European Core Health Indicators - status and perspectives.

The European Core Health Indicators (ECHI) are a key source of comparable health information for the European Union (EU) and its Member States (MS). The ECHI shortlist contains 88 indicators which were developed by experts from MS and international organisations. Most indicators are derived from data sources at the EU's statistical office (Eurostat), the World Health Organisation (WHO) and the Organisation for Economic Co-operation and Development (OECD) and are available for most MS. The remaining indicators on the shortlist are at different stages of conceptual and/or methodological development. The indicators have been reviewed in the past against scientific developments, changes in data collections and emerging policy needs, yet not as part of a systematic and sustainable procedure. There is also no regular inventory of problems met by the MS in collecting the necessary data. Work package 4 of the BRIDGE Health project aimed at updating and improving the existing ECHI-indicator knowledge and expertise and at strengthening the scientific base that supports the effective development and use of health indicators for health policy evaluation and prioritization by the EU and its MS. The aim of this paper is to present a first overview of its outcomes and to explore issues concerning the ECHI data availability, content and policy relevance, update process and accessibility to stakeholders, in light of working towards a sustainable future

On ‘Organized Crime’ in the illicit antiquities trade: moving beyond the definitional debate

The extent to which ‘organized crime’ is involved in illicit antiquities trafficking is unknown and frequently debated. This paper explores the significance and scale of the illicit antiquities trade as a unique transnational criminal phenomenon that is often said to be perpetrated by and exhibit traits of so-called ‘organized crime.’ The definitional debate behind the term ‘organized crime’ is considered as a potential problem impeding our understanding of its existence or extent in illicit antiquities trafficking, and a basic progression-based model is then suggested as a new tool to move beyond the definitional debate for future research that may help to elucidate the actors, processes and criminal dynamics taking place within the illicit antiquities trade from source to market. The paper concludes that researchers should focus not on the question of whether organized criminals- particularly in a traditionally conceived, mafia-type stereotypical sense- are involved in the illicit antiquities trade, but instead on the structure and progression of antiquities trafficking itself that embody both organized and criminal dynamics

Use of specific Green's functions for solving direct problems involving a heterogeneous rigid frame porous medium slab solicited by acoustic waves

A domain integral method employing a specific Green's function (i.e., incorporating some features of the global problem of wave propagation in an inhomogeneous medium) is developed for solving direct and inverse scattering problems relative to slab-like macroscopically inhomogeneous porous obstacles. It is shown how to numerically solve such problems, involving both spatially-varying density and compressibility, by means of an iterative scheme initialized with a Born approximation. A numerical solution is obtained for a canonical problem involving a two-layer slab.Comment: submitted to Math.Meth.Appl.Sc

Centrosome defects cause microcephaly by activating the 53BP1-USP28-TP53 mitotic surveillance pathway

Mutations in centrosome genes deplete neural progenitor cells (NPCs) during brain development, causing microcephaly. While NPC attrition is linked to TP53-mediated cell death in several microcephaly models, how TP53 is activated remains unclear. In cultured cells, mitotic delays resulting from centrosome loss prevent the growth of unfit daughter cells by activating a pathway involving 53BP1, USP28, and TP53, termed the mitotic surveillance pathway. Whether this pathway is active in the developing brain is unknown. Here, we show that the depletion of centrosome proteins in NPCs prolongs mitosis and increases TP53-mediated apoptosis. Cell death after a delayed mitosis was rescued by inactivation of the mitotic surveillance pathway. Moreover, 53BP1 or USP28 deletion restored NPC proliferation and brain size without correcting the upstream centrosome defects or extended mitosis. By contrast, microcephaly caused by the loss of the non-centrosomal protein SMC5 is also TP53-dependent but is not rescued by loss of 53BP1 or USP28. Thus, we propose that mutations in centrosome genes cause microcephaly by delaying mitosis and pathologically activating the mitotic surveillance pathway in the developing brain

Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy

Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed

Genetic instability from a single S phase after whole-genome duplication

Diploid and stable karyotypes are associated with health and fitness in animals. By contrast, whole-genome duplications—doublings of the entire complement of chromosomes—are linked to genetic instability and frequently found in human cancers(1–3). It has been established that whole-genome duplications fuel chromosome instability through abnormal mitosis(4–8); however, the immediate consequences of tetraploidy in the first interphase are not known. This is a key question because single whole-genome duplication events such as cytokinesis failure can promote tumorigenesis(9). Here we find that human cells undergo high rates of DNA damage during DNA replication in the first S phase following induction of tetraploidy. Using DNA combing and single-cell sequencing, we show that DNA replication dynamics is perturbed, generating under- and over-replicated regions. Mechanistically, we find that these defects result from a shortage of proteins during the G1/S transition, which impairs the fidelity of DNA replication. This work shows that within a single interphase, unscheduled tetraploid cells can acquire highly abnormal karyotypes. These findings provide an explanation for the genetic instability landscape that favours tumorigenesis after tetraploidization

Nitrifying and heterotrophic population dynamics in biofilm reactors: effects of hydraulic retention time and the presence of organic carbon

Two biofilmreactors operated with hydraulic retention times of 0.8 and 5.0 h were used to study the links between population dynamics and reactor operation performance during a shift in process operation from pure nitrification to combined nitrification and organic carbon removal. The ammonium and the organic carbon loads were identical for both reactors. The composition and dynamics of the microbial consortia were quantified by fluorescence in situ hybridization (FISH) with rRNA-targeted oligonucleotide probes combined with confocal laser scanning microscopy, and digital image analysis. In contrast to past research, after addition of acetate as organic carbon nitrification performance decreased more drastically in the reactor with longer hydraulic retention time. FISH analysis showed that this effect was caused by the unexpected formation of a heterotrophic microorganism layer on top of the nitrifying biofilm that limited nitrifiers oxygen supply. Our results demonstrate that extension of the hydraulic retention time might be insufficient to improve combined nitrification and organic carbon removal in biofilm reactors.Ministério da Ciência, Tecnologia e Ensino Superior. Fundação para a Ciência e a Tecnologia (FCT) - PRAXIS XXI BD/15943/98). Deutscher Akademischer Austauschdienst (A/99/06961). European Comission - T.M.R. BioToBio project. Deutsche Forschungsgemeinschaft

Corporate social responsibility disclosures in international construction business: trends and prospects

There is increasing sophistication in corporate social responsibility (CSR) disclosures by international construction companies (ICCs). Nevertheless, a systematic analysis of the trends and prospects is yet to appear. This study fills that knowledge gap by providing an understanding of the idiosyncrasies of CSR disclosure and by offering suggestions for future reporting exercises. By examining the top fifty ICCs’ CSR/sustainability reports using content analysis, it found that the more negative impacts a company may have, the more remedial strategies it will disclose in a CSR report. ICCs from economically more developed countries maintain a high level of CSR disclosure, while their counterparts from developing countries have caught up in this CSR cause. As a way to improve the consistency and integrity of disclosed information, ICCs are increasingly adopting CSR reporting guidance frameworks and using third-party assurances. CSR disclosures present a high degree of uniformity while they also show nuanced and intriguing diversity. This research helps understand comprehensively the trends of CSR disclosure in international construction. It will help ICCs extrapolate their future CSR reporting exercises.postprin

Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial

Objective. To compare the effects of aggressive tight control therapy and conventional care on radiographic progression and disease activity in patients with early mild inflammatory arthritis