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Silicon image sensor technology for in vivo detection of surfactant-induced corneocyte swelling and drying.

BACKGROUND: Several instrumental methods can indirectly assess some specific aspects of cutaneous irritation at the level of the stratum corneum (SC). OBJECTIVE: There is a need for developing more sensitive approaches in this field. METHODS: We assessed a recently introduced innovative tool (SkinChip) based on capacitive pixel-sensing technology in its potential to detect early discrete manifestations of skin irritation. The sensor generates a detailed non-optical picture corresponding to a capacitance map of the skin surface reaching 50 microm pixel resolution. Some topographical details can be easily disclosed and the SC hydration as well. Two surfactant solutions were tested on volunteers. These solutions were applied under test patches for 2 days on the volar forearms. Clinical and SkinChip assessments were performed 3 h after removing the patch. RESULTS: The generated images allowed a precise observation of skin irritation which appeared as a two-step process. Early changes consisted of darker pixels corresponding to overhydrated swollen corneocytes at the irritated sites. Two days later, the same area appeared as white pixels, indicating the loss of corneocyte hydration. CONCLUSION: The SkinChip device appears to be a very sensitive tool for detecting the early steps of surfactant-induced skin irritation affecting the SC.

Dermatitis, Irritant↗

Detection and quantitation of human immunodeficiency virus type 1 using molecular DNA/RNA technology.

The direct detection and quantitation of human immunodeficiency virus type 1 are becoming increasingly important for diagnosis and viral load determinations in human immunodeficiency virus type 1 infection. Traditional molecular-based assays such as Southern, Northern, and in situ hybridization have had limited application in this area due to the relatively low number of proviral copies per cell, the low percentage of infected cells, and transcriptional dormancy in many of the infected cells. Recent technological advances in polymerase chain reaction assays promise a number of useful applications in the clinical research and clinical laboratory setting.

Acquired Immunodeficiency Syndrome↗

Biosensor technology for real-time detection of the cystic fibrosis W1282X mutation in CFTR.

In the present paper, biospecific interaction analysis (BIA) was performed using surface plasmon resonance (SPR) and biosensor technologies to detect the Trp1282Ter mutation (W1282X) of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene. We first immobilized on a SA5 sensor chip a single-stranded biotinylated oligonucleotide containing the sequence involved in this mutation, and the efficiency of hybridization of oligonucleotide probes differing in length was determined. Second, we immobilized on different SA5 sensor chips biotinylated polymerase-chain reaction (PCR) products from a normal subject as well as from heterozygous and homozygous W1282X samples. The results obtained show that both allele-specific 10- and 12-mer oligonucleotides are suitable probes to detect W1282X mutations of the cystic fibrosis gene under standard BIA experimental conditions. During the association phase performed at 25 degrees C, discrimination between mismatched and full matched hybrids was readily and reproducibly observed by using the 10-mer W1282X probes. By contrast, when the 12-mer DNA probes were employed, discrimination between mismatched and full matched hybrids was observed during the dissociation phase. Taken together, the results presented suggest that BIA is an easy, speedy, and automatable approach to detect point mutations leading to cystic fibrosis. By this procedure, it is possible to perform real-time monitoring of hybridization between target single stranded PCR products obtained by using as substrates DNA isolated from normal or heterozygous subjects, and homozygous W1282X CF samples and oligonucleotide probes, therefore enabling a one-step, non-radioactive protocol to perform diagnosis.

Automation↗

SARS and population health technology.

The recent global outbreak of SARS (severe acute respiratory syndrome) provides an opportunity to study the use and impact of public health informatics and population health technology to detect and fight a global epidemic. Population health technology is the umbrella term for technology applications that have a population focus and the potential to improve public health. This includes the Internet, but also other technologies such as wireless devices, mobile phones, smart appliances, or smart homes. In the context of an outbreak or bioterrorism attack, such technologies may help to gather intelligence and detect diseases early, and communicate and exchange information electronically worldwide. Some of the technologies brought forward during the SARS epidemic may have been primarily motivated by marketing efforts, or were more directed towards reassuring people that "something is being done," ie, fighting an "epidemic of fear." To understand "fear epidemiology" is important because early warning systems monitoring data from a large number of people may not be able to discriminate between a biological epidemic and an epidemic of fear. The need for critical evaluation of all of these technologies is stressed.

Communicable Diseases↗

[Microcytomorphometric video-image detection of nuclear chromatin in ovarian cancer].

UNLABELLED: Technology of detection of tissue preparates precisious evaluates contents of nuclear chromatine, largeness and shape of cellular nucleus, indicators of mitosis, DNA index, ploidy, phase-S fraction and other parameters. Methods of detection of picture are: microcytomorphometry video-image (MCMM-VI), flow, double flow and activated by fluorescence. Diagnostic methods of malignant neoplasm of ovary are still nonspecific and not precise, that is a reason of unsatisfied results of treatment. OBJECTIVE: Evaluation of microcytomorphometric measurements of nuclear chromatine histopathologic tissue preparates (HP) of ovarian cancer and comparison to normal ovarian tissue. MATERIAL AND METHODS: Estimated 10 paraffin embedded tissue preparates of serous ovarian cancer, 4 preparates mucinous cancer and 2 cases of tumor Kruckenberg patients operated in Clinic of Perinatology and Gynaecology Silesian Medical Academy in Zabrze in period 2001-2002, MCMM-VI estimation based on computer aided analysis system: microscope Axioscop 20, camera tv JVCTK-C 1380, CarlZeiss KS Vision 400 rel.3.0 software. Following MCMM-VI parameters assessed: count of pathologic nucleus, diameter of nucleus, area, min/max diameter ratio, equivalent circle diameter (Dcircle), mean of brightness (mean D), integrated optical density (IOD = area x mean D), DNA index and 2.5 c exceeding rate percentage (2.5 c ER%). MCMM-VI performed on the 160 areas of 16 preparates of cancer and 100 areas of normal ovarian tissue. Statistical analysis was performed by used t-Student test. RESULTS: We obtained stastistically significant higher values parameters of nuclear chromatine, DI, 2.5 c ER of mucinous cancer and tumor Kruckenberg comparison to serous cancer. MCMM-VI parameters of chromatine malignant ovarian neoplasm were statistically significantly higher than normal ovarian tissue. CONCLUSION: Cytometric and karyometric parametres of nuclear chromatine estimated MCMM-VI are useful in the diagnostics and prognosis of ovarian cancer.

Cell Nucleus↗

Evaluation of the accuracy of SNAP technology sleep sonography in detecting obstructive sleep apnea in adults compared to standard polysomnography.

OBJECTIVE: To determine the accuracy of snoring and apnea analysis by SNAP (SNAP Laboratories; Glenview, IL), a technology that uses snoring recorded by a home microphone system and nasal airflow, to diagnose obstructive sleep apnea (OSA) as well as determine its severity. METHODS: For all patients who had undergone a prior SNAP study and were referred to the Sleep Disorders Center of Lifespan Hospitals for polysomnography testing from January 2000 through December 2001, we compared the results of the SNAP study to standard polysomnography (polysomnography). The severity of each apnea-hypopnea index (AHI) [mild, moderate, or severe, as defined by the AHI Severity Task Force of the American Academy of Sleep Medicine] recorded by SNAP was compared to that of the polysomnography result. All polysomnography tests were scored independently and without the prior knowledge of any SNAP results. RESULTS: For the 31 patients on whom data were available, the mean age, body mass index, and Epworth sleepiness scale scores were 50.3 years (range, 29 to 77 years), 31.6 kg/m(2) (range, 24 to 44 kg/m(2)), and 11.3 (range, 1 to 20), respectively. The mean follow-up time between the two studies was 5 months. The severity criteria indicated by the SNAP study accurately assessed the true severity confirmed by polysomnography in only 11 of 31 patients (35.5%). When the AHI severity score from the SNAP study was compared to polysomnography using a kappa statistic measure of agreement, there was overall agreement with a kappa value of 0.23 (p = 0.008), but the agreement was only fair. SNAP study severity scores were overestimated in 13 of 31 patients (41.9%) compared to the polysomnography results. In the majority of these subjects (8 of the 13 "overestimated" patients or 8 of 31 total patients [25.8%]), the SNAP study diagnosed OSA when the patient had a normal polysomnography finding. CONCLUSION: Although there may be some night-to-night variability in polysomnography testing, these results suggest that SNAP studies do not appear to accurately assess the severity of OSA.

Adult↗

Detection of dermcidin-derived peptides in sweat by ProteinChip technology.

Recently, a novel antimicrobial peptide DCD-1, derived from the Dermcidin (DCD) gene and secreted by sweat glands, has been described by Schittek et al. [Nat. Immunol. 2 (2001) 1133.]. Here we describe the application of the surface-enhanced laser desorption/ionisation (SELDI) technology for the detection of DCD-1 and other dermcidin-derived peptides directly from microlitre amounts of human sweat. The advantages of the technique are as follows: (a) it can be carried out with ease and rapidity; (b) multiple samples can be processed simultaneously; (c) prior purification is not required; and (d) only a limited sample volume is necessary for both protein profiling and semiquantitation. Profiling of human sweat from various donors revealed that in addition to DCD-1, other DCD-derived peptide species were also present in significant quantities. Four of five identified peptides were DCD-1 related, while the fifth corresponded to a portion of the DCD protein outside the DCD-1 core. This provides clues as to how the novel protein is processed to its active form, though further work remains to elucidate this fully. Thus, we have demonstrated the applicability of such technology to the detection of DCD-1 and for the protein profiling of sweat in general. Such studies could reveal valuable new biomarkers for diagnosis and treatment of skin and sweat gland disorders.

Amino Acid Sequence↗

Caries detection and diagnosis: novel technologies.

Recent years have seen an increase in research activity surrounding diagnostic methods, particularly in the assessment of early caries lesions. The drive for this has come from two disparate directions. The first is from the dentifrice industry who are keen to develop techniques that would permit caries clinical trials (CCTs) to be reduced in duration and subject numbers to permit the investigation of novel new anti-caries actives. The second is from clinicians who, armed with the therapies to remineralise early lesions are now seeking methods to reliably detect such demineralised areas and implement true preventative dentistry. This review examines novel technologies and the research supporting their use. Techniques based on visual, optical, radiographic and some emerging technologies are discussed. Each have their benefits although systems based on the auto-fluorescence (such as QLF) of teeth and electrical resistance (such as ECM) seem to offer the most hope for achieving reliable, accurate detection of the earliest stages of enamel demineralisation.

Dental Caries↗

Cervical false negative cases detected by neural network-based technology. Critical review of cytologic errors.

OBJECTIVE: To analyze the cytological errors made in the manual screening of cervical smears and to evaluate the usefulness of neural network-based technology (nnbt) in the detection of different kinds of errors. STUDY DESIGN: We reviewed 1,981 cervical smears by nnbt. Twelve false negatives (FNs) were detected and selected for study. The number of cell images showing atypical keratosis or atypical cells was evaluated on the monitor. The cellular features of the atypical cells (cellularity, cell type, nuclear and cytoplasmic changes, cellular arrangement and location on the slide) were analyzed by optic microscopy. Considering these qualitative and quantitative cytologic parameters and the diagnosis made by manual screening, we classified the errors into two groups: screening and interpretation related. RESULTS: Four FNs were screening errors. Five FNs were classified as errors of interpretation. In three cases the cause of the cytologic errors could not be ascertained. CONCLUSION: Our results confirm previous studies demonstrating that nnbt is useful for detecting screening errors. We also showed that it might be an adjunctive tool in the interpretation of abnormal cells, reducing the number of false negatives.

Diagnostic Errors↗

Airborne rhinovirus detection and effect of ultraviolet irradiation on detection by a semi-nested RT-PCR assay.

BACKGROUND: Rhinovirus, the most common cause of upper respiratory tract infections, has been implicated in asthma exacerbations and possibly asthma deaths. Although the method of transmission of rhinoviruses is disputed, several studies have demonstrated that aerosol transmission is a likely method of transmission among adults. As a first step in studies of possible airborne rhinovirus transmission, we developed methods to detect aerosolized rhinovirus by extending existing technology for detecting infectious agents in nasal specimens. METHODS: We aerosolized rhinovirus in a small aerosol chamber. Experiments were conducted with decreasing concentrations of rhinovirus. To determine the effect of UV irradiation on detection of rhinoviral aerosols, we also conducted experiments in which we exposed aerosols to a UV dose of 684 mJ/m2. Aerosols were collected on Teflon filters and rhinovirus recovered in Qiagen AVL buffer using the Qiagen QIAamp Viral RNA Kit (Qiagen Corp., Valencia, California) followed by semi-nested RT-PCR and detection by gel electrophoresis. RESULTS: We obtained positive results from filter samples that had collected at least 1.3 TCID50 of aerosolized rhinovirus. Ultraviolet irradiation of airborne virus at doses much greater than those used in upper-room UV germicidal irradiation applications did not inhibit subsequent detection with the RT-PCR assay. CONCLUSION: The air sampling and extraction methodology developed in this study should be applicable to the detection of rhinovirus and other airborne viruses in the indoor air of offices and schools. This method, however, cannot distinguish UV inactivated virus from infectious viral particles.

Air Microbiology↗

Women and medicalisation: an empirical examination of the extent of women's dependence on medical technology in the early detection of breast cancer.

Recent criticisms of the thesis of medicalisation focusing at the level of doctor-patient interaction have suggested that patient dependency on or addiction to modern scientific medicine and in particular medical scientific technology is overstated. However, empirical research to examine this is difficult to find. The study presented here throws some light on this issue as it looks at women's beliefs and feelings about breast screening and breast self-examination and the prospect of attending for breast screening or a class which teaches BSE. The results show that the generalised concept of patient dependence is limited although there was more support for women's dependence on medical technology than choosing to be directly responsible for identifying abnormalities themselves and managing them.

Attitude↗

Rapid diagnostics: the detection of neuraminidase activity as a technology for high-specificity targets.

The accurate detection of influenza by clinical symptoms is challenging since multiple pathogenic viruses and bacteria mimic similar symptoms in a patient. With new and more effective influenza therapeutics available, there is a growing need for highly accurate and rapid diagnosis of influenza, particularly when the window of opportunity for proper treatment is measured in hours. A parallel technology, which is also used in the treatment of influenza, was developed for the rapid diagnosis of influenza by exploiting the enzymatic activity of influenza neuraminidase. This technology, which is called Pathozyme, offers the high specificity inherent from the conservation of the neuraminidase active site. The ZstatFlu test uses a small molecule derivative of sialic acid chemically coupled to a reporter group together with simple point-of-care reagents for directly detecting influenza from a patient specimen with high specificity. A second-generation platform technology using this neuraminidase detection system coupled with a more sensitive chemiluminescent reporter has been developed and formatted for reading on high-speed instant film. This modification resulted in a platform technology many-fold more sensitive than the former while maintaining its inherent high specificity. Preliminary data from a prototype tested during the mild 2000-2001 influenza season demonstrated that an optimized chemiluminescent test system could approach the accuracy of 14 day viral culture in a convenient 10-20 min test. This platform technology is currently being explored for the rapid detection of other pathogenic organisms where sensitivity, specificity and speed are essential in a point-of-care setting.

Amino Acid Sequence↗

Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review.

Medium chain acyl-CoA dehydrogenase (MCAD) is a tetrameric flavoprotein essential for the beta-oxidation of medium chain fatty acids. MCAD deficiency (MCADD) is an inherited error of fatty acid metabolism. The gene for MCAD is located on chromosome one (1p31). One variant of the MCAD gene, G985A, a point mutation causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD protein, has been found in 90% of the alleles in MCADD patients identified retrospectively. There is a high frequency of MCADD among people of Northern European descent, which is believed to be due to a founder effect. MCADD is inherited in an autosomal recessive manner. Of patients clinically diagnosed with MCADD, 81% who have been identified retrospectively are homozygous for K304E, and 18% are compound heterozygotes for K304E. Clinical data on the probability of clinical disease indicates that MCADD patients are at risk for the following outcomes: hypoglycemia, vomiting, lethargy, encephalopathy, respiratory arrest, hepatomegaly, seizures, apnea, cardiac arrest, coma, and sudden and unexpected death. Long-term outcomes include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit disorder (ADD). Differences in clinical disease specific to allelic variants have not been documented. Factors that may increase risk for disease onset or modify disease severity are age when the first episode occurred, fasting, and presence of infection. Acute attacks must be treated immediately with appropriate intravenous doses of glucose. For those diagnosed, long-term management of the disease includes preventing stress caused by fasting and maintaining a high-carbohydrate, reduced-fat diet, and carnitine supplementation. Hospitalization costs attributable to morbidity and mortality from MCADD are unknown; MCADD is not a diagnosis in the International Classification of Disease, 10th Revision (ICD-10) codebook. Furthermore, the penetrance of the MCAD genotypes is unknown; there appears to be a substantial number of asymptomatic MCADD individuals and some uncertainty regarding which individuals will manifest symptoms and which individuals will remain asymptomatic. Several technologies are available to detect MCADD. Diagnostic technologies include DNA-based tests for K304E mutations using the polymerase chain reaction (PCR), and the detection of abnormal metabolites in urine. Screening technologies include tandem mass spectrometry (MS/MS), which detects abnormal metabolites mostly in blood. State programs are beginning to offer screening in newborns for MCADD using MS/MS. In addition, a private company currently offers voluntary supplemental newborn screening for MCADD to birthing centers.

Acyl-CoA Dehydrogenases↗

Detection of mononucleotide repeat sequence alterations in a large background of normal DNA for screening high-frequency microsatellite instability cancers.

PURPOSE: Mutations in mononucleotide repeat sequence (MRS) are good indicators of high-frequency microsatellite instability (MSI-H) cancers, but it has been a challenge to detect such mutations in a large background of wild-type DNA; as in this setting, PCR errors often generate false positive mutant alleles. In this study, we developed a general strategy, referred to as probe clamping primer extension-PCR (PCPE-PCR), to detect MRS alterations in a large background of wild-type DNA. EXPERIMENTAL DESIGN: In PCPE-PCR, genomic DNA is first subjected to PCPE, in which mutant single-strand DNA molecules are preferentially produced. Next, genomic DNA is removed to enrich for the mutant DNA fraction. Thereafter, PCR is carried out using the remaining single-strand DNA molecules as templates. Finally, the PCR products are analyzed to reveal the MSI-H status. In this study, the sensitivity of this new method was first examined by spiking mutant DNA into wild-type DNA at specific ratios followed by studying whether this method is applicable to fecal DNA testing. RESULTS: We showed that PCPE-PCR could detect both mutated BAT26 and transforming growth factor-beta-RII (A)10 markers in the presence of 500-fold excess of normal DNA and that as few as three copies of mutated DNA could be detected. In addition, we showed that this technology could detect MSI-H colorectal cancer by fecal DNA analysis. CONCLUSION: PCPE-PCR is sensitive. In addition, PCPE-PCR is simple and amendable to a cost-effective and high-throughput screening operation. This technology may be applicable to noninvasive screening of MSI-H cancer.

Acetyltransferases↗

[Comparison of detectability of visual field abnormality by frequency doubling technology in primary open-angle glaucoma and normal-tension glaucoma].

PURPOSE: To compare the effectiveness of frequency doubling technology(FDT) in detecting abnormalities in primary open-angle glaucoma(POAG) and normal-tension glaucoma(NTG). SUBJECTS AND METHODS: Twenty-nine POAG patients (29 eyes) and 27 NTG-patients(27 eyes) were studied. All subjects underwent testing with program C-20 of FDT with appropriate corrective lenses. RESULTS: No significant differences were observed between the two groups in mean age, mean deviation(MD), and pattern standard deviation(PSD) measured by the Humphrey Field Analyzer(HFA). The correlation between MD values determined by HFA(x) and FDT(y) is represented by y = 0.60x - 2.7 (r = 0.78, p < 0.01) in the POAG group and y = 0.59x + 0.6 (r = 0.81, p < 0.001) in the NTG group. No significant difference was found in the average PSD between the two groups. In early glaucoma cases (MD > or = -5 dB by HFA), a larger proportion of cases in the POAG group than the NTG group had a lower significance level of MD determined by FDT than by HFA (p < 0.02). At many test points on the temporal periphery in FDT the mean sensitivity was lower in the POAG group than in the NTG group; whereas no significant differences among HFA test points were observed. CONCLUSIONS: FDT detected visual field abnormalities in POAG cases more sensitively than in NTG cases. This finding indicates that the pathogenesis of My-cell damage is different in POAG and NTG.

Glaucoma↗

Genomic DNA detection using cycling probe technology and capillary gel electrophoresis with laser-induced fluorescence.

Cycling probe technology (CPT) is an isothermal DNA analysis method that has been shown to be useful for identifying genetic markers of antibiotic-resistant bacteria in clinical settings. CPT assays have previously employed several assay methods that include polyacrylamide gel electrophoresis and magnetic beads for separations and radioisotopic and colorimetric detection for detection. Capillary gel electrophoresis with laser-induced fluorescence (CGE-LIF) is an alternative separation and detection method that offers attributes such as low sample consumption, short analysis times, no radiation hazards and potential for high throughput. We report on the development of a CGE-LIF CPT assay for genomic DNA from Erwinia herbicola and the comparison of this assay with a conventional 32p radioisotopic PAGE CPT assay. Separation and detection of intact and cleaved fluorescein-labeled CPT probe molecules by CGE-LIF was achieved in under 4 min through a gel-filled capillary (7 cm separation length to detector). Total time, from setup to detection, was about 1 h for the complete assay versus several hours (3-12 h) for the radioisotopic PAGE CPT assay. Similar detection limits of 10(5)-10(6) copies of genomic target DNA were observed with each assay method. This study demonstrated that CGE-LIF CPT is a suitable analysis method for the detection of genomic DNA sequences.

DNA Probes↗

Case study of the morphologic variation of circulating tumor cells.

We report a detailed cytomorphologic evaluation of the circulating component of widely metastatic breast carcinoma. A previously healthy 38-year-old woman was diagnosed with breast cancer. Wide local excision revealed a 1.7-cm infiltrating ductal adenocarcinoma, BSR score 7/9 with angiolymphatic invasion, and 4/20 lymph nodes positive for carcinoma. Five years later, a bone marrow biopsy revealed involvement of bone marrow by metastatic breast carcinoma, and shortly thereafter, metastases were identified in the liver and lung hilum. She enrolled in a clinical investigation for the detection of circulating tumor cells (CTCs) in breast carcinoma. A total of 659 CTCs were identified in a 10-mL blood sample using an immunofluorescent protocol targeting cytokeratins and detected using fiber-optic array scanning technology. The detected CTCs were subsequently stained with a Wright-Giemsa stain, and representative cells were evaluated in detail by light microscopy for morphologic evaluation. We find that the patient's CTCs exhibit a high degree of pleomorphism including CTCs with high and low nuclear-to-cytoplasmic ratios along with CTCs exhibiting early and late apoptotic changes. In addition, in comparison with her tumor cells in other sites, the full morphologic spectrum of cancer cells present in primary and metastatic tumor is also present in peripheral blood circulation.

Adult↗

Frequency doubling technology and confocal scanning ophthalmoscopic optic disc analysis in open-angle glaucoma with hemifield defects.

PURPOSE: To evaluate the potential of frequency doubling technology for detecting early glaucomatous damage. PATIENTS AND METHODS: Forty-nine eyes of 49 patients with open-angle glaucoma with visual field defects only in one hemifield according to the Humphrey Field Analyzer 30-2 program were included. Forty-five healthy patients were also included as control subjects. In each patient, frequency doubling technology with the threshold N-30 program and optic disc analysis using the Heidelberg Retina Tomograph was performed. Frequency doubling technology test results and the Humphrey Field Analyzer test results were compared. Optic disc parameters corresponding to the hemifield designated intact by the Humphrey Field Analyzer were compared between the eyes in which the hemifield was normal by frequency doubling technology and those in which the hemifield was abnormal. RESULTS: Forty-one percent of the 49 hemifields designated intact by the Humphrey Field Analyzer were abnormal based on frequency doubling technology, whereas 98% of the 49 hemifields designated defective by the Humphrey Field Analyzer were abnormal and 12% of the 90 hemifields designated intact by the Humphrey Field Analyzer were abnormal in healthy patients. The percentage of the hemifields designated abnormal by frequency doubling technology was significantly higher than that in healthy patients (P < 0.001). The rim volume was significantly smaller in eyes with abnormal results based on frequency doubling technology than in eyes with normal results (P < 0.05, paired t test, with Bonferroni correction for multiple comparison). CONCLUSION: Frequency doubling technology can detect glaucomatous damage earlier than conventional static perimetry can.

False Positive Reactions↗