Positive ID Research Articles

Evaluation of the ID NOW among symptomatic individuals during the Omicron wave.

Introduction. Starting in December, 2020, the ID NOW was implemented throughout the province of Alberta, Canada (population 4.4 million) in various settings.Gap statement. ID NOW's test performance with SARS-CoV-2 Omicron variant BA.1 is unknown.Aim. To assess the ID NOW performance among symptomatic individuals during the BA.1 Omicron wave and compare it to previous SARS-CoV-2 variant waves.Methodology. The ID NOW was assessed in two locations among symptomatic individuals: rural hospitals and community assessment centres (AC) during the period 5-18 January 2022. Starting 5 January, Omicron represented >95 % of variants detected in our population. For every individual tested, two swabs were collected: one for ID NOW testing and the other for either reverse-transcriptase polymerase chain reaction (RT-PCR) confirmation of negative ID NOW results or for variant testing of positive ID NOW results.Results. A total of 3041 paired samples were analysed (1139 RT-PCR positive). From this, 1873 samples were from 42 COVID-19 AC and 1168 from 69 rural hospitals. ID NOW sensitivity for symptomatic individuals presenting to community AC and rural hospitals was 96.0 % [95 % confidence interval (CI) 94.5-97.3 %, n=830 RT-PCR positive], and 91.6 % (95 % CI 87.9-94.4 %, n=309 RT-PCR positive), respectively. SARS-CoV-2 positivity rate was very high for both populations (44.3 % at AC, 26.5 % in hospital).Conclusions. Sensitivity of ID NOW SARS-CoV-2, compared to RT-PCR, is very high during the BA.1 Omicron wave, and is significantly higher when compared to previous SARS-CoV-2 variant waves.

Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized with NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR)

Introduction: Proteasome inhibitors (PI) and immunomodulatory drugs have become the backbone of therapy for multiple myeloma (MM). The oral boron-containing selective and reversible proteasome inhibitor ixazomib has shown to induce deep and durable responses (Kumar RK et la, Blood 2016. 128(20):2415-2422). Triplets containing ixazomib, has shown to be more efficacious than doublet regimens in the relapse setting (Moreau P, et al. N Engl J Med 2016. 374:1621-1634).However, to date, there is not companion diagnostics capable of predicting PI response. We have recently discovered that MM patients resistant to PI lack of the ankyrin (ANK) and death domain (DD) present in the 3'-end of NFKB2. Loss of NFKB2 3'end frequently resulted from a structural rearrangements. We found that NFKB2-ANK and -DD are crucial at initiating bortezomib's apoptotic signal by facilitating caspase-8 activation (unpublished data). Based on this findings, we designed this study to examine the efficacy of NFKB2 break apart FISH to predict the response to ixazomib and dexamethasone (Id) vs. ixazomib, lenalidomide and dexamethasone (IRd) in early relapse MM patients. Methods: In this phase 2 biomarker-driven open-label trial, relapsed patients with <4 lines of therapy were randomized to ixazomib 4 mg weekly 3 of 4 weeks and 40 mg weekly dexamethasone vs. Id plus 25 mg of lenalidomide daily days 21/28, based on the status of NFKB2 rearrangement in plasma cells. Patients were screened for NFKB2 rearrangement detected by NFKB2 break apart FISH. Patients without NFKB2 rearrangement received Id and patients with NFKB2 rearrangement were subsequently randomized in a 1:1 fashion to receive Id or IRd. The primary endpoint is to compare the response rate (MR or better) of Id or IRd at 4 cycles according to the rearrangement status of NFKB2 Results: At the moment of the interim analysis, 69 out of 71 patients have achieved 4 cycles of treatment. All treatment groups (NFKB2 FISH [-] Id, n=27, NFKB2 FISH [+] Id, n=21 and IRd, n=21) received a median of 2 prior lines of therapy. A trend to higher ORR was observed in NFKB2 FISH negative treated with Id compared with NFKB2 FISH positive (59% CI:43.6%-74.4% vs. 42% CI:17.5%-67.3%, P=0.2, target p-value goal 0.15), including significantly higher rates of ≥ very good partial response, ≥ partial response, ≥ minimal response (15%, 25%, 15% vs. 4.7%, 23.8%, 14.2%, respectively). ORR for IRd arm was higher the patients with an NFKB2 positive FISH treated with Id (65%:CI:48.5%-81.5% vs. 42% CI:17.5%-67.3%, P=0.15). Progression free survival (PFS) at 12 and 24 months was higher in patients treated with Id with negative NFKB2 FISH than those with positive FISH ( 40.7 % CI:20.3-60% and 35% CI:15.6-55% vs 21% CI 7-41%, p-value 0.012 and 35% CI:15.6-55% vs 10.7% CI: 1.8- 28.7%, p-value:0.002, respectively). Treatment with IRd in patients with positive NFKB2 FISH demonstrated higher PFS at 12 months compared to those treated with Id (46% CI: 23-67% vs 21% CI 7-41%, p-value of 0.004). However, this difference disappeared after 18 months. Interestingly, >G2 treatment related adverse events were higher in Arm A (66%) and Arm C (55%) vs Arm B (28%). The most common (≥10%) ≥ grade 3 include URI/pneumonia 15% and diarrhea 22% in Id NFKB2 FISH negative vs. URI 10% (10%) in the Id NFKB2 FISH positive arm. Treatment discontinuations only occurred in 3 NFKB2 FISH positive Id treated patient (13%). Conclusion: Interim analysis demonstrates a trend higher efficacy and significantly better PFS in ixazomib with dexamethasone in MM patients with negative NFKB2 break-apart FISH compared to those with a positive test. Efficacy and toxicity of the triplet regimen are somewhat lower than what is seen in the Tourmaline 1 trial. This study is registered clinicaltrials.gov# NCT02765854

Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized with NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR)

Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized with NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR)

M010 DIAGNOSTIC CHALLENGE IN EVALUATING THE RISK AND MANAGEMENT OF ALLERGIC REACTION(S) TO SARS-COV-2 VACCINES

The frequency of immediate hypersensitivity reactions following immunization with either the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) mRNA vaccines poses a clinical challenge for the allergist-immunologist. Anaphylaxis to the mRNA COVID-19 vaccines is currently estimated to occur in 2.5 to 11.1 cases per 1 million doses. Although excipients [polyethylene glycol (PEG), and polysorbate] and specific mRNA and Ad26.COV2.S components in COVID-19 vaccines have been cited as potential causative allergens, PEG is considered the likely culprit in mRNA vaccines. However, several skin testing published protocols using PEG have yielded conflicting results. We present a patient who developed anaphylaxis after the first dose of BNT 162b2 who was evaluated by PEG, polysorbate, and COVID-19 vaccine skin testing. A 49-year-old female, with a known atopic history, was evaluated for an anaphylactic reaction to BNT 162B2 vaccine occurring within 30 minutes after the first dose. Pruritic symptoms, facial urticaria, tongue swelling, and wheezing progressed to full body hives and difficulty breathing. Following treatment with epinephrine, IV diphenhydramine, and IV steroids, her symptoms improved. SPT and ID skin testing to PEG, polysorbate 80, and the BNT 162B2 and JNJ-78436735 (Johnson and Johnson) were negative except for positive ID testing to polysorbate 80. Negative SPT and ID skin testing with both excipients and vaccine specific components argues against an IgE-mediated mechanism and suggests a non-IgE mechanism. IgE skin testing may have no value as a predictive biomarker of susceptibility to allergic reactions of the mRNA COVID-19 vaccines and will require more research focused on non-IgE mechanisms.

Expose the true and false faces of the Asian Giant Hornets

The goal of this article is to build a dynamics prediction model, in order to estimate the propagation characteristics of Asian giant hornets in Washington State. We expect to implement some strategies for the Washington State Department of Agriculture to reduce the losses caused by the biological invasion. This paper build up to Hornet's dynamics prediction model. About this Model, firstly produce the positive ID data visualization points, then use the vector radial circle to examine the estimated propagation direction. Then, according to the Leslie population growth model [1], a propagation dynamics model (time series model) was established. Then, the model was used to construct a propagation diffusion map for the next few years.

Evaluation of MicroScan Bacterial Identification Panels for Low-Resource Settings.

Bacterial identification is challenging in low-resource settings (LRS). We evaluated the MicroScan identification panels (Beckman Coulter, Brea, CA, USA) as part of Médecins Sans Frontières’ Mini-lab Project. The MicroScan Dried Overnight Positive ID Type 3 (PID3) panels for Gram-positive organisms and Dried Overnight Negative ID Type 2 (NID2) panels for Gram-negative organisms were assessed with 367 clinical isolates from LRS. Robustness was studied by inoculating Gram-negative species on the Gram-positive panel and vice versa. The ease of use of the panels and readability of the instructions for use (IFU) were evaluated. Of species represented in the MicroScan database, 94.6% (185/195) of Gram-negative and 85.9% (110/128) of Gram-positive isolates were correctly identified up to species level. Of species not represented in the database (e.g., Streptococcus suis and Bacillus spp.), 53.1% out of 49 isolates were incorrectly identified as non-related bacterial species. Testing of Gram-positive isolates on Gram-negative panels and vice versa (n = 144) resulted in incorrect identifications for 38.2% of tested isolates. The readability level of the IFU was considered too high for LRS. Inoculation of the panels was favorably evaluated, whereas the visual reading of the panels was considered error-prone. In conclusion, the accuracy of the MicroScan identification panels was excellent for Gram-negative species and good for Gram-positive species. Improvements in stability, robustness, and ease of use have been identified to assure adaptation to LRS constraints.

Safety of yellow fever vaccine administration in confirmed egg-allergic patients

Yellow fever vaccine (YFV) is recommended in endemic areas but represents a risk for egg-allergic patients, as it is cultivated in embryonated eggs. This study aims to describe the outcomes of yellow fever vaccination in patients with confirmed egg allergy (EA). Methods:A prospective study was conducted from January 2018 to September 2019. EA was diagnosed through positive oral food challenge (OFC), recent history of anaphylaxis following egg contact (anaphylaxis in the last 6 months) or immediate allergic reaction in the last 2 months with positive specific IgE. A skinprick test (SPT) with YFV was performed. If the SPT was negative, an intradermal test (ID) was performed at a 1:100 dilution. If the ID was negative, a full dose of YFV was administered. If the skin prick test or ID were positive, the YFV was administered using a graded dosing protocol. Results: It was included 58 patients with confirmed egg allergy (36 M:22F), with a median age of 2.3 years (0.7–13.9 y/o). Forty-two patients had a positive OFC. Nine reported recent anaphylaxis. The other 7 had reactions in the last 2 months with positive specific IgE. During OFC, 15 presented anaphylaxis, while the other 27 presented hives and/or angioedema or vomiting. SPT with YFV was negative in all patients. ID was negative in 48 patients who uneventfully received a full dose of YFV. Ten patients had a positive ID and received YFV in graded doses. Six patients presented a mild reaction controlled with antihistamines, and 4 patients received the vaccine without reactions. Positive ID was significantly related to the vaccine reaction (p < 0.0001). Administration of YFV using a specific protocol was safe even in anaphylactic patients. However, we recommend performing the ID, which can help predict a higher risk of vaccine reaction. An appropriate setting is required to control adverse events.

Safety of yellow fever vaccine administration in confirmed egg-allergic patients

The yellow fever vaccine (YFV) is recommended in endemic areas but represents a risk for egg-allergic patients, as it is cultivated in chicken embryos. This study aims to describe the outcomes of yellow fever vaccination in patients with confirmed egg allergy (EA). Prospective study in a quaternary hospital, from January 2018 to September 2019. EA was diagnosed through oral food challenge (OFC) or recent history of anaphylaxis following egg contact (anaphylaxis in the last 6 months) or allergic reaction in the last 2 months with positive specific IgE. Skin prick test (SPT) with YFV was performed in all participants. If negative SPT, an intradermal test (ID) was performed at 1:100 dilution. If negative ID, a full dose of YFV was administered. If positive skin test, the YFV was administered using a graded-dose protocol. Among 100 patients with prior EA history, 58 were confirmed (36M:22F), median age of 2.35y (0,7 a 13,9Y). Forty-two patients had a positive OFC. Nine reported recent anaphylaxis. The other 7 had reaction in the last 2 months with positive specific IgE. During OFC, 15 presented anaphylaxis and the other (27) presented urticaria and/or angioedema or vomiting. SPT with YFV was negative in all patients. ID was negative in 48 patients, who received a full dose of YFV in usual manner, uneventfully. Ten patients had a positive ID and received the YFV in graded doses, six of them presented a mild reaction controlled with antihistamines and four patients received the vaccine without reactions. Positive ID was significantly related to vaccine reaction (p=0,0001). Administration of YFV using a specific protocol was safe even in anaphylactic patients. We only recommend performing the ID test which contributed to predicting a higher risk of vaccine reaction. An appropriate setting is required in order to control adverse events.

Concordance of confirmatory prostate biopsy in active surveillance with national guidelines: An analysis from the multi-institutional PURC cohort

PurposeNational Comprehensive Cancer Network (NCCN) guidelines recommend confirmatory biopsy within 12 months of active surveillance (AS) enrollment. With <10 cores on initial biopsy, re-biopsy should occur within 6 months. Our objective was to determine if patients on AS within practices in the Pennsylvania Urologic Regional Collaborative (PURC) receive guideline concordant confirmatory biopsies. Materials and MethodsWithin PURC, a prospective collaborative of diverse urology practices in Pennsylvania and New Jersey, we identified men enrolled in AS after first biopsy, analyzing time to re-biopsy and factors associated with various intervals of re-biopsy. ResultsIn total, 1,047 patients were enrolled in AS for a minimum of 12 months after initial biopsy. Four hundred seventy-seven (45%) underwent second biopsy at 1 of the 9 PURC practices. The number of patients undergoing re-biopsy within 6 months, 6 to 12 months, 12 to 18 months, and >18 months was 71 (14%), 218 (45.7%), 134 (28%), and 54 (11%), respectively. Sixty percent underwent confirmatory biopsy within 12 months. On multivariate analysis, re-biopsy interval was associated with number of positive cores, perineural invasion, and practice ID (all P < 0.05). Adjusted multivariable regression did not identify factors predictive of re-biopsy interval. ConclusionOf patients who underwent confirmatory biopsy at PURC practices, 60.5% were within 12 months per NCCN guidelines. This suggests area for improvement in guideline adherence after enrollment in AS. All practices that offer AS should periodically perform similar analyses to monitor their performance. In an era of value-based care, adherence to guideline based active surveillance practices may eventually comprise national quality metrics affecting provider reimbursement.

Ceftriaxone allergy in a pediatric cohort

Ceftriaxone allergy in children is common and in this small cohort we aimed to characterize the demographic and clinical histories of 14 children with reported immediate drug hypersensitivity to ceftriaxone. Data was collected from children presenting to the Montreal Children’s Hospital with suspected ceftriaxone allergy. A standardized questionnaire was completed by the patient’s parents about the suspected allergic reaction. We had a total of 14 children who had history of allergic reaction after receiving ceftriaxone. Among the 14 patients with suspected ceftriaxone allergy,60% were males and median age was 7 (IQR: 2.90,13.13). Among all,12 (85%) underwent skin testing to ceftriaxone including prick tests and intradermal (ID 20mg/ml ).Three patients (25%) had a positive ID test and were instructed to avoid ceftriaxone and 9 patients (75%) had a negative skin test. Among the group with negative skin tests, three (33 %) had a negative challenge to ceftriaxone,4 patients (44%) had a negative oral challenge to cephalosporins but were not interested in ceftriaxone challenge and one patient was instructed to avoid all cephalosporins completely given a history of mild liver disturbance and eosinophilia which was suggestive of DRESS.There was one patient with negative skin testing and a pending IV ceftriaxone challenge. The majority of children in this cohort with a history of immediate hypersensitivity reactions to ceftriaxone had negative skin testing and one-third had a successful challenge to IV ceftriaxone. We aim to extend our cohort to determine factors associated with true ceftriaxone allergy.

Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized with NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR)

Introduction: Proteasome inhibitors (PI) and immunomodulatory drugs have become the backbone of therapy for multiple myeloma (MM). The oral boron-containing selective and reversible proteasome inhibitor ixazomib has shown to induce deep and durable responses (Kumar RK et la, Blood 2016. 128(20):2415-2422). Triplets containing ixazomib, has shown to be more efficacious than doublet regimens in the relapse setting (Moreau P, et al. N Engl J Med 2016. 374:1621-1634).However, to date, there is not companion diagnostics capable of predicting PI response. We have recently discovered that MM patients resistant to PI lack of the ankyrin (ANK) and death domain (DD) present in the 3'-end of NFKB2. Loss of NFKB2 3'end frequently resulted from a structural rearrangements. We found that NFKB2-ANK and -DD are crucial at initiating bortezomib's apoptotic signal by facilitating caspase-8 activation (unpublished data). Based on this findings, we designed this study to examine the efficacy of NFKB2 break apart FISH to predict the response to ixazomib and dexamethasone (Id) vs. ixazomib, lenalidomide and dexamethasone (IRd) in early relapse MM patients. Methods: In this phase 2 biomarker-driven open-label trial, relapsed patients with &lt;4 lines of therapy were randomized to ixazomib 4 mg weekly 3 of 4 weeks and 40 mg weekly dexamethasone vs. Id plus 25 mg of lenalidomide daily days 21/28, based on the status of NFKB2 rearrangement in plasma cells. Patients were screened for NFKB2 rearrangement detected by NFKB2 break apart FISH. Patients without NFKB2 rearrangement received Id and patients with NFKB2 rearrangement were subsequently randomized in a 1:1 fashion to receive Id or IRd. The primary endpoint is to compare the response rate (MR or better) of Id or IRd at 4 cycles according to the rearrangement status of NFKB2 Results: At the moment of the interim analysis, 50 patients have achieved 4 cycles of treatment. All treatment groups (NFKB2 FISH [-] Id, n=24, NFKB2 FISH [+] Id, n=13 and IRd, n=12) received a median of 2 prior lines of therapy. A trend to higher ORR was observed in NFKB2 FISH negative treated with Id compared with NFKB2 FISH positive (48% CI:58%-97% vs. 23% CI:8%-60%, P=0.1), including significantly higher rates of ≥ very good partial response, ≥ partial response, ≥ minimal response (16%, 29%, 12.5% vs. 0.7%, 18%, 18%, respectively). ORR for IRd arm is for now 54% CI:27%-80%. Interestingly, &gt;G3 treatment related adverse events were higher in Arm A (45%) and Arm C (60%) vs Arm B (15%). The most common (≥10%) ≥ grade 3 include URI/pneumonia 16% and diarrhea 12% in Id NFKB2 FISH negative vs. neutropenia 18% and diarrhea (10%) in the IRd NFKB2 FISH positive arm. Treatment discontinuations only occurred in 3 NFKB2 FISH positive Id treated patient (13%). Conclusion: Interim analysis demonstrates a trend higher efficacy and ≥G3 toxicity of ixazomib with dexamethasone in MM patients with negative NFKB2 break-apart FISH compared to those with a positive test. Efficacy and toxicity of the triplet regimen are comparable to what is seen in the Tourmaline 1 trial. This study is registered clinicaltrials.gov# NCT02765854 Disclosures Bernal-Mizrachi: TAKEDA: Research Funding; Winship Cancer Institute: Employment, Patents &amp; Royalties; Kodikas Therapeutic Solutions, Inc: Equity Ownership. Nooka:GSK: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation; GSK: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation; Janssen: Honoraria, Other: advisory board participation; Celgene: Honoraria, Other: advisory board participation; BMS: Honoraria, Other: advisory board participation; Takeda: Honoraria, Other: advisory board participation; Amgen: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation; BMS: Honoraria, Other: advisory board participation. Ye:Portola Pharmaceuticals: Research Funding; MingSight: Research Funding; Janssen: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Onyx: Research Funding; Celgene: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Vij:Takeda: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Genentech: Honoraria. Hofmeister:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Nektar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Imbrium: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees. Rushton:KSLBiomedical: Employment. Lonial:Genentech: Consultancy; Karyopharm: Consultancy; Celgene Corporation: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy; BMS: Consultancy; Janssen: Consultancy, Research Funding; GSK: Consultancy. Kaufman:Amgen: Consultancy; Winship Cancer Institute of Emory University: Employment; AbbVie: Consultancy; Takeda: Consultancy; Celgene: Consultancy; TG Therapeutics: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria.

The administration of blood components: a British Society for Haematology Guideline.

The administration of blood components: a British Society for Haematology Guideline.

Using a new molecular genetic of genotype and liquid culture medium for rapid diagnosis tb

This paper presents the results of molecular genetic test system GenoType multyresistentens MTBDRplus. It was established that the presence of mutations associated with resistance to isoniazid, only 93.1 % of cases of MBT to isoniazid during the test in a liquid medium. Work carried out under the National Programme to combat tuberculosis Materials and methods. We investigated the clinical sputum samples from patients with pulmonary tuberculosis. The applied system GenoType. Principle DNA strip technology GenoType is that the DNA-coated strip specific test that are complementary to the derived PCR amplicon. After the single-stranded amplicon denaturation associated with tests on strip (hybridize), and visualized in a sequential enzymatic reaction with streptavydynom and alkaline phosphatase. Evaluation of hybridization is performed automatically. For culturing sputum liquid culture medium used - Middlebrook broth 7N9 VASTES MGIT system. Results and discussion . The results of molecular genetic studies of samples of sputum-concentrated and concentrated by a system GenoType not differed (P>0.05). Diagnostic value of two methods (molecular and genetic – system GenoType and phenotype – VASTES MGIT 960 system) was very high (100%). Two systems have tested positive in the study 756 (95.5 %) Mycobacterium strains that were identified in the system VASTES MGIT 960, formed Cord Factor and the results were positive identification test ID MTB MGIT they attributed to Mycobacterium tuberculosis complex. 36 (4.5 %) samples from positive MGIT tubes were negative. As a result of molecular-genetic identification of nontuberculous mycobacteria complex it was found that 18 (2.3 %) strains of mycobacteria belonging to the M. avium-intracellulare, 12 (1.5 %) mycobacterial cultures were attributed to M. kansasii, 6 (0, 7 %) cultures were identified as M. fortuitum. The results of the molecular study of MS on Mycobacterium resistance profile INN + RIF coincided in 95.5 % (894 strains) the results of testing by phenotypic proportions. In the presence of mutations associated with resistance to INH, only 93.1 % of cases observed MC M. tuberculosis to INH during TMCH in a liquid medium Middlebrook 7N9. In the presence of mutations in the genes responsible for resistance to the presence of Q, in a liquid medium only 288 (90.6 %) strains of M. tuberculosis have MS to Ofx. The strains of mycobacteria DNA were detected mutations in genes associated with MS to aminoglycosides / cyclic peptides in 299 (94.0%) cases were resistant to Am and 302 (94.9 %) cases were resistant to the results Cm DST system VASTES MGIT 960. In determining the resistance to E major differences were found between the productivity of molecular genetic and phenotypic research methods – only 206 (64, 2 %) strains of M. tuberculosis were resistant to the analysis system VASTES MGIT 960. Conclusions. GenoType system allows you to quickly carry out the identification and differentiation of Mycobacterium strains of nontuberculous mycobacteria. The results of the molecular genetic studies multyrezystents system GenoType MTBDRplus match in 95,5 % of the phenotypic test results by proportions. Using DNA strip technology GenoType to determine mutations in the genes of Mycobacterium responsible for the IPU to TDC, necessarily requires a parallel DST setting in a liquid medium

Intradermal penicillin skin test is more likely to be positive compared to prick skin test in patients with a history of penicillin allergy

Background Penicillin skin testing (PST) with the major determinant (benzyl-penicilloyl) and minor determinant mix (penicillin G, benzyl-penicilloate, and benzyl-penilloate) is one of the major diagnostic tools in the evaluation of a penicillin allergy mediated by IgE. The PST begins with a skin prick test (SP) with the above components and, if negative, then proceeds to an intradermal testing (ID). However, it is unclear in the literature, how often the PST is positive to SP compared to ID testing. Hence, we conducted this study to determine the rates of positive PST to SP compared to ID skin test. Methods Basic demographics (gender and age) and rates of positive ID PST compared to SP PST were determined in patients with a history of penicillin allergy undergoing penicillin allergy evaluation from June 1, 2002 to June 30, 2004. A wheal and flare 3x3mm greater than the negative control was defined as a positive PST. The gender and rates of ID versus SP PST were presented as percentages and the age in years. Using Fisher’s exact test, we compared the difference in the proportion of males and females who had a positive SP vs. ID PST. P 0.05 was considered statistically significant. The IRB approved the study and all subjects signed a written informed consent. Results 1,759 patients with a history of penicillin allergy underwent PST. The mean age (SD) was 60 iA 15 years (5517 years in the positive PST group versus 60 15 years in the negative PST group). Among the positive PST, 53 (83%) were females and 11 (17%) were males. 64 of 1759 (4%) had a positive PST to either SP or ID testing. Among the positive PST patients, 3 of 64 (5%) had a positive SP compared to 61 (95%) ID skin testing. Gender did not appear to increase the rates of positive ID PST compared to SP [2 of 3 (66%) females were positive to SP PST compared 51 of 61 (84%) females were positive ID PST; p=0.44]. Conclusion ID PST is more likely to be positive compared to SP PST in patients with a history penicillin allergy.

Design and Evaluation of a Variable-Flux Flux-Intensifying Interior Permanent-Magnet Machine

This paper presents a design approach for interior permanent-magnet (IPM) machines with variable-flux characteristics using low-coercive-force magnets for improved efficiency and extended operating speed range. A flux-intensifying IPM type with is used in the design due to positive Id operation and reduced loaded Iq effects. Design considerations of machine structures and variable-flux machine attributes are discussed. In addition, leakage flux in a rotor is particularly designed to also obtain another flux-varying capability. Evaluation of the designed machine is provided by finite-element analysis simulations and experiments on a proof-of-principle machine. The designed machine shows benefits in increasing efficiency and speed range in a low-torque region when variable magnetization control of the low-coercive-force magnets or the design of the leakage flux proposed in this paper is implemented.

Massive Mortality Associated with Streptococcus agalactiae Infection in Cage-cultured Red Hybrid Tilapia Oreochromis niloticus in Como River, Kenyir Lake, Malaysia

Massive mortality of cage-cultured red hybrid tilapia Oreochromis niloticus in Como River, Kenyir Lake, Malaysia was investigated. Moribund fish showing erratic swimming, sluggishness and hemorrhagic eyes were collected for the study. Water quality parameters were measured on-site. The highest temperature was 32.70°C at the surface while lower temperature was 30.85°C at 6 m. Dissolved Oxygen (DO) was highest 7.05 mg L-1 at 4 m while lowest 6.15 mg L-1 at 10 m. The pH value was highest 8.28 at 6 m and lowest 7.52 at surface. The result has shown that un-ionized ammonia levels ranged from 0.00046-0.01 ppm within the optimum range. While Nitrite (0.003 ppm) and Nitrate values (0.1-0.7 ppm). The water quality parameters were showed their values within the accepted range of water quality for aquaculture. Bacteria were isolated from diseased fish using blood and nutrient agars, and identified using BBL Crystal™ Enteric/Non-fermenter ID and Gram Positive ID Systems and subjected to antibiotic susceptibility analysis. Results showed the presence of Streptococcus agalactiae, Burkholderia cepacia in the fish liver and Staphylococcus aureus in the fish eyes, suggesting a possible case of warm-water streptococcosis associated with S. agalactiae with multiple bacterial complications. Nevertheless, a continuous long term monitoring is essential for the sustainable development of cage aquaculture in Como river of Lake Kenyir Malaysia.

Neuropathic Pain in Breast Cancer Survivors: Using the ID Pain as a Screening Tool

Neuropathic pain (NP) is a debilitating symptom experienced by a number of patients with cancer. We evaluated the validity of ID Pain as a screening tool for NP in breast cancer survivors using the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and a reported diagnosis of NP as criterion measures. Two hundred forty breast cancer survivors with a mean age of 58 years (standard deviation=16) participated in this survey. Forty-five percent of the sample reported having pain in the past week. Of those reporting pain, 33% reported that they had been diagnosed by their health care provider with NP, 39% had a positive ID Pain (> or = 2) score, and 19% had a positive S-LANSS score. The most commonly endorsed ID Pain item was "hot/burning" (n=48) followed by feeling "numb" (n=47) and "pins and needles" (n=45). Total ID Pain score was significantly associated with a clinical diagnosis of NP (r=0.41; P<0.001) and the S-LANSS total score (r=0.54; P<0.001). Receiver operating curve analysis demonstrated that ID Pain has a predictive validity of 0.72 and 0.70 for diagnosis of NP as made by clinicians and the S-LANSS, respectively. We also found that an ID Pain score greater than or equal to 2 corresponded with the likelihood of NP in this sample, consistent with the original ID Pain development study. This study provides evidence for ID Pain as a valid screening measure for NP in breast cancer survivors.

Modular Automation Platforms: A Case Study of a Flexible NMR Sample Preparation Robot

A variety of features used by our Department in the design and integration of Automation Platforms are presented here. A challenging project for any automation group is the automation of NMR sample preparation. The dispensing of highly volatile or viscous solutions into the typical 5 mm ID NMR glass tube, and the subsequent capping of the tube, presents unique problems. An angled incremental single-channel dispensing technique prevents bubble formation when a 10-mM protein—based solute is used. A novel gripper finger design, used in conjunction with in-house fabricated Teflon caps, allows reliable capping of NMR tubes. In situ vortexing minimizes vial handling with increased throughput. Magnetic mounting of robot tools (hands) provides precise snap-in positioning with collision-safe breakaway. This simplifies crash recovery during development testing and production use. A wraparound Safety Enclosure with modular safety circuit fulfills ANSI/RIA R15.06–1999 Safety Requirements. Flexible control software permits run interruption for loading and preparation of additional NMR tubes. Prepared samples may be removed during run interruption. A “Fly-By” barcode scanning tool enables positive compound sample ID with improved throughput. Preexisting instrument control software is conveniently interfaced to a Scheduler application through an open-architecture instrument integration framework. This framework allows the development of automation platform—independent Middleware for schedule and assay portability. A new generation of low-power, lightweight, portable and expandable platforms is also presented where a building block tandem approach is used in conjunction with the Rent-a-robot concept for robot recycling.

Health effects of a mold-contaminated automobile

Rationale Most reactions to indoor mold exposure have been reported from mold-contaminated homes, office buildings or schools. We report a patient who experienced symptoms from exposure to a contaminated air-conditioner in her automobile. Methods A patient with a two-year history of generalized symptoms that continued despite taking two months off of work was skin tested and administered the Rhinitis Outcome Questionnaire (ROQ) and Cognitive Questionnaire (CQ) to assess her symptoms. Her indoor environments were also tested for mold contamination. Her home was tested using the Allergenco MK-3 Sampler for which we consider normal indoor counts below 1000 spores/M 3. The mold counts in the patient's car were tested using an Anderson Sampler for which we consider normal counts less than 200 CFU/M 3. Results The patient had positive ID testing to Alternaria, Aspergillus, Penicillium and Cladosporium. The indoor mold counts in her home did not indicate indoor mold growth. The ROQ and CQ both gave similar results, showing low, non-allergic symptom scores before exposure, then moderate to severe symptoms at the height of exposure and a return to baseline upon avoidance of exposure. The result of testing her car with the ventilation system running was high: 1,740 CFU/M 3, Penicillium (42%) and Aspergillus (58%). Avoidance of the car brought about a marked improvement in symptoms and she was able to return to work. Conclusions This case demonstrates that we should be testing work environments, homes and schools for mold contamination and must now add automobiles to our testing regimen where indicated.

Molecular and idiotypic analyses of the antibody response to Cryptococcus neoformans glucuronoxylomannan-protein conjugate vaccine in autoimmune and nonautoimmune mice.

The antibody response to Cryptococcus neoformans capsular glucuronoxylomannan (GXM) in BALB/c mice frequently expresses the 2H1 idiotype (Id) and is restricted in variable gene usage. This study examined the immunogenicity of GXM-protein conjugates, V (variable)-region usage, and 2H1 Id expression in seven mouse strains: BALB/c, C57BL/6, A/J, C3H, NZB, NZW, and (NZB x NZW)F(1) (NZB/W). All mouse strains responded to vaccination with GXM conjugated to tetanus toxoid (TT), the relative magnitude of the antibody response being BALB/c approximately C3H > C57BL/6 approximately NZB approximately NZW approximately NZB/W > A/J. Analysis of serum antibody responses to GXM with polyclonal and monoclonal antibodies to the 2H1 Id revealed significant inter- and intrastrain differences in idiotype expression. Thirteen monoclonal antibodies (MAbs) (two immunoglobulin M [IgM], three IgG3, one IgG1, three IgG2a, two IgG2b, and two IgA) to GXM were generated from one NZB/W mouse and one C3H/He mouse. The MAbs from the NZB/W mouse were all 2H1 Id positive (Id(+)) and structurally similar to those previously generated in BALB/c mice, including the usage of a V(H) from the 7183 family and Vkappa5.1. Administration of both 2H1 Id(+) and Id(-) MAbs from NZB/W and C3H/H3 mice prolonged survival in a mouse model of cryptococcosis. Our results demonstrate (i) that V-region restriction as indicated by the 2H1 Id is a feature of both primary and secondary responses of several mouse strains; and (ii) that there is conservation of V-region usage and length of the third complementarity-determining region in antibodies from three mouse strains. The results suggest that V-region restriction is a result of antibody structural requirements necessary for binding an immunodominant antigen in GXM.