Real-life clinical sensitivity of SARS-CoV-2 RT-PCR test in symptomatic patients

Background Understanding the false negative rates of SARS-CoV-2 RT-PCR testing is pivotal for the management of the COVID-19 pandemic and it has implications for patient management. Our aim was to determine the real-life clinical sensitivity of SARS-CoV-2 RT-PCR. Methods This population-based retrospective study was conducted in March-April 2020 in the Helsinki Capital Region, Finland. Adults who were clinically suspected of SARS-CoV-2 infection and underwent SARS-CoV-2 RT-PCR testing, with sufficient data in their medical records for grading of clinical suspicion were eligible. In addition to examining the first RT-PCR test of repeat-tested individuals, we also used high clinical suspicion for COVID-19 as the reference standard for calculating the sensitivity of SARS-CoV-2 RT-PCR. Results All 1,194 inpatients (mean [SD] age, 63.2 [18.3] years; 45.2% women) admitted to COVID-19 cohort wards during the study period were included. The outpatient cohort of 1,814 individuals (mean [SD] age, 45.4 [17.2] years; 69.1% women) was sampled from epidemiological line lists by systematic quasi-random sampling. The sensitivity (95% CI) for laboratory confirmed cases (repeat-tested patients) was 85.7% (81.5-89.1%) inpatients; 95.5% (92.2-97.5%) outpatients, 89.9% (88.2-92.1%) all. When also patients that were graded as high suspicion but never tested positive were included in the denominator, the sensitivity (95% CI) was: 67.5% (62.9-71.9%) inpatients; 34.9% (31.4-38.5%) outpatients; 47.3% (44.4-50.3%) all. Conclusions The clinical sensitivity of SARS-CoV-2 RT-PCR testing was only moderate at best. The relatively high false negative rates of SARS-CoV-2 RT-PCR testing need to be accounted for in clinical decision making, epidemiological interpretations, and when using RT-PCR as a reference for other tests.Peer reviewe

Discrimination of conventional and organic white cabbage from a long-term field trial study using untargeted LC-MS-based metabolomics

The influence of organic and conventional farming practices on the content of single nutrients in plants is disputed in the scientific literature. Here, large-scale untargeted LC-MS-based metabolomics was used to compare the composition of white cabbage from organic and conventional agriculture, measuring 1,600 compounds. Cabbage was sampled in 2 years from one conventional and two organic farming systems in a rigidly controlled long-term field trial in Denmark. Using Orthogonal Projection to Latent Structures-Discriminant Analysis (OPLS-DA), we found that the production system leaves a significant (p = 0.013) imprint in the white cabbage metabolome that is retained between production years. We externally validated this finding by predicting the production system of samples from one year using a classification model built on samples from the other year, with a correct classification in 83% of cases. Thus, it was concluded that the investigated conventional and organic management practices have a systematic impact on the metabolome of white cabbage. This emphasizes the potential of untargeted metabolomics for authenticity testing of organic plant products

Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease

RNase MRP is a conserved endoribonuclease, in humans consisting of a 267-nucleotide RNA associated with 7–10 proteins. Mutations in its RNA component lead to several autosomal recessive skeletal dysplasias, including cartilage-hair hypoplasia (CHH). Because the known substrates of mammalian RNase MRP, pre-ribosomal RNA, and RNA involved in mitochondrial DNA replication are not likely involved in CHH, we analyzed the effects of RNase MRP (and the structurally related RNase P) depletion on mRNAs using DNA microarrays. We confirmed the upregulation of the interferon-inducible viperin mRNA by RNAi experiments and this appeared to be independent of the interferon response. We detected two cleavage sites for RNase MRP/RNase P in the coding sequence of viperin mRNA. This is the first study providing direct evidence for the cleavage of a mRNA by RNase MRP/RNase P in human cells. Implications for the involvement in the pathophysiology of CHH are discussed

Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine

Idiopathic pulmonary fibrosis (IPF) is characterized by activation and injury of epithelial cells, the accumulation of connective tissue and changes in the inflammatory microenvironment. The bone morphogenetic protein (BMP) inhibitor protein gremlin-1 is associated with the progression of fibrosis both in human and mouse lung. We generated a transgenic mouse model expressing gremlin-1 in type II lung epithelial cells using the surfactant protein C (SPC) promoter and the Cre-LoxP system. Gremlin-1 protein expression was detected specifically in the lung after birth and did not result in any signs of respiratory insufficiency. Exposure to silicon dioxide resulted in reduced amounts of lymphocyte aggregates in transgenic lungs while no alteration in the fibrotic response was observed. Microarray gene expression profiling and analyses of bronchoalveolar lavage fluid cytokines indicated a reduced lymphocytic response and a downregulation of interferon-induced gene program. Consistent with reduced Th1 response, there was a downregulation of the mRNA and protein expression of the anti-fibrotic chemokine CXCL10, which has been linked to IPF. In human IPF patient samples we also established a strong negative correlation in the mRNA expression levels of gremlin-1 and CXCL10. Our results suggest that in addition to regulation of epithelial-mesenchymal crosstalk during tissue injury, gremlin-1 modulates inflammatory cell recruitment and anti-fibrotic chemokine production in the lung.Peer reviewe

Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer

Peer reviewe

Approaching Strategic Sustainable Materials Management

Society’s sustainability challenges relatedto materials management have been an area of concern for policymakers, industry and the public for decades. However, if those challenges are managed in a strategic way, they are not only aproblem, but could also bring in new opportunity for companies and other organizations to improve their competitiveness through developingproduct-service systems that promote sustainable development of society. The overall aim of this thesis is to explore how aframework for strategic sustainable development (FSSD) can support the development and design of sustainable materials management strategies in product innovation. This is achieved by four studies investigating howsustainability considerations are, or could be, integrated in decisions regarding materials selection. The studies are informed by the FSSD, Maxwell’s model for qualitative research design and the design research methodology. The first study is a theoretical discussion which provides a base for the following three exploratory studies. The exploratory studies have, through literature reviews and semi-structured interviews, investigated general sustainabilityconsiderations in companies, made a comparison of the strategic potential of two product improvement strategies and finally studied what considerations that are in focus and what types of solutions that are revealed when companies apply a strategic sustainability perspective to materials management. The studies have shown that decisions regarding materials management often arebased on compliance with legislation and on avoiding substances with characteristics commonly considered problematic (such as toxicity, persistency, etc.), and that decision support regarding how materials could be managed in a sustainable way are lacking. However, the results also include some examples from companies that have successfully developed pro-active strategies towards sustainable materials management. They have approached this through managing materials in closedtechnical loops, enabled material substitution through value chain collaboration and reduced material flows through new and innovative design. Most importantly, they have assessedactions not only regarding their potential to reduce a selection of current socio-ecological impacts but also regarding their potential to link toforthcoming actions towards the full scope of socio-ecological sustainability. Through this approach, they have found several ways by which materials with characteristics that are commonly considered problematic can be. The results highlight the possibility of enabling sustainable materials management practices by using a strategic sustainability perspective in combination with material characteristics knowledge and that a static division of “sustainable” vs. “unsustainable” materials (e.g., through lists of forbidden and allowed materials) is not necessarily serving the purpose in the best way. More subtle considerations are needed. By not applying a strategic sustainability perspective to materials management, organizations risk using “sustainable” materials in unsustainable ways or phasing out “unsustainable” materials that, managed differently, could be helpful for sustainable development. Developing decision support for materials management that integrates this new way of thinking will be the focus of future work

Material substitution and weight reduction as steps towards a sustainable disposable diaper

Increasing market demands for 'sustainable products' has in the development of disposable diapers resulted in a focus on material substitution and weight reduction. In this study we have compared the strategic potential of these two approaches for development of the absorbing core of the product. The study indicates that regardless what strategy a company selects for reducing a products socio-ecological impact, both society and environment would benefit from a stronger focus on the long term goal of a sustainably product, instead of the milestones.http://www.lcm2011.org/papers.htm

Analysis of policy frameworks for ‘children in care’ in Sweden

In a joint South African and Swedish research study, policy frameworks for children in care were analysed in regard to children’s rights and accessibility to participate in decisions on care. The research group has during phase one in the study developed a series of questions to analyse the most relevant legislations in regard to children in care. Thus, for the Swedish part of the analysis four legislations were selected; the Social Services Act (SSA), the Children and Parents Code (CPC), the Care of Young Persons Act (CYPA) and the UN Convention on the Rights of the Child (CRC) (since 2020 a part of the Swedish legislation). An analysis model was applied to these legislations, posing the following seven questions on children’s participation. What participation is, different understandings of children’s participation. Further, participation Concerning what? that is, in what decisions? Why participation, which includes the reasons and values underlying children’s participation. How, when, and where participation should be exercised. Also, Who should participate, with the added underlying question of who should promote participation. These questions were applied to the different legislations in order to scrutinize the access for children to become active agents in their own care. This form of inclusion could also become a model for an empower-driven participative influence in the decisions of fundamental importance to the society’s future well-being. Results from the analysis will be presented at the conference

Material substitution and weight reduction as steps towards a sustainable disposable diaper

Increasing market demands for 'sustainable products' has in the development of disposable diapers resulted in a focus on material substitution and weight reduction. In this study we have compared the strategic potential of these two approaches for development of the absorbing core of the product. The study indicates that regardless what strategy a company selects for reducing a products socio-ecological impact, both society and environment would benefit from a stronger focus on the long term goal of a sustainably product, instead of the milestones.http://www.lcm2011.org/papers.htm

The San Giovenale pottery : production and raw material

San Giovenale is a small inland Etruscan community approximately 60 km north of Rome. The site was excavated between 1956 and 1965 and the focus of the research has been aimed at the archaic period as well as the proto- Villanova period. The Late Etruscan period has up to now been more or less neglected. This resent work is to a large extent based on pottery and one cornerstone of the study is the belief that a majority of this Late Etruscan pottery is locally produced, not only the coarse ware but also the simpler tableware such as Late Creamware. One possible way to verify the hypotheses of a local production is by comparing the raw material components of the coarse ware and the tableware as well as clay deposits around the San Giovenale site. Very little of this kind of combined work between clay surveying, laboratory analyses of clays and pottery (thin-section analyses, thermal analyses, XRF-analyses, Carbon analyse and Mössbauerspectroscopy) and traditional studies of vessel shape, decoration and vessel function has previously been done on the small Etruscan inland settlements