Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal ...sensitivity and can be time‐consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well‐controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well‐characterized patients with DHR and to develop new tests for diagnosis.
•Detecting M. bovis antibodies in cattle sera after a tuberculin skin test (TST) may improve bovine tuberculosis control.•Used as an anamnestic test, the ELISA reported herein had high levels of ...specificity and positive predictive value.•The ELISA fulfilled the World Organization for Animal Health criteria.•This serological ELISA used 15–17 days after a negative TST could be used on dairy farms to improve livestock health.
Programs for the eradication of bovine tuberculosis (bTB) focus on the tuberculin skin test (TST) and slaughter of reactor cattle. However, the disease remains an animal health concern in several countries and improving the efficiency of the TST has become a critical issue. The detection of Mycobacterium bovis antibodies in serum, within weeks after the TST, may be a rapid and inexpensive way to improve bTB control. This study reports the validation of an enzyme-linked immunosorbent assay (ELISA) to detect bovine tuberculosis as an ancillary test to TST in dairy farms in Argentina.
The estimated validation parameters were within the established requirements of the World Organization for Animal Health (OIE). The test demonstrated high repeatability, with coefficients of variation <25%. High test reproducibility through interlaboratory testing was also found, with an estimated Pearson coefficient of 0.9648 (95% confidence intervals 0.9315–0.9820). The ELISA detected tuberculous cattle unidentified by the TST. Of 43 animals sent to slaughterhouses that were ELISA positive 15–17 days after a negative TST, 36 were confirmed as infected with M. bovis by histopathology and IS6110 PCR. According to ROC curve analysis of results of 145 cattle from M. bovis-free herds and the 36 M. bovis-infected cattle, at a corrected optical density cut-off point of 0.3853, specificity was 95.95% and the positive predictive value at this cut-off was 83.72%. The ELISA detection test validated in this study could be readily applied in dairy farms, to complement a prior TST and improve livestock health.
Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. A prespecified aim of WASID was to ...identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy.
WASID was a randomized, double-blinded, multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50% to 99% stenosis of a major intracranial artery. Median time from qualifying event to randomization was 17 days, and mean follow-up was 1.8 years. Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of these strokes were in the territory of the stenotic artery. Risk of stroke in the territory of the stenotic artery was highest with severe stenosis > or =70% (hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P=0.0025) and in patients enrolled early (< or =17 days) after the qualifying event (hazard ratio 1.69; 95% confidence interval 1.06 to 2.72; P=0.028). Women were also at increased risk, although this was of borderline significance (hazard ratio 1.59; 95% confidence interval 1.00 to 2.55; P=0.051). Location of stenosis, type of qualifying event, and prior use of antithrombotic medications were not associated with increased risk.
Among patients with symptomatic intracranial stenosis, the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis > or =70%, after recent symptoms, and in women.
The first observing run of Advanced LIGO spanned 4 months, from 12 September 2015 to 19 January 2016, during which gravitational waves were directly detected from two binary black hole systems, ...namely GW150914 and GW151226. Confident detection of gravitational waves requires an understanding of instrumental transients and artifacts that can reduce the sensitivity of a search. Studies of the quality of the detector data yield insights into the cause of instrumental artifacts and data quality vetoes specific to a search are produced to mitigate the effects of problematic data. In this paper, the systematic removal of noisy data from analysis time is shown to improve the sensitivity of searches for compact binary coalescences. The output of the PyCBC pipeline, which is a python-based code package used to search for gravitational wave signals from compact binary coalescences, is used as a metric for improvement. GW150914 was a loud enough signal that removing noisy data did not improve its significance. However, the removal of data with excess noise decreased the false alarm rate of GW151226 by more than two orders of magnitude, from 1 in 770 yr to less than 1 in 186 000 yr.
The chemical coupling of a protoplasmatic antigen from Mycobacterium avium subsp. paratubeculosis onto core-shell carboxylated particles was investigated with the aim of producing latex-protein ...complexes to be used in immunoagglutination assays capable of detecting bovine paratuberculosis disease. For this purpose, sensitizations were carried out using both colored and not colored carboxylated latexes as well as the protoplasmatic antigen at pH close to its isoelectric point to favor the antigenic protein to approach the particle surface. In all cases, higher fractions of proteins were chemically-bound to carboxyl groups on the surface of the particles. The assessment of the performance of the visual immunoagglutination assays consisted of evaluating 111 sera from healthy and infected bovines with Mycobacterium avium subsp. paratuberculosis. Complexes obtained from the colored latex allowed an acceptable visual discrimination between the studied positive and negative sera. Most of the positive samples showed strong to very strong agglutination and only a few samples reacted weakly, i.e. a sensitivity of 70%. The specificity of the assay, on the other hand, was 86%. Therefore, this rapid detection technique allows an easy and inexpensive identification of animals possibly infected with paratuberculosis “in situ” in the herds.
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•A visual immunoagglutination assay for the diagnosis of bovine paratuberculosis was developed.•The reagent is based on colored latex particles and a commercial paratuberculosis protoplasmic antigen.•The agglutination can be read after 5 min “in situ” in the herds and it is easy to implement.•The agglutination test may be a rapid and inexpensive diagnostic strategy to control PTB.
In a previous study, we evaluated the degree of virulence of Mycobacterium avium subsp. paratuberculosis (Map) strains isolated from cattle in Argentina in a murine model. This assay allowed us to ...differentiate between high-virulent MapARG1347 and low-virulent MapARG1543 strains. To corroborate whether the differences in virulence could be attributed to genetic differences between the strains, we performed Whole Genome Sequencing and compared the genomes and gene content between them and determined the differences related to the reference strain MapK10. We found 233 SNPs/INDELS in one or both strains relative to Map K10. The two strains share most of the variations, but we found 15 mutations present in only one of the strains. Considering NS-SNP/INDELS that produced a severe effect in the coding sequence, we focus the analysis on four predicted proteins, putatively related to virulence. Survival of MapARG1347 strain in bMDM was higher than MapARG1543 and was more resistant to acidic pH and H2O2 stresses than MapK10. The genomic differences between the two strains found in genes MAP1203 (a putative peptidoglycan hydrolase), MAP0403 (a putative serine protease) MAP1003c (a member of the PE-PPE family) and MAP4152 (a putative mycofactocin binding protein) could contribute to explain the contrasting phenotype previously observed in mice models.
•WGS of Argentinian isolates with contrasting pathogenic phenotypes.•Phylogenetic analysis with whole genome sequences available from GenBank.•Identification of NS-SNP and INDELS by comparative genomic analysis.
There are limited data on the relationship between control of vascular risk factors and vascular events in patients with symptomatic intracranial arterial stenosis.
We utilized the Warfarin Aspirin ...Symptomatic Intracranial Disease study database to analyze vascular and lifestyle risk factors at baseline and averaged over the course of the trial. Cutoff levels defining good control for each factor were prespecified based on national guidelines. Endpoints evaluated included 1) ischemic stroke, myocardial infarction, or vascular death or 2) ischemic stroke alone. Univariate associations were assessed using the log-rank test and multivariable analysis was done using Cox proportional hazards regression.
From baseline until year 2 follow-up, there was not a significant improvement in blood pressure control. During the same period, there were improvements in patients with total cholesterol <200 mg/dL (54.6% to 79.2%, p < 0.001) or low-density lipoprotein <100 mg/dL (28.7% to 55.9%, p < 0.001). Multivariable analysis showed that systolic blood pressure >or=140 mm Hg (HR = 1.79, p = 0.0009, 95% confidence limits 1.27 to 2.52), no alcohol consumption (HR 1.69, 1.21 to 2.39, p = 0.002), and cholesterol >or=200 mg/dL (HR 1.44, 1.004 to 2.07, p = 0.048) were associated with an increased risk of stroke, myocardial infarction, or vascular death. The same risk factors were predictors of ischemic stroke alone in multivariable analysis.
Elevated blood pressure and cholesterol levels in symptomatic patients with intracranial stenosis are associated with an increased risk of stroke and other major vascular events.
The WASID trial showed no advantage of warfarin over aspirin for preventing the primary endpoint of ischemic stroke, brain hemorrhage, or vascular death. In analyses of selected subgroups, there was ...no definite benefit from warfarin. Warfarin reduced the risk of the primary endpoint among patients with basilar artery stenosis, but there was no reduction in stroke in the basilar artery territory or benefit for vertebral artery stenosis or posterior circulation disease in general.
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