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Abstract The biological aspects of infancy within late Upper Palaeolithic populations and the role of southern refugia at the end of the Last Glacial Maximum are not yet fully understood. This study presents a multidisciplinary, high temporal resolution investigation of an Upper Palaeolithic infant from Grotta delle Mura (Apulia, southern Italy) combining palaeogenomics, dental palaeohistology, spatially-resolved geochemical analyses, direct radiocarbon dating, and traditional anthropological studies. The skeletal remains of the infant – Le Mura 1 – were directly dated to 17,320-16,910 cal BP. The results portray a biological history of the infant’s development, early life, health and death (estimated at ~72 weeks). They identify, several phenotypic traits and a potential congenital disease in the infant, the mother’s low mobility during gestation, and a high level of endogamy. Furthermore, the genomic data indicates an early spread of the Villabruna-like components along the Italian peninsula, confirming a population turnover around the time of the Last Glacial Maximum, and highlighting a general reduction in genetic variability from northern to southern Italy. Overall, Le Mura 1 contributes to our better understanding of the early stages of life and the genetic puzzle in the Italian peninsula at the end of the Last Glacial Maximum.

Abstract Background The introduction of newborn screening (NBS) for spinal muscular atrophy (SMA) has increased the early diagnosis of 5q-associated SMA in presymptomatic and symptomatic preterm infants. National and international recommendations for treating preterms and newborns

Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR’s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.

Summary: Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19–2.25]), 26 months (1.20 [95% CI 0.48–1.91]), and 38 months (1.52 [95% CI 0.74–2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43–1.07]), 26 months (mean difference 0.65 [95% CI 0.27–1.03]), and 38 months (mean difference 0.72 [95% CI 0.25–1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34–43.38]), 26 months (mean difference 29.26 m [95% CI 14.87–43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32–54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.

Appropriate techniques for promoting reading fluency are difficult to implement in the classroom. There is little time to provide students with individualized feedback on reading aloud or to motivate them to do so. In this context, Virtual Reality (VR) can be beneficial for learning because it allows for individualized feedback and for increasing learner engagement. Studies that analyze established methods of language learning in VR at school are thus far lacking. Therefore, this pilot study is one of the first to analyze student acceptance of reading fluency training in desktop VR at a secondary school. The interview guide was developed in accordance with the Technology Acceptance Model. The desktop VR environment is web-based and provides individual and collaborative opportunities for training reading fluency, giving, and receiving feedback, and deepening content understanding of reading texts. To analyze the acceptance of the desktop VR environment, five guided interviews were conducted. The results reveal that despite various technical challenges within the VR environment, students not only accepted but also appreciated the reading fluency training in VR. The integration of established concepts of reading fluency training in foreign language classrooms has great potential as an additional value in addressing the challenges of face-to-face instruction.

Intorduction: Most studies on the progression of childhood-onset multiple sclerosis (MS) involve relatively short follow-up periods, focusing primarily on neurological outcomes and disability progression. The influence of these and other factors on the health-related quality of life is not known. To gain a comprehensive understanding of early-onset MS, it is crucial to evaluate the effects of treatment and the disease on quality of life. Method: This pilot project aimed to evaluate the feasibility of using an online survey tool for long-term follow-up data collection from patients with childhood-onset MS. An anonymized, monocentric, prospective survey was conducted on a convenience cohort of patients treated at a certified centre for neuromuscular diseases in childhood between 2007 and 2019. Results: A total of 27 patients completed the survey. There were no mandatory items, therefore some patients chose not to answer all the questions in the questionnaire. Patients exhibited promising educational achievements, low neurological disease burden, and high resilience. However, anxiety, depression, and pain significantly impacted their perceived health status. Conclusion:This single-centre study has yielded new insights into childhood-onset MS. To enable more accurate comparisons across different centres and countries, it is essential to establish a minimum data set and questionnaire subset for patients with paediatric-onset MS transitioning into adulthood.

Abstract The Eocene (56–34 million years ago) is characterized by declining sea surface temperatures (SSTs) in the low latitudes (∼4°C) and high southern latitudes (∼8–11°C), in accord with decreasing CO2 estimates. However, in the mid‐to‐high northern latitudes there is no evidence for surface water cooling, suggesting thermal decoupling between northern and southern hemispheres and additional non‐CO2 controls. To explore this further, we present a multi‐proxy (Mg/Ca, δ18O, TEX86) SST record from Bass River in the western North Atlantic. Our compiled multi‐proxy SST record confirms a net decline in SSTs (∼4°C) between the early Eocene Climatic Optimum (53.3–49.1 Ma) and mid‐Eocene (∼44–41 Ma), supporting declining atmospheric CO2 as the primary mechanism of Eocene cooling. However, from the mid‐Eocene onwards, east‐west North Atlantic temperature gradients exhibit different trends, which we attribute to incursion of warmer waters into the eastern North Atlantic and inception of Northern Component Water across the early‐middle Eocene transition.

Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG and LEMS have an autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature. Generalized MG requires increasingly differentiated therapeutic strategies that consider the enormous therapeutic developments of recent years. To include the newest therapy recommendations, a comprehensive update of the available German-language guideline ‘Diagnostics and therapy of myasthenic syndromes’ has been published by the German Neurological society with the aid of an interdisciplinary expert panel. This paper is an adapted translation of the updated and partly newly developed treatment guideline. It defines the rapid achievement of complete disease control in myasthenic patients as a central treatment goal. The use of standard therapies, as well as modern immunotherapeutics, is subject to a staged regimen that takes into account autoantibody status and disease activity. With the advent of modern, fast-acting immunomodulators, disease activity assessment has become pivotal and requires evaluation of the clinical course, including severity and required therapies. Applying MG-specific scores and classifications such as Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Foundation of America allows differentiation between mild/moderate and (highly) active (including refractory) disease. Therapy decisions must consider age, thymic pathology, antibody status, and disease activity. Glucocorticosteroids and the classical immunosuppressants (primarily azathioprine) are the basic immunotherapeutics to treat mild/moderate to (highly) active generalized MG/young MG and ocular MG. Thymectomy is indicated as a treatment for thymoma-associated MG and generalized MG with acetylcholine receptor antibody (AChR-Ab)-positive status. In (highly) active generalized MG, complement inhibitors (currently eculizumab and ravulizumab) or neonatal Fc receptor modulators (currently efgartigimod) are recommended for AChR-Ab-positive status and rituximab for muscle-specific receptor tyrosine kinase (MuSK)-Ab-positive status. Specific treatment for myasthenic crises requires plasmapheresis, immunoadsorption, or IVIG. Specific aspects of ocular, juvenile, and congenital myasthenia are highlighted. The guideline will be further developed based on new study results for other immunomodulators and biomarkers that aid the accurate measurement of disease activity.

Abstract The Early Iron Age in Italy (end of the tenth to the eighth century BCE) was characterized by profound changes which influenced the subsequent political and cultural scenario in the peninsula. At the end of this period people from the eastern Mediterranean (e.g. Phoenicians and Greek people) settled along the Italian, Sardinian and Sicilian coasts. Among local populations, the so-called Villanovan culture group—mainly located on the Tyrrhenian side of central Italy and in the southern Po plain—stood out since the beginning for the extent of their geographical expansion across the peninsula and their leading position in the interaction with diverse groups. The community of Fermo (ninth–fifth century BCE), related to the Villanovan groups but located in the Picene area (Marche), is a model example of these population dynamics. This study integrates archaeological, osteological, carbon (δ13C), nitrogen (δ15N) (n = 25 human) and strontium (87Sr/86Sr) isotope data (n = 54 human, n = 11 baseline samples) to explore human mobility through Fermo funerary contexts. The combination of these different sources enabled us to confirm the presence of non-local individuals and gain insight into community connectivity dynamics in Early Iron Age Italian frontier sites. This research contributes to one of the leading historical questions of Italian development in the first millennium BCE.

Abstract Shells of the giant clam Tridacna can provide decade‐long records of past environmental conditions via their geochemical composition and structurally through growth banding. Counting the daily bands can give an accurate internal age model with high temporal resolution, but daily banding is not always visually retrievable, especially in fossil specimens. We show that daily geochemical cycles (e.g., Mg/Ca) are resolvable via highly spatially resolved laser‐ablation inductively coupled plasma mass spectrometry (LA‐ICPMS; 3 × 33 μm laser slit) in our Miocene (∼10 Ma) specimen, even in areas where daily banding is not visually discernible. By applying wavelet transformation on the measured daily geochemical cycles, we quantify varying daily growth rates throughout the shell. These growth rates are thus used to build an internal age model independent of optical daily band countability. Such an age model can be used to convert the measured elemental ratios from a function of distance to a function of time, which helps evaluate paleoenvironmental proxy data, for example, regarding the timing of sub‐seasonal events. Furthermore, the quantification of daily growth rates across the shell facilitates the evaluation of (co)dependencies between growth rates and corresponding elemental compositions.

Abstract We present the results of a multi-disciplinary investigation on a deciduous human tooth (Pradis 1), recently recovered from the Epigravettian layers of the Grotte di Pradis archaeological site (Northeastern Italian Prealps). Pradis 1 is an exfoliated deciduous molar (Rdm2), lost during life by an 11–12-year-old child. A direct radiocarbon date provided an age of 13,088–12,897 cal BP (95% probability, IntCal20). Amelogenin peptides extracted from tooth enamel and analysed through LC–MS/MS indicate that Pradis 1 likely belonged to a male. Time-resolved 87Sr/86Sr analyses by laser ablation mass spectrometry (LA-MC-ICPMS), combined with dental histology, were able to resolve his movements during the first year of life (i.e. the enamel mineralization interval). Specifically, the Sr isotope ratio of the tooth enamel differs from the local baseline value, suggesting that the child likely spent his first year of life far from Grotte di Pradis. Sr isotopes are also suggestive of a cyclical/seasonal mobility pattern exploited by the Epigravettian human group. The exploitation of Grotte di Pradis on a seasonal, i.e. summer, basis is also indicated by the faunal spectra. Indeed, the nearly 100% occurrence of marmot remains in the entire archaeozoological collection indicates the use of Pradis as a specialized marmot hunting or butchering site. This work represents the first direct assessment of sub-annual movements observed in an Epigravettian hunter-gatherer group from Northern Italy.

The Horizon Europe project ISIDORe is dedicated to pandemic preparedness and responsiveness research. It brings together 17 research infrastructures (RIs) and networks to provide a broad range of services to infectious disease researchers. An efficient and structured treatment of data is central to ISIDORe’s aim to furnish seamless access to its multidisciplinary catalogue of services, and to ensure that users’ results are treated FAIRly. ISIDORe therefore requires a data management plan (DMP) covering both access management and research outputs, applicable over a broad range of disciplines, and compatible with the constraints and existing practices of its diverse partners. Here, we describe how, to achieve that aim, we undertook an iterative, step-by-step, process to build a community-approved living document, identifying good practices and processes, on the basis of use cases, presented as proof of concepts. International fora such as the RDA and EOSC, and primarily the BY-COVID project, furnished registries, tools and online data platforms, as well as standards, and the support of data scientists. Together, these elements provide a path for building an umbrella, FAIR-compliant DMP, aligned as fully as possible with FAIR principles, which could also be applied as a framework for data management harmonisation in other large-scale, challenge-driven projects. Finally, we discuss how data management and reuse can be further improved through the use of knowledge models when writing DMPs and, how, in the future, an inter-RI network of data stewards could contribute to the establishment of a community of practice, to be integrated subsequently into planned trans-RI competence centres.

As augmented reality (AR) becomes a promising technology for use in science and engineering teaching, the need for generally valid criteria and frameworks for the analysis, development, and setup of AR applications arises. In this article, we present an evaluations matrix to analyze current augmented reality approaches for life science teaching (biology, chemistry) and engineering and simultaneously provide directives for future augmented reality application designs. Based on an extensive literature review followed by focus group discussions with experts, the evaluation matrix combines domain-specific aspects, technical features, and subject and media didactical principles to determine seven select parameters. This ensures adequate coverage of the broad range of key considerations in the development of augmented reality technology for science and engineering teaching. Through cluster analysis, two groups of applications could be identified. The first group comprises applications whose development was more technology-driven. Applications in the second group take more didactic criteria into account and are to be considered more holistically from an instructional perspective. No correlation could be observed between the design of the AR application and the intended learning effects. The parameters derived for the evaluation matrix contribute to specifying relevant criteria for the development of AR applications.

Abstract Background 5q spinal muscular atrophy (SMA) is a disabling and life-limiting neuromuscular disease. In recent years, novel therapies have shown to improve clinical outcomes. Yet, the absence of reliable biomarkers renders clinical assessment and prognosis of possibly already affected newborns with a positive newborn screening result for SMA imprecise and difficult. Therapeutic decisions and stratification of individualized therapies remain challenging, especially in symptomatic children. The aim of this proof-of-concept and feasibility study was to explore the value of 1H-nuclear magnetic resonance (NMR)-based metabolic profiling in identifying non-invasive diagnostic and prognostic urinary fingerprints in children and adolescents with SMA. Results Urine samples were collected from 29 treatment-naïve SMA patients (5 pre-symptomatic, 9 SMA 1, 8 SMA 2, 7 SMA 3), 18 patients with Duchenne muscular dystrophy (DMD) and 444 healthy controls. Using machine-learning algorithms, we propose a set of prediction models built on urinary fingerprints that showed potential diagnostic value in discriminating SMA patients from controls and DMD, as well as predictive properties in separating between SMA types, allowing predictions about phenotypic severity. Interestingly, preliminary results of the prediction models suggest additional value in determining biochemical onset of disease in pre-symptomatic infants with SMA identified by genetic newborn screening and furthermore as potential therapeutic monitoring tool. Conclusions This study provides preliminary evidence for the use of 1H-NMR-based urinary metabolic profiling as diagnostic and prognostic biomarker in spinal muscular atrophy.

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR’s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.

Improving learners' reading is of importance. The digital world is centred on the written word, and today's labour market requires high literacy levels. Furthermore, the development of school and foreign language skills among learners, especially those of weaker learners, is crucial as the effects of globalisation allow for increased work mobility and the necessity for lifelong learning. GameLet provides effective training scenarios for reading fluency, a prerequisite for reading comprehension, in schools with gamified, self-guided, personalised, media-based individual and collaborative learning, thereby allowing educators to intensify and extend learning activities to out-of-school settings. At the core of GameLet lies the production of a podcast by the learners that encourages them to read repeatedly, hence improving their reading fluency, and to successfully record their role in a digital Recording Studio. Increasing reading fluency is targeted by means of media-supported individual and cooperative learning phases with various training methods. Furthermore, GameLet implements meaningful digital media-based Gamification mechanisms for the purpose of increasing student motivation. The software is web-based and was developed with a focus on user-centred design and an agile and design-based approach. Prototype development followed an iterative and participative process, in which students and teachers of three participating partner countries interacted with the developed materials. Artefacts were tested in both face-to-face and online settings. GameLet exemplifies the successful application of Gamification for improving and extending classical learning scenarios at school as well as the design of effective learning technologies that are meaningful, gamified, effective and usable.

Abstract Background Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. Since motor neuron injury is usually not reversible, early diagnosis and treatment are essential to prevent major disability. Our objective was to assess the impact of genetic newborn screening for SMA on outcome. Methods We provided clinical data from 43 SMA patients, identified via polymerase chain reaction of the SMN1 gene from dried blood spots between January 2018 and January 2020 in Germany. Follow-up included neurophysiological examinations and standardized physiotherapeutic testing. Results Detection of SMA with newborn screening was consistent with known incidence in Germany. Birth prevalence was 1:6910; 39.5% had 2 SMN2 copies, 23% had 3 SMN2 copies, 32.5% had 4 copies, and 4.5% had 5 copies of the SMN2 gene. Treatment with SMA-specific medication could be started at the age of 14–39 days in 21 patients. Pre-symptomatically treated patients remained throughout asymptomatic within the observation period. 47% of patients with 2 SMN2 copies showed early, presumably intrauterine onset of disease. These patients reached motor milestones with delay; none of them developed respiratory symptoms. Untreated children with 2 SMN2 copies died. Untreated children with 3 SMN2 copies developed proximal weakness in their first year. In patients with ≥ 4 SMN2 copies, a follow-up strategy of “watchful waiting” was applied despite the fact that one of them was treated from the age of 6 months. Two infant siblings with 4 SMN2 copies were identified with a missed diagnosis of SMA type 3. Conclusion Identification of newborns with infantile SMA and prompt SMA-specific treatment substantially improves neurodevelopmental outcome, and we recommend implementation in the public newborn screening in countries where therapy is available. Electrophysiology is a relevant parameter to support the urgency of therapy. There has to be a short time interval between a positive screening result and referral to a therapy-ready specialized treatment center.

Abstract Background Quantitative data reports are widely produced to inform health policy decisions. Policymakers are expected to critically assess provided information in order to incorporate the best available evidence into the decision-making process. Many other factors are known to influence this process, but little is known about how quantitative data reports are actually read. We explored the reading behavior of (future) health policy decision-makers, using innovative methods. Methods We conducted a computer-assisted laboratory study, involving starting and advanced students in medicine and health sciences, and professionals as participants. They read a quantitative data report to inform a decision on the use of resources for long-term care in dementia in a hypothetical decision scenario. Data were collected through eye-tracking, questionnaires, and a brief interview. Eye-tracking data were used to generate ‘heatmaps’ and five measures of reading behavior. The questionnaires provided participants’ perceptions of understandability and helpfulness as well as individual characteristics. Interviews documented reasons for attention to specific report sections. The quantitative analysis was largely descriptive, complemented by Pearson correlations. Interviews were analyzed by qualitative content analysis. Results In total, 46 individuals participated [students (85%), professionals (15%)]. Eye-tracking observations showed that the participants spent equal time and attention for most parts of the presented report, but were less focused when reading the methods section. The qualitative content analysis identified 29 reasons for attention to a report section related to four topics. Eye-tracking measures were largely unrelated to participants’ perceptions of understandability and helpfulness of the report. Conclusions Eye-tracking data added information on reading behaviors that were not captured by questionnaires or interviews with health decision-makers.

Abstract Mobility of people and goods during the Upper Paleolithic has proven difficult to reconstruct given the relative rareness of remains. Nevertheless, archaeological contexts like the Late Pleistocene horizon of Borsuka Cave (Southern Poland) represent a unique opportunity to explore patterns of objects’ transportation across Central Europe. We investigated the origin of four ornaments made of European elk (Alces alces L.) incisors recovered at Borsuka Cave – the oldest known burial site in Poland, possibly a child grave. Laser-ablation plasma source mass spectrometric analyses of trace elements and Sr isotopic compositions revealed that one elk was roaming within a geologically uniform area while the others changed their pastures during their lifetimes. The non-local origin of the elk teeth is inferred from their exotic Sr isotopic compositions and the lack of evidence for the presence of elk in this territory during the Pleistocene. Instead, the elks’ Sr isotopic composition show good agreement with sites near the Austria-Slovakia border region and northern Hungary, ~250 km away from the study site. We argue that the artefacts were most likely brought to Borsuka Cave by humans or by a network of exchange, so far never reported in the time range 32.5–28.8 ka cal BP for Southern Poland.

The discourse about borders, frontiers and all sorts of liminal phenomena, including transbordering or border-crossing, seems to be older than the current one on globalization and post-colonialism. The idea that globalization will wipe out all borders and limitations is problematic, and the strange, a result of cultural construction, will not disappear. Borders are never only limes, borders, fences, or walls, but at the same time they are also spaces between contact zones. Human space is always constructed by limitation; it means separation and connection at once. Drawing on Bachelard’s Poetics of Space, I will outline a poetry of a space in between, of different modes of limitations, such as the threshold, the bridge, the door, the wall, the fence, and the barrier. Starting from the «real» spatial aspect, I will differentiate between three different kinds of in-between situations that are related to practices of crossing over: phenomena of entering and initiation; transgression; and the idea of overcoming on the vertical plane. I will conclude the article with an analysis of a film about various liminal dimensions, Iñárritu’s film Babel, which does not expose a great narrative of globalization, but it introduces the global world as an obscurely intertwined network of small narratives.

The aim of this study was to assess the psychosocial burden in parents of children with spinal muscular atrophy (SMA), detected by newborn screening (NBS), for which first pilot projects started in January 2018 in Germany. The survey, performed 1–2 years after children’s diagnosis of SMA via NBS, included 3 parent-related questionnaires to evaluate the psychosocial burden, quality of life (QoL)/satisfaction and work productivity and activity impairment in the families. 42/44 families, detected between January 2018 and February 2020, could be investigated. Interestingly, statistical analysis revealed a significant difference between families with children that received SMN-targeted therapy vs. children with a wait-and-see strategy as to social burden (p = 0.016) and personal strain/worries about the future (p = 0.02). However, the evaluation of QoL showed no significant differences between treated vs. untreated children. Fathers of treated children felt more negative impact regarding their productivities at work (p = 0.005) and more negative effects on daily activities (p = 0.022) than fathers of untreated children. Thus, NBS in SMA has a psychosocial impact on families, not only in terms of diagnosis but especially in terms of treatment, and triggers concerns about the future, emphasizing the need for comprehensive multidisciplinary care. Understanding the parents’ perspective allows genetic counselors and NBS programs to proactively develop a care plan for parents during the challenging time of uncertainty, anxiety, frustration, and fear of the unknown.

doch erfüllen Studienprotokolle, eingesetzte Erhebungsinstrumente und erhobene Daten die Anforderungen der FAIR-Prinzipien nicht in ausreichendem Maße. NFDI4Health wird daher eine Struktur schaffen, die eine zentrale Suche nach existierenden, dezentral verwalteten Datenkörpern und zugehörigen Dokumenten sowie einen FAIRen Zugang zu diesen erleichtert. Dazu werden die Auffindbarkeit und der Zugang zu strukturierten Gesundheitsdaten aus Registern, administrativen Gesundheitsdatenbanken, klinischen und epidemiologischen sowie Public Health-Studien verbessert und die Qualität und Harmonisierung der zugrundeliegenden Daten optimiert. Eine weitere Herausforderung entsteht durch die Verwendung personenbezogener Gesundheitsdaten. Diese sind hoch sensibel, so dass ihre Nutzung restriktive Datenschutzbestimmungen und informierte Einwilligungserklärungen der Studienteilnehmenden erfordert, was jedoch ihre Wiederverwendbarkeit einschränkt. NFDI4Health zielt daher darauf ab, den Austausch und die Verknüpfung von personenbezogenen Gesundheitsdaten sowie verteilte Datenanalysen unter Einhaltung datenschutzrechtlicher und ethischer Bestimmungen zu erleichtern. Um dies möglichst effizient zu erreichen, wird NFDI4Health die Entwicklung neuer, maschinenprozessierbarer Zustimmungsmöglichkeiten sowie innovativer Datenzugriffsservices auf Grundlage der FAIR-Prinzipien vorantreiben und die Interoperabilität von IT-Lösungen für Metadatenrepositorien stärken. Komplementiert wird dies durch die Entwicklung entsprechender Angebote für Training und Ausbildung, um der Herausforderung der Umsetzung der Lösungen in den Universitäten und Forschungseinrichtungen zu begegnen. Schließlich wird durch die gemeinsame Arbeit in der NFDI4Health die Kooperation zwischen klinischer und epidemiologischer/Public Health-Forschung gestärkt.

Disturbances in IP3 receptor-mediated release of Ca2+ from the endoplasmatic reticulum are associated with neurodegenerative disease. Here, the authors identify in four families with hereditary spastic paraplegia biallelic mutations in RNF170 that associate with increased basal levels of IP3 receptors.

Abstract Background The protein O-mannosyltransferase 1, encoded by the POMT1 gene, is a key enzyme in the glycosylation of α-dystroglycan. POMT1–related disorders belong to the group of dystroglycanopathies characterized by a proximally pronounced muscular dystrophy with structural or functional involvement of the brain and/or the eyes. The phenotypic spectrum ranges from the severe Walker-Warburg syndrome (WWS) to milder forms of limb girdle muscular dystrophy (LGMD). The phenotypic severity of POMT1-related dystroglycanopathies depends on the residual enzyme activity. A genotype-phenotype correlation can be assumed. Results The clinical, neuroradiological, and genetic findings of 35 patients with biallelic POMT1 mutations (15 WWS, 1 MEB (muscle-eye-brain disease), 19 LGMD) from 27 independent families are reported. The representative clinical course of an infant with WWS and the long-term course of a 32 years old patient with LGMD are described in more detail. Specific features of 15 patients with the homozygous founder mutation p.Ala200Pro are defined as a distinct and mildly affected LGMD subgroup. Ten previously reported and 8 novel POMT1 mutations were identified. Type and location of each of the POMT1 mutations are evaluated in detail and a list of all POMT1 mutations reported by now is provided. Patients with two mutations leading to premature protein termination had a WWS phenotype, while the presence of at least one missense mutation was associated with milder phenotypes. In the patient with MEB-like phenotype two missense mutations were observed within the catalytic active domain of the enzyme. Conclusions Our large cohort confirms the importance of type and location of each POMT1 mutation for the individual clinical manifestation and thereby expands the knowledge on the genotype-phenotype correlation in POMT1-related dystroglycanopathies. This genotype-phenotype correlation is further supported by the observation of an intrafamiliar analogous clinical manifestation observed in all affected 13 siblings from 5 independent families. Our data confirm the progressive nature of the disease also in milder LGMD phenotypes, ultimately resulting in loss of ambulation at a variable age. Our data define two major clinical POMT1 phenotypes, which should prompt genetic testing including the POMT1 gene: patients with a severe WWS manifestation predominantly present with profound neonatal muscular hypotonia and a severe and progressive hydrocephalus with involvement of brainstem and/or cerebellum. The presence of an occipital encephalocele in a WWS patient might point to POMT1 as causative gene within the different genes associated with WWS. The milder LGMD phenotypes constantly show markedly elevated creatine kinase values in combination with microcephaly and cognitive impairment.

Abstract Background X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the β-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function. Methods Trial design Sixteen weeks single-arm open run-in therapy with enalapril and metoprolol followed by a two-arm 1:1 randomized double-blind placebo-controlled treatment in a multicenter setting. Inclusion criteria: DMD boys aged 10–14 years with left ventricular fractional shortening [LV-FS] ≥ 30% in echocardiography. Primary endpoint: time from randomization to first occurrence of LV-FS

Unlike other great novels on the decline and fall of the Habsburg Empire, such as Radetzkymarsch by Joseph Roth or Der Mann ohne Eigenschaften by Robert Musil, Winder's novels on this subject matter reveal a strong matriarchal determination of male protagonists which, however, is broken down in many ways. In Der Thronfolger (1937), the neurotic agility of the Austrian heir to the throne is actually an implant, or even a loan from female mother figures (including his wife) of the novel, which themselves have in turn adopted many compensational behaviour patterns originating from their fathers. Even stronger oedipal motives are exposed in the power-obsessed, capitalist siege of a small Bohemia town by Adam Dupic, a mysterious foreigner, in Winder's 1927 novel Die nachgeholten Freuden. Both novels can thus be read as a specific version of the 'Habsburg complex', displaying yet another aspect of the fragility of the modern condition in Central Europe.

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been-so far-no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies.

Abstract Background Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- and practice-based strategies in order to harmonize diagnosis, treatment and monitoring of JDM. Methods The JDM working group was established in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and dermatologists with expertise in the management of JDM. Current practice patterns of management in JDM had previously been identified via an online survey among pediatric rheumatologists and neurologists. Using a consensus process consisting of online surveys and a face-to-face consensus conference statements were defined regarding the diagnosis, treatment and monitoring of JDM. During the conference consensus was achieved via nominal group technique. Voting took place using an electronic audience response system, and at least 80% consensus was required for individual statements. Results Overall 10 individual statements were developed, finally reaching a consensus of 92 to 100% regarding (1) establishing a diagnosis, (2) case definitions for the application of the strategies (moderate and severe JDM), (3) initial diagnostic testing, (4) monitoring and documentation, (5) treatment targets within the context of a treat-to-target strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target strategy, (8) various glucocorticoid regimens, including intermittent intravenous methylprednisolone pulse and high-dose oral glucocorticoid therapies with tapering, (9) initial glucocorticoid-sparing therapy and (10) management of refractory disease. Conclusion Using a consensus process among JDM experts, statements regarding the management of JDM were defined. These statements and the strategies aid in the management of patients with moderate and severe JDM.

Disorders of the peripheral nerves can be caused by a broad spectrum of acquired or hereditary aetiologies. The objective of these practice guidelines is to provide the reader with information about the differential diagnostic workup for a target-oriented diagnosis. Following an initiative of the German-speaking Society of Neuropaediatrics, delegates from 10 German societies dedicated to neuroscience worked in close co-operation to write this guideline. Applying the Delphi methodology, the authors carried out a formal consensus process to develop practice recommendations. These covered the important diagnostic steps both for acquired neuropathies (traumatic, infectious, inflammatory) and the spectrum of hereditary Charcot–Marie–Tooth (CMT) diseases. Some of our most important recommendations are that: (i) The indication for further diagnostics must be based on the patient’s history and clinical findings; (ii) Potential toxic neuropathy also has to be considered; (iii) For focal and regional neuropathies of unknown aetiology, nerve sonography and MRI should be performed; and (iv) For demyelinated hereditary neuropathy, genetic diagnostics should first address PMP22 gene deletion: once that has been excluded, massive parallel sequencing including an analysis of relevant CMT-genes should be performed. This article contains a short version of the guidelines. The full-length text (in German) can be found at the Website of the “Arbeitsgemeinschaft der Wissenschftlichen Medizinischen Fachgesellschaften e.V. (AWMF), Germany.

Augmented e-books are books that employ advanced digital media to enhance the reading experience. Augmented e-books have the potential to promote reader’s engagement, yet the potential of such technologies have been so far under-explored. In this article, we study the potential of literally transforming the space where reading takes place, in order to create superior reading experiences. This will foster the emergence of an immersive story universe, placing the reader in an imagined time and space, nurturing imagination, emotion, and creativity. In this article, we present ongoing work on STREEN, a research oriented smart environment for story reading. STREEN employs technical infrastructures that proactively and reactively trigger digital media enrichment depending on the reading performance and the stage of a narrative. We explain our innovation methodology that is based on an analysis of the design space to create a framework for a design thinking process. Additionally, we describe the first steps of using this methodology to explore and design STREEN solutions for primary school children.

Two species of Amphistegina were cultured under four variable DIC concentrations (2340–2570 μM). The variability of trace elements within the foraminiferal shells was measured in the knob area of three individuals for each DIC treatment using LA-ICPMS. In individuals that showed significant growth (identified via 135Ba-enriched seawater), B, Na, and Sr showed an increase with DIC, while K and Mg were slightly lower or unchanged. Sharp transition zones between natural 135Ba and the ∼10-fold increased 135Ba in the shells represent one quarter of a new additional chamber, which occurs roughly once a week. The shape of the transition zone is best described by a logistic equation for population growth. We propose that this reflects the dynamics of seawater vacuoles that serve the biomineralization process and provide Ca and DIC for calcification of Amphistegina as described in previous publications (e.g., Bentov et al., 2009). LA-ICPMS profiles in the central knob (∼70 μm depth) also revealed previously described cyclical changes in concentration of Mg, each apparently representing a growth of a new chamber. Additional elements such as K, Na and U showed similar cycles with the same frequency and phase as the Mg cycles. Sr showed variability with similar frequency but not in-phase to those of the Mg. These multi-element cycles were found both in the newly grown calcite (elevated-135Ba) and in the natural skeleton regardless of the DIC treatments. These high Mg and multi-element cycles seem to be an essential part of the calcification process. They may originate from the interaction with the organic matrix resulting in elevated Mg and other elements in primary calcite while secondary calcite of the lamination process shows lower concentrations. It is also possible that primary calcite is enriched in trace elements if an Amorphous CaCO3 (ACC) or vaterite precursors are involved. In addition, Rayleigh fractionation from a semi-closed reservoir, the presence of high Mg in the lattice or any combination of the previous causes may explain the trace elements enrichment. Changes in the DIC did not affect the pattern of elemental cycles in these foraminifera, suggesting that this variability is inherent to the biomineralization process.

In many disciplines, data are highly decentralized across thousands of online databases (repositories, registries, and knowledgebases). Wringing value from such databases depends on the discipline of data science and on the humble bricks and mortar that make integration possible; identifiers are a core component of this integration infrastructure. Drawing on our experience and on work by other groups, we outline 10 lessons we have learned about the identifier qualities and best practices that facilitate large-scale data integration. Specifically, we propose actions that identifier practitioners (database providers) should take in the design, provision and reuse of identifiers. We also outline the important considerations for those referencing identifiers in various circumstances, including by authors and data generators. While the importance and relevance of each lesson will vary by context, there is a need for increased awareness about how to avoid and manage common identifier problems, especially those related to persistence and web-accessibility/resolvability. We focus strongly on web-based identifiers in the life sciences; however, the principles are broadly relevant to other disciplines.

Der vorliegende Beitrag diskutiert mit der Erfassung von Medienkompetenzen einen zentralen Aspekt des derzeitigen wissenschaftlichen Diskurses, der insbesondere innerhalb der Medienpädagogik wie auch in zunehmendem Maße in der empirischen Bildungsforschung geführt wird. In einem ersten Schritt führen die Autoren über das Skizzieren der Notwendigkeit einer medienbezogenen Grundbildung im Bereich der Lehrerbildung hin zur Thematik der Medienkompetenzerfassung. Auf Basis der im Kontext der Erfassung von Medienkompetenzen gegebenen Vielfalt an Kontexten, Zusammenhängen und Instrumenten stellen die Autoren fest, dass es u. a. aufgrund der Abhängigkeit vom jeweiligen Kontext kaum ein einzelnes, flächendeckend geeignetes Instrument geben kann und dass darüber hinaus verwendete Instrumente oftmals nicht den gängigen Gütekriterien entsprechen. Als gangbaren Lösungsweg für diese Problematik schlagen die Autoren den Ansatz der Media Literacy Assessment Design Patterns vor, der als theoretische Grundlage und Ausgangspunkt für die bislang kaum diskutierte empirisch ausgerichtete Erfassung von Medienkompetenzen im Sinne einer Möglichkeit zur Strukturierung und Sammlung von Best Practices dienen kann.

This review addresses the causes of observed climate variations across the industrial period, from 1750 to present. It focuses on long-term changes, both in response to external forcing and to climate variability in the ocean and atmosphere. A synthesis of results from attribution studies based on palaeoclimatic reconstructions covering the recent few centuries to the 20th century, and instrumental data shows how greenhouse gases began to cause warming since the beginning of industrialization, causing trends that are attributable to greenhouse gases by 1900 in proxy-based temperature reconstructions. Their influence increased over time, dominating recent trends. However, other forcings have caused substantial deviations from this emerging greenhouse warming trend: volcanic eruptions have caused strong cooling following a period of unusually heavy activity, such as in the early 19th century; or warming during periods of low activity, such as in the early-to-mid 20th century. Anthropogenic aerosol forcing most likely masked some global greenhouse warming over the 20th century, especially since the accelerated increase in sulphate aerosol emissions starting around 1950. Based on modelling and attribution studies, aerosol forcing has also influenced regional temperatures, caused long-term changes in monsoons and imprinted on Atlantic variability. Multi-decadal variations in atmospheric modes can also cause long-term climate variability, as apparent for the example of the North Atlantic Oscillation, and have influenced Atlantic ocean variability. Long-term precipitation changes are more difficult to attribute to external forcing due to spatial sparseness of data and noisiness of precipitation changes, but the observed pattern of precipitation response to warming from station data supports climate model simulated changes and with it, predictions. The long-term warming has also led to significant differences in daily variability as, for example, visible in long European station data. Extreme events over the historical record provide valuable samples of possible extreme events and their mechanisms.

In November 2012, a group of 7 persons who participated in a hare hunt in North Rhine-Westphalia, Germany, acquired tularemia. Two F. tularensis subsp. holarctica isolates were cultivated from human and hare biopsy material. Both isolates belonged to the FTN002–00 genetic subclade (derived for single nucleotide polymorphisms B.10 and B.18), thus indicating likely hare-to-human transmission.

„Założony przez Nancy i ogłoszony Uniwersytetem europejskim”. Wkład Archiwum Uniwersytetu Kraju Saary w zabezpieczenie śladów przeszłości oraz w badania nad historią UniwersytetuArtykuł zawiera krótki zarys historii Uniwersytetu Kraju Saary, a także informacje dotyczące rozwoju, działalności i publikacji naukowych Archiwum Uniwersyteckiego. Uniwersytet Kraju Saary – uczelnia otwarta na Europę i łącząca w sobie niemieckie i francuskie tradycje kształcenia – powstał w listopadzie 1948 roku. W tym czasie była to uczelnia dwujęzyczna. Ta pierwsza powojenna szkoła wyższa, jaką założono po lewobrzeżnej stronie Renu, rozpoczęła swoją działalność pod patronatem Francji i Uniwersytetu w Nancy, w szczególnej sytuacji politycznej i gospodarczej. Kraj Saary funkcjonował bowiem wówczas jako częściowo autonomiczne państwo, związane z Francją unią gospodarczą i walutową. 3 kwietnia 1950 roku opublikowano statut, który określał struktury administracyjne tej fi nansowanej wspólnie przez Kraj Saary oraz Francję uczelni. Natomiast w listopadzie tego samego roku drugi rektor saarlandzkiego Uniwersytetu, francuski germanista Joseph-François Angelloz, nazwał go „Uniwersytetem europejskim”. W artykule prześledzono losy uczelni w układzie chronologicznym, do czasów współczesnych, nie zapominając przy tym o licznych przykładach współpracy międzynarodowej, w ramach której na przykład już w roku 1983 uczelnia zawarła partnerstwo z Uniwersytetem Warszawskim. Archiwum Uniwersyteckie, powołane do życia w roku 1991, służy systematycznemu zabezpieczaniu uczelnianych archiwaliów oraz dokumentowaniu historii Uniwersytetu. Swoje zadania Archiwum wypełnia między innymi dzięki ścisłej współpracy z uniwersyteckim serwisem informacyjnym, a także prowadząc rozmowy z naocznymi świadkami istotnych dla uczelni wydarzeń, co pozwala na archiwizację wspomnień i prywatnych zbiorów. Natomiast opracowane przez uniwersyteckiego archiwistę edycje, publikacje i przyczynki, będące zawsze efektem dogłębnych badań, a dotyczące historii poszczególnych instytutów wypełniają lukę w zachowywaniu i przekazywaniu informacji o przeszłości oraz pokazują, w jak ścisłym związku pozostają główne zadania archiwistyki z badaniami nad historią uniwersytetu. W dalszej części artykułu przedstawiono aktualna wersję Profilu dokumentacji dla archiwów instytucji naukowych, dokumentu opracowanego w 2009 roku przez grupę archiwistów pracujących w archiwach uniwersyteckich i instytucji naukowych skupionych w Związku Niemieckich Archiwistek i Archiwistów. Ze względu na niejednolity sposób zarządzania dokumentacją archiwalną przez poszczególne jednostki uniwersyteckie właściwa ocena i selekcja materiału stanowi dla Archiwum nie lada wyzwanie. Profi l dokumentacji zawiera nie tylko przegląd różnorodnych rodzajów archiwaliów, które występują w formie piśmienniczej i rzeczowej na uniwersytetach, lecz także zalecenia co do metod archiwistycznej oceny opracowywanych dokumentów i spuścizn.Tłumaczenie/Übersetzt von Barbara Sapała

Fluorescence imaging using FM® 1-43 and related styryl dyes has provided invaluable insights into presynaptic function of synapses in culture preparations, but has been limited in use for studying central synapses in vivo or in brain slices, because of excessive fluorescence background due to nonspecific membrane binding of dye. We demonstrate here that focal excitation of FM dyes using two-photon laser-scanning microscopy (TPLSM) provides high resolution of FM 1-43-labeled nerve terminals in brain slices by suppressing out-of-focus background and that a readily releasable pool of vesicles can be selectively and stably labeled by hypertonic shock despite slice diffusion barriers. We find direct TPLSM of FM 1-43-labeled nerve terminals to be superior to treatment of slices with either the fluorescent quencher sulforhodamine 101 or dye scavenger ADVASEP-7 in resolving nerve terminal against background fluorescence, enabling continuous monitoring of vesicular uptake, and release of styryl dyes from individual nerve terminals in brain slices.\

In 2005 to 2007 45 skeletons of adults and subadults were excavated at the Lombard period cemetery at Szólád (6th century A.D.), Hungary. Embedded into the well-recorded historical context, the article presents the results obtained by an integrative investigation including anthropological, molecular genetic and isotopic (δ(15)N, δ(13)C, (87)Sr/(86)Sr) analyses. Skeletal stress markers as well as traces of interpersonal violence were found to occur frequently. The mitochondrial DNA profiles revealed a heterogeneous spectrum of lineages that belong to the haplogroups H, U, J, HV, T2, I, and K, which are common in present-day Europe and in the Near East, while N1a and N1b are today quite rare. Evidence of possible direct maternal kinship was identified in only three pairs of individuals. According to enamel strontium isotope ratios, at least 31% of the individuals died at a location other than their birthplace and/or had moved during childhood. Based on the peculiar 87 Sr/86 Sr ratio distribution between females, males, and subadults in comparison to local vegetation and soil samples, we propose a three-phase model of group movement. An initial patrilocal group with narrower male but wider female Sr isotope distribution settled at Szólád, whilst the majority of subadults represented in the cemetery yielded a distinct Sr isotope signature. Owing to the virtual absence of Szólád-born adults in the cemetery, we may conclude that the settlement was abandoned after approx. one generation. Population heterogeneity is furthermore supported by the carbon and nitrogen isotope data. They indicate that a group of high-ranking men had access to larger shares of animal-derived food whilst a few individuals consumed remarkable amounts of millet. The inferred dynamics of the burial community are in agreement with hypotheses of a highly mobile lifestyle during the Migration Period and a short-term occupation of Pannonia by Lombard settlers as conveyed by written sources.

The transition from mobile to sedentary life was one of the greatest social challenges of the human past. Yet little is known about the impact of this fundamental change on social interactions amongst early Neolithic communities, which are best recorded in the Near East. The importance of social processes associated with these economic and ecological changes has long been underestimated. However, ethnographic observations demonstrate that generalized reciprocity - such as open access to resources and land - had to be reduced to a circumscribed group before regular farming and herding could be successfully established. Our aim was thus to investigate the role of familial relationships as one possible factor within this process of segregation as recorded directly in the skeletal remains, rather than based on hypothetical correlations such as house types and social units. Here we present the revealing results of the systematically recorded epigenetic characteristics of teeth and skulls of the late Pre-Pottery Neolithic community of Basta in Southern Jordan (Figure S1). Additionally, mobility was reconstructed via a systematic strontium (Sr) isotope analysis of tooth enamel of the Basta individuals. The frequency of congenitally missing maxillary lateral incisors in the 9,000-year-old community of Basta is exceptionally high (35.7%). Genetic studies and a worldwide comparison of the general rate of this dental anomaly in modern and historic populations show that the enhanced frequency can only be explained by close familial relationships akin to endogamy. This is supported by strontium isotope analyses of teeth, indicating a local origin of almost all investigated individuals. Yet, the accompanying archaeological finds document far-reaching economic exchange with neighboring groups and a population density hitherto unparalleled. We thus conclude that endogamy in the early Neolithic village of Basta was not due to geographic isolation or a lack of exogamous mating partners but a socio-cultural choice.

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR’s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.

The article discusses city contests as an instrument of urban development. It describes different forms of city contests and shows, how those correspond with different interests and expectations of the contractee and the participating cities. Taking the city contest T-City of the Deutsche Telekom as an example, characteristic issues and the process, expectations of the participants and results of the contest are described. Finally, some conclusions are drawn as to who benefits from contests and what the benefits are.