Validation of the Accuracy of Automatic Measurement of Blood Volume in Culture Bottles for Blood Culture

Several manufacturers have developed systems that automatically measure the amount of blood in culture bottles. We compared the volumes measured automatically by the Virtuo instrument (bioMérieux, France) (height-based volumes) and those calculated by weighing the bottles. In all, 150 pairs of aerobic and anaerobic blood culture bottles (BacT/ALERT FA/FN Plus, bioMérieux) were randomly selected over two periods to compare the height- and weight-based volumes and analyze the effect of foam. We also estimated the limit of detection (LOD) and the cut-off value for 5 mL equine blood. The mean height-based volume was approximately 0.67 mL greater than the weight-based volume, particularly in anaerobic culture bottles. Foam did not have a significant effect. The LOD for the automatic height-based volume of equine blood was 0.2–0.4 mL. The 5 mL cut-off was 4–4.2 mL. Therefore, when reporting or monitoring blood volume within culture bottles in the laboratory, these performance characteristics should be adequately considered

Evaluation of SARS-CoV-2 Detection Systems Using Clinical Samples and Standard Material: A Comparative Study

Due to the decreasing trends in daily confirmed COVID-19 cases and daily confirmed tests, there is a need for a new testing system capable of quickly and efficiently testing small amounts of samples. Therefore, we compared and evaluated the testing performance of the Aptima SARS-CoV-2 assay, an automated testing system that allows continuous loading of samples, and the Real-Q Direct SARS-CoV-2 detection kit that is currently being used in our laboratory. We compared the results of the two testing systems using 259 residual individual nasopharyngeal specimens and 91 residual pooled nasopharyngeal specimens that were submitted for COVID-19 testing in January and February 2023. The 95% limit of detection (LoD) for the Aptima SARS-CoV-2 assay determined using reference material for SARS-CoV-2 nucleic acid was confirmed to be 17.793 copies/mL, while the LoD for the Real-Q Direct SARS-CoV-2 detection kit was determined to be 131.842 copies/mL for the RdRP gene and 241.77 copies/mL for the E gene. The comparative study using clinical specimens showed almost perfect agreement. Our data showed that the Aptima SARS-CoV-2 assay has a very low LoD. In addition, the Aptima SARS-CoV-2 assay and Real-Q Direct detection kit have comparable clinical performance for SARS-CoV-2 for individual and pooled samples

Yield ratios of the isomeric pair 85 m,gSr formed in natSr(γ,xn) reactions

The yield ratios of 85m,gSr were measured in the natSr(γ,xn)85m,gSr reactions with the bremsstrahlung end-point energies of 55-, 60-, and 65-MeV. The experiment was carried out by the activation method in combination with high resolution HPGe γ-ray spectroscopy. In order to improve the accuracy of the experimental results, appropriate experimental procedure was used to reduce the influence of the strong annihilation peak (511 keV) to the 514 keV γ-ray peak of 85gSr. The experimental results are compared to theoretical predictions using code TALYS- 1.6. The present results for 55-, and 60-MeV bremsstrahlung end-point energies have been measured for the first time.11Nsciescopu

Deep learning–based automated detection algorithm for active pulmonary tuberculosis on chest radiographs: diagnostic performance in systematic screening of asymptomatic individuals

Objectives: Performance of deep learning–based automated detection (DLAD) algorithms in systematic screening for active pulmonary tuberculosis is unknown. We aimed to validate DLAD algorithm for detection of active pulmonary tuberculosis and any radiologically identifiable relevant abnormality on chest radiographs (CRs) in this setting. Methods: We performed out-of-sample testing of a pre-trained DLAD algorithm, using CRs from 19.686 asymptomatic individuals (ages, 21.3 ± 1.9 years) as part of systematic screening for tuberculosis between January 2013 and July 2018. Area under the receiver operating characteristic curves (AUC) for diagnosis of tuberculosis and any relevant abnormalities were measured. Accuracy measures including sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated at pre-defined operating thresholds (high sensitivity threshold, 0.16; high specificity threshold, 0.46). Results: All five CRs from four individuals with active pulmonary tuberculosis were correctly classified as having abnormal findings by DLAD with specificities of 0.959 and 0.997, PPVs of 0.006 and 0.068, and NPVs of both 1.000 at high sensitivity and high specificity thresholds, respectively. With high specificity thresholds, DLAD showed comparable diagnostic measures with the pooled radiologists (p values > 0.05). For the radiologically identifiable relevant abnormality (n = 28), DLAD showed an AUC value of 0.967 (95% confidence interval, 0.938–0.996) with sensitivities of 0.821 and 0.679, specificities of 0.960 and 0.997, PPVs of 0.028 and 0.257, and NPVs of both 0.999 at high sensitivity and high specificity thresholds, respectively. Conclusions: In systematic screening for tuberculosis in a low-prevalence setting, DLAD algorithm demonstrated excellent diagnostic performance, comparable with the radiologists in the detection of active pulmonary tuberculosis. Key Points: • Deep learning–based automated detection algorithm detected all chest radiographs with active pulmonary tuberculosis with high specificities and negative predictive values in systematic screening. • Deep learning–based automated detection algorithm had comparable diagnostic measures with the radiologists for detection of active pulmonary tuberculosis on chest radiographs. • For the detection of radiologically identifiable relevant abnormalities on chest radiographs, deep learning–based automated detection algorithm showed excellent diagnostic performance in systematic screening

Neutron capture yields and resonance parameters of dysprosium isotopes measured at Japan Proton Accelerator Research Complex

.Neutron capture yields of dysprosium isotopes (Dy-161, Dy-162, Dy-163, and Dy-164) were measured using the time-of-flight method with a NaI(Tl) spectrometer locate at 27.9m from the spallation neutron target in the ANNRI beamline at the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Research Complex. The resonance parameters were determined using the multilevel R-matrix Bayesian code SAMMY in the neutron energy range of 1 to 300eV. Five resonances of the Dy-161 isotope, reported by Shin et al. but not presented in ENDF/B-VII.1, were confirmed in this study. One resonance of the Dy-164 isotope presented in ENDF/B-VII.1 was not observed in this study. The measured average level spacings were 2.31 +/- 0.23 eV for Dy-161 and 6.91 +/- 0.69 eV for Dy-163. The statistical distributions of the resonance parameters reasonably agreed with the Porter-Tomas distributions and multiple exit channel theory.11Nsciescopu

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics