Everolimus zur Therapie der fortgeschrittenen steroidresistenten chronischen Graft-versus-Host Erkrankung nach allogener hämatopoetischer Stammzelltransplantation

Die Behandlung der chronischen GvHD (cGvHD) stellt auch nach langjähriger Etablierung der allogenen Stammzelltransplantation eine besondere Herausforderung dar. Die retrospektive Analyse untersucht die Therapie mit Everolimus, welches bei Versagen der primären Standardtherapie mit Kortikosteroiden als Zweitlinienbehandlung und als höhergradige Salvagetherapie in Kombination mit Prednisolon und/oder Mycophenolat (MMF) und/oder ECP bei 38 Patienten (Pat.) eingesetzt wurde. Mit Reklassifizierung dieser Studienpopulation nach den NIH-Kriterien 2005 wurden das allgemeine Therapieansprechen, die Ansprechzeit, das Überleben, die organbezogene Therapiewirksamkeit, die Nebenwirkungen und Toxizitäten dieser Therapie überprüft. Die mediane Behandlungszeit betrug 7,1 Monate. Eine Verbesserung des Gesamtschweregrades nach NIH-Kriterien konnte bei 20 Pat. (52,6%) erreicht werden. Bei 4 Pat. (10,5%) war eine CR und bei 13 Pat. (34,2%) eine PR zu verzeichnen. Von denen bei 11 Pat. (28,9%) eine Reduktion der Steroiddosis unter Everolimus ermöglicht wurde. Unter 21 Pat. die zusätzlich MMF erhielten, konnte eine Beendigung dieses Ko-Therapeutikums zu 33,3% erreicht werden. Organbezogenes Ansprechen zeigte sich bei cGvHD der Haut in 63,6%, bei cGvHD der Mundschleimhaut in 61,6%, bei cGvHD der Augen in 30,0%, bei cGvHD des Gastrointestinaltraktes in 33,3%, bei hepatischer cGvHD in 45,0% und bei cGvHD der Faszien und Gelenke in 60,0%. Während einer medianen Beobachtungszeit von 977 Tagen überlebten 78,9% der Pat.. Das Nebenwirkungsspektrum war moderat mit einer besonderen Häufigkeit für Lipidstoffwechselstörungen (21,9%). Hervorzuheben ist die signifikant geringe CMV-Reaktivierungsrate (p=0,0001). Diese CMV-Protektion unter immunsuppressiver Medikation ist aus dem Bereich der Stammzelltransplantation so bisher noch nicht beschrieben worden. Die NIH-Klassifikation 2005 mit Weiterentwicklung von 2014 erhöht die Trennschärfe der Beurteilung cGvHD und eine mögliches Ansprechen im Verlauf

Ribosome specificity of archaebacterial elongation factor 2 Studies with hybrid polyphenylalanine synthesis systems

AbstractPolyphenylalanine synthesis with ribosomes and two separated, partially purified elongation factors (EF) was measured in cell-free systems from the archaebacteria Thermoplasma acidophilum and Methanococcus vannielii, in an eukaryotic system from rat liver and an eubacterial one with Escherichia coli ribosomes and factors from Thermus thermophilus. By substitution of heterologous EF-2 or EF-G, respectively, for the homologous factors, ribosome specificity was shown to be restricted to factors from the same kingdom. In contrast EF-1 from T. thermophilus significantly cooperated with ribosomes from T. acidophilum

Internet Safety: Positioning VCU as a National Leader in Internet Safety

While a multitude of information from a host of sources exists on how to keep children safe on the Internet, there is not a unified effort to combine it all and get it to the right people. This is not a plan to teach college students about Internet safety. This is a proposal to begin much earlier, targeting middle-school aged children and their parents, many of whom have no idea of the dangers – and opportunities – that exist in cyberspace

Core Competencies for Successful Watershed Management Practitioners

We surveyed participants from three watershed leadership education programs to identify competencies critical to successful watershed management. Participants rated 26 competency areas identified from literature and watershed education curricula for extent of criticality and listed additional competencies needed for successful watershed management. On the basis of those ratings and listings, we propose that competency in the following areas is required: establishing and maintaining partnerships/collaborating, outreach and communication, project and organizational management, landowner interaction/interpersonal skills, facilitative leadership, and, possibly, developing and maintaining a vision for the future. Our findings have implications for designing professional development activities and developing position descriptions for hiring watershed leaders

Effect of a regular consumption of traditional and roasted oat and barley flakes on blood lipids and glucose metabolism–A randomized crossover trial

Background Regular consumption of the soluble dietary fiber β-glucan is associated with decreased total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and blood glucose. Barley and oat flakes as natural sources of β-glucan were roasted to improve sensory quality. The aim of this study was to investigate whether roasting of barley and oat flakes changes the physiological impact of the β-glucan-rich flakes on glucose and lipid metabolism. Method A five-armed randomized crossover trial design was used. The intervention study was conducted from May 2018 to May 2019 and included 32 healthy subjects with moderately increased LDL cholesterol (≥2.5 mmol/L). During the 3-week intervention periods, 80 g of roasted or traditional barley or oat flakes, or four slices of white toast bread per day were consumed for breakfast. At the start and the end of each intervention, fasting and postprandial blood was taken. The intervention periods were separated by 3-week wash-out periods. Results During the interventions with the cereal flakes, TC and LDL cholesterol concentrations were significantly reduced compared to baseline values by mean differences of 0.27–0.33 mmol/L and 0.21–0.30 mmol/L, respectively ( p < 0.05), while high-density lipoprotein (HDL) cholesterol was only reduced after the intervention with barley flakes ( p < 0.05). After the intervention period with toast, TC and HDL cholesterol increased ( p < 0.05). The fasting levels of triglycerides, fasting blood glucose and insulin did not change in any group. The effects of traditional and roasted varieties on blood lipids did not differ between the groups. Conclusion The regular consumption of traditional or roasted barley and oat flakes contributes to the management of cardiovascular diseases by improving TC and LDL cholesterol. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT03648112 , identifier NCT03648112

Synthesis reveals approximately balanced biotic differentiation and homogenization

This work was supported by the German Research Foundation (FZT 118, to S.A.B., T.E., A.S., R.v.K., W.-B.X., and J.M.C.) and ERC GA 101044975 and the Leverhulme Centre for Anthropocene Biodiversity (to M.D.). This work was also supported by the German Research Foundation (DFG) project “Establishment of the National Research Data Infrastructure (NFDI)” in the consortium NFDI4Biodiversity (project number 442032008) (to T.E.), European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 894644 (to I.S.M.), USDA Hatch grant MAFES #1011538 and NSF EPSCOR Track II grant #2019470 (to B.M.), and NSF Track II grant #2019470 (to N.J.G.).It is commonly thought that the biodiversity crisis includes widespread declines in the spatial variation of species composition, called biotic homogenization. Using a typology relating homogenization and differentiation to local and regional diversity changes, we synthesize patterns across 461 metacommunities surveyed for 10 to 91 years, and 64 species checklists (13 to 500+ years). Across all datasets, we found that no change was the most common outcome, but with many instances of homogenization and differentiation. A weak homogenizing trend of a 0.3% increase in species shared among communities/year on average was driven by increased numbers of widespread (high occupancy) species and strongly associated with checklist data that have longer durations and large spatial scales. At smaller spatial and temporal scales, we show that homogenization and differentiation can be driven by changes in the number and spatial distributions of both rare and common species. The multiscale perspective introduced here can help identify scale-dependent drivers underpinning biotic differentiation and homogenization.Peer reviewe

Supplementary information files for Regional occupancy increases for widespread species but decreases for narrowly distributed species in metacommunity time series

Supplementary files for article Regional occupancy increases for widespread species but decreases for narrowly distributed species in metacommunity time series   While human activities are known to elicit rapid turnover in species composition through time, the properties of the species that increase or decrease their spatial occupancy underlying this turnover are less clear. Here, we used an extensive dataset of 238 metacommunity time series of multiple taxa spread across the globe to evaluate whether species that are more widespread (large-ranged species) differed in how they changed their site occupancy over the10-90 years the metacommunities were monitored relative to species that are more narrowly distributed (small-ranged species). We found that on average, large-ranged species tended to increase in occupancy through time, whereas small-ranged species tended to decrease. These relationships were stronger in marine than in terrestrial and freshwater realms. However, in terrestrial regions, the directional changes in occupancy were less extreme in protected areas. Our findings provide evidence for systematic decreases in occupancy of small-ranged species, and that habitat protection could mitigate these losses in the face of environmental change.</p

Growth response of syndromic versus non-syndromic children born small for gestational age (SGA) to growth hormone therapy: a Belgian study

IntroductionA substantial proportion of SGA patients present with a syndrome underlying their growth restriction. Most SGA cohorts comprise both syndromic and non-syndromic patients impeding delineation of the recombinant human growth hormone (rhGH) response. We present a detailed characterization of a SGA cohort and analyze rhGH response based on adult height (AH).MethodsClinical and auxological data of SGA patients treated with rhGH, who had reached AH, were retrieved from BELGROW, a national database of all rhGH treated patients held by BESPEED (BElgian Society for PEdiatric Endocrinology and Diabetology). SGA patients were categorized in syndromic or non-syndromic patients.Results272 patients were included, 42 classified as syndromic (most frequent diagnosis (n=6): fetal alcohol syndrome and Silver-Russell syndrome). Compared with non-syndromic patients, syndromic were younger [years (median (P10/P90)] 7.43 (4.3/12.37) vs 10.21 (5.43/14.03), p=0.0005), shorter (height SDS -3.39 (-5.6/-2.62) vs -3.07 (-3.74/-2.62), p=0.0253) and thinner (BMI -1.70 (-3.67/0.04) vs -1.14 (-2.47/0.27) SDS, p=0.0054) at start of rhGH treatment. First year rhGH response was comparable (delta height SDS +0.54 (0.24/0.94) vs +0.56 (0.26/0.92), p=0.94). Growth pattern differed with syndromic patients having a higher prepubertal (SDS +1.26 vs +0.83, p=0.0048), but a lower pubertal height gain compared to the non-syndromic group (SDS -0.28 vs 0.44, p=0.0001). Mean rhGH dose was higher in syndromic SGA patients (mg/kg body weight/day 0.047 (0.039/0.064) vs 0.043 (0.035/0.056), p=0.0042). AH SDS was lower in syndromic SGA patients (-2.59 (-4.99/-1.57) vs -2.32 (-3.3/-1.2), p=0.0107). The majority in both groups remained short (&lt;-2 SDS: syndromic 71%, non-syndromic 63%). Total height gain was comparable in both groups (delta height SDS +0.76 (-0.70/1.48) vs +0.86 (-0.12/1.86), p=0.41).ConclusionsCompared to non-syndromic SGA patients, syndromic SGA patients were shorter when starting rhGH therapy, started rhGH therapy earlier, and received a higher dose of rhGH. At AH, syndromic SGA patients were shorter than non-syndromic ones, but their height gain under rhGH therapy was comparable

Cross-realm assessment of climate change impacts on species' abundance trends

Climate change, land-use change, pollution and exploitation are among the main drivers of species' population trends; however, their relative importance is much debated. We used a unique collection of over 1,000 local population time series in 22 communities across terrestrial, freshwater and marine realms within central Europe to compare the impacts of long-term temperature change and other environmental drivers from 1980 onwards. To disentangle different drivers, we related species' population trends to species- and driver-specific attributes, such as temperature and habitat preference or pollution tolerance. We found a consistent impact of temperature change on the local abundances of terrestrial species. Populations of warm-dwelling species increased more than those of cold-dwelling species. In contrast, impacts of temperature change on aquatic species' abundances were variable. Effects of temperature preference were more consistent in terrestrial communities than effects of habitat preference, suggesting that the impacts of temperature change have become widespread for recent changes in abundance within many terrestrial communities of central Europe.Additionally, we appreciate the open access marine data provided by the International Council for the Exploration of the Sea. We thank the following scientists for taxonomic or technical advice: C. Brendel, T. Caprano, R. Claus, K. Desender, A. Flakus, P. R. Flakus, S. Fritz, E.-M. Gerstner, J.-P. Maelfait, E.-L. Neuschulz, S. Pauls, C. Printzen, I. Schmitt and H. Turin, and I. Bartomeus for comments on a previous version of the manuscript. R.A. was supported by the EUproject LIMNOTIP funded under the seventh European Commission Framework Programme (FP7) ERA-Net Scheme (Biodiversa, 01LC1207A) and the long-term ecological research program at the Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB). R.W.B. was supported by the Scottish Government Rural and Environment Science and Analytical Services Division (RESAS) through Theme 3 of their Strategic Research Programme. S.D. acknowledges support of the German Research Foundation DFG (grant DO 1880/1-1). S.S. acknowledges the support from the FP7 project EU BON (grant no. 308454). S.K., I.Kü. and O.S. acknowledge funding thorough the Helmholtz Association’s Programme Oriented Funding, Topic ‘Land use, biodiversity, and ecosystem services: Sustaining human livelihoods’. O.S. also acknowledges the support from FP7 via the Integrated Project STEP (grant no. 244090). D.E.B. was funded by a Landes–Offensive zur Entwicklung Wissenschaftlich–ökonomischer Exzellenz (LOEWE) excellence initiative of the Hessian Ministry for Science and the Arts and the German Research Foundation (DFG: Grant no. BO 1221/23-1).Peer Reviewe

"Classicism versus Mediaevalism in Victorian-Edwardian England: E. M. Forter's "A Room with a View" as an example

Podeu consultar la versió en castellà a: http://hdl.handle.net/2445/12153 ; i en català a: http://hdl.handle.net/2445/12154The aim of this article is to illustrate the well-known opposition classicism / medievalism in the Victorian-Edwardian England by analysing accurately E. M. Forster's A Room with a View from the point of view of the Classical Tradition and, therefore, focusing on both the meaning and significance of all its classical -Greek and Roman- references