Provision and Quality Assurance of Preimplantation Genetic Diagnosis in Europe

Preimplantation genetic diagnosis (PGD) is now well established and provided in many European countries. However, regulations, professional standards and accreditation requirements can differ notably. Furthermore, no comprehensive independent data exist either about practice and provision in Europe or about the quality assurance practices and procedures designed to optimize the quality of the results. Consequently, a study was launched to obtain knowledge, currently lacking, of the provision and quality assurance of PGD services and cross-border activities in Europe. An online questionnaire was developed and sent to PGD providers, and expert opinions were obtained through interviews with professionals in specific countries. Information was gathered from 53 centres offering PGD in 17 European countries. There is a diverse array of tests available, with a trend for custom-made services. Although half of the centres have a designated quality manager, just 33% have achieved or are preparing for accreditation or certification. About 66% of the centres responded that they did not participate in external quality assessment, a problem exacerbated by the lack of existing PGD-specific schemes. Approximately 19% of the centres do not keep data on accuracy and 9% do not even follow up until birth. PGD is an expanding activity with an increasing international flow that accounts for approximately one-third of the activity reported. The survey highlights a significant need for improvement in quality assurance in PGD centres. On the positive side, important improvements in the quality management of these services are expected with the European Tissue Directive entering into force.JRC.J.5-Agriculture and Life Sciences in the Econom

Aportaciones al estudio de las bases moleculares de la enfermedad de Alzheimer

Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Genética, leída el 22-02-1996El objetivo general de esta tesis es la detección y caracterización a nivel celular y molecular de las posibles alteraciones estructurales de los genes implicados en la etiopatogenia de la enfermedad de alzheimer.la enfermedad de alzheimer (ea) es la causa mas comun de demencia en los individuos de mediana y avanzada edad. Un estudio europeo a gran escala encontró que 0,4% de las mujeres y 0,3% de los hombres entre los 60 y 69 años, y que 11,2% de mujeres y 10% de los hombre entre los 80 y 89 de la población padecen ea (rocca y col, 1991). Teniendo en cuenta la tendencia de la expectativa de vida media a alargarse, se entiende que la ea se esta convirtiendo en un grave problema para la salud publica. Hemos establecido un banco de líneas celulares inmortales de enfermos de alhzeimer mediante transformación de linfocitos b con virus de epstein barr. Este modelo experimental, además de obviar las dificultades de obtención de material, ha permitido el estudio de perturbaciones funcionales de índole variada. El análisis estructural de regiones relevantes del gen que codifica la proteína precursora del peptido b-amiloide en mas de 100 casos de enfermos de alzheimer no ha desvelado la existencia de anomalías. Se ha observado un aumento considerable en la frecuencia del alelo de la apolipoproteina e en casos familiares de la enfermedad de alzheimer de aparición tardía en el área de Madrid. Hemos puesto de manifiesto que en la demencia de alzheimer existen cambios significativos en la homeostasis de que podrían estar implicados en la etiopatogenia de este proceso. Cambios de esta naturaleza en el medio intracelular pueden ser la causa de alteraciones en la expresion, procesamiento, solubilidad, y/o función de múltiples proteinasDepto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEpu

Global warming and human impacts of heat and cold extremes in the EU

During intense heatwaves in June and July 2019, all-time temperature records were broken in many locations in Europe. These events are projected to happen more frequently and become more intense with climate change. Projections show that the number of citizens in the EU and UK exposed to heatwaves will grow from 10 million/year (average 1981-2010) to nearly 300 million/year, or more than half the EU population, in a scenario with 3°C global average warming by the end of this century. In case of no adaptation this could result in 96,000 fatalities/year from extreme heat, compared to 2,750 annual deaths at present. Curbing global warming to 1.5°C would limit mortality from extreme heat to around 30,000 fatalities/year. The rise in exposure to and projected fatalities from extreme heat is most pronounced in southern Europe. Milder winters will reduce significantly exposure to and fatalities from extreme cold, nearly 10-fold with 3°C global average warming by the end of this century.JRC.E.1-Disaster Risk Managemen

Adaptation to climate change: a comparative analysis of modelling methods for heat-related mortality

Background: Multiple methods are employed for modelling adaptation when projecting the impact of climate change on heat-related mortality. The sensitivity of impacts to each is unknown because they have never been systematically compared. In addition, little is known on the relative sensitivity of impacts to “adaptation uncertainty” (i.e. the inclusion/exclusion of adaptation modelling), relative to using multiple climate models and emissions scenarios. Objectives: (1) Compare the range in projected impacts that arises from using different adaptation modelling methods; (2) compare the range in impacts that arises from adaptation uncertainty to ranges from using multiple climate models and emissions scenarios; (3) recommend modelling method(s) to use in future impact assessments. Methods: We estimated impacts for 2070-2099, for 14 European cities, applying six different methods for modelling adaptation; also with climate projections from five climate models, run under two emissions scenarios to explore the relative effects of climate modelling and emissions uncertainty. Results: The range of the difference (%) in impacts between including and excluding adaptation, irrespective of climate modelling and emissions uncertainty, can be as low as 28% with one method and up to 103% with another (mean across 14 cities). In 13 of 14 cities the ranges in projected impacts due to adaptation uncertainty are larger than those associated with climate modelling and emissions uncertainty. Conclusions: Researchers should carefully consider how to model adaptation because it is a source of uncertainty that can be greater than the uncertainty in emissions and climate modelling. We recommend absolute threshold shifts and reductions in slope

Biobanks in Europe: Prospects for Harmonisation and Networking

Biobanks (i.e. the organised collections consisting of biological samples and associated data, have gained great significance for research and personalised medicine) are increasingly recognised as a crucial infrastructure for research. However, at the same time the widely varied practices in biobanking regarding for example collection, storage and consent procedures may also pose a barrier to cross-border research and collaboration by limiting access to samples and data. In this context, a recent study indicates that the limited sharing and linkage of samples is a key barrier for research, such as pharmacogenetics. Wide variation is observed in the implementation of relevant existing regulation, which may add further burden to harnessing the public health benefit of these collections. Therefore, it has been suggested that there is a strong need for a harmonised approach on biobanking practices and improved networking of existing and new collections. This Report shows information on the extent of biobanking in Europe, collected through a survey of existing European biobanks regarding both technical aspects (e.g. storage conditions) and aspects of governance and ethics (e.g. sample and data sharing, consent procedures, collaborations etc.). In total, 126 biobanks from 23 countries in Europe were surveyed. Significant lack of harmonisation has been found, especially in the legal aspects (e.g. data protection, consent). This may be partly attributed to the varied interpretation and implementation of EC directives covering aspects of biobanking by national authorities. One of the main complications is that, although the field of data protection is harmonised through the EC directive on data protection, the collection, storage, and sharing of samples is not. Furthermore, in countries that have introduced special biobanks acts it is not always clear where the borderline lies between the scope of these acts and that of the Directive. Indeed, according to the survey, biobanks within the same country reported different practices, suggesting that the problems of harmonization might be higher than expected and claimed. Not only are there different national laws, but apparently within EU member states biobanks do not implement homogenous practices on privacy and data protection issues. Desk research and expert interviews were done to complete the picture presented by the survey. Experts widely recognised the need to improve collaboration and networking among the numerous existing biobanks, as well as new initiatives in Europe (and world-wide). Efficient organisation of these resources through the development, for example, of an infrastructure would potentially facilitate financial sustainability and greatly contribute to the rapid progress of research and development of better diagnostic and therapeutic approaches. The most favoured model involved the development of a virtual biobank that would allow networking of biobanks across different countries and centralisation of data rather than samples. However, several organisational challenges (wide variation in biospecimen collection, storage techniques, data comparability, etc.) may hamper such an effort. The lack of uniform regulatory and ethical requirements and/or practices may pose an additional barrier. The European Commission has already recognised the importance of international biobank projects and many of them have been funded and established in the context of the EU Framework Programmes. To help promote networking of biobanks and thus maximise public health benefits, at least some degree of harmonisation must be achieved. Whether this should be achieved solely at the level of legal/regulatory requirements and practices and/or by technical standardisation requires further investigation. Experts suggested the establishment of an international (rathen than just a European) umbrella (or network) organization, which would establish common operating procedures.JRC.DDG.J.2-The economics of climate change, energy and transpor

The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues

The interface between assisted reproductive technologies (ART) and genetics comprises several sensitive and important issues that affect infertile couples, families with severe genetic diseases, potential children, professionals in ART and genetics, health care, researchers and the society in general. Genetic causes have a considerable involvement in infertility. Genetic conditions may also be transmitted to the offspring and hence create transgenerational infertility or other serious health problems. Several studies also suggest a slightly elevated risk of birth defects in children born following ART. Preimplantation genetic diagnosis (PGD) has become widely practiced throughout the world for various medical indications, but its limits are being debated. The attitudes towards ART and PGD vary substantially within Europe. The purpose of the present paper was to outline a framework for development of guidelines to be issued jointly by European Society of Human Genetics and European Society of Human Reproduction and Embryology for the interface between genetics and ART. Technical, social, ethical and legal issues of ART and genetics will be reviewed.JRC.J.5-Agriculture and Life Sciences in the Econom

Cost-effectiveness of pharmacogenomics in clinical practice: a case study of thiopurine methyltransferase genotyping in acute lymphoblastic leukemia in Europe. Pharmacogenomics

Only a few studies have addressed the cost-effectiveness of pharmacogenetics interventions in healthcare. Lack of health economics data on aspects of pharmacogenetics is perceived as one of the barriers hindering its implementation for improving drug safety. Thus, a recent Institute for Prospective Technological Studies (IPTS) study, entitled 'Pharmacogenetics and pharmacogenomics: State-of-the-art and potential socio-economic impact in the EU' included an explorative cost-effectiveness review for a pharmacogenetic treatment strategy compared with traditional medical practice. The selected case study examined the cost-effectiveness of thiopurine methyltransferase (TMPT) genotyping prior to thiopurine treatment in children with acute lymphoblastic leukemia (ALL). Information for the cost-effectiveness model parameters was collected from literature surveys and interviews with experts from four European countries (Germany, Ireland, the Netherlands and the UK). The model has established that TPMT testing in ALL patients has a favorable cost-effectiveness ratio. This conclusion was based on parameters collected for TPMT genotyping costs, estimates for frequency of TMPT deficiency, rates of thiopurinemediated myelosuppression in TPMT-deficient individuals, and myelosuppression-related hospitalization costs in each of the four countries studied. The mean calculated cost per life-year gained by TPMT genotyping in ALL patients in the four study countries was €2100 (or €4800 after 3% discount) based on genotyping costs of €150 per patient. Cost per lifeyear gained is expected to further improve following the introduction of the wider use of TMPT genotyping and the availability of lower cost genotyping methods. Our analysis indicates that TPMT genotyping should be seriously considered as an integral part of healthcare prior to the initiation of therapy with thiopurine drugs

Climate change impacts and adaptation in Europe

The JRC PESETA IV study shows that ecosystems, people and economies in the EU will face major impacts from climate change if we do not urgently mitigate greenhouse gas emissions or adapt to climate change. The burden of climate change shows a clear north-south divide, with southern regions in Europe much more impacted, through the effects of extreme heat, water scarcity, drought, forest fires and agriculture losses. Limiting global warming to well below 2°C would considerably reduce climate change impacts in Europe. Adaptation to climate change would further minimize unavoidable impacts in a cost-effective manner, with considerable co-benefits from nature-based solutions.JRC.C.6-Economics of Climate Change, Energy and Transpor

Comparison of weather station and climate reanalysis data for modelling temperature-related mortality

Multi-Country Multi-City (MCC) Collaborative Research Network: Barrak Alahmad, Rosana Abrutzky, Paulo Hilario Nascimento Saldiva, Patricia Matus Correa, Nicolás Valdés Orteg, Haidong Kan, Samuel Osorio, Ene Indermitte, Jouni J K Jaakkola, Niilo Ryti, Alexandra Schneider, Veronika Huber, Klea Katsouyanni, Antonis Analitis, Alireza Entezari, Fatemeh Mayvaneh, Paola Michelozzi, Francesca de'Donato, Masahiro Hashizume, Yoonhee Kim, Magali Hurtado Diaz, César De la Cruz Valencia, Ala Overcenco, Danny Houthuijs, Caroline Ameling, Shilpa Rao, Xerxes Seposo, Baltazar Nunes, Iulian-Horia Holobaca, Ho Kim, Whanhee Lee, Carmen Íñiguez, Bertil Forsberg, Christofer Åström, Martina S Ragettli, Yue-Liang Leon Guo, Bing-Yu Chen, Valentina Colistro, Antonella Zanobetti, Joel Schwartz, Tran Ngoc Dang, Do Van DungErratum in: Author Correction: Sci Rep. 2022 May 13;12(1):7960. doi: 10.1038/s41598-022-11769-6. https://www.nature.com/articles/s41598-022-11769-6Epidemiological analyses of health risks associated with non-optimal temperature are traditionally based on ground observations from weather stations that offer limited spatial and temporal coverage. Climate reanalysis represents an alternative option that provide complete spatio-temporal exposure coverage, and yet are to be systematically explored for their suitability in assessing temperature-related health risks at a global scale. Here we provide the first comprehensive analysis over multiple regions to assess the suitability of the most recent generation of reanalysis datasets for health impact assessments and evaluate their comparative performance against traditional station-based data. Our findings show that reanalysis temperature from the last ERA5 products generally compare well to station observations, with similar non-optimal temperature-related risk estimates. However, the analysis offers some indication of lower performance in tropical regions, with a likely underestimation of heat-related excess mortality. Reanalysis data represent a valid alternative source of exposure variables in epidemiological analyses of temperature-related risk.The study was primarily supported by Grants from the European Commission’s Joint Research Centre Seville (Research Contract ID: JRC/SVQ/2020/MVP/1654), Medical Research Council-UK (Grant ID: MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/R009384/1), European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). The following individual Grants also supported this work: J.K and A.U were supported by the Czech Science Foundation, project 20-28560S. A.T was supported by MCIN/AEI/10.13039/501100011033, Grant CEX2018-000794-S. V.H was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant agreement No 101032087.info:eu-repo/semantics/publishedVersio

Comparison of weather station and climate reanalysis data for modelling temperature-related mortality.

Epidemiological analyses of health risks associated with non-optimal temperature are traditionally based on ground observations from weather stations that offer limited spatial and temporal coverage. Climate reanalysis represents an alternative option that provide complete spatio-temporal exposure coverage, and yet are to be systematically explored for their suitability in assessing temperature-related health risks at a global scale. Here we provide the first comprehensive analysis over multiple regions to assess the suitability of the most recent generation of reanalysis datasets for health impact assessments and evaluate their comparative performance against traditional station-based data. Our findings show that reanalysis temperature from the last ERA5 products generally compare well to station observations, with similar non-optimal temperature-related risk estimates. However, the analysis offers some indication of lower performance in tropical regions, with a likely underestimation of heat-related excess mortality. Reanalysis data represent a valid alternative source of exposure variables in epidemiological analyses of temperature-related risk