Teil 2: Handlungsoptionen entwickeln und Entscheidungen treffen

Technologieentwicklungen frühzeitig und richtig einzuschätzen ist ausschlaggebend für den nachhaltigen Erfolg von Technologieunternehmen. Durch die weltweite Zunahme und Beschleunigung der Forschungs- und Entwicklungsaktivitäten sowie steigende Verflechtung von Wertschöpfungsketten wird dies zunehmend schwieriger. In Teil eins dieses Praxisleitfadens wurde ein Überblick über unterschiedliche Indikatoren zur Bewertung und Einstufung von Technologien geschaffen. Ziel dieses Leitfadens ist es, eine Anleitung zu geben, um mit Hilfe der Indikatoren die Entwicklungsaktivitäten technologischer Innovationen abbilden zu können. Unter Berücksichtigung unternehmensspezifischer Stärken und Schwächen, dient dies als Entscheidungshilfe zur Wahl der passenden Timing- und Technologiestrategie

How to assess technological developments in basic research? Enabling formative interventions regarding sustainability, ethics, and consumer issues at an early stage

In an era of ever faster and more momentous technological development, both technology assessment and transdisciplinary interventions are in danger of structurally lagging behind the speed of innovation. This paper proposes a new tiered approach to technology assessment at low Technology Readiness Levels that enables a both rapid and concerted interdisciplinary science response to this Great Acceleration. Covering sustainability, ethics, and consumer issues, this approach encourages and enables the innovators themselves to conduct assessments embedded in the innovation process as early as possible. Suitable tools for early engagement that help facilitate development-integrated assessments are introduced and described. The design and use of these instruments in the field of basic research is illustrated using the Cluster of Excellence livMatS as an example.In einer Ära immer rascherer und folgenreicherer technologischer Entwicklungen laufen sowohl die Technologiebewertung als auch transdisziplinäre Interventionen Gefahr, strukturell hinter der Dynamik von Innovationen zurückzubleiben. In diesem Beitrag wird ein neuer gestufter Ansatz für die Technikfolgenabschätzung für niedrige Technology Readiness Levels vorgeschlagen, der eine schnelle und konzertierte interdisziplinäre Reaktion der Wissenschaft auf diese "große Beschleunigung" ermöglicht. Dieser Ansatz, der Nachhaltigkeits-, Ethik- und Verbraucherfragen abdeckt, ermutigt und befähigt die Innovatoren, in den Innovationsprozess eingebettete Bewertungen so früh wie möglich selbst durchzuführen. Geeignete Instrumente für entwicklungsintegrierte Bewertungen werden vorgestellt und beschrieben. Die Konzeption und Anwendung dieser Instrumente im Bereich der Grundlagenforschung wird am Beispiel des Exzellenzclusters livMatS veranschaulicht

An R-Package for the Deconvolution and Integration of 1D NMR Data: MetaboDecon1D

NMR spectroscopy is a widely used method for the detection and quantification of metabolites in complex biological fluids. However, the large number of metabolites present in a biological sample such as urine or plasma leads to considerable signal overlap in one-dimensional NMR spectra, which in turn hampers both signal identification and quantification. As a consequence, we have developed an easy to use R-package that allows the fully automated deconvolution of overlapping signals in the underlying Lorentzian line-shapes. We show that precise integral values are computed, which are required to obtain both relative and absolute quantitative information. The algorithm is independent of any knowledge of the corresponding metabolites, which also allows the quantitative description of features of yet unknown identity

Comparison of Structural Subscapularis Integrity After Latarjet Procedure Versus Iliac Crest Bone Graft Transfer

Background: Although clinical outcome scores are comparable after coracoid transfer procedure (Latarjet) and iliac crest bone graft transfer (ICBGT) for anterior shoulder instability with glenoid bone loss, a significant decrease in internal rotation capacity has been reported for the Latarjet procedure. Hypothesis: The subscapularis (SSC) musculotendinous integrity will be less compromised by ICBGT than by the Latarjet procedure. Study Design: Cohort study; Level of evidence, 3. Methods: We retrospectively analyzed pre- and postoperative computed tomography (CT) scans at short-term follow-up of 52 patients (26 Latarjet, 26 ICBGT) previously assessed in a prospective randomized controlled trial. Measurements included the preoperative glenoid defect area and graft area protruding the glenoid rim at follow-up and tendon thickness assessed through SSC and infraspinatus (ISP) ratios. Fatty muscle infiltration was graded according to Goutallier, quantified with muscle attenuation in Hounsfield units, and additionally calculated as percentages. We measured 3 angles to describe rerouting of the SSC musculotendinous unit around the bone grafts. Results: SSC fatty muscle infiltration was 2.0% ± 2.2% in the Latarjet group versus 2.4% ± 2.2% in ICBGT (P = .546) preoperatively and showed significantly higher values in the Latarjet group at follow-up (5.3% ± 4.5% vs 2.3% ± 1.7%; P = .001). In total, 4 patients (15.4%) in the Latarjet group showed a progression from grade 0 to grade 1 at follow-up, whereas no changes in the ICBGT group were noted. The measured rerouting angle of the SSC muscle was significantly increased in the Latarjet group (11.8° ± 2.1°) compared with ICBGT (7.5° ± 1.3°; P < .001) at follow-up, with a significant positive correlation between this angle and fatty muscle infiltration (R = 0.447; P = .008). Ratios of SSC/ISP tendon thickness were 1.03 ± 0.3 in the Latarjet group versus 0.97 ± 0.3 (P = .383) in ICBGT preoperatively and showed significantly lower ratios in the Latarjet group (0.7 ± 0.3 vs 1.0 ± 0.2; P < .001) at follow-up. Conclusion: Although clinical outcome scores after anterior shoulder stabilization with a Latarjet procedure and ICBGT are comparable, this study shows that the described decline in internal rotation capacity after Latarjet procedure has a radiographic structural correlate in terms of marked thinning and rerouting of the SSC tendon as well as slight fatty degeneration of the muscle

Conservative treatment of acute traumatic posterior shoulder dislocations (Type A) is a viable option especially in patients with centred joint, low gamma angle, and middle or old age

Purpose: Purpose of this study was to evaluate the mid- to long-term outcome after conservatively treated first-time posterior shoulder dislocations and to determine structural defects associated with failure. Methods: In this multi-centric retrospective study, 29 shoulders in 28 patients with first-time acute posterior shoulder dislocation (Type A1 or A2 according to the ABC classification) and available cross-sectional imaging were included. Outcome scores as well as radiological and magnetic resonance imaging were obtained at a mean follow-up of 8.3 +/- 2.7 years (minimum: 5 years). The association of structural defects with redislocation, need for secondary surgery, and inferior clinical outcomes were analysed. Results: Redislocation occurred in six (21%) shoulders and nine shoulders (31%) underwent secondary surgery due to persistent symptoms. The posttraumatic posterior glenohumeral subluxation was higher in the redislocation group compared to the no redislocation group; however, statistical significance was not reached (61.9 +/- 12.5% vs. 50.6 +/- 6.4%). Furthermore, a higher adapted gamma angle was observed in the failed conservative treatment group versus the conservative treatment group, similarly without statistically significant difference (97.8 degrees +/- 7.2 degrees, vs. 93.3 degrees +/- 9.7 degrees). The adapted gamma angle was higher than 90 degrees in all patients of failed conservative therapy and the redislocation group. An older age at the time of dislocation showed a significant correlation with better clinical outcomes (SSV: r = 0.543, p = 0.02; ROWE: r = 0.418, p = 0.035 and WOSI: r = 0.478, p = 0.045). Posterior glenohumeral subluxation after trauma correlated with a worse WOSI (r = - 0.59, p = 0.02) and follow-up posterior glenohumeral decentring (r = 0.68, p = 0.007). The gamma angle (r = 0.396, p = 0.039) and depth of the reverse Hill-Sachs lesion (r = 0.437, p = 0.023) correlated significantly with the grade of osteoarthritis at follow-up. Conclusion: Conservative treatment is a viable option in patients with an acute traumatic posterior shoulder dislocation with good outcome after mid- and long-term follow-up especially in patients with centred joint, low gamma angle, and middle or old age

The 1356 Basel earthquake: an interdisciplinary revision

Within historical times one of the most damaging events in intra-plate Europe was the 1356 Basel earthquake. Given its significance for assessing regional seismic hazard in central Europe, an interdisciplinary project was launched in 2005 to re-explore this event. Our effort aimed to incorporate techniques from history, seismology, archaeology, paleoseismology and engineering. New and reinterpreted historical data from Basel and its surroundings plus archaeological findings on buildings that survived the event and still exist enabled this macroseismic assessment. Palaeoseismological studies combined with historical evidence provided additional data. For the surrounding areas, archaeology offers sparse information on some castles and churches, sometimes supported by historical records. A contemporary source allows some reconstruction of the stronger fore- and aftershocks. This expanded information base improves our sense of the event's damage and consequences. For the city of Basel, the relatively abundant archaeological data allowed us to assess statistically the macroseismic intensity at IX, although the pattern of damage was scattered. Data points for the expected area of damage around Basel are not distributed regularly. The absence of historical and archaeological findings for southern Germany might be due to archival problems; future investigation may improve this situation. Our results confirm that the Basel earthquake was the most destructive known for central Europe. Intensities up to VIII are found within a radius of about 30 km. Analysing the macroseismic field confirms our former assessment of the event and shows an epicenter located about 10 km south of Basel. The most probable range for the moment magnitude Mw is between 6.7 and 7.

Empagliflozin increases kidney weight due to increased cell size in the proximal tubule S3 segment and the collecting duct

The inhibition of renal SGLT2 glucose reabsorption has proven its therapeutic efficacy in chronic kidney disease. SGLT2 inhibitors (SGLTi) have been intensively studied in rodent models to identify the mechanisms of SGLT2i-mediated nephroprotection. So far, the overwhelming effects from clinical trials, could only partially be reproduced in rodent models of renal injury. However, a commonly disregarded observation from these studies, is the increase in kidney weight after SGLT2i administration. Increased kidney mass often relies on tubular growth in response to reabsorption overload during glomerular hyperfiltration. Since SGLT2i suppress hyperfiltration but concomitantly increase renal weight, it seems likely that SGLT2i have a growth promoting effect on the kidney itself, independent of GFR control. This study aimed to investigate the effect of SGLT2i on kidney growth in wildtype animals, to identify enlarged nephron segments and classify the size increase as hypertrophic/hyperplastic growth or cell swelling. SGLT2i empagliflozin increased kidney weight in wildtype mice by 13% compared to controls, while bodyweight and other organs were not affected. The enlarged nephron segments were identified as SGLT2-negative distal segments of proximal tubules and as collecting ducts by histological quantification of tubular cell area. In both segments protein/DNA ratio, a marker for hypertrophic growth, was increased by 6% and 12% respectively, while tubular nuclei number (hyperplasia) was unchanged by empagliflozin. SGLT2-inhibition in early proximal tubules induces a shift of NaCl resorption along the nephron causing compensatory NaCl and H2O reabsorption and presumably cell growth in downstream segments. Consistently, in collecting ducts of empagliflozin-treated mice, mRNA expression of the Na+-channel ENaC and the H2O-channels Aqp-2/Aqp-3 were increased. In addition, the hypoxia marker Hif1α was found increased in intercalated cells of the collecting duct together with evidence for increased proton secretion, as indicated by upregulation of carbonic anhydrases and acidified urine pH in empagliflozin-treated animals. In summary, these data show that SGLT2i induce cell enlargement by hypertrophic growth and possibly cell swelling in healthy kidneys, probably as a result of compensatory glucose, NaCl and H2O hyperreabsorption of SGLT2-negative segments. Particularly affected are the SGLT2-negative proximal tubules (S3) and the collecting duct, areas of low O2 availability

Estrategias y coordinación en el subsistema de agronegocios de cacao orgánico en la región de San Martín : el caso ACOPAGRO

Actualmente grandes cambios en las cadenas agroalimentarias causadas por los consumidores, han generado el desarrollo de productos diferenciados, que en su mayoría son producidos por pequeños productores, tal es el caso del cacao orgánico. Durante los últimos años el Perú se ha consolidado como un importante exportador de cacao fino, aromático y orgánico, siendo San Martín una de las principales regiones productoras. Este subsistema de agronegocios, presentaba serias perturbaciones, tales como, inacceso a créditos para productores, inexistencia de alianzas estratégicas, y una baja coordinación entre los actores del sistema, así mismo la existencia de intermediarios que generaban gran oportunismo e incertidumbre por el precio del cacao que percibían los productores; todo ello ocasionaba elevados costos en las transacciones. Es en este contexto que se crea la Cooperativa Agraria Cacaotera ACOPAGRO, que se ha desempeñado de manera exitosa en los últimos años, siendo líder en la exportación de cacao orgánico. De aquí parte el objetivo de esta investigación, la cual es conocer las nuevas estrategias y formas de coordinación en agronegocios, utilizando el caso ACOPAGRO. La metodología utilizada fue la epistemología fenomenológica a través de un estudio de caso. Sustentada teóricamente en la Nueva Economía Institucional aplicada a los Negocios Agroalimentarios, fundamentalmente la economía de los costos de transacción. Los resultados obtenidos definen a ACOPAGRO como subsistema estrictamente coordinado, producto de la acción colectiva, con objeto de abastecer al mercado internacional exigente. Pues esta cooperativa se ha desarrollado eficientemente, adaptándose a las distintas perturbaciones y oportunidades de mercado; estratégicamente con una innovación en su diseño organizacional que permitió implementar tecnología, crear incentivos y poder adecuar controles. Además de convertirse en el coordinador del subsistema, ACOPAGRO optó en nuevas formas de gobernancia en sus transacciones, alineándolas de tal forma que permitan salvaguardar los activos específicos invertidos por los productores y reducir la incertidumbre, bajando así los costos de transacción

Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys

The natriuretic peptides (NPs) ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide) mediate their widespread effects by activating the natriuretic peptide receptor-A (NPR-A), while C-type natriuretic peptide (CNP) acts via natriuretic peptide receptor-B (NPR-B). NPs are removed from the circulation by internalization via the natriuretic peptide clearance receptor natriuretic peptide receptor-C (NPR-C). In addition to their well-known functions, for instance on blood pressure, all three NPs confer significant cardioprotection and renoprotection. Since neither the NP-mediated renal functions nor the renal target cells of renoprotection are completely understood, we performed systematic localization studies of NP receptors using in situ hybridization (RNAscope) in mouse kidneys. NPR-A mRNA is highly expressed in glomeruli (mainly podocytes), renal arterioles, endothelial cells of peritubular capillaries, and PDGFR-receptor β positive (PDGFR-β) interstitial cells. No NPR-A mRNA was detected by RNAscope in the tubular system. In contrast, NPR-B expression is highest in proximal tubules. NPR-C is located in glomeruli (mainly podocytes), in endothelial cells and PDGFR-β positive cells. To test for a possible regulation of NPRs in kidney diseases, their distribution was studied in adenine nephropathy. Signal intensity of NPR-A and NPR-B mRNA was reduced while their spatial distribution was unaltered compared with healthy kidneys. In contrast, NPR-C mRNA signal was markedly enhanced in cell clusters of myofibroblasts in fibrotic areas of adenine kidneys. In conclusion, the primary renal targets of ANP and BNP are glomerular, vascular, and interstitial cells but not the tubular compartment, while the CNP receptor NPR-B is highly expressed in proximal tubules. Further studies are needed to clarify the function and interplay of this specific receptor expression pattern

Empagliflozin Reduces Renal Hyperfiltration in Response to Uninephrectomy, but Is Not Nephroprotective in UNx/DOCA/Salt Mouse Models

Large-scale clinical outcome studies demonstrated the efficacy of SGLT2 inhibitors in patients with type II diabetes. Besides their therapeutic efficacy in diabetes, significant renoprotection was observed in non-diabetic patients with chronic kidney disease (CKD), suggesting the existence of glucose-independent beneficial effects of SGLT2 inhibitors. However, the relevant mechanisms by which SGLT2 inhibition delays the progression of renal injury are still largely unknown and speculative. Previous studies showed that SGLT2 inhibitors reduce diabetic hyperfiltration, which is likely a key element in renoprotection. In line with this hypothesis, this study aimed to investigate the nephroprotective effects of the SGLT2 inhibitor empagliflozin (EMPA) in different mouse models with non-diabetic hyperfiltration and progressing CKD to identify the underlying diabetes-independent cellular mechanisms. Non-diabetic hyperfiltration was induced by unilateral nephrectomy (UNx). Since UNx alone does not result in renal damage, renal disease models with varying degrees of glomerular damage and albuminuria were generated by combining UNx with high NaCl diets ± deoxycorticosterone acetate (DOCA) in different mouse strains with and without genetic predisposition for glomerular injury. Renal parameters (GFR, albuminuria, urine volume) were monitored for 4–6 weeks. Application of EMPA via the drinking water resulted in sufficient EMPA plasma concentration and caused glucosuria, diuresis and in some models renal hypertrophy. EMPA had no effect on GFR in untreated wildtype animals, but significantly reduced hyperfiltration after UNx by 36%. In contrast, EMPA did not reduce UNx induced hyperfiltration in any of our kidney disease models, regardless of their degree of glomerular damage caused by DOCA/salt treatment. Consistent with the lack of reduction in glomerular hyperfiltration, EMPA-treated animals developed albuminuria and renal fibrosis to a similar extent as H2O control animals. Taken together, the data clearly indicate that blockade of SGLT2 has the potential to reduce non-diabetic hyperfiltration in otherwise untreated mice. However, no effects on hyperfiltration or progression of renal injury were observed in hypervolemic kidney disease models, suggesting that high salt intake and extracellular volume might attenuate the protective effects of SGLT2 blockers