The Early Royal Society and Visual Culture

Recent studies have fruitfully examined the intersection between early modern science and visual culture by elucidating the functions of images in shaping and disseminating scientific knowledge. Given its rich archival sources, it is possible to extend this line of research in the case of the Royal Society to an examination of attitudes towards images as artefacts –manufactured objects worth commissioning, collecting and studying. Drawing on existing scholarship and material from the Royal Society Archives, I discuss Fellows’ interests in prints, drawings, varnishes, colorants, images made out of unusual materials, and methods of identifying the painter from a painting. Knowledge of production processes of images was important to members of the Royal Society, not only as connoisseurs and collectors, but also as those interested in a Baconian mastery of material processes, including a “history of trades”. Their antiquarian interests led to discussion of painters’ styles, and they gradually developed a visual memorial to an institution through portraits and other visual records.AH/M001938/1 (AHRC

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

<p>Abstract</p> <p>Background</p> <p>Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events.</p> <p>Methods</p> <p>The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism.</p> <p>Discussion</p> <p>patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).</p> <p>Trial Registration</p> <p>Trial listed in ClinicalTrials.gov as <a href="http://www.clinicaltrials.gov/ct2/show/NCT00166257">NCT00166257</a> and sponsored by AGA Medical, Plymouth, MN, USA</p

A decade with vamdc: Results and ambitions

This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&amp;M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&amp;M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&amp;M data from more than one database. Finally, we present our vision for the future of VAMDC.</jats:p

A Decade with VAMDC: Results and Ambitions

This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&M data from more than one database. Finally, we present our vision for the future of VAMDC

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial

Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001). Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term

UKESM1: description and evaluation of the UK Earth System Model

We document the development of the first version of the United Kingdom Earth System Model UKESM1. The model represents a major advance on its predecessor HadGEM2‐ES, with enhancements to all component models and new feedback mechanisms. These include: a new core physical model with a well‐resolved stratosphere; terrestrial biogeochemistry with coupled carbon and nitrogen cycles and enhanced land management; tropospheric‐stratospheric chemistry allowing the holistic simulation of radiative forcing from ozone, methane and nitrous oxide; two‐moment, five‐species, modal aerosol; and ocean biogeochemistry with two‐way coupling to the carbon cycle and atmospheric aerosols. The complexity of coupling between the ocean, land and atmosphere physical climate and biogeochemical cycles in UKESM1 is unprecedented for an Earth system model. We describe in detail the process by which the coupled model was developed and tuned to achieve acceptable performance in key physical and Earth system quantities, and discuss the challenges involved in mitigating biases in a model with complex connections between its components. Overall the model performs well, with a stable pre‐industrial state, and good agreement with observations in the latter period of its historical simulations. However, global mean surface temperature exhibits stronger‐than‐observed cooling from 1950 to 1970, followed by rapid warming from 1980 to 2014. Metrics from idealised simulations show a high climate sensitivity relative to previous generations of models: equilibrium climate sensitivity (ECS) is 5.4 K, transient climate response (TCR) ranges from 2.68 K to 2.85 K, and transient climate response to cumulative emissions (TCRE) is 2.49 K/TtC to 2.66 K/TtC

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570