Regulation of Lymphatic GM-CSF Expression by the E3 Ubiquitin Ligase Cbl-b

Genome-wide association studies as well as lymphatic expression analyses have linked both Cbl-b and GM-CSF to human multiple sclerosis as well as other autoimmune diseases. Both Cbl-b and GM-CSF have been shown to play a prominent role in the development of murine encephalomyelitis; however, no functional connection between the two has yet been established. In this study, we show that Cblb knockout mice demonstrated significantly exacerbated severity of experimental autoimmune encephalomyelitis (EAE), augmented T cell infiltration into the central nervous system (CNS) and strongly increased production of GM-CSF in T cells in vitro and in vivo.GM-CSF neutralization demonstrated that the increased susceptibility of Cblb−/− mice to EAE was dependent on GM-CSF. Mechanistically, p50 binding to the GM-CSF promoter and the IL-3/GM-CSF enhancer element “CNSa” was strongly increased in nuclear extracts from Cbl-b-deficient T cells. This study suggests that Cbl-b limits autoimmunity by preventing the pathogenic effects of GM-CSF overproduction in T cells

A Crowdsourced Approach for the Documentation and Transcription of Graffiti in Public Restrooms

In this short paper we introduce graffiti in public restrooms – also known as latrinalia – as a promising object of research. We present an application that uses crowdsourcing techniques to upload and transcribe images of latrinalia on a public web site. This article describes the basic design and functions of the application, presents the status quo of the current dataset, and also gives an outlook on the next steps and future work

Successful direct acting antiviral (DAA) treatment of HCV/HIV-coinfected patients before and after liver transplantation

Objectives The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively. Methods When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1);MELD range 7-21;HCC (n = 2);HCV genotype la (n = 8), 1 b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1)). Results Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy;subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in followup. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation;in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up. Conclusion DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted

A massive, Late Neolithic pit structure associated with Durrington Walls Henge

YesA series of massive geophysical anomalies, located south of the Durrington Walls henge monument, were identified during fluxgate gradiometer survey undertaken by the Stonehenge Hidden Landscapes Project (SHLP). Initially interpreted as dewponds, these data have been re-evaluated, along with information on similar features revealed by archaeological contractors undertaking survey and excavation to the north of the Durrington Walls henge. Analysis of the available data identified a total of 20 comparable features, which align within a series of arcs adjacent to Durrington Walls. Further geophysical survey, supported by mechanical coring, was undertaken on several geophysical anomalies to assess their nature, and to provide dating and environmental evidence. The results of fieldwork demonstrate that some of these features, at least, were massive, circular pits with a surface diameter of 20m or more and a depth of at least 5m. Struck flint and bone were recovered from primary silts and radiocarbon dating indicates a Late Neolithic date for the lower silts of one pit. The degree of similarity across the 20 features identified suggests that they could have formed part of a circuit of large pits around Durrington Walls, and this may also have incorporated the recently discovered Larkhill causewayed enclosure. The diameter of the circuit of pits exceeds 2km and there is some evidence that an intermittent, inner post alignment may have existed within the circuit of pits. One pit may provide evidence for a recut; suggesting that some of these features could have been maintained through to the Middle Bronze Age. Together, these features represent a unique group of features related to the henge at Durrington Walls, executed at a scale not previously recorded.The University of Bradford Research Development Fund and the University of St Andrews funded this open access publication.Supplementary data can be found at https://intarch.ac.uk/journal/issue55/4/supp-text.htm

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The impact of moisture on salt treated and 2-step mineralized wood

A treatment to improve the reaction to fire of wood is the wood mineralization. Besides the reaction to fire of the mineralized wood, other mechanical and physical properties are less investigated. In this study, beech and oak were treated in a 2-step mineralization process to obtain calcium oxalate mineralized wood. The 2-step mineralization process is carried out by impregnating two salts diluted in water into the wood, consecutively. Two formulations were applied. For Formulation 1, potassium oxalate and calcium acetate and for Formulation 2 potassium oxalate and calcium chloride were used. Aim of the study is to investigate the impact of the treatments and in combination of the moisture on some selected properties of the mineralized wood. These properties are the swelling due to the mineralization treatment, the Brinell hardness and the volatile organic compounds emissions. The 2-step mineralization treatments increased the moisture adsorption of wood. However, the removal of unreacted precursors due to leaching provides a material with comparable moisture dynamics to untreated wood. Swelling, hardness and volatile organic compounds emissions are decreased by the mineralization. However, leaching of the reaction by-products leads to a material with comparable properties to those of untreated wood

Utilization-focused scientific policy advice: a six-point checklist

Knowledge utilization depends on how well the scientific community communicates knowledge to its target audiences’ needs. We argue that policy-relevant science communication can increase the real-life impact of scientific evidence by moving beyond political agenda-setting and providing concrete advice to policy drafters. Agenda-setting seeks to raise politicians’ and the wider public’s awareness of a problem (problem advice). However, for scientific evidence to translate into effective policy interventions, the scientific community and non-governmental organizations (NGOs) must also provide policy drafters with advice on policy design and implementation (policy advice). Political attention is volatile, and – except for particularly policy-driven and solution-focused actors – politicians have little incentive to address long-term issues such as climate change if voters do not punish short-term thinking. In contrast, the public administration (government agencies) carries out long-term expert work. Government agencies are therefore the primary recipients of evidence-based knowledge transfer that aims to create concrete policy solutions. We develop hands-on recommendations for tailoring scientific advice to the needs of policy drafters through a six-point checklist. Based on utilization-focused evaluation research, we argue that scientific evidence should not only address the causes of public problems but also the effectiveness of proposed policy solutions and the consequences of policy decisions. We also highlight the need to assess the political feasibility of a given policy proposal (potential oppositions and stumbling blocks) and its practical implementability (likely reaction of the target groups). Ensuring effective policy advice requires transdisciplinary dialogue between natural, social, and policy scientists, as well as dialogue between research and government agencies. Key policy insights There is a gap between public and political awareness of climate change issues and effective policy solutions. Due to their respective roles within the policy process, politicians and government agencies have different knowledge needs. In addition to providing politicians and the general public with problem advice, a specific form of policy advice, that is, policy-prescriptive evidence-based information, should be developed and provided for policy drafters within government agencies. Natural, social and policy scientists must team up to provide policy advice that is not only evidence-based but also utilization-focused

Communication scientifique dans la lutte contre le changement climatique

Afin de favoriser l’utilisation des résultats de la recherche dans le processus politique, les scientifiques doivent communiquer avec différents types de publics ayant des besoins et des caractéristiques propres. Alors que la phase de mise à l’agenda politique d’un problème tend à retenir l’attention en raison de sa forte visibilité, l’action publique ne s’arrête pas aux portes de la prise de décision politique. Pour assurer la mise en œuvre d’une réponse publique à des problématiques telles que le changement climatique, il s’agit d’une part de susciter la prise de conscience des éluꞏeꞏs et du grand public (communication scientifique axée sur le problème), mais aussi d’autre part de mettre à disposition des administrations une expertise portant sur le contenu des politiques publiques (communication scientifique axée sur les politiques publiques). Les savoirs et savoir­faire accumulés en évaluation des politiques publiques constituent à cet égard une ressource essentielle