Questions of quality: the Danish State Serum Institute, Thorvald Madsen and biological standardisation

The opening of the Danish State Serum Institute (SSI) in Copenhagen on 9 September 1902 was a festive occasion, attended by renowned figures from the wider bacteriological community including the German scientists Paul Ehrlich, Carl Weigert, and Julius Morgenroth, future Nobel prize-winner Svante Arrhenius from Sweden, Ole Malm and Armauer Hansen from Norway, and William Bulloch and German Sims Woodhead from England.1 Established as a national resource for the production of diphtheria antitoxin, the SSI was from its inception concerned to deliver a quality product at a minimum price, and to link pharmaceutical production with research into, and further development of, biological products. In the course of the twentieth century, the institute acquired an international reputation for the quality of its products and its cutting edge research, and, in the 1920s, achieved international authority as the League of Nations Health Commission’s central laboratory for the preservation and distribution of all standard sera and bacterial products.2 The rise of the SSI to international prominence came about through a combination of factors, personal, scientific and political, but above all, perhaps, from its early association with questions of quality in the production of the new generation biological medicines, of which diphtheria antitoxin was the first to emerge

Simulation of Soil Organic Carbon Effects on Long-Term Winter Wheat (Triticum aestivum) Production Under Varying Fertilizer Inputs

Acknowledgments We appreciate the financial support from EC SMARTSOIL project (Project number: 289694) for funding the collation of long-term experimental data from the project partners and Mr. Per Abrahamsen for helping with the DAISY model. The support from LANDMARK (Grant Agreement No: 635201), WaterFARMING (Grant Agreement No: 689271), and SustainFARM (Grant Agreement No: 652615) projects are acknowledged to carry out revisions and improvement of the scientific content for resubmission of the manuscriptPeer reviewedPublisher PD

Messing with nature? Exploring public perceptions of geoengineering in the UK

Anthropogenic influence on the climate – and possible societal responses to it – offers a unique window through which to examine the way people think about and relate to the natural world. This paper reports data from four, one-day deliberative workshops conducted with members of the UK public during early 2012. The workshops focused on geoengineering – the deliberate, large-scale manipulation of the planetary environment – as one of three possible responses to climate change (alongside mitigation and adaptation). Here, we explore one of the most pervasive and wide-ranging themes to emerge from the workshops: whether geoengineering represented an unprecedented human intervention into ‘nature’, and what the moral consequences of this might be. Using the concept of ‘messing with nature’ as an analytical lens, we explore public perceptions of geoengineering. We also reflect on why ‘messing with nature’ was such a focal point for debate and disagreement, and whether the prospect of geoengineering may reveal new dimensions to the way that people think about the natural world, and their relationship to it

Rationalizing polyp matching criteria in colon capsule endoscopy: an international expert consensus through RAND (modified DELPHI) process

Background: Colon capsule endoscopy (CCE) has gained momentum as an alternative modality for the investigation of the lower gastrointestinal tract. Of the few challenges that remain, the comparison and – eventually – matching of polyps at different timestamps leads to the potential for double reporting and can contribute to false-positive findings and inaccuracies. With the impending artificial intelligence integration, the risk of double reporting the same polyp due to the lack of information on spatial orientation underscores the necessity for establishing criteria for polyp matching. Objectives: This RAND/University of California, Los Angeles (modified Delphi) process aims to identify the key factors or components used to match polyps within a CCE video. This involves exploring the attributes of each factor to create comprehensive polyp-matching criteria based on international expert consensus. Design: A systematic qualitative study using surveys. Methods: A panel of 11 international CCE experts convened to assess a survey comprised of 60 statements. Participants anonymously rated statement appropriateness on a 1–9 scale (1–3: inappropriate, 4–6: uncertain and 7–9: appropriate). Following a virtual group discussion of the Round 1 results, a Round 2 survey was developed and completed before the final analysis. Results: The factors that were agreed to be essential for polyp matching include (1) timestamp, (2) polyp localization, (3) polyp vascular pattern, (4) polyp size, (5) time interval of the polyp appearance between the green and yellow camera, (6) surrounding tissue, (7) polyp morphology and (8) polyp surface and contour. When five or more factors are satisfied, it was agreed that the comparing polyps are likely the same polyp. Conclusion: This study has established the first complete criteria for polyp matching in CCE. While it might not provide a definitive solution for matching difficult, small and common polyps, these criteria serve as a framework to guide and facilitate the process of polyp-matching

Multimorbidity and survival for patients with acute myocardial infarction in England and Wales: Latent class analysis of a nationwide population-based cohort

Background: There is limited knowledge of the scale and impact of multimorbidity for patients who have had an acute myocardial infarction (AMI). Therefore, this study aimed to determine the extent to which multimorbidity is associated with long-term survival following AMI. Methods and findings: This national observational study included 693,388 patients (median age 70.7 years, 452,896 [65.5%] male) from the Myocardial Ischaemia National Audit Project (England and Wales) who were admitted with AMI between 1 January 2003 and 30 June 2013. There were 412,809 (59.5%) patients with multimorbidity at the time of admission with AMI, i.e., having at least 1 of the following long-term health conditions: diabetes, chronic obstructive pulmonary disease or asthma, heart failure, renal failure, cerebrovascular disease, peripheral vascular disease, or hypertension. Those with heart failure, renal failure, or cerebrovascular disease had the worst outcomes (39.5 [95% CI 39.0–40.0], 38.2 [27.7–26.8], and 26.6 [25.2–26.4] deaths per 100 person-years, respectively). Latent class analysis revealed 3 multimorbidity phenotype clusters: (1) a high multimorbidity class, with concomitant heart failure, peripheral vascular disease, and hypertension, (2) a medium multimorbidity class, with peripheral vascular disease and hypertension, and (3) a low multimorbidity class. Patients in class 1 were less likely to receive pharmacological therapies compared with class 2 and 3 patients (including aspirin, 83.8% versus 87.3% and 87.2%, respectively; β-blockers, 74.0% versus 80.9% and 81.4%; and statins, 80.6% versus 85.9% and 85.2%). Flexible parametric survival modelling indicated that patients in class 1 and class 2 had a 2.4-fold (95% CI 2.3–2.5) and 1.5-fold (95% CI 1.4–1.5) increased risk of death and a loss in life expectancy of 2.89 and 1.52 years, respectively, compared with those in class 3 over the 8.4-year follow-up period. The study was limited to all-cause mortality due to the lack of available cause-specific mortality data. However, we isolated the disease-specific association with mortality by providing the loss in life expectancy following AMI according to multimorbidity phenotype cluster compared with the general age-, sex-, and year-matched population. Conclusions: Multimorbidity among patients with AMI was common, and conferred an accumulative increased risk of death. Three multimorbidity phenotype clusters that were significantly associated with loss in life expectancy were identified and should be a concomitant treatment target to improve cardiovascular outcomes