scholarly journals A novel method for removing polyethyleneimine from biopharmaceutical samples: improving assay sensitivity of residual DNA qPCR

BioTechniques ◽  
2020 ◽  
Vol 68 (6) ◽  
pp. 353-358
Author(s):  
Shu-Min Zhang ◽  
Matthew Roberts ◽  
Marisa Jones ◽  
Jacob Zeitler ◽  
Greg Kilby ◽  
...  
Keyword(s):  
Sodium Dodecyl ◽  
Significant Risk ◽  
Regulatory Requirements ◽  
Assay Sensitivity ◽  
Real Time Quantitative Pcr ◽  
Dna Quantitation ◽  
Novel Method ◽  
The Cost ◽  
Very High ◽  
Quantitative Pcr Assay

Polyethyleneimine (PEI) is a flocculent that is widely used in the downstream purification of monoclonal antibodies. It is an in-process residual that is carried through the drug purification process and strongly inhibits residual DNA quantitation by real-time quantitative PCR assay. Very high sample dilutions (e.g., 1:10,000) can overcome the interference of PEI, but at the cost of DNA assay sensitivity. Diluting samples poses a significant risk to the assay sensitivity needed to satisfy regulatory requirements on the quantitation of residual genomic DNA present per dose (i.e., 10 ng/dose). Removing PEI while retaining DNA, by the use of sodium dodecyl sulfate, heparin and/or sarkosyl can overcome the interference of PEI and allow a more accurate quantitation of residual DNA.

Distinguishing Bacteriolytic from Bacteriostatic Activity of an Antibiotic Agent by Real-Time Quantitative PCR

2011 ◽  
Vol 343-344 ◽  
pp. 357-360
Author(s):  
Zhi Ping Wang
Keyword(s):  
Real Time ◽  
Quantitative Pcr ◽  
Bacteriostatic Activity ◽  
Antibiotic Agent ◽  
Pcr Assay ◽  
Assay Sensitivity ◽  
Real Time Quantitative Pcr ◽  
Pcr Product ◽  
Dna Template ◽  
Quantitative Pcr Assay

A simple and rapid real-time quantitative PCR assay was devised to discriminate bacteriolytic from bacteriostatic activity for a given antibacterial agent. Bacteria suspension was incubated with the compound solution, the mixture was centrifuged and supernatant was removed completely, the obtained pellet was then used as the DNA template for PCR. Then the bacteriostatic and bacteriolytic activity can be inferred by the quantity of PCR product. Moreover, the parameters that influence the assay sensitivity was discussed.

scholarly journals Increasing both specificity and sensitivity of SARS-CoV-2 antibody tests by using an adaptive orthogonal testing approach

2020 ◽  
Author(s):  
Thomas Perkmann ◽  
Nicole Perkmann-Nagele ◽  
Maria Oszvar-Kozma ◽  
Thomas Koller ◽  
Marie-Kathrin Breyer ◽  
...  
Keyword(s):  
Confirmatory Test ◽  
Assay Sensitivity ◽  
Remarkable Improvement ◽  
Test Strategy ◽  
Specificity And Sensitivity ◽  
Protein Receptor ◽  
Overall Performance ◽  
The Cost ◽  
Antibody Tests ◽  
Very High

ABSTRACTBackgroundSARS-CoV-2 antibody tests have undergone a remarkable improvement in performance. However, due to the low seroprevalence in several areas, very high demands are made on their specificity. Furthermore, the low antibody-response in some individuals requires high test sensitivity to avoid underestimating true seroprevalence. Optimization of testing has been reported through lowering manufacturer cut-offs to improve SARS-CoV-2 assay sensitivity or by combining two tests to improve specificity at the cost of sensitivity. However, these strategies have thus far been used in isolation of each other.MethodsTo increase sensitivity, cut-offs of three commercially available SARS-CoV-2 automated assays (Roche, Abbott, and DiaSorin) were reduced according to published values in a pre-pandemic specificity cohort (n=1117) and a SARS-CoV-2 positive cohort (n=64). All three testing systems were combined in an orthogonal approach with a confirmatory test, which was one of the remaining automated assays or one of two commercial ELISAs directed against the spike protein receptor binding-domain (RBD) or the nucleocapsid antigen (NP).ResultsThe modified orthogonal test strategy resulted in an improved specificity of at least 99.8%, often even 100%, in all 12 tested combinations with no significant decline in sensitivity. In our cohort, regardless of whether the assays were used for screening or confirmation, combining Roche and Abbott delivered the best overall performance (+∼10% sensitivity compared to the single tests and 100% specificity).ConclusionHere we propose a novel orthogonal assay strategy that approaches 100% specificity while maintaining or even significantly improving the screening test’s sensitivity.

scholarly journals Cost per DALY averted in low, middle- and high-income countries: evidence from the global burden of disease study to estimate the cost-effectiveness thresholds

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rajabali Daroudi ◽  
Ali Akbari Sari ◽  
Azin Nahvijou ◽  
Ahmad Faramarzi
Keyword(s):  
Cost Effectiveness ◽  
Inverse Correlation ◽  
Gdp Per Capita ◽  
Middle Income ◽  
Capita Health Expenditure ◽  
Per Capita ◽  
Healthcare Interventions ◽  
Disease Study ◽  
The Cost ◽  
Very High

Abstract Background Determining the cost-effectiveness thresholds for healthcare interventions has been a severe challenge for policymakers, especially in low- and middle-income countries. This study aimed to estimate the cost per disability-adjusted life-year (DALY) averted for countries with different levels of Human Development Index (HDI) and Gross Domestic Product (GDP). Methods The data about DALYs, per capita health expenditure (HE), HDI, and GDP per capita were extracted for 176 countries during the years 2000 to 2016. Then we examined the trends on these variables. Panel regression analysis was performed to explore the correlation between DALY and HE per capita. The results of the regression models were used to calculate the cost per DALY averted for each country. Results Age-standardized rate (ASR) DALY (DALY per 100,000 population) had a nonlinear inverse correlation with HE per capita and a linear inverse correlation with HDI. One percent increase in HE per capita was associated with an average of 0.28, 0.24, 0.18, and 0.27% decrease on the ASR DALY in low HDI, medium HDI, high HDI, and very high HDI countries, respectively. The estimated cost per DALY averted was $998, $6522, $23,782, and $69,499 in low HDI, medium HDI, high HDI, and very high HDI countries. On average, the cost per DALY averted was 0.34 times the GDP per capita in low HDI countries. While in medium HDI, high HDI, and very high HDI countries, it was 0.67, 1.22, and 1.46 times the GDP per capita, respectively. Conclusions This study suggests that the cost-effectiveness thresholds might be less than a GDP per capita in low and medium HDI countries and between one and two GDP per capita in high and very high HDI countries.

scholarly journals Cost Analysis of a Novel Method for Ecological Compensation—A Study of the Translocation of Dead Wood

2021 ◽  
Vol 13 (11) ◽  
pp. 6075
Author(s):  
Ola Lindroos ◽  
Malin Söderlind ◽  
Joel Jensen ◽  
Joakim Hjältén
Keyword(s):  
Cost Efficiency ◽  
Dead Wood ◽  
Road Transportation ◽  
Ecological Value ◽  
Ecological Compensation ◽  
Work Time ◽  
Delivery Times ◽  
Novel Method ◽  
Cost Efficient ◽  
The Cost

Translocation of dead wood is a novel method for ecological compensation and restoration that could, potentially, provide a new important tool for biodiversity conservation. With this method, substrates that normally have long delivery times are instantly created in a compensation area, and ideally many of the associated dead wood dwelling organisms are translocated together with the substrates. However, to a large extent, there is a lack of knowledge about the cost efficiency of different methods of ecological compensation. Therefore, the costs for different parts of a translocation process and its dependency on some influencing factors were studied. The observed cost was 465 SEK per translocated log for the actual compensation measure, with an additional 349 SEK/log for work to enable evaluation of the translocation’s ecological results. Based on time studies, models were developed to predict required work time and costs for different transportation distances and load sizes. Those models indicated that short extraction and insertion distances for logs should be prioritized over road transportation distances to minimize costs. They also highlighted a trade-off between costs and time until a given ecological value is reached in the compensation area. The methodology used can contribute to more cost-efficient operations and, by doing so, increase the use of ecological compensation and the benefits from a given input.

scholarly journals The Application of Electromagnetic Sensors for Determination of Cherenkov Cone Inside and in the Vicinity of the Detector Volume in Any Environment Known

Sensors ◽  
2021 ◽  
Vol 21 (3) ◽  
pp. 992
Author(s):  
Valeriu Savu ◽  
Mădălin Ion Rusu ◽  
Dan Savastru
Keyword(s):  
Energy Levels ◽  
Cherenkov Detector ◽  
Electromagnetic Sensors ◽  
The Cost ◽  
Information Errors ◽  
The Universe ◽  
Large Frequency ◽  
Very High ◽  
Detector Volume

The neutrinos of cosmic radiation, due to interaction with any known medium in which the Cherenkov detector is used, produce energy radiation phenomena in the form of a Cherenkov cone, in very large frequency spectrum. These neutrinos carry with them the information about the phenomena that produced them and by detecting the electromagnetic energies generated by the Cherenkov cone, we can find information about the phenomena that formed in the universe, at a much greater distance, than possibility of actually detection with current technologies. At present, a very high number of sensors for detection electromagnetic energy is required. Thus, some sensors may detect very low energy levels, which can lead to the erroneous determination of the Cherenkov cone, thus leading to information errors. As a novelty, we propose, to use these sensors for determination of the dielectrically permittivity of any known medium in which the Cherenkov detector is used, by preliminary measurements, the subsequent simulation of the data and the reconstruction of the Cherenkov cone, leading to a significant reduction of problems and minimizing the number of sensors, implicitly the cost reductions. At the same time, we offer the possibility of reconstructing the Cherenkov cone outside the detector volume.

scholarly journals Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis

2019 ◽  
Vol 70 (1) ◽  
pp. 26-29 ◽  
Author(s):  
Tinevimbo Shiri ◽  
Angela Loyse ◽  
Lawrence Mwenge ◽  
Tao Chen ◽  
Shabir Lakhi ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Cost Effectiveness ◽  
Cryptococcal Meningitis ◽  
Cost Effective ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
The Cost ◽  
The Impact ◽  
Costing Analysis ◽  
Very High

Abstract Background Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. Methods The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. Results The mean costs per patient were US $847 (95% confidence interval [CI] $776–927) for FLU+5FC, and US $628 (95% CI $557–709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9–41.7%) with FLU+5FC and 53.8% (95% CI 43.1–64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28–208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. Conclusions The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus–infected persons in Africa.

PROSTATE CANCER IN RURAL NIGERIA: DIMENSIONS, CULTURAL INTERPRETATIONS, COSTAND CARE

2021 ◽  
Vol 6 ◽  
pp. 36
Author(s):  
Sola Aluko-Arowolo, ◽  
Saheed Akinmayowa Lawal ◽  
Isaac A. Adedeji ◽  
Ebun O. Oduwole ◽  
Victor Kolo
Keyword(s):  
Prostate Cancer ◽  
Rural Areas ◽  
Significant Risk ◽  
Female Gender ◽  
Coping Resources ◽  
General Context ◽  
Rural Nigeria ◽  
Health Related ◽  
The Cost ◽  
Rural Dwellers

In connection with the global prevalence of prostate cancer, the incidence of prostate cancer in Nigeria is an emerging burden that requires urgent attention. While most health policies have focused on the female gender and children, it has left most men at significant risk of health problems and challenges which are dire. In the general context of cancer and its predominance in the population of people aged 40 and over, middle aged and older men have been found to be increasingly at risk. Hence the paper examines the dimension of prostate cancer in rural Nigeria. Although socio-cultural and economic factors play significant role in the health-related decisions of the human population, the paper discusses the cultural interpretations associated with prostate cancer. It also engages previous studies being a review paper on the cost and care for people affected with the disease. In conclusion, the lack of commensurate coping resources, rural dwellers are disproportionally impacted, both by the disease and the socio-economic burdens of prostate cancer, hence the need for more policies/action to address prostate cancer prevalence and incidence in rural areas of Nigeria

scholarly journals Embedding Undersampling Rotation Forest for Imbalanced Problem

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Huaping Guo ◽  
Xiaoyu Diao ◽  
Hongbing Liu
Keyword(s):  
Imbalanced Data ◽  
Feature Space ◽  
Original Data ◽  
Training Set ◽  
Data Set ◽  
Minority Class ◽  
Rotation Forest ◽  
Novel Method ◽  
Individual Classifier ◽  
The Cost

Rotation Forest is an ensemble learning approach achieving better performance comparing to Bagging and Boosting through building accurate and diverse classifiers using rotated feature space. However, like other conventional classifiers, Rotation Forest does not work well on the imbalanced data which are characterized as having much less examples of one class (minority class) than the other (majority class), and the cost of misclassifying minority class examples is often much more expensive than the contrary cases. This paper proposes a novel method called Embedding Undersampling Rotation Forest (EURF) to handle this problem (1) sampling subsets from the majority class and learning a projection matrix from each subset and (2) obtaining training sets by projecting re-undersampling subsets of the original data set to new spaces defined by the matrices and constructing an individual classifier from each training set. For the first method, undersampling is to force the rotation matrix to better capture the features of the minority class without harming the diversity between individual classifiers. With respect to the second method, the undersampling technique aims to improve the performance of individual classifiers on the minority class. The experimental results show that EURF achieves significantly better performance comparing to other state-of-the-art methods.

scholarly journals Investor Protection and Agency Theory in Corporate Governance in Pakistan

2021 ◽  
Vol 3 (1) ◽  
pp. 12-21
Author(s):  
Imtiaz Ahmed Khan ◽  
Altaf Hussain Abro ◽  
Farooque Ahmed Leghari
Keyword(s):  
Corporate Governance ◽  
Agency Theory ◽  
Agency Cost ◽  
Corporate Structure ◽  
Minority Shareholders ◽  
Private Benefits ◽  
Controlling Shareholders ◽  
Global Trend ◽  
The Cost ◽  
Very High

The paper discusses the minority shareholders’ protection under the quantumof agency cost in corporate governance in Pakistan. The agency theory statesthat in most of the cases, the controlling shareholders and the topmanagement are normally involved in expropriating the funds of the company.This phenomenon increases the agency cost. The agency cost is directlyproportional to the cost of functioning of the company. In other words, theagency cost is inversely proportional to the profit of the company. Accordingto the agency theory, if the agency cost is decreased, the profit for investorincreases. The Pakistani corporate sector is dominated by the businessfamilies, the state and an opportunity to get the private benefits at the cost ofother stakeholders. There are the different mechanisms as discussed andapplied around the world to minimize the agency cost so as to make companyfinancially strong and better profit for the investors. In Pakistan, the agencycost is very high. Hence, there is a need to revamp the corporate governancemechanism to reduce the agency cost in order to provide a better protection tominority shareholders in a particular in the context of the global trend keepingin the view of the nature of corporate structure in Pakistan.

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