Current Developments in Diagnostic Assays for Laboratory Confirmation and Investigation of Botulism

2021 ◽  
Author(s):  
Dominick A. Centurioni ◽  
Christina T. Egan ◽  
Michael J. Perry
Keyword(s):  
Gold Standard ◽  
Botulinum Neurotoxin ◽  
Mouse Bioassay ◽  
Environmental Matrices ◽  
Animal Testing ◽  
Gold Standard Method ◽  
Diagnostic Assays ◽  
Technical Performance ◽  
Laboratory Confirmation ◽  
Testing Algorithms

Detection of botulinum neurotoxin or isolation of the toxin producing organism is required for the laboratory confirmation of botulism in clinical specimens. In an effort to reduce animal testing required by the gold standard method of botulinum neurotoxin detection, the mouse bioassay, many technologies have been developed to detect and characterize the causative agent of botulism. Recent advancements in these technologies have led to improvements in technical performance of diagnostic assays; however, many emerging assays have not been validated for the detection of all serotypes in complex clinical and environmental matrices. Improvements to culture protocols, endopeptidase-based assays, and a variety of immunological and molecular methods have provided laboratories with a variety of testing options to evaluate and incorporate into their testing algorithms. While significant advances have been made to improve these assays, additional work is necessary to evaluate these methods in various clinical matrices and to establish standardized criteria for data analysis and interpretation.

An International Multi-Center Study To Define the Application of Microarray-Based Gene Expression Profiling in the Diagnosis and Sub-Classification of Leukemia (MILE Study): Analysis of Completed Stage I with 2030 Patients Achieved a 95.4% Accuracy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3169-3169
Author(s):  
Torsten Haferlach ◽  
Alexander Kohlmann ◽  
Giuseppe Basso ◽  
Marie-Christine Bene ◽  
James R. Downing ◽  
...  
Keyword(s):  
Gold Standard ◽  
Signal To Noise Ratio ◽  
Quality Criteria ◽  
Normal Karyotype ◽  
Stage I ◽  
Technical Failure ◽  
Complex Karyotype ◽  
Diagnostic Assays ◽  
Technical Performance ◽  
Multi Center Study

Abstract In 2005, the MILE (Microarray Innovations in LEukemia) study research program was initiated with 11 centers: 7 from the European Leukemia Network (ELN, WP13), 3 from the US, and 1 in Singapore. The first stage was designed to assess the ability of GEP to classify leukemias into 17 recognized categories as compared to conventional diagnostic assays (“Gold Standards”). These include: mature B-ALL with t(8;14), pro-B-ALL with t(11q23)/MLL, c-ALL/pre-B-ALL with t(9;22), T-ALL, ALL with t(12;21), ALL with t(1;19), ALL with hyperdiploid karyotype, c-ALL/pre-B-ALL without specific genetic abnormalities, i.e. t(9;22), AML with t(8;21), AML with t(15;17), AML with inv(16)/t(16;16), AML with t(11q23)/MLL, AML with normal karyotype, AML with complex karyotype, CML, CLL, and MDS, as well as non-leukemic and healthy bone marrow samples as controls. We now report the data from the completed MILE Stage I, which included 2030 adult and pediatric samples utilizing HG U133 Plus 2.0 (Affymetrix). 102 (5%) were removed from the study for protocol violations, most often for an incomplete “Gold Standard”. All microarrays were also assessed for their technical performance (e.g. micorarray scaling factor, signal to noise ratio, etc.). In total only 36 samples (1.9%) failed these technical quality criteria. Cross validation accuracy (average of three 30-fold cross validations) of the remaining 1892 MILE Stage I samples is 95.4% concordant with the “Gold Standard” diagnosis. In ten classes the concordance was ≥97% i.e. for pro-B-ALL with t(11q23)/MLL, T-ALL, AML with t(8;21), AML with inv(16)/t(16;16), AML with normal karyotype, CLL, CML and MDS, as well as for the healthy or non-leukemia samples. The following classes showed lower sensitivities (range 74%-91%): mature B-ALL with t(8;14), c-ALL/pre-B-ALL with t(9;22), ALL with t(1;19), ALL with hyperdiploid karyotype, c-ALL/pre-B-ALL without specific abnormalities, AML with t(11q23)/MLL, and AML with complex karyotype. This can largely be explained by biological heterogeneity and weak “gold standard” definitions. It is notable that all these classes showed specificities above 98.4%. The second stage now prospectively process additional 1000 samples on a custom designed microarray using 1,449 probe sets only. So far 755 samples have been analyzed and will represent an independent and blinded test set for the algorithms developed in stage I. In conclusion, the MILE research study confirms that standardized microarray-based GEP may accurately classify leukemia samples into known diagnostic and prognostic sub-categories with a low technical failure rate and a very high accuracy.

scholarly journals Quantum chemical benchmark databases of gold-standard dimer interaction energies

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Alexander G. Donchev ◽  
Andrew G. Taube ◽  
Elizabeth Decolvenaere ◽  
Cory Hargus ◽  
Robert T. McGibbon ◽  
...  
Keyword(s):  
Machine Learning ◽  
Gold Standard ◽  
Training Data ◽  
Structure Theory ◽  
Cluster Method ◽  
Coupled Cluster ◽  
Interaction Energies ◽  
Gold Standard Method ◽  
Representative Subset ◽  
Semi Empirical

AbstractAdvances in computational chemistry create an ongoing need for larger and higher-quality datasets that characterize noncovalent molecular interactions. We present three benchmark collections of quantum mechanical data, covering approximately 3,700 distinct types of interacting molecule pairs. The first collection, which we refer to as DES370K, contains interaction energies for more than 370,000 dimer geometries. These were computed using the coupled-cluster method with single, double, and perturbative triple excitations [CCSD(T)], which is widely regarded as the gold-standard method in electronic structure theory. Our second benchmark collection, a core representative subset of DES370K called DES15K, is intended for more computationally demanding applications of the data. Finally, DES5M, our third collection, comprises interaction energies for nearly 5,000,000 dimer geometries; these were calculated using SNS-MP2, a machine learning approach that provides results with accuracy comparable to that of our coupled-cluster training data. These datasets may prove useful in the development of density functionals, empirically corrected wavefunction-based approaches, semi-empirical methods, force fields, and models trained using machine learning methods.

scholarly journals Evaluation of four different HPLC devices for hemoglobinopathy screening

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Müjgan Ercan Karadağ ◽  
Emiş Deniz Akbulut ◽  
Esin Avcı ◽  
Esra Fırat Oğuz ◽  
Saadet Kader ◽  
...  
Keyword(s):  
Gold Standard ◽  
High Performance ◽  
Public Health Problem ◽  
Reference Value ◽  
Comparison Study ◽  
Gold Standard Method ◽  
Blood Samples ◽  
Systematic Biases ◽  
Hemoglobin Variants ◽  
Thalassemia Screening

AbstractObjectiveHemoglobinopathies are a common public health problem in Turkey. In the screening of these disorders in population, cation-exchange high performance liquid chromatography (HPLC) is accepted as the gold standard method. In this study, the aim was to assess four different HPLC devices used in hemoglobinopathy screening.Materials and methodsA total of 58 blood samples were analyzed with four different HPLC methods (Bio-Rad variant II, Agilent 1100, Tosoh G8 and Trinity Ultra2 trademarks).ResultsThe comparison study demonstrated a good correlation between the results of each HPLC analyzer and the reference value obtained by averaging all the HbA2 results belonging to the methods tested in the study [ (Tosoh G8 (r=0.988), Bio-Rad variant II (r=0.993), Agilent 1100 (r=0.98) and Trinity Ultra2 (r=0.992) ]. HbA2 determination in the presence of HbE was interfered in both Bio-Rad variant II and Tosoh G8.ConclusionThe analyzers were found to have compatible HbA2 results but with accompanying different degrees of proportional and systematic biases. HPLC analyzers may be affected by different hemoglobin variants at different HbA2 concentrations, which is an important point to take into consideration during the evaluation of HbA2 results in thalassemia screening.

scholarly journals Rapid Diagnosis of Malaria by Antigen Detection

2009 ◽  
Vol 3 (1) ◽  
pp. 14-16
Author(s):  
Mesbah Uddin Ahmed ◽  
Md Akram Hossain ◽  
AKM Shamsuzzaman ◽  
Md Murshed Alam ◽  
Abdul Hossain Khan ◽  
...  
Keyword(s):  
Thin Films ◽  
Sensitivity And Specificity ◽  
Standard Method ◽  
Gold Standard ◽  
Rapid Diagnosis ◽  
Healthy Controls ◽  
Immunochromatographic Test ◽  
Gold Standard Method ◽  
Malaria Antigen ◽  
Age And Sex

The study was conducted to evaluate the sensitivity and specificity of Immunochromatographic test (ICT) for antigen, using microscopy as the "gold standard" method for diagnosis of malaria. A total of 98 clinically suspected malaria patients and another 30 age and sex-matched healthy controls were included in this study. Thick and thin films were also prepared and examined under microscope as well as Immunochromatographic test (ICT) was performed for malaria antigen. Sensitivity and specificity of ICT for antigen were 93.22% and 94.87% respectively. Keywords: Detection of malaria antigen, Immunochromatographic test   doi: 10.3329/bjmm.v3i1.2965 Bangladesh J Med Microbiol 2009; 03 (01): 14-16

scholarly journals Use of Circulating Tumour DNA (ctDNA) for Measurement of Therapy Predictive Biomarkers in Patients with Cancer

2022 ◽  
Vol 12 (1) ◽  
pp. 99
Author(s):  
Michael J. Duffy ◽  
John Crown
Keyword(s):  
Gold Standard ◽  
Kinase Inhibitors ◽  
Predictive Biomarkers ◽  
Lower Sensitivity ◽  
Cancer Therapies ◽  
Gold Standard Method ◽  
Biomarker Analysis ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Biomarker Testing ◽  
Circulating Tumour Dna

Biomarkers that predict likely response or resistance to specific therapies are critical in personalising treatment for cancer patients. Such biomarkers are now available for an increasing number of anti-cancer therapies, especially targeted therapy and immunotherapy. The gold-standard method for determining predictive biomarkers requires tumour tissue. Obtaining tissue, however, is not always possible and even if possible, the amount or quality of tissue obtained may be inadequate for biomarker analysis. Tumour DNA, however, can be released into the bloodstream, giving rise to what is referred to as circulating tumour DNA (ctDNA). In contrast to tissue, blood can be obtained from effectively all patients in a minimally invasive and safe manner. Other advantages of blood over tissue for biomarker testing include a shorter turn-around time and an ability to perform serial measurements. Furthermore, blood should provide a more complete profile of mutations present in heterogeneous tumours than a single-needle tissue biopsy. A limitation of blood vis-à-vis tissue, however, is lower sensitivity and, thus, the possibility of missing an actionable mutation. Despite this limitation, blood-based predictive biomarkers, such as mutant EGFR for predicting response to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer and mutant PIK3CA for predicting response to alpelisib in combination with fulvestrant in advanced breast cancer, may be used when tissue is unavailable. Although tissue remains the gold standard for detecting predictive biomarkers, it is likely that several further blood-based assays will soon be validated and used when tissue is unavailable or unsuitable for analysis.

scholarly journals Evaluation of distilled water as buffered water replacement during 3% Giemsa’s solution preparation in Malaria diagnosis

2019 ◽  
Vol 10 (SPL1) ◽  
Author(s):  
Lai Yan Xia ◽  
Hamidah Abu Bakar
Keyword(s):  
Standard Method ◽  
Gold Standard ◽  
Malaria Diagnosis ◽  
Cost Effective ◽  
Peripheral Blood Smear ◽  
Blood Film ◽  
Distilled Water ◽  
Malaria Parasites ◽  
Gold Standard Method ◽  
Modified Method

Malaria is a life-threatening disease which has claimed many lives. Giemsa's stain is the gold standard method in malaria diagnosis. Generally, Giemsa's stain is diluted with buffered water. However, sometimes, it produces poor staining of the blood smears, in which can create a major challenge in detecting and identifying positive malaria parasites in a peripheral blood smear. This can lead to misdiagnosis and mistreatment to a patient. The present study examined the effect of replacing the buffered water to distilled water during the preparation of 3% Giemsa's solution. Blood specimens were collected from selected positive (n=80) and negative (n=300) malaria cases in EDTA tube. The modified method employed distilled water and different concentrations of buffered water for diluting Giemsa’s solution stock. The microscopy observation was performed on each set of blood film stained by both modified and standard Giemsa staining methods by two WHO’s qualified technicians. All Giemsa solutions with different diluents were comparable in detecting malaria parasites in the blood films. There was no difference between distilled water and different concentrations of buffered water. Furthermore, distilled water produced homogeneous staining and clearer background of the blood films, which enables different species of malaria to be identified. The present study demonstrates that the modified staining using distilled water in malaria parasites identification is comparable to the gold standard method. In addition, the modified method is rapid, easily available, cost-effective, and reliable.

scholarly journals The Functional Polymorphism of DDAH2 rs9267551 Is an Independent Determinant of Arterial Stiffness

2022 ◽  
Vol 8 ◽  
Author(s):  
Carolina Averta ◽  
Elettra Mancuso ◽  
Rosangela Spiga ◽  
Sofia Miceli ◽  
Elena Succurro ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Gold Standard ◽  
Asymmetric Dimethylarginine ◽  
Pulse Wave ◽  
European Ancestry ◽  
Causative Role ◽  
Gold Standard Method ◽  
Multivariable Regression Model ◽  
Multivariable Regression ◽  
Independent Determinant

Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA.Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P < 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P < 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels.Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.

349 LAPAROSCOPIC MANAGEMENT OF ACHALASIA CARDIA IN CHILDREN

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
K Haravu Ramprasad ◽  
P Agarwal
Keyword(s):  
Gold Standard ◽  
Treatment Modality ◽  
The Body ◽  
Barium Swallow ◽  
Pneumatic Dilation ◽  
Complication Rates ◽  
Gold Standard Method ◽  
Efficient Treatment ◽  
Achalasia Cardia ◽  
Primary Treatment Modality

Abstract   Achalasia Cardia is a rare motility disorder of esophagus and is characterized by increased pressure of Lower Esophageal Sphincter (LES) and reduced motility of the body. This results in functional obstruction and failure of relaxation of LES. This condition is relatively rare in young children (about 0.11/100,000 children) Methods A retrospective study was done on 16 Paediatric patients with Achalasia Cardia over a 9 year period from 2010–2018. All patients underwent Barium Swallow and also upper GI endoscopy. Among the 16 patients, 8 of the patients underwent CT scanning and 6 patients had undergone manometry which is the gold standard method for diagnosis. Laparoscopic Heller’s Cardiomyotomy is the primary treatment modality for Achalasia Cardia. All patients underwent Cardiomyotomy along with Anterior Dor Fundoplication. Of the 16 patients, 6 had undergone Pneumatic Dilation previously. Results Of the 16 patients, 14 underwent Laparoscopic Heller’s Cardiomyotomy and 2 had open surgery. There were no intraoperative or postoperative complications. Normal feeds were started after 24 hours and the feeds were well tolerated. All the patients had complete resolution of dysphagia with score reducing from 4 to 0. All of them were discharged within 2–3 days. Conclusion Laparoscopic Heller’s Cardiomyotomy is the gold standard treatment for treating Achalasia Cardia. It is a safe, successful and efficient treatment modality for children with Achalasia Cardia due to shorter hospital stay, lower complication rates due to increased level of expertise and immediate and long lasting symptomatic relief.

scholarly journals Role of Laparoscopy in Management of Ectopic Pregnancy

2015 ◽  
Vol 5 (3) ◽  
pp. 170-174
Author(s):  
Hasina Banu ◽  
Ju Wen Hui ◽  
Liu Hua
Keyword(s):  
Ectopic Pregnancy ◽  
Gold Standard ◽  
Literature Search ◽  
Operating Time ◽  
Review Article ◽  
Laparoscopic Treatment ◽  
Gold Standard Method ◽  
Delay In Diagnosis ◽  
Future Fertility

Ectopic pregnancy means implantation of fertilized ovum outside the endometrial lining of the uterus. It remains the leading cause of early pregnancy-related death. Delay in diagnosis and treatment puts the life of women at risk. Laparoscopic surgery is increasingly becoming the preferred approach for ectopic pregnancy management. Laparoscopic treatment in ectopic pregnancy raises question of safety and feasibility when compared to laparotomy. In this review article our objective is to summarize the role of laparoscopy in management of ectopic pregnancy in comparison to laparotomy. For this, a literature search was done by using Google and PubMed. The selected articles were analyzed on laparoscopic treatment outcomes such as surgery success rate, operating time, intraoperative and postoperative complications, hospital stay, future fertility, postoperative recurrent ectopic pregnancy, cost-effectiveness in comparison to laparotomy. After analyzing all selected articles, it can be concluded that the laparoscopic management of ectopic pregnancy is safe, effective, and economical in comparision to laparotomy. So, for the patients’ benefit, laparoscopy should be considered as the gold standard method in management of ectopic pregnancy and is worthy to be popularized in clinical practice.J Enam Med Col 2015; 5(3): 170-174

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