Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program

Aims Mass antigen testing programs have been challenged because of an alleged insufficient specificity, leading to a large number of false positives. The objective of this study is to derive a lower bound of the specificity of the SD Biosensor Standard Q Ag-Test in large scale practical use. Methods Based on county data from the nationwide tests for SARS-CoV-2 in Slovakia between 31.10.–1.11. 2020 we calculate a lower confidence bound for the specificity. As positive test results were not systematically verified by PCR tests, we base the lower bound on a worst case assumption, assuming all positives to be false positives. Results 3,625,332 persons from 79 counties were tested. The lowest positivity rate was observed in the county of Rožňava where 100 out of 34307 (0.29%) tests were positive. This implies a test specificity of at least 99.6% (97.5% one-sided lower confidence bound, adjusted for multiplicity). Conclusion The obtained lower bound suggests a higher specificity compared to earlier studies in spite of the underlying worst case assumption and the application in a mass testing setting. The actual specificity is expected to exceed 99.6% if the prevalence in the respective regions was non-negligible at the time of testing. To our knowledge, this estimate constitutes the first bound obtained from large scale practical use of an antigen test.

Evaluation of the Japanese Fatigue Test Data in Gr.91 for Elevated Temperature Design

The ASME Boiler and Pressure Vessel Code (ASME BPVC) Section III, Division 5, Subsection HB, Subpart B provided only one design fatigue curve for Grade 91 steel (Gr.91) at 540 °C (or 1000 °F) in 2019 and earlier versions. To overcome this disadvantage, The ASME Section III Working Group on Creep-Fatigue and Negligible Creep (WG-CFNC) had taken an action to incorporate the temperature-dependent design fatigue curves for Gr. 91 developed by Japan Society of Mechanical Engineers (JSME) into ASME BPVC Section III Division 5. As a result, the temperature dependent design fatigue curves are provided in the 2021 edition of the ASME BPVC. To clear the features of the best-fit fatigue curve equation developed by the JSME, 305 data stored in the database were analyzed. Details of the database and relationship between the best-fit fatigue curve equation and the data including the statistic values and the values of 95% and 99% lower confidence bound calculated by failure probability assessment were clarified through analysis. In addition to the best-fit fatigue curve equation, an equation for dynamic stress-strain response showing the behavior of Gr.91 steel under cyclic loading of is also provided based on the same database. Moreover, some additional available data of fatigue and creep-fatigue tests obtained in Japan are also provided for considering the creep-fatigue damage evaluation under elevated temperature condition.

Improved Gaussian Process Acquisition for Targeted Bayesian Optimization

A black-box optimization problem is considered, in which the function to be optimized can only be expressed in terms of a complicated stochastic algorithm that takes a long time to evaluate. The value returned is required to be sufficiently near to a target value, and uses data that has a significant noise component. Bayesian Optimization with an underlying Gaussian Process is used as an optimization solution, and its effectiveness is measured in terms of the number of function evaluations required to attain the target. To improve results, a simple modification of the Gaussian Process ‘Lower Confidence Bound’ (LCB) acquisition function is proposed. The expression used for the confidence bound is squared in order to better comply with the target requirement. With this modification, much improved results compared to random selection methods and to other commonly used acquisition functions are obtained.

Analysis of the specificity of the SD Biosensor Standard Q Ag-Test based on Slovak mass testing data

From 31.10. - 1.11.2020 Slovakia has used the SD Biosensor Standard Q Ag-Test for nationwide tests for SARS-CoV-2, in which 3,625,332 persons from 79 counties were tested. Based on this data, we calculate that the specificity of the test is at least 99.6% (with a 97.5% one-sided lower confidence bound). Our analysis is based on a worst case approach in which all positives are assumed to be false positives. Therefore, the actual specificity is expected to exceed 99.6%.

Exact Inference for an Exponential Parameter under Generalized Adaptive Progressive Hybrid Censored Competing Risks Data

It is known that the lifetimes of items may not be recorded exactly. In addition, it is known that more than one risk factor (RisF) may be present at the same time. In this paper, we discuss exact likelihood inference for competing risk model (CoRiM) with generalized adaptive progressive hybrid censored exponential data. We derive the conditional moment generating function (ConMGF) of the maximum likelihood estimators of scale parameters of exponential distribution (ExpD) and the resulting lower confidence bound under generalized adaptive progressive hybrid censoring scheme (GeAdPHCS). From the example data, it can be seen that the PDF of MLE is almost symmetrical.

Exact Likelihood Inference for an Exponential Parameter under Generalized Adaptive Progressive Hybrid Censoring

In this paper, we propose a new type censoring scheme named a generalized adaptive progressive hybrid censoring scheme (GenAdPrHyCS). In this new type censoring scheme, the experiment is assured to stop at a pre-assigned time. This censoring scheme is designed to correct the drawbacks in the AdPrHyCS. Furthermore, we discuss inference for one parameter exponential distribution (ExD) under GenAdPrHyCS. We derive the moment generating function of the maximum likelihood estimator (MLE) of scale parameter of ExD and the resulting lower confidence bound under GenAdPrHyCS.

Overall responses with coordinated pembrolizumab and high dose IL-2 (5-in-a-row schedule) for therapy of metastatic clear cell renal cancer: A single center, single arm trial.

657 Background: Ligation of IL-2 receptor or blockade of PD-1 receptor may change lymphocytes to induce regression of cancers with diverse histology or site of origin. Single agent objective response rates of 14-25% have been reported for IL-2 therapy of metastatic clear cell RCC (ccRCC). A response rate of 33% was observed in pembrolizumab treated ccRCC patients. Nivolumab treated ccRCC patients were observed to have early intratumoral migration of lymphocytes. A case report of IL-2 induced major regression right after no change on nivolumab therapy suggested that combining the two means of lymphocyte stimulation could be effective. Other trials combining IL-2 receptor agonists (NKTR-214) and PD-1 blockade have also reported regression of ccRCC. Distinctive attributes of high dose IL-2 therapy are the required inpatient stay and the durability of the complete responses. Methods: This single-institution, single arm study addresses the safety and feasibility of the combination of IL-2 and pembrolizumab in the treatment of metastatic ccRCC. Subjects are treated on four nine-week blocks, as follows: Pembrolizumab is given on weeks 1, 4, and 7 of each block. Patients are admitted for 5 doses of high dose IL-2 (given over ~ 33 hours/3 days) on weeks 2, 3, 5, and 6 of blocks 2 and 3. Safety is monitored by a Pocock boundary of .05 likelihood of 0.15 dose limiting toxicity rate. The Simon 2-stage alternative hypothesis for the sample size was a 45+% major response rate vs null hypothesis < 20%, at alpha = 0.10, 90% power. Results: No accrual stop for safety was triggered. Thirteen of the first 18 patients responded, substantially exceeding the requirement of 8+/24 combination-treated patients to reject the null. Seven patients responded after receiving pembrolizumab alone, six after starting combination therapy in block 2. Accrual is completed; at 27. Kaplan-Meier analysis projects ORR of 69%, with ORR 90%-lower confidence bound of 55%. Conclusions: The combination of high dose IL-2 and pembrolizumab is feasible, with a high response rate, justifying further exploration of this dual immune treatment of metastatic ccRCC. Clinical trial information: NCT02964078.