and 17,500 FWHM for dd-MS 2 stage with the experimentally measured mass deviations of less than 2ppm (parts per million) for quasi-molecular ions and 5ppm for characteristic fragment ions for each individual analyte. An accurate-mass database and a mass spectral library were built in house for searching the 100 target compounds. Broad screening was conducted by comparing the experimentally measured exact mass of precursor and fragment ions, retention time, isotopic pattern, and ionic ratio with the accurate-mass database and by matching the acquired MS/MS spectra against the mass spectral library. The developed methodology was evaluated and validated in terms of limits of detection (LODs), limits of quantitation (LOQs), linearity, stability, accuracy, and matrix effect. The UHPLC-Q-Orbitrap HRMS approach was applied for the analysis of 100 target illicit ingredients in 123 genuine cosmetic samples, and exhibited great potential for high-throughput, sensitive, and reliable screening of multi-class illicit compounds in cosmetics. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect-directed analysis to explore the polar bear exposome: identification of thyroid hormone disrupting compounds in plasma.

PubMed

Simon, Eszter; van Velzen, Martin; Brandsma, Sicco H; Lie, Elisabeth; Løken, Katharina; de Boer, Jacob; Bytingsvik, Jenny; Jenssen, Bjørn M; Aars, Jon; Hamers, Timo; Lamoree, Marja H

2013-08-06

Compounds with transthyretin (TTR)-binding potency in the blood plasma of polar bear cubs were identified with effect-directed analysis (EDA). This approach contributes to the understanding of the thyroid disrupting exposome of polar bears. The selection of these samples for in-depth EDA was based on the difference between the observed TTR-binding potency on the one hand and the calculated potency (based on known concentrations of TTR-binding compounds and their relative potencies) on the other. A library-based identification was applied to the liquid chromatography-time-of-flight-mass spectrometry (LC-ToF-MS) data by screening for matches between compound lists and the LC-ToF-MS data regarding accurate mass and isotope pattern. Then, isotope cluster analysis (ICA) was applied to the LC-ToF-MS data allowing specific screening for halogen isotope patterns. The presence of linear and branched nonylphenol (NP) was observed for the first time in polar bears. Furthermore, the presence of one di- and two monohydroxylated octachlorinated biphenyls (octaCBs) was revealed in the extracts. Linear and branched NP, 4'-OH-CB201 and 4,4'-OH-CB202 could be successfully confirmed with respect to their retention time in the analytical system. In addition, branched NP, mono- and dihydroxylated-octaCBs showed TTR-binding potencies and could explain another 32 ± 2% of the total measured activities in the extracts.

The challenges of developing a generic extraction procedure to analyze multi-class veterinary drug residues in milk and honey using ultra-high pressure liquid chromatography quadrupole time-of-flight mass spectrometry.

PubMed

Wang, Jian; Leung, Daniel

2012-08-01

This paper discusses the analytical challenges to develop a generic extraction procedure to analyze or screen multi-class veterinary drugs in milk and honey using ultra-high pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC QqTOF MS). The veterinary drugs in this study included aminoglycosides, endectocides, fluoroquinolones, ionophores, β-lactams or penicillins, macrolides, NSAIDs, phenicols, sulfonamides and tetracyclines. Veterinary drugs were extracted using a QuEChERS (quick, easy, cheap, effective, rugged, and safe) method, which entailed the use of acetonitrile containing 1% acetic acid, sodium acetate, ethylenediaminetetra acetic acid disodium (EDTA) and magnesium sulfate, and no clean-up was performed. Chromatographic separation was achieved on a reversed-phase Acquity UPLC BEH C(18) , 100 × 2.1 mm, 1.7 µm column with 0.1% formic acid and 10 mM ammonium formate in water, and acetonitrile as mobile phases. Due to poor chromatographic retention, aminoglycosides were first dropped from the list, and because of poor extractability, β-lactams and tetracyclines were also excluded from the method. The method was able to quantify 31 or screen up to 54 drugs (unbound) in honey, and to quantify 34 or screen up to 59 drugs in milk. UHPLC QqTOF data were acquired in TOF MS full-scan mode that allowed both quantification and confirmation of veterinary drugs and identification of their degradation products in samples. The method could achieve detection limits as low as 1 µg/kg with analytical range from 1 to 100 µg/kg. The developed method was intended to be used for screening of as many analytes as possible in one single analysis, or unequivocal confirmation of positive findings and degradation product identification based on accurate mass measurement and isotopic patterns. © Her Majesty the Queen in Right of Canada 2012. Reproduced with the permission of the Minister of Agriculture.

Suspect screening of large numbers of emerging contaminants in environmental waters using artificial neural networks for chromatographic retention time prediction and high resolution mass spectrometry data analysis.

PubMed

Bade, Richard; Bijlsma, Lubertus; Miller, Thomas H; Barron, Leon P; Sancho, Juan Vicente; Hernández, Felix

2015-12-15

The recent development of broad-scope high resolution mass spectrometry (HRMS) screening methods has resulted in a much improved capability for new compound identification in environmental samples. However, positive identifications at the ng/L concentration level rely on analytical reference standards for chromatographic retention time (tR) and mass spectral comparisons. Chromatographic tR prediction can play a role in increasing confidence in suspect screening efforts for new compounds in the environment, especially when standards are not available, but reliable methods are lacking. The current work focuses on the development of artificial neural networks (ANNs) for tR prediction in gradient reversed-phase liquid chromatography and applied along with HRMS data to suspect screening of wastewater and environmental surface water samples. Based on a compound tR dataset of >500 compounds, an optimized 4-layer back-propagation multi-layer perceptron model enabled predictions for 85% of all compounds to within 2min of their measured tR for training (n=344) and verification (n=100) datasets. To evaluate the ANN ability for generalization to new data, the model was further tested using 100 randomly selected compounds and revealed 95% prediction accuracy within the 2-minute elution interval. Given the increasing concern on the presence of drug metabolites and other transformation products (TPs) in the aquatic environment, the model was applied along with HRMS data for preliminary identification of pharmaceutically-related compounds in real samples. Examples of compounds where reference standards were subsequently acquired and later confirmed are also presented. To our knowledge, this work presents for the first time, the successful application of an accurate retention time predictor and HRMS data-mining using the largest number of compounds to preliminarily identify new or emerging contaminants in wastewater and surface waters. Copyright © 2015 Elsevier B.V. All rights reserved.

Mobile health is worth it! Economic benefit and impact on health of a population-based mobile screening program in new Mexico.

PubMed

Brown-Connolly, Nancy E; Concha, Jeannie B; English, Jennifer

2014-01-01

HABITS for Life was a 3-year initiative to broadly deliver a statewide biometric and retinal screening program via a mobile unit throughout New Mexico at no charge to participants. The program goal-to identify health risk and improve population health status-was tested over a 3-year period. Value to participants and impact to the healthcare system were measured to quantify impact and value of investing in prevention at the community level. We used the Mobile Health Map Return-on-Investment Calculator, a mobile screening unit, biometric screening, retinography, and community coordination. Our systems included satellite, DSL, and 3G connectivity, a Tanita® (Arlington Heights, IL) automated body mass index-measuring scale, the Cholestec® (Alere™, Waltham, MA) system for biomarkers and glycosylated hemoglobin, a Canon (Melville, NY) CR-1 Mark II camera, and the Picture Archiving Communication System. In this report for the fiscal year 2011 time frame, 6,426 individuals received biometric screening, and 5,219 received retinal screening. A 15:1 return on investment was calculated; this excluded retinal screening for the under-65 year olds, estimated at $10 million in quality-adjusted life years saved. Statistically significant improvement in health status evidenced by sequential screening included a decrease in total cholesterol level (p=0.002) (n=308) and an increase in high-density lipoprotein level after the first and second screening (p=0.02 and p=0.01, respectively), but a decrease in mean random glucose level was not statistically significant (p=0.62). Retinal results indicate 28.4% (n=1,482) with a positive/abnormal finding, of which 1.79% (n=93) required immediate referral for sight-threatening retinopathy and 27% (n=1,389) required follow-up of from 3 months to 1 year. Screening programs are cost-effective and provide value in preventive health efforts. Broad use of screening programs should be considered in healthcare redesign efforts. Community-based screening is an effective strategy to identify health risk, improve access, provide motivation to change health habits, and improve physical status while returning significant value.

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

PubMed Central

2018-01-01

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

PubMed

Vu, Hoan; Pedro, Liliana; Mak, Tin; McCormick, Brendan; Rowley, Jessica; Liu, Miaomiao; Di Capua, Angela; Williams-Noonan, Billy; Pham, Ngoc B; Pouwer, Rebecca; Nguyen, Bao; Andrews, Katherine T; Skinner-Adams, Tina; Kim, Jessica; Hol, Wim G J; Hui, Raymond; Crowther, Gregory J; Van Voorhis, Wesley C; Quinn, Ronald J

2018-04-13

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.

Collaborative Review: Risk-Based Prostate Cancer Screening

PubMed Central

Zhu, Xiaoye; Albertsen, Peter C.; Andriole, Gerald L.; Roobol, Monique J.; Schröder, Fritz H.; Vickers, Andrew J.

2016-01-01

Context Widespread mass screening of prostate cancer (PCa) is not recommended because the balance between benefits and harms is still not well established. The achieved mortality reduction comes with considerable harm such as unnecessary biopsies, overdiagnoses, and overtreatment. Therefore, patient stratification with regard to PCa risk and aggressiveness is necessary to identify those men who are at risk and may actually benefit from early detection. Objective This review critically examines the current evidence regarding risk-based PCa screening. Evidence acquisition A search of the literature was performed using the Medline database. Further studies were selected based on manual searches of reference lists and review articles. Evidence synthesis Prostate-specific antigen (PSA) has been shown to be the single most significant predictive factor for identifying men at increased risk of developing PCa. Especially in men with no additional risk factors, PSA alone provides an appropriate marker up to 30 yr into the future. After assessment of an early PSA test, the screening frequency may be determined based on individualized risk. A limited list of additional factors such as age, comorbidity, prostate volume, family history, ethnicity, and previous biopsy status have been identified to modify risk and are important for consideration in routine practice. In men with a known PSA, risk calculators may hold the promise of identifying those who are at increased risk of having PCa and are therefore candidates for biopsy. Conclusions PSA testing may serve as the foundation for a more risk-based assessment. However, the decision to undergo early PSA testing should be a shared one between the patient and his physician based on information balancing its advantages and disadvantages. PMID:22134009

Rapid profiling of antimicrobial compounds characterising B. subtilis TR50 cell-free filtrate by high-performance liquid chromatography coupled to high-resolution Orbitrap™ mass spectrometry.

PubMed

Monaci, Linda; Quintieri, Laura; Caputo, Leonardo; Visconti, Angelo; Baruzzi, Federico

2016-01-15

Several Bacillus strains, typically isolated from different food sources, represent renowned producers of a multitude of low and high molecular weight compounds, including lipopeptides and macrolactones, with an importance for their antimicrobial activity. The high homology shared by many of these compounds also occurring as closely related isoforms poses a challenge in their prompt detection. Identification and structural elucidation is generally achieved by matrix-assisted laser desorption/ionization (MALDI) or liquid chromatography (LC) coupled to mass spectrometry (MS) after a pre-fractionation and/or purification step of the extract. In this paper we report the application of a method based on LC separation and high-resolution Orbitrap™-based MS for the rapid screening of raw filtrate of the strain Bacillus subtilis TR50 endowed with antimicrobial activity, without requiring any sample pre-treatment. Upon direct analysis of the cell-free filtrate of Bacillus subtilis TR50 by high-resolution mass spectrometry (HRMS), different compounds families, that proved to exert a remarked antimicrobial activity against several foodborne pathogens, can be readily displayed along the chromatographic run. Among them, three different classes were identified and characterized belonging to the iturin, fengycin and surfactin groups. The high resolving power and accurate mass accuracy provided by the HRMS system in use ensured an enhanced selectivity compared to other mass spectrometers. In addition, after activation of the HCD cell, the HR-MS/MS spectra can provide insights in the structural elucidation of several compounds. The acquisition of HRMS spectra of raw filtrates of subtilis strains allows untargeted analysis of the major classes of compounds produced to be performed, thus facilitating identification of other unknown bioactive molecules after retrospective analysis. These features make this approach a fast tool applicable to the rapid screening and further identification of antimicrobial compounds released by Bacillus strains in raw filtrates. Copyright © 2015 John Wiley & Sons, Ltd.

Rapid screening of pharmaceutical drugs using thermal desorption - SALDI mass spectrometry

NASA Astrophysics Data System (ADS)

Grechnikov, A. A.; Kubasov, A. E.; Georgieva, V. B.; Borodkov, A. S.; Nikiforov, S. M.; Simanovsky, Ya O.; Alimpiev, S. S.

2012-12-01

A novel approach to the rapid screening of pharmaceutical drugs by surface assisted laser desorption-ionization (SALDI) mass spectrometry with the rotating ball interface coupled with temperature programmed thermal desorption has been developed. Analytes were thermally desorbed and deposited onto the surface of amorphous silicon substrate attached to the rotating ball. The ball was rotated and the deposited analytes were analyzed using SALDI. The effectiveness of coupling SALDI mass spectrometry with thermal desorption was evaluated by the direct and rapid analysis of tablets containing lidocaine, diphenhydramine and propranolol without any sample pretreatment. The overall duration of the screening procedure was 30÷40 sec. Real urine samples were studied for drug analysis. It is shown that with simple preparation steps, urine samples can be quantitatively analyzed using the proposed technique with the detection limits in the range of 0.2÷0.5 ng/ml.

Increasing Cervical Cancer Screening Among US Hispanics/Latinas: A Qualitative Systematic Review

PubMed Central

Mann, Lilli; Foley, Kristie L.; Tanner, Amanda E.; Sun, Christina J.; Rhodes, Scott D.

2014-01-01

Purpose Hispanic/Latina women experience the highest cervical cancer incidence rates of any racial/ethnic group in the United States (US), and tend to present with more severe cases and experience higher mortality compared to most other populations. The goal of this qualitative systematic review was to explore existing interventions to increase cervical cancer screening among US Hispanics/Latinas and to identify characteristics of effective interventions and research gaps. Materials and Methods Six online databases were searched from their inception through June 30, 2013, using designated search terms and keywords. Peer-reviewed articles that documented an intervention designed to improve screening for cervical cancer among Hispanics/Latinas ages 18 years and older living in the US were reviewed. Data were abstracted using a standardized form to document intervention characteristics and results. Results Forty-five articles, describing 32 unique interventions, met inclusion criteria. Identified interventions consisted primarily of educational programs and/or provision of screening. Interventions used lay health advisors (LHAs), clinic-based outreach/delivery strategies, partnerships with churches, and mass media campaigns. Twelve interventions resulted in significant increases in cervical cancer screening rates. Conclusions Interventions developed utilizing theory, applying community-based participatory research approaches, and using lay health advisors were identified as having the greatest potential for improving cervical cancer screening among Hispanics/Latinas. There continues to be a need for the development of interventions in geographic areas with new and emerging Hispanic/Latino populations and that are comprehensive, follow participants for longer periods of time, and broaden the roles and build the capacities of LHAs. PMID:25154515

Rapid detection and differentiation of avian infectious bronchitis virus: an application of Mass genotype by melting temperature analysis in RT-qPCR using SYBR Green I

PubMed Central

OKINO, Cintia Hiromi; MONTASSIER, Maria de Fátima Silva; de OLIVEIRA, Andressa Peres; MONTASSIER, Helio José

2018-01-01

A method based on Melting Temperature analysis of Hypervariable regions (HVR) of S1 gene within a RT-qPCR was developed to detect different genotypes of avian infectious bronchitis virus (IBV) and identify the Mass genotype. The method was able to rapidly identify the Mass genotype among IBV field isolates, vaccine attenuated strains and reference M41 strain in allantoic liquid and also directly in tissues. The RT-qPCR developed detected the virus in both tracheal and pulmonary samples from M41-infected or H120-infected birds, in a larger post-infection period compared to detection by standard method of virus isolation. RT-qPCR method tested provided a sensitivity and rapid approach for screening on IBV detection and Mass genotyping from IBV isolates. PMID:29491226

Dereplication of peptidic natural products through database search of mass spectra

PubMed Central

Mohimani, Hosein; Gurevich, Alexey; Mikheenko, Alla; Garg, Neha; Nothias, Louis-Felix; Ninomiya, Akihiro; Takada, Kentaro; Dorrestein, Pieter C.; Pevzner, Pavel A.

2016-01-01

Peptidic Natural Products (PNPs) are widely used compounds that include many antibiotics and a variety of other bioactive peptides. While recent breakthroughs in PNP discovery raised the challenge of developing new algorithms for their analysis, identification of PNPs via database search of tandem mass spectra remains an open problem. To address this problem, natural product researchers utilize dereplication strategies that identify known PNPs and lead to the discovery of new ones even in cases when the reference spectra are not present in existing spectral libraries. DEREPLICATOR is a new dereplication algorithm that enabled high-throughput PNP identification and that is compatible with large-scale mass spectrometry-based screening platforms for natural product discovery. After searching nearly one hundred million tandem mass spectra in the Global Natural Products Social (GNPS) molecular networking infrastructure, DEREPLICATOR identified an order of magnitude more PNPs (and their new variants) than any previous dereplication efforts. PMID:27820803

An Evidence-Based Case Study of Unilateral Shin Splints: Do Red Flags Function in Paediatric Osteosarcoma?

PubMed Central

2015-01-01

ABSTRACT Physiotherapists use red flags to screen for serious pathology. Paediatric osteosarcoma is a rare disease, occurring predominantly in the area of the knee and shoulder, and it is not always included by physiotherapists on a differential diagnosis list. Traditional red flags do not always correspond to the initial signs and symptoms of osteosarcoma. Physiotherapists should routinely palpate along the length of the bone to detect a potential mass. The detection of a mass or symptoms that do not follow the expected course indicates the need for reassessment and possibly referral for further investigation. PMID:27504036

An in vitro AChE inhibition assay combined with UF-HPLC-ESI-Q-TOF/MS approach for screening and characterizing of AChE inhibitors from roots of Coptis chinensis Franch.

PubMed

Zhao, Hengqiang; Zhou, Siduo; Zhang, Minmin; Feng, Jinhong; Wang, Shanshan; Wang, Daijie; Geng, Yanling; Wang, Xiao

2016-02-20

In this study, an in vitro acetylcholinesterase (AChE) inhibition assay based on microplate reader combined with ultrafiltration high performance liquid chromatography-electrospray quadrupole time of flight mass (UF-HPLC-ESI-Q-TOF/MS) was developed for the rapid screening and identification of acetylcholinesterase inhibitors (AChEI) from roots of Coptis chinensis Franch. Incubation conditions such as enzyme concentration, incubation time, incubation temperature and co-solvent was optimized so as to get better screening results. Five alkaloids including columbamine, jatrorrhizine, coptisine, palmatine and berberine were found with AChE inhibition activity in the 80% ethanol extract of C. chinensis Franch. The screened compounds were identified by HPLC-DAD-ESI-Q-TOF/MS compared with the reference stands and literatures. The screened results were verified by in vitro AChE inhibition assays, palmatine showed the best AChE inhibitory activities with IC50 values of 36.6μM among the five compounds. Results of the present study indicated that the combinative method using in vitro AChE inhibition assay and UF-HPLC-ESI-Q-TOF/MS could be widely applied for rapid screening and identification of AChEI from complex TCM extract. Copyright © 2015 Elsevier B.V. All rights reserved.

Estimated Cost of Crashes in Commercial Drivers Supports Screening and Treatment of Obstructive Sleep Apnea

PubMed Central

Gurubhagavatula, Indira; Nkwuo, Jonathan E.; Maislin, Greg; Pack, Allan I.

2009-01-01

Sleep apnea among commercial drivers may increase the risk of fall-asleep crashes, which incur large expenses. Drivers of passenger cars whose apnea is treated experience lower crash risk. Among community-based holders of commercial driver’s licenses, we considered three methods for identifying sleep apnea syndrome: 1) in-lab polysomnography; 2) selective in-lab polysomnography for high-risk drivers, where high risk is first identified by body mass index, age and gender, followed by oximetry in a subset of drivers; and 3) not screening. The costs for each of these three programs equaled the sum of the costs of testing, treatment of identified cases, and crashes. Assuming that treatment prevents apnea-related crashes, polysomnography is not cost-effective, because it was more expensive than the cost of crashes when no screening is done. Screening with BMI, age and gender, however, with confirmatory in-lab polysomnography only on high-risk drivers was cost-effective, as long as a high proportion (73.8%) of screened drivers accepts treatment. These findings indicate that strategies that reduce reliance on in-laboratory polysomnography may be more cost-effective than not screening, and that treatment acceptance may need to be a condition of employment for affected drivers. PMID:18215538

Analysis of suspicious powders following the post 9/11 anthrax scare.

PubMed

Wills, Brandon; Leikin, Jerrold; Rhee, James; Saeedi, Bijan

2008-06-01

Following the 9/11 terrorist attacks, SET Environmental, Inc., a Chicago-based environmental and hazardous materials management company received a large number of suspicious powders for analysis. Samples of powders were submitted to SET for anthrax screening and/or unknown identification (UI). Anthrax screening was performed on-site using a ruggedized analytical pathogen identification device (R.A.P.I.D.) (Idaho Technologies, Salt Lake City, UT). UI was performed at SET headquarters (Wheeling, IL) utilizing a combination of wet chemistry techniques, infrared spectroscopy, and gas chromatography/mass spectroscopy. Turnaround time was approximately 2-3 hours for either anthrax or UI. Between October 10, 2001 and October 11, 2002, 161 samples were analyzed. Of these, 57 were for anthrax screening only, 78 were for anthrax and UI, and 26 were for UI only. Sources of suspicious powders included industries (66%), U.S. Postal Service (19%), law enforcement (9%), and municipalities (7%). There were 0/135 anthrax screens that were positive. There were no positive anthrax screens performed by SET in the Chicago area following the post-9/11 anthrax scare. The only potential biological or chemical warfare agent identified (cyanide) was provided by law enforcement. Rapid anthrax screening and identification of unknown substances at the scene are useful to prevent costly interruption of services and potential referral for medical evaluation.

Pion quasiparticle in the low-temperature phase of QCD

NASA Astrophysics Data System (ADS)

Brandt, Bastian B.; Francis, Anthony; Meyer, Harvey B.; Robaina, Daniel

2015-11-01

We investigate the properties of the pion quasiparticle in the low-temperature phase of two-flavor QCD on the lattice with support from chiral effective theory. We find that the pion quasiparticle mass is significantly reduced compared to its value in the vacuum, in contrast with the static screening mass, which increases with temperature. By a simple argument, near the chiral limit the two masses are expected to determine the quasiparticle dispersion relation. Analyzing two-point functions of the axial charge density at nonvanishing spatial momentum, we find that the predicted dispersion relation and the residue of the pion pole are consistent with the lattice data at low momentum. This test, based on fits to the correlation functions, is confirmed by a second analysis using the Backus-Gilbert method.

Reference Centile Curves for Body Fat Percentage, Fat-free Mass, Muscle Mass and Bone Mass Measured by Bioelectrical Impedance in Asian Indian Children and Adolescents.

PubMed

Chiplonkar, Shashi; Kajale, Neha; Ekbote, Veena; Mandlik, Rubina; Parthasarathy, Lavanya; Borade, Ashwin; Patel, Pinal; Patel, Prerna; Khadilkar, Vaman; Khadilkar, Anuradha

2017-12-15

To create gender-specific percentile curves for percent body fat (%BF) by Bio electrical Impedance Analysis (BIA) for screening adiposity and risk of hypertension in Indian children and generate reference curves for percent fat-free mass (%FFM), muscle mass (%LM) and bone mineral content (BMC) by using bioelectrical impedance. Secondary analysis of data from previous multicenter cross-sectional studies. Private schools from five regions of India. A random sample of 3850 healthy school children (2067 boys) (5-17 yr) from private schools in five major Indian cities. Anthropometry, blood pressure (BP) and body composition were measured by bioelectrical impedance. Reference curves were generated by the LMS method. %BF, %FFM, %LM, BMC and BP. Median %BF increased by 6% from 5 to 13 years of age and declined (around 2%) up to 17 years in boys. In girls, %BF increased by 8% from 5 to 14 years and thereafter declined by 3%. Based upon the risk of hypertension, the new cut-offs of 75th and 85th percentile of %BF were proposed for detecting over fatness and excess fatness in children. Median %FFM was 90% at 5 yrs and decreased till 12 years, and then showed a slight increase to 84% at 17 yrs in boys. In girls, it was 86% at 5 yrs and decreased till 15 yrs, and plateaued at 71.8% at 17 yrs. Reference curves for percent body fat for Indian children would be useful to screen children for health risk in clinical set up.

MRM screening/biomarker discovery with linear ion trap MS: a library of human cancer-specific peptides.

PubMed

Yang, Xu; Lazar, Iulia M

2009-03-27

The discovery of novel protein biomarkers is essential in the clinical setting to enable early disease diagnosis and increase survivability rates. To facilitate differential expression analysis and biomarker discovery, a variety of tandem mass spectrometry (MS/MS)-based protein profiling techniques have been developed. For achieving sensitive detection and accurate quantitation, targeted MS screening approaches, such as multiple reaction monitoring (MRM), have been implemented. MCF-7 breast cancer protein cellular extracts were analyzed by 2D-strong cation exchange (SCX)/reversed phase liquid chromatography (RPLC) separations interfaced to linear ion trap MS detection. MS data were interpreted with the Sequest-based Bioworks software (Thermo Electron). In-house developed Perl-scripts were used to calculate the spectral counts and the representative fragment ions for each peptide. In this work, we report on the generation of a library of 9,677 peptides (p < 0.001), representing approximately 1,572 proteins from human breast cancer cells, that can be used for MRM/MS-based biomarker screening studies. For each protein, the library provides the number and sequence of detectable peptides, the charge state, the spectral count, the molecular weight, the parameters that characterize the quality of the tandem mass spectrum (p-value, DeltaM, Xcorr, DeltaCn, Sp, no. of matching a, b, y ions in the spectrum), the retention time, and the top 10 most intense product ions that correspond to a given peptide. Only proteins identified by at least two spectral counts are listed. The experimental distribution of protein frequencies, as a function of molecular weight, closely matched the theoretical distribution of proteins in the human proteome, as provided in the SwissProt database. The amino acid sequence coverage of the identified proteins ranged from 0.04% to 98.3%. The highest-abundance proteins in the cellular extract had a molecular weight (MW)<50,000. Preliminary experiments have demonstrated that putative biomarkers, that are not detectable by conventional data dependent MS acquisition methods in complex un-fractionated samples, can be reliable identified with the information provided in this library. Based on the spectral count, the quality of a tandem mass spectrum and the m/z values for a parent peptide and its most abundant daughter ions, MRM conditions can be selected to enable the detection of target peptides and proteins.

MRM screening/biomarker discovery with linear ion trap MS: a library of human cancer-specific peptides

PubMed Central

2009-01-01

Background The discovery of novel protein biomarkers is essential in the clinical setting to enable early disease diagnosis and increase survivability rates. To facilitate differential expression analysis and biomarker discovery, a variety of tandem mass spectrometry (MS/MS)-based protein profiling techniques have been developed. For achieving sensitive detection and accurate quantitation, targeted MS screening approaches, such as multiple reaction monitoring (MRM), have been implemented. Methods MCF-7 breast cancer protein cellular extracts were analyzed by 2D-strong cation exchange (SCX)/reversed phase liquid chromatography (RPLC) separations interfaced to linear ion trap MS detection. MS data were interpreted with the Sequest-based Bioworks software (Thermo Electron). In-house developed Perl-scripts were used to calculate the spectral counts and the representative fragment ions for each peptide. Results In this work, we report on the generation of a library of 9,677 peptides (p < 0.001), representing ~1,572 proteins from human breast cancer cells, that can be used for MRM/MS-based biomarker screening studies. For each protein, the library provides the number and sequence of detectable peptides, the charge state, the spectral count, the molecular weight, the parameters that characterize the quality of the tandem mass spectrum (p-value, DeltaM, Xcorr, DeltaCn, Sp, no. of matching a, b, y ions in the spectrum), the retention time, and the top 10 most intense product ions that correspond to a given peptide. Only proteins identified by at least two spectral counts are listed. The experimental distribution of protein frequencies, as a function of molecular weight, closely matched the theoretical distribution of proteins in the human proteome, as provided in the SwissProt database. The amino acid sequence coverage of the identified proteins ranged from 0.04% to 98.3%. The highest-abundance proteins in the cellular extract had a molecular weight (MW)<50,000. Conclusion Preliminary experiments have demonstrated that putative biomarkers, that are not detectable by conventional data dependent MS acquisition methods in complex un-fractionated samples, can be reliable identified with the information provided in this library. Based on the spectral count, the quality of a tandem mass spectrum and the m/z values for a parent peptide and its most abundant daughter ions, MRM conditions can be selected to enable the detection of target peptides and proteins. PMID:19327145

Diagnosis of glutathione synthetase deficiency in newborn screening.

PubMed

Simon, E; Vogel, M; Fingerhut, R; Ristoff, E; Mayatepek, E; Spiekerkötter, U

2009-12-01

Glutathione synthetase (GSS) deficiency is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with haemolytic anaemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low GSS activity in erythrocytes or cultured skin fibroblasts. Diagnosis can be confirmed by mutational analysis. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. The most important determinants for outcome and survival in patients with GSS deficiency are early diagnosis and early initiation of treatment. The case of a newborn with GSS deficiency diagnosed by tandem mass spectrometry (MS/MS)-based newborn screening is described. After onset of clinical symptoms on the 2nd day of life, expanded newborn screening revealed normal results for all disorders included in the German screening programme; however, selective MS/MS screening revealed a >10-fold elevation of 5-oxoproline in dried blood, leading to the presumptive diagnosis of GSS deficiency by the 5th day of life. Diagnosis was later confirmed by detection of markedly reduced glutathione concentration in erythrocytes and mutational analysis of the GSS gene. Presently, GSS deficiency is not included in newborn screening programmes in Europe. As outcome depends significantly on early start of treatment, routine inclusion of this disorder in newborn screening panels should be considered.

Sickle Cell Screening: Medical, Legal, Ethical, Psychological and Social Problems; A Sickle Cell Crisis.

ERIC Educational Resources Information Center

Bowman, James E.

In recent years, sickle cell screening programs have been initiated by community groups, health centers, hospitals, medical schools, health departments, school systems, city and State governments, various branches of the Federal Government, fraternal and social clubs, and other organizations. Problems have resulted from mass sickle cell screening,…

10 CFR 960.3-2-1 - Site screening for potentially acceptable sites.

Code of Federal Regulations, 2010 CFR

2010-01-01

... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-2-1 Site screening for... first repository, the process shall begin with site-screening activities that consider large land masses... repositories, the Secretary shall first identify the State within which the site is located in a decision-basis...

Direct analysis of prostaglandin-E2 and -D2 produced in an inflammatory cell reaction and its application for activity screening and potency evaluation using turbulent flow chromatography liquid chromatography-high resolution mass spectrometry.

PubMed

Shin, Jeong-Sook; Peng, Lei; Kang, Kyungsu; Choi, Yongsoo

2016-09-09

Direct analysis of prostaglandin-E2 (PGE2) and -D2 (PGD2) produced from a RAW264.7 cell-based reaction was performed by liquid chromatography high-resolution mass spectrometry (LC-HRMS), which was online coupled with turbulent flow chromatography (TFC). The capability of this method to accurately measure PG levels in cell reaction medium containing cytokines or proteins as a reaction byproduct was cross-validated by two conventional methods. Two methods, including an LC-HRMS method after liquid-liquid extraction (LLE) of the sample and a commercial PGE2 enzyme-linked immunosorbent assay (ELISA), showed PGE2 and/or PGD2 levels almost similar to those obtained by TFC LC-HRMS over the reaction time after LPS stimulation. After the cross-validation, significant analytical throughputs, allowing simultaneous screening and potency evaluation of 80 natural products including 60 phytochemicals and 20 natural product extracts for the inhibition of the PGD2 produced in the cell-based inflammatory reaction, were achieved using the TFC LC-HRMS method developed. Among the 60 phytochemicals screened, licochalcone A and formononetin inhibited PGD2 production the most with IC50 values of 126 and 151nM, respectively. For a reference activity, indomethacin and diclofenac were used, measuring IC50 values of 0.64 and 0.21nM, respectively. This method also found a butanol extract of Akebia quinata Decne (AQ) stem as a promising natural product for PGD2 inhibition. Direct and accurate analysis of PGs in the inflammatory cell reaction using the TFC LC-HRMS method developed enables the high-throughput screening and potency evaluation of as many as 320 samples in less than 48h without changing a TFC column. Copyright © 2016 Elsevier B.V. All rights reserved.

Sarcopenia Screened by the SARC-F Questionnaire and Physical Performances of Elderly Women: A Cross-Sectional Study.

PubMed

Rolland, Yves; Dupuy, Charlotte; Abellan Van Kan, Gabor; Cesari, Matteo; Vellas, Bruno; Faruch, Marie; Dray, Cedric; de Souto Barreto, Philipe

2017-10-01

Screening for sarcopenia in daily practice can be challenging. Our objective was to explore whether the SARC-F questionnaire is a valid screening tool for sarcopenia (defined by the Foundation for the National Institutes of Health [FNIH] criteria). Moreover, we evaluated the physical performance of older women according to the SARC-F questionnaire. Cross-sectional study. Data from the Toulouse and Lyon EPIDémiologie de l'OStéoporose study (EPIDOS) on 3025 women living in the community (mean age: 80.5 ± 3.9 years), without a previous history of hip fracture, were assessed. The SARC-F self-report questionnaire score ranges from 0 to 10: a score ≥4 defines sarcopenia. The FNIH criteria uses handgrip strength (GS) and appendicular lean mass (ALM; assessed by DXA) divided by body mass index (BMI) to define sarcopenia. Outcome measures were the following performance-based tests: knee-extension strength, 6-m gait speed, and a repeated chair-stand test. The associations of sarcopenia with performance-based tests was examined using bootstrap multiple linear-regression models; adjusted R 2 determined the percentage variation for each outcome explained by the model. Prevalence of sarcopenia was 16.7% (n = 504) according to the SARC-F questionnaire and 1.8% (n = 49) using the FNIH criteria. Sensibility and specificity of the SARC-F to diagnose sarcopenia (defined by FNIH criteria) were 34% and 85%, respectively. Sarcopenic women defined by SARC-F had significantly lower physical performance than nonsarcopenic women. The SARC-F improved the ability to predict poor physical performance. The validity of the SARC-F questionnaire to screen for sarcopenia, when compared with the FNIH criteria, was limited. However, sarcopenia defined by the SARC-F questionnaire substantially improved the predictive value of clinical characteristics of patients to predict poor physical performance. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Screening of polar components of petroleum products by electrospray ionization mass spectrometry

USGS Publications Warehouse

Rostad, Colleen E.

2005-01-01

The polar components of fuels may enable differentiation between fuel types or commercial fuel sources. Screening for these components in the hydrocarbon product is difficult due to their very low concentrations in such a complex matrix. Various commercial fuels from several sources were analyzed by flow injection analysis/electrospray ionization/mass spectrometry without extensive sample preparation, separation, or chromatography. This technique enabled screening for unique polar components at very low concentrations in commercial hydrocarbon products. This analysis was then applied to hydrocarbon samples collected from the subsurface with a different extent of biodegradation or weathering. Although the alkane and isoprenoid portion had begun to biodegrade or weather, the polar components had changed little over time. Because these polar compounds are unique in different fuels, this screening technique can provide source information on hydrocarbons released into the environment.

Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching.

PubMed

Dresen, S; Ferreirós, N; Gnann, H; Zimmermann, R; Weinmann, W

2010-04-01

The multi-target screening method described in this work allows the simultaneous detection and identification of 700 drugs and metabolites in biological fluids using a hybrid triple-quadrupole linear ion trap mass spectrometer in a single analytical run. After standardization of the method, the retention times of 700 compounds were determined and transitions for each compound were selected by a "scheduled" survey MRM scan, followed by an information-dependent acquisition using the sensitive enhanced product ion scan of a Q TRAP hybrid instrument. The identification of the compounds in the samples analyzed was accomplished by searching the tandem mass spectrometry (MS/MS) spectra against the library we developed, which contains electrospray ionization-MS/MS spectra of over 1,250 compounds. The multi-target screening method together with the library was included in a software program for routine screening and quantitation to achieve automated acquisition and library searching. With the help of this software application, the time for evaluation and interpretation of the results could be drastically reduced. This new multi-target screening method has been successfully applied for the analysis of postmortem and traffic offense samples as well as proficiency testing, and complements screening with immunoassays, gas chromatography-mass spectrometry, and liquid chromatography-diode-array detection. Other possible applications are analysis in clinical toxicology (for intoxication cases), in psychiatry (antidepressants and other psychoactive drugs), and in forensic toxicology (drugs and driving, workplace drug testing, oral fluid analysis, drug-facilitated sexual assault).

The current revolution in newborn screening: new technology, old controversies.

PubMed

Tarini, Beth A

2007-08-01

Newborn screening has provided a model of a successful public health screening program for the past 40 years. However, the history of newborn screening is not without controversy. Many of these controversies have been rekindled with the introduction of tandem mass spectrometry, a technology that has greatly increased our ability to detect potential disease in asymptomatic newborns. This review highlights the challenges raised by this and future technological advances as we strive to maintain the success of newborn screening in the 21st century.

Protein Changes in Macrophages Induced by Plasma from Rats Exposed to 35-GHz Millimeter Waves

DTIC Science & Technology

2010-12-01

HumanEffectiveness Directorate, Air Force Research Laboratory, Brooks City-Base,Texas A macrophage assay and proteomic screening were used to...mW/cm2 until core temperature reached 41.0 8C. Two-dimensional polyacrylamide gel electrophoresis, image analysis, and Western blotting were used to...stimulation. Proteins of interest were identified using peptide mass fingerprinting. Compared to plasma from sham- exposed rats, plasma from

Development of a loop-mediated isothermal amplification method for rapid mass-screening of sand flies for Leishmania infection.

PubMed

Nzelu, Chukwunonso O; Gomez, Eduardo A; Cáceres, Abraham G; Sakurai, Tatsuya; Martini-Robles, Luiggi; Uezato, Hiroshi; Mimori, Tatsuyuki; Katakura, Ken; Hashiguchi, Yoshihisa; Kato, Hirotomo

2014-04-01

Entomological monitoring of Leishmania infection in leishmaniasis endemic areas offers epidemiologic advantages for predicting the risk and expansion of the disease, as well as evaluation of the effectiveness of control programs. In this study, we developed a highly sensitive loop-mediated isothermal amplification (LAMP) method for the mass screening of sand flies for Leishmania infection based on the 18S rRNA gene. The LAMP technique could detect 0.01 parasites, which was more sensitive than classical PCR. The method was robust and could amplify the target DNA within 1h from a crude sand fly template without DNA purification. Amplicon detection could be accomplished by the newly developed colorimetric malachite green (MG)--mediated naked eye visualization. Pre-addition of MG to the LAMP reaction solution did not inhibit amplification efficiency. The field applicability of the colorimetric MG-based LAMP assay was demonstrated with 397 field-caught samples from the endemic areas of Ecuador and eight positive sand flies were detected. The robustness, superior sensitivity, and ability to produce better visual discriminatory reaction products than existing LAMP fluorescence and turbidity assays indicated the field potential usefulness of this new method for surveillance and epidemiological studies of leishmaniasis in developing countries. Copyright © 2013 Elsevier B.V. All rights reserved.

Integration of magnetic solid phase fishing and off-line two-dimensional high-performance liquid chromatography-diode array detector-mass spectrometry for screening and identification of human serum albumin binders from Radix Astragali.

PubMed

Zhang, Yuping; Nie, Mingkun; Shi, Shuyun; You, Qingping; Guo, Junfang; Liu, Liangliang

2014-03-01

Radix Astragali is one of the most popular traditional medicinal herb and healthy dietary supplement. Isoflavonoids and astragalosides are the main bioactive ingredients. However, the systematic bioactive component analysis is inadequate so far. Then a facile method based on Fe3O4@SiO2-human serum albumin (Fe3O4@SiO2-HSA) magnetic solid phase fishing integrated with two-dimensional high-performance liquid chromatography-diode array detector-mass spectrometry (2D HPLC-DAD-MS(n)) was developed to fish out and identify HSA binders from Radix Astragali. The immobilized HSA displayed a high stability with 96.2% retained after ten consecutive cycles. 2D HPLC system (size exclusion chromatography×reversed phase chromatography, SEC×RP) were developed and optimised. Forty-seven bioactive compounds including thirty-four isoflavonoids and thirteen astragalosides were screened and identified or tentatively deduced based on their retention time, ultraviolet (UV), accurate molecular weight and diagnostic fragment ions. The results indicated that the integrated method could be widely applied for systematical fishing and identification of bioactive compounds, especially for low-abundance and overlapped compounds, from complex mixtures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Direct analysis in real time high resolution mass spectrometry as a tool for rapid characterization of mind-altering plant materials and revelation of supplement adulteration--The case of Kanna.

PubMed

Lesiak, Ashton D; Cody, Robert B; Ubukata, Masaaki; Musah, Rabi A

2016-03-01

We demonstrate the utility of direct analysis in real time ionization coupled with high resolution time-of-flight mass spectrometry (DART-HRTOFMS) in revealing the adulteration of commercially available Sceletium tortuosum, a mind-altering plant-based drug commonly known as Kanna. Accurate masses consistent with alkaloids previously isolated from S. tortuosum plant material enabled identification of the products as Kanna, and in-source collision-induced dissociation (CID) confirmed the presence of one of these alkaloids, hordenine, while simultaneously revealing the presence of an adulterant. The stimulant ephedrine, which has been banned in herbal products and supplements, was confirmed to be present in a sample through the use of in-source CID. High-throughput DART-HRTOFMS was shown to be a powerful tool to not only screen plant-based drugs of abuse for psychotropic alkaloids, but also to reveal the presence of scheduled substances and adulterants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Avoiding Misannotation of In-Source Fragmentation Products as Cellular Metabolites in Liquid Chromatography–Mass Spectrometry-Based Metabolomics

DOE PAGES

Xu, Yi-Fan; Lu, Wenyun; Rabinowitz, Joshua D.

2015-01-15

Liquid chromatography–mass spectrometry (LC-MS) technology allows for rapid quantitation of cellular metabolites, with metabolites identified by mass spectrometry and chromatographic retention time. Recently, with the development of rapid scanning high-resolution high accuracy mass spectrometers and the desire for high throughput screening, minimal or no chromatographic separation has become increasingly popular. Furthermore, when analyzing complex cellular extracts, however, the lack of chromatographic separation could potentially result in misannotation of structurally related metabolites. Here, we show that, even using electrospray ionization, a soft ionization method, in-source fragmentation generates unwanted byproducts of identical mass to common metabolites. For example, nucleotide-triphosphates generate nucleotide-diphosphates, andmore » hexose-phosphates generate triose-phosphates. We also evaluated yeast intracellular metabolite extracts and found more than 20 cases of in-source fragments that mimic common metabolites. Finally and accordingly, chromatographic separation is required for accurate quantitation of many common cellular metabolites.« less

Screened exchange hybrid density functional for accurate and efficient structures and interaction energies.

PubMed

Brandenburg, Jan Gerit; Caldeweyher, Eike; Grimme, Stefan

2016-06-21

We extend the recently introduced PBEh-3c global hybrid density functional [S. Grimme et al., J. Chem. Phys., 2015, 143, 054107] by a screened Fock exchange variant based on the Henderson-Janesko-Scuseria exchange hole model. While the excellent performance of the global hybrid is maintained for small covalently bound molecules, its performance for computed condensed phase mass densities is further improved. Most importantly, a speed up of 30 to 50% can be achieved and especially for small orbital energy gap cases, the method is numerically much more robust. The latter point is important for many applications, e.g., for metal-organic frameworks, organic semiconductors, or protein structures. This enables an accurate density functional based electronic structure calculation of a full DNA helix structure on a single core desktop computer which is presented as an example in addition to comprehensive benchmark results.

Screening for Natural Inhibitors of Topoisomerases I from Rhamnus davurica by Affinity Ultrafiltration and High-Performance Liquid Chromatography–Mass Spectrometry

PubMed Central

Chen, Guilin; Guo, Mingquan

2017-01-01

Topoisomerase I (Topo I) catalyzes topological interconversion of duplex DNA during DNA replication and transcription, and has been deemed as important antineoplastic targets. In this study, the fraction R.d-60 from ethyl acetate extracts of Rhamnus davurica showed higher inhibitory rates against SGC-7901 and HT-29 compared with the R.d-30 fraction in vitro. However, the specific active components of R.d-60 fraction remain elusive. To this end, a method based on bio-affinity ultrafiltration and high performance liquid chromatography/electrospray mass spectrometry (HPLC- ESI-MS/MS) was developed to rapidly screen and identify the Topo I inhibitors in this fraction. The enrichment factors (EFs) were calculated to evaluate the binding affinities between the bioactive constituents and Topo I. As a result, eight ligands were identified and six of which with higher EFs showed more potential antitumor activity. Furthermore, antiproliferative assays in vitro (IC50 values) with two representative candidates (apigenin, quercetin) against SGC-7901, HT-29 and Hep G2 cells were conducted and further validated. Finally, the structure-activity relationships revealed that flavones contain a C2-C3 double bond of C ring exhibited higher bio-affinities to Topo I than those without it. This integrated method combining Topo I ultrafiltration with HPLC-MS/MS proved to be very efficient in rapid screening and identification of potential Topo I inhibitors from the complex extracts of medicinal plants, and could be further explored as a valuable high-throughput screening platform in the early drug discovery stage. PMID:28919906

Two-dimensional turbulent flow chromatography coupled on-line to liquid chromatography-mass spectrometry for solution-based ligand screening against multiple proteins.

PubMed

Zhou, Jian-Liang; An, Jing-Jing; Li, Ping; Li, Hui-Jun; Jiang, Yan; Cheng, Jie-Fei

2009-03-20

We present herein a novel bioseparation/chemical analysis strategy for protein-ligand screening and affinity ranking in compound mixtures, designed to increase screening rates and improve sensitivity and ruggedness in performance. The strategy is carried out by combining on-line two-dimensional turbulent flow chromatography (2D-TFC) with liquid chromatography-mass spectrometry (LC-MS), and accomplished through the following steps: (1) a reversed-phase TFC stage to separate the protein/ligand complex from the unbound free molecules, (2) an on-line dissociation process to release the bound ligands from the complexes, and (3) a second mixed-mode cation-exchange/reversed-phase TFC stage to trap the bound ligands and to remove the proteins and salts, followed by LC-MS analysis for identification and determination of the binding affinities. The technique can implement an ultra-fast isolation of protein/ligand complex with the retention time of a complex peak in about 5s, and on-line prepare the "clean" sample to be directly compatible with the LC-MS analysis. The improvement in performance of this 2D-TFC/LC-MS approach over the conventional approach has been demonstrated by determining affinity-selected ligands of the target proteins acetylcholinesterase and butyrylcholinesterase from a small library with known binding affinities and a steroidal alkaloid library composed of structurally similar compounds. Our results show that 2D-TFC/LC-MS is a generic and efficient tool for high-throughput screening of ligands with low-to-high binding affinities, and structure-activity relationship evaluation.

Rapid Screening and Characterization of Acetylcholinesterase Inhibitors from Yinhuang Oral Liquid Using Ultrafiltration-liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry

PubMed Central

Zhang, Haomin; Guo, Yinan; Meng, Lingwen; Sun, Hui; Yang, Yinping; Gao, Ying; Sun, Jiaming

2018-01-01

Background: At present, approximately 17–25 million people in the world suffer from Alzheimer's disease (AD). The most efficacious and acceptable therapeutic drug clinically are the acetylcholinesterase inhibitors (AChEIs). Yinhuang oral liquid is a Chinese medicine preparation which contains AChEIs according to the literatures. However, no strategy has been presented for rapid screening and identification of AChEIs from Yinhuang oral liquid. Objective: To develop a method for rapid screening and identification of AChEIs from Yinhuang oral liquid using ultrafiltration–liquid chromatography–electrospray ionization tandem mass spectrometry (UF-LC-ESI-MS/MS). Materials and Methods: In this study, UF incubation conditions such as enzyme concentration, incubation time, and incubation temperature were optimized so as to get better screening results. The AChEIs from Yinhuang oral liquid were identified by high-performance liquid chromatography-ESI-MS and the improved Ellman method was used for the AChE inhibitory activity test in vitro. Results: The results showed that Yinhuang oral liquid can inhibit the activity of AChE. We screened and identified seven compounds with potential AChE inhibitory activity from Yinhuang oral liquid, which provided experimental basis for the treatment and prevention of AD. Conclusion: The current technique was used to directly screen the active ingredients with acetylcholinesterase inhibition from complex traditional Chinese medicine, which was simple, rapid, accurate, and suitable for high-throughput screening of AChEI from complex systems. SUMMARY A UF-LC-ESI-MS/MS method for rapid screening and identification of AChEIs from Yinhuang oral liquid was developedSeven compounds were screened and identified with potential AChE inhibitory activity from Yinhuang oral liquidIt provided experimental basis of Yinhuang oral liquid for the treating and preventing AD. Abbreviations used: (AD): Alzheimer's disease; (UF-LC-ESI-MS/MS): ultrafiltration–liquid chromatography–electrospray ionization tandem mass spectrometry; (AChEIs): acetylcholinesterase inhibitors. PMID:29720840

Patterns of colorectal cancer screening uptake in newly-eligible men and women

PubMed Central

Wernli, Karen J.; Hubbard, Rebecca A.; Johnson, Eric; Chubak, Jessica; Kamineni, Aruna; Green, Beverly B.; Rutter, Carolyn M.

2014-01-01

Background We describe patterns of colorectal cancer screening uptake in a U.S. insured population as individuals become newly-eligible for screening at age 50 and assess temporal trends and patient characteristics with screening uptake. Methods We identified a cohort of 81,223 men and women who were members of Group Health and turned 50 years old from 1996 – 2010. We ascertained receipt of colorectal cancer screening within five years. Time to screening was estimated by year of cohort entry using cumulative incidence curves and Cox proportional hazards models estimated patient characteristics associated with screening uptake. Results Stool-based screening tests were the most common, 72% of first screening tests. The proportion of individuals initiating colorectal cancer screening via colonoscopy increased from 8% in 1996–98 to 33% in 2008–10. Patient factors associated with increased colorectal cancer screening were: turning 50 more recently (2008–10) (p-trend<0.0001) or Asian race (HR=1.14, 95% CI 1.10–1.19). Patient factors associated with decreased screening were: being a woman (HR=0.70, 95% CI 0.68–0.72), Native American (HR=0.68, 95% CI 0.60–0.78) or Pacific Islander race (HR=0.82, 95% CI 0.72–0.95), and having prevalent diabetes (HR=0.78, 95% CI 0.75–0.82) and higher body mass index (p-trend<0.0001). Conclusions Patient characteristics associated with initiation of colorectal cancer screening in a newly-eligible population are similar to characteristics associated with overall screening participation in all age-eligible adults. Our results identify patient populations to target in outreach programs. Impact Disparities in receipt of colorectal cancer screening are evident from onset of an age-eligible cohort, identifying key groups for future interventions for screening. PMID:24793956

The shape dependence of chameleon screening

NASA Astrophysics Data System (ADS)

Burrage, Clare; Copeland, Edmund J.; Moss, Adam; Stevenson, James A.

2018-01-01

Chameleon scalar fields can screen their associated fifth forces from detection by changing their mass with the local density. These models are an archetypal example of a screening mechanism, and have become an important target for both cosmological surveys and terrestrial experiments. In particular there has been much recent interest in searching for chameleon fifth forces in the laboratory. It is known that the chameleon force is less screened around non-spherical sources, but only the field profiles around a few simple shapes are known analytically. In this work we introduce a numerical code that solves for the chameleon field around arbitrary shapes with azimuthal symmetry placed in a spherical vacuum chamber. We find that deviations from spherical symmetry can increase the chameleon acceleration experienced by a test particle, and that the least screened objects are those which minimize some internal dimension. For the shapes considered in this work, keeping the mass, density and background environment fixed, the accelerations due to the source varied by a factor of ~ 3.

Edge-directed inference for microaneurysms detection in digital fundus images

NASA Astrophysics Data System (ADS)

Huang, Ke; Yan, Michelle; Aviyente, Selin

2007-03-01

Microaneurysms (MAs) detection is a critical step in diabetic retinopathy screening, since MAs are the earliest visible warning of potential future problems. A variety of algorithms have been proposed for MAs detection in mass screening. Different methods have been proposed for MAs detection. The core technology for most of existing methods is based on a directional mathematical morphological operation called "Top-Hat" filter that requires multiple filtering operations at each pixel. Background structure, uneven illumination and noise often cause confusion between MAs and some non-MA structures and limits the applicability of the filter. In this paper, a novel detection framework based on edge directed inference is proposed for MAs detection. The candidate MA regions are first delineated from the edge map of a fundus image. Features measuring shape, brightness and contrast are extracted for each candidate MA region to better exclude false detection from true MAs. Algorithmic analysis and empirical evaluation reveal that the proposed edge directed inference outperforms the "Top-Hat" based algorithm in both detection accuracy and computational speed.

Criterion for excipients screening in the development of nanoemulsion formulation of three anti-inflammatory drugs.

PubMed

Shakeel, Faiyaz

2010-01-01

The present study was undertaken for screening of different excipients in the development of nanoemulsion formulations of three anti-inflammatory drugs namely ketoprofen, celecoxib (CXB) and meloxicam. Based on solubility profiles of each drug in oil, Triacetin (ketoprofen and CXB) and Labrafil (meloxicam) were selected as the oil phase. Based on maximum solubilization potential of oil in different surfactants, Cremophor-EL (ketoprofen and CXB) and Tween-80 (meloxicam) were selected as surfactants. Based on maximum nanoemulsion region in the pseudoternary phase diagrams, Transcutol-HP was selected as cosurfactant for all three drugs. 1:1 (ketoprofen and CXB) and 2:1 (meloxicam) mass ratio of surfactant to cosurfactant was selected for selection of different nanoemulsions on the basis of maximum nanoemulsion region in the phase diagrams. All selected nanoemulsion formulations were found thermodynamically stable. Results of these studies showed that all excipients were properly optimized for the development of nanoemulsion formulation of ketoprofen, CXB and meloxicam.

Trends in Biometric Health Indices Within an Employer-Sponsored Wellness Program With Outcome-Based Incentives.

PubMed

Fu, Patricia Lin; Bradley, Kent L; Viswanathan, Sheila; Chan, June M; Stampfer, Meir

2016-07-01

To evaluate changes in employees' biometrics over time relative to outcome-based incentive thresholds. Retrospective cohort analysis of biometric screening participants (n = 26 388). Large employer primarily in Western United States. Office, retail, and distribution workforce. A voluntary outcome-based biometric screening program, incentivized with health insurance premium discounts. Body mass index (BMI), cholesterol, blood glucose, blood pressure, and nicotine. Followed were participants from their first year of participation, evaluating changes in measures. On average, participants who did not meet the incentive threshold at baseline decreased their BMI (1%), glucose (8%), blood pressure (systolic 9%, diastolic 8%), and total cholesterol (8%) by year 2 with improvements generally sustained or continued during each additional year of participation. On average, individuals at high health risk who participated in a financially incentivized biometric assessment program improved their health indices over time. Further research is needed to understand key determinants that drive health improvement indicated here. © The Author(s) 2016.

Screening and Rapid Molecular Diagnosis of Tuberculosis in Prisons in Russia and Eastern Europe: A Cost-Effectiveness Analysis

PubMed Central

Winetsky, Daniel E.; Negoescu, Diana M.; DeMarchis, Emilia H.; Almukhamedova, Olga; Dooronbekova, Aizhan; Pulatov, Dilshod; Vezhnina, Natalia; Owens, Douglas K.; Goldhaber-Fiebert, Jeremy D.

2012-01-01

Background Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission. Methods and Findings We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics. Conclusions In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time. Please see later in the article for the Editors' Summary PMID:23209384

Integration of an In Situ MALDI-Based High-Throughput Screening Process: A Case Study with Receptor Tyrosine Kinase c-MET.

PubMed

Beeman, Katrin; Baumgärtner, Jens; Laubenheimer, Manuel; Hergesell, Karlheinz; Hoffmann, Martin; Pehl, Ulrich; Fischer, Frank; Pieck, Jan-Carsten

2017-12-01

Mass spectrometry (MS) is known for its label-free detection of substrates and products from a variety of enzyme reactions. Recent hardware improvements have increased interest in the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS for high-throughput drug discovery. Despite interest in this technology, several challenges remain and must be overcome before MALDI-MS can be integrated as an automated "in-line reader" for high-throughput drug discovery. Two such hurdles include in situ sample processing and deposition, as well as integration of MALDI-MS for enzymatic screening assays that usually contain high levels of MS-incompatible components. Here we adapt our c-MET kinase assay to optimize for MALDI-MS compatibility and test its feasibility for compound screening. The pros and cons of the Echo (Labcyte) as a transfer system for in situ MALDI-MS sample preparation are discussed. We demonstrate that this method generates robust data in a 1536-grid format. We use the MALDI-MS to directly measure the ratio of c-MET substrate and phosphorylated product to acquire IC50 curves and demonstrate that the pharmacology is unaffected. The resulting IC50 values correlate well between the common label-based capillary electrophoresis and the label-free MALDI-MS detection method. We predict that label-free MALDI-MS-based high-throughput screening will become increasingly important and more widely used for drug discovery.

The effect of a healthy lifestyle programme on 8-9 year olds from social disadvantage.

PubMed

Breslin, Gavin; Brennan, Deirdre; Rafferty, Ruth; Gallagher, Alison M; Hanna, Donncha

2012-07-01

This study assessed the efficacy of a school-based healthy lifestyle intervention (Sport for LIFE) for increasing physical activity, decreasing sedentary behaviour, reducing screen time behaviour, encouraging healthy attitudes and behaviour to nutrition, and reducing body mass index (BMI) in 8-9-year-old primary school children from lower socioeconomic backgrounds in Northern Ireland. A non-randomised controlled trial of 416 children from 24 schools took part. Schools were randomly assigned to one of two groups, an intervention or control group with 12 schools in each group. The intervention group received a 12-week school-based programme based on social cognitive theory. At baseline and follow-up, groups completed questionnaires assessing physical activity, screen time behaviour and dietary patterns. On each occasion anthropometric assessments of height and weight were taken. Physical activity and sedentary behaviour were measured by accelerometry. Significant effects were observed for vigorous, moderate and light activity for the intervention group at follow-up. Sedentary behaviour was significantly reduced for the intervention group but not for the control group. No significant effects of the intervention on BMI, screen time behaviour or attitudes to nutrition, with the exception of non-core foods, were shown. The programme was effective in increasing physical activity and reducing sedentary behaviour, however no significant changes in screen time behaviour and attitude to nutrition, with the exception of non-core foods, were observed. Future research ideas are offered for tackling low levels of physical activity in children.

Computer-aided detection of breast masses: Four-view strategy for screening mammography

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

Wei Jun; Chan Heangping; Zhou Chuan

2011-04-15

Purpose: To improve the performance of a computer-aided detection (CAD) system for mass detection by using four-view information in screening mammography. Methods: The authors developed a four-view CAD system that emulates radiologists' reading by using the craniocaudal and mediolateral oblique views of the ipsilateral breast to reduce false positives (FPs) and the corresponding views of the contralateral breast to detect asymmetry. The CAD system consists of four major components: (1) Initial detection of breast masses on individual views, (2) information fusion of the ipsilateral views of the breast (referred to as two-view analysis), (3) information fusion of the corresponding viewsmore » of the contralateral breast (referred to as bilateral analysis), and (4) fusion of the four-view information with a decision tree. The authors collected two data sets for training and testing of the CAD system: A mass set containing 389 patients with 389 biopsy-proven masses and a normal set containing 200 normal subjects. All cases had four-view mammograms. The true locations of the masses on the mammograms were identified by an experienced MQSA radiologist. The authors randomly divided the mass set into two independent sets for cross validation training and testing. The overall test performance was assessed by averaging the free response receiver operating characteristic (FROC) curves of the two test subsets. The FP rates during the FROC analysis were estimated by using the normal set only. The jackknife free-response ROC (JAFROC) method was used to estimate the statistical significance of the difference between the test FROC curves obtained with the single-view and the four-view CAD systems. Results: Using the single-view CAD system, the breast-based test sensitivities were 58% and 77% at the FP rates of 0.5 and 1.0 per image, respectively. With the four-view CAD system, the breast-based test sensitivities were improved to 76% and 87% at the corresponding FP rates, respectively. The improvement was found to be statistically significant (p<0.0001) by JAFROC analysis. Conclusions: The four-view information fusion approach that emulates radiologists' reading strategy significantly improves the performance of breast mass detection of the CAD system in comparison with the single-view approach.« less

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

Rapid screening and identification of chemical hazards in surface and drinking water using high resolution mass spectrometry and a case-control filter.

PubMed

Kaserzon, Sarit L; Heffernan, Amy L; Thompson, Kristie; Mueller, Jochen F; Gomez Ramos, Maria Jose

2017-09-01

Access to clean, safe drinking water poses a serious challenge to regulators, and requires analytical strategies capable of rapid screening and identification of potentially hazardous chemicals, specifically in situations when threats to water quality or security require rapid investigations and potential response. This study describes a fast and efficient chemical hazard screening strategy for characterising trace levels of polar organic contaminants in water matrices, based on liquid chromatography high resolution mass spectrometry with post-acquisition 'case-control' data processing. This method allowed for a rapid response time of less than 24 h for the screening of target, suspect and non-target unknown chemicals via direct injection analysis, and a second, more sensitive analysis option requiring sample pre-concentration. The method was validated by fortifying samples with a range of pesticides, pharmaceuticals and personal care products (n = 46); with >90% of target compounds positively screened in samples at 1 ng mL -1 , and 46% at 0.1 ng mL -1 when analysed via direct injection. To simulate a contamination event samples were fortified with compounds not present in the commercial library (designated 'non-target compounds'; fipronil and fenitrothion), tentatively identified at 0.2 and 1 ng mL -1 , respectively; and a compound not included in any known commercial library or public database (designated 'unknown' compounds; 8Cl - perfluorooctanesulfonic acid), at 0.8 ng mL -1 . The method was applied to two 'real-case' scenarios: (1) the assessment of drinking water safety during a high-profile event in Brisbane, Australia; and (2) to screen treated, re-circulated drinking water and pre-treated (raw) water. The validated workflow was effective for rapid prioritisation and screening of suspect and non-target potential hazards at trace levels, and could be applied to a wide range of matrices and investigations where comparison of organic contaminants between an affected and control site and or timeframe is warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activity screening of carrier domains within nonribosomal peptide synthetases using complex substrate mixtures and large molecule mass spectrometry.

PubMed

Dorrestein, Pieter C; Blackhall, Jonathan; Straight, Paul D; Fischbach, Michael A; Garneau-Tsodikova, Sylvie; Edwards, Daniel J; McLaughlin, Shaun; Lin, Myat; Gerwick, William H; Kolter, Roberto; Walsh, Christopher T; Kelleher, Neil L

2006-02-14

For screening a pool of potential substrates that load carrier domains found in nonribosomal peptide synthetases, large molecule mass spectrometry is shown to be a new, unbiased assay. Combining the high resolving power of Fourier transform mass spectrometry with the ability of adenylation domains to select their own substrates, the mass change that takes place upon formation of a covalent intermediate thus identifies the substrate. This assay has an advantage over traditional radiochemical assays in that many substrates, the substrate pool, can be screened simultaneously. Using proteins on the nikkomycin, clorobiocin, coumermycin A1, yersiniabactin, pyochelin, and enterobactin biosynthetic pathways as proof of principle, preferred substrates are readily identified from substrate pools. Furthermore, this assay can be used to provide insight into the timing of tailoring events of biosynthetic pathways as demonstrated using the bromination reaction found on the jamaicamide biosynthetic pathway. Finally, this assay can provide insight into the role and function of orphan gene clusters for which the encoded natural product is unknown. This is demonstrated by identifying the substrates for two NRPS modules from the pksN and pksJ genes that are found on an orphan NRPS/PKS hybrid cluster from Bacillus subtilis. This new assay format is especially timely for activity screening in an era when new types of thiotemplate assembly lines that defy classification are being discovered at an accelerating rate.

Urban-rural difference in the acceptance of mass health examination in north-eastern Japan.

PubMed

Ikeda, M; Nakatsuka, H; Watanabe, T; Hisamichi, S; Shimizu, H; Fujisaku, S; Ichinowatari, Y; Konno, J; Kuroda, S; Hirai, J

1989-05-01

Over 40,000 residents (less than or equal to 40 years of age) in a city (Sendai; the city group), a town (Shiroishi; the town group) and two villages (Wakuya and Tajiri; the village group) in Miyagi prefecture in north-eastern Japan responded in a questionnaire survey on their attitude towards mass health examinations (i.e., whether they underwent in the previous year and if so where) on 4 items of blood pressure measurement, chest x-ray examination and screening tests for stomach and cervical cancer. The coverage rates were about 70% on an average both for blood pressure measurement and for chest x-ray examination, whereas the rates for cancer screening were between 30-40%. As for the opportunity of the former two examinations, the workplace mass examination played a large role in the case of the city and town groups (especially among men but not women) in addition to visit to clinics, in contrast to the case of the village group in which people depended much on regional mass examination service. The trend was essentially reproducible in stomach cancer screening although the over-all coverage rate was low, whereas women in the three groups almost exclusively utilized clinics for cervical cancer screening with one exception that the mobile unit service appeared to be equally accepted in the village group.

Associations of American Indian children's screen-time behavior with parental television behavior, parental perceptions of children's screen time, and media-related resources in the home.

PubMed

Barr-Anderson, Daheia J; Fulkerson, Jayne A; Smyth, Mary; Himes, John H; Hannan, Peter J; Holy Rock, Bonnie; Story, Mary

2011-09-01

American Indian children have high rates of overweight and obesity, which may be partially attributable to screen-time behavior. Young children's screen-time behavior is strongly influenced by their environment and their parents' behavior. We explored whether parental television watching time, parental perceptions of children's screen time, and media-related resources in the home are related to screen time (ie, television, DVD/video, video game, and computer use) among Oglala Lakota youth residing on or near the Pine Ridge Reservation in South Dakota. We collected baseline data from 431 child and parent/caregiver pairs who participated in Bright Start, a group-randomized, controlled, school-based obesity prevention trial to reduce excess weight gain. Controlling for demographic characteristics, we used linear regression analysis to assess associations between children's screen time and parental television watching time, parental perceptions of children's screen time, and availability of media-related household resources. The most parsimonious model for explaining child screen time included the children's sex, parental body mass index, parental television watching time, how often the child watched television after school or in the evening, parental perception that the child spent too much time playing video games, how often the parent limited the child's television time, and the presence of a VCR/DVD player or video game player in the home (F(7,367) = 14.67; P < .001; adjusted R(2) = .37). The presence of a television in the bedroom did not contribute significantly to the model. Changes in parental television watching time, parental influence over children's screen-time behavior, and availability of media-related resources in the home could decrease screen time and may be used as a strategy for reducing overweight and obesity in American Indian children.

Lifestyle predictors for non-participation and outcome in the second round of faecal immunochemical test in colorectal cancer screening.

PubMed

Knudsen, Markus Dines; Berstad, Paula; Hjartåker, Anette; Gulichsen, Elisabeth Haagensen; Hoff, Geir; de Lange, Thomas; Bernklev, Tomm; Botteri, Edoardo

2017-08-08

To reduce colorectal cancer (CRC) mortality through population-based screening programmes using faecal tests, it is important that individuals continue to participate in the repeated rounds of screening. We aimed to identify lifestyle predictors for discontinuation of faecal immunochemical test (FIT) screening after the first round, as well as lifestyle predictors for colorectal neoplasia detected in the second-round FIT screening. In this longitudinal study, we invited 6959 individuals aged 50-74 years from south-east Norway for a first round of FIT screening and to complete a self-reported lifestyle questionnaire on demographic factors, body mass index (BMI, kg m -2 ), smoking habits, physical activity, consumption of alcohol and dietary items. Two years later, we estimated the associations between these factors, non-participation and screening results in the second round of FIT screening using adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Of the 3114 responders to the questionnaire who completed the first-round FIT and who were invited to participate in second-round FIT screening, 540 (17%) did not participate. The OR and (95% CI) for discontinuation of FIT screening after the first round was 1.61 (1.24-2.10) for current smoking compared with non-smoking; 2.01 (1.25-3.24) for BMI⩾35 kg m -2 compared with BMI 16.9-24.9 kg m -2 and 0.70 (0.52-0.94) for physical activity in the third quartile vs the first. Among participants, smoking, high BMI and high alcohol consumption were associated with an increased odds of detecting colorectal neoplasia (n=107). These results may indicate that Norwegian FIT screening participants who discontinue after the first round have lifestyle behaviours associated with increased risk of CRC.

[The crypto-hem test in screening for colon cancer].

PubMed

Prokorov, V V; Shabarov, V L

1988-01-01

The paper discusses the reliability of crypto-hem test (detection of occult blood in feces) in diagnosing large bowel tumors in the course of a mass screening. 1573 healthy subjects aged 45 years and older were examined. The results were positive in 24 (2%) out of 1190 screenees who were involved in the test and in 58 (4.9%) subjects the results were suspicious. Tumors were detected in 23 (95.9%) test-positive screenees: cancer--12.5, polyps--54.2 and villous tumor--29.2%. Crypto-hem test proved instrumental in mass screening. Due to its application, symptom-free rectal cancer was diagnosed in 0.2, villous tumor--0.6, and single adenomatous polyps--1.1%.

Broad screening and identification of β-agonists in feed and animal body fluid and tissues using ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry combined with spectra library search.

PubMed

Li, Tingting; Cao, Jingjing; Li, Zhen; Wang, Xian; He, Pingli

2016-02-01

Broad screening and identification of β-agonists in feed, serum, urine, muscle and liver samples was achieved in a quick and highly sensitive manner using ultra high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) combined with a spectra library search. Solid-phase extraction technology was employed for sample purification and enrichment. After extraction and purification, the samples were analyzed using a Q-Orbitrap high-resolution mass spectrometer under full-scan and data-dependent MS/MS mode. The acquired mass spectra were compared with an in-house library (compound library and MS/MS mass spectral library) built with TraceFinder Software which contained the M/Z of the precursor ion, chemical formula, retention time, character fragment ions and the entire MS/MS spectra of 32 β-agonist standards. Screening was achieved by comparing 5 key mass spectral results and positive matches were marked. Using the developed method, the identification results from 10 spiked samples and 238 actual samples indicated that only 2% of acquired mass spectra produced false identities. The method validation results showed that the limit of detection ranged from 0.021-3.854 μg kg(-1)and 0.015-1.198 ng mL(-1) for solid and liquid samples, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Contaminant screening of wastewater with HPLC-IM-qTOF-MS and LC+LC-IM-qTOF-MS using a CCS database.

PubMed

Stephan, Susanne; Hippler, Joerg; Köhler, Timo; Deeb, Ahmad A; Schmidt, Torsten C; Schmitz, Oliver J

2016-09-01

Non-target analysis has become an important tool in the field of water analysis since a broad variety of pollutants from different sources are released to the water cycle. For identification of compounds in such complex samples, liquid chromatography coupled to high resolution mass spectrometry are often used. The introduction of ion mobility spectrometry provides an additional separation dimension and allows determining collision cross sections (CCS) of the analytes as a further physicochemical constant supporting the identification. A CCS database with more than 500 standard substances including drug-like compounds and pesticides was used for CCS data base search in this work. A non-target analysis of a wastewater sample was initially performed with high performance liquid chromatography (HPLC) coupled to an ion mobility-quadrupole-time of flight mass spectrometer (IM-qTOF-MS). A database search including exact mass (±5 ppm) and CCS (±1 %) delivered 22 different compounds. Furthermore, the same sample was analyzed with a two-dimensional LC method, called LC+LC, developed in our group for the coupling to IM-qTOF-MS. This four dimensional separation platform revealed 53 different compounds, identified over exact mass and CCS, in the examined wastewater sample. It is demonstrated that the CCS database can also help to distinguish between isobaric structures exemplified for cyclophosphamide and ifosfamide. Graphical Abstract Scheme of sample analysis and database screening.

Detection and identification of carprofen and its in vivo metabolites in greyhound urine by capillary gas chromatography-mass spectrometry.

PubMed

Dumasia, M C; Ginn, A; Hyde, W; Peterson, J; Houghton, E

2003-05-25

Rimadyl (carprofen) was administered orally to the racing greyhound at a dose of 2.2 mg kg(-1). Following both alkaline and enzymatic hydrolysis, postadministration urine samples were extracted by mixed mode solid-phase extraction (SPE) cartridges to identify target analyte(s) for forensic screening and confirmatory analysis methods. The acidic isolates were derivatised as trimethylsilyl ethers (TMS) and analysed by gas chromatography-mass spectrometry (GC-MS). Carprofen and five phase I metabolites were identified. Positive ion electron ionisation (EI(+)) mass spectra of the TMS derivatives of carprofen and its metabolites show a diagnostic base peak at M(+)*. -117 corresponding to the loss of COO-Si-(CH(3))(3) group as a radical. GC-MS with positive ion ammonia chemical ionisation (CI(+)) of the compounds provided both derivatised molecular mass and some structural information. Deutromethylation-TMS derivatisation was used to distinguish between aromatic and aliphatic oxidations of carprofen. The drug is rapidly absorbed, extensively metabolised and excreted as phase II conjugates in urine. Carprofen, three aromatic hydroxy and a minor N-hydroxy metabolite were detected for up to 48 h. For samples collected between 2 and 8 h after administration, the concentration of total carprofen ranged between 200 and 490 ng ml(-1). The major metabolite, alpha-hydroxycarprofen was detected for over 72 h and therefore can also be used as a marker for the forensic screening of carprofen in greyhound urine.

Speeding up the screening of steroids in urine: development of a user-friendly library.

PubMed

Galesio, M; López-Fdez, H; Reboiro-Jato, M; Gómez-Meire, Silvana; Glez-Peña, D; Fdez-Riverola, F; Lodeiro, Carlos; Diniz, M E; Capelo, J L

2013-12-11

This work presents a novel database search engine - MLibrary - designed to assist the user in the detection and identification of androgenic anabolic steroids (AAS) and its metabolites by matrix assisted laser desorption/ionization (MALDI) and mass spectrometry-based strategies. The detection of the AAS in the samples was accomplished by searching (i) the mass spectrometric (MS) spectra against the library developed to identify possible positives and (ii) by comparison of the tandem mass spectrometric (MS/MS) spectra produced after fragmentation of the possible positives with a complete set of spectra that have previously been assigned to the software. The urinary screening for anabolic agents plays a major role in anti-doping laboratories as they represent the most abused drug class in sports. With the help of the MLibrary software application, the use of MALDI techniques for doping control is simplified and the time for evaluation and interpretation of the results is reduced. To do so, the search engine takes as input several MALDI-TOF-MS and MALDI-TOF-MS/MS spectra. It aids the researcher in an automatic mode by identifying possible positives in a single MS analysis and then confirming their presence in tandem MS analysis by comparing the experimental tandem mass spectrometric data with the database. Furthermore, the search engine can, potentially, be further expanded to other compounds in addition to AASs. The applicability of the MLibrary tool is shown through the analysis of spiked urine samples. Copyright © 2013 Elsevier Inc. All rights reserved.

Screening of 439 Pesticide Residues in Fruits and Vegetables by Gas Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry Based on TOF Accurate Mass Database and Q-TOF Spectrum Library.

PubMed

Li, Jian-Xun; Li, Xiao-Ying; Chang, Qiao-Ying; Li, Yan; Jin, Ling-He; Pang, Guo-Fang; Fan, Chun-Lin

2018-05-03

Because of its unique characteristics of accurate mass full-spectrum acquisition, high resolution, and fast acquisition rates, GC-quadrupole-time-of-flight MS (GC-Q-TOF/MS) has become a powerful tool for pesticide residue analysis. In this study, a TOF accurate mass database and Q-TOF spectrum library of 439 pesticides were established, and the parameters of the TOF database were optimized. Through solid-phase extraction (SPE), whereby pesticides are extracted from fruit and vegetable substrates by using 40 mL 1% acetic acid in acetonitrile (v/v), purified by the Carbon/NH₂ SPE cartridge, and finally detected by GC-Q-TOF/MS, the rapid analysis of 439 pesticides in fruits and vegetables can be achieved. The methodology verification results show that more than 70 and 91% of pesticides, spiked in fruits and vegetables with concentrations of 10 and 100 μg/kg, respectively, saw recoveries that conform to the European Commission's criterion of between 70 and 120% with RSD ≤20%. Eighty-one percent of pesticides have screening detection limits lower than 10 μg/kg, which makes this a reliable analysis technology for the monitoring of pesticide residues in fruits and vegetables. This technology was further validated for its characteristics of high precision, high speed, and high throughput through successful detection of 9817 samples during 2013-2015.

Systematic forensic toxicological analysis by liquid-chromatography-quadrupole-time-of-flight mass spectrometry in serum and comparison to gas chromatography-mass spectrometry.

PubMed

Grapp, Marcel; Kaufmann, Christoph; Streit, Frank; Binder, Lutz

2018-06-01

Comprehensive screening procedures for psychoactive agents in body fluids are an essential task in clinical and forensic toxicology. With the continuous emergence and adaption of new psychoactive substances (NPS) keeping a screening method up to date is challenging. To meet these demands, hyphenated high-resolution mass spectrometry has gained interest as extensive and expandable screening approach. Here we present a comprehensive method for systematic toxicological analysis of serum by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) with data independent acquisition. The potential of this method was demonstrated by analysis of 247 authentic serum- and 12 post-mortem femoral blood samples. Thus 950 compounds, comprising 185 different drugs and metabolites could be identified. For the detected substances, including pharmaceutical substances, illicit drugs as well as NPS, serum concentrations were confirmed ranging from traces to toxic values indicating the capability for forensic toxicological requirements. Positive identification of drugs was achieved by accurate mass measurement (±5ppm for [M+H] + ; ±10ppm for [M-H] - ), retention time (±0.35min), isotopic pattern match (less than 10 m/z RMS [ppm]), isotope match intensity (less than 20% RMS) and the presence of at least two fragment ions. The LC-QTOF-MS procedure was shown to be superior to serum screening by GC-MS, since 240% (335 versus 141) more drugs were identified in serum samples compared to GC-MS. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous Screening and Quantification of Basic, Neutral and Acidic Drugs in Blood Using UPLC-QTOF-MS.

PubMed

Bidny, Sergei; Gago, Kim; Chung, Phuong; Albertyn, Desdemona; Pasin, Daniel

2017-04-01

An analytical method using ultra performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) was developed and validated for the targeted toxicological screening and quantification of commonly used pharmaceuticals and drugs of abuse in postmortem blood using 100 µL sample. It screens for more than 185 drugs and metabolites and quantifies more than 90 drugs. The selected compounds include classes of pharmaceuticals and drugs of abuse such as: antidepressants, antipsychotics, analgesics (including narcotic analgesics), anti-inflammatory drugs, benzodiazepines, beta-blockers, amphetamines, new psychoactive substances (NPS), cocaine and metabolites. Compounds were extracted into acetonitrile using a salting-out assisted liquid-liquid extraction (SALLE) procedure. The extracts were analyzed using a Waters ACQUITY UPLC coupled with a XEVO QTOF mass spectrometer. Separation of the analytes was achieved by gradient elution using Waters ACQUITY HSS C18 column (2.1 mm x 150 mm, 1.8 μm). The mass spectrometer was operated in both positive and negative electrospray ionization modes. The high-resolution mass spectrometry (HRMS) data was acquired using a patented Waters MSE acquisition mode which collected low and high energy spectra alternatively during the same acquisition. Positive identification of target analytes was based on accurate mass measurements of the molecular ion, product ion, peak area ratio and retention times. Calibration curves were linear over the concentration range 0.05-2 mg/L for basic and neutral analytes and 0.1-6 mg/L for acidic analytes with the correlation coefficients (r2) > 0.96 for most analytes. The limits of detection (LOD) were between 0.001-0.05 mg/L for all analytes. Good recoveries were achieved ranging from 80% to 100% for most analytes using the SALLE method. The method was validated for sensitivity, selectivity, accuracy, precision, stability, carryover and matrix effects. The developed method was tested on a number of authentic forensic samples producing consistent results that correlated with results obtained from other validated methods. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Screening-level estimates of mass discharge uncertainty from point measurement methods

EPA Science Inventory

The uncertainty of mass discharge measurements associated with point-scale measurement techniques was investigated by deriving analytical solutions for the mass discharge coefficient of variation for two simplified, conceptual models. In the first case, a depth-averaged domain w...

Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer's disease by direct infusion mass spectrometry.

PubMed

González-Domínguez, Raúl; García-Barrera, Tamara; Vitorica, Javier; Gómez-Ariza, José Luis

2015-01-01

The identification of pathological mechanisms underlying to Alzheimer's disease is of great importance for the discovery of potential markers for diagnosis and disease monitoring. In this study, we investigated regional metabolic alterations in brain from the APP/PS1 mice, a transgenic model that reproduces well some of the neuropathological and cognitive deficits observed in human Alzheimer's disease. For this purpose, hippocampus, cortex, cerebellum and olfactory bulbs were analyzed using a high-throughput metabolomic approach based on direct infusion mass spectrometry. Metabolic fingerprints showed significant differences between transgenic and wild-type mice in all brain tissues, being hippocampus and cortex the most affected regions. Alterations in numerous metabolites were detected including phospholipids, fatty acids, purine and pyrimidine metabolites, acylcarnitines, sterols and amino acids, among others. Furthermore, metabolic pathway analysis revealed important alterations in homeostasis of lipids, energy management, and metabolism of amino acids and nucleotides. Therefore, these findings demonstrate the potential of metabolomic screening and the use of transgenic models for understanding pathogenesis of Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Significantly enhanced UV luminescence by plasmonic metal on ZnO nanorods patterned by screen-printing.

PubMed

Zhao, Jun; Cui, Shuyuan; Zhang, Xingang; Li, Wenqing

2018-08-31

A smart synthetic method is conceived to construct large batches of ZnO nanostructures to meet market demand for light-emitting diodes. Utilizing the localized surface plasmon resonance of metal nanoparticles (NPs) facilitates the recombination of electron-hole pairs and the release of photons. Compared to raw ZnO nanorods (NRs), ZnO NRs@HfO 2 @Al NPs show a ∼120× enhancement in ultraviolet (UV) photoluminescence (PL), while ZnO NRs@HfO 2 @Ag NPs show a six-fold enhancement. Because the surface plasmon energy of Al is nearer the ZnO band gap, the PL enhancement of ZnO NRs covered with Al is stronger than that of those covered with Ag. Based on this analysis, three-dimensional graphical ZnO NR arrays were manufactured by screen-printing, a mass production technique. After covering the arrays with layers of HfO 2 and Al NPs, the UV PL intensities of the corresponding substrates were increased by approximately 16×. This indicates the potential to mass-produce highly efficient optoelectronic devices.

Cinema Screen Advertising: An Old Technology with New Promise for Consumer Marketing.

ERIC Educational Resources Information Center

Austin, Bruce A.

Few individuals think of the theatrically exhibited motion picture as supported by advertising like other major forms of mass communications. Cinema screen advertising can be defined as the presentation of individual advertising messages on movie theatre screens in a distinct and discrete fashion. Screenvision ads run prior to the start of each…

High- and low-throughput scoring of fat mass and body fat distribution in C. elegans

PubMed Central

Wählby, Carolina; Lee-Conery, Annie; Bray, Mark-Anthony; Kamentsky, Lee; Larkins-Ford, Jonah; Sokolnicki, Katherine L.; Veneskey, Matthew; Michaels, Kerry; Carpenter, Anne E.; O’Rourke, Eyleen J.

2014-01-01

Fat accumulation is a complex phenotype affected by factors such as neuroendocrine signaling, feeding, activity, and reproductive output. Accordingly, the most informative screens for genes and compounds affecting fat accumulation would be those carried out in whole living animals. Caenorhabditis elegans is a well-established and effective model organism, especially for biological processes that involve organ systems and multicellular interactions, such as metabolism. Every cell in the transparent body of C. elegans is visible under a light microscope. Consequently, an accessible and reliable method to visualize worm lipid-droplet fat depots would make C. elegans the only metazoan in which genes affecting not only fat mass but also body fat distribution could be assessed at a genome-wide scale. Here we present a radical improvement in oil red O worm staining together with high-throughput image-based phenotyping. The three-step sample preparation method is robust, formaldehyde-free, and inexpensive, and requires only 15 minutes of hands-on time to process a 96-well plate. Together with our free and user-friendly automated image analysis package, this method enables C. elegans sample preparation and phenotype scoring at a scale that is compatible with genome-wide screens. Thus we present a feasible approach to small-scale phenotyping and large-scale screening for genetic and/or chemical perturbations that lead to alterations in fat quantity and distribution in whole animals. PMID:24784529

Validation of LC–TOF-MS Screening for Drugs, Metabolites, and Collateral Compounds in Forensic Toxicology Specimens

PubMed Central

Guale, Fessessework; Shahreza, Shahriar; Walterscheid, Jeffrey P.; Chen, Hsin-Hung; Arndt, Crystal; Kelly, Anna T.; Mozayani, Ashraf

2013-01-01

Liquid chromatography time-of-flight mass spectrometry (LC–TOF-MS) analysis provides an expansive technique for identifying many known and unknown analytes. This study developed a screening method that utilizes automated solid-phase extraction to purify a wide array of analytes involving stimulants, benzodiazepines, opiates, muscle relaxants, hypnotics, antihistamines, antidepressants and newer synthetic “Spice/K2” cannabinoids and cathinone “bath salt” designer drugs. The extract was applied to LC–TOF-MS analysis, implementing a 13 min chromatography gradient with mobile phases of ammonium formate and methanol using positive mode electrospray. Several common drugs and metabolites can share the same mass and chemical formula among unrelated compounds, but they are structurally different. In this method, the LC–TOF-MS was able to resolve many isobaric compounds by accurate mass correlation within 15 ppm mass units and a narrow retention time interval of less than 10 s of separation. Drug recovery yields varied among spiked compounds, but resulted in overall robust area counts to deliver an average match score of 86 when compared to the retention time and mass of authentic standards. In summary, this method represents a rapid, enhanced screen for blood and urine specimens in postmortem, driving under the influence, and drug facilitated sexual assault forensic toxicology casework. PMID:23118149

Validation of LC-TOF-MS screening for drugs, metabolites, and collateral compounds in forensic toxicology specimens.

PubMed

Guale, Fessessework; Shahreza, Shahriar; Walterscheid, Jeffrey P; Chen, Hsin-Hung; Arndt, Crystal; Kelly, Anna T; Mozayani, Ashraf

2013-01-01

Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) analysis provides an expansive technique for identifying many known and unknown analytes. This study developed a screening method that utilizes automated solid-phase extraction to purify a wide array of analytes involving stimulants, benzodiazepines, opiates, muscle relaxants, hypnotics, antihistamines, antidepressants and newer synthetic "Spice/K2" cannabinoids and cathinone "bath salt" designer drugs. The extract was applied to LC-TOF-MS analysis, implementing a 13 min chromatography gradient with mobile phases of ammonium formate and methanol using positive mode electrospray. Several common drugs and metabolites can share the same mass and chemical formula among unrelated compounds, but they are structurally different. In this method, the LC-TOF-MS was able to resolve many isobaric compounds by accurate mass correlation within 15 ppm mass units and a narrow retention time interval of less than 10 s of separation. Drug recovery yields varied among spiked compounds, but resulted in overall robust area counts to deliver an average match score of 86 when compared to the retention time and mass of authentic standards. In summary, this method represents a rapid, enhanced screen for blood and urine specimens in postmortem, driving under the influence, and drug facilitated sexual assault forensic toxicology casework.

The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention

PubMed Central

Lee, Yi-Chia; Chiu, Han-Mo; Shun, Chia-Tung; Chiang, Hung; Liu, Tzeng-Ying; Wu, Ming-Shiang; Lin, Jaw-Town

2013-01-01

Objective To evaluate the benefit of mass eradication of Helicobacter pylori infection in reducing premalignant gastric lesions. Design Mass eradication of H pylori infection was started from 2004 for a Taiwanese population with prevalent H pylori infection, who were >30 years of age. Participants positive for the 13C-urea breath test underwent endoscopic screening and 1-week clarithromycin-based triple therapy. For subjects whose initial treatment failed, 10-day levofloxacin-based triple therapy was administered. The main outcome measures were changes in the prevalence of H pylori infection and premalignant gastric lesions, and changes in the incidence of premalignant gastric lesions and gastric cancer before (1995–2003) and after (2004–2008) chemoprevention using various comparators. Results The reduction in H pylori infection was 78.7% (95% CI 76.8% to 80.7%), and the estimated incidence of re-infection/recrudescence was 1% (95% CI 0.6% to 1.4%) per person-year. The effectiveness of reducing the incidence of gastric atrophy resulting from chemoprevention was significant at 77.2% (95% CI 72.3% to 81.2%), while the reduction in intestinal metaplasia was not significant. Compared with the 5-year period before chemoprevention and in the absence of endoscopic screening, the effectiveness in reducing gastric cancer incidence during the chemoprevention period was 25% (rate ratio 0.753, 95% CI 0.372 to 1.524). The reduction in peptic ulcer disease was 67.4% (95% CI 52.2% to 77.8%), while the incidence of oesophagitis was 6% (95% CI 5.1% to 6.9%) after treatment. Conclusions Population-based eradication of H pylori infection has led to a significant reduction in gastric atrophy at the expense of increased oesophagitis. The ultimate benefit in reducing gastric cancer incidence and its mortality should be validated by a further long-term follow-up. Trial registration number NCT00155389. PMID:22698649

[Clinical application of mass spectrometry in the pediatric field: current topics].

PubMed

Yamaguchi, Seiji

2013-09-01

Mass spectrometry, including tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), is becoming prominent in the diagnosis of metabolic disorders in the pediatric field. It enables biochemical diagnosis of metabolic disorders from the metabolic profiles obtained by MS/MS and/or GC/MS. In neonatal mass screening for inherited metabolic disease (IMD) using MS/MS, amino acids and acylcarnitines on dried blood spots are analyzed. The target diseases include amino acidemia, urea cycle disorder, organic acidemia, and fatty acid oxidation disorder. In the MS/MS screening, organic acid analysis using GC/MS is required for differential and/or definite diagnosis of the IMDs. GC/MS data processing, however, is difficult, and metabolic diagnosis often requires the necessary skills and expertize. We developed an automated system of GC/MS data processing and autodiagnosis, and the biochemical diagnosis using GC/MS became markedly easier and user-friendly. Mass spectrometric techniques will expand from research laboratories to clinical laboratories in the near future.

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

Zhang, Jing, E-mail: jing.zhang2@duke.edu; Ghate, Sujata V.; Yoon, Sora C.

Purpose: Mammography is the most widely accepted and utilized screening modality for early breast cancer detection. Providing high quality mammography education to radiology trainees is essential, since excellent interpretation skills are needed to ensure the highest benefit of screening mammography for patients. The authors have previously proposed a computer-aided education system based on trainee models. Those models relate human-assessed image characteristics to trainee error. In this study, the authors propose to build trainee models that utilize features automatically extracted from images using computer vision algorithms to predict likelihood of missing each mass by the trainee. This computer vision-based approach tomore » trainee modeling will allow for automatically searching large databases of mammograms in order to identify challenging cases for each trainee. Methods: The authors’ algorithm for predicting the likelihood of missing a mass consists of three steps. First, a mammogram is segmented into air, pectoral muscle, fatty tissue, dense tissue, and mass using automated segmentation algorithms. Second, 43 features are extracted using computer vision algorithms for each abnormality identified by experts. Third, error-making models (classifiers) are applied to predict the likelihood of trainees missing the abnormality based on the extracted features. The models are developed individually for each trainee using his/her previous reading data. The authors evaluated the predictive performance of the proposed algorithm using data from a reader study in which 10 subjects (7 residents and 3 novices) and 3 experts read 100 mammographic cases. Receiver operating characteristic (ROC) methodology was applied for the evaluation. Results: The average area under the ROC curve (AUC) of the error-making models for the task of predicting which masses will be detected and which will be missed was 0.607 (95% CI,0.564-0.650). This value was statistically significantly different from 0.5 (p < 0.0001). For the 7 residents only, the AUC performance of the models was 0.590 (95% CI,0.537-0.642) and was also significantly higher than 0.5 (p = 0.0009). Therefore, generally the authors’ models were able to predict which masses were detected and which were missed better than chance. Conclusions: The authors proposed an algorithm that was able to predict which masses will be detected and which will be missed by each individual trainee. This confirms existence of error-making patterns in the detection of masses among radiology trainees. Furthermore, the proposed methodology will allow for the optimized selection of difficult cases for the trainees in an automatic and efficient manner.« less

Biosurfactant production by Pseudomonas strains isolated from floral nectar.

PubMed

Ben Belgacem, Z; Bijttebier, S; Verreth, C; Voorspoels, S; Van de Voorde, I; Aerts, G; Willems, K A; Jacquemyn, H; Ruyters, S; Lievens, B

2015-06-01

To screen and identify biosurfactant-producing Pseudomonas strains isolated from floral nectar; to characterize the produced biosurfactants; and to investigate the effect of different carbon sources on biosurfactant production. Four of eight nectar Pseudomonas isolates were found to produce biosurfactants. Phylogenetic analysis based on three housekeeping genes (16S rRNA gene, rpoB and gyrB) classified the isolates into two groups, including one group closely related to Pseudomonas fluorescens and another group closely related to Pseudomonas fragi and Pseudomonas jessenii. Although our nectar pseudomonads were able to grow on a variety of water-soluble and water-immiscible carbon sources, surface active agents were only produced when using vegetable oil as sole carbon source, including olive oil, sunflower oil or waste frying sunflower oil. Structural characterization based on thin layer chromatography (TLC) and ultra high performance liquid chromatography-accurate mass mass spectrometry (UHPLC-amMS) revealed that biosurfactant activity was most probably due to the production of fatty acids (C16:0; C18:0; C18:1 and C18:2), and mono- and diglycerides thereof. Four biosurfactant-producing nectar pseudomonads were identified. The active compounds were identified as fatty acids (C16:0; C18:0; C18:1 and C18:2), and mono- and diglycerides thereof, produced by hydrolysis of triglycerides of the feedstock. Studies on biosurfactant-producing micro-organisms have mainly focused on microbes isolated from soils and aquatic environments. Here, for the first time, nectar environments were screened as a novel source for biosurfactant producers. As nectars represent harsh environments with high osmotic pressure and varying pH levels, further screening of nectar habitats for biosurfactant-producing microbes may lead to the discovery of novel biosurfactants with broad tolerance towards different environmental conditions. © 2015 The Society for Applied Microbiology.

Risk-Based Questionnaires Fail to Detect Adolescent Iron Deficiency and Anemia.

PubMed

Sekhar, Deepa L; Murray-Kolb, Laura E; Schaefer, Eric W; Paul, Ian M

2017-08-01

To evaluate the predictive ability of screening questionnaires to identify adolescent women at high-risk for iron deficiency or iron deficiency anemia who warrant objective laboratory testing. Cross-sectional study of 96 female individuals 12-21 years old seen at an academic medical center. Participants completed an iron deficiency risk assessment questionnaire including the 4 Bright Futures Adolescent Previsit Questionnaire anemia questions, along with depression, attention, food insecurity, and daytime sleepiness screens. Multiple linear regression controlling for age, race, and hormonal contraception use compared the predictive ability of 2 models for adolescent iron deficiency (defined as ferritin <12 mcg/L) and anemia (hemoglobin <12 g/dL). Model 1, the Bright Futures questions, was compared with model 2, which included the 4 aforementioned screens and body mass index percentile. Among participants, 18% (17/96) had iron deficiency and 5% (5/96) had iron deficiency anemia. Model 1 (Bright Futures) poorly predicted ferritin and hemoglobin values (R 2  = 0.03 and 0.08, respectively). Model 2 demonstrated similarly poor predictive ability (R 2  = 0.05 and 0.06, respectively). Mean differences for depressive symptoms (0.3, 95% CI -0.2, 0.8), attention difficulty (-0.1, 95% CI -0.5, 0.4), food insecurity (0.04, 95% CI -0.5, 0.6), daytime sleepiness (0.1, 95% CI -0.1, 0.3), and body mass index percentile (-0.04, 95% CI -0.3, 0.2) were not significantly associated with ferritin in model 2. Mean differences for hemoglobin were also nonsignificant. Risk-based surveys poorly predict objective measures of iron status using ferritin and hemoglobin. Next steps are to establish the optimal timing for objective assessment of adolescent iron deficiency and anemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Direct screening of herbal blends for new synthetic cannabinoids by MALDI-TOF MS.

PubMed

Gottardo, Rossella; Chiarini, Anna; Dal Prà, Ilaria; Seri, Catia; Rimondo, Claudia; Serpelloni, Giovanni; Armato, Ubaldo; Tagliaro, Franco

2012-01-01

Since 2004, a number of herbal blends containing different synthetic compounds mimicking the pharmacological activity of cannabinoids and displaying a high toxicological potential have appeared in the market. Their availability is mainly based on the so-called "e-commerce", being sold as legal alternatives to cannabis and cannabis derivatives. Although highly selective, sensitive, accurate, and quantitative methods based on GC-MS and LC-MS are available, they lack simplicity, rapidity, versatility and throughput, which are required for product monitoring. In this context, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) offers a simple and rapid operation with high throughput. Thus, the aim of the present work was to develop a MALDI-TOF MS method for the rapid qualitative direct analysis of herbal blend preparations for synthetic cannabinoids to be used as front screening of confiscated clandestine preparations. The sample preparation was limited to herbal blend leaves finely grinding in a mortar and loading onto the MALDI plate followed by addition of 2 µl of the matrix/surfactant mixture [α-cyano-4-hydroxy-cinnamic acid/cetyltrimethylammonium bromide (CTAB)]. After drying, the sample plate was introduced into the ion source for analysis. MALDI-TOF conditions were as follows: mass spectra were analyzed in the range m/z 150-550 by averaging the data from 50 laser shots and using an accelerating voltage of 20 kV. The described method was successfully applied to the screening of 31 commercial herbal blends, previously analyzed by GC-MS. Among the samples analyzed, 21 contained synthetic cannabinoids (namely JWH-018, JWH-073, JWH-081, JWH-250, JWH-210, JWH-019, and AM-694). All the results were in agreement with GC-MS, which was used as the reference technique. Copyright © 2012 John Wiley & Sons, Ltd.

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

Multiplex tandem mass spectrometry assay for newborn screening of X-linked adrenoleukodystrophy, biotinidase deficiency, and galactosemia with flexibility to assay other enzyme assays and biomarkers.

PubMed

Hong, Xinying; Kumar, Arun Babu; Ronald Scott, C; Gelb, Michael H

2018-03-29

All States screen for biotinidase deficiency and galactosemia, and X-linked adrenoleukodystrophy (X-ALD) has recently been added to the Recommended Uniform Screening Panel (RUSP).We sought to consolidate these tests by combining them into a single multiplex tandem mass spectrometry assay as well as to improve the current protocol for newborn screening of galactosemia.A 3 mm punch of a dried blood spot (DBS) was extracted with organic solvent for analysis of the C26:0-lysophosphatidylcholine biomarker for X-ALD.An additional punch was used to assay galactose-1-phosphate uridyltransferase (GALT) and biotinidase.All assays were combined for a single injection for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (2.3 min per sample).The GALT LC-MS/MS assay does not give a false positive for galactosemia if glucose-6-phosphate dehydrogenase is deficient.The multiplex assay shows acceptable reproducibility and provides for rapid analysis of X-ALD, biotinidase deficiency, and galactosemia.The throughput and ease of sample preparation are acceptable for newborn screening laboratories.We also show that the LC-MS/MS assay is expandable to include several other diseases including Pompe and Hurler diseases (enzymatic activities and biomarkers).Because of consolidation of assays, less manpower is needed compared to running individual assays on separate platforms.The flexibility of the LC-MS/MS platform allows each newborn screening laboratory to analyze the set of diseases offered in their panel. Copyright © 2018 Elsevier Inc. All rights reserved.

Rapid screening of abused drugs by direct analysis in real time (DART) coupled to time-of-flight mass spectrometry (TOF-MS) combined with ion mobility spectrometry (IMS).

PubMed

Lian, Ru; Wu, Zhongping; Lv, Xiaobao; Rao, Yulan; Li, Haiyang; Li, Jinghua; Wang, Rong; Ni, Chunfang; Zhang, Yurong

2017-10-01

Increasing in cases involving drugs of abuse leads to heavy burden for law enforcement agencies, exacerbating demand for rapid screening technique. In this study, atmospheric pressure ionization technologies including direct analysis in real time (DART) ion source coupled to a time-of-flight mass spectrometer (DART-TOF-MS)as well asdopant-assisted positive photoionization ion mobility spectrometry (DAPP-IMS) without radioactivity were utilized together as the powerful analytical tool for the rapid screening and identification of 53 abused drugs.The limits of detection (LOD) were 0.05-2μg/mL when using DART-TOF-MS and 0.02-2μg when using DAPP-IMS which could satisfy the actual requirement in forensic science laboratory. The advantages of this method included fast response, high-throughput potential, high specificity, and minimal sample preparation. A screening library of reduced mobility (K 0 ), accurate mass of informative precursor ion ([M+H] + ) and fragment ions was established respectively by employing a bench-top DAPP-IMS and TOF-MS in-source collision induced dissociation (CID) mode. Then the standardized screening procedure was developed with criteria for the confirmation of positive result. A total of 50 seized drug samples provided by local forensic laboratory we reanalyzed to testify the utility of the method. This study suggests that a method combing DART-TOF-MS and DAPP-IMS is promising for the rapid screening and identification of abused drugs with minimal sample preparation and absence of chromatography. Copyright © 2017 Elsevier B.V. All rights reserved.

A Balanced Approach to Funding Homeland Security

DTIC Science & Technology

2014-12-01

73 1. Informed Culture ...74 2. Reporting Culture ........................................................................75 3. Just Culture ... Cultural Resources Risk Management for Protection Programs and Activities Mass Care Services Screening, Search, and Detection Mass Search and

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

PubMed

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

2017-10-01

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

Experimental Strategies for Functional Annotation and Metabolism Discovery: Targeted Screening of Solute Binding Proteins and Unbiased Panning of Metabolomes

DOE PAGES

Vetting, Matthew W.; Al-Obaidi, Nawar; Zhao, Suwen; ...

2014-12-25

The rate at which genome sequencing data is accruing demands enhanced methods for functional annotation and metabolism discovery. Solute binding proteins (SBPs) facilitate the transport of the first reactant in a metabolic pathway, thereby constraining the regions of chemical space and the chemistries that must be considered for pathway reconstruction. Here in this paper, we describe high-throughput protein production and differential scanning fluorimetry platforms, which enabled the screening of 158 SBPs against a 189 component library specifically tailored for this class of proteins. Like all screening efforts, this approach is limited by the practical constraints imposed by construction of themore » library, i.e., we can study only those metabolites that are known to exist and which can be made in sufficient quantities for experimentation. To move beyond these inherent limitations, we illustrate the promise of crystallographic- and mass spectrometric-based approaches for the unbiased use of entire metabolomes as screening libraries. Together, our approaches identified 40 new SBP ligands, generated experiment-based annotations for 2084 SBPs in 71 isofunctional clusters, and defined numerous metabolic pathways, including novel catabolic pathways for the utilization of ethanolamine as sole nitrogen source and the use of D-Ala-D-Ala as sole carbon source. These efforts begin to define an integrated strategy for realizing the full value of amassing genome sequence data.« less

Three-Component Reaction Discovery Enabled by Mass Spectrometry of Self-Assembled Monolayers

PubMed Central

Montavon, Timothy J.; Li, Jing; Cabrera-Pardo, Jaime R.; Mrksich, Milan; Kozmin, Sergey A.

2011-01-01

Multi-component reactions have been extensively employed in many areas of organic chemistry. Despite significant progress, the discovery of such enabling transformations remains challenging. Here, we present the development of a parallel, label-free reaction-discovery platform, which can be used for identification of new multi-component transformations. Our approach is based on the parallel mass spectrometric screening of interfacial chemical reactions on arrays of self-assembled monolayers. This strategy enabled the identification of a simple organic phosphine that can catalyze a previously unknown condensation of siloxy alkynes, aldehydes and amines to produce 3-hydroxy amides with high efficiency and diastereoselectivity. The reaction was further optimized using solution phase methods. PMID:22169871

Lab on a CD.

PubMed

Madou, Marc; Zoval, Jim; Jia, Guangyao; Kido, Horacio; Kim, Jitae; Kim, Nahui

2006-01-01

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.

Hog Charm II tetracycline test screening results compared with a liquid chromatography tandem mass spectrometry 10-μg/kg method.

PubMed

Salter, Robert; Holmes, Steven; Legg, David; Coble, Joel; George, Bruce

2012-02-01

Pork tissue samples that tested positive and negative by the Charm II tetracycline test screening method in the slaughter plant laboratory were tested with the modified AOAC International liquid chromatography tandem mass spectrometry (LC-MS-MS) method 995.09 to determine the predictive value of the screening method at detecting total tetracyclines at 10 μg/kg of tissue, in compliance with Russian import regulations. There were 218 presumptive-positive tetracycline samples of 4,195 randomly tested hogs. Of these screening test positive samples, 83% (182) were positive, >10 μg/kg by LC-MS-MS; 12.8% (28) were false violative, greater than limit of detection (LOD) but <10 μg/kg; and 4.2% (8) were not detected at the LC-MS-MS LOD. The 36 false-violative and not-detected samples represent 1% of the total samples screened. Twenty-seven of 30 randomly selected tetracycline screening negative samples tested below the LC-MS-MS LOD, and 3 samples tested <3 μg/kg chlortetracycline. Results indicate that the Charm II tetracycline test is effective at predicting hogs containing >10 μg/kg total tetracyclines in compliance with Russian import regulations.

Review: LC coupled to low- and high-resolution mass spectrometry for new psychoactive substance screening in biological matrices - Where do we stand today?

PubMed

Meyer, Markus R; Maurer, Hans H

2016-07-13

The field of new psychoactive substances (NPS) is highly dynamic and the situation changes from year to year. Therefore, the current review provides a timely update about the latest developments to help analysts keep the pace with NPS distribution. It covers PubMed-listed studies published between January 2014 and January 2016 dealing with the application of liquid chromatography (LC) coupled low- and high-resolution mass spectrometry (MS) for broad screenings for NPS in clinical (CT) and forensic (FT) toxicology. Latest developments and applications are highlighted and selected papers critically discussed. Comprehensive tables summarizing all discussed articles complete the overview. Finally, an outlook on the future of LC coupled MS in CT and FT is provided and readers will learn why low-resolution mass spectrometry might remain the standard for the next couple of years at least for easy-to-use quantitative screening procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

Mapping posttranscriptional modifications in 5S ribosomal RNA by MALDI mass spectrometry.

PubMed

Kirpekar, F; Douthwaite, S; Roepstorff, P

2000-02-01

We present a method to screen RNA for posttranscriptional modifications based on Matrix Assisted Laser Desorption/Ionization mass spectrometry (MALDI-MS). After the RNA is digested to completion with a nucleotide-specific RNase, the fragments are analyzed by mass spectrometry. A comparison of the observed mass data with the data predicted from the gene sequence identifies fragments harboring modified nucleotides. Fragments larger than dinucleotides were valuable for the identification of posttranscriptional modifications. A more refined mapping of RNA modifications can be obtained by using two RNases in parallel combined with further fragmentation by Post Source Decay (PSD). This approach allows fast and sensitive screening of a purified RNA for posttranscriptional modification, and has been applied on 5S rRNA from two thermophilic microorganisms, the bacterium Bacillus stearothermophilus and the archaeon Sulfolobus acidocaldarius, as well as the halophile archaea Halobacterium halobium and Haloarcula marismortui. One S. acidocaldarius posttranscriptional modification was identified and was further characterized by PSD as a methylation of cytidine32. The modified C is located in a region that is clearly conserved with respect to both sequence and position in B. stearothermophilus and H. halobium and to some degree also in H. marismortui. However, no analogous modification was identified in the latter three organisms. We further find that the 5' end of H. halobium 5S rRNA is dephosphorylated, in contrast to the other 5S rRNA species investigated. The method additionally gives an immediate indication of whether the expected RNA sequence is in agreement with the observed fragment masses. Discrepancies with two of the published 5S rRNA sequences were identified and are reported here.

Mapping posttranscriptional modifications in 5S ribosomal RNA by MALDI mass spectrometry.

PubMed Central

Kirpekar, F; Douthwaite, S; Roepstorff, P

2000-01-01

We present a method to screen RNA for posttranscriptional modifications based on Matrix Assisted Laser Desorption/Ionization mass spectrometry (MALDI-MS). After the RNA is digested to completion with a nucleotide-specific RNase, the fragments are analyzed by mass spectrometry. A comparison of the observed mass data with the data predicted from the gene sequence identifies fragments harboring modified nucleotides. Fragments larger than dinucleotides were valuable for the identification of posttranscriptional modifications. A more refined mapping of RNA modifications can be obtained by using two RNases in parallel combined with further fragmentation by Post Source Decay (PSD). This approach allows fast and sensitive screening of a purified RNA for posttranscriptional modification, and has been applied on 5S rRNA from two thermophilic microorganisms, the bacterium Bacillus stearothermophilus and the archaeon Sulfolobus acidocaldarius, as well as the halophile archaea Halobacterium halobium and Haloarcula marismortui. One S. acidocaldarius posttranscriptional modification was identified and was further characterized by PSD as a methylation of cytidine32. The modified C is located in a region that is clearly conserved with respect to both sequence and position in B. stearothermophilus and H. halobium and to some degree also in H. marismortui. However, no analogous modification was identified in the latter three organisms. We further find that the 5' end of H. halobium 5S rRNA is dephosphorylated, in contrast to the other 5S rRNA species investigated. The method additionally gives an immediate indication of whether the expected RNA sequence is in agreement with the observed fragment masses. Discrepancies with two of the published 5S rRNA sequences were identified and are reported here. PMID:10688367

Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome.

PubMed

Aranda, G; Careaga, M; Hanzu, F A; Patrascioiu, I; Ríos, P; Mora, M; Morales-Romero, B; Jiménez, W; Halperin, I; Casals, G

2016-10-01

Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.

Screening and investigation of triplex DNA binders from Stephania tetrandra S. Moore by a combination of peak area-fading UHPLC with orbitrap MS and optical spectroscopies.

PubMed

Yang, Hongmei; Wang, Yihan; Yu, Wenjing; Shi, Lei; Wang, Hongfeng; Su, Rui; Chen, Changbao; Liu, Shuying

2018-05-15

The identification and screening of triplex DNA binders are important because these compounds, in many cases, are potential anticancer agents as well as promising drug candidates. Therefore, the ability to screen for these compounds in a high-throughput mode could dramatically improve the drug screening process. A method involving a combination of 96-well plate format and peak area-fading ultra high performance liquid chromatography coupled with Orbitrap mass spectrometry was employed for screening bioactive compounds binding to the triplex DNA from the extracts of Stephania tetrandra S. Moore. Two compounds were screened out and identified as fangchinoline and tetrandrine, based on the comparison of retention time and MS 2 data with those of standards. The binding mechanisms of fangchinoline and tetrandrine at the molecular level were explored using MS 2 , fluorescence spectroscopy, ultraviolet-visible spectroscopy, and circular dichroism. Collision-induced dissociation experiments showed that the complexes with fangchinoline and tetrandrine were dissociated by ligand elimination. According to these measurements, an intercalating binding is the most appropriate binding mode of these two alkaloids to the triplex DNA. The current work provides not only deep insight into alkaloid-triplex DNA complexes but also useful guidelines for the design of efficient anticancer agents. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Identification of Eight Synthetic Cannabinoids, Including 5F-AKB48 in Seized Herbal Products Using DART-TOF-MS and LC-QTOF-MS as Nontargeted Screening Methods.

PubMed

Moore, Katherine N; Garvin, Demetra; Thomas, Brian F; Grabenauer, Megan

2017-09-01

Synthetic cannabinoids are sprayed onto plant material and smoked for their marijuana-like effects. Clandestine manufacturers modify synthetic cannabinoid structures by creating closely related analogs. Forensic laboratories are tasked with detection of these analog compounds, but targeted analytical methods are often thwarted by the structural modifications. Here, direct analysis in real time coupled to accurate mass time-of-flight mass spectrometry (DART-TOF-MS) in combination with liquid chromatography quadruple time-of-flight mass spectrometry (LC-QTOF-MS) are presented as a screening and nontargeted confirmation method, respectively. Methanol extracts of herbal material were run using both methods. Spectral data from four different herbal products were evaluated by comparing fragmentation pattern, accurate mass and retention time to available reference standards. JWH-018, JWH-019, AM2201, JWH-122, 5F-AKB48, AKB48-N-(4-pentenyl) analog, UR144, and XLR11 were identified in the products. Results demonstrate that DART-TOF-MS affords a useful approach for rapid screening of herbal products for the presence and identification of synthetic cannabinoids. © 2017 American Academy of Forensic Sciences.

The use of trichloroacetic acid imprinted polymer coated quartz crystal microbalance as a screening method for determination of haloacetic acids in drinking water.

PubMed

Suedee, Roongnapa; Intakong, Wimon; Dickert, Franz L

2006-08-15

An alternative screening method for haloacetic acids (HAAs) disinfection by-products in drinking water is described. The method is based on the use of piezoelectric quartz crystal microbalance (QCM) transducing system, where the electrode is coated with a trichloacetic acid-molecularly imprinted polymer (TCAA-MIP). This MIP comprises a crosslinked poly(ethyleneglycoldimethacrylate-co-4-vinylpyridine). The coated QCM is able to specifically detect the analytes in water samples in terms of the mass change in relation to acid-base interactions of the analytes with the MIP. The TCAA-MIP coated QCM showed high specificity for the determination of TCAA in aqueous solutions containing inorganic anions, but its sensitivity reduced in water samples containing hydrochloric acid due to a mass loss at the sensor surface. Cross-reactivity studies with HAA analogs (dichloro-, monochloro-, tribromo-, dibromo-, and monobromo-acetic acids) and non-structurally related TCAA molecules (acetic acid and malonic acid) indicated that recognition of the structurally related TCAA compounds by the TCAA-MIP-based QCM is due to a carboxylic acid functional group, and probably involves a combination of both size and shape selectivity. The total response time of sensor is in the order of 10min. The achieved limits of detection for HAAs (20-50mugl(-1)) are at present higher than the actual concentrations found in real-life samples, but below the guidelines for the maximum permissible levels (60mugl(-1) for mixed HAAs). Recovery studies with drinking water samples spiked with TCAA or spiked with mixtures of HAAs revealed the reproducibility and precision of the method. The present work has demonstrated that the proposed assay can be a fast, reliable and inexpensive screening method for HAA contaminants in water samples, but further refinement is required to improve the limits of detection.

Stanford GEMS phase 2 obesity prevention trial for low-income African-American girls: design and sample baseline characteristics.

PubMed

Robinson, Thomas N; Kraemer, Helena C; Matheson, Donna M; Obarzanek, Eva; Wilson, Darrell M; Haskell, William L; Pruitt, Leslie A; Thompson, Nikko S; Haydel, K Farish; Fujimoto, Michelle; Varady, Ann; McCarthy, Sally; Watanabe, Connie; Killen, Joel D

2008-01-01

African-American girls and women are at high risk of obesity and its associated morbidities. Few studies have tested obesity prevention strategies specifically designed for African-American girls. This report describes the design and baseline findings of the Stanford GEMS (Girls health Enrichment Multi-site Studies) trial to test the effect of a two-year community- and family-based intervention to reduce weight gain in low-income, pre-adolescent African-American girls. Randomized controlled trial with measurements scheduled in girls' homes at baseline, 6, 12, 18 and 24 month post-randomization. Low-income areas of Oakland, CA. Eight, nine and ten year old African-American girls and their parents/caregivers. Girls are randomized to a culturally-tailored after-school dance program and a home/family-based intervention to reduce screen media use versus an information-based community health education Active-Placebo Comparison intervention. Interventions last for 2 years for each participant. Change in body mass index over the two-year study. Recruitment and enrollment successfully produced a predominately low-socioeconomic status sample. Two-hundred sixty one (261) families were randomized. One girl per family is randomly chosen for the analysis sample. Randomization produced comparable experimental groups with only a few statistically significant differences. The sample had a mean body mass index (BMI) at the 74 th percentile on the 2000 CDC BMI reference, and one-third of the analysis sample had a BMI at the 95th percentile or above. Average fasting total cholesterol and LDL cholesterol were above NCEP thresholds for borderline high classifications. Girls averaged low levels of moderate to vigorous physical activity, more than 3 h per day of screen media use, and diets high in energy from fat. The Stanford GEMS trial is testing the benefits of culturally-tailored after-school dance and screen-time reduction interventions for obesity prevention in low-income, pre-adolescent African-American girls.

Validity of Indian Diabetes Risk Score and its association with body mass index and glycosylated hemoglobin for screening of diabetes in and around areas of Lucknow

PubMed Central

Khan, Mohammad Mustufa; Sonkar, Gyanendra Kumar; Alam, Roshan; Mehrotra, Sudhir; Khan, M. Salman; Kumar, Ajay; Sonkar, Satyendra Kumar

2017-01-01

Objectives: The present study aimed to assess the validity of Indian Diabetes Risk Score (IDRS) and its association with body mass index (BMI) and glycosylated hemoglobin (HbA1c) for screening of diabetes and obesity. Methodology: A cross-sectional study was designed, and samples were randomly enrolled from Lucknow and its adjoining areas. Totally, 405 subjects were included in the study. We used diabetes risk factors (age, waist circumference, physical activity, and family history of diabetes) for screening of diabetes and abdominal obesity (AO) and BMI for screening of general obesity. HbA1c was used for confirming the diabetes patients in this population. Statistical analysis was applied to all data using SPSS software (version 20.0). P < 0.05 was considered statistically significant. Results: All 405 subjects were assessed for diabetic risk factors, BMI, and glycated hemoglobin. Of these, 56.3% subjects were aged ≥50 years. 1° and 2° AO was found in 47.9% and 40% subjects, respectively. About 27.1% subjects were found to have sedentary lifestyle, and 72.6% were found to have no family history of diabetes. According to IDRS, 272 subjects (67.2%) were found at high risk of diabetes (score ≥60). Based on BMI calculation, 198 subjects were obese, of which 79.3% were found at high risk for diabetes. A significant association was found between subjects with higher risk score and BMI (P < 0.001). Assessment of HbA1c showed that 97 (23.9%) were prediabetic and 204 (50.4%) were diabetic, of which 63.9% and 77%, respectively was at high risk for diabetes as per IDRS. A significant association was found between subjects with higher risk score and HbA1c (P < 0.001). Conclusion: Our study fully supports the validity of IDRS, as it can be used as a cost-effective tool for primary mass screening of diabetes. Moreover, its combination with BMI value and HbA1c can be used for strict monitoring for diabetes and obesity at primary health care centers to reduce the early development of diabetes complications and severe obesity comorbidities. PMID:29302549

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

Gratia, Pierre; Hu, Wayne; Enrico Fermi Institute and Kavli Institute for Cosmological Physics, University of Chicago,South Ellis Avenue, Chicago, IL 60637

Attempts to modify gravity in the infrared typically require a screening mechanism to ensure consistency with local tests of gravity. These screening mechanisms fit into three broad classes; we investigate theories which are capable of exhibiting more than one type of screening. Specifically, we focus on a simple model which exhibits both Vainshtein and kinetic screening. We point out that due to the two characteristic length scales in the problem, the type of screening that dominates depends on the mass of the sourcing object, allowing for different phenomenology at different scales. We consider embedding this double screening phenomenology in amore » broader cosmological scenario and show that the simplest examples that exhibit double screening are radiatively stable.« less

Obstacles to colorectal screening in general practice: a qualitative study of GPs and patients.

PubMed

Aubin-Auger, Isabelle; Mercier, Alain; Lebeau, Jean-Pierre; Baumann, Laurence; Peremans, Lieve; Van Royen, Paul

2011-12-01

The faecal occult blood test (FOBT) has proven efficiency at screening populations for an average risk of colorectal cancer. Mortality related to this cancer decreases by 15-18% among adults, 50-74 years old, tested every 2 years. A participation rate of at least 50% is desirable. This rate has not yet been reached in most French regions. To explore the obstacles to mass colorectal screening in France. In 2009, five focus groups were conducted in different areas to explore physicians' obstacles to FOBT screening. The patients' obstacles were assessed in semi-structured interviews. A purposive sampling had been carried out for both GPs and patients. The focus groups were coded using Nvivo 8(®) software by three researchers; the interviews manually coded by two researchers. GPs reported insufficient training and some doubted the relevance of screening. They expressed concern of having insufficient time for the test during a consultation, as well as practical and administrative obstacles. Some GPs experienced difficulty persuading patients who had no signs of colorectal disease. Obstacles for patients were mainly difficulties in doing screening themselves and a perception of health care that didn't match with screening. Information and organization were also important points to improve. The screening process was considered complex both by GPs and by patients. Numerous obstacles to colorectal screening, from both the physicians' and the patients' perspectives, were found. The major goal to improve mass screening may be to increase awareness and understanding of both physicians and patients regarding this process.

Fractal Analysis of Visual Search Activity for Mass Detection During Mammographic Screening

DOE PAGES

Alamudun, Folami T.; Yoon, Hong-Jun; Hudson, Kathy; ...

2017-02-21

Purpose: The objective of this study was to assess the complexity of human visual search activity during mammographic screening using fractal analysis and to investigate its relationship with case and reader characteristics. Methods: The study was performed for the task of mammographic screening with simultaneous viewing of four coordinated breast views as typically done in clinical practice. Eye-tracking data and diagnostic decisions collected for 100 mammographic cases (25 normal, 25 benign, 50 malignant) and 10 readers (three board certified radiologists and seven radiology residents), formed the corpus data for this study. The fractal dimension of the readers’ visual scanning patternsmore » was computed with the Minkowski–Bouligand box-counting method and used as a measure of gaze complexity. Individual factor and group-based interaction ANOVA analysis was performed to study the association between fractal dimension, case pathology, breast density, and reader experience level. The consistency of the observed trends depending on gaze data representation was also examined. Results: Case pathology, breast density, reader experience level, and individual reader differences are all independent predictors of the visual scanning pattern complexity when screening for breast cancer. No higher order effects were found to be significant. Conclusions: Fractal characterization of visual search behavior during mammographic screening is dependent on case properties and image reader characteristics.« less

Breast cancer risk assessment and diagnosis model using fuzzy support vector machine based expert system

NASA Astrophysics Data System (ADS)

Dheeba, J.; Jaya, T.; Singh, N. Albert

2017-09-01

Classification of cancerous masses is a challenging task in many computerised detection systems. Cancerous masses are difficult to detect because these masses are obscured and subtle in mammograms. This paper investigates an intelligent classifier - fuzzy support vector machine (FSVM) applied to classify the tissues containing masses on mammograms for breast cancer diagnosis. The algorithm utilises texture features extracted using Laws texture energy measures and a FSVM to classify the suspicious masses. The new FSVM treats every feature as both normal and abnormal samples, but with different membership. By this way, the new FSVM have more generalisation ability to classify the masses in mammograms. The classifier analysed 219 clinical mammograms collected from breast cancer screening laboratory. The tests made on the real clinical mammograms shows that the proposed detection system has better discriminating power than the conventional support vector machine. With the best combination of FSVM and Laws texture features, the area under the Receiver operating characteristic curve reached .95, which corresponds to a sensitivity of 93.27% with a specificity of 87.17%. The results suggest that detecting masses using FSVM contribute to computer-aided detection of breast cancer and as a decision support system for radiologists.

Precursor ion scan driven fast untargeted screening and semi-determination of caffeoylquinic acid derivatives in Cynara scolymus L.

PubMed

Shen, Qing; Lu, Yanbin; Dai, Zhiyuan; Cheung, Hon-Yeung

2015-01-01

A precursor ion scan (PIS) technique based strategy was developed for rapid screening and semi-determination of caffeoylquinic acid derivatives (CADs) in artichoke (Cynara scolymus L.) using ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. 1,5-Dicaffeoylquinic acid and 5-caffeoylquinic acid were used for studying the fragmentation behaviour of two classes of CADs, setting m/z 191 as a diagnostic moiety. When it was applied to artichoke sample, ten CADs were detected and elucidated in a single PIS run. Furthermore, method validation was implemented including: specificity (no interference), linearity (≥0.9993), limit of detection (LOD<0.12 ng mL(-1)) and limit of quantification (LOQ<0.25 ng mL(-1)), precision (RSD≤3.6), recovery (91.4-95.9%) and stability (at least 12 h). This approach was proven to be a powerful, selective and sensitive tool for rapid screening and semi-determination of untargeted components in natural products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comprehensive characterisation of flame retardants in textile furnishings by ambient high resolution mass spectrometry, gas chromatography-mass spectrometry and environmental forensic microscopy.

PubMed

Ionas, Alin C; Ballesteros Gómez, Ana; Uchida, Natsuyo; Suzuki, Go; Kajiwara, Natsuko; Takata, Kyoko; Takigami, Hidetaka; Leonards, Pim E G; Covaci, Adrian

2015-10-01

The presence and levels of flame retardants (FRs), such as polybrominated diphenyl ethers (PBDEs) and organophosphate flame retardants (PFRs), was determined in textile home furnishings, such as carpets and curtains from stores in Belgium. A comprehensive characterisation of FRs in textile was done by ambient high resolution mass spectrometry (qualitative screening), gas chromatography-mass spectrometry (GC-MS) (quantitation), and environmental forensic microscopy (surface distribution). Ambient ionisation coupled to a time-of-flight (TOF) high resolution mass spectrometer (direct probe-TOF-MS) was investigated for the rapid screening of FRs. Direct probe-TOF-MS proved to be useful for a first screening step of textiles to detect FRs below the levels required to impart flame retardancy and to reduce, in this way, the number of samples for further quantitative analysis. Samples were analysed by GC-MS to confirm the results obtained by ambient mass spectrometry and to obtain quantitative information. The levels of PBDEs and PFRs were typically too low to impart flame retardancy. Only high levels of BDE-209 (11-18% by weight) were discovered and investigated in localised hotspots by employing forensic microscopy techniques. Most of the samples were made of polymeric materials known to be inherently flame retarded to some extent, so it is likely that other alternative and halogen-free FR treatments/solutions are preferred for the textiles on the Belgian market. Copyright © 2015 Elsevier Inc. All rights reserved.

First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass

PubMed Central

Wang, Guangliang; Rajpurohit, Surendra K; Delaspre, Fabien; Walker, Steven L; White, David T; Ceasrine, Alexis; Kuruvilla, Rejji; Li, Ruo-jing; Shim, Joong S; Liu, Jun O; Parsons, Michael J; Mumm, Jeff S

2015-01-01

Whole-organism chemical screening can circumvent bottlenecks that impede drug discovery. However, in vivo screens have not attained throughput capacities possible with in vitro assays. We therefore developed a method enabling in vivo high-throughput screening (HTS) in zebrafish, termed automated reporter quantification in vivo (ARQiv). In this study, ARQiv was combined with robotics to fully actualize whole-organism HTS (ARQiv-HTS). In a primary screen, this platform quantified cell-specific fluorescent reporters in >500,000 transgenic zebrafish larvae to identify FDA-approved (Federal Drug Administration) drugs that increased the number of insulin-producing β cells in the pancreas. 24 drugs were confirmed as inducers of endocrine differentiation and/or stimulators of β-cell proliferation. Further, we discovered novel roles for NF-κB signaling in regulating endocrine differentiation and for serotonergic signaling in selectively stimulating β-cell proliferation. These studies demonstrate the power of ARQiv-HTS for drug discovery and provide unique insights into signaling pathways controlling β-cell mass, potential therapeutic targets for treating diabetes. DOI: http://dx.doi.org/10.7554/eLife.08261.001 PMID:26218223

Screening and identification of apolipoprotein A-I as a potential hepatoblastoma biomarker in children, excluding inflammatory factors

PubMed Central

ZHAO, WEI; LI, JUAN; ZHANG, YILIN; GAO, PENGFEI; ZHANG, JUNJIE; GUO, FEI; YU, JIEKAI; ZHENG, SHU; WANG, JIAXIANG

2015-01-01

The aim of the present study was to identify a child hepatoblastoma serum biomarker that is unaffected by inflammatory factors, with the ultimate aim of finding an effective method for the early diagnosis of hepatoblastoma. The magnetic bead-based weak cation exchange chromatography technique was used to process serum harvested from 30 children with hepatoblastoma, 20 children with systemic inflammatory response syndrome (SIRS) and 20 healthy children. Proteins differentially expressed in SIRS were excluded from consideration as biomarkers for hepatoblastoma. Proteins differentially expressed in hepatoblastoma and healthy controls were screened using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). Target proteins were purified by SDS-PAGE, and matrix-assisted laser desorption/ionization (MALDI)-TOF-MS was used to determine their amino acid sequences. Protein matches were searched in the SwissProt database. Quantitative polymerase chain reaction (qPCR) and ELISA were employed to confirm the expression of target proteins. Following screening to exclude inflammatory factors, SELDI-TOF-MS revealed a protein with a mass-to-charge ratio of 9,348 Da that was expressed at significantly lower levels in the serum of children with hepatoblastoma compared with healthy controls (P<0.01). Sequence analysis identified this protein as apolipoprotein A-1 (Apo A-I). qPCR and ELISA confirmed that the expression of Apo A-I mRNA and protein were significantly lower in children with hepatoblastoma compared with healthy controls (P<0.05). These results indicate that Apo A-I is a non-inflammatory protein marker for hepatoblastoma with the potential for use in early diagnosis of hepatoblastoma. In addition, the present study demonstrates the feasibility of proteomic screening for the identification of proteins that can serve as markers for a specific tumor. PMID:26171005

Screening and identification of apolipoprotein A-I as a potential hepatoblastoma biomarker in children, excluding inflammatory factors.

PubMed

Zhao, Wei; Li, Juan; Zhang, Yilin; Gao, Pengfei; Zhang, Junjie; Guo, Fei; Yu, Jiekai; Zheng, Shu; Wang, Jiaxiang

2015-07-01

The aim of the present study was to identify a child hepatoblastoma serum biomarker that is unaffected by inflammatory factors, with the ultimate aim of finding an effective method for the early diagnosis of hepatoblastoma. The magnetic bead-based weak cation exchange chromatography technique was used to process serum harvested from 30 children with hepatoblastoma, 20 children with systemic inflammatory response syndrome (SIRS) and 20 healthy children. Proteins differentially expressed in SIRS were excluded from consideration as biomarkers for hepatoblastoma. Proteins differentially expressed in hepatoblastoma and healthy controls were screened using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). Target proteins were purified by SDS-PAGE, and matrix-assisted laser desorption/ionization (MALDI)-TOF-MS was used to determine their amino acid sequences. Protein matches were searched in the SwissProt database. Quantitative polymerase chain reaction (qPCR) and ELISA were employed to confirm the expression of target proteins. Following screening to exclude inflammatory factors, SELDI-TOF-MS revealed a protein with a mass-to-charge ratio of 9,348 Da that was expressed at significantly lower levels in the serum of children with hepatoblastoma compared with healthy controls (P<0.01). Sequence analysis identified this protein as apolipoprotein A-1 (Apo A-I). qPCR and ELISA confirmed that the expression of Apo A-I mRNA and protein were significantly lower in children with hepatoblastoma compared with healthy controls (P<0.05). These results indicate that Apo A-I is a non-inflammatory protein marker for hepatoblastoma with the potential for use in early diagnosis of hepatoblastoma. In addition, the present study demonstrates the feasibility of proteomic screening for the identification of proteins that can serve as markers for a specific tumor.

Fate of SO2 and Particulate SO4 Based on Airborne Measurements in the Oil Sands Region of Alberta, Canada

NASA Astrophysics Data System (ADS)

Hayden, K. L.; Li, S. M.; McLaren, R.; Liu, P.; O'brien, J.; Gordon, M.; Darlington, A.; Liggio, J.; Mittermeier, R. L.; Staebler, R. M.; Makar, P.; Stroud, C.; Akingunola, A.; Leithead, A.; Moussa, S.

2016-12-01

An intensive airborne measurement campaign was undertaken in August to September 2013 to support the objectives of the Joint Oil Sands Monitoring (JOSM) program. The overarching objectives of the study were to characterize air pollutants being emitted, to determine the extent of atmospheric transport and chemical transformation, to support air quality model prediction capabilities, and to compare measurements with satellite column retrievals. Sulphur dioxide (SO2) and particulate sulphate (p-SO4) were among the pollutants studied. SO2 is emitted from elevated stacks within the oil sands facilities and undergoes atmospheric transformation into p-SO4. Deposition of these species from the atmosphere to the surface can lead to impacts on ecosystems downwind of the facilities. The processes of emission, transformation, transport, and deposition of SO2 and p-SO4 were investigated in detail using data collected during aircraft flights that were designed to study pollution transformation. The aircraft was flown at increasing distances downwind of the oil sands facilities, sampling the same plume at different times as it was transported away from the sources. Flight tracks were perpendicular to the wind direction at multiple altitudes to create virtual flight screens that encompassed the entire plume. Fluxes across each of the virtual screens were determined using the wind speed vector normal to the screen and the pollutant concentrations; the flux integration across the two-dimensional plume transect on the screen yielded the pollutant transfer rates at that particular screen location. Transformation of SO2 to p-SO4 between screens was determined based on OH radical levels estimated using concurrently measured concentrations of a suite of hydrocarbons. Based on mass balance between screens using the transfer rates, SO2 oxidation rates and p-SO4 formation rates, the deposition rates of both species are estimated along the plume transport path downwind of the oil sands operations. These observation-derived estimates are compared to corresponding predicted results from a nested air-quality model (GEM-MACH) operating for the same time period.

Impact of comorbid conditions on participation in an organised colorectal cancer screening programme: a cross-sectional study.

PubMed

Guiriguet, Carolina; Pera, Guillem; Castells, Antoni; Toran, Pere; Grau, Jaume; Rivero, Irene; Buron, Andrea; Macià, Francesc; Vela-Vallespín, Carmen; Vilarrubí-Estrella, Mercedes; Marzo-Castillejo, Mercedes

2017-08-07

There is controversy regarding how comorbidity impacts on colorectal cancer screening, especially in the context of organised programmes. The aim of this study is to assess the effect of comorbidities on participation in the Barcelona population-based colorectal cancer screening programme (BCCSP). Cross-sectional study carried out in ten primary care centres involved in the BCCSP. Individuals aged 50 to 69, at average risk of colorectal cancer, who were invited to participate in the first round of the faecal immunochemical test-based BCCSP were included (2011-2012). The main variable was participation in the BCCSP. Comorbidity was assessed by clinical risk group status. Other adjusting variables were age, sex, socioeconomic deprivation, visits to primary care, smoking, alcohol consumption and body mass index. Logistic regression models were used to test the association between participation in the programme and potential explanatory variables. The results were given as incidence rate ratios (IRR) and their 95% confidence intervals (CI). Of the 36,208 individuals included, 17,404 (48%) participated in the BCCSP. Participation was statistically significantly higher in women, individuals aged 60 to 64, patients with intermediate socioeconomic deprivation, and patients with more medical visits. There was a higher rate of current smoking, high-risk alcohol intake, obesity and individuals in the highest comorbidity categories in the non-participation group. In the adjusted analysis, only individuals with multiple minor chronic diseases were more likely to participate in the BCCSP (IRR 1.14; 95% CI [1.06 to 1.22]; p < 0.001). In contrast, having three or more dominant chronic diseases was associated with lower participation in the screening programme (IRR 0.76; 95% CI [0.65 to 0.89]; p = 0.001). Having three or more dominant chronic diseases, was associated with lower participation in a faecal immunochemical test-based colorectal cancer screening programme, whereas individuals with multiple minor chronic diseases were more likely to participate. Further research is needed to explore comorbidity as a cause of non-participation in colorectal cancer screening programmes and which individuals could benefit most from colorectal cancer screening.

Analysis of legal high materials by ultra-performance liquid chromatography with time of flight mass spectrometry as part of a toxicology vigilance system: what are the most popular novel psychoactive substances in the UK?

PubMed

Ford, Loretta T; Berg, Jonathan D

2017-03-01

Introduction Legal highs also known as novel psychoactive substances mimic the effects of classic drugs of abuse. Challenges to developing screening services for novel psychoactive substances include identifying which novel psychoactive substances are available to target. Using new techniques such as exact mass time of flight can help identify common novel psychoactive substances to target for screening patient samples by routine methods such as tandem mass spectrometry. We demonstrate this strategy working in our own clinical toxicology laboratory after qualitative analysis of 98 suspect materials for novel psychoactive substances by ultra-performance liquid chromatography with time of flight mass spectrometry. Results From July 2014 to July 2015 we received 98 requests to test a range of different suspect materials for novel psychoactive substances including herbs, tobacco, liquids, pills and powders. Overall, 87% of the suspect materials tested positive for novel psychoactive substances, and 15% for controlled drugs. Three common novel psychoactive substances were present in 74% of the suspect materials: methiopropamine, a methamphetamine analogue; ethylphenidate, a cocaine mimic; and the third generation synthetic cannabinoid 5F-AKB-48. For the 55 branded products we tested only 24% of the stated contents matched exactly the compounds we detected. Conclusion Testing suspect materials using ultra-performance liquid chromatography with time of flight mass spectrometry has identified three common novel psychoactive substances in use in the UK, simplifying the development of a relevant novel psychoactive substances screening service to our population. By incorporating this into our routine liquid chromatography tandem mass spectrometry drugs of abuse screen, then offers a clinically relevant novel psychoactive substances service to our users. This strategy ensures our clinical toxicology service continues to remain effective to meet the challenges of the changing drug use in the UK.

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

PubMed

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

2017-06-01

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

An actor-based model of social network influence on adolescent body size, screen time, and playing sports.

PubMed

Shoham, David A; Tong, Liping; Lamberson, Peter J; Auchincloss, Amy H; Zhang, Jun; Dugas, Lara; Kaufman, Jay S; Cooper, Richard S; Luke, Amy

2012-01-01

Recent studies suggest that obesity may be "contagious" between individuals in social networks. Social contagion (influence), however, may not be identifiable using traditional statistical approaches because they cannot distinguish contagion from homophily (the propensity for individuals to select friends who are similar to themselves) or from shared environmental influences. In this paper, we apply the stochastic actor-based model (SABM) framework developed by Snijders and colleagues to data on adolescent body mass index (BMI), screen time, and playing active sports. Our primary hypothesis was that social influences on adolescent body size and related behaviors are independent of friend selection. Employing the SABM, we simultaneously modeled network dynamics (friendship selection based on homophily and structural characteristics of the network) and social influence. We focused on the 2 largest schools in the National Longitudinal Study of Adolescent Health (Add Health) and held the school environment constant by examining the 2 school networks separately (N = 624 and 1151). Results show support in both schools for homophily on BMI, but also for social influence on BMI. There was no evidence of homophily on screen time in either school, while only one of the schools showed homophily on playing active sports. There was, however, evidence of social influence on screen time in one of the schools, and playing active sports in both schools. These results suggest that both homophily and social influence are important in understanding patterns of adolescent obesity. Intervention efforts should take into consideration peers' influence on one another, rather than treating "high risk" adolescents in isolation.

[Maternal and neonatal vitamin B12 deficiency detected by expanded newborn screening].

PubMed

Papp, Ferenc; Rácz, Gábor; Lénárt, István; Kóbor, Jenő; Bereczki, Csaba; Karg, Eszter; Baráth, Ákos

2017-12-01

Infant vitamin B 12 deficiency can manifest as a severe neurodegenerative disorder and is usually caused by maternal deficiency due to vegetarian diet or pernicious anaemia. Its early recognition and treatment can prevent potentially serious and irreversible neurologic damage. Biochemically, vitamin B 12 deficiency leads to an accumulation of methylmalonic acid, homocysteine, and propionylcarnitine. Expanded newborn screening using tandem mass spectrometry may identify neonatal and maternal vitamin B 12 deficiency by measurement of propionylcarnitine and other metabolites in the dried blood spot sample of newborns. To summarize our experiences gained by screening for vitamin B 12 deficiency. Clinical and laboratory data of vitamin B 12 -deficient infants diagnosed in Szeged Screening Centre were retrospectively analysed. In Hungary, expanded newborn screening was introduced in 2007. Since then approximately 395 000 newborns were screened in our centre and among them, we identified four newborns with vitamin B 12 deficiency based on their screening results. In three cases an elevated propionylcarnitine level and in the fourth one a low methionine level were indicative of vitamin B 12 deficiency. We also detected an additional vitamin B 12 -deficient infant with neurological symptoms at 4 months of age, after a normal newborn screening, because of elevated urinary methylmalonic acid concentration. Vitamin B 12 deficiency was secondary to maternal autoimmune pernicious anaemia in all the five infants. As a result of the recognized cases the incidence of infant vitamin B 12 deficiency in the East-Hungarian region was 1.26/100 000 births, but the real frequency may be higher. Conslusions: Optimizing the cut off values of current screening parameters and measuring of methylmalonic acid and/or homocysteine in the dried blood spot, as a second tier test, can improve recognition rate of vitamin B 12 deficiency. Orv Hetil. 2017; 158(48): 1909-1918.

Computer-aided classification of mammographic masses using the deep learning technology: a preliminary study

NASA Astrophysics Data System (ADS)

Qiu, Yuchen; Yan, Shiju; Tan, Maxine; Cheng, Samuel; Liu, Hong; Zheng, Bin

2016-03-01

Although mammography is the only clinically acceptable imaging modality used in the population-based breast cancer screening, its efficacy is quite controversy. One of the major challenges is how to help radiologists more accurately classify between benign and malignant lesions. The purpose of this study is to investigate a new mammographic mass classification scheme based on a deep learning method. In this study, we used an image dataset involving 560 regions of interest (ROIs) extracted from digital mammograms, which includes 280 malignant and 280 benign mass ROIs, respectively. An eight layer deep learning network was applied, which employs three pairs of convolution-max-pooling layers for automatic feature extraction and a multiple layer perception (MLP) classifier for feature categorization. In order to improve robustness of selected features, each convolution layer is connected with a max-pooling layer. A number of 20, 10, and 5 feature maps were utilized for the 1st, 2nd and 3rd convolution layer, respectively. The convolution networks are followed by a MLP classifier, which generates a classification score to predict likelihood of a ROI depicting a malignant mass. Among 560 ROIs, 420 ROIs were used as a training dataset and the remaining 140 ROIs were used as a validation dataset. The result shows that the new deep learning based classifier yielded an area under the receiver operation characteristic curve (AUC) of 0.810+/-0.036. This study demonstrated the potential superiority of using a deep learning based classifier to distinguish malignant and benign breast masses without segmenting the lesions and extracting the pre-defined image features.

Characterization and quantitative analysis of surfactants in textile wastewater by liquid chromatography/quadrupole-time-of-flight mass spectrometry.

PubMed

González, Susana; Petrović, Mira; Radetic, Maja; Jovancic, Petar; Ilic, Vesna; Barceló, Damià

2008-05-01

A method based on the application of ultra-performance liquid chromatography (UPLC) coupled to hybrid quadrupole-time-of-flight mass spectrometry (QqTOF-MS) with an electrospray (ESI) interface has been developed for the screening and confirmation of several anionic and non-ionic surfactants: linear alkylbenzenesulfonates (LAS), alkylsulfate (AS), alkylethersulfate (AES), dihexyl sulfosuccinate (DHSS), alcohol ethoxylates (AEOs), coconut diethanolamide (CDEA), nonylphenol ethoxylates (NPEOs), and their degradation products (nonylphenol carboxylate (NPEC), octylphenol carboxylate (OPEC), 4-nonylphenol (NP), 4-octylphenol (OP) and NPEO sulfate (NPEO-SO4). The developed methodology permits reliable quantification combined with a high accuracy confirmation based on the accurate mass of the (de)protonated molecules in the TOFMS mode. For further confirmation of the identity of the detected compounds the QqTOF mode was used. Accurate masses of product ions obtained by performing collision-induced dissociation (CID) of the (de)protonated molecules of parent compounds were matched with the ions obtained for a standard solution. The method was applied for the quantitative analysis and high accuracy confirmation of surfactants in complex mixtures in effluents from the textile industry. Positive identification of the target compounds was based on accurate mass measurement of the base peak, at least one product ion and the LC retention time of the analyte compared with that of a standard. The most frequently surfactants found in these textile effluents were NPEO and NPEO-SO4 in concentrations ranging from 0.93 to 5.68 mg/L for NPEO and 0.06 to 4.30 mg/L for NPEO-SO4. AEOs were also identified.

UPLC/Q-TOFMS/MS as a powerful technique for rapid identification of polymethoxylated flavones in Fructus aurantii.

PubMed

Zhou, Da-Yong; Zhang, Xiu-Li; Xu, Qing; Xue, Xing-Ya; Zhang, Fei-Fang; Liang, Xin-Miao

2009-08-15

Polymethoxylated flavones (PMFs), as potential cancer chemopreventive agents, are widely distributed in Citrus genus. In this study, a selected ion monitoring-tandem mass (SIM-MS/MS) method for the rapid identification of PMFs in Fructus aurantii (F. aurantii) with ultra-performance liquid chromatography (UPLC) coupled to quadrupole, hybrid orthogonal acceleration time-of-flight tandem mass spectrometer (Q-TOFMS/MS) was proposed. The MS data for candidates, containing accurate mass and isotopic patterns for both precursors and their fragment ions, were acquired selectively. Based on the MS data, the mass spectrometric fingerprint (MSFP) for candidates, consisting of chemical formula and dissociation pattern, was determined. Comparing the MSFPs of the observed compounds with the diagnostic MSFP of the species, 44 PMFs were tentatively identified. The method was validated by tangeretin and sinensetin, two representative compounds of PMFs, and was considered to be suitable for the rapid screening of PMFs in crude and partially purified samples.

The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

PubMed

la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria Luisa; Canessa, Clementina; Lippi, Francesca; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

2014-01-01

Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program. We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine <0.09μmol/L, adenosine <1.61μmol/L). We also developed a second tier test to distinguish true positives from false positives and improve the positive predictive value of an initial abnormal result. In the first 18 months, the pilot project has identified a newborn with a genetically confirmed defect in adenosine deaminase (ADA) gene. The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program. Copyright © 2013 Elsevier B.V. All rights reserved.

Characterization of screenings from three municipal wastewater treatment plants in the Region Rhône-Alpes.

PubMed

Le Hyaric, R; Canler, J-P; Barillon, B; Naquin, P; Gourdon, R

2009-01-01

The objective of this study was to analyze the composition of the screenings sampled from three municipal wastewater treatment plants (wwtp) located in the Region Rhône-Alpes, France. The plants were equipped with multi screening stages with gap sizes ranging from 60 to 3 mm. Waste production flows from each plant were monitored over at least 48 hours in each sampling campaign in order to calculate average production rates. Waste samples of at least 7 kg were collected from each screening stage in each plant at different seasons to evaluate the influence of different parameters on the composition of the waste. An overall 30 samples were thereby collected between May 2007 and February 2008, dried at 80 degrees C for a week, and subsequently hand sorted into 10 fractions of waste materials. Results showed that the average production varied between 0.53 and 3.49 kg (wet mass) per capita per year. The highest production rates were observed during or immediately after rainy weather conditions. The dry matter content ranged between 14.4 and 29.2% of wet mass, and the volatile matter content was between 70.0 and 90.5% of dry mass. The predominant materials in the screenings were found to be sanitary textiles which accounted for 65.2% to 73.6% of dry weight and fines (<20 mm) which accounted for 15.2% to 18.2% of dry weight. These proportions were relatively similar in each plant and each sampling campaign.

Screening for colorectal cancer with FOBT, virtual colonoscopy and optical colonoscopy: study protocol for a randomized controlled trial in the Florence district (SAVE study)

PubMed Central

2013-01-01

Background Colorectal cancer (CRC) is the most frequent cancer in Europe. Randomized clinical trials demonstrated that screening with fecal occult blood test (FOBT) reduces mortality from CRC. Accordingly, the European Community currently recommends population-based screening with FOBT. Other screening tests, such as computed tomography colonography (CTC) and optical colonoscopy (OC), are highly accurate for examining the entire colon for adenomas and CRC. Acceptability represents a critical determinant of the impact of a screening program. We designed a randomized controlled trial to compare participation rate and diagnostic yield of FOBT, CTC with computer-aided diagnosis, and OC as primary tests for population-based screening. Methods/Design A total of 14,000 subjects aged 55 to 64 years, living in the Florence district and never screened for CRC, will be randomized in three arms: group 1 (5,000 persons) invited to undergo CTC (divided into: subgroup 1A with reduced cathartic preparation and subgroup 1B with standard bowel preparation); group 2 (8,000 persons) invited to undergo a biannual FOBT for three rounds; and group 3 (1,000 persons) invited to undergo OC. Subjects of each group will be invited by mail to undergo the selected test. All subjects with a positive FOBT or CTC test (that is, mass or at least one polyp ≥6 mm) will be invited to undergo a second-level OC. Primary objectives of the study are to compare the participation rate to FOBT, CTC and OC; to compare the detection rate for cancer or advanced adenomas of CTC versus three rounds of biannual FOBT; to evaluate referral rate for OC induced by primary CTC versus three rounds of FOBT; and to estimate costs of the three screening strategies. A secondary objective of the study is to create a biological bank of blood and stool specimens from subjects undergoing CTC and OC. Discussion This study will provide information about participation/acceptability, diagnostic yield and costs of screening with CTC in comparison with the recommended test (FOBT) and OC. Trial registration ClinicalTrials.gov Identifier: NCT01651624. PMID:23497601

Application of a novel metabolomic approach based on atmospheric pressure photoionization mass spectrometry using flow injection analysis for the study of Alzheimer's disease.

PubMed

González-Domínguez, Raúl; García-Barrera, Tamara; Gómez-Ariza, José Luis

2015-01-01

The use of atmospheric pressure photoionization is not widespread in metabolomics, despite its considerable potential for the simultaneous analysis of compounds with diverse polarities. This work considers the development of a novel analytical approach based on flow injection analysis and atmospheric pressure photoionization mass spectrometry for rapid metabolic screening of serum samples. Several experimental parameters were optimized, such as type of dopant, flow injection solvent, and their flows, given that a careful selection of these variables is mandatory for a comprehensive analysis of metabolites. Toluene and methanol were the most suitable dopant and flow injection solvent, respectively. Moreover, analysis in negative mode required higher solvent and dopant flows (100 µl min(-1) and 40 µl min(-1), respectively) compared to positive mode (50 µl min(-1) and 20 µl min(-1)). Then, the optimized approach was used to elucidate metabolic alterations associated with Alzheimer's disease. Thereby, results confirm the increase of diacylglycerols, ceramides, ceramide-1-phosphate and free fatty acids, indicating membrane destabilization processes, and reduction of fatty acid amides and several neurotransmitters related to impairments in neuronal transmission, among others. Therefore, it could be concluded that this metabolomic tool presents a great potential for analysis of biological samples, considering its high-throughput screening capability, fast analysis and comprehensive metabolite coverage. Copyright © 2014 Elsevier B.V. All rights reserved.

A novel brominated triazine-based flame retardant (TTBP-TAZ) in plastic consumer products and indoor dust.

PubMed

Ballesteros-Gómez, Ana; de Boer, Jacob; Leonards, Pim E G

2014-04-15

The presence of a novel brominated flame retardant named 2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) is reported for the first time in plastic parts of consumer products and indoor dust samples. TTBP-TAZ was identified by untargeted screening and can be a replacement of the banned polybrominated diphenyl ethers. Analysis techniques based on ambient mass spectrometry and on liquid chromatography with atmospheric pressure chemical ionization combined with high resolution time-of-flight mass spectrometry were developed for the screening, detection and quantification of this low volatility and high molecular weight compound. TTBP-TAZ was present in 8 of 13 plastic parts of consumer products (from mainly electric and electronic equipment acquired in 2012) at estimated concentrations of 0.01-1.9% by weight of the product (%, w/w). It was not present in any of the older 13 plastic samples that were collected in a recycling park (manufacture date before 2006), this suggests a recent use of TTBP-TAZ. It was also found in 9 of 17 house dust samples in the range of 160-22150 ng g(-1), with the highest levels being found in samples collected on electronic and electrical equipment. These preliminary results highlight the need for further research on TTBP-TAZ and the potential of using alternative analysis methods for the identification of new flame retardants.

[Ultrasound screening of abdominal aortic aneurysm: Lessons from Vesale 2013].

PubMed

Laroche, J P; Becker, F; Baud, J M; Miserey, G; Jaussent, A; Picot, M C; Bura-Rivière, A; Quéré, I

2015-12-01

Although aneurysm of the abdominal infra-renal aorta (AAA) meets criteria warranting B mode ultrasound screening, the advantages of mass screening versus selective targeted opportunistic screening remain a subject of debate. In France, the French Society of Vascular Medicine (SFMV) and the Health Authority (HAS) published recommendations for targeted opportunistic screening in 2006 and 2013 respectively. The SFMV held a mainstream communication day on November 21, 2013 in France involving participants from metropolitan France and overseas departments that led to a proposal for free AAA ultrasound screening: the Vesalius operation. Being a consumer operation, the selection criteria were limited to age (men and women between 60 and 75 years); the age limit was lowered to 50 years in case of direct family history of AAA. More than 7000 people (as many women as men) were screened in 83 centers with a 1.70% prevalence of AAA in the age-based target population (3.12% for men, 0.27% for women). The median diameter of detected AAA was 33 mm (range 20 to 74 mm). The prevalence of AAA was 1.7% in this population. Vesalius data are consistent with those of the literature both in terms of prevalence and for cardiovascular risk factors with the important role of smoking. Lessons from Vesalius to take into consideration are: screening is warranted in men 60 years and over, especially smokers, and in female smokers. Screening beyond 75 years should be discussed. Given the importance of screening, the SFMV set up a year of national screening for AAA (Vesalius operation 2014/2015) in order to increase public and physician awareness about AAA detection, therapeutic management, and monitoring. AAA is a serious, common, disease that kills 6000 people each year. The goal of screening is cost-effective reduction in the death toll. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A PROTEOMIC (SELDI-TOF-MS) APPROACH TO ESTROGEN AGONIST SCREENING

EPA Science Inventory

A small fish model and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI) were used to investigate plasma protein expression as a means to screen chemicals for estrogenic activity. Adult male sheepshead minnows (Cyprinodon variegatus) were place...

Improved design of electrophoretic equipment for rapid sickle-cell-anemia screening

NASA Technical Reports Server (NTRS)

Reddick, J. M.; Hirsch, I.

1974-01-01

Effective mass screening may be accomplished by modifying existing electrophoretic equipment in conjunction with multisample applicator used with cellulose-acetate-matrix test paper. Using this method, approximately 20 to 25 samples can undergo electrophoresis in 5 to 6 minutes.

A new screening method for flunitrazepam in vodka and tequila by fluorescence spectroscopy.

PubMed

Leesakul, Nararak; Pongampai, Sirintip; Kanatharana, Proespichaya; Sudkeaw, Pravit; Tantirungrotechai, Yuthana; Buranachai, Chittanon

2013-01-01

A new screening method for flunitrazepam in colourless alcoholic beverages based on a spectroscopic technique is proposed. Absorption and steady-state fluorescence of flunitrazepam and its protonated form with various acids were investigated. The redshift of the wavelength of maximum absorption was distinctively observed in protonated flunitrazepam. An emissive fluorescence at 472 nm was detected in colourless spirits (vodka and tequila) at room temperature. 2-M perchloric acid was the most appropriated proton source. By using electron ionization mass spectrometry and time-dependent density functional theory calculations, the possible structure of protonated flunitrazepam was identified to be 2-nitro-N-methylacridone, an acridone derivative as opposed to 2-methylamino-5-nitro-2'-fluorobenzophenone, a benzophenone derivative. Copyright © 2012 John Wiley & Sons, Ltd.

Improved Reagents for Newborn Screening of Mucopolysaccharidosis Types I, II, and VI by Tandem Mass Spectrometry

PubMed Central

2015-01-01

Tandem mass spectrometry for the multiplex and quantitative analysis of enzyme activities in dried blood spots on newborn screening cards has emerged as a powerful technique for early assessment of lysosomal storage diseases. Here we report the design and process-scale synthesis of substrates for the enzymes α-l-iduronidase, iduronate-2-sulfatase, and N-acetylgalactosamine-4-sulfatase that are used for newborn screening of mucopolysaccharidosis types I, II, and VI. The products contain a bisamide unit that is hypothesized to readily protonate in the gas phase, which improves detection sensitivity by tandem mass spectrometry. The products contain a benzoyl group, which provides a useful site for inexpensive deuteration, thus facilitating the preparation of internal standards for the accurate quantification of enzymatic products. Finally, the reagents are designed with ease of synthesis in mind, thus permitting scale-up preparation to support worldwide newborn screening of lysosomal storage diseases. The new reagents provide the most sensitive assay for the three lysosomal enzymes reported to date as shown by their performance in reactions using dried blood spots as the enzyme source. Also, the ratio of assay signal to that measured in the absence of blood (background) is superior to all previously reported mucopolysaccharidosis types I, II, and VI assays. PMID:24694010

Novel heparan sulfate assay by using automated high-throughput mass spectrometry: application to monitoring and screening for mucopolysaccharidoses

PubMed Central

Shimada, Tsutomu; Kelly, Joan; LaMarr, William A; van Vlies, Naomi; Yasuda, Eriko; Mason, Robert W.; Mackenzie, William; Kubaski, Francyne; Giugliani, Roberto; Chinen, Yasutsugu; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E.; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

2014-01-01

Mucopolysaccharidoses (MPS) are caused by deficiency of one of a group of specific lysosomal enzymes, resulting in excessive accumulation of glycosaminoglycans (GAGs). We previously developed GAG assay methods using liquid chromatography tandem mass spectrometry (LC-MS/MS); however, it takes 4–5 min per sample for analysis. For the large numbers of samples in a screening program, a more rapid process is desirable. The automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) integrates a solid phase extraction robot to concentrate and desalt samples prior to direction into the MS/MS without chromatographic separation; thereby allowing each sample to be processed within ten seconds (enabling screening of more than one million samples per year). The aim of this study was to develop a higher throughput system to assay heparan sulfate (HS) using HT-MS/MS, and to compare its reproducibility, sensitivity and specificity with conventional LC-MS/MS. HS levels were measured in blood (plasma and serum) from control subjects and patients with MPS II, III, or IV and in dried blood spots (DBS) from newborn controls and patients with MPS I, II, or III. Results obtained from HT-MS/MS showed 1) that there was a strong correlation of levels of disaccharides derived from HS in blood, between those calculated using conventional LC-MS/MS and HT-MS/MS, 2) that levels of HS in blood were significantly elevated in patients with MPS II and III, but not in MPS IVA, 3) that the level of HS in patients with a severe form of MPS II was higher than that in an attenuated form, 4) that reduction of blood HS level was observed in MPS II patients treated with enzyme replacement therapy or hematopoietic stem cell transplantation, and 5) that levels of HS in newborn DBS were elevated in patients with MPS I, II or III, compared to control newborns. In conclusion, HT-MS/MS provides much higher throughput than LC-MS/MS-based methods with similar sensitivity and specificity in an HS assay, indicating that HT-MS/MS may be feasible for diagnosis, monitoring, and newborn screening of MPS. PMID:25092413

Novel strategy for the determination of illegal adulterants in health foods and herbal medicines using high-performance liquid chromatography with high-resolution mass spectrometry.

PubMed

Wang, Zhe; Wu, Caisheng; Wang, Gangli; Zhang, Qingsheng; Zhang, Jinlan

2015-03-01

The detection, confirmation, and quantification of multiple illegal adulterants in health foods and herbal medicines by using a single analytical method are a challenge. This paper reports on a new strategy to meet this challenge by employing high-performance liquid chromatography coupled with high-resolution mass spectrometry and a mass spectral tree similarity filter technique. This analytical method can rapidly collect high-resolution, high-accuracy, optionally multistage mass data for compounds in samples. After a preliminary screening by retention time and high-resolution mass spectral data, known illegal adulterants can be detected. The mass spectral tree similarity filter technique has been applied to rapidly confirm these adulterants and simultaneously discover unknown ones. By using full-scan mass spectra as stem and data-dependent subsequent stage mass spectra to form branches, mass spectrometry data from detected compounds are converted into mass spectral trees. The known or unknown illegal adulterants in the samples are confirmed or discovered based on the similarity between their mass spectral trees and those of the references in a library, and they are finally quantified against standard curves. This new strategy has been tested by using 50 samples, and the illegal adulterants were rapidly and effectively detected, confirmed and quantified. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Smart Screening System (S3) In Taconite Processing

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

Daryoush Allaei; Ryan Wartman; David Tarnowski

2006-03-01

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

Tablets at the bedside - iPad-based visual field test used in the diagnosis of Intrasellar Haemangiopericytoma: a case report.

PubMed

Nesaratnam, Nisha; Thomas, Peter B M; Kirollos, Ramez; Vingrys, Algis J; Kong, George Y X; Martin, Keith R

2017-04-24

In the assessment of a pituitary mass, objective visual field testing represents a valuable means of evaluating mass effect, and thus in deciding whether surgical management is warranted. In this vignette, we describe a 73 year-old lady who presented with a three-week history of frontal headache, and 'blurriness' in the left side of her vision, due to a WHO grade III anaplastic haemangiopericytoma compressing the optic chiasm. We report how timely investigations, including an iPad-based visual field test (Melbourne Rapid Field, (MRF)) conducted at the bedside aided swift and appropriate management of the patient. We envisage such a test having a role in assessing bed-bound patients in hospital where access to formal visual field testing is difficult, or indeed in rapid testing of visual fields at the bedside to screen for post-operative complications, such as haematoma.

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.

Triclosan and methyl-triclosan monitoring study in the northeast of Spain using a magnetic particle enzyme immunoassay and confirmatory analysis by gas chromatography mass spectrometry

NASA Astrophysics Data System (ADS)

Kantiani, Lina; Farré, Marinella; Asperger, Danijela; Rubio, Fernando; González, Susana; López de Alda, Maria J.; Petrović, Mira; Shelver, Weilin L.; Barceló, Damià

2008-10-01

SummaryFor the first time, the occurrence of triclosan and its metabolite methyl-triclosan was investigated in a typical Mediterranean area using a two-step methodology based on screening using a magnetic particle immunoassay (IA) and confirmatory analysis by solid phase extraction (SPE) followed by gas chromatography-mass spectrometry (GC-MS). In this study, 95 environmental samples were analyzed. A commercial immunoassay was assessed for use in the different types of water selected for this study. A large monitoring study was performed on the influent and the effluent of eight wastewater treatment plants (WWTPs), water samples from Ebro and Llobregat rivers, and drinking water. All wastewater samples tested in this study (influents and effluents) showed the presence of triclosan, with concentrations for raw influents being high (10 μg/L as average value). The percentages of triclosan removal for the WWTPs were evaluated (30-70%) along the different treatment processes showing that the best removal rates were obtained by the processes equipped with membrane bioreactors (MBRs). However, important concentrations of triclosan were detected even after treatment by MBRs. The presence of this biocide was confirmed in 50% of the river samples analyzed. Twenty two drinking water samples from the Barcelona city area were investigated, and in this case no triclosan was detected. Due to its properties and the widespread usage of triclosan, there is a need for monitoring and controlling the amounts present in wastewater effluents, river water, drinking water catchments areas, and drinking water. To this end, we present a feasible methodology using a magnetic particle-based immunoassay as a screening, followed by confirmatory analysis using solid phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS).

Multiloop atom interferometer measurements of chameleon dark energy in microgravity

NASA Astrophysics Data System (ADS)

Chiow, Sheng-wey; Yu, Nan

2018-02-01

Chameleon field is one of the promising candidates of dark energy scalar fields. As in all viable candidate field theories, a screening mechanism is implemented to be consistent with all existing tests of general relativity. The screening effect in the chameleon theory manifests its influence limited only to the thin outer layer of a bulk object, thus producing extra forces orders of magnitude weaker than that of the gravitational force of the bulk. For pointlike particles such as atoms, the depth of screening is larger than the size of the particle, such that the screening mechanism is ineffective and the chameleon force is fully expressed on the atomic test particles. Extra force measurements using atom interferometry are thus much more sensitive than bulk mass based measurements, and indeed have placed the most stringent constraints on the parameters characterizing chameleon field. In this paper, we present a conceptual measurement approach for chameleon force detection using atom interferometry in microgravity, in which multiloop atom interferometers exploit specially designed periodic modulation of chameleon fields. We show that major systematics of the dark energy force measurements, i.e., effects of gravitational forces and their gradients, can be suppressed below all hypothetical chameleon signals in the parameter space of interest.

Bulk viscous corrections to screening and damping in QCD at high temperatures

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

Du, Qianqian; Dumitru, Adrian; Guo, Yun

2017-01-01

Non-equilibrium corrections to the distribution functions of quarks and gluons in a hot and dense QCD medium modify the \\hard thermal loops" (HTL). The HTLs determine the retarded, advanced, and symmetric (time-ordered) propagators for gluons with soft momenta as well as the Debye screening and Landau damping mass scales. Here, we compute such corrections to a thermal as well as to a non-thermal fixed point. The screening and damping mass scales are sensitive to the bulk pressure and hence to (pseudo-) critical dynamical scaling of the bulk viscosity in the vicinity of a second-order critical point. This could be reectedmore » in the properties of quarkonium bound states in the deconfined phase and in the dynamics of soft gluon fields.« less

Environmental screening of dark matter haloes in f(R) gravity

NASA Astrophysics Data System (ADS)

Shi, Difu; Li, Baojiu; Han, Jiaxin

2017-07-01

In certain theories of modified gravity, Solar system constraints on deviations from general relativity (GR) are satisfied by virtue of a so-called screening mechanism, which enables the theory to revert to GR in regions where the matter density is high or the gravitational potential is deep. In the case of chameleon theories, the screening has two contributions - self-screening, which is due to the mass of an object itself, and environmental screening, which is caused by the surrounding matter - which are often entangled, with the second contribution being more crucial for less massive objects. A quantitative understanding of the effect of the environment on the screening can prove critical in observational tests of such theories using systems such as the Local Group and dwarf galaxies, for which the environment may be inferred in various ways. We use the high-resolution liminality simulation of Shi et al. to test the fidelity of different definitions of environment. We find that, although the different ways to define environment in practice do not agree with one another perfectly, they can provide useful guidance, and cross checks about how well a dark matter halo is screened. In addition, the screening of subhaloes in dark matter haloes is primarily determined by the environment, with the subhalo mass playing a minor role, which means that lower resolution simulations where subhaloes are not well resolved can still be useful for understanding the modification of gravity inside subhaloes.

Diagnosis, treatment and outcome of glutaric aciduria type I in Zhejiang Province, China

PubMed Central

Yang, Lili; Yin, Huaiming; Yang, Rongwang; Huang, Xinwen

2011-01-01

Summary Background Glutaric aciduria type I (GA I; MIM 231670) is a rare autosomal recessive disorder resulting from glutaryl-CoA dehydrogenase deficiency. This article reports our experience in the diagnosis, treatment and outcome of GA I patients in Zhejiang Province, China. Material/Methods A total of 129,415 newborns (accounting for approximately one-tenth of the annual births in Zhejiang Province) and 9640 high-risk infants were screened for inborn errors of metabolism in the Neonatal Screening Center of Zhejiang Province during a 3-year period. Tandem mass spectrometry and gas chromatography-mass spectrometry were used for diagnosis of the patients. Dietary modification, carnitine supplementation and aggressive treatment of intercurrent illnesses were adapted for GA I patients. Results Three infants were diagnosed with GA I by high-risk screening (detection rate: 1/3,213) and 2 were diagnosed by newborn screening (incidence: 1/64,708). Four patients (3 by high-risk screening and 1 by neonatal screening) undergoing MRI examination showed remarkable changes on T2-weighted image. Four patients accepted timely treatment, and in the patient diagnosed by neonatal screening, treatment was delayed until hypotonia appeared 3 months later. Neuropsychological assessment showed mental and motor retardation in 3 patients after treatment, including the patient diagnosed by neonatal screening. Conclusions Individualized timely treatment and close monitoring of GA I patients needs to be optimized in China. Appropriate communication with parents may help to achieve successful management of GA I patients. PMID:21709643

Factors associated with objectively measured total sedentary time and screen time in children aged 9-11 years.

PubMed

Ferrari, Gerson Luis de Moraes; Pires, Carlos; Solé, Dirceu; Matsudo, Victor; Katzmarzyk, Peter T; Fisberg, Mauro

2018-01-04

To identify factors associated with total sedentary time and screen time in children aged 9-11 years. For seven consecutive days, 328 children (51.5% boys) used accelerometers to monitor total sedentary time. Screen time was calculated by the self-reporting method. Individual, family, family environment, and school environment questionnaires were filled out. Body composition was measured using a Tanita scale. The mean sedentary time was 500min/day (boys: 489, girls: 511, p=0.005), and mean screen time was 234min/day (boys: 246, girls: 222, p=0.053). In both genders, factors associated with sedentary time were healthy dietary pattern and moderate-to-vigorous physical activity. In boys, only moderate-to-vigorous physical activity was significant; in girls, the healthy dietary pattern, moderate-to-vigorous physical activity, and transportation to school were significant. As for the screen time, the associated factors were body mass index and healthy dietary pattern (both genders). In boys, the associated factors were body mass index, healthy dietary pattern, and television in the bedroom. In girls, the associated factors were healthy dietary pattern, transportation to school, and physical activity policies or practice at school. Several associated factors were identified in the association between total sedentary time and screen time in children; however, only the healthy dietary pattern was common between sedentary time and screen time. Copyright © 2017. Published by Elsevier Editora Ltda.

Direct chemical profiling of olive (Olea europaea) fruit epicuticular waxes by direct electrospray-ultrahigh resolution mass spectrometry.

PubMed

Vichi, Stefania; Cortés-Francisco, Nuria; Romero, Agustí; Caixach, Josep

2015-03-01

In the present paper, an electrospray ionization (ESI)-Orbitrap method is proposed for the direct chemical profiling of epicuticular wax (EW) from Olea europaea fruit. It constitutes a rapid and efficient tool suitable for a wide-ranging screening of a large number of samples. In a few minutes, the method provides a comprehensive characterization of total EW extracts, based on the molecular formula of their components. Accurate mass measurements are obtained by ultrahigh resolution mass spectrometry, and compositional restrictions are set on the basis of the information available from previous studies of olive EW. By alternating positive and negative ESI modes within the same analysis, complementary results are obtained and a wide range of chemical species is covered. This provides a detailed compositional overview that otherwise would only be available by applying multiple analytical techniques. Copyright © 2015 John Wiley & Sons, Ltd.

A new CAD approach for improving efficacy of cancer screening

NASA Astrophysics Data System (ADS)

Zheng, Bin; Qian, Wei; Li, Lihua; Pu, Jiantao; Kang, Yan; Lure, Fleming; Tan, Maxine; Qiu, Yuchen

2015-03-01

Since performance and clinical utility of current computer-aided detection (CAD) schemes of detecting and classifying soft tissue lesions (e.g., breast masses and lung nodules) is not satisfactory, many researchers in CAD field call for new CAD research ideas and approaches. The purpose of presenting this opinion paper is to share our vision and stimulate more discussions of how to overcome or compensate the limitation of current lesion-detection based CAD schemes in the CAD research community. Since based on our observation that analyzing global image information plays an important role in radiologists' decision making, we hypothesized that using the targeted quantitative image features computed from global images could also provide highly discriminatory power, which are supplementary to the lesion-based information. To test our hypothesis, we recently performed a number of independent studies. Based on our published preliminary study results, we demonstrated that global mammographic image features and background parenchymal enhancement of breast MR images carried useful information to (1) predict near-term breast cancer risk based on negative screening mammograms, (2) distinguish between true- and false-positive recalls in mammography screening examinations, and (3) classify between malignant and benign breast MR examinations. The global case-based CAD scheme only warns a risk level of the cases without cueing a large number of false-positive lesions. It can also be applied to guide lesion-based CAD cueing to reduce false-positives but enhance clinically relevant true-positive cueing. However, before such a new CAD approach is clinically acceptable, more work is needed to optimize not only the scheme performance but also how to integrate with lesion-based CAD schemes in the clinical practice.

A New Scoring System to Predict the Risk for High-risk Adenoma and Comparison of Existing Risk Calculators.

PubMed

Murchie, Brent; Tandon, Kanwarpreet; Hakim, Seifeldin; Shah, Kinchit; O'Rourke, Colin; Castro, Fernando J

2017-04-01

Colorectal cancer (CRC) screening guidelines likely over-generalizes CRC risk, 35% of Americans are not up to date with screening, and there is growing incidence of CRC in younger patients. We developed a practical prediction model for high-risk colon adenomas in an average-risk population, including an expanded definition of high-risk polyps (≥3 nonadvanced adenomas), exposing higher than average-risk patients. We also compared results with previously created calculators. Patients aged 40 to 59 years, undergoing first-time average-risk screening or diagnostic colonoscopies were evaluated. Risk calculators for advanced adenomas and high-risk adenomas were created based on age, body mass index, sex, race, and smoking history. Previously established calculators with similar risk factors were selected for comparison of concordance statistic (c-statistic) and external validation. A total of 5063 patients were included. Advanced adenomas, and high-risk adenomas were seen in 5.7% and 7.4% of the patient population, respectively. The c-statistic for our calculator was 0.639 for the prediction of advanced adenomas, and 0.650 for high-risk adenomas. When applied to our population, all previous models had lower c-statistic results although one performed similarly. Our model compares favorably to previously established prediction models. Age and body mass index were used as continuous variables, likely improving the c-statistic. It also reports absolute predictive probabilities of advanced and high-risk polyps, allowing for more individualized risk assessment of CRC.