Die Ausdifferenzierung nationaler Innovationssysteme: Deutschland und Österreich im Vergleich

'Ausgehend von der Debatte über nationale Innovationssysteme und den zahlreichen Varianten zur systemischen Analyse von Innovationsprozessen, schlägt dieser Artikel ein integriertes Analysekonzept vor, indem er argumentiert, dass es nicht zur Herausbildung autonomer Innovationssysteme auf lokaler, regionaler oder gar europäischer und internationaler Ebene gekommen ist, sondern dass sich vielmehr das nationale Innovationssystem territorial ausdifferenziert hat. Im empirischen Teil wird am Beispiel Deutschlands und Österreichs das Ausmaß der Ausdifferenzierung nationaler Innovationssysteme in Richtung auf die europäische/ internationale Ebene oder auf die regionallokale Ebene anhand der von Lundvall eingeführten Indikatoren überprüft: formale Institutionen und Normen, Finanzsystem, Public Policies, Forschungs- und Bildungssystem sowie Unternehmensaktivitäten. Der Beitrag kommt zu dem Ergebnis, dass die nationalen Innovationssysteme einem beständigen Wandel unterliegen. Diese Ausdifferenzierung variiert wiederum innerhalb der Indikatoren und zwischen den Untersuchungsstaaten. Insgesamt soll dieser Ansatz ermöglichen, die Dynamik des gesamten Ausdifferenzierungsprozesses zu verdeutlichen, da er die wachsende Bedeutung sowohl der regionalen als auch der internationalen Ebene erfasst.' (Autorenreferat)'Starting from the debate about national systems of innovation and the various systemic analyses of innovation processes, this article proposes an integrated framework of analysis which argues that neither autonomous local or regional nor European or global systems of innovation have emerged, but rather that national systems of innovation have undergone a territorial transformation process. In its empirical part, the article investigates for the cases of Germany and Austria the extent to which the national innovation systems have been reconfigurated towards territorial levels above and below the national level according to Lundvall's indicators, i. e. formal institutions and norms, financial systems, public policies, science and education systems, and business activities. The article concludes that national systems of innovation are subject to continuous transformation. This territorial transformation in turn varies among indicators as well as across countries. Overall, the suggested approach allows for a better understanding of the whole transformation process since it captures the increasing significance of both the regional and international levels.' (author's abstract

A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response

The aim was to evaluate whether adjunctive T3 can help accelerate the antidepressant response and improve overall outcomes when used under naturalistic conditions. Fifty consecutive psychiatric outpatients diagnosed with major depressive disorder who were initiated on antidepressant therapy were randomized to receive adjunctive T3 or placebo in a double-blind manner over the course of 6 wk. There were no restrictions placed on the selection of antidepressant agent, dosing, ancillary medications, or psychotherapy, and there were few exclusion criteria. A positive response was defined as a > or = 50% reduction in Montgomery-Asberg Depression Rating Scale scores. Response rates were higher for the adjunctive T3 cohort compared to the adjunctive placebo cohort after 1 wk (45% vs. 24%) and 2 wk (57% vs. 33%) of treatment. The likelihood of experiencing a positive response at any point over the 6-wk trial was 4.5 times greater in the adjunctive T3 cohort (95% CI 1.3-15.7). The study provides preliminary evidence that T3 can successfully be used in clinical practice to accelerate the antidepressant response and improve overall outcomes. The effectiveness model may be an untapped mechanism for evaluating the value of psychopharmacological agents

Topological Entanglement Entropy in Chern-Simons Theories and Quantum Hall Fluids

We compute directly the entanglement entropy of spatial regions in Chern-Simons gauge theories in 2+1 dimensions using surgery. We use these results to determine the universal topological piece of the entanglement entropy for Abelian and non-Abelian quantum Hall fluids.Comment: 17 figures

Effect of ABCG2, OCT1, and ABCB1(MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial

Introduction Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated. Materials and Methods RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated. Results The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (‰) was retained as the only significant variable (P = .02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P = .04). Patients with an ABCG2/GUSB transcript level >4.5‰ (n = 93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (≤4.5‰; n = 39) had a 12-month TFR rate of 72% (95% CI, 55%-82%). Conclusion In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation

Coral δ18O evidence for Pacific Ocean mediated decadal variability in Panamanian ITCZ rainfall back to the early 1700s

In Central America, seasonal and interannual shifts in the position of the Intertropical Convergence Zone (ITCZ) control the hydrologic budget. To better understand long-term changes in regional ITCZ-driven precipitation we re-examined a coral δ18O record from a Porites lobata coral head near Secas Island (Core ID: S1) (7°59′ N, 82°3′ W) in the Gulf of Chiriquí on the Pacific side of Panamá. Linsley et al., (1994) originally published the 277-year time series and first described the presence of a narrow-band decadal cycle (period near 9–12 years) in δ18O. The original study did not present potential drivers for the decadal cycle, although they ruled out the influence of the sun spot cycle. Our re-analysis of this record supports the original interpretation that coral δ18O is largely responding to variations in precipitation and associated river discharge, but with a new proposed mechanism to explain the decadal mode. There is no similar decadal cycle in gridded instrumental sea surface temperature from the area, suggesting that the decadal coral δ18O signal results from hydrologic changes that influence coastal δ18O seawater. The decadal component in S1 δ18O is also coherent with a decadal mode embedded in the Pacific Decadal Oscillation (PDO) Index that we suggest has tropical origins. We speculate that the coral's temporary δ18O deviation (1900–1930) in the decadal mode from the corresponding bands in rainfall and the PDO can be ascribed to a weak PDO in addition to local Panama gap wind variability and its effect on moisture transport from the Atlantic to the Pacific. Ultimately, the Secas Island coral δ18O series records ITCZ-driven precipitation dictated by both the Atlantic and Pacific basins

Influenza Infection in Wild Raccoons

Raccoons can transmit avian and human influenza Influenza Infection in Wild Raccoon

A tracer study of the Arctic Ocean's liquid freshwater export variability

We present an analysis of the variability of the liquid Arctic freshwater (FW) export, using a simulation from the Community Climate System Model Version 3 (CCSM3) that includes passive tracers for FW from different sources. It is shown that the FW exported through the western Canadian Arctic Archipelago (CAA) comes mainly from the Pacific and from North American runoff. The variability of the FW export from both of these sources is generally in phase, due to the strong influence of variations of the velocity anomaly on the CAA FW export variability. The velocity anomaly in the CAA is in turn mainly governed by variations in the large-scale atmospheric circulation (i.e., the Arctic Oscillation). In Fram Strait, the FW export is mainly composed of Eurasian runoff and FW of Pacific origin. The variability of the Fram Strait FW export is governed both by changes in the velocity and in the FW concentration, and the variability of the FW concentration from the two largest sources is not in phase. The Eurasian runoff export through Fram Strait depends strongly on the release of FW from the Eurasian shelf, which occurs during years with an anticyclonic circulation anomaly (negative Vorticity index) and takes 3 years to reach Fram Strait after leaving the shelf. In contrast, the variability of the Pacific FW export through Fram Strait is mainly controlled by changes in the Pacific FW storage in the Beaufort Gyre, with an increased export during years with a cyclonic circulation anomaly (positive Vorticity index)

Atlantic Water advection versus sea-ice advances in the eastern Fram Strait during the last 9 ka - multiproxy evidence for a two-phase Holocene

A sediment core from the West Spitsbergen continental margin was studied to reconstruct climate and paleoceanographic variability during the last ~9 ka in the eastern Fram Strait. Our multiproxy evidence suggests that the establishment of the modern oceanographic configuration in the eastern Fram Strait occurred stepwise, in response to the postglacial sea-level rise and the related onset of modern sea-ice production on the shallow Siberian shelves. The late Early and Mid Holocene interval (9 to 5 ka) was generally characterized by relatively unstable conditions. High abundance of the subpolar planktic foraminifer species Turborotalita quinqueloba implies strong intensity of Atlantic Water (AW) inflow with high productivity and/or high AW temperatures, resulting in a strong heat flux to the Arctic. A series of short-lived cooling events (8.2, 6.9. and 6.1 ka) occurred superimposed on the warm late Early and Mid Holocene conditions. Our proxy data imply that simultaneous to the complete postglacial flooding of Arctic shallow shelves and the initiation of modern sea-ice production, strong advance of polar waters initiated modern oceanographic conditions in the eastern Fram Strait at ~5.2 ka. The Late Holocene was marked by the dominance of the polar planktic foraminifer species Neogloboquadrina pachyderma, a significant expansion of sea ice/icebergs, and strong stratification of the water column. Although planktic foraminiferal assemblages as well as sea surface and subsurface temperatures suggest a return of slightly strengthened advection of subsurface Atlantic Water after 3 ka, a relatively stable cold-water layer prevailed at the sea surface and the study site was probably located within the seasonally fluctuating marginal ice zone during the Neoglacial period

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe