Diagnostic Utility of the ImmunoCyt/uCyt+ Test in Bladder Cancer

Bladder cancer is a common malignancy in the United States. Although urine cytology is a useful adjunct in both diagnosis and follow-up and is highly sensitive for detecting high-grade tumors, it is limited by decreased sensitivity in detecting low-grade tumors, which constitute the majority of new diagnoses. Additional screening tests with high sensitivity and specificity for urothelial tumors of all grades are indicated to help improve the diagnostic ability of urine cytology as well as to reduce the need for frequent cystoscopies, especially in those with low-risk disease. Several assays have been developed, with the ImmunoCyt/uCyt+ test (DiagnoCure, Inc., Québec, Canada) being especially promising. Recent studies on the applicability and efficacy of ImmunoCyt/uCyt+ testing are reviewed, as are its sensitivity, specificity, and predictive value in the follow-up and screening of urothelial malignancies.     

Testing the Utility of a Data-Driven Approach for Assessing BMI from Face Images

Several lines of evidence suggest that facial cues of adiposity may be important for human social interaction. However, tests for quantifiable cues of body mass index (BMI) in the face have examined only a small number of facial proportions and these proportions were found to have relatively low predictive power. Here we employed a data-driven approach in which statistical models were built using principal components (PCs) derived from objectively defined shape and color characteristics in face images. The predictive power of these models was then compared with models based on previously studied facial proportions (perimeter-to-area ratio, width-to-height ratio, and cheek-to-jaw width). Models based on 2D shape-only PCs, color-only PCs, and 2D shape and color PCs combined each performed significantly and substantially better than models based on one or more of the previously studied facial proportions. A non-linear PC model considering both 2D shape and color PCs was the best predictor of BMI. These results highlight the utility of a “bottom-up”, data-driven approach for assessing BMI from face images.     

Clinical Utility of the Cryptococcal Antigen Lateral Flow Assay in a Diagnostic Mycology Laboratory

Background

Cryptococcus neoformans causes life-threatening meningitis. A recently introduced lateral flow immunoassay (LFA) to detect cryptococcal antigen (CRAG) is reportedly more rapid and convenient than standard latex agglutination (LA), but has not yet been evaluated in a diagnostic laboratory setting.

Methods

One hundred and six serum, 42 cerebrospinal fluid (CSF), and 20 urine samples from 92 patients with known or suspected cryptococcosis were tested by LA and LFA, and titres were compared. Results were correlated with laboratory-confirmed cryptococcosis. Serial samples were tested in nine treated patients.

Results

Twenty-five of 92 patients had confirmed cryptococcosis; all sera (n = 56) from these patients were positive by LFA (sensitivity 100%, 95% confidence interval (CI) 93.6–100%) compared with 51/56 positive by LA (sensitivity 91.1%, 95% CI 80.7–96.1%). Fifty sera from 67 patients without cryptococcosis tested negative in both assays. While LA yielded more false negative results (5/56) this did not reach statistical significance (p = 0.063). Nine CSF samples from patients with cryptococcal meningitis yielded positive results using both assays while 17/18 urine samples from patients with cryptococcosis were positive by the LFA. The LFA detected CRAG in C. gattii infection (n = 4 patients). Agreement between titres obtained by both methods (n = 38 samples) was imperfect; correlation between log-transformed titres (r) was 0.84. Turn-around-time was 20 minutes for the LFA and 2 h for LA. The cost per qualitative sample was 18USD and 91 USD, respectively and per quantitative sample was 38USD and 144USD, respectively.

Conclusions

Qualitative agreement between the LFA and LA assays performed on serum and CSF was good but agreement between titres was imperfect. Ease of performance of the LFA and the capacity for testing urine suggest it has a role in the routine laboratory as a rapid diagnostic test or point-of-care test.     

Recent Advances in the Development of a Diagnostic Test for Irradiated Foodstuffs

Recent advances in the development and application of diagnostic tests for irradiated foodstuffs are reviewed. Exposure of water, the major chemical constituent of most foodstuffs to a source of ionising radiation initially generates the highly reactive radical species H', -OH and e^- (aq) which react very rapidly with a wide variety of biological molecules. The detection of foodstuffs subjected to irradiation processing requires the identification and/or quantification of ‘unnatural’ chemical species (i.e. those not usually formed by normal metabolic processes) produced by the attack of ·OH radical or e^-(aq) on suitable ‘target’ molecules. Modern methods for the analysis of a series of these ‘unnatural’ products arising from the interaction of radiolytically-generated ·OH radical or e^-(aq) with polyunsaturated fatty acids, DNA, aromatic compounds and other biologically important scavenger molecules are examined. It is concluded that the analytical test to be conducted is highly dependent on the nature of the foodstuff to be tested.     

Recent Advances in the Development of a Diagnostic Test for Irradiated Foodstuffs

Recent advances in the development and application of diagnostic tests for irradiated foodstuffs are reviewed. Exposure of water, the major chemical constituent of most foodstuffs to a source of ionising radiation initially generates the highly reactive radical species H', -OH and e^- (aq) which react very rapidly with a wide variety of biological molecules. The detection of foodstuffs subjected to irradiation processing requires the identification and/or quantification of 'unnatural' chemical species (i.e. those not usually formed by normal metabolic processes) produced by the attack of ·OH radical or e^-(aq) on suitable 'target' molecules. Modern methods for the analysis of a series of these 'unnatural' products arising from the interaction of radiolytically-generated ·OH radical or e^-(aq) with polyunsaturated fatty acids, DNA, aromatic compounds and other biologically important scavenger molecules are examined. It is concluded that the analytical test to be conducted is highly dependent on the nature of the foodstuff to be tested.     

Community Phylogenetics: Assessing Tree Reconstruction Methods and the Utility of DNA Barcodes

Studies examining phylogenetic community structure have become increasingly prevalent, yet little attention has been given to the influence of the input phylogeny on metrics that describe phylogenetic patterns of co-occurrence. Here, we examine the influence of branch length, tree reconstruction method, and amount of sequence data on measures of phylogenetic community structure, as well as the phylogenetic signal (Pagel’s λ) in morphological traits, using Trichoptera larval communities from Churchill, Manitoba, Canada. We find that model-based tree reconstruction methods and the use of a backbone family-level phylogeny improve estimations of phylogenetic community structure. In addition, trees built using the barcode region of cytochrome c oxidase subunit I (COI) alone accurately predict metrics of phylogenetic community structure obtained from a multi-gene phylogeny. Input tree did not alter overall conclusions drawn for phylogenetic signal, as significant phylogenetic structure was detected in two body size traits across input trees. As the discipline of community phylogenetics continues to expand, it is important to investigate the best approaches to accurately estimate patterns. Our results suggest that emerging large datasets of DNA barcode sequences provide a vast resource for studying the structure of biological communities.     

Diagnostic Utility of DNA from Aspergillus in Whole Blood Specimens

For several years, PCR-based detection of Aspergillus DNA has been considered a promising tool for the diagnosis of invasive aspergillosis, but its broader implementation has been hampered by a lack of standardization and the uncertain diagnostic accuracy of the wide variety of published protocols. Recently, new attempts have been made to address this problem and define a quality standard for diagnostic Aspergillus PCR. This review summarizes technical aspects of up-to-date protocols, focusing on the recently proposed guidelines of the European Aspergillus PCR Initiative (EAPCRI) for whole blood PCR testing.     

Diagnostic Utility of Neutrophil CD64 as a Marker for Early-Onset Sepsis in Preterm Neonates

Introduction

Neutrophil CD64 has been proposed as an early marker of sepsis. This study aims to evaluate the diagnostic utility of neutrophil CD64 for identification of early-onset sepsis in preterm neonates.

Methods

The prospective study was conducted in a neonatal intensive care unit between November 2010 and June 2011. Preterm neonates in whom infection was suspected when they were <12 hours of age were enrolled. Complete blood count with differential, blood culture, neutrophil CD11b and CD64 measurement were performed. Receiver operating characteristic curve analysis was performed to evaluate the performance of neutrophil CD64 as biomarker of sepsis.

Results

A total of 158 preterm neonates was enrolled, 88 of whom were suspected infection. The suspected sepsis group was of lesser gestational age (P<0.001) and lower birth weight (P<0.001), compared with controls. The hematologic profiles of the suspected sepsis group were characterized by higher white blood cell count, neutrophil counts and C-reactive protein. The suspected sepsis neonates had significantly higher neutrophil CD64 expression compared with controls. Neutrophil CD64 had an area value under the curve of 0.869 with an optimal cutoff values of 1010 phycoerythrin molecules bound/cell and it had a high sensitivity (81.82%) and negative predictive value (77.4%). The level of neutrophil CD64 was independent of antibiotic therapy within 24 hours after the onset of sepsis in preterm neonates.

Conclusions

Neutrophil CD64 is a highly sensitive marker for suspected early-onset sepsis in preterm neonates. Our study suggests that neutrophil CD64 may be incorporated as a valuable marker to diagnose infection.     

Evaluation of a Rapid Diagnostic Test for Yaws Infection in a Community Surveillance Setting

Yaws is a non-venereal treponemal infection caused by Treponema pallidum ssp. pertenue. The WHO has launched a worldwide control programme, which aims to eradicate yaws by 2020. The development of a rapid diagnostic test (RDT) for serological diagnosis in the isolated communities affected by yaws is a key requirement for the successful implementation of the WHO strategy. We conducted a study to evaluate the utility of the DPP test in screening for yaws, utilizing samples collected as part of a community prevalence survey conducted in the Solomon Islands. 415 serum samples were tested using both traditional syphilis serology (TPPA and quantitative RPR) and the Chembio DPP Syphilis Screen and Confirm RDT. We calculated the sensitivity and specificity of the RDT as compared to gold standard serology. The sensitivity of the RDT against TPPA was 58.5% and the specificity was 97.6%. The sensitivity of the RDT against RPR was 41.7% and the specificity was 95.2%. The sensitivity of the DPP was strongly related to the RPR titre with a sensitivity of 92.0% for an RPR titre of >1/16. Wider access to DPP testing would improve our understanding of worldwide yaws case reporting and the test may play a key role in assessing patients presenting with yaws like lesions in a post-mass drug administration (MDA) setting.     

Rapid and Biosecure Diagnostic Test for Tuberculosis

Early and rapid detection of the causative organism is necessary in tuberculosis. We present here an integrated and dedicated molecular biology system for tuberculosis diagnosis. One hundred and eighty-nine (189) biologic specimens from patients strongly suspected by clinical parameters of tuberculosis were studied by Ziehl–Neelsen staining, cultivation on a solid medium, and by a balanced heminested fluorometric PCR system (Orange G3TB) that preserves worker safety and produces a rather pure material free of potential inhibitors. DNA amplification was carried out in a low cost using a tuberculosis thermocycler-fluorometer. The double stranded DNA produced is fluorometrically detected. The whole reaction is carried out in one single tube which is never opened after adding the processed sample, thus minimizing the risk of cross contamination with amplicons. The assay is able to detect 30 bacilli/ml of sample having a 99.8 % inter-assay coefficient of variation. PCR was positive in 36 (18.9 %) tested samples (33 of them were smear-negative). In our study, it yields a preliminary overall sensitivity of 97.4 %. In addition, its overall specificity is 98.7 %. The total run time of the test is 4 h with two and a half real working hours. All PCR-positive samples also had a positive result by microbiological culture and clinical criteria. The results obtained showed that it could be a very useful tool to increase efficiency in detecting the tuberculosis disease in low bacillus inoculum samples. Furthermore, its low cost and friendly usage make it feasible to be used in regions with poor development.     

Standard Test Set and a Computer-generated Diagnostic Register for Gram negative Fermentative Rods

A simple two-step method for the identification of Gram negative fermentative rods is based on interpretation of test results by means of a computer-generated diagnostic register. The first step is based on 10 tests, the second on six. Of 1451 strains routinely isolated in clinical laboratories 84% were identified in the first step. If the second step was included, the efficacy of the system rose to 99.17%. Disagreements with the conventional method in the first step are discussed.     

Sensitivity and Specificity of a New Vertical Flow Rapid Diagnostic Test for the Serodiagnosis of Human Leptospirosis

Background: Leptospirosis is a growing public health concern in many tropical and subtropical countries. However, its diagnosis is difficult because of non-specific symptoms and concurrent other endemic febrile diseases. In many regions, the laboratory diagnosis is not available due to a lack of preparedness and simple diagnostic assay or difficult access to reference laboratories. Yet, an early antibiotic treatment is decisive to the outcome. The need for Rapid Diagnostic Tests (RDTs) for bedside diagnosis of leptospirosis has been recognized. We developed a vertical flow immunochromatography strip RDT detecting anti-Leptospira human IgM and evaluated it in patients from New Caledonia, France, and French West Indies. Methodology/Principal Findings: Whole killed Leptospira fainei cells were used as antigen for the test line and purified human IgM as the control line. The mobile phase was made of gold particles conjugated with goat anti-human IgM. Standards for Reporting of Diagnostic Accuracy criteria were used to assess the performance of this RDT. The Microscopic Agglutination Test (MAT) was used as the gold standard with a cut-off titer of ≥400. The sensitivity was 89.8% and the specificity 93.7%. Positive and negative Likelihood Ratios of 14.18 and 0.108 respectively, and a Diagnostic Odds Ratio of 130.737 confirmed its usefulness. This RDT had satisfactory reproducibility, repeatability, thermal tolerance and shelf-life. The comparison with MAT evidenced the earliness of the RDT to detect seroconversion. When compared with other RDT, the Vertical Flow RDT developed displayed good diagnostic performances.

Conclusions/Significance

This RDT might be used as a point of care diagnostic tool in limited resources countries. An evaluation in field conditions and in other epidemiological contexts should be considered to assess its validity over a wider range of serogroups or when facing different endemic pathogens. It might prove useful in endemic contexts or outbreak situations.     

Tourniquet Test for Dengue Diagnosis: Systematic Review and Meta-analysis of Diagnostic Test Accuracy

BackgroundDengue fever is a ubiquitous arboviral infection in tropical and sub-tropical regions, whose incidence has increased over recent decades. In the absence of a rapid point of care test, the clinical diagnosis of dengue is complex. The World Health Organisation has outlined diagnostic criteria for making the diagnosis of dengue infection, which includes the use of the tourniquet test (TT).PurposeTo assess the quality of the evidence supporting the use of the TT and perform a diagnostic accuracy meta-analysis comparing the TT to antibody response measured by ELISA.ConclusionThe tourniquet test is widely used in resource poor settings despite currently available evidence demonstrating only a marginal benefit in making a diagnosis of dengue infection alone.RegistrationThe protocol for this systematic review was registered at PROSPERO: CRD42015020323.     

S100A1 as a Potential Diagnostic Biomarker for Assessing Cardiotoxicity and Implications for the Chemotherapy of Certain Cancers

This study examined the value of blood marker S100A1 in detecting cardiotoxicity induced by chemotherapy agents; trastuzumab and lapatinib, in normal rat heart. The rats were divided into three groups: control (n = 8, no treatment), T (n = 8, one time ip treatment with 10 mg/kg trastuzumab) and L (n = 8, oral treatment with 100 mg/kg/day lapatinib for 7 days). The activities of oxidative stress parameters Malondialdehyde (MDA), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) were measured from the extracted cardiac tissues. The levels of troponinI and S100A1 expressions were measured from blood samples. All biomarkers responded to the treatments as they exhibited alterations from their normative values, validating the chemically induced cardiotoxicity. S100A1 expression attenuated significantly (75%), which made the sensitive detection of cardiotoxicity feasible. Assessment of cardiotoxicity with S100A1 may be a valuable alternative in clinical oncology of cancers in some organs such as breast and prostate, as they do not overexpress it to compete against.     

Evaluation of a Density-Based Rapid Diagnostic Test for Sickle Cell Disease in a Clinical Setting in Zambia

Although simple and low-cost interventions for sickle cell disease (SCD) exist in many developing countries, child mortality associated with SCD remains high, in part, because of the lack of access to diagnostic tests for SCD. A density-based test using aqueous multiphase systems (SCD-AMPS) is a candidate for a low-cost, point-of-care diagnostic for SCD. In this paper, the field evaluation of SCD-AMPS in a large (n = 505) case-control study in Zambia is described. Of the two variations of the SCD-AMPS used, the best system (SCD-AMPS-2) demonstrated a sensitivity of 86% (82–90%) and a specificity of 60% (53–67%). Subsequent analysis identified potential sources of false positives that include clotting, variation between batches of SCD-AMPS, and shipping conditions. Importantly, SCD-AMPS-2 was 84% (62–94%) sensitive in detecting SCD in children between 6 months and 1 year old. In addition to an evaluation of performance, an assessment of end-user operability was done with health workers in rural clinics in Zambia. These health workers rated the SCD-AMPS tests to be as simple to use as lateral flow tests for malaria and HIV.