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BackgroundDigital health tools comprise a wide range of technologies to support health processes. The potential of these technologies to effectively support health care transformation is widely accepted. However, wide scale implementation is uneven among countries and regions. Identification of common factors facilitating and hampering the implementation process may be useful for future policy recommendations. ObjectiveThe aim of this study was to analyze the implementation of digital health tools to support health care and social care services, as well as to facilitate the longitudinal assessment of these services, in 17 selected integrated chronic care (ICC) programs from 8 European countries. MethodsA program analysis based on thick descriptions—including document examinations and semistructured interviews with relevant stakeholders—of ICC programs in Austria, Croatia, Germany, Hungary, the Netherlands, Norway, Spain, and the United Kingdom was performed. A total of 233 stakeholders (ie, professionals, providers, patients, carers, and policymakers) were interviewed from November 2014 to September 2016. The overarching analysis focused on the use of digital health tools and program assessment strategies. ResultsSupporting digital health tools are implemented in all countries, but different levels of maturity were observed among the programs. Only few ICC programs have well-established strategies for a comprehensive longitudinal assessment. There is a strong relationship between maturity of digital health and proper evaluation strategies of integrated care. ConclusionsNotwithstanding the heterogeneity of the results across countries, most programs aim to evolve toward a digital transformation of integrated care, including implementation of comprehensive assessment strategies. It is widely accepted that the evolution of digital health tools alongside clear policies toward their adoption will facilitate regional uptake and scale-up of services with embedded digital health tools.

• Within rift zones, fast splitting directions are sub-parallel to Cenozoic structures. • Changes in fast splitting direction over short distances indicate shallow sources. • Delay time, δt , increases in areas of magmatism and plate stretching. • Oriented melt pockets and along-axis flow may contribute >1 s to δt. The East African rift overlies one or more mantle upwellings and it traverses heterogeneous Archaean-Paleozoic lithosphere rifted in Mesozoic and Cenozoic time. We re-analyze XKS shear wave splitting at publicly available stations to evaluate models for rifting above mantle plumes. We use consistent criteria to compare and contrast both splitting direction and strength, infilling critical gaps with new data from the Turkana Depression and North Tanzania Divergence sectors of the East African rift system. Our results show large spatial variations in the amount of splitting (0.1–2.5 s), with fast axes predominantly sub-parallel to the orientation of Cenozoic rifts underlain by thinned lithosphere with and without surface magmatism. The amount of splitting increases with lithospheric thinning and magmatic modification. Nowhere are fast axes perpendicular to the rift, arguing against the development of extensional strain fabrics. Thick cratons are characterized by small amounts of splitting (≤0.5 s) with a variety of orientations that may characterize mantle plume flow. Splitting rotates to rift parallel and increases in strength over short distances into rift zones, implying a shallow depth range for the anisotropy in some places. The shallow source and correlation between splitting direction and the shape of upper mantle thin zones suggests that the combination of channel flow and oriented melt pockets contribute > 1 s to the observed splitting delays. Enhanced flow, metasomatism, and melt intrusion at the lithosphere-asthenosphere boundary suggest that fluid infiltration to the base of the lithosphere may facilitate rifting of cratonic lithosphere. [ABSTRACT FROM AUTHOR]

We analyze volcanic tremor from Oldoinyo Lengai, Tanzania, which is currently the only active volcano on Earth producing carbonatitic lavas. Here, we use data from the recent SEISVOL deployment and focus on a co-located seismic and infrasound station about 200 m below the summit. We show the very first observations of seismo-acoustic tremor caused by carbonatitic eruptions. This seismo-acoustic tremor is highly variable throughout the ∼one year of data which we characterize by analyzing its seismic amplitude, duration, recurrence, dominant seismic frequency and harmonics. Frequency gliding occurs frequently and over short (minutes to hours) to long time scales (hours to days) and likely reflects different time-dependent mechanisms, such as evenly-spaced repeating events with a change in inter-event times, crater dynamics that alter resonators, and dike intrusions. Seismic and acoustic wavefields correlate well for stronger eruptive sequences but are only partially coherent which suggests that high-frequency seismic tremor (up to 25 Hz) may be caused by the low viscosity of the carbonatitic melt and not by ground-coupled airwaves. In addition, the comparison between seismic-acoustic and satellite InfraRed thermal data allows us to infer different volcanic activity styles which partially alternate throughout the year: intrusive activity and the construction of hornitos, degassing, activity from a lava pond, and varying styles of extrusive activity, in particular spattering. Our study provides important insights into the eruption dynamics of this peculiar volcano which suggests shallow melt storage within the crater floor. • We show the first observations of seismo-acoustic tremor at Oldoinyo Lengai, the world's only active carbonatite volcano. • We observe significant changes in seismic and acoustic tremor properties and their correlation in one year of data collection. • Using satellite-based thermal data, we identify different volcanic processes (degassing, lava pond dynamics and spattering). [ABSTRACT FROM AUTHOR]

Introduction: Severe drug addiction can in general not be regarded as an isolated condition, but is typically associated with various other health and social problems. Drug users might therefore particularly benefit from care approaches that integrate services across different sectors and disciplines, such as the Sociomedical Centre Liebenau (SMC). The SMC is a bottom-up pioneer model providing health and social care predominantly to vulnerable groups in a socioeconomically deprived district in Graz, Austria. The study aims to perform a multi-criteria decision analysis (MCDA) of the SMC, investigating whether the services provided by the SMC for drug users in the context of opioid substitution therapy are associated with improved health and well-being, improved care experience and reduced costs in comparison to standard care. The study is one of 17 case studies conducted in the course of the Horizon2020-funded project SELFIE (Sustainable intEgrated care modeLs for multi-morbidity: delivery, FInancing and performancE). Methods: The MCDA is conducted as part of a cross-sectional and quasi-experimental controlled study. The two data sources used are questionnaire data collected at one point in time and administrative claims data linked to the questionnaire data. Propensity score matching is used to improve comparability between intervention group (persons receiving substitution therapy at the SMC) and control group (persons receiving substitution therapy in facilities in Graz other than the SMC). Performance is measured with respect to ten outcomes pertaining to one of the three domains of the triple aim - i.e. health/well-being, experience of care and resource utilization/costs. Results: A first analysis based on the data that are currently available yields the following results. The estimation of treatment effects indicates that care experience, measured by personcenteredness and continuity of care, is significantly better in the SMC compared to the control group. While most parameters pertaining to health and well-being do not show significant effects, enjoyment of life and self-sufficiency of patients appear to be poorer in the SMC compared to the control group. Data on costs will mostly be derived from administrative claims data and are yet to be retrieved. Discussion/Conclusion: Preliminary results suggest that care experience for persons receiving substitution therapy is better in the integrated care approach of the SMC than in standard care. For health and well-being, results are currently inconclusive. Results are expected to be subject to change when additional data are available. Final results are expected for the end of 2018. Re2i ss; In tegration of health and social care services for persons in opioid substitution therapy - results of a case study in Austria. [ABSTRACT FROM AUTHOR]

Seismic observations of the lowermost mantle show that this deep part of the earth's interior is highly heterogeneous. This includes the presence of two large low shear velocity provinces (LLSVPs), and the presence of seismic anisotropy, particularly at the margins of the LLSVPs. Here, we investigate the lowermost mantle in the vicinity of the African LLSVP using shear-wave splitting discrepancies of teleseismic SKS and SKKS phases for the same station-event pairs. Though these phases are traditionally used to study anisotropy in the upper mantle and infer past and present mantle flow processes, discrepancies in their splitting measurements can be exploited to resolve lowermost mantle anisotropy because of their divergent pathways in the lowermost mantle. To measure shear-wave splitting, we use the transverse energy minimization and multi-channel splitting intensity method (Silver & Chan, 1991; Chevrot, 2000). Overall, we present observations from 375 stations and ~900 SKS-SKKS pairs. This data set comprises all publicly available permanent stations in Africa and temporary experiments since 1990. This enables us to map the spatial distribution of the anisotropic and isotropic regions of the lowermost mantle with unprecedented resolution.Of our observations, one third of the SKS-SKKS pairs is highly discrepant as defined by the difference in the splitting intensity. Discrepant pairs are roughly localized in three areas: at the northern and southeastern border of the LLSVP, inside the LLSVP beneath central Africa, and outside of the LLSVP atop and east of the Afar plume. To explain these observations, we invoke different mechanism for seismic anisotropy. Discrepant pairs located across the border of the LLSVP indicate that SKS-SKKS pairs pierce an isotropic LLSVP and an anisotropic cold/fast D" outside the LLSVP. As observations of strong discrepancies inside the LLSVP coincide with a previously mapped ULVZ, anisotropy is best explained by SPO inside the ULVZ due to martial melting, compositional heterogeneities or the highly anisotropic magnesiowüstite. Finally, observations of discrepant pairs in the cold/fast part of the D" are thought to elucidate a change in the flow geometry from horizontal to vertical. Considering all observations, our analyses suggest that LLSVPs are passive thermochemical piles in which subduction driven horizontal flow at the base of the mantle induces a vertical flow component at the LLSVP boundary. Inside the LLSVP, an ULVZ may slowly be swept towards the LLSVP boundary. In the center of both, the deep-rooted Afar plume impinges from the CMB. Accordingly, we present a significant contribution towards lower mantle dynamics and processes which also control the upper mantle. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most frequent sustained arrhythmia and can lead to structural cardiac changes, known as tachycardia-induced cardiomyopathy (TIC). HCN4 is implicated in spontaneous excitation of the sinoatrial node, while channel dysfunction has been associated with sinus bradycardia, AF and structural heart disease. We here asked whether HCN4 mutations may contribute to the development of TIC, as well. Mutation scanning of HCN4 in 60 independent patients with AF and suspected TIC followed by panel sequencing in carriers of HCN4 variants identified the HCN4 variant P883R [minor allele frequency (MAF): 0,88%], together with the KCNE1 variant S38G (MAF: 65%) in three unrelated patients. Family histories revealed additional cases of AF, sudden cardiac death and cardiomyopathy. Patch-clamp recordings of HCN4-P883R channels expressed in HEK293 cells showed remarkable alterations of channel properties shifting the half-maximal activation voltage to more depolarized potentials, while channel deactivation was faster compared to wild-type (WT). Co-transfection of WT and mutant subunits, resembling the heterozygous cellular situation of our patients, revealed significantly higher current densities compared to WT. In conclusion HCN4-P883R may increase ectopic trigger and maintenance of AF by shifting the activation voltage of I f to more positive potentials and producing higher current density. Together with the common KCNE1 variant S38G, previously proposed as a genetic modifier of AF, HCN4-P883R may provide a substrate for the development of AF and TIC. • HCN4 -P883R is linked to atrial fibrillation and tachycardia-induced cardiomyopathy. • Activation of P883R channels is shifted to depolarized potentials. • Deactivation of P883R channels is faster compared to wild-type. • Heteromeric P883R/wild-type channels reveal increased current density. • P883R may provide a substrate for AF-associated structural heart disease. [ABSTRACT FROM AUTHOR]

Eukaryotic plasma membranes assemble actin filaments within seconds of activation of many receptors, especially during chemotaxis. Here, serum or sphingosine-1-phosphate stimulation of J774 and RAW macrophages released ADP within seconds into the extracellular medium, along with an adenylate kinase activity that converted ADP to ATP. ATP then activated the P2X7 receptor (P2X7R) that was necessary for a peak of plasma-membrane actin assembly within 5 to 10 seconds in P2X7R-expressing J774, RAW and primary macrophages. Neither actin assembly nor characteristic P2X7R channel activity was seen in response to ATP in P2X7R-knockout macrophages, as detected by patch-clamp analysis. Since P2X7R has been shown previously to form a macromolecular complex with actin we propose that it is involved in the membrane assembly of actin. Our data reveal a surprisingly rapid and complex relay of signaling and externalization events that precede and control actin assembly induced by sphingosine-1-phosphate. The overall model we present is strongly supported by the data presented in the accompanying paper that focuses on latex bead phagosomes. [ABSTRACT FROM AUTHOR]