European Union's Horizon Research Articles

EHealth policy framework in Low and Lower Middle-Income Countries; a PRISMA systematic review and analysis

BackgroundLow and lower middle-income countries suffer lack of healthcare providers and proper workforce education programs, a greater spread of illnesses, poor surveillance, efficient management, etc., which are addressable by a central policy framework implementation. Accordingly, an eHealth policy framework is required specifically for these countries to successfully implement eHealth solutions. This study explores existing frameworks and fills the gap by proposing an eHealth policy framework in the context of developing countries.MethodsThis PRISMA-based (PRISMA Preferred Reporting Items For Systematic Reviews and Meta-Analyses) systematic review used Google Scholar, IEEE, Web of Science, and PubMed latest on 23rd May 2022, explored 83 publications regarding eHealth policy frameworks, and extracted 11 publications scrutinizing eHealth policy frameworks in their title, abstract, or keywords. These publications were analyzed by using both expert opinion and Rstudio programming tools. They were explored based on their developing/developed countries’ context, research approach, main contribution, constructs/dimensions of the framework, and related categories. In addition, by using cloudword and latent semantic space techniques, the most discussed concepts and targeted keywords were explored and a correlation test was conducted to depict the important concepts mentioned in the related literature and extract their relation with the targeted keywords in the interest of this study.ResultsMost of these publications do not develop or synthesize new frameworks for eHealth policy implementation, but rather introduce eHealth implementation frameworks, explain policy dimensions, identify and extract relevant components of existing frameworks or point out legal or other relevant eHealth implementation issues.ConclusionAfter a thorough exploration of related literature, this study identified the main factors affecting an effective eHealth policy framework, found a gap in the context of developing countries, and proposed a four-step eHealth policy implementation guideline for successful implementation of eHealth in the context of developing. The limitation of this study is the lack of a proper amount of practically implemented eHealth policy framework cases in developing countries published in the literature for the review. Ultimately, this study is part of the BETTEReHEALTH (More information about the BETTEReHEALTH project at https://betterehealth.eu) project funded by the European Union Horizon’s 2020 under agreement number 101017450.

Defining genomic epidemiology thresholds for common-source bacterial outbreaks: a modelling study

Epidemiological surveillance relies on microbial strain typing, which defines genomic relatedness among isolates to identify case clusters and their potential sources. Although predefined thresholds are often applied, known outbreak-specific features such as pathogen mutation rate and duration of source contamination are rarely considered. We aimed to develop a hypothesis-based model that estimates genetic distance thresholds and mutation rates for point-source single-strain food or environmental outbreaks. In this modelling study, we developed a forward model to simulate bacterial evolution at a specific mutation rate (μ) over a defined outbreak duration (D). From the distribution of genetic distances expected under the given outbreak parameters and sample isolation dates, we estimated a distance threshold beyond which isolates should not be considered as part of the outbreak. We embedded the model into a Markov Chain Monte Carlo inference framework to estimate the most probable mutation rate or time since source contamination, which are both often imprecisely documented. A simulation study validated the model over realistic durations and mutation rates. We then identified and analysed 16 published datasets of bacterial source-related outbreaks; datasets were included if they were from an identified foodborne outbreak and if whole-genome sequence data and collection dates for the described isolates were available. Analysis of simulated data validated the accuracy of our framework in both discriminating between outbreak and non-outbreak cases and estimating the parameters D and μ from outbreak data. Precision of estimation was much higher for high values of D and μ. Sensitivity of outbreak cases was always very high, and specificity in detecting non-outbreak cases was poor for low mutation rates. For 14 of the 16 outbreaks, the classification of isolates as being outbreak-related or sporadic is consistent with the original dataset. Four of these outbreaks included outliers, which were correctly classified as being beyond the threshold of exclusion estimated by our model, except for one isolate of outbreak 4. For two outbreaks, both foodborne Listeria monocytogenes, conclusions from our model were discordant with published results: in one outbreak two isolates were classified as outliers by our model and in another outbreak our algorithm separated food samples into one cluster and human samples into another, whereas the isolates were initially grouped together based on epidemiological and genetic evidence. Re-estimated values of the duration of outbreak or mutation rate were largely consistent with a priori defined values. However, in several cases the estimated values were higher and improved the fit with the observed genetic distance distribution, suggesting that early outbreak cases are sometimes missed. We propose here an evolutionary approach to the single-strain conundrum by estimating the genetic threshold and proposing the most probable cluster of cases for a given outbreak, as determined by its particular epidemiological and microbiological properties. This forward model, applicable to foodborne or environmental-source single point case clusters or outbreaks, is useful for epidemiological surveillance and may inform control measures. European Union Horizon 2020 Research and Innovation Programme.

XMM2ATHENA, the H2020 project to improve XMM‐Newton analysis software and prepare for Athena

AbstractXMM‐Newton, a European Space Agency observatory, has been observing the X‐ray, ultra‐violet, and optical sky for 23 years. During this time, astronomy has evolved from mainly studying single sources to populations and from a single wavelength, to multi‐wavelength/messenger data. We are also moving into an era of time domain astronomy. New software and methods are required to accompany evolving astronomy and prepare for the next‐generation X‐ray observatory, Athena. Here we present XMM2ATHENA, a program funded by the European Union's Horizon 2020 research and innovation program. XMM2ATHENA builds on foundations laid by the XMM‐Newton Survey Science Centre (XMM‐SSC), including key members of this consortium and the Athena Science ground segment, along with members of the X‐ray community. The project is developing and testing new methods and software to allow the community to follow the X‐ray transient sky in quasi‐real time, identify multi‐wavelength/messenger counterparts of XMM‐Newton sources and determine their nature using machine learning. We detail here the first milestone delivery of the project, a new online, sensitivity estimator. We also outline other products, including the forthcoming innovative stacking procedure and detection algorithms, to detect the faintest sources. These tools will then be adapted for Athena and the newly detected/identified sources will enhance preparation for observing the Athena X‐ray sky.

The Microbiome-Gut-Brain axis regulates social cognition &craving in young binge drinkers.

Binge drinking is the consumption of an excessive amount of alcohol in a short period of time. This pattern of consumption is highly prevalent during the crucial developmental period of adolescence. Recently, the severity of alcohol use disorders (AUDs) has been linked with microbiome alterations suggesting a role for the gut microbiome in its development. Furthermore, a strong link has emerged too between microbiome composition and socio-emotional functioning across different disorders including AUD. The aim of this study was to investigate the potential link (and its predictive value) between alcohol-related altered microbial profile, social cognition, impulsivity and craving. Young people (N=71) aged 18-25 reported their alcohol use and underwent a neuropsychological evaluation. Craving was measured at baseline and three months later. Diet was controlled for. Blood, saliva and hair samples were taken for inflammatory, kynurenine and cortisol analysis. Stool samples were provided for shotgun metagenomic sequencing and short-chain fatty acids (SCFAs) were measured. Binge drinking was associated with distinct microbiome alterations and emotional recognition difficulties. Associations were found for several microbiome species with emotional processing and impulsivity. Craving showed a strong link with alterations in microbiome composition and neuroactive potential over time. In conclusion, this research demonstrates alterations in the gut microbiome of young binge drinkers (BDs) and identifies early biomarkers of craving. Associations between emotional processing and microbiome composition further support the growing literature on the gut microbiome as a regulator of social cognition. These findings are of relevance for new gut-derived interventions directed at improving early alcohol-related alterations during the vulnerability period of adolescence. C.C. and R.G-C. received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 754535. APC Microbiome Ireland is a research centre funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan [grant no. SFI/12/RC/2273_P2]. J.F.C has research support from Cremo, Pharmavite, DuPont and Nutricia. He has spoken at meetings sponsored by food and pharmaceutical companies. G.C. has received honoraria from Janssen, Probi, and Apsen as an invited speaker; is in receipt of research funding from Pharmavite, Fonterra, Nestle and Reckitt; and is a paid consultant for Yakult, Zentiva and Heel pharmaceuticals. All the authors declare no competing interests.

Effectiveness, reach, uptake, and feasibility of digital health interventions for adults with hypertension: a systematic review and meta-analysis of randomised controlled trials.

Digital health interventions are effective for hypertension self-management, but a comparison of the effectiveness and implementation of the different modes of interventions is not currently available. This study aimed to compare the effectiveness of SMS, smartphone application, and website interventions on improving blood pressure in adults with hypertension, and to report on their reach, uptake, and feasibility. In this systematic review and meta-analysis we searched CINAHL Complete, Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid MEDLINE, and APA PsycInfo on May 25, 2022, for randomised controlled trials (RCTs) published in English from Jan 1, 2009, that examined the effectiveness of digital health interventions on reducing blood pressure in adults with hypertension. Screening was carried out using Covidence, and data were extracted following Cochrane's guidelines. The primary endpoint was change in the mean of systolic blood pressure. Risk of bias was assessed with Cochrane Risk of Bias 2. Data on systolic and diastolic blood pressure reduction were synthesised in a meta-analysis, and data on reach, uptake and feasibility were summarised narratively. Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to evaluate the level of evidence. The study was registered with PROSPERO CRD42021247845. Of the 3235 records identified, 29 RCTs from 13 regions (n=7592 participants) were included in the systematic review, and 28 of these RCTs (n=7092 participants) were included in the meta-analysis. 11 studies used SMS as the primary mode of delivery of the digital health intervention, 13 used smartphone applications, and five used websites. Overall, digital health intervention group participants had a -3·62 mm Hg (95% CI -5·22 to -2·02) greater reduction in systolic blood pressure, and a -2·45 mm Hg (-3·83 to -1·07) greater reduction in diastolic blood pressure, compared with control group participants. No statistically significant differences between the three different modes of delivery were observed for both the systolic (p=0·73) and the diastolic blood pressure (p=0·80) outcomes. Smartphone application interventions had a statistically significant reduction in diastolic blood pressure (-2·45 mm Hg [-4·15 to -0·74]); however, there were no statistically significant reductions for SMS interventions (-1·80 mm Hg [-4·60 to 1·00]) or website interventions (-3·43 mm Hg [-7·24 to 0·38]). Due to the considerable heterogeneity between included studies and the high risk of bias in some, the level of evidence was assigned a low overall score. Interventions were more effective among people with greater severity of hypertension at baseline. SMS interventions reported higher reach and smartphone application studies reported higher uptake, but differences were not statistically significant. SMS, smartphone application, and website interventions were associated with statistically and clinically significant systolic and diastolic blood pressure reductions, compared with usual care, regardless of the mode of delivery of the intervention. This conclusion is tempered by the considerable heterogeneity of included studies and the high risk of bias in most. Future studies need to describe in detail the mediators and moderators of the effectiveness and implementation of these interventions, to both further improve their effectiveness as well as increase their reach, uptake, and feasibility. European Union's Horizon 2020 Research and Innovation Programme.

Mindfulness, Attention, and Impulsivity in Bipolar Disorder

IntroductionBipolar disorder (BD) is a chronic mental disorder characterized by mood instability1. BD is further related to neurocognitive and functional disruptions that remain remarkably stable even when patients are euthymic, leading to poor well-being and quality of life. Mindfulness means paying attention on purpose, in the present moment, and involves different facets such as observing, describing, acting with awareness, non-judging and non-reacting of inner experience. It remains unclear whether mindfulness and its specific facets are differentially associated with different aspects of attention and trait impulsivity in individuals with BD.ObjectivesTo examine associations between different mindfulness facets, and different aspects of attention and trait impulsivity in BD.MethodsThis study was approved by the Hospital Clínic Ethics and Research Board (HCB/2017/0432). After informed consent, 94 outpatients, M age = 45.57, SD = 9.8, range 19-61 years, 41.5% Male, 63.8% BD-I according to DSM-5 criteria, in partial or total remission based on Young Mania Rating Scale (YMRS; M = 1.81, SD = 2.11) and Hamilton Depression Rating Scale (HDRS; M = 5.46, SD = 3.71) were enrolled in this study. Participants were evaluated using the Five Facet Mindfulness Questionnaire (FFMQ) to assess Mindfulness, the Trail Making Test (TMT-A) and the Conner’s Continuous Performance test (CPT-II) to assess Attention, and the Barratt Impulsiveness Scale (BIS-11) to assess Impulsivity. Pearson correlations were performed, and statistical significance was evaluated two-sided at the 5% threshold.ResultsMindfulness-Describing was negatively associated with Cognitive and Non-Planning Impulsivity (r = -.43 and -.28, p < .001), Mindfulness-Acting with Awareness was negatively associated with Cognitive, Motor and Non-Planning Impulsivity (r = -.27 to -.45, p < .001), Mindfulness Non-Judging (r = -.33 and -.34, p < .001) and Non-Reacting (r = -.30 and -.46, p < .001) of inner experience were negatively associated with Cognitive and Motor Impulsivity. No associations were found between neither Mindfulness nor Impulsivity with any aspects of Attention.ConclusionsPreliminary findings suggest that better performance in specific facets of mindfulness (describing, acting with awareness, non-judging or reacting of inner experience) may be related to a decrease in different aspects of trait impulsivity. Further longitudinal and interventional research is needed on underlying mechanisms. Nonetheless, our study suggests the need for including mindfulness-based approaches to improve behavioral and functional outcomes for those with BD.FundingThis work was supported by the European Union Horizon 2020 research and innovation program (EU.3.1.3. Treating and managing disease: Grant 945151), CIBERSAM, FIS PI17/00941 ISCIII, European Regional Development Fund.

Empower: Design of a digital intervention for workplace stress and mental health. A European study

IntroductionWork stress, anxiety and depression have an enormous impact on the well-being of employees, their employers, and society. Due to the loss of productivity, common mental disorders have a substantial economic impact. Major depression alone has been attributed to 50% of long-term absences from work, and depressive symptoms are related to lowered productivity while at work. Anxiety also contributes to loss of productivity and sickness absence. Treatment of common mental disorders in a work setting may improve symptoms, however, that does not automatically lead to improved work productivity. Addressing mental well-being at the workplace might improve work functioning, and digital interventions have been introduced with that objective. However, their evaluation in research has been limited.The European Intervention to Promote Wellbeing and Health in the Workplace (EMPOWER) digital intervention is designed to provide and evaluate an integrative user programme that meets the needs of employees and employers in addressing work stress.This work was supported by the European Union Horizon 2020 Research and Innovation Programme Health (grant number APP1195937, 848180). The EMPOWER project started 1.1.2020 and is currently ongoing.ObjectivesWe aim to1) describe the design and development of the digital intervention.2) culturally validate the intervention in three countries3) test the prototype and beta version for its usability in the RCT to evaluate its effect in four countries that is currently ongoing.MethodsA user-centred design process was followed from January 2020 until November 2021 to create a beta version for usability testing. A tailored algorithm was developed to provide support at the individual employee level and the company level. Each element of the digital intervention was translated and culturally validated in four languages in Spain, the United Kingdom, Poland, and Finland. Usability testing was conducted in each country (n=31) to explore validity, usability, and user experience.ResultsThe digital intervention consists of a website and a mobile application (app). The website has a public section and an employer portal that provides recommendations to reduce psychosocial risks in their company based upon clustered input from employees. The app provides algorithm-based personalised content after assessing a user’s physical and psychological symptoms, work functioning, and psychosocial risk factors for work stress. The usability testing improved the flow through the app and high ease of use and completion of tasks by participants.ConclusionsThe EMPOWER digital intervention is a tailored multimodal intervention addressing wellbeing, work stress, mental and physical health problems, and work productivity. Usability testing provided validation of the app as version to be evaluated in the EMPOWER RCT.Disclosure of InterestNone Declared

Assessing the Efficacy of a Virtual Assistant in the Remote Cardiac Rehabilitation of Heart Failure and Ischemic Heart Disease Patients: Case-Control Study of Romanian Adult Patients.

Cardiovascular diseases (CVDs) are the leading cause of mortality in Europe, with potentially more than 60 million deaths per year, with an age-standardized rate of morbidity-mortality higher in men than women, exceeding deaths from cancer. Heart attacks and strokes account for more than four out of every five CVD fatalities globally. After a patient overcomes an acute cardiovascular event, they are referred for rehabilitation to help them to restore most of their normal cardiac functions. One effective way to provide this activity regimen is via virtual models or telerehabilitation, where the patient can avail themselves of the rehabilitation services from the comfort of their homes at designated timings. Under the funding of the European Union's Horizon 2020 Research and Innovation program, grant no 769807, a virtual rehabilitation assistant has been designed for elderly patients (vCare), with the overall objective of supporting recovery and an active life at home, enhancing patients' quality of life, lowering disease-specific risk factors, and ensuring better adherence to a home rehabilitation program. In the vCare project, the Carol Davila University of Bucharest (UMFCD) was in charge of the heart failure (HF) and ischemic heart disease (IHD) groups of patients. By creating a digital environment at patients' homes, the vCare system's effectiveness, use, and feasibility was evaluated. A total of 30 heart failure patients and 20 ischemic heart disease patients were included in the study. Despite the COVID-19 restrictions and a few technical difficulties, HF and IHD patients who performed cardiac rehabilitation using the vCare system had similar results compared to the ambulatory group, and better results compared to the control group.

Socioeconomic inequalities in cancer mortality between and within countries in Europe: a population-based study.

Reducing socioeconomic inequalities in cancer is a priority for the public health agenda. A systematic assessment and benchmarking of socioeconomic inequalities in cancer across many countries and over time in Europe is not yet available. Census-linked, whole-of-population cancer-specific mortality data by socioeconomic position, as measured by education level, and sex were collected, harmonized, analysed, and compared across 18 countries during 1990-2015, in adults aged 40-79. We computed absolute and relative educational inequalities; temporal trends using estimated-annual-percentage-changes; the share of cancer mortality linked to educational inequalities. Everywhere in Europe, lower-educated individuals have higher mortality rates for nearly all cancer-types relative to their more highly-educated counterparts, particularly for tobacco/infection-related cancers [relative risk of lung cancer mortality for lower- versus higher-educated=2.4 (95% confidence intervals: 2.1-2.8) among men;=1.8 (95% confidence intervals: 1.5-2.1) among women]. However, the magnitude of inequalities varies greatly by country and over time, predominantly due to differences in cancer mortality among lower-educated groups, as for many cancer-types higher-educated have more similar (and lower) rates, irrespective of the country. Inequalities were generally greater in Baltic/Central/East-Europe and smaller in South-Europe, although among women large and rising inequalities were found in North-Europe (relative risk of all cancer mortality for lower- versus higher-educated ≥1.4 in Denmark, Norway, Sweden, Finland and the England/Wales). Among men, rate differences (per 100,000 person-years) in total-cancer mortality for lower-vs-higher-educated groups ranged from 110 (Sweden) to 559 (Czech Republic); among women from approximately null (Slovenia, Italy, Spain) to 176 (Denmark). Lung cancer was the largest contributor to inequalities in total-cancer mortality (between-country range: men, 29-61%; women, 10-56%). 32% of cancer deaths in men and 16% in women (but up to 46% and 24%, respectively in Baltic/Central/East-Europe) were associated with educational inequalities. Cancer mortality in Europe is largely driven by levels and trends of cancer mortality rates in lower-education groups. Even Nordic-countries, with a long-established tradition of equitable welfare and social justice policies, witness increases in cancer inequalities among women. These results call for a systematic measurement, monitoring and action upon the remarkable socioeconomic inequalities in cancer existing in Europe. This study was done as part of the LIFEPATH project, which has received financial support from the European Commission (Horizon 2020 grant number 633666), and the DEMETRIQ project, which received support from the European Commission (grant numbers FP7-CP-FP and 278511). SV and WN were supported by the French Institut National du Cancer (INCa) (Grant number 2018-116). PM was supported by the Academy of Finland (#308247, # 345219) and the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement No 101019329). The work by Mall Leinsalu was supported by the Estonian Research Council (grant PRG722).

Mechanisms by which water-mediated hydrogen-bond networks govern pH-dependent reactions at membrane interfaces.

pH-dependent reactions at membrane interfaces are used by cells to maintain pH homeostasis and to ensure normal cell function. Membrane-bound proteins and peptide systems that sense pH typically bind protons using a few titratable sidechains that communicate with the bulk. The identity of these pH-sensing sidechains is central to hypotheses about protein reaction mechanisms and for the rational design of proton detectors. But, as protein groups hypothesized to sense pH in proteins and peptide systems are part of dynamic water-mediated networks, evaluating their pH-sensing functionality may prove difficult. We developed efficient graph-based algorithms and methodologies to evaluate dynamic hydrogen-bond networks of protein and peptide systems known to have a pH-sensing functionality, and to identify sites of hydrogen-bond networks where protons are likely to bind. We find that the assembly of dynamic water-mediated hydrogen-bond networks that include potential proton-sensing groups is a key event along the reaction coordinates of pH-dependent membrane proteins and membrane-bound peptides, and implement graph-based algorithms to characterize the dynamics of these water networks. We further find that polar and basic protein sidechains largely govern the dynamics of the water-mediated hydrogen-bond networks of proton-binding groups, and help maintain acidic sidechains within clusters that collectively can bind and store protons. Taken together, the ensemble of hydrogen-bond network computations we performed for pH-coupled proteins and peptide systems provide a framework to decipher the roles of dynamic water-mediated hydrogen-bond networks in proton binding at membrane interfaces. Research was supported in part by the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie grant agreement No 860592, Innovative Training Network ‘Proton and proton-coupled transport’, and by computing time from the Physics Department of the Freie Universität Berlin and from the Forschungszentrum Jülich (JURECA-DC, allocation PHDPORES).

Potential of Small‐Angle Neutron Scattering for Evaluating Protein Locus within a Polymersome

Macromol. Chem. Phys. 2023, 224, 2200300 DOI: https://doi.org/10.1002/macp.202200300 In the original publication of this article, a funding source is missing in the Acknowledgements. The missing funding statement is as follows: “U.L.M. acknowledges the funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 898878 (USOME).”

Chloride Ion‐Containing Polymeric Ionic Liquids for Application as Electrolytes in Solid‐State Batteries

Macromol. Chem. Phys. 2023, 224, 2200317 DOI: https://doi.org/10.1002/macp.202200317 In the original publication of this article, a funding source is missing in the Acknowledgements. The missing funding statement is as follows: “U.L.M. acknowledges the funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 898878 (USOME).”

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene-drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug-gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug-gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug-gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54-0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61-0·79]; p <0·0001). Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. European Union Horizon 2020.

Cooling cities through urban green infrastructure: a health impact assessment of European cities

High ambient temperatures are associated with many health effects, including premature mortality. The combination of global warming due to climate change and the expansion of the global built environment mean that the intensification of urban heat islands (UHIs) is expected, accompanied by adverse effects on population health. Urban green infrastructure can reduce local temperatures. We aimed to estimate the mortality burden that could be attributed to UHIs and the mortality burden that would be prevented by increasing urban tree coverage in 93 European cities. We did a quantitative health impact assessment for summer (June 1-Aug 31), 2015, of the effect of UHIs on all-cause mortality for adults aged 20 years or older in 93 European cities. We also estimated the temperature reductions that would result from increasing tree coverage to 30% for each city and estimated the number of deaths that could be potentially prevented as a result. We did all analyses at a high-resolution grid-cell level (250 × 250 m). We propagated uncertainties in input analyses by using Monte Carlo simulations to obtain point estimates and 95% CIs. We also did sensitivity analyses to test the robustness of our estimates. The population-weighted mean city temperature increase due to UHI effects was 1·5°C (SD 0·5; range 0·5-3·0). Overall, 6700 (95% CI 5254-8162) premature deaths could be attributable to the effects of UHIs (corresponding to around 4·33% [95% CI 3·37-5·28] of all summer deaths). We estimated that increasing tree coverage to 30% would cool cities by a mean of 0·4°C (SD 0·2; range 0·0-1·3). We also estimated that 2644 (95% CI 2444-2824) premature deaths could be prevented by increasing city tree coverage to 30%, corresponding to 1·84% (1·69-1·97) of all summer deaths. Our results showed the deleterious effects of UHIs on mortality and highlighted the health benefits of increasing tree coverage to cool urban environments, which would also result in more sustainable and climate-resilient cities. GoGreenRoutes, Spanish Ministry of Science and Innovation, Institute for Global Health, UK Medical Research Council, European Union's Horizon 2020 Project Exhaustion.

Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts. Samples were collected from 9361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N=4256; ALSPAC, N=4622), and in TwinsUK only in November 2021-January 2022 (N=3575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables. Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had threefold greater odds of SARS-CoV-2 infection over the next 6-9 months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (two- to fourfold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies. Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC ([MC_PC_20030] and [MC_PC_20059]). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant [COV-LT-0009]). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: [217065/Z/19/Z]) and the University of Bristol provide core support for ALSPAC.

Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial

The combination of infliximab and immunosuppressant therapy is a standard management strategy for patients with Crohn's disease. Concerns regarding the implications of long-term combination therapy provided the rationale for a formal clinical trial of treatment de-escalation. Our aim was to compare the relapse rate and the time spent in remission over 2 years between patients continuing combination therapy and those stopping infliximab or immunosuppressant therapy. This multicentre, open-label, randomised controlled trial was performed in 64 hospitals in seven countries in Europe and Australia. Adult patients with Crohn's disease in steroid-free clinical remission for more than 6 months, on combination therapy of infliximab and immunosuppressant therapy for at least 8 months were randomly assigned (1:1:1) to either continue combination therapy (combination group), discontinue infliximab (infliximab withdrawal group), or discontinue immunosuppressant therapy (immunosuppressant withdrawal group). Randomisation was stratified according to disease duration before start of first anti-TNF treatment (≤2 or >2 years), failure of immunosuppressant therapy before start of infliximab, and presence of ulcers at baseline endoscopy. The patient number and group of each stratum were assigned by a central online randomisation website. Treatment was optimised or resumed in case of relapse in all groups. Participants, those assessing outcomes, and those analysing the data were not masked to group assignment. The coprimary endpoints were the relapse rate (superiority analysis) and time in remission over 2 years (non-inferiority analysis, non-inferiority margin 35 days). Analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT02177071, and with EU Clinical Trials Register, EUDRACT 2014-002311-41. The trial was completed in April, 2021. Between Nov 2, 2015, and April 24, 2019, 254 patients were screened. Of these, 211 were randomised and 207 were included in the final analysis (n=67 in the combination group, n=71 in the infliximab withdrawal group, and n=69 in the immunosuppressant withdrawal group). 39 patients had a relapse (eight [12%] of 67 in the combination group, 25 [35%] of 71 in the infliximab withdrawal group, six [9%] of 69 in the immunosuppressant withdrawal group). 2-year relapse rates were 14% (95% CI 4-23) in the combination group, 36% (24-47) in the infliximab withdrawal group, and 10% (2-18) in the immunosuppressant withdrawal group (hazard ratio [HR] 3·45 [95% CI 1·56-7·69], p=0·003, for infliximab withdrawal vs combination, and 4·76 [1·92-11·11], p=0·0004, for infliximab withdrawal vs immunosuppressant withdrawal). Of 28 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 25 patients (one of two in the combination group, 22 of 23 in the infliximab withdrawal group, and two of three in the immunosuppressant withdrawal group). The mean time spent in remission over 2 years was 698 days (95% CI 668-727) in the combination group, 684 days (651-717) in the infliximab withdrawal group, and 706 days (682-730) in the immunosuppressant withdrawal group. The difference in restricted mean survival time in remission was -14 days (95% CI -56 to 27) between the infliximab withdrawal group and the combination group and -22 days (-62 to 16) between the infliximab withdrawal group and the immunosuppressant withdrawal group. The 95% CIs contained the non-inferiority threshold (-35 days). We recorded 31 serious adverse events, in 20 patients, with no difference in frequency between groups. The most frequent serious adverse events were infections (four in the combination group, two in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group) and Crohn's disease exacerbation (three in the combination group, four in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group). No death nor malignancy was recorded. In patients with Crohn's disease in sustained steroid-free remission under combination therapy with infliximab and immunosuppressant therapy, withdrawal of infliximab should only be considered after careful assessment of risks and benefits for each patient, whereas withdrawal of immunosuppressant therapy could generally represent a preferable strategy when considering treatment de-escalation. European Union's Horizon 2020.

URBAN FARMING AS A TOOL OF FOOD SECURITY IN FRONT-LINE KHARKIV: GLOBAL PROBLEMS FROM MICROSOCIOLOGICAL PERSPECTIVE

The article is devoted to the problem that belongs to the interdisciplinary topic’s social measurements of food security. Ukrainian sociology missing somehow notable bodies of works in these thematic planes. That is why the article is a statement of the problem and has an orienting character. The task of the authors is to problematize sociological means relevant to the frontline city transformation of food practices. The article aimed to characterize the sociological potential of the military factor of the global food crisis through the prism of challenges to food security in Ukrainian frontline city. It represents the results of the original reconnaissance case study, which the authors did in Kharkiv from May to August 2022 as part of the project FUSILLI (a Food and natural resources project, funded by the European Union's Horizon 2020 Research and Innovation Program under Grant Agreement No.101000717). Based on the received results the authors formulated assumptions about the main directions of transformation of food practices of the residents of a large city, in which underway combat actions. The authors also offered methods and directions of possible sociological research that allow verifying this assumption.

Guest Editorial: Ecological knowledge co‐production and the contested imaginaries of development in Southeast Asia

Guest Editorial: Ecological knowledge co‐production and the contested imaginaries of development in Southeast Asia

A Logistic Platform to ensure a sustainable transportation of Waste from Electrical and Electronic Equipment

The C-SERVEES project, funded by European Union's Horizon 2020 programme, aims to boost a resource-efficient circular economy in the electrical and electronic (E&E) sector through the development, testing and validation of new circular economic business models. Product recovery is an emerging business area which shall be attractive from both economic and environmental point of view. Several points contribute to the success of this action, such as costs, time and safety for disassembling products, availability and costs of raw materials, disposal costs of end-of-life products and transport impact of reverse logistics. In this context, the Logistic Platform, developed by RINA-C, aims to ensure a sustainable transportation of the WEEE (Waste from Electrical and Electronic Equipment) among the stakeholders to enable the re-use of the recovered materials and to re-insert them in the process.

Effective project management of 3rd party funding in European Union Horizon Industry4.0 projects: sharing experiences from two use cases

To reduce the risk and the required bureaucracy for accessing public funding, the EC has developed a mechanism to grant money to consortia to be used to fund to startups, SMEs and Midcaps to start, evolve or transition their offer to increase their competitivity in the market, in turn providing benefit for the entire European economy.This paper presents the experience in managing what is actually 3rd party (or cascading) funding in two different European Innovation Action Projects in the manufacturing domain. The paper discusses the design and implementation phases and provides the detail on how to manage the processes to ensure fairness, efficiency, and effectiveness that is lacking from the EC's formal documentation.