Benefits and challenges of molecular diagnostics for childhood tuberculosis.

PubMed

Gutierrez, Cristina

2016-12-01

Expanding tuberculosis (TB)-diagnostic services, including access to rapid tests, is a World Health Organization (WHO) strategy to accelerate progress toward ending TB. Faster and more sensitive molecular tests capable of diagnosing TB and drug-resistant TB have the technical capacity to address limitations associated with smears and cultures by increasing accuracy and shortening turnaround times as compared with those of these conventional laboratory methods. Nucleic acid amplification assays used to detect and analyze Mycobacterium tuberculosis (MTB)-complex nucleic acids can be used directly on specimens from patients suspected of having TB. Recently, several commercial molecular tests were developed to detect MTB and determine the drug resistance (DR) based on detection of specific genetic mutations conferring resistance. The first to be endorsed by the WHO was molecular line-probe assay technology. This test uses polymerase chain reaction (PCR) and reverse-hybridization methods to rapidly identify MTB and DR-related mutations simultaneously. More recently, the WHO endorsed Xpert MTB/RIF, Cepheid Inc, CA, USA, a fully automated assay used for TB diagnosis that relies upon PCR techniques for detection of TB and rifampicin resistance-related mutations. Other promising molecular TB assays for simplifying PCR-based testing protocols and increasing their accuracy are under development and evaluation. Although we lack a practical gold standard for the diagnosis of childhood TB, its bacteriological confirmation is always recommended to be sought whenever possible prior to a diagnostic decision being made. Conventional diagnostic laboratory TB tests are less efficient for children as compared with adults, because sufficient sputum samples are more difficult to collect from infants and young children, and their disease is often paucibacillary, resulting in smear-negative disease. These inherent challenges associated with childhood TB are due to immunological- and pathophysiological-response differences relative to those observed in adults. Several recent meta-analyses showed low sensitivity estimates of PCR-based TB assays for paucibacillary forms of TB (extrapulmonary TB and smear-negative pulmonary disease), which represent the vast majority of childhood TB cases. Despite the lack of evidence regarding use of the rapid molecular assays to identify TB and detect DR in children, and due to the clinical nature of childhood TB, TB-expert groups recommend including rapid methods for TB identification and DR detection in diagnostic algorithms for children suspected of both smear-positive and -negative pulmonary or extrapulmonary TB, both with or without human immunodeficiency virus (HIV)-coinfection, when combined with standard methods (including clinical, microbiological, and radiological assessment) for diagnosing active TB and conventional DR. Since 2011, the WHO has specifically recommended use of the Xpert MTB/RIF test as an initial diagnostic tool for children with suspected HIV-associated TB or multidrug-resistant TB based on successful treatment data related to adults. Implementation of the rapid molecular assays for rapid detection of TB and DR should occur in laboratories with proven capability to run molecular tests and where quality control systems are implemented. Molecular approaches should be more largely tested in children, given their status as the group in whom the diagnostic dilemma is most pronounced. These tests should also be included in specific childhood TB diagnostic algorithms adapted to the local/national context in combination with other strategies for improving diagnostics, including more effective specimen collection. Copyright © 2016.

[Role of cytology in hematopathological diagnostics].

PubMed

Bode, B; Tinguely, M

2012-07-01

The role of cytology has so far been underrecognized in the diagnostic process of hematopathological questions. This article presents an algorithm which allows a stepwise work-up of cytology specimens obtained by minimally invasive ultrasound-guided fine needle aspiration in patients with unexplained lymph node swelling. Moreover, it is shown how the selective separation of cytology specimens allows the application of immunophenotypic analysis including flow cytometry and immunohistochemistry as well as molecular analyses, such as fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) strategies. With the integrative procedure presented, cytology offers an excellent cost-effective tool for the diagnostic approach of patients with suspected hematopathological malignancies allowing a high diagnostic accuracy, ideal for initial diagnosis or follow-up.

Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review.

PubMed

Bruno, Rossella; Alì, Greta; Fontanini, Gabriella

2018-01-01

Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure. Histopathological analysis of pleural tissues is the gold standard for diagnosis; however, it can be difficult to differentiate malignant from benign pleural lesions. The purpose of this review is to describe the most important biomarkers and new diagnostic tools suggested for this differential diagnosis. There are many studies concerning the separation between MPM and benign pleural proliferations from both pleural tissues or effusions; most of them are based on the evaluation of one or few biomarkers by immunohistochemistry (IHC) or enzyme-linked immunosorbent assays (ELISAs), whereas others focused on the identification of MPM signatures given by microRNA (miRNA) or gene expression profiles as well as on the combination of molecular data and classification algorithms. None of the reported biomarkers showed adequate diagnostic accuracy, except for p16 [evaluated by fluorescent in situ hybridization (FISH)] and BAP1 (evaluated by IHC), both biomarkers are recommended by the International Mesothelioma Interest Group guidelines for histological and cytological diagnosis. BAP1 and p16 showed a specificity of 100% in discerning malignant from benign lesions because they are exclusively unexpressed or deleted in MPM. However, their sensitivity, even when used together, is not completely sufficient, and absence of their alterations cannot confirm the benign nature of the lesion. Recently, the availability of new techniques and increasing knowledge regarding MPM genetics led to the definition of some molecular panels, including genes or miRNAs specifically deregulated in MPM, that are extremely valuable for differential diagnosis. Moreover, the development of classification algorithms is facilitating the application of molecular data for clinical practice. Data regarding new diagnostic tools and MPM signatures are absolutely promising; however, before their application in clinical practice, a prospective validation is necessary, as these approaches could surely improve the differential diagnosis between malignant and benign pleural lesions.

Twenty-four cases of imported zika virus infections diagnosed by molecular methods.

PubMed

Alejo-Cancho, Izaskun; Torner, Nuria; Oliveira, Inés; Martínez, Ana; Muñoz, José; Jane, Mireia; Gascón, Joaquim; Requena-Méndez, Ana; Vilella, Anna; Marcos, M Ángeles; Pinazo, María Jesús; Gonzalo, Verónica; Rodriguez, Natalia; Martínez, Miguel J

2016-10-01

Zika virus is an emerging flavivirus widely spreading through Latin America. Molecular diagnosis of the infection can be performed using serum, urine and saliva samples, although a well-defined diagnostic algorithm is not yet established. We describe a series of 24 cases of imported zika virus infection into Catalonia (northeastern Spain). Based on our findings, testing of paired serum and urine samples is recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel algorithm for simplification of complex gene classifiers in cancer

PubMed Central

Wilson, Raphael A.; Teng, Ling; Bachmeyer, Karen M.; Bissonnette, Mei Lin Z.; Husain, Aliya N.; Parham, David M.; Triche, Timothy J.; Wing, Michele R.; Gastier-Foster, Julie M.; Barr, Frederic G.; Hawkins, Douglas S.; Anderson, James R.; Skapek, Stephen X.; Volchenboum, Samuel L.

2013-01-01

The clinical application of complex molecular classifiers as diagnostic or prognostic tools has been limited by the time and cost needed to apply them to patients. Using an existing fifty-gene expression signature known to separate two molecular subtypes of the pediatric cancer rhabdomyosarcoma, we show that an exhaustive iterative search algorithm can distill this complex classifier down to two or three features with equal discrimination. We validated the two-gene signatures using three separate and distinct data sets, including one that uses degraded RNA extracted from formalin-fixed, paraffin-embedded material. Finally, to demonstrate the generalizability of our algorithm, we applied it to a lung cancer data set to find minimal gene signatures that can distinguish survival. Our approach can easily be generalized and coupled to existing technical platforms to facilitate the discovery of simplified signatures that are ready for routine clinical use. PMID:23913937

Engineering integrated digital circuits with allosteric ribozymes for scaling up molecular computation and diagnostics.

PubMed

Penchovsky, Robert

2012-10-19

Here we describe molecular implementations of integrated digital circuits, including a three-input AND logic gate, a two-input multiplexer, and 1-to-2 decoder using allosteric ribozymes. Furthermore, we demonstrate a multiplexer-decoder circuit. The ribozymes are designed to seek-and-destroy specific RNAs with a certain length by a fully computerized procedure. The algorithm can accurately predict one base substitution that alters the ribozyme's logic function. The ability to sense the length of RNA molecules enables single ribozymes to be used as platforms for multiple interactions. These ribozymes can work as integrated circuits with the functionality of up to five logic gates. The ribozyme design is universal since the allosteric and substrate domains can be altered to sense different RNAs. In addition, the ribozymes can specifically cleave RNA molecules with triplet-repeat expansions observed in genetic disorders such as oculopharyngeal muscular dystrophy. Therefore, the designer ribozymes can be employed for scaling up computing and diagnostic networks in the fields of molecular computing and diagnostics and RNA synthetic biology.

[Molecular pathology of pulmonary carcinomas].

PubMed

Rohan, Zdeněk; Matějčková, Milada; Matěj, Radoslav

2014-04-01

The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular has led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Therefore, pathologists closely involved in the diagnostics of lung tumors significantly contribute to the diagnostic-therapeutical algorithm. Analysis of EGFR gene mutations in lung adenocarcinomas is already routinely performed and the presence of activating mutations in EGFR is the main indication for the administration of tyrosinkinase inhibitors. Besides EGFR mutations, EML4-ALK rearrangement is also being analysed and there is potential in analysing BRAF mutations as well. The aim of this review is to summarize the role of the most relevant molecules that also serve as the therapeutic target for practicing pathologists.

Application of a molecular diagnostic algorithm for haemophilia A and B using next-generation sequencing of entire F8, F9 and VWF genes.

PubMed

Bastida, Jose Maria; González-Porras, Jose Ramon; Jiménez, Cristina; Benito, Rocio; Ordoñez, Gonzalo R; Álvarez-Román, Maria Teresa; Fontecha, M Elena; Janusz, Kamila; Castillo, David; Fisac, Rosa María; García-Frade, Luis Javier; Aguilar, Carlos; Martínez, María Paz; Bermejo, Nuria; Herrero, Sonia; Balanzategui, Ana; Martin-Antorán, Jose Manuel; Ramos, Rafael; Cebeiro, Maria Jose; Pardal, Emilia; Aguilera, Carmen; Pérez-Gutierrez, Belen; Prieto, Manuel; Riesco, Susana; Mendoza, Maria Carmen; Benito, Ana; Hortal Benito-Sendin, Ana; Jiménez-Yuste, Víctor; Hernández-Rivas, Jesus Maria; García-Sanz, Ramon; González-Díaz, Marcos; Sarasquete, Maria Eugenia

2017-01-05

Currently, molecular diagnosis of haemophilia A and B (HA and HB) highlights the excess risk-inhibitor development associated with specific mutations, and enables carrier testing of female relatives and prenatal or preimplantation genetic diagnosis. Molecular testing for HA also helps distinguish it from von Willebrand disease (VWD). Next-generation sequencing (NGS) allows simultaneous investigation of several complete genes, even though they may span very extensive regions. This study aimed to evaluate the usefulness of a molecular algorithm employing an NGS approach for sequencing the complete F8, F9 and VWF genes. The proposed algorithm includes the detection of inversions of introns 1 and 22, an NGS custom panel (the entire F8, F9 and VWF genes), and multiplex ligation-dependent probe amplification (MLPA) analysis. A total of 102 samples (97 FVIII- and FIX-deficient patients, and five female carriers) were studied. IVS-22 screening identified 11 out of 20 severe HA patients and one female carrier. IVS-1 analysis did not reveal any alterations. The NGS approach gave positive results in 88 cases, allowing the differential diagnosis of mild/moderate HA and VWD in eight cases. MLPA confirmed one large exon deletion. Only one case did have no pathogenic variants. The proposed algorithm had an overall success rate of 99 %. In conclusion, our evaluation demonstrates that this algorithm can reliably identify pathogenic variants and diagnose patients with HA, HB or VWD.

Operational modelling: the mechanisms influencing TB diagnostic yield in an Xpert® MTB/RIF-based algorithm.

PubMed

Dunbar, R; Naidoo, P; Beyers, N; Langley, I

2017-04-01

Cape Town, South Africa. To compare the diagnostic yield for smear/culture and Xpert® MTB/RIF algorithms and to investigate the mechanisms influencing tuberculosis (TB) yield. We developed and validated an operational model of the TB diagnostic process, first with the smear/culture algorithm and then with the Xpert algorithm. We modelled scenarios by varying TB prevalence, adherence to diagnostic algorithms and human immunodeficiency virus (HIV) status. This enabled direct comparisons of diagnostic yield in the two algorithms to be made. Routine data showed that diagnostic yield had decreased over the period of the Xpert algorithm roll-out compared to the yield when the smear/culture algorithm was in place. However, modelling yield under identical conditions indicated a 13.3% increase in diagnostic yield from the Xpert algorithm compared to smear/culture. The model demonstrated that the extensive use of culture in the smear/culture algorithm and the decline in TB prevalence are the main factors contributing to not finding an increase in diagnostic yield in the routine data. We demonstrate the benefits of an operational model to determine the effect of scale-up of a new diagnostic algorithm, and recommend that policy makers use operational modelling to make appropriate decisions before new diagnostic algorithms are scaled up.

Molecular spectral imaging system for quantitative immunohistochemical analysis of early diabetic retinopathy.

PubMed

Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng

2009-12-01

A molecular spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring molecular spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some molecular spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from molecular spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of molecular spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.

Molecular diagnosis of α-thalassemia in a multiethnic population.

PubMed

Gilad, Oded; Shemer, Orna Steinberg; Dgany, Orly; Krasnov, Tanya; Nevo, Michal; Noy-Lotan, Sharon; Rabinowicz, Ron; Amitai, Nofar; Ben-Dor, Shifra; Yaniv, Isaac; Yacobovich, Joanne; Tamary, Hannah

2017-06-01

α-Thalassemia, one of the most common genetic diseases, is caused by deletions or point mutations affecting one to four α-globin genes. Molecular diagnosis is important to prevent the most severe forms of the disease. However, the diagnosis of α-thalassemia is complex due to a high variability of the genetic defects involved, with over 250 described mutations. We summarize herein the findings of genetic analyses of DNA samples referred to our laboratory for the molecular diagnosis of α-thalassemia, along with a detailed clinical description. We utilized a diagnostic algorithm including Gap-PCR, to detect known deletions, followed by sequencing of the α-globin gene, to identify known and novel point mutations, and multiplex ligation-dependent probe amplification (MLPA) for the diagnosis of rare or novel deletions. α-Thalassemia was diagnosed in 662 of 975 samples referred to our laboratory. Most commonly found were deletions (75.3%, including two novel deletions previously described by us); point mutations comprised 25.4% of the cases, including five novel mutations. Our population included mostly Jews (of Ashkenazi and Sephardic origin) and Muslim Arabs, who presented with a higher rate of point mutations and hemoglobin H disease. Overall, we detected 53 different genotype combinations causing a spectrum of clinical phenotypes, from asymptomatic to severe anemia. Our work constitutes the largest group of patients with α-thalassemia originating in the Mediterranean whose clinical characteristics and molecular basis have been determined. We suggest a diagnostic algorithm that leads to an accurate molecular diagnosis in multiethnic populations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

PubMed

Manegold, Christian

2014-09-01

The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources. Copyright © 2014. Published by Elsevier Urban & Partner Sp. z o.o.

Poor concordance among nine immunohistochemistry classifiers of cell-of-origin for Diffuse Large B-cell Lymphoma: implications for therapeutic strategies

PubMed Central

Coutinho, Rita; Clear, Andrew James; Owen, Andrew; Wilson, Andrew; Matthews, Janet; Lee, Abigail; Alvarez, Rute; da Silva, Maria Gomes; Cabeçadas, José; Calaminici, Maria; Gribben, John G.

2014-01-01

Purpose The opportunity to improve therapeutic choices on the basis of molecular features of the tumour cells is on the horizon in Diffuse Large B-cell Lymphoma (DLBCL). Agents such as bortezomib exhibit selective activity against the poor outcome activated B-cell type DLBCL. In order for targeted therapies to succeed in this disease, robust strategies that segregate patients into molecular groups with high reliability are needed. While molecular studies are considered gold standard, several immunohistochemistry (IHC) algorithms have been published that claim to be able to stratify patients according to their cell-of-origin and to be relevant for patient outcome. However results are poorly reproducible by independent groups. Experimental design We investigated nine IHC algorithms for molecular classification in a dataset of DLBCL diagnostic biopsies, incorporating immunostaining for CD10, BCL6, BCL2, MUM1, FOXP1, GCET1 and LMO2. IHC profiles were assessed and agreed among three expert observers. A consensus matrix based on all scoring combinations and the number of subjects for each combination allowed to assess reliability. The survival impact of individual markers and classifiers was evaluated using Kaplan-Meier curves and the log-rank test. Results The concordance in patient’s classification across the different algorithms was low. Only 4% the tumors have been classified as GCB and 21% as ABC/non-GCB by all methods. None of the algorithms provided prognostic information in the R-CHOP treated cohort. Conclusion Further work is required to standardize IHC algorithms for DLBCL cell-of-origin classification for these to be considered reliable alternatives to molecular-based methods to be used for clinical decisions. PMID:24122791

Poor concordance among nine immunohistochemistry classifiers of cell-of-origin for diffuse large B-cell lymphoma: implications for therapeutic strategies.

PubMed

Coutinho, Rita; Clear, Andrew James; Owen, Andrew; Wilson, Andrew; Matthews, Janet; Lee, Abigail; Alvarez, Rute; Gomes da Silva, Maria; Cabeçadas, José; Calaminici, Maria; Gribben, John G

2013-12-15

The opportunity to improve therapeutic choices on the basis of molecular features of the tumor cells is on the horizon in diffuse large B-cell lymphoma (DLBCL). Agents such as bortezomib exhibit selective activity against the poor outcome activated B-cell type (ABC) DLBCL. In order for targeted therapies to succeed in this disease, robust strategies that segregate patients into molecular groups with high reliability are needed. Although molecular studies are considered gold standard, several immunohistochemistry (IHC) algorithms have been published that claim to be able to stratify patients according to their cell-of-origin and to be relevant for patient outcome. However, results are poorly reproducible by independent groups. We investigated nine IHC algorithms for molecular classification in a dataset of DLBCL diagnostic biopsies, incorporating immunostaining for CD10, BCL6, BCL2, MUM1, FOXP1, GCET1, and LMO2. IHC profiles were assessed and agreed among three expert observers. A consensus matrix based on all scoring combinations and the number of subjects for each combination allowed us to assess reliability. The survival impact of individual markers and classifiers was evaluated using Kaplan-Meier curves and the log-rank test. The concordance in patient's classification across the different algorithms was low. Only 4% of the tumors have been classified as germinal center B-cell type (GCB) and 21% as ABC/non-GCB by all methods. None of the algorithms provided prognostic information in the R-CHOP (rituximab plus cyclophosphamide-adriamycin-vincristine-prednisone)-treated cohort. Further work is required to standardize IHC algorithms for DLBCL cell-of-origin classification for these to be considered reliable alternatives to molecular-based methods to be used for clinical decisions. ©2013 AACR.

Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

2017-02-01

Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

Current status and future perspectives on molecular and serological methods in diagnostic mycology.

PubMed

Lau, Anna; Chen, Sharon; Sleiman, Sue; Sorrell, Tania

2009-11-01

Invasive fungal infections are an important cause of infectious morbidity. Nonculture-based methods are increasingly used for rapid, accurate diagnosis to improve patient outcomes. New and existing DNA amplification platforms have high sensitivity and specificity for direct detection and identification of fungi in clinical specimens. Since laboratories are increasingly reliant on DNA sequencing for fungal identification, measures to improve sequence interpretation should support validation of reference isolates and quality control in public gene repositories. Novel technologies (e.g., isothermal and PNA FISH methods), platforms enabling high-throughput analyses (e.g., DNA microarrays and Luminex xMAP) and/or commercial PCR assays warrant further evaluation for routine diagnostic use. Notwithstanding the advantages of molecular tests, serological assays remain clinically useful for patient management. The serum Aspergillus galactomannan test has been incorporated into diagnostic algorithms of invasive aspergillosis. Both the galactomannan and the serum beta-D-glucan test have value for diagnosing infection and monitoring therapeutic response.

Multiplex PCR Tests for Detection of Pathogens Associated with Gastroenteritis

PubMed Central

Zhang, Hongwei; Morrison, Scott; Tang, Yi-Wei

2016-01-01

Synopsis A wide range of enteric pathogens can cause infectious gastroenteritis. Conventional diagnostic algorithms including culture, biochemical identification, immunoassay and microscopic examination are time consuming and often lack sensitivity and specificity. Advances in molecular technology have as allowed its use as clinical diagnostic tools. Multiplex PCR based testing has made its way to gastroenterology diagnostic arena in recent years. In this article we present a review of recent laboratory developed multiplex PCR tests and current commercial multiplex gastrointestinal pathogen tests. We will focus on two FDA cleared commercial syndromic multiplex tests: Luminex xTAG GPP and Biofire FimArray GI test. These multiplex tests can detect and identify multiple enteric pathogens in one test and provide results within hours. Multiplex PCR tests have shown superior sensitivity to conventional methods for detection of most pathogens. The high negative predictive value of these multiplex tests has led to the suggestion that they be used as screening tools especially in outbreaks. Although the clinical utility and benefit of multiplex PCR test are to be further investigated, implementing these multiplex PCR tests in gastroenterology diagnostic algorithm has the potential to improve diagnosis of infectious gastroenteritis. PMID:26004652

Next-generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity.

PubMed

Catenacci, Daniel V T

2015-05-01

The promise of 'personalized cancer care' with therapies toward specific molecular aberrations has potential to improve outcomes. However, there is recognized heterogeneity within any given tumor-type from patient to patient (inter-patient heterogeneity), and within an individual (intra-patient heterogeneity) as demonstrated by molecular evolution through space (primary tumor to metastasis) and time (after therapy). These issues have become hurdles to advancing cancer treatment outcomes with novel molecularly targeted agents. Classic trial design paradigms are challenged by heterogeneity, as they are unable to test targeted therapeutics against low frequency genomic 'oncogenic driver' aberrations with adequate power. Usual accrual difficulties to clinical trials are exacerbated by low frequencies of any given molecular driver. To address these challenges, there is need for innovative clinical trial designs and strategies implementing novel diagnostic biomarker technologies to account for inter-patient molecular diversity and scarce tissue for analysis. Importantly, there is also need for pre-defined treatment priority algorithms given numerous aberrations commonly observed within any one individual sample. Access to multiple available therapeutic agents simultaneously is crucial. Finally intra-patient heterogeneity through time may be addressed by serial biomarker assessment at the time of tumor progression. This report discusses various 'next-generation' biomarker-driven trial designs and their potentials and limitations to tackle these recognized molecular heterogeneity challenges. Regulatory hurdles, with respect to drug and companion diagnostic development and approval, are considered. Focus is on the 'Expansion Platform Design Types I and II', the latter demonstrated with a first example, 'PANGEA: Personalized Anti-Neoplastics for Gastro-Esophageal Adenocarcinoma'. Applying integral medium-throughput genomic and proteomic assays along with a practical biomarker assessment and treatment algorithm, 'PANGEA' attempts to address the problem of heterogeneity towards successful implementation of molecularly targeted therapies. Copyright © 2014 The Author. Published by Elsevier B.V. All rights reserved.

Laboratory Diagnosis of Infective Endocarditis

PubMed Central

Liesman, Rachael M.; Pritt, Bobbi S.; Maleszewski, Joseph J.

2017-01-01

ABSTRACT Infective endocarditis is life-threatening; identification of the underlying etiology informs optimized individual patient management. Changing epidemiology, advances in blood culture techniques, and new diagnostics guide the application of laboratory testing for diagnosis of endocarditis. Blood cultures remain the standard test for microbial diagnosis, with directed serological testing (i.e., Q fever serology, Bartonella serology) in culture-negative cases. Histopathology and molecular diagnostics (e.g., 16S rRNA gene PCR/sequencing, Tropheryma whipplei PCR) may be applied to resected valves to aid in diagnosis. Herein, we summarize recent knowledge in this area and propose a microbiologic and pathological algorithm for endocarditis diagnosis. PMID:28659319

Narrowing of the Diagnostic Gap of Acute Gastroenteritis in Children 0-6 Years of Age Using a Combination of Classical and Molecular Techniques, Delivers Challenges in Syndromic Approach Diagnostics.

PubMed

Steyer, Andrej; Jevšnik, Monika; Petrovec, Miroslav; Pokorn, Marko; Grosek, Štefan; Fratnik Steyer, Adela; Šoba, Barbara; Uršič, Tina; Cerar Kišek, Tjaša; Kolenc, Marko; Trkov, Marija; Šparl, Petra; Duraisamy, Raja; Lipkin, W Ian; Terzić, Sara; Kolnik, Mojca; Mrvič, Tatjana; Kapoor, Amit; Strle, Franc

2016-09-01

Twenty-five percent to 50% of acute gastroenteritis (AGE) cases remain etiologically undiagnosed. Our main aim was to determine the most appropriate list of enteric pathogens to be included in the daily diagnostics scheme of AGE, ensuring the lowest possible diagnostic gap. Two hundred ninety seven children ≤6 years of age, admitted to hospital in Slovenia, October 2011 to October 2012, with AGE, and 88 ≤6 years old healthy children were included in the study. A broad spectrum of enteric pathogens was targeted with molecular methods, including 8 viruses, 6 bacteria and 2 parasites. At least one enteric pathogen was detected in 91.2% of cases with AGE and 27.3% of controls. Viruses were the most prevalent (82.5% and 15.9%), followed by bacteria (27.3% and 10.2%) and parasites (3.0% and 1.1%) in cases and controls, respectively. A high proportion (41.8%) of mixed infections was observed in the cases. For cases with undetermined etiology (8.8%), stool samples were analyzed with next generation sequencing, and a potential viral pathogen was detected in 17 additional samples (5.8%). Our study suggests that tests for rotaviruses, noroviruses genogroup II, adenoviruses 40/41, astroviruses, Campylobacter spp. and Salmonella sp. should be included in the initial diagnostic algorithm, which revealed the etiology in 83.5% of children tested. The use of molecular methods in diagnostics of gastroenteritis is preferable because of their high sensitivity, specificity, fast performance and the possibility of establishing the concentration of the target. The latter may be valuable for assessing the clinical significance of the detected enteric, particularly viral pathogens.

Diffuse Gliomas for Nonneuropathologists: The New Integrated Molecular Diagnostics.

PubMed

Lee, Sunhee C

2018-05-18

Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified. Incorporating information on a few genetic parameters (IDH, ATRX and/or p53, and chromosome 1p19q codeletion), a relatively straightforward diagnostic algorithm has been generated with robust and reproducible results that correlate with patients' survival far better than relying on conventional histology alone. Evidence also supports the conclusion that the vast majority of diffuse gliomas without IDH mutations (IDH-wild-type astrocytomas) behave like IDH-wild-type glioblastomas ("molecular GBM"). Together, these changes reflect a big shift in the practice of diagnostic neuropathology in which tumor risk stratification aligns better with molecular information than histology/grading. The purpose of this review is to provide the readers with a brief synopsis of the changes in the 2016 World Health Organization update with an emphasis on diffuse gliomas and to summarize key gene abnormalities on which these classifications are based. Practical points involved in day-to-day diagnostic workup are also discussed, along with a comparison of the various diagnostic tests, including immunohistochemistry, with an emphasis on targeted next-generation sequencing panel technology as a future universal approach.

Iron deficiency anemia: diagnosis and management.

PubMed

Clark, Susan F

2009-03-01

Iron deficiency anemia (IDA) still remains universally problematic worldwide. The primary focus of this review is to critique articles published over the past 18 months that describe strategies for the diagnosis and management of this prevalent condition. The medical community continues to lack consensus when identifying the optimal approach for the diagnosis and management of IDA. Current diagnostic recommendations revolve around the validity and practicality of current biomarkers such as soluble transferrin-receptor concentrations and others, and cause-based diagnostics that potentially include endoscopy. Management of IDA is based on supplementation combined with effective etiological treatment. Advances in oral and parenteral low-molecular-weight iron preparations has expanded and improved treatment modalities for IDA. Since the introduction of low versus high-molecular-weight intravenous iron administration, there have been fewer serious adverse events associated with parenteral iron preparations. Best practice guidelines for diagnosing and managing IDA should include the design of an algorithm that is inclusive of multiple biomarkers and cause-based diagnostics, which will provide direction in managing IDA, and distinguish between IDA from the anemia of chronic disease.

Diagnostic pitfalls in newborns and babies with blisters and erosions.

PubMed

Nischler, Elke; Klausegger, Alfred; Hüttner, Clemens; Pohla-Gubo, Gabriele; Diem, Anja; Bauer, Johann W; Hintner, Helmut

2009-01-01

Establishing the correct diagnosis in newborns presenting with blisters and erosions is not always a straightforward process. Many different disease entities including acquired (i.e., infectious, immunobullous, traumatic) and inherited disorders have to be taken into consideration. Similarities in clinical appearance, colonization and/or superinfections of preexisting skin lesions, as well as the absence of late changes in the neonate often pose significant diagnostic challenges. In this paper we discuss by giving examples the process of making an accurate diagnosis of blistering skin diseases in the neonatal period on the basis of a diagnostic algorithm. In addition, we provide an overview of the rational use and the limitations of laboratory procedures such as microbial testing, routine light microscopy, immunofluorescence antigen mapping, transmission electron microscopy, and molecular genetic analysis.

Molecular genetics and genomics progress in urothelial bladder cancer.

PubMed

Netto, George J

2013-11-01

The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers. © 2013 Published by Elsevier Inc.

Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma.

PubMed

McDonald, William C; Banerji, Nilanjana; McDonald, Kelsey N; Ho, Bridget; Macias, Virgilia; Kajdacsy-Balla, Andre

2017-01-01

-Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. -To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. -We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. -The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. -Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

The dilemma of diagnostic testing for Prader-Willi syndrome

PubMed Central

Hung, Dorothy

2017-01-01

Although Prader-Willi syndrome (PWS) is a well-described clinical dysmorphic syndrome, DNA testing is required for a definitive diagnosis. A definitive diagnosis can be made in approximately 99% of cases using DNA testing; there are a number of DNA tests that can be used for this purpose, although there is no set standard algorithm of testing. The dilemma arises because of the complex genetic mechanisms at the basis of PWS, which need to be elucidated. To establish the molecular mechanism with a complete work up, involves at least 2 tests. Here we discuss the commonly used tests currently available and suggest a cost—effective approach to diagnostic testing. PMID:28164030

Molecular Pathology of Patient Tumors, Patient-Derived Xenografts, and Cancer Cell Lines.

PubMed

Guo, Sheng; Qian, Wubin; Cai, Jie; Zhang, Likun; Wery, Jean-Pierre; Li, Qi-Xiang

2016-08-15

The Cancer Genome Atlas (TCGA) project has generated abundant genomic data for human cancers of various histopathology types and enabled exploring cancer molecular pathology per big data approach. We developed a new algorithm based on most differentially expressed genes (DEG) per pairwise comparisons to calculate correlation coefficients to be used to quantify similarity within and between cancer types. We systematically compared TCGA cancers, demonstrating high correlation within types and low correlation between types, thus establishing molecular specificity of cancer types and an alternative diagnostic method largely equivalent to histopathology. Different coefficients for different cancers in study may reveal that the degree of the within-type homogeneity varies by cancer types. We also performed the same calculation using the TCGA-derived DEGs on patient-derived xenografts (PDX) of different histopathology types corresponding to the TCGA types, as well as on cancer cell lines. We, for the first time, demonstrated highly similar patterns for within- and between-type correlation between PDXs and patient samples in a systematic study, confirming the high relevance of PDXs as surrogate experimental models for human diseases. In contrast, cancer cell lines have drastically reduced expression similarity to both PDXs and patient samples. The studies also revealed high similarity between some types, for example, LUSC and HNSCC, but low similarity between certain subtypes, for example, LUAD and LUSC. Our newly developed algorithm seems to be a practical diagnostic method to classify and reclassify a disease, either human or xenograft, with better accuracy than traditional histopathology. Cancer Res; 76(16); 4619-26. ©2016 AACR. ©2016 American Association for Cancer Research.

Integration of On-Line and Off-Line Diagnostic Algorithms for Aircraft Engine Health Management

NASA Technical Reports Server (NTRS)

Kobayashi, Takahisa; Simon, Donald L.

2007-01-01

This paper investigates the integration of on-line and off-line diagnostic algorithms for aircraft gas turbine engines. The on-line diagnostic algorithm is designed for in-flight fault detection. It continuously monitors engine outputs for anomalous signatures induced by faults. The off-line diagnostic algorithm is designed to track engine health degradation over the lifetime of an engine. It estimates engine health degradation periodically over the course of the engine s life. The estimate generated by the off-line algorithm is used to update the on-line algorithm. Through this integration, the on-line algorithm becomes aware of engine health degradation, and its effectiveness to detect faults can be maintained while the engine continues to degrade. The benefit of this integration is investigated in a simulation environment using a nonlinear engine model.

[Relevance of big data for molecular diagnostics].

PubMed

Bonin-Andresen, M; Smiljanovic, B; Stuhlmüller, B; Sörensen, T; Grützkau, A; Häupl, T

2018-04-01

Big data analysis raises the expectation that computerized algorithms may extract new knowledge from otherwise unmanageable vast data sets. What are the algorithms behind the big data discussion? In principle, high throughput technologies in molecular research already introduced big data and the development and application of analysis tools into the field of rheumatology some 15 years ago. This includes especially omics technologies, such as genomics, transcriptomics and cytomics. Some basic methods of data analysis are provided along with the technology, however, functional analysis and interpretation requires adaptation of existing or development of new software tools. For these steps, structuring and evaluating according to the biological context is extremely important and not only a mathematical problem. This aspect has to be considered much more for molecular big data than for those analyzed in health economy or epidemiology. Molecular data are structured in a first order determined by the applied technology and present quantitative characteristics that follow the principles of their biological nature. These biological dependencies have to be integrated into software solutions, which may require networks of molecular big data of the same or even different technologies in order to achieve cross-technology confirmation. More and more extensive recording of molecular processes also in individual patients are generating personal big data and require new strategies for management in order to develop data-driven individualized interpretation concepts. With this perspective in mind, translation of information derived from molecular big data will also require new specifications for education and professional competence.

Diagnostic Algorithm Benchmarking

NASA Technical Reports Server (NTRS)

Poll, Scott

2011-01-01

A poster for the NASA Aviation Safety Program Annual Technical Meeting. It describes empirical benchmarking on diagnostic algorithms using data from the ADAPT Electrical Power System testbed and a diagnostic software framework.

Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia.

PubMed

Ahmad, Riris Andono; Matthys, Francine; Dwihardiani, Bintari; Rintiswati, Ning; de Vlas, Sake J; Mahendradhata, Yodi; van der Stuyft, Patrick

2012-02-15

Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.

Toward real-time quantification of fluorescence molecular probes using target/background ratio for guiding biopsy and endoscopic therapy of esophageal neoplasia.

PubMed

Jiang, Yang; Gong, Yuanzheng; Rubenstein, Joel H; Wang, Thomas D; Seibel, Eric J

2017-04-01

Multimodal endoscopy using fluorescence molecular probes is a promising method of surveying the entire esophagus to detect cancer progression. Using the fluorescence ratio of a target compared to a surrounding background, a quantitative value is diagnostic for progression from Barrett's esophagus to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). However, current quantification of fluorescent images is done only after the endoscopic procedure. We developed a Chan-Vese-based algorithm to segment fluorescence targets, and subsequent morphological operations to generate background, thus calculating target/background (T/B) ratios, potentially to provide real-time guidance for biopsy and endoscopic therapy. With an initial processing speed of 2 fps and by calculating the T/B ratio for each frame, our method provides quasireal-time quantification of the molecular probe labeling to the endoscopist. Furthermore, an automatic computer-aided diagnosis algorithm can be applied to the recorded endoscopic video, and the overall T/B ratio is calculated for each patient. The receiver operating characteristic curve was employed to determine the threshold for classification of HGD/EAC using leave-one-out cross-validation. With 92% sensitivity and 75% specificity to classify HGD/EAC, our automatic algorithm shows promising results for a surveillance procedure to help manage esophageal cancer and other cancers inspected by endoscopy.

Benchmarking Diagnostic Algorithms on an Electrical Power System Testbed

NASA Technical Reports Server (NTRS)

Kurtoglu, Tolga; Narasimhan, Sriram; Poll, Scott; Garcia, David; Wright, Stephanie

2009-01-01

Diagnostic algorithms (DAs) are key to enabling automated health management. These algorithms are designed to detect and isolate anomalies of either a component or the whole system based on observations received from sensors. In recent years a wide range of algorithms, both model-based and data-driven, have been developed to increase autonomy and improve system reliability and affordability. However, the lack of support to perform systematic benchmarking of these algorithms continues to create barriers for effective development and deployment of diagnostic technologies. In this paper, we present our efforts to benchmark a set of DAs on a common platform using a framework that was developed to evaluate and compare various performance metrics for diagnostic technologies. The diagnosed system is an electrical power system, namely the Advanced Diagnostics and Prognostics Testbed (ADAPT) developed and located at the NASA Ames Research Center. The paper presents the fundamentals of the benchmarking framework, the ADAPT system, description of faults and data sets, the metrics used for evaluation, and an in-depth analysis of benchmarking results obtained from testing ten diagnostic algorithms on the ADAPT electrical power system testbed.

Lung tumor diagnosis and subtype discovery by gene expression profiling.

PubMed

Wang, Lu-yong; Tu, Zhuowen

2006-01-01

The optimal treatment of patients with complex diseases, such as cancers, depends on the accurate diagnosis by using a combination of clinical and histopathological data. In many scenarios, it becomes tremendously difficult because of the limitations in clinical presentation and histopathology. To accurate diagnose complex diseases, the molecular classification based on gene or protein expression profiles are indispensable for modern medicine. Moreover, many heterogeneous diseases consist of various potential subtypes in molecular basis and differ remarkably in their response to therapies. It is critical to accurate predict subgroup on disease gene expression profiles. More fundamental knowledge of the molecular basis and classification of disease could aid in the prediction of patient outcome, the informed selection of therapies, and identification of novel molecular targets for therapy. In this paper, we propose a new disease diagnostic method, probabilistic boosting tree (PB tree) method, on gene expression profiles of lung tumors. It enables accurate disease classification and subtype discovery in disease. It automatically constructs a tree in which each node combines a number of weak classifiers into a strong classifier. Also, subtype discovery is naturally embedded in the learning process. Our algorithm achieves excellent diagnostic performance, and meanwhile it is capable of detecting the disease subtype based on gene expression profile.

Molecular Tools for Diagnosis of Visceral Leishmaniasis: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

PubMed Central

de Ruiter, C. M.; van der Veer, C.; Leeflang, M. M. G.; Deborggraeve, S.; Lucas, C.

2014-01-01

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. PMID:24829226

The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores

ERIC Educational Resources Information Center

Hus, Vanessa; Lord, Catherine

2014-01-01

The recently published Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) includes revised diagnostic algorithms and standardized severity scores for modules used to assess younger children. A revised algorithm and severity scores are not yet available for Module 4, used with verbally fluent adults. The current study revises the Module 4…

Improved Diagnostic Validity of the ADOS Revised Algorithms: A Replication Study in an Independent Sample

ERIC Educational Resources Information Center

Oosterling, Iris; Roos, Sascha; de Bildt, Annelies; Rommelse, Nanda; de Jonge, Maretha; Visser, Janne; Lappenschaar, Martijn; Swinkels, Sophie; van der Gaag, Rutger Jan; Buitelaar, Jan

2010-01-01

Recently, Gotham et al. ("2007") proposed revised algorithms for the Autism Diagnostic Observation Schedule (ADOS) with improved diagnostic validity. The aim of the current study was to replicate predictive validity, factor structure, and correlations with age and verbal and nonverbal IQ of the ADOS revised algorithms for Modules 1 and 2…

Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia

PubMed Central

2012-01-01

Background Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. Methods We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. Results Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. Conclusions The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care. PMID:22333111

Systematic Benchmarking of Diagnostic Technologies for an Electrical Power System

NASA Technical Reports Server (NTRS)

Kurtoglu, Tolga; Jensen, David; Poll, Scott

2009-01-01

Automated health management is a critical functionality for complex aerospace systems. A wide variety of diagnostic algorithms have been developed to address this technical challenge. Unfortunately, the lack of support to perform large-scale V&V (verification and validation) of diagnostic technologies continues to create barriers to effective development and deployment of such algorithms for aerospace vehicles. In this paper, we describe a formal framework developed for benchmarking of diagnostic technologies. The diagnosed system is the Advanced Diagnostics and Prognostics Testbed (ADAPT), a real-world electrical power system (EPS), developed and maintained at the NASA Ames Research Center. The benchmarking approach provides a systematic, empirical basis to the testing of diagnostic software and is used to provide performance assessment for different diagnostic algorithms.

Addressing Loss of Efficiency Due to Misclassification Error in Enriched Clinical Trials for the Evaluation of Targeted Therapies Based on the Cox Proportional Hazards Model.

PubMed

Tsai, Chen-An; Lee, Kuan-Ting; Liu, Jen-Pei

2016-01-01

A key feature of precision medicine is that it takes individual variability at the genetic or molecular level into account in determining the best treatment for patients diagnosed with diseases detected by recently developed novel biotechnologies. The enrichment design is an efficient design that enrolls only the patients testing positive for specific molecular targets and randomly assigns them for the targeted treatment or the concurrent control. However there is no diagnostic device with perfect accuracy and precision for detecting molecular targets. In particular, the positive predictive value (PPV) can be quite low for rare diseases with low prevalence. Under the enrichment design, some patients testing positive for specific molecular targets may not have the molecular targets. The efficacy of the targeted therapy may be underestimated in the patients that actually do have the molecular targets. To address the loss of efficiency due to misclassification error, we apply the discrete mixture modeling for time-to-event data proposed by Eng and Hanlon [8] to develop an inferential procedure, based on the Cox proportional hazard model, for treatment effects of the targeted treatment effect for the true-positive patients with the molecular targets. Our proposed procedure incorporates both inaccuracy of diagnostic devices and uncertainty of estimated accuracy measures. We employed the expectation-maximization algorithm in conjunction with the bootstrap technique for estimation of the hazard ratio and its estimated variance. We report the results of simulation studies which empirically investigated the performance of the proposed method. Our proposed method is illustrated by a numerical example.

A Hybrid Neural Network-Genetic Algorithm Technique for Aircraft Engine Performance Diagnostics

NASA Technical Reports Server (NTRS)

Kobayashi, Takahisa; Simon, Donald L.

2001-01-01

In this paper, a model-based diagnostic method, which utilizes Neural Networks and Genetic Algorithms, is investigated. Neural networks are applied to estimate the engine internal health, and Genetic Algorithms are applied for sensor bias detection and estimation. This hybrid approach takes advantage of the nonlinear estimation capability provided by neural networks while improving the robustness to measurement uncertainty through the application of Genetic Algorithms. The hybrid diagnostic technique also has the ability to rank multiple potential solutions for a given set of anomalous sensor measurements in order to reduce false alarms and missed detections. The performance of the hybrid diagnostic technique is evaluated through some case studies derived from a turbofan engine simulation. The results show this approach is promising for reliable diagnostics of aircraft engines.

[Molecular-Genetic Diagnosis and Molecular-Targeted Therapy in Cancer: Challenges in the Era of Precision Medicine].

PubMed

Miyachi, Hayato

2015-10-01

Elucidation of the molecular pathogenesis of neoplasms and application of emerging technologies for testing and therapy have resulted in a series of paradigm shifts in patient care, from conventional to personalized medicine. This has been promoted by companion diagnostics and molecular targeted therapy, tailoring the treatment to the individual characteristics of each patient. Precision oncology has been accelerated by integrating the enhanced resolution of molecular analysis, mechanism clarity, and therapeutic relevance through genomic knowledge. In its clinical implementation, there are laboratory challenges concerning accurate measurement using stored samples, differentiation between driver and passenger mutations as well as between germline and somatic mutations, bioinformatics availability, practical decision-making algorithms, and ethical issues regarding incidental findings. The medical laboratory has a new role in providing not only testing services but also an instructive approach to users to ensure the sample quality and privacy protection of personal genome information, supporting the quality of patient practice based on laboratory diagnosis.

The Added Value of the Combined Use of the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule: Diagnostic Validity in a Clinical Swedish Sample of Toddlers and Young Preschoolers

ERIC Educational Resources Information Center

Zander, Eric; Sturm, Harald; Bölte, Sven

2015-01-01

The diagnostic validity of the new research algorithms of the Autism Diagnostic Interview-Revised and the revised algorithms of the Autism Diagnostic Observation Schedule was examined in a clinical sample of children aged 18-47 months. Validity was determined for each instrument separately and their combination against a clinical consensus…

New Autism Diagnostic Interview-Revised Algorithms for Toddlers and Young Preschoolers from 12 to 47 Months of Age

ERIC Educational Resources Information Center

Kim, So Hyun; Lord, Catherine

2012-01-01

Autism Diagnostic Interview-Revised (Rutter et al. in "Autism diagnostic interview-revised." Western Psychological Services, Los Angeles, 2003) diagnostic algorithms specific to toddlers and young preschoolers were created using 829 assessments of children aged from 12 to 47 months with ASD, nonspectrum disorders, and typical development. The…

Usefulness of magnifying endoscopy with narrow-band imaging for diagnosis of depressed gastric lesions

PubMed Central

SUMIE, HIROAKI; SUMIE, SHUJI; NAKAHARA, KEITA; WATANABE, YASUTOMO; MATSUO, KEN; MUKASA, MICHITA; SAKAI, TAKESHI; YOSHIDA, HIKARU; TSURUTA, OSAMU; SATA, MICHIO

2014-01-01

The usefulness of magnifying endoscopy with narrow-band imaging (ME-NBI) for the diagnosis of early gastric cancer is well known, however, there are no evaluation criteria. The aim of this study was to devise and evaluate a novel diagnostic algorithm for ME-NBI in depressed early gastric cancer. Between August, 2007 and May, 2011, 90 patients with a total of 110 depressed gastric lesions were enrolled in the study. A diagnostic algorithm was devised based on ME-NBI microvascular findings: microvascular irregularity and abnormal microvascular patterns (fine network, corkscrew and unclassified patterns). The diagnostic efficiency of the algorithm for gastric cancer and histological grade was assessed by measuring its mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Furthermore, inter- and intra-observer variation were measured. In the differential diagnosis of gastric cancer from non-cancerous lesions, the mean sensitivity, specificity, PPV, NPV, and accuracy of the diagnostic algorithm were 86.7, 48.0, 94.4, 26.7, and 83.2%, respectively. Furthermore, in the differential diagnosis of undifferentiated adenocarcinoma from differentiated adenocarcinoma, the mean sensitivity, specificity, PPV, NPV, and accuracy of the diagnostic algorithm were 61.6, 86.3, 69.0, 84.8, and 79.1%, respectively. For the ME-NBI final diagnosis using this algorithm, the mean κ values for inter- and intra-observer agreement were 0.50 and 0.77, respectively. In conclusion, the diagnostic algorithm based on ME-NBI microvascular findings was convenient and had high diagnostic accuracy, reliability and reproducibility in the differential diagnosis of depressed gastric lesions. PMID:24649321

Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy.

PubMed

de Ruiter, C M; van der Veer, C; Leeflang, M M G; Deborggraeve, S; Lucas, C; Adams, E R

2014-09-01

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Computer-aided US diagnosis of breast lesions by using cell-based contour grouping.

PubMed

Cheng, Jie-Zhi; Chou, Yi-Hong; Huang, Chiun-Sheng; Chang, Yeun-Chung; Tiu, Chui-Mei; Chen, Kuei-Wu; Chen, Chung-Ming

2010-06-01

To develop a computer-aided diagnostic algorithm with automatic boundary delineation for differential diagnosis of benign and malignant breast lesions at ultrasonography (US) and investigate the effect of boundary quality on the performance of a computer-aided diagnostic algorithm. This was an institutional review board-approved retrospective study with waiver of informed consent. A cell-based contour grouping (CBCG) segmentation algorithm was used to delineate the lesion boundaries automatically. Seven morphologic features were extracted. The classifier was a logistic regression function. Five hundred twenty breast US scans were obtained from 520 subjects (age range, 15-89 years), including 275 benign (mean size, 15 mm; range, 5-35 mm) and 245 malignant (mean size, 18 mm; range, 8-29 mm) lesions. The newly developed computer-aided diagnostic algorithm was evaluated on the basis of boundary quality and differentiation performance. The segmentation algorithms and features in two conventional computer-aided diagnostic algorithms were used for comparative study. The CBCG-generated boundaries were shown to be comparable with the manually delineated boundaries. The area under the receiver operating characteristic curve (AUC) and differentiation accuracy were 0.968 +/- 0.010 and 93.1% +/- 0.7, respectively, for all 520 breast lesions. At the 5% significance level, the newly developed algorithm was shown to be superior to the use of the boundaries and features of the two conventional computer-aided diagnostic algorithms in terms of AUC (0.974 +/- 0.007 versus 0.890 +/- 0.008 and 0.788 +/- 0.024, respectively). The newly developed computer-aided diagnostic algorithm that used a CBCG segmentation method to measure boundaries achieved a high differentiation performance. Copyright RSNA, 2010

Molecular Risk Factors for Schizophrenia.

PubMed

Modai, Shira; Shomron, Noam

2016-03-01

Schizophrenia (SZ) is a complex and strongly heritable mental disorder, which is also associated with developmental-environmental triggers. As opposed to most diagnosable diseases (yet similar to other mental disorders), SZ diagnosis is commonly based on psychiatric evaluations. Recently, large-scale genetic and epigenetic approaches have been applied to SZ research with the goal of potentially improving diagnosis. Increased computational analyses and applied statistical algorithms may shed some light on the complex genetic and epigenetic pathways contributing to SZ pathogenesis. This review discusses the latest advances in molecular risk factors and diagnostics for SZ. Approaches such as these may lead to a more accurate definition of SZ and assist in creating extended and reliable clinical diagnoses with the potential for personalized treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diagnostic Performance of a Novel Coronary CT Angiography Algorithm: Prospective Multicenter Validation of an Intracycle CT Motion Correction Algorithm for Diagnostic Accuracy.

PubMed

Andreini, Daniele; Lin, Fay Y; Rizvi, Asim; Cho, Iksung; Heo, Ran; Pontone, Gianluca; Bartorelli, Antonio L; Mushtaq, Saima; Villines, Todd C; Carrascosa, Patricia; Choi, Byoung Wook; Bloom, Stephen; Wei, Han; Xing, Yan; Gebow, Dan; Gransar, Heidi; Chang, Hyuk-Jae; Leipsic, Jonathon; Min, James K

2018-06-01

Motion artifact can reduce the diagnostic accuracy of coronary CT angiography (CCTA) for coronary artery disease (CAD). The purpose of this study was to compare the diagnostic performance of an algorithm dedicated to correcting coronary motion artifact with the performance of standard reconstruction methods in a prospective international multicenter study. Patients referred for clinically indicated invasive coronary angiography (ICA) for suspected CAD prospectively underwent an investigational CCTA examination free from heart rate-lowering medications before they underwent ICA. Blinded core laboratory interpretations of motion-corrected and standard reconstructions for obstructive CAD (≥ 50% stenosis) were compared with ICA findings. Segments unevaluable owing to artifact were considered obstructive. The primary endpoint was per-subject diagnostic accuracy of the intracycle motion correction algorithm for obstructive CAD found at ICA. Among 230 patients who underwent CCTA with the motion correction algorithm and standard reconstruction, 92 (40.0%) had obstructive CAD on the basis of ICA findings. At a mean heart rate of 68.0 ± 11.7 beats/min, the motion correction algorithm reduced the number of nondiagnostic scans compared with standard reconstruction (20.4% vs 34.8%; p < 0.001). Diagnostic accuracy for obstructive CAD with the motion correction algorithm (62%; 95% CI, 56-68%) was not significantly different from that of standard reconstruction on a per-subject basis (59%; 95% CI, 53-66%; p = 0.28) but was superior on a per-vessel basis: 77% (95% CI, 74-80%) versus 72% (95% CI, 69-75%) (p = 0.02). The motion correction algorithm was superior in subgroups of patients with severely obstructive (≥ 70%) stenosis, heart rate ≥ 70 beats/min, and vessels in the atrioventricular groove. The motion correction algorithm studied reduces artifacts and improves diagnostic performance for obstructive CAD on a per-vessel basis and in selected subgroups on a per-subject basis.

Regulation Effects by Programmed Molecules for Transcription-Based Diagnostic Automata towards Therapeutic Use

NASA Astrophysics Data System (ADS)

Hirabayashi, Miki; Ohashi, Hirotada; Kubo, Tai

We have presented experimental analysis on the controllability of our transcription-based diagnostic biomolecular automata by programmed molecules. Focusing on the noninvasive transcriptome diagnosis by salivary mRNAs, we already proposed the novel concept of diagnostic device using DNA computation. This system consists of the main computational element which has a stem shaped promoter region and a pseudo-loop shaped read-only memory region for transcription regulation through the conformation change caused by the recognition of disease-related biomarkers. We utilize the transcription of malachite green aptamer sequence triggered by the target recognition for observation of detection. This algorithm makes it possible to release RNA-aptamer drugs multiply, different from the digestion-based systems by the restriction enzyme which was proposed previously, for the in-vivo use, however, the controllability of aptamer release is not enough at the previous stage. In this paper, we verified the regulation effect on aptamer transcription by programmed molecules in basic conditions towards the developm! ent of therapeutic automata. These results would bring us one step closer to the realization of new intelligent diagnostic and therapeutic automata based on molecular circuits.

Using qualitative research to inform development of a diagnostic algorithm for UTI in children.

PubMed

de Salis, Isabel; Whiting, Penny; Sterne, Jonathan A C; Hay, Alastair D

2013-06-01

Diagnostic and prognostic algorithms can help reduce clinical uncertainty. The selection of candidate symptoms and signs to be measured in case report forms (CRFs) for potential inclusion in diagnostic algorithms needs to be comprehensive, clearly formulated and relevant for end users. To investigate whether qualitative methods could assist in designing CRFs in research developing diagnostic algorithms. Specifically, the study sought to establish whether qualitative methods could have assisted in designing the CRF for the Health Technology Association funded Diagnosis of Urinary Tract infection in Young children (DUTY) study, which will develop a diagnostic algorithm to improve recognition of urinary tract infection (UTI) in children aged <5 years presenting acutely unwell to primary care. Qualitative methods were applied using semi-structured interviews of 30 UK doctors and nurses working with young children in primary care and a Children's Emergency Department. We elicited features that clinicians believed useful in diagnosing UTI and compared these for presence or absence and terminology with the DUTY CRF. Despite much agreement between clinicians' accounts and the DUTY CRFs, we identified a small number of potentially important symptoms and signs not included in the CRF and some included items that could have been reworded to improve understanding and final data analysis. This study uniquely demonstrates the role of qualitative methods in the design and content of CRFs used for developing diagnostic (and prognostic) algorithms. Research groups developing such algorithms should consider using qualitative methods to inform the selection and wording of candidate symptoms and signs.

Efficacy of the FilmArray blood culture identification panel for direct molecular diagnosis of infectious diseases from samples other than blood.

PubMed

Micó, Miquel; Navarro, Ferran; de Miniac, Daniela; González, Yésica; Brell, Albert; López, Cristina; Sánchez-Reus, Ferran; Mirelis, Beatriz; Coll, Pere

2015-12-01

Molecular-based techniques reduce the delay in diagnosing infectious diseases and therefore contribute to better patient outcomes. We assessed the FilmArray blood culture identification (BCID) panel (Biofire Diagnostics/bioMérieux) directly on clinical specimens other than blood: cerebrospinal, joint, pleural and ascitic fluids, bronchoscopy samples and abscesses. We compared the results from 88 samples obtained by culture-based techniques. The percentage of agreement between the two methods was 75 % with a Cohen κ value of 0.51. Global sensitivity and specificity using the FilmArray BCID panel were 71 and 97 %, respectively. Sensitivity was poorer in samples with a low bacterial load, such as ascitic and pleural fluids (25 %), whereas the sensitivity for abscess samples was high (89 %). These findings suggest that the FilmArray BCID panel could be useful to perform microbiological diagnosis directly from samples other than positive blood cultures, as it offers acceptable sensitivity and moderate agreement with conventional microbiological methods. Nevertheless, cost-benefit studies should be performed before introducing this method into algorithms for microbiological diagnostics.

Molecular pathology curriculum for medical laboratory scientists: A report of the association for molecular pathology training and education committee.

PubMed

Taylor, Sara; Bennett, Katie M; Deignan, Joshua L; Hendrix, Ericka C; Orton, Susan M; Verma, Shalini; Schutzbank, Ted E

2014-05-01

Molecular diagnostics is a rapidly growing specialty in the clinical laboratory assessment of pathology. Educational programs in medical laboratory science and specialized programs in molecular diagnostics must address the training of clinical scientists in molecular diagnostics, but the educational curriculum for this field is not well defined. Moreover, our understanding of underlying genetic contributions to specific diseases and the technologies used in molecular diagnostics laboratories change rapidly, challenging providers of training programs in molecular diagnostics to keep their curriculum current and relevant. In this article, we provide curriculum recommendations to molecular diagnostics training providers at both the baccalaureate and master's level of education. We base our recommendations on several factors. First, we considered National Accrediting Agency for Clinical Laboratory Sciences guidelines for accreditation of molecular diagnostics programs, because educational programs in clinical laboratory science should obtain its accreditation. Second, the guidelines of several of the best known certifying agencies for clinical laboratory scientists were incorporated into our recommendations. Finally, we relied on feedback from current employers of molecular diagnostics scientists, regarding the skills and knowledge that they believe are essential for clinical scientists who will be performing molecular testing in their laboratories. We have compiled these data into recommendations for a molecular diagnostics curriculum at both the baccalaureate and master's level of education. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Replication and Comparison of the Newly Proposed ADOS-2, Module 4 Algorithm in ASD without ID: A Multi-Site Study

ERIC Educational Resources Information Center

Pugliese, Cara E.; Kenworthy, Lauren; Bal, Vanessa Hus; Wallace, Gregory L.; Yerys, Benjamin E.; Maddox, Brenna B.; White, Susan W.; Popal, Haroon; Armour, Anna Chelsea; Miller, Judith; Herrington, John D.; Schultz, Robert T.; Martin, Alex; Anthony, Laura Gutermuth

2015-01-01

Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised…

Raman spectral feature selection using ant colony optimization for breast cancer diagnosis.

PubMed

Fallahzadeh, Omid; Dehghani-Bidgoli, Zohreh; Assarian, Mohammad

2018-06-04

Pathology as a common diagnostic test of cancer is an invasive, time-consuming, and partially subjective method. Therefore, optical techniques, especially Raman spectroscopy, have attracted the attention of cancer diagnosis researchers. However, as Raman spectra contain numerous peaks involved in molecular bounds of the sample, finding the best features related to cancerous changes can improve the accuracy of diagnosis in this method. The present research attempted to improve the power of Raman-based cancer diagnosis by finding the best Raman features using the ACO algorithm. In the present research, 49 spectra were measured from normal, benign, and cancerous breast tissue samples using a 785-nm micro-Raman system. After preprocessing for removal of noise and background fluorescence, the intensity of 12 important Raman bands of the biological samples was extracted as features of each spectrum. Then, the ACO algorithm was applied to find the optimum features for diagnosis. As the results demonstrated, by selecting five features, the classification accuracy of the normal, benign, and cancerous groups increased by 14% and reached 87.7%. ACO feature selection can improve the diagnostic accuracy of Raman-based diagnostic models. In the present study, features corresponding to ν(C-C) αhelix proline, valine (910-940), νs(C-C) skeletal lipids (1110-1130), and δ(CH2)/δ(CH3) proteins (1445-1460) were selected as the best features in cancer diagnosis.

Molecular diagnosis of Legionella infections--Clinical utility of front-line screening as part of a pneumonia diagnostic algorithm.

PubMed

Gadsby, Naomi J; Helgason, Kristjan O; Dickson, Elizabeth M; Mills, Jonathan M; Lindsay, Diane S J; Edwards, Giles F; Hanson, Mary F; Templeton, Kate E

2016-02-01

Urinary antigen testing for Legionella pneumophila serogroup 1 is the leading rapid diagnostic test for Legionnaires' Disease (LD); however other Legionella species and serogroups can also cause LD. The aim was to determine the utility of front-line L. pneumophila and Legionella species PCR in a severe respiratory infection algorithm. L. pneumophila and Legionella species duplex real-time PCR was carried out on 1944 specimens from hospitalised patients over a 4 year period in Edinburgh, UK. L. pneumophila was detected by PCR in 49 (2.7%) specimens from 36 patients. During a LD outbreak, combined L. pneumophila respiratory PCR and urinary antigen testing had optimal sensitivity and specificity (92.6% and 98.3% respectively) for the detection of confirmed cases. Legionella species was detected by PCR in 16 (0.9%) specimens from 10 patients. The 5 confirmed and 1 probable cases of Legionella longbeachae LD were both PCR and antibody positive. Front-line L. pneumophila and Legionella species PCR is a valuable addition to urinary antigen testing as part of a well-defined algorithm. Cases of LD due to L. longbeachae might be considered laboratory-confirmed when there is a positive Legionella species PCR result and detection of L. longbeachae specific antibody response. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques.

PubMed

Duraipandian, Shiyamala; Zheng, Wei; Ng, Joseph; Low, Jeffrey J H; Ilancheran, A; Huang, Zhiwei

2011-10-21

This study aimed to evaluate the clinical utility of applying near-infrared (NIR) Raman spectroscopy and genetic algorithm-partial least squares-discriminant analysis (GA-PLS-DA) to identify biomolecular changes of cervical tissues associated with dysplastic transformation during colposcopic examination. A total of 105 in vivo Raman spectra were measured from 57 cervical sites (35 normal and 22 precancer sites) of 29 patients recruited, in which 65 spectra were from normal sites, while 40 spectra were from cervical precancerous lesions (i.e., 7 low-grade CIN and 33 high-grade CIN). The GA feature selection technique incorporated with PLS was utilized to study the significant biochemical Raman bands for differentiation between normal and precancer cervical tissues. The GA-PLS-DA algorithm with double cross-validation (dCV) identified seven diagnostically significant Raman bands in the ranges of 925-935, 979-999, 1080-1090, 1240-1260, 1320-1340, 1400-1420, and 1625-1645 cm(-1) related to proteins, nucleic acids and lipids in tissue, and yielded a diagnostic accuracy of 82.9% (sensitivity of 72.5% (29/40) and specificity of 89.2% (58/65)) for precancer detection. The results of this exploratory study suggest that Raman spectroscopy in conjunction with GA-PLS-DA and dCV methods has the potential to provide clinically significant discrimination between normal and precancer cervical tissues at the molecular level.

Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

PubMed

Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

2016-03-01

Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

A new assay based on terminal restriction fragment length polymorphism of homocitrate synthase gene fragments for Candida species identification.

PubMed

Szemiako, Kasjan; Śledzińska, Anna; Krawczyk, Beata

2017-08-01

Candida sp. have been responsible for an increasing number of infections, especially in patients with immunodeficiency. Species-specific differentiation of Candida sp. is difficult in routine diagnosis. This identification can have a highly significant association in therapy and prophylaxis. This work has shown a new application of the terminal restriction fragment length polymorphism (t-RFLP) method in the molecular identification of six species of Candida, which are the most common causes of fungal infections. Specific for fungi homocitrate synthase gene was chosen as a molecular target for amplification. The use of three restriction enzymes, DraI, RsaI, and BglII, for amplicon digestion can generate species-specific fluorescence labeled DNA fragment profiles, which can be used to determine the diagnostic algorithm. The designed method can be a cost-efficient high-throughput molecular technique for the identification of six clinically important Candida species.

Statistical inference on censored data for targeted clinical trials under enrichment design.

PubMed

Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

Performance of amplicon-based next generation DNA sequencing for diagnostic gene mutation profiling in oncopathology.

PubMed

Sie, Daoud; Snijders, Peter J F; Meijer, Gerrit A; Doeleman, Marije W; van Moorsel, Marinda I H; van Essen, Hendrik F; Eijk, Paul P; Grünberg, Katrien; van Grieken, Nicole C T; Thunnissen, Erik; Verheul, Henk M; Smit, Egbert F; Ylstra, Bauke; Heideman, Daniëlle A M

2014-10-01

Next generation DNA sequencing (NGS) holds promise for diagnostic applications, yet implementation in routine molecular pathology practice requires performance evaluation on DNA derived from routine formalin-fixed paraffin-embedded (FFPE) tissue specimens. The current study presents a comprehensive analysis of TruSeq Amplicon Cancer Panel-based NGS using a MiSeq Personal sequencer (TSACP-MiSeq-NGS) for somatic mutation profiling. TSACP-MiSeq-NGS (testing 212 hotspot mutation amplicons of 48 genes) and a data analysis pipeline were evaluated in a retrospective learning/test set approach (n = 58/n = 45 FFPE-tumor DNA samples) against 'gold standard' high-resolution-melting (HRM)-sequencing for the genes KRAS, EGFR, BRAF and PIK3CA. Next, the performance of the validated test algorithm was assessed in an independent, prospective cohort of FFPE-tumor DNA samples (n = 75). In the learning set, a number of minimum parameter settings was defined to decide whether a FFPE-DNA sample is qualified for TSACP-MiSeq-NGS and for calling mutations. The resulting test algorithm revealed 82% (37/45) compliance to the quality criteria and 95% (35/37) concordant assay findings for KRAS, EGFR, BRAF and PIK3CA with HRM-sequencing (kappa = 0.92; 95% CI = 0.81-1.03) in the test set. Subsequent application of the validated test algorithm to the prospective cohort yielded a success rate of 84% (63/75), and a high concordance with HRM-sequencing (95% (60/63); kappa = 0.92; 95% CI = 0.84-1.01). TSACP-MiSeq-NGS detected 77 mutations in 29 additional genes. TSACP-MiSeq-NGS is suitable for diagnostic gene mutation profiling in oncopathology.

Diagnostic Utility of the ADI-R and DSM-5 in the Assessment of Latino Children and Adolescents.

PubMed

Magaña, Sandy; Vanegas, Sandra B

2017-05-01

Latino children in the US are systematically underdiagnosed with Autism Spectrum Disorder (ASD); therefore, it is important that recent changes to the diagnostic process do not exacerbate this pattern of under-identification. Previous research has found that the Autism Diagnostic Interview-Revised (ADI-R) algorithm, based on the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition, Text Revision (DSM-IV-TR), has limitations with Latino children of Spanish speaking parents. We evaluated whether an ADI-R algorithm based on the new DSM-5 classification for ASD would be more sensitive in identifying Latino children of Spanish speaking parents who have a clinical diagnosis of ASD. Findings suggest that the DSM-5 algorithm shows better sensitivity than the DSM-IV-TR algorithm for Latino children.

Comparison of dermatoscopic diagnostic algorithms based on calculation: The ABCD rule of dermatoscopy, the seven-point checklist, the three-point checklist and the CASH algorithm in dermatoscopic evaluation of melanocytic lesions.

PubMed

Unlu, Ezgi; Akay, Bengu N; Erdem, Cengizhan

2014-07-01

Dermatoscopic analysis of melanocytic lesions using the CASH algorithm has rarely been described in the literature. The purpose of this study was to compare the sensitivity, specificity, and diagnostic accuracy rates of the ABCD rule of dermatoscopy, the seven-point checklist, the three-point checklist, and the CASH algorithm in the diagnosis and dermatoscopic evaluation of melanocytic lesions on the hairy skin. One hundred and fifteen melanocytic lesions of 115 patients were examined retrospectively using dermatoscopic images and compared with the histopathologic diagnosis. Four dermatoscopic algorithms were carried out for all lesions. The ABCD rule of dermatoscopy showed sensitivity of 91.6%, specificity of 60.4%, and diagnostic accuracy of 66.9%. The seven-point checklist showed sensitivity, specificity, and diagnostic accuracy of 87.5, 65.9, and 70.4%, respectively; the three-point checklist 79.1, 62.6, 66%; and the CASH algorithm 91.6, 64.8, and 70.4%, respectively. To our knowledge, this is the first study that compares the sensitivity, specificity and diagnostic accuracy of the ABCD rule of dermatoscopy, the three-point checklist, the seven-point checklist, and the CASH algorithm for the diagnosis of melanocytic lesions on the hairy skin. In our study, the ABCD rule of dermatoscopy and the CASH algorithm showed the highest sensitivity for the diagnosis of melanoma. © 2014 Japanese Dermatological Association.

Self-Reported HIV-Positive Status But Subsequent HIV-Negative Test Result Using Rapid Diagnostic Testing Algorithms Among Seven Sub-Saharan African Military Populations

DTIC Science & Technology

2017-07-07

RESEARCH ARTICLE Self-reported HIV-positive status but subsequent HIV-negative test result using rapid diagnostic testing algorithms among seven sub...America * judith.harbertson.ctr@mail.mil Abstract HIV rapid diagnostic tests (RDTs) combined in an algorithm are the current standard for HIV diagnosis...in many sub-Saharan African countries, and extensive laboratory testing has con- firmed HIV RDTs have excellent sensitivity and specificity. However

Improving single molecule force spectroscopy through automated real-time data collection and quantification of experimental conditions

PubMed Central

Scholl, Zackary N.; Marszalek, Piotr E.

2013-01-01

The benefits of single molecule force spectroscopy (SMFS) clearly outweigh the challenges which include small sample sizes, tedious data collection and introduction of human bias during the subjective data selection. These difficulties can be partially eliminated through automation of the experimental data collection process for atomic force microscopy (AFM). Automation can be accomplished using an algorithm that triages usable force-extension recordings quickly with positive and negative selection. We implemented an algorithm based on the windowed fast Fourier transform of force-extension traces that identifies peaks using force-extension regimes to correctly identify usable recordings from proteins composed of repeated domains. This algorithm excels as a real-time diagnostic because it involves <30 ms computational time, has high sensitivity and specificity, and efficiently detects weak unfolding events. We used the statistics provided by the automated procedure to clearly demonstrate the properties of molecular adhesion and how these properties change with differences in the cantilever tip and protein functional groups and protein age. PMID:24001740

Morphological spot counting from stacked images for automated analysis of gene copy numbers by fluorescence in situ hybridization.

PubMed

Grigoryan, Artyom M; Dougherty, Edward R; Kononen, Juha; Bubendorf, Lukas; Hostetter, Galen; Kallioniemi, Olli

2002-01-01

Fluorescence in situ hybridization (FISH) is a molecular diagnostic technique in which a fluorescent labeled probe hybridizes to a target nucleotide sequence of deoxyribose nucleic acid. Upon excitation, each chromosome containing the target sequence produces a fluorescent signal (spot). Because fluorescent spot counting is tedious and often subjective, automated digital algorithms to count spots are desirable. New technology provides a stack of images on multiple focal planes throughout a tissue sample. Multiple-focal-plane imaging helps overcome the biases and imprecision inherent in single-focal-plane methods. This paper proposes an algorithm for global spot counting in stacked three-dimensional slice FISH images without the necessity of nuclei segmentation. It is designed to work in complex backgrounds, when there are agglomerated nuclei, and in the presence of illumination gradients. It is based on the morphological top-hat transform, which locates intensity spikes on irregular backgrounds. After finding signals in the slice images, the algorithm groups these together to form three-dimensional spots. Filters are employed to separate legitimate spots from fluorescent noise. The algorithm is set in a comprehensive toolbox that provides visualization and analytic facilities. It includes simulation software that allows examination of algorithm performance for various image and algorithm parameter settings, including signal size, signal density, and the number of slices.

[Monogenic and syndromic symptoms of morbid obesity. Rare but important].

PubMed

Wiegand, S; Krude, H

2015-02-01

Monogenic and syndromic obesity are rare diseases with variable manifestation. Therefore diagnosis is difficult and often delayed. The purpose of this work was to develop a clinical diagnostic algorithm for earlier diagnosis. Available publications for clinical symptoms and molecular defects of monogenic and syndromic obesity cases were evaluated. Monogenic and syndromic obesity can be expected in cases with early manifestation before the age of 5 years and a BMI above 40 or above the 99th percentile. Syndromic cases are mostly associated with a low IQ and dwarfism. Monogenic cases are associated with additional endocrine defects. Measurement of serum leptin proves the treatable leptin deficiency. Sequencing of the melanocortin-4 receptor gene (MC4R) allows diagnosis of the most frequent monogenic form of obesity. Treatment with a melanocyte-stimulating hormone (MSH) analog can be expected in the future. Early treatment of children with Prader-Willi syndrome can prevent severe obesity. Because in some cases treatment is available, monogenic and syndromic obesity should be diagnosed early. Based on the disease symptoms, serum leptin, and MC4R sequencing, a diagnostic algorithm is proposed, which can be used to diagnose cases of morbid obesity.

Small business development for molecular diagnostics.

PubMed

Anagostou, Anthanasia; Liotta, Lance A

2012-01-01

Molecular profiling, which is the application of molecular diagnostics technology to tissue and blood -specimens, is an integral element in the new era of molecular medicine and individualized therapy. Molecular diagnostics is a fertile ground for small business development because it can generate products that meet immediate demands in the health-care sector: (a) Detection of disease risk, or early-stage disease, with a higher specificity and sensitivity compared to previous testing methods, and (b) "Companion diagnostics" for stratifying patients to receive a treatment choice optimized to their individual disease. This chapter reviews the promise and challenges of business development in this field. Guidelines are provided for the creation of a business model and the generation of a marketing plan around a candidate molecular diagnostic product. Steps to commercialization are outlined using existing molecular diagnostics companies as learning examples.

The Impact of a Line Probe Assay Based Diagnostic Algorithm on Time to Treatment Initiation and Treatment Outcomes for Multidrug Resistant TB Patients in Arkhangelsk Region, Russia.

PubMed

Eliseev, Platon; Balantcev, Grigory; Nikishova, Elena; Gaida, Anastasia; Bogdanova, Elena; Enarson, Donald; Ornstein, Tara; Detjen, Anne; Dacombe, Russell; Gospodarevskaya, Elena; Phillips, Patrick P J; Mann, Gillian; Squire, Stephen Bertel; Mariandyshev, Andrei

2016-01-01

In the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy. The PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes. A culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm. Among smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes were better in LPA-based algorithm compared to culture-based algorithm (p = 0.003). Treatment success rates at 20 months of treatment were higher in patients diagnosed with the LPA-based algorithm (65.2%) as compared to those diagnosed with the culture-based algorithm (44.8%). Mortality was also lower in the LPA-based algorithm group (7.6%) compared to the culture-based algorithm group (15.9%). There was no statistically significant difference in smear and culture conversion rates between the two algorithms. The results of the study suggest that the introduction of LPA leads to faster time to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics.

Enabling Equal Access to Molecular Diagnostics: What Are the Implications for Policy and Health Technology Assessment?

PubMed

Plun-Favreau, Juliette; Immonen-Charalambous, Kaisa; Steuten, Lotte; Strootker, Anja; Rouzier, Roman; Horgan, Denis; Lawler, Mark

2016-01-01

Molecular diagnostics can offer important benefits to patients and are a key enabler of the integration of personalised medicine into health care systems. However, despite their promise, few molecular diagnostics are embedded into clinical practice (especially in Europe) and access to these technologies remains unequal across countries and sometimes even within individual countries. If research translation and the regulatory environments have proven to be more challenging than expected, reimbursement and value assessment remain the main barriers to providing patients with equal access to molecular diagnostics. Unclear or non-existent reimbursement pathways, together with the lack of clear evidence requirements, have led to significant delays in the assessment of molecular diagnostics technologies in certain countries. Additionally, the lack of dedicated diagnostics budgets and the siloed nature of resource allocation within certain health care systems have significantly delayed diagnostics commissioning. This article will consider the perspectives of different stakeholders (patients, health care payers, health care professionals, and manufacturers) on the provision of a research-enabled, patient-focused molecular diagnostics platform that supports optimal patient care. Through the discussion of specific case studies, and building on the experience from countries that have successfully integrated molecular diagnostics into clinical practice, this article will discuss the necessary evolutions in policy and health technology assessment to ensure that patients can have equal access to appropriate molecular diagnostics. © 2016 S. Karger AG, Basel.

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics.

PubMed

Paschke, Ralf; Cantara, Silvia; Crescenzi, Anna; Jarzab, Barbara; Musholt, Thomas J; Sobrinho Simoes, Manuel

2017-07-01

Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF , NRAS , HRAS , KRAS , PAX8/PPARG , RET/PTC ) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation.

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics

PubMed Central

Paschke, Ralf; Cantara, Silvia; Crescenzi, Anna; Jarzab, Barbara; Musholt, Thomas J.; Sobrinho Simoes, Manuel

2017-01-01

Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation. PMID:28785538

Molecular Testing of Brain Tumor

PubMed Central

Park, Sung-Hye; Won, Jaekyung; Kim, Seong-Ik; Lee, Yujin; Park, Chul-Kee; Kim, Seung-Ki; Choi, Seung-Hong

2017-01-01

The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53, and ATRX, oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC, FUBP1, and the promoter region of telomerase reverse transcriptase (TERTp). IDH-wildtype (primary) glioblastomas typically lack mutations in IDH, but are characterized by copy number variations of EGFR, PTEN, CDKN2A/B, PDGFRA, and NF1 as well as mutations of TERTp. High-grade pediatric gliomas differ from those of adult gliomas, consisting of mutations in H3F3A, ATRX, and DAXX, but not in IDH genes. In contrast, well-circumscribed low-grade neuroepithelial tumors in children, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often have mutations or activating rearrangements in the BRAF, FGFR1, and MYB genes. Other CNS tumors, such as ependymomas, neuronal and glioneuronal tumors, embryonal tumors, meningothelial, and other mesenchymal tumors have important genetic alterations, many of which are diagnostic, prognostic, and predictive markers and therapeutic targets. Therefore, the neuropathological evaluation of brain tumors is increasingly dependent on molecular genetic tests for proper classification, prediction of biological behavior and patient management. Identifying these gene abnormalities requires cost-effective and high-throughput testing, such as next-generation sequencing. Overall, this paper reviews the global guidelines and diagnostic algorithms for molecular genetic testing of brain tumors. PMID:28535583

[Advances of Molecular Diagnostic Techniques Application in Clinical Diagnosis.

PubMed

Ying, Bin-Wu

2016-11-01

Over the past 20 years,clinical molecular diagnostic technology has made rapid development,and became the most promising field in clinical laboratory medicine.In particular,with the development of genomics,clinical molecular diagnostic methods will reveal the nature of clinical diseases in a deeper level,thus guiding the clinical diagnosis and treatments.Many molecular diagnostic projects have been routinely applied in clinical works.This paper reviews the advances on application of clinical diagnostic techniques in infectious disease,tumor and genetic disorders,including nucleic acid amplification,biochip,next-generation sequencing,and automation molecular system,and so on.

Replication and Comparison of the Newly Proposed ADOS-2, Module 4 Algorithm in ASD Without ID: A Multi-site Study.

PubMed

Pugliese, Cara E; Kenworthy, Lauren; Bal, Vanessa Hus; Wallace, Gregory L; Yerys, Benjamin E; Maddox, Brenna B; White, Susan W; Popal, Haroon; Armour, Anna Chelsea; Miller, Judith; Herrington, John D; Schultz, Robert T; Martin, Alex; Anthony, Laura Gutermuth

2015-12-01

Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised algorithm demonstrated increased sensitivity, but lower specificity in the overall sample. Estimates were highest for females, individuals with a verbal IQ below 85 or above 115, and ages 16 and older. Best practice diagnostic procedures should include the Module 4 in conjunction with other assessment tools. Balancing needs for sensitivity and specificity depending on the purpose of assessment (e.g., clinical vs. research) and demographic characteristics mentioned above will enhance its utility.

The autism diagnostic observation schedule, module 4: revised algorithm and standardized severity scores.

PubMed

Hus, Vanessa; Lord, Catherine

2014-08-01

The recently published Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) includes revised diagnostic algorithms and standardized severity scores for modules used to assess younger children. A revised algorithm and severity scores are not yet available for Module 4, used with verbally fluent adults. The current study revises the Module 4 algorithm and calibrates raw overall and domain totals to provide metrics of autism spectrum disorder (ASD) symptom severity. Sensitivity and specificity of the revised Module 4 algorithm exceeded 80 % in the overall sample. Module 4 calibrated severity scores provide quantitative estimates of ASD symptom severity that are relatively independent of participant characteristics. These efforts increase comparability of ADOS scores across modules and should facilitate efforts to examine symptom trajectories from toddler to adulthood.

Implementation of an Algorithm for Prosthetic Joint Infection: Deviations and Problems.

PubMed

Mühlhofer, Heinrich M L; Kanz, Karl-Georg; Pohlig, Florian; Lenze, Ulrich; Lenze, Florian; Toepfer, Andreas; von Eisenhart-Rothe, Ruediger; Schauwecker, Johannes

The outcome of revision surgery in arthroplasty is based on a precise diagnosis. In addition, the treatment varies based on whether the prosthetic failure is caused by aseptic or septic loosening. Algorithms can help to identify periprosthetic joint infections (PJI) and standardize diagnostic steps, however, algorithms tend to oversimplify the treatment of complex cases. We conducted a process analysis during the implementation of a PJI algorithm to determine problems and deviations associated with the implementation of this algorithm. Fifty patients who were treated after implementing a standardized algorithm were monitored retrospectively. Their treatment plans and diagnostic cascades were analyzed for deviations from the implemented algorithm. Each diagnostic procedure was recorded, compared with the algorithm, and evaluated statistically. We detected 52 deviations while treating 50 patients. In 25 cases, no discrepancy was observed. Synovial fluid aspiration was not performed in 31.8% of patients (95% confidence interval [CI], 18.1%-45.6%), while white blood cell counts (WBCs) and neutrophil differentiation were assessed in 54.5% of patients (95% CI, 39.8%-69.3%). We also observed that the prolonged incubation of cultures was not requested in 13.6% of patients (95% CI, 3.5%-23.8%). In seven of 13 cases (63.6%; 95% CI, 35.2%-92.1%), arthroscopic biopsy was performed; 6 arthroscopies were performed in discordance with the algorithm (12%; 95% CI, 3%-21%). Self-critical analysis of diagnostic processes and monitoring of deviations using algorithms are important and could increase the quality of treatment by revealing recurring faults.

The Development of a Post-Baccalaureate Certificate Program in Molecular Diagnostics

PubMed Central

Williams, Gail S.; Brown, Judith D.; Keagle, Martha B.

2000-01-01

A post-baccalaureate certificate program in diagnostic molecular sciences was created in 1995 by the Diagnostic Genetic Sciences Program in the School of Allied Health at the University of Connecticut. The required on-campus lecture and laboratory courses include basic laboratory techniques, health care issues, cell biology, immunology, human genetics, research, management, and molecular diagnostic techniques and laboratory in molecular diagnostics. These courses precede a 6-month, full-time practicum at an affiliated full-service molecular laboratory. The practicum includes amplification and blotting methods, a research project, and a choice of specialized electives including DNA sequencing, mutagenesis, in situ hybridization methods, or molecular diagnostic applications in microbiology. Graduates of the program are immediately eligible to sit for the National Credentialing Agency examination in molecular biology to obtain the credential Clinical Laboratory Specialist in Molecular Biology (CLSp(MB). This description of the University of Connecticut program may assist other laboratory science programs in creating similar curricula. PMID:11232107

MARS spectral molecular imaging of lamb tissue: data collection and image analysis

NASA Astrophysics Data System (ADS)

Aamir, R.; Chernoglazov, A.; Bateman, C. J.; Butler, A. P. H.; Butler, P. H.; Anderson, N. G.; Bell, S. T.; Panta, R. K.; Healy, J. L.; Mohr, J. L.; Rajendran, K.; Walsh, M. F.; de Ruiter, N.; Gieseg, S. P.; Woodfield, T.; Renaud, P. F.; Brooke, L.; Abdul-Majid, S.; Clyne, M.; Glendenning, R.; Bones, P. J.; Billinghurst, M.; Bartneck, C.; Mandalika, H.; Grasset, R.; Schleich, N.; Scott, N.; Nik, S. J.; Opie, A.; Janmale, T.; Tang, D. N.; Kim, D.; Doesburg, R. M.; Zainon, R.; Ronaldson, J. P.; Cook, N. J.; Smithies, D. J.; Hodge, K.

2014-02-01

Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20-140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we are one of the first to present data from multi-energy photon-processing small animal CT systems, we make the raw, partial and fully processed data available with the intention that others can analyze it using their familiar routines. The raw, partially processed and fully processed data of lamb tissue along with the phantom calibration data can be found at http://hdl.handle.net/10092/8531.

The impact of new trends in POCTs for companion diagnostics, non-invasive testing and molecular diagnostics.

PubMed

Huckle, David

2015-06-01

Point-of-care diagnostics have been slowly developing over several decades and have taken on a new importance in current healthcare delivery for both diagnostics and development of new drugs. Molecular diagnostics have become a key driver of technology change and opened up new areas in companion diagnostics for use alongside pharmaceuticals and in new clinical approaches such as non-invasive testing. Future areas involving smartphone and other information technology advances, together with new developments in molecular biology, microfluidics and surface chemistry are adding to advances in the market. The focus for point-of-care tests with molecular diagnostic technologies is focused on advancing effective applications.

Diagnostic rules and algorithms for the diagnosis of non-acute heart failure in patients 80 years of age and older: a diagnostic accuracy and validation study.

PubMed

Smeets, Miek; Degryse, Jan; Janssens, Stefan; Matheï, Catharina; Wallemacq, Pierre; Vanoverschelde, Jean-Louis; Aertgeerts, Bert; Vaes, Bert

2016-10-06

Different diagnostic algorithms for non-acute heart failure (HF) exist. Our aim was to compare the ability of these algorithms to identify HF in symptomatic patients aged 80 years and older and identify those patients at highest risk for mortality. Diagnostic accuracy and validation study. General practice, Belgium. 365 patients with HF symptoms aged 80 years and older (BELFRAIL cohort). Participants underwent a full clinical assessment, including a detailed echocardiographic examination at home. The diagnostic accuracy of 4 different algorithms was compared using an intention-to-diagnose analysis. The European Society of Cardiology (ESC) definition of HF was used as the reference standard for HF diagnosis. Kaplan-Meier curves for 5-year all-cause mortality were plotted and HRs and corresponding 95% CIs were calculated to compare the mortality risk predicting abilities of the different algorithms. Net reclassification improvement (NRI) was calculated. The prevalence of HF was 20% (n=74). The 2012 ESC algorithm yielded the highest sensitivity (92%, 95% CI 83% to 97%) as well as the highest referral rate (71%, n=259), whereas the Oudejans algorithm yielded the highest specificity (73%, 95% CI 68% to 78%) and the lowest referral rate (36%, n=133). These differences could be ascribed to differences in N-terminal probrain natriuretic peptide cut-off values (125 vs 400 pg/mL). The Kelder and Oudejans algorithms exhibited NRIs of 12% (95% CI 0.7% to 22%, p=0.04) and 22% (95% CI 9% to 32%, p<0.001), respectively, compared with the ESC algorithm. All algorithms detected patients at high risk for mortality (HR 1.9, 95% CI 1.4 to 2.5; Kelder) to 2.3 (95% CI 1.7 to 3.1; Oudejans). No significant differences were observed among the algorithms with respect to mortality risk predicting abilities. Choosing a diagnostic algorithm for non-acute HF in elderly patients represents a trade-off between sensitivity and specificity, mainly depending on differences between cut-off values for natriuretic peptides. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Point of Injury Sampling Technology for Battlefield Molecular Diagnostics

DTIC Science & Technology

2011-11-14

Injury" Sampling Technology for Battlefield Molecular Diagnostics November 14, 2011 Sponsored by Defense Advanced Research Projects Agency (DOD...Date of Contract: April 25, 2011 Short Title of Work: "Point of Injury" Sampling Technology for Battlefield Molecular Diagnostics " Contract...PHASE I FINAL REPORT: Point of Injury, Sampling Technology for Battlefield Molecular Diagnostics . W31P4Q-11-C-0222 (UNCLASSIFIED) P.I: Bernardo

Cancer imaging phenomics toolkit: quantitative imaging analytics for precision diagnostics and predictive modeling of clinical outcome.

PubMed

Davatzikos, Christos; Rathore, Saima; Bakas, Spyridon; Pati, Sarthak; Bergman, Mark; Kalarot, Ratheesh; Sridharan, Patmaa; Gastounioti, Aimilia; Jahani, Nariman; Cohen, Eric; Akbari, Hamed; Tunc, Birkan; Doshi, Jimit; Parker, Drew; Hsieh, Michael; Sotiras, Aristeidis; Li, Hongming; Ou, Yangming; Doot, Robert K; Bilello, Michel; Fan, Yong; Shinohara, Russell T; Yushkevich, Paul; Verma, Ragini; Kontos, Despina

2018-01-01

The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.

Portable Health Algorithms Test System

NASA Technical Reports Server (NTRS)

Melcher, Kevin J.; Wong, Edmond; Fulton, Christopher E.; Sowers, Thomas S.; Maul, William A.

2010-01-01

A document discusses the Portable Health Algorithms Test (PHALT) System, which has been designed as a means for evolving the maturity and credibility of algorithms developed to assess the health of aerospace systems. Comprising an integrated hardware-software environment, the PHALT system allows systems health management algorithms to be developed in a graphical programming environment, to be tested and refined using system simulation or test data playback, and to be evaluated in a real-time hardware-in-the-loop mode with a live test article. The integrated hardware and software development environment provides a seamless transition from algorithm development to real-time implementation. The portability of the hardware makes it quick and easy to transport between test facilities. This hard ware/software architecture is flexible enough to support a variety of diagnostic applications and test hardware, and the GUI-based rapid prototyping capability is sufficient to support development execution, and testing of custom diagnostic algorithms. The PHALT operating system supports execution of diagnostic algorithms under real-time constraints. PHALT can perform real-time capture and playback of test rig data with the ability to augment/ modify the data stream (e.g. inject simulated faults). It performs algorithm testing using a variety of data input sources, including real-time data acquisition, test data playback, and system simulations, and also provides system feedback to evaluate closed-loop diagnostic response and mitigation control.

Feasibility of the TBDx automated digital microscopy system for the diagnosis of pulmonary tuberculosis.

PubMed

Nabeta, Pamela; Havumaki, Joshua; Ha, Dang Thi Minh; Caceres, Tatiana; Hang, Pham Thu; Collantes, Jimena; Thi Ngoc Lan, Nguyen; Gotuzzo, Eduardo; Denkinger, Claudia M

2017-01-01

Improved and affordable diagnostic or triage tests are urgently needed at the microscopy centre level. Automated digital microscopy has the potential to overcome issues related to conventional microscopy, including training time requirement and inconsistencies in results interpretation. For this blinded prospective study, sputum samples were collected from adults with presumptive pulmonary tuberculosis in Lima, Peru and Ho Chi Minh City, Vietnam. TBDx performance was evaluated as a stand-alone and as a triage test against conventional microscopy and Xpert, with culture as the reference standard. Xpert was used to confirm positive cases. A total of 613 subjects were enrolled between October 2014 and March 2015, with 539 included in the final analysis. The sensitivity of TBDx was 62·2% (95% CI 56·6-67·4) and specificity was 90·7% (95% CI 85·9-94·2) compared to culture. The algorithm assessing TBDx as a triage test achieved a specificity of 100% while maintaining sensitivity. While the diagnostic performance of TBDx did not reach the levels obtained by experienced microscopists in reference laboratories, it is conceivable that it would exceed the performance of less experienced microscopists. In the absence of highly sensitive and specific molecular tests at the microscopy centre level, TBDx in a triage-testing algorithm would optimize specificity and limit overall cost without compromising the number of patients receiving up-front drug susceptibility testing for rifampicin. However, the algorithm would miss over one third of patients compared to Xpert alone.

Performance of Dengue Diagnostic Tests in a Single-Specimen Diagnostic Algorithm.

PubMed

Hunsperger, Elizabeth A; Muñoz-Jordán, Jorge; Beltran, Manuela; Colón, Candimar; Carrión, Jessica; Vazquez, Jesus; Acosta, Luz Nereida; Medina-Izquierdo, Juan F; Horiuchi, Kalanthe; Biggerstaff, Brad J; Margolis, Harold S

2016-09-15

Anti-dengue virus (DENV) immunoglobulin M (IgM) seroconversion has been the reference standard for dengue diagnosis. However, paired specimens are rarely obtained, and the interval for this testing negates its usefulness in guiding clinical case management. The presence of DENV viremia and appearance of IgM during the febrile phase of dengue provides the framework for dengue laboratory diagnosis by using a single serum specimen. Archived paired serum specimens (n = 1234) from patients with laboratory-confirmed dengue from 2005 through 2011 were used to determine the diagnostic performance of real-time reverse transcription polymerase chain reaction (RT-PCR), for detection of DENV serotypes 1-4, and enzyme-linked immunosorbent assays (ELISAs), for detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM. During 1-3 days after illness onset, real-time RT-PCR and NS1 antigen testing detected 82%-69% and 90%-84% of cases, respectively, as viremia levels declined, while anti-DENV IgM ELISA detected 5%-41% of cases as antibody appeared. Over the 10-day period of the febrile phase of dengue, the cumulative effect of using these 3 types of tests in a diagnostic algorithm confirmed ≥90% of dengue cases. The use of molecular or NS1 antigen tests to detect DENV and one to detect anti-DENV IgM in a single serum specimen collected during the first 10 days of illness accurately identified ≥90% of dengue primary and secondary cases. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Replication and Comparison of the Newly Proposed ADOS-2, Module 4 Algorithm in ASD without ID: A Multi-site Study

PubMed Central

Pugliese, Cara E.; Kenworthy, Lauren; Bal, Vanessa Hus; Wallace, Gregory L; Yerys, Benjamin E; Maddox, Brenna B.; White, Susan W.; Popal, Haroon; Armour, Anna Chelsea; Miller, Judith; Herrington, John D.; Schultz, Robert T.; Martin, Alex; Anthony, Laura Gutermuth

2015-01-01

Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised algorithm demonstrated increased sensitivity, but lower specificity in the overall sample. Estimates were highest for females, individuals with a verbal IQ below 85 or above 115, and ages 16 and older. Best practice diagnostic procedures should include the Module 4 in conjunction with other assessment tools. Balancing needs for sensitivity and specificity depending on the purpose of assessment (e.g., clinical vs. research) and demographic characteristics mentioned above will enhance its utility. PMID:26385796

’Point of Injury’ Sampling Technology for Battlefield Molecular Diagnostics

DTIC Science & Technology

2012-03-17

Injury" Sampling Technology for Battlefield Molecular Diagnostics March 17,2012 Sponsored by Defense Advanced Research Projects Agency (DOD) Defense...Contract: April 25, 2011 Short Title of Work: "Point of Injury" Sampling Technology for Battlefield Molecular Diagnostics " Contract Expiration Date...SBIR PHASE I OPTION REPORT: Point of Injury, Sampling Technology for Battlefield Molecular Diagnostics . W31P4Q-1 l-C-0222 (UNCLASSIFIED) P.I

Computer-aided biochemical programming of synthetic microreactors as diagnostic devices.

PubMed

Courbet, Alexis; Amar, Patrick; Fages, François; Renard, Eric; Molina, Franck

2018-04-26

Biological systems have evolved efficient sensing and decision-making mechanisms to maximize fitness in changing molecular environments. Synthetic biologists have exploited these capabilities to engineer control on information and energy processing in living cells. While engineered organisms pose important technological and ethical challenges, de novo assembly of non-living biomolecular devices could offer promising avenues toward various real-world applications. However, assembling biochemical parts into functional information processing systems has remained challenging due to extensive multidimensional parameter spaces that must be sampled comprehensively in order to identify robust, specification compliant molecular implementations. We introduce a systematic methodology based on automated computational design and microfluidics enabling the programming of synthetic cell-like microreactors embedding biochemical logic circuits, or protosensors , to perform accurate biosensing and biocomputing operations in vitro according to temporal logic specifications. We show that proof-of-concept protosensors integrating diagnostic algorithms detect specific patterns of biomarkers in human clinical samples. Protosensors may enable novel approaches to medicine and represent a step toward autonomous micromachines capable of precise interfacing of human physiology or other complex biological environments, ecosystems, or industrial bioprocesses. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Image quality enhancement for skin cancer optical diagnostics

NASA Astrophysics Data System (ADS)

Bliznuks, Dmitrijs; Kuzmina, Ilona; Bolocko, Katrina; Lihachev, Alexey

2017-12-01

The research presents image quality analysis and enhancement proposals in biophotonic area. The sources of image problems are reviewed and analyzed. The problems with most impact in biophotonic area are analyzed in terms of specific biophotonic task - skin cancer diagnostics. The results point out that main problem for skin cancer analysis is the skin illumination problems. Since it is often not possible to prevent illumination problems, the paper proposes image post processing algorithm - low frequency filtering. Practical results show diagnostic results improvement after using proposed filter. Along that, filter do not reduces diagnostic results' quality for images without illumination defects. Current filtering algorithm requires empirical tuning of filter parameters. Further work needed to test the algorithm in other biophotonic applications and propose automatic filter parameter selection.

The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores

PubMed Central

Hus, Vanessa; Lord, Catherine

2014-01-01

The Autism Diagnostic Observation Schedule, 2nd Edition includes revised diagnostic algorithms and standardized severity scores for modules used to assess children and adolescents of varying language abilities. Comparable revisions have not yet been applied to the Module 4, used with verbally fluent adults. The current study revises the Module 4 algorithm and calibrates raw overall and domain totals to provide metrics of ASD symptom severity. Sensitivity and specificity of the revised Module 4 algorithm exceeded 80% in the overall sample. Module 4 calibrated severity scores provide quantitative estimates of ASD symptom severity that are relatively independent of participant characteristics. These efforts increase comparability of ADOS scores across modules and should facilitate efforts to increase understanding of adults with ASD. PMID:24590409

Microfluidic technology for molecular diagnostics.

PubMed

Robinson, Tom; Dittrich, Petra S

2013-01-01

Molecular diagnostics have helped to improve the lives of millions of patients worldwide by allowing clinicians to diagnose patients earlier as well as providing better ongoing therapies. Point-of-care (POC) testing can bring these laboratory-based techniques to the patient in a home setting or to remote settings in the developing world. However, despite substantial progress in the field, there still remain many challenges. Progress in molecular diagnostics has benefitted greatly from microfluidic technology. This chapter aims to summarise the more recent advances in microfluidic-based molecular diagnostics. Sections include an introduction to microfluidic technology, the challenges of molecular diagnostics, how microfluidic advances are working to solve these issues, some alternative design approaches, and detection within these systems.

The Autism Diagnostic Observation Schedule, Module 4: Application of the Revised Algorithms in an Independent, Well-Defined, Dutch Sample (N = 93)

ERIC Educational Resources Information Center

de Bildt, Annelies; Sytema, Sjoerd; Meffert, Harma; Bastiaansen, Jojanneke A. C. J.

2016-01-01

This study examined the discriminative ability of the revised Autism Diagnostic Observation Schedule module 4 algorithm (Hus and Lord in "J Autism Dev Disord" 44(8):1996-2012, 2014) in 93 Dutch males with Autism Spectrum Disorder (ASD), schizophrenia, psychopathy or controls. Discriminative ability of the revised algorithm ASD cut-off…

Surface-enhanced Raman spectroscopy for differentiation between benign and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Li, Zuanfang; Li, Chao; Lin, Duo; Huang, Zufang; Pan, Jianji; Chen, Guannan; Lin, Juqiang; Liu, Nenrong; Yu, Yun; Feng, Shangyuan; Chen, Rong

2014-04-01

The aim of this study was to evaluate the potential of applying silver nano-particle based surface-enhanced Raman scattering (SERS) to discriminate different types of human thyroid tissues. SERS measurements were performed on three groups of tissue samples including thyroid cancers (n = 32), nodular goiters (n = 20) and normal thyroid tissues (n = 25). Tentative assignments of the measured tissue SERS spectra suggest interesting cancer specific biomolecular differences. The principal component analysis (PCA) and linear discriminate analysis (LDA) together with the leave-one-out, cross-validated technique yielded diagnostic sensitivities of 92%, 75% and 87.5%; and specificities of 82.6%, 89.4% and 84.4%, respectively, for differentiation among normal, nodular and malignant thyroid tissue samples. This work demonstrates that tissue SERS spectroscopy associated with multivariate analysis diagnostic algorithms has great potential for detection of thyroid cancer at the molecular level.

Morphological diagnostics of star formation in molecular clouds

NASA Astrophysics Data System (ADS)

Beaumont, Christopher Norris

Molecular clouds are the birth sites of all star formation in the present-day universe. They represent the initial conditions of star formation, and are the primary medium by which stars transfer energy and momentum back to parsec scales. Yet, the physical evolution of molecular clouds remains poorly understood. This is not due to a lack of observational data, nor is it due to an inability to simulate the conditions inside molecular clouds. Instead, the physics and structure of the interstellar medium are sufficiently complex that interpreting molecular cloud data is very difficult. This dissertation mitigates this problem, by developing more sophisticated ways to interpret morphological information in molecular cloud observations and simulations. In particular, I have focused on leveraging machine learning techniques to identify physically meaningful substructures in the interstellar medium, as well as techniques to inter-compare molecular cloud simulations to observations. These contributions make it easier to understand the interplay between molecular clouds and star formation. Specific contributions include: new insight about the sheet-like geometry of molecular clouds based on observations of stellar bubbles; a new algorithm to disambiguate overlapping yet morphologically distinct cloud structures; a new perspective on the relationship between molecular cloud column density distributions and the sizes of cloud substructures; a quantitative analysis of how projection effects affect measurements of cloud properties; and an automatically generated, statistically-calibrated catalog of bubbles identified from their infrared morphologies.

Multiclass cancer diagnosis using tumor gene expression signatures

DOE PAGES

Ramaswamy, S.; Tamayo, P.; Rifkin, R.; ...

2001-12-11

The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is difficult or impossible because of atypical clinical presentation or histopathology. To determine whether the diagnosis of multiple common adult malignancies could be achieved purely by molecular classification, we subjected 218 tumor samples, spanning 14 common tumor types, and 90 normal tissue samples to oligonucleotide microarray gene expression analysis. The expression levels of 16,063 genes and expressed sequence tags were used to evaluate the accuracy of a multiclass classifier based on a supportmore » vector machine algorithm. Overall classification accuracy was 78%, far exceeding the accuracy of random classification (9%). Poorly differentiated cancers resulted in low-confidence predictions and could not be accurately classified according to their tissue of origin, indicating that they are molecularly distinct entities with dramatically different gene expression patterns compared with their well differentiated counterparts. Taken together, these results demonstrate the feasibility of accurate, multiclass molecular cancer classification and suggest a strategy for future clinical implementation of molecular cancer diagnostics.« less

Nano-particle drag prediction at low Reynolds number using a direct Boltzmann-BGK solution approach

NASA Astrophysics Data System (ADS)

Evans, B.

2018-01-01

This paper outlines a novel approach for solution of the Boltzmann-BGK equation describing molecular gas dynamics applied to the challenging problem of drag prediction of a 2D circular nano-particle at transitional Knudsen number (0.0214) and low Reynolds number (0.25-2.0). The numerical scheme utilises a discontinuous-Galerkin finite element discretisation for the physical space representing the problem particle geometry and a high order discretisation for molecular velocity space describing the molecular distribution function. The paper shows that this method produces drag predictions that are aligned well with the range of drag predictions for this problem generated from the alternative numerical approaches of molecular dynamics codes and a modified continuum scheme. It also demonstrates the sensitivity of flow-field solutions and therefore drag predictions to the wall absorption parameter used to construct the solid wall boundary condition used in the solver algorithm. The results from this work has applications in fields ranging from diagnostics and therapeutics in medicine to the fields of semiconductors and xerographics.

Molecular Diagnosis in Autoimmune Skin Blistering Conditions

PubMed Central

Otten, J.V.; Hashimoto, T.; Hertl, M.; Payne, A.S.; Sitaru, C.

2014-01-01

Blister formation in skin and mucous membranes results from a loss of cell-cell or cell-matrix adhesion and is a common outcome of pathological events in a variety of conditions, including autoimmune and genetic diseases, viral and bacterial infections, or injury by physical and chemical factors. Autoantibodies against structural components maintaining cell-cell and cell-matrix adhesion induce tissue damage in autoimmune blistering diseases. Detection of these autoantibodies either tissue-bound or circulating in serum is essential to diagnose the autoimmune nature of disease. Various immunofluorescence methods as well as molecular immunoassays, including enzyme-linked immunosorbent assay and immunoblotting, belong to the modern diagnostic algorithms for these disorders. There is still a considerable need to increase awareness of the rare autoimmune blistering diseases, which often show a severe, chronic-relapsing course, among physicians and the public. This review article describes the immunopathological features of autoimmune bullous diseases and the molecular immunoassays currently available for their diagnosis and monitoring. PMID:24160488

[CONTEMPORARY MOLECULAR-GENETIC METHODS USED FOR ETIOLOGIC DIAGNOSTICS OF SEPSIS].

PubMed

Gavrilov, S N; Skachkova, T S; Shipulina, O Yu; Savochkina, Yu A; Shipulin, G A; Maleev, V V

2016-01-01

Etiologic diagnostics of sepsis is one of the most difficult problems of contemporary medicine due to a wide variety of sepsis causative agents, many of which are components of normal human microflora. Disadvantages of contemporary "golden standard" of microbiologic diagnostics of sepsis etiology by seeding of blood for sterility are duration of cultivation, limitation in detection of non-cultivable forms of microorganisms, significant effect of preliminary empiric antibiotics therapy on results of the analysis. Methods of molecular diagnostics that are being actively developed and integrated during the last decade are deprived of these disadvantages. Main contemporary methods of molecular-biological diagnostics are examined in the review, actualdata on their diagnostic characteristic are provided. Special attention is given to methods of PCR-diagnostics, including novel Russian developments. Methods of nucleic acid hybridization and proteomic analysis are examined in comparative aspect. Evaluation of application and perspectives of development of methods of molecular diagnostics of sepsis is given.

The Diagnostic Challenge Competition: Probabilistic Techniques for Fault Diagnosis in Electrical Power Systems

NASA Technical Reports Server (NTRS)

Ricks, Brian W.; Mengshoel, Ole J.

2009-01-01

Reliable systems health management is an important research area of NASA. A health management system that can accurately and quickly diagnose faults in various on-board systems of a vehicle will play a key role in the success of current and future NASA missions. We introduce in this paper the ProDiagnose algorithm, a diagnostic algorithm that uses a probabilistic approach, accomplished with Bayesian Network models compiled to Arithmetic Circuits, to diagnose these systems. We describe the ProDiagnose algorithm, how it works, and the probabilistic models involved. We show by experimentation on two Electrical Power Systems based on the ADAPT testbed, used in the Diagnostic Challenge Competition (DX 09), that ProDiagnose can produce results with over 96% accuracy and less than 1 second mean diagnostic time.

Clinical study of quantitative diagnosis of early cervical cancer based on the classification of acetowhitening kinetics

NASA Astrophysics Data System (ADS)

Wu, Tao; Cheung, Tak-Hong; Yim, So-Fan; Qu, Jianan Y.

2010-03-01

A quantitative colposcopic imaging system for the diagnosis of early cervical cancer is evaluated in a clinical study. This imaging technology based on 3-D active stereo vision and motion tracking extracts diagnostic information from the kinetics of acetowhitening process measured from the cervix of human subjects in vivo. Acetowhitening kinetics measured from 137 cervical sites of 57 subjects are analyzed and classified using multivariate statistical algorithms. Cross-validation methods are used to evaluate the performance of the diagnostic algorithms. The results show that an algorithm for screening precancer produced 95% sensitivity (SE) and 96% specificity (SP) for discriminating normal and human papillomavirus (HPV)-infected tissues from cervical intraepithelial neoplasia (CIN) lesions. For a diagnostic algorithm, 91% SE and 90% SP are achieved for discriminating normal tissue, HPV infected tissue, and low-grade CIN lesions from high-grade CIN lesions. The results demonstrate that the quantitative colposcopic imaging system could provide objective screening and diagnostic information for early detection of cervical cancer.

SEOM-SERAM-SEMNIM guidelines on the use of functional and molecular imaging techniques in advanced non-small-cell lung cancer.

PubMed

Fernández Pérez, G; Sánchez Escribano, R; García Vicente, A M; Luna Alcalá, A; Ceballos Viro, J; Delgado Bolton, R C; Vilanova Busquets, J C; Sánchez Rovira, P; Fierro Alanis, M P; García Figueiras, R; Alés Martínez, J E

2018-05-25

Imaging in oncology is an essential tool for patient management but its potential is being profoundly underutilized. Each of the techniques used in the diagnostic process also conveys functional information that can be relevant in treatment decision making. New imaging algorithms and techniques enhance our knowledge about the phenotype of the tumor and its potential response to different therapies. Functional imaging can be defined as the one that provides information beyond the purely morphological data, and include all the techniques that make it possible to measure specific physiological functions of the tumor, whereas molecular imaging would include techniques that allow us to measure metabolic changes. Functional and molecular techniques included in this document are based on multi-detector computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), magnetic resonance imaging (MRI), and hybrid equipments, integrating PET with CT (PET/CT) or MRI (PET-MRI). Lung cancer is one of the most frequent and deadly tumors although survival is increasing thanks to advances in diagnostic methods and new treatments. This increased survival poises challenges in terms of proper follow-up and definitions of response and progression, as exemplified by immune therapy-related pseudoprogression. In this consensus document, the use of functional and molecular imaging techniques will be addressed to exploit their current potential and explore future applications in the diagnosis, evaluation of response and detection of recurrence of advanced NSCLC. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

FPGA based charge acquisition algorithm for soft x-ray diagnostics system

NASA Astrophysics Data System (ADS)

Wojenski, A.; Kasprowicz, G.; Pozniak, K. T.; Zabolotny, W.; Byszuk, A.; Juszczyk, B.; Kolasinski, P.; Krawczyk, R. D.; Zienkiewicz, P.; Chernyshova, M.; Czarski, T.

2015-09-01

Soft X-ray (SXR) measurement systems working in tokamaks or with laser generated plasma can expect high photon fluxes. Therefore it is necessary to focus on data processing algorithms to have the best possible efficiency in term of processed photon events per second. This paper refers to recently designed algorithm and data-flow for implementation of charge data acquisition in FPGA. The algorithms are currently on implementation stage for the soft X-ray diagnostics system. In this paper despite of the charge processing algorithm is also described general firmware overview, data storage methods and other key components of the measurement system. The simulation section presents algorithm performance and expected maximum photon rate.

Minimally Invasive Molecular Staging (MIMS) RT-PCR Breast Cancer Study

DTIC Science & Technology

2007-03-31

per se. 15. SUBJECT TERMS Breast cancer, real-time PCR, molecular diagnostics , micrometastases 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF 18...a superior molecular marker for detection of non- small cell lung cancer in peripheral blood. Journal of Molecular Diagnostics . 5:23 7-42, 2003. With...Journal of Molecular Diagnostics . 5:237-42, 2003 10. Mikhitarian K, Allen A, Reott S, Hoover L, Allen A, Cole DJ, Gillanders WE, and Mitas M. Enhanced

Discrimination of premalignant lesions and cancer tissues from normal gastric tissues using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Luo, Shuwen; Chen, Changshui; Mao, Hua; Jin, Shaoqin

2013-06-01

The feasibility of early detection of gastric cancer using near-infrared (NIR) Raman spectroscopy (RS) by distinguishing premalignant lesions (adenomatous polyp, n=27) and cancer tissues (adenocarcinoma, n=33) from normal gastric tissues (n=45) is evaluated. Significant differences in Raman spectra are observed among the normal, adenomatous polyp, and adenocarcinoma gastric tissues at 936, 1003, 1032, 1174, 1208, 1323, 1335, 1450, and 1655 cm-1. Diverse statistical methods are employed to develop effective diagnostic algorithms for classifying the Raman spectra of different types of ex vivo gastric tissues, including principal component analysis (PCA), linear discriminant analysis (LDA), and naive Bayesian classifier (NBC) techniques. Compared with PCA-LDA algorithms, PCA-NBC techniques together with leave-one-out, cross-validation method provide better discriminative results of normal, adenomatous polyp, and adenocarcinoma gastric tissues, resulting in superior sensitivities of 96.3%, 96.9%, and 96.9%, and specificities of 93%, 100%, and 95.2%, respectively. Therefore, NIR RS associated with multivariate statistical algorithms has the potential for early diagnosis of gastric premalignant lesions and cancer tissues in molecular level.

Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and Antimicrobial Stewardship.

PubMed

Messacar, Kevin; Parker, Sarah K; Todd, James K; Dominguez, Samuel R

2017-03-01

New rapid molecular diagnostic technologies for infectious diseases enable expedited accurate microbiological diagnoses. However, diagnostic stewardship and antimicrobial stewardship are necessary to ensure that these technologies conserve, rather than consume, additional health care resources and optimally affect patient care. Diagnostic stewardship is needed to implement appropriate tests for the clinical setting and to direct testing toward appropriate patients. Antimicrobial stewardship is needed to ensure prompt appropriate clinical action to translate faster diagnostic test results in the laboratory into improved outcomes at the bedside. This minireview outlines the roles of diagnostic stewardship and antimicrobial stewardship in the implementation of rapid molecular infectious disease diagnostics. Copyright © 2017 American Society for Microbiology.

Multidisciplinary molecular diagnostics: the 9th European meeting on molecular diagnostics.

PubMed

Loonen, Anne J M; Schuurman, Rob; van den Brule, Adriaan J C

2016-01-01

This report presents a summary of the 9th European Meeting on Molecular Diagnostics held in Noordwijk, The Netherlands, 14-16 October 2015. This 3-day conference covered many relevant topics in the field of molecular diagnostics in humans, including infectious disease, oncology, outbreak management, population-based cancer screening, standardization and quality control, chronic diseases and pharmacogenetics. Beyond these different areas, shared values are new technologies and novel technical and clinical applications. Approximately 450 participants, the majority coming from European countries, attended the meeting. Besides high quality scientific presentations, more than 35 diagnostic companies presented their latest innovations, altogether in an informal and inspiring scientific ambience.

Integrating molecular diagnostics into histopathology training: the Belfast model.

PubMed

Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

2014-07-01

Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Biomarkers for personalized oncology: recent advances and future challenges.

PubMed

Kalia, Madhu

2015-03-01

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and gastrointestinal tumors; anaplastic lymphoma kinase (ALK) inhibitors in lung cancer with EML4-ALk fusion; HER2/neu blockage in HER2/neu-positive breast cancer; and epidermal growth factor receptors (EGFR) inhibition in EGFR-mutated lung cancer. This review presents the current state of our knowledge of biomarkers in five selected cancers: chronic myeloid leukemia, colorectal cancer, breast cancer, non-small cell lung cancer and melanoma. Copyright © 2015 Elsevier Inc. All rights reserved.

[X-ray endoscopic semiotics and diagnostic algorithm of radiation studies of preneoplastic gastric mucosa changes].

PubMed

Akberov, R F; Gorshkov, A N

1997-01-01

The X-ray endoscopic semiotics of precancerous gastric mucosal changes (epithelial dysplasia, intestinal epithelial rearrangement) was examined by the results of 1574 gastric examination. A diagnostic algorithm was developed for radiation studies in the diagnosis of the above pathology.

The clinical evaluation of infantile nystagmus: What to do first and why

PubMed Central

Bertsch, Morgan; Floyd, Michael; Kehoe, Taylor; Pfeifer, Wanda; Drack, Arlene V.

2017-01-01

Introduction Infantile nystagmus has many causes, some life threatening. We determined the most common diagnoses in order to develop a testing algorithm. Methods Retrospective chart review. Exclusion criteria were no nystagmus, acquired after 6 months, or lack of examination. Data collected: pediatric eye examination findings, ancillary testing, order of testing, referral, and final diagnoses. Final diagnosis was defined as meeting published clinical criteria and/or confirmed by diagnostic testing. Patients with a diagnosis not meeting the definition were “unknown.” Patients with incomplete testing were “incomplete.” Patients with multiple plausible etiologies were “multifactorial.” Patients with negative complete workup were “motor.” Results 284 charts were identified; 202 met inclusion criteria. The 3 most common causes were Albinism(19%), Leber Congenital Amaurosis(LCA)(14%) and Non-LCA retinal dystrophy (13%). Anatomic retinal disorders comprised 10%, motor another 10%. The most common first test was MRI (74/202) with a diagnostic yield of 16%. For 28 MRI-first patients, nystagmus alone was the indication; for 46 MRI-first patients other neurologic signs were present. 0/28 nystagmus-only patients had a diagnostic MRI while 14/46 (30%) with neurologic signs did. Yield of ERG as first test was 56%, OCT 55%, and molecular genetic testing 47%. 90% of patients had an etiology identified. Conclusion The most common causes of infantile nystagmus were retinal disorders (56%), however the most common first test was brain MRI. For patients without other neurologic stigmata complete pediatric eye examination, ERG, OCT and molecular genetic testing had a higher yield than MRI scan. If MRI is not diagnostic, a complete ophthalmologic workup should be pursued. PMID:28177849

Combination of culture, antigen and toxin detection, and cytotoxin neutralization assay for optimal Clostridium difficile diagnostic testing

PubMed Central

Alfa, Michelle J; Sepehri, Shadi

2013-01-01

BACKGROUND: There has been a growing interest in developing an appropriate laboratory diagnostic algorithm for Clostridium difficile, mainly as a result of increases in both the number and severity of cases of C difficile infection in the past decade. A C difficile diagnostic algorithm is necessary because diagnostic kits, mostly for the detection of toxins A and B or glutamate dehydrogenase (GDH) antigen, are not sufficient as stand-alone assays for optimal diagnosis of C difficile infection. In addition, conventional reference methods for C difficile detection (eg, toxigenic culture and cytotoxin neutralization [CTN] assays) are not routinely practiced in diagnostic laboratory settings. OBJECTIVE: To review the four-step algorithm used at Diagnostic Services of Manitoba sites for the laboratory diagnosis of toxigenic C difficile. RESULT: One year of retrospective C difficile data using the proposed algorithm was reported. Of 5695 stool samples tested, 9.1% (n=517) had toxigenic C difficile. Sixty per cent (310 of 517) of toxigenic C difficile stools were detected following the first two steps of the algorithm. CTN confirmation of GDH-positive, toxin A- and B-negative assays resulted in detection of an additional 37.7% (198 of 517) of toxigenic C difficile. Culture of the third specimen, from patients who had two previous negative specimens, detected an additional 2.32% (12 of 517) of toxigenic C difficile samples. DISCUSSION: Using GDH antigen as the screening and toxin A and B as confirmatory test for C difficile, 85% of specimens were reported negative or positive within 4 h. Without CTN confirmation for GDH antigen and toxin A and B discordant results, 37% (195 of 517) of toxigenic C difficile stools would have been missed. Following the algorithm, culture was needed for only 2.72% of all specimens submitted for C difficile testing. CONCLUSION: The overview of the data illustrated the significance of each stage of this four-step C difficile algorithm and emphasized the value of using CTN assay and culture as parts of an algorithm that ensures accurate diagnosis of toxigenic C difficile. PMID:24421808

Autism Diagnostic Interview-Revised (ADI-R) Algorithms for Toddlers and Young Preschoolers: Application in a Non-US Sample of 1,104 Children

ERIC Educational Resources Information Center

de Bildt, Annelies; Sytema, Sjoerd; Zander, Eric; Bölte, Sven; Sturm, Harald; Yirmiya, Nurit; Yaari, Maya; Charman, Tony; Salomone, Erica; LeCouteur, Ann; Green, Jonathan; Bedia, Ricardo Canal; Primo, Patricia García; van Daalen, Emma; de Jonge, Maretha V.; Guðmundsdóttir, Emilía; Jóhannsdóttir, Sigurrós; Raleva, Marija; Boskovska, Meri; Rogé, Bernadette; Baduel, Sophie; Moilanen, Irma; Yliherva, Anneli; Buitelaar, Jan; Oosterling, Iris J.

2015-01-01

The current study aimed to investigate the Autism Diagnostic Interview-Revised (ADI-R) algorithms for toddlers and young preschoolers (Kim and Lord, "J Autism Dev Disord" 42(1):82-93, 2012) in a non-US sample from ten sites in nine countries (n = 1,104). The construct validity indicated a good fit of the algorithms. The diagnostic…

Systematic review of dermoscopy and digital dermoscopy/ artificial intelligence for the diagnosis of melanoma.

PubMed

Rajpara, S M; Botello, A P; Townend, J; Ormerod, A D

2009-09-01

Dermoscopy improves diagnostic accuracy of the unaided eye for melanoma, and digital dermoscopy with artificial intelligence or computer diagnosis has also been shown useful for the diagnosis of melanoma. At present there is no clear evidence regarding the diagnostic accuracy of dermoscopy compared with artificial intelligence. To evaluate the diagnostic accuracy of dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis and to compare the diagnostic accuracy of the different dermoscopic algorithms with each other and with digital dermoscopy/artificial intelligence for the detection of melanoma. A literature search on dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis was performed using several databases. Titles and abstracts of the retrieved articles were screened using a literature evaluation form. A quality assessment form was developed to assess the quality of the included studies. Heterogeneity among the studies was assessed. Pooled data were analysed using meta-analytical methods and comparisons between different algorithms were performed. Of 765 articles retrieved, 30 studies were eligible for meta-analysis. Pooled sensitivity for artificial intelligence was slightly higher than for dermoscopy (91% vs. 88%; P = 0.076). Pooled specificity for dermoscopy was significantly better than artificial intelligence (86% vs. 79%; P < 0.001). Pooled diagnostic odds ratio was 51.5 for dermoscopy and 57.8 for artificial intelligence, which were not significantly different (P = 0.783). There were no significance differences in diagnostic odds ratio among the different dermoscopic diagnostic algorithms. Dermoscopy and artificial intelligence performed equally well for diagnosis of melanocytic skin lesions. There was no significant difference in the diagnostic performance of various dermoscopy algorithms. The three-point checklist, the seven-point checklist and Menzies score had better diagnostic odds ratios than the others; however, these results need to be confirmed by a large-scale high-quality population-based study.

Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer.

PubMed

Ehteshami Bejnordi, Babak; Veta, Mitko; Johannes van Diest, Paul; van Ginneken, Bram; Karssemeijer, Nico; Litjens, Geert; van der Laak, Jeroen A W M; Hermsen, Meyke; Manson, Quirine F; Balkenhol, Maschenka; Geessink, Oscar; Stathonikos, Nikolaos; van Dijk, Marcory Crf; Bult, Peter; Beca, Francisco; Beck, Andrew H; Wang, Dayong; Khosla, Aditya; Gargeya, Rishab; Irshad, Humayun; Zhong, Aoxiao; Dou, Qi; Li, Quanzheng; Chen, Hao; Lin, Huang-Jing; Heng, Pheng-Ann; Haß, Christian; Bruni, Elia; Wong, Quincy; Halici, Ugur; Öner, Mustafa Ümit; Cetin-Atalay, Rengul; Berseth, Matt; Khvatkov, Vitali; Vylegzhanin, Alexei; Kraus, Oren; Shaban, Muhammad; Rajpoot, Nasir; Awan, Ruqayya; Sirinukunwattana, Korsuk; Qaiser, Talha; Tsang, Yee-Wah; Tellez, David; Annuscheit, Jonas; Hufnagl, Peter; Valkonen, Mira; Kartasalo, Kimmo; Latonen, Leena; Ruusuvuori, Pekka; Liimatainen, Kaisa; Albarqouni, Shadi; Mungal, Bharti; George, Ami; Demirci, Stefanie; Navab, Nassir; Watanabe, Seiryo; Seno, Shigeto; Takenaka, Yoichi; Matsuda, Hideo; Ahmady Phoulady, Hady; Kovalev, Vassili; Kalinovsky, Alexander; Liauchuk, Vitali; Bueno, Gloria; Fernandez-Carrobles, M Milagro; Serrano, Ismael; Deniz, Oscar; Racoceanu, Daniel; Venâncio, Rui

2017-12-12

Application of deep learning algorithms to whole-slide pathology images can potentially improve diagnostic accuracy and efficiency. Assess the performance of automated deep learning algorithms at detecting metastases in hematoxylin and eosin-stained tissue sections of lymph nodes of women with breast cancer and compare it with pathologists' diagnoses in a diagnostic setting. Researcher challenge competition (CAMELYON16) to develop automated solutions for detecting lymph node metastases (November 2015-November 2016). A training data set of whole-slide images from 2 centers in the Netherlands with (n = 110) and without (n = 160) nodal metastases verified by immunohistochemical staining were provided to challenge participants to build algorithms. Algorithm performance was evaluated in an independent test set of 129 whole-slide images (49 with and 80 without metastases). The same test set of corresponding glass slides was also evaluated by a panel of 11 pathologists with time constraint (WTC) from the Netherlands to ascertain likelihood of nodal metastases for each slide in a flexible 2-hour session, simulating routine pathology workflow, and by 1 pathologist without time constraint (WOTC). Deep learning algorithms submitted as part of a challenge competition or pathologist interpretation. The presence of specific metastatic foci and the absence vs presence of lymph node metastasis in a slide or image using receiver operating characteristic curve analysis. The 11 pathologists participating in the simulation exercise rated their diagnostic confidence as definitely normal, probably normal, equivocal, probably tumor, or definitely tumor. The area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.556 to 0.994. The top-performing algorithm achieved a lesion-level, true-positive fraction comparable with that of the pathologist WOTC (72.4% [95% CI, 64.3%-80.4%]) at a mean of 0.0125 false-positives per normal whole-slide image. For the whole-slide image classification task, the best algorithm (AUC, 0.994 [95% CI, 0.983-0.999]) performed significantly better than the pathologists WTC in a diagnostic simulation (mean AUC, 0.810 [range, 0.738-0.884]; P < .001). The top 5 algorithms had a mean AUC that was comparable with the pathologist interpreting the slides in the absence of time constraints (mean AUC, 0.960 [range, 0.923-0.994] for the top 5 algorithms vs 0.966 [95% CI, 0.927-0.998] for the pathologist WOTC). In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints. Whether this approach has clinical utility will require evaluation in a clinical setting.

Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

PubMed

Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

2016-04-01

With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

Recommendations for the inclusion of Fabry disease as a rare febrile condition in existing algorithms for fever of unknown origin.

PubMed

Manna, Raffaele; Cauda, Roberto; Feriozzi, Sandro; Gambaro, Giovanni; Gasbarrini, Antonio; Lacombe, Didier; Livneh, Avi; Martini, Alberto; Ozdogan, Huri; Pisani, Antonio; Riccio, Eleonora; Verrecchia, Elena; Dagna, Lorenzo

2017-10-01

Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.

Progress in the molecular diagnosis of Lyme disease.

PubMed

Ružić-Sabljić, Eva; Cerar, Tjaša

2017-01-01

Current laboratory testing of Lyme borreliosis mostly relies on serological methods with known limitations. Diagnostic modalities enabling direct detection of pathogen at the onset of the clinical signs could overcome some of the limitations. Molecular methods detecting borrelial DNA seem to be the ideal solution, although there are some aspects that need to be considered. Areas covered: This review represent summary and discussion of the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) together with our own experience on molecular diagnosis of Lyme disease. Expert commentary: Molecular methods are promising and currently serve as supporting diagnostic testing in Lyme borreliosis. Since the field of molecular diagnostics is under rapid development, molecular testing could become an important diagnostic modality.

Myophosphorylase (PYGM) mutations determined by next generation sequencing in a cohort from Turkey with McArdle disease.

PubMed

Inal-Gültekin, Güldal; Toptaş-Hekimoğlu, Bahar; Görmez, Zeliha; Gelişin, Özlem; Durmuş, Hacer; Ergüner, Bekir; Demirci, Hüseyin; Sağıroğlu, Mahmut Ş; Parman, Yeşim; Deymeer, Feza; Yılmaz-Aydoğan, Hülya; Pençe, Sadrettin; Bekircan-Kurt, Can Ebru; Tan, Ersin; Erdem-Özdamar, Sevim; Üstek, Duran; Giger, Urs; Öztürk, Oğuz; Serdaroğlu-Oflazer, Piraye

2017-11-01

This study aimed to identify PYGM mutations in patients with McArdle disease from Turkey by next generation sequencing (NGS). Genomic DNA was extracted from the blood of the McArdle patients (n = 67) and unrelated healthy volunteers (n = 53). The PYGM gene was sequenced with NGS and the observed mutations were validated by direct Sanger sequencing. A diagnostic algorithm was developed for patients with suspected McArdle disease. A total of 16 deleterious PYGM mutations were identified, of which 5 were novel, including 1 splice-site donor, 1 frame-shift, and 3 non-synonymous variants. The p.Met1Val (27-patients/11-families) was the most common PYGM mutation, followed by p.Arg576* (6/4), c.1827+7A>G (5/4), c.772+2_3delTG (5/3), p.Phe710del (4/2), p.Lys754Asnfs (2/1), and p.Arg50* (1/1). A molecular diagnostic flowchart is proposed for the McArdle patients in Turkey, covering the 6 most common PYGM mutations found in Turkey as well as the most common mutation in Europe. The diagnostic algorithm may alleviate the need for muscle biopsies in 77.6% of future patients. A prevalence of any of the mutations to a geographical region in Turkey was not identified. Furthermore, the NGS approach to sequence the entire PYGM gene was successful in detecting a common missense mutation and discovering novel mutations in this population study. Copyright © 2017 Elsevier B.V. All rights reserved.

Qualitative Event-Based Diagnosis: Case Study on the Second International Diagnostic Competition

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Roychoudhury, Indranil

2010-01-01

We describe a diagnosis algorithm entered into the Second International Diagnostic Competition. We focus on the first diagnostic problem of the industrial track of the competition in which a diagnosis algorithm must detect, isolate, and identify faults in an electrical power distribution testbed and provide corresponding recovery recommendations. The diagnosis algorithm embodies a model-based approach, centered around qualitative event-based fault isolation. Faults produce deviations in measured values from model-predicted values. The sequence of these deviations is matched to those predicted by the model in order to isolate faults. We augment this approach with model-based fault identification, which determines fault parameters and helps to further isolate faults. We describe the diagnosis approach, provide diagnosis results from running the algorithm on provided example scenarios, and discuss the issues faced, and lessons learned, from implementing the approach

Parallel, stochastic measurement of molecular surface area.

PubMed

Juba, Derek; Varshney, Amitabh

2008-08-01

Biochemists often wish to compute surface areas of proteins. A variety of algorithms have been developed for this task, but they are designed for traditional single-processor architectures. The current trend in computer hardware is towards increasingly parallel architectures for which these algorithms are not well suited. We describe a parallel, stochastic algorithm for molecular surface area computation that maps well to the emerging multi-core architectures. Our algorithm is also progressive, providing a rough estimate of surface area immediately and refining this estimate as time goes on. Furthermore, the algorithm generates points on the molecular surface which can be used for point-based rendering. We demonstrate a GPU implementation of our algorithm and show that it compares favorably with several existing molecular surface computation programs, giving fast estimates of the molecular surface area with good accuracy.

Point-of-care technologies for molecular diagnostics using a drop of blood.

PubMed

Song, Yujun; Huang, Yu-Yen; Liu, Xuewu; Zhang, Xiaojing; Ferrari, Mauro; Qin, Lidong

2014-03-01

Molecular diagnostics is crucial for prevention, identification, and treatment of disease. Traditional technologies for molecular diagnostics using blood are limited to laboratory use because they rely on sample purification and sophisticated instruments, are labor and time intensive, expensive, and require highly trained operators. This review discusses the frontiers of point-of-care (POC) diagnostic technologies using a drop of blood obtained from a finger prick. These technologies, including emerging biotechnologies, nanotechnologies, and microfluidics, hold the potential for rapid, accurate, and inexpensive disease diagnostics. Copyright © 2014 Elsevier Ltd. All rights reserved.

Advancing the education in molecular diagnostics: the IFCC-Initiative "Clinical Molecular Biology Curriculum" (C-CMBC); a ten-year experience.

PubMed

Lianidou, Evi; Ahmad-Nejad, Parviz; Ferreira-Gonzalez, Andrea; Izuhara, Kenji; Cremonesi, Laura; Schroeder, Maria-Eugenia; Richter, Karin; Ferrari, Maurizio; Neumaier, Michael

2014-09-25

Molecular techniques are becoming commonplace in the diagnostic laboratory. Their applications influence all major phases of laboratory medicine including predisposition/genetic risk, primary diagnosis, therapy stratification and prognosis. Readily available laboratory hardware and wetware (i.e. consumables and reagents) foster rapid dissemination to countries that are just establishing molecular testing programs. Appropriate skill levels extending beyond the technical procedure are required for analytical and diagnostic proficiency that is mandatory in molecular genetic testing. An international committee (C-CMBC) of the International Federation for Clinical Chemistry (IFCC) was established to disseminate skills in molecular genetic testing in member countries embarking on the respective techniques. We report the ten-year experience with different teaching and workshop formats for beginners in molecular diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

A Framework to Debug Diagnostic Matrices

NASA Technical Reports Server (NTRS)

Kodal, Anuradha; Robinson, Peter; Patterson-Hine, Ann

2013-01-01

Diagnostics is an important concept in system health and monitoring of space operations. Many of the existing diagnostic algorithms utilize system knowledge in the form of diagnostic matrix (D-matrix, also popularly known as diagnostic dictionary, fault signature matrix or reachability matrix) gleaned from physical models. But, sometimes, this may not be coherent to obtain high diagnostic performance. In such a case, it is important to modify this D-matrix based on knowledge obtained from other sources such as time-series data stream (simulated or maintenance data) within the context of a framework that includes the diagnostic/inference algorithm. A systematic and sequential update procedure, diagnostic modeling evaluator (DME) is proposed to modify D-matrix and wrapper logic considering least expensive solution first. This iterative procedure includes conditions ranging from modifying 0s and 1s in the matrix, or adding/removing the rows (failure sources) columns (tests). We will experiment this framework on datasets from DX challenge 2009.

Eosinophilic pustular folliculitis: A proposal of diagnostic and therapeutic algorithms.

PubMed

Nomura, Takashi; Katoh, Mayumi; Yamamoto, Yosuke; Miyachi, Yoshiki; Kabashima, Kenji

2016-11-01

Eosinophilic pustular folliculitis (EPF) is a sterile inflammatory dermatosis of unknown etiology. In addition to classic EPF, which affects otherwise healthy individuals, an immunocompromised state can cause immunosuppression-associated EPF (IS-EPF), which may be referred to dermatologists in inpatient services for assessments. Infancy-associated EPF (I-EPF) is the least characterized subtype, being observed mainly in non-Japanese infants. Diagnosis of EPF is challenging because its lesions mimic those of other common diseases, such as acne and dermatomycosis. Furthermore, there is no consensus regarding the treatment for each subtype of EPF. Here, we created procedure algorithms that facilitate the diagnosis and selection of therapeutic options on the basis of published work available in the public domain. Our diagnostic algorithm comprised a simple flowchart to direct physicians toward proper diagnosis. Recommended regimens were summarized in an easy-to-comprehend therapeutic algorithm for each subtype of EPF. These algorithms would facilitate the diagnostic and therapeutic procedure of EPF. © 2016 Japanese Dermatological Association.

Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach.

PubMed

Südmeyer, Martin; Antke, Christina; Zizek, Tanja; Beu, Markus; Nikolaus, Susanne; Wojtecki, Lars; Schnitzler, Alfons; Müller, Hans-Wilhelm

2011-05-01

In vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration and sympathetic cardiac innervation with SPECT is used to distinguish idiopathic Parkinson disease (PD) from atypical parkinsonian disorder (APD). However, the diagnostic accuracy of these imaging approaches as stand-alone procedures is often unsatisfying. The aim of this study was therefore to evaluate to which extent diagnostic accuracy can be increased by their combined use together with a multidimensional statistical algorithm. The SPECT radiotracers (123)I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide (IBZM), (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (FP-CIT), and meta-(123)I-iodobenzylguanidine (MIBG) were used to assess striatal postsynaptic D(2) receptor binding, striatal presynaptic dopamine transporter binding, and myocardial adrenergic innervation, respectively. Thirty-one PD and 17 APD patients were prospectively investigated. PD and APD diagnoses were established using consensus criteria and reevaluated after 37.4 ± 12.4 and 26 ± 11.6 mo in PD and APD, respectively. Test accuracy (TA) for PD-APD differentiation was computed for all logical (Boolean) combinations of imaging modalities by receiver-operating-characteristic analysis--that is, after multidimensional optimization of cutoff values. Analysis showed moderate TA for PD-APD differentiation using each molecular approach alone (IBZM, 79%; MIBG, 73%; and FP-CIT, 73%). For combined use, the highest TA resulted under the assumption that at least 2 of the 3 biologic markers had to be positive for APD using the following cutoff values: 1.46 or less for IBZM, less than 2.10 for FP-CIT, and greater than 1.43 for MIBG. This algorithm distinguished APD from PD with a sensitivity of 94%, specificity of 94% (TA, 94%), positive predictive value of 89%, and negative predictive value of 97%. Results suggest that the multidimensional combination of FP-CIT, IBZM, and MIBG scintigraphy is likely to significantly increase TA in differentiating PD from APD. The differential diagnosis of degenerative parkinsonism may thus be facilitated.

Laboratory practice guidelines for detecting and reporting JAK2 and MPL mutations in myeloproliferative neoplasms: a report of the Association for Molecular Pathology.

PubMed

Gong, Jerald Z; Cook, James R; Greiner, Timothy C; Hedvat, Cyrus; Hill, Charles E; Lim, Megan S; Longtine, Janina A; Sabath, Daniel; Wang, Y Lynn

2013-11-01

Recurrent mutations in JAK2 and MPL genes are genetic hallmarks of BCR-ABL1-negative myeloproliferative neoplasms. Detection of JAK2 and MPL mutations has been incorporated into routine diagnostic algorithms for these diseases. This Special Article summarizes results from a nationwide laboratory survey of JAK2 and MPL mutation analysis. Based on the current practice pattern and the literature, this Special Article provides recommendations and guidelines for laboratory practice for detection of mutations in the JAK2 and MPL genes, including clinical manifestations for prompting the mutation analysis, current and recommended methodologies for testing the mutations, and standardization for reporting the test results. This Special Article also points to future directions for genomic testing in BCR-ABL1-negative myeloproliferative neoplasms. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

[Hereditary ectopia lentis].

PubMed

Neuhann, T M

2015-03-01

If not due to trauma, ectopia lentis is usually caused genetically. It is a main symptom of several syndromal disorders such as Marfan syndrome or homocystinuria. Also other connective tissue disorders convey an elevated risk for ectopia lentis. Isolated ectopia lentis is frequently caused by genetic alterations as well, most commonly due to mutations in ADAMTSL4. Depending on the molecular basis, the consequences for the management of patients may differ significantly: On the one hand, possible accompanying symptoms may require a specific surveillance and treatment. Also, the risk for other family members to develop ectopia lentis or accompanying symptoms can only be determined if the genetic cause and thus inheritance pattern are known. This review describes the different types and genetic causes of syndromal and isolated ectopia lentis as well as possible consequences for the patients; also it presents a sensible algorithm for the molecular diagnostic approach. Georg Thieme Verlag KG Stuttgart · New York.

Real-time Raman spectroscopy for in vivo, online gastric cancer diagnosis during clinical endoscopic examination.

PubMed

Duraipandian, Shiyamala; Sylvest Bergholt, Mads; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Bok Yan So, Jimmy; Shabbir, Asim; Huang, Zhiwei

2012-08-01

Optical spectroscopic techniques including reflectance, fluorescence and Raman spectroscopy have shown promising potential for in vivo precancer and cancer diagnostics in a variety of organs. However, data-analysis has mostly been limited to post-processing and off-line algorithm development. In this work, we develop a fully automated on-line Raman spectral diagnostics framework integrated with a multimodal image-guided Raman technique for real-time in vivo cancer detection at endoscopy. A total of 2748 in vivo gastric tissue spectra (2465 normal and 283 cancer) were acquired from 305 patients recruited to construct a spectral database for diagnostic algorithms development. The novel diagnostic scheme developed implements on-line preprocessing, outlier detection based on principal component analysis statistics (i.e., Hotelling's T2 and Q-residuals) for tissue Raman spectra verification as well as for organ specific probabilistic diagnostics using different diagnostic algorithms. Free-running optical diagnosis and processing time of < 0.5 s can be achieved, which is critical to realizing real-time in vivo tissue diagnostics during clinical endoscopic examination. The optimized partial least squares-discriminant analysis (PLS-DA) models based on the randomly resampled training database (80% for learning and 20% for testing) provide the diagnostic accuracy of 85.6% [95% confidence interval (CI): 82.9% to 88.2%] [sensitivity of 80.5% (95% CI: 71.4% to 89.6%) and specificity of 86.2% (95% CI: 83.6% to 88.7%)] for the detection of gastric cancer. The PLS-DA algorithms are further applied prospectively on 10 gastric patients at gastroscopy, achieving the predictive accuracy of 80.0% (60/75) [sensitivity of 90.0% (27/30) and specificity of 73.3% (33/45)] for in vivo diagnosis of gastric cancer. The receiver operating characteristics curves further confirmed the efficacy of Raman endoscopy together with PLS-DA algorithms for in vivo prospective diagnosis of gastric cancer. This work successfully moves biomedical Raman spectroscopic technique into real-time, on-line clinical cancer diagnosis, especially in routine endoscopic diagnostic applications.

Real-time Raman spectroscopy for in vivo, online gastric cancer diagnosis during clinical endoscopic examination

NASA Astrophysics Data System (ADS)

Duraipandian, Shiyamala; Sylvest Bergholt, Mads; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Bok Yan So, Jimmy; Shabbir, Asim; Huang, Zhiwei

2012-08-01

Optical spectroscopic techniques including reflectance, fluorescence and Raman spectroscopy have shown promising potential for in vivo precancer and cancer diagnostics in a variety of organs. However, data-analysis has mostly been limited to post-processing and off-line algorithm development. In this work, we develop a fully automated on-line Raman spectral diagnostics framework integrated with a multimodal image-guided Raman technique for real-time in vivo cancer detection at endoscopy. A total of 2748 in vivo gastric tissue spectra (2465 normal and 283 cancer) were acquired from 305 patients recruited to construct a spectral database for diagnostic algorithms development. The novel diagnostic scheme developed implements on-line preprocessing, outlier detection based on principal component analysis statistics (i.e., Hotelling's T2 and Q-residuals) for tissue Raman spectra verification as well as for organ specific probabilistic diagnostics using different diagnostic algorithms. Free-running optical diagnosis and processing time of < 0.5 s can be achieved, which is critical to realizing real-time in vivo tissue diagnostics during clinical endoscopic examination. The optimized partial least squares-discriminant analysis (PLS-DA) models based on the randomly resampled training database (80% for learning and 20% for testing) provide the diagnostic accuracy of 85.6% [95% confidence interval (CI): 82.9% to 88.2%] [sensitivity of 80.5% (95% CI: 71.4% to 89.6%) and specificity of 86.2% (95% CI: 83.6% to 88.7%)] for the detection of gastric cancer. The PLS-DA algorithms are further applied prospectively on 10 gastric patients at gastroscopy, achieving the predictive accuracy of 80.0% (60/75) [sensitivity of 90.0% (27/30) and specificity of 73.3% (33/45)] for in vivo diagnosis of gastric cancer. The receiver operating characteristics curves further confirmed the efficacy of Raman endoscopy together with PLS-DA algorithms for in vivo prospective diagnosis of gastric cancer. This work successfully moves biomedical Raman spectroscopic technique into real-time, on-line clinical cancer diagnosis, especially in routine endoscopic diagnostic applications.

The Autism Diagnostic Observation Schedule, Module 4: Application of the Revised Algorithms in an Independent, Well-Defined, Dutch Sample (n = 93).

PubMed

de Bildt, Annelies; Sytema, Sjoerd; Meffert, Harma; Bastiaansen, Jojanneke A C J

2016-01-01

This study examined the discriminative ability of the revised Autism Diagnostic Observation Schedule module 4 algorithm (Hus and Lord in J Autism Dev Disord 44(8):1996-2012, 2014) in 93 Dutch males with Autism Spectrum Disorder (ASD), schizophrenia, psychopathy or controls. Discriminative ability of the revised algorithm ASD cut-off resembled the original algorithm ASD cut-off: highly specific for psychopathy and controls, lower sensitivity than Hus and Lord (2014; i.e. ASD .61, AD .53). The revised algorithm AD cut-off improved sensitivity over the original algorithm. Discriminating ASD from schizophrenia was still challenging, but the better-balanced sensitivity (.53) and specificity (.78) of the revised algorithm AD cut-off may aide clinicians' differential diagnosis. Findings support using the revised algorithm, being conceptually conform the other modules, thus improving comparability across the lifespan.

Comparison of biotyping methods as alternative identification tools to molecular typing of pathogenic Cryptococcus species in sub-Saharan Africa

PubMed Central

Nyazika, Tinashe K.; Robertson, Valerie J.; Nherera, Brenda; Mapondera, Prichard T.; Meis, Jacques F.; Hagen, Ferry

2015-01-01

Summary Cryptococcal meningitis is the leading fungal infection and AIDS defining opportunistic illness in patients with late stage HIV infection, particularly in South-East Asia and sub-Saharan Africa. Given the high mortality, clinical differences and the extensive ecological niche of Cryptococcus neoformans and Cryptococcus gattii species complexes, there is need for laboratories in sub-Sahara African countries to adopt new and alternative reliable diagnostic algorithms that rapidly identify and distinguish these species. We biotyped 74 and then amplified fragment length polymorphism (AFLP) genotyped 66 Cryptococcus isolates from a cohort of patients with HIV-associated cryptococcal meningitis. Cryptococcus gattii sensu lato was isolated at a prevalence of 16.7% (n = 11/66) and C. neoformans sensu stricto was responsible for 83.3% (n = 55/66) of the infections. l-Canavanine glycine bromothymol blue, yeast-carbon-base-d-proline-d-tryptophan and creatinine dextrose bromothymol blue thymine were able to distinguish pathogenic C. gattii sensu lato from C. neoformans sensu stricto species when compared with amplified fragment length polymorphism genotyping. This study demonstrates high C. gattii sensu lato prevalence in Zimbabwe. In addition, biotyping methods can be used as alternative diagnostic tools to molecular typing in resource-limited areas for differentiating pathogenic Cryptococcus species. PMID:26661484

Clinical application of high throughput molecular screening techniques for pharmacogenomics

PubMed Central

Wiita, Arun P; Schrijver, Iris

2011-01-01

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing. PMID:23226057

Comparison of biotyping methods as alternative identification tools to molecular typing of pathogenic Cryptococcus species in sub-Saharan Africa.

PubMed

Nyazika, Tinashe K; Robertson, Valerie J; Nherera, Brenda; Mapondera, Prichard T; Meis, Jacques F; Hagen, Ferry

2016-03-01

Cryptococcal meningitis is the leading fungal infection and AIDS defining opportunistic illness in patients with late stage HIV infection, particularly in South-East Asia and sub-Saharan Africa. Given the high mortality, clinical differences and the extensive ecological niche of Cryptococcus neoformans and Cryptococcus gattii species complexes, there is need for laboratories in sub-Sahara African countries to adopt new and alternative reliable diagnostic algorithms that rapidly identify and distinguish these species. We biotyped 74 and then amplified fragment length polymorphism (AFLP) genotyped 66 Cryptococcus isolates from a cohort of patients with HIV-associated cryptococcal meningitis. C. gattii sensu lato was isolated at a prevalence of 16.7% (n = 11/66) and C. neoformans sensu stricto was responsible for 83.3% (n = 55/66) of the infections. l-Canavanine glycine bromothymol blue, yeast-carbon-base-d-proline-d-tryptophan and creatinine dextrose bromothymol blue thymine were able to distinguish pathogenic C. gattii sensu lato from C. neoformans sensu stricto species when compared with AFLP genotyping. This study demonstrates high C. gattii sensu lato prevalence in Zimbabwe. In addition, biotyping methods can be used as alternative diagnostic tools to molecular typing in resource-limited areas for differentiating pathogenic Cryptococcus species. © 2015 Blackwell Verlag GmbH.

Isolation of RNA From Peripheral Blood Cells: A Validation Study for Molecular Diagnostics by Microarray and Kinetic RT-PCR Assays - Application in Aerospace Medicine

DTIC Science & Technology

2004-01-01

of RNA From Peripheral Blood Cells: A Validation Study for Molecular Diagnostics by Microarray and Kinetic RT-PCR Assays  Application in...VALIDATION STUDY FOR MOLECULAR DIAGNOSTICS BY MICROARRAY AND KINETIC RT-PCR ASSAYS  APPLICATION IN AEROSPACE MEDICINE INTRODUCTION Extraction of cellular

Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea.

PubMed

Severson, Carl A; Pendharkar, Sachin R; Ronksley, Paul E; Tsai, Willis H

2015-01-01

To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA. The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP-Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data. Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing-determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP-Bang or ANC, but required fewer questions and calculations. These data suggest that a two-step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP-Bang or ANC.

The role of molecular diagnostic testing in the management of thyroid nodules.

PubMed

Moore, Maureen D; Panjwani, Suraj; Gray, Katherine D; Finnerty, Brendan M; Zarnegar, Rasa; Fahey, Thomas J

2017-06-01

Fine needle aspiration (FNA) with cytologic examination remains the standard of care for investigation of thyroid nodules. However, as many as 30% of FNA samples are cytologically indeterminate for malignancy, which confounds clinical management. To reduce the burden of repeat diagnostic testing and unnecessary surgery, there has been extensive investigation into molecular markers that can be detected on FNA specimens to more accurately stratify a patient's risk of malignancy. Areas covered: In this review, the authors discuss recent evidence and progress in molecular markers used in the diagnosis of thyroid cancer highlighting somatic gene alterations, molecular technologies and microRNA analysis. Expert commentary: The goal of molecular markers is to improve diagnostic accuracy and aid clinicians in the preoperative management of thyroid lesions. Modalities such as direct mutation analysis, mRNA gene expression profiling, next-generation sequencing, and miRNA expression profiling have been explored to improve the diagnostic accuracy of thyroid nodule FNA. Although no perfect test has been discovered, molecular diagnostic testing has revolutionized the management of thyroid nodules.

A rational regulatory approach for positron emission tomography imaging probes: from "first in man" to NDA approval and reimbursement.

PubMed

Barrio, Jorge R; Marcus, Carol S; Hung, Joseph C; Keppler, Jennifer S

2004-01-01

We propose a new regulatory approach for positron emission tomography (PET) molecular imaging probes, essential tools in today's medicine. Even though the focus of this paper is on positron-emitting labeled probes, it is also justified to extend this proposed regulatory approach to other diagnostic nuclear medicine radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular imaging probes would be placed in a "no significant risk" category, similar to that category for devices in current Food and Drug Administration (FDA) regulations, based on overwhelming scientific evidence that demonstrates their faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research Committee (RDRC) will oversee all diagnostic research with these probes. The newly defined RDRC should approve "first in man" use; supervise a broader spectrum of diagnostic research protocols, including those looking to demonstrate initial efficacy, as well as multicenter clinical trials and the use of molecular imaging probes as a screening tool in drug discovery. The current investigational new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval (i.e., NDA) will be sought. The review will be done by a newly constituted Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the professional societies, who would provide a binding assessment of the adequacy of the safety and efficacy data. When the RDAC recommends its diagnostic use on scientific and medical grounds, the molecular imaging probe becomes FDA approved. After a molecular imaging probe is approved for a diagnostic indication, the existing mechanism to seek reimbursement will be utilized; and (4) the FDA would retain its direct oversight function for traditional manufacturers engaged in commercial distribution of the approved diagnostic molecular imaging probes (i.e., under NDA) to monitor compliance with existing US Pharmacopeia (USP) requirements. With abbreviated and more appropriate regulations, new PET molecular imaging probes for diagnostic use would be then rapidly incorporated into the mainstream diagnostic medicine. Equally importantly, this approach would facilitate the use of molecular imaging in drug discovery and development, which would substantially reduce the costs and time required to bring new therapeutic drugs to market.

Hybrid Neural-Network: Genetic Algorithm Technique for Aircraft Engine Performance Diagnostics Developed and Demonstrated

NASA Technical Reports Server (NTRS)

Kobayashi, Takahisa; Simon, Donald L.

2002-01-01

As part of the NASA Aviation Safety Program, a unique model-based diagnostics method that employs neural networks and genetic algorithms for aircraft engine performance diagnostics has been developed and demonstrated at the NASA Glenn Research Center against a nonlinear gas turbine engine model. Neural networks are applied to estimate the internal health condition of the engine, and genetic algorithms are used for sensor fault detection, isolation, and quantification. This hybrid architecture combines the excellent nonlinear estimation capabilities of neural networks with the capability to rank the likelihood of various faults given a specific sensor suite signature. The method requires a significantly smaller data training set than a neural network approach alone does, and it performs the combined engine health monitoring objectives of performance diagnostics and sensor fault detection and isolation in the presence of nominal and degraded engine health conditions.

Elucidating the Mechanism of p27 Inactivation by the Bcr-Abl Tyrosine Kinase

DTIC Science & Technology

2005-10-01

Grants 2002- Leukemia Research Fund Membership in Scientific Committees 2000- Molecular diagnostics (German competence network acute...transplantation, including reduced intensity conditioning. Hematological Diagnostics Standard morphology. Supervised molecular diagnostics in the

The PHQ-8 as a measure of current depression in the general population.

PubMed

Kroenke, Kurt; Strine, Tara W; Spitzer, Robert L; Williams, Janet B W; Berry, Joyce T; Mokdad, Ali H

2009-04-01

The eight-item Patient Health Questionnaire depression scale (PHQ-8) is established as a valid diagnostic and severity measure for depressive disorders in large clinical studies. Our objectives were to assess the PHQ-8 as a depression measure in a large, epidemiological population-based study, and to determine the comparability of depression as defined by the PHQ-8 diagnostic algorithm vs. a PHQ-8 cutpoint > or = 10. Random-digit-dialed telephone survey of 198,678 participants in the 2006 Behavioral Risk Factor Surveillance Survey (BRFSS), a population-based survey in the United States. Current depression as defined by either the DSM-IV based diagnostic algorithm (i.e., major depressive or other depressive disorder) of the PHQ-8 or a PHQ-8 score > or = 10; respondent sociodemographic characteristics; number of days of impairment in the past 30 days in multiple domains of health-related quality of life (HRQoL). The prevalence of current depression was similar whether defined by the diagnostic algorithm or a PHQ-8 score > or = 10 (9.1% vs. 8.6%). Depressed patients had substantially more days of impairment across multiple domains of HRQoL, and the impairment was nearly identical in depressed groups defined by either method. Of the 17,040 respondents with a PHQ-8 score > or = 10, major depressive disorder was present in 49.7%, other depressive disorder in 23.9%, depressed mood or anhedonia in another 22.8%, and no evidence of depressive disorder or depressive symptoms in only 3.5%. The PHQ-8 diagnostic algorithm rather than an independent structured psychiatric interview was used as the criterion standard. The PHQ-8 is a useful depression measure for population-based studies, and either its diagnostic algorithm or a cutpoint > or = 10 can be used for defining current depression.

An Efficient Reachability Analysis Algorithm

NASA Technical Reports Server (NTRS)

Vatan, Farrokh; Fijany, Amir

2008-01-01

A document discusses a new algorithm for generating higher-order dependencies for diagnostic and sensor placement analysis when a system is described with a causal modeling framework. This innovation will be used in diagnostic and sensor optimization and analysis tools. Fault detection, diagnosis, and prognosis are essential tasks in the operation of autonomous spacecraft, instruments, and in-situ platforms. This algorithm will serve as a power tool for technologies that satisfy a key requirement of autonomous spacecraft, including science instruments and in-situ missions.

Prosthetic joint infection development of an evidence-based diagnostic algorithm.

PubMed

Mühlhofer, Heinrich M L; Pohlig, Florian; Kanz, Karl-Georg; Lenze, Ulrich; Lenze, Florian; Toepfer, Andreas; Kelch, Sarah; Harrasser, Norbert; von Eisenhart-Rothe, Rüdiger; Schauwecker, Johannes

2017-03-09

Increasing rates of prosthetic joint infection (PJI) have presented challenges for general practitioners, orthopedic surgeons and the health care system in the recent years. The diagnosis of PJI is complex; multiple diagnostic tools are used in the attempt to correctly diagnose PJI. Evidence-based algorithms can help to identify PJI using standardized diagnostic steps. We reviewed relevant publications between 1990 and 2015 using a systematic literature search in MEDLINE and PUBMED. The selected search results were then classified into levels of evidence. The keywords were prosthetic joint infection, biofilm, diagnosis, sonication, antibiotic treatment, implant-associated infection, Staph. aureus, rifampicin, implant retention, pcr, maldi-tof, serology, synovial fluid, c-reactive protein level, total hip arthroplasty (THA), total knee arthroplasty (TKA) and combinations of these terms. From an initial 768 publications, 156 publications were stringently reviewed. Publications with class I-III recommendations (EAST) were considered. We developed an algorithm for the diagnostic approach to display the complex diagnosis of PJI in a clear and logically structured process according to ISO 5807. The evidence-based standardized algorithm combines modern clinical requirements and evidence-based treatment principles. The algorithm provides a detailed transparent standard operating procedure (SOP) for diagnosing PJI. Thus, consistently high, examiner-independent process quality is assured to meet the demands of modern quality management in PJI diagnosis.

A randomized controlled trial of a diagnostic algorithm for symptoms of uncomplicated cystitis at an out-of-hours service

PubMed Central

Grude, Nils; Lindbaek, Morten

2015-01-01

Objective. To compare the clinical outcome of patients presenting with symptoms of uncomplicated cystitis who were seen by a doctor, with patients who were given treatment following a diagnostic algorithm. Design. Randomized controlled trial. Setting. Out-of-hours service, Oslo, Norway. Intervention. Women with typical symptoms of uncomplicated cystitis were included in the trial in the time period September 2010–November 2011. They were randomized into two groups. One group received standard treatment according to the diagnostic algorithm, the other group received treatment after a regular consultation by a doctor. Subjects. Women (n = 441) aged 16–55 years. Mean age in both groups 27 years. Main outcome measures. Number of days until symptomatic resolution. Results. No significant differences were found between the groups in the basic patient demographics, severity of symptoms, or percentage of urine samples with single culture growth. A median of three days until symptomatic resolution was found in both groups. By day four 79% in the algorithm group and 72% in the regular consultation group were free of symptoms (p = 0.09). The number of patients who contacted a doctor again in the follow-up period and received alternative antibiotic treatment was insignificantly higher (p = 0.08) after regular consultation than after treatment according to the diagnostic algorithm. There were no cases of severe pyelonephritis or hospital admissions during the follow-up period. Conclusion. Using a diagnostic algorithm is a safe and efficient method for treating women with symptoms of uncomplicated cystitis at an out-of-hours service. This simplification of treatment strategy can lead to a more rational use of consultation time and a stricter adherence to National Antibiotic Guidelines for a common disorder. PMID:25961367

A randomized controlled trial of a diagnostic algorithm for symptoms of uncomplicated cystitis at an out-of-hours service.

PubMed

Bollestad, Marianne; Grude, Nils; Lindbaek, Morten

2015-06-01

To compare the clinical outcome of patients presenting with symptoms of uncomplicated cystitis who were seen by a doctor, with patients who were given treatment following a diagnostic algorithm. Randomized controlled trial. Out-of-hours service, Oslo, Norway. Women with typical symptoms of uncomplicated cystitis were included in the trial in the time period September 2010-November 2011. They were randomized into two groups. One group received standard treatment according to the diagnostic algorithm, the other group received treatment after a regular consultation by a doctor. Women (n = 441) aged 16-55 years. Mean age in both groups 27 years. Number of days until symptomatic resolution. No significant differences were found between the groups in the basic patient demographics, severity of symptoms, or percentage of urine samples with single culture growth. A median of three days until symptomatic resolution was found in both groups. By day four 79% in the algorithm group and 72% in the regular consultation group were free of symptoms (p = 0.09). The number of patients who contacted a doctor again in the follow-up period and received alternative antibiotic treatment was insignificantly higher (p = 0.08) after regular consultation than after treatment according to the diagnostic algorithm. There were no cases of severe pyelonephritis or hospital admissions during the follow-up period. Using a diagnostic algorithm is a safe and efficient method for treating women with symptoms of uncomplicated cystitis at an out-of-hours service. This simplification of treatment strategy can lead to a more rational use of consultation time and a stricter adherence to National Antibiotic Guidelines for a common disorder.

Disruption of Fibroblast Growth Factor Receptor (FGFR) Signaling as an Approach to Prostate Cancer Therapy

DTIC Science & Technology

2006-04-01

and the abstract was published in the Journal of Molecular Diagnostics . The full length manuscript entitled “Increased expression and activity of...Recurrence. The Journal of Molecular Diagnostics 2004, (6)4: 431. Ozen M, Dixit S and Ittmann M: Molecular profiling of differentially expressed genes...in response to FGFR disruption in prostate cancer. the Journal of Molecular Diagnostics 7 (5): 680, 2005. Full Articles: 1. Ozen M and Ittmann M

Intellectual property considerations for molecular diagnostic development with emphasis on companion diagnostics.

PubMed

Glorikian, Harry; Warburg, Richard Jeremy; Moore, Kelly; Malinowski, Jennifer

2018-02-01

The development of molecular diagnostics is a complex endeavor, with multiple regulatory pathways to consider and numerous approaches to development and commercialization. Companion diagnostics, devices which are "essential for the safe and effective use of a corresponding drug or diagnostic product" (see U.S. Food & Drug Administration, In Vitro Diagnostics - Companion Diagnostics, U.S. Dept. of Health & Human Services(2016), available at https://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ucm407297.htm ) and complementary diagnostics, which are more broadly associated with a class of drug, are becoming increasingly important as integral components of the implementation of precision medicine. Areas covered: The following article will highlight the intellectual property ('IP') considerations pertinent to molecular diagnostics development with special emphasis on companion diagnostics. Expert opinion/commentary Summary: For all molecular diagnostics, intellectual property (IP) concerns are of paramount concern, whether the device will be marketed only in the United States or abroad. Taking steps to protect IP at each stage of product development is critical to optimize profitability of a diagnostic product. Also the legal framework around IP protection of diagnostic technologies has been changing over the previous few years and can be expected to continue to change in the foreseeable near future, thus, a comprehensive IP strategy should take into account the fact that changes in the law can be expected.

Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer

PubMed Central

Veta, Mitko; Johannes van Diest, Paul; van Ginneken, Bram; Karssemeijer, Nico; Litjens, Geert; van der Laak, Jeroen A. W. M.; Hermsen, Meyke; Manson, Quirine F; Balkenhol, Maschenka; Geessink, Oscar; Stathonikos, Nikolaos; van Dijk, Marcory CRF; Bult, Peter; Beca, Francisco; Beck, Andrew H; Wang, Dayong; Khosla, Aditya; Gargeya, Rishab; Irshad, Humayun; Zhong, Aoxiao; Dou, Qi; Li, Quanzheng; Chen, Hao; Lin, Huang-Jing; Heng, Pheng-Ann; Haß, Christian; Bruni, Elia; Wong, Quincy; Halici, Ugur; Öner, Mustafa Ümit; Cetin-Atalay, Rengul; Berseth, Matt; Khvatkov, Vitali; Vylegzhanin, Alexei; Kraus, Oren; Shaban, Muhammad; Rajpoot, Nasir; Awan, Ruqayya; Sirinukunwattana, Korsuk; Qaiser, Talha; Tsang, Yee-Wah; Tellez, David; Annuscheit, Jonas; Hufnagl, Peter; Valkonen, Mira; Kartasalo, Kimmo; Latonen, Leena; Ruusuvuori, Pekka; Liimatainen, Kaisa; Albarqouni, Shadi; Mungal, Bharti; George, Ami; Demirci, Stefanie; Navab, Nassir; Watanabe, Seiryo; Seno, Shigeto; Takenaka, Yoichi; Matsuda, Hideo; Ahmady Phoulady, Hady; Kovalev, Vassili; Kalinovsky, Alexander; Liauchuk, Vitali; Bueno, Gloria; Fernandez-Carrobles, M. Milagro; Serrano, Ismael; Deniz, Oscar; Racoceanu, Daniel; Venâncio, Rui

2017-01-01

Importance Application of deep learning algorithms to whole-slide pathology images can potentially improve diagnostic accuracy and efficiency. Objective Assess the performance of automated deep learning algorithms at detecting metastases in hematoxylin and eosin–stained tissue sections of lymph nodes of women with breast cancer and compare it with pathologists’ diagnoses in a diagnostic setting. Design, Setting, and Participants Researcher challenge competition (CAMELYON16) to develop automated solutions for detecting lymph node metastases (November 2015-November 2016). A training data set of whole-slide images from 2 centers in the Netherlands with (n = 110) and without (n = 160) nodal metastases verified by immunohistochemical staining were provided to challenge participants to build algorithms. Algorithm performance was evaluated in an independent test set of 129 whole-slide images (49 with and 80 without metastases). The same test set of corresponding glass slides was also evaluated by a panel of 11 pathologists with time constraint (WTC) from the Netherlands to ascertain likelihood of nodal metastases for each slide in a flexible 2-hour session, simulating routine pathology workflow, and by 1 pathologist without time constraint (WOTC). Exposures Deep learning algorithms submitted as part of a challenge competition or pathologist interpretation. Main Outcomes and Measures The presence of specific metastatic foci and the absence vs presence of lymph node metastasis in a slide or image using receiver operating characteristic curve analysis. The 11 pathologists participating in the simulation exercise rated their diagnostic confidence as definitely normal, probably normal, equivocal, probably tumor, or definitely tumor. Results The area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.556 to 0.994. The top-performing algorithm achieved a lesion-level, true-positive fraction comparable with that of the pathologist WOTC (72.4% [95% CI, 64.3%-80.4%]) at a mean of 0.0125 false-positives per normal whole-slide image. For the whole-slide image classification task, the best algorithm (AUC, 0.994 [95% CI, 0.983-0.999]) performed significantly better than the pathologists WTC in a diagnostic simulation (mean AUC, 0.810 [range, 0.738-0.884]; P < .001). The top 5 algorithms had a mean AUC that was comparable with the pathologist interpreting the slides in the absence of time constraints (mean AUC, 0.960 [range, 0.923-0.994] for the top 5 algorithms vs 0.966 [95% CI, 0.927-0.998] for the pathologist WOTC). Conclusions and Relevance In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints. Whether this approach has clinical utility will require evaluation in a clinical setting. PMID:29234806

Classifying syndromes in Chinese medicine using multi-label learning algorithm with relevant features for each label.

PubMed

Xu, Jin; Xu, Zhao-Xia; Lu, Ping; Guo, Rui; Yan, Hai-Xia; Xu, Wen-Jie; Wang, Yi-Qin; Xia, Chun-Ming

2016-11-01

To develop an effective Chinese Medicine (CM) diagnostic model of coronary heart disease (CHD) and to confifirm the scientifific validity of CM theoretical basis from an algorithmic viewpoint. Four types of objective diagnostic data were collected from 835 CHD patients by using a self-developed CM inquiry scale for the diagnosis of heart problems, a tongue diagnosis instrument, a ZBOX-I pulse digital collection instrument, and the sound of an attending acquisition system. These diagnostic data was analyzed and a CM diagnostic model was established using a multi-label learning algorithm (REAL). REAL was employed to establish a Xin (Heart) qi defificiency, Xin yang defificiency, Xin yin defificiency, blood stasis, and phlegm fifive-card CM diagnostic model, which had recognition rates of 80.32%, 89.77%, 84.93%, 85.37%, and 69.90%, respectively. The multi-label learning method established using four diagnostic models based on mutual information feature selection yielded good recognition results. The characteristic model parameters were selected by maximizing the mutual information for each card type. The four diagnostic methods used to obtain information in CM, i.e., observation, auscultation and olfaction, inquiry, and pulse diagnosis, can be characterized by these parameters, which is consistent with CM theory.

Seizures in the elderly: development and validation of a diagnostic algorithm.

PubMed

Dupont, Sophie; Verny, Marc; Harston, Sandrine; Cartz-Piver, Leslie; Schück, Stéphane; Martin, Jennifer; Puisieux, François; Alecu, Cosmin; Vespignani, Hervé; Marchal, Cécile; Derambure, Philippe

2010-05-01

Seizures are frequent in the elderly, but their diagnosis can be challenging. The objective of this work was to develop and validate an expert-based algorithm for the diagnosis of seizures in elderly people. A multidisciplinary group of neurologists and geriatricians developed a diagnostic algorithm using a combination of selected clinical, electroencephalographical and radiological criteria. The algorithm was validated by multicentre retrospective analysis of data of patients referred for specific symptoms and classified by the experts as epileptic patients or not. The algorithm was applied to all the patients, and the diagnosis provided by the algorithm was compared to the clinical diagnosis of the experts. Twenty-nine clinical, electroencephalographical and radiological criteria were selected for the algorithm. According to criteria combination, seizures were classified in four levels of diagnosis: certain, highly probable, possible or improbable. To validate the algorithm, the medical records of 269 elderly patients were analyzed (138 with epileptic seizures, 131 with non-epileptic manifestations). Patients were mainly referred for a transient focal deficit (40%), confusion (38%), unconsciousness (27%). The algorithm best classified certain and probable seizures versus possible and improbable seizures, with 86.2% sensitivity and 67.2% specificity. Using logistical regression, 2 simplified models were developed, the first with 13 criteria (Se 85.5%, Sp 90.1%), and the second with 7 criteria only (Se 84.8%, Sp 88.6%). In conclusion, the present study validated the use of a revised diagnostic algorithm to help diagnosis epileptic seizures in the elderly. A prospective study is planned to further validate this algorithm. Copyright 2010 Elsevier B.V. All rights reserved.

Inaccuracy of Wolff-Parkinson-white accessory pathway localization algorithms in children and patients with congenital heart defects.

PubMed

Bar-Cohen, Yaniv; Khairy, Paul; Morwood, James; Alexander, Mark E; Cecchin, Frank; Berul, Charles I

2006-07-01

ECG algorithms used to localize accessory pathways (AP) in patients with Wolff-Parkinson-White (WPW) syndrome have been validated in adults, but less is known of their use in children, especially in patients with congenital heart disease (CHD). We hypothesize that these algorithms have low diagnostic accuracy in children and even lower in those with CHD. Pre-excited ECGs in 43 patients with WPW and CHD (median age 5.4 years [0.9-32 years]) were evaluated and compared to 43 consecutive WPW control patients without CHD (median age 14.5 years [1.8-18 years]). Two blinded observers predicted AP location using 2 adult and 1 pediatric WPW algorithms, and a third blinded observer served as a tiebreaker. Predicted locations were compared with ablation-verified AP location to identify (a) exact match for AP location and (b) match for laterality (left-sided vs right-sided AP). In control children, adult algorithms were accurate in only 56% and 60%, while the pediatric algorithm was correct in 77%. In 19 patients with Ebstein's anomaly, diagnostic accuracy was similar to controls with at times an even better ability to predict laterality. In non-Ebstein's CHD, however, the algorithms were markedly worse (29% for the adult algorithms and 42% for the pediatric algorithms). A relatively large degree of interobserver variability was seen (kappa values from 0.30 to 0.58). Adult localization algorithms have poor diagnostic accuracy in young patients with and without CHD. Both adult and pediatric algorithms are particularly misleading in non-Ebstein's CHD patients and should be interpreted with caution.

Comparison of Diagnostic Algorithms for Detecting Toxigenic Clostridium difficile in Routine Practice at a Tertiary Referral Hospital in Korea.

PubMed

Moon, Hee-Won; Kim, Hyeong Nyeon; Hur, Mina; Shim, Hee Sook; Kim, Heejung; Yun, Yeo-Min

2016-01-01

Since every single test has some limitations for detecting toxigenic Clostridium difficile, multistep algorithms are recommended. This study aimed to compare the current, representative diagnostic algorithms for detecting toxigenic C. difficile, using VIDAS C. difficile toxin A&B (toxin ELFA), VIDAS C. difficile GDH (GDH ELFA, bioMérieux, Marcy-l'Etoile, France), and Xpert C. difficile (Cepheid, Sunnyvale, California, USA). In 271 consecutive stool samples, toxigenic culture, toxin ELFA, GDH ELFA, and Xpert C. difficile were performed. We simulated two algorithms: screening by GDH ELFA and confirmation by Xpert C. difficile (GDH + Xpert) and combined algorithm of GDH ELFA, toxin ELFA, and Xpert C. difficile (GDH + Toxin + Xpert). The performance of each assay and algorithm was assessed. The agreement of Xpert C. difficile and two algorithms (GDH + Xpert and GDH+ Toxin + Xpert) with toxigenic culture were strong (Kappa, 0.848, 0.857, and 0.868, respectively). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of algorithms (GDH + Xpert and GDH + Toxin + Xpert) were 96.7%, 95.8%, 85.0%, 98.1%, and 94.5%, 95.8%, 82.3%, 98.5%, respectively. There were no significant differences between Xpert C. difficile and two algorithms in sensitivity, specificity, PPV and NPV. The performances of both algorithms for detecting toxigenic C. difficile were comparable to that of Xpert C. difficile. Either algorithm would be useful in clinical laboratories and can be optimized in the diagnostic workflow of C. difficile depending on costs, test volume, and clinical needs.

Use of machine learning to improve autism screening and diagnostic instruments: effectiveness, efficiency, and multi-instrument fusion

PubMed Central

Bone, Daniel; Bishop, Somer; Black, Matthew P.; Goodwin, Matthew S.; Lord, Catherine; Narayanan, Shrikanth S.

2016-01-01

Background Machine learning (ML) provides novel opportunities for human behavior research and clinical translation, yet its application can have noted pitfalls (Bone et al., 2015). In this work, we fastidiously utilize ML to derive autism spectrum disorder (ASD) instrument algorithms in an attempt to improve upon widely-used ASD screening and diagnostic tools. Methods The data consisted of Autism Diagnostic Interview-Revised (ADI-R) and Social Responsiveness Scale (SRS) scores for 1,264 verbal individuals with ASD and 462 verbal individuals with non-ASD developmental or psychiatric disorders (DD), split at age 10. Algorithms were created via a robust ML classifier, support vector machine (SVM), while targeting best-estimate clinical diagnosis of ASD vs. non-ASD. Parameter settings were tuned in multiple levels of cross-validation. Results The created algorithms were more effective (higher performing) than current algorithms, were tunable (sensitivity and specificity can be differentially weighted), and were more efficient (achieving near-peak performance with five or fewer codes). Results from ML-based fusion of ADI-R and SRS are reported. We present a screener algorithm for below (above) age 10 that reached 89.2% (86.7%) sensitivity and 59.0% (53.4%) specificity with only five behavioral codes. Conclusions ML is useful for creating robust, customizable instrument algorithms. In a unique dataset comprised of controls with other difficulties, our findings highlight limitations of current caregiver-report instruments and indicate possible avenues for improving ASD screening and diagnostic tools. PMID:27090613

Use of machine learning to improve autism screening and diagnostic instruments: effectiveness, efficiency, and multi-instrument fusion.

PubMed

Bone, Daniel; Bishop, Somer L; Black, Matthew P; Goodwin, Matthew S; Lord, Catherine; Narayanan, Shrikanth S

2016-08-01

Machine learning (ML) provides novel opportunities for human behavior research and clinical translation, yet its application can have noted pitfalls (Bone et al., 2015). In this work, we fastidiously utilize ML to derive autism spectrum disorder (ASD) instrument algorithms in an attempt to improve upon widely used ASD screening and diagnostic tools. The data consisted of Autism Diagnostic Interview-Revised (ADI-R) and Social Responsiveness Scale (SRS) scores for 1,264 verbal individuals with ASD and 462 verbal individuals with non-ASD developmental or psychiatric disorders, split at age 10. Algorithms were created via a robust ML classifier, support vector machine, while targeting best-estimate clinical diagnosis of ASD versus non-ASD. Parameter settings were tuned in multiple levels of cross-validation. The created algorithms were more effective (higher performing) than the current algorithms, were tunable (sensitivity and specificity can be differentially weighted), and were more efficient (achieving near-peak performance with five or fewer codes). Results from ML-based fusion of ADI-R and SRS are reported. We present a screener algorithm for below (above) age 10 that reached 89.2% (86.7%) sensitivity and 59.0% (53.4%) specificity with only five behavioral codes. ML is useful for creating robust, customizable instrument algorithms. In a unique dataset comprised of controls with other difficulties, our findings highlight the limitations of current caregiver-report instruments and indicate possible avenues for improving ASD screening and diagnostic tools. © 2016 Association for Child and Adolescent Mental Health.

Diagnostic strategies using myoglobin measurement in myocardial infarction.

PubMed

Plebani, M; Zaninotto, M

1998-04-06

Myoglobin, a low molecular-weight heme protein (17800 D) present in both cardiac and skeletal muscle, is an old test with new perspectives. Advantages and disadvantages of myoglobin determination are well known. Myoglobin is the earliest known, commercially available, biochemical marker of acute myocardial infarction (AMI) and its rapid kinetics make it an early, good marker of reperfusion. However, since myoglobin is present in both skeletal and cardiac muscle, any damage to these muscle types results in its release into blood. Serum myoglobin levels are falsely elevated in conditions unrelated to AMI as skeletal muscle and neuromuscular disorders, renal failure, intramuscular injection, strenuous exercise, and after several toxins and drugs intake. New strategies for myoglobin measurement may resolve this limitation. These strategies include both the combined measurement of myoglobin and a skeletal specific marker (carbonic anhydrase III) or a cardiac specific marker (troponin I), as well as the myoglobin evaluation on serial samples. In particular, the diagnostic algorithm based on the combined measurement of myoglobin and troponin I, assuring a satisfactory analytical turnaround time, significantly improves the diagnostic efficiency of laboratory assessment of suspected AMI patients, allowing the successive monitoring of coronary reperfusion.

Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

PubMed

Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

2015-01-01

In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

The contour-buildup algorithm to calculate the analytical molecular surface.

PubMed

Totrov, M; Abagyan, R

1996-01-01

A new algorithm is presented to calculate the analytical molecular surface defined as a smooth envelope traced out by the surface of a probe sphere rolled over the molecule. The core of the algorithm is the sequential build up of multi-arc contours on the van der Waals spheres. This algorithm yields substantial reduction in both memory and time requirements of surface calculations. Further, the contour-buildup principle is intrinsically "local", which makes calculations of the partial molecular surfaces even more efficient. Additionally, the algorithm is equally applicable not only to convex patches, but also to concave triangular patches which may have complex multiple intersections. The algorithm permits the rigorous calculation of the full analytical molecular surface for a 100-residue protein in about 2 seconds on an SGI indigo with R4400++ processor at 150 Mhz, with the performance scaling almost linearly with the protein size. The contour-buildup algorithm is faster than the original Connolly algorithm an order of magnitude.

Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency.

PubMed

Shin, Ha Kyung; Grahame, George; McCandless, Shawn E; Kerr, Douglas S; Bedoyan, Jirair K

2017-11-01

Pyruvate dehydrogenase complex (PDC) deficiency is a major cause of primary lactic acidemia in children. Prompt and correct diagnosis of PDC deficiency and differentiating between specific vs generalized, or secondary deficiencies has important implications for clinical management and therapeutic interventions. Both genetic and enzymatic testing approaches are being used in the diagnosis of PDC deficiency. However, the diagnostic efficacy of such testing approaches for individuals affected with PDC deficiency has not been systematically investigated in this disorder. We sought to evaluate the diagnostic sensitivity and variability of the various PDC enzyme assays in females and males at the Center for Inherited Disorders of Energy Metabolism (CIDEM). CIDEM data were filtered by lactic acidosis and functional PDC deficiency in at least one cell/tissue type (blood lymphocytes, cultured fibroblasts or skeletal muscle) identifying 186 subjects (51% male and 49% female), about half were genetically resolved with 78% of those determined to have a pathogenic PDHA1 mutation. Assaying PDC in cultured fibroblasts in cases where the underlying genetic etiology is PDHA1, was highly sensitive irrespective of gender; 97% (95% confidence interval [CI]: 90%-100%) and 91% (95% CI: 82%-100%) in females and males, respectively. In contrast to the fibroblast-based testing, the lymphocyte- and muscle-based testing were not sensitive (36% [95% CI: 11%-61%, p=0.0003] and 58% [95% CI: 30%-86%, p=0.014], respectively) for identifying known PDC deficient females with pathogenic PDHA1 mutations. In males with a known PDHA1 mutation, the sensitivity of the various cell/tissue assays (75% lymphocyte, 91% fibroblast and 88% muscle) were not statistically different, and the discordance frequency due to the specific cell/tissue used for assaying PDC was 0.15±0.11. Based on this data, a practical diagnostic algorithm is proposed accounting for current molecular approaches, enzyme testing sensitivity, and variability due to gender, cell/tissue type used for testing, and successive repeat testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Graph-drawing algorithms geometries versus molecular mechanics in fullereness

NASA Astrophysics Data System (ADS)

Kaufman, M.; Pisanski, T.; Lukman, D.; Borštnik, B.; Graovac, A.

1996-09-01

The algorithms of Kamada-Kawai (KK) and Fruchterman-Reingold (FR) have been recently generalized (Pisanski et al., Croat. Chem. Acta 68 (1995) 283) in order to draw molecular graphs in three-dimensional space. The quality of KK and FR geometries is studied here by comparing them with the molecular mechanics (MM) and the adjacency matrix eigenvectors (AME) algorithm geometries. In order to compare different layouts of the same molecule, an appropriate method has been developed. Its application to a series of experimentally detected fullerenes indicates that the KK, FR and AME algorithms are able to reproduce plausible molecular geometries.

Rapid molecular diagnostics for multi-drug resistant tuberculosis in India.

PubMed

Ramachandran, Rajeswari; Muniyandi, M

2018-03-01

Rapid molecular diagnostic methods help in the detection of TB and Rifampicin resistance. These methods detect TB early, are accurate and play a crucial role in reducing the burden of drug resistant tuberculosis. Areas covered: This review analyses rapid molecular diagnostic tools used in the diagnosis of MDR-TB in India, such as the Line Probe Assay and GeneXpert. We have discussed the burden of MDR-TB and the impact of recent diagnostic tools on case detection and treatment outcomes. This review also discusses the costs involved in establishing these new techniques in India. Expert commentary: Molecular methods have considerable advantages for the programmatic management of drug resistant TB. These include speed, standardization of testing, potentially high throughput and reduced laboratory biosafety requirements. There is a desperate need for India to adopt modern, rapid, molecular tools with point-of-care tests being currently evaluated. New molecular diagnostic tests appear to be cost effective and also help in detecting missing cases. There is enough evidence to support the scaling up of these new tools in India.

Vibrational monitor of early demineralization in tooth enamel after in vitro exposure to phosphoridic liquid

NASA Astrophysics Data System (ADS)

Pezzotti, Giuseppe; Adachi, Tetsuya; Gasparutti, Isabella; Vincini, Giulio; Zhu, Wenliang; Boffelli, Marco; Rondinella, Alfredo; Marin, Elia; Ichioka, Hiroaki; Yamamoto, Toshiro; Marunaka, Yoshinori; Kanamura, Narisato

2017-02-01

The Raman spectroscopic method has been applied to quantitatively assess the in vitro degree of demineralization in healthy human teeth. Based on previous evaluations of Raman selection rules (empowered by an orientation distribution function (ODF) statistical algorithm) and on a newly proposed analysis of phonon density of states (PDOS) for selected vibrational modes of the hexagonal structure of hydroxyapatite, a molecular-scale evaluation of the demineralization process upon in vitro exposure to a highly acidic beverage (i.e., CocaCola™ Classic, pH = 2.5) could be obtained. The Raman method proved quite sensitive and spectroscopic features could be directly related to an increase in off-stoichiometry of the enamel surface structure since the very early stage of the demineralization process (i.e., when yet invisible to other conventional analytical techniques). The proposed Raman spectroscopic algorithm might possess some generality for caries risk assessment, allowing a prompt non-contact diagnostic practice in dentistry.

HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at six testing sites

PubMed Central

Kosack, Cara S.; Shanks, Leslie; Beelaert, Greet; Benson, Tumwesigye; Savane, Aboubacar; Ng’ang’a, Anne; Andre, Bita; Zahinda, Jean-Paul BN; Fransen, Katrien; Page, Anne-Laure

2017-01-01

Abstract Introduction: We evaluated the diagnostic accuracy of HIV testing algorithms at six programmes in five sub-Saharan African countries. Methods: In this prospective multisite diagnostic evaluation study (Conakry, Guinea; Kitgum, Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic Republic of Congo), samples from clients (greater than equal to five years of age) testing for HIV were collected and compared to a state-of-the-art algorithm from the AIDS reference laboratory at the Institute of Tropical Medicine, Belgium. The reference algorithm consisted of an enzyme-linked immuno-sorbent assay, a line-immunoassay, a single antigen-enzyme immunoassay and a DNA polymerase chain reaction test. Results: Between August 2011 and January 2015, over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites. Of those, 2786 (median age: 30; 38.1% males) were included in the study. Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry. Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed, with 16 false-positive and 8 false-negative results. Six false-negative specimens were retested with the on-site algorithm on the same sample and were found to be positive. Conversely, 13 false-positive specimens were retested: 8 remained false-positive with the on-site algorithm. Conclusions: The performance of algorithms at several sites failed to meet expectations and thresholds set by the World Health Organization, with unacceptably high rates of false results. Alongside the careful selection of rapid diagnostic tests and the validation of algorithms, strictly observing correct procedures can reduce the risk of false results. In the meantime, to identify false-positive diagnoses at initial testing, patients should be retested upon initiating antiretroviral therapy. PMID:28691437

HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at six testing sites.

PubMed

Kosack, Cara S; Shanks, Leslie; Beelaert, Greet; Benson, Tumwesigye; Savane, Aboubacar; Ng'ang'a, Anne; Andre, Bita; Zahinda, Jean-Paul Bn; Fransen, Katrien; Page, Anne-Laure

2017-07-03

We evaluated the diagnostic accuracy of HIV testing algorithms at six programmes in five sub-Saharan African countries. In this prospective multisite diagnostic evaluation study (Conakry, Guinea; Kitgum, Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic Republic of Congo), samples from clients (greater than equal to five years of age) testing for HIV were collected and compared to a state-of-the-art algorithm from the AIDS reference laboratory at the Institute of Tropical Medicine, Belgium. The reference algorithm consisted of an enzyme-linked immuno-sorbent assay, a line-immunoassay, a single antigen-enzyme immunoassay and a DNA polymerase chain reaction test. Between August 2011 and January 2015, over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites. Of those, 2786 (median age: 30; 38.1% males) were included in the study. Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry. Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed, with 16 false-positive and 8 false-negative results. Six false-negative specimens were retested with the on-site algorithm on the same sample and were found to be positive. Conversely, 13 false-positive specimens were retested: 8 remained false-positive with the on-site algorithm. The performance of algorithms at several sites failed to meet expectations and thresholds set by the World Health Organization, with unacceptably high rates of false results. Alongside the careful selection of rapid diagnostic tests and the validation of algorithms, strictly observing correct procedures can reduce the risk of false results. In the meantime, to identify false-positive diagnoses at initial testing, patients should be retested upon initiating antiretroviral therapy.

Molecular diagnostics of neurodegenerative disorders.

PubMed

Agrawal, Megha; Biswas, Abhijit

2015-01-01

Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer's and Parkinson's disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

Sex-specific performance of pre-imaging diagnostic algorithms for pulmonary embolism.

PubMed

van Mens, T E; van der Pol, L M; van Es, N; Bistervels, I M; Mairuhu, A T A; van der Hulle, T; Klok, F A; Huisman, M V; Middeldorp, S

2018-05-01

Essentials Decision rules for pulmonary embolism are used indiscriminately despite possible sex-differences. Various pre-imaging diagnostic algorithms have been investigated in several prospective studies. When analysed at an individual patient data level the algorithms perform similarly in both sexes. Estrogen use and male sex were associated with a higher prevalence in suspected pulmonary embolism. Background In patients suspected of pulmonary embolism (PE), clinical decision rules are combined with D-dimer testing to rule out PE, avoiding the need for imaging in those at low risk. Despite sex differences in several aspects of the disease, including its diagnosis, these algorithms are used indiscriminately in women and men. Objectives To compare the performance, defined as efficiency and failure rate, of three pre-imaging diagnostic algorithms for PE between women and men: the Wells rule with fixed or with age-adjusted D-dimer cut-off, and a recently validated algorithm (YEARS). A secondary aim was to determine the sex-specific prevalence of PE. Methods Individual patient data were obtained from six studies using the Wells rule (fixed D-dimer, n = 5; age adjusted, n = 1) and from one study using the YEARS algorithm. All studies prospectively enrolled consecutive patients with suspected PE. Main outcomes were efficiency (proportion of patients in which the algorithm ruled out PE without imaging) and failure rate (proportion of patients with PE not detected by the algorithm). Outcomes were estimated using (multilevel) logistic regression models. Results The main outcomes showed no sex differences in any of the separate algorithms. With all three, the prevalence of PE was lower in women (OR, 0.66, 0.68 and 0.74). In women, estrogen use, adjusted for age, was associated with lower efficiency and higher prevalence and D-dimer levels. Conclusions The investigated pre-imaging diagnostic algorithms for patients suspected of PE show no sex differences in performance. Male sex and estrogen use are both associated with a higher probability of having the disease. © 2018 International Society on Thrombosis and Haemostasis.

Keeping up with the times: revising the dermatology residency curriculum in the era of molecular diagnostics and personalized medicine.

PubMed

LaChance, Avery; Murphy, Michael J

2014-11-01

The clinical use of molecular diagnostics, genomics, and personalized medicine is increasing and improving rapidly over time. However, medical education incorporating the practical application of these techniques is lagging behind. Although instruction in these areas should be expanded upon and improved at all levels of training, residency provides a concentrated period of time in which to hone in on skills that are practically applicable to a trainee's specialty of choice. Although residencies in some fields, such as pathology, have begun to incorporate practical molecular diagnostics training, this area remains a relative gap in dermatology residency programs. Herein, we advocate for the incorporation of training in molecular diagnostics and personalized medicine into dermatology residency programs and propose a basic curriculum template for how to begin approaching these topics. By incorporating molecular diagnostics into dermatology residency training, dermatologists have the opportunity to lead the way and actively shape the specialty's transition into the era of personalized medicine. © 2014 The International Society of Dermatology.

The market trend analysis and prospects of cancer molecular diagnostics kits.

PubMed

Seo, Ju Hwan; Lee, Joon Woo; Cho, Daemyeong

2018-01-01

The molecular diagnostics market can be broadly divided into PCR (rt-PCR, d-PCR), NGS(Next Generation Sequencing), Microarray, FISH(Fluorescent in situ-hybridization) and other categories, based on the diagnostic technique. Also, depending on the disease being diagnosed, the market can also be divided into cancer, infectious diseases, HIV/STDs (herpes, syphilis), and women's health issues such as breast cancer, cervical cancer, ovarian cancer, HPV(human papillomavirus), and vaginitis.Chromosome analysis (including Fluorescent In-situ Hybridization) is one type of blood cancer diagnostic method, which involves the direct detection of individual cells with chromosomal translocation, but there have been problems of sensitivity when using this method. PCR targeting individual genes or the RT (reverse transcription)-PCR method offers outstanding sensitivity, but one drawback is the risk of false-positive reaction caused by contamination of samples, etc. Blood cancer molecular diagnostics kits allow us to overcome these shortcomings, and related products have been under development, with a focus on improving detection sensitivity, enabling multiple tests, and reducing the cost and diagnostic time. Blood cancer molecular diagnostics is usually performed based on platforms such as PCR. The global market for blood cancer molecular diagnostics kits is $ 335.9 million as of 2016 and is expected to reach $ 6980 million in 2026 with an average annual growth rate of 32.9%. The market in South Korea is anticipated to grow at an average annual rate of 28.9%, from $ 3.75 million as of 2016 to $ 60.89 million in 2026. The Market for blood cancer molecular diagnostics kits is judged to be higher in growth possibility due to the increase in the number of cancer patients.

The effects of automated artifact removal algorithms on electroencephalography-based Alzheimer's disease diagnosis

PubMed Central

Cassani, Raymundo; Falk, Tiago H.; Fraga, Francisco J.; Kanda, Paulo A. M.; Anghinah, Renato

2014-01-01

Over the last decade, electroencephalography (EEG) has emerged as a reliable tool for the diagnosis of cortical disorders such as Alzheimer's disease (AD). EEG signals, however, are susceptible to several artifacts, such as ocular, muscular, movement, and environmental. To overcome this limitation, existing diagnostic systems commonly depend on experienced clinicians to manually select artifact-free epochs from the collected multi-channel EEG data. Manual selection, however, is a tedious and time-consuming process, rendering the diagnostic system “semi-automated.” Notwithstanding, a number of EEG artifact removal algorithms have been proposed in the literature. The (dis)advantages of using such algorithms in automated AD diagnostic systems, however, have not been documented; this paper aims to fill this gap. Here, we investigate the effects of three state-of-the-art automated artifact removal (AAR) algorithms (both alone and in combination with each other) on AD diagnostic systems based on four different classes of EEG features, namely, spectral, amplitude modulation rate of change, coherence, and phase. The three AAR algorithms tested are statistical artifact rejection (SAR), blind source separation based on second order blind identification and canonical correlation analysis (BSS-SOBI-CCA), and wavelet enhanced independent component analysis (wICA). Experimental results based on 20-channel resting-awake EEG data collected from 59 participants (20 patients with mild AD, 15 with moderate-to-severe AD, and 24 age-matched healthy controls) showed the wICA algorithm alone outperforming other enhancement algorithm combinations across three tasks: diagnosis (control vs. mild vs. moderate), early detection (control vs. mild), and disease progression (mild vs. moderate), thus opening the doors for fully-automated systems that can assist clinicians with early detection of AD, as well as disease severity progression assessment. PMID:24723886

Molecular Diagnostics in Transfusion Medicine: In Capillary, on a Chip, in Silico, or in Flight?

PubMed Central

Garritsen, Henk S.P.; Xiu-Cheng Fan, Alex; Lenz, Daniela; Hannig, Horst; Yan Zhong, Xiao; Geffers, Robert; Lindenmaier, Werner; Dittmar, Kurt E.J.; Wörmann, Bernhard

2009-01-01

Summary Serology, defined as antibody-based diagnostics, has been regarded as the diagnostic gold standard in transfusion medicine. Nowadays however the impact of molecular diagnostics in transfusion medicine is rapidly growing. Molecular diagnostics can improve tissue typing (HLA typing), increase safety of blood products (NAT testing of infectious diseases), and enable blood group typing in difficult situations (after transfusion of blood products or prenatal non-invasive RhD typing). Most of the molecular testing involves the determination of the presence of single nucleotide polymorphisms (SNPs). Antigens (e.g. blood group antigens) mostly result from single nucleotide differences in critical positions. However, most blood group systems cannot be determined by looking at a single SNP. To identify members of a blood group system a number of critical SNPs have to be taken into account. The platforms which are currently used to perform molecular diagnostics are mostly gel-based, requiring time-consuming multiple manual steps. To implement molecular methods in transfusion medicine in the future the development of higher-throughput SNP genotyping non-gel-based platforms which allow a rapid, cost-effective screening are essential. Because of its potential for automation, high throughput and cost effectiveness the special focus of this paper is a relative new technique: SNP genotyping by MALDI-TOF MS analysis. PMID:21113259

Leveling the Playing Field: Bringing Development of Biomarkers and Molecular Diagnostics up to the Standards for Drug Development

PubMed Central

Poste, George; Carbone, David P.; Parkinson, David R.; Verweij, Jaap; Hewitt, Stephen; Jessup, J. Milburn

2012-01-01

Molecular diagnostics are increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, or to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify pharmocogenetic risk of adverse drug reactions. The articles of this CCR Focus section on Molecular Diagnosis describe the development and use of markers for medical decision-making in the cancer patient. They define the sources of preanalytic variability to minimize as well as the regulatory and financial challenges in diagnostic development and integration into clinical practice. They also outline an NCI program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation with sufficient sensitivity, specificity and validity that is comparable to that used for development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval. A way to accomplish this is to emphasize Phase IV post-marketing hypothesis driven clinical trials with biological characterization that permits accurate definition of the association of low prevalence gene alterations with toxicity or response in large cohorts. PMID:22422403

Leveling the playing field: bringing development of biomarkers and molecular diagnostics up to the standards for drug development.

PubMed

Poste, George; Carbone, David P; Parkinson, David R; Verweij, Jaap; Hewitt, Stephen M; Jessup, J Milburn

2012-03-15

Molecular diagnostics are becoming increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, and to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify the pharmacogenetic risk of adverse drug reactions. The articles in this CCR Focus section on molecular diagnosis describe the development and use of markers to guide medical decisions regarding cancer patients. They define sources of preanalytic variability that need to be minimized, as well as the regulatory and financial challenges involved in developing diagnostics and integrating them into clinical practice. They also outline a National Cancer Institute program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation, with sensitivity, specificity, and validity comparable to those required for the development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome-sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval can be achieved. One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts.

N-terminal pro-B-type natriuretic peptide diagnostic algorithm versus American Heart Association algorithm for Kawasaki disease.

PubMed

Dionne, Audrey; Meloche-Dumas, Léamarie; Desjardins, Laurent; Turgeon, Jean; Saint-Cyr, Claire; Autmizguine, Julie; Spigelblatt, Linda; Fournier, Anne; Dahdah, Nagib

2017-03-01

Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test. We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm. The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001). This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm. © 2016 Japan Pediatric Society.

Effect of Watermarking on Diagnostic Preservation of Atherosclerotic Ultrasound Video in Stroke Telemedicine.

PubMed

Dey, Nilanjan; Bose, Soumyo; Das, Achintya; Chaudhuri, Sheli Sinha; Saba, Luca; Shafique, Shoaib; Nicolaides, Andrew; Suri, Jasjit S

2016-04-01

Embedding of diagnostic and health care information requires secure encryption and watermarking. This research paper presents a comprehensive study for the behavior of some well established watermarking algorithms in frequency domain for the preservation of stroke-based diagnostic parameters. Two different sets of watermarking algorithms namely: two correlation-based (binary logo hiding) and two singular value decomposition (SVD)-based (gray logo hiding) watermarking algorithms are used for embedding ownership logo. The diagnostic parameters in atherosclerotic plaque ultrasound video are namely: (a) bulb identification and recognition which consists of identifying the bulb edge points in far and near carotid walls; (b) carotid bulb diameter; and (c) carotid lumen thickness all along the carotid artery. The tested data set consists of carotid atherosclerotic movies taken under IRB protocol from University of Indiana Hospital, USA-AtheroPoint™ (Roseville, CA, USA) joint pilot study. ROC (receiver operating characteristic) analysis was performed on the bulb detection process that showed an accuracy and sensitivity of 100 % each, respectively. The diagnostic preservation (DPsystem) for SVD-based approach was above 99 % with PSNR (Peak signal-to-noise ratio) above 41, ensuring the retention of diagnostic parameter devalorization as an effect of watermarking. Thus, the fully automated proposed system proved to be an efficient method for watermarking the atherosclerotic ultrasound video for stroke application.

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

PubMed

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

2018-01-01

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

Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population.

PubMed

Maeda, Akiko; Yoshida, Akiko; Kawai, Kanako; Arai, Yuki; Akiba, Ryutaro; Inaba, Akira; Takagi, Seiji; Fujiki, Ryoji; Hirami, Yasuhiko; Kurimoto, Yasuo; Ohara, Osamu; Takahashi, Masayo

2018-05-21

Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. Evaluation of diagnostic technology, Prospective, Clinical and experimental study. A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.

Gearbox vibration diagnostic analyzer

NASA Technical Reports Server (NTRS)

1992-01-01

This report describes the Gearbox Vibration Diagnostic Analyzer installed in the NASA Lewis Research Center's 500 HP Helicopter Transmission Test Stand to monitor gearbox testing. The vibration of the gearbox is analyzed using diagnostic algorithms to calculate a parameter indicating damaged components.

Anatomy-Based Algorithms for Detecting Oral Cancer Using Reflectance and Fluorescence Spectroscopy

PubMed Central

McGee, Sasha; Mardirossian, Vartan; Elackattu, Alphi; Mirkovic, Jelena; Pistey, Robert; Gallagher, George; Kabani, Sadru; Yu, Chung-Chieh; Wang, Zimmern; Badizadegan, Kamran; Grillone, Gregory; Feld, Michael S.

2010-01-01

Objectives We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc). Methods In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed. Results Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC], 0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the tongue) yielded an ROC-AUC of 0.71. Conclusions Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined. PMID:19999369

Molecular Isotopic Distribution Analysis (MIDAs) with Adjustable Mass Accuracy

NASA Astrophysics Data System (ADS)

Alves, Gelio; Ogurtsov, Aleksey Y.; Yu, Yi-Kuo

2014-01-01

In this paper, we present Molecular Isotopic Distribution Analysis (MIDAs), a new software tool designed to compute molecular isotopic distributions with adjustable accuracies. MIDAs offers two algorithms, one polynomial-based and one Fourier-transform-based, both of which compute molecular isotopic distributions accurately and efficiently. The polynomial-based algorithm contains few novel aspects, whereas the Fourier-transform-based algorithm consists mainly of improvements to other existing Fourier-transform-based algorithms. We have benchmarked the performance of the two algorithms implemented in MIDAs with that of eight software packages (BRAIN, Emass, Mercury, Mercury5, NeutronCluster, Qmass, JFC, IC) using a consensus set of benchmark molecules. Under the proposed evaluation criteria, MIDAs's algorithms, JFC, and Emass compute with comparable accuracy the coarse-grained (low-resolution) isotopic distributions and are more accurate than the other software packages. For fine-grained isotopic distributions, we compared IC, MIDAs's polynomial algorithm, and MIDAs's Fourier transform algorithm. Among the three, IC and MIDAs's polynomial algorithm compute isotopic distributions that better resemble their corresponding exact fine-grained (high-resolution) isotopic distributions. MIDAs can be accessed freely through a user-friendly web-interface at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/midas/index.html.

Molecular Isotopic Distribution Analysis (MIDAs) with adjustable mass accuracy.

PubMed

Alves, Gelio; Ogurtsov, Aleksey Y; Yu, Yi-Kuo

2014-01-01

In this paper, we present Molecular Isotopic Distribution Analysis (MIDAs), a new software tool designed to compute molecular isotopic distributions with adjustable accuracies. MIDAs offers two algorithms, one polynomial-based and one Fourier-transform-based, both of which compute molecular isotopic distributions accurately and efficiently. The polynomial-based algorithm contains few novel aspects, whereas the Fourier-transform-based algorithm consists mainly of improvements to other existing Fourier-transform-based algorithms. We have benchmarked the performance of the two algorithms implemented in MIDAs with that of eight software packages (BRAIN, Emass, Mercury, Mercury5, NeutronCluster, Qmass, JFC, IC) using a consensus set of benchmark molecules. Under the proposed evaluation criteria, MIDAs's algorithms, JFC, and Emass compute with comparable accuracy the coarse-grained (low-resolution) isotopic distributions and are more accurate than the other software packages. For fine-grained isotopic distributions, we compared IC, MIDAs's polynomial algorithm, and MIDAs's Fourier transform algorithm. Among the three, IC and MIDAs's polynomial algorithm compute isotopic distributions that better resemble their corresponding exact fine-grained (high-resolution) isotopic distributions. MIDAs can be accessed freely through a user-friendly web-interface at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/midas/index.html.

Sporotrichosis: From KOH to Molecular Biology.

PubMed

Arenas, Roberto; Sánchez-Cardenas, Carlos D; Ramirez-Hobak, Lourdes; Ruíz Arriaga, Leon Felipe; Vega Memije, Ma Elisa

2018-05-23

Sporotrichosis is a cosmopolitan, chronic granulomatous mycosis, acquired by traumatic inoculation and caused by Sporothrix schenckii complex . Several methods of diagnostic are available, from KOH to molecular biology. In this review, we describe from the simplest (clinical diagnosis) to the most advanced diagnostic techniques (molecular biology).

Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique.

PubMed

Floridia, Marco; Ciccacci, Fausto; Andreotti, Mauro; Hassane, Archa; Sidumo, Zita; Magid, Nurja A; Sotomane, Horacio; David, Muhlavasse; Mutemba, Elsa; Cebola, Junia; Mugunhe, Remigio Josè; Riccardi, Fabio; Marazzi, Maria Cristina; Giuliano, Marina; Palombi, Leonardo; Mancinelli, Sandro

2017-11-13

Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/μL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation in very advanced HIV/tuberculosis disease. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Validated methods for identifying tuberculosis patients in health administrative databases: systematic review.

PubMed

Ronald, L A; Ling, D I; FitzGerald, J M; Schwartzman, K; Bartlett-Esquilant, G; Boivin, J-F; Benedetti, A; Menzies, D

2017-05-01

An increasing number of studies are using health administrative databases for tuberculosis (TB) research. However, there are limitations to using such databases for identifying patients with TB. To summarise validated methods for identifying TB in health administrative databases. We conducted a systematic literature search in two databases (Ovid Medline and Embase, January 1980-January 2016). We limited the search to diagnostic accuracy studies assessing algorithms derived from drug prescription, International Classification of Diseases (ICD) diagnostic code and/or laboratory data for identifying patients with TB in health administrative databases. The search identified 2413 unique citations. Of the 40 full-text articles reviewed, we included 14 in our review. Algorithms and diagnostic accuracy outcomes to identify TB varied widely across studies, with positive predictive value ranging from 1.3% to 100% and sensitivity ranging from 20% to 100%. Diagnostic accuracy measures of algorithms using out-patient, in-patient and/or laboratory data to identify patients with TB in health administrative databases vary widely across studies. Use solely of ICD diagnostic codes to identify TB, particularly when using out-patient records, is likely to lead to incorrect estimates of case numbers, given the current limitations of ICD systems in coding TB.

Intelligent Diagnostic Assistant for Complicated Skin Diseases through C5's Algorithm.

PubMed

Jeddi, Fatemeh Rangraz; Arabfard, Masoud; Kermany, Zahra Arab

2017-09-01

Intelligent Diagnostic Assistant can be used for complicated diagnosis of skin diseases, which are among the most common causes of disability. The aim of this study was to design and implement a computerized intelligent diagnostic assistant for complicated skin diseases through C5's Algorithm. An applied-developmental study was done in 2015. Knowledge base was developed based on interviews with dermatologists through questionnaires and checklists. Knowledge representation was obtained from the train data in the database using Excel Microsoft Office. Clementine Software and C5's Algorithms were applied to draw the decision tree. Analysis of test accuracy was performed based on rules extracted using inference chains. The rules extracted from the decision tree were entered into the CLIPS programming environment and the intelligent diagnostic assistant was designed then. The rules were defined using forward chaining inference technique and were entered into Clips programming environment as RULE. The accuracy and error rates obtained in the training phase from the decision tree were 99.56% and 0.44%, respectively. The accuracy of the decision tree was 98% and the error was 2% in the test phase. Intelligent diagnostic assistant can be used as a reliable system with high accuracy, sensitivity, specificity, and agreement.

Technological Innovations for High-Throughput Approaches to In Vitro Allergy Diagnosis.

PubMed

Chapman, Martin D; Wuenschmann, Sabina; King, Eva; Pomés, Anna

2015-07-01

Allergy diagnostics is being transformed by the advent of in vitro IgE testing using purified allergen molecules, combined with multiplex technology and biosensors, to deliver discriminating, sensitive, and high-throughput molecular diagnostics at the point of care. Essential elements of IgE molecular diagnostics are purified natural or recombinant allergens with defined purity and IgE reactivity, planar or bead-based multiplex systems to enable IgE to multiple allergens to be measured simultaneously, and, most recently, nanotechnology-based biosensors that facilitate rapid reaction rates and delivery of test results via mobile devices. Molecular diagnostics relies on measurement of IgE to purified allergens, the "active ingredients" of allergenic extracts. Typically, this involves measuring IgE to multiple allergens which is facilitated by multiplex technology and biosensors. The technology differentiates between clinically significant cross-reactive allergens (which could not be deduced by conventional IgE assays using allergenic extracts) and provides better diagnostic outcomes. Purified allergens are manufactured under good laboratory practice and validated using protein chemistry, mass spectrometry, and IgE antibody binding. Recently, multiple allergens (from dog) were expressed as a single molecule with high diagnostic efficacy. Challenges faced by molecular allergy diagnostic companies include generation of large panels of purified allergens with known diagnostic efficacy, access to flexible and robust array or sensor technology, and, importantly, access to well-defined serum panels form allergic patients for product development and validation. Innovations in IgE molecular diagnostics are rapidly being brought to market and will strengthen allergy testing at the point of care.

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

PubMed

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Comprehensive Carrier Screening and Molecular Diagnostic Testing for Recessive Childhood Diseases

PubMed Central

Kingsmore, Stephen

2012-01-01

Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~18% of pediatric hospitalizations. Molecular diagnostic testing is currently available for only ~300 recessive disorders. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening and molecular diagnostic testing to most recessive disease genes has hitherto been impractical. Recently, we reported a preconception carrier screen / molecular diagnostic test for 448 recessive childhood diseases. The current status of this test is reviewed here. Currently, this reports analytical validity of the comprehensive carrier test. As the clinical validity and clinical utility in the contexts described is ascertained, this article will be updated. PMID:22872815

Combined algorithmic and GPU acceleration for ultra-fast circular conebeam backprojection

NASA Astrophysics Data System (ADS)

Brokish, Jeffrey; Sack, Paul; Bresler, Yoram

2010-04-01

In this paper, we describe the first implementation and performance of a fast O(N3logN) hierarchical backprojection algorithm for cone beam CT with a circular trajectory1,developed on a modern Graphics Processing Unit (GPU). The resulting tomographic backprojection system for 3D cone beam geometry combines speedup through algorithmic improvements provided by the hierarchical backprojection algorithm with speedup from a massively parallel hardware accelerator. For data parameters typical in diagnostic CT and using a mid-range GPU card, we report reconstruction speeds of up to 360 frames per second, and relative speedup of almost 6x compared to conventional backprojection on the same hardware. The significance of these results is twofold. First, they demonstrate that the reduction in operation counts demonstrated previously for the FHBP algorithm can be translated to a comparable run-time improvement in a massively parallel hardware implementation, while preserving stringent diagnostic image quality. Second, the dramatic speedup and throughput numbers achieved indicate the feasibility of systems based on this technology, which achieve real-time 3D reconstruction for state-of-the art diagnostic CT scanners with small footprint, high-reliability, and affordable cost.

External quality assessment studies for laboratory performance of molecular and serological diagnosis of Chikungunya virus infection.

PubMed

Jacobsen, Sonja; Patel, Pranav; Schmidt-Chanasit, Jonas; Leparc-Goffart, Isabelle; Teichmann, Anette; Zeller, Herve; Niedrig, Matthias

2016-03-01

Since the re-emergence of Chikungunya virus (CHIKV) in Reunion in 2005 and the recent outbreak in the Caribbean islands with an expansion to the Americas the CHIK diagnostic became very important. We evaluate the performance of laboratories regarding molecular and serological diagnostic of CHIK worldwide. A panel of 12 samples for molecular and 13 samples for serology were provided to 60 laboratories in 40 countries for evaluating the sensitivity and specificity of molecular and serology testing. The panel for molecular diagnostic testing was analysed by 56 laboratories returning 60 data sets of results whereas the 56 and 60 data sets were returned for IgG and IgM diagnostic from the participating laboratories. Twenty-three from 60 data sets performed optimal, 7 acceptable and 30 sets of results require improvement. From 50 data sets only one laboratory shows an optimal performance for IgM detection, followed by 9 data sets with acceptable and the rest need for improvement. From 46 IgG serology data sets 20 provide an optimal, 2 an acceptable and 24 require improvement performance. The evaluation of some of the diagnostic performances allows linking the quality of results to the in-house methods or commercial assays used. The external quality assurance for CHIK diagnostics provides a good overview on the laboratory performance regarding sensitivity and specificity for the molecular and serology diagnostic required for the quick and reliable analysis of suspected CHIK patients. Nearly half of the laboratories have to improve their diagnostic profile to achieve a better performance. Copyright © 2016 Z. Published by Elsevier B.V. All rights reserved.

CLINICAL APPROACH TO THE DIAGNOSTIC EVALUATION OF HERDITARY AND ACQUIRED NEUROMUSCULAR DISEASES

PubMed Central

McDonald, Craig M.

2012-01-01

SYNOPSIS In the context of a neuromuscular disease diagnostic evaluation, the clinician still must be able to obtain a relevant patient and family history and perform focused general, musculoskeletal, neurologic and functional physical examinations to direct further diagnostic evaluations. Laboratory studies for hereditary neuromuscular diseases include relevant molecular genetic studies. The EMG and nerve conduction studies remain an extension of the physical examination and help to guide further diagnostic studies such as molecular genetic studies, and muscle and nerve biopsies. All diagnostic information needs to be interpreted not in isolation, but within the context of relevant historical information, family history, physical examination findings, and laboratory data, electrophysiologic findings, pathologic findings, and molecular genetic findings if obtained. PMID:22938875

Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer?

PubMed

Halliday, C L; Kidd, S E; Sorrell, T C; Chen, S C-A

2015-04-01

Rapid, accurate diagnostic laboratory tests are needed to improve clinical outcomes of invasive fungal disease (IFD). Traditional direct microscopy, culture and histological techniques constitute the 'gold standard' against which newer tests are judged. Molecular diagnostic methods, whether broad-range or fungal-specific, have great potential to enhance sensitivity and speed of IFD diagnosis, but have varying specificities. The use of PCR-based assays, DNA sequencing, and other molecular methods including those incorporating proteomic approaches such as matrix-assisted laser desorption ionisation-time of flight mass spectroscopy (MALDI-TOF MS) have shown promising results. These are used mainly to complement conventional methods since they require standardisation before widespread implementation can be recommended. None are incorporated into diagnostic criteria for defining IFD. Commercial assays may assist standardisation. This review provides an update of molecular-based diagnostic approaches applicable to biological specimens and fungal cultures in microbiology laboratories. We focus on the most common pathogens, Candida and Aspergillus, and the mucormycetes. The position of molecular-based approaches in the detection of azole and echinocandin antifungal resistance is also discussed.

A new full-field digital mammography system with and without the use of an advanced post-processing algorithm: comparison of image quality and diagnostic performance.

PubMed

Ahn, Hye Shin; Kim, Sun Mi; Jang, Mijung; Yun, Bo La; Kim, Bohyoung; Ko, Eun Sook; Han, Boo-Kyung; Chang, Jung Min; Yi, Ann; Cho, Nariya; Moon, Woo Kyung; Choi, Hye Young

2014-01-01

To compare new full-field digital mammography (FFDM) with and without use of an advanced post-processing algorithm to improve image quality, lesion detection, diagnostic performance, and priority rank. During a 22-month period, we prospectively enrolled 100 cases of specimen FFDM mammography (Brestige®), which was performed alone or in combination with a post-processing algorithm developed by the manufacturer: group A (SMA), specimen mammography without application of "Mammogram enhancement ver. 2.0"; group B (SMB), specimen mammography with application of "Mammogram enhancement ver. 2.0". Two sets of specimen mammographies were randomly reviewed by five experienced radiologists. Image quality, lesion detection, diagnostic performance, and priority rank with regard to image preference were evaluated. Three aspects of image quality (overall quality, contrast, and noise) of the SMB were significantly superior to those of SMA (p < 0.05). SMB was significantly superior to SMA for visualizing calcifications (p < 0.05). Diagnostic performance, as evaluated by cancer score, was similar between SMA and SMB. SMB was preferred to SMA by four of the five reviewers. The post-processing algorithm may improve image quality with better image preference in FFDM than without use of the software.

Colonoscopy video quality assessment using hidden Markov random fields

NASA Astrophysics Data System (ADS)

Park, Sun Young; Sargent, Dusty; Spofford, Inbar; Vosburgh, Kirby

2011-03-01

With colonoscopy becoming a common procedure for individuals aged 50 or more who are at risk of developing colorectal cancer (CRC), colon video data is being accumulated at an ever increasing rate. However, the clinically valuable information contained in these videos is not being maximally exploited to improve patient care and accelerate the development of new screening methods. One of the well-known difficulties in colonoscopy video analysis is the abundance of frames with no diagnostic information. Approximately 40% - 50% of the frames in a colonoscopy video are contaminated by noise, acquisition errors, glare, blur, and uneven illumination. Therefore, filtering out low quality frames containing no diagnostic information can significantly improve the efficiency of colonoscopy video analysis. To address this challenge, we present a quality assessment algorithm to detect and remove low quality, uninformative frames. The goal of our algorithm is to discard low quality frames while retaining all diagnostically relevant information. Our algorithm is based on a hidden Markov model (HMM) in combination with two measures of data quality to filter out uninformative frames. Furthermore, we present a two-level framework based on an embedded hidden Markov model (EHHM) to incorporate the proposed quality assessment algorithm into a complete, automated diagnostic image analysis system for colonoscopy video.

New method for detection of gastric cancer by hyperspectral imaging: a pilot study

NASA Astrophysics Data System (ADS)

Kiyotoki, Shu; Nishikawa, Jun; Okamoto, Takeshi; Hamabe, Kouichi; Saito, Mari; Goto, Atsushi; Fujita, Yusuke; Hamamoto, Yoshihiko; Takeuchi, Yusuke; Satori, Shin; Sakaida, Isao

2013-02-01

We developed a new, easy, and objective method to detect gastric cancer using hyperspectral imaging (HSI) technology combining spectroscopy and imaging A total of 16 gastroduodenal tumors removed by endoscopic resection or surgery from 14 patients at Yamaguchi University Hospital, Japan, were recorded using a hyperspectral camera (HSC) equipped with HSI technology Corrected spectral reflectance was obtained from 10 samples of normal mucosa and 10 samples of tumors for each case The 16 cases were divided into eight training cases (160 training samples) and eight test cases (160 test samples) We established a diagnostic algorithm with training samples and evaluated it with test samples Diagnostic capability of the algorithm for each tumor was validated, and enhancement of tumors by image processing using the HSC was evaluated The diagnostic algorithm used the 726-nm wavelength, with a cutoff point established from training samples The sensitivity, specificity, and accuracy rates of the algorithm's diagnostic capability in the test samples were 78.8% (63/80), 92.5% (74/80), and 85.6% (137/160), respectively Tumors in HSC images of 13 (81.3%) cases were well enhanced by image processing Differences in spectral reflectance between tumors and normal mucosa suggested that tumors can be clearly distinguished from background mucosa with HSI technology.

Molecular beacon sequence design algorithm.

PubMed

Monroe, W Todd; Haselton, Frederick R

2003-01-01

A method based on Web-based tools is presented to design optimally functioning molecular beacons. Molecular beacons, fluorogenic hybridization probes, are a powerful tool for the rapid and specific detection of a particular nucleic acid sequence. However, their synthesis costs can be considerable. Since molecular beacon performance is based on its sequence, it is imperative to rationally design an optimal sequence before synthesis. The algorithm presented here uses simple Microsoft Excel formulas and macros to rank candidate sequences. This analysis is carried out using mfold structural predictions along with other free Web-based tools. For smaller laboratories where molecular beacons are not the focus of research, the public domain algorithm described here may be usefully employed to aid in molecular beacon design.

Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

PubMed

Mariño-Enríquez, Adrián; Bovée, Judith V M G

2016-09-01

Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Vertigo in childhood: proposal for a diagnostic algorithm based upon clinical experience.

PubMed

Casani, A P; Dallan, I; Navari, E; Sellari Franceschini, S; Cerchiai, N

2015-06-01

The aim of this paper is to analyse, after clinical experience with a series of patients with established diagnoses and review of the literature, all relevant anamnestic features in order to build a simple diagnostic algorithm for vertigo in childhood. This study is a retrospective chart review. A series of 37 children underwent complete clinical and instrumental vestibular examination. Only neurological disorders or genetic diseases represented exclusion criteria. All diagnoses were reviewed after applying the most recent diagnostic guidelines. In our experience, the most common aetiology for dizziness is vestibular migraine (38%), followed by acute labyrinthitis/neuritis (16%) and somatoform vertigo (16%). Benign paroxysmal vertigo was diagnosed in 4 patients (11%) and paroxysmal torticollis was diagnosed in a 1-year-old child. In 8% (3 patients) of cases, the dizziness had a post-traumatic origin: 1 canalolithiasis of the posterior semicircular canal and 2 labyrinthine concussions, respectively. Menière's disease was diagnosed in 2 cases. A bilateral vestibular failure of unknown origin caused chronic dizziness in 1 patient. In conclusion, this algorithm could represent a good tool for guiding clinical suspicion to correct diagnostic assessment in dizzy children where no neurological findings are detectable. The algorithm has just a few simple steps, based mainly on two aspects to be investigated early: temporal features of vertigo and presence of hearing impairment. A different algorithm has been proposed for cases in which a traumatic origin is suspected.

Current status of gene expression profiling in the diagnosis and management of acute leukaemia.

PubMed

Bacher, Ulrike; Kohlmann, Alexander; Haferlach, Torsten

2009-06-01

Gene expression profiling (GEP) enables the simultaneous investigation of the expression of tens of thousands of genes and was successfully introduced in leukaemia research a decade ago. Aiming to better understand the diversity of genetic aberrations in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL), pioneer studies investigated and confirmed the predictability of many cytogenetic and molecular subclasses in AML and ALL. In addition, GEP can define new prognostic subclasses within distinct leukaemia subgroups, as illustrated in AML with normal karyotype. Another approach is the development of treatment-specific sensitivity assays, which might contribute to targeted therapy studies. Finally, GEP might enable the detection of new molecular targets for therapy in patients with acute leukaemia. Meanwhile, large multicentre studies, e.g. the Microarray Innovations in LEukaemia (MILE) study, prepare for a standardised introduction of GEP in leukaemia diagnostic algorithms, aiming to translate this novel methodology into clinical routine for the benefit of patients with the complex disorders of AML and ALL.

77 FR 77032 - Healthcare Trade Mission to Russia, June 3-7, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-31

... humans. The world market for biotechnology (used for molecular genetics diagnostic technologies) was $13... generation vaccines, antibiotics and bacteriophages) 2. Biomedicine (molecular diagnostics, personalized...

78 FR 32369 - Healthcare Trade Mission to Russia, October 21-25, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-30

... environment on humans. The world market of biotechnology (used for molecular genetics diagnostic technologies..., phytomedicines, new generation vaccines, antibiotics and bacteriophages). Biomedicine (molecular diagnostics...

Scratching the surface of tomorrow's diagnostics: the Editor-in-Chief's opinion at the 15th year of Expert Review of Molecular Diagnostics.

PubMed

Lorincz, Attila; Raison, Claire

2015-01-01

Interview with Attila Lorincz by Claire Raison (Commissioning Editor) To mark the beginning of the 15th year of Expert Review of Molecular Diagnostics, the journal's Editor-in-Chief shares his expert knowledge on translational diagnostics, his opinion on recent controversies and his predictions for molecular diagnostics in 2015 and beyond. Attila Lorincz received his doctorate from Trinity College, Dublin, Republic of Ireland, and went on to become a research fellow at the University of California, Santa Barbara, CA, USA. During Professor Lorincz's research on human papillomavirus (HPV), he found several important and novel carcinogenic HPV types and pioneered the use of HPV DNA testing for clinical diagnostics. In 1988, Professor Lorincz's team produced the first HPV test to be FDA-approved for patients and in 2003, for general population cervical precancer screening. Now Professor of Molecular Epidemiology at the Centre for Cancer Prevention, Queen Mary University of London, UK, he and his team are furthering translational research into DNA methylation assays for cancer risk prediction.

What is the actual epidemiology of familial hypercholesterolemia in Italy? Evidence from a National Primary Care Database.

PubMed

Guglielmi, Valeria; Bellia, Alfonso; Pecchioli, Serena; Medea, Gerardo; Parretti, Damiano; Lauro, Davide; Sbraccia, Paolo; Federici, Massimo; Cricelli, Iacopo; Cricelli, Claudio; Lapi, Francesco

2016-11-15

There are some inconsistencies on prevalence estimates of familial hypercholesterolemia (FH) in general population across Europe due to variable application of its diagnostic criteria. We aimed to investigate the FH epidemiology in Italy applying the Dutch Lipid Clinical Network (DLCN) score, and two alternative diagnostic algorithms to a primary care database. We performed a retrospective population-based study using the Health Search IMS Health Longitudinal Patient Database (HSD) and including active (alive and currently registered with their general practitioners (GPs)) patients on December 31, 2014. Cases of FH were identified by applying DLCN score. Two further algorithms, based on either ICD9CM coding for FH or some clinical items adopted by the DLCN, were tested towards DLCN itself as gold standard. We estimated a prevalence of 0.01% for "definite" and 0.18% for "definite" plus "probable" cases as per the DLCN. Algorithms 1 and 2 reported a FH prevalence of 0.9 and 0.13%, respectively. Both algorithms resulted in consistent specificity (1: 99.10%; 2: 99.9%) towards DLCN, but Algorithm 2 considerably better identified true positive (sensitivity=85.90%) than Algorithm 1 (sensitivity=10.10%). The application of DLCN or valid diagnostic alternatives in the Italian primary care setting provides estimates of FH prevalence consistent with those reported in other screening studies in Caucasian population. These diagnostic criteria should be therefore fostered among GPs. In the perspective of FH new therapeutic options, the epidemiological picture of FH is even more relevant to foresee the costs and to plan affordable reimbursement programs in Italy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Development of companion diagnostics

DOE PAGES

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.; ...

2015-12-12

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods asmore » companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. Lastly, the review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic.« less

Development of companion diagnostics

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

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods asmore » companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. Lastly, the review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic.« less

Pre-examination factors affecting molecular diagnostic test results and interpretation: A case-based approach.

PubMed

Payne, Deborah A; Baluchova, Katarina; Peoc'h, Katell H; van Schaik, Ron H N; Chan, K C Allen; Maekawa, Masato; Mamotte, Cyril; Russomando, Graciela; Rousseau, François; Ahmad-Nejad, Parviz

2017-04-01

Multiple organizations produce guidance documents that provide opportunities to harmonize quality practices for diagnostic testing. The International Organization for Standardization ISO 15189 standard addresses requirements for quality in management and technical aspects of the clinical laboratory. One technical aspect addresses the complexities of the pre-examination phase prior to diagnostic testing. The Committee for Molecular Diagnostics of the International Federation for Clinical Chemistry and Laboratory Medicine (also known as, IFCC C-MD) conducted a survey of international molecular laboratories and determined ISO 15189 to be the most referenced guidance document. In this review, the IFCC C-MD provides case-based examples illustrating the value of select pre-examination processes as these processes relate to molecular diagnostic testing. Case-based examples in infectious disease, oncology, inherited disease and pharmacogenomics address the utility of: 1) providing information to patients and users, 2) designing requisition forms, 3) obtaining informed consent and 4) maintaining sample integrity prior to testing. The pre-examination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. The clinical vignettes presented in this paper illustrate the value of applying select ISO 15189 recommendations for general laboratory to the more specialized area of Molecular Diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of Companion Diagnostics

PubMed Central

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.; Pryma, Daniel A.

2016-01-01

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods as companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. The review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic. PMID:26687857

Next generation diagnostic molecular pathology: critical appraisal of quality assurance in Europe.

PubMed

Dubbink, Hendrikus J; Deans, Zandra C; Tops, Bastiaan B J; van Kemenade, Folkert J; Koljenović, S; van Krieken, Han J M; Blokx, Willeke A M; Dinjens, Winand N M; Groenen, Patricia J T A

2014-06-01

Tumor evaluation in pathology is more and more based on a combination of traditional histopathology and molecular analysis. Due to the rapid development of new cancer treatments that specifically target aberrant proteins present in tumor cells, treatment decisions are increasingly based on the molecular features of the tumor. Not only the number of patients eligible for targeted precision medicine, but also the number of molecular targets per patient and tumor type is rising. Diagnostic molecular pathology, the discipline that determines the molecular aberrations present in tumors for diagnostic, prognostic or predictive purposes, is faced with true challenges. The laboratories have to meet the need of comprehensive molecular testing using only limited amount of tumor tissue, mostly fixed in formalin and embedded in paraffin (FFPE), in short turnaround time. Choices must be made for analytical methods that provide accurate, reliable and cost-effective results. Validation of the test procedures and results is essential. In addition, participation and good performance in internal (IQA) and external quality assurance (EQA) schemes is mandatory. In this review, we critically evaluate the validation procedure for comprehensive molecular tests as well as the organization of quality assurance and assessment of competence of diagnostic molecular pathology laboratories within Europe. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Determining the Optimal Number of Core Needle Biopsy Passes for Molecular Diagnostics.

PubMed

Hoang, Nam S; Ge, Benjamin H; Pan, Lorraine Y; Ozawa, Michael G; Kong, Christina S; Louie, John D; Shah, Rajesh P

2018-03-01

The number of core biopsy passes required for adequate next-generation sequencing is impacted by needle cut, needle gauge, and the type of tissue involved. This study evaluates diagnostic adequacy of core needle lung biopsies based on number of passes and provides guidelines for other tissues based on simulated biopsies in ex vivo porcine organ tissues. The rate of diagnostic adequacy for pathology and molecular testing from lung biopsy procedures was measured for eight operators pre-implementation (September 2012-October 2013) and post-implementation (December 2013-April 2014) of a standard protocol using 20-gauge side-cut needles for ten core biopsy passes at a single academic hospital. Biopsy pass volume was then estimated in ex vivo porcine muscle, liver, and kidney using side-cut devices at 16, 18, and 20 gauge and end-cut devices at 16 and 18 gauge to estimate minimum number of passes required for adequate molecular testing. Molecular diagnostic adequacy increased from 69% (pre-implementation period) to 92% (post-implementation period) (p < 0.001) for lung biopsies. In porcine models, both 16-gauge end-cut and side-cut devices require one pass to reach the validated volume threshold to ensure 99% adequacy for molecular characterization, while 18- and 20-gauge devices require 2-5 passes depending on needle cut and tissue type. Use of 20-gauge side-cut core biopsy needles requires a significant number of passes to ensure diagnostic adequacy for molecular testing across all tissue types. To ensure diagnostic adequacy for molecular testing, 16- and 18-gauge needles require markedly fewer passes.

Diagnostic Utility of the ADI-R and DSM-5 in the Assessment of Latino Children and Adolescents

ERIC Educational Resources Information Center

Magaña, Sandy; Vanegas, Sandra B.

2017-01-01

Latino children in the US are systematically underdiagnosed with Autism Spectrum Disorder (ASD); therefore, it is important that recent changes to the diagnostic process do not exacerbate this pattern of under-identification. Previous research has found that the Autism Diagnostic Interview-Revised (ADI-R) algorithm, based on the Diagnostic and…

Current challenges in diagnostic imaging of venous thromboembolism.

PubMed

Huisman, Menno V; Klok, Frederikus A

2015-01-01

Because the clinical diagnosis of deep-vein thrombosis and pulmonary embolism is nonspecific, integrated diagnostic approaches for patients with suspected venous thromboembolism have been developed over the years, involving both non-invasive bedside tools (clinical decision rules and D-dimer blood tests) for patients with low pretest probability and diagnostic techniques (compression ultrasound for deep-vein thrombosis and computed tomography pulmonary angiography for pulmonary embolism) for those with a high pretest probability. This combination has led to standardized diagnostic algorithms with proven safety for excluding venous thrombotic disease. At the same time, it has become apparent that, as a result of the natural history of venous thrombosis, there are special patient populations in which the current standard diagnostic algorithms are not sufficient. In this review, we present 3 evidence-based patient cases to underline recent developments in the imaging diagnosis of venous thromboembolism. © 2015 by The American Society of Hematology. All rights reserved.

[Chronic diarrhoea: Definition, classification and diagnosis].

PubMed

Fernández-Bañares, Fernando; Accarino, Anna; Balboa, Agustín; Domènech, Eugeni; Esteve, Maria; Garcia-Planella, Esther; Guardiola, Jordi; Molero, Xavier; Rodríguez-Luna, Alba; Ruiz-Cerulla, Alexandra; Santos, Javier; Vaquero, Eva

2016-10-01

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

The diagnostic management of upper extremity deep vein thrombosis: A review of the literature.

PubMed

Kraaijpoel, Noémie; van Es, Nick; Porreca, Ettore; Büller, Harry R; Di Nisio, Marcello

2017-08-01

Upper extremity deep vein thrombosis (UEDVT) accounts for 4% to 10% of all cases of deep vein thrombosis. UEDVT may present with localized pain, erythema, and swelling of the arm, but may also be detected incidentally by diagnostic imaging tests performed for other reasons. Prompt and accurate diagnosis is crucial to prevent pulmonary embolism and long-term complications as the post-thrombotic syndrome of the arm. Unlike the diagnostic management of deep vein thrombosis (DVT) of the lower extremities, which is well established, the work-up of patients with clinically suspected UEDVT remains uncertain with limited evidence from studies of small size and poor methodological quality. Currently, only one prospective study evaluated the use of an algorithm, similar to the one used for DVT of the lower extremities, for the diagnostic workup of clinically suspected UEDVT. The algorithm combined clinical probability assessment, D-dimer testing and ultrasonography and appeared to safely and effectively exclude UEDVT. However, before recommending its use in routine clinical practice, external validation of this strategy and improvements of the efficiency are needed, especially in high-risk subgroups in whom the performance of the algorithm appeared to be suboptimal, such as hospitalized or cancer patients. In this review, we critically assess the accuracy and efficacy of current diagnostic tools and provide clinical guidance for the diagnostic management of clinically suspected UEDVT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnostic Performance of SRU and ATA Thyroid Nodule Classification Algorithms as Tested With a 1 Million Virtual Thyroid Nodule Model.

PubMed

Boehnke, Mitchell; Patel, Nayana; McKinney, Kristin; Clark, Toshimasa

The Society of Radiologists in Ultrasound (SRU 2005) and American Thyroid Association (ATA 2009 and ATA 2015) have published algorithms regarding thyroid nodule management. Kwak et al. and other groups have described models that estimate thyroid nodules' malignancy risk. The aim of our study is to use Kwak's model to evaluate the tradeoffs of both sensitivity and specificity of SRU 2005, ATA 2009 and ATA 2015 management algorithms. 1,000,000 thyroid nodules were modeled in MATLAB. Ultrasound characteristics were modeled after published data. Malignancy risk was estimated per Kwak's model and assigned as a binary variable. All nodules were then assessed using the published management algorithms. With the malignancy variable as condition positivity and algorithms' recommendation for FNA as test positivity, diagnostic performance was calculated. Modeled nodule characteristics mimic those of Kwak et al. 12.8% nodules were assigned as malignant (malignancy risk range of 2.0-98%). FNA was recommended for 41% of nodules by SRU 2005, 66% by ATA 2009, and 82% by ATA 2015. Sensitivity and specificity is significantly different (< 0.0001): 49% and 60% for SRU; 81% and 36% for ATA 2009; and 95% and 20% for ATA 2015. SRU 2005, ATA 2009 and ATA 2015 algorithms are used routinely in clinical practice to determine whether thyroid nodule biopsy is indicated. We demonstrate significant differences in these algorithms' diagnostic performance, which result in a compromise between sensitivity and specificity. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions

PubMed Central

Czaja, Albert J.

2016-01-01

Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms. PMID:26934884

Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma

PubMed Central

Roncalli, Massimo; Sciarra, Amedeo; Tommaso, Luca Di

2016-01-01

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. PMID:27189732

Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy

NASA Astrophysics Data System (ADS)

Chandra, Malavika; Scheiman, James; Simeone, Diane; McKenna, Barbara; Purdy, Julianne; Mycek, Mary-Ann

2010-01-01

Pancreatic adenocarcinoma is one of the leading causes of cancer death, in part because of the inability of current diagnostic methods to reliably detect early-stage disease. We present the first assessment of the diagnostic accuracy of algorithms developed for pancreatic tissue classification using data from fiber optic probe-based bimodal optical spectroscopy, a real-time approach that would be compatible with minimally invasive diagnostic procedures for early cancer detection in the pancreas. A total of 96 fluorescence and 96 reflectance spectra are considered from 50 freshly excised tissue sites-including human pancreatic adenocarcinoma, chronic pancreatitis (inflammation), and normal tissues-on nine patients. Classification algorithms using linear discriminant analysis are developed to distinguish among tissues, and leave-one-out cross-validation is employed to assess the classifiers' performance. The spectral areas and ratios classifier (SpARC) algorithm employs a combination of reflectance and fluorescence data and has the best performance, with sensitivity, specificity, negative predictive value, and positive predictive value for correctly identifying adenocarcinoma being 85, 89, 92, and 80%, respectively.

Ten years of R&D and full automation in molecular diagnosis.

PubMed

Greub, Gilbert; Sahli, Roland; Brouillet, René; Jaton, Katia

2016-01-01

A 10-year experience of our automated molecular diagnostic platform that carries out 91 different real-time PCR is described. Progresses and future perspectives in molecular diagnostic microbiology are reviewed: why automation is important; how our platform was implemented; how homemade PCRs were developed; the advantages/disadvantages of homemade PCRs, including the critical aspects of troubleshooting and the need to further reduce the turnaround time for specific samples, at least for defined clinical settings such as emergencies. The future of molecular diagnosis depends on automation, and in a novel perspective, it is time now to fully acknowledge the true contribution of molecular diagnostic and to reconsider the indication for PCR, by also using these tests as first-line assays.

Molecular diagnostics in medical microbiology: yesterday, today and tomorrow.

PubMed

van Belkum, Alex

2003-10-01

Clinical microbiology is clearly on the move, and various new diagnostic technologies have been introduced into laboratory practice over the past few decades. However, Henri D Isenberg recently stated that molecular biology techniques promised to revolutionise the diagnosis of infectious disease, but that, to date, this promise is still in its infancy. Molecular diagnostics have now surpassed these early stages and have definitely reached puberty. Currently, a second generation of automated molecular approaches is already within the microbiologists' reach. Quantitative amplification tests in combination with genomics, transcriptomics, proteomics and related methodologies will pave the way to further enhancement of innovative microbial detection and identification.

Biomedical visual data analysis to build an intelligent diagnostic decision support system in medical genetics.

PubMed

Kuru, Kaya; Niranjan, Mahesan; Tunca, Yusuf; Osvank, Erhan; Azim, Tayyaba

2014-10-01

In general, medical geneticists aim to pre-diagnose underlying syndromes based on facial features before performing cytological or molecular analyses where a genotype-phenotype interrelation is possible. However, determining correct genotype-phenotype interrelationships among many syndromes is tedious and labor-intensive, especially for extremely rare syndromes. Thus, a computer-aided system for pre-diagnosis can facilitate effective and efficient decision support, particularly when few similar cases are available, or in remote rural districts where diagnostic knowledge of syndromes is not readily available. The proposed methodology, visual diagnostic decision support system (visual diagnostic DSS), employs machine learning (ML) algorithms and digital image processing techniques in a hybrid approach for automated diagnosis in medical genetics. This approach uses facial features in reference images of disorders to identify visual genotype-phenotype interrelationships. Our statistical method describes facial image data as principal component features and diagnoses syndromes using these features. The proposed system was trained using a real dataset of previously published face images of subjects with syndromes, which provided accurate diagnostic information. The method was tested using a leave-one-out cross-validation scheme with 15 different syndromes, each of comprised 5-9 cases, i.e., 92 cases in total. An accuracy rate of 83% was achieved using this automated diagnosis technique, which was statistically significant (p<0.01). Furthermore, the sensitivity and specificity values were 0.857 and 0.870, respectively. Our results show that the accurate classification of syndromes is feasible using ML techniques. Thus, a large number of syndromes with characteristic facial anomaly patterns could be diagnosed with similar diagnostic DSSs to that described in the present study, i.e., visual diagnostic DSS, thereby demonstrating the benefits of using hybrid image processing and ML-based computer-aided diagnostics for identifying facial phenotypes. Copyright © 2014. Published by Elsevier B.V.

MoleculeNet: a benchmark for molecular machine learning† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02664a

PubMed Central

Wu, Zhenqin; Ramsundar, Bharath; Feinberg, Evan N.; Gomes, Joseph; Geniesse, Caleb; Pappu, Aneesh S.; Leswing, Karl

2017-01-01

Molecular machine learning has been maturing rapidly over the last few years. Improved methods and the presence of larger datasets have enabled machine learning algorithms to make increasingly accurate predictions about molecular properties. However, algorithmic progress has been limited due to the lack of a standard benchmark to compare the efficacy of proposed methods; most new algorithms are benchmarked on different datasets making it challenging to gauge the quality of proposed methods. This work introduces MoleculeNet, a large scale benchmark for molecular machine learning. MoleculeNet curates multiple public datasets, establishes metrics for evaluation, and offers high quality open-source implementations of multiple previously proposed molecular featurization and learning algorithms (released as part of the DeepChem open source library). MoleculeNet benchmarks demonstrate that learnable representations are powerful tools for molecular machine learning and broadly offer the best performance. However, this result comes with caveats. Learnable representations still struggle to deal with complex tasks under data scarcity and highly imbalanced classification. For quantum mechanical and biophysical datasets, the use of physics-aware featurizations can be more important than choice of particular learning algorithm. PMID:29629118

Modeling Complex Workflow in Molecular Diagnostics

PubMed Central

Gomah, Mohamed E.; Turley, James P.; Lu, Huimin; Jones, Dan

2010-01-01

One of the hurdles to achieving personalized medicine has been implementing the laboratory processes for performing and reporting complex molecular tests. The rapidly changing test rosters and complex analysis platforms in molecular diagnostics have meant that many clinical laboratories still use labor-intensive manual processing and testing without the level of automation seen in high-volume chemistry and hematology testing. We provide here a discussion of design requirements and the results of implementation of a suite of lab management tools that incorporate the many elements required for use of molecular diagnostics in personalized medicine, particularly in cancer. These applications provide the functionality required for sample accessioning and tracking, material generation, and testing that are particular to the evolving needs of individualized molecular diagnostics. On implementation, the applications described here resulted in improvements in the turn-around time for reporting of more complex molecular test sets, and significant changes in the workflow. Therefore, careful mapping of workflow can permit design of software applications that simplify even the complex demands of specialized molecular testing. By incorporating design features for order review, software tools can permit a more personalized approach to sample handling and test selection without compromising efficiency. PMID:20007844

Cancer diagnostics: The journey from histomorphology to molecular profiling.

PubMed

Ahmed, Atif A; Abedalthagafi, Malak

2016-09-06

Although histomorphology has made significant advances into the understanding of cancer etiology, classification and pathogenesis, it is sometimes complicated by morphologic ambiguities, and other shortcomings that necessitate the development of ancillary tests to complement its diagnostic value. A new approach to cancer patient management consists of targeting specific molecules or gene mutations in the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic profiling methods are increasingly being developed to identify tumor targeted molecular profile that is the basis of targeted therapy. Novel targeted therapy has revolutionized the treatment of gastrointestinal stromal tumor, renal cell carcinoma and other cancers that were previously difficult to treat with standard chemotherapy. In this review, we discuss the role of histomorphology in cancer diagnosis and management and the rising role of molecular profiling in targeted therapy. Molecular profiling in certain diagnostic and therapeutic difficulties may provide a practical and useful complement to histomorphology and opens new avenues for targeted therapy and alternative methods of cancer patient management.

Democratizing molecular diagnostics for the developing world.

PubMed

Abou Tayoun, Ahmad N; Burchard, Paul R; Malik, Imran; Scherer, Axel; Tsongalis, Gregory J

2014-01-01

Infectious diseases that are largely treatable continue to pose a tremendous burden on the developing world despite the availability of highly potent drugs. The high mortality and morbidity rates of these diseases are largely due to a lack of affordable diagnostics that are accessible to resource-limited areas and that can deliver high-quality results. In fact, modified molecular diagnostics for infectious diseases were rated as the top biotechnology to improve health in developing countries. In this review, we describe the characteristics of accessible molecular diagnostic tools and discuss the challenges associated with implementing such tools at low infrastructure sites. We highlight our experience as part of the "Grand Challenge" project supported by the Gates Foundation for addressing global health inequities and describe issues and solutions associated with developing adequate technologies or molecular assays needed for broad access in the developing world. We believe that sharing this knowledge will facilitate the development of new molecular technologies that are extremely valuable for improving global health.

Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.

PubMed

Tammimies, Kristiina; Marshall, Christian R; Walker, Susan; Kaur, Gaganjot; Thiruvahindrapuram, Bhooma; Lionel, Anath C; Yuen, Ryan K C; Uddin, Mohammed; Roberts, Wendy; Weksberg, Rosanna; Woodbury-Smith, Marc; Zwaigenbaum, Lonnie; Anagnostou, Evdokia; Wang, Zhuozhi; Wei, John; Howe, Jennifer L; Gazzellone, Matthew J; Lau, Lynette; Sung, Wilson W L; Whitten, Kathy; Vardy, Cathy; Crosbie, Victoria; Tsang, Brian; D'Abate, Lia; Tong, Winnie W L; Luscombe, Sandra; Doyle, Tyna; Carter, Melissa T; Szatmari, Peter; Stuckless, Susan; Merico, Daniele; Stavropoulos, Dimitri J; Scherer, Stephen W; Fernandez, Bridget A

2015-09-01

The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). All probands underwent CMA, with WES performed for 95 proband-parent trios. The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.

MOlecular MAterials Property Prediction Package (MOMAP) 1.0: a software package for predicting the luminescent properties and mobility of organic functional materials

NASA Astrophysics Data System (ADS)

Niu, Yingli; Li, Wenqiang; Peng, Qian; Geng, Hua; Yi, Yuanping; Wang, Linjun; Nan, Guangjun; Wang, Dong; Shuai, Zhigang

2018-04-01

MOlecular MAterials Property Prediction Package (MOMAP) is a software toolkit for molecular materials property prediction. It focuses on luminescent properties and charge mobility properties. This article contains a brief descriptive introduction of key features, theoretical models and algorithms of the software, together with examples that illustrate the performance. First, we present the theoretical models and algorithms for molecular luminescent properties calculation, which includes the excited-state radiative/non-radiative decay rate constant and the optical spectra. Then, a multi-scale simulation approach and its algorithm for the molecular charge mobility are described. This approach is based on hopping model and combines with Kinetic Monte Carlo and molecular dynamics simulations, and it is especially applicable for describing a large category of organic semiconductors, whose inter-molecular electronic coupling is much smaller than intra-molecular charge reorganisation energy.

[Diagnostic work-up of pulmonary nodules : Management of pulmonary nodules detected with low‑dose CT screening].

PubMed

Wormanns, D

2016-09-01

Pulmonary nodules are the most frequent pathological finding in low-dose computed tomography (CT) scanning for early detection of lung cancer. Early stages of lung cancer are often manifested as pulmonary nodules; however, the very commonly occurring small nodules are predominantly benign. These benign nodules are responsible for the high percentage of false positive test results in screening studies. Appropriate diagnostic algorithms are necessary to reduce false positive screening results and to improve the specificity of lung cancer screening. Such algorithms are based on some of the basic principles comprehensively described in this article. Firstly, the diameter of nodules allows a differentiation between large (>8 mm) probably malignant and small (<8 mm) probably benign nodules. Secondly, some morphological features of pulmonary nodules in CT can prove their benign nature. Thirdly, growth of small nodules is the best non-invasive predictor of malignancy and is utilized as a trigger for further diagnostic work-up. Non-invasive testing using positron emission tomography (PET) and contrast enhancement as well as invasive diagnostic tests (e.g. various procedures for cytological and histological diagnostics) are briefly described in this article. Different nodule morphology using CT (e.g. solid and semisolid nodules) is associated with different biological behavior and different algorithms for follow-up are required. Currently, no obligatory algorithm is available in German-speaking countries for the management of pulmonary nodules, which reflects the current state of knowledge. The main features of some international and American recommendations are briefly presented in this article from which conclusions for the daily clinical use are derived.

Cost-effective Diagnostic Checklists for Meningitis in Resource Limited Settings

PubMed Central

Durski, Kara N.; Kuntz, Karen M.; Yasukawa, Kosuke; Virnig, Beth A.; Meya, David B.; Boulware, David R.

2013-01-01

Background Checklists can standardize patient care, reduce errors, and improve health outcomes. For meningitis in resource-limited settings, with high patient loads and limited financial resources, CNS diagnostic algorithms may be useful to guide diagnosis and treatment. However, the cost-effectiveness of such algorithms is unknown. Methods We used decision analysis methodology to evaluate the costs, diagnostic yield, and cost-effectiveness of diagnostic strategies for adults with suspected meningitis in resource limited settings with moderate/high HIV prevalence. We considered three strategies: 1) comprehensive “shotgun” approach of utilizing all routine tests; 2) “stepwise” strategy with tests performed in a specific order with additional TB diagnostics; 3) “minimalist” strategy of sequential ordering of high-yield tests only. Each strategy resulted in one of four meningitis diagnoses: bacterial (4%), cryptococcal (59%), TB (8%), or other (aseptic) meningitis (29%). In model development, we utilized prevalence data from two Ugandan sites and published data on test performance. We validated the strategies with data from Malawi, South Africa, and Zimbabwe. Results The current comprehensive testing strategy resulted in 93.3% correct meningitis diagnoses costing $32.00/patient. A stepwise strategy had 93.8% correct diagnoses costing an average of $9.72/patient, and a minimalist strategy had 91.1% correct diagnoses costing an average of $6.17/patient. The incremental cost effectiveness ratio was $133 per additional correct diagnosis for the stepwise over minimalist strategy. Conclusions Through strategically choosing the order and type of testing coupled with disease prevalence rates, algorithms can deliver more care more efficiently. The algorithms presented herein are generalizable to East Africa and Southern Africa. PMID:23466647

Exploring Genome-Wide Expression Profiles Using Machine Learning Techniques.

PubMed

Kebschull, Moritz; Papapanou, Panos N

2017-01-01

Although contemporary high-throughput -omics methods produce high-dimensional data, the resulting wealth of information is difficult to assess using traditional statistical procedures. Machine learning methods facilitate the detection of additional patterns, beyond the mere identification of lists of features that differ between groups.Here, we demonstrate the utility of (1) supervised classification algorithms in class validation, and (2) unsupervised clustering in class discovery. We use data from our previous work that described the transcriptional profiles of gingival tissue samples obtained from subjects suffering from chronic or aggressive periodontitis (1) to test whether the two diagnostic entities were also characterized by differences on the molecular level, and (2) to search for a novel, alternative classification of periodontitis based on the tissue transcriptomes.Using machine learning technology, we provide evidence for diagnostic imprecision in the currently accepted classification of periodontitis, and demonstrate that a novel, alternative classification based on differences in gingival tissue transcriptomes is feasible. The outlined procedures allow for the unbiased interrogation of high-dimensional datasets for characteristic underlying classes, and are applicable to a broad range of -omics data.

A utility/cost analysis of breast cancer risk prediction algorithms

NASA Astrophysics Data System (ADS)

Abbey, Craig K.; Wu, Yirong; Burnside, Elizabeth S.; Wunderlich, Adam; Samuelson, Frank W.; Boone, John M.

2016-03-01

Breast cancer risk prediction algorithms are used to identify subpopulations that are at increased risk for developing breast cancer. They can be based on many different sources of data such as demographics, relatives with cancer, gene expression, and various phenotypic features such as breast density. Women who are identified as high risk may undergo a more extensive (and expensive) screening process that includes MRI or ultrasound imaging in addition to the standard full-field digital mammography (FFDM) exam. Given that there are many ways that risk prediction may be accomplished, it is of interest to evaluate them in terms of expected cost, which includes the costs of diagnostic outcomes. In this work we perform an expected-cost analysis of risk prediction algorithms that is based on a published model that includes the costs associated with diagnostic outcomes (true-positive, false-positive, etc.). We assume the existence of a standard screening method and an enhanced screening method with higher scan cost, higher sensitivity, and lower specificity. We then assess expected cost of using a risk prediction algorithm to determine who gets the enhanced screening method under the strong assumption that risk and diagnostic performance are independent. We find that if risk prediction leads to a high enough positive predictive value, it will be cost-effective regardless of the size of the subpopulation. Furthermore, in terms of the hit-rate and false-alarm rate of the of the risk prediction algorithm, iso-cost contours are lines with slope determined by properties of the available diagnostic systems for screening.

Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics-Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer.

PubMed

Plönes, Till; Engel-Riedel, Walburga; Stoelben, Erich; Limmroth, Christina; Schildgen, Oliver; Schildgen, Verena

2016-01-15

Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

Molecular diagnostics: the changing culture of medical microbiology.

PubMed

Bullman, Susan; Lucey, Brigid; Sleator, Roy D

2012-01-01

Diagnostic molecular biology is arguably the fastest growing area in current laboratory-based medicine. Growth of the so called 'omics' technologies has, over the last decade, led to a gradual migration away from the 'one test, one pathogen' paradigm, toward multiplex approaches to infectious disease diagnosis, which have led to significant improvements in clinical diagnostics and ultimately improved patient care.

Molecular diagnostics of inflammatory disease: New tools and perspectives.

PubMed

Garzorz-Stark, Natalie; Lauffer, Felix

2017-08-01

This essay reviews current approaches to establish novel molecular diagnostic tools for inflammatory skin diseases. Moreover, it highlights the importance of stratifying patients according to molecular signatures and revising current outdated disease classification systems to eventually reach the goal of personalized medicine. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multispectral optical tweezers for molecular diagnostics of single biological cells

NASA Astrophysics Data System (ADS)

Butler, Corey; Fardad, Shima; Sincore, Alex; Vangheluwe, Marie; Baudelet, Matthieu; Richardson, Martin

2012-03-01

Optical trapping of single biological cells has become an established technique for controlling and studying fundamental behavior of single cells with their environment without having "many-body" interference. The development of such an instrument for optical diagnostics (including Raman and fluorescence for molecular diagnostics) via laser spectroscopy with either the "trapping" beam or secondary beams is still in progress. This paper shows the development of modular multi-spectral imaging optical tweezers combining Raman and Fluorescence diagnostics of biological cells.

Interaction sorting method for molecular dynamics on multi-core SIMD CPU architecture.

PubMed

Matvienko, Sergey; Alemasov, Nikolay; Fomin, Eduard

2015-02-01

Molecular dynamics (MD) is widely used in computational biology for studying binding mechanisms of molecules, molecular transport, conformational transitions, protein folding, etc. The method is computationally expensive; thus, the demand for the development of novel, much more efficient algorithms is still high. Therefore, the new algorithm designed in 2007 and called interaction sorting (IS) clearly attracted interest, as it outperformed the most efficient MD algorithms. In this work, a new IS modification is proposed which allows the algorithm to utilize SIMD processor instructions. This paper shows that the improvement provides an additional gain in performance, 9% to 45% in comparison to the original IS method.

Information engineering for molecular diagnostics.

PubMed Central

Sorace, J. M.; Ritondo, M.; Canfield, K.

1994-01-01

Clinical laboratories are beginning to apply the recent advances in molecular biology to the testing of patient samples. The emerging field of Molecular Diagnostics will require a new Molecular Diagnostics Laboratory Information System which handles the data types, samples and test methods found in this field. The system must be very flexible in regards to supporting ad-hoc queries. The requirements which are shaping the developments in this field are reviewed and a data model developed. Several queries which demonstrate the data models ability to support the information needs of this area have been developed and run. These results demonstrate the ability of the purposed data model to meet the current and projected needs of this rapidly expanding field. PMID:7949937

Foraging on the potential energy surface: a swarm intelligence-based optimizer for molecular geometry.

PubMed

Wehmeyer, Christoph; Falk von Rudorff, Guido; Wolf, Sebastian; Kabbe, Gabriel; Schärf, Daniel; Kühne, Thomas D; Sebastiani, Daniel

2012-11-21

We present a stochastic, swarm intelligence-based optimization algorithm for the prediction of global minima on potential energy surfaces of molecular cluster structures. Our optimization approach is a modification of the artificial bee colony (ABC) algorithm which is inspired by the foraging behavior of honey bees. We apply our modified ABC algorithm to the problem of global geometry optimization of molecular cluster structures and show its performance for clusters with 2-57 particles and different interatomic interaction potentials.

Foraging on the potential energy surface: A swarm intelligence-based optimizer for molecular geometry

NASA Astrophysics Data System (ADS)

Wehmeyer, Christoph; Falk von Rudorff, Guido; Wolf, Sebastian; Kabbe, Gabriel; Schärf, Daniel; Kühne, Thomas D.; Sebastiani, Daniel

2012-11-01

We present a stochastic, swarm intelligence-based optimization algorithm for the prediction of global minima on potential energy surfaces of molecular cluster structures. Our optimization approach is a modification of the artificial bee colony (ABC) algorithm which is inspired by the foraging behavior of honey bees. We apply our modified ABC algorithm to the problem of global geometry optimization of molecular cluster structures and show its performance for clusters with 2-57 particles and different interatomic interaction potentials.

Disruption of Fibroblast Growth Factor Receptor (FGFR) Signaling as an Approach to Prostate Cancer Therapy

DTIC Science & Technology

2005-04-01

presented in tenth Annual Meeting of Association of Molecular Pathology and the abstract was published in the Journal of Molecular Diagnostics . The full...CDC25C Phosphatase Activity in Prostate Cancer: Correlation to Biochemical Recurrence. Journal of Molecular Diagnostics 2004, (6)4: 431. A manuscript in...receptor signaling. Clinical Cancer Research (in press). Acceptance letter for the above manuscript An abstract published in the Journal of Molecular

Quality Assurance Assessment of Diagnostic and Radiation Therapy–Simulation CT Image Registration for Head and Neck Radiation Therapy: Anatomic Region of Interest–based Comparison of Rigid and Deformable Algorithms

PubMed Central

Mohamed, Abdallah S. R.; Ruangskul, Manee-Naad; Awan, Musaddiq J.; Baron, Charles A.; Kalpathy-Cramer, Jayashree; Castillo, Richard; Castillo, Edward; Guerrero, Thomas M.; Kocak-Uzel, Esengul; Yang, Jinzhong; Court, Laurence E.; Kantor, Michael E.; Gunn, G. Brandon; Colen, Rivka R.; Frank, Steven J.; Garden, Adam S.; Rosenthal, David I.

2015-01-01

Purpose To develop a quality assurance (QA) workflow by using a robust, curated, manually segmented anatomic region-of-interest (ROI) library as a benchmark for quantitative assessment of different image registration techniques used for head and neck radiation therapy–simulation computed tomography (CT) with diagnostic CT coregistration. Materials and Methods Radiation therapy–simulation CT images and diagnostic CT images in 20 patients with head and neck squamous cell carcinoma treated with curative-intent intensity-modulated radiation therapy between August 2011 and May 2012 were retrospectively retrieved with institutional review board approval. Sixty-eight reference anatomic ROIs with gross tumor and nodal targets were then manually contoured on images from each examination. Diagnostic CT images were registered with simulation CT images rigidly and by using four deformable image registration (DIR) algorithms: atlas based, B-spline, demons, and optical flow. The resultant deformed ROIs were compared with manually contoured reference ROIs by using similarity coefficient metrics (ie, Dice similarity coefficient) and surface distance metrics (ie, 95% maximum Hausdorff distance). The nonparametric Steel test with control was used to compare different DIR algorithms with rigid image registration (RIR) by using the post hoc Wilcoxon signed-rank test for stratified metric comparison. Results A total of 2720 anatomic and 50 tumor and nodal ROIs were delineated. All DIR algorithms showed improved performance over RIR for anatomic and target ROI conformance, as shown for most comparison metrics (Steel test, P < .008 after Bonferroni correction). The performance of different algorithms varied substantially with stratification by specific anatomic structures or category and simulation CT section thickness. Conclusion Development of a formal ROI-based QA workflow for registration assessment demonstrated improved performance with DIR techniques over RIR. After QA, DIR implementation should be the standard for head and neck diagnostic CT and simulation CT allineation, especially for target delineation. © RSNA, 2014 Online supplemental material is available for this article. PMID:25380454

Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis.

PubMed

van't Hoog, Anna H; Cobelens, Frank; Vassall, Anna; van Kampen, Sanne; Dorman, Susan E; Alland, David; Ellner, Jerrold

2013-01-01

High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

Using molecular diagnostic testing to personalize the treatment of patients with gastrointestinal stromal tumors.

PubMed

Bannon, Amber E; Klug, Lillian R; Corless, Christopher L; Heinrich, Michael C

2017-05-01

The diagnosis and treatment of gastrointestinal stromal tumor (GIST) has emerged as a paradigm for modern cancer treatment ('precision medicine'), as it highlights the importance of matching molecular defects with specific therapies. Over the past two decades, the molecular classification and diagnostic work up of GIST has been radically transformed, accompanied by the development of molecular therapies for specific subgroups of GIST. This review summarizes the developments in the field of molecular diagnosis of GIST, particularly as they relate to optimizing medical therapy. Areas covered: Based on an extensive literature search of the molecular and clinical aspects of GIST, the authors review the most important developments in this field with an emphasis on the differential diagnosis of GIST including mutation testing, therapeutic implications of each molecular subtype, and emerging technologies relevant to the field. Expert commentary: The use of molecular diagnostics to classify GIST has been shown to be successful in optimizing patient treatment, but these methods remain under-utilized. In order to facilitate efficient and comprehensive molecular testing, the authors have developed a decision tree to aid clinicians.

DHB Task Force Review of DoD Biodefense Infrastructure and Biological Research Portfolio

DTIC Science & Technology

2009-04-29

Center and Biological Defense and Research Directorate (BORD) biodefense research portfolio includes vaccines, molecular diagnostics , genomics, and...human monoclonal antibodies, and innate immune agonists); molecular diagnostics (including recombinant reagents, assay development, reagent production

Evaluation of the Revised Algorithm of Autism Diagnostic Observation Schedule (ADOS) in the Diagnostic Investigation of High-Functioning Children and Adolescents with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kamp-Becker, Inge; Ghahreman, Mardjan; Heinzel-Gutenbrunner, Monika; Peters, Mira; Remschmidt, Helmut; Becker, Katja

2013-01-01

The Autism Diagnostic Observation Schedule (ADOS) is a semi-structured, standardized assessment designed for use in diagnostic evaluation of individuals with suspected autism spectrum disorder (ASD). The ADOS has been effective in categorizing children who definitely have autism or not, but has lower specificity and sometimes sensitivity for…

Assessing value of innovative molecular diagnostic tests in the concept of predictive, preventive, and personalized medicine.

PubMed

Akhmetov, Ildar; Bubnov, Rostyslav V

2015-01-01

Molecular diagnostic tests drive the scientific and technological uplift in the field of predictive, preventive, and personalized medicine offering invaluable clinical and socioeconomic benefits to the key stakeholders. Although the results of diagnostic tests are immensely influential, molecular diagnostic tests (MDx) are still grudgingly reimbursed by payers and amount for less than 5 % of the overall healthcare costs. This paper aims at defining the value of molecular diagnostic test and outlining the most important components of "value" from miscellaneous assessment frameworks, which go beyond accuracy and feasibility and impact the clinical adoption, informing healthcare resource allocation decisions. The authors suggest that the industry should facilitate discussions with various stakeholders throughout the entire assessment process in order to arrive at a consensus about the depth of evidence required for positive marketing authorization or reimbursement decisions. In light of the evolving "value-based healthcare" delivery practices, it is also recommended to account for social and ethical parameters of value, since these are anticipated to become as critical for reimbursement decisions and test acceptance as economic and clinical criteria.

The sonographic features of malignant mediastinal lymph nodes and a proposal for an algorithmic approach for sampling during endobronchial ultrasound.

PubMed

Alici, Ibrahim Onur; Yılmaz Demirci, Nilgün; Yılmaz, Aydın; Karakaya, Jale; Özaydın, Esra

2016-09-01

There are several papers on the sonographic features of mediastinal lymph nodes affected by several diseases, but none gives the importance and clinical utility of the features. In order to find out which lymph node should be sampled in a particular nodal station during endobronchial ultrasound, we investigated the diagnostic performances of certain sonographic features and proposed an algorithmic approach. We retrospectively analyzed 1051 lymph nodes and randomly assigned them into a preliminary experimental and a secondary study group. The diagnostic performances of the sonographic features (gray scale, echogeneity, shape, size, margin, presence of necrosis, presence of calcification and absence of central hilar structure) were calculated, and an algorithm for lymph node sampling was obtained with decision tree analysis in the experimental group. Later, a modified algorithm was applied to the patients in the study group to give the accuracy. The demographic characteristics of the patients were not statistically significant between the primary and the secondary groups. All of the features were discriminative between malignant and benign diseases. The modified algorithm sensitivity, specificity, and positive and negative predictive values and diagnostic accuracy for detecting metastatic lymph nodes were 100%, 51.2%, 50.6%, 100% and 67.5%, respectively. In this retrospective analysis, the standardized sonographic classification system and the proposed algorithm performed well in choosing the node that should be sampled in a particular station during endobronchial ultrasound. © 2015 John Wiley & Sons Ltd.

Validation of administrative data used for the diagnosis of upper gastrointestinal events following nonsteroidal anti-inflammatory drug prescription.

PubMed

Abraham, N S; Cohen, D C; Rivers, B; Richardson, P

2006-07-15

To validate veterans affairs (VA) administrative data for the diagnosis of nonsteroidal anti-inflammatory drug (NSAID)-related upper gastrointestinal events (UGIE) and to develop a diagnostic algorithm. A retrospective study of veterans prescribed an NSAID as identified from the national pharmacy database merged with in-patient and out-patient data, followed by primary chart abstraction. Contingency tables were constructed to allow comparison with a random sample of patients prescribed an NSAID, but without UGIE. Multivariable logistic regression analysis was used to derive a predictive algorithm. Once derived, the algorithm was validated in a separate cohort of veterans. Of 906 patients, 606 had a diagnostic code for UGIE; 300 were a random subsample of 11 744 patients (control). Only 161 had a confirmed UGIE. The positive predictive value (PPV) of diagnostic codes was poor, but improved from 27% to 51% with the addition of endoscopic procedural codes. The strongest predictors of UGIE were an in-patient ICD-9 code for gastric ulcer, duodenal ulcer and haemorrhage combined with upper endoscopy. This algorithm had a PPV of 73% when limited to patients >or=65 years (c-statistic 0.79). Validation of the algorithm revealed a PPV of 80% among patients with an overlapping NSAID prescription. NSAID-related UGIE can be assessed using VA administrative data. The optimal algorithm includes an in-patient ICD-9 code for gastric or duodenal ulcer and gastrointestinal bleeding combined with a procedural code for upper endoscopy.

GENE-07. MOLECULAR NEUROPATHOLOGY 2.0 - INCREASING DIAGNOSTIC ACCURACY IN PEDIATRIC NEUROONCOLOGY

PubMed Central

Sturm, Dominik; Jones, David T.W.; Capper, David; Sahm, Felix; von Deimling, Andreas; Rutkoswki, Stefan; Warmuth-Metz, Monika; Bison, Brigitte; Gessi, Marco; Pietsch, Torsten; Pfister, Stefan M.

2017-01-01

Abstract The classification of central nervous system (CNS) tumors into clinically and biologically distinct entities and subgroups is challenging. Children and adolescents can be affected by >100 histological variants with very variable outcomes, some of which are exceedingly rare. The current WHO classification has introduced a number of novel molecular markers to aid routine neuropathological diagnostics, and DNA methylation profiling is emerging as a powerful tool to distinguish CNS tumor classes. The Molecular Neuropathology 2.0 study aims to integrate genome wide (epi-)genetic diagnostics with reference neuropathological assessment for all newly-diagnosed pediatric brain tumors in Germany. To date, >350 patients have been enrolled. A molecular diagnosis is established by epigenetic tumor classification through DNA methylation profiling and targeted panel sequencing of >130 genes to detect diagnostically and/or therapeutically useful DNA mutations, structural alterations, and fusion events. Results are aligned with the reference neuropathological diagnosis, and discrepant findings are discussed in a multi-disciplinary tumor board including reference neuroradiological evaluation. Ten FFPE sections as input material are sufficient to establish a molecular diagnosis in >95% of tumors. Alignment with reference pathology results in four broad categories: a) concordant classification (~77%), b) discrepant classification resolvable by tumor board discussion and/or additional data (~5%), c) discrepant classification without currently available options to resolve (~8%), and d) cases currently unclassifiable by molecular diagnostics (~10%). Discrepancies are enriched in certain histopathological entities, such as histological high grade gliomas with a molecularly low grade profile. Gene panel sequencing reveals predisposing germline events in ~10% of patients. Genome wide (epi-)genetic analyses add a valuable layer of information to routine neuropathological diagnostics. Our study provides insight into CNS tumors with divergent histopathological and molecular classification, opening new avenues for research discoveries and facilitating optimization of clinical management for affected patients in the future.

Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings.

PubMed

Sabiiti, W; Mtafya, B; Kuchaka, D; Azam, K; Viegas, S; Mdolo, A; Farmer, E C W; Khonga, M; Evangelopoulos, D; Honeyborne, I; Rachow, A; Heinrich, N; Ntinginya, N E; Bhatt, N; Davies, G R; Jani, I V; McHugh, T D; Kibiki, G; Hoelscher, M; Gillespie, S H

2016-08-01

The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert(®) MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.

VLPs of HCV local isolates for HCV immunoassay diagnostic approach in Indonesia

NASA Astrophysics Data System (ADS)

Prasetyo, Afiono Agung

2017-01-01

Hepatitis C Virus (HCV) infection is a major global disease which often leads to morbidity and mortality. Low survival is related to the lack of adequate diagnostic because HCV infection is frequently asymptomatic and there are no specific diagnostic tests due to the fast transformation of the virus. Here, we investigated the VLPs (virus-like particles) of HCV local isolate as an immunoassay diagnostic approach to detect HCV infection, especially in Indonesia. The core, E1, and E2 of HCV local isolate genes were cloned and molecular analyzed, either as single or in recombinant-VLP form, to determine the molecular and chemical characteristics of each VLPs related to their potential use as an immunoassay detection method for HCV infection. The results indicated the molecular and chemical character of each VLPs are comparable. Conclusion: VLPs of HCV has the potential as an immunoassay diagnostic approach to detect HCV infection.

Is introducing rapid culture into the diagnostic algorithm of smear-negative tuberculosis cost-effective?

PubMed

Yakhelef, N; Audibert, M; Varaine, F; Chakaya, J; Sitienei, J; Huerga, H; Bonnet, M

2014-05-01

In 2007, the World Health Organization recommended introducing rapid Mycobacterium tuberculosis culture into the diagnostic algorithm of smear-negative pulmonary tuberculosis (TB). To assess the cost-effectiveness of introducing a rapid non-commercial culture method (thin-layer agar), together with Löwenstein-Jensen culture to diagnose smear-negative TB at a district hospital in Kenya. Outcomes (number of true TB cases treated) were obtained from a prospective study evaluating the effectiveness of a clinical and radiological algorithm (conventional) against the alternative algorithm (conventional plus M. tuberculosis culture) in 380 smear-negative TB suspects. The costs of implementing each algorithm were calculated using a 'micro-costing' or 'ingredient-based' method. We then compared the cost and effectiveness of conventional vs. culture-based algorithms and estimated the incremental cost-effectiveness ratio. The costs of conventional and culture-based algorithms per smear-negative TB suspect were respectively €39.5 and €144. The costs per confirmed and treated TB case were respectively €452 and €913. The culture-based algorithm led to diagnosis and treatment of 27 more cases for an additional cost of €1477 per case. Despite the increase in patients started on treatment thanks to culture, the relatively high cost of a culture-based algorithm will make it difficult for resource-limited countries to afford.

Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders.

PubMed

Mesa, Ruben A

2007-01-01

The diagnosis and management of the BCR-ABL-negative myeloproliferative disorders (MPDs) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are at an explosive crossroads of scientific investigation and evolving paradigms since the discovery of the tyrosine kinase-activating JAK2V617F mutation in 2005. Additional discovery of relevant molecular lesions (JAK2 exon 12 mutations and c-MplW515L/K) have only further enriched our understanding of MPD pathogenesis. The improved diagnostic certainty these molecular markers provide have resulted in the modification, and simplification, of the World Health Organization (WHO) diagnostic algorithms for MPDs. Despite these scientific advances, however, the initial management of MPDs continues to rely upon a risk-based strategy to minimize the risk of vascular events with control of erythrocytosis, targeted antiplatelet therapy, and risk-based myelosuppressive therapy. No current medical therapy has altered the natural trend of the MPDs to lead to overt severe myelofibrosis or acute leukemia. Investigations into targeted therapies for MPDs are proceeding at a brisk pace with agents aimed at immunomodulation, decreasing marrow stromal reaction to the aberrant clone, DNA hypomethylation, or the inhibition of tyrosine kinases. Specific inhibition of JAK2 itself appears promising by in vitro investigations, and clinical trials with multiple agents are planned to commence enrollment in 2007. The potential impact of JAK2 inhibitors on the manifestations of the MPDs is unclear, but is awaited with great interest.

Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

NASA Astrophysics Data System (ADS)

Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

2015-05-01

This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and 1582-1587 cm-1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.

Molecular malaria diagnostics: A systematic review and meta-analysis.

PubMed

Roth, Johanna M; Korevaar, Daniël A; Leeflang, Mariska M G; Mens, Pètra F

2016-01-01

Accurate diagnosis of malaria is essential for identification and subsequent treatment of the disease. Currently, microscopy and rapid diagnostic tests are the most commonly used diagnostics, next to treatment based on clinical signs only. These tests are easy to deploy, but have a relatively high detection limit. With declining prevalence in many areas, there is an increasing need for more sensitive diagnostics. Molecular tools may be a suitable alternative, although costs and technical requirements currently hamper their implementation in resource limited settings. A range of (near) point-of-care diagnostics is therefore under development, including simplifications in sample preparation, amplification and/or read-out of the test. Accuracy data, in combination with technical characteristics, are essential in determining which molecular test, if any, would be the most promising to be deployed. This review presents a comprehensive overview of the currently available molecular malaria diagnostics, ranging from well-known tests to platforms in early stages of evaluation, and systematically evaluates their published accuracy. No important difference in accuracy was found between the most commonly used PCR-based assays (conventional, nested and real-time PCR), with most of them having high sensitivity and specificity, implying that there are no reasons other than practical ones to choose one technique over the other. Loop-mediated isothermal amplification and other (novel) diagnostics appear to be highly accurate as well, with some offering potential to be used in resource-limited settings.

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines.

PubMed

Conwell, Darwin L; Lee, Linda S; Yadav, Dhiraj; Longnecker, Daniel S; Miller, Frank H; Mortele, Koenraad J; Levy, Michael J; Kwon, Richard; Lieb, John G; Stevens, Tyler; Toskes, Phillip P; Gardner, Timothy B; Gelrud, Andres; Wu, Bechien U; Forsmark, Christopher E; Vege, Santhi S

2014-11-01

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Raptor: A Portable Biosensor Upgraded for Reliability and Sensitivity

DTIC Science & Technology

2003-07-01

Research Center for Molecular Diagnostics and Therapy. The F. tularensis antigen (killed vaccine strain), affinity-purified rabbit anti-B...Russian Research Center of Molecular Diagnostics and Therapies, for their generous donations materials. The views expressed here are those of the

Spectroscopic diagnosis of laryngeal carcinoma using near-infrared Raman spectroscopy and random recursive partitioning ensemble techniques.

PubMed

Teh, Seng Khoon; Zheng, Wei; Lau, David P; Huang, Zhiwei

2009-06-01

In this work, we evaluated the diagnostic ability of near-infrared (NIR) Raman spectroscopy associated with the ensemble recursive partitioning algorithm based on random forests for identifying cancer from normal tissue in the larynx. A rapid-acquisition NIR Raman system was utilized for tissue Raman measurements at 785 nm excitation, and 50 human laryngeal tissue specimens (20 normal; 30 malignant tumors) were used for NIR Raman studies. The random forests method was introduced to develop effective diagnostic algorithms for classification of Raman spectra of different laryngeal tissues. High-quality Raman spectra in the range of 800-1800 cm(-1) can be acquired from laryngeal tissue within 5 seconds. Raman spectra differed significantly between normal and malignant laryngeal tissues. Classification results obtained from the random forests algorithm on tissue Raman spectra yielded a diagnostic sensitivity of 88.0% and specificity of 91.4% for laryngeal malignancy identification. The random forests technique also provided variables importance that facilitates correlation of significant Raman spectral features with cancer transformation. This study shows that NIR Raman spectroscopy in conjunction with random forests algorithm has a great potential for the rapid diagnosis and detection of malignant tumors in the larynx.

Methods for Real-Time PCR-Based Diagnosis of Chlamydia pneumoniae, Chlamydia psittaci, and Chlamydia abortus Infections in an Opened Molecular Diagnostic Platform.

PubMed

Opota, Onya; Brouillet, René; Greub, Gilbert; Jaton, Katia

2017-01-01

The advances in molecular biology of the last decades have dramatically improved the field of diagnostic bacteriology. In particular, PCR-based technologies have impacted the diagnosis of infections caused by obligate intracellular bacteria such as pathogens from the Chlamydiacae family. Here, we describe a real-time PCR-based method using the Taqman technology for the diagnosis of Chlamydia pneumoniae, Chlamydia psittaci, and Chlamydia abortus infection. The method presented here can be applied to various clinical samples and can be adapted on opened molecular diagnostic platforms.

The Effect of Molecular Diagnostics on the Treatment of Glioma.

PubMed

Bush, Nancy Ann Oberheim; Butowski, Nicholas

2017-04-01

This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions. Several of these markers are also being used as therapeutic targets. We review the use of several molecular diagnostics in gliomas and discuss their impact on drug development and clinical trial design. In the future, molecular characterization based on a specific genomic, proteomic as well as transcriptomes for bioformatics analysis will provide clinicians the ability to rationally select drugs with actionable targets for each patient.

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

PubMed

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

[Diagnostic molecular pathology of lymphatic and myeloid neoplasms].

PubMed

Klapper, W; Kreipe, H

2015-03-01

Molecular pathology has been an integral part of the diagnostics of tumors of the hematopoietic system substantially longer than for solid neoplasms. In contrast to solid tumors, the primary objective of molecular pathology in hematopoietic neoplasms is not the prediction of drug efficacy but the diagnosis itself by excluding reactive proliferation and by using molecular features for tumor classification. In the case of malignant lymphomas, the most commonly applied molecular tests are those for gene rearrangements for immunoglobulin heavy chains and T-cell receptors. However, this article puts the focus on new and diagnostically relevant assays in hematopathology. Among these are mutations of MYD88 codon 265 in lymphoplasmacytic lymphomas, B-raf V600E in hairy cell leukemia and Stat3 exon 21 in indolent T-cell lymphomas. In myeloproliferative neoplasms, MPL W515, calreticulin exon 9 and the BCR-ABL and JAK2 V617F junctions are the most frequently analyzed differentiation series. In myelodysplastic and myeloproliferative neoplasms, SRSF2, SETBP1 and CSF3R mutations provide important differential diagnostic information. Genes mutated in myelodysplastic syndromes (MDS) are particularly diverse but their analysis significantly improves the differential diagnostics between reactive conditions and MDS. The most frequent changes in MDS include mutations of TET2 and various genes encoding splicing factors.

A multi-emitter fitting algorithm for potential live cell super-resolution imaging over a wide range of molecular densities.

PubMed

Takeshima, T; Takahashi, T; Yamashita, J; Okada, Y; Watanabe, S

2018-05-25

Multi-emitter fitting algorithms have been developed to improve the temporal resolution of single-molecule switching nanoscopy, but the molecular density range they can analyse is narrow and the computation required is intensive, significantly limiting their practical application. Here, we propose a computationally fast method, wedged template matching (WTM), an algorithm that uses a template matching technique to localise molecules at any overlapping molecular density from sparse to ultrahigh density with subdiffraction resolution. WTM achieves the localization of overlapping molecules at densities up to 600 molecules μm -2 with a high detection sensitivity and fast computational speed. WTM also shows localization precision comparable with that of DAOSTORM (an algorithm for high-density super-resolution microscopy), at densities up to 20 molecules μm -2 , and better than DAOSTORM at higher molecular densities. The application of WTM to a high-density biological sample image demonstrated that it resolved protein dynamics from live cell images with subdiffraction resolution and a temporal resolution of several hundred milliseconds or less through a significant reduction in the number of camera images required for a high-density reconstruction. WTM algorithm is a computationally fast, multi-emitter fitting algorithm that can analyse over a wide range of molecular densities. The algorithm is available through the website. https://doi.org/10.17632/bf3z6xpn5j.1. © 2018 The Authors. Journal of Microscopy published by JohnWiley & Sons Ltd on behalf of Royal Microscopical Society.

Development of PET projection data correction algorithm

NASA Astrophysics Data System (ADS)

Bazhanov, P. V.; Kotina, E. D.

2017-12-01

Positron emission tomography is modern nuclear medicine method used in metabolism and internals functions examinations. This method allows to diagnosticate treatments on their early stages. Mathematical algorithms are widely used not only for images reconstruction but also for PET data correction. In this paper random coincidences and scatter correction algorithms implementation are considered, as well as algorithm of PET projection data acquisition modeling for corrections verification.

Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia.

PubMed

Raschke, R A; Gallo, T; Curry, S C; Whiting, T; Padilla-Jones, A; Warkentin, T E; Puri, A

2017-08-01

Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. Background Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have suboptimal operating characteristics. We previously developed a diagnostic algorithm for HIT that incorporated 'four Ts' (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% confidence interval [CI], 0.93-1.00). Objectives The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care. Methods A retrospective cohort comprised patients who had undergone anti-PF4/H ELISA and serotonin release assay (SRA) testing in our healthcare system from 2010 to 2014. We determined the algorithm recommendation for each patient, compared recommendations with the clinical care received, and enumerated consequences of discrepancies. Operating characteristics were calculated for algorithm recommendations using SRA as the reference standard. Results Analysis was performed on 181 patients, 10 of whom were ruled in for HIT. The algorithm accurately stratified 98% of patients (95% CI, 95-99%), ruling out HIT in 158, ruling in HIT in 10 and recommending an SRA in 13 patients. Algorithm adherence would have obviated 165 SRAs and prevented 30 courses of unnecessary antithrombotic therapy for HIT. Diagnostic sensitivity was 0.82 (95% CI, 0.48-0.98), specificity 0.99 (95% CI, 0.97-1.00), PPV 0.90 (95% CI, 0.56-0.99) and NPV 0.99 (95% CI, 0.96-1.00). Conclusions An algorithm incorporating 4Ts scoring and a stratified interpretation of the anti-PF4/H ELISA has good operating characteristics and the potential to improve management of suspected HIT patients. © 2017 International Society on Thrombosis and Haemostasis.

Current and proposed molecular diagnostics in a genitourinary service line laboratory at a tertiary clinical institution.

PubMed

Udager, Aaron M; Alva, Ajjai; Mehra, Rohit

2014-01-01

The idea that detailed knowledge of molecular oncogenesis will drive diagnostic, prognostic, and therapeutic clinical decision making in an increasingly multidisciplinary practice of oncologic care has been anticipated for many years. With the recent rapid advancement in our understanding of the molecular underpinnings of genitourinary malignancies, this concept is now starting to take shape in the fields of prostate, kidney, bladder, testicular, and penile cancer. Such breakthroughs necessitate the development of robust clinical-grade assays that can be quickly made available for patients to facilitate diagnosis in challenging cases, risk-stratify patients for subsequent clinical management, select the appropriate targeted therapy from among increasingly diverse and numerous options, and enroll patients in advanced clinical trials. This rapid translation of basic and clinical cancer research requires a streamlined, multidisciplinary approach to clinical assay development, termed here the molecular diagnostics service line laboratory. In this review, we summarize the current state and explore the future of molecular diagnostics in genitourinary oncology to conceptualize a genitourinary service line laboratory at a tertiary clinical institution.

Validation of Living Donor Nephrectomy Codes

PubMed Central

Lam, Ngan N.; Lentine, Krista L.; Klarenbach, Scott; Sood, Manish M.; Kuwornu, Paul J.; Naylor, Kyla L.; Knoll, Gregory A.; Kim, S. Joseph; Young, Ann; Garg, Amit X.

2018-01-01

Background: Use of administrative data for outcomes assessment in living kidney donors is increasing given the rarity of complications and challenges with loss to follow-up. Objective: To assess the validity of living donor nephrectomy in health care administrative databases compared with the reference standard of manual chart review. Design: Retrospective cohort study. Setting: 5 major transplant centers in Ontario, Canada. Patients: Living kidney donors between 2003 and 2010. Measurements: Sensitivity and positive predictive value (PPV). Methods: Using administrative databases, we conducted a retrospective study to determine the validity of diagnostic and procedural codes for living donor nephrectomies. The reference standard was living donor nephrectomies identified through the province’s tissue and organ procurement agency, with verification by manual chart review. Operating characteristics (sensitivity and PPV) of various algorithms using diagnostic, procedural, and physician billing codes were calculated. Results: During the study period, there were a total of 1199 living donor nephrectomies. Overall, the best algorithm for identifying living kidney donors was the presence of 1 diagnostic code for kidney donor (ICD-10 Z52.4) and 1 procedural code for kidney procurement/excision (1PC58, 1PC89, 1PC91). Compared with the reference standard, this algorithm had a sensitivity of 97% and a PPV of 90%. The diagnostic and procedural codes performed better than the physician billing codes (sensitivity 60%, PPV 78%). Limitations: The donor chart review and validation study was performed in Ontario and may not be generalizable to other regions. Conclusions: An algorithm consisting of 1 diagnostic and 1 procedural code can be reliably used to conduct health services research that requires the accurate determination of living kidney donors at the population level. PMID:29662679

Development and improvement of the operating diagnostics systems of NPO CKTI works for turbine of thermal and nuclear power plants

NASA Astrophysics Data System (ADS)

Kovalev, I. A.; Rakovskii, V. G.; Isakov, N. Yu.; Sandovskii, A. V.

2016-03-01

The work results on the development and improvement of the techniques, algorithms, and software-hardware of continuous operating diagnostics systems of rotating units and parts of turbine equipment state are presented. In particular, to ensure the full remote service of monitored turbine equipment using web technologies, the web version of the software of the automated systems of vibration-based diagnostics (ASVD VIDAS) was developed. The experience in the automated analysis of data obtained by ASVD VIDAS form the basis of the new algorithm of early detection of such dangerous defects as rotor deflection, crack in the rotor, and strong misalignment of supports. The program-technical complex of monitoring and measuring the deflection of medium pressure rotor (PTC) realizing this algorithm will alert the electric power plant staff during a deflection and indicate its value. This will give the opportunity to take timely measures to prevent the further extension of the defect. Repeatedly, recorded cases of full or partial destruction of shrouded shelves of rotor blades of the last stages of low-pressure cylinders of steam turbines defined the need to develop a version of the automated system of blade diagnostics (ASBD SKALA) for shrouded stages. The processing, analysis, presentation, and backup of data characterizing the mechanical state of blade device are carried out with a newly developed controller of the diagnostics system. As a result of the implementation of the works, the diagnosed parameters determining the operation security of rotating elements of equipment was expanded and the new tasks on monitoring the state of units and parts of turbines were solved. All algorithmic solutions and hardware-software implementations mentioned in the article were tested on the test benches and applied at some power plants.

NCCN Oncology Research Program's Investigator Steering Committee and NCCN Best Practices Committee Molecular Profiling Surveys.

PubMed

Kurzrock, Razelle; Colevas, A Dimitrios; Olszanski, Anthony; Akerley, Wallace; Arteaga, Carlos L; Carson, William E; Clark, Jeffrey W; DiPersio, John F; Ettinger, David S; Morgan, Robert J; Schwartzberg, Lee S; Venook, Alan P; Gocke, Christopher D; Tait, Jonathan; Stewart, F Marc

2015-11-01

With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, "molecular profiling/diagnostics" was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care. Copyright © 2015 by the National Comprehensive Cancer Network.

Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea

PubMed Central

Camilleri, Michael; Sellin, Joseph H.; Barrett, Kim E.

2016-01-01

Chronic watery diarrhea poses a diagnostic and therapeutic challenge and is often a disabling condition for patients. Although acute diarrhea is likely to be caused by infection, the causes of chronic diarrhea (more than 4 weeks in duration) are more elusive. We review on the pathophysiology, diagnosis, and treatment of chronic diarrhea. Drawing on recent insights into the molecular mechanisms of intestinal epithelial transport and barrier function, we discuss how diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both, as well as derangements in barrier properties. We also describe the various extra-epithelial factors that activate diarrheal mechanisms. Finally, clinical evaluation and tests used in assessment of patients presenting with chronic diarrhea are reviewed, and an algorithm guiding therapeutic decisions and pharmacotherapy is presented. PMID:27773805

A fast Monte Carlo EM algorithm for estimation in latent class model analysis with an application to assess diagnostic accuracy for cervical neoplasia in women with AGC

PubMed Central

Kang, Le; Carter, Randy; Darcy, Kathleen; Kauderer, James; Liao, Shu-Yuan

2013-01-01

In this article we use a latent class model (LCM) with prevalence modeled as a function of covariates to assess diagnostic test accuracy in situations where the true disease status is not observed, but observations on three or more conditionally independent diagnostic tests are available. A fast Monte Carlo EM (MCEM) algorithm with binary (disease) diagnostic data is implemented to estimate parameters of interest; namely, sensitivity, specificity, and prevalence of the disease as a function of covariates. To obtain standard errors for confidence interval construction of estimated parameters, the missing information principle is applied to adjust information matrix estimates. We compare the adjusted information matrix based standard error estimates with the bootstrap standard error estimates both obtained using the fast MCEM algorithm through an extensive Monte Carlo study. Simulation demonstrates that the adjusted information matrix approach estimates the standard error similarly with the bootstrap methods under certain scenarios. The bootstrap percentile intervals have satisfactory coverage probabilities. We then apply the LCM analysis to a real data set of 122 subjects from a Gynecologic Oncology Group (GOG) study of significant cervical lesion (S-CL) diagnosis in women with atypical glandular cells of undetermined significance (AGC) to compare the diagnostic accuracy of a histology-based evaluation, a CA-IX biomarker-based test and a human papillomavirus (HPV) DNA test. PMID:24163493

A simple algorithm for beam profile diagnostics using a thermographic camera

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

Katagiri, Ken; Hojo, Satoru; Honma, Toshihiro

2014-03-15

A new algorithm for digital image processing apparatuses is developed to evaluate profiles of high-intensity DC beams from temperature images of irradiated thin foils. Numerical analyses are performed to examine the reliability of the algorithm. To simulate the temperature images acquired by a thermographic camera, temperature distributions are numerically calculated for 20 MeV proton beams with different parameters. Noise in the temperature images which is added by the camera sensor is also simulated to account for its effect. Using the algorithm, beam profiles are evaluated from the simulated temperature images and compared with exact solutions. We find that niobium ismore » an appropriate material for the thin foil used in the diagnostic system. We also confirm that the algorithm is adaptable over a wide beam current range of 0.11–214 μA, even when employing a general-purpose thermographic camera with rather high noise (ΔT{sub NETD} ≃ 0.3 K; NETD: noise equivalent temperature difference)« less

Diagnostic Accuracy Comparison of Artificial Immune Algorithms for Primary Headaches.

PubMed

Çelik, Ufuk; Yurtay, Nilüfer; Koç, Emine Rabia; Tepe, Nermin; Güllüoğlu, Halil; Ertaş, Mustafa

2015-01-01

The present study evaluated the diagnostic accuracy of immune system algorithms with the aim of classifying the primary types of headache that are not related to any organic etiology. They are divided into four types: migraine, tension, cluster, and other primary headaches. After we took this main objective into consideration, three different neurologists were required to fill in the medical records of 850 patients into our web-based expert system hosted on our project web site. In the evaluation process, Artificial Immune Systems (AIS) were used as the classification algorithms. The AIS are classification algorithms that are inspired by the biological immune system mechanism that involves significant and distinct capabilities. These algorithms simulate the specialties of the immune system such as discrimination, learning, and the memorizing process in order to be used for classification, optimization, or pattern recognition. According to the results, the accuracy level of the classifier used in this study reached a success continuum ranging from 95% to 99%, except for the inconvenient one that yielded 71% accuracy.

Molecular diagnostic experience of whole-exome sequencing in adult patients.

PubMed

Posey, Jennifer E; Rosenfeld, Jill A; James, Regis A; Bainbridge, Matthew; Niu, Zhiyv; Wang, Xia; Dhar, Shweta; Wiszniewski, Wojciech; Akdemir, Zeynep H C; Gambin, Tomasz; Xia, Fan; Person, Richard E; Walkiewicz, Magdalena; Shaw, Chad A; Sutton, V Reid; Beaudet, Arthur L; Muzny, Donna; Eng, Christine M; Yang, Yaping; Gibbs, Richard A; Lupski, James R; Boerwinkle, Eric; Plon, Sharon E

2016-07-01

Whole-exome sequencing (WES) is increasingly used as a diagnostic tool in medicine, but prior reports focus on predominantly pediatric cohorts with neurologic or developmental disorders. We describe the diagnostic yield and characteristics of WES in adults. We performed a retrospective analysis of consecutive WES reports for adults from a diagnostic laboratory. Phenotype composition was determined using Human Phenotype Ontology terms. Molecular diagnoses were reported for 17.5% (85/486) of adults, which is lower than that for a primarily pediatric population (25.2%; P = 0.0003); the diagnostic rate was higher (23.9%) for those 18-30 years of age compared to patients older than 30 years (10.4%; P = 0.0001). Dual Mendelian diagnoses contributed to 7% of diagnoses, revealing blended phenotypes. Diagnoses were more frequent among individuals with abnormalities of the nervous system, skeletal system, head/neck, and growth. Diagnostic rate was independent of family history information, and de novo mutations contributed to 61.4% of autosomal dominant diagnoses. Early WES experience in adults demonstrates molecular diagnoses in a substantial proportion of patients, informing clinical management, recurrence risk, and recommendations for relatives. A positive family history was not predictive, consistent with molecular diagnoses often revealed by de novo events, informing the Mendelian basis of genetic disease in adults.Genet Med 18 7, 678-685.

Isothermal multiple displacement amplification: a methodical approach enhancing molecular routine diagnostics of microcarcinomas and small biopsies.

PubMed

Mairinger, Fabian D; Walter, Robert Fh; Vollbrecht, Claudia; Hager, Thomas; Worm, Karl; Ting, Saskia; Wohlschläger, Jeremias; Zarogoulidis, Paul; Zarogoulidis, Konstantinos; Schmid, Kurt W

2014-01-01

Isothermal multiple displacement amplification (IMDA) can be a powerful tool in molecular routine diagnostics for homogeneous and sequence-independent whole-genome amplification of notably small tumor samples, eg, microcarcinomas and biopsies containing a small amount of tumor. Currently, this method is not well established in pathology laboratories. We designed a study to confirm the feasibility and convenience of this method for routine diagnostics with formalin-fixed, paraffin-embedded samples prepared by laser-capture microdissection. A total of 250 μg DNA (concentration 5 μg/μL) was generated by amplification over a period of 8 hours with a material input of approximately 25 cells, approximately equivalent to 175 pg of genomic DNA. In the generated DNA, a representation of all chromosomes could be shown and the presence of elected genes relevant for diagnosis in clinical samples could be proven. Mutational analysis of clinical samples could be performed without any difficulty and showed concordance with earlier diagnostic findings. We established the feasibility and convenience of IMDA for routine diagnostics. We also showed that small amounts of DNA, which were not analyzable with current molecular methods, could be sufficient for a wide field of applications in molecular routine diagnostics when they are preamplified with IMDA.

Molecular Diagnostic Experience of Whole-Exome Sequencing in Adult Patients

PubMed Central

Posey, Jennifer E.; Rosenfeld, Jill A.; James, Regis A.; Bainbridge, Matthew; Niu, Zhiyv; Wang, Xia; Dhar, Shweta; Wiszniewski, Wojciech; Akdemir, Zeynep H.C.; Gambin, Tomasz; Xia, Fan; Person, Richard E.; Walkiewicz, Magdalena; Shaw, Chad A.; Sutton, V. Reid; Beaudet, Arthur L.; Muzny, Donna; Eng, Christine M.; Yang, Yaping; Gibbs, Richard A.; Lupski, James R.; Boerwinkle, Eric; Plon, Sharon E.

2015-01-01

Purpose Whole exome sequencing (WES) is increasingly used as a diagnostic tool in medicine, but prior reports focus on predominantly pediatric cohorts with neurologic or developmental disorders. We describe the diagnostic yield and characteristics of whole exome sequencing in adults. Methods We performed a retrospective analysis of consecutive WES reports for adults from a diagnostic laboratory. Phenotype composition was determined using Human Phenotype Ontology terms. Results Molecular diagnoses were reported for 17.5% (85/486) of adults, lower than a primarily pediatric population (25.2%; p=0.0003); the diagnostic rate was higher (23.9%) in those 18–30 years of age compared to patients over 30 years (10.4%; p=0.0001). Dual Mendelian diagnoses contributed to 7% of diagnoses, revealing blended phenotypes. Diagnoses were more frequent among individuals with abnormalities of the nervous system, skeletal system, head/neck, and growth. Diagnostic rate was independent of family history information, and de novo mutations contributed to 61.4% of autosomal dominant diagnoses. Conclusion Early WES experience in adults demonstrates molecular diagnoses in a substantial proportion of patients, informing clinical management, recurrence risk and recommendations for relatives. A positive family history was not predictive, consistent with molecular diagnoses often revealed by de novo events, informing the Mendelian basis of genetic disease in adults. PMID:26633545

Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology

PubMed Central

Sciacchitano, Salvatore; Lavra, Luca; Ulivieri, Alessandra; Magi, Fiorenza; De Francesco, Gian Paolo; Bellotti, Carlo; Salehi, Leila B.; Trovato, Maria; Drago, Carlo; Bartolazzi, Armando

2017-01-01

Since it is impossible to recognize malignancy at fine needle aspiration (FNA) cytology in indeterminate thyroid nodules, surgery is recommended for all of them. However, cancer rate at final histology is <30%. Many different test-methods have been proposed to increase diagnostic accuracy in such lesions, including Galectin-3-ICC (GAL-3-ICC), BRAF mutation analysis (BRAF), Gene Expression Classifier (GEC) alone and GEC+BRAF, mutation/fusion (M/F) panel, alone, M/F panel+miRNA GEC, and M/F panel by next generation sequencing (NGS), FDG-PET/CT, MIBI-Scan and TSHR mRNA blood assay. We performed systematic reviews and meta-analyses to compare their features, feasibility, diagnostic performance and cost. GEC, GEC+BRAF, M/F panel+miRNA GEC and M/F panel by NGS were the best in ruling-out malignancy (sensitivity = 90%, 89%, 89% and 90% respectively). BRAF and M/F panel alone and by NGS were the best in ruling-in malignancy (specificity = 100%, 93% and 93%). The M/F by NGS showed the highest accuracy (92%) and BRAF the highest diagnostic odds ratio (DOR) (247). GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%) and high DOR (27) and is one of the cheapest (113 USD) and easiest one to be performed in different clinical settings. In conclusion, the more accurate molecular-based test-methods are still expensive and restricted to few, highly specialized and centralized laboratories. GAL-3-ICC, although limited by some false negatives, represents the most suitable screening test-method to be applied on a large-scale basis in the diagnostic algorithm of indeterminate thyroid lesions. PMID:28472764

Bio-inspired algorithms applied to molecular docking simulations.

PubMed

Heberlé, G; de Azevedo, W F

2011-01-01

Nature as a source of inspiration has been shown to have a great beneficial impact on the development of new computational methodologies. In this scenario, analyses of the interactions between a protein target and a ligand can be simulated by biologically inspired algorithms (BIAs). These algorithms mimic biological systems to create new paradigms for computation, such as neural networks, evolutionary computing, and swarm intelligence. This review provides a description of the main concepts behind BIAs applied to molecular docking simulations. Special attention is devoted to evolutionary algorithms, guided-directed evolutionary algorithms, and Lamarckian genetic algorithms. Recent applications of these methodologies to protein targets identified in the Mycobacterium tuberculosis genome are described.

[Future perspectives for diagnostic imaging in urology: from anatomic and functional to molecular imaging].

PubMed

Macis, Giuseppe; Di Giovanni, Silvia; Di Franco, Davide; Bonomo, Lorenzo

2013-01-01

The future approach of diagnostic imaging in urology follows the technological progress, which made the visualization of in vivo molecular processes possible. From anatomo-morphological diagnostic imaging and through functional imaging molecular radiology is reached. Based on molecular probes, imaging is aimed at assessing the in vivo molecular processes, their physiology and function at cellular level. The future imaging will investigate the complex tumor functioning as metabolism, aerobic glycolysis in particular, angiogenesis, cell proliferation, metastatic potential, hypoxia, apoptosis and receptors expressed by neoplastic cells. Methods for performing molecular radiology are CT, MRI, PET-CT, PET-MRI, SPECT and optical imaging. Molecular ultrasound combines technological advancement with targeted contrast media based on microbubbles, this allowing the selective registration of microbubble signal while that of stationary tissues is suppressed. An experimental study was carried out where the ultrasound molecular probe BR55 strictly bound to prostate tumor results in strong enhancement in the early phase after contrast, this contrast being maintained in the late phase. This late enhancement is markedly significant for the detection of prostatic cancer foci and to guide the biopsy sampling. The 124I-cG250 molecular antibody which is strictly linked to cellular carbonic anhydrase IX of clear cell renal carcinoma, allows the acquisition of diagnostic PET images of clear cell renal carcinoma without biopsy. This WG-250 (RENCAREX) antibody was used as a therapy in metastatic clear cell renal carcinoma. Future advancements and applications will result in early cancer diagnosis, personalized therapy that will be specific according to the molecular features of cancer and leading to the development of catheter-based multichannel molecular imaging devices for cystoscopy-based molecular imaging diagnosis and intervention.

Pediatric chest HRCT using the iDose4 Hybrid Iterative Reconstruction Algorithm: Which iDose level to choose?

NASA Astrophysics Data System (ADS)

Smarda, M.; Alexopoulou, E.; Mazioti, A.; Kordolaimi, S.; Ploussi, A.; Priftis, K.; Efstathopoulos, E.

2015-09-01

Purpose of the study is to determine the appropriate iterative reconstruction (IR) algorithm level that combines image quality and diagnostic confidence, for pediatric patients undergoing high-resolution computed tomography (HRCT). During the last 2 years, a total number of 20 children up to 10 years old with a clinical presentation of chronic bronchitis underwent HRCT in our department's 64-detector row CT scanner using the iDose IR algorithm, with almost similar image settings (80kVp, 40-50 mAs). CT images were reconstructed with all iDose levels (level 1 to 7) as well as with filtered-back projection (FBP) algorithm. Subjective image quality was evaluated by 2 experienced radiologists in terms of image noise, sharpness, contrast and diagnostic acceptability using a 5-point scale (1=excellent image, 5=non-acceptable image). Artifacts existance was also pointed out. All mean scores from both radiologists corresponded to satisfactory image quality (score ≤3), even with the FBP algorithm use. Almost excellent (score <2) overall image quality was achieved with iDose levels 5 to 7, but oversmoothing artifacts appearing with iDose levels 6 and 7 affected the diagnostic confidence. In conclusion, the use of iDose level 5 enables almost excellent image quality without considerable artifacts affecting the diagnosis. Further evaluation is needed in order to draw more precise conclusions.

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.

Clinical Predictors of Shigella and Campylobacter Infection in Children in the United States

PubMed Central

Smith, Timothy; Ye, Xiangyang; Stockmann, Chris; Cohen, Daniel; Leber, Amy; Daly, Judy; Jackson, Jami; Selvarangan, Rangaraj; Kanwar, Neena; Bender, Jeffery; Bard, Jennifer Dien; Festekjian, Ara; Duffy, Susan; Larsen, Chari; Baca, Tanya; Holmberg, Kristen; Bourzac, Kevin; Chapin, Kimberle C; Pavia, Andrew; Leung, Daniel

2017-01-01

Abstract Background Infectious gastroenteritis is a major cause of morbidity and mortality among children worldwide. While most episodes are self-limiting, for select pathogens such as Shigella and Campylobacter, etiological diagnosis may allow effective antimicrobial therapy and aid public health interventions. Unfortunately, clinical predictors of such pathogens are not well established and are based on small studies using bacterial culture for identification. Methods We used prospectively collected data from a multi-center study of pediatric gastroenteritis employing multi-pathogen molecular diagnostics to determine clinical predictors associated with 1) Shigella and 2) Shigella or Campylobacter infection. We used machine learning algorithms for clinical predictor identification, then performed logistic regression on features extracted plus pre-selected variables of interest. Results Of 993 children enrolled with acute diarrhea, we detected Shigella spp. in 56 (5.6%) and Campylobacter spp. in 24 (2.4%). Compared with children who had neither pathogen detected (of whom, >70% had ≥1 potential pathogen identified), bloody diarrhea (odds ratio 4.0), headache (OR 2.2), fever (OR 7.1), summer (OR 3.3), and sick contact with GI illness (OR 2.2), were positively associated with Shigella, and out-of-state travel (OR 0.3) and vomiting and/or nausea (OR 0.4) were negatively associated (Table). For Shigella or Campylobacter, predictors were similar but season was no longer significantly associated with infection. Conclusion These results can create prediction models and assist clinicians with identifying patients who would benefit from diagnostic testing and earlier antibiotic treatment. This may curtail unnecessary antibiotic use, and help to direct and target appropriate use of stool diagnostics. Disclosures A. Leber, BioFIre Diagnostics: Research Contractor and Scientific Advisor, Research support, Speaker honorarium and Travel expenses J. Daly, Biofire: Grant Investigator, Grant recipient R. Selvarangan, BioFire Diagnostics: Board Member and Investigator, Consulting fee and Research grant Luminex Diagnostics: Investigator, Research grant J. Dien Bard, BioFire: Consultant and Investigator, Research grant and Speaker honorarium K. Holmberg, BioFire Diagnostics: Employee, Salary K. Bourzac, BioFire Diagnostics: Employee, Salary K. C. Chapin, BioFire Diagnstics: Investigator, Research support A. Pavia, BioFire Diagnostics: Grant Investigator, Research grant

Improved Temperature Diagnostic for Non-Neutral Plasmas with Single-Electron Resolution

NASA Astrophysics Data System (ADS)

Shanman, Sabrina; Evans, Lenny; Fajans, Joel; Hunter, Eric; Nelson, Cheyenne; Sierra, Carlos; Wurtele, Jonathan

2016-10-01

Plasma temperature diagnostics in a Penning-Malmberg trap are essential for reliably obtaining cold, non-neutral plasmas. We have developed a setup for detecting the initial electrons that escape from a trapped pure electron plasma as the confining electrode potential is slowly reduced. The setup minimizes external noise by using a silicon photomultiplier to capture light emitted from an MCP-amplified phosphor screen. To take advantage of this enhanced resolution, we have developed a new plasma temperature diagnostic analysis procedure which takes discrete electron arrival times as input. We have run extensive simulations comparing this new discrete algorithm to our existing exponential fitting algorithm. These simulations are used to explore the behavior of these two temperature diagnostic procedures at low N and at high electronic noise. This work was supported by the DOE DE-FG02-06ER54904, and the NSF 1500538-PHY.

Molecular diagnostics in the neoplasms of the pancreas, liver, gall bladder, and extrahepatic biliary tract.

PubMed

Weindel, Michael; Zulfiqar, Muhammad; Bhalla, Amarpreet; Shidham, Vinod B

2013-12-01

Pancreatic neoplasms, including ductal adenocarcinoma, intraductal papillary mucinous neoplasm, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and ampullary carcinoma, are associated with different genetic abnormalities. Liver neoplasms, including hepatic adenomas, hepatocellular carcinomas, and cholangiocarcinomas, are associated with identifiable risk factors and genetic changes. Gall bladder adenomas and adenocarcinomas arise from distinct molecular pathways. The molecular abnormalities seen in these tumors are not used routinely in the molecular diagnostic laboratory. Copyright © 2013 Elsevier Inc. All rights reserved.

Embedded Reasoning Supporting Aerospace IVHM

DTIC Science & Technology

2007-01-01

c method (BIT or health assessment algorithm) which the monitoring diagnostic relies on input information tics and Astronautics In the diagram...viewing of the current health state of all monitored subsystems, while also providing a means to probe deeper in the event anomalous operation is...seeks to integrate detection , diagnostic, and prognostic capabilities with a hierarchical diagnostic reasoning architecture into a single

An algorithm for improving the quality of structural images of turbid media in endoscopic optical coherence tomography

NASA Astrophysics Data System (ADS)

Potlov, A. Yu.; Frolov, S. V.; Proskurin, S. G.

2018-04-01

High-quality OCT structural images reconstruction algorithm for endoscopic optical coherence tomography of biological tissue is described. The key features of the presented algorithm are: (1) raster scanning and averaging of adjacent Ascans and pixels; (2) speckle level minimization. The described algorithm can be used in the gastroenterology, urology, gynecology, otorhinolaryngology for mucous membranes and skin diagnostics in vivo and in situ.

An algorithmic approach to the brain biopsy--part I.

PubMed

Kleinschmidt-DeMasters, B K; Prayson, Richard A

2006-11-01

The formulation of appropriate differential diagnoses for a slide is essential to the practice of surgical pathology but can be particularly challenging for residents and fellows. Algorithmic flow charts can help the less experienced pathologist to systematically consider all possible choices and eliminate incorrect diagnoses. They can assist pathologists-in-training in developing orderly, sequential, and logical thinking skills when confronting difficult cases. To present an algorithmic flow chart as an approach to formulating differential diagnoses for lesions seen in surgical neuropathology. An algorithmic flow chart to be used in teaching residents. Algorithms are not intended to be final diagnostic answers on any given case. Algorithms do not substitute for training received from experienced mentors nor do they substitute for comprehensive reading by trainees of reference textbooks. Algorithmic flow diagrams can, however, direct the viewer to the correct spot in reference texts for further in-depth reading once they hone down their diagnostic choices to a smaller number of entities. The best feature of algorithms is that they remind the user to consider all possibilities on each case, even if they can be quickly eliminated from further consideration. In Part I, we assist the resident in learning how to handle brain biopsies in general and how to distinguish nonneoplastic lesions that mimic tumors from true neoplasms.

An algorithmic approach to the brain biopsy--part II.

PubMed

Prayson, Richard A; Kleinschmidt-DeMasters, B K

2006-11-01

The formulation of appropriate differential diagnoses for a slide is essential to the practice of surgical pathology but can be particularly challenging for residents and fellows. Algorithmic flow charts can help the less experienced pathologist to systematically consider all possible choices and eliminate incorrect diagnoses. They can assist pathologists-in-training in developing orderly, sequential, and logical thinking skills when confronting difficult cases. To present an algorithmic flow chart as an approach to formulating differential diagnoses for lesions seen in surgical neuropathology. An algorithmic flow chart to be used in teaching residents. Algorithms are not intended to be final diagnostic answers on any given case. Algorithms do not substitute for training received from experienced mentors nor do they substitute for comprehensive reading by trainees of reference textbooks. Algorithmic flow diagrams can, however, direct the viewer to the correct spot in reference texts for further in-depth reading once they hone down their diagnostic choices to a smaller number of entities. The best feature of algorithms is that they remind the user to consider all possibilities on each case, even if they can be quickly eliminated from further consideration. In Part II, we assist the resident in arriving at the correct diagnosis for neuropathologic lesions containing granulomatous inflammation, macrophages, or abnormal blood vessels.

Economic evaluation of the one-hour rule-out and rule-in algorithm for acute myocardial infarction using the high-sensitivity cardiac troponin T assay in the emergency department.

PubMed

Ambavane, Apoorva; Lindahl, Bertil; Giannitsis, Evangelos; Roiz, Julie; Mendivil, Joan; Frankenstein, Lutz; Body, Richard; Christ, Michael; Bingisser, Roland; Alquezar, Aitor; Mueller, Christian

2017-01-01

The 1-hour (h) algorithm triages patients presenting with suspected acute myocardial infarction (AMI) to the emergency department (ED) towards "rule-out," "rule-in," or "observation," depending on baseline and 1-h levels of high-sensitivity cardiac troponin (hs-cTn). The economic consequences of applying the accelerated 1-h algorithm are unknown. We performed a post-hoc economic analysis in a large, diagnostic, multicenter study of hs-cTnT using central adjudication of the final diagnosis by two independent cardiologists. Length of stay (LoS), resource utilization (RU), and predicted diagnostic accuracy of the 1-h algorithm compared to standard of care (SoC) in the ED were estimated. The ED LoS, RU, and accuracy of the 1-h algorithm was compared to that achieved by the SoC at ED discharge. Expert opinion was sought to characterize clinical implementation of the 1-h algorithm, which required blood draws at ED presentation and 1h, after which "rule-in" patients were transferred for coronary angiography, "rule-out" patients underwent outpatient stress testing, and "observation" patients received SoC. Unit costs were for the United Kingdom, Switzerland, and Germany. The sensitivity and specificity for the 1-h algorithm were 87% and 96%, respectively, compared to 69% and 98% for SoC. The mean ED LoS for the 1-h algorithm was 4.3h-it was 6.5h for SoC, which is a reduction of 33%. The 1-h algorithm was associated with reductions in RU, driven largely by the shorter LoS in the ED for patients with a diagnosis other than AMI. The estimated total costs per patient were £2,480 for the 1-h algorithm compared to £4,561 for SoC, a reduction of up to 46%. The analysis shows that the use of 1-h algorithm is associated with reduction in overall AMI diagnostic costs, provided it is carefully implemented in clinical practice. These results need to be prospectively validated in the future.

Molecular diagnostics for hereditary hearing loss in children.

PubMed

Sommen, Manou; Wuyts, Wim; Van Camp, Guy

2017-08-01

Hearing loss (HL) is the most common birth defect in industrialized countries with far-reaching social, psychological and cognitive implications. It is an extremely heterogeneous disease, complicating molecular testing. The introduction of next-generation sequencing (NGS) has resulted in great progress in diagnostics allowing to study all known HL genes in a single assay. The diagnostic yield is currently still limited, but has the potential to increase substantially. Areas covered: In this review the utility of NGS and the problems for comprehensive molecular testing for HL are evaluated and discussed. Expert commentary: Different publications have proven the appropriateness of NGS for molecular testing of heterogeneous diseases such as HL. However, several problems still exist, such as pseudogenic background of some genes and problematic copy number variant analysis on targeted NGS data. Another main challenge for the future will be the establishment of population specific mutation-spectra to achieve accurate personalized comprehensive molecular testing for HL.

Molecular Pathology: Predictive, Prognostic, and Diagnostic Markers in Uterine Tumors.

PubMed

Ritterhouse, Lauren L; Howitt, Brooke E

2016-09-01

This article focuses on the diagnostic, prognostic, and predictive molecular biomarkers in uterine malignancies, in the context of morphologic diagnoses. The histologic classification of endometrial carcinomas is reviewed first, followed by the description and molecular classification of endometrial epithelial malignancies in the context of histologic classification. Taken together, the molecular and histologic classifications help clinicians to approach troublesome areas encountered in clinical practice and evaluate the utility of molecular alterations in the diagnosis and subclassification of endometrial carcinomas. Putative prognostic markers are reviewed. The use of molecular alterations and surrogate immunohistochemistry as prognostic and predictive markers is also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

A grid matrix-based Raman spectroscopic method to characterize different cell milieu in biopsied axillary sentinel lymph nodes of breast cancer patients.

PubMed

Som, Dipasree; Tak, Megha; Setia, Mohit; Patil, Asawari; Sengupta, Amit; Chilakapati, C Murali Krishna; Srivastava, Anurag; Parmar, Vani; Nair, Nita; Sarin, Rajiv; Badwe, R

2016-01-01

Raman spectroscopy which is based upon inelastic scattering of photons has a potential to emerge as a noninvasive bedside in vivo or ex vivo molecular diagnostic tool. There is a need to improve the sensitivity and predictability of Raman spectroscopy. We developed a grid matrix-based tissue mapping protocol to acquire cellular-specific spectra that also involved digital microscopy for localizing malignant and lymphocytic cells in sentinel lymph node biopsy sample. Biosignals acquired from specific cellular milieu were subjected to an advanced supervised analytical method, i.e., cross-correlation and peak-to-peak ratio in addition to PCA and PC-LDA. We observed decreased spectral intensity as well as shift in the spectral peaks of amides and lipid bands in the completely metastatic (cancer cells) lymph nodes with high cellular density. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to create an automated smart diagnostic tool for bench side screening of sampled lymph nodes. Spectral library of normal lymphocytes and metastatic cancer cells created using the cellular specific mapping technique can be utilized to develop an automated smart diagnostic tool for bench side screening of sampled lymph nodes supported by ongoing global research in developing better technology and signal and big data processing algorithms.

Molecular diagnostics for Chagas disease: up to date and novel methodologies.

PubMed

Alonso-Padilla, Julio; Gallego, Montserrat; Schijman, Alejandro G; Gascon, Joaquim

2017-07-01

Chagas disease is caused by the parasite Trypanosoma cruzi. It affects 7 million people, mainly in Latin America. Diagnosis is usually made serologically, but at some clinical scenarios serology cannot be used. Then, molecular detection is required for early detection of congenital transmission, treatment response follow up, and diagnosis of immune-suppression reactivation. However, present tests are technically demanding and require well-equipped laboratories which make them unfeasible in low-resources endemic regions. Areas covered: Available molecular tools for detection of T. cruzi DNA, paying particular attention to quantitative PCR protocols, and to the latest developments of user-friendly molecular diagnostic methodologies. Expert commentary: In the absence of appropriate biomarkers, molecular diagnosis is the only option for the assessment of treatment response. Besides, it is very useful for the early detection of acute infections, like congenital cases. Since current Chagas disease molecular tests are restricted to referential labs, research efforts must focus in the implementation of easy-to-use diagnostic tools in order to overcome the access to diagnosis gap.

A Comparative Analysis of the ADOS-G and ADOS-2 Algorithms: Preliminary Findings.

PubMed

Dorlack, Taylor P; Myers, Orrin B; Kodituwakku, Piyadasa W

2018-06-01

The Autism Diagnostic Observation Schedule (ADOS) is a widely utilized observational assessment tool for diagnosis of autism spectrum disorders. The original ADOS was succeeded by the ADOS-G with noted improvements. More recently, the ADOS-2 was introduced to further increase its diagnostic accuracy. Studies examining the validity of the ADOS have produced mixed findings, and pooled relationship trends between the algorithm versions are yet to be analyzed. The current review seeks to compare the relative merits of the ADOS-G and ADOS-2 algorithms, Modules 1-3. Eight studies met inclusion criteria for the review, and six were selected for paired comparisons of the sensitivity and specificity of the ADOS. Results indicate several contradictory findings, underscoring the importance of further study.

Automatic analysis and classification of surface electromyography.

PubMed

Abou-Chadi, F E; Nashar, A; Saad, M

2001-01-01

In this paper, parametric modeling of surface electromyography (EMG) algorithms that facilitates automatic SEMG feature extraction and artificial neural networks (ANN) are combined for providing an integrated system for the automatic analysis and diagnosis of myopathic disorders. Three paradigms of ANN were investigated: the multilayer backpropagation algorithm, the self-organizing feature map algorithm and a probabilistic neural network model. The performance of the three classifiers was compared with that of the old Fisher linear discriminant (FLD) classifiers. The results have shown that the three ANN models give higher performance. The percentage of correct classification reaches 90%. Poorer diagnostic performance was obtained from the FLD classifier. The system presented here indicates that surface EMG, when properly processed, can be used to provide the physician with a diagnostic assist device.

Molecular Diagnostics of Fusion and Laboratory Plasmas

NASA Astrophysics Data System (ADS)

Fantz, U.

2005-05-01

The presence of molecules in the cold scrape-off layer of fusion experiments and industrial plasmas requires an understanding of the molecular dynamics in these low temperature plasmas. Suitable diagnostic methods can provide an insight in molecular processes in the plasma volume as well as for plasma surface interactions. A very simple but powerful technique is the molecular emission spectroscopy. Spectra are obtained easily, whereas interpretation might be very complex and relies on the availability of atomic and molecular data. Examples are given for hydrogen plasmas and plasmas with hydrocarbons which both are of importance in industrial applications as well as in fusion experiments.

GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.

PubMed

Hess, Berk; Kutzner, Carsten; van der Spoel, David; Lindahl, Erik

2008-03-01

Molecular simulation is an extremely useful, but computationally very expensive tool for studies of chemical and biomolecular systems. Here, we present a new implementation of our molecular simulation toolkit GROMACS which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines. The code encompasses a minimal-communication domain decomposition algorithm, full dynamic load balancing, a state-of-the-art parallel constraint solver, and efficient virtual site algorithms that allow removal of hydrogen atom degrees of freedom to enable integration time steps up to 5 fs for atomistic simulations also in parallel. To improve the scaling properties of the common particle mesh Ewald electrostatics algorithms, we have in addition used a Multiple-Program, Multiple-Data approach, with separate node domains responsible for direct and reciprocal space interactions. Not only does this combination of algorithms enable extremely long simulations of large systems but also it provides that simulation performance on quite modest numbers of standard cluster nodes.

Molecular Approaches to Thyroid Cancer Diagnosis

PubMed Central

Hsiao, Susan J.; Nikiforov, Yuri E.

2014-01-01

Thyroid nodules are common, and the accurate diagnosis of cancer or benign disease is important for the effective clinical management of these patients. Molecular markers are a helpful diagnostic tool, particularly for cytologically indeterminate thyroid nodules. In the past few years, significant progress has been made in developing molecular markers for clinical use in fine needle aspiration (FNA) specimens, including gene mutation panels and gene expression classifiers. With the availability of next generation sequencing technology, gene mutation panels can be expanded to interrogate multiple genes simultaneously and to provide yet more accurate diagnostic information. In addition, recently several new molecular markers in thyroid cancer have been identified that offer diagnostic, prognostic, and therapeutic information that could potentially be of value in guiding individualized management of patients with thyroid nodules. PMID:24829266

Intestinal cestodes.

PubMed

Webb, Camille; Cabada, Miguel M

2017-10-01

Cestodes infections in humans are among the most prevalent parasitosis worldwide. Although tapeworm infection is often asymptomatic, they can be associated with a range of symptoms. The landscape of cestode infections is changing with rapid diagnosis techniques and advanced molecular diagnosis aiding in identification of species specific epidemiology. Traditional descriptions of species by location have been challenged with molecular diagnostic techniques, which show variation in distribution of species, thought to be because of globalization and importation of disease. Epidemiology, molecular diagnostic techniques. Infection by tapeworms is often asymptomatic or accompanied by mild symptoms though can occasionally cause severe disease and contribute to anemia and malnutrition. Tapeworm infection is most prevalent in resource-poor countries but the distribution is worldwide. Epidemiology of infection is changing because of molecular diagnostics, which allow more accurate tracking of species.

A new molecular diagnostic tool for quantitatively detecting and genotyping “Candidatus Liberibacter species”

USDA-ARS?s Scientific Manuscript database

A new molecular diagnostic method was developed for quantitative detection of “Candidatus Liberibacter” species associated with citrus Huanglongbing (“Ca. Liberibacter asiaticus”, “Ca. Liberibacter africanus” and “Ca. Liberibacter americanus”) and potato zebra chip disorder (“Ca. Liberibacter solana...

Deep learning based syndrome diagnosis of chronic gastritis.

PubMed

Liu, Guo-Ping; Yan, Jian-Jun; Wang, Yi-Qin; Zheng, Wu; Zhong, Tao; Lu, Xiong; Qian, Peng

2014-01-01

In Traditional Chinese Medicine (TCM), most of the algorithms used to solve problems of syndrome diagnosis are superficial structure algorithms and not considering the cognitive perspective from the brain. However, in clinical practice, there is complex and nonlinear relationship between symptoms (signs) and syndrome. So we employed deep leaning and multilabel learning to construct the syndrome diagnostic model for chronic gastritis (CG) in TCM. The results showed that deep learning could improve the accuracy of syndrome recognition. Moreover, the studies will provide a reference for constructing syndrome diagnostic models and guide clinical practice.

Open Energy Information System version 2.0

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

OpenEIS was created to provide standard methods for authoring, sharing, testing, using, and improving algorithms for operational building energy efficiency with building managers and building owners. OpenEIS is designed as a no-cost/low-cost solution that will propagate the fault detection and diagnostic (FDD) solutions into the marketplace by providing state- of- the-art analytical and diagnostic algorithms. As OpenEIS penetrates the market, demand by control system manufacturers and integrators serving small and medium commercial customers will help push these types of commercial software tool offerings into the broader marketplace.

Deep Learning Based Syndrome Diagnosis of Chronic Gastritis

PubMed Central

Liu, Guo-Ping; Wang, Yi-Qin; Zheng, Wu; Zhong, Tao; Lu, Xiong; Qian, Peng

2014-01-01

In Traditional Chinese Medicine (TCM), most of the algorithms used to solve problems of syndrome diagnosis are superficial structure algorithms and not considering the cognitive perspective from the brain. However, in clinical practice, there is complex and nonlinear relationship between symptoms (signs) and syndrome. So we employed deep leaning and multilabel learning to construct the syndrome diagnostic model for chronic gastritis (CG) in TCM. The results showed that deep learning could improve the accuracy of syndrome recognition. Moreover, the studies will provide a reference for constructing syndrome diagnostic models and guide clinical practice. PMID:24734118

A national study of breast and colorectal cancer patients' decision-making for novel personalized medicine genomic diagnostics.

PubMed

Issa, Amalia M; Tufail, Waqas; Atehortua, Nelson; McKeever, John

2013-05-01

Molecular diagnostics are increasingly being used to help guide decision-making for personalized medical treatment of breast and colorectal cancer patients. The main aim of this study was to better understand and determine breast and colorectal cancer patients' decision-making strategies and the trade-offs they make in deciding about characteristics of molecular genomic diagnostics for breast and colorectal cancer. We surveyed a nationally representative sample of 300 breast and colorectal cancer patients using a previously developed web-administered instrument. Eligibility criteria included patients aged 18 years and older with either breast or colorectal cancer. We explored several attributes and attribute levels of molecular genomic diagnostics in 20 scenarios. Our analysis revealed that both breast and colorectal cancer patients weighted the capability of molecular genomic diagnostics to determine the probability of treatment efficacy as being of greater importance than information provided to detect adverse events. The probability of either false-positive or -negative results was ranked highly as a potential barrier by both breast and colorectal patients. However, 78.6% of breast cancer patients ranked the possibility of a 'false-negative test result leading to undertreatment' higher than the 'chance of a false positive, which may lead to overtreatment' (68%). This finding contrasted with the views of colorectal cancer patients who ranked the chance of a false positive as being of greater concern than a false negative (72.8 vs 63%). Overall, cancer patients exhibited a high willingness to accept and pay for genomic diagnostic tests, especially among breast cancer patients. Cancer patients seek a test accuracy rate of 90% or higher. Breast and colorectal cancer patients' decisions about genomic diagnostics are influenced more by the probability of being cured than by avoiding potential severe adverse events. This study provides insights into the relative weight that breast and colorectal cancer patients place on various aspects of molecular genomic diagnostics, and the trade-offs they are willing to make among attributes of such tests.

A stochastic thermostat algorithm for coarse-grained thermomechanical modeling of large-scale soft matters: Theory and application to microfilaments

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

Li, Tong; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au

As all-atom molecular dynamics method is limited by its enormous computational cost, various coarse-grained strategies have been developed to extend the length scale of soft matters in the modeling of mechanical behaviors. However, the classical thermostat algorithm in highly coarse-grained molecular dynamics method would underestimate the thermodynamic behaviors of soft matters (e.g. microfilaments in cells), which can weaken the ability of materials to overcome local energy traps in granular modeling. Based on all-atom molecular dynamics modeling of microfilament fragments (G-actin clusters), a new stochastic thermostat algorithm is developed to retain the representation of thermodynamic properties of microfilaments at extra coarse-grainedmore » level. The accuracy of this stochastic thermostat algorithm is validated by all-atom MD simulation. This new stochastic thermostat algorithm provides an efficient way to investigate the thermomechanical properties of large-scale soft matters.« less

Targeted Next Generation Sequencing with ThyroSeq v2.1 for Indeterminate Thyroid Nodules in Clinical Practice.

PubMed

Witt, Robert L

2016-12-01

To determine if patients elect molecular testing over diagnostic surgery or repeat fine needle aspiration for indeterminate thyroid nodules. Can ThyroSeq v2.1 molecular testing reduce diagnostic thyroid surgery and rule out cancer? Retrospective review Setting: Single institution, single-practice surgeon. Fifteen month retrospective review of indeterminate thyroid nodules that went on to ThyroSeq v2.1 testing. 286 patients met American Thyroid Association guideline criteria for surgeon- performed, ultrasound-guided fine needle aspiration for a thyroid nodule with on-site cytopathology. The indeterminate (Bethesda III or IV) fine needle aspiration cytology rate was 9.1 percent. Prevalence of malignancy in indeterminate nodules was 19 percent. 26/26 (100 percent) patients with indeterminate thyroid nodules elected molecular testing. 16 patients had no mutation, 9 had one or more mutations, and I had no result. 16 of 25 (64 percent) patients with no mutation elected not to undergo diagnostic surgery for indeterminate thyroid nodules. Patients demonstrated a strong preference for molecular testing instead of diagnostic thyroid surgery for indeterminate thyroid nodules. All patients in this series, 25/25 (100 percent) with indeterminate thyroid nodules elected molecular testing instead of repeat biopsy or diagnostic thyroid surgery. 16 of 25 (64 percent) patients tested had no mutation. All 16/16 (100 percent) patients with no mutation on ThyroSeq "rule out" testing elected active surveillance rather than surgery or biopsy, reducing diagnostic surgery. The risk of malignancy among mutation negative patients was not definitively established. There are a number of factors currently that may mute the power of "rule in" testing.

Conventional and molecular diagnostic strategies for prosthetic joint infections.

PubMed

Esteban, Jaime; Sorlí, Luisa; Alentorn-Geli, Eduard; Puig, Lluís; Horcajada, Juan P

2014-01-01

An accurate diagnosis of prosthetic joint infection (PJI) is the mainstay for an optimized clinical management. This review analyzes different diagnostic strategies of PJI, with special emphasis on molecular diagnostic tools and their current and future applications. Until now, the culture of periprosthetic tissues has been considered the gold standard for the diagnosis of PJI. However, sonication of the implant increases the sensitivity of those cultures and is being increasingly adopted by many centers. Molecular diagnostic methods compared with intraoperative tissue culture, especially if combined with sonication, have a higher sensitivity, a faster turnaround time and are not influenced by previous antimicrobial therapy. However, they still lack a system for detection of antimicrobial susceptibility, which is crucial for an optimized and less toxic therapy of PJI. More studies are needed to assess the clinical value of these methods and their cost-effectiveness.

Novel molecular diagnostic tools for malaria elimination: a review of options from the point of view of high-throughput and applicability in resource limited settings.

PubMed

Britton, Sumudu; Cheng, Qin; McCarthy, James S

2016-02-16

As malaria transmission continues to decrease, an increasing number of countries will enter pre-elimination and elimination. To interrupt transmission, changes in control strategies are likely to require more accurate identification of all carriers of Plasmodium parasites, both symptomatic and asymptomatic, using diagnostic tools that are highly sensitive, high throughput and with fast turnaround times preferably performed in local health service settings. Currently available immunochromatographic lateral flow rapid diagnostic tests and field microscopy are unlikely to consistently detect infections at parasite densities less than 100 parasites/µL making them insufficiently sensitive for detecting all carriers. Molecular diagnostic platforms, such as PCR and LAMP, are currently available in reference laboratories, but at a cost both financially and in turnaround time. This review describes the recent progress in developing molecular diagnostic tools in terms of their capacity for high throughput and potential for performance in non-reference laboratories for malaria elimination.

New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

PubMed Central

Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

2011-01-01

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC. PMID:22028706

New aspects in the differential diagnosis and therapy of bladder pain syndrome/interstitial cystitis.

PubMed

Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

2011-01-01

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical "columns": (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.

Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics.

PubMed

M'Koma, Amosy E

2014-11-27

Accurate diagnosis of predominantly colonic inflammatory bowel disease (IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn's colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry (MS) and imaging (I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed.

Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics

PubMed Central

M’Koma, Amosy E

2014-01-01

Accurate diagnosis of predominantly colonic inflammatory bowel disease (IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn’s colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry (MS) and imaging (I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed. PMID:25429322

A Testbed for Data Fusion for Helicopter Diagnostics and Prognostics

DTIC Science & Technology

2003-03-01

and algorithm design and tuning in order to develop advanced diagnostic and prognostic techniques for air craft health monitoring . Here a...and development of models for diagnostics, prognostics , and anomaly detection . Figure 5 VMEP Server Browser Interface 7 Download... detections , and prognostic prediction time horizons. The VMEP system and in particular the web component are ideal for performing data collection

Using Standardized Diagnostic Instruments to Classify Children with Autism in the Study to Explore Early Development

ERIC Educational Resources Information Center

Wiggins, Lisa D.; Reynolds, Ann; Rice, Catherine E.; Moody, Eric J.; Bernal, Pilar; Blaskey, Lisa; Rosenberg, Steven A.; Lee, Li-Ching; Levy, Susan E.

2015-01-01

The Study to Explore Early Development (SEED) is a multi-site case-control study designed to explore the relationship between autism spectrum disorder (ASD) phenotypes and etiologies. The goals of this paper are to (1) describe the SEED algorithm that uses the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule…

Multisite Study of New Autism Diagnostic Interview-Revised (ADI-R) Algorithms for Toddlers and Young Preschoolers

ERIC Educational Resources Information Center

Kim, So Hyun; Thurm, Audrey; Shumway, Stacy; Lord, Catherine

2013-01-01

Using two independent datasets provided by National Institute of Health funded consortia, the Collaborative Programs for Excellence in Autism and Studies to Advance Autism Research and Treatment (n = 641) and the National Institute of Mental Health (n = 167), diagnostic validity and factor structure of the new Autism Diagnostic Interview (ADI-R)…

Using next-generation sequencing to develop molecular diagnostics for Pseudoperonospora cubensis, the cucurbit downy mildew pathogen

USDA-ARS?s Scientific Manuscript database

Advances in Next Generation Sequencing (NGS) allow for rapid development of genomics resources needed to generate molecular diagnostics assays for infectious agents. NGS approaches are particularly helpful for organisms that cannot be cultured, such as the downy mildew pathogens, a group of biotrop...

Biosensor Detection of Neuropathy Target Esterase in Whole Blood as a Biomarker of Exposure to Neuropathic Organophosphorus Compounds

DTIC Science & Technology

2002-10-15

Chernogolovka, Moscow Region, Russia Arkady V. Eremenko Research Center for Molecular Diagnostics and Therapy, Moscow, Russia Ilya N. Kurochkin...Faculty of Chemistry, M. V. Lomonosov Moscow State University, and Research Center for Molecular Diagnostics and Therapy, Moscow, Russia Vladimir V

Hemlock woolly adelgid biological control: molecular methods to distinguish Laricobius nigrinus, L. rubidus, and their hybrids

Treesearch

Nathan P. Havill; Gina Davis; Joanne Klein; Adalgisa Caccone; Scott Salom

2011-01-01

Molecular diagnostics use DNA-based methods to assign unknown organisms to species. As such, they rely on a priori species designation by taxonomists and require validation with enough samples to capture the variation within species for accurately selecting diagnostic characters.

78 FR 21128 - Molecular Diagnostic Instruments With Combined Functions; Draft Guidance for Industry and Food...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0258] Molecular Diagnostic Instruments With Combined Functions; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food...

A new computerized diagnostic algorithm for quantitative evaluation of binocular misalignment in patients with strabismus

NASA Astrophysics Data System (ADS)

Nam, Kyoung Won; Kim, In Young; Kang, Ho Chul; Yang, Hee Kyung; Yoon, Chang Ki; Hwang, Jeong Min; Kim, Young Jae; Kim, Tae Yun; Kim, Kwang Gi

2012-10-01

Accurate measurement of binocular misalignment between both eyes is important for proper preoperative management, surgical planning, and postoperative evaluation of patients with strabismus. In this study, we proposed a new computerized diagnostic algorithm that can calculate the angle of binocular eye misalignment photographically by using a dedicated three-dimensional eye model mimicking the structure of the natural human eye. To evaluate the performance of the proposed algorithm, eight healthy volunteers and eight individuals with strabismus were recruited in this study, the horizontal deviation angle, vertical deviation angle, and angle of eye misalignment were calculated and the angular differences between the healthy and the strabismus groups were evaluated using the nonparametric Mann-Whitney test and the Pearson correlation test. The experimental results demonstrated a statistically significant difference between the healthy and strabismus groups (p = 0.015 < 0.05), but no statistically significant difference between the proposed method and the Krimsky test (p = 0.912 > 0.05). The measurements of the two methods were highly correlated (r = 0.969, p < 0.05). From the experimental results, we believe that the proposed diagnostic method has the potential to be a diagnostic tool that measures the physical disorder of the human eye to diagnose non-invasively the severity of strabismus.

Non-invasive optical detection of esophagus cancer based on urine surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Huang, Shaohua; Wang, Lan; Chen, Weiwei; Lin, Duo; Huang, Lingling; Wu, Shanshan; Feng, Shangyuan; Chen, Rong

2014-09-01

A surface-enhanced Raman spectroscopy (SERS) approach was utilized for urine biochemical analysis with the aim to develop a label-free and non-invasive optical diagnostic method for esophagus cancer detection. SERS spectrums were acquired from 31 normal urine samples and 47 malignant esophagus cancer (EC) urine samples. Tentative assignments of urine SERS bands demonstrated esophagus cancer specific changes, including an increase in the relative amounts of urea and a decrease in the percentage of uric acid in the urine of normal compared with EC. The empirical algorithm integrated with linear discriminant analysis (LDA) were employed to identify some important urine SERS bands for differentiation between healthy subjects and EC urine. The empirical diagnostic approach based on the ratio of the SERS peak intensity at 527 to 1002 cm-1 and 725 to 1002 cm-1 coupled with LDA yielded a diagnostic sensitivity of 72.3% and specificity of 96.8%, respectively. The area under the receive operating characteristic (ROC) curve was 0.954, which further evaluate the performance of the diagnostic algorithm based on the ratio of the SERS peak intensity combined with LDA analysis. This work demonstrated that the urine SERS spectra associated with empirical algorithm has potential for noninvasive diagnosis of esophagus cancer.

Autism in the Faroe Islands: Diagnostic Stability from Childhood to Early Adult Life

PubMed Central

Kočovská, Eva; Billstedt, Eva; Ellefsen, Asa; Kampmann, Hanna; Gillberg, I. Carina; Biskupstø, Rannvá; Andorsdóttir, Guðrið; Stóra, Tormóður; Minnis, Helen; Gillberg, Christopher

2013-01-01

Childhood autism or autism spectrum disorder (ASD) has been regarded as one of the most stable diagnostic categories applied to young children with psychiatric/developmental disorders. The stability over time of a diagnosis of ASD is theoretically interesting and important for various diagnostic and clinical reasons. We studied the diagnostic stability of ASD from childhood to early adulthood in the Faroe Islands: a total school age population sample (8–17-year-olds) was screened and diagnostically assessed for AD in 2002 and 2009. This paper compares both independent clinical diagnosis and Diagnostic Interview for Social and Communication Disorders (DISCO) algorithm diagnosis at two time points, separated by seven years. The stability of clinical ASD diagnosis was perfect for AD, good for “atypical autism”/PDD-NOS, and less than perfect for Asperger syndrome (AS). Stability of the DISCO algorithm subcategory diagnoses was more variable but still good for AD. Both systems showed excellent stability over the seven-year period for “any ASD” diagnosis, although a number of clear cases had been missed at the original screening in 2002. The findings support the notion that subcategories of ASD should be collapsed into one overarching diagnostic entity with subgrouping achieved on other “non-autism” variables, such as IQ and language levels and overall adaptive functioning. PMID:23476144

Investigating the Link Between Radiologists Gaze, Diagnostic Decision, and Image Content

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

Tourassi, Georgia; Voisin, Sophie; Paquit, Vincent C

2013-01-01

Objective: To investigate machine learning for linking image content, human perception, cognition, and error in the diagnostic interpretation of mammograms. Methods: Gaze data and diagnostic decisions were collected from six radiologists who reviewed 20 screening mammograms while wearing a head-mounted eye-tracker. Texture analysis was performed in mammographic regions that attracted radiologists attention and in all abnormal regions. Machine learning algorithms were investigated to develop predictive models that link: (i) image content with gaze, (ii) image content and gaze with cognition, and (iii) image content, gaze, and cognition with diagnostic error. Both group-based and individualized models were explored. Results: By poolingmore » the data from all radiologists machine learning produced highly accurate predictive models linking image content, gaze, cognition, and error. Merging radiologists gaze metrics and cognitive opinions with computer-extracted image features identified 59% of the radiologists diagnostic errors while confirming 96.2% of their correct diagnoses. The radiologists individual errors could be adequately predicted by modeling the behavior of their peers. However, personalized tuning appears to be beneficial in many cases to capture more accurately individual behavior. Conclusions: Machine learning algorithms combining image features with radiologists gaze data and diagnostic decisions can be effectively developed to recognize cognitive and perceptual errors associated with the diagnostic interpretation of mammograms.« less

On-line experimental validation of a model-based diagnostic algorithm dedicated to a solid oxide fuel cell system

NASA Astrophysics Data System (ADS)

Polverino, Pierpaolo; Esposito, Angelo; Pianese, Cesare; Ludwig, Bastian; Iwanschitz, Boris; Mai, Andreas

2016-02-01

In the current energetic scenario, Solid Oxide Fuel Cells (SOFCs) exhibit appealing features which make them suitable for environmental-friendly power production, especially for stationary applications. An example is represented by micro-combined heat and power (μ-CHP) generation units based on SOFC stacks, which are able to produce electric and thermal power with high efficiency and low pollutant and greenhouse gases emissions. However, the main limitations to their diffusion into the mass market consist in high maintenance and production costs and short lifetime. To improve these aspects, the current research activity focuses on the development of robust and generalizable diagnostic techniques, aimed at detecting and isolating faults within the entire system (i.e. SOFC stack and balance of plant). Coupled with appropriate recovery strategies, diagnosis can prevent undesired system shutdowns during faulty conditions, with consequent lifetime increase and maintenance costs reduction. This paper deals with the on-line experimental validation of a model-based diagnostic algorithm applied to a pre-commercial SOFC system. The proposed algorithm exploits a Fault Signature Matrix based on a Fault Tree Analysis and improved through fault simulations. The algorithm is characterized on the considered system and it is validated by means of experimental induction of faulty states in controlled conditions.

Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance

PubMed Central

Gonzalez de Castro, D; Clarke, P A; Al-Lazikani, B; Workman, P

2013-01-01

The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution. PMID:23361103

Efficient fault diagnosis of helicopter gearboxes

NASA Technical Reports Server (NTRS)

Chin, H.; Danai, K.; Lewicki, D. G.

1993-01-01

Application of a diagnostic system to a helicopter gearbox is presented. The diagnostic system is a nonparametric pattern classifier that uses a multi-valued influence matrix (MVIM) as its diagnostic model and benefits from a fast learning algorithm that enables it to estimate its diagnostic model from a small number of measurement-fault data. To test this diagnostic system, vibration measurements were collected from a helicopter gearbox test stand during accelerated fatigue tests and at various fault instances. The diagnostic results indicate that the MVIM system can accurately detect and diagnose various gearbox faults so long as they are included in training.

New web-based algorithm to improve rigid gas permeable contact lens fitting in keratoconus.

PubMed

Ortiz-Toquero, Sara; Rodriguez, Guadalupe; de Juan, Victoria; Martin, Raul

2017-06-01

To calculate and validate a new web-based algorithm for selecting the back optic zone radius (BOZR) of spherical gas permeable (GP) lens in keratoconus eyes. A retrospective calculation (n=35; multiple regression analysis) and a posterior prospective validation (new sample of 50 keratoconus eyes) of a new algorithm to select the BOZR of spherical KAKC design GP lenses (Conoptica) in keratoconus were conducted. BOZR calculated with the new algorithm, manufacturer guidelines and APEX software were compared with the BOZR that was finally prescribed. Number of diagnostic lenses, ordered lenses and visits to achieve optimal fitting were recorded and compared those obtained for a control group [50 healthy eyes fitted with spherical GP (BIAS design; Conoptica)]. The new algorithm highly correlated with the final BOZR fitted (r 2 =0.825, p<0.001). BOZR of the first diagnostic lens using the new algorithm demonstrated lower difference with the final BOZR prescribed (-0.01±0.12mm, p=0.65; 58% difference≤0.05mm) than with the manufacturer guidelines (+0.12±0.22mm, p<0.001; 26% difference≤0.05mm) and APEX software (-0.14±0.16mm, p=0.001; 34% difference≤0.05mm). Close numbers of diagnostic lens (1.6±0.8, 1.3±0.5; p=0.02), ordered lens (1.4±0.6, 1.1±0.3; P<0.001), and visits (3.4±0.7, 3.2±0.4; p=0.08) were required to fit keratoconus and healthy eyes, respectively. This new algorithm (free access at www.calculens.com) improves spherical KAKC GP fitting in keratoconus and can reduce the practitioner and patient chair time to achieve a final acceptable fit in keratoconus. This algorithm reduces differences between keratoconus GP fitting (KAKC design) and standard GP (BIAS design) lenses fitting in healthy eyes. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Validation of existing diagnosis of autism in mainland China using standardised diagnostic instruments.

PubMed

Sun, Xiang; Allison, Carrie; Auyeung, Bonnie; Zhang, Zhixiang; Matthews, Fiona E; Baron-Cohen, Simon; Brayne, Carol

2015-11-01

Research to date in mainland China has mainly focused on children with autistic disorder rather than Autism Spectrum Conditions and the diagnosis largely depended on clinical judgment without the use of diagnostic instruments. Whether children who have been diagnosed in China before meet the diagnostic criteria of Autism Spectrum Conditions is not known nor how many such children would meet these criteria. The aim of this study was to evaluate children with a known diagnosis of autism in mainland China using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised to verify that children who were given a diagnosis of autism made by Chinese clinicians in China were mostly children with severe autism. Of 50 children with an existing diagnosis of autism made by Chinese clinicians, 47 children met the diagnosis of autism on the Autism Diagnostic Observation Schedule algorithm and 44 children met the diagnosis of autism on the Autism Diagnostic Interview-Revised algorithm. Using the Gwet's alternative chance-corrected statistic, the agreement between the Chinese diagnosis and the Autism Diagnostic Observation Schedule diagnosis was very good (AC1 = 0.94, p < 0.005, 95% confidence interval (0.86, 1.00)), so was the agreement between the Chinese diagnosis and the Autism Diagnostic Interview-Revised (AC1 = 0.91, p < 0.005, 95% confidence interval (0.81, 1.00)). The agreement between the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised was lower but still very good (AC1 = 0.83, p < 0.005). © The Author(s) 2015.

Validation of existing diagnosis of autism in mainland China using standardised diagnostic instruments

PubMed Central

Sun, Xiang; Allison, Carrie; Auyeung, Bonnie; Zhang, Zhixiang; Matthews, Fiona E; Baron-Cohen, Simon; Brayne, Carol

2016-01-01

Research to date in mainland China has mainly focused on children with autistic disorder rather than Autism Spectrum Conditions and the diagnosis largely depended on clinical judgment without the use of diagnostic instruments. Whether children who have been diagnosed in China before meet the diagnostic criteria of Autism Spectrum Conditions is not known nor how many such children would meet these criteria. The aim of this study was to evaluate children with a known diagnosis of autism in mainland China using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised to verify that children who were given a diagnosis of autism made by Chinese clinicians in China were mostly children with severe autism. Of 50 children with an existing diagnosis of autism made by Chinese clinicians, 47 children met the diagnosis of autism on the Autism Diagnostic Observation Schedule algorithm and 44 children met the diagnosis of autism on the Autism Diagnostic Interview–Revised algorithm. Using the Gwet’s alternative chance-corrected statistic, the agreement between the Chinese diagnosis and the Autism Diagnostic Observation Schedule diagnosis was very good (AC1 = 0.94, p < 0.005, 95% confidence interval (0.86, 1.00)), so was the agreement between the Chinese diagnosis and the Autism Diagnostic Interview–Revised (AC1 = 0.91, p < 0.005, 95% confidence interval (0.81, 1.00)). The agreement between the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised was lower but still very good (AC1 = 0.83, p < 0.005). PMID:25757721

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: Evidence-Based Report on Diagnostic Guidelines

PubMed Central

Conwell, Darwin L.; Lee, Linda S.; Yadav, Dhiraj; Longnecker, Daniel S.; Miller, Frank H.; Mortele, Koenraad J.; Levy, Michael J.; Kwon, Richard; Lieb, John G.; Stevens, Tyler; Toskes, Philip P.; Gardner, Timothy B.; Gelrud, Andres; Wu, Bechien U.; Forsmark, Christopher E.; Vege, Santhi S.

2016-01-01

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed and evidence based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable or insufficient evidence. A diagnostic (STEP-wise; S-survey, T-tomography, E-endoscopy and P-pancreas function testing) algorithm is proposed that proceeds from a non-invasive to a more invasive approach. This algorithm maximizes specificity (low false positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Futhermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (T-toxic, I-idiopathic, G-genetic, A- autoimmune, R-recurrent and O-obstructive) etiology, gland morphology (Cambridge criteria) and physiologic state (exocrine, endocrine function) for uniformity across future multi-center research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves. PMID:25333398

Decentralized diagnostics based on a distributed micro-genetic algorithm for transducer networks monitoring large experimental systems.

PubMed

Arpaia, P; Cimmino, P; Girone, M; La Commara, G; Maisto, D; Manna, C; Pezzetti, M

2014-09-01

Evolutionary approach to centralized multiple-faults diagnostics is extended to distributed transducer networks monitoring large experimental systems. Given a set of anomalies detected by the transducers, each instance of the multiple-fault problem is formulated as several parallel communicating sub-tasks running on different transducers, and thus solved one-by-one on spatially separated parallel processes. A micro-genetic algorithm merges evaluation time efficiency, arising from a small-size population distributed on parallel-synchronized processors, with the effectiveness of centralized evolutionary techniques due to optimal mix of exploitation and exploration. In this way, holistic view and effectiveness advantages of evolutionary global diagnostics are combined with reliability and efficiency benefits of distributed parallel architectures. The proposed approach was validated both (i) by simulation at CERN, on a case study of a cold box for enhancing the cryogeny diagnostics of the Large Hadron Collider, and (ii) by experiments, under the framework of the industrial research project MONDIEVOB (Building Remote Monitoring and Evolutionary Diagnostics), co-funded by EU and the company Del Bo srl, Napoli, Italy.

Periprosthetic joint infections: a clinical practice algorithm.

PubMed

Volpe, Luigi; Indelli, Pier Francesco; Latella, Leonardo; Poli, Paolo; Yakupoglu, Jale; Marcucci, Massimiliano

2014-01-01

periprosthetic joint infection (PJI) accounts for 25% of failed total knee arthroplasties (TKAs) and 15% of failed total hip arthroplasties (THAs). The purpose of the present study was to design a multidisciplinary diagnostic algorithm to detect a PJI as cause of a painful TKA or THA. from April 2010 to October 2012, 111 patients with suspected PJI were evaluated. The study group comprised 75 females and 36 males with an average age of 71 years (range, 48 to 94 years). Eighty-four patients had a painful THA, while 27 reported a painful TKA. The stepwise diagnostic algorithm, applied in all the patients, included: measurement of serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels; imaging studies, including standard radiological examination, standard technetium-99m-methylene diphosphonate (MDP) bone scan (if positive, confirmation by LeukoScan was obtained); and joint aspiration with analysis of synovial fluid. following application of the stepwise diagnostic algorithm, 24 out of our 111 screened patients were classified as having a suspected PJI (21.7%). CRP and ESR levels were negative in 84 and positive in 17 cases; 93.7% of the patients had a positive technetium-labeled bone scan, and 23% a positive LeukoScan. Preoperative synovial fluid analysis was positive in 13.5%; analysis of synovial fluid obtained by preoperative aspiration showed a leucocyte count of > 3000 cells μ/l in 52% of the patients. the present study showed that the diagnosis of PJI requires the application of a multimodal diagnostic protocol in order to avoid complications related to surgical revision of a misdiagnosed "silent" PJI. Level IV, therapeutic case series.

Probability scores and diagnostic algorithms in pulmonary embolism: are they followed in clinical practice?

PubMed

Sanjuán, Pilar; Rodríguez-Núñez, Nuria; Rábade, Carlos; Lama, Adriana; Ferreiro, Lucía; González-Barcala, Francisco Javier; Alvarez-Dobaño, José Manuel; Toubes, María Elena; Golpe, Antonio; Valdés, Luis

2014-05-01

Clinical probability scores (CPS) determine the pre-test probability of pulmonary embolism (PE) and assess the need for the tests required in these patients. Our objective is to investigate if PE is diagnosed according to clinical practice guidelines. Retrospective study of clinically suspected PE in the emergency department between January 2010 and December 2012. A D-dimer value ≥ 500 ng/ml was considered positive. PE was diagnosed on the basis of the multislice computed tomography angiography and, to a lesser extent, with other imaging techniques. The CPS used was the revised Geneva scoring system. There was 3,924 cases of suspected PE (56% female). Diagnosis was determined in 360 patients (9.2%) and the incidence was 30.6 cases per 100,000 inhabitants/year. Sensitivity and the negative predictive value of the D-dimer test were 98.7% and 99.2% respectively. CPS was calculated in only 24 cases (0.6%) and diagnostic algorithms were not followed in 2,125 patients (54.2%): in 682 (17.4%) because clinical probability could not be estimated and in 482 (37.6%), 852 (46.4%) and 109 (87.9%) with low, intermediate and high clinical probability, respectively, because the diagnostic algorithms for these probabilities were not applied. CPS are rarely calculated in the diagnosis of PE and the diagnostic algorithm is rarely used in clinical practice. This may result in procedures with potential significant side effects being unnecessarily performed or to a high risk of underdiagnosis. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

New frontier in hypericin-mediated diagnosis of cancer with current optical technologies.

PubMed

Olivo, Malini; Fu, Chit Yaw; Raghavan, Vijaya; Lau, Weber Kam On

2012-02-01

Photosensitizers (PSs) have shown great potentials as molecular contrast agents in photodynamic diagnosis (PDD) of cancer. While the diagnostic values of PSs have been proven previously, little efforts have been put into developing optical imaging and diagnostic algorithms. In this article, we review the recent development of optical probes that have been used in conjunction with a potent PS, hypericin (HY). Various fluorescence techniques such as laser confocal microscopy, fluorescence urine cytology, endoscopy and endomicroscopy are covered. We will also discuss about image processing and classification approaches employed for accurate PDD. We anticipate that continual efforts in these developments could lead to an objective PDD and complete surgical clearance of tumors. Recent advancements in nanotechnology have also opened new horizons for PSs. The use of biocompatible gold nanoparticles as carrier for enhanced targeted delivery of HY has been attained. In addition, plasmonic properties of nanoparticles were harnessed to induce localized hyperthermia and to manage the release of PS molecules, enabling a better therapeutic outcome of a combined photodynamic and photothermal therapy. Finally, we discuss how nanoparticles can be used as contrast agents for other optical techniques such as optical coherence tomography and surface-enhanced Raman scattering imaging.

Molecular diagnosis and precision medicine in allergy management.

PubMed

Riccio, Anna Maria; De Ferrari, Laura; Chiappori, Alessandra; Ledda, Sabina; Passalacqua, Giovanni; Melioli, Giovanni; Canonica, Giorgio Walter

2016-11-01

Precision medicine (PM) can be defined as a structural model aimed at customizing healthcare, with medical decisions/products tailored on an individual patient at a highly detailed level. In this sense, allergy diagnostics based on molecular allergen components allows to accurately define the patient's IgE repertoire. The availability of highly specialized singleplexed and multiplexed platforms support allergists with an advanced diagnostic armamentarium. The therapeutic intervention, driven by the standard diagnostic approach, but further supported by these innovative tools may result, for instance, in a more appropriate prescription of allergen immunotherapy (AIT). Also, the phenotyping of patients, which may have relevant effects on the treatment strategy, could be take advantage by the molecular allergy diagnosis.

Development of Multi-perspective Diagnostics and Analysis Algorithms with Applications to Subsonic and Supersonic Combustors

NASA Astrophysics Data System (ADS)

Wickersham, Andrew Joseph

There are two critical research needs for the study of hydrocarbon combustion in high speed flows: 1) combustion diagnostics with adequate temporal and spatial resolution, and 2) mathematical techniques that can extract key information from large datasets. The goal of this work is to address these needs, respectively, by the use of high speed and multi-perspective chemiluminescence and advanced mathematical algorithms. To obtain the measurements, this work explored the application of high speed chemiluminescence diagnostics and the use of fiber-based endoscopes (FBEs) for non-intrusive and multi-perspective chemiluminescence imaging up to 20 kHz. Non-intrusive and full-field imaging measurements provide a wealth of information for model validation and design optimization of propulsion systems. However, it is challenging to obtain such measurements due to various implementation difficulties such as optical access, thermal management, and equipment cost. This work therefore explores the application of FBEs for non-intrusive imaging to supersonic propulsion systems. The FBEs used in this work are demonstrated to overcome many of the aforementioned difficulties and provided datasets from multiple angular positions up to 20 kHz in a supersonic combustor. The combustor operated on ethylene fuel at Mach 2 with an inlet stagnation temperature and pressure of approximately 640 degrees Fahrenheit and 70 psia, respectively. The imaging measurements were obtained from eight perspectives simultaneously, providing full-field datasets under such flow conditions for the first time, allowing the possibility of inferring multi-dimensional measurements. Due to the high speed and multi-perspective nature, such new diagnostic capability generates a large volume of data and calls for analysis algorithms that can process the data and extract key physics effectively. To extract the key combustion dynamics from the measurements, three mathematical methods were investigated in this work: Fourier analysis, proper orthogonal decomposition (POD), and wavelet analysis (WA). These algorithms were first demonstrated and tested on imaging measurements obtained from one perspective in a sub-sonic combustor (up to Mach 0.2). The results show that these algorithms are effective in extracting the key physics from large datasets, including the characteristic frequencies of flow-flame interactions especially during transient processes such as lean blow off and ignition. After these relatively simple tests and demonstrations, these algorithms were applied to process the measurements obtained from multi-perspective in the supersonic combustor. compared to past analyses (which have been limited to data obtained from one perspective only), the availability of data at multiple perspective provide further insights into the flame and flow structures in high speed flows. In summary, this work shows that high speed chemiluminescence is a simple yet powerful combustion diagnostic. Especially when combined with FBEs and the analyses algorithms described in this work, such diagnostics provide full-field imaging at high repetition rate in challenging flows. Based on such measurements, a wealth of information can be obtained from proper analysis algorithms, including characteristic frequency, dominating flame modes, and even multi-dimensional flame and flow structures.

Design and testing of artifact-suppressed adaptive histogram equalization: a contrast-enhancement technique for display of digital chest radiographs.

PubMed

Rehm, K; Seeley, G W; Dallas, W J; Ovitt, T W; Seeger, J F

1990-01-01

One of the goals of our research in the field of digital radiography has been to develop contrast-enhancement algorithms for eventual use in the display of chest images on video devices with the aim of preserving the diagnostic information presently available with film, some of which would normally be lost because of the smaller dynamic range of video monitors. The ASAHE algorithm discussed in this article has been tested by investigating observer performance in a difficult detection task involving phantoms and simulated lung nodules, using film as the output medium. The results of the experiment showed that the algorithm is successful in providing contrast-enhanced, natural-looking chest images while maintaining diagnostic information. The algorithm did not effect an increase in nodule detectability, but this was not unexpected because film is a medium capable of displaying a wide range of gray levels. It is sufficient at this stage to show that there is no degradation in observer performance. Future tests will evaluate the performance of the ASAHE algorithm in preparing chest images for video display.

Diagnosing breast cancer using Raman spectroscopy: prospective analysis

NASA Astrophysics Data System (ADS)

Haka, Abigail S.; Volynskaya, Zoya; Gardecki, Joseph A.; Nazemi, Jon; Shenk, Robert; Wang, Nancy; Dasari, Ramachandra R.; Fitzmaurice, Maryann; Feld, Michael S.

2009-09-01

We present the first prospective test of Raman spectroscopy in diagnosing normal, benign, and malignant human breast tissues. Prospective testing of spectral diagnostic algorithms allows clinicians to accurately assess the diagnostic information contained in, and any bias of, the spectroscopic measurement. In previous work, we developed an accurate, internally validated algorithm for breast cancer diagnosis based on analysis of Raman spectra acquired from fresh-frozen in vitro tissue samples. We currently evaluate the performance of this algorithm prospectively on a large ex vivo clinical data set that closely mimics the in vivo environment. Spectroscopic data were collected from freshly excised surgical specimens, and 129 tissue sites from 21 patients were examined. Prospective application of the algorithm to the clinical data set resulted in a sensitivity of 83%, a specificity of 93%, a positive predictive value of 36%, and a negative predictive value of 99% for distinguishing cancerous from normal and benign tissues. The performance of the algorithm in different patient populations is discussed. Sources of bias in the in vitro calibration and ex vivo prospective data sets, including disease prevalence and disease spectrum, are examined and analytical methods for comparison provided.

Advanced power system protection and incipient fault detection and protection of spaceborne power systems

NASA Technical Reports Server (NTRS)

Russell, B. Don

1989-01-01

This research concentrated on the application of advanced signal processing, expert system, and digital technologies for the detection and control of low grade, incipient faults on spaceborne power systems. The researchers have considerable experience in the application of advanced digital technologies and the protection of terrestrial power systems. This experience was used in the current contracts to develop new approaches for protecting the electrical distribution system in spaceborne applications. The project was divided into three distinct areas: (1) investigate the applicability of fault detection algorithms developed for terrestrial power systems to the detection of faults in spaceborne systems; (2) investigate the digital hardware and architectures required to monitor and control spaceborne power systems with full capability to implement new detection and diagnostic algorithms; and (3) develop a real-time expert operating system for implementing diagnostic and protection algorithms. Significant progress has been made in each of the above areas. Several terrestrial fault detection algorithms were modified to better adapt to spaceborne power system environments. Several digital architectures were developed and evaluated in light of the fault detection algorithms.

A Diagnostic Approach for Electro-Mechanical Actuators in Aerospace Systems

NASA Technical Reports Server (NTRS)

Balaban, Edward; Saxena, Abhinav; Bansal, Prasun; Goebel, Kai Frank; Stoelting, Paul; Curran, Simon

2009-01-01

Electro-mechanical actuators (EMA) are finding increasing use in aerospace applications, especially with the trend towards all all-electric aircraft and spacecraft designs. However, electro-mechanical actuators still lack the knowledge base accumulated for other fielded actuator types, particularly with regard to fault detection and characterization. This paper presents a thorough analysis of some of the critical failure modes documented for EMAs and describes experiments conducted on detecting and isolating a subset of them. The list of failures has been prepared through an extensive Failure Modes and Criticality Analysis (FMECA) reference, literature review, and accessible industry experience. Methods for data acquisition and validation of algorithms on EMA test stands are described. A variety of condition indicators were developed that enabled detection, identification, and isolation among the various fault modes. A diagnostic algorithm based on an artificial neural network is shown to operate successfully using these condition indicators and furthermore, robustness of these diagnostic routines to sensor faults is demonstrated by showing their ability to distinguish between them and component failures. The paper concludes with a roadmap leading from this effort towards developing successful prognostic algorithms for electromechanical actuators.

Using the brain's fight-or-flight response for predicting mental illness on the human space flight program

NASA Astrophysics Data System (ADS)

Losik, L.

A predictive medicine program allows disease and illness including mental illness to be predicted using tools created to identify the presence of accelerated aging (a.k.a. disease) in electrical and mechanical equipment. When illness and disease can be predicted, actions can be taken so that the illness and disease can be prevented and eliminated. A predictive medicine program uses the same tools and practices from a prognostic and health management program to process biological and engineering diagnostic data provided in analog telemetry during prelaunch readiness and space exploration missions. The biological and engineering diagnostic data necessary to predict illness and disease is collected from the pre-launch spaceflight readiness activities and during space flight for the ground crew to perform a prognostic analysis on the results from a diagnostic analysis. The diagnostic, biological data provided in telemetry is converted to prognostic (predictive) data using the predictive algorithms. Predictive algorithms demodulate telemetry behavior. They illustrate the presence of accelerated aging/disease in normal appearing systems that function normally. Mental illness can predicted using biological diagnostic measurements provided in CCSDS telemetry from a spacecraft such as the ISS or from a manned spacecraft in deep space. The measurements used to predict mental illness include biological and engineering data from an astronaut's circadian and ultranian rhythms. This data originates deep in the brain that is also damaged from the long-term exposure to cortisol and adrenaline anytime the body's fight or flight response is activated. This paper defines the brain's FOFR; the diagnostic, biological and engineering measurements needed to predict mental illness, identifies the predictive algorithms necessary to process the behavior in CCSDS analog telemetry to predict and thus prevent mental illness from occurring on human spaceflight missions.

Patterns of diagnostic marker assessment in adult diffuse glioma: a survey of the European Confederation of Neuropathological Societies (Euro-CNS)

PubMed Central

Woehrer, Adelheid; Kristensen, Bjarne W.; Vital, Anne; Hainfellner, Johannes A.

2017-01-01

The 2016 update of the WHO classification has introduced an integrated diagnostic approach that incorporates both tumor morphology and molecular information. This conceptual change has far-reaching implications, especially for neuropathologists who are in the forefront of translating molecular markers to routine diagnostic use. Adult diffuse glioma is a prototypic example for a group of tumors that underwent substantial regrouping, and it represents a major workload for surgical neuropathologists. Hence, we conducted a survey among members of the European Confederation of Neuropathological Societies (Euro-CNS) in order to assess 1) the extent to which molecular markers have already been incorporated in glioma diagnoses, 2) which molecular techniques are in daily use, and 3) to set a baseline for future surveys in this field. Based on 130 responses from participants across 40 nations neuropathologists uniformly rate molecular marker testing as highly relevant and already incorporate molecular information in their diagnostic assessments. At the same time however, the survey documents substantial differences in access to crucial biomarkers and molecular techniques across geographic regions and within individual countries. Concerns are raised concerning the validity of test assays with MGMT, 1p19q, and ATRX; being perceived as most problematic. Neuropathologists advocate the need for international harmonization of standards and consensus guidelines, and the majority is willing to actively engage in interlaboratory trials aiming at quality control (Figure 1). PMID:27966427

Multi-grid finite element method used for enhancing the reconstruction accuracy in Cerenkov luminescence tomography

NASA Astrophysics Data System (ADS)

Guo, Hongbo; He, Xiaowei; Liu, Muhan; Zhang, Zeyu; Hu, Zhenhua; Tian, Jie

2017-03-01

Cerenkov luminescence tomography (CLT), as a promising optical molecular imaging modality, can be applied to cancer diagnostic and therapeutic. Most researches about CLT reconstruction are based on the finite element method (FEM) framework. However, the quality of FEM mesh grid is still a vital factor to restrict the accuracy of the CLT reconstruction result. In this paper, we proposed a multi-grid finite element method framework, which was able to improve the accuracy of reconstruction. Meanwhile, the multilevel scheme adaptive algebraic reconstruction technique (MLS-AART) based on a modified iterative algorithm was applied to improve the reconstruction accuracy. In numerical simulation experiments, the feasibility of our proposed method were evaluated. Results showed that the multi-grid strategy could obtain 3D spatial information of Cerenkov source more accurately compared with the traditional single-grid FEM.

Determination of HER2 amplification status in breast cancer cells using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Bi, Xiaohong; Rexer, Brent; Arteaga, Carlos L.; Guo, Mingsheng; Li, Ming; Mahadevan-Jansen, Anita

2010-02-01

The overexpression of HER2 (human epidermal growth factor receptor 2) in breast cancer is associated with increased disease recurrence and worse prognosis. Current diagnosis of HER2 positive breast cancer is time consuming with an estimated 20% inaccuracy. Raman spectroscopy is a proven method for pathological diagnosis based on the molecular composition of tissues. This study aimed to determine the feasibility of Raman spectroscopy to differentially identify the amplification of HER2 in cells. Three cell lines including BT474 (HER2 overexpressing breast cancer cell), MCF-10A (human breast epithelial cell), and MCF-10A with overexpressing HER2, were investigated using a bench top confocal Raman system. A diagnostic algorithm based on generalized linear model (GLM) with elastic-net penalties was established to discriminate 318 spectra collected from the cells, and to identify the spectra regions that differentiate the cell lines. The algorithm was able to differentially identify BT474 breast cancer cells with an overall sensitivity of 100% and specificity of 99%. The results demonstrate the capability of Raman spectroscopy to determine HER2 status in cells. Raman spectroscopy shows promise for application in the diagnosis of HER2 positive breast cancer in clinical practice.

[Allergy and autoimmunity: Molecular diagnostics, therapy, and presumable pathogenesis].

PubMed

Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu

2017-01-01

Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.

Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone

PubMed Central

Im, Hyungsoon; Castro, Cesar M.; Shao, Huilin; Liong, Monty; Song, Jun; Pathania, Divya; Fexon, Lioubov; Min, Changwook; Avila-Wallace, Maria; Zurkiya, Omar; Rho, Junsung; Magaoay, Brady; Tambouret, Rosemary H.; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho

2015-01-01

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts. PMID:25870273

Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone.

PubMed

Im, Hyungsoon; Castro, Cesar M; Shao, Huilin; Liong, Monty; Song, Jun; Pathania, Divya; Fexon, Lioubov; Min, Changwook; Avila-Wallace, Maria; Zurkiya, Omar; Rho, Junsung; Magaoay, Brady; Tambouret, Rosemary H; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho

2015-05-05

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts.

Diagnostic accuracy of administrative data algorithms in the diagnosis of osteoarthritis: a systematic review.

PubMed

Shrestha, Swastina; Dave, Amish J; Losina, Elena; Katz, Jeffrey N

2016-07-07

Administrative health care data are frequently used to study disease burden and treatment outcomes in many conditions including osteoarthritis (OA). OA is a chronic condition with significant disease burden affecting over 27 million adults in the US. There are few studies examining the performance of administrative data algorithms to diagnose OA. The purpose of this study is to perform a systematic review of administrative data algorithms for OA diagnosis; and, to evaluate the diagnostic characteristics of algorithms based on restrictiveness and reference standards. Two reviewers independently screened English-language articles published in Medline, Embase, PubMed, and Cochrane databases that used administrative data to identify OA cases. Each algorithm was classified as restrictive or less restrictive based on number and type of administrative codes required to satisfy the case definition. We recorded sensitivity and specificity of algorithms and calculated positive likelihood ratio (LR+) and positive predictive value (PPV) based on assumed OA prevalence of 0.1, 0.25, and 0.50. The search identified 7 studies that used 13 algorithms. Of these 13 algorithms, 5 were classified as restrictive and 8 as less restrictive. Restrictive algorithms had lower median sensitivity and higher median specificity compared to less restrictive algorithms when reference standards were self-report and American college of Rheumatology (ACR) criteria. The algorithms compared to reference standard of physician diagnosis had higher sensitivity and specificity than those compared to self-reported diagnosis or ACR criteria. Restrictive algorithms are more specific for OA diagnosis and can be used to identify cases when false positives have higher costs e.g. interventional studies. Less restrictive algorithms are more sensitive and suited for studies that attempt to identify all cases e.g. screening programs.

Pitfalls Associated With the Use of Molecular Diagnostic Panels in the Diagnosis of Cryptococcal Meningitis.

PubMed

O'Halloran, Jane A; Franklin, Alexander; Lainhart, William; Burnham, Carey-Ann; Powderly, William; Dubberke, Erik

2017-01-01

We report the case of a kidney transplantation patient on chronic immunosuppressive therapy presenting with subacute meningitis. The final diagnosis of cryptococcal meningitis was delayed due to 2 false-negative cryptococcal results on a molecular diagnostic panel. Caution with such platforms in suspected cryptococcal meningitis is needed.

External Quality Assessment for Zika Virus Molecular Diagnostic Testing, Brazil.

PubMed

Fischer, Carlo; Pedroso, Celia; Mendrone, Alfredo; Bispo de Filippis, Ana Maria; Vallinoto, Antonio Carlos Rosário; Ribeiro, Bergmann Morais; Durigon, Edison Luiz; Marques, Ernesto T A; Campos, Gubio S; Viana, Isabelle F T; Levi, José Eduardo; Scarpelli, Luciano Cesar; Nogueira, Mauricio Lacerda; Bastos, Michele de Souza; Souza, Nathalia C Santiago; Khouri, Ricardo; Lira, Sanny; Komninakis, Shirley Vasconcelos; Baronti, Cécile; Charrel, Rémi N; Kümmerer, Beate M; Drosten, Christian; Brites, Carlos; de Lamballerie, Xavier; Niedrig, Matthias; Netto, Eduardo Martins; Drexler, Jan Felix

2018-05-01

We conducted an external quality assessment of Zika virus molecular diagnostic tests in Brazil using a new Zika virus standard. Of 15 laboratories, 73% showed limited sensitivity and specificity. Viral load estimates varied significantly. Continuous quality assurance is needed to adequately estimate risk for Zika virus-associated disease and determine patient care.

DNA barcodes and molecular diagnostics to distinguish an introduced and native Laricobius (Coleoptera: Derodontidae) species in eastern North America

Treesearch

G.A. Davis; N.P. Havill; Z.N. Adelman; A. Caccone; L.T. Kok; S.M. Salom

2011-01-01

Molecular diagnostics based on DNA barcodes can be powerful identification tools in the absence of distinctive morphological characters for distinguishing between closely related species. A specific example is distinguishing the endemic species Laricobius rubidus from Laricobius nigrinus, a biological control agent of hemlock...

Effect of hormonal variation on in vivo high wavenumber Raman spectra improves cervical precancer detection

NASA Astrophysics Data System (ADS)

Duraipandian, Shiyamala; Zheng, Wei; Ng, Joseph; Low, Jeffrey J. H.; Ilancheran, A.; Huang, Zhiwei

2012-03-01

Raman spectroscopy is a unique analytical probe for molecular vibration and is capable of providing specific spectroscopic fingerprints of molecular compositions and structures of biological tissues. The aim of this study is to improve the classification accuracy of cervical precancer by characterizing the variations in the normal high wavenumber (HW - 2800-3700cm-1) Raman spectra arising from the menopausal status of the cervix. A rapidacquisition near-infrared (NIR) Raman spectroscopic system was used for in vivo tissue Raman measurements at 785 nm excitation. Individual HW Raman spectrum was measured with a 5s exposure time from both normal and precancer tissue sites of 15 patients recruited. The acquired Raman spectra were stratified based on the menopausal status of the cervix before the data analysis. Significant differences were noticed in Raman intensities of prominent band at 2924 cm-1 (CH3 stretching of proteins) and the broad water Raman band (in the 3100-3700 cm-1 range) with a peak at 3390 cm-1 in normal and dysplasia cervical tissue sites. Multivariate diagnostic decision algorithm based on principal component analysis (PCA) and linear discriminant analysis (LDA) was utilized to successfully differentiate the normal and precancer cervical tissue sites. By considering the variations in the Raman spectra of normal cervix due to the hormonal or menopausal status of women, the diagnostic accuracy was improved from 71 to 91%. By incorporating these variations prior to tissue classification, we can significantly improve the accuracy of cervical precancer detection using HW Raman spectroscopy.

Artificial intelligence in hematology.

PubMed

Zini, Gina

2005-10-01

Artificial intelligence (AI) is a computer based science which aims to simulate human brain faculties using a computational system. A brief history of this new science goes from the creation of the first artificial neuron in 1943 to the first artificial neural network application to genetic algorithms. The potential for a similar technology in medicine has immediately been identified by scientists and researchers. The possibility to store and process all medical knowledge has made this technology very attractive to assist or even surpass clinicians in reaching a diagnosis. Applications of AI in medicine include devices applied to clinical diagnosis in neurology and cardiopulmonary diseases, as well as the use of expert or knowledge-based systems in routine clinical use for diagnosis, therapeutic management and for prognostic evaluation. Biological applications include genome sequencing or DNA gene expression microarrays, modeling gene networks, analysis and clustering of gene expression data, pattern recognition in DNA and proteins, protein structure prediction. In the field of hematology the first devices based on AI have been applied to the routine laboratory data management. New tools concern the differential diagnosis in specific diseases such as anemias, thalassemias and leukemias, based on neural networks trained with data from peripheral blood analysis. A revolution in cancer diagnosis, including the diagnosis of hematological malignancies, has been the introduction of the first microarray based and bioinformatic approach for molecular diagnosis: a systematic approach based on the monitoring of simultaneous expression of thousands of genes using DNA microarray, independently of previous biological knowledge, analysed using AI devices. Using gene profiling, the traditional diagnostic pathways move from clinical to molecular based diagnostic systems.

Breast Cancer Diagnostic System Final Report CRADA No. TC02098.0

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

Rubenchik, A. M.; DaSilva, L. B.

This was a collaborative effort between Lawrence Livermore National Security, LLC (formerly The Regents of the University of California)/Lawrence Liver more National Laboratory (LLNL) and BioTelligent, Inc. together with a Russian Institution (BioFil, Ltd.), to develop a new system ( diagnostic device, operating procedures, algorithms and software) to accurately distinguish between benign and malignant breast tissue (Breast Cancer Diagnostic System, BCDS).

[EBOLA HEMORRHAGIC FEVER: DIAGNOSTICS, ETIOTROPIC AND PATHOGENETIC THERAPY, PREVENTION].

PubMed

Zhdanov, K V; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fisun, A Ya

2015-01-01

The data on diagnostics, etiotropic and pathogenetic therapy, prevention of Ebola hemorrhagic fever are presented including diagnostic algorithms for different clinical situations. Fundamentals of pathogenetic therapy are described. Various groups of medications used for antiviral therapy of conditions caused by Ebola virus are characterized. Experimental drugs at different stages of clinical studies are considered along with candidate vaccines being developed for the prevention of the disease.

Toward DSM-V: An Item Response Theory Analysis of the Diagnostic Process for DSM-IV Alcohol Abuse and Dependence in Adolescents

ERIC Educational Resources Information Center

Gelhorn, Heather; Hartman, Christie; Sakai, Joseph; Stallings, Michael; Young, Susan; Rhee, So Hyun; Corley, Robin; Hewitt, John; Hopger, Christian; Crowley, Thomas D.

2008-01-01

Clinical interviews of approximately 5,587 adolescents revealed that DSM-IV diagnostic categories were found to be different in terms of the severity of alcohol use disorders (AUDs). However, a substantial inconsistency and overlap was found in severity of AUDs across categories. The need for an alternative diagnostic algorithm which considers all…

A fast recursive algorithm for molecular dynamics simulation

NASA Technical Reports Server (NTRS)

Jain, A.; Vaidehi, N.; Rodriguez, G.

1993-01-01

The present recursive algorithm for solving molecular systems' dynamical equations of motion employs internal variable models that reduce such simulations' computation time by an order of magnitude, relative to Cartesian models. Extensive use is made of spatial operator methods recently developed for analysis and simulation of the dynamics of multibody systems. A factor-of-450 speedup over the conventional O(N-cubed) algorithm is demonstrated for the case of a polypeptide molecule with 400 residues.

Fully 3D printed integrated reactor array for point-of-care molecular diagnostics.

PubMed

Kadimisetty, Karteek; Song, Jinzhao; Doto, Aoife M; Hwang, Young; Peng, Jing; Mauk, Michael G; Bushman, Frederic D; Gross, Robert; Jarvis, Joseph N; Liu, Changchun

2018-06-30

Molecular diagnostics that involve nucleic acid amplification tests (NAATs) are crucial for prevention and treatment of infectious diseases. In this study, we developed a simple, inexpensive, disposable, fully 3D printed microfluidic reactor array that is capable of carrying out extraction, concentration and isothermal amplification of nucleic acids in variety of body fluids. The method allows rapid molecular diagnostic tests for infectious diseases at point of care. A simple leak-proof polymerization strategy was developed to integrate flow-through nucleic acid isolation membranes into microfluidic devices, yielding a multifunctional diagnostic platform. Static coating technology was adopted to improve the biocompatibility of our 3D printed device. We demonstrated the suitability of our device for both end-point colorimetric qualitative detection and real-time fluorescence quantitative detection. We applied our diagnostic device to detection of Plasmodium falciparum in plasma samples and Neisseria meningitides in cerebrospinal fluid (CSF) samples by loop-mediated, isothermal amplification (LAMP) within 50 min. The detection limits were 100 fg for P. falciparum and 50 colony-forming unit (CFU) for N. meningitidis per reaction, which are comparable to that of benchtop instruments. This rapid and inexpensive 3D printed device has great potential for point-of-care molecular diagnosis of infectious disease in resource-limited settings. Copyright © 2018 Elsevier B.V. All rights reserved.

Morphological and molecular diagnostics of Phytoseiulus persimilis and Phytoseiulus macropilis (Acari: Phytoseiidae).

PubMed

Okassa, Mireille; Tixier, Marie-Stéphane; Kreiter, Serge

2010-11-01

This study focuses on the diagnostics of two natural enemy species, belonging to the genus Phytoseiulus in the family Phytoseiidae (sub-family Amblyseiinae): P. macropilis and P. persimilis. These two species are of primary importance in biological control all over the world. However, they are morphologically very similar and specific diagnostics is difficult. This study utilizes mitochondrial molecular markers (12S rRNA and Cytb mtDNA) to differentiate these two species. Morphological analyses showed significant differences between P. persimilis and P. macropilis for 17 morphological characters of the 32 considered. However, despite these significant differences, the ranges of all characters overlap. Only the serration of the macroseta on the basitarsus (StIV) allows the differentiation between P. persimilis and P. macropilis. Despite these small morphological differences, molecular results, for both mitochondrial DNA fragments considered (rRNA and Cytb mtDNA), showed a clear delineation between the specimens of P. macropilis and P. persimilis. This study emphasizes (i) that only one morphological character (serration of the seta StIV) clearly separates these two species, and (ii) the usefulness of an automatical molecular and simple diagnostic tool for accurate differentiation of the two species and ensure the morphological diagnostics. Further studies are proposed, including more DNA sequences especially for P. macropilis.

Molecular Diagnostics in Pathology: Time for a Next-Generation Pathologist?

PubMed

Fassan, Matteo

2018-03-01

- Comprehensive molecular investigations of mainstream carcinogenic processes have led to the use of effective molecular targeted agents in most cases of solid tumors in clinical settings. - To update readers regarding the evolving role of the pathologist in the therapeutic decision-making process and the introduction of next-generation technologies into pathology practice. - Current literature on the topic, primarily sourced from the PubMed (National Center for Biotechnology Information, Bethesda, Maryland) database, were reviewed. - Adequate evaluation of cytologic-based and tissue-based predictive diagnostic biomarkers largely depends on both proper pathologic characterization and customized processing of biospecimens. Moreover, increased requests for molecular testing have paralleled the recent, sharp decrease in tumor material to be analyzed-material that currently comprises cytology specimens or, at minimum, small biopsies in most cases of metastatic/advanced disease. Traditional diagnostic pathology has been completely revolutionized by the introduction of next-generation technologies, which provide multigene, targeted mutational profiling, even in the most complex of clinical cases. Combining traditional and molecular knowledge, pathologists integrate the morphological, clinical, and molecular dimensions of a disease, leading to a proper diagnosis and, therefore, the most-appropriate tailored therapy.

Current and future molecular diagnostics for ocular infectious diseases.

PubMed

Doan, Thuy; Pinsky, Benjamin A

2016-11-01

Confirmation of ocular infections can pose great challenges to the clinician. A fundamental limitation is the small amounts of specimen that can be obtained from the eye. Molecular diagnostics can circumvent this limitation and have been shown to be more sensitive than conventional culture. The purpose of this review is to describe new molecular methods and to discuss the applications of next-generation sequencing-based approaches in the diagnosis of ocular infections. Efforts have focused on improving the sensitivity of pathogen detection using molecular methods. This review describes a new molecular target for Toxoplasma gondii-directed polymerase chain reaction assays. Molecular diagnostics for Chlamydia trachomatis and Acanthamoeba species are also discussed. Finally, we describe a hypothesis-free approach, metagenomic deep sequencing, which can detect DNA and RNA pathogens from a single specimen in one test. In some cases, this method can provide the geographic location and timing of the infection. Pathogen-directed PCRs have been powerful tools in the diagnosis of ocular infections for over 20 years. The use of next-generation sequencing-based approaches, when available, will further improve sensitivity of detection with the potential to improve patient care.

[Role of contemporary pathological diagnostics in the personalized treatment of cancer].

PubMed

Tímár, József

2013-03-01

Due to the developments of pathology in the past decades (immunohistochemistry and molecular pathology) classification of cancers changed fundamentally, laying a ground for personalized management of cancer patients. Our picture of cancer is more complex today, identifying the genetic basis of the morphological variants. On the other hand, this picture has a much higher resolution enabling us to subclassify similar histological cancer types based on molecular markers. This redefined classification of cancers helps us to better predict the possible biological behavior of the disease and/or the therapeutic sensitivity, opening the way toward a more personalized treatment of this disease. The redefined molecular classification of cancer may affect the universal application of treatment protocols. To achieve this goal molecular diagnostics must be an integral and reimbursed part of the routine pathological diagnostics. On the other hand, it is time to extend the multidisciplinary team with molecular pathologist to improve the decision making process of the management of cancer patients.

Detection and Characterization of Viral Species/Subspecies Using Isothermal Recombinase Polymerase Amplification (RPA) Assays.

PubMed

Glais, Laurent; Jacquot, Emmanuel

2015-01-01

Numerous molecular-based detection protocols include an amplification step of the targeted nucleic acids. This step is important to reach the expected sensitive detection of pathogens in diagnostic procedures. Amplifications of nucleic acid sequences are generally performed, in the presence of appropriate primers, using thermocyclers. However, the time requested to amplify molecular targets and the cost of the thermocycler machines could impair the use of these methods in routine diagnostics. Recombinase polymerase amplification (RPA) technique allows rapid (short-term incubation of sample and primers in an enzymatic mixture) and simple (isothermal) amplification of molecular targets. RPA protocol requires only basic molecular steps such as extraction procedures and agarose gel electrophoresis. Thus, RPA can be considered as an interesting alternative to standard molecular-based diagnostic tools. In this paper, the complete procedures to set up an RPA assay, applied to detection of RNA (Potato virus Y, Potyvirus) and DNA (Wheat dwarf virus, Mastrevirus) viruses, are described. The proposed procedure allows developing species- or subspecies-specific detection assay.

An improved molecular dynamics algorithm to study thermodiffusion in binary hydrocarbon mixtures

NASA Astrophysics Data System (ADS)

Antoun, Sylvie; Saghir, M. Ziad; Srinivasan, Seshasai

2018-03-01

In multicomponent liquid mixtures, the diffusion flow of chemical species can be induced by temperature gradients, which leads to a separation of the constituent components. This cross effect between temperature and concentration is known as thermodiffusion or the Ludwig-Soret effect. The performance of boundary driven non-equilibrium molecular dynamics along with the enhanced heat exchange (eHEX) algorithm was studied by assessing the thermodiffusion process in n-pentane/n-decane (nC5-nC10) binary mixtures. The eHEX algorithm consists of an extended version of the HEX algorithm with an improved energy conservation property. In addition to this, the transferable potentials for phase equilibria-united atom force field were employed in all molecular dynamics (MD) simulations to precisely model the molecular interactions in the fluid. The Soret coefficients of the n-pentane/n-decane (nC5-nC10) mixture for three different compositions (at 300.15 K and 0.1 MPa) were calculated and compared with the experimental data and other MD results available in the literature. Results of our newly employed MD algorithm showed great agreement with experimental data and a better accuracy compared to other MD procedures.

The role of molecular genetic analysis in the diagnosis of primary ciliary dyskinesia.

PubMed

Kim, Raymond H; A Hall, David; Cutz, Ernest; Knowles, Michael R; Nelligan, Kathleen A; Nykamp, Keith; Zariwala, Maimoona A; Dell, Sharon D

2014-03-01

Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disorder of motile cilia. The diagnosis of PCD has previously relied on ciliary analysis with transmission electron microscopy or video microscopy. However, patients with PCD may have normal ultrastructural appearance, and ciliary analysis has limited accessibility. Alternatively, PCD can be diagnosed by demonstrating biallelic mutations in known PCD genes. Genetic testing is emerging as a diagnostic tool to complement ciliary analysis where interpretation and access may delay diagnosis. To determine the diagnostic yield of genetic testing of patients with a confirmed or suspected diagnosis of PCD in a multiethnic urban center. Twenty-eight individuals with confirmed PCD on transmission electron microscopy of ciliary ultrastructure and 24 individuals with a probable diagnosis of PCD based on a classical PCD phenotype and low nasal nitric oxide had molecular analysis of 12 genes associated with PCD. Of 49 subjects who underwent ciliary biopsy, 28 (57%) were diagnosed with PCD through an ultrastructural defect. Of the 52 individuals who underwent molecular genetic analysis, 22 (42%) individuals had two mutations in known PCD genes. Twenty-four previously unreported mutations in known PCD genes were observed. Combining both diagnostic modalities of biopsy and molecular genetics, the diagnostic yield increased to 69% compared with 57% based on biopsy alone. The diagnosis of PCD is challenging and has traditionally relied on ciliary biopsy, which is unreliable as the sole criterion for a definitive diagnosis. Molecular genetic analysis can be used as a complementary test to increase the diagnostic yield.

Diagnosis of Posttraumatic Stress Disorder in Preschool Children

ERIC Educational Resources Information Center

De Young, Alexandra C.; Kenardy, Justin A.; Cobham, Vanessa E.

2011-01-01

This study investigated the existing diagnostic algorithms for posttraumatic stress disorder (PTSD) to determine the most developmentally sensitive and valid approach for diagnosing this disorder in preschoolers. Participants were 130 parents of unintentionally burned children (1-6 years). Diagnostic interviews were conducted with parents to…

Integrating Oil Debris and Vibration Measurements for Intelligent Machine Health Monitoring. Degree awarded by Toledo Univ., May 2002

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.

2003-01-01

A diagnostic tool for detecting damage to gears was developed. Two different measurement technologies, oil debris analysis and vibration were integrated into a health monitoring system for detecting surface fatigue pitting damage on gears. This integrated system showed improved detection and decision-making capabilities as compared to using individual measurement technologies. This diagnostic tool was developed and evaluated experimentally by collecting vibration and oil debris data from fatigue tests performed in the NASA Glenn Spur Gear Fatigue Rig. An oil debris sensor and the two vibration algorithms were adapted as the diagnostic tools. An inductance type oil debris sensor was selected for the oil analysis measurement technology. Gear damage data for this type of sensor was limited to data collected in the NASA Glenn test rigs. For this reason, this analysis included development of a parameter for detecting gear pitting damage using this type of sensor. The vibration data was used to calculate two previously available gear vibration diagnostic algorithms. The two vibration algorithms were selected based on their maturity and published success in detecting damage to gears. Oil debris and vibration features were then developed using fuzzy logic analysis techniques, then input into a multi sensor data fusion process. Results show combining the vibration and oil debris measurement technologies improves the detection of pitting damage on spur gears. As a result of this research, this new diagnostic tool has significantly improved detection of gear damage in the NASA Glenn Spur Gear Fatigue Rigs. This research also resulted in several other findings that will improve the development of future health monitoring systems. Oil debris analysis was found to be more reliable than vibration analysis for detecting pitting fatigue failure of gears and is capable of indicating damage progression. Also, some vibration algorithms are as sensitive to operational effects as they are to damage. Another finding was that clear threshold limits must be established for diagnostic tools. Based on additional experimental data obtained from the NASA Glenn Spiral Bevel Gear Fatigue Rig, the methodology developed in this study can be successfully implemented on other geared systems.

Approximation algorithms for a genetic diagnostics problem.

PubMed

Kosaraju, S R; Schäffer, A A; Biesecker, L G

1998-01-01

We define and study a combinatorial problem called WEIGHTED DIAGNOSTIC COVER (WDC) that models the use of a laboratory technique called genotyping in the diagnosis of an important class of chromosomal aberrations. An optimal solution to WDC would enable us to define a genetic assay that maximizes the diagnostic power for a specified cost of laboratory work. We develop approximation algorithms for WDC by making use of the well-known problem SET COVER for which the greedy heuristic has been extensively studied. We prove worst-case performance bounds on the greedy heuristic for WDC and for another heuristic we call directional greedy. We implemented both heuristics. We also implemented a local search heuristic that takes the solutions obtained by greedy and dir-greedy and applies swaps until they are locally optimal. We report their performance on a real data set that is representative of the options that a clinical geneticist faces for the real diagnostic problem. Many open problems related to WDC remain, both of theoretical interest and practical importance.

Recurrent Pneumonia in Children: A Reasoned Diagnostic Approach and a Single Centre Experience.

PubMed

Montella, Silvia; Corcione, Adele; Santamaria, Francesca

2017-01-29

Recurrent pneumonia (RP), i.e., at least two episodes of pneumonia in one year or three episodes ever with intercritical radiographic clearing of densities, occurs in 7.7%-9% of children with community-acquired pneumonia. In RP, the challenge is to discriminate between children with self-limiting or minor problems, that do not require a diagnostic work-up, and those with an underlying disease. The aim of the current review is to discuss a reasoned diagnostic approach to RP in childhood. Particular emphasis has been placed on which children should undergo a diagnostic work-up and which tests should be performed. A pediatric case series is also presented, in order to document a single centre experience of RP. A management algorithm for the approach to children with RP, based on the evidence from a literature review, is proposed. Like all algorithms, it is not meant to replace clinical judgment, but it should drive physicians to adopt a systematic approach to pediatric RP and provide a useful guide to the clinician.

Mean field analysis of algorithms for scale-free networks in molecular biology

PubMed Central

2017-01-01

The sampling of scale-free networks in Molecular Biology is usually achieved by growing networks from a seed using recursive algorithms with elementary moves which include the addition and deletion of nodes and bonds. These algorithms include the Barabási-Albert algorithm. Later algorithms, such as the Duplication-Divergence algorithm, the Solé algorithm and the iSite algorithm, were inspired by biological processes underlying the evolution of protein networks, and the networks they produce differ essentially from networks grown by the Barabási-Albert algorithm. In this paper the mean field analysis of these algorithms is reconsidered, and extended to variant and modified implementations of the algorithms. The degree sequences of scale-free networks decay according to a powerlaw distribution, namely P(k) ∼ k−γ, where γ is a scaling exponent. We derive mean field expressions for γ, and test these by numerical simulations. Generally, good agreement is obtained. We also found that some algorithms do not produce scale-free networks (for example some variant Barabási-Albert and Solé networks). PMID:29272285

Mean field analysis of algorithms for scale-free networks in molecular biology.

PubMed

Konini, S; Janse van Rensburg, E J

2017-01-01

The sampling of scale-free networks in Molecular Biology is usually achieved by growing networks from a seed using recursive algorithms with elementary moves which include the addition and deletion of nodes and bonds. These algorithms include the Barabási-Albert algorithm. Later algorithms, such as the Duplication-Divergence algorithm, the Solé algorithm and the iSite algorithm, were inspired by biological processes underlying the evolution of protein networks, and the networks they produce differ essentially from networks grown by the Barabási-Albert algorithm. In this paper the mean field analysis of these algorithms is reconsidered, and extended to variant and modified implementations of the algorithms. The degree sequences of scale-free networks decay according to a powerlaw distribution, namely P(k) ∼ k-γ, where γ is a scaling exponent. We derive mean field expressions for γ, and test these by numerical simulations. Generally, good agreement is obtained. We also found that some algorithms do not produce scale-free networks (for example some variant Barabási-Albert and Solé networks).

Simulated tempering based on global balance or detailed balance conditions: Suwa-Todo, heat bath, and Metropolis algorithms.

PubMed

Mori, Yoshiharu; Okumura, Hisashi

2015-12-05

Simulated tempering (ST) is a useful method to enhance sampling of molecular simulations. When ST is used, the Metropolis algorithm, which satisfies the detailed balance condition, is usually applied to calculate the transition probability. Recently, an alternative method that satisfies the global balance condition instead of the detailed balance condition has been proposed by Suwa and Todo. In this study, ST method with the Suwa-Todo algorithm is proposed. Molecular dynamics simulations with ST are performed with three algorithms (the Metropolis, heat bath, and Suwa-Todo algorithms) to calculate the transition probability. Among the three algorithms, the Suwa-Todo algorithm yields the highest acceptance ratio and the shortest autocorrelation time. These suggest that sampling by a ST simulation with the Suwa-Todo algorithm is most efficient. In addition, because the acceptance ratio of the Suwa-Todo algorithm is higher than that of the Metropolis algorithm, the number of temperature states can be reduced by 25% for the Suwa-Todo algorithm when compared with the Metropolis algorithm. © 2015 Wiley Periodicals, Inc.

Cost-effectiveness analysis of microscopic observation drug susceptibility test versus Xpert MTB/Rif test for diagnosis of pulmonary tuberculosis in HIV patients in Uganda.

PubMed

Walusimbi, Simon; Kwesiga, Brendan; Rodrigues, Rashmi; Haile, Melles; de Costa, Ayesha; Bogg, Lennart; Katamba, Achilles

2016-10-10

Microscopic Observation Drug Susceptibility (MODS) and Xpert MTB/Rif (Xpert) are highly sensitive tests for diagnosis of pulmonary tuberculosis (PTB). This study evaluated the cost effectiveness of utilizing MODS versus Xpert for diagnosis of active pulmonary TB in HIV infected patients in Uganda. A decision analysis model comparing MODS versus Xpert for TB diagnosis was used. Costs were estimated by measuring and valuing relevant resources required to perform the MODS and Xpert tests. Diagnostic accuracy data of the tests were obtained from systematic reviews involving HIV infected patients. We calculated base values for unit costs and varied several assumptions to obtain the range estimates. Cost effectiveness was expressed as costs per TB patient diagnosed for each of the two diagnostic strategies. Base case analysis was performed using the base estimates for unit cost and diagnostic accuracy of the tests. Sensitivity analysis was performed using a range of value estimates for resources, prevalence, number of tests and diagnostic accuracy. The unit cost of MODS was US$ 6.53 versus US$ 12.41 of Xpert. Consumables accounted for 59 % (US$ 3.84 of 6.53) of the unit cost for MODS and 84 % (US$10.37 of 12.41) of the unit cost for Xpert. The cost effectiveness ratio of the algorithm using MODS was US$ 34 per TB patient diagnosed compared to US$ 71 of the algorithm using Xpert. The algorithm using MODS was more cost-effective compared to the algorithm using Xpert for a wide range of different values of accuracy, cost and TB prevalence. The cost (threshold value), where the algorithm using Xpert was optimal over the algorithm using MODS was US$ 5.92. MODS versus Xpert was more cost-effective for the diagnosis of PTB among HIV patients in our setting. Efforts to scale-up MODS therefore need to be explored. However, since other non-economic factors may still favour the use of Xpert, the current cost of the Xpert cartridge still needs to be reduced further by more than half, in order to make it economically competitive with MODS.

Molecular markers in well-differentiated thyroid cancer.

PubMed

D'Cruz, Anil K; Vaish, Richa; Vaidya, Abhishek; Nixon, Iain J; Williams, Michelle D; Vander Poorten, Vincent; López, Fernando; Angelos, Peter; Shaha, Ashok R; Khafif, Avi; Skalova, Alena; Rinaldo, Alessandra; Hunt, Jennifer L; Ferlito, Alfio

2018-06-01

Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

CT-guided transthoracic core needle biopsy for small pulmonary lesions: diagnostic performance and adequacy for molecular testing.

PubMed

Tian, Panwen; Wang, Ye; Li, Lei; Zhou, Yongzhao; Luo, Wenxin; Li, Weimin

2017-02-01

Computed tomography (CT)-guided transthoracic needle biopsy is a well-established, minimally invasive diagnostic tool for pulmonary lesions. Few large studies have been conducted on the diagnostic performance and adequacy for molecular testing of transthoracic core needle biopsy (TCNB) for small pulmonary lesions. This study included CT-guided TCNB with 18-gauge cutting needles in 560 consecutive patients with small (≤3 cm) pulmonary lesions from January 2012 to January 2015. There were 323 males and 237 females, aged 51.8±12.7 years. The size of the pulmonary lesions was 1.8±0.6 cm. The sensitivity, specificity, accuracy and complications of the biopsies were investigated. The risk factors of diagnostic failure were assessed using univariate and multivariate analyses. The sample's adequacy for molecular testing of non-small cell lung cancer (NSCLC) was analyzed. The overall sensitivity, specificity, and accuracy for diagnosis of malignancy were 92.0% (311/338), 98.6% (219/222), and 94.6% (530/560), respectively. The incidence of bleeding complications was 22.9% (128/560), and the incidence of pneumothorax was 10.4% (58/560). Logistic multivariate regression analysis showed that the independent risk factors for diagnostic failure were a lesion size ≤1 cm [odds ratio (OR), 3.95; P=0.007], lower lobe lesions (OR, 2.83; P=0.001), and pneumothorax (OR, 1.98; P=0.004). Genetic analysis was successfully performed on 95.45% (168/176) of specimens diagnosed as NSCLC. At least 96.8% of samples with two or more passes from a lesion were sufficient for molecular testing. The diagnostic yield of small pulmonary lesions by CT-guided TCNB is high, and the procedure is relatively safe. A lesion size ≤1 cm, lower lobe lesions, and pneumothorax are independent risk factors for biopsy diagnostic failure. TCNB specimens could provide adequate tissues for molecular testing.

A Multi-Scale Method for Dynamics Simulation in Continuum Solvent Models I: Finite-Difference Algorithm for Navier-Stokes Equation.

PubMed

Xiao, Li; Cai, Qin; Li, Zhilin; Zhao, Hongkai; Luo, Ray

2014-11-25

A multi-scale framework is proposed for more realistic molecular dynamics simulations in continuum solvent models by coupling a molecular mechanics treatment of solute with a fluid mechanics treatment of solvent. This article reports our initial efforts to formulate the physical concepts necessary for coupling the two mechanics and develop a 3D numerical algorithm to simulate the solvent fluid via the Navier-Stokes equation. The numerical algorithm was validated with multiple test cases. The validation shows that the algorithm is effective and stable, with observed accuracy consistent with our design.

Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice.

PubMed

Nemtsova, Marina V; Strelnikov, Vladimir V; Tanas, Alexander S; Bykov, Igor I; Zaletaev, Dmitry V; Rudenko, Viktoria V; Glukhov, Alexander I; Kchorobrich, Tatiana V; Li, Yi; Tarasov, Vadim V; Barreto, George E; Aliev, Gjumrakch

2017-10-01

We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied. The selected parameters comprise a system of molecular markers that can be used in both diagnostics of gastric cancer and in dynamic monitoring of patients after surgery. Special attention was paid to the use of molecular markers for the diagnostics of malignant process in the material obtained endoscopically since the efficacy of morphological diagnostics in biopsies is compromised by intratumoral heterogeneity, which may prevent reliable identification of tumor cells in the sampling. Our data indicated that certain molecular genetic events provided more sensitive yet specific markers of the tumor. We demonstrated that molecular profiles detected in preoperative biopsies were confirmed by the material obtained intra-operatively. The use of endoscopic material facilitates gastric tumors pre-operative diagnostics, improving early detection of gastric cancer and potential effective treatment strategies.

Code-based Diagnostic Algorithms for Idiopathic Pulmonary Fibrosis. Case Validation and Improvement.

PubMed

Ley, Brett; Urbania, Thomas; Husson, Gail; Vittinghoff, Eric; Brush, David R; Eisner, Mark D; Iribarren, Carlos; Collard, Harold R

2017-06-01

Population-based studies of idiopathic pulmonary fibrosis (IPF) in the United States have been limited by reliance on diagnostic code-based algorithms that lack clinical validation. To validate a well-accepted International Classification of Diseases, Ninth Revision, code-based algorithm for IPF using patient-level information and to develop a modified algorithm for IPF with enhanced predictive value. The traditional IPF algorithm was used to identify potential cases of IPF in the Kaiser Permanente Northern California adult population from 2000 to 2014. Incidence and prevalence were determined overall and by age, sex, and race/ethnicity. A validation subset of cases (n = 150) underwent expert medical record and chest computed tomography review. A modified IPF algorithm was then derived and validated to optimize positive predictive value. From 2000 to 2014, the traditional IPF algorithm identified 2,608 cases among 5,389,627 at-risk adults in the Kaiser Permanente Northern California population. Annual incidence was 6.8/100,000 person-years (95% confidence interval [CI], 6.1-7.7) and was higher in patients with older age, male sex, and white race. The positive predictive value of the IPF algorithm was only 42.2% (95% CI, 30.6 to 54.6%); sensitivity was 55.6% (95% CI, 21.2 to 86.3%). The corrected incidence was estimated at 5.6/100,000 person-years (95% CI, 2.6-10.3). A modified IPF algorithm had improved positive predictive value but reduced sensitivity compared with the traditional algorithm. A well-accepted International Classification of Diseases, Ninth Revision, code-based IPF algorithm performs poorly, falsely classifying many non-IPF cases as IPF and missing a substantial proportion of IPF cases. A modification of the IPF algorithm may be useful for future population-based studies of IPF.

Development and validation of risk models and molecular diagnostics to permit personalized management of cancer.

PubMed

Pu, Xia; Ye, Yuanqing; Wu, Xifeng

2014-01-01

Despite the advances made in cancer management over the past few decades, improvements in cancer diagnosis and prognosis are still poor, highlighting the need for individualized strategies. Toward this goal, risk prediction models and molecular diagnostic tools have been developed, tailoring each step of risk assessment from diagnosis to treatment and clinical outcomes based on the individual's clinical, epidemiological, and molecular profiles. These approaches hold increasing promise for delivering a new paradigm to maximize the efficiency of cancer surveillance and efficacy of treatment. However, they require stringent study design, methodology development, comprehensive assessment of biomarkers and risk factors, and extensive validation to ensure their overall usefulness for clinical translation. In the current study, the authors conducted a systematic review using breast cancer as an example and provide general guidelines for risk prediction models and molecular diagnostic tools, including development, assessment, and validation. © 2013 American Cancer Society.

Molecular Methods and Platforms for Infectious Diseases Testing

PubMed Central

Emmadi, Rajyasree; Boonyaratanakornkit, Jerry B.; Selvarangan, Rangaraj; Shyamala, Venkatakrishna; Zimmer, Barbara L.; Williams, Laurina; Bryant, Bonita; Schutzbank, Ted; Schoonmaker, Michele M.; Amos Wilson, Jean A.; Hall, Leslie; Pancholi, Preeti; Bernard, Kathryn

2011-01-01

The superior sensitivity and specificity associated with the use of molecular assays has greatly improved the field of infectious disease diagnostics by providing clinicians with results that are both accurate and rapidly obtained. Herein, we review molecularly based infectious disease diagnostic tests that are Food and Drug Administration approved or cleared and commercially available in the United States as of December 31, 2010. We describe specific assays and their performance, as stated in the Food and Drug Administration's Summary of Safety and Effectiveness Data or the Office of In Vitro Diagnostic Device Evaluation and Safety's decision summaries, product inserts, or peer-reviewed literature. We summarize indications for testing, limitations, and challenges related to implementation in a clinical laboratory setting for a wide variety of common pathogens. The information presented in this review will be particularly useful for laboratories that plan to implement or expand their molecular offerings in the near term. PMID:21871973

Molecular engineering of antibodies for therapeutic and diagnostic purposes

PubMed Central

Ducancel, Frédéric; Muller, Bruno H.

2012-01-01

During the past ten years, monoclonal antibodies (mAbs) have taken center stage in the field of targeted therapy and diagnosis. This increased interest in mAbs is due to their binding accuracy (affinity and specificity) together with the original molecular and structural rules that govern interactions with their cognate antigen. In addition, the effector properties of antibodies constitute a second major advantage associated with their clinical use. The development of molecular and structural engineering and more recently of in vitro evolution of antibodies has opened up new perspectives in the de novo design of antibodies more adapted to clinical and diagnostic use. Thus, efforts are regularly made by researchers to improve or modulate antibody recognition properties, to adapt their pharmacokinetics, engineer their stability, and control their immunogenicity. This review presents the latest molecular engineering results on mAbs with therapeutic and diagnostic applications. PMID:22684311

Conversion-Integration of MSFC Nonlinear Signal Diagnostic Analysis Algorithms for Realtime Execution of MSFC's MPP Prototype System

NASA Technical Reports Server (NTRS)

Jong, Jen-Yi

1996-01-01

NASA's advanced propulsion system Small Scale Magnetic Disturbances/Advanced Technology Development (SSME/ATD) has been undergoing extensive flight certification and developmental testing, which involves large numbers of health monitoring measurements. To enhance engine safety and reliability, detailed analysis and evaluation of the measurement signals are mandatory to assess its dynamic characteristics and operational condition. Efficient and reliable signal detection techniques will reduce the risk of catastrophic system failures and expedite the evaluation of both flight and ground test data, and thereby reduce launch turn-around time. During the development of SSME, ASRI participated in the research and development of several advanced non- linear signal diagnostic methods for health monitoring and failure prediction in turbomachinery components. However, due to the intensive computational requirement associated with such advanced analysis tasks, current SSME dynamic data analysis and diagnostic evaluation is performed off-line following flight or ground test with a typical diagnostic turnaround time of one to two days. The objective of MSFC's MPP Prototype System is to eliminate such 'diagnostic lag time' by achieving signal processing and analysis in real-time. Such an on-line diagnostic system can provide sufficient lead time to initiate corrective action and also to enable efficient scheduling of inspection, maintenance and repair activities. The major objective of this project was to convert and implement a number of advanced nonlinear diagnostic DSP algorithms in a format consistent with that required for integration into the Vanderbilt Multigraph Architecture (MGA) Model Based Programming environment. This effort will allow the real-time execution of these algorithms using the MSFC MPP Prototype System. ASRI has completed the software conversion and integration of a sequence of nonlinear signal analysis techniques specified in the SOW for real-time execution on MSFC's MPP Prototype. This report documents and summarizes the results of the contract tasks; provides the complete computer source code; including all FORTRAN/C Utilities; and all other utilities/supporting software libraries that are required for operation.

Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

PubMed

Santiago, Jose A; Potashkin, Judith A

2013-01-01

Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that increased expression of APP in blood may modulate the neurodegenerative phenotype in type 2 diabetes patients.

EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH).

PubMed

Porto, Graça; Brissot, Pierre; Swinkels, Dorine W; Zoller, Heinz; Kamarainen, Outi; Patton, Simon; Alonso, Isabel; Morris, Michael; Keeney, Steve

2016-04-01

Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. The vast majority (typically >90%) of patients with clinically characterized HH are homozygous for the p.C282Y variant in the HFE gene, referred to as HFE-related HH. Since 1996, HFE genotyping was implemented in diagnostic algorithms for suspected HH, allowing its early diagnosis and prevention. However, the penetrance of disease in p.C282Y homozygotes is incomplete. Hence, homozygosity for p.C282Y is not sufficient to diagnose HH. Neither is p.C282Y homozygosity required for diagnosis as other rare forms of HH exist, generally referred to as non-HFE-related HH. These pose significant challenges when defining criteria for referral, testing protocols, interpretation of test results and reporting practices. We present best practice guidelines for the molecular genetic diagnosis of HH where recommendations are classified, as far as possible, according to the level and strength of evidence. For clarification, the guidelines' recommendations are preceded by a detailed description of the methodology and results obtained with a series of actions taken in order to achieve a wide expert consensus, namely: (i) a survey on the current practices followed by laboratories offering molecular diagnosis of HH; (ii) a systematic literature search focused on some identified controversial topics; (iii) an expert Best Practice Workshop convened to achieve consensus on the practical recommendations included in the guidelines.

EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)

PubMed Central

Porto, Graça; Brissot, Pierre; Swinkels, Dorine W; Zoller, Heinz; Kamarainen, Outi; Patton, Simon; Alonso, Isabel; Morris, Michael; Keeney, Steve

2016-01-01

Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. The vast majority (typically >90%) of patients with clinically characterized HH are homozygous for the p.C282Y variant in the HFE gene, referred to as HFE-related HH. Since 1996, HFE genotyping was implemented in diagnostic algorithms for suspected HH, allowing its early diagnosis and prevention. However, the penetrance of disease in p.C282Y homozygotes is incomplete. Hence, homozygosity for p.C282Y is not sufficient to diagnose HH. Neither is p.C282Y homozygosity required for diagnosis as other rare forms of HH exist, generally referred to as non-HFE-related HH. These pose significant challenges when defining criteria for referral, testing protocols, interpretation of test results and reporting practices. We present best practice guidelines for the molecular genetic diagnosis of HH where recommendations are classified, as far as possible, according to the level and strength of evidence. For clarification, the guidelines' recommendations are preceded by a detailed description of the methodology and results obtained with a series of actions taken in order to achieve a wide expert consensus, namely: (i) a survey on the current practices followed by laboratories offering molecular diagnosis of HH; (ii) a systematic literature search focused on some identified controversial topics; (iii) an expert Best Practice Workshop convened to achieve consensus on the practical recommendations included in the guidelines. PMID:26153218

Rapid diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis using a molecular-based diagnostic algorithm.

PubMed

Simons, S O; van der Laan, T; Mulder, A; van Ingen, J; Rigouts, L; Dekhuijzen, P N R; Boeree, M J; van Soolingen, D

2014-10-01

There is an urgent need for rapid and accurate diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis (MDR-TB). No diagnostic algorithm has been validated in this population. We hypothesized that pncA sequencing added to rpoB mutation analysis can accurately identify patients with pyrazinamide-resistant MDR-TB. We identified from the Dutch national database (2007-11) patients with a positive Mycobacterium tuberculosis culture containing a mutation in the rpoB gene. In these cases, we prospectively sequenced the pncA gene. Results from the rpoB and pncA mutation analysis (pncA added to rpoB) were compared with phenotypic susceptibility testing results to rifampicin, isoniazid and pyrazinamide (reference standard) using the Mycobacterial Growth Indicator Tube 960 system. We included 83 clinical M. tuberculosis isolates containing rpoB mutations in the primary analysis. Rifampicin resistance was seen in 72 isolates (87%), isoniazid resistance in 73 isolates (88%) and MDR-TB in 65 isolates (78%). Phenotypic reference testing identified pyrazinamide-resistant MDR-TB in 31 isolates (48%). Sensitivity of pncA sequencing added to rpoB mutation analysis for detecting pyrazinamide-resistant MDR-TB was 96.8%, the specificity was 94.2%, the positive predictive value was 90.9%, the negative predictive value was 98.0%, the positive likelihood was 16.8 and the negative likelihood was 0.03. In conclusion, pyrazinamide-resistant MDR-TB can be accurately detected using pncA sequencing added to rpoB mutation analysis. We propose to include pncA sequencing in every isolate with an rpoB mutation, allowing for stratification of MDR-TB treatment according to pyrazinamide susceptibility. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Centronuclear myopathies: genotype-phenotype correlation and frequency of defined genetic forms in an Italian cohort.

PubMed

Fattori, Fabiana; Maggi, Lorenzo; Bruno, Claudio; Cassandrini, Denise; Codemo, Valentina; Catteruccia, Michela; Tasca, Giorgio; Berardinelli, Angela; Magri, Francesca; Pane, Marika; Rubegni, Anna; Santoro, Lucio; Ruggiero, Lucia; Fiorini, Patrizio; Pini, Antonella; Mongini, Tiziana; Messina, Sonia; Brisca, Giacomo; Colombo, Irene; Astrea, Guja; Fiorillo, Chiara; Bragato, Cinzia; Moroni, Isabella; Pegoraro, Elena; D'Apice, Maria Rosaria; Alfei, Enrico; Mora, Marina; Morandi, Lucia; Donati, Alice; Evilä, Anni; Vihola, Anna; Udd, Bjarne; Bernansconi, Pia; Mercuri, Eugenio; Santorelli, Filippo Maria; Bertini, Enrico; D'Amico, Adele

2015-07-01

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype-phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four 'canonical' genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1 and one in TTN. Among the 13 patients with a childhood-adolescence onset, mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in DNM2, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations.

Molecular phylogenetic analysis of Enterobius vermicularis and development of an 18S ribosomal DNA-targeted diagnostic PCR.

PubMed

Zelck, Ulrike E; Bialek, Ralf; Weiss, Michael

2011-04-01

We genetically characterized pinworms obtained from 37 children from different regions of Germany and established new species-specific molecular diagnostic tools. No ribosomal DNA diversity was found; the phylogenetic position of Enterobius vermicularis within the Oxyurida order and its close relationship to the Ascaridida and Spirurida orders was confirmed.

ACVP-02: Plasma SIV/SHIV RNA Viral Load Measurements through the AIDS and Cancer Virus Program Quantitative Molecular Diagnostics Core | Frederick National Laboratory for Cancer Research

Cancer.gov

The SIV plasma viral load assay performed by the Quantitative Molecular Diagnostics Core (QMDC) utilizes reagents specifically designed to detect and accurately quantify the full range of SIV/SHIV viral variants and clones in common usage in the rese

[Haemolytic uremic syndrome and thrombotic thrombocytopenic purpura: classification based on molecular etiology and review of recent developments in diagnostics].

PubMed

Prohászka, Zoltán

2008-07-06

Haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are overlapping clinical entities based on historical classification. Recent developments in the unfolding of the pathomechanisms of these diseases resulted in the creation of a molecular etiology-based classification. Understanding of some causative relationships yielded detailed diagnostic approaches, novel therapeutic options and thorough prognostic assortment of the patients. Although haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are rare diseases with poor prognosis, the precise molecular etiology-based diagnosis might properly direct the therapy of the affected patients. The current review focuses on the theoretical background and detailed description of the available diagnostic possibilities, and some practical information necessary for the interpretation of their results.

Different CT perfusion algorithms in the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

PubMed

Cremers, Charlotte H P; Dankbaar, Jan Willem; Vergouwen, Mervyn D I; Vos, Pieter C; Bennink, Edwin; Rinkel, Gabriel J E; Velthuis, Birgitta K; van der Schaaf, Irene C

2015-05-01

Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose.

Development and assessment of molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoea: a multicentre study.

PubMed

Liu, Jie; Kabir, Furqan; Manneh, Jainaba; Lertsethtakarn, Paphavee; Begum, Sharmin; Gratz, Jean; Becker, Steve M; Operario, Darwin J; Taniuchi, Mami; Janaki, Lalitha; Platts-Mills, James A; Haverstick, Doris M; Kabir, Mamun; Sobuz, Shihab U; Nakjarung, Kaewkanya; Sakpaisal, Pimmada; Silapong, Sasikorn; Bodhidatta, Ladaporn; Qureshi, Shahida; Kalam, Adil; Saidi, Queen; Swai, Ndealilia; Mujaga, Buliga; Maro, Athanasia; Kwambana, Brenda; Dione, Michel; Antonio, Martin; Kibiki, Gibson; Mason, Carl J; Haque, Rashidul; Iqbal, Najeeha; Zaidi, Anita K M; Houpt, Eric R

2014-08-01

Childhood diarrhoea can be caused by many pathogens that are difficult to assay in the laboratory. Molecular diagnostic techniques provide a uniform method to detect and quantify candidate enteropathogens. We aimed to develop and assess molecular tests for identification of enteropathogens and their association with disease. We developed and assessed molecular diagnostic tests for 15 enteropathogens across three platforms-PCR-Luminex, multiplex real-time PCR, and TaqMan array card-at five laboratories worldwide. We judged the analytical and clinical performance of these molecular techniques against comparator methods (bacterial culture, ELISA, and PCR) using 867 diarrhoeal and 619 non-diarrhoeal stool specimens. We also measured molecular quantities of pathogens to predict the association with diarrhoea, by univariate logistic regression analysis. The molecular tests showed very good analytical and clinical performance at all five laboratories. Comparator methods had limited sensitivity compared with the molecular techniques (20-85% depending on the target) but good specificity (median 97·3%, IQR 96·5-98·9; mean 95·2%, SD 9·1). Positive samples by comparator methods usually had higher molecular quantities of pathogens than did negative samples, across almost all platforms and for most pathogens (p<0·05). The odds ratio for diarrhoea at a given quantity (measured by quantification cycle, Cq) showed that for most pathogens associated with diarrhoea-including Campylobacter jejuni and Campylobacter coli, Cryptosporidium spp, enteropathogenic Escherichia coli, heat-stable enterotoxigenic E coli, rotavirus, Shigella spp and enteroinvasive E coli, and Vibrio cholerae-the strength of association with diarrhoea increased at higher pathogen loads. For example, Shigella spp at a Cq range of 15-20 had an odds ratio of 8·0 (p<0·0001), but at a Cq range of 25-30 the odds ratio fell to 1·7 (p=0·043). Molecular diagnostic tests can be implemented successfully and with fidelity across laboratories around the world. In the case of diarrhoea, these techniques can detect pathogens with high sensitivity and ascribe diarrhoeal associations based on quantification, including in mixed infections, providing rich and unprecedented measurements of infectious causes. Bill & Melinda Gates Foundation Next Generation Molecular Diagnostics Project. Copyright © 2014 Elsevier Ltd. All rights reserved.

Recommendations for accreditation of laboratories in molecular biology of hematologic malignancies.

PubMed

Flandrin-Gresta, Pascale; Cornillet, Pascale; Hayette, Sandrine; Gachard, Nathalie; Tondeur, Sylvie; Mauté, Carole; Cayuela, Jean-Michel

2015-01-01

Over recent years, the development of molecular biology techniques has improved the hematological diseases diagnostic and follow-up. Consequently, these techniques are largely used in the biological screening of these diseases; therefore the Hemato-oncology molecular diagnostics laboratories must be actively involved in the accreditation process according the ISO 15189 standard. The French group of molecular biologists (GBMHM) provides requirements for the implementation of quality assurance for the medical molecular laboratories. This guideline states the recommendations for the pre-analytical, analytical (methods validation procedures, quality controls, reagents), and post-analytical conditions. In addition, herein we state a strategy for the internal quality control management. These recommendations will be regularly updated.

Effects of Child Characteristics on the Autism Diagnostic Interview-Revised: Implications for Use of Scores as a Measure of ASD Severity

ERIC Educational Resources Information Center

Hus, Vanessa; Lord, Catherine

2013-01-01

The Autism Diagnostic Interview-Revised (ADI-R) is commonly used to inform diagnoses of autism spectrum disorders (ASD). Considering the time dedicated to using the ADI-R, it is of interest to expand the ways in which information obtained from this interview is used. The current study examines how algorithm totals reflecting past (ADI-Diagnostic)…

Spatial enhancement of ECG using diagnostic similarity score based lead selective multi-scale linear model.

PubMed

Nallikuzhy, Jiss J; Dandapat, S

2017-06-01

In this work, a new patient-specific approach to enhance the spatial resolution of ECG is proposed and evaluated. The proposed model transforms a three-lead ECG into a standard twelve-lead ECG thereby enhancing its spatial resolution. The three leads used for prediction are obtained from the standard twelve-lead ECG. The proposed model takes advantage of the improved inter-lead correlation in wavelet domain. Since the model is patient-specific, it also selects the optimal predictor leads for a given patient using a lead selection algorithm. The lead selection algorithm is based on a new diagnostic similarity score which computes the diagnostic closeness between the original and the spatially enhanced leads. Standard closeness measures are used to assess the performance of the model. The similarity in diagnostic information between the original and the spatially enhanced leads are evaluated using various diagnostic measures. Repeatability and diagnosability are performed to quantify the applicability of the model. A comparison of the proposed model is performed with existing models that transform a subset of standard twelve-lead ECG into the standard twelve-lead ECG. From the analysis of the results, it is evident that the proposed model preserves diagnostic information better compared to other models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a novel diagnostic algorithm to predict NASH in HCV-positive patients.

PubMed

Gallotta, Andrea; Paneghetti, Laura; Mrázová, Viera; Bednárová, Adriana; Kružlicová, Dáša; Frecer, Vladimir; Miertus, Stanislav; Biasiolo, Alessandra; Martini, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2018-05-01

Non-alcoholic steato-hepatitis (NASH) is a severe disease characterised by liver inflammation and progressive hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that in hepatitis C virus patients steatosis and NASH are associated with faster fibrosis progression and hepatocellular carcinoma. A safe and reliable non-invasive diagnostic method to detect NASH at its early stages is still needed to prevent progression of the disease. We prospectively enrolled 91 hepatitis C virus-positive patients with histologically proven chronic liver disease: 77 patients were included in our study; of these, 10 had NASH. For each patient, various clinical and serological variables were collected. Different algorithms combining squamous cell carcinoma antigen-immunoglobulin-M (SCCA-IgM) levels with other common clinical data were created to provide the probability of having NASH. Our analysis revealed a statistically significant correlation between the histological presence of NASH and SCCA-IgM, insulin, homeostasis model assessment, haemoglobin, high-density lipoprotein and ferritin levels, and smoke. Compared to the use of a single marker, algorithms that combined four, six or seven variables identified NASH with higher accuracy. The best diagnostic performance was obtained with the logistic regression combination, which included all seven variables correlated with NASH. The combination of SCCA-IgM with common clinical data shows promising diagnostic performance for the detection of NASH in hepatitis C virus patients.

Diagnosing Sexual Dysfunction in Men and Women: Sexual History Taking and the Role of Symptom Scales and Questionnaires.

PubMed

Hatzichristou, Dimitris; Kirana, Paraskevi-Sofia; Banner, Linda; Althof, Stanley E; Lonnee-Hoffmann, Risa A M; Dennerstein, Lorraine; Rosen, Raymond C

2016-08-01

A detailed sexual history is the cornerstone for all sexual problem assessments and sexual dysfunction diagnoses. Diagnostic evaluation is based on an in-depth sexual history, including sexual and gender identity and orientation, sexual activity and function, current level of sexual function, overall health and comorbidities, partner relationship and interpersonal factors, and the role of cultural and personal expectations and attitudes. To propose key steps in the diagnostic evaluation of sexual dysfunctions, with special focus on the use of symptom scales and questionnaires. Critical assessment of the current literature by the International Consultation on Sexual Medicine committee. A revised algorithm for the management of sexual dysfunctions, level of evidence, and recommendation for scales and questionnaires. The International Consultation on Sexual Medicine proposes an updated algorithm for diagnostic evaluation of sexual dysfunction in men and women, with specific recommendations for sexual history taking and diagnostic evaluation. Standardized scales, checklists, and validated questionnaires are additional adjuncts that should be used routinely in sexual problem evaluation. Scales developed for specific patient groups are included. Results of this evaluation are presented with recommendations for clinical and research uses. Defined principles, an algorithm and a range of scales may provide coherent and evidence based management for sexual dysfunctions. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

A preface on advances in diagnostics for infectious and parasitic diseases: detecting parasites of medical and veterinary importance.

PubMed

Stothard, J Russell; Adams, Emily

2014-12-01

There are many reasons why detection of parasites of medical and veterinary importance is vital and where novel diagnostic and surveillance tools are required. From a medical perspective alone, these originate from a desire for better clinical management and rational use of medications. Diagnosis can be at the individual-level, at close to patient settings in testing a clinical suspicion or at the community-level, perhaps in front of a computer screen, in classification of endemic areas and devising appropriate control interventions. Thus diagnostics for parasitic diseases has a broad remit as parasites are not only tied with their definitive hosts but also in some cases with their vectors/intermediate hosts. Application of current diagnostic tools and decision algorithms in sustaining control programmes, or in elimination settings, can be problematic and even ill-fitting. For example in resource-limited settings, are current diagnostic tools sufficiently robust for operational use at scale or are they confounded by on-the-ground realities; are the diagnostic algorithms underlying public health interventions always understood and well-received within communities which are targeted for control? Within this Special Issue (SI) covering a variety of diseases and diagnostic settings some answers are forthcoming. An important theme, however, throughout the SI is to acknowledge that cross-talk and continuous feedback between development and application of diagnostic tests is crucial if they are to be used effectively and appropriately.

Maximum likelihood phase-retrieval algorithm: applications.

PubMed

Nahrstedt, D A; Southwell, W H

1984-12-01

The maximum likelihood estimator approach is shown to be effective in determining the wave front aberration in systems involving laser and flow field diagnostics and optical testing. The robustness of the algorithm enables convergence even in cases of severe wave front error and real, nonsymmetrical, obscured amplitude distributions.

Diagnosis and treatment of gastroesophageal reflux disease complicated by Barrett's esophagus.

PubMed

Stasyshyn, Andriy

2017-08-31

The aim of the study was to evaluate the effectiveness of a diagnostic and therapeutic algorithm for gastroesophageal reflux disease complicated by Barrett's esophagus in 46 patients. A diagnostic and therapeutic algorithm for complicated GERD was developed. To describe the changes in the esophagus with reflux esophagitis, the Los Angeles classification was used. Intestinal metaplasia of the epithelium in the lower third of the esophagus was assessed using videoendoscopy, chromoscopy, and biopsy. Quality of life was assessed with the Gastro-Intestinal Quality of Life Index. The used methods were modeling, clinical, analytical, comparative, standardized, and questionnaire-based. Results and their discussion. Among the complications of GERD, Barrett's esophagus was diagnosed in 9 (19.6 %), peptic ulcer in the esophagus in 10 (21.7 %), peptic stricture of the esophagus in 4 (8.7 %), esophageal-gastric bleeding in 23 (50.0 %), including Malory-Weiss syndrome in 18, and erosive ulcerous bleeding in 5 people. Hiatal hernia was diagnosed in 171 (87.7 %) patients (sliding in 157 (91.8%), paraesophageal hernia in 2 (1.2%), and mixed hernia in 12 (7.0%) cases). One hundred ninety-five patients underwent laparoscopic surgery. Nissen fundoplication was conducted in 176 (90.2%) patients, Toupet fundoplication in 14 (7.2%), and Dor fundoplication in 5 (2.6%). It was established that the use of the diagnostic and treatment algorithm promoted systematization and objectification of changes in complicated GERD, contributed to early diagnosis, helped in choosing treatment, and improved quality of life. Argon coagulation and use of PPIs for 8-12 weeks before surgery led to the regeneration of the mucous membrane in the esophagus. The developed diagnostic and therapeutic algorithm facilitated systematization and objectification of changes in complicated GERD, contributed to early diagnosis, helped in choosing treatment, and improved quality of life.

Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)

PubMed Central

Quint, Jennifer K; Müllerova, Hana; DiSantostefano, Rachael L; Forbes, Harriet; Eaton, Susan; Hurst, John R; Davis, Kourtney; Smeeth, Liam

2014-01-01

Objectives The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. Setting 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. Primary outcome measure The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. Results 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5–92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7–94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2–44.4%). Conclusions Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. PMID:25056980

A simple and robust classification tree for differentiation between benign and malignant lesions in MR-mammography.

PubMed

Baltzer, Pascal A T; Dietzel, Matthias; Kaiser, Werner A

2013-08-01

In the face of multiple available diagnostic criteria in MR-mammography (MRM), a practical algorithm for lesion classification is needed. Such an algorithm should be as simple as possible and include only important independent lesion features to differentiate benign from malignant lesions. This investigation aimed to develop a simple classification tree for differential diagnosis in MRM. A total of 1,084 lesions in standardised MRM with subsequent histological verification (648 malignant, 436 benign) were investigated. Seventeen lesion criteria were assessed by 2 readers in consensus. Classification analysis was performed using the chi-squared automatic interaction detection (CHAID) method. Results include the probability for malignancy for every descriptor combination in the classification tree. A classification tree incorporating 5 lesion descriptors with a depth of 3 ramifications (1, root sign; 2, delayed enhancement pattern; 3, border, internal enhancement and oedema) was calculated. Of all 1,084 lesions, 262 (40.4 %) and 106 (24.3 %) could be classified as malignant and benign with an accuracy above 95 %, respectively. Overall diagnostic accuracy was 88.4 %. The classification algorithm reduced the number of categorical descriptors from 17 to 5 (29.4 %), resulting in a high classification accuracy. More than one third of all lesions could be classified with accuracy above 95 %. • A practical algorithm has been developed to classify lesions found in MR-mammography. • A simple decision tree consisting of five criteria reaches high accuracy of 88.4 %. • Unique to this approach, each classification is associated with a diagnostic certainty. • Diagnostic certainty of greater than 95 % is achieved in 34 % of all cases.

Fourier analysis algorithm for the posterior corneal keratometric data: clinical usefulness in keratoconus.

PubMed

Sideroudi, Haris; Labiris, Georgios; Georgantzoglou, Kimon; Ntonti, Panagiota; Siganos, Charalambos; Kozobolis, Vassilios

2017-07-01

To develop an algorithm for the Fourier analysis of posterior corneal videokeratographic data and to evaluate the derived parameters in the diagnosis of Subclinical Keratoconus (SKC) and Keratoconus (KC). This was a cross-sectional, observational study that took place in the Eye Institute of Thrace, Democritus University, Greece. Eighty eyes formed the KC group, 55 eyes formed the SKC group while 50 normal eyes populated the control group. A self-developed algorithm in visual basic for Microsoft Excel performed a Fourier series harmonic analysis for the posterior corneal sagittal curvature data. The algorithm decomposed the obtained curvatures into a spherical component, regular astigmatism, asymmetry and higher order irregularities for averaged central 4 mm and for each individual ring separately (1, 2, 3 and 4 mm). The obtained values were evaluated for their diagnostic capacity using receiver operating curves (ROC). Logistic regression was attempted for the identification of a combined diagnostic model. Significant differences were detected in regular astigmatism, asymmetry and higher order irregularities among groups. For the SKC group, the parameters with high diagnostic ability (AUC > 90%) were the higher order irregularities, the asymmetry and the regular astigmatism, mainly in the corneal periphery. Higher predictive accuracy was identified using diagnostic models that combined the asymmetry, regular astigmatism and higher order irregularities in averaged 3and 4 mm area (AUC: 98.4%, Sensitivity: 91.7% and Specificity:100%). Fourier decomposition of posterior Keratometric data provides parameters with high accuracy in differentiating SKC from normal corneas and should be included in the prompt diagnosis of KC. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

Diagnostic algorithm for relapsing acquired demyelinating syndromes in children.

PubMed

Hacohen, Yael; Mankad, Kshitij; Chong, W K; Barkhof, Frederik; Vincent, Angela; Lim, Ming; Wassmer, Evangeline; Ciccarelli, Olga; Hemingway, Cheryl

2017-07-18

To establish whether children with relapsing acquired demyelinating syndromes (RDS) and myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) show distinctive clinical and radiologic features and to generate a diagnostic algorithm for the main RDS for clinical use. A panel reviewed the clinical characteristics, MOG-Ab and aquaporin-4 (AQP4) Ab, intrathecal oligoclonal bands, and Epstein-Barr virus serology results of 110 children with RDS. A neuroradiologist blinded to the diagnosis scored the MRI scans. Clinical, radiologic, and serologic tests results were compared. The findings showed that 56.4% of children were diagnosed with multiple sclerosis (MS), 25.4% with neuromyelitis optica spectrum disorder (NMOSD), 12.7% with multiphasic disseminated encephalomyelitis (MDEM), and 5.5% with relapsing optic neuritis (RON). Blinded analysis defined baseline MRI as typical of MS in 93.5% of children with MS. Acute disseminated encephalomyelitis presentation was seen only in the non-MS group. Of NMOSD cases, 30.7% were AQP4-Ab positive. MOG-Ab were found in 83.3% of AQP4-Ab-negative NMOSD, 100% of MDEM, and 33.3% of RON. Children with MOG-Ab were younger, were less likely to present with area postrema syndrome, and had lower disability, longer time to relapse, and more cerebellar peduncle lesions than children with AQP4-Ab NMOSD. A diagnostic algorithm applicable to any episode of CNS demyelination leads to 4 main phenotypes: MS, AQP4-Ab NMOSD, MOG-Ab-associated disease, and antibody-negative RDS. Children with MS and AQP4-Ab NMOSD showed features typical of adult cases. Because MOG-Ab-positive children showed notable and distinctive clinical and MRI features, they were grouped into a unified phenotype (MOG-Ab-associated disease), included in a new diagnostic algorithm. © 2017 American Academy of Neurology.

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.

Diagnostic Abilities of Variable and Enhanced Corneal Compensation Algorithms of GDx in Different Severities of Glaucoma.

PubMed

Yadav, Ravi K; Begum, Viquar U; Addepalli, Uday K; Senthil, Sirisha; Garudadri, Chandra S; Rao, Harsha L

2016-02-01

To compare the abilities of retinal nerve fiber layer (RNFL) parameters of variable corneal compensation (VCC) and enhanced corneal compensation (ECC) algorithms of scanning laser polarimetry (GDx) in detecting various severities of glaucoma. Two hundred and eighty-five eyes of 194 subjects from the Longitudinal Glaucoma Evaluation Study who underwent GDx VCC and ECC imaging were evaluated. Abilities of RNFL parameters of GDx VCC and ECC to diagnose glaucoma were compared using area under receiver operating characteristic curves (AUC), sensitivities at fixed specificities, and likelihood ratios. After excluding 5 eyes that failed to satisfy manufacturer-recommended quality parameters with ECC and 68 with VCC, 56 eyes of 41 normal subjects and 161 eyes of 121 glaucoma patients [36 eyes with preperimetric glaucoma, 52 eyes with early (MD>-6 dB), 34 with moderate (MD between -6 and -12 dB), and 39 with severe glaucoma (MD<-12 dB)] were included for the analysis. Inferior RNFL, average RNFL, and nerve fiber indicator parameters showed the best AUCs and sensitivities both with GDx VCC and ECC in diagnosing all severities of glaucoma. AUCs and sensitivities of all RNFL parameters were comparable between the VCC and ECC algorithms (P>0.20 for all comparisons). Likelihood ratios associated with the diagnostic categorization of RNFL parameters were comparable between the VCC and ECC algorithms. In scans satisfying the manufacturer-recommended quality parameters, which were significantly greater with ECC than VCC algorithm, diagnostic abilities of GDx ECC and VCC in glaucoma were similar.

Fast parallel molecular algorithms for DNA-based computation: factoring integers.

PubMed

Chang, Weng-Long; Guo, Minyi; Ho, Michael Shan-Hui

2005-06-01

The RSA public-key cryptosystem is an algorithm that converts input data to an unrecognizable encryption and converts the unrecognizable data back into its original decryption form. The security of the RSA public-key cryptosystem is based on the difficulty of factoring the product of two large prime numbers. This paper demonstrates to factor the product of two large prime numbers, and is a breakthrough in basic biological operations using a molecular computer. In order to achieve this, we propose three DNA-based algorithms for parallel subtractor, parallel comparator, and parallel modular arithmetic that formally verify our designed molecular solutions for factoring the product of two large prime numbers. Furthermore, this work indicates that the cryptosystems using public-key are perhaps insecure and also presents clear evidence of the ability of molecular computing to perform complicated mathematical operations.

Quantum Dots for Molecular Diagnostics of Tumors

PubMed Central

Zdobnova, T.A.; Lebedenko, E.N.; Deyev, S.М.

2011-01-01

Semiconductor quantum dots (QDs) are a new class of fluorophores with unique physical and chemical properties, which allow to appreciably expand the possibilities for the current methods of fluorescent imaging and optical diagnostics. Here we discuss the prospects of QD application for molecular diagnostics of tumors ranging from cancer-specific marker detection on microplates to non-invasive tumor imagingin vivo. We also point out the essential problems that require resolution in order to clinically promote QD, and we indicate innovative approaches to oncology which are implementable using QD. PMID:22649672

Identifying FGA peptides as nasopharyngeal carcinoma-associated biomarkers by magnetic beads.

PubMed

Tao, Ya-Lan; Li, Yan; Gao, Jin; Liu, Zhi-Gang; Tu, Zi-Wei; Li, Guo; Xu, Bing-Qing; Niu, Dao-Li; Jiang, Chang-Bin; Yi, Wei; Li, Zhi-Qiang; Li, Jing; Wang, Yi-Ming; Cheng, Zhi-Bin; Liu, Qiao-Dan; Bai, Li; Zhang, Chun; Zhang, Jing-Yu; Zeng, Mu-Sheng; Xia, Yun-Fei

2012-07-01

Early diagnosis and treatment is known to improve prognosis for nasopharyngeal carcinoma (NPC). The study determined the specific peptide profiles by comparing the serum differences between NPC patients and healthy controls, and provided the basis for the diagnostic model and identification of specific biomarkers of NPC. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can be used to detect the molecular mass of peptides. Mass spectra of peptides were generated after extracting and purification of 40 NPC samples in the training set, 21 in the single center validation set and 99 in the multicenter validation set using weak cationic-exchanger magnetic beads. The spectra were analyzed statistically using FlexAnalysis™ and ClinProt™ bioinformatics software. The four most significant peaks were selected out to train a genetic algorithm model to diagnose NPC. The diagnostic sensitivity and specificity were 100% and 100% in the training set, 90.5% and 88.9% in the single center validation set, 91.9% and 83.3% in the multicenter validation set, and the false positive rate (FPR) and false negative rate (FNR) were obviously lower in the NPC group (FPR, 16.7%; FNR, 8.1%) than in the other cancer group (FPR, 39%; FNR, 61%), respectively. So, the diagnostic model including four peptides can be suitable for NPC but not for other cancers. FGA peptide fragments identified may serve as tumor-associated biomarkers for NPC. Copyright © 2012 Wiley Periodicals, Inc.

Synthetic biology devices for in vitro and in vivo diagnostics.

PubMed

Slomovic, Shimyn; Pardee, Keith; Collins, James J

2015-11-24

There is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms.

Synthetic biology devices for in vitro and in vivo diagnostics

PubMed Central

Slomovic, Shimyn; Pardee, Keith; Collins, James J.

2015-01-01

There is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms. PMID:26598662

Paper-based sample-to-answer molecular diagnostic platform for point-of-care diagnostics.

PubMed

Choi, Jane Ru; Tang, Ruihua; Wang, ShuQi; Wan Abas, Wan Abu Bakar; Pingguan-Murphy, Belinda; Xu, Feng

2015-12-15

Nucleic acid testing (NAT), as a molecular diagnostic technique, including nucleic acid extraction, amplification and detection, plays a fundamental role in medical diagnosis for timely medical treatment. However, current NAT technologies require relatively high-end instrumentation, skilled personnel, and are time-consuming. These drawbacks mean conventional NAT becomes impractical in many resource-limited disease-endemic settings, leading to an urgent need to develop a fast and portable NAT diagnostic tool. Paper-based devices are typically robust, cost-effective and user-friendly, holding a great potential for NAT at the point of care. In view of the escalating demand for the low cost diagnostic devices, we highlight the beneficial use of paper as a platform for NAT, the current state of its development, and the existing challenges preventing its widespread use. We suggest a strategy involving integrating all three steps of NAT into one single paper-based sample-to-answer diagnostic device for rapid medical diagnostics in the near future. Copyright © 2015 Elsevier B.V. All rights reserved.

Incremental Yield of Including Determine-TB LAM Assay in Diagnostic Algorithms for Hospitalized and Ambulatory HIV-Positive Patients in Kenya.

PubMed

Huerga, Helena; Ferlazzo, Gabriella; Bevilacqua, Paolo; Kirubi, Beatrice; Ardizzoni, Elisa; Wanjala, Stephen; Sitienei, Joseph; Bonnet, Maryline

2017-01-01

Determine-TB LAM assay is a urine point-of-care test useful for TB diagnosis in HIV-positive patients. We assessed the incremental diagnostic yield of adding LAM to algorithms based on clinical signs, sputum smear-microscopy, chest X-ray and Xpert MTB/RIF in HIV-positive patients with symptoms of pulmonary TB (PTB). Prospective observational cohort of ambulatory (either severely ill or CD4<200cells/μl or with Body Mass Index<17Kg/m2) and hospitalized symptomatic HIV-positive adults in Kenya. Incremental diagnostic yield of adding LAM was the difference in the proportion of confirmed TB patients (positive Xpert or MTB culture) diagnosed by the algorithm with LAM compared to the algorithm without LAM. The multivariable mortality model was adjusted for age, sex, clinical severity, BMI, CD4, ART initiation, LAM result and TB confirmation. Among 474 patients included, 44.1% were severely ill, 69.6% had CD4<200cells/μl, 59.9% had initiated ART, 23.2% could not produce sputum. LAM, smear-microscopy, Xpert and culture in sputum were positive in 39.0% (185/474), 21.6% (76/352), 29.1% (102/350) and 39.7% (92/232) of the patients tested, respectively. Of 156 patients with confirmed TB, 65.4% were LAM positive. Of those classified as non-TB, 84.0% were LAM negative. Adding LAM increased the diagnostic yield of the algorithms by 36.6%, from 47.4% (95%CI:39.4-55.6) to 84.0% (95%CI:77.3-89.4%), when using clinical signs and X-ray; by 19.9%, from 62.2% (95%CI:54.1-69.8) to 82.1% (95%CI:75.1-87.7), when using clinical signs and microscopy; and by 13.4%, from 74.4% (95%CI:66.8-81.0) to 87.8% (95%CI:81.6-92.5), when using clinical signs and Xpert. LAM positive patients had an increased risk of 2-months mortality (aOR:2.7; 95%CI:1.5-4.9). LAM should be included in TB diagnostic algorithms in parallel to microscopy or Xpert request for HIV-positive patients either ambulatory (severely ill or CD4<200cells/μl) or hospitalized. LAM allows same day treatment initiation in patients at higher risk of death and in those not able to produce sputum.

Feeding Disorders in Children with Developmental Disabilities.

ERIC Educational Resources Information Center

Schwarz, Steven M.

2003-01-01

This article describes an approach to evaluating and managing feeding disorders in children with developmental disabilities and examines effects of these management strategies on growth and clinical outcomes. A structured approach is stressed and a diagnostic and treatment algorithm is presented. Use with 79 children found that diagnostic-specific…

UK NEQAS survey of allergen component testing across the United Kingdom and other European countries

PubMed Central

Saleem, R.; Keymer, C.; Patel, D.; Egner, W.

2017-01-01

Summary The clinical utility of molecular diagnostic approaches in allergy investigation is being recognized increasingly to play a significant role in the management of allergic patients. Determining the sensitization pattern, which is best achieved through the use of component resolved diagnostics (CRD), allows effective risk stratification, appropriate treatment and patient selection for immunotherapy. In order to assess the diagnostic service provisions for in‐vitro allergy testing across Europe, a survey was carried out via the total immunoglobulin (Ig)E and specific IgE external quality assurance schemes run by UK National External Quality Assessment Service (NEQAS) Immunology, Immunochemistry and Allergy. This survey assessed allergy testing, and in particular allergen components offered by the laboratories, and found a wide variability in service provision, particularly between the United Kingdom and other European Union (EU) countries. Furthermore, there was lack of standardization for acquisition of clinical information to aid allergen (and component) selection, gating strategy, testing algorithms and clinical interpretation. Interestingly, a significant proportion of laboratories (the majority from EU) stated that they ‘used’ the results for peanut components for risk stratification. However, the vast majority of participants were unaware of guidelines relating to the use of allergen component testing, and agreed that further education would assist in reaching a common platform. Hence, this survey has highlighted that although CRD has been adopted into routine diagnostics across Europe, it is potentially compromised by lack of standardized protocols and guidance sources. Consequently, there is a need for local or national standards and education through External Quality Assurance services on the performance and application of CRD into allergy investigation. PMID:28423454

Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: Recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†

PubMed Central

Schiffman, Eric; Ohrbach, Richard; Truelove, Edmond; Look, John; Anderson, Gary; Goulet, Jean-Paul; List, Thomas; Svensson, Peter; Gonzalez, Yoly; Lobbezoo, Frank; Michelotti, Ambra; Brooks, Sharon L.; Ceusters, Werner; Drangsholt, Mark; Ettlin, Dominik; Gaul, Charly; Goldberg, Louis J.; Haythornthwaite, Jennifer A.; Hollender, Lars; Jensen, Rigmor; John, Mike T.; De Laat, Antoon; de Leeuw, Reny; Maixner, William; van der Meulen, Marylee; Murray, Greg M.; Nixdorf, Donald R.; Palla, Sandro; Petersson, Arne; Pionchon, Paul; Smith, Barry; Visscher, Corine M.; Zakrzewska, Joanna; Dworkin, Samuel F.

2015-01-01

Aims The original Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I diagnostic algorithms have been demonstrated to be reliable. However, the Validation Project determined that the RDC/TMD Axis I validity was below the target sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Consequently, these empirical results supported the development of revised RDC/TMD Axis I diagnostic algorithms that were subsequently demonstrated to be valid for the most common pain-related TMD and for one temporomandibular joint (TMJ) intra-articular disorder. The original RDC/TMD Axis II instruments were shown to be both reliable and valid. Working from these findings and revisions, two international consensus workshops were convened, from which recommendations were obtained for the finalization of new Axis I diagnostic algorithms and new Axis II instruments. Methods Through a series of workshops and symposia, a panel of clinical and basic science pain experts modified the revised RDC/TMD Axis I algorithms by using comprehensive searches of published TMD diagnostic literature followed by review and consensus via a formal structured process. The panel's recommendations for further revision of the Axis I diagnostic algorithms were assessed for validity by using the Validation Project's data set, and for reliability by using newly collected data from the ongoing TMJ Impact Project—the follow-up study to the Validation Project. New Axis II instruments were identified through a comprehensive search of the literature providing valid instruments that, relative to the RDC/TMD, are shorter in length, are available in the public domain, and currently are being used in medical settings. Results The newly recommended Diagnostic Criteria for TMD (DC/TMD) Axis I protocol includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain-related TMD (sensitivity ≥ 0.86, specificity ≥ 0.98) and for one intra-articular disorder (sensitivity of 0.80 and specificity of 0.97). Diagnostic criteria for other common intra-articular disorders lack adequate validity for clinical diagnoses but can be used for screening purposes. Inter-examiner reliability for the clinical assessment associated with the validated DC/TMD criteria for pain-related TMD is excellent (kappa ≥ 0.85). Finally, a comprehensive classification system that includes both the common and less common TMD is also presented. The Axis II protocol retains selected original RDC/TMD screening instruments augmented with new instruments to assess jaw function as well as behavioral and additional psychosocial factors. The Axis II protocol is divided into screening and comprehensive self-report instrument sets. The screening instruments’ 41 questions assess pain intensity, pain-related disability, psychological distress, jaw functional limitations, and parafunctional behaviors, and a pain drawing is used to assess locations of pain. The comprehensive instruments, composed of 81 questions, assess in further detail jaw functional limitations and psychological distress as well as additional constructs of anxiety and presence of comorbid pain conditions. Conclusion The recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings. More comprehensive instruments augment short and simple screening instruments for Axis I and Axis II. These validated instruments allow for identification of patients with a range of simple to complex TMD presentations. PMID:24482784

Influenza detection and prediction algorithms: comparative accuracy trial in Östergötland county, Sweden, 2008-2012.

PubMed

Spreco, A; Eriksson, O; Dahlström, Ö; Timpka, T

2017-07-01

Methods for the detection of influenza epidemics and prediction of their progress have seldom been comparatively evaluated using prospective designs. This study aimed to perform a prospective comparative trial of algorithms for the detection and prediction of increased local influenza activity. Data on clinical influenza diagnoses recorded by physicians and syndromic data from a telenursing service were used. Five detection and three prediction algorithms previously evaluated in public health settings were calibrated and then evaluated over 3 years. When applied on diagnostic data, only detection using the Serfling regression method and prediction using the non-adaptive log-linear regression method showed acceptable performances during winter influenza seasons. For the syndromic data, none of the detection algorithms displayed a satisfactory performance, while non-adaptive log-linear regression was the best performing prediction method. We conclude that evidence was found for that available algorithms for influenza detection and prediction display satisfactory performance when applied on local diagnostic data during winter influenza seasons. When applied on local syndromic data, the evaluated algorithms did not display consistent performance. Further evaluations and research on combination of methods of these types in public health information infrastructures for 'nowcasting' (integrated detection and prediction) of influenza activity are warranted.

Comparison of Traditional and Reverse Syphilis Screening Algorithms in Medical Health Checkups.

PubMed

Nah, Eun Hee; Cho, Seon; Kim, Suyoung; Cho, Han Ik; Chai, Jong Yil

2017-11-01

The syphilis diagnostic algorithms applied in different countries vary significantly depending on the local syphilis epidemiology and other considerations, including the expected workload, the need for automation in the laboratory and budget factors. This study was performed to investigate the efficacy of traditional and reverse syphilis diagnostic algorithms during general health checkups. In total, 1,000 blood specimens were obtained from 908 men and 92 women during their regular health checkups. Traditional screening and reverse screening were applied to the same specimens using automatic rapid plasma regain (RPR) and Treponema pallidum latex agglutination (TPLA) tests, respectively. Specimens that were reverse algorithm (TPLA) reactive, were subjected to a second treponemal test performed by using the chemiluminescent microparticle immunoassay (CMIA). Of the 1,000 specimens tested, 68 (6.8%) were reactive by reverse screening (TPLA) compared with 11 (1.1%) by traditional screening (RPR). The traditional algorithm failed to detect 48 specimens [TPLA(+)/RPR(-)/CMIA(+)]. The median TPLA cutoff index (COI) was higher in CMIA-reactive cases than in CMIA-nonreactive cases (90.5 vs 12.5 U). The reverse screening algorithm could detect the subjects with possible latent syphilis who were not detected by the traditional algorithm. Those individuals could be provided with opportunities for evaluating syphilis during their health checkups. The COI values of the initial TPLA test may be helpful in excluding false-positive TPLA test results in the reverse algorithm. © The Korean Society for Laboratory Medicine

Simulated quantum computation of molecular energies.

PubMed

Aspuru-Guzik, Alán; Dutoi, Anthony D; Love, Peter J; Head-Gordon, Martin

2005-09-09

The calculation time for the energy of atoms and molecules scales exponentially with system size on a classical computer but polynomially using quantum algorithms. We demonstrate that such algorithms can be applied to problems of chemical interest using modest numbers of quantum bits. Calculations of the water and lithium hydride molecular ground-state energies have been carried out on a quantum computer simulator using a recursive phase-estimation algorithm. The recursive algorithm reduces the number of quantum bits required for the readout register from about 20 to 4. Mappings of the molecular wave function to the quantum bits are described. An adiabatic method for the preparation of a good approximate ground-state wave function is described and demonstrated for a stretched hydrogen molecule. The number of quantum bits required scales linearly with the number of basis functions, and the number of gates required grows polynomially with the number of quantum bits.

Single-pass incremental force updates for adaptively restrained molecular dynamics.

PubMed

Singh, Krishna Kant; Redon, Stephane

2018-03-30

Adaptively restrained molecular dynamics (ARMD) allows users to perform more integration steps in wall-clock time by switching on and off positional degrees of freedoms. This article presents new, single-pass incremental force updates algorithms to efficiently simulate a system using ARMD. We assessed different algorithms for speedup measurements and implemented them in the LAMMPS MD package. We validated the single-pass incremental force update algorithm on four different benchmarks using diverse pair potentials. The proposed algorithm allows us to perform simulation of a system faster than traditional MD in both NVE and NVT ensembles. Moreover, ARMD using the new single-pass algorithm speeds up the convergence of observables in wall-clock time. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Smartphone-Based Mobile Detection Platform for Molecular Diagnostics and Spatiotemporal Disease Mapping.

PubMed

Song, Jinzhao; Pandian, Vikram; Mauk, Michael G; Bau, Haim H; Cherry, Sara; Tisi, Laurence C; Liu, Changchun

2018-04-03

Rapid and quantitative molecular diagnostics in the field, at home, and at remote clinics is essential for evidence-based disease management, control, and prevention. Conventional molecular diagnostics requires extensive sample preparation, relatively sophisticated instruments, and trained personnel, restricting its use to centralized laboratories. To overcome these limitations, we designed a simple, inexpensive, hand-held, smartphone-based mobile detection platform, dubbed "smart-connected cup" (SCC), for rapid, connected, and quantitative molecular diagnostics. Our platform combines bioluminescent assay in real-time and loop-mediated isothermal amplification (BART-LAMP) technology with smartphone-based detection, eliminating the need for an excitation source and optical filters that are essential in fluorescent-based detection. The incubation heating for the isothermal amplification is provided, electricity-free, with an exothermic chemical reaction, and incubation temperature is regulated with a phase change material. A custom Android App was developed for bioluminescent signal monitoring and analysis, target quantification, data sharing, and spatiotemporal mapping of disease. SCC's utility is demonstrated by quantitative detection of Zika virus (ZIKV) in urine and saliva and HIV in blood within 45 min. We demonstrate SCC's connectivity for disease spatiotemporal mapping with a custom-designed website. Such a smart- and connected-diagnostic system does not require any lab facilities and is suitable for use at home, in the field, in the clinic, and particularly in resource-limited settings in the context of Internet of Medical Things (IoMT).

Molecular Phylogenetic Analysis of Enterobius vermicularis and Development of an 18S Ribosomal DNA-Targeted Diagnostic PCR▿

PubMed Central

Zelck, Ulrike E.; Bialek, Ralf; Weiß, Michael

2011-01-01

We genetically characterized pinworms obtained from 37 children from different regions of Germany and established new species-specific molecular diagnostic tools. No ribosomal DNA diversity was found; the phylogenetic position of Enterobius vermicularis within the Oxyurida order and its close relationship to the Ascaridida and Spirurida orders was confirmed. PMID:21248085

Subatomic turf wars. Molecular imaging holds the promise of personalized medicine, while pitting radiologists against oncologists, others over diagnostic role.

PubMed

Becker, Cinda

2004-11-29

Molecular imaging is expanding radiologists' territory and holds the promise of personalizing treatment. But a turf war is looming over who has the diagnostic role-radiologists, oncologists or others. "We're talking about a whole new way of thinking in terms of diagnosing and treating diseases," David Rollo says.

Emerging Pathogens: Challenges and Successes of Molecular Diagnostics

PubMed Central

Dong, Jianli; Olano, Juan P.; McBride, Jere W.; Walker, David H.

2008-01-01

More than 50 emerging and reemerging pathogens have been identified during the last 40 years. Until 1992 when the Institute of Medicine issued a report that defined emerging infectious diseases, medicine had been complacent about such infectious diseases despite the alarm bells of infections with human immunodeficiency virus. Molecular tools have proven useful in discovering and characterizing emerging viruses and bacteria such as Sin Nombre virus (hantaviral pulmonary syndrome), hepatitis C virus, Bartonella henselae (cat scratch disease, bacillary angiomatosis), and Anaplasma phagocytophilum (human granulocytotropic anaplasmosis). The feasibility of applying molecular diagnostics to dangerous, fastidious, and uncultivated agents for which conventional tests do not yield timely diagnoses has achieved proof of concept for many agents, but widespread use of cost-effective, validated commercial assays has yet to occur. This review presents representative emerging viral respiratory infections, hemorrhagic fevers, and hepatitides, as well as bacterial and parasitic zoonotic, gastrointestinal, and pulmonary infections. Agent characteristics, epidemiology, clinical manifestations, and diagnostic methods are tabulated for another 22 emerging viruses and five emerging bacteria. The ongoing challenge to the field of molecular diagnostics is to apply contemporary knowledge to facilitate agent diagnosis as well as to further discoveries of novel pathogens. PMID:18403608

Kinase Pathway Dependence in Primary Human Leukemias Determined by Rapid Inhibitor Screening

PubMed Central

Tyner, Jeffrey W.; Yang, Wayne F.; Bankhead, Armand; Fan, Guang; Fletcher, Luke B.; Bryant, Jade; Glover, Jason M.; Chang, Bill H.; Spurgeon, Stephen E.; Fleming, William H.; Kovacsovics, Tibor; Gotlib, Jason R.; Oh, Stephen T.; Deininger, Michael W.; Zwaan, C. Michel; Den Boer, Monique L.; van den Heuvel-Eibrink, Marry M.; O’Hare, Thomas; Druker, Brian J.; Loriaux, Marc M.

2012-01-01

Kinases are dysregulated in most cancer but the frequency of specific kinase mutations is low, indicating a complex etiology in kinase dysregulation. Here we report a strategy to rapidly identify functionally important kinase targets, irrespective of the etiology of kinase pathway dysregulation, ultimately enabling a correlation of patient genetic profiles to clinically effective kinase inhibitors. Our methodology assessed the sensitivity of primary leukemia patient samples to a panel of 66 small-molecule kinase inhibitors over 3 days. Screening of 151 leukemia patient samples revealed a wide diversity of drug sensitivities, with 70% of the clinical specimens exhibiting hypersensitivity to one or more drugs. From this data set, we developed an algorithm to predict kinase pathway dependence based on analysis of inhibitor sensitivity patterns. Applying this algorithm correctly identified pathway dependence in proof-of-principle specimens with known oncogenes, including a rare FLT3 mutation outside regions covered by standard molecular diagnostic tests. Interrogation of all 151 patient specimens with this algorithm identified a diversity of gene targets and signaling pathways that could aid prioritization of deep sequencing data sets, permitting a cumulative analysis to understand kinase pathway dependence within leukemia subsets. In a proof-of-principle case, we showed that in vitro drug sensitivity could predict both a clinical response and the development of drug resistance. Taken together, our results suggested that drug target scores derived from a comprehensive kinase inhibitor panel could predict pathway dependence in cancer cells while simultaneously identifying potential therapeutic options. PMID:23087056

PCA-based artifact removal algorithm for stroke detection using UWB radar imaging.

PubMed

Ricci, Elisa; di Domenico, Simone; Cianca, Ernestina; Rossi, Tommaso; Diomedi, Marina

2017-06-01

Stroke patients should be dispatched at the highest level of care available in the shortest time. In this context, a transportable system in specialized ambulances, able to evaluate the presence of an acute brain lesion in a short time interval (i.e., few minutes), could shorten delay of treatment. UWB radar imaging is an emerging diagnostic branch that has great potential for the implementation of a transportable and low-cost device. Transportability, low cost and short response time pose challenges to the signal processing algorithms of the backscattered signals as they should guarantee good performance with a reasonably low number of antennas and low computational complexity, tightly related to the response time of the device. The paper shows that a PCA-based preprocessing algorithm can: (1) achieve good performance already with a computationally simple beamforming algorithm; (2) outperform state-of-the-art preprocessing algorithms; (3) enable a further improvement in the performance (and/or decrease in the number of antennas) by using a multistatic approach with just a modest increase in computational complexity. This is an important result toward the implementation of such a diagnostic device that could play an important role in emergency scenario.

Mental Health Risk Adjustment with Clinical Categories and Machine Learning.

PubMed

Shrestha, Akritee; Bergquist, Savannah; Montz, Ellen; Rose, Sherri

2017-12-15

To propose nonparametric ensemble machine learning for mental health and substance use disorders (MHSUD) spending risk adjustment formulas, including considering Clinical Classification Software (CCS) categories as diagnostic covariates over the commonly used Hierarchical Condition Category (HCC) system. 2012-2013 Truven MarketScan database. We implement 21 algorithms to predict MHSUD spending, as well as a weighted combination of these algorithms called super learning. The algorithm collection included seven unique algorithms that were supplied with three differing sets of MHSUD-related predictors alongside demographic covariates: HCC, CCS, and HCC + CCS diagnostic variables. Performance was evaluated based on cross-validated R 2 and predictive ratios. Results show that super learning had the best performance based on both metrics. The top single algorithm was random forests, which improved on ordinary least squares regression by 10 percent with respect to relative efficiency. CCS categories-based formulas were generally more predictive of MHSUD spending compared to HCC-based formulas. Literature supports the potential benefit of implementing a separate MHSUD spending risk adjustment formula. Our results suggest there is an incentive to explore machine learning for MHSUD-specific risk adjustment, as well as considering CCS categories over HCCs. © Health Research and Educational Trust.

Molecular diagnostics for human leptospirosis.

PubMed

Waggoner, Jesse J; Pinsky, Benjamin A

2016-10-01

The definitive diagnosis of leptospirosis, which results from infection with spirochetes of the genus Leptospira, currently relies on the use of culture, serological testing (microscopic agglutination testing), and molecular detection. The purpose of this review is to describe new molecular diagnostics for Leptospira and discuss advancements in the use of available methods. Efforts have been focused on improving the clinical sensitivity of Leptospira detection using molecular methods. In this review, we describe a reoptimized pathogenic species-specific real-time PCR (targeting lipL32) that has demonstrated improved sensitivity, findings by two groups that real-time reverse-transcription PCR assays targeting the 16S rrs gene can improve detection, and two new loop-mediated amplification techniques. Quantitation of leptospiremia, detection in different specimen types, and the complementary roles played by molecular detection and microscopic agglutination testing will be discussed. Finally, a protocol for Leptospira strain subtyping using variable number tandem repeat targets and high-resolution melting will be described. Molecular diagnostics have an established role for the diagnosis of leptospirosis and provide an actionable diagnosis in the acute setting. The use of real-time reverse-transcription PCR for testing serum/plasma and cerebrospinal fluid, when available, may improve the detection of Leptospira without decreasing clinical specificity.

A Multi-Scale Method for Dynamics Simulation in Continuum Solvent Models I: Finite-Difference Algorithm for Navier-Stokes Equation

PubMed Central

Xiao, Li; Cai, Qin; Li, Zhilin; Zhao, Hongkai; Luo, Ray

2014-01-01

A multi-scale framework is proposed for more realistic molecular dynamics simulations in continuum solvent models by coupling a molecular mechanics treatment of solute with a fluid mechanics treatment of solvent. This article reports our initial efforts to formulate the physical concepts necessary for coupling the two mechanics and develop a 3D numerical algorithm to simulate the solvent fluid via the Navier-Stokes equation. The numerical algorithm was validated with multiple test cases. The validation shows that the algorithm is effective and stable, with observed accuracy consistent with our design. PMID:25404761

Unsupervised Cryo-EM Data Clustering through Adaptively Constrained K-Means Algorithm

PubMed Central

Xu, Yaofang; Wu, Jiayi; Yin, Chang-Cheng; Mao, Youdong

2016-01-01

In single-particle cryo-electron microscopy (cryo-EM), K-means clustering algorithm is widely used in unsupervised 2D classification of projection images of biological macromolecules. 3D ab initio reconstruction requires accurate unsupervised classification in order to separate molecular projections of distinct orientations. Due to background noise in single-particle images and uncertainty of molecular orientations, traditional K-means clustering algorithm may classify images into wrong classes and produce classes with a large variation in membership. Overcoming these limitations requires further development on clustering algorithms for cryo-EM data analysis. We propose a novel unsupervised data clustering method building upon the traditional K-means algorithm. By introducing an adaptive constraint term in the objective function, our algorithm not only avoids a large variation in class sizes but also produces more accurate data clustering. Applications of this approach to both simulated and experimental cryo-EM data demonstrate that our algorithm is a significantly improved alterative to the traditional K-means algorithm in single-particle cryo-EM analysis. PMID:27959895

Unsupervised Cryo-EM Data Clustering through Adaptively Constrained K-Means Algorithm.

PubMed

Xu, Yaofang; Wu, Jiayi; Yin, Chang-Cheng; Mao, Youdong

2016-01-01

In single-particle cryo-electron microscopy (cryo-EM), K-means clustering algorithm is widely used in unsupervised 2D classification of projection images of biological macromolecules. 3D ab initio reconstruction requires accurate unsupervised classification in order to separate molecular projections of distinct orientations. Due to background noise in single-particle images and uncertainty of molecular orientations, traditional K-means clustering algorithm may classify images into wrong classes and produce classes with a large variation in membership. Overcoming these limitations requires further development on clustering algorithms for cryo-EM data analysis. We propose a novel unsupervised data clustering method building upon the traditional K-means algorithm. By introducing an adaptive constraint term in the objective function, our algorithm not only avoids a large variation in class sizes but also produces more accurate data clustering. Applications of this approach to both simulated and experimental cryo-EM data demonstrate that our algorithm is a significantly improved alterative to the traditional K-means algorithm in single-particle cryo-EM analysis.

Accessing primary care Big Data: the development of a software algorithm to explore the rich content of consultation records.

PubMed

MacRae, J; Darlow, B; McBain, L; Jones, O; Stubbe, M; Turner, N; Dowell, A

2015-08-21

To develop a natural language processing software inference algorithm to classify the content of primary care consultations using electronic health record Big Data and subsequently test the algorithm's ability to estimate the prevalence and burden of childhood respiratory illness in primary care. Algorithm development and validation study. To classify consultations, the algorithm is designed to interrogate clinical narrative entered as free text, diagnostic (Read) codes created and medications prescribed on the day of the consultation. Thirty-six consenting primary care practices from a mixed urban and semirural region of New Zealand. Three independent sets of 1200 child consultation records were randomly extracted from a data set of all general practitioner consultations in participating practices between 1 January 2008-31 December 2013 for children under 18 years of age (n=754,242). Each consultation record within these sets was independently classified by two expert clinicians as respiratory or non-respiratory, and subclassified according to respiratory diagnostic categories to create three 'gold standard' sets of classified records. These three gold standard record sets were used to train, test and validate the algorithm. Sensitivity, specificity, positive predictive value and F-measure were calculated to illustrate the algorithm's ability to replicate judgements of expert clinicians within the 1200 record gold standard validation set. The algorithm was able to identify respiratory consultations in the 1200 record validation set with a sensitivity of 0.72 (95% CI 0.67 to 0.78) and a specificity of 0.95 (95% CI 0.93 to 0.98). The positive predictive value of algorithm respiratory classification was 0.93 (95% CI 0.89 to 0.97). The positive predictive value of the algorithm classifying consultations as being related to specific respiratory diagnostic categories ranged from 0.68 (95% CI 0.40 to 1.00; other respiratory conditions) to 0.91 (95% CI 0.79 to 1.00; throat infections). A software inference algorithm that uses primary care Big Data can accurately classify the content of clinical consultations. This algorithm will enable accurate estimation of the prevalence of childhood respiratory illness in primary care and resultant service utilisation. The methodology can also be applied to other areas of clinical care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Molecular diagnostics of ALK-positive lung cancer].

PubMed

Tímár, József; Lotz, Gábor; Rásó, Erzsébet; Moldvay, Judit

2017-09-20

ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH). In case of cytological samples FISH technique must be used as ALK diagnostics. In equivocal cases the genetic alteration of ALK can be confirmed by alternative molecular techniques such as next generation sequencing or RNAbased PCR methods. Upon administration of ALK inhibitors, acquired resistance is frequent which is mostly due to ALK amplification and/or mutation. It is evident that the diagnostics of these secondary ALK gene alterations must be done from recurrent tumors or circulating nucleic acids.

The cobas® 6800/8800 System: a new era of automation in molecular diagnostics.

PubMed

Cobb, Bryan; Simon, Christian O; Stramer, Susan L; Body, Barbara; Mitchell, P Shawn; Reisch, Natasa; Stevens, Wendy; Carmona, Sergio; Katz, Louis; Will, Stephen; Liesenfeld, Oliver

2017-02-01

Molecular diagnostics is a key component of laboratory medicine. Here, the authors review key triggers of ever-increasing automation in nucleic acid amplification testing (NAAT) with a focus on specific automated Polymerase Chain Reaction (PCR) testing and platforms such as the recently launched cobas® 6800 and cobas® 8800 Systems. The benefits of such automation for different stakeholders including patients, clinicians, laboratory personnel, hospital administrators, payers, and manufacturers are described. Areas Covered: The authors describe how molecular diagnostics has achieved total laboratory automation over time, rivaling clinical chemistry to significantly improve testing efficiency. Finally, the authors discuss how advances in automation decrease the development time for new tests enabling clinicians to more readily provide test results. Expert Commentary: The advancements described enable complete diagnostic solutions whereby specific test results can be combined with relevant patient data sets to allow healthcare providers to deliver comprehensive clinical recommendations in multiple fields ranging from infectious disease to outbreak management and blood safety solutions.

[Molecular and immunohistochemical diagnostics in melanoma].

PubMed

Schilling, B; Griewank, K G

2016-07-01

To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.

The development, evaluation and performance of molecular diagnostics for detection of Mycobacterium tuberculosis.

PubMed

Bates, Matthew; Zumla, Alimuddin

2016-01-01

The unique pathogenesis of tuberculosis (TB) poses several barriers to the development of accurate diagnostics: a) the establishment of life-long latency by Mycobacterium tuberculosis (M.tb) after primary infection confounds the development of classical antibody or antigen based assays; b) our poor understanding of the molecular pathways that influence progression from latent to active disease; c) the intracellular nature of M.tb infection in tissues means that M.tb and/or its components, are not readily detectable in peripheral specimens; and d) the variable presence of M.tb bacilli in specimens from patients with extrapulmonary TB or children. The literature on the current portfolio of molecular diagnostics tests for TB is reviewed here and the developmental pipeline is summarized. Also reviewed are data from recently published operational research on the GeneXpert MTB/RIF assay and discussed are the lessons that can be taken forward for the design of studies to evaluate the impact of TB diagnostics.

Using comparative genomics to develop a molecular diagnostic for the identification of an emerging pest Drosophila suzukii.

PubMed

Murphy, K A; Unruh, T R; Zhou, L M; Zalom, F G; Shearer, P W; Beers, E H; Walton, V M; Miller, B; Chiu, J C

2015-06-01

Drosophila suzukii (Spotted Wing Drosophila) has recently become a serious invasive pest of fruit crops in the USA, Canada, and Europe, leading to substantial economic losses. D. suzukii is a direct pest, ovipositing directly into ripe or ripening fruits; in contrast, other Drosophilids utilize decaying or blemished fruits and are nuisance pests at worst. Immature stages of D. suzukii are difficult to differentiate from other Drosophilids, posing problems for research and for meeting quarantine restrictions designed to prevent the spread of this pest in fruit exports. Here we used a combined phylogenetic and bioinformatic approach to discover genetic markers suitable for a species diagnostic protocol of this agricultural pest. We describe a molecular diagnostic for rapid identification of single D. suzukii larva using multiplex polymerase chain reaction. Our molecular diagnostic was validated using nine different species of Drosophila for specificity and 19 populations of D. suzukii from different geographical regions to ensure utility within species.

Development of a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees.

PubMed

Murphy, Michael J; Shahriari, Neda; Payette, Michael; Mnayer, Laila; Elaba, Zendee

2016-10-01

Results of molecular studies are redefining the diagnosis and management of a wide range of skin disorders. Dermatology training programs maintain a relative gap in relevant teaching. To develop a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees at our institution. The aim is to provide trainees with a specialty-appropriate, working knowledge in clinical molecular dermatology. The Departments of Dermatology and Pathology and Laboratory Medicine collaborated on the design and implementation of educational objectives and teaching modalities for the new curriculum. A multidisciplinary curriculum was developed. It comprises: (i) assigned reading from the medical literature and reference textbook; (ii) review of teaching sets; (iii) two 1 hour lectures; (iv) trainee presentations; (v) 1-week rotation in a clinical molecular pathology and cytogenetics laboratory; and (vi) assessments and feedback. Residents who participated in the curriculum to date have found the experience to be of value. Our curriculum provides a framework for other dermatology residency programs to develop their own specific approach to molecular diagnostics education. Such training will provide a foundation for lifelong learning as molecular testing evolves and becomes integral to the practice of dermatology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Solitary thyroid metastasis from colon cancer: fine-needle aspiration cytology and molecular biology approach.

PubMed

Onorati, M; Uboldi, P; Bianchi, C L; Nicola, M; Corradini, G M; Veronese, S; Fascì, A I; Di Nuovo, F

2015-01-01

Thyroid gland is one of the most vascularized organs of the body, nevertheless clinical and surgical series report an incidence of secondary malignancies in this gland of only 3%. Colorectal carcinoma metastatic to the thyroid gland is not as uncommon as previously believed, infact the number of cases seems to be increased in recent years due to the more frequent use of fine-needle aspiration cytology (FNAC) guided by ultrasonography. Although kidney, breast and lung metastases to the thyroid are frequent, metastasis from colon cancer is clinically rare with 52 cases reported in the literature in the last 5 decades and three cases described as solitary thyroid metastasis from the colon cancer without any other visceral metastases. To the best of our knowledge, we report the fourth case of solitary, asymptomatic thyroid metastasis from colon cancer without involvement of other organs. We discuss the importance of FNAC to detect metastatazing process as a compulsory step of the diagnostic and therapeutic management algorithm, combined with a molecular biology approach. A review of the last 5 decades literature, to update the number of cases described to date, is also included.

ArrayVigil: a methodology for statistical comparison of gene signatures using segregated-one-tailed (SOT) Wilcoxon's signed-rank test.

PubMed

Khan, Haseeb Ahmad

2005-01-28

Due to versatile diagnostic and prognostic fidelity molecular signatures or fingerprints are anticipated as the most powerful tools for cancer management in the near future. Notwithstanding the experimental advancements in microarray technology, methods for analyzing either whole arrays or gene signatures have not been firmly established. Recently, an algorithm, ArraySolver has been reported by Khan for two-group comparison of microarray gene expression data using two-tailed Wilcoxon signed-rank test. Most of the molecular signatures are composed of two sets of genes (hybrid signatures) wherein up-regulation of one set and down-regulation of the other set collectively define the purpose of a gene signature. Since the direction of a selected gene's expression (positive or negative) with respect to a particular disease condition is known, application of one-tailed statistics could be a more relevant choice. A novel method, ArrayVigil, is described for comparing hybrid signatures using segregated-one-tailed (SOT) Wilcoxon signed-rank test and the results compared with integrated-two-tailed (ITT) procedures (SPSS and ArraySolver). ArrayVigil resulted in lower P values than those obtained from ITT statistics while comparing real data from four signatures.

The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis

PubMed Central

Chowdhury, R; Ganeshan, B; Irshad, S; Lawler, K; Eisenblätter, M; Milewicz, H; Rodriguez-Justo, M; Miles, K; Ellis, P; Groves, A; Punwani, S

2014-01-01

Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm. PMID:24597512

How recent advances in molecular tests could impact the diagnosis of pneumonia.

PubMed

Murdoch, David R

2016-01-01

Molecular diagnostic tests have been the single major development in pneumonia diagnostics over recent years. Nucleic acid detection tests (NATs) have greatly improved the ability to detect respiratory viruses and bacterial pathogens that do not normally colonize the respiratory tract. In contrast, NATs do not yet have an established role for diagnosing pneumonia caused by bacteria that commonly colonize the nasopharynx due to difficulties discriminating between pathogens and coincidental carriage strains. New approaches are needed to distinguish infection from colonization, such as through use of quantitative methods and identification of discriminating cut-off levels. The recent realization that the lung microbiome exists has provided new insights into the pathogenesis of pneumonia involving the interaction between multiple microorganisms. New developments in molecular diagnostics must account for this new paradigm.

Significance and integration of molecular diagnostics in the framework of veterinary practice.

PubMed

Aranaz, Alicia

2015-01-01

The field of molecular diagnostics in veterinary practice is rapidly evolving. An array of molecular techniques of different complexity is available to facilitate the fast and specific diagnosis of animal diseases. The choice for the adequate technique is dependent on the mission and attributions of the laboratory and requires both a knowledge of the molecular biology basis and of its limitations. The ability to quickly detect pathogens and their characteristics would allow for precise decision-making and target measures such as prophylaxis, appropriate therapy, and biosafety plans to control disease outbreaks. In practice, taking benefit of the huge amount of data that can be obtained using molecular techniques highlights the need of collaboration between veterinarians in the laboratory and practitioners.

Multipole Algorithms for Molecular Dynamics Simulation on High Performance Computers.

NASA Astrophysics Data System (ADS)

Elliott, William Dewey

1995-01-01

A fundamental problem in modeling large molecular systems with molecular dynamics (MD) simulations is the underlying N-body problem of computing the interactions between all pairs of N atoms. The simplest algorithm to compute pair-wise atomic interactions scales in runtime {cal O}(N^2), making it impractical for interesting biomolecular systems, which can contain millions of atoms. Recently, several algorithms have become available that solve the N-body problem by computing the effects of all pair-wise interactions while scaling in runtime less than {cal O}(N^2). One algorithm, which scales {cal O}(N) for a uniform distribution of particles, is called the Greengard-Rokhlin Fast Multipole Algorithm (FMA). This work describes an FMA-like algorithm called the Molecular Dynamics Multipole Algorithm (MDMA). The algorithm contains several features that are new to N-body algorithms. MDMA uses new, efficient series expansion equations to compute general 1/r^{n } potentials to arbitrary accuracy. In particular, the 1/r Coulomb potential and the 1/r^6 portion of the Lennard-Jones potential are implemented. The new equations are based on multivariate Taylor series expansions. In addition, MDMA uses a cell-to-cell interaction region of cells that is closely tied to worst case error bounds. The worst case error bounds for MDMA are derived in this work also. These bounds apply to other multipole algorithms as well. Several implementation enhancements are described which apply to MDMA as well as other N-body algorithms such as FMA and tree codes. The mathematics of the cell -to-cell interactions are converted to the Fourier domain for reduced operation count and faster computation. A relative indexing scheme was devised to locate cells in the interaction region which allows efficient pre-computation of redundant information and prestorage of much of the cell-to-cell interaction. Also, MDMA was integrated into the MD program SIgMA to demonstrate the performance of the program over several simulation timesteps. One MD application described here highlights the utility of including long range contributions to Lennard-Jones potential in constant pressure simulations. Another application shows the time dependence of long range forces in a multiple time step MD simulation.

Introducing minimum Fisher regularisation tomography to AXUV and soft x-ray diagnostic systems of the COMPASS tokamak

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

Mlynar, J.; Weinzettl, V.; Imrisek, M.

2012-10-15

The contribution focuses on plasma tomography via the minimum Fisher regularisation (MFR) algorithm applied on data from the recently commissioned tomographic diagnostics on the COMPASS tokamak. The MFR expertise is based on previous applications at Joint European Torus (JET), as exemplified in a new case study of the plasma position analyses based on JET soft x-ray (SXR) tomographic reconstruction. Subsequent application of the MFR algorithm on COMPASS data from cameras with absolute extreme ultraviolet (AXUV) photodiodes disclosed a peaked radiating region near the limiter. Moreover, its time evolution indicates transient plasma edge cooling following a radial plasma shift. In themore » SXR data, MFR demonstrated that a high resolution plasma positioning independent of the magnetic diagnostics would be possible provided that a proper calibration of the cameras on an x-ray source is undertaken.« less

A wave model of refraction of laser beams with a discrete change in intensity in their cross section and their application for diagnostics of extended nonstationary phase objects

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

Raskovskaya, I L

2015-08-31

A beam model with a discrete change in the cross-sectional intensity is proposed to describe refraction of laser beams formed on the basis of diffractive optical elements. In calculating the wave field of the beams of this class under conditions of strong refraction, in contrast to the traditional asymptotics of geometric optics which assumes a transition to the infinite limits of integration and obtaining an analytical solution, it is proposed to calculate the integral in the vicinity of stationary points. This approach allows the development of a fast algorithm for correct calculation of the wave field of the laser beamsmore » that are employed in probing and diagnostics of extended optically inhomogeneous media. Examples of the algorithm application for diagnostics of extended nonstationary objects in liquid are presented. (laser beams)« less

Analyzing milestoning networks for molecular kinetics: definitions, algorithms, and examples.

PubMed

Viswanath, Shruthi; Kreuzer, Steven M; Cardenas, Alfredo E; Elber, Ron

2013-11-07

Network representations are becoming increasingly popular for analyzing kinetic data from techniques like Milestoning, Markov State Models, and Transition Path Theory. Mapping continuous phase space trajectories into a relatively small number of discrete states helps in visualization of the data and in dissecting complex dynamics to concrete mechanisms. However, not only are molecular networks derived from molecular dynamics simulations growing in number, they are also getting increasingly complex, owing partly to the growth in computer power that allows us to generate longer and better converged trajectories. The increased complexity of the networks makes simple interpretation and qualitative insight of the molecular systems more difficult to achieve. In this paper, we focus on various network representations of kinetic data and algorithms to identify important edges and pathways in these networks. The kinetic data can be local and partial (such as the value of rate coefficients between states) or an exact solution to kinetic equations for the entire system (such as the stationary flux between vertices). In particular, we focus on the Milestoning method that provides fluxes as the main output. We proposed Global Maximum Weight Pathways as a useful tool for analyzing molecular mechanism in Milestoning networks. A closely related definition was made in the context of Transition Path Theory. We consider three algorithms to find Global Maximum Weight Pathways: Recursive Dijkstra's, Edge-Elimination, and Edge-List Bisection. The asymptotic efficiency of the algorithms is analyzed and numerical tests on finite networks show that Edge-List Bisection and Recursive Dijkstra's algorithms are most efficient for sparse and dense networks, respectively. Pathways are illustrated for two examples: helix unfolding and membrane permeation. Finally, we illustrate that networks based on local kinetic information can lead to incorrect interpretation of molecular mechanisms.

ePMV embeds molecular modeling into professional animation software environments.

PubMed

Johnson, Graham T; Autin, Ludovic; Goodsell, David S; Sanner, Michel F; Olson, Arthur J

2011-03-09

Increasingly complex research has made it more difficult to prepare data for publication, education, and outreach. Many scientists must also wade through black-box code to interface computational algorithms from diverse sources to supplement their bench work. To reduce these barriers we have developed an open-source plug-in, embedded Python Molecular Viewer (ePMV), that runs molecular modeling software directly inside of professional 3D animation applications (hosts) to provide simultaneous access to the capabilities of these newly connected systems. Uniting host and scientific algorithms into a single interface allows users from varied backgrounds to assemble professional quality visuals and to perform computational experiments with relative ease. By enabling easy exchange of algorithms, ePMV can facilitate interdisciplinary research, smooth communication between broadly diverse specialties, and provide a common platform to frame and visualize the increasingly detailed intersection(s) of cellular and molecular biology. Copyright © 2011 Elsevier Ltd. All rights reserved.

ePMV Embeds Molecular Modeling into Professional Animation Software Environments

PubMed Central

Johnson, Graham T.; Autin, Ludovic; Goodsell, David S.; Sanner, Michel F.; Olson, Arthur J.

2011-01-01

SUMMARY Increasingly complex research has made it more difficult to prepare data for publication, education, and outreach. Many scientists must also wade through black-box code to interface computational algorithms from diverse sources to supplement their bench work. To reduce these barriers, we have developed an open-source plug-in, embedded Python Molecular Viewer (ePMV), that runs molecular modeling software directly inside of professional 3D animation applications (hosts) to provide simultaneous access to the capabilities of these newly connected systems. Uniting host and scientific algorithms into a single interface allows users from varied backgrounds to assemble professional quality visuals and to perform computational experiments with relative ease. By enabling easy exchange of algorithms, ePMV can facilitate interdisciplinary research, smooth communication between broadly diverse specialties and provide a common platform to frame and visualize the increasingly detailed intersection(s) of cellular and molecular biology. PMID:21397181

Algorithms for the diagnosis and treatment of restless legs syndrome in primary care

PubMed Central

2011-01-01

Background Restless legs syndrome (RLS) is a neurological disorder with a lifetime prevalence of 3-10%. in European studies. However, the diagnosis of RLS in primary care remains low and mistreatment is common. Methods The current article reports on the considerations of RLS diagnosis and management that were made during a European Restless Legs Syndrome Study Group (EURLSSG)-sponsored task force consisting of experts and primary care practioners. The task force sought to develop a better understanding of barriers to diagnosis in primary care practice and overcome these barriers with diagnostic and treatment algorithms. Results The barriers to diagnosis identified by the task force include the presentation of symptoms, the language used to describe them, the actual term "restless legs syndrome" and difficulties in the differential diagnosis of RLS. Conclusion The EURLSSG task force reached a consensus and agreed on the diagnostic and treatment algorithms published here. PMID:21352569

Evidence of clinical utility: an unmet need in molecular diagnostics for patients with cancer.

PubMed

Parkinson, David R; McCormack, Robert T; Keating, Susan M; Gutman, Steven I; Hamilton, Stanley R; Mansfield, Elizabeth A; Piper, Margaret A; Deverka, Patricia; Frueh, Felix W; Jessup, J Milburn; McShane, Lisa M; Tunis, Sean R; Sigman, Caroline C; Kelloff, Gary J

2014-03-15

This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussion is complementary to theoretical frameworks described in previously published guidance and literature reports by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments-certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

Case-Deletion Diagnostics for Nonlinear Structural Equation Models

ERIC Educational Resources Information Center

Lee, Sik-Yum; Lu, Bin

2003-01-01

In this article, a case-deletion procedure is proposed to detect influential observations in a nonlinear structural equation model. The key idea is to develop the diagnostic measures based on the conditional expectation of the complete-data log-likelihood function in the EM algorithm. An one-step pseudo approximation is proposed to reduce the…

Sequential Test Strategies for Multiple Fault Isolation

NASA Technical Reports Server (NTRS)

Shakeri, M.; Pattipati, Krishna R.; Raghavan, V.; Patterson-Hine, Ann; Kell, T.

1997-01-01

In this paper, we consider the problem of constructing near optimal test sequencing algorithms for diagnosing multiple faults in redundant (fault-tolerant) systems. The computational complexity of solving the optimal multiple-fault isolation problem is super-exponential, that is, it is much more difficult than the single-fault isolation problem, which, by itself, is NP-hard. By employing concepts from information theory and Lagrangian relaxation, we present several static and dynamic (on-line or interactive) test sequencing algorithms for the multiple fault isolation problem that provide a trade-off between the degree of suboptimality and computational complexity. Furthermore, we present novel diagnostic strategies that generate a static diagnostic directed graph (digraph), instead of a static diagnostic tree, for multiple fault diagnosis. Using this approach, the storage complexity of the overall diagnostic strategy reduces substantially. Computational results based on real-world systems indicate that the size of a static multiple fault strategy is strictly related to the structure of the system, and that the use of an on-line multiple fault strategy can diagnose faults in systems with as many as 10,000 failure sources.

When the bell tolls on Bell's palsy: finding occult malignancy in acute-onset facial paralysis.

PubMed

Quesnel, Alicia M; Lindsay, Robin W; Hadlock, Tessa A

2010-01-01

This study reports 4 cases of occult parotid malignancy presenting with sudden-onset facial paralysis to demonstrate that failure to regain tone 6 months after onset distinguishes these patients from Bell's palsy patients with delayed recovery and to propose a diagnostic algorithm for this subset of patients. A case series of 4 patients with occult parotid malignancies presenting with acute-onset unilateral facial paralysis is reported. Initial imaging on all 4 patients did not demonstrate a parotid mass. Diagnostic delays ranged from 7 to 36 months from time of onset of facial paralysis to time of diagnosis of parotid malignancy. Additional physical examination findings, especially failure to regain tone, as well as properly protocolled radiologic studies reviewed with dedicated head and neck radiologists, were helpful in arriving at the diagnosis. An algorithm to minimize diagnostic delays in this subset of acute facial paralysis patients is presented. Careful attention to facial tone, in addition to movement, is important in the diagnostic evaluation of acute-onset facial paralysis. Copyright 2010 Elsevier Inc. All rights reserved.

Soft learning vector quantization and clustering algorithms based on ordered weighted aggregation operators.

PubMed

Karayiannis, N B

2000-01-01

This paper presents the development and investigates the properties of ordered weighted learning vector quantization (LVQ) and clustering algorithms. These algorithms are developed by using gradient descent to minimize reformulation functions based on aggregation operators. An axiomatic approach provides conditions for selecting aggregation operators that lead to admissible reformulation functions. Minimization of admissible reformulation functions based on ordered weighted aggregation operators produces a family of soft LVQ and clustering algorithms, which includes fuzzy LVQ and clustering algorithms as special cases. The proposed LVQ and clustering algorithms are used to perform segmentation of magnetic resonance (MR) images of the brain. The diagnostic value of the segmented MR images provides the basis for evaluating a variety of ordered weighted LVQ and clustering algorithms.

Breakpoint structure of the Anopheles gambiae 2Rb chromosomal inversion.

PubMed

Lobo, Neil F; Sangaré, Djibril M; Regier, Allison A; Reidenbach, Kyanne R; Bretz, David A; Sharakhova, Maria V; Emrich, Scott J; Traore, Sekou F; Costantini, Carlo; Besansky, Nora J; Collins, Frank H

2010-10-25

Alternative arrangements of chromosome 2 inversions in Anopheles gambiae are important sources of population structure, and are associated with adaptation to environmental heterogeneity. The forces responsible for their origin and maintenance are incompletely understood. Molecular characterization of inversion breakpoints provides insight into how they arose, and provides the basis for development of molecular karyotyping methods useful in future studies. Sequence comparison of regions near the cytological breakpoints of 2Rb allowed the molecular delineation of breakpoint boundaries. Comparisons were made between the standard 2R+b arrangement in the An. gambiae PEST reference genome and the inverted 2Rb arrangements in the An. gambiae M and S genome assemblies. Sequence differences between alternative 2Rb arrangements were exploited in the design of a PCR diagnostic assay, which was evaluated against the known chromosomal banding pattern of laboratory colonies and field-collected samples from Mali and Cameroon. The breakpoints of the 7.55 Mb 2Rb inversion are flanked by extensive runs of the same short (72 bp) tandemly organized sequence, which was likely responsible for chromosomal breakage and rearrangement. Application of the molecular diagnostic assay suggested that 2Rb has a single common origin in An. gambiae and its sibling species, Anopheles arabiensis, and also that the standard arrangement (2R+b) may have arisen twice through breakpoint reuse. The molecular diagnostic was reliable when applied to laboratory colonies, but its accuracy was lower in natural populations. The complex repetitive sequence flanking the 2Rb breakpoint region may be prone to structural and sequence-level instability. The 2Rb molecular diagnostic has immediate application in studies based on laboratory colonies, but its usefulness in natural populations awaits development of complementary molecular tools.

A novel computer-assisted image analysis of [123I]β-CIT SPECT images improves the diagnostic accuracy of parkinsonian disorders.

PubMed

Goebel, Georg; Seppi, Klaus; Donnemiller, Eveline; Warwitz, Boris; Wenning, Gregor K; Virgolini, Irene; Poewe, Werner; Scherfler, Christoph

2011-04-01

The purpose of this study was to develop an observer-independent algorithm for the correct classification of dopamine transporter SPECT images as Parkinson's disease (PD), multiple system atrophy parkinson variant (MSA-P), progressive supranuclear palsy (PSP) or normal. A total of 60 subjects with clinically probable PD (n = 15), MSA-P (n = 15) and PSP (n = 15), and 15 age-matched healthy volunteers, were studied with the dopamine transporter ligand [(123)I]β-CIT. Parametric images of the specific-to-nondisplaceable equilibrium partition coefficient (BP(ND)) were generated. Following a voxel-wise ANOVA, cut-off values were calculated from the voxel values of the resulting six post-hoc t-test maps. The percentages of the volume of an individual BP(ND) image remaining below and above the cut-off values were determined. The higher percentage of image volume from all six cut-off matrices was used to classify an individual's image. For validation, the algorithm was compared to a conventional region of interest analysis. The predictive diagnostic accuracy of the algorithm in the correct assignment of a [(123)I]β-CIT SPECT image was 83.3% and increased to 93.3% on merging the MSA-P and PSP groups. In contrast the multinomial logistic regression of mean region of interest values of the caudate, putamen and midbrain revealed a diagnostic accuracy of 71.7%. In contrast to a rater-driven approach, this novel method was superior in classifying [(123)I]β-CIT-SPECT images as one of four diagnostic entities. In combination with the investigator-driven visual assessment of SPECT images, this clinical decision support tool would help to improve the diagnostic yield of [(123)I]β-CIT SPECT in patients presenting with parkinsonism at their initial visit.

Endorsing good quality assurance practices in molecular pathology: risks and recommendations for diagnostic laboratories and external quality assessment providers.

PubMed

Tembuyser, Lien; Dequeker, Elisabeth M C

2016-01-01

Quality assurance is an indispensable element in a molecular diagnostic laboratory. The ultimate goal is to warrant patient safety. Several risks that can compromise high quality procedures are at stake, from sample collection to the test performed by the laboratory, the reporting of test results to clinicians, and the organization of effective external quality assessment schemes. Quality assurance should therefore be safeguarded at each level and should imply a holistic multidisciplinary approach. This review aims to provide an overview of good quality assurance practices and discusses certain risks and recommendations to promote and improve quality assurance for both diagnostic laboratories and for external quality assessment providers. The number of molecular targets is continuously rising, and new technologies are evolving. As this poses challenges for clinical implementation and increases the demand for external quality assessment, the formation of an international association for improving quality assurance in molecular pathology is called for.

Computational Algorithmization: Limitations in Problem Solving Skills in Computational Sciences Majors at University of Oriente

ERIC Educational Resources Information Center

Castillo, Antonio S.; Berenguer, Isabel A.; Sánchez, Alexander G.; Álvarez, Tomás R. R.

2017-01-01

This paper analyzes the results of a diagnostic study carried out with second year students of the computational sciences majors at University of Oriente, Cuba, to determine the limitations that they present in computational algorithmization. An exploratory research was developed using quantitative and qualitative methods. The results allowed…

Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

PubMed Central

Abdo, Joe; Bertellotti, Carrie A.; Cornell, David L.; Agrawal, Devendra K.; Mittal, Sumeet K.

2017-01-01

There has been an alarming rise in the incidence of esophageal adenocarcinoma which continues to have poor survival rates primarily due to lack of effective chemotherapy and presentation at advanced stages. Over a dozen chemotherapeutic agents are FDA approved for esophageal cancer (EC), and a two or three-drug combination is typically prescribed as first-line therapy for the majority of EC patients, administered either pre or post-operatively with esophageal resection. We have noticed significant variability in adjuvant and neoadjuvant regimens used in the community setting. The aim of this study was to review the various drug regimens used in the neoadjuvant setting for EC patients with adenocarcinoma undergoing resection at a single tertiary referral center in the Midwest. A total of 123 patients (stage II–III) underwent esophageal resection after neoadjuvant treatment at the center. Overall, 18 distinct drug regimens were used in 123 patients including two patients who received targeted therapy. Median survival post-surgery for this group was 11.2 months with no single regimen offering a survival advantage. These results reveal an unclear algorithm of how accepted regimens are prescribed in the community setting as well as a dire need for agents that are more effective. Additionally, it was noted that although proteomic markers have been found to predict drug response to 92% of the FDA-approved drugs in EC (12 of 13), according to pathology reports, molecular diagnostic testing was not used to direct treatment in this cohort. We therefore propose potential strategies to improve clinical outcomes including the use of a robust molecular oncology diagnostic panel and discuss the potential role for targeted chemotherapy and/or immunotherapy in the management of EC patients. PMID:28770168

An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

PubMed

Eisenberger, Tobias; Decker, Christian; Hiersche, Milan; Hamann, Ruben C; Decker, Eva; Neuber, Steffen; Frank, Valeska; Bolz, Hanno J; Fehrenbach, Henry; Pape, Lars; Toenshoff, Burkhard; Mache, Christoph; Latta, Kay; Bergmann, Carsten

2015-01-01

Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs). Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.

Prevalence and predictors of Lymphogranuloma venereum in a high risk population attending a STD outpatients clinic in Italy.

PubMed

Foschi, Claudio; Marangoni, Antonella; D'Antuono, Antonietta; Nardini, Paola; Compri, Monica; Bellavista, Sara; Filippini, Andrea; Bacchi Reggiani, Maria Letizia; Cevenini, Roberto

2014-04-09

We evaluated LGV prevalence and predictors in a high risk population attending a STI Outpatients Clinic in the North of Italy. A total of 108 patients (99 MSM and 9 women), with a history of unsafe anal sexual intercourses, were enrolled. Anorectal swabs and urine samples were tested for Chlamydia trachomatis (CT) DNA detection by Versant CT/GC DNA 1.0 Assay (Siemens Healthcare Diagnostics Terrytown, USA). RFLP analysis was used for CT molecular typing. L2 CT genotype was identified in 13/108 (12%) rectal swabs. All LGV cases were from MSM, declaring high-risk sexual behaviour and complaining anorectal symptoms. Patients first attending the STI Outpatient Clinic received a significant earlier LGV diagnosis than those first seeking care from general practitioners or gastroenterologists (P = 0.0046). LGV prevalence and characteristics found in our population are in agreement with international reports. Statistical analysis showed that LGV positive patients were older (P = 0.0008) and presented more STIs (P = 0.0023) than LGV negative ones, in particular due to syphilis (P < 0.001), HIV (P < 0.001) and HBV (P = 0.001).Multivariate logistic regression analysis revealed that HIV and syphilis infections are strong risk factors for LGV presence (respectively, P = 0.001 and P = 0.010). Even if our results do not provide sufficient evidence to recommend routine screening of anorectal swabs in high-risk population, they strongly suggest to perform CT NAAT tests and genotyping on rectal specimens in presence of ulcerative proctitis in HIV and/or syphilis-positive MSM. In this context, CT DNA detection by Versant CT/GC DNA 1.0 Assay, followed by RFLP analysis for molecular typing demonstrated to be an excellent diagnostic algorithm for LGV identification.

Diagnostic Accuracy of the Veteran Affairs' Traumatic Brain Injury Screen.

PubMed

Louise Bender Pape, Theresa; Smith, Bridget; Babcock-Parziale, Judith; Evans, Charlesnika T; Herrold, Amy A; Phipps Maieritsch, Kelly; High, Walter M

2018-01-31

To comprehensively estimate the diagnostic accuracy and reliability of the Department of Veterans Affairs (VA) Traumatic Brain Injury (TBI) Clinical Reminder Screen (TCRS). Cross-sectional, prospective, observational study using the Standards for Reporting of Diagnostic Accuracy criteria. Three VA Polytrauma Network Sites. Operation Iraqi Freedom, Operation Enduring Freedom veterans (N=433). TCRS, Comprehensive TBI Evaluation, Structured TBI Diagnostic Interview, Symptom Attribution and Classification Algorithm, and Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale. Forty-five percent of veterans screened positive on the TCRS for TBI. For detecting occurrence of historical TBI, the TCRS had a sensitivity of .56 to .74, a specificity of .63 to .93, a positive predictive value (PPV) of 25% to 45%, a negative predictive value (NPV) of 91% to 94%, and a diagnostic odds ratio (DOR) of 4 to 13. For accuracy of attributing active symptoms to the TBI, the TCRS had a sensitivity of .64 to .87, a specificity of .59 to .89, a PPV of 26% to 32%, an NPV of 92% to 95%, and a DOR of 6 to 9. The sensitivity was higher for veterans with PTSD (.80-.86) relative to veterans without PTSD (.57-.82). The specificity, however, was higher among veterans without PTSD (.75-.81) relative to veterans with PTSD (.36-.49). All indices of diagnostic accuracy changed when participants with questionably valid (QV) test profiles were eliminated from analyses. The utility of the TCRS to screen for mild TBI (mTBI) depends on the stringency of the diagnostic reference standard to which it is being compared, the presence/absence of PTSD, and QV test profiles. Further development, validation, and use of reproducible diagnostic algorithms for symptom attribution after possible mTBI would improve diagnostic accuracy. Published by Elsevier Inc.

Towards a Standard Psychometric Diagnostic Interview for Subjects at Ultra High Risk of Psychosis: CAARMS versus SIPS

PubMed Central

Fusar-Poli, P.; Cappucciati, M.; Rutigliano, G.; Lee, T. Y.; Beverly, Q.; Bonoldi, I.; Lelli, J.; Kaar, S. J.; Gago, E.; Rocchetti, M.; Patel, R.; Bhavsar, V.; Tognin, S.; Badger, S.; Calem, M.; Lim, K.; Kwon, J. S.; Perez, J.; McGuire, P.

2016-01-01

Background. Several psychometric instruments are available for the diagnostic interview of subjects at ultra high risk (UHR) of psychosis. Their diagnostic comparability is unknown. Methods. All referrals to the OASIS (London) or CAMEO (Cambridgeshire) UHR services from May 13 to Dec 14 were interviewed for a UHR state using both the CAARMS 12/2006 and the SIPS 5.0. Percent overall agreement, kappa, the McNemar-Bowker χ 2 test, equipercentile methods, and residual analyses were used to investigate diagnostic outcomes and symptoms severity or frequency. A conversion algorithm (CONVERT) was validated in an independent UHR sample from the Seoul Youth Clinic (Seoul). Results. There was overall substantial CAARMS-versus-SIPS agreement in the identification of UHR subjects (n = 212, percent overall agreement = 86%; kappa = 0.781, 95% CI from 0.684 to 0.878; McNemar-Bowker test = 0.069), with the exception of the brief limited intermittent psychotic symptoms (BLIPS) subgroup. Equipercentile-linking table linked symptoms severity and frequency across the CAARMS and SIPS. The conversion algorithm was validated in 93 UHR subjects, showing excellent diagnostic accuracy (CAARMS to SIPS: ROC area 0.929; SIPS to CAARMS: ROC area 0.903). Conclusions. This study provides initial comparability data between CAARMS and SIPS and will inform ongoing multicentre studies and clinical guidelines for the UHR psychometric diagnostic interview. PMID:27314005

[Cost-effectiveness of the deep vein thrombosis diagnosis process in primary care].

PubMed

Fuentes Camps, Eva; Luis del Val García, José; Bellmunt Montoya, Sergi; Hmimina Hmimina, Sara; Gómez Jabalera, Efren; Muñoz Pérez, Miguel Ángel

2016-04-01

To analyse the cost effectiveness of the application of diagnostic algorithms in patients with a first episode of suspected deep vein thrombosis (DVT) in Primary Care compared with systematic referral to specialised centres. Observational, cross-sectional, analytical study. Patients from hospital emergency rooms referred from Primary Care to complete clinical evaluation and diagnosis. A total of 138 patients with symptoms of a first episode of DVT were recruited; 22 were excluded (no Primary Care report, symptoms for more than 30 days, anticoagulant treatment, and previous DVT). Of the 116 patients finally included, 61% women and the mean age was 71 years. Variables from the Wells and Oudega clinical probability scales, D-dimer (portable and hospital), Doppler ultrasound, and direct costs generated by the three algorithms analysed: all patients were referred systematically, referral according to Wells and Oudega scale. DVT was confirmed in 18.9%. The two clinical probability scales showed a sensitivity of 100% (95% CI: 85.1 to 100) and a specificity of about 40%. With the application of the scales, one third of all referrals to hospital emergency rooms could have been avoided (P<.001). The diagnostic cost could have been reduced by € 8,620 according to Oudega and € 9,741 according to Wells, per 100 patients visited. The application of diagnostic algorithms when a DVT is suspected could lead to better diagnostic management by physicians, and a more cost effective process. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Accuracy of administrative data for surveillance of healthcare-associated infections: a systematic review

PubMed Central

van Mourik, Maaike S M; van Duijn, Pleun Joppe; Moons, Karel G M; Bonten, Marc J M; Lee, Grace M

2015-01-01

Objective Measuring the incidence of healthcare-associated infections (HAI) is of increasing importance in current healthcare delivery systems. Administrative data algorithms, including (combinations of) diagnosis codes, are commonly used to determine the occurrence of HAI, either to support within-hospital surveillance programmes or as free-standing quality indicators. We conducted a systematic review evaluating the diagnostic accuracy of administrative data for the detection of HAI. Methods Systematic search of Medline, Embase, CINAHL and Cochrane for relevant studies (1995–2013). Methodological quality assessment was performed using QUADAS-2 criteria; diagnostic accuracy estimates were stratified by HAI type and key study characteristics. Results 57 studies were included, the majority aiming to detect surgical site or bloodstream infections. Study designs were very diverse regarding the specification of their administrative data algorithm (code selections, follow-up) and definitions of HAI presence. One-third of studies had important methodological limitations including differential or incomplete HAI ascertainment or lack of blinding of assessors. Observed sensitivity and positive predictive values of administrative data algorithms for HAI detection were very heterogeneous and generally modest at best, both for within-hospital algorithms and for formal quality indicators; accuracy was particularly poor for the identification of device-associated HAI such as central line associated bloodstream infections. The large heterogeneity in study designs across the included studies precluded formal calculation of summary diagnostic accuracy estimates in most instances. Conclusions Administrative data had limited and highly variable accuracy for the detection of HAI, and their judicious use for internal surveillance efforts and external quality assessment is recommended. If hospitals and policymakers choose to rely on administrative data for HAI surveillance, continued improvements to existing algorithms and their robust validation are imperative. PMID:26316651

The diagnosis of urinary tract infections in young children (DUTY): protocol for a diagnostic and prospective observational study to derive and validate a clinical algorithm for the diagnosis of UTI in children presenting to primary care with an acute illness.

PubMed

Downing, Harriet; Thomas-Jones, Emma; Gal, Micaela; Waldron, Cherry-Ann; Sterne, Jonathan; Hollingworth, William; Hood, Kerenza; Delaney, Brendan; Little, Paul; Howe, Robin; Wootton, Mandy; Macgowan, Alastair; Butler, Christopher C; Hay, Alastair D

2012-07-19

Urinary tract infection (UTI) is common in children, and may cause serious illness and recurrent symptoms. However, obtaining a urine sample from young children in primary care is challenging and not feasible for large numbers. Evidence regarding the predictive value of symptoms, signs and urinalysis for UTI in young children is urgently needed to help primary care clinicians better identify children who should be investigated for UTI. This paper describes the protocol for the Diagnosis of Urinary Tract infection in Young children (DUTY) study. The overall study aim is to derive and validate a cost-effective clinical algorithm for the diagnosis of UTI in children presenting to primary care acutely unwell. DUTY is a multicentre, diagnostic and prospective observational study aiming to recruit at least 7,000 children aged before their fifth birthday, being assessed in primary care for any acute, non-traumatic, illness of ≤ 28 days duration. Urine samples will be obtained from eligible consented children, and data collected on medical history and presenting symptoms and signs. Urine samples will be dipstick tested in general practice and sent for microbiological analysis. All children with culture positive urines and a random sample of children with urine culture results in other, non-positive categories will be followed up to record symptom duration and healthcare resource use. A diagnostic algorithm will be constructed and validated and an economic evaluation conducted.The primary outcome will be a validated diagnostic algorithm using a reference standard of a pure/predominant growth of at least >103, but usually >105 CFU/mL of one, but no more than two uropathogens.We will use logistic regression to identify the clinical predictors (i.e. demographic, medical history, presenting signs and symptoms and urine dipstick analysis results) most strongly associated with a positive urine culture result. We will then use economic evaluation to compare the cost effectiveness of the candidate prediction rules. This study will provide novel, clinically important information on the diagnostic features of childhood UTI and the cost effectiveness of a validated prediction rule, to help primary care clinicians improve the efficiency of their diagnostic strategy for UTI in young children.

The diagnosis of urinary tract infections in young children (DUTY): protocol for a diagnostic and prospective observational study to derive and validate a clinical algorithm for the diagnosis of UTI in children presenting to primary care with an acute illness

PubMed Central

2012-01-01

Background Urinary tract infection (UTI) is common in children, and may cause serious illness and recurrent symptoms. However, obtaining a urine sample from young children in primary care is challenging and not feasible for large numbers. Evidence regarding the predictive value of symptoms, signs and urinalysis for UTI in young children is urgently needed to help primary care clinicians better identify children who should be investigated for UTI. This paper describes the protocol for the Diagnosis of Urinary Tract infection in Young children (DUTY) study. The overall study aim is to derive and validate a cost-effective clinical algorithm for the diagnosis of UTI in children presenting to primary care acutely unwell. Methods/design DUTY is a multicentre, diagnostic and prospective observational study aiming to recruit at least 7,000 children aged before their fifth birthday, being assessed in primary care for any acute, non-traumatic, illness of ≤ 28 days duration. Urine samples will be obtained from eligible consented children, and data collected on medical history and presenting symptoms and signs. Urine samples will be dipstick tested in general practice and sent for microbiological analysis. All children with culture positive urines and a random sample of children with urine culture results in other, non-positive categories will be followed up to record symptom duration and healthcare resource use. A diagnostic algorithm will be constructed and validated and an economic evaluation conducted. The primary outcome will be a validated diagnostic algorithm using a reference standard of a pure/predominant growth of at least >103, but usually >105 CFU/mL of one, but no more than two uropathogens. We will use logistic regression to identify the clinical predictors (i.e. demographic, medical history, presenting signs and symptoms and urine dipstick analysis results) most strongly associated with a positive urine culture result. We will then use economic evaluation to compare the cost effectiveness of the candidate prediction rules. Discussion This study will provide novel, clinically important information on the diagnostic features of childhood UTI and the cost effectiveness of a validated prediction rule, to help primary care clinicians improve the efficiency of their diagnostic strategy for UTI in young children. PMID:22812651

Computer-aided diagnosis workstation and teleradiology network system for chest diagnosis using the web medical image conference system with a new information security solution

NASA Astrophysics Data System (ADS)

Satoh, Hitoshi; Niki, Noboru; Eguchi, Kenji; Ohmatsu, Hironobu; Kaneko, Masahiro; Kakinuma, Ryutaro; Moriyama, Noriyuki

2010-03-01

Diagnostic MDCT imaging requires a considerable number of images to be read. Moreover, the doctor who diagnoses a medical image is insufficient in Japan. Because of such a background, 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. We also have developed the teleradiology network system by using web medical image conference system. In the teleradiology network system, the security of information network is very important subjects. Our teleradiology network system can perform Web medical image conference in the medical institutions of a remote place using the web medical image conference system. We completed the basic proof experiment of the web medical image conference system with information security solution. 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 the workstation that builds in some diagnostic assistance methods. Biometric face authentication used on site of teleradiology makes "Encryption of file" and "Success in login" effective. Our Privacy and information security technology of information security solution ensures compliance with Japanese regulations. 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 teleradiology 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 teleradiology network system can increase diagnostic speed, diagnostic accuracy and security improvement of medical information.

[Managment of acute low back pain without trauma - an algorithm].

PubMed

Melcher, Carolin; Wegener, Bernd; Jansson, Volkmar; Mutschler, Wolf; Kanz, Karl-Georg; Birkenmaier, Christof

2018-05-14

Low back pain is a common problem for primary care providers, outpatient clinics and A&E departments. The predominant symptoms are those of so-called "unspecific back pain", but serious pathologies can be concealed by the clinical signs. Especially less experienced colleagues have problems in treating these patients, as - despite the multitude of recommendations and guidelines - there is no generally accepted algorithm. After a literature search (Medline/Cochrane), 158 articles were selected from 15,000 papers and classified according to their level of evidence. These were attuned to the clinical guidelines of the orthopaedic and pain-physician associations in Europe, North America and overseas and the experience of specialists at LMU Munich, in order to achieve consistency with literature recommendations, as well as feasibility in everyday clinical work and optimised with practical relevance. An algorithm was formed to provide the crucial differential diagnosis of lumbar back pain according to its clinical relevance and to provide a plan of action offering reasonable diagnostic and therapeutic steps. As a consequence of distinct binary decisions, low back patients should be treated at any given time according to the guidelines, with emergencies detected, unnecessary diagnostic testing and interventions averted and reasonable treatment initiated pursuant to the underlying pathology. In the context of the available evidence, a clinical algorithm has been developed that translates the complex diagnostic testing of acute low back pain into a transparent, structured and systematic guideline. Georg Thieme Verlag KG Stuttgart · New York.

A diagnostic algorithm to optimize data collection and interpretation of Ripple Maps in atrial tachycardias.

PubMed

Koa-Wing, Michael; Nakagawa, Hiroshi; Luther, Vishal; Jamil-Copley, Shahnaz; Linton, Nick; Sandler, Belinda; Qureshi, Norman; Peters, Nicholas S; Davies, D Wyn; Francis, Darrel P; Jackman, Warren; Kanagaratnam, Prapa

2015-11-15

Ripple Mapping (RM) is designed to overcome the limitations of existing isochronal 3D mapping systems by representing the intracardiac electrogram as a dynamic bar on a surface bipolar voltage map that changes in height according to the electrogram voltage-time relationship, relative to a fiduciary point. We tested the hypothesis that standard approaches to atrial tachycardia CARTO™ activation maps were inadequate for RM creation and interpretation. From the results, we aimed to develop an algorithm to optimize RMs for future prospective testing on a clinical RM platform. CARTO-XP™ activation maps from atrial tachycardia ablations were reviewed by two blinded assessors on an off-line RM workstation. Ripple Maps were graded according to a diagnostic confidence scale (Grade I - high confidence with clear pattern of activation through to Grade IV - non-diagnostic). The RM-based diagnoses were corroborated against the clinical diagnoses. 43 RMs from 14 patients were classified as Grade I (5 [11.5%]); Grade II (17 [39.5%]); Grade III (9 [21%]) and Grade IV (12 [28%]). Causes of low gradings/errors included the following: insufficient chamber point density; window-of-interest<100% of cycle length (CL); <95% tachycardia CL mapped; variability of CL and/or unstable fiducial reference marker; and suboptimal bar height and scar settings. A data collection and map interpretation algorithm has been developed to optimize Ripple Maps in atrial tachycardias. This algorithm requires prospective testing on a real-time clinical platform. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Identification of mycobacteria to the species level by molecular methods in the Public Health Laboratory of Bogotá, Colombia].

PubMed

Hernández-Toloza, Johana Esther; Rincón-Serrano, María de Pilar; Celis-Bustos, Yamile Adriana; Aguillón, Claudia Inés

2016-01-01

Global epidemiology of non-tuberculous mycobacteria (NTM) is unknown due to the fact that notification is not required in many countries, however the number of infection reports and outbreaks caused by NTM suggest a significant increase in the last years. Traditionally, mycobacteria identification is made through biochemical profiles which allow to differentiate M. tuberculosis from NTM, and in some cases the mycobacteria species. Nevertheless, these methods are technically cumbersome and time consuming. On the other hand, the introduction of methods based on molecular biology has improved the laboratory diagnosis of NTM. To establish the NTM frequency in positive cultures for acid-fast bacilli (AAFB) which were sent to Laboratorio de Salud Pública de Bogotá over a 12 month period. A total of 100 positive cultures for acid-fast bacilli from public and private hospitals from Bogotá were identified by both biochemical methods and the molecular methods PRA (PCR-restriction enzyme analysis) and multiplex-PCR. Furthermore, low prevalence mycobacteria species and non-interpretable results were confirmed by 16SrDNA sequentiation analysis. Identification using the PRA method showed NMT occurrence in 11% of cultures. In addition, this molecular methodology allowed to detect the occurrence of more than one mycobacteria in 4% of the cultures. Interestingly, a new M. kubicae pattern of PCR-restriction analysis is reported in our study. Using a mycobacteria identification algorithm, which includes the molecular method PRA, improves the diagnostic power of conventional methods and could help to advance both NTM epidemiology knowledge and mycobacteriosis control. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays

PubMed Central

Sozhamannan, Shanmuga; Holland, Mitchell Y.; Hall, Adrienne T.; Negrón, Daniel A.; Ivancich, Mychal; Koehler, Jeffrey W.; Minogue, Timothy D.; Campbell, Catherine E.; Berger, Walter J.; Christopher, George W.; Goodwin, Bruce G.; Smith, Michael A.

2015-01-01

Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

Evaluation of Machine Learning and Rules-Based Approaches for Predicting Antimicrobial Resistance Profiles in Gram-negative Bacilli from Whole Genome Sequence Data.

PubMed

Pesesky, Mitchell W; Hussain, Tahir; Wallace, Meghan; Patel, Sanket; Andleeb, Saadia; Burnham, Carey-Ann D; Dantas, Gautam

2016-01-01

The time-to-result for culture-based microorganism recovery and phenotypic antimicrobial susceptibility testing necessitates initial use of empiric (frequently broad-spectrum) antimicrobial therapy. If the empiric therapy is not optimal, this can lead to adverse patient outcomes and contribute to increasing antibiotic resistance in pathogens. New, more rapid technologies are emerging to meet this need. Many of these are based on identifying resistance genes, rather than directly assaying resistance phenotypes, and thus require interpretation to translate the genotype into treatment recommendations. These interpretations, like other parts of clinical diagnostic workflows, are likely to be increasingly automated in the future. We set out to evaluate the two major approaches that could be amenable to automation pipelines: rules-based methods and machine learning methods. The rules-based algorithm makes predictions based upon current, curated knowledge of Enterobacteriaceae resistance genes. The machine-learning algorithm predicts resistance and susceptibility based on a model built from a training set of variably resistant isolates. As our test set, we used whole genome sequence data from 78 clinical Enterobacteriaceae isolates, previously identified to represent a variety of phenotypes, from fully-susceptible to pan-resistant strains for the antibiotics tested. We tested three antibiotic resistance determinant databases for their utility in identifying the complete resistome for each isolate. The predictions of the rules-based and machine learning algorithms for these isolates were compared to results of phenotype-based diagnostics. The rules based and machine-learning predictions achieved agreement with standard-of-care phenotypic diagnostics of 89.0 and 90.3%, respectively, across twelve antibiotic agents from six major antibiotic classes. Several sources of disagreement between the algorithms were identified. Novel variants of known resistance factors and incomplete genome assembly confounded the rules-based algorithm, resulting in predictions based on gene family, rather than on knowledge of the specific variant found. Low-frequency resistance caused errors in the machine-learning algorithm because those genes were not seen or seen infrequently in the test set. We also identified an example of variability in the phenotype-based results that led to disagreement with both genotype-based methods. Genotype-based antimicrobial susceptibility testing shows great promise as a diagnostic tool, and we outline specific research goals to further refine this methodology.

Target prioritization and strategy selection for active case-finding of pulmonary tuberculosis: a tool to support country-level project planning.

PubMed

Nishikiori, Nobuyuki; Van Weezenbeek, Catharina

2013-02-02

Despite the progress made in the past decade, tuberculosis (TB) control still faces significant challenges. In many countries with declining TB incidence, the disease tends to concentrate in vulnerable populations that often have limited access to health care. In light of the limitations of the current case-finding approach and the global urgency to improve case detection, active case-finding (ACF) has been suggested as an important complementary strategy to accelerate tuberculosis control especially among high-risk populations. The present exercise aims to develop a model that can be used for county-level project planning. A simple deterministic model was developed to calculate the number of estimated TB cases diagnosed and the associated costs of diagnosis. The model was designed to compare cost-effectiveness parameters, such as the cost per case detected, for different diagnostic algorithms when they are applied to different risk populations. The model was transformed into a web-based tool that can support national TB programmes and civil society partners in designing ACF activities. According to the model output, tuberculosis active case-finding can be a costly endeavor, depending on the target population and the diagnostic strategy. The analysis suggests the following: (1) Active case-finding activities are cost-effective only if the tuberculosis prevalence among the target population is high. (2) Extensive diagnostic methods (e.g. X-ray screening for the entire group, use of sputum culture or molecular diagnostics) can be applied only to very high-risk groups such as TB contacts, prisoners or people living with human immunodeficiency virus (HIV) infection. (3) Basic diagnostic approaches such as TB symptom screening are always applicable although the diagnostic yield is very limited. The cost-effectiveness parameter was sensitive to local diagnostic costs and the tuberculosis prevalence of target populations. The prioritization of appropriate target populations and careful selection of cost-effective diagnostic strategies are critical prerequisites for rational active case-finding activities. A decision to conduct such activities should be based on the setting-specific cost-effectiveness analysis and programmatic assessment. A web-based tool was developed and is available to support national tuberculosis programmes and partners in the formulation of cost-effective active case-finding activities at the national and subnational levels.

Concepts and applications of "natural computing" techniques in de novo drug and peptide design.

PubMed

Hiss, Jan A; Hartenfeller, Markus; Schneider, Gisbert

2010-05-01

Evolutionary algorithms, particle swarm optimization, and ant colony optimization have emerged as robust optimization methods for molecular modeling and peptide design. Such algorithms mimic combinatorial molecule assembly by using molecular fragments as building-blocks for compound construction, and relying on adaptation and emergence of desired pharmacological properties in a population of virtual molecules. Nature-inspired algorithms might be particularly suited for bioisosteric replacement or scaffold-hopping from complex natural products to synthetically more easily accessible compounds that are amenable to optimization by medicinal chemistry. The theory and applications of selected nature-inspired algorithms for drug design are reviewed, together with practical applications and a discussion of their advantages and limitations.

Promise and pitfalls of molecular markers of thyroid nodules

PubMed Central

Jadhav, S.; Lila, Anurag; Bandgar, Tushar; Shah, Nalini

2012-01-01

Thyroid nodules are common in the general population with a prevalence of 5-7% The initial evaluation of thyroid nodules commonly involves thyroid function tests, an ultrasound (USG) and fine needle aspiration biopsy (FNAB). The optimal management of patients with thyroid nodules with indeterminate cytology is plagued by the lack of highly sensitive and specific diagnostic modalities In this article we attempt to review the available literature on the molecular markers which are increasingly being studied for their diagnostic utility in assessing thyroid nodules. The various molecular markers consist of gene mutations, gene re arrangements, RNA based assays and immunohistochemical markers. The molecular markers definitely would help to optimise the management of such patients. PMID:23565369

Nucleic Acid-Based Approaches for Detection of Viral Hepatitis

PubMed Central

Behzadi, Payam; Ranjbar, Reza; Alavian, Seyed Moayed

2014-01-01

Context: To determining suitable nucleic acid diagnostics for individual viral hepatitis agent, an extensive search using related keywords was done in major medical library and data were collected, categorized, and summarized in different sections. Results: Various types of molecular biology tools can be used to detect and quantify viral genomic elements and analyze the sequences. These molecular assays are proper technologies for rapidly detecting viral agents with high accuracy, high sensitivity, and high specificity. Nonetheless, the application of each diagnostic method is completely dependent on viral agent. Conclusions: Despite rapidity, automation, accuracy, cost-effectiveness, high sensitivity, and high specificity of molecular techniques, each type of molecular technology has its own advantages and disadvantages. PMID:25789132

Diagnosis and prediction of periodontally compromised teeth using a deep learning-based convolutional neural network algorithm.

PubMed

Lee, Jae-Hong; Kim, Do-Hyung; Jeong, Seong-Nyum; Choi, Seong-Ho

2018-04-01

The aim of the current study was to develop a computer-assisted detection system based on a deep convolutional neural network (CNN) algorithm and to evaluate the potential usefulness and accuracy of this system for the diagnosis and prediction of periodontally compromised teeth (PCT). Combining pretrained deep CNN architecture and a self-trained network, periapical radiographic images were used to determine the optimal CNN algorithm and weights. The diagnostic and predictive accuracy, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve, area under the ROC curve, confusion matrix, and 95% confidence intervals (CIs) were calculated using our deep CNN algorithm, based on a Keras framework in Python. The periapical radiographic dataset was split into training (n=1,044), validation (n=348), and test (n=348) datasets. With the deep learning algorithm, the diagnostic accuracy for PCT was 81.0% for premolars and 76.7% for molars. Using 64 premolars and 64 molars that were clinically diagnosed as severe PCT, the accuracy of predicting extraction was 82.8% (95% CI, 70.1%-91.2%) for premolars and 73.4% (95% CI, 59.9%-84.0%) for molars. We demonstrated that the deep CNN algorithm was useful for assessing the diagnosis and predictability of PCT. Therefore, with further optimization of the PCT dataset and improvements in the algorithm, a computer-aided detection system can be expected to become an effective and efficient method of diagnosing and predicting PCT.

An algorithm based on OmniView technology to reconstruct sagittal and coronal planes of the fetal brain from volume datasets acquired by three-dimensional ultrasound.

PubMed

Rizzo, G; Capponi, A; Pietrolucci, M E; Capece, A; Aiello, E; Mammarella, S; Arduini, D

2011-08-01

To describe a novel algorithm, based on the new display technology 'OmniView', developed to visualize diagnostic sagittal and coronal planes of the fetal brain from volumes obtained by three-dimensional (3D) ultrasonography. We developed an algorithm to image standard neurosonographic planes by drawing dissecting lines through the axial transventricular view of 3D volume datasets acquired transabdominally. The algorithm was tested on 106 normal fetuses at 18-24 weeks of gestation and the visualization rates of brain diagnostic planes were evaluated by two independent reviewers. The algorithm was also applied to nine cases with proven brain defects. The two reviewers, using the algorithm on normal fetuses, found satisfactory images with visualization rates ranging between 71.7% and 96.2% for sagittal planes and between 76.4% and 90.6% for coronal planes. The agreement rate between the two reviewers, as expressed by Cohen's kappa coefficient, was > 0.93 for sagittal planes and > 0.89 for coronal planes. All nine abnormal volumes were identified by a single observer from among a series including normal brains, and eight of these nine cases were diagnosed correctly. This novel algorithm can be used to visualize standard sagittal and coronal planes in the fetal brain. This approach may simplify the examination of the fetal brain and reduce dependency of success on operator skill. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Biomedical analysis of formalin-fixed, paraffin-embedded tissue samples: The Holy Grail for molecular diagnostics.

PubMed

Donczo, Boglarka; Guttman, Andras

2018-06-05

More than a century ago in 1893, a revolutionary idea about fixing biological tissue specimens was introduced by Ferdinand Blum, a German physician. Since then, a plethora of fixation methods have been investigated and used. Formalin fixation with paraffin embedment became the most widely used types of fixation and preservation method, due to its proper architectural conservation of tissue structures and cellular shape. The huge collection of formalin-fixed, paraffin-embedded (FFPE) sample archives worldwide holds a large amount of unearthed information about diseases that could be the Holy Grail in contemporary biomarker research utilizing analytical omics based molecular diagnostics. The aim of this review is to critically evaluate the omics options for FFPE tissue sample analysis in the molecular diagnostics field. Copyright © 2018. Published by Elsevier B.V.

Diagnostic algorithm for detection of targetable driver mutations in lung adenocarcinomas: Comprehensive analyses of 205 cases with immunohistochemistry, real-time PCR and fluorescence in situ hybridization methods.

PubMed

Kao, Hua-Lin; Yeh, Yi-Chen; Lin, Chin-Hsuan; Hsu, Wei-Fang; Hsieh, Wen-Yu; Ho, Hsiang-Ling; Chou, Teh-Ying

2016-11-01

Analysis of the targetable driver mutations is now recommended in all patients with advanced lung adenocarcinoma. Molecular-based methods are usually adopted, however, along with the implementation of highly sensitive and/or mutation-specific antibodies, immunohistochemistry (IHC) has been considered an alternative method for identifying driver mutations in lung adenocarcinomas. A total of 205 lung adenocarcinomas were examined for EGFR mutations and ALK and ROS1 rearrangements using real-time PCR, fluorescence in situ hybridization (FISH) and IHC in parallel. The performance of different commercially available IHC antibody clones toward targetable driver mutations was evaluated. The association between these driver mutations and clinicopathological characteristics was also analyzed. In 205 cases we studied, 58.5% were found to harbor EGFR mutations, 6.3% ALK rearrangements and 1.0% ROS1 rearrangements. Compared to molecular-based methods, IHC of EGFR mutations showed an excellent specificity but the sensitivity is suboptimal, while IHC of ALK and ROS1 rearrangements demonstrated high sensitivity and specificity. No significant difference regarding the performance of different antibody clones toward these driver mutations was observed, except that clone SP125 showed a higher sensitivity than 43B2 in the detection of p.L858R of EGFR. In circumstances such as poor quality of nucleic acids or low content of tumor cells, IHC of EGFR mutation-specific antibodies could be used as an alternative method. Patients negative for EGFR mutations are subjected to further analysis on ALK and ROS1 rearrangements using IHC methods. Herein, we proposed a lung adenocarcinoma testing algorithm for the application of IHC in therapeutic diagnosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

PubMed Central

Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M. Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

2015-01-01

Background Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Methodology/Principal Findings Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). Conclusion The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study. PMID:26161864