Entwicklung der Förderung des Landtourismus - Statusbericht zur Entwicklung der Förderung des Landtourismus durch das Sächsische Staatsministerium für Umwelt und Landwirtschaft

Statusbericht zur Entwicklung der Förderung des Landtourismus durch das Sächsische Staatsministerium für Umwelt und Landwirtschaft Organisatorisch ist der Landtourismus sehr breit aufgestellt. Das erfordert weiterhin klare Zielstellungen, die Wahrnehmung von Verantwortlichkeiten und die aktive Mitwirkung der Beteiligten. Zur Fortführung des bisher Erreichten müssen insbesondere Profilierung und Qualität weiterhin im Zentrum aller Aktivitäten stehen. Der Landtourismus ist ein eigenständiger Produktbereich und sollte darum weiterhin professionell vermarktet werden. Aufgrund der Vielfalt des Landtourismus und der Schnittstellen mit anderen Tourismussegmenten wird eine Vielzahl von Entwicklungseinschnitten durch das gesamtsächsische Tourismusgeschehen beeinflusst. Einen Schwerpunkt bildet die Tourismusförderung über die Gemeinschaftsaufgabe 'Verbesserung der regionalen Wirtschaftsstruktur' und die Gemeinschaftsinitiativen INTERREG und LEADER. Die möglichen Synergien müssen stärker genutzt werden. Dazu muss unter anderem der regionale Ansatz gestärkt werden, wie es im Rahmen der Integrierten ländlichen Entwicklung erfolgen soll. Mit der ELER-VO sind somit beste Voraussetzungen gegeben, um einen weiteren Qualitätssprung im sächsischen Landtourismus zu schaffen

The impact of ocean warming and acidification on the behaviour of two co-occurring Gadid species, Boreogadus saida and Gadus morhua from Svalbard

Ocean acidification induces strong behavioural alterations in marine fish as a conse- quence of acid−base regulatory processes in response to increasing environmental CO2 partial pressure. While these changes have been investigated in tropical and temperate fish species, nothing is known about behavioural effects on polar species. In particular, fishes of the Arctic Ocean will experience much greater acidification and warming than temperate or tropical species. Also, possible interactions of ocean warming and acidification are still understudied. Here we analysed the combined effects of warming and acidification on behavioural patterns of 2 fish species co-occurring around Svalbard, viz. polar cod Boreogadus saida and Atlantic cod Gadus morhua. We found a significant temperature effect on the spontaneous activity of B. saida, but not of G. morhua. Environmental CO2 did not significantly influence activity of either species. In con- trast, behavioural laterality of B. saida was affected by CO2 but not by temperature. Behavioural laterality of G. morhua was not affected by temperature or CO2; however, in this species, a possi- ble temperature dependency of CO2 effects on relative laterality may have been missed due to sample size restrictions. This study indicates that fish in polar ecosystems may undergo some, albeit less intense, behavioural disturbances under ocean acidification and in combination with ocean warming than observed in tropical species. It further accentuates species-specific differ- ences in vulnerability

Bewertung des Reittourismus in Sachsen

Der Freistaat Sachsen engagiert sich seit 1999 im Reittourismus. Schwerpunkte sind die Schaffung eines attraktiven Wegenetzes, die Entwicklung und Qualifizierung reittouristischer Angebote und deren Vermarktung. Die Marke 'Sachsen mit Pferd' ist konsequent weiterentwickelt worden und Bestandteil des Marketings der Landestouristik. Die Zwischenbilanz der Förderung des Reittourismus weist vielfältige Erfolge auf: Die Marke 'Sachsen mit Pferd' wurde entwickelt (Logo, PR, Angebote), rd. 600 Anbieter sind unter dem Produkt 'Sachsen mit Pferd'; zusammengefasst, Leitbild und Marketingstrategie wurden entwickelt, die reittouristischen Angebote wurden in die Marketingkampagne „SACHSENLand erleben“ aufgenommen, ein Zertifizierungssystem für die Reittourismusbetriebe wurde eingerichtet, das Internetportal „Sachsen mit Pferd“ ist seit 2003 online. Etwa 7 000 km Reitwege wurden beschildert. 15 (von 23 geplanten) Reitkarten sind erschienen. Der FN-Wettbewerb 'Pferdefreundliche Gemeinde'; wird auch in Sachsen durchgeführt, der Landes-Wettbewerb 'Pferdefreundliche Gaststätte' findet seit 2003 statt. Weiterbildungsmaßnahmen für Reitbetriebe (und reiterfreundliche Anbieter) wurden entwickelt, 2006 wurde der IHK-Zertifikatskurs 'Fachkraft für Reittourismus' etabliert, im Oktober 2007 gab es die beiden ersten erfolgreichen Absolventinnen. Die Förderung des Reittourismus in Sachsen verfolgt - neben den markenstrategischen und imagebezogenen Zielen - das Ziel der Förderung des ländlichen Raumes und die Unterstützung derlandwirtschaftlichen Betriebe. Stichworte sind u. a. Agrartourismus, Diversifizierung des Angebotes der landwirtschaftlichen Betriebe, Stärkung des Tourismus im ländlichen Raum. Die vorliegende Studie dient als Grundlage, um eine Zwischenbilanz der bisherigen Aktivitäten zu ziehen. Im Mittelpunkt der Überlegungen steht die Weichenstellung für die zukünftige Ausrichtung des Projektes 'Sachsen mit Pferd'

B and T cell acute lymphoblastic leukemia evade chemotherapy at distinct sites in the bone marrow

Persistence of residual disease after induction chemotherapy is a strong predictor of relapse in acute lymphoblastic leukemia (ALL). The bone marrow microenvironment may support treatment escape. Using 3D fluorescence imaging of 10 primary ALL xenografts we identify sites of predilection in the bone marrow for resistance to induction with dexamethasone, vincristine and doxorubicin. We detect B-cell precursor ALL cells predominantly in the perisinusoidal space at early engraftment and after chemotherapy. The spatial distribution of T-ALL cells was more widespread with contacts to endosteum, nestin+ pericytes and sinusoids. Dispersion of T-ALL cells in the bone marrow increased under chemotherapeutic pressure. A subset of slowly dividing ALL cells was transiently detected upon short-term chemotherapy, but not at residual disease after chemotherapy, challenging the notion that ALL cells escape treatment by direct induction of a dormant state in the niche. These lineage-dependent differences point to niche interactions that may be more specifically exploitable to improve treatment

Mutant IDH1 Differently Affects Redox State and Metabolism in Glial Cells of Normal and Tumor Origin

IDH1R132H (isocitrate dehydrogenase 1) mutations play a key role in the development of low-grade gliomas. IDH1wt converts isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+), whereas IDH1R132H uses α-ketoglutarate and NADPH to generate the oncometabolite 2-hydroxyglutarate (2-HG). While the effects of 2-HG have been the subject of intense research, the 2-HG independent effects of IDH1R132H are still ambiguous. The present study demonstrates that IDH1R132H expression but not 2-HG alone leads to significantly decreased tricarboxylic acid (TCA) cycle metabolites, reduced proliferation, and enhanced sensitivity to irradiation in both glioblastoma cells and astrocytes in vitro. Glioblastoma cells, but not astrocytes, showed decreased NADPH and NAD+ levels upon IDH1R132H transduction. However, in astrocytes IDH1R132H led to elevated expression of the NAD-synthesizing enzyme nicotinamide phosphoribosyltransferase (NAMPT). These effects were not 2-HG mediated. This suggests that IDH1R132H cells utilize NAD+ to restore NADP pools, which only astrocytes could compensate via induction of NAMPT. We found that the expression of NAMPT is lower in patient-derived IDH1-mutant glioma cells and xenografts compared to IDH1-wildtype models. The Cancer Genome Atlas (TCGA) data analysis confirmed lower NAMPT expression in IDH1-mutant versus IDH1-wildtype gliomas. We show that the IDH1 mutation directly affects the energy homeostasis and redox state in a cell-type dependent manner. Targeting the impairments in metabolism and redox state might open up new avenues for treating IDH1-mutant gliomas.publishedVersio

Disruption of Coronin 1 Signaling in T Cells Promotes Allograft Tolerance while Maintaining Anti-Pathogen Immunity

The ability of the immune system to discriminate self from non-self is essential for eradicating microbial pathogens but is also responsible for allograft rejection. Whether it is possible to selectively suppress alloresponses while maintaining anti-pathogen immunity remains unknown. We found that mice deficient in coronin 1, a regulator of naive T cell homeostasis, fully retained allografts while maintaining T cell-specific responses against microbial pathogens. Mechanistically, coronin 1-deficiency increased cyclic adenosine monophosphate (cAMP) concentrations to suppress allo-specific T cell responses. Costimulation induced on microbe-infected antigen presenting cells was able to overcome cAMP-mediated immunosuppression to maintain anti-pathogen immunity. In vivo pharmacological modulation of this pathway or a prior transfer of coronin 1-deficient T cells actively suppressed allograft rejection. These results define a coronin 1-dependent regulatory axis in T cells important for allograft rejection and suggest that modulation of this pathway may be a promising approach to achieve long-term acceptance of mismatched allografts

Pediatric T-ALL type-1 and type-2 relapses develop along distinct pathways of clonal evolution

The mechanisms underlying T-ALL relapse remain essentially unknown. Multilevel-omics in 38 matched pairs of initial and relapsed T-ALL revealed 18 (47%) type-1 (defined by being derived from the major ancestral clone) and 20 (53%) type-2 relapses (derived from a minor ancestral clone). In both types of relapse, we observed known and novel drivers of multidrug resistance including MDR1 and MVP, NT5C2 and JAK-STAT activators. Patients with type-1 relapses were specifically characterized by IL7R upregulation. In remarkable contrast, type-2 relapses demonstrated (1) enrichment of constitutional cancer predisposition gene mutations, (2) divergent genetic and epigenetic remodeling, and (3) enrichment of somatic hypermutator phenotypes, related to BLM, BUB1B/PMS2 and TP53 mutations. T-ALLs that later progressed to type-2 relapses exhibited a complex subclonal architecture, unexpectedly, already at the time of initial diagnosis. Deconvolution analysis of ATAC-Seq profiles showed that T-ALLs later developing into type-1 relapses resembled a predominant immature thymic T-cell population, whereas T-ALLs developing into type-2 relapses resembled a mixture of normal T-cell precursors. In sum, our analyses revealed fundamentally different mechanisms driving either type-1 or type-2 T-ALL relapse and indicate that differential capacities of disease evolution are already inherent to the molecular setup of the initial leukemia

Clusters of galaxies : observational properties of the diffuse radio emission

Clusters of galaxies, as the largest virialized systems in the Universe, are ideal laboratories to study the formation and evolution of cosmic structures...(abridged)... Most of the detailed knowledge of galaxy clusters has been obtained in recent years from the study of ICM through X-ray Astronomy. At the same time, radio observations have proved that the ICM is mixed with non-thermal components, i.e. highly relativistic particles and large-scale magnetic fields, detected through their synchrotron emission. The knowledge of the properties of these non-thermal ICM components has increased significantly, owing to sensitive radio images and to the development of theoretical models. Diffuse synchrotron radio emission in the central and peripheral cluster regions has been found in many clusters. Moreover large-scale magnetic fields appear to be present in all galaxy clusters, as derived from Rotation Measure (RM) studies. Non-thermal components are linked to the cluster X-ray properties, and to the cluster evolutionary stage, and are crucial for a comprehensive physical description of the intracluster medium. They play an important role in the cluster formation and evolution. We review here the observational properties of diffuse non-thermal sources detected in galaxy clusters: halos, relics and mini-halos. We discuss their classification and properties. We report published results up to date and obtain and discuss statistical properties. We present the properties of large-scale magnetic fields in clusters and in even larger structures: filaments connecting galaxy clusters. We summarize the current models of the origin of these cluster components, and outline the improvements that are expected in this area from future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics Review. 58 pages, 26 figure

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707