scholarly journals Assessment of diagnostic accuracy of biomarkers to assess lung consolidation in calves with induced bacterial pneumonia using receiver operating characteristic (ROC) curves

Author(s):  
M Martin ◽  
M D Kleinhenz ◽  
S R Montgomery ◽  
D A Blasi ◽  
K M Almes ◽  
...  

Abstract Bovine respiratory disease (BRD) is the most economically significant disease for cattle producers in the U.S. Cattle with advanced lung lesions at harvest have reduced average daily gain, yield grades and carcass quality outcomes. The identification of biomarkers and clinical signs that accurately predict lung lesions could benefit livestock producers in determining a BRD prognosis. Receiver operating characteristic (ROC) curves are graphical plots that illustrate the diagnostic ability of a biomarker or clinical sign. Previously we used the area under the ROC curve (AUC) to identify cortisol, hair cortisol and infrared thermography imaging as having acceptable (AUC > 0.7) diagnostic accuracy for detecting pain in cattle. Herein, we used ROC curves to assess the sensitivity and specificity of biomarkers and clinical signs associated with lung lesions after experimentally induced bovine respiratory disease (BRD). We hypothesized pain biomarkers and clinical signs assessed at specific timepoints after induction of BRD could be used to predict lung consolidation at necropsy. Lung consolidation of >10% was retrospectively assigned at necropsy as a true positive indicator of BRD. Calves with a score of <10% were considered negative for BRD. The biomarkers and clinical signs analyzed were serum cortisol; infrared thermography (IRT); mechanical nociceptive threshold (MNT); substance P; kinematic gait analysis; a visual analog scale (VAS); clinical illness score (CIS); computerized lung score (CLS); average activity levels; prostaglandin E2 metabolite (PGEM); serum amyloid A and rectal temperature. A total of 5,122 biomarkers and clinical signs were collected from 26 calves, eighteen of which were inoculated with M. haemolytica. All statistics were performed using JMP Pro 14.0. Results comparing calves with significant lung lesions to those without yielded the best diagnostic accuracy (AUC > 0.75) for right front stride length at 0 h; gait velocity at 32 h; VAS, CIS, average activity and rumination levels, step count and rectal temperature, all at 48 h; PGEM at 72 h; gait distance at 120 h; cortisol at 168 h; and IRT, right front force and serum amyloid A, all at 192 h. These results show ROC analysis can be a useful indicator of the predictive value of pain biomarkers and clinical signs in cattle with induced bacterial pneumonia. AUC values for VAS score, average activity levels, step count, and rectal temperature seemed to yield good diagnostic accuracy (AUC > 0.75) at multiple timepoints while MNT values, substance P concentrations, and CLS did not (all AUC values < 0.75).

2021 ◽  
Vol 74 (1) ◽  
Author(s):  
Inmaculada Cuevas-Gómez ◽  
Mark McGee ◽  
José María Sánchez ◽  
Edward O’Riordan ◽  
Nicky Byrne ◽  
...  

Abstract Background Bovine respiratory disease (BRD) is the main cause of mortality among 1-to-5 month old calves in Ireland, accounting for approximately one-third of deaths. Despite widespread use of clinical respiratory signs for diagnosing BRD, lung lesions are detected, using thoracic ultrasonography (TUS) or following post-mortem, in calves showing no clinical signs. This highlights the limitation of clinical respiratory signs as a method of detecting sub-clinical BRD. Using 53 purchased artificially-reared male dairy calves, the objectives of this study were to: (i) characterise the BRD incidence detected by clinical respiratory signs and/or TUS, (ii) investigate the association between clinical respiratory signs and lung lesions detected by TUS, and (iii) assess the effect of BRD on pre-weaning growth. Results Clinical BRD (based on Wisconsin clinical respiratory score and/or rectal temperature > 39.6 ºC) was detected in 43 % and sonographic changes (lung lesions) were detected in 64 % of calves from purchase (23 (SD; 6.2) days of age) until weaning, 53 days post-arrival. Calves with clinical BRD were treated. Sixty-one per cent calves affected with clinical BRD had lung lesions 10.5 days (median) before detection of clinical signs. Moderate correlations (rsp 0.70; P < 0.05) were found between cough and severe lung lesions on arrival day, and between rectal temperature > 39.6 ºC and lung lesions ≥ 2 cm2 on day 7 (rsp 0.40; P < 0.05) post-arrival. Mean average daily live weight gain (ADG) of calves from purchase to weaning was 0.75 (SD; 0.10) kg; calves with or without clinical BRD did not differ in ADG (P > 0.05), whereas ADG of those with severe lung lesions (lung lobe completely consolidated or pulmonary emphysema) was 0.12 kg/d less (P < 0.05) than calves without lung lesions. Conclusions Thoracic ultrasonography detected lung consolidation in calves that did not show signs of respiratory disease. The presence of severe lung lesions was associated with reduced pre-weaning growth. These findings emphasise the importance of using TUS in addition to clinical respiratory scoring of calves for an early and accurate detection of clinical and sub-clinical BRD.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Justyna Gornowicz-Porowska ◽  
Monika Bowszyc-Dmochowska ◽  
Agnieszka Seraszek-Jaros ◽  
Elżbieta Kaczmarek ◽  
Marian Dmochowski

Dermatitis herpetiformis (DH) is an autoimmunity-driven inflammatory blistering dermatosis associated with a gluten-dependent enteropathy. Tissue transglutaminase (tTG) and nonapeptides of gliadin (npG) are considered in its pathomechanism/diagnostics. Here, the diagnostic accuracy of anti-tTG/anti-npG IgA ELISAs in Slavic DH patients with active skin rash was assessed through creating receiver operating characteristic (ROC) curves, determining cutoff values, and calculating correlations between levels of anti-tTG/anti-npG IgA in DH, IgA/neutrophil-mediated non-DH patients and healthy persons. Altogether, sera from 80 Slavic individuals were examined. There were negligible differences between cutoff points obtained by the ELISAs manufacturer and those in this study. There were statistically significant correlations between levels of anti-tTG/anti-npG IgA in both DH group and the group of IgA/neutrophil-mediated non-DH dermatoses. There was no such correlation in healthy controls. It seems that IgA autoantibodies to tTG and npG in the IgA/neutrophil-mediated DH are produced in the coordinated way implying their causal relationship.


Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1059
Author(s):  
Sarah Atef Fahim ◽  
Mahmoud Salah Abdullah ◽  
Nancy A. Espinoza-Sánchez ◽  
Hebatallah Hassan ◽  
Ayman M. Ibrahim ◽  
...  

Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 (ZEB2) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC.


2020 ◽  
Vol 98 (11) ◽  
Author(s):  
Inmaculada Cuevas-Gómez ◽  
Mark McGee ◽  
Matthew McCabe ◽  
Paul Cormican ◽  
Edward O’Riordan ◽  
...  

Abstract This study investigated 1) the effect of clinical bovine respiratory disease (BRD) and associated lung consolidations on growth performance and hematological profiles of recently weaned beef calves and 2) the relationship between clinical respiratory signs and lung consolidation detected by thoracic ultrasonography (TUS). One hundred and fifty-three weaned beef calves (209 days old [SD: 35.8] and 306 kg [SD: 26.3], at arrival) purchased and transported from auction markets were accommodated indoors in concrete slatted floor pens. Calves were weighed weekly from arrival until day 28 and on day 65 post-arrival. Assessment of BRD and blood sample collection for hematological profiles were performed on scheduled days (at arrival, on days 7, 14, and 28) and on other days upon BRD diagnosis. Animals were assessed for BRD using a total clinical respiratory score (CRS) of five clinical signs (rectal temperature, ear position, cough, nasal secretion, and eye secretion with each ranging from normal [0] to abnormal [3]) and TUS scores (normal [0] to lung consolidation ≥ 1 cm2 [2]). Based on CRS, 35% of calves were CRS+ (CRS ≥ 5) and 65% were CRS− (CRS &lt; 5). Although no lung consolidations (TUS−) were detected at arrival, 34% of calves developed lung consolidation (≥1 cm2) (TUS+) during the first 28 d post-arrival. Only fever (&gt;39.6 °C) and nasal discharge were weakly associated (r = 0.19, P &lt;0.05) with lung consolidation. On the day of BRD detection, neutrophil number and neutrophil:lymphocyte ratio were 58% and 73% greater, respectively, in BRD calves with lung consolidation compared with healthy calves. From day 0 to 65, calf average daily gain (ADG) did not differ (P &gt;0.05) between CRS+ and CRS− calves but was 0.09 kg/d lower (P &lt; 0.05) for TUS+ compared with TUS− calves. Calves classified as BRD (CRS + TUS ≥ 5) with lung consolidation had lower (P &lt; 0.05) ADG from arrival until day 28 than healthy calves and BRD calves without lung consolidation (0.11 ± 0.10 vs. 0.53 ± 0.07 vs. 0.57 ± 0.10 kg/d, respectively); however, no differences in ADG were observed from day 0 to 65. Conventional methods to diagnose BRD failed to detect calves with lung lesions. TUS is a useful tool to detect lung lesions and its implementation in combination with CRS should provide a more accurate and early diagnosis of BRD, which is fundamental to successful treatment, animal welfare, and growth performance.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Pilar Cacho-Martínez ◽  
Ángel García-Muñoz ◽  
María Teresa Ruiz-Cantero

Purpose. To analyze the diagnostic validity of accommodative and binocular tests in a sample of patients with a large near exophoria with moderate to severe symptoms.Methods. Two groups of patients between 19 and 35 years were recruited from a university clinic: 33 subjects with large exophoria at near vision and moderate or high visual discomfort and 33 patients with normal heterophoria and low visual discomfort. Visual discomfort was defined using the Conlon survey. A refractive exam and an exhaustive evaluation of accommodation and vergence were assessed. Diagnostic validity by means of receiver operator characteristic (ROC) curves, sensitivity (S), specificity (Sp), and positive and negative likelihood ratios (LR+, LR−) were assessed. This analysis was also carried out considering multiple tests as serial testing strategy.Results. ROC analysis showed the best diagnostic accuracy for receded near point of convergence (NPC) recovery (area = 0.929) and binocular accommodative facility (BAF) (area = 0.886). Using the cut-offs obtained with ROC analysis, the best diagnostic validity was obtained for the combination of NPC recovery and BAF (S  =  0.77, Sp = 1, LR+ = value tending to infinity, LR− = 0.23) and the combination of NPC break and recovery with BAF (S  =  0.73, Sp = 1, LR+ = tending to infinity, LR− = 0.27).Conclusions. NPC and BAF tests were the tests with the best diagnostic accuracy for subjects with large near exophoria and moderate to severe symptoms.


2011 ◽  
Vol 37 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Yaacov Petscher ◽  
Young-Suk Kim

Letter-name identification has been widely used as part of early screening to identify children who might be at risk for future word reading difficulty. The goal of the present study was to examine whether a reduced set of letters could have similar diagnostic accuracy rather than a full set (i.e., 26 letters) when used as a screen. First, we examined whether a hierarchical scale existed among letters by using a Mokken scale analysis. Then, we contrasted diagnostic accuracy among the 5, 10, 15, and 20 easiest letters, with all 26 letters by using receiver operating characteristic (ROC) curves and indices of sensitivity, specificity, positive predictive power, and negative predictive power. Results demonstrated that a hierarchical scale existed among items in the letter-name knowledge test. In addition, assessing students on the easiest 15 letters was not statistically distinguished from all 26 letters in diagnostic accuracy. The implications of the results for the use of a Mokken scale analysis in educational research are discussed.


2006 ◽  
Vol 45 (01) ◽  
pp. 49-56 ◽  
Author(s):  
N. Özdemir-Sahin ◽  
P. Hipp ◽  
W. Mier ◽  
M. Eisenhut ◽  
J. Debus ◽  
...  

Summary Aim was to evaluates the diagnostic accuracy of the SPECTtracers 3-123I-α-methyl-L-tyrosine (IMT) and 99mTc(I)- hexakis(2-methoxyisobutylisonitrile) (MIBI) as well as the PET-tracer 2-18F-2-deoxyglucose (FDG) for detecting tumour progression in irradiated low grade astrocytomas (LGA). Patients, methods: We examined 91 patients (56 males; 35 females; 44.7 ± 11.5 years), initially suffering from histologically proven LGAs (mean WHO grade II) and treated by stereotactic radiotherapy (59.0 ± 4.6 Gy). On average 21.9 ± 11.2 months after radiotherapy, patients presented new Gd-DTPA enhancing lesions on MRI, which did not allow a differentiation between progressive tumour (PT) and non-PT (nPT) at this point of time. PET scans (n=82) were acquired 45 min after injection of 208 ± 32 MBq FDG. SPECT scans started 10 min after injection of 269 ± 73 MBq IMT (n=68) and 15 min after injection of 706 ± 63 MBq MIBI (n=34). Lesions were classified as PT and nPT based on prospective follow-up (clinically, MRI) for 17.2 ± 9.9 months after PET/SPECT. Lesion-to-normal ratios (L/N) were calculated using contra lateraly mirrored reference regions for the SPECT examinations and reference regions in the contra lateral grey (GM) and white matter (WM) for FDG PET. Ratios were evaluated by Receiver Operating Characteristic (ROC) analysis. Results: In the patient groups nPT and PT, L/N ratios for FDG (GS) were 0.6 ± 0.3 vs. 1.2 ± 0.5 (p = 0.003), for FDG (WS) 1.2 ± 0.4 vs. 2.6 ± 0.4 (p <0.001), for IMT 1.1 ± 0.1 vs. 1.8 ± 0.4 (p <0.001) and for MIBI 1.6 ± 0.7 vs. 2.6 ± 2.2 (p = 0.554). Areas under the non-parametric ROC-curves were: 0.738 ± 0.059 for FDG (GS), 0.790 ± 0.057 for FDG (WS), 0.937 ± 0.037 for IMT and 0.564 ± 0.105 for MIBI. Conclusion: MIBI-SPECT examinations resulted in a low accuracy and especially in a poor sensitivity even at modest specificity values. A satisfying diagnostic accuracy was reached with FDG PET. Using WM as reference region for FDG PET, a slightly higher AUC as compared to GM was calculated. IMT yielded the best ROC characteristics and the highest diagnostic accuracy for differentiating between PT and nPT in irradiated LGA.


1978 ◽  
Vol 17 (03) ◽  
pp. 157-161 ◽  
Author(s):  
F. T. De Dombal ◽  
Jane C. Horrocks

This paper uses simple receiver operating characteristic (ROC) curves (i) to study the effect of varying computer confidence of threshold levels and (ii) to evaluate clinical performance in the diagnosis of acute appendicitis. Over 1300 patients presenting to five centres with abdominal pain of short duration were studied in varying detail. Clinical and computer-aided diagnostic predictions were compared with the »final« diagnosis. From these studies it is concluded the simplistic setting of a 50/50 confidence threshold for the computer program is as »good« as any other. The proximity of a computer-aided system changed clinical behaviour patterns; a higher overall performance level was achieved and clinicians performance levels became associated with the »mildly conservative« end of the computers ROC curve. Prior forecasts of over-confidence or ultra-caution amongst clinicians using the computer-aided system have not been fulfilled.


Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 949
Author(s):  
Cecil J. Weale ◽  
Don M. Matshazi ◽  
Saarah F. G. Davids ◽  
Shanel Raghubeer ◽  
Rajiv T. Erasmus ◽  
...  

This cross-sectional study investigated the association of miR-1299, -126-3p and -30e-3p with and their diagnostic capability for dysglycaemia in 1273 (men, n = 345) South Africans, aged >20 years. Glycaemic status was assessed by oral glucose tolerance test (OGTT). Whole blood microRNA (miRNA) expressions were assessed using TaqMan-based reverse transcription quantitative-PCR (RT-qPCR). Receiver operating characteristic (ROC) curves assessed the ability of each miRNA to discriminate dysglycaemia, while multivariable logistic regression analyses linked expression with dysglycaemia. In all, 207 (16.2%) and 94 (7.4%) participants had prediabetes and type 2 diabetes mellitus (T2DM), respectively. All three miRNAs were significantly highly expressed in individuals with prediabetes compared to normotolerant patients, p < 0.001. miR-30e-3p and miR-126-3p were also significantly more expressed in T2DM versus normotolerant patients, p < 0.001. In multivariable logistic regressions, the three miRNAs were consistently and continuously associated with prediabetes, while only miR-126-3p was associated with T2DM. The ROC analysis indicated all three miRNAs had a significant overall predictive ability to diagnose prediabetes, diabetes and the combination of both (dysglycaemia), with the area under the receiver operating characteristic curve (AUC) being significantly higher for miR-126-3p in prediabetes. For prediabetes diagnosis, miR-126-3p (AUC = 0.760) outperformed HbA1c (AUC = 0.695), p = 0.042. These results suggest that miR-1299, -126-3p and -30e-3p are associated with prediabetes, and measuring miR-126-3p could potentially contribute to diabetes risk screening strategies.


Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 298
Author(s):  
Esther Dirks ◽  
Phebe de Heus ◽  
Anja Joachim ◽  
Jessika-M. V. Cavalleri ◽  
Ilse Schwendenwein ◽  
...  

A 23-year-old pregnant warmblood mare from Güssing, Eastern Austria, presented with apathy, anemia, fever, tachycardia and tachypnoea, and a severely elevated serum amyloid A concentration. The horse had a poor body condition and showed thoracic and pericardial effusions, and later dependent edema and icteric mucous membranes. Blood smear and molecular analyses revealed an infection with Theileria equi. Upon treatment with imidocarb diproprionate, the mare improved clinically, parasites were undetectable in blood smears, and 19 days after hospitalization the horse was discharged from hospital. However, 89 days after first hospitalization, the mare again presented to the hospital with an abortion, and the spleen of the aborted fetus was also PCR-positive for T. equi. On the pasture, where the horse had grazed, different developmental stages of Dermacentor reticulatus ticks were collected and subjected to PCR, and one engorged specimen was positive for T. equi. All three amplicon sequences were identical (T. equi genotype E). It is suspected that T. equi may repeatedly be transmitted in the area where the infected mare had grazed, and it could be shown that transmission to the fetus had occurred. Due to the chronic nature of equine theileriosis and the possible health implications of infection, it is advised to include this disease in the panel of differential diagnoses in horses with relevant clinical signs, including horses without travel disease, and to be aware of iatrogenic transmission from inapparent carrier animals.


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