Reformationsperspektiver. Acta Jutlandica LXII:3. (Aarhus Universitetsforlag, 1987). 128 s., 148 kr.

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Handling value added tax (VAT) in economic evaluations should prices include VAT?

In health economic evaluations, value added tax is commonly treated as a transfer payment. Following this argument, resources are valued equal to their net-of-tax prices in economic evaluations applying a societal perspective. In this article we argue that if there is the possibility that a new healthcare intervention may expand the healthcare budget, the social cost of input factors should be the gross-of-tax prices and not the net-of-tax prices. The rising interest in cost-benefit analysis and the use of absolute thresholds, net benefit estimates and acceptability curves in cost-effectiveness analysis makes this argument highly relevant for an appropriate use of these tools in prioritisation

Handling Value Added Tax (VAT) in Economic Evaluations: Should Prices Include VAT?

In health economic evaluations, value added tax is commonly treated as a transfer payment. Following this argument, resources are valued equal to their net-of-tax prices in economic evaluations applying a societal perspective. In this article we argue that if there is the possibility that a new healthcare intervention may expand the healthcare budget, the social cost of input factors should be the gross-of-tax prices and not the net-of-tax prices. The rising interest in cost-benefit analysis and the use of absolute thresholds, net benefit estimates and acceptability curves in cost-effectiveness analysis makes this argument highly relevant for an appropriate use of these tools in prioritisation.Cost-analysis, Economic-implications

The Presumed Polyomavirus Viroporin VP4 of Simian Virus 40 or Human BK Polyomavirus Is Not Required for Viral Progeny Release

The minor capsid protein of human BK polyomavirus (BKPyV), VP2, and its N-terminally truncated form, VP3, are both important for viral entry. The closely related simian virus 40 (SV40) reportedly produces an additional truncated form of VP2/3, denoted VP4, apparently functioning as a viroporin promoting progeny release. The VP4 open reading frame is conserved in some polyomaviruses, including BKPyV. In this study, we investigated the role of VP4 in BKPyV replication. By transfecting viral genomes into primary human renal proximal tubule epithelial cells, we demonstrated that unaltered BKPyV and mutants with start codon substitutions in VP4 (VP2M229I and VP2M229A) abolishing putative VP4 production were released at the same level to supernatants. However, during infection studies, VP2M229I and VP2M229A exhibited 90% and 65% reduced infectivity, respectively, indicating that isoleucine substitution inadvertently disrupted VP2/3 function to the detriment of viral entry, while inhibition of VP4 production during late infection was well tolerated. Unexpectedly, and similarly to BKPyV, wild-type SV40 and the corresponding VP4 start codon mutants (VP2M228I and VP2M228A) transfected into monkey kidney cell lines were also released at equal levels. Upon infection, only the VP2M228I mutant exhibited reduced infectivity, a 43% reduction, which also subsequently led to delayed host cell lysis. Mass spectrometry analysis of nuclear extracts from SV40-infected cells failed to identify VP4. Our results suggest that neither BKPyV nor SV40 require VP4 for progeny release. Moreover, our results reveal an important role in viral entry for the amino acid in VP2/VP3 unavoidably changed by VP4 start codon mutagenesis

Validation of an LC-HRMS-based untargeted metabolomics analytical platform for a long-term clinical metabolomics study

Untargeted metabolomics by LC-HRMS is a powerful tool when searching for new biomarkers to enhance our knowledge of pathophysiological processes. When used for large-scale clinical studies, it is crucial to have a comprehensive and robust setup and that the laboratory’s ability to collect reliable data is documented. This study aimed to establish a robust analytical platform for a long-term clinical metabolomics study, assessing the method\u27s fitness-for-purpose. Samples were prepared with an automated liquid handler and four analytical methods were developed and evaluated. The method validation study spanned three batches with twelve runs using individual serum samples and quality control samples. Data was acquired with untargeted acquisition and only metabolites identified with a local mass spectral library including retention time (level 1 identification) were evaluated. Validation parameters included reproducibility, repeatability, stability, and identification selectivity, emphasizing dataset intrinsic variance. Of the four methods tested, two were selected for validation. A total of 47 metabolites in RPLC-ESI+-and 55 metabolites in HILIC-ESI--HRMS met specified validation criteria, and full validation reports are presented. Quality assurance involved system suitability testing, sample release, run release, and batch release. Concentrated and diluted pooled quality control samples were introduced to correct for variance in response linearity across batches. The acquired data files can further be revisited for ad hoc validation of future metabolome and exposome features detected with the same setup. The validated methods proved fit-for-purpose. The laboratory demonstrated its capability to produce reliable results for large-scale, clinical, untargeted metabolomics. This study underscores the value of validation of an assays performance before commencing larger studies to enhance the reliability and impact of the generated hypotheses