European Source Research Articles

B-075 Evaluation of patients with monoclonal gammopathy of undetermined significance using Optilite Freelite assays

Abstract Background Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant disorder with a progression risk to multiple myeloma of 1% per year. Patients with MGUS may produce monoclonal intact immunoglobulins (Ig) and/or free light chains (FLC). The International Myeloma Working Group (IMWG) recommendations for the use of FLC measurements in MGUS are to establish the diagnosis of light chain only MGUS (LC-MGUS) and further to risk-stratify newly diagnosed MGUS. Once identified, MGUS is longitudinally monitored at intervals dependent on the risk of transformation. The IMWG recommends serum protein electrophoresis (SPEP) for monitoring of known MGUS with intact Ig, however others have published benefits of additionally monitoring with FLC. In this study, we evaluated the diagnostic sensitivity and specificity of the Optilite® Freelite® Kappa Free Kit and the Optilite Freelite Lambda Free Kit (The Binding Site, part of Thermo Fisher Scientific) in patients with MGUS, and the monitoring performance of Freelite results measured in serial samples from patients with clinically stable and progressive MGUS. Methods Serum samples from 234 patients with clinically diagnosed MGUS and 140 disease controls, taken at single time points, and serial samples (≥3) from 49 patients with MGUS were tested with the Freelite assays. Intact M-protein presence and isotype was confirmed in MGUS samples with immunofixation electrophoresis (IFE). In patients clinically diagnosed with LC-MGUS, the presence of detectable M protein on IFE was not required. The disease control cohort (non-MGUS) had disorders commonly associated with elevated polyclonal immunoglobulins (e.g autoimmune, liver, and renal diseases), confirmed by total IgG and/or IgA and/or IgM results and the absence of M-protein by IFE. Patients represented a diverse population from both European and US sources. Results The overall diagnostic sensitivity of the Optilite Freelite assays was 59.4%, calculated as the frequency of abnormal free light chain ratio (rFLC) in intact immunoglobulin MGUS, and abnormal rFLC with concurrent elevated involved FLC level in LC-MGUS. The diagnostic sensitivity was: 58.0% in non-IgM MGUS, 41.7% in IgM MGUS, 66.7% in biclonal MGUS and 100% in LC-MGUS. In intact (IgG/IgA/IgM) kappa MGUS, the diagnostic sensitivity was 67.5%, versus 41.5% in intact (IgG/IgA/IgM) lambda MGUS. The diagnostic specificity was 86.4%. In the 49 patients with serial samples, concentrations of involved FLC were stable in 93.3% of patients with clinically stable MGUS, whereas in patients with clinically progressive MGUS an increasing trend was seen in 50% of cases. Conclusions These results demonstrate that the Optilite Freelite Kappa and Lambda assays produce clinically relevant results that are useful in the evaluation of MGUS.

Semi-Supervised Triply Robust Inductive Transfer Learning

In this work, we propose a Semi-supervised Triply Robust Inductive transFer LEarning (STRIFLE) approach, which integrates heterogeneous data from a label-rich source population and a label-scarce target population and uses a large amount of unlabeled data simultaneously to improve the learning accuracy in the target population. Specifically, we consider a high dimensional covariate shift setting and employ two nuisance models, a density ratio model and an imputation model, to combine transfer learning and surrogate-assisted semi-supervised learning strategies effectively and achieve triple robustness. While the STRIFLE approach assumes the target and source populations to share the same conditional distribution of outcome Y given both the surrogate features S and predictors X , it allows the true underlying model of Y⏧ X to differ between the two populations due to the potential covariate shift in S and X . Different from double robustness, even if both nuisance models are misspecified or the distribution of Y⏧ S , X is not the same between the two populations when the shifted source population and the target population share enough similarities, the triply robust STRIFLE estimator can still partially use the source population when the shifted source population and the target population share enough similarities. Moreover, it is guaranteed to be no worse than the target-only surrogate-assisted semi-supervised estimator with an additional error term from transferability detection. These desirable properties of our estimator are established theoretically and verified in finite samples via extensive simulation studies. We use the STRIFLE estimator to train a Type II diabetes polygenic risk prediction model for the African American target population by transferring knowledge from electronic health records linked genomic data observed in a larger European source population. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.

Writing Confucian History in an Indian Language

Abstract This article uses a case study of an Urdu translation of the classical Chinese Shujing (Book of Documents) to bring to light a process of multiperson, mediated, and ultimately transimperial translation in which European source texts played crucial roles in transmitting detailed knowledge of China to the Indian public sphere. After outlining the theoretical approach of transimperial history and its value for Asian intellectual history, the article positions the Urdu Shujing in relation to earlier Indian and Middle Eastern accounts of China whose triangulated transmission—from East Asia to Europe and thence to South or West Asia—set various precedents for the translation of the Shujing from a prior English translation. The article then focuses on the Urdu version to reveal the transimperial mechanisms it used to not only translate and transliterate classical Chinese, but also to “transcalculate” dates and render Chinese history comparable to both Europe's and India's past. The conclusions argue that, from Ming China via the early modern Catholic empires to the occult subcurrents of British colonial culture, the transimperial pathways along which Confucian history reached India were ultimately Eurasian rather than narrowly inter-Asian in scope. This reliance on earlier European translations would later recur with the spread of “world literature” in the postcolonial era.

Linking Between Molecular and Biodiversity Data: A BiCIKL Perspective

Molecular sequencing data generation is being driven by global and regional efforts to discover, understand and monitor biodiversity. To fully explore this data in biodiversity research we need a network of connected data resources, linking sequence data with natural history collections, taxonomy and literature. The BiCIKL project (Biodiversity Community Integrated Knowledge Library, Penev et al. 2022) has set the groundwork towards creating this network of linked data and fostering FAIR (Findable, Accessible, Interoperable and Reusable) practices in the biodiversity domain. Connecting biodiversity and molecular data along the biodiversity research cycle requires a foundation of well-structured and rich metadata in the molecular sequence databases. Referencing the physical specimens is important as this provides context about the source of the material that was used for generating the molecular sequence data, including information about origin and species identification. To connect biodiversity and molecular data, we developed tools and workflows for improving and standardising metadata, federated searches and validations for specimen reference in sequence data, such as the SpASe tool, which enables the discovery of links between natural history collections and sequences, and the European Nucleotide Archive Source Attribute Helper API, which facilitates the construction of specimen attributes in a structured format. This work was done in close collaboration with DiSSCo (Distributed System of Scientific Collections) and some biodiversity genomics projects (e.g. Biodiversity Genomics Europe, BGE). Furthermore, we enabled community curation of biological source annotations such as specimen references in sequence data through the PlutoF platform and the ELIXIR Contextual Data Clearinghouse (Abarenkov et al. 2021, Balavenkataraman Kadhirvelu et al. 2022) and increased bidirectional linking from sequences in the European Nucleotide Archive (ENA) to collections, taxonomy and literature services (e.g., Plazi TreatmentBank, OpenBioDiv). We also worked closely with the community to enable the structured publication of environmental DNA data, promoting and engaging in the definition of standards and developing tools to facilitate data deposition and retrieval. Overall, the project has contributed significantly to strengthen the connections between the biodiversity and genomics communities towards higher data integration and interoperability. Structured, enriched, accessible and linked sequence data will provide a strong foundation for the application of biodiversity knowledge in the response to global challenges, such as biodiversity loss, ecosystem change and food security. Beyond BiCIKL, we will continue our work as a community to promote a culture of FAIR linked molecular data, towards a fully integrated biodiversity knowledge ecosystem.

Microstructural changes in the welding of titanium-stabilized steels

Abstract At the Central Institute for Engineering, electronics, and Analytics (ZEA-1 by its acronym in German) of the Jülich Research Center GmbH, a cryostat was developed for the European Spallation Neutron Source (ESS) and manufactured from a titanium-stabilized austenitic stainless steel alloy (EN 1.4571). After tungsten inert gas welding, the welds exhibited a black, patchy discoloration. After materialographic preparation, the phenomena were examined using microscopic methods to assess their impact on the strength of the weld and thus on the usability of the cryostat. Not only could the impact on the cryostat operation be assessed, but the formation mechanism could be elucidated and suitable measures could be outlined to avoid the black, patchy discoloration.

Antimicrobial susceptibility in Clostridioides difficile varies according to European region and isolate source.

Clostridioides difficile epidemiology is evolving with country-associated emerging and resistant ribotypes (RT). Antimicrobial susceptibility testing of C. difficile isolated from clinical and animal samples collected across Europe in 2018 was performed to provide antimicrobial resistance data and according to C. difficile RTs and source. Samples were cultured for C. difficile and isolates PCR ribotyped. Metronidazole, vancomycin, fidaxomicin, moxifloxacin, clindamycin, imipenem, tigecycline, linezolid, rifampicin and meropenem minimum inhibitory concentrations (MICs) for 280 clinical and 126 animal isolates were determined by Wilkins-Chalgren agar dilution. Fidaxomicin was the most active antimicrobial (all isolates geometric mean MIC = 0.03 mg/L) with no evidence of reduced susceptibility. Metronidazole MICs were elevated among RT027 (1.87 mg/L) and RT181 clinical isolates (1.03 mg/L). RT027 and RT181 had elevated geometric mean moxifloxacin MICs (14.49 mg/L, 16.88 mg/L); clindamycin (7.5 mg/L, 9.1 mg/L) and rifampicin (0.6 mg/L, 21.5 mg/L). Five isolates (RT002, RT010 and RT016) were metronidazole resistant (MIC = 8 mg/L) and 10 (RT027; RT198) had intermediate resistance (4 mg/L). Metronidazole MICs were not elevated in animal isolates. Increased geometric mean vancomycin MICs were observed among RT078, mostly isolated from animals, but there was no resistance (MIC ≥ 4 mg/L). Clinical and animal isolates of multiple RTs showed resistance to moxifloxacin and clindamycin. No resistance to imipenem or meropenem was observed. Increased antimicrobial resistance was detected in eastern Europe and mostly associated with RT027 and related emerging RT181, while clinical isolates from northern and western Europe had the lowest general levels of resistance.

Infections in residents of long- term care facilities in southern Poland, 12-month surveillance preliminary results

Long-Term Care Facility (LTCF) residents are particularly vulnerable to infections due to factors such as advanced age, co-morbidities, and regular medication use. Data from American and European sources indicate an anticipated occurrence rate of 2 to 11 infections per 1000 patient-days (pds) in LTCFs. The incidence rate of Clostridioides difficile infections (CDI) is reported at 0.52 per 10,000 resident days. The research objectives aimed to assess infection epidemiology in Polish LTCFs. An observational prospective study was conducted on residents from five LTCFs (2 residential homes and 3 nursing homes) in southern Poland between September 2022 and September 2023, utilizing the definition from the pan-European HALT study. The study received approval from the Bioethics Committee of the JU (1072.6120.73.2022) and was funded by the Polish NCN grant No.2021/41/B/NZ6/00749. CDI was defined by positive toxins A and B enzyme immunoassays (EIA) and positive glutamate dehydrogenase (DHA) EIA. Results from the study, involving 250 residents, revealed 157 cases of Healthcare-Associated Infections (HAIs) excluding gastrointestinal and CDI, with an incidence rate of 1.97/1000 pds. Lower respiratory tract infections dominated with 77 cases, including 36 pneumonia cases (47%). Additionally, 25 cases of gastrointestinal infections were reported, including only 7 CDI cases, resulting in an incidence rate of 0.88 CDI per 10,000 pds. Norovirus was detected in only one case, while the microbiological results were negative in the remaining cases. The incidence rate among Polish LTCF residents was lower than expected, contrasting with the CDI incidence that aligned with other research findings. Notably, the etiology of diarrhea remained undetermined in 68% of cases.

The ‘pre-Shakespearean’ balcony and outdoor spaces from the European sources to Romeo and Juliet

This article shows how the balcony scene has been represented in Romeo and Juliet's narrative sources and how it has been treated by Shakespeare and on seventeenth- and eighteenth-century stages. It focuses on the absence of any balcony in Shakespeare's play and on the actual presence of a balcony in one of the Italian indirect sources of the play, Luigi Da Porto's novella; it also explores how all the spatial, gender, and power connotations of the balcony have been ‘translated’ from the sources to Shakespeare, where they are conveyed by the use of a ‘window’ and an ‘orchard’. The article shows how, thanks to the SENS: Shakespeare's Narrative Sources: Italian Novellas and their European Dissemination digital archive a comparison of multiple texts at a time, focusing on the words ‘balcony’, ‘window’, ‘garden’, and ‘orchard’, favours the investigation of the way in which these liminal spaces are represented.

New developments of hydrogen impurity online-monitoring in liquid lithium of IFMIF-DONES

On the way to future nuclear fusion power plants, the International Fusion Materials Irradiation Facility (IFMIF) – DEMO Oriented Neutron Source (DONES), is an important key element between ITER and DEMO to study before the influence of DEMO-neutron irradiation on foreseen fusion materials. The core of DONES, currently under construction near Granada, Spain, is based on a circuit containing liquid lithium at elevated temperatures acting as a functional material for the (d,n)-Li reaction in a materials test cell. In addition to this actual function of DONES, there are important aspects of maintenance in which hydrogen isotopes are generated under operating conditions and dissolved in this aggressive and very reactive alkali metal. This implies strong unfavourable effects on the applied structural materials, e.g. hydrogen embrittlement and others.To counteract these unfavourable effects, endangering the safe operation, an Impurity Control System (ICS) is an integral part of the DONES instrumentation. As part of the tasks of the European Neutron Source (ENS) to develop redundant systems for monitoring impurities, a special sub-task was defined for the development of an electrochemical H-sensor for concentrations in liquid lithium, ECHSLL. It is determined by detecting the electrical potentials of the lithium melts compared to a standard Li-based chemical reference system. This allows an inherent material property to be directly correlated (i.e. through appropriate electrochemical instrumentation) with chemical concentration values. This article presents important advancements in the applied ECHSLL technique, such as improving laboratory measurements from stagnant conditions to dynamic and realistic flow conditions of the liquid lithium material, as well as appropriate approaches to overcome the challenges in distinguishing the hydrogen isotopes by ECHSLL system (protium and deuterium among given laboratory conditions).

The Role of Armenian Forces in the Defense of Tabriz (September 1724)

This study delves into the hitherto unexplored involvement of Armenian troops in the defense of Tabriz in 1724, drawing on an extensive analysis of historical materials. In 1723-1724, the Ottoman Empire launched invasions into Safavid Iran from several directions. By September 1724, one Ottoman army, led by Abdullah Pasha of Van, advanced towards Tabriz and attempted to storm the city. During the ensuing battle, the Turkish forces were soundly defeated and driven back, suffering approximately 20,000 casualties. European sources emphasize the significant role played by Armenian military units in the decisive victory at the Battle of Tabriz, the sole triumph for Persian forces during the 1724 campaign. Notably, the majority of these units arrived from Karabakh. The Armenian troops were instrumental in virtually annihilating the elite Janissary corps within Abdullah Pasha's army. This article identifies the Armenian detachments involved in the defense of Tabriz, listing their commanders: Parsadan-bek, Melik-Egan, Pilibek Basaurov, David, Abidjan, Aghajan, Akhnazar, Balig, among others.

Formal long-term care, individualisation and filial responsibility: a multi-level analysis of 21 European countries

PurposeDue to the rapid ageing of the continent's population, a significant surge in long-term care expenses for the elderly is expected across Europe in the coming years. Could a potential solution to this challenge involve the increased informal care provided by adult children? In this context, we examined a general view or moral duty of European citizens regarding whether adult children should assume responsibility for providing long-term care to the elderly.Design/methodology/approachOur multilevel analysis draws on individual-level data from the 2017 European Value Study and country-level data from various European sources encompassing participants from 21 member countries of the European Union.FindingsThe findings reveal that in nations where public long-term care services are sufficiently available and of superior quality, there is a negative sentiment towards the notion that adult children should bear the responsibility for elderly care. In total, 71% of the country-level variance in our dependent variable was explained by the availability and quality of formal long-term care in a country. Furthermore, various individual-level attributes contribute to shaping attitudes towards care-giving responsibility. We observed that women, middle-aged individuals, those without religious affiliations, those with modern gender role attitudes and non-immigrants tended to hold unfavourable attitudes towards the responsibility of adult children in long-term care provision.Originality/valueThere are relatively many studies on the general attitude of the population towards filial obligation. However, so far there have been very few studies available that examine the population's attitude towards the obligation of adult children to commit to their parents' long-term care. Our research explains the variation of the phenomenon in Europe with both country-level and individual-level factors.

Selective treatment of clinical mastitis: Assessment of the Net Cash Impact on Dairy Farms Under Diverse Scenarios. A European Perspective.

Selective treatment of clinical mastitis (STCM) potentially reduces antimicrobial use without negative implications on cow's milk production or health. However, this approach comes with additional costs. The aim of this study was to evaluate the net cash impact (NCI) of implementing STCM compared with blanket treatment of clinical mastitis (BTCM) under different diagnostic-test turnaround times (24 h, 14 h, and 8 h) using a stochastic partial budget analysis with Monte Carlo simulation. The target population was European commercial dairy herds; therefore, the model inputs were primarily from European sources. Additionally, variables associated with dairy management programs were obtained from USDA sources, worldwide multisite clinical trials, and expert opinion. The output was calculated by subtracting the cost of STCM from the cost of BTCM and it represented the expected NCI if a herd switched from BTCM to STCM. Depending on the time-to-treatment efficiency and diagnostic-test turnaround time, the expected mean NCI, assuming that STCM has no impact on the cow's future health or production, ranged from +€8.7 to +€12.4 per case with 72.4% to 84.8% of the iterations being ≥ €0. Moreover, using the numerically favorable health and production effects of STCM reported in the literature, the expected mean NCI ranged from +€44.5 to +€48.1 per case with 93.6% to 95.4% of the iterations being ≥ €0. The variables with the greatest contribution to NCI variance were proportion of gram-positive cases (39.2% of the variance) and days out of the tank for treated cows (22.0%). However, if future cow's health and production were accounted for, culling risk (24.6%), recurrence risk (19.4%), and milk yield (10.6%) would have the greatest contribution to NCI. The sensitivity analysis indicated that farms with high clinical mastitis incidence, low proportion of gram-positive cases, large number of days out of the tank for treated cows, higher milking frequency or using automatic milking systems, not using the highest priced diagnostic tests, and having high antimicrobial treatment costs are the best candidates for STCM. Improving time-to-treatment efficiency, for example, by using a rapid diagnostic test, leads to a favorable NCI, while high daily milk yield and milk price enhances the NCI in already positive scenarios. Finally, the cash flow entirely depends on future cow's health and milk yield. In conclusion, results indicate that overall, STCM is a practice that positively impacts the NCI of many herds.

Influence of wildfire emissions to carbon dioxide (CO2) observed at the Mt. Cimone station (Italy, 2165 m asl): A multi-year investigation

This work aimed at investigating on a multi-year framework (2015–2021) the contributions of wildfire emissions to atmospheric CO2 observed at the ICOS atmospheric class-2 station Mt. Cimone (CMN, 2165 m a.s.l. - Italy). Based on the analysis of a case study occurred in March 2020, a methodology providing indications about the possible presence of wildfire plumes from different European source regions was implemented. The methodology used observed CO at CMN, active fire detection by MODIS and air mass back-trajectories. An alternative detection method based on the use of a reanalysis dataset (CAMS) providing information about the amount of PM10 tagged to wildfires was also used.The results suggested that CMN could be affected by wildfire plumes for a fraction of time ranging from 1% to 10% (as a function of the adopted methodology setting). Over the studied period, we found a potentially important contribution of plumes from eastern Europe during October–April, while during May–September there was a prevalence from the Mediterranean sectors.Looking at the possible impact of these events to the observed CO2, we detected a notable increase of CO2 residuals with respect to periods not affected by fire perturbations during October–April (from +1.8 to +3.9 ppm, on average). We did not find evident impacts during the summer months, possibly due to a contribution by biospheric uptake during air mass transport to CMN (at least for a fraction of selected events).We discussed the sensitivity of results as a function of the selection methodology settings, suggesting that the strictest set-up based on the detection of large CO excesses could trace “major” events. A medium level of agreement was found when comparing the results of our selection methodology with CAMS reanalysis (fraction of PM10 emitted by wildfires).Even if it is still preliminary, our study indicated that the observations from CMN can represent, if supported by adequate diagnostic tools, a powerful dataset to evaluate the impact of wildfires to the atmospheric CO2 variability.

European effort to improve highly charged heavy ion beam capabilities with ECR ion sources (invited)

The European Electron Cyclotron Resonance Ion Source (ECRIS) community has more than 20 years of experience working together in various EU-funded projects. In the recent project, called ERIBS (European Research Infrastructure – Beam Services), the community will focus on improving ion beam services for the EURO-LABS (European-Laboratories for Accelerator Based Sciences) research infrastructures. The EURO-LABS is a four-year project funded by the Horizon Europe program of the European Commission for years 2022 - 2026. In the ERIBS collaboration the best expertise, know-how and practices of the ECRIS community will be exploited and transferred between the partners to take full advantage of the European ion source infrastructure. The aim is to extend the beam variety available for the European user community by developing beam production methods and techniques. This development includes further improvement of technologies related to high temperature ovens, axial sputtering and MIVOC method for all the participating laboratories. We will also aim to improve both short- and long-term plasma and beam stability, as well as methods for online monitoring of these conditions. This can be realized, for example, by optical emission spectroscopy, identifying kinetic plasma instabilities by means of hard x-ray detection and using online beam current monitoring systems. An example of the recent developments is the new collaboration proposed by the CNRS-IPHC team to synthesize enriched MIVOC compounds for the other ERIBS partners. For example, the team successfully prepared an enriched chromocene compounds, which were needed to produce intensive 54Cr and 50Cr beams for the JYFL and GANIL nuclear physics programs, respectively.

No recognised ethical standards, no broad consent: navigating the quandary in computational social science research

Recital 33 GDPR has often been interpreted as referring to ‘broad consent’. This version of informed consent was intended to allow data subjects to provide their consent for certain areas of research, or parts of research projects, conditional to the research being in line with ‘recognised ethical standards’. In this article, we argue that broad consent is applicable in the emerging field of Computational Social Science (CSS), which lies at the intersection of data science and social science. However, the lack of recognised ethical standards specific to CSS poses a practical barrier to the use of broad consent in this field and other fields that lack recognised ethical standards. Upon examining existing research ethics standards in social science and data science, we argue that they are insufficient for CSS. We further contend that the fragmentation of European Union (EU) law and research ethics sources makes it challenging to establish universally recognised ethical standards for scientific research. As a result, CSS researchers and other researchers in emerging fields that lack recognised ethical standards are left without sufficient guidance on the use of broad consent as provided for in the GDPR. We conclude that responsible EU bodies should provide additional guidance to facilitate the use of broad consent in CSS research.

The Australian Constitutional Framers and the Languages of Virtue

The historiography of the political concept of virtue has been dominated by examinations of western European and North American sources. This article aims to widen the historical scope for our understanding of the influence of the concept of political virtue by examining how Anglophone conceptions of virtue were employed by the framers of the Australian Constitution during the Federation debates and the impact of those conceptions on the Constitution itself. It examines the strands of thought that provided the backdrop for the colonial adoption of the Victorian‐era British conception of political virtue, subsequently showing how the Australian constitutional framers adopted these languages and concepts in their own writings and speeches. The Australian framers were concerned with the virtue of both the people and their political leaders, applying this concern in their contributions to legal and political discourse in the latter part of the nineteenth century. However, rather than a direct transfer of the more typical languages of republican virtue, the colonial context examined here offers evidence of a shift of emphasis from virtue into the concept of “character”. The framers demonstrated an interest in the question of character as they wrote and deliberated around the constitutional problems of political parties, bicameralism, and responsible government. So, too, they showed an acute concern for the importance of character in their institutional designs for a future federal commonwealth. This article demonstrates that the framers existed within the tradition of thought which held virtue, or character, to be central to the vitality of the polity, and that the framers adapted that language in their deliberations and the institutional design of the Constitution.

Availability and Access to Orphan Drugs for Rare Cancers in Bulgaria: Analysis of Delays and Public Expenditures.

Rare cancers are defined by an annual incidence of fewer than 6 per 100,000. Bearing similarities to rare diseases, they are associated with substantial health inequalities due to diagnostic complexity and delayed access to innovative therapies. This situation is further aggravated in Southeastern European countries like Bulgaria, where limited public resources and expertise underscore the need for additional policy and translational research on rare cancers. This study aimed to explore the availability and access to orphan drugs for rare cancers in Bulgaria for the period of 2020-2023. We cross-compared data from both the European Union and national public sources to evaluate the number of available and accessible orphan drugs for rare cancers, the delay from market authorization to reimbursement, the dynamics of public expenditures, and regional disparities in access across the country. We juxtaposed the main characteristics of oncological and non-oncological orphan drugs as well. Only 15 out of 50 oncological orphan drugs that were authorized by the European Medicine Agency were accessible for rare cancer patients in Bulgaria. The median delay between market authorization and inclusion in the Bulgarian Positive Drug List was 760 days. The total expenditures for all orphan drugs for rare cancers amounted to EUR 74,353,493 from 2020 to 2023. The budgetary impact of this group rose from 0.24% to 3.77% of total public medicinal product expenditures for the study period. Rare cancer patients represent a vulnerable population that often faces limited to no access to treatment. We call for targeted European and national policies to address this major inequality.

Landscape analysis of available European data sources amenable for machine learning and recommendations on usability for rare diseases screening

BackgroundPatient registries and databases are essential tools for advancing clinical research in the area of rare diseases, as well as for enhancing patient care and healthcare planning. The primary aim of this study is a landscape analysis of available European data sources amenable to machine learning (ML) and their usability for Rare Diseases screening, in terms of findable, accessible, interoperable, reusable(FAIR), legal, and business considerations. Second, recommendations will be proposed to provide a better understanding of the health data ecosystem.MethodsIn the period of March 2022 to December 2022, a cross-sectional study using a semi-structured questionnaire was conducted among potential respondents, identified as main contact person of a health-related databases. The design of the self-completed questionnaire survey instrument was based on information drawn from relevant scientific publications, quantitative and qualitative research, and scoping review on challenges in mapping European rare disease (RD) databases. To determine database characteristics associated with the adherence to the FAIR principles, legal and business aspects of database management Bayesian models were fitted.ResultsIn total, 330 unique replies were processed and analyzed, reflecting the same number of distinct databases (no duplicates included). In terms of geographical scope, we observed 24.2% (n = 80) national, 10.0% (n = 33) regional, 8.8% (n = 29) European, and 5.5% (n = 18) international registries coordinated in Europe. Over 80.0% (n = 269) of the databases were still active, with approximately 60.0% (n = 191) established after the year 2000 and 71.0% last collected new data in 2022. Regarding their geographical scope, European registries were associated with the highest overall FAIR adherence, while registries with regional and “other” geographical scope were ranked at the bottom of the list with the lowest proportion. Responders’ willingness to share data as a contribution to the goals of the Screen4Care project was evaluated at the end of the survey. This question was completed by 108 respondents; however, only 18 of them (16.7%) expressed a direct willingness to contribute to the project by sharing their databases. Among them, an equal split between pro-bono and paid services was observed.ConclusionsThe most important results of our study demonstrate not enough sufficient FAIR principles adherence and low willingness of the EU health databases to share patient information, combined with some legislation incapacities, resulting in barriers to the secondary use of data.

Cupping and myotomy of the tail muscles as cosmetic operations in horses in European printed sources of the XVII- XVIII centuries

Relevance and goals. Tail amputation or surgical correction in domestic animals, especially in horses, is not accepted by society and is prohibited by law in many countries, except when performed for medicinal purposes. They are not encouraged by the rules and regulations of international sports and breeding associations, as mutilating, and have a very limited distribution. The authors of the historical sources we have taken agree that the operation of tail amputation in horses in the middle of the 17th century was already a common procedure performed quite successfully. By studying and comparing these sources, features and differences in anatomical description, surgical techniques, and postoperative care, one can come closer to understanding the development of veterinary medicine in Europe and Russia at that time.Materials and methods. A number of printed European sources of the 17th-18th centuries were analyzed, which contain descriptions of surgical procedures aimed at correcting the length and position of a horse's tail. Among the selected sources are books in English and Spanish, including books translated into Russian, published in printed form and representing guides for specialists and animal owners.Results. The sources we have studied present two main operations on the horse’s tail. These are tail amputation (caudotomy) and tail myotomy. We studied anatomical descriptions of the structure of the horse's tail, indications of the qualifications of surgeons, descriptions of surgical techniques, methods of fixing animals, postoperative care and complications.

Modern Japanese Images of Turks and Turkey

Modern Japanese Images of Turks and Turkey Nobuo Misawa (Toyo University, Japan) The image of Turks and Turkey in Modern Japan had been heavily influenced by the image of European and American sources described in this paper. For example, even after 1924, the Japanese merchants and officers of various ministries continued to adopt the divisions of European Turkey and Asiatic Turkey. We can find examples in the bulletin of the Japanese Commercial Museum in Istanbul, published in 1928- 37. The Museum still calculated and sent the statistics of imports and exports about Turkey, not as a single country but divided into two divisions, European Turkey and Asiatic Turkey, even after the establishment of the Republic of Turkey! It was only after the Japanese defeat in WWII in 1945, that Japan adopted a single name and area concept of Turkey. In addition, the Ministry of Education ordered the government’s official textbook writers to describe the name of the country as the Ottoman Empire (1299-1922) and the Republic of Turkey (1923- ). In these circumstances, private publications had begun to follow the government’s official textbooks, while some of them still used the outdated name, “Ottoman Turkey”, which neither the Europeans nor the Americans were no longer using.