Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14th century

We report genome-wide data from 33 Ashkenazi Jews (AJ), dated to the 14th century, obtained following a salvage excavation at the medieval Jewish cemetery of Erfurt, Germany. The Erfurt individuals are genetically similar to modern AJ, but they show more variability in Eastern European-related ancestry than modern AJ. A third of the Erfurt individuals carried a mitochondrial lineage common in modern AJ and eight carried pathogenic variants known to affect AJ today. These observations, together with high levels of runs of homozygosity, suggest that the Erfurt community had already experienced the major reduction in size that affected modern AJ. The Erfurt bottleneck was more severe, implying substructure in medieval AJ. Overall, our results suggest that the AJ founder event and the acquisition of the main sources of ancestry pre-dated the 14th century and highlight late medieval genetic heterogeneity no longer present in modern AJ

Permanently online and permanently connected : development and validation of the Online Vigilance Scale

Smartphones and other mobile devices have fundamentally changed patterns of Internet use in everyday life by making online access constantly available. The present paper offers a theoretical explication and empirical assessment of the concept of online vigilance, referring to users’ permanent cognitive orientation towards online content and communication as well as their disposition to exploit these options constantly. Based on four studies, a validated and reliable self-report measure of online vigilance was developed. In combination, the results suggest that the Online Vigilance Scale (OVS) shows a stable factor structure in various contexts and user populations and provides future work in communication, psychology, and other social sciences with a new measure of the individual cognitive orientation towards ubiquitous online communication

Mechanical Systems with Symmetry, Variational Principles, and Integration Algorithms

This paper studies variational principles for mechanical systems with symmetry and their applications to integration algorithms. We recall some general features of how to reduce variational principles in the presence of a symmetry group along with general features of integration algorithms for mechanical systems. Then we describe some integration algorithms based directly on variational principles using a discretization technique of Veselov. The general idea for these variational integrators is to directly discretize Hamilton’s principle rather than the equations of motion in a way that preserves the original systems invariants, notably the symplectic form and, via a discrete version of Noether’s theorem, the momentum map. The resulting mechanical integrators are second-order accurate, implicit, symplectic-momentum algorithms. We apply these integrators to the rigid body and the double spherical pendulum to show that the techniques are competitive with existing integrators

Permanently online and permanently connected: Development and validation of the Online Vigilance Scale

Smartphones and other mobile devices have fundamentally changed patterns of Internet use in everyday life by making online access constantly available. The present paper offers a theoretical explication and empirical assessment of the concept of online vigilance, referring to users' permanent cognitive orientation towards online content and communication as well as their disposition to exploit these options constantly. Based on four studies, a validated and reliable self-report measure of online vigilance was developed. In combination, the results suggest that the Online Vigilance Scale (OVS) shows a stable factor structure in various contexts and user populations and provides future work in communication, psychology, and other social sciences with a new measure of the individual cognitive orientation towards ubiquitous online communication

A Peptide-binding Motif for I-Ag7, the Class II Major Histocompatibility Complex (MHC) Molecule of NOD and Biozzi AB/H Mice

The class II major histocompatibility complex molecule I-Ag7 is strongly linked to the development of spontaneous insulin-dependent diabetes mellitus (IDDM) in non obese diabetic mice and to the induction of experimental allergic encephalomyelitis in Biozzi AB/H mice. Structurally, it resembles the HLA-DQ molecules associated with human IDDM, in having a non-Asp residue at position 57 in its β chain. To identify the requirements for peptide binding to I-Ag7 and thereby potentially pathogenic T cell epitopes, we analyzed a known I-Ag7-restricted T cell epitope, hen egg white lysozyme (HEL) amino acids 9–27. NH2- and COOH-terminal truncations demonstrated that the minimal epitope for activation of the T cell hybridoma 2D12.1 was M12-R21 and the minimum sequence for direct binding to purified I-Ag7 M12-Y20/ K13-R21. Alanine (A) scanning revealed two primary anchors for binding at relative positions (p) 6 (L) and 9 (Y) in the HEL epitope. The critical role of both anchors was demonstrated by incorporating L and Y in poly(A) backbones at the same relative positions as in the HEL epitope. Well-tolerated, weakly tolerated, and nontolerated residues were identified by analyzing the binding of peptides containing multiple substitutions at individual positions. Optimally, p6 was a large, hydrophobic residue (L, I, V, M), whereas p9 was aromatic and hydrophobic (Y or F) or positively charged (K, R). Specific residues were not tolerated at these and some other positions. A motif for binding to I-Ag7 deduced from analysis of the model HEL epitope was present in 27/30 (90%) of peptides reported to be I-Ag7–restricted T cell epitopes or eluted from I-Ag7. Scanning a set of overlapping peptides encompassing human proinsulin revealed the motif in 6/6 good binders (sensitivity = 100%) and 4/13 weak or non-binders (specificity = 70%). This motif should facilitate identification of autoantigenic epitopes relevant to the pathogenesis and immunotherapy of IDDM

Potentially inappropriate medication in older participants of the Berlin Aging Study II (BASE-II) - Sex differences and associations with morbidity and medication use

INTRODUCTION: Multimorbidity in advanced age and the need for drug treatment may lead to polypharmacy, while pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug events (ADEs). OBJECTIVE: The aim of this study was to determine the proportion of subjects using potentially inappropriate medication (PIM) in a cohort of older and predominantly healthy adults in relation to polypharmacy and morbidity. METHODS: Cross-sectional data were available from 1,382 study participants (median age 69 years, IQR 67-71, 51.3% females) of the Berlin Aging Study II (BASE-II). PIM was classified according to the EU(7)-PIM and German PRISCUS (representing a subset of the former) list. Polypharmacy was defined as the concomitant use of at least five drugs. A morbidity index (MI) largely based on the Charlson Index was applied to evaluate the morbidity burden. RESULTS: Overall, 24.1% of the participants were affected by polypharmacy. On average, men used 2 (IQR 1-4) and women 3 drugs (IQR 1-5). According to PRISCUS and EU(7)-PIM, 5.9% and 22.6% of participants received at least one PIM, while use was significantly more prevalent in females (25.5%) compared to males (19.6%) considering EU(7)-PIM (p = 0.01). In addition, morbidity in males receiving PIM according to EU(7)-PIM was higher (median MI 1, IQR 1-3) compared to males without PIM use (median MI 1, IQR 0-2, p<0.001). CONCLUSION: PIM use occurred more frequently in women than in men, while it was associated with higher morbidity in males. As expected, EU(7)-PIM identifies more subjects as PIM users than the PRISCUS list but further studies are needed to investigate the differential impact of both lists on ADEs and outcome. KEY POINTS: We found PIM use to be associated with a higher number of regular medications and with increased morbidity. Additionally, we detected a higher prevalence of PIM use in females compared to males, suggesting that women and people needing intensive drug treatment are patient groups, who are particularly affected by PIM use

An exploration of how young people and parents use online support in the context of living with cystic fibrosis

Background: There is increasing recognition of the Internet's potential role in providing information and support for people living with long-term conditions. However, how young people and parents use online forms of self-care support in the context of living with childhood chronic illness has been under-researched. Objective: To explore how online peer support is used by young people and parents to support self-care in relation to cystic fibrosis (CF). Setting and participants: Online forum for young people and parents based on a CF charity website. A total of 279 individuals participated in the forum during the study. Design: An online ethnographical approach, involving observing, downloading and analysing discussion group postings. All postings made over a random 4-month period were included (151 discussion threads). Results: The online setting enabled a physically disconnected group to connect and create a safe space to collectively share experiences and receive support to manage and live with cystic fibrosis. Participants exchanged experientially derived advice and views on how to manage treatments, emotions, relationships, identity and support from services. While parents sought information and support on managing specific therapies/services and ways of maintaining their child's health, the information and support young people desired appeared to be more directed at how to 'fit' CF into their everyday lives. Discussion and conclusions: Online support groups appear to supplement professional support in relation to self-management. They enable young people and parents to share experiences, feelings and strategies for living with long-term conditions with peers and develop the expertise to empower them in interactions with health-care professionals

Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14th century

We report genome-wide data from 33 Ashkenazi Jews (AJ), dated to the 14th century, obtained following a salvage excavation at the medieval Jewish cemetery of Erfurt, Germany. The Erfurt individuals are genet-ically similar to modern AJ, but they show more variability in Eastern European-related ancestry than mod-ern AJ. A third of the Erfurt individuals carried a mitochondrial lineage common in modern AJ and eight carried pathogenic variants known to affect AJ today. These observations, together with high levels of runs of homozygosity, suggest that the Erfurt community had already experienced the major reduction in size that affected modern AJ. The Erfurt bottleneck was more severe, implying substructure in medieval AJ. Overall, our results suggest that the AJ founder event and the acquisition of the main sources of ancestry pre-dated the 14th century and highlight late medieval genetic heterogeneity no longer present in modern AJ.The study was funded by the Israel Science Foundation grant 407/17 and the United States-Israel Binational Science Foundation grant 2017024 to S.C., by the National Science Foundation (USA) grants 1912776 and 0922374 to V.R., by the MCIN/AEI/10.13039/501100011033 and by "ESF Investing in your future" grant "Ayudas para contratos Ramon y Cajal" to I.O., and by the following grants to D.R.: NIH grants GM100233 and HG012287; the Allen Discovery Center program, a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation; John Templeton Foundation grant 61220; a private gift from Jean-Francois Clin; and the Howard Hughes Medical Institute

Engaging with Health Markets in Low and Middle-Income Countries

Many low and middle-income countries have pluralistic health systems with a variety of providers of health-related goods and services in terms of their level of training, their ownership (public or private) and their relationship with the regulatory system. The development of institutional arrangements to influence their performance has lagged behind the spread of these markets. This paper presents a framework for analysing a pluralistic health system. The relationships between private providers of health services and government, or other organisations that represent the public interest, strongly influence their performance in meeting the needs of the poor. Their impact on the pattern of service delivery depends on how the relationships are managed and the degree to which they respond to the interests of the population. Many governments of low and middle-income countries are under pressure to increase access to safe, effective and affordable health services. In a context of economic growth, it should be possible to improve access by the poor to health services substantially. Innovations in information technologies and in low cost diagnostics are creating important new opportunities for achieving this. It will be important to mobilise both public and private providers of health-related goods and services. This will involve big changes in the roles and responsibilities of all health sector actors. Governments, businesses and civil society organizations will need to learn how to make pluralist health systems work better through experimentation and systematic learning about what works and why