: Final report

63 p.Interest in cities is growing again in Europe. Theories of "growth poles" forgotten since the 1960s re-emerge, although in different form, without the idea of building new cities in the desert. Metropolitanisation, although sometimes difficult to grasp empirically, is recognized as a post-fordist phenomena, with a gain of the importance of large cities, linked to the increasing need for size-based agglomeration effect in the global, networked knowledge economy. And European policy makers are once again discussing the need of and the form for new urban policies at European (as witnessed by the above quote), but also at national scale. From the outset, this project has had two, complementary, but not always easily reconcilable orientations: provide a broad overview of the current and future issues relevant to urban development in all of Europe, advance scientifically beyond the established and well-known data and analyses, provide innovative research. As this report was elaborated in parallel to the new State of European Cities report to be published by DG Regio, we also aimed at complementarity with that report, not wanting to repeat the same analyses based on the same data. In this project, we, therefore, worked in three parallel strands. First, all teams went through the current literature to extract the knowledge about trends, perspectives and, most importantly, driving forces for urban development in their thematic fields. Second, each of the teams focused on one or two innovative empirical research questions, generally tapping new data sources. Finally, our scenario team has taken the work of the other teams, and substantially augmented it through additional literature review, aiming at covering an even larger horizon and to provide a complete knowledge base on urban development, necessary for integrated prospective thinking. On this basis the scenarios were developed. The structure of the report reflects these three strands, adding a fourth, new strand, which consists in an assessment of the current national policy visions on urban issues across Europe. Details of all the literature reviews and analyses are presented in the scientific report

: Final report

63 p.Interest in cities is growing again in Europe. Theories of "growth poles" forgotten since the 1960s re-emerge, although in different form, without the idea of building new cities in the desert. Metropolitanisation, although sometimes difficult to grasp empirically, is recognized as a post-fordist phenomena, with a gain of the importance of large cities, linked to the increasing need for size-based agglomeration effect in the global, networked knowledge economy. And European policy makers are once again discussing the need of and the form for new urban policies at European (as witnessed by the above quote), but also at national scale. From the outset, this project has had two, complementary, but not always easily reconcilable orientations: provide a broad overview of the current and future issues relevant to urban development in all of Europe, advance scientifically beyond the established and well-known data and analyses, provide innovative research. As this report was elaborated in parallel to the new State of European Cities report to be published by DG Regio, we also aimed at complementarity with that report, not wanting to repeat the same analyses based on the same data. In this project, we, therefore, worked in three parallel strands. First, all teams went through the current literature to extract the knowledge about trends, perspectives and, most importantly, driving forces for urban development in their thematic fields. Second, each of the teams focused on one or two innovative empirical research questions, generally tapping new data sources. Finally, our scenario team has taken the work of the other teams, and substantially augmented it through additional literature review, aiming at covering an even larger horizon and to provide a complete knowledge base on urban development, necessary for integrated prospective thinking. On this basis the scenarios were developed. The structure of the report reflects these three strands, adding a fourth, new strand, which consists in an assessment of the current national policy visions on urban issues across Europe. Details of all the literature reviews and analyses are presented in the scientific report

Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Monitoring of the Sublingual Microcirculation During Cardiac Surgery:Current Knowledge and Future Directions

Handheld vital microscopes allow for direct observation of the sublingual microcirculatory perfusion during cardiac surgery. Through the use of handheld vital microscopes, it has been shown that cardiac surgery with cardiopulmonary bypass is associated with reduced and heterogenous microcirculatory perfusion. Microcirculatory impairment can result in inadequate tissue perfusion, leading to perioperative complications and poor outcome. Because microcirculatory impairment can occur despite stable or improved global hemodynamics, there is a yet unmet need for specific monitoring of the microcirculation. Technological advancements may facilitate point-of-care monitoring of microcirculatory perfusion using automated real-time analysis of microcirculatory measurements. Thus, microcirculatory monitoring may create new opportunities for specific microcirculatory treatment as part of hemodynamic management. The implementation of microcirculatory variables into personalized treatment concepts has the potential to improve hemodynamic management during cardiac surgery and thereby improve patient outcomes. Therefore, specific treatment strategies need to be developed to prevent or treat alterations of the microcirculatory perfusion. In the future, the use of handheld vital microscopes for microcirculatory monitoring may help to improve hemodynamic management and outcomes for patients undergoing cardiac surgical procedures

Thermal modeling of lesion growth with radiofrequency ablation devices

BACKGROUND: Temperature is a frequently used parameter to describe the predicted size of lesions computed by computational models. In many cases, however, temperature correlates poorly with lesion size. Although many studies have been conducted to characterize the relationship between time-temperature exposure of tissue heating to cell damage, to date these relationships have not been employed in a finite element model. METHODS: We present an axisymmetric two-dimensional finite element model that calculates cell damage in tissues and compare lesion sizes using common tissue damage and iso-temperature contour definitions. The model accounts for both temperature-dependent changes in the electrical conductivity of tissue as well as tissue damage-dependent changes in local tissue perfusion. The data is validated using excised porcine liver tissues. RESULTS: The data demonstrate the size of thermal lesions is grossly overestimated when calculated using traditional temperature isocontours of 42°C and 47°C. The computational model results predicted lesion dimensions that were within 5% of the experimental measurements. CONCLUSION: When modeling radiofrequency ablation problems, temperature isotherms may not be representative of actual tissue damage patterns

Methicillin-Susceptible ST398 Staphylococcus aureus Responsible for Bloodstream Infections: An Emerging Human-Adapted Subclone?

In the course of an annual 3-month bloodstream infections (BSI) survey conducted during a four-year period in 31 healthcare institutions located in three noncontiguous French regions, we report 18 ST398 Staphylococcus aureus BSI. ST398 BSI incidence showed a seven-fold increase during the study period (0.002 per 1,000 patient days in 2007 vs. 0.014 in 2010). ST398 BSI isolates differed from the pig-borne multiresistant clone: 17/18 BSI isolates were methicillin susceptible and none was of t011, t034 or t108 pig-borne spa-types. ST398 BSI isolates had homogenous resistance patterns (15/18 with only Eryr) and prophagic content (all harboured the hlb-converting Sau3int phage). The clustering of BSI and pig-borne isolates by spa-typing and MLVA, the occurrence of Sau3int phage in BSI isolates and the lack of this phage in pig-borne isolates suggest that the emergence of BSI isolates could have arisen from horizontal transfer, at least of the Sau3int phage, in genetically diverse MSSA ST398 isolates. The acquisition of the phage likely plays a role in the increasing ability of the lysogenic ST398 isolates to colonize human. The mode of acquisition of the non pig-borne ST398 isolates by our 18 patients remains unclear. ST398 BSI were diagnosed in patients lacking livestock exposure and were significantly associated with digestive portals of entry (3/18 [16.7%] for ST398 vs. 19/767 [2.5%] for non ST398 BSI; p = .012). This raises the question of possible foodborne human infections. We suggest the need for active surveillance to study and control the spread of this human-adapted subclone increasingly isolated in the hospital setting

Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome

The autosomal recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite the identification of the underlying gene defects, it is unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates its auto-poly(ADP-ribosyl)ation. The zinc-finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, through its association with poly(ADP-ribose) chains, ZBTB24 protects them from degradation by poly(ADP-ribose) glycohydrolase (PARG). This facilitates the poly(ADP-ribose)-dependent assembly of the LIG4/XRCC4 complex at DNA breaks, thereby promoting error-free NHEJ. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF2 syndrome

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations