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- A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma (2010)
- Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
- Extended pancreas donor program – the EXPAND study rationale and study protocol (2013)
- Background: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients. Methods/Design: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation. Discussion: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future. Trial registered at: NCT01384006
- Successful transplantation of a hart’s tongue fern population (Asplenium scolopendrium L.) with ten years of monitoring (2010)
- At the edge of the Harz Mountains in Lower Saxony a population of the hart’s tongue fern (Asplenium scolopendrium) threatened by destruction by a gypsum quarry were transplanted into a dolina which was not populated by the species at that time, and the new population was followed over ten years. 90% of the 59 transplanted plants survived this period and grew larger during the first six years after transplantation. Progenies appeared in the third year after transplantation. Nowadays, in the tenth year after transplantation, there are 1110 progenies, 171 of which are reproducing. Overall, the population increased by 1781% in the ten years. Plants that were planted on a rocky slope or a boulder heap in the new habitat, where soil was available, grew better than plants in rock faces without soil. In contrast, in the rock faces, where substrate was not covered with autumn foliage, more juveniles established. The distance between juveniles and mother plants rarely exceeded three meters, which indicates a limited dispersal potential of the hart’s tongue fern and may explain together with low diaspore pressure as a result of local rarity of the species that the dolina had not been colonized spontaneously. We conclude that transplantations of adult plants or introduction of spores are a suitable measure for preserving hart’s tongue fern populations that are endangered by destruction. In the long run, however, such measures cannot compensate for ongoing destruction of natural habitats by mining activities in the gypsum karst region at the southern edge of the Harz Mountains.
- Dry grasslands: species interactions and distribution – Editorial to the Special Feature with contributions from the 6th European Dry Grassland Meeting 2009 in Halle (Saale) (2010)
- In our contribution, we report on the 6th European Dry Grassland Meeting held from 31 August to 1 September 2009 in Halle (Saale), Germany. The meeting was attended by 40 participants, who gave 15 oral and 17 poster presentations. The rapid positive development of the European Dry Grassland Group (EDGG), the organiser of this conference, is mentioned: the inclusion of the EDGG in the International Association for Vegetation Science (IAVS) as a working group, the establishment of two new subgroups focussing on Mediterranean and South-East European dry grasslands, respectively, and the organisation of the first EDGG research expedition in 2010 belong to the most important events. In the last part of our contribution, we give a short introduction to the six articles of this Special Feature. Two of them deal with phytosociological classification of semi-natural grassland communities, one with vegetation- environment relationships. Two papers are concerned with conservational topics, one focussing on the population structure of endangered Pulsatilla patens, the other dealing with conservation of xeric grasslands in Transylvania. The last paper examines temporal changes in calcareous grasslands with regard to species diversity.
- Biodiversity, syntaxonomy, and management – Editorial to the 7th Dry Grassland Special Feature (with a bibliometrical evaluation of the series) (2012)
- We report on the activities of the European Dry Grassland Group (EDGG) during the last year, namely the 8th European Dry Grassland Meeting in Uman’, Ukraine in June 2011, the 3rd EDGG Research Expedition in Bulgaria in August 2011, the 4th EDGG Research Expedition in Sicily in April 2012, as well as the completed and forthcoming EDGG-coordinated special features in international journals. Then we provide a brief bibliometrical analysis of the Dry Grassland Special Features in Tuexenia since 2005. The 32 contributions of the years 2005–2011 constituted approx. 17% of the overall content of Tuexenia in this period. Including this 7th Dry Grassland Special Feature, sixty-one authors from 12 countries have contributed to these Special Features, guest-edited by yearly changing teams from a total of 16 guest editors. In the years with statistically reliable data, contributions in the Dry Grassland Special Features have been cited approximately four times as much as regular Tuexenia contributions. It is likely that this fact together with the internationality of the Special Features has contributed to the final inclusion of the journal in the Web of Science in 2011. Finally, we introduce the four research articles of this 7th Dry Grassland Special Feature. Two of them are focusing on vegetation change and restoration issues of cryptogam-rich sand dunes in the Netherlands and calcareous grasslands in Bavaria (Germany), respectively. The others, dealing with siliceous grasslands in Hesse (central Germany) and the results of EDGG Research Expedition 2009 to Transylvania (Romania), focus on syntaxonomy.
- Nutrient-poor grasslands on siliceous soil in the lower Aar valley (Middle Hesse, Germany) – neglected vegetation types in the intersection range of four classes (2012)
- In the lower siliceous uplands of Central Europe, various types of nutrient-poor grasslands are widespread and grow intermingled. These species-rich grasslands, often dominated by taxa of the Festuca ovina aggregate, comprise various phytosociological classes. They are remnants of a historic rural lands - cape and are of conservation importance. Few studies on such grasslands are available and there has been disagreement in assigning them to appropriate habitat types or syntaxa. We investigated such nutrient-poor grasslands in the lower Aar valley (Middle Hesse, Rhenish Massif). We surveyed 104 vegetation plots distributed throughout the valley and identified syntaxa to (sub)association level. We carried out supervised classification combining cluster analysis, a priori assignment to classes based on prevailing diagnostic species, and regional refinement based on phi-value maximisation of the units. As a result, we classified five associations within four classes: Polytricho piliferi-Festucetum tenuifoliae/Galio harcynici-Deschampsietum flexuosae and Festuco rubrae-Genistelletum sagittalis (Calluno- Ulicetea), Jasiono montanae-Festucetum ovinae (Koelerio-Corynephoretea), Gentiano-Koelerietum pyramidatae (Festuco-Brometea) and Arrhenatheretum elatioris (Molinio-Arrhenatheretea). Ecologically, soil acidity (resulting from Ca concentrations of the bedrock) was the main cause of floristic dissimilarity of the grasslands and thus community differentiation. Many stands grew on soils with intermediate pH and showed a peculiar mixture of basiphilous and acidophilous species. We conclude that (i) our approach of supervised classification yields convincing reproducible results when a syntaxonomic system is adapted top-down to a geographically restricted area, (ii) nutrient-poor siliceous grasslands dominated by taxa of the Festuca ovina aggregate can be well assigned to ecologically meaningful syntaxa, and (iii) the nutrient-poor siliceous grasslands of the Lahn-Dill Highlands are of high conservation relevance and in urgent need of protection.
- Festuco-Brometea communities of the Transylvanian Plateau (Romania) – a preliminary overview on syntaxonomy, ecology, and biodiversity (2012)
- The Transylvanian Plateau in Romania is well known to host large areas of a variety of dry grassland types, still traditionally managed by low-intensity mowing or grazing. While this natural heritage is now under threat from changes in agricultural practices, the diversity of Transylvanian dry grasslands is still little understood. There is a lack of both field data sampled with standardised methods and a syntaxonomic treatment with modern statistical methods and supra-regional perspective. Therefore, the European Dry Grassland Group (EDGG) carried out its first international Research Expedition in Transylvania 2009 to study syntaxonomy, vegetation-environment relationships, and biodiversity patterns of these communities. In various locations across Transylvania, we sampled 10-m² vegetation plots (n = 82) and nested-plot series from 0.0001 m² to 100 m² (n = 20), including all vascular plant, bryophyte, and lichen species, as well as structural and soil data. The vegetation classification was carried out with modified TWINSPAN, followed by determination of diagnostic species with phi values and a small-scale re-assignment of relevés with the aim of crispness maximisation. Both TWINSPAN and ordination revealed three major groups of syntaxa, which were matched to three orders from the class of basiphilous dry grasslands, Festuco-Brometea, represented by one alliance each: rocky dry grasslands (Stipo pulcherrimae-Festucetalia pallentis: Seslerion rigidae); xeric grasslands on deep soils (Festucetalia valesiacae: Stipion lessingianae) and meso-xeric grasslands on deep soils (Brachypodietalia pinnati: Cirsio-Brachypodion pinnati). We accepted nine association-level units plus two that potentially merit association status but were only represented by one relevé each. Most of the units could be identified with one or several previously described associations. To support nomenclatural stability, we provide a nomenclatural revision and designate nomenclatural types where previously there were none. Further, we used DCA ordination and analysis of variance to determine the main environmental drivers of floristic differentiation and to determine ecological and structural differences between the vegetation types. The strongest differentiation occurred along the aridity gradient with the dense, particularly diverse stands on more or less level sites on the one hand (Brachypodietalia pinnati) and the more open, less diverse stands on steep south-facing slopes on the other end of the gradient (Stipo pulcherrimae- Festucetalia pallentis, Festucetalia valesiacae). The two xeric orders were then separated along the second DCA axis, with the Stipo pulcherrimae-Festucetalia pallentis inhabiting the stone-rich sites at higher altitudes while the Festucetalia valesiacae occur on soft, deep substrata at lower altitudes. The analysed dry grassland communities have extraordinarily high -diversity at all spatial scales for all plants and for vascular plants, but are relatively poor in bryophytes and lichens. Some formerly mown stands of the Festuco sulcatae-Brachypodietum pinnati (Brachypodietalia pinnati) are even richer in vascular plant species than any other recorded vegetation type worldwide on the spatial scales of 0.1 m² (43) and 10 m² (98); the respective relevés are documented here for the first time. Also, the -diversity of the grasslands was unexpectedly high, with a mean z-value of 0.275. Despite its limited extent, the methodological thoroughness of this study allows us to shed new light on the syntaxonomy of dry grasslands in Romania and to raise the awareness that Transylvania still hosts High Nature Value grasslands that are bio - diversity hotspots at a global scale but at the same time are highly endangered through changes in agricultural practices.