Diagnostic Testing Methods Research Articles

Diagnosis of Metal Hypersensitivity in Orthopedics

The pathology of early aseptic implant failure has been linked in basic science, case, and group studies to metal implant debris–induced delayed-type hypersensitivity (DTH) responses (or metal allergy). However, a precondition of metal DTH does not always result in implant failure. The methods of diagnosing metal DTH responses measure cell-mediated adaptive immunity, where conditioned lymphocytes respond to specific stimuli. Metal-sensitivity testing is a direct test of an individual’s immune response to metal challenge, which has been in use for over the past half century to measure delayed-type responses to drugs (such as antibiotics) where the results indicate levels of immune reactivity. Currently approved methods for human diagnostic testing for metal DTH include both skin testing (patch testing) and in vitro blood testing using lymphocyte transformation testing (LTT). LTT testing may be better suited for diagnosing implant-related sensitivity, given the ability of dermal exposure to metals to induce DTH responses. Metal sensitivity among the general population has been well established with a rate of 10%-15%, where hypersensitivity to nickel is the most common. However, it remains unknown about the exact percentage of these presensitized people that will go on to develop pathogenic metal-sensitivity responses to their implant. Recent studies show that when exposure to metal implant debris is minimized, the chances of metal DTH reactivity are also minimized. Further, past basic science studies, case studies, and cohort studies indicate the clinical utility of metal-sensitivity testing in specific patient populations. Continuing clinical outcome studies are needed to relate positive patch and metal-LTT test results with other clinical determinants to more definitively predict and prevent pathologic reactivity to implants.

Towards degradation decomposition for voice communication system assessment

This article presents the current development of degradation decomposition tools for the assessment of voice communications. Overall quality scores, represented as Mean Opinion Scores (MOS) produced by subjective test methodologies such as ITU-T P.800 Absolute Category Rating (ACR), remains the most popular quality metric in the industry. While MOS is a great indicator to evaluate quality issues, it does not provide information on the cause of issues. To address this gap, work items are currently active within ITU-T to provide the industry with means to understand the cause of lower scores by perceptual or technical degradation decompositions. The goal is to produce objective models that enable automated degradation decomposition. The first step in such a development is the construction of databases for model training and validation. For this, in sum four experiments using a potential diagnostic test method discussed within ITU-T are conducted. In addition, two optional improvements for the test method are presented and discussed. The results of the experiments show that for standardization the analyzed test method still leaves room for validation and further improvements.

Comparison of the diagnostic performance of bacterial culture of nasopharyngeal swab and bronchoalveolar lavage fluid samples obtained from calves with bovine respiratory disease.

OBJECTIVE To compare predictive values, extent of agreement, and gamithromycin susceptibility between bacterial culture results of nasopharyngeal swab (NPS) and bronchoalveolar lavage fluid (BALF) samples obtained from calves with bovine respiratory disease (BRD). ANIMALS 28 beef calves with clinical BRD. PROCEDURES Pooled bilateral NPS samples and BALF samples were obtained for bacterial culture from calves immediately before and at various times during the 5 days after gamithromycin (6 mg/kg, SC, once) administration. For each culture-positive sample, up to 12 Mannheimia haemolytica, 6 Pasteurella multocida, and 6 Histophilus somni colonies underwent gamithromycin susceptibility testing. Whole-genome sequencing was performed on all M haemolytica isolates. For paired NPS and BALF samples collected 5 days after gamithromycin administration, the positive and negative predictive values for culture results of NPS samples relative to those of BALF samples and the extent of agreement between the sampling methods were determined. RESULTS Positive and negative predictive values of NPS samples were 67% and 100% for M haemolytica, 75% and 100% for P multocida, and 100% and 96% for H somni. Extent of agreement between results for NPS and BALF samples was substantial for M haemolytica (κ, 0.71) and H somni (κ, 0.78) and almost perfect for P multocida (κ, 0.81). Gamithromycin susceptibility varied within the same sample and between paired NPS and BALF samples. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated culture results of NPS and BALF samples from calves with BRD should be interpreted cautiously considering disease prevalence within the population, sample collection relative to antimicrobial administration, and limitations of diagnostic testing methods.

Accuracy in measuring hemoglobin concentration using portable hemoglobinometer method

Introduction. Anemia is defined as a condition that arises due to as low concentration of hemoglobin in blood. Anemia affects a variety of population groups, cutting across different geographical boundaries and income groups, affecting all, including low-, middle-, and high-income countries.1 Anemia can cause cognitive disorder, affecting performance in both work and school and reduce the earning capacity of the affected individuals.2 In Indonesia, based on RISKESDAS data in 2007, it was found that 11.3% women, 12.2% men, and 12.8% children suffered anemia.3 And the WHO data collected between 1993 and 2005 globally revealed that 47.4% preschool-age children, 41.8% pregnant women, 30.2% non-pregnant women, 25.4% school-age children, 23.9% older adults, and 12.7% men suffer anemia.4 Anemia is a public health challenge in Indonesia and mostly affects preschool children and women of reproductive age.Numerous methods have been used and developed to measure hemoglobin concentration in human blood, but not all of the methods are easy and sensitive and effective in diagnosing anemia. The objective of this study is to know the extent of accuracy in measuring hemoglobin concentration using the well-known portable hemoglobinometer method.Research Design and Methods. This study was a diagnostic test and cross-sectional methods were used. The sampling technique used was total sampling. The total study sample comprised 48 participants. The study was conducted in the Public Elementary School 101747, Klumpang Kebun, Hamparan Perak District, between March and December 2016. Analysis was performed using a 2x2 table, in order to calculate a variety of item measures, including the following: sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and an ROC graph was made to determine the cut-off point.Results. The study results were as follows: sensitivity 0%, specificity 95.8%, positive predictive value 0%, negative predictive value 95.8%, positive likelihood ratio 0, negative likelihood ratio 1, and area under the curve of ROC graph 50%.Conclusion. The study findings encourage us to conclude that the results arrived at were specific, given the high specificity (95.8%) and high negative predictive value (95.8%). However, the sensitivity of this method as well as its positive predictive value were zero. Â

Diagnostic testing methods for Clostridium difficile infection: A statewide survey of Ohio acute care hospitals.

We surveyed Ohio acute care hospitals on laboratory testing used for diagnosis of Clostridium difficile infection (CDI). Of 146 hospitals surveyed, 109 (84%) used nucleic acid amplification tests (NAATs) as stand-alone diagnostic assays. Only 53 (42.4%) hospitals using NAATs had a mechanism in place to prevent repeat CDI testing.

Breathing Maneuvers as a Vasoactive Stimulus for Detecting Inducible Myocardial Ischemia - An Experimental Cardiovascular Magnetic Resonance Study.

BackgroundBreathing maneuvers can elicit a similar vascular response as vasodilatory agents like adenosine; yet, their potential diagnostic utility in the presence of coronary artery stenosis is unknown. The objective of the study is to investigate if breathing maneuvers can non-invasively detect inducible ischemia in an experimental animal model when the myocardium is imaged with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR).Methods and FindingsIn 11 anesthetised swine with experimentally induced significant stenosis (fractional flow reserve <0.75) of the left anterior descending coronary artery (LAD) and 9 control animals, OS-CMR at 3T was performed during two different breathing maneuvers, a long breath-hold; and a combined maneuver of 60s of hyperventilation followed by a long breath-hold. The resulting change of myocardial oxygenation was compared to the invasive measurements of coronary blood flow, blood gases, and oxygen extraction. In control animals, all breathing maneuvers could significantly alter coronary blood flow as hyperventilation decreased coronary blood flow by 34±23%. A long breath-hold alone led to an increase of 97±88%, while the increase was 346±327% (p<0.001), when the long breath-hold was performed after hyperventilation. In stenosis animals, the coronary blood flow response was attenuated after both hyperventilation and the following breath-hold. This was matched by the observed oxygenation response as breath-holds following hyperventilation consistently yielded a significant difference in the signal of the MRI images between the perfusion territory of the stenosis LAD and remote myocardium. There was no difference between the coronary territories during the other breathing maneuvers or in the control group at any point.ConclusionIn an experimental animal model, the response to a combined breathing maneuver of hyperventilation with subsequent breath-holding is blunted in myocardium subject to significant coronary artery stenosis. This maneuver may allow for detecting severe coronary artery stenosis and have a significant clinical potential as a non-pharmacological method for diagnostic testing in patients with suspected coronary artery disease.

Comparison of The Means of Argyrophilic Nucleolar Organizer Region (mAgNOR) Pre- and Post-Therapy in Nasopharyngeal Carcinoma Patients at Wahidin Sudirohusodo General Hospital Makassar

BACKGROUND: Nasopharyngeal carcinoma (NPC) is malignant tumor growing in nasopharynx with a predilection in fossa Rossenmuller and nasopharyngeal roof. This research aimed to prove whether the means of argyrophilic nucleolar organizer region (mAgNOR) can predict the success of treatment in nasopharyngeal carcinoma patients.METHODS: We used diagnostic test method with longitudinal design and purposive sampling technique. Endoscopic biopsy examination was performed on 15 nasopharyngeal carcinoma patients before and after therapy, 13 patients underwent chemotherapy and other two underwent chemoradiotherapy. Tumor tissues were stained and AgNOR was calculated.RESULTS: Based on the tumor stage, sample characteristic showed 3 patients (20%) were in stage II, 3 patients (20%) in stage III, and 9 patients (60%) in stage IV, with pre- and post-therapy mAgNOR were 1.610±0.988 and 1.000±0.000, respectively in stage II, 1.100±0.092 and 1.000±0.000, respectively in stage III, 1.226±0.265 and 1.107±0.164, respectively in stage IV patients. Based on histopathology type, 4 patients (26.7%) had non keratinizing squamous cell carcinoma with pre- and post-therapy mAgNOR were 1.117±0.134 and 1.060±0.120, respectively, while 11 patients (73.3%) had undifferentiated squamous cell carcinoma with pre- and post-therapy mAgNOR were 1.335±0.528 and 1.065±0.146, respectively. Overall the pre-therapy were significantly higher than post-therapy mAgNOR. In subgroups there are significant differences in stage IV and type 3.CONCLUSION: The values of AgNOR were decreased in all NPC stages and significantly decreased in undifferentiated squamous cell carcinoma. AgNOR can be used to predict the successfulness of therapy in NPC.KEYWORDS: nasopharyngeal carcinoma, therapy, proliferation, mAgNOR

Evaluation of a rapid diagnostic test method in kala-azar &amp; Pkdl cases in a tertiary care centre of Eastern India

Background & objectives: Definitive diagnosis of kala-azar requires demonstration of parasites in tissue or bone marrow. In the present study, the diagnostic utility of rK-39 immunochromatographic test (ICT) strip for the diagnosis of kala-azar and post kala-azar dermal leishmaniasis (PKDL) at a tertiary care centre of Eastern India was done. Methods: The study was conducted from January 2011 to December 2011 on 100 suspected kala-azar and PKDL cases. Results: Of the 100 samples, 36 were positive by ICT; of which, 32 were diagnosed as kala-azar (25 males mainly in children of age group 0-20 yrs -(7)) and 4 as PKDL (all 4 males) The rest 64 controls included individuals with malignancies, haemolytic disorders, chronic liver diseases, etc. All had fever of duration ranging from <1 month to 1.5 yr (median 4.5 months). All PKDL patients gave past history of kala-azar and their slit skin test smears were microscopically positive for Leishman-Donovan (LD) bodies. The strip test was positive in all the cases of kala-azar and PKDL (sensitivity 100%) and negative in all control sera (specificity 100%).

Influence of moisture on dielectric condition of high power Insulated Gate Bipolar Transistor modules

Moisture in a high power Insulated Gate Bipolar Transistor (IGBT) module raises serious concern on component and system level reliability. Employing diagnostic test methods on high power IGBT modules might provide an opportunity in detection and estimation of moisture, however has not received wide attention. This paper investigates on understanding the influence of moisture in high power IGBT modules through time and frequency dependent dielectric response measurements and partial discharge analysis. The moisture in the main insulation of an IGBT module under DC excitation produces a sharp rise in its response current introducing deviation in their respective time dependent dielectric properties. Alternatively, the frequency dependent dielectric response measurements under wide frequencies provide more information than their DC counterpart. This method enables discrimination of various defects such as moisture, physical defects, etc., thereby revealing a clear picture about the actual status. In particular, the lower frequencies reveal longer range ion movements, hence could be used for more accurate estimation of moisture. The higher frequencies though not accurate in moisture estimation reveal deviation in the material properties. These deviations alter the apparent dielectric characteristics such as loss factor, permittivity, etc., of the IGBT samples which becomes clear through simple comparative analysis. In conclusion, the findings in this paper might help in understanding the influence of moisture over the dielectric integrity of a high power IGBT module. Additionally, the permissible or acceptable level of moisture which might act as a threshold to initiate necessary precautionary measures could be subsequently developed.

Studies on incidence of malaria and comparative efficacy of diagnostic test methods for plasmodium falciparum and p. vivax

Background: Diagnostic methods are becoming a crucial component of malaria control and prevention. Improved ability to diagnose malaria may prevent many unnecessary antimalarial treatments and should also allow prompt attention to other causes of fever when malaria is ruled out. Methods & Materials: This study compared the diagnostic accuracy of Bioline SD (HRP-2) and ACON (HRP-2/Aldolase) based RDTs with microscopy. Blood samples were collected from 200 asymptomatic and 60 symptomatic subjects in Ado-Odo/Ota LGA, Ogun state. The blood samples collected were first analyzed using the Rapid Diagnostic Tests and then stained with Giemsa stain and viewed under the microscope. Results: Out of the samples collected from asymptomatic subjects, 44% were males while 66% were females. Among the samples from symptomatic patients, 58.3% were females. The overall incidence of falciparum malaria among the study population by microscopy was 32.3%. Among the asymptomatic patients only, the percentage incidence from microscopy was 26.5% with 11% males and 15.5% females; by Bioline SD (HRP-2) kits, the incidence was 17%with 6.5% males and 10.5% females; while by ACON (HRP-2/Aldolase), percentage incidence was 18% for P. falciparum, 6%were males and 12% were females. Among the symptomatic subjects, incidence rate of P. falciparum malaria was 42% by ACON kits, 38.3% by Bioline SD and 51.7% microscopic method with 58.1% males and 41.9% females.Two samples were positive for P. vivax when diagnosed with ACON (HRP 2/ Pan) but was not detected by microscopy Conclusion: There is the need to improve on the efficacy of available Rapid Diagnostic Test methods and their sensitivity in indicating the presence of P. falciparum and P. vivax antigens in the blood

Non-invasive monitoring of lower-limb ulcers via exudate fingerprinting using BIONOTE

Liquid fingerprinting represents a non-invasive and easy method for diagnostic and screening medical tests. BIONOTE is a sensor system including voltammetric liquid sensors consisting of screen printed electrodes controlled by a high stable electronic interface. Bacterial colonization of lower-limb ulcers gives a huge production of volatile and semi volatile compounds which could modify the electrochemical pattern of ulcer’s exudate. The main goal of this study was to test the electrochemical fingerprinting of biological samples in solution in term of diagnostic accuracy and of feasibility when applied to the study of lower-limb ulcers, where the biological sample consists of ulcer’s exudate. To this scope, BIONOTE’s liquid sensors have been tested in a single-center pilot study. A total number of 30 clinical parameters have been collected for the medical characterization of each patient. A data fusion of the clinical parameters and of the BIONOTE data have been successful in discriminating ulcers evolution. In particular, the correct discrimination percentage between the ulcer analyzed at the first and at the second clinical evaluation (after therapy) was of 75%, 90% and 97.5% when based on clinical data, BIONOTE data and data fusion respectively. The consistency of BIONOTE ability in ulcer monitoring has been also confirmed by a good sensor’s prediction ability with respect to three key-parameters: Leg Ulcer Measurement Tool (LUMT), peripheral oxygen saturation of hemoglobin (SpO2), Transcutaneous oxygen pressure (TcPO2).

A novel orellanine containing mushroom Cortinarius armillatus

Orellanine (3,3′,4,4′-tetrahydroxy-2,2′-bipyridine-1,1′-dioxide) is a tetrahydroxylated di-N-oxidized bipyridine compound. The toxin, present in certain species of Cortinarius mushrooms, is structurally similar to herbicides Paraquat and Diquat. Cortinarius orellanus and Cortinarius rubellus are the major orellanine-containing mushrooms. Cortinarius mushrooms are widely reported in Europe where they have caused human poisoning and deaths through accidental ingestion of the poisonous species mistaken for the edible ones. In North America, Cortinarius orellanosus mushroom poisoning was recently reported to cause renal failure in a Michigan patient. Cortinarius mushroom poisoning is characterized by delayed acute renal failure, with some cases progressing to end-stage kidney disease. There is debate whether other Cortinarius mushroom contain orellanine or not, especially in North America. Currently, there are no veterinary diagnostic laboratories in North America with established test methods for detection and quantitation of orellanine. We have developed two diagnostic test methods based on HPLC and LC-MSMS for identification and quantitation of orellanine in mushrooms. Using these methods, we have identified Cortinarius armillatus as a novel orellanine-containing mushroom in North America. The mean toxin concentration of 145 ug/g was <1% of that of the more toxic C. rubellus. The HPLC method can detect orellanine at 17 μg g−1 while the LC-MSMS method is almost 2000 times more sensitive and can detect orellanine at 30 ng g−1. Both tests are quantitative, selective and are now available for veterinary diagnostic applications.

Methicillin-resistant Staphylococcus aureus multiple sites surveillance: a systemic review of the literature.

PurposeThe objective of this study was to evaluate the optimal number of sampling sites for detection of methicillin-resistant Staphylococcus aureus (MRSA) colonization.MethodsWe performed a Medline search from January 1966 to February 2014 for articles that reported the prevalence of MRSA at different body sites. Studies were characterized by study design, country and period of the study, number of patients and/or isolates of MRSA, specimen type, sites of MRSA isolation, study population sampled, diagnostic testing method, and percentage of the MRSA isolates at each site in relation to the total number of sites.ResultsWe reviewed 3,211 abstracts and 177 manuscripts, of which 17 met the criteria for analysis (n=52,642 patients). MRSA colonization prevalence varied from 8% to 99% at different body sites. The nasal cavity as a single site had MRSA detection sensitivity of 68% (34%–91%). The throat and nares gave the highest detection rates as single sites. A combination of two swabs improved MRSA detection rates with the best combination being groin/throat (89.6%; 62.5%–100%). A combination of three swab sites improved MRSA detection rate to 94.2% (81%–100%) with the best combination being groin/nose/throat. Certain combinations were associated with low detection rates. MRSA detection rates also varied with different culture methods.ConclusionA combination of three swabs from different body sites resulted in the highest detection rate for MRSA colonization. The use of three swab sites would likely improve the recognition and treatment of MRSA colonization, which may in turn reduce infection and transmission of MRSA to other patients.

Lupus erythematosus cells in vivo (pleural fluid): An unusual presentation of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. In earlier times, the diagnosis of SLE included the lupus erythematosus (LE) cell assay. Though the LE cell test has now been declared obsolete, its presence carries importance especially when one finds LE cells in vivo. We report an unusual case of SLE in a 27-year-old female who presented with acute shortness of breath, fever, and cough. On initial outpatient basis investigations, the patient was detected with anemia, bilateral pleural effusion, synovitis, and juxta-articular swelling of the soft tissues. Her chest radiograph effusion was tapped and sent to the cytopathology laboratory. The cytological examination of the pleural fluid revealed numerous LE cells that prompted the diagnosis of SLE. Autoimmune serology techniques such as antinuclear antibody staining have replaced the LE cell assay. However, as presented in this report and found in a review of the literature, the in vivo finding of LE cells by cytopathology can provide an important clue to the diagnosis of SLE. This case is interesting because although pleural effusion is common, very rarely LE Cells are encountered in vivo. There are very few case reports of SLE diagnosed in a cytopathology laboratory. Moreover, our finding of LE cells in the pleural fluid of the patient led to swift diagnosis, helped rule out the differential diagnosis of rheumatoid arthritis and prompted the immediate initiation of treatment. Furthermore, our case highlights the fact that no matter the advances in diagnostic testing methods, practitioners must always keep an eye open for the basic pathognomonic findings of diseases.

Sequence Variant Interpretation 2.0: Perspective on New Guidelines for Sequence Variant Classification.

Diagnostic tests based on next-generation sequencing (NGS),5 including gene-panel, exome, and whole-genome sequencing, are routinely performed worldwide. Although the technical validity of NGS-based tests continues to improve rapidly, the community is working to demonstrate the clinical validity and utility of these methods, which largely depend on our ability to interpret all sequence variants in a thorough, reproducible, timely, and clinically relevant manner. Accurately interpreting variants is challenging. The large volume of variants; the lack of curated information regarding the relationship between variants, gene functions, and clinical consequences; and the lack of consistent roles that capture all aspects of a variant's impact on the normal functions of a gene product are some of the challenges faced by medical geneticists, genetic counselors, and molecular pathologists specializing in molecular diagnostic services. The American College of Medical Genetics and Genomics (ACMG), the Association for Molecular Pathology, and the College of American Pathologists recently jointly released standards and guidelines for the interpretation of sequence variants (1). This collective effort by society leadership groups and the whole genetics community aims to address the above challenges and represents a milestone in NGS-based diagnostic testing. The first set of ACMG variant interpretation guidelines was released in 2008, at a time when Sanger sequencing was the main method of single gene variant detection and molecular diagnostic testing (2). In the 2008 version of these guidelines (referred to here as guidelines 1.0), the decision tree for interpreting a sequence variant started with whether a variant was previously reported as causative of the disease and followed with a prediction based on the nature or type of a variant. Because NGS-based tests often detect numerous previously unreported variants, a classification system based on previously reported variants is of very limited use. Furthermore, population-based exome and whole-genome sequencing projects suggest that many …

Identifying health outcomes in healthcare databases.

The purpose of this review is to assist researchers in developing, using, and interpreting case-identifying algorithms in electronic healthcare databases. We review clinical characteristics of health outcomes, data settings and informatics, and epidemiologic and statistical methods aspects as they pertain to the development and use of case-identifying algorithms. We offer a framework for thinking critically about the use of electronic health insurance data and electronic health records to identify the occurrence of health outcomes. Accuracy of case ascertainment in database research depends on many factors, including clinical and behavioral aspects of the health outcome, and details of database construction as it pertains to completeness and reliability of database content. Existing methods for diagnostic and screening tests, misclassification, validation studies, and predictive modelling can be usefully applied to improve case ascertainment in database research. Good case-identifying algorithms are based on a sound understanding of care-seeking behavior and patterns of clinical diagnosis and treatment in the study population and details about the construction and characteristics of the database. Researchers should use quantitative bias analyses to take into account the performance characteristics of case-identifying algorithms and their impact on study results.

Dielectric and partial discharge investigations on high power insulated gate bipolar transistor modules

This paper investigates on dielectric condition assessment of high power Insulated Gate Bipolar Transistor (IGBT) modules through modern dielectric and diagnostic test methods. Two groups of IGBT samples (new and aged) are selected for this purpose. The new IGBT samples are grouped as 'set-1/virgin' and marked as 'A', 'B', 'C', 'D' and 'E' respectively. Amongst all, a fault (electric puncture) is introduced into the sample 'E'. The samples 'A' and 'B' are maintained virgin while samples 'C', 'D' and 'E' are subjected to partial discharge measurements as recommended by IEC60270. The samples are qualitatively ranked based on their PD level. Subsequently, the dielectric condition of each sample is measured and analyzed over a wide span and frequency. Following this, similar experiments are carried out on IGBT samples that were aged under service and their behaviour over a wide frequency is analyzed. In conclusion, the present study might provide an opportunity in improvement of diagnostic and quality control test methods that are currently exercised on IGBT modules and power conversion devices. Also, these findings enable discrimination of electrical discharges caused by IGBT modules in power conversion equipments which might help in accurate determination of their dielectric condition and reliability.

A 'difficult' insect allergy patient: reliable history of a sting, but all testing negative.

Few conditions are as treatable as allergy to stinging insects, with venom immunotherapy (VIT) providing up to 98% protection to subsequent stings. The challenge with VIT is not in the treatment, but in the diagnosis. To offer VIT, one must determine a history of a systemic reaction to a stinging insect in conjunction with the presence venom-specific IgE. Current diagnostic methods, although sensitive and specific, are imperfect, and some newer testing options are not widely available. A conundrum occasionally faced is the patient with a reliable and compelling history of a systemic allergic reaction yet negative venom-specific testing. This diagnostic dilemma presents an opportunity to consider possible causes for this diagnostic challenge. Our evolving understanding of the role of occult mast cell disease may begin to help us understand this situation and develop appropriate management strategies. Venom-specific skin testing has long been the cornerstone of the evaluation of venom sensitivity and is often combined with in-vitro assays to add clarity, but even these occasionally may fall short. Exploring novel venom diagnostic testing methods may help to fill in some of the diagnostic gaps. Do currently available venom vaccines contain all the key venom species? Are there enough differences between insect species that we may simply be missing the relevant allergens? What is the significance of the antigenicity of carbohydrate moieties in venoms? What is the role of recombinant venom extracts? VIT is the definitive treatment for insect allergic individuals. To utilize VIT, identification of the relevant Hymenoptera is necessary. Unfortunately, this cannot always be accomplished. This deficiency can have several causes: a potential comorbid condition such as occult mast cell disease, limitations of currently available diagnostic resources, or testing vaccines with an insufficient coverage of relevant venom allergens. Exploring these potential causes may help to provide important insight into this important diagnostic conundrum. The use of a case report may help clarify this challenge.

Anti-PLA2R-associated membranous nephropathy: a review with emphasis on diagnostic testing methods.

The majority of cases of primary membranous nephropathy (MN) are associated with auto-antibodies against the podocyte antigen M-type phospholipase A2 receptor (PLA2R). This particular subset of MN can be diagnosed by identifying anti-PLA2R within patient sera or by detecting PLA2R antigen within glomerular immune complexes in renal biopsy tissue. Since the discovery of anti-PLA2R in 2009, there has been an abundance of literature regarding PLA2R testing as a tool in the diagnosis and management of MN, and these tests are increasingly being implemented in clinical practice. However, questions still remain about a variety of issues such as PLA2R testing in the setting of presumably secondary MN and the significance of PLA2R negative primary MN. The goal of this review is to summarize the current PLA2R testing methods and highlight special features of anti- PLA2R-associated MN.

Evaluation of Diagnostic Systems

Diagnostic tools can help schools more consistently and fairly match instructional resources to the needs of their students. To ensure the best educational outcome for each child, diagnostic decision-making systems seek to balance time, clarity, and accuracy. However, recent research notes that many educational decisions tend to be made using professional judgment alone. Judgments grounded on data, statistical models, and even informal prediction models, however, outperform those based on intuition alone. The purpose of this manuscript is to describe the theoretical basis for signal detection and methods for statistically evaluating diagnostic decisions in education. We make recommendations to help test developers and consumers apply this methodology to other diagnostic systems in education and interpret the use of signal detection methods for educational screeners and diagnostic tests.