European Case Research Articles

12500 Objective Evaluation Of Clustering Methods For Resolving The Heterogeneity Of PCOS

Abstract Disclosure: K. Brewer: None. R. Sisk: None. M. Dapas: None. C. Li: None. A. Dunaif: Consulting Fee; Self; AcaciaBio, Inc, Neurocine Biosciences, Inc. Speaker; Self; Quest Diagnostics. Other; Self; Co-Editor Endocrine Today, Healio, Slack Inc. Clustering methods have been used to resolve heterogeneity within complex diseases to elucidate underlying biologic mechanisms. We (Dapas et al. PLoS Med, 2020) and others have applied these methods to PCOS and identified discrete subtypes, including those that capture distinct reproductive or metabolic features. We objectively compared two widely used methods, hierarchical clustering (HC), which recursively merges subjects based on their similarity, and k-means (Km), which iteratively groups individuals to minimize their distance to cluster centroids. The number of clusters (k) was predefined in both approaches. We compared HC vs Km in 874 European ancestry PCOS cases diagnosed by NIH criteria using 8 traits (BMI, testosterone, SHBG, DHEAS, LH, FSH, fasting insulin, fasting glucose) and 9 traits with the addition of AMH. The ConsensusClusterPlus R package was used to evaluate cluster stability of both approaches with k=2, 3, or 4, using 8 or 9 traits. Genomewide association study (GWAS) meta-analysis was performed as reported with a discovery cohort (620 cases, 2951 controls) and a replication cohort (371 cases, 926 controls), except that genotypes were imputed to the newer TOPMED (r2) panel. Clustering using 8 traits and k=3 resulted in the best cluster stability for both HC and Km (pairwise consensus proportion: HC 0.98, Km 0.93) compared to k=2 with 8 traits (HC 0.88, Km 0.88) or 9 traits (HC 0.95, Km 0.92). No stability was observed for k=4 with 8 or 9 traits using either method (range: 0.35-0.66). Km showed slightly better cluster separation than HC (average silhouette width: Km 0.12 vs HC 0.09) with k=3 and 8 traits. The biologic relevance of the three PCOS subtypes, which we have designated as reproductive (cases with higher LH, FSH, SHBG), metabolic (higher BMI, insulin, glucose), and background, was assessed by GWAS, an orthogonal (i.e., uncorrelated) approach for subtype confirmation. The subtypes identified with HC had genomewide significant associations (metabolic subtype, c9orf3/FANCC, rs10761370, minor allele frequency [MAF] 0.47, p=1.21 x 10-8; background subtype, FSHB/ARL14EP, rs10835649, MAF 0.17, p=8.49 x 10-[1]0). There were no genomewide significant signals when the subtypes were identified with Km despite having a better cluster separation. In summary, only HC clusters appeared to capture biologically meaningful differences since two of the three subtypes thus identified were associated with genomewide significant loci. Neither the addition of AMH nor increasing the number of groups improved clustering metrics. Our results emphasize the importance of independent validation of clustering approaches using an orthogonal confirmation strategy such as GWAS. We conclude that HC clustering using 8 traits is superior to Km for resolving the genetic heterogeneity of PCOS. Presentation: 6/2/2024

12500 Objective Evaluation Of Clustering Methods For Resolving The Heterogeneity Of PCOS

Abstract Disclosure: K. Brewer: None. R. Sisk: None. M. Dapas: None. C. Li: None. A. Dunaif: Consulting Fee; Self; AcaciaBio, Inc, Neurocine Biosciences, Inc. Speaker; Self; Quest Diagnostics. Other; Self; Co-Editor Endocrine Today, Healio, Slack Inc. Clustering methods have been used to resolve heterogeneity within complex diseases to elucidate underlying biologic mechanisms. We (Dapas et al. PLoS Med, 2020) and others have applied these methods to PCOS and identified discrete subtypes, including those that capture distinct reproductive or metabolic features. We objectively compared two widely used methods, hierarchical clustering (HC), which recursively merges subjects based on their similarity, and k-means (Km), which iteratively groups individuals to minimize their distance to cluster centroids. The number of clusters (k) was predefined in both approaches. We compared HC vs Km in 874 European ancestry PCOS cases diagnosed by NIH criteria using 8 traits (BMI, testosterone, SHBG, DHEAS, LH, FSH, fasting insulin, fasting glucose) and 9 traits with the addition of AMH. The ConsensusClusterPlus R package was used to evaluate cluster stability of both approaches with k=2, 3, or 4, using 8 or 9 traits. Genomewide association study (GWAS) meta-analysis was performed as reported with a discovery cohort (620 cases, 2951 controls) and a replication cohort (371 cases, 926 controls), except that genotypes were imputed to the newer TOPMED (r2) panel. Clustering using 8 traits and k=3 resulted in the best cluster stability for both HC and Km (pairwise consensus proportion: HC 0.98, Km 0.93) compared to k=2 with 8 traits (HC 0.88, Km 0.88) or 9 traits (HC 0.95, Km 0.92). No stability was observed for k=4 with 8 or 9 traits using either method (range: 0.35-0.66). Km showed slightly better cluster separation than HC (average silhouette width: Km 0.12 vs HC 0.09) with k=3 and 8 traits. The biologic relevance of the three PCOS subtypes, which we have designated as reproductive (cases with higher LH, FSH, SHBG), metabolic (higher BMI, insulin, glucose), and background, was assessed by GWAS, an orthogonal (i.e., uncorrelated) approach for subtype confirmation. The subtypes identified with HC had genomewide significant associations (metabolic subtype, c9orf3/FANCC, rs10761370, minor allele frequency [MAF] 0.47, p=1.21 x 10-8; background subtype, FSHB/ARL14EP, rs10835649, MAF 0.17, p=8.49 x 10-[1]0). There were no genomewide significant signals when the subtypes were identified with Km despite having a better cluster separation. In summary, only HC clusters appeared to capture biologically meaningful differences since two of the three subtypes thus identified were associated with genomewide significant loci. Neither the addition of AMH nor increasing the number of groups improved clustering metrics. Our results emphasize the importance of independent validation of clustering approaches using an orthogonal confirmation strategy such as GWAS. We conclude that HC clustering using 8 traits is superior to Km for resolving the genetic heterogeneity of PCOS. Presentation: 6/2/2024

Heat in the news: Geothermal energy in Chilean newspaper coverage

Although Chile has abundant geothermal resources and is home to the first geothermal power plant in South America, the country faces uncertainties regarding the future development of geothermal energy. Lack of economic incentives, insufficient regulatory framework, and social opposition to geothermal power plant projects are some of the main challenges faced in the last years. To reflect on the pitfalls of the geothermal energy public debate and promote the integration of social aspects in the geothermal energy discussion, this study examines how geothermal energy has been portrayed in two influential Chilean newspapers from 2008 to 2021. Based on the idea that the mass media plays a critical role in public perception, this paper presents a framing analysis of 259 newspaper press to reflect on the public discourse of geothermal energy. The study shows that the media focused mainly on deep, high-enthalpy geothermal projects and the energy concession market. Geothermal energy has been mostly part of the finance discussion, and the coverage has been primarily event-driven, with limited visibility beyond specific events. Two events, the controversial exploration project in El Tatio (2009) and the successful commissioning of the first geothermal plant Cerro Pabellón (2017) attracted significant attention and presented geothermal energy from contrasting perspectives. Geothermal energy is mainly portrayed as an abundant, clean, and renewable energy source. However, geothermal development is described as a “business” or a “resource to be exploited”. There is a notable absence of discussion regarding the success of Latin American geothermal initiatives. Instead, European cases are the most prevalent in the discourse, serving as exemplars for potential future action. This result calls for the promotion of a new geothermal narrative and relationship with geothermal energy that acknowledges the experience from Latin American countries such as Costa Rica or El Salvador, the importance that geothermal energy has had for Indigenous peoples and promotes its use in the light of social demands for a more sustainable relationship with the environment, instead the main geothermal frame reproduces the commodification of natural resources in Chile.

Abstract C102: Polyethnic-1000: Advancing cancer genomics by studying ethnically diverse, underserved patient populations in New York

Abstract Prompted by the considerable biases toward European ancestry cases in large cancer genomics repositories, the New York Genome Center initiated an effort to diversify the public datasets that are forming the foundations of current cancer research, in order to optimize the unbiased applications of modern genomically-driven discoveries to a larger population. Our effort was focused on 8 cancer types (breast, prostate, bladder, lung, pancreatic, colon and endometrial cancer, as well as multiple myeloma) and generated Illumina tumor-normal whole-genome sequencing and tumor transcriptome sequencing. The majority of the samples were retrospectively obtained in clinics and hospitals of the New York region and the analyses are conducted with collaborators in these institutions. Our dataset is currently composed of 851 tumor-normal WGS and 471 RNASeq, and is progressively being distributed to the scientific community in partnership with ICGC-ARGO. Overall, 75% of the cohort is predominantly of non-European ancestry, as estimated by genetic ancestry analysis using the 1000Genomes continental references.We analyzed the samples with NYGC’s somatic variant calling pipeline and will present results from the 8 cancer types related to germline and somatic variants (single-nucleotide variants, indels, copy-number alterations, complex structural variants) as well as mutational signatures, neoantigen prediction, fusion genes and expression profiles, in relation to genetic ancestry estimation and clinical features of the patients. We anticipate that the dataset will significantly diversify the genetic ancestry of tumor profiles in public databases, and serve to form hypotheses regarding the contribution of ancestry on cancer disparities. The experience of the Polyethnic-1000 project informs our contribution to the Cancer Grand Challenge SAMBAI, which focuses on breast, prostate and pancreatic cancers in the African Diaspora. SAMBAI will further investigate the causes of cancer disparity by combining genomic data with social determinants of health and exposomics information, deeper immune profiling and new genomics technologies such as long reads sequencing and the use of a pangenome reference. Citation Format: Nicolas Robine, Lara Winterkorn, Tim Chu, Zoe Goldstein, Will Hooper, Ali Oku, Heather M. Geiger, Melissa B. Davis, Onyinye Balogun. Polyethnic-1000: Advancing cancer genomics by studying ethnically diverse, underserved patient populations in New York [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C102.

Three Faces of Innovation Competition: Choosing the Framework for Horizontal Merger Assessment

Abstract This article discusses the assessment of horizontal mergers and harm to innovation when there is innovation competition. The goal is to establish a methodology for selecting the appropriate analytical framework for each situation, outlining mechanisms for recognizing innovation competition, defining relevant markets, evaluating the competitive significance of firms, identifying suitable theories of harm, and gathering pertinent evidence for each scenario. We review the literature on Competition Policy and on Economics of Innovation and take examples from the US and European case law. We also briefly discuss the strategic management literature to provide insights for the assessment. Considering post-merger reductions on innovation incentives as harm to innovation, we find differences of traditional merger procedure adequacy and challenges to build evidence, considering three faces of innovation, including possible combinations of these faces within a same merger case: (i) continuous innovation efforts in the product market, (ii) ongoing innovation efforts for developing new products, and (iii) future innovation efforts. In instances where the conventional approach to mergers falls short, exploring a capabilities-based assessment is recommended. Given the gaps found in the existing literature, we provide insights to the analysis as steps towards an agenda of capabilities-based merger assessment.

Predicting demand for new products in fashion retailing using censored data

In today’s highly competitive fashion retail market, it is crucial to have accurate demand forecasting systems, namely for new products. Many experts have used machine learning techniques to forecast product sales. However, sales that do not happen due to lack of product availability are often ignored, resulting in censored demand and service levels that are lower than expected. Motivated by the relevance of this issue, we developed a two-stage approach to forecast the demand for new products in the fashion retail industry. In the first stage, we compared four methods of transforming historical sales into historical demand for products already commercialized. Three methods used sales-weighted averages to estimate demand on the days with stock-outs, while the fourth method employed an Expectation-Maximization (EM) algorithm to account for potential substitute products affected by stock-outs of preferred products. We then evaluated the performance of these methods and selected the most accurate one for calculating the primary demand for these historical products. In the second stage, we predicted the demand for the products of the following collection using Random Forest, Deep Neural Networks, and Support Vector Regression algorithms. In addition, we applied a model that consisted of weighting the demands previously calculated for the products of past collections that were most similar to the new products. We validated the proposed methodology using a European fashion retailer case study. The results revealed that the method using the Expectation-Maximization algorithm had the highest potential, followed by the Random Forest algorithm. We believe that this approach will lead to more assertive and better-aligned decisions in production management.

Gene-based association analysis of a large patient cohort provides insights into genetics of atypical femur fractures.

Several small genetic association studies have been conducted for atypical femur fracture (AFF) without replication of results. We assessed previously implicated and novel genes associated with AFFs in a larger set of unrelated AFF cases using whole exome sequencing (WES). We performed gene-based association analysis on 139 European AFF cases and 196 controls matched for bisphosphonate use. We tested all rare, protein-altering variants using both candidate gene and hypothesis-free approaches. In the latter, genes suggestively associated with AFFs (uncorrected p-values <.01) were investigated in a Swedish whole-genome sequencing replication study and assessed in 46 non-European cases. In the candidate gene analysis, PLOD2 showed a suggestive signal. The hypothesis-free approach revealed 10 tentative associations, with XRN2, SORD, and PLOD2 being the most likely candidates for AFF. XRN2 and PLOD2 showed consistent direction of effect estimates in the replication analysis, albeit not statistically significant. Three SNPs associated with SORD expression according to the GTEx portal were in linkage disequilibrium (R2 ≥ 0.2) with an SNP previously reported in a genome-wide association study of AFF. The prevalence of carriers of variants for both PLOD2 and SORD was higher in Asian versus European cases. While we did not identify genes enriched for damaging variants, we found suggestive evidence of a role for XRN2, PLOD2, and SORD, which requires further investigation. Our findings indicate that genetic factors responsible for AFFs are not widely shared among AFF cases. The study provides a stepping-stone for future larger genetic studies of AFF.

Case series on monoclonal antibodies targeting calcitonin gene-related peptide in migraine patients during pregnancy: Enhancing safety data.

Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP-mAbs) are approved for adult migraine prevention but pose safety concerns in pregnancy. We assess the safety of CGRP-mAbs in the periconceptional period through a case series and literature review. Six migraine-diagnosed women received CGRP-mAbs; treatment ceased upon pregnancy. We collected data and conducted safety assessments. To provide a comprehensive context, we performed a literature review. The series includes three erenumab, two fremanezumab and one galcanezumab case. A fremanezumab recipient experienced miscarriage; severe perinatal asphyxia linked to dystocia occurred with erenumab (140 mg). Database reviews revealed 63 spontaneous abortions, eight premature births, and seven birth defects among 286 World Health Organization and 65 European Medicines Agency cases. These rates align with untreated population rates. CGRP-mAbs use in the periconceptional period does not lead to clinically significant increase in pregnancy-related pathology or adverse effects on newborns within our case series and the literature reviewed.

813. SELF-DILATATION FOR THE MANAGEMENT OF REFRACTORY BENIGN OESOPHAGEAL STRICTURES: OUTCOMES FROM THE LARGEST EUROPEAN TERTIARY CENTRE EXPERIENCE TO DATE

Abstract Background Benign oesophageal strictures are commonly encountered in endoscopy and are often effectively managed with endoscopic dilatation. However, up to 40% of patients may develop refractory benign oesophageal strictures (RBES), necessitating frequent endoscopic interventions that are often challenging, pose a greater risk of complications, and negatively impact quality of life. Oesophageal self-dilatation (SD) offers an alternative treatment that potentially reduces the need for repeat hospital visits while allowing patients greater autonomy in managing their condition. We describe the efficacy and safety of oesophageal SD at a tertiary referral centre. Methods We retrospectively reviewed the electronic records of patients with RBES (n=43) who were referred for SD to our centre between 2013 and 2024. The primary outcomes were the endoscopic dilatation-free interval (EDFI; longest period of time patients did not require endoscopic dilatation) and the number of endoscopic procedures performed within 12 months of starting SD. Secondary outcomes included the technical success rate of learning SD, improvement in the Dakkak and Bennett dysphagia score, and complications. Results are reported as median (interquartile range). Results 41/43 patients (median age 57 years) with various RBES aetiologies (32% peptic, 19.5% post-radiation, 12% post-surgical, 11.6% post-endoscopic resection, 24.9% other) and locations (24.4% proximal, 29.3% middle, 34.1% lower, 12.2% multi-segment) successfully learned SD. Median follow-up was 23.2 months. The EDFI increased from 68.5 (41-106) to 161 (121-279) days (P&amp;lt;0.001) while endoscopic interventions decreased from 7 (4.7-10) to 1 (0.75-3) (P&amp;lt;0.001) within 12 months before and after SD. The all-time EDFI was 405 days (130-705) and dysphagia score improved from 2 at baseline to 0 after SD. One patient experienced clinically significant haematemesis and one presumed SD-related oesophageal perforation. Conclusion To our knowledge, we have described the largest European case series of oesophageal SD that has been published to date. Oesophageal SD appears to be an effective, well-tolerated, and safe approach in managing often complex patients with RBES providing a viable alternative to conventional endoscopic interventions. However, the occurrence of adverse events highlights the importance of careful patient selection and ongoing monitoring. Further research is warranted to validate these findings and identify predictive factors for treatment success.

Balancing privacy and public interest in the fight against illicit financial flows: Lessons from an European Case Study

Illicit Financial Flows (IFF) – such as corruption and money laundering – have a significant negative impact on the enjoyment of human rights. Combating IFF is an integral part of the 2030 Agenda for Sustainable Development. SDG 16 explicitly promulgates the relation between the rule of law, social security and the fight against IFF. Cross-border data access and exchange by enforcement authorities is crucial to map and disrupt IFF, punish suspects and take away their criminally earned assets. At the same time, human rights restrain national enforcement authorities when combatting IFF. States must abstain from undue interference with individuals’ privacy rights, such as the storage of information relating to an individual’s private life and the sharing of such information. Pursuant to article 8 ECHR, interference with the right to respect for private – in accordance with the law – is only permissible if this is necessary in a democratic society, e.g. in the interests of national security and public safety. In this article we explore the balance between individual rights and states’ responsibilities in the fight against IFF; between privacy and the common good of fighting bad money. To what extent may privacy concerns be an obstacle to investigate global IFF? Our conclusion is that there is an imbalance. We suggest that human dignity and human security should be given more weight in the balancing of human rights in this context.

Volatility Spillover Effect from Energy Markets to Foreign Exchange Markets: The Case of Central and Eastern European and Eurasian Countries

Volatility Spillover Effect from Energy Markets to Foreign Exchange Markets: The Case of Central and Eastern European and Eurasian Countries

Association between blood mitochondrial DNA copy number and mental disorders: A bidirectional two-sample mendelian randomization study

BackgroundMitochondria is essential for cellular energy production, oxidative stress, and apoptosis. Mitochondrial DNA (mtDNA) encodes essential proteins for mitochondrial function. Although several studies have explored the association between changes in mtDNA copy number (mtDNA-CN) and risk of mental disorders, the results remain debated. This study used a bidirectional two-sample Mendelian randomization (MR) analysis to examine the genetic causality between mtDNA-CN and mental disorders. MethodsGenome-wide association study (GWAS) data for mtDNA-CN were sourced from UK biobank, involving 383,476 European cases. GWAS data for seven mental disorders—attention deficit/hyperactivity disorder, autism spectrum disorder (ASD), schizophrenia, bipolar disorder, major depressive disorder, anxiety, and obsessive-compulsive disorder—were primarily obtained from the Psychiatric Genomics Consortium. Causal associations were assessed using inverse variance weighting, with sensitivity analyses via the weighted median and MR-Egger methods. Reverse MR considered the seven mental disorders as exposures. All analyses were replicated with additional mtDNA-CN GWAS data from 465,809 individuals in the Heart and Ageing Research in Genomic Epidemiology consortium and the UK Biobank. ResultsForward MR observed a 27 % decrease in the risk of ASD per standard deviation increase in genetically determined blood mtDNA-CN (OR = 0.73, 95%CI: 0.58–0.92, p = 0.002), with no causal effects on other disorders. Additionally, reverse MR did not indicate a causal association between any of the mental disorders and mtDNA-CN. Validation analyses corroborated these findings, indicating their robustness. ConclusionsOur study supports the potential causal association between mtDNA-CN and the risk of ASD, suggesting that mtDNA-CN could serve as a promising biomarker for early screening of ASD.

Electricity supply configurations for green hydrogen hubs: A European case study on decarbonizing urban transport

In this study, a techno-economic analysis tool for conducting detailed feasibility studies on the deployment of green hydrogen hubs for fuel cell bus fleets is developed. The study evaluates and compares five green hydrogen hub configurations' operational and economic performance under a typical metropolitan bus fleet refuelling schedule. Each configuration differs based on its electricity sourcing characteristics such as the mix of energy sources, capacity sizing, financial structure, and grid interaction. A detailed comparative analysis of distinct green hydrogen hub configurations for decarbonising a fleet of fuel-cell buses is conducted. Among the key findings is that a hybrid renewable electricity source and hydrogen storage are essential for cost-optimal operation across all configurations. Furthermore, bi-directional grid-interactive configurations are the most cost-efficient and can benefit the electricity grid by flattening the duck curve. Lastly, the paper highlights the potential for cost reduction when the fleet refuelling schedule is co-optimized with the green hydrogen hub electricity supply configuration.

Opportunities and Challenges of Geothermal Energy: A Comparative Analysis of Three European Cases—Belgium, Iceland, and Italy

Opportunities and Challenges of Geothermal Energy: A Comparative Analysis of Three European Cases—Belgium, Iceland, and Italy

State aid for broadband network deployment: National and subnational governance mechanisms, 2003–2023

This paper examines the governance models of State aid measures for broadband network deployment in European Union Member States. The research is based on 199 decision letters collected from the European Commission's competition cases database, published between 2003 and 2023. Deploying a theory-driven content analysis approach, the analysis reveals and categorises a variety of governance models. These models vary regarding the authority responsible for the decision-making and, in the case of national schemes, the authority responsible for the implementation, including centralised and decentralised arrangements. Different legacies and institutional set-ups explain the governance models, including the typology of state structures, the constitutional powers, the traditions of participation in the telecommunication sector, policy diffusion and regional development. There are several possible pathways to a gradual transition from one model to another. The design of flexible national schemes, which offer subnational authorities the option to implement them in their regions or to rely on central management agencies for specific tasks adapted to their interests, resources and capacities, could be the optimal solution to prevent the launch of ad hoc measures by subnational authorities and to adapt to different institutional arrangements.

Co-creation in partnerships contributing to the sustainability of food systems: insights from 52 case studies in Europe

Institutions worldwide call for joint actions of multiple actors in partnerships to accelerate the transitions towards sustainable food systems and reach food security for everybody, allways. This requires insights into co-creating processes. Here, 52 European food system cases are analyzed. A methodology based on the game structure is used that permits standardizing data collection and extracting generic and cases-specific findings. Game building blocks correspond with key elements of co-creation processes, like defining mutually accepted objectives, engaging in types of activities, and efficient use of resources, boundary conditions, timings, and scales of operations. Results further indicate that different types of inclusive partnerships emerge, in which especially innovative private, including smallholders, and academic actors co-create value, all contributing to sustainability. The public and civil society actors emerge as important initiators, enablers, and organizers of scales of interaction, allowing generating snowball effects. Findings lead to an adapted concept for co-creating partnerships in food systems and recommendations for the European Partnership on sustainable food systems.

How wind forecast updates are balanced in coupled European intraday markets

AbstractThe market coupling of adjacent market zones is a key element in terms of coping with rising levels of uncertainty in the European energy system due to the adoption of more volatile renewable energy sources. An adequate analysis of this issue yet requires an appropriate consideration of uncertainty along with a detailed modelling of market coupling. Thus, we present a novel approach combining a comprehensive unit commitment and dispatch model with a sophisticated methodology to reflect the uncertainty of wind power generation by considering forecast updates for the German market region in the market clearing process. Subsequently, we investigate the impact of uncertainty on cross‐border electricity flows in a European case study. Our results show that all adjacent market zones and all relevant technologies significantly contribute to balancing forecast updates in Germany, underlining the benefits of intraday market coupling. Further, we observe that a joint and unrestricted intraday market is the most cost‐efficient market solution. Finally, our analyses show that more extensive market coupling is indispensable for the further integration of renewable energy sources in the future.

Prion protein gene (PRNP) variation in German and Danish cervids

The structure of cellular prion proteins encoded by the prion protein gene (PRNP) impacts susceptibility to transmissible spongiform encephalopathies, including chronic wasting disease (CWD) in deer. The recent emergence of CWD in Northern European reindeer (Rangifer tarandus), moose (Alces alces alces) and red deer (Cervus elaphus), in parallel with the outbreak in North America, gives reason to investigate PRNP variation in European deer, to implement risk assessments and adjust CWD management for deer populations under threat. We here report PRNP-sequence data from 911 samples of German red, roe (Capreolus capreolus), sika (Cervus nippon) and fallow deer (Dama dama) as well as additional data from 26 Danish red deer close to the German border and four zoo species not native to Germany. No PRNP sequence variation was observed in roe and fallow deer, as previously described for populations across Europe. In contrast, a broad PRNP variation was detected in red deer, with non-synonymous polymorphisms at codons 98, 226 and 247 as well as synonymous mutations at codons 21, 78, 136 and 185. Moreover, a novel 24 bp deletion within the octapeptide repeat was detected. In summary, 14 genotypes were seen in red deer with significant differences in their geographical distribution and frequencies, including geographical clustering of certain genotypes, suggesting “PRNP-linages” in this species. Based on data from North American CWD and the genotyping results of the European CWD cases, we would predict that large proportions of wild cervids in Europe might be susceptible to CWD once introduced to naive populations.

Understanding solidarity in the European Union: an analytical framework

Solidarity is a key concept in the European Union. However, the concept of solidarity lacks systematic theoretical examination to enable a sufficient understanding of its contextual meaning and to provide an operationalisable benchmark for analysis. To address this research gap, I propose an analytical framework for solidarity in the European Union that features four necessary conditions: particularity, instrumentality, reciprocity, and responsibility. I develop the framework through a transdisciplinary conceptual history approach, substantiated with a thorough document and legal analysis of European integration and CJEU case law. I demonstrate the robustness and validity of the proposed framework by using EU asylum policy as a test case, a field where the question of solidarity is notoriously salient, which is exemplified by an area-specific expression of the concept: fair sharing of responsibility between the EU member states. Moreover, I show that the EU’s solidarity principle is necessary to maintain the bloc’s raison d’être.

Community Resilience Assessment: Implementation of a Novel Resilience Framework in Four Different European Case Study Areas

Community Resilience Assessment: Implementation of a Novel Resilience Framework in Four Different European Case Study Areas