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This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.
ABSTRACT IMPACT: Melanoma leptomeningeal disease (LMD) is a devastating subtype of central nervous system (CNS) metastatic disease that is associated with limited treatment options and an extremely poor prognosis, thus requiring the development of preclinical models of LMD for therapeutic development. OBJECTIVES/GOALS:
1. Develop an immunocompetent murine model of melanoma LMD with tumors bearing genetic mutations commonly found in patients, specifically BRAF(V600E)/PTEN-/-
2. Assess the safety of intrathecal (IT) immunotherapy, specifically anti-PD1 antibody (aPD1)
3. Evaluate the therapeutic efficacy of IT aPD1 checkpoint blockade in murine melanoma LMD METHODS/STUDY POPULATION: To develop BRAF(V600E)/PTEN-/- LMD models, we acquired BP, D4M, and D4M-UV2 (irradiated) murine melanoma cell lines and luciferase-tagged them. 1.5x10^4 cells were suspended in 10 uL serum-free media and injected into the cisterna magna of female C57BL/6 mice. Brain and spinal cord were harvested for histologic assessment once mice were moribund. To assess safety of IT aPD1, we injected IT control IgG or IT aPD1 (13 ug, 26 ug, 39 ug) and monitored weights or harvested at days 7 or 14 for IHC staining of inflammation markers. To evaluate therapeutic efficacy of IT aPD1, BP cells were directly injected as above. After 3 days, mice underwent imaging to confirm tumor uptake and randomization to receive 13 ug IT control IgG or aPD1 once + 200 ug systemic (Sys) control IgG or aPD1 (days 0, 3, and 5), and then monitored for survival. RESULTS/ANTICIPATED RESULTS: For LMD development, all mice survived cisternal injection of BP, D4M, and D4M-UV2 cells and median survival was 17, 19, and 30 days, respectively. Presence of leptomeningeal deposits was confirmed for all tumor-bearing mice by IHC for MART1. For safety of IT aPD1, all mice survived the procedure and no mice displayed morbidity or >10% weight loss over 14 days of observation. IHC assessment of brain and spinal cord samples from mice treated with 13 ug aPD1 revealed focal ischemia related to injection site and no other signs of neurological damage or inflammation. IT aPD1 treatment of mice with BP leptomeningeal tumors demonstrated no significant survival advantage, although both IT aPD1 +/- Sys aPD1 had mice live up to days 29 and 26, respectively, compared to both IT control IgG +/- Sys aPD1, for which all mice died by day 22. DISCUSSION/SIGNIFICANCE OF FINDINGS: We demonstrate that cisternal injection of murine BRAF(V600E)/PTEN-/- melanoma cell lines yield LMD with reproducible survival and that treatment with IT aPD1 in this model is feasible and safe. Together these findings establish a new model to facilitate the development of more effective immunotherapy strategies for melanoma patients with LMD.
The present study explored associations between food choice motives, attitudes towards and intention to adopt personalised nutrition, to inform communication strategies based on consumer priorities and concerns.
Design/Setting
A survey was administered online which included the Food Choice Questionnaire (FCQ) and items assessing attitudes towards and intention to adopt personalised nutrition.
Subjects
Nationally representative samples were recruited in nine EU countries (n 9381).
Results
Structural equation modelling indicated that the food choice motives ‘weight control’, ‘mood’, ‘health’ and ‘ethical concern’ had a positive association and ‘price’ had a negative association with attitude towards, and intention to adopt, personalised nutrition. ‘Health’ was positively associated and ‘familiarity’ negatively associated with attitude towards personalised nutrition. The effects of ‘weight control’, ‘ethical concern’, ‘mood’ and ‘price’ on intention to adopt personalised nutrition were partially mediated by attitude. The effects of ‘health’ and ‘familiarity’ were fully mediated by attitude. ‘Sensory appeal’ was negatively and directly associated with intention to adopt personalised nutrition.
Conclusions
Personalised nutrition providers may benefit from taking into consideration the importance of underlying determinants of food choice in potential users, particularly weight control, mood and price, when promoting services and in tailoring communications that are motivationally relevant.
One of the most independent thinkers in German intellectual history, the Enlightenment author Gotthold Ephraim Lessing (1729-1781) contributed in decisive and lasting fashion to literature, philosophy, theology, criticism, and drama theory. Lessing invented the bürgerliches Trauerspiel (bourgeois tragedy) and wrote one of the first successful German tragedies as well as one of the finest German comedies. In his final dramatic masterpiece, Nathan der Weise, he writes of Christianity, Judaism, and Islam, of religious tolerance and intolerance and the clash of civilizations. Lessing's dramas are the oldest German theater pieces still regularly performed (both in Germany and internationally), and both his plays and his drama theory have influenced such writers as Goethe, Schiller, Hebbel, Hauptmann, Ibsen, Strindberg, Schnitzler, and Brecht. Addressing an audience ranging from graduate students to seasoned scholars, this volume introduces Lessing's life and times and places him within the broader context of the European Enlightenment. It discusses his pathbreaking dramas, his equally revolutionary theoretical, critical, and aesthetic writings, his original fables, his innovative work in philosophy and theology, and his significant contributions to Jewish emancipation. The volume concludes by examining 20th-century reception of Lessing and his oeuvre.
Contributors: Barbara Fischer, Thomas C. Fox, Steven D. Martinson, Klaus L. Berghahn, John Pizer, Beate Allert, H. B. Nisbet, Arno Schilson, Willi Goetschel, Peter Höyng, Karin A. Wurst, Ann Schmiesing, Reinhart Meyer, Hans-Joachim Kertscher, Hinrich C. Seeba, Dieter Fratzke, Helmut Berthold, Herbert Rowland.
Barbara Fischer is Associate Professor of German and Thomas C. Fox is Professor of German, both at the University of Alabama.
Personalised nutrition (PN) has the potential to reduce disease risk and optimise health and performance. Although previous research has shown good acceptance of the concept of PN in the UK, preferences regarding the delivery of a PN service (e.g. online v. face-to-face) are not fully understood. It is anticipated that the presence of a free at point of delivery healthcare system, the National Health Service (NHS), in the UK may have an impact on end-user preferences for deliverances. To determine this, supplementary analysis of qualitative data obtained from focus group discussions on PN service delivery, collected as part of the Food4Me project in the UK and Ireland, was undertaken. Irish data provided comparative analysis of a healthcare system that is not provided free of charge at the point of delivery to the entire population. Analyses were conducted using the ‘framework approach’ described by Rabiee (Focus-group interview and data analysis. Proc Nutr Soc 63, 655-660). There was a preference for services to be led by the government and delivered face-to-face, which was perceived to increase trust and transparency, and add value. Both countries associated paying for nutritional advice with increased commitment and motivation to follow guidelines. Contrary to Ireland, however, and despite the perceived benefit of paying, UK discussants still expected PN services to be delivered free of charge by the NHS. Consideration of this unique challenge of free healthcare that is embedded in the NHS culture will be crucial when introducing PN to the UK.
The notion of educating the public through generic healthy eating messages has pervaded dietary health promotion efforts over the years and continues to do so through various media, despite little evidence for any enduring impact upon eating behaviour. There is growing evidence, however, that tailored interventions such as those that could be delivered online can be effective in bringing about healthy dietary behaviour change. The present paper brings together evidence from qualitative and quantitative studies that have considered the public perspective of genomics, nutrigenomics and personalised nutrition, including those conducted as part of the EU-funded Food4Me project. Such studies have consistently indicated that although the public hold positive views about nutrigenomics and personalised nutrition, they have reservations about the service providers’ ability to ensure the secure handling of health data. Technological innovation has driven the concept of personalised nutrition forward and now a further technological leap is required to ensure the privacy of online service delivery systems and to protect data gathered in the process of designing personalised nutrition therapies.
Wie lange währts, so bin ich hin, Und einer Nachwelt untern Füßen? Was braucht sie wen sie tritt zu wissen? Weiß ich nur wer ich bin.
— G. E. Lessing, “Ich”
Wir verlieren viel viel an ihm, mehr als wir glauben.
— J. W. Goethe to Charlotte von Stein
We can only speculate as to what Gotthold Ephraim Lessing's self-analysis, cited above, might have revealed. By the same token we have no certitude as to what Goethe meant when he responded to Lessing's death in 1781 with the remark that we have lost much, much more than we know. Yet if we summarize the many tributes of the past centuries to Lessing, the great man of letters born in a modest Lutheran parsonage, the following statement captures some of his salient traits: Lessing lived and worked at an important point in German intellectual history. He stands between the rationalist philosophy of Spinoza and Leibniz and emergent German idealism. In literature he helped Germans navigate away from Gottsched's neoclassicism, based on French models, to the Storm and Stress period, with its admiration of Shakespeare, and then to a new understanding of classicism with Goethe and Schiller. In religion he mediated between orthodox Christianity and the radical deists of his age. He did all this at a time when there existed no unified German nation.
Lessing worked in many spheres: literature and literary criticism, theology and philosophy, criticism, journalism, and translation. Despite the magnitude and versatility of his oeuvre, one can discern several recurring and unifying characteristics. Lessing employed a highly flexible, multidimensional, dialectical mode of thought. For him, thinking meant searching; the anti-dogmatic idea that no fixed truth exists (except with God) served him as guide. As a result, regardless of Lessing's sphere of activity, he vigorously put everything into question. He attacked prevalent opinions and “truths” with a polemical energy that proved often rude but always brilliant. He believed in development through contradiction, in progress through education. In his early, unfinished Das Christentum der Vernunft (The Christianity of Reason, published posthumously in 1784) he expresses his belief that humankind can approach perfection, the absolute perfection reserved for God alone.
One of the most independent thinkers in European intellectual history, a combative critic and major playwright, Gotthold Ephraim Lessing (1729–1781) contributed in decisive and lasting fashion to the discussion of philosophy, theology, and literature within the German-speaking countries and beyond. Lessing lived during the period of German Enlightenment, that liminal point between the age of religious authority and the more secular culture of modern times. He supplied new impulses to Christian theology, initiating one of the major theological disputes of the eighteenth century while contributing to debates on religious tolerance and on the emancipation of the German Jews. He published Laokoon (Laocoon, 1766) a trailblazing treatise on aesthetics, a work still influential today, particularly in semiotics and media theory. Long before Germany became a unified nation-state, Lessing supported the first attempt to create a German national theater, one financed by citizens and independent of any court. He wrote with great originality on drama theory, reinterpreting Aristotle for the eighteenth century, reforming German drama and opening it to contemporary social concerns of the rising middle class. As a playwright, Lessing employed a dramatic genre that was new to Germany, and in so doing wrote Miß Sara Sampson (1755), the first successful German “domestic” or “bourgeois” tragedy. He is also the author of one of the finest German comedies, Minna von Barnhelm (1767). In his final dramatic masterpiece, Nathan der Weise (Nathan the Wise, 1779), he writes of Christianity, Judaism, and Islam, of religious intolerance and the clash of civilizations. The centerpiece of that play, the parable of the rings, has entered the world's cultural heritage. Still resonating today, Lessing's dramas are the oldest theater pieces in German that continue to be performed regularly on German-speaking and international stages. Lessing's plays and his drama theory influenced Goethe, Schiller, Hebbel, Hauptmann, Ibsen, Strindberg, Schnitzler, and Brecht, among many others. F. J. Lamport in fact calls Lessing not merely the founder of modern German drama but of modern European drama.
The “first German intellectual in the modern sense of the word,”Lessing authored not only dramatic works, but also poetry, fables, and parables.
