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Background: We assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria. Methods: Cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by computer tomography or magnetic resonance imaging perfusion with automated software (RAPID or OLEA). We excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days. Results: Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46 [1.02–2.10]; P =0.04) and lower odds of all-cause mortality within 90 days (aOR, 0.59 [0.37–0.93]; P =0.02). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P =0.63). Conclusions: Two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.

Effective risk factor modification is the prerequisite to prevent neurovascular disease such as stroke or vascular dementia. Non-traditional vascular risk factors (nt-vrfs) including stress significantly add to the risk of neurovascular disease arising from traditional vascular risk factors (t-vrfs). In order to discover sex-specific changes that may underlie previously reported inclines in the prevalence of neurovascular and cardiovascular disease in women, 10-year trends in the prevalence of vrfs in Switzerland were assessed.Anonymized data from 22,134 participants (51% women) of the governmental Swiss Health Survey, performed every 5 years (2007, 2012 and 2017), were obtained. Epidemiological parameters, t-vrfs and nt-vrfs were analyzed in a cross-sectional study design.Over the observation period, the number of women having full-time jobs increased considerably (2007 38%, 2012 39%, 2017 44%). This was accompanied by a substantial rise in the prevalence of nt-vrfs in women and men including stress at work (2007, not available; 2012 women/men 58%/60%; 2017 women/men 66%/65%), low locus of control (women/men: 2007 21%/19%, 2012 22%/19%, 2017 25%/22%) and sleep disorders (women/men: 2007 30%/22%, 2012 28%/20%, 2017 32%/26%). Amongst t-vrfs, only the prevalence of obesity and hypercholesterolemia increased over time in both sexes, whilst other t-vrfs remained stable (hypertension [27%], diabetes [5%]) or decreased (smoking [9.4 cigarettes/day]).A rise in women's economic participation alongside a higher affection with nt-vrfs in the female Swiss population emphasizes the need to improve vascular risk stratification and implement effective preventive measures for neurovascular and cardiovascular disease.

Climate change not only impacts production and market consumption but also the relative scarcity of nonmarket goods, such as environmental amenities. We study fundamental drivers of the resulting relative price changes, their potential magnitude, and their implications for climate policy in Nordhaus’s Dynamic Integrated Climate-Economy (DICE) model, thereby addressing one of its key criticisms. We propose plausible ranges for these relative prices changes based on best available evidence. Our central calibration reveals that accounting for relative prices is equivalent to decreasing pure time preference by 0.6 percentage points and leads to a more than 50 percent higher social cost of carbon. (JEL D61, H43, Q51, Q54, Q58)

The extent of future climate change is a policy choice. Using an integrated climate-economy assessment model, we estimate climate policy curves (CPCs) that link the price of carbon dioxide (CO2) to subsequent global temperatures. The resulting downward sloping CPCs quantify the inverse relationship between carbon prices and future temperatures and illustrate how climate policy choices determine climate outcomes. Our analysis can account for a variety of climate policies – for example, carbon or fuel taxes, emissions trading programs, green subsidies, and energy-efficiency regulations – all of which can be summarized by means of an effective CO2 price. Importantly, we also examine CPC uncertainty, for example, by perturbing the model's equilibrium climate sensitivity to trace out the temperature range associated with a given CO2 price. Finally, based on the latest Intergovernmental Panel on Climate Change (IPCC) integrated-assessment model scenarios, we estimate an implicit CPC, which provides a high-level IPCC summary of the climate policy actions required to achieve global climate targets.

In many medical applications, interpretable models with high prediction performance are sought. Often, those models are required to handle semi-structured data like tabular and image data. We show how to apply deep transformation models (DTMs) for distributional regression which fulfill these requirements. DTMs allow the data analyst to specify (deep) neural networks for different input modalities making them applicable to various research questions. Like statistical models, DTMs can provide interpretable effect estimates while achieving the state-of-the-art prediction performance of deep neural networks. In addition, the construction of ensembles of DTMs that retain model structure and interpretability allows quantifying epistemic and aleatoric uncertainty. In this study, we compare several DTMs, including baseline-adjusted models, trained on a semi-structured data set of 407 stroke patients with the aim to predict ordinal functional outcome three months after stroke. We follow statistical principles of model-building to achieve an adequate trade-off between interpretability and flexibility while assessing the relative importance of the involved data modalities. We evaluate the models for an ordinal and dichotomized version of the outcome as used in clinical practice. We show that both, tabular clinical and brain imaging data, are useful for functional outcome prediction, while models based on tabular data only outperform those based on imaging data only. There is no substantial evidence for improved prediction when combining both data modalities. Overall, we highlight that DTMs provide a powerful, interpretable approach to analyzing semi-structured data and that they have the potential to support clinical decision making., Preprint under review

We model a stylized economy dependent on agriculture and fisheries to study optimal environmental policy in the face of interacting external effects of ocean acidification, global warming, and eutrophication. This allows us to capture some of the latest insights from research on ocean acidification. Using a static two-sector general equilibrium model we derive optimal rules for national taxes on (Formula presented.) emissions and agricultural run-off and show how they depend on both isolated and interacting damage effects. In addition, we derive a second-best rule for a tax on agricultural run-off of fertilizers for the realistic case that effective internalization of (Formula presented.) externalities is lacking. The results contribute to a better understanding of the social costs of ocean acidification in coastal economies when there is interaction with other environmental stressors. Recommendations for Resource Managers: Marginal environmental damages from (Formula presented.) emissions should be internalized by a tax on (Formula presented.) emissions that is high enough to not only reflect marginal damages from temperature increases, but also marginal damages from ocean acidification and the interaction of both with regional sources of acidification like nutrient run-off from agriculture. In the absence of serious national policies that fully internalize externalities, a sufficiently high tax on regional nutrient run-off of fertilizers used in agricultural production can limit not only marginal environmental damages from nutrient run-off but also account for unregulated carbon emissions. Putting such regional policies in place that consider multiple important drivers of environmental change will be of particular importance for developing coastal economies that are likely to suffer the most from ocean acidification.

We develop a model of optimal carbon taxation and redistribution taking into account horizontal equity concerns by considering heterogeneous energy efficiencies. By deriving first- and second-best rules for policy instruments including carbon taxes, transfers and energy subsidies, we then investigate analytically how horizontal equity is considered in the social welfare maximizing tax structure. We calibrate the model to German household data and a 30 percent emission reduction goal. Our results show that energy-intensive households should receive more redistributive resources than energy-efficient households if and only if social inequality aversion is sufficiently high. We further find that redistribution of carbon tax revenue via household-specific transfers is the first-best policy. Equal per-capita transfers do not suffer from informational problems, but increase mitigation costs by around 15 percent compared to the first- best for unity inequality aversion. Adding renewable energy subsidies or non-linear energy subsidies, reduces mitigation costs further without relying on observability of households’ energy efficiency.

We develop a model of optimal carbon taxation and redistribution taking into account horizontal equity concerns by considering heterogeneous energy efficiencies. By deriving first- and second-best rules for policy instruments including carbon taxes, transfers and energy subsidies, we then investigate analytically how horizontal equity is considered in the social welfare maximizing tax structure. We calibrate the model to German household data and a 30 percent emission reduction goal. Our results show that energy-intensive households should receive more redistributive resources than energy-efficient households if and only if social inequality aversion is sufficiently high. We further find that redistribution of carbon tax revenue via household-specific transfers is the first-best policy. Equal per-capita transfers do not suffer from informational problems, but increase mitigation costs by around 15 percent compared to the first- best for unity inequality aversion. Adding renewable energy subsidies or non-linear energy subsidies, reduces mitigation costs further without relying on observability of households’ energy efficiency., CEPA Discussion Papers; 28

Climate change not only impacts production and market consumption, but also the relative scarcity of non-market goods, such as environmental amenities. We study fundamental drivers of the resulting relative price changes, their potential magnitude, and their implications for climate policy in Nordhaus' prominent DICE model, thereby addressing one of its key criticisms. We propose plausible ranges for these relative prices changes based on best available evidence. Our central calibration reveals that accounting for relative prices is equivalent to decreasing pure time preference by 0.6 percentage points and leads to a more than 50 percent higher social cost of carbon.

We study how the scarcity of non-market goods, such as environmental amenities, affects the economic appraisal of climate policy. To this end, we perform a comprehensive analysis of the change in relative prices of non-market goods in the widespread climate-economy model DICE. We show that DICE already contains relative prices implicitly and that the impact of the scarcity of non-market goods on climate policy evaluation is therefore more pervasive than previously suggested. We calibrate DICE based on empirical evidence and propose a plausible range for relative price changes. The uncertainty is substantial, with relative price changes ranging from 1.3 to 9.6 percent in 2020. For our central calibration, the relative price change amounts to 4.4 percent in 2020. Neglecting relative prices leads to an underestimation of the social cost of carbon in 2020 of more than 40 percent. Accounting for these changes is equivalent to a decrease in pure time preference by more than a half percentage point. Our findings support initiatives to consider relative prices in governmental project appraisal and offer guidance for the evaluation of climate policy.

The Arctic Ocean is an early warning system for indicators and effects of climate change. We use a novel combination of experimental and time-series data on effects of ocean warming and acidification on the commercially important Northeast Arctic cod (Gadus morhua) to incorporate these physiological processes into the recruitment model of the fish population. By running an ecological-economic optimization model, we investigate how the interaction of ocean warming, acidification and fishing pressure affects the sustainability of the fishery in terms of ecological, economic, social and consumer-related indicators, ranging from present day conditions up to future climate change scenarios. We find that near-term climate change will benefit the fishery, but under likely future warming and acidification this large fishery is at risk of collapse by the end of the century, even with the best adaptation effort in terms of reduced fishing pressure.

This doctoral thesis addresses central aspects of climate change economics including economic damages from climate change, discounting and intergenerational equity as well as sustainability in the light of increasing scarcity of non-market goods. Chapter 2 studies how the optimal global effort to mitigate carbon dioxide depends on conceptions of intergenerational equity by avoiding explicit discounting choices, but instead directly specifying alternative intertemporal distributions of well-being. The advantage of this approach is that it becomes very clear that the social cost of carbon is largely determined by normative conceptions of intergenerational distributive justice. Chapter 3 is concerned with the increasing scarcity of non-market goods due to climate change. It provides a comprehensive analysis of the change in the relative price of non-market goods in terms of market goods, its determinants and its impact on climate policy evaluation. For the central calibration neglecting relative price changes would lead to a considerable underestimation of the social cost of carbon of almost 50 percent for the current generation. The changing relative price of non-market goods in terms of market goods is of considerable magnitude compared to established determinants of economic evaluation. Chapter 4 assesses how economic damages from climate change can be mitigated when global warming interacts with other global and local environmental change within a national economy. It describes a developing economy that depends on agriculture and fisheries to study optimal and second-best environmental policy in the face of interacting external effects of ocean acidification, global warming and eutrophication. The last chapter of my dissertation reveals that although climate change is a global phenomenon and only a global solution can tackle it entirely, it can be vital to design national policy instruments that capture regional distinctiveness of environmental change under increasing carbon dioxide levels.

Human-induced climate change such as ocean warming and acidification, threatens marine ecosystems and associated fisheries. In the Western Baltic cod stock socio-ecological links are particularly important, with many relying on cod for their livelihoods. A series of recent experiments revealed that cod populations are negatively affected by climate change, but an ecological-economic assessment of the combined effects, and advice on optimal adaptive management are still missing. For Western Baltic cod, the increase in larval mortality due to ocean acidification has experimentally been quantified. Time-series analysis allows calculating the temperature effect on recruitment. Here, we include both processes in a stock-recruitment relationship, which is part of an ecological-economic optimization model. The goal was to quantify the effects of climate change on the triple bottom line (ecological, economic, social) of the Western Baltic cod fishery. Ocean warming has an overall negative effect on cod recruitment in the Baltic. Optimal management would react by lowering fishing mortality with increasing temperature, to create a buffer against climate change impacts. The negative effects cannot be fully compensated, but even at 3 °C warming above the 2014 level, a reduced but viable fishery would be possible. However, when accounting for combined effects of ocean warming and acidification, even optimal fisheries management cannot adapt to changes beyond a warming of +1.5° above the current level. Our results highlight the need for multi-factorial climate change research, in order to provide the best available, most realistic, and precautionary advice for conservation of exploited species as well as their connected socio-economic systems.

We explore how the intertemporal distribution of well-being affects the social cost of carbon. In contrast to the literature that studies parameters of a particular social welfare function, such as the discount rate, we shift the focus and directly assume a parametric form for the intertemporal distribution of well-being. This has the advantage of avoiding explicit discounting choices, which has initiated much debate. Specifically, we consider a set of intertemporal distributions that reach a steady-state at a pre-specified level of “sufficient” well-being, or equivalently after a pre-specified “end-of-growth horizon”. We numerically illustrate our results in DICE and find that the social cost of carbon increases over-proportionally with the sufficiency level of well-being. While the social cost of carbon in 2015 is US$ 7 if the sufficiency level is four-fold the present level, it is US$ 30 if the sufficiency level is 15-fold, and US$ 100 if the sufficiency level is 26-fold the present level. This shows in a transparent way how conceptions of intergenerational distributive justice drive the social cost of carbon.

A broad range of immunosuppressive and immunomodulatory effects of heat shock protein 90 (Hsp90) blockade has been described in models of autoimmune bullous diseases, but the direct contribution of this chaperone to neutrophil effector pathways in the context of autoantibody-driven blistering is generally unknown. Therefore, this has been addressed in the current study on the basis of the subepidermal blistering disease epidermolysis bullosa acquisita (EBA) characterized by autoantibodies against type VII collagen, in which a crucial role of neutrophils and both their reactive oxygen species and matrix metalloproteinases in mediating tissue injury has been established. First, the Hsp90 antagonist 17-DMAG dose-dependently inhibited dermal-epidermal separation ex vivo in cryosections of human skin induced by co-incubation of EBA patient autoantibodies with neutrophils from healthy blood donors. Next, 17-DMAG dose-dependently suppressed production and release of reactive oxygen species by human neutrophils induced by both fMLP ± LPS and EBA-specific immune complexes. In addition, co-immunoprecipitation studies revealed that extracellular Hsp90 interacted with secreted matrix metalloproteinases 2 and 12 in sera of EBA patients, suggesting that these basement membrane-degrading proteolytic enzymes are client proteins of Hsp90 and dependent on its chaperone function. Our findings add to the knowledge of the multimodal anti-inflammatory effects of Hsp90 blockade and implicate that Hsp90 is closely involved in the effector mechanisms of neutrophil-driven autoantibody-induced tissue damage, thus being a relevant therapeutic target in patients with neutrophil-mediated autoimmune diseases such as inflammatory types of EBA.

In mehrjährigen Stoppelbearbeitungsversuchen mit Grubbern, Scheiben- und Kreiseleggen sollten Einsatzhinweise zur Verringerung der Bodenerosion bei pflugloser Bodenbearbeitung für verschiedene Maschinentypen entwickelt werden. Dazu wurde vor allem die Bodenbedeckung mit Mulchmaterial als wichtiger Indikator für den Schutzgrad beobachtet. Zusätzlich wurden Daten zur Stroheinarbeitung in den Boden sowie zur Ausprägung der Bodenoberflächen und Bearbeitungssohlen ermittelt und der Zugleistungsbedarf für die Geräte gemessen. Im Ergebnis konnte der Bodenbedeckungsgrad nur wenig durch Veränderung der Einsatzbedingungen der Stoppelbearbeitungsmaschinen beeinflusst werden. In erosionsgefährdeten Gebieten kommt daher dem Zwischenfruchtanbau und Bodenbearbeitungsverfahren, die einen hohen Bodenbedeckungsgrad gewährleisten (Streifenbodenbearbeitung, Direktsaat), eine entscheidende Rolle zu. Der Bericht enthält die vollständigen Ergebnisse der Untersuchung.

Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps, and migration. Phagocytic ability and autoantibody-induced, neutrophil-dependent tissue injury ex vivo was also impaired by DMF. Regarding the mode of action, DMF modulates—in a stimulus-dependent manner-neutrophil activation using the phosphoinositide 3-kinase/Akt-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 pathways. For in vivo validation, mouse models of epidermolysis bullosa acquisita, an organ-specific autoimmune disease caused by autoantibodies to type VII collagen, were employed. In the presence of DMF, blistering induced by injection of anti-type VII collagen antibodies into mice was significantly impaired. DMF treatment of mice with clinically already-manifested epidermolysis bullosa acquisita led to disease improvement. Collectively, we demonstrate a profound inhibitory activity of DMF on neutrophil functions. These findings encourage wider use of DMF in patients with neutrophil-mediated diseases.

Im Bericht wird das Anbauverfahren für den ökologischen Speisekartoffelanbau komprimiert dargestellt. Eingeschlossen sind Angaben zur verlustarmen Lagerung und Aufbereitung sowie eine wirtschaftliche Bewertung des gesamten Anbauverfahrens. Ein Kapitel ist auch der Pflanzkartoffelerzeugung gewidmet.

Die Broschüre gibt grundlegende Hinweise zum Ablauf einer Umstellung auf die ökologische Wirtschaftsweise. Sie beschreibt die gesetzlichen Rahmenbedingungen, die Spezifika bei Pflanzenbau und Tierhaltung, die Bedeutung der Absatzwege und die finanzielle Förderung im Freistaat Sachsen. Adressen zu Kontrollstellen, Beratung und Verbänden sowie eine Zusammenstellung wichtiger Fachliteratur sind für die frühe Informations- und Planungsphase nützlich.

Kombiniert mit Versuchsergebnissen und Erfahrungsberichten aus der Praxis fasst die Broschüre die wichtigsten Anbauinformationen über die Ölfrüchte im ökologischen Landbau zusammen. Neben Raps, Sonnenblumen und Lein werden Aspekte des Anbaus von der Aussaat bis zur Ernte von bislang kaum angebauten Arten wie Senf, Leindotter, Ölmohn, Saflor und Sojabohnen beschrieben.

Nachhaltigkeit in der Landwirtschaft beinhaltet auch, Bodenerosion weitestgehend zu verhindern. Die Bodenbearbeitung bietet dafür einen wichtigen Ansatzpunkt. Technische Möglichkeiten, den Boden mit einer teilschlagspezifischen Variation der Arbeitstiefe beim Grubbern gezielter vor Abtrag zu schützen, wurden erstmals in Sachsen geprüft. Darüber hinaus zeigte eine Testreihe von technischen und pflanzenbaulichen Verfahren Wege auf, auch im Ökologischen Landbau den Bodenabtrag durch Niederschlagswasser noch weiter einzugrenzen.

Im Rahmen des Projektes „Unternehmensauswertung Ökologischer Landbau“ der Sächsischen Landesanstalt für Landwirtschaft wurden 16 ökologisch wirtschaftende Landwirtschaftsbetriebe über drei Wirtschaftsjahre betriebswirtschaftlich ausgewertet und einzelne Betriebszweige analysiert. Sechs der 16 Betriebe waren milchviehhaltende, sechs weitere mutterkuhhaltende Betriebe sowie weitere vier reine Marktfruchtbaubetriebe. Die Analysen bezogen sich auf den Marktfruchtbau, den Futterbau sowie die Milchvieh- bzw. Mutterkuhhaltung. Im Bereich des Futterbaus wurden die Erzeugungskosten einzelner Futtermittelarten ermittelt und die Einzelfuttermittel bewertet. Dabei stellte sich im Laufe der Analyse heraus, dass die Betriebsleiterangaben zu den Futterbauverfahren, insbesondere zu den Erträgen, häufig sehr ungenau waren. Teilweise waren keine Mengenaufzeichnungen im Betrieb vorhanden, teilweise wurden nur einfach zählbare Futtermittel quantitativ erfasst (Heuballen, Silageballen), jedoch nicht die in Fahrsilos gelagerten Futtermittel. Die Angaben zu den Einzelgewichten der zählbaren Futtermittel waren häufig geschätzt. Dies führte zu Grundfutterkosten, die nur bedingt belastbar sind. Besondere Schwierigkeiten bereitete die extreme Witterung des Jahres 2003. Viele Betriebsleiter konnten lediglich angeben, dass wesentlich weniger Futter gewachsen ist als in durchschnittlichen Jahren. Genauere Angaben zu Ertragseinbußen konnten nur diejenigen Betriebsleiter machen, die einen Antrag auf Dürrebeihilfe gestellt hatten, weil im Zuge des Antragsverfahrens die Erträge des Jahres 2003 ermittelt und mit den Erträgen der letzten drei Jahre verglichen wurden. Diese Erfahrung führte zu der Entscheidung, innerhalb des Projektes „Unternehmensauswertung Ökologischer Landbau“ genauere Erhebungen im Futterbau durchzuführen. Ziel der Untersuchung war daher vor allem die Erfassung der Nutzungen und die Ermittlung der Futtermittelmengen über eine Vegetationsperiode.

Berichte: Nährstoffgehalte der Fruchtarten im Ökologischen Landbau --- Wirkungsgrad organischer Düngemittel auf Ertrag und Qualität von Kartoffeln im Ökologischen Landbau --- Bekämpfung der Kraut- und Knollenfäule im Ökokartoffelanbau --- Anforderungen an die Humusbilanzierung in der Praxis des Ökologischen Landbaus --- Zur Intensität des Striegeleinsatzes gemessen an der Bodenbewegung unter Laborbedingungen und an einem Feldbestand von Wintergerste

Two varieties of peas and two species of cereals have been tested sole and inter-cropped during three years with respect to yield and weed competition on a fruitful soil in saxony. A randomized complete block design with four replications was used. Yield of grain was highest with sole cropped spring wheat and lowest with a variety of pea. Intercropping of peas with wheat or barley did not increase total grain yield signifi-cantly compared to the pure stands of cereals. In mixed crops grain yield of pea seed was low at harvest and weed competition was only slightly enhanced. Nitrogen yield was highest with sole cropped peas.