Cause Of False Positives Research Articles

A novel approach for wild fish monitoring at aquaculture sites: wild fish presence analysis using computer vision

Aquaculture in open sea-cages attracts large numbers of wild fish. Such aggregations may have various impacts on farmed and wild fish, the environment, fish farming, and fisheries activities. Therefore, it is important to understand the patterns and amount of wild fish aggregations at aquaculture sites. In recent years, the use of artificial intelligence (AI) for automated detection of fish has seen major advancements, and this technology can be applied to wild fish abundance monitoring. We present a monitoring procedure that uses a combination of multiple cameras and automatic fish detection by AI. Wild fish in images collected around commercial salmon cages in Norway were automatically identified and counted by a system based on the real-time object detector framework YOLOv4, and the results were compared with manual human counts. Overall, the automatic system resulted in higher fish numbers than the manual counts. The performance of the system was satisfactory regarding false negatives (i.e. non-detected fish), while the false positive (i.e. objects wrongly detected as fish) rate was above 7%, which was considered an acceptable limit of error in comparison with the manual counts. The main causes of false positives were confusing backgrounds and mismatches between detection thresholds for automated and manual counts. However, these issues can be overcome by using training images that represent real scenarios (i.e. various backgrounds and fish densities) and setting proper detection thresholds. We present here a procedure with great potential for autonomous monitoring of wild fish abundance at aquaculture sites.

Establishment and validation of a computer-assisted colonic polyp localization system based on deep learning.

BACKGROUNDArtificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice.AIMTo train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies.METHODSWith high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital.RESULTSThe CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively).CONCLUSIONCADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.

The Effect of Genomic DNA Contamination on the Detection of Circulating Long Non-Coding RNAs: The Paradigm of MALAT1.

The presence of contaminating gDNA in RNA preparations is a frequent cause of false positives in RT-PCR-based analysis. However, in some cases, this cannot be avoided, especially when there are no exons–intron junctions in the lncRNA sequences. Due to the lack of exons in few of long noncoding RNAs (lncRNAs) and the lack of DNAse treatment step in most studies reported so far, serious questions are raised about the specificity of lncRNA detection and the potential of reporting false-positive results. We hypothesized that minute amounts of gDNA usually co-extracted with RNA could give false-positive signals since primers would specifically bind to gDNA due to the lack of junction. In the current study, we evaluated the effect of gDNA and other forms of DNA like extrachromosomal circular DNAs (eccDNAs) contamination and the importance of including a DNAse treatment step on lncRNAsexpression.As a model, we have chosen as one of the most widely studied lncRNAs in cancer namely MALAT1, which lacks exons. When we tested this hypothesis in plasma and primary tissue samples from NSCLC patients, our findings clearly indicated that results on MALAT1 expression are highly affected by the presence of DNA contamination and that the DNAse treatment step is absolutely necessary to avoid false positive results.

Specular Detection on Glossy Surface Using Geometric Characteristics of Specularity in Top-View Images.

In an autonomous driving assistance system (ADAS), top views effectively represent objects around the vehicle on a 2D plane. Top-view images are therefore widely used to detect lines in ADAS applications such as lane-keeping assistance and parking assistance. Because line detection is a crucial step for these applications, the false positive detection of lines can lead to failure of the system. Specular reflections from a glossy surface are often the cause of false positives, and since certain specular patterns resemble actual lines in the top-view image, their presence induces false positive lines. Incorrect positions of the lines or parking stalls can thus be obtained. To alleviate this problem, we propose two methods to estimate specular pixels in the top-view image. The methods use a geometric property of the specular region: the shape of the specular region is stretched long in the direction of the camera as the distance between the camera and the light source becomes distant, resulting in a straight line. This property can be used to distinguish the specular region in images. One estimates the pixel-wise probability of the specularity using gradient vectors obtained from an edge detector and the other estimates specularity using the line equation of each line segment obtained by line detection. To evaluate the performance of the proposed method, we added our methods as a pre-processing step to existing parking stall detection methods and investigated changes in their performance. The proposed methods improved line detection performance by accurately estimating specular components in the top-view images.

Basic Verification of β-D Glucan in Leukocyte-Rich Plasma for the Diagnosis of Deep Mycosis.

BackgroundCurrently, supplementary serological testing for β-D glucan (BDG) is often selected to diagnose deep mycosis in care covered by the health insurance in Japan. The Wako method used by our center has low sensitivity, and different studies have used different cut-off values due to factors that cause false positives and false negatives. One possible cause of false negatives is the use of platelet-rich plasma (PRP) as the sample material. Because phagocytic white blood cells (WBC) are precipitated by centrifugation and only plasma is measured, it seems unlikely that the actual amount of BDG is being measured when using PRP. Further, a frequent cause of false positives is contamination from blood products and gauze containing BDG. To resolve these issues, the blood cell separator, hydroxyethyl starch, is used to precipitate only the red blood cells to obtain leukocyte-rich plasma (LRP). We hypothesized that it might be possible to improve the diagnostic rate of deep mycosis by measuring the BDG content of plasma containing WBC and fungal components and by comparing the BDG content of PRP and LRP measured simultaneously.Materials and MethodsHealthy human blood, albumin-added blood, wrung-out gauze fluid-added blood, and fungal solution-added blood were prepared, and PRP and LRP were prepared using hydroxyethyl starch. The BDG content of each sample was measured using the Wako method and compared. In addition, PRP and LRP of fungal-added blood were Gram-stained and examined under a microscope, and the number of WBCs and phagocytosed fungi was counted visually and compared.ResultsMeasuring the BDG content of LRP confirmed that there were no false positives with LRP, and in vitro experiments comparing albumin-added false-positive blood to fungal-added blood showed significant differences between PRP and LRP only in the fungal-added blood.ConclusionCalculating the BDG-ratio (LRP/PRP) by measuring both LRP and PRP may eliminate false positives and false negatives of true deep mycosis and improve the diagnostic rate.

Public’s understanding of swab test results for SARS-CoV-2: an online behavioural experiment during the April 2020 lockdown

ObjectiveAlthough widespread testing for SARS-CoV-2 is in place, little is known about how well the public understands these results. We aimed to provide a comprehensive overview of the general public’s...

238. Novel Way to Evaluate Antibiotic Use Appropriateness: Moving Towards the “Never Event” Classification by Electronic Algorithm

BackgroundAntibiotic use is commonly tracked electronically by antimicrobial stewardship programs (ASPs). Traditionally, evaluating the appropriateness of antibiotic use requires time- and labor-intensive manual review of each drug order. A drug-specific “appropriateness” algorithm applied electronically would improve the efficiency of ASPs. We thus created an antibiotic “never event” (NE) algorithm to evaluate vancomycin use, and sought to determine the performance characteristics of the electronic data capture strategy.MethodsAn antibiotic NE algorithm was developed to characterize vancomycin use (Figure) at a large academic institution (1/2016–8/2019). Patients were electronically classified according to the NE algorithm using data abstracted from their electronic health record. Type 1 NEs, defined as continued use of vancomycin after a vancomycin non-susceptible pathogen was identified, were the focus of this analysis. Type 1 NEs identified by automated data capture were reviewed manually for accuracy by either an infectious diseases (ID) physician or an ID pharmacist. The positive predictive value (PPV) of the electronic data capture was determined.Antibiotic Never Event (NE) Algorithm to Characterize Vancomycin Use ResultsA total of 38,774 unique cases of vancomycin use were available for screening. Of these, 0.6% (n=225) had a vancomycin non-susceptible pathogen identified, and 12.4% (28/225) were classified as a Type 1 NE by automated data capture. All 28 cases included vancomycin-resistant Enterococcus spp (VRE). Upon manual review, 11 cases were determined to be true positives resulting in a PPV of 39.3%. Reasons for the 17 false positives are given in Table 1. Asymptomatic bacteriuria (ASB) due to VRE in scenarios where vancomycin was being appropriately used to treat a concomitant vancomycin-susceptible infection was the most common reason for false positivity, accounting for 64.7% of false positive cases. After removing urine culture source (n=15) from the algorithm, PPV improved to 53.8%.ConclusionAn automated vancomycin NE algorithm identified 28 Type 1 NEs with a PPV of 39%. ASB was the most common cause of false positivity and removing urine culture as a source from the algorithm improved PPV. Future directions include evaluating Type 2 NEs (Figure) and prospective, real-time application of the algorithm.DisclosuresMarc H. Scheetz, PharmD, MSc, Merck and Co. (Grant/Research Support)

IsoDiff

Weak isolation levels, such as Read Committed and Snapshot Isolation, are widely used by databases for their higher concurrency, but may introduce subtle correctness errors in applications that only experts can identify. This paper proposes IsoDiff, a tool to help a developer debug the anomalies caused by weak isolation for an application. To address the challenge that the number of anomalies can be non-polynomial with respect to the number of types of transactions, IsoDiff finds a representative subset of anomalies involving different transactions, operations, and problematic patterns. To reduce false positives, IsoDiff proposes two novel methods (correlation detection and timing relationship check) to eliminate as many false positives as possible and further provides a mechanism to incorporate the developer's feedback to eliminate the remaining ones. The evaluation of IsoDiff on TPC-C and seven real applications under Snapshot Isolation and Read Committed isolation shows that IsoDiff can balance computation time and the coverage of anomalies; it can automatically eliminate a significant portion of false positives; and its feedback mechanism allows a developer to express the root cause of false positives, which can eliminate many false positives with only a small number of developer hints.

Validation of the OptiSafe™ eye irritation test

Purpose OptiSafe is an in chemico test method that identifies potential eye irritants based on macromolecular damage following test chemical exposure. The OptiSafe protocol includes a prescreen assessment that identifies test chemicals that are outside the applicability domain of the test method and thus determines the optimal procedure. We assessed the usefulness and limitations of the OptiSafe test method for identifying chemicals not requiring classification for ocular irritation (i.e. bottom-up testing strategy). Materials and methods Seventeen chemicals were selected by the lead laboratory and tested as an independent study. Ninety-five unique coded chemicals were selected by a validation management team to assess the intra- and interlaboratory reproducibility and accuracy of OptiSafe in a multilaboratory, three-phased validation study. Three laboratories (lead laboratory and two naïve laboratories) evaluated 35 chemicals, with the remaining 60 chemicals evaluated by the lead laboratory only. Test method performance was assessed by comparing classifications based on OptiSafe results to classifications based on available retrospective in vivo data, using both the EPA and GHS eye irritation hazard classification systems. No prospective in vivo testing was conducted. Results Phase I testing of five chemicals showed that the method could be transferred to naïve laboratories; within-lab reproducibility ranged from 93% to 100% for both classification systems. Thirty coded chemicals were evaluated in Phase II of the validation study to demonstrate both intra- and interlaboratory reproducibility. Intralaboratory reproducibility for both EPA and GHS classification systems for Phase II of the validation study ranged from 93% to 99%, while interlaboratory reproducibility was 91% for both systems. Test method accuracy for the EPA and GHS classification systems based on results from individual laboratories ranged from 82% to 88% and from 78% to 88%, respectively, among the three laboratories; false negative rates ranged from 0% to 7% (EPA) and 0% to 15% (GHS). When results across all three laboratories were combined based on the majority classification, test method accuracy and false negative rates were 89% and 0%, respectively, for both classification systems, while false positive rates were 25% and 23% for the EPA and GHS classification systems, respectively. Validation study Phase III evaluation of an additional 60 chemicals by the lead laboratory provided a comprehensive assessment of test method accuracy and defined the applicability domain of the method. Based on chemicals tested in Phases II and III by the lead laboratory, test method accuracy was 83% and 79% for the EPA and GHS classification systems, respectively; false negative rates were 4% (EPA) and 0% (GHS); and false positive rates were 40% (EPA) and 42% (GHS). Potential causes of false positives in certain chemical (e.g. ethers and alcohols) or hazard classes are being further investigated. Conclusion The OptiSafe test method is useful for identifying nonsurfactant substances not requiring classification for ocular irritancy. OptiSafe represents a new tool for the in vitro assessment of ocular toxicity in a tiered-testing strategy where chemicals can be initially tested and identified as not requiring hazard classification.

Comparison of the Effect of Atrial Fibrillation Detection Algorithms in Patients With Cryptogenic Stroke Using Implantable Loop Recorders

Occult atrial fibrillation (AF) can be the underlying cause for cryptogenic stroke (CS). Implantable loop recorders (ILRs) have become an important tool for long-term arrhythmia monitoring in CS patients. Office-based ILR implantation by nonelectrophysiologist physicians is increasingly common. To report the real world diagnostic yield and accuracy of remote ILR monitoring in high risk CS patients, we retrospectively analyzed 145 consecutive patients with CS who underwent ILR implantation between October 2014 and October 2018 at New York University Langone Health. A certified device technician and an electrophysiologist adjudicated all transmissions. The yield and accuracy of Reveal LINQ Intra Cardiac Monitor (ICM), a fourth generation device, was compared to that of TruRhythm Detection algorithm (fifth generation device). AF was diagnosed in 17 patients (12%) over a mean follow-up of 28 ± 12 months. The median time to diagnosis was 7.4 ± 21.3 months. A total of 1,637 remote transmissions (scheduled- and auto-triggered alerts: 756; patient-triggered: 881) were adjudicated. The positive predictive value for AF episodes in the scheduled interrogations increased from 4% in the Reveal LINQ ICM to 16% in the TruRhythm LINQ. Of 881 patient-triggered transmissions, none were found to be true positive. In the Reveal LINQ ICM, for scheduled transmissions, primary causes of false positive (FP) were atrial ventricular premature complexes (80%). In the TruRhythm LINQ, for scheduled transmissions, primary cause of FP were T-wave over-sensing (87%). In conclusion, the real world diagnostic yield of ILR for patients with CS remains suboptimal, with at least 84% of AF alerts being FP. Patient-riggered events did not correlate with arrhythmia and the necessity of patient triggering in this population should be questioned. Expert interpretation of recordings is critical to assure accurate diagnosis.

Non-coronarogenic causes of increased cardiac troponins in the practice of physicians (literature review)

Cardiac isoforms of troponins are the most sensitive and specific biomarkers of myocardial damage and new high-sensitivity methods can reveal very minor damages on the heart muscle. However, elevated troponin levels indicate cardiac damage, but do not define the cause of the damage. Therefore, cardiac troponin elevations are common in many disease states and do not necessarily indicate the presence of acute myocardial infarction. In clinical practice, interpretation of positive troponins may be challenging. In our article, we consider the main non-coronarogenic causes of increased cardiac troponins. The first part of the review discusses the mechanisms of increase and the diagnostic value of cardiac troponins during physical exertion, inflammatory and toxic myocardial injuries (endocarditis, myocarditis, sepsis), and renal failure. The second part of the literature review describes the mechanisms of increase and the diagnostic value of troponins in pulmonary thromboembolism, dissecting aortic aneurysms, neurogenic pathologies (stroke, subarachnoid hemorrhages), and treatment with cardiotoxic drugs (chemotherapy). Special attention is paid to the false positive causes of elevation of troponins.

Levels of TB-IGRA may help to differentiate between intestinal tuberculosis and Crohn's disease in patients with positive results.

Aim:The aim of this study was to investigate the significance of positive tuberculosis interferon gamma release assay (TB-IGRA) in the differential diagnosis of intestinal tuberculosis (ITB) and Crohn’s disease (CD) patients, and to find a suitable threshold to help distinguishing CD from tuberculosis (TB), so as to provide better recommendations for clinical treatment.Methods:A retrospective study was performed including 484 patients who underwent TB-IGRA testing for suspected CD or ITB treated in the Shanghai Tenth People’s Hospital of Tongji University between January 2015 and May 2018. According to the diagnostic criteria, 307 patients, including 272 CD and 35 ITB patients, were recruited for the final analysis. We comprehensively and systematically collected their clinical manifestations, and analyzed the influence of TB-IGRA values referring to diagnosis criteria, and the possible causes of false positives. The receiver operator characteristic (ROC) curve and the cut-off value were applied to distinguish between ITB and CD patients.Results:Of the 56 patients with suspected CD enrolled, 23 were finally diagnosed with CD and 33 with ITB. In patients with TB-IGRA ⩾ 100 pg/ml, 4 cases were CD and 29 cases were ITB, while 19 cases were CD and 4 cases were ITB in patients with TB-IGRA < 100 pg/ml (p < 0.05). TB-IGRA ⩾ 100 pg/ml indicated a high possibility of TB infection, with a sensitivity of 88% and a specificity of 74%. Three out of the four CD patients with TB-IGRA ⩾ 100 pg/ml had a history of tuberculosis, while only 1 of the 19 CD patients with TB-IGRA < 100 pg/ml had a history of tuberculosis (p < 0.05). The average duration of ITB was 7 months, and that of CD was 46.8 months, thus a significant difference (p < 0.05) was observed. Perianal lesions such as anal fistula or abscess were found in all CD patients. Among ITB patients, 8 out of 15 patients with TB-IGRA ⩾ 400 pg/ml experienced weight loss, while only 1 out of 18 patients with TB-IGRA < 400 pg/ml underwent weight loss (p < 0.05).Conclusion:Patients with CD have longer duration of disease, and perianal lesions are more common in CD. ITB patients with TB-IGRA ⩾ 400 pg/ml experience weight loss more readily, which indicates that TB-IGRA value may be correlated positively with the severity of ITB. In patients with CD and ITB, TB-IGRA = 100 pg/ml may be a cut-off value of TB-IGRA. For patients with TB-IGRA ⩾ 100 pg/ml, it is recommended to use diagnostic anti-TB treatment first. Comprehensive analysis and judgment are required for patients with TB-IGRA from 14 pg/ml to 99 pg/ml. TB-IGRA false positivity may occur in patients with a history of TB infection.

Dual time point [18F]Flurodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) with water gastric distension in differentiation between malignant and benign gastric lesions

ObjectivesTo assess diagnostic accuracy and added value of dual time point 18F-FDG PET/CT after gastric distention using oral water in differentiating malignant from benign gastric lesions. MethodsPatients (n = 30, 19 males, mean age 58.6 ± 16.4 years). All patients are known or suspected oncology patients. All patients underwent whole body 18F-FDG PET/CT scan and 2 h delayed PET/CT abdominal images following oral water gastric distension. The best cut off values for early SUVmax (SUVmax1), delayed SUVmax (SUVmax2) and SUVmax2-SUVmax1 (ΔSUVmax) to differentiate benign from malignant lesions were set based on ROC analysis. Data analyzed included in addition; age, sex and 18F-FDG uptake pattern in delayed images. Suspicious gastric lesions were correlated with biopsy in 18 patients (60 %) and with clinical and follow-up imaging (18F-FDG PET/CT, CT or MRI) in 12 patients (40 %). Unpaired t-test was used to compare the mean deference in continuous variables between patients with gastric malignancy and those with benign gastric lesions. Fisher’s exact test was used to analyze categorical variables. Logistic regression analysis was performed to identify the most powerful factors to predict malignant lesions. ResultsFifteen patients (50 %) had confirmed malignant gastric lesions. Patients with confirmed gastric malignancy were older (65 ± 13 vs 52 ± 17; p = 0.023) and had significantly higher mean ΔSUVmax (1.29 ± 1.76 vs −0.89 ± 1.59; p = 0.003). The mean SUVmax1 (6.99 ± 6.66 vs 5.31 ± 2.53; p = 0.367) and SUVmax2 (8.29 ± 7.41 vs 4.44 ± 3.34; p = 0.077) although both higher in patients with malignant lesions, they did not reach statistical significance. Sensitivity, specificity, PPV, NPV, and accuracy to detect malignant gastric lesions were highest for lesions with localized uptake pattern in delayed images post water oral contrast as well as for lesions with ΔSUVmax>0. Regression analysis revealed both variables as independent predictors for malignant lesions with odd ratios of 22.9 and 9.5 respectively and final model Chi-Square of 19.9 (p < 0.0001). The model correctly identified 12/15 (80 %) malignant lesions and 13/15 (86.7 %) benign lesions with 2 false positives confirmed as chronic active gastritis with helicobacter pylori and 3 false negatives including 1 signet ring gastric cancer and 1 low grade gastrointestinal stromal tumor (GIST), both with poor 18 F-FDG uptake. ConclusionLocalized uptake pattern in delayed PET/CT images following gastric distention with oral water contrast as well as ΔSUVmax>0 are powerful independent variables to identify malignant gastric lesions with fairly high sensitivity and reasonable accuracy. Malignancies with inherently low 18F-FDG avidity are the main cause of false negatives while active gastritis is the main cause of false positives.

Cost­effectiveness in mathematical modelling of the power unit control

The authors of the study have analysed the criteria for increasing cost-effectiveness in the operation of power-generating equipment of power units at TPPs and NPPs. The existing methods of calculating the cost-effectiveness disregard factors that lead to economic costs during shutdowns of the power unit and reduce the energy consumer load. A significant factor in increasing cost-effectiveness of the automated control systems at a power unit of a power plant is the compulsory checking to detect a low level of information reliability. It is proved that reliability of the power unit technological equipment substantially depends on the effectiveness of emergency automated control when an unpermitted shutdown of a power unit occurs due to false positives. It is shown that the cause of false positives is low reliability of the data on the power unit technological process parameters. It is revealed that unforeseen unpermitted shutdown of a power unit and a decrease in the energy consumer load leads to significant economic and material losses, and, consequently, to a decrease in economic efficiency of automated control of a power unit. It is shown that the existing economic models do not take into account the financial and material costs that occur due to unpermitted shutdown of the power unit and decrease in the energy consumer load in case of false positives in real time. The authors of the study have devised a unified integrated economic and mathematical model, which allows calculating the economic effect taking into account changes in the reliability of the technological equipment, due to the timely prompt detection of false positives and low-reliability data. The proposed emergency modular unit coupled with modules for detecting and control of false alarms, which takes into account static and operational economic components, allows calculating the economic effect based on the devised unified integrated economic and mathematical model. The authors of the study give practical recommendations for applying the economic module in the hardware and software complex of the power unit, which allows calculating the economic effect on the basis of static data coming from the data memory and current data from the power unit

The Effect of Promiscuous Aggregation on in Vitro Drug Metabolism Assays.

Many bioactive molecules show a type of solution phase behavior, termed promiscuous aggregation, whereby at micromolar concentrations, colloidal drug-rich aggregates are formed in aqueous solution. These aggregates are known to be a major cause of false positives and false negatives in select enzymatic high-throughput screening assays. The goal of this study was to investigate the impact of drug-rich aggregates on in vitro drug screening metabolism assays. Cilnidipine was selected as an aggregate former and its impact on drug metabolism was evaluated against rCYP2D6, rCYP1A2, rCYP2C9 and human liver microsomes. The cilnidipine aggregates were shown to non-specifically inhibit multiple cytochrome P450 enzymes with an IC50 comparable with the IC50 of potent model inhibitors. This newly demonstrated mode of "promiscuous inhibition" is of great importance as it can lead to false positives during drug metabolism evaluations and thus it needs to be considered in the future to better predict in vivo drug-drug interactions.

Zinc Sulphate Turbidity as a Screening Test of Passive Transfer of Immunity in Newborn Foals

Background: Passive immunity acquired by colostrum ingestion is essential to prevent neonatal infections. Failure of passive transfer (FPT) of maternal immunity occurs in foals that fail to absorb enough immunoglobulins within 24 h after birth. Foals with FPT are at increased risk of infections and death. Serum samples from neonatal foals might be examined for FPT using the zinc sulphate turbidity (ZST) test. The aim of this study was to investigate the accuracy of the ZST test, performed at two different times after first suckling (12 and 18 h), to detect FPT in newborn foals. The effect of temperature on the turbidity intensity resulting from the ZST reaction was also investigated.Materials, Methods &amp; Results: Blood samples were collected from 112 newborn foals at 12 h after the first colostrum intake. In 36 foals, additional serum samples were collected at 18 h after first colostrum intake. The serum samples were tested with the ZST test and, later, in the laboratory setting, the ZST test was repeated. The IgG levels were measured by single radial immunodiffusion (SRID), which was used as the reference method. The standard solution used for the interpretation of results had a turbidity corresponding to approximately 800 mg/dL of immunoglobulins (IgG). The mean IgG concentration measured at 12 and 18 h after the first colostrum intake was analyzed using the t-test for paired samples. Values of absorbance of ZST test under different temperatures were analyzed using a one-way analysis of variance, and means were compared using the Tukey test. The relationship between the temperature of the solution and absorbance was determined using the Pearson’s correlation coefficient. Based on SRID results, 12 foals (10.7%) had serum IgG concentration &lt; 400 mg and 26 foals (23.2%) had IgG levels between 400 and 800 mg/dL. Serum levels of IgG determined by SRID in 36 foals were similar (P &gt; 0.05) between 12 h (943.9 ± 508.6 mg/dL) and 18 h (975.9 ± 525.6 mg/dL) after the first colostrum intake. The sensitivity values were 76.3% and 71.0% (P &gt; 0.05) for tests performed at farm and laboratory, respectively. The specificity was higher (P &lt; 0.05) for ZST tests performed at laboratory (94.6%) than at farms (73.0%). Twenty-nine of the 38 foals (76.3%) with IgG &lt; 800 mg/dL were correctly detected using the ZST test at farms. There was a strong correlation (r = 0.92; P &lt; 0.0001) between the temperature of the solution test and the degree of turbidity. The absorbance after the reaction of serum with zinc sulphate was similar between the temperatures of 30, 34 and 37ºC, which had higher values than 20 and 25ºC.Discussion: The ZST test can be performed at 12 h after the first suckling. The lower specificity of tests run at farms compared to laboratory resulted in more foals with false positive diagnosis. The main cause of false positives at farms was probably the low temperature of the zinc sulphate solution at the time of testing, delaying the reaction and underestimating the IgG concentration. This assumption was reinforced by the increased specificity observed when the test was repeated with the same serum samples under controlled temperature of a laboratory. Additionally, the positive correlation observed between the temperature and degree of turbidity confirms that the reaction is temperature dependent. In the Southern hemisphere, most Thoroughbred foals are born during winter, when room temperature is far below the ideal temperature for good performance of the ZST test. Therefore, the number of false positives will likely be reduced if tests are performed at the farms under adequate temperature of solution (between 30 and 37ºC). This will reduce the number of foals receiving unnecessary treatment.

Burden of Thyroid and Lipid disorders among Elderly Depressed Patient: A cross sectional study in Nepal

Background and Objectives: Depression is common psychiatric illness among geriatric population however it remains underdiagnosed and undertreated. Majority of thyroid and lipid disorders are asymptomatic or have vague symptoms unless they land with emergency medical conditions. The burden of thyroid and lipid disorder are under reported in elderly population especially depressed one. The objective of the study was to measure the burden of thyroid and lipid disorders among Elderly Depressed Patient.&#x0D; Materials and methods: A hospital based cross-sectional study was conducted at BP Koirala Institute of Health Sciences, Dharan. All written consent patients more than 60 years of age with diagnosed of depression using ICD 10 criteria were screened for thyroid and lipid disorders as per hospital protocol. Those cases found to have thyroid and lipid disorders were reevaluated by physician for possibilities to rule out the false positive causes.&#x0D; Results: The prevalence of thyroid disorder and dyslipidemia was 29% and 62.7% respectively among 51 elderly depressed patient. Subclinical hypothyroidism was associated with 25% of the cohort. Hypertriglyceridemia (54.9%) was the most common form of lipid disorders followed by 47.1% increased total cholesterol level, 19.6% increased LDL level and 13.7% low HDL level. The presence of thyroid and lipid disorders were not significantly associated with types of depression (mild, moderate, severe and recurrent).&#x0D; Conclusion: Low threshold should be kept to screen subclinical hypothyroidism and dyslipidemia among geriatric depressed population due to alarming burden and adverse impact on quality of life and longevity.

Up in Smoke: Uncovering a Lack of Evidence for Proton Pump Inhibitors as a Source of Tetrahydrocannabinol Immunoassay False Positives.

It is recommended that positives in immunoassay drug screens be followed up with more specific confirmatory testing. The drug package insert for pantoprazole mentions reports of false-positive urine screening tests for tetrahydrocannabinol in patients receiving proton pump inhibitors, but no method details or data are given, referenced, or found in literature searches. Thus, we investigated this using our laboratory's assay. A spiked sample and samples from 32 patients taking a proton pump inhibitor were analyzed using the EMIT II Plus Cannabinoid assay with a 20 ng/mL cutoff. Additionally, we examined urine samples from 50 patients with false-positive or low-positive screens for evidence of a proton pump inhibitor. To determine whether O-desmethyl pantoprazole sulfate, the major metabolite, shares any structural or electrostatic similarity to suggest a basis for cross-reactivity in the immunoassay, we used computational techniques for analyses. Molecular electrostatic potential energy (MEP) maps were calculated for the global minimum conformers, and the maximum common substructure Tanimoto similarity was calculated for the modeled compounds. Neither the spiked sample nor the patient samples were found to screen positive. None of the false-positive or low-positive screens were found to contain a proton pump inhibitor. Computational studies showed very little similarity in shape or electrostatics between the two molecules. We find no supporting evidence of pantoprazole as the cause of false positives in the EMIT II Plus Cannabinoid assay and caution the use of proton pump inhibitors as an explanation for tetrahydrocannabinol immunoassay false positives.

18F-FDG PET/CT and histology for diagnosing recurrent/remnant tumors in head and neck cancer patients treated with radiotherapy.

The aim of this study was to assess the diagnostic performance of fluorine-18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for locoregional recurrent/residual tumor in patients with head and neck cancer (HNC) who underwent previous radiotherapy (RT). 18F-FDG PET/CT images from patients with HNC who previously underwent RT were retrospectively reviewed. Only cases with histological confirmation within 4 weeks of PET/CT imaging were included. Standardized uptake values were obtained for lesions and PET/CT findings were compared with histological results. Of 181 cases, 114 (63%) were histologically confirmed as malignant and 67 (37%) as benign. The sensitivity, specificity, and accuracy of PET/CT were 93%, 64%, and 82%, respectively. Inflammation was the most common cause of false positives and small tumor volume and low 18F-FDG avidity were the causes of false negatives. PET/CT had 100% sensitivity and 56% specificity for detecting recurrent or residual disease within 12 weeks after RT and 93% sensitivity and 64% specificity, more than 12 weeks after RT. The frequency of false positives in PET/CT images within 12 weeks of RT was similar to the results obtained 12 weeks after RT (15% vs. 14%). False positives were more frequent in PET/CT cases after two-dimensional or three-dimensional conformal RT than in those after intensity-modulated RT, although not statistically significant (15% vs. 9%, p>0.05). 18F-FDG PET/CT might aid the diagnosis of locoregional residual/recurrent tumors in patients with HNC previously treated with RT. Inflammation was the main cause of false positives regardless of the interval between RT and PET/CT, even several years after RT. Therefore, histological verification of positive PET/CT findings should be conducted during follow-up of HNC patients treated with RT.

The Direct Antiglobulin Test: Indications, Interpretation, and Pitfalls.

The direct antiglobulin test (DAT; sometimes referred to as the "Coombs" test) continues to be one of the most widely used assays in laboratory medicine. First described about 70 years ago, it is elegantly simple in design, yet it is widely complex in its applications and interpretations, and it is prone to false-positive and false-negative results. The overall objective of our review is to provide practicing pathologists with a guide to identify situations when the DAT is useful and to highlight disease-specific shortcomings as well as general pitfalls of the test. To accomplish these goals, this review will discuss the following: (1) the history of the DAT, (2) how the test is performed in the clinical laboratory, (3) clinical situations for its use, (4) its interpretation, and (5) the pitfalls associated with DAT assays, including causes of false positivity.