Robocar and Urban Space Evolution:

How can we create more human-centered, resilient, and sustainable cities in the tech age? Can we make use of technology and the opportunities presented rather than resisting its fast-paced evolution? What are the biggest and most likely spatial changes that autonomous vehicles will bring in cities? How can this change in mobility contribute to a better urban environment? To what extent do the spatial opportunities created by automated mobility respond to current urban issues and what is the role of urban design and spatial planning in this debate? Autonomous cars—Robocars—will dramatically change urban environments and the practice of urbanism, potentially making cities less dependent on and less dominated by cars. Driverless and mainly guided by digital infrastructure, Robocars can open up new opportunities for urban development. If guided by sustainable development goals, the automation of mobility can lead to urban evolution—a shared paradigm shift in mobility and urban design. However, if Robocars are introduced as profit-driven products rather than tools to improve cities, they can cause sprawl, undermine public transport and reduce active mobility, ultimately affecting people’s health and wellbeing. Consequently, it is necessary to explore how the Robocars’ technological capabilities can provide solutions to pressing urban issues, such as growth, climate change, environmental quality, social inequality and the energy transition. On September 13, 2018, the Section of Urban Design at the Faculty of Architecture and the Built Environment, TU Delft, organised a public debate with international and Dutch experts to discuss the spatial changes that autonomous cars may bring about in cities. Subsequently, this publication gathers illustrated contributions by the key speakers at the symposium, which present ideas and further reflection points on Robocars’ relation to the urban environment. The three thematic sessions of the symposium were video recorded and are available online at robocarevolution.com. The symposium and the publication aim to raise awareness about the importance of the topic for the field of urban design and other disciplines dealing with various aspects of urban sustainability. To date, the topic of autonomous cars has mainly been addressed by car industries, technology companies and transportation planning groups. The current discourse is predominantly driven by business and marketing goals, potentially leading to cities shaped around technology. In this context, the symposium and the publication are a step forward to engaging various experts in a debate around Robocars and urban design. They propose a complementary approach to the current tech discourse on automated mobility by emphasising the importance of an urban design and spatial planning perspective, thus exploring Robocars as a spatial project. Automated vehicles can bring a mobility revolution: traffic systems and infrastructure can be reinvented, public and private transport modes can blend, and the logic of mobility in cities can be reformed, as time spent in the car will no longer be lost. Such changes create spatial opportunities and can help cities respond better to sustainable development goals; for instance, the space made available if Robocars could park themselves can be redesigned and, instead of parked cars, streets can accommodate more green space and larger sidewalks, revaluing streets as public spaces. The goal of the Robocar and Urban Space Evolution symposium and publication is to start a more inclusive debate about Robocars and their impact on the urban environment and to explore the potential of this new technology beyond market-oriented goals. The experts involved came from multiple disciplines, including spatial planning, urban design, architecture, ecology, psychology, environmental engineering and transportation planning. They discussed why and how we need to engage with the topic, given that mobility automation will dramatically shape the urban environment in different contexts and societies in the coming decades. The publication includes contributions by Rients Dijkstra and Anca Ioana Ionescu, Dominic Stead, Víctor Muñoz Sanz, David Hamers, Salvador Rueda, Nico Larco, Emilia Bruck and Mathias Mitteregger

Learning analytics in European higher education–trends and barriers

Learning analytics (LA) as a research field has grown rapidly over the last decade. However, adoption of LA is mostly found to be small in scale and isolated at the instructor level. This paper presents an exploratory study on institutional approaches to LA in European higher education and discusses prominent challenges that impede LA from reaching its potential. Based on a series of consultations with senior managers from 83 different higher education institutions in 24 European countries, we observe that LA is primarily perceived as a tool to enhance teaching and institutional management. As a result, teaching and support staff are found to be the main users of LA and the target audience of training support. In contrast, there is little evidence of active engagement with students or using LA to develop self-regulated learning skills. We highlight the importance of grounding LA in learning sciences and including students as a key stakeholder in the design and implementation of LA. This paper contributes to our understanding of the development of LA in European higher education and highlights areas to address in both practice and research. © 2020 Elsevier LtdThis work was supported by the Erasmus+ Programme of the European Union [562080-EPP- 1-2015-1-BE-EPPKA3-PI-FORWARD]. The European Commission support for the production of this publication does not constitute an endorsement of the contents which reflects the views only of the authors, and the Commission will not be held responsible for any use which may be made of the information contained therein. We would like to thank the participant of this study for their generous contributions

TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms

[EN] Objective Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer usually arising on a background of chronic liver injury involving inflammatory and hepatic regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM-2) is predominantly expressed in hepatic non-parenchymal cells and inhibits Toll-like receptor signalling, protecting the liver from various hepatotoxic injuries, yet its role in liver cancer is poorly defined. Here, we investigated the impact of TREM-2 on liver regeneration and hepatocarcinogenesis. Design TREM-2 expression was analysed in liver tissues of two independent cohorts of patients with HCC and compared with control liver samples. Experimental HCC and liver regeneration models in wild type and Trem-2-/- mice, and in vitro studies with hepatic stellate cells (HSCs) and HCC spheroids were conducted. Results TREM-2 expression was upregulated in human HCC tissue, in mouse models of liver regeneration and HCC. Trem-2-/- mice developed more liver tumours irrespective of size after diethylnitrosamine (DEN) administration, displayed exacerbated liver damage, inflammation, oxidative stress and hepatocyte proliferation. Administering an antioxidant diet blocked DEN-induced hepatocarcinogenesis in both genotypes. Similarly, Trem-2-/- animals developed more and larger tumours in fibrosis-associated HCC models. Trem-2-/- livers showed increased hepatocyte proliferation and inflammation after partial hepatectomy. Conditioned media from human HSCs overexpressing TREM-2 inhibited human HCC spheroid growth in vitro through attenuated Wnt ligand secretion. Conclusion TREM-2 plays a protective role in hepatocarcinogenesis via different pleiotropic effects, suggesting that TREM-2 agonism should be investigated as it might beneficially impact HCC pathogenesis in a multifactorial manner.Spanish Ministry of Economy and Competitiveness and ’Instituto de Salud Carlos III’ grants (MJP (PI14/00399, PI17/00022 and Ramon y Cajal Programme RYC-2015–17755); JMB (PI12/00380, PI15/01132, PI18/01075, Miguel Servet Programme CON14/00129 and CPII19/00008) cofinanced by ’Fondo Europeo de Desarrollo Regional’ (FEDER); CIBERehd: MJP, JMB and LB), Spain; IKERBASQUE, Basque foundation for Science (MJP and JMB), Spain; ’Diputación Foral de Gipuzkoa’ (MJP: DFG18/114, DFG19/081; JMB: DFG15/010, DFG16/004); BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/ BD to JMB); Department of Health of the Basque Country (MJP: 2015111100 and 2019111024; JMB: 2017111010), Euskadi RIS3 (JMB: 2016222001, 2017222014, 2018222029, 2019222054, 2020333010) Department of Industry of the Basque Country (JMB: Elkartek: KK-2020/00008) and AECC Scientific Foundation (JMB). AE-B was funded by the University of the Basque Country (UPV/EHU) (PIF2014/11) and by the short-term training fellowship Andrew K Burroughs (European Association for the Study of the Liver, EASL). IL and AA-L were funded by the Department of Education, Language Policy and Culture of the Basque Government (PRE_2016_1_0152 and PRE_2018_1_0184). OS and SK were funded by the Austrian Science Fund (FWF25801-B22, FWF-P35168 to OS and L-Mac: F 6104-B21 to SK). FO and DAM were funded by a UK Medical Research Council programme Grant MR/R023026/1. DAM was also funded by the CRUK programme grant C18342/A23390, CRUK/AECC/AIRC Accelerator Award A26813 and the MRC MICA programme grant MR/R023026/1. JBA is supported by the Danish Medical Research Council, Danish Cancer Society, Nordisk Foundation, and APM Foundation. CJO’R and PM-G are supported by Marie Sklodowska-Curie Programme and EASL Sheila Sherlock postdoctoral fellowships

Salud escolar en tiempos de Covid

El regreso a los centros educativos tras los meses de confinamiento por la pandemia de COVID-19 ha supuesto un reto para todos los países del mundo. En el caso de Europa, y concretamente España, la vuelta a las aulas ha sido un proceso complejo en el que el papel de la enfermera escolar ha sido fundamental. El objetivo del proyecto es analizar el impacto de la pandemia sobre los estudiantes de todos los niveles, así como las dificultades más relevantes encontradas en la incorporación a la educación y el papel de la enfermera en ello. Los resultados detallan los problemas más prevalentes a nivel sanitario, socioeconómico y legislativo que han surgido a raíz de la pandemia a nivel europeo, estatal y comunitario en el caso de la Comunidad de Madrid y desarrollan la labor fundamental de las enfermeras escolares en el cumplimiento de los protocolos elaborados para la reincorporación de los estudiantes a la educación semi-presencial. En las conclusiones se recogen las principales consecuencias sobre la salud bio-psico-social de los estudiantes de todos los niveles a raíz de la pandemia, la repercusión que tuvo sobre su educación, el cambio a la modalidad virtual durante el confinamiento iniciado en el mes de marzo y la posterior adaptación al sistema semi-presencial, donde uno de los protagonistas es la enfermera escolar. Su labor se basa en asegurar el cumplimiento de los protocolos y medidas de protección instauradas en todos los centros educativos y velar por la seguridad de todas las personas implicadas.Coming back to schools after months of lockdown due to the COVID-19 pandemic has been a challenge for all countries in the world. In the case of Europe, and specifically Spain, the return to the classroom has been a complex process in which the role of the school nurse has been key. The aim of the project is to analyse the impact of the pandemic on students at all levels, as well as the most relevant difficulties encountered in the incorporation into education and the role of the nurse in this. The results detail the most prevalent problems at a health, socio-economic and legislative level that have arisen as a result of the pandemic at a European, Spanish and regional level in the case of the Community of Madrid and develop the fundamental work of school nurses in the fulfilment of the protocols drawn up for the reincorporation of students into semi-attendance education. The conclusions include the main consequences on the bio-psycho-social health of students at all levels as a result of the pandemic, the impact on their education of the change to the virtual modality during the confinement that began in March and the subsequent adaptation to the blended learning system, where one of the protagonists is the school nurse. Their work is based on ensuring compliance with the protocols and protective measures established in all educational centres and ensuring the safety of all those involved

Multicentre, randomised, single-blind, parallel group trial to compare the effectiveness of a Holter for Parkinson's symptoms against other clinical monitoring methods: study protocol

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson's disease patients (Parkinson's Holter). The effectiveness of these monitoring devices for improving clinical control is not known. Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson?s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months. The primary outcome is the efficiency of the Parkinson?s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor?patient contacts will be analysed. The noninferiority of the Parkinson's Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective. Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson's Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Funding This work is supported by AbbVie S.L.U, the Instituto de Salud Carlos III [DTS17/00195] and the European Fund for Regional Development, 'A way to make Europe'

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID‑19

Background. COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods. A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results. The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). Conclusions. SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.This work was supported by awards from the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 – 170357), Research Nova Scotia (DJK), Atlantic Genome/Genome Canada (DJK), Li-Ka Shing Foundation (DJK), Dalhousie Medical Research Foundation (DJK), the “Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS‐CoV2, causante del COVID‐19”, FONDO–COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and fnally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la fnanciación de proyectos de investigación en enfermedad COVID-19” (GRS COVID 53/A/20) (CA). DJK is a recipient of the Canada Research Chair in Translational Vaccinology and Infammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world