PB1 as a potential target for increasing the breadth of T-cell mediated immunity to Influenza A

Recently, we showed that combined intranasal and subcutaneous immunization with a non-replicating adenoviral vector expressing NP of influenza A, strain PR8, induced long-standing protection against a range of influenza A viruses. However, H-2(b) mice challenged with an influenza A strain mutated in the dominant NP(366) epitope were not efficiently protected. To address this problem, we envision the use of a cocktail of adenovectors targeting different internal proteins of influenza A virus. Consequently, we investigated the possibility of using PB1 as a target for an adenovector-based vaccine against influenza A. Our results showed that PB1 is not as immunogenic as the NP protein. However, by tethering PB1 to the murine invariant chain we were able to circumvent this problem and raise quite high numbers of PB1-specific CD8(+) T cells in the circulation. Nevertheless, mice immunized against PB1 were not as efficiently protected against influenza A challenge as similarly NP-vaccinated animals. The reason for this is not a difference in the quality of the primed cells, nor in functional avidity. However, under similar conditions of immunization fewer PB1-specific cells were recruited to the airways, and surface expression of the dominant PB1 peptide, PB1(703), was less stable than in the case of NP(366)

Combined local and systemic immunization is essential for durable T-cell mediated heterosubtypic immunity against influenza A virus

The threat from unpredictable influenza virus pandemics necessitates the development of a new type of influenza vaccine. Since the internal proteins are highly conserved, induction of T cells targeting these antigens may provide the solution. Indeed, adenoviral (Ad) vectors expressing flu nucleoprotein have previously been found to induce short-term protection in mice. In this study we confirm that systemic (subcutaneous (s.c.) immunization rapidly induced heterosubtypic protection predominantly mediated by CD8 T cells, but within three months clinical protection completely disappeared. Local (intranasal (i.n.)) immunization elicited delayed, but more lasting protection despite relatively inefficient immunization. However, by far, the most robust protection was induced by simultaneous, combined (i.n. + s.c.) vaccination, and, notably, in this case clinical protection lasted at least 8 months without showing any evidence of fading. Interestingly, the superior ability of the latter group to resist reinfection correlated with a higher number of antigen-specific CD8 T cells in the spleen. Thus, detailed analysis of the underlying CD8 T cell responses highlights the importance of T cells already positioned in the lungs prior to challenge, but at the same time underscores an important back-up role for circulating antigen-specific cells with the capacity to expand and infiltrate the infected lungs

Inclusion of sex chromosomes in noninvasive prenatal testing in Asia, Australia, Europe and the USA: A survey study

Objective: To examine the extent to which sex chromosomes are included in current noninvasive prenatal testing (NIPT) and the reporting practices with respect to fetal chromosomal sex and sex chromosome aberrations (SCAs), in addition to an update on the general implementation of NIPT. Method: A questionnaire addressing the research objectives was distributed by email to fetal medicine and clinical genetics experts in Asia, Australia, Europe and the USA. Results: Guidelines on NIPT are available in the majority of the included countries. Not all existing guidelines address reporting of fetal chromosomal sex and SCAs. In most settings, NIPT frequently includes sex chromosomes (five Australian states, China, Hong Kong, Israel, Singapore, Thailand, USA and 23 of 31 European countries). This occurs most often by default or when parents wish to know fetal sex. In most settings, a potential SCA is reported by stating the risk hereof as “low” or “high” and/or by naming the SCA. Less than 50% of all pregnant women receive NIPT according to respondents from three Australian states, China, Israel, Singapore, Thailand and 24 of 31 European countries. However, this percentage, the genomic coverage of NIPT and its application as primary or secondary screening vary by setting. Conclusion: In most of the studied countries/states, NIPT commonly includes sex chromosomes. The reporting practices concerning fetal chromosomal sex and SCAs are diverse and most commonly not addressed by guidelines. In general, NIPT is variably implemented across countries/states

Research needs and data gaps of importance for food safety and protection of biodiversity. Summary report from VKM’s scientific opinions in the period 2005 - 2015.

Related version: VKM Report 2016: 48 : https://vkm.no/download/18.7e19596115dabec04172717/1501849448865/30664700ba.pdfThe aim of the present report is to highlight research needs and data gaps that are of future importance for food safety and protection of biodiversity. The Norwegian Scientific Committee for Food Safety (VKM) produces and communicates scientific opinions, i.e. risk-and risk-benefitassessments, with the main goal of securing food safety and protection of biodiversity

Research needs and data gaps of importance for food safety and protection of biodiversity. From VKM’s scientific opinions in the period 2005 - 2015

Source at https://vkm.no/The aim of the present report is to highlight research needs and data gaps that are of future importance for food safety and protection of biodiversity. The Norwegian Scientific Committee for Food Safety (VKM) produces and communicates scientific opinions, i.e. risk-and risk-benefitassessments, with the main goal of securing food safety and protection of biodiversity.Food safety is one of the prerequisites for good health, and is on the agenda both nationally and internationally. Since food production, food products on the market and dietary habits as well as the presence of potentialhazardsare constantly changing, there is a continuous need for new knowledge to ensure safe foodMålet med denne rapporten er å synliggjøre kunnskapsbehov som er viktige for å sikre trygg mat og opprettholdelse avbiologisk mangfold i årene som kommer.Vitenskapskomiteen for mattrygghet (VKM) utarbeider og kommunisereruavhengige, vitenskapelige uttalelser, blant annet risikovurderinger og nytte-risikovurderinger. Hovedmålet til VKM er å sikre trygg mat og opprettholdelse av biologisk mangfold.Trygg mat er en av forutsetningene for god helseog vies mye oppmerksomhetbåde nasjonalt og internasjonalt. Stadige endringer i hvordan maten produseres, hvilke matvarer som er tilgjengelige, hva befolkningen spiser og hvilke potensielle farer som følger med maten skaper et kontinuerlig behov for ny kunnskap for å sikre at maten er trygg

Improving shared decision-making about cancer treatment through design-based data-driven decision-support tools and redesigning care paths:an overview of the 4D PICTURE project

Background: Patients with cancer often have to make complex decisions about treatment, with the options varying in risk profiles and effects on survival and quality of life. Moreover, inefficient care paths make it hard for patients to participate in shared decision-making. Data-driven decision-support tools have the potential to empower patients, support personalized care, improve health outcomes and promote health equity. However, decision-support tools currently seldom consider quality of life or individual preferences, and their use in clinical practice remains limited, partly because they are not well integrated in patients' care paths.Aim and objectives: The central aim of the 4D PICTURE project is to redesign patients' care paths and develop and integrate evidence-based decision-support tools to improve decision-making processes in cancer care delivery. This article presents an overview of this international, interdisciplinary project.Design, methods and analysis: In co-creation with patients and other stakeholders, we will develop data-driven decision-support tools for patients with breast cancer, prostate cancer and melanoma. We will support treatment decisions by using large, high-quality datasets with state-of-the-art prognostic algorithms. We will further develop a conversation tool, the Metaphor Menu, using text mining combined with citizen science techniques and linguistics, incorporating large datasets of patient experiences, values and preferences. We will further develop a promising methodology, MetroMapping, to redesign care paths. We will evaluate MetroMapping and these integrated decision-support tools, and ensure their sustainability using the Nonadoption, Abandonment, Scale-Up, Spread, and Sustainability (NASSS) framework. We will explore the generalizability of MetroMapping and the decision-support tools for other types of cancer and across other EU member states.Ethics: Through an embedded ethics approach, we will address social and ethical issues.Discussion: Improved care paths integrating comprehensive decision-support tools have the potential to empower patients, their significant others and healthcare providers in decision-making and improve outcomes. This project will strengthen health care at the system level by improving its resilience and efficiency.Improving the cancer patient journey and respecting personal preferences: an overview of the 4D PICTURE projectThe 4D PICTURE project aims to help cancer patients, their families and healthcare providers better undertstand their options. It supports their treatment and care choices, at each stage of disease, by drawing on large amounts of evidence from different types of European data. The project involves experts from many different specialist areas who are based in nine European countries. The overall aim is to improve the cancer patient journey and ensure personal preferences are respected

Microplastics; occurrence, levels and implications for environment and human health related to food. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

Report from the Norwegian Scientific Committee for Food Safety (VKM) 2019:16. Microplastics; occurrence, levels and implications for environment and human health related to food. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment. Source at https://www.vkm.no/. The steering committee of VKM has self-initiated a mandate for an opinion on microplastics based on recently published international and/or national reports complemented with literature from December 2016 to February 2019. The mandate requested a summary of the state of knowledge on the presence of microplastics in the environment and the implications for the ecosystem, terrestrial and aquatic organisms, food production and human health. An overview of main national and international ongoing initiatives was also requested, and highlighting of data gaps where specific Norwegian data was needed

Microplastics; occurrence, levels and implications for environment and human health related to food. Scientific opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

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Kunnskapsbehov av betydning for mattrygghet og biologisk mangfold. Oppsummering fra VKMs vitenskapelige uttalelser i perioden 2005 – 2015

Related version: VKM Report 2016: 48 : https://vkm.no/download/18.7e19596115dabec04172717/1501849448865/30664700ba.pdfMålet med denne rapporten er å synliggjøre kunnskapsbehov som er viktige for å sikre trygg mat og opprettholdelse avbiologisk mangfold i årene som kommer.Vitenskapskomiteen for mattrygghet (VKM) utarbeider og kommunisereruavhengige, vitenskapelige uttalelser, blant annet risikovurderinger og nytte-risikovurderinger. Hovedmålet til VKM er å sikre trygg mat og opprettholdelse av biologisk mangfold