Predictors of Adherence Among Patients With Multiple Sclerosis Using the BETACONNECT® Autoinjector: A Prospective Observational Cohort Study

Background: In patients with multiple sclerosis (MS), non-adherence to disease-modifying drug therapy is associated with an increased rate of MS relapses. Early identification of patients at risk of non-adherence would allow provision of timely and individualized support. The aim of the BETAPREDICT study was to investigate potential predictors of adherence in patients with MS in Germany treated with interferon β-1b (IFNβ-1b) using the BETACONNECT® autoinjector. Methods: BETAPREDICT was a national, multi-center, prospective, non-interventional, single-arm, 24-month cohort study of patients with relapsing–remitting MS or clinically isolated syndrome receiving IFNβ-1b via the BETACONNECT® autoinjector (ClinicalTrials.gov: NCT02486640). Injection data were captured by the autoinjector. The primary objective was to determine baseline predictors of compliance, persistence, and adherence to IFNβ-1b treatment after 12- and 24 months using multivariable-adjusted regression. Secondary objectives included evaluation of satisfaction with the autoinjector, injection site pain, vitamin and nutrient supplementation, clinical course, and patient-related outcome measures. Results: Of 165 patients enrolled, 153 were available for analysis (120 with autoinjector data). Seventy-two patients left the study prematurely. Compliance (N = 120), persistence (N = 153), and adherence (N = 120) at 24 months were 89.1, 53.6, and 41.7%, respectively. Compliance at 12- and 24 months was predicted by intake of vitamin D supplements and absence of specific injection site reactions. Positive predictors of persistence included age (at 12- and 24 months) and previous duration of treatment (at 12 months), while intake of vitamins/nutrients other than vitamin D was a negative predictor (at 12 months). Positive predictors of adherence at 24 months were age and being experienced with IFNβ-1b. Higher scores in specific SF-36 subscales were positive predictors of medication-taking behavior at 24 months. Satisfaction with the autoinjector was high at baseline and 24 months (median score: 9 out of 10). Conclusions: Compliance with IFNβ-1b treatment among participants still under observation remained high over a 24-month period, while persistence and adherence continuously declined. Multiple factors affected medication-taking behavior, including patient characteristics, treatment history, injection site reactions, patients’ perception of their health and support programs. The importance of these factors may differ among patients according to their individual situation

Living with Uncertainty

The last few years have seen a major rethinking of some of the hallowed assumptions of range ecology and range management practice. This book examines the management of policy implications of this new ecological thinking for pastoral development in dryland areas. With examples drawn from all over Africa, the contributors examine the consequences of living with uncertainty for pastoral development planning, range and fodder management, drought responses, livestock marketing, resource tenure, institutional development and pastoral administration

Living with Uncertainty

The last few years have seen a major rethinking of some of the hallowed assumptions of range ecology and range management practice. This book examines the management of policy implications of this new ecological thinking for pastoral development in dryland areas. With examples drawn from all over Africa, the contributors examine the consequences of living with uncertainty for pastoral development planning, range and fodder management, drought responses, livestock marketing, resource tenure, institutional development and pastoral administration

Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

BACKGROUND: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. RESULTS: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. CONCLUSIONS: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities

Resiliente Digitalisierung der kritischen Infrastruktur Landwirtschaft - mobil, dezentral, ausfallsicher

Diese Arbeit befasst sich mit der zunehmenden Digitalisierung der kritischen Infrastruktur Ernährungswirtschaft und setzt den Fokus insbesondere auf die dadurch resultierenden informationstechnologischen Folgen bezüglich der Angriffs- und Ausfallsicherheit in der Landwirtschaft und von ihr abhängigen Sektoren. In diesem Kontext wird die Modernisierungen der Landmaschinen und deren Vernetzung sowie das Cloud-Computing in der Landwirtschaft analysiert und zu treffende Maßnahmen bezüglich einer resilienten Struktur erläutert. In vielen Bereichen wird dabei aufgezeigt, dass das Ausfallrisiko der Produktion zugunsten von Vorteilen wie Ertrags- und Qualitätssteigerung vernachlässigt wird. Dieser Beitrag plädiert für eine resiliente Digitalisierung in der Landwirtschaft mit gebrauchstauglichen Sicherheitslösungen, um keine zusätzlichen Aufwände für die Nutzer zu erzeugen und somit die praktische Sicherheit zu erhöhen

Nitrogen Isotope Fractionation During Archaeal Ammonia Oxidation: Coupled Estimates From Measurements of Residual Ammonium and Accumulated Nitrite

The naturally occurring nitrogen (N) isotopes,N-15 and(14)N, exhibit different reaction rates during many microbial N transformation processes, which results in N isotope fractionation. Such isotope effects are critical parameters for interpreting natural stable isotope abundances as proxies for biological process rates in the environment across scales. The kinetic isotope effect of ammonia oxidation (AO) to nitrite (NO2-), performed by ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB), is generally ascribed to the enzyme ammonia monooxygenase (AMO), which catalyzes the first step in this process. However, the kinetic isotope effect of AMO, or epsilon(AMO), has been typically determined based on isotope kinetics during product formation (cumulative product, NO2-) alone, which may have overestimated epsilon(AMO)due to possible accumulation of chemical intermediates and alternative sinks of ammonia/ammonium (NH3/NH4+). Here, we analyzed(15)N isotope fractionation during archaeal ammonia oxidation based on both isotopic changes in residual substrate (RS, NH4+) and cumulative product (CP, NO2-) pools in pure cultures of the soil strainNitrososphaera viennensisEN76 and in highly enriched cultures of the marine strainNitrosopumilus adriaticusNF5, under non-limiting substrate conditions. We obtained epsilon(AMO)values of 31.9-33.1 parts per thousand for both strains based on RS (delta(NH4+)-N-15) and showed that estimates based on CP (delta(NO2-)-N-15) give larger isotope fractionation factors by 6-8 parts per thousand. Complementary analyses showed that, at the end of the growth period, microbial biomass was(15)N-enriched (10.1 parts per thousand), whereas nitrous oxide (N2O) was highly(15)N depleted (-38.1 parts per thousand) relative to the initial substrate. Although we did not determine the isotope effect of NH(4)(+)assimilation (biomass formation) and N2O production by AOA, our results nevertheless show that the discrepancy between epsilon(AMO)estimates based on RS and CP might have derived from the incorporation of(15)N-enriched residual NH(4)(+)after AMO reaction into microbial biomass and that N2O production did not affect isotope fractionation estimates significantly

Rangelands at equilibrium and non-equilibrium recent developments in the debate around rangeland ecology and management

The debate on equilibrium vs non-equilibrium dynamics in pastoral systems emerged in the early 1980s, when economists, ecologists and social scientists began to challenge the widespread claims of overgrazing and degradation in African rangelands and subsequent interventions based on rangeland succession theory and correct stocking rates (for example, Sandford 1982; 1983; Homewood & Rodgers 1987; Ellis & Swift 1988; Abel & Blaikie 1989; Westoby et al. 1989). The debate gained momentum in the early 1990s after two international workshops around emergent new paradigms in rangeland ecology and socio-economics (Woburn I and II), which resulted in the publication of two books, Range Ecology at Disequilibrium edited by Behnke et al. (1993) and Living with Uncertainty edited by Scoones (1994). The ‘new rangeland ecology’ argued that the traditional, equilibrium-based rangeland models did not take into account the considerable spatial heterogeneity and climatic variability of semi-arid rangelands, and that mobility, variable stocking rates and adaptive management were essential for the effective and sustainable utilisation of semi-arid and arid rangelands