Flavor Singlet Meson Mass in the Continuum Limit in Two-Flavor Lattice QCD

We present results for the mass of the eta-prime meson in the continuum limit for two-flavor lattice QCD, calculated on the CP-PACS computer, using a renormalization-group improved gauge action, and Sheikholeslami and Wohlert's fermion action with tadpole-improved csw. Correlation functions are measured at three values of the coupling constant beta corresponding to the lattice spacing a approx. 0.22, 0.16, 0.11 fm and for four values of the quark mass parameter kappa corresponding to mpi over mrho approx. 0.8, 0.75, 0.7 and 0.6. For each beta, kappa pair, 400-800 gauge configurations are used. The two-loop diagrams are evaluated using a noisy source method. We calculate eta-prime propagators using local sources, and find that excited state contributions are much reduced by smearing. A full analysis for the smeared propagators gives metaprime=0.960(87)+0.036-0.248 GeV, in the continuum limit, where the second error represents the systematic uncertainty coming from varying the functional form for chiral and continuum extrapolations.Comment: 9 pages, 19 figures, 4 table

Proteostasis regulators modulate proteasomal activity and gene expression to attenuate multiple phenotypes in Fabry disease

The lysosomal storage disorder Fabry disease is characterized by a deficiency of the lysosomal enzyme \u3b1-Galactosidase A. The observation that missense variants in the encoding GLA gene often lead to structural destabilization, endoplasmic reticulum retention and proteasomal degradation of the misfolded, but otherwise catalytically functional enzyme has resulted in the exploration of alternative therapeutic approaches. In this context, we have investigated proteostasis regulators (PRs) for their potential to increase cellular enzyme activity, and to reduce the disease-specific accumulation of the biomarker globotriaosylsphingosine in patient-derived cell culture. The PRs also acted synergistically with the clinically approved 1-deoxygalactonojirimycine, demonstrating the potential of combination treatment in a therapeutic application. Extensive characterization of the effective PRs revealed inhibition of the proteasome and elevation of GLA gene expression as paramount effects. Further analysis of transcriptional patterns of the PRs exposed a variety of genes involved in proteostasis as potential modulators. We propose that addressing proteostasis is an effective approach to discover new therapeutic targets for diseases involving folding and trafficking-deficient protein mutants

Flavor Singlet Axial Vector Coupling of the Proton with Dynamical Wilson Fermions

We present the results of a full QCD lattice calculation of the flavor singlet axial vector coupling $G_A^1$ of the proton. The simulation has been carried out on a $16^3\times 32$ lattice at $\beta=5.6$ with $n_f=2$ dynamical Wilson fermions. It turns out that the statistical quality of the connected contribution to $G_A^1$ is excellent, whereas the disconnected part is accessible but suffers from large statistical fluctuations. Using a 1st order tadpole improved renormalization constant $Z_A$, we estimate $G_A^1 = 0.20(12)$.Comment: 13 pages, 5 eps figures, minor changes to text and citation

The Pion-Nucleon sigma-Term with Dynamical Wilson Fermions

We calculate connected and disconnected contributions to the flavour singlet scalar density amplitude of the nucleon in a full QCD lattice simulation with $n_f=2$ dynamical Wilson fermions at $\beta=5.6$ on a $16^3 \times 32$ lattice. We find that both contributions are of similar size at the light quark mass. We arrive at the estimate $\sigma_{\pi N} = 18(5)$MeV. Its smallness is directly related to the apparent decrease of $u$, $d$ quark masses when unquenching QCD lattice simulations. The $y$ parameter can be estimated from a semi-quenched analysis, in which there are no strange quarks in the sea, the result being $y=0.59(13)$.}Comment: Final version, accepted for publication in Phys. Rev. D, minor changes to the text, 1 new figure, 17 page

Comparing patients’ and other stakeholders’ preferences for outcomes of integrated care for multimorbidity: a discrete choice experiment in eight European countries

Objectives To measure relative preferences for outcomes of integrated care of patients with multimorbidity from eight European countries and compare them to the preferences of other stakeholders within these countries. Design A discrete choice experiment (DCE) was conducted in each country, asking respondents to choose between two integrated care programmes for persons with multimorbidity. Setting Preference data collected in Austria (AT), Croatia (HR), Germany (DE), Hungary (HU), the Netherlands (NL), Norway (NO), Spain (ES), and UK. Participants Patients with multimorbidity, partners and other informal caregivers, professionals, payers and policymakers. Main outcome measures Preferences of participants regarding outcomes of integrated care described as health/well-being, experience with care and cost outcomes, that is, physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person-centredness, continuity of care and total costs. Each outcome had three levels of performance. Results 5122 respondents completed the DCE. In all countries, patients with multimorbidity, as well as most other stakeholder groups, assigned the (second) highest preference to enjoyment of life. The patients top-three most frequently included physical functioning, psychological well-being and continuity of care. Continuity of care also entered the top-three of professionals, payers and policymakers in four countries (AT, DE, HR and HU). Of the five stakeholder groups, preferences of professionals differed most often from preferences of patients. Professionals assigned lower weights to physical functioning in AT, DE, ES, NL and NO and higher weights to person-centredness in AT, DE, ES and HU. Payers and policymakers assigned higher weights than patients to costs, but these weights were relatively low. Conclusion The well-being outcome enjoyment of life is the most important outcome of integrated care in multimorbidity. This calls for a greater involvement of social and mental care providers. The difference in opinion between patients and professionals calls for shared decision-making, whereby efforts to improve well-being and person-centredness should not divert attention from improving physical functioning

The patient at the centre: evidence from 17 European integrated care programmes for persons with complex needs

Background: As the prevalence of multi-morbidity increases in ageing societies, health and social care systems face the challenge of providing adequate care to persons with complex needs. Approaches that integrate care across sectors and disciplines have been increasingly developed and implemented in European countries in order to tackle this challenge. The aim of the article is to identify success factors and crucial elements in the process of integrated care delivery for persons with complex needs as seen from the practical perspective of the involved stakeholders (patients, professionals, informal caregivers, managers, initiators, payers). Methods: Seventeen integrated care programmes for persons with complex needs in 8 European countries were investigated using a qualitative approach, namely thick description, based on semi-structured interviews and document analysis. In total, 233 face-to-face interviews were conducted with stakeholders of the programmes between March and September 2016. Meta-analysis of the individual thick description reports was performed with a focus on the process of care delivery. Results: Four categories that emerged from the overarching analysis are discussed in the article: (1) a holistic view of the patient, considering both mental health and the social situation in addition to physical health, (2) continuity of care in the form of single contact points, alignment of services and good relationships between patients and professionals, (3) relationships between professionals built on trust and facilitated by continuous communication, and (4) patient involvement in goal-setting and decision-making, allowing patients to adapt to reorganised service delivery. Conclusions: We were able to identify several key aspects for a well-functioning integrated care process for complex patients and how these are put into actual practice. The article sets itself apart from the existing literature by specifically focussing on the growing share of the population with complex care needs and by providing an analysis of actual processes and interpersonal relationships that shape integrated care in practice, incorporating evidence from a variety of programmes in several countries

ELGAR - A European Laboratory for Gravitation and Atom-interferometric Research

Gravitational waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way toward multi-band GW astronomy, but will leave the infrasound (0.1–10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space–time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of 3.3 x 10 [hoch]-20 / [Wurzel] Hz at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology

The epithelial cholinergic system of the airways

Acetylcholine (ACh), a classical transmitter of parasympathetic nerve fibres in the airways, is also synthesized by a large number of non-neuronal cells, including airway surface epithelial cells. Strongest expression of cholinergic traits is observed in neuroendocrine and brush cells but other epithelial cell types—ciliated, basal and secretory—are cholinergic as well. There is cell type-specific expression of the molecular pathways of ACh release, including both the vesicular storage and exocytotic release known from neurons, and transmembrane release from the cytosol via organic cation transporters. The subcellular distribution of the ACh release machineries suggests luminal release from ciliated and secretory cells, and basolateral release from neuroendocrine cells. The scenario as known so far strongly suggests a local auto-/paracrine role of epithelial ACh in regulating various aspects on the innate mucosal defence mechanisms, including mucociliary clearance, regulation of macrophage function and modulation of sensory nerve fibre activity. The proliferative effects of ACh gain importance in recently identified ACh receptor disorders conferring susceptibility to lung cancer. The cell type-specific molecular diversity of the epithelial ACh synthesis and release machinery implies that it is differently regulated than neuronal ACh release and can be specifically targeted by appropriate drugs

ELGAR -- a European Laboratory for Gravitation and Atom-interferometric Research

Gravitational Waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way towards multi-band GW astronomy, but will leave the infrasound (0.1 Hz to 10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space-time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of $4.1 \times 10^{-22}/\sqrt{\text{Hz}}$ at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology