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The discursive form of human understanding as the source of the transcendental illusionerstanding
No full textKant famously claims that pure reason is subject to a transcendental illusion in which the subjective validity and the regulative use of a principle of reason are conflated with its objective validity and constitutive use. His doctrine of transcendental illusion is puzzling for he insists that this illusion is natural as well as necessary. The two dominant interpretation strategies cannot make sense of this puzzle because they turn out to be either too strong or too weak: they either struggle to account for the legitimate, regulative use of the transcendental principle of reason or fall short of explaining the necessity of the transcendental illusion. In contrast, I shall argue that it is possible to account for the fact that the transcendental illusion is natural and necessary because it has its source in the discursive form of our human understanding, and that this illusion can nevertheless be known to be illusory because our discursive nature can be recognised as a merely particular form of understanding by comparing it with a possible, intuitive form of understanding in an act of critical self-reflection
The dispersal potential of endangered plants versus non-native garden escapees
No full text1. Amidst climate change, enhancing plant dispersal pathways is crucial for adapting ecosystems and preserving biodiversity. In our human-dominated landscapes,
urban and rural green spaces, especially gardens, are promising conduits for plant
dispersal. Non-native plants are known to benefit from these spaces, yet the potential benefits for at-risk native plants remain unclear.
2. Here, I synthesized data on dispersal traits, comparing endangered native plants
with non-endangered and non-native species in Germany. To make my analysis
pertinent to understanding the potential role of gardens in aiding the dispersal of
at-risk native plants, I further contrasted the dispersal ecology of garden-friendly
endangered plants with non-native plants known to escape gardens. I analysed
several traits including seed weight, terminal velocity, dispersal distance, germination rate, dispersal mode, seed structures and seedbank type.
3. Overall, dispersal traits between native and non-native plants showed minor, but
in some cases statistically significant differences. Endangered plants were more
often wind-dispersed and more frequently had seed appendages conducive to a
wider range of dispersal vectors. Conversely, non-native plants leaned more towards non-assisted local dispersal, heavier seeds and more persistent seed banks.
Other traits were largely consistent across groups.
4. This research shows that endangered native plants possess a dispersal ecology
similar to non-native species, which frequently spread from green spaces like
gardens. Thus, integrating endangered flora into our green spaces could help to
promote an essential aspect of species survival: dispersal
The threat of a major tree pathogen to forest soil mesofauna food webs and ecosystem functioning
No full textTree pathogens threaten the survival of many forest foundation tree species worldwide. However, there is limited knowledge of how dieback of foundation tree species may threaten other components of forest ecosystems, such as soil biodiversity and associated ecosystem functions. Kauri (Agathis australis), threatened by the root-borne pathogen Phytophthora agathidicida, are culturally and ecologically significant tree species that exert great influence on soil properties. We aimed to characterise soil mesofauna community structure and energy fluxes in kauri forests and assess the potential threat that tree pathogens such as P. agathidicida pose to belowground ecosystems. We sampled soil mesofauna communities and identified specimens to functional feeding groups at 24 pairs of kauri and adjacent broadleaf trees in sites across the Waitākere Ranges Regional Park, Aotearoa – New Zealand. We attributed kauri canopy health scores, measured tree diameter, slope, forest floor depth, and soil carbon dioxide efflux. We also analysed soil samples for P. agathidicida presence, total carbon, and total nitrogen. We constructed soil mesofauna food webs associated with kauri and broadleaf trees, and assessed the uniqueness of food webs associated with kauri and the impacts of P. agathidicida on density, biomass, mean body mass, and energy fluxes of mesofauna taxonomic and trophic groups. We found omnivores with larger body mass at kauri where P. agathidicida was detected (i.e., P. agathidicida-positive soils). Compared to broadleaf trees, mesofauna density and biomass were lower in soils under kauri, and body masses of Symphyla and omnivores were smaller in soils under kauri. Differences in mesofauna community response variables between tree types were mainly modulated by the soil C:N ratio, which had positive effects under broadleaf and neutral to negative effects under kauri. Energy fluxes to detritivores and fungivores were greater under larger trees, regardless of tree type or P. agathidicida detection status. Our findings suggest that kauri support soil mesofauna food webs that are distinctly different from those found under broadleaf trees in the same habitat. A decreased presence of this foundation species may be linked to future impacts on soil mesofauna in this forest ecosystem with increasingly advanced stages of kauri dieback
Minderjährige in klinischen Prüfungen: Ethische Abwägungen ihres Einbezugs am Beispiel der indizierten Prävention psychotischer Erkrankungen
No full textMinderjährige sind als vulnerable Gruppe in Studien besonders zu schützen. Daher sind Forscher_innen bei der Studieninitiierung und Ethikkommissionen bei der Studienbewilligung oft zurückhaltend, so dass Minderjährigen von der Studienteilnahme häufig ausgeschlossen sind. Dieser Ausschluss kann dazu führen, dass Forscher_innen und Kliniker_innen nur unvollständige Daten erhalten oder auf erwachsenenbasierte Erkenntnisse zur Behandlung von Minderjährigen zurückgreifen müssen. Am Beispiel der als sonstige klinische Prüfung nach der Verordnung über Medizinprodukte durchgeführten Studie „Computer-assistierte Risiko-Evaluation in der Früherkennung psychotischer Erkrankungen“ (CARE) soll ein Argumentationsstrang zum Einschluss von Minderjährigen aufgezeigt werden, der die ethischen Prinzipien des Nicht-Schadens (insbesondere in Bezug auf etwaige Stigmatisierungen), der Fürsorge, der Autonomie und der Fairness abwägt, die Notwendigkeit des Einschlusses von Minderjährigen anhand der entwicklungsspezifischen Unterschiede in Diagnostik und Frühintervention aufzeigt sowie die spezifischen Schutzmaßnahmen darstellt. Die dargestellte Argumentation lässt sich beispielhaft auch auf andere Krankheitsbilder mit Beginn im Kindes- und Jugendalter übertragen und soll damit helfen, Minderjährige nicht von einer geeigneten evidenzbasierten Versorgung durch eine mangelhafte Studienlage auszuschließen.As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study “Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders” (CARE), which was conducted as an ‘other clinical investigation’ according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies
Isoflurane lowers the cerebral metabolic rate of oxygen and prevents hypoxia during cortical spreading depolarization in vitro: An integrative experimental and modeling study
No full textCortical spreading depolarization (SD) imposes a massive increase in energy demand and therefore evolves as a target for treatment following acute brain injuries. Anesthetics are empirically used to reduce energy metabolism in critical brain conditions, yet their effect on metabolism during SD remains largely unknown. We investigated oxidative metabolism during SD in brain slices from Wistar rats. Extracellular potassium ([K+]o), local field potential and partial tissue oxygen pressure (ptiO2) were measured simultaneously. The cerebral metabolic rate of oxygen (CMRO2) was calculated using a reaction-diffusion model. By that, we tested the effect of clinically relevant concentrations of isoflurane on CMRO2 during SD and modeled tissue oxygenation for different capillary pO2 values. During SD, CMRO2 increased 2.7-fold, resulting in transient hypoxia in the slice core. Isoflurane decreased CMRO2, reduced peak [K+]o, and prolonged [K+]o clearance, which indicates reduced synaptic transmission and sodium-potassium ATPase inhibition. Modeling tissue oxygenation during SD illustrates the need for increased capillary pO2 levels to prevent hypoxia. In the absence thereof, isoflurane could improve tissue oxygenation by lowering CMRO2. Therefore, isoflurane is a promising candidate for pre-clinical studies on neuronal survival in conditions involving SD
Legal Reasoning and the Constitutional Foundations of the EU – A Reflection on the Past, Present and Future of the European Court of Justice
No full textThis work analyses the European Court of Justice’s (ECJ) legal reasoning, its legitimacy and the role it plays in the European legal order. It examines how the role of the ECJ is changing as this legal order is increasingly characterised by conflicts over its foundations. Reflecting on the past, it revisits the debate about the ECJ in the context of early European integration, which was shaped by textualist and originalist accounts of legal reasoning. Turning to the present, it explains how the context in which the ECJ operates has changed and what challenges arise in the new context. Underlying many of the difficult legal issues raised in recent cases before the ECJ is the overarching question of whether illiberal democracies can participate unimpededly in the European legal order or whether that legal order allows to oppose and sanction them. Looking to the future, this work discusses how the ECJ can best respond to this question. It suggests that the ECJ should adopt a ‘contractarian’ approach to legal reasoning, consisting of a particular kind of constructive interpretation. Constructive interpretation recognises that interpretation involves subjective elements and judgments, but also provides a framework for making these explicit, for putting them up for debate, and for developing constraints on interpretation without paralysing the judiciary. The proposed contractarian version of constructive interpretation takes the free choice of Member States to join and remain part of the EU as basis for justifying sanctions imposed on them. It responds to important concerns underlying textualist and originalist criticisms of the ECJ but does not lead into the same dead ends. Contractarian reasoning enables the ECJ to protect the liberal nature of the European legal order in a legitimate and effective manner, regardless of autocratic tendencies within Member States.:CONTENTS
INTRODUCTION 1
PART I: 17
THE PAST – THE ECJ’S LEGAL REASONING IN THE CONTEXT OF EARLY EUROPEAN INTEGRATION 17
I. THE CRITICISM OF THE ECJ’S LEGAL REASONING 18
A. The Criticism of an ‘Activist’ Court 18
1. Introduction to the Criticism 18
a. Overview 19
b. Judicial activism 24
2. Theories of Interpretation 30
a. Objecting to positivist explanations 30
b. Textualism 33
c. Originalism 35
B. Justifying the Criticism of the ECJ 39
1. Terminology and Analytical Framework 40
a. Legal interpretation, legal reasoning and legitimacy 40
b. Theories of interpretation and theories of justification 44
2. The Rule of Law 47
3. Democracy 52
4. Sovereignty 56
5. Institutional Balance 61
6. “Political Messianism” 64
C. Conclusions 67
II. LIMITATIONS AND CONTEXT OF THE CRITICISM 68
A. Objections Against the Textualist and Originalist Criticism of the ECJ 69
1. Textualism 69
2. Originalism 70
a. Intentions of the constituent authorities 71
b. Non-originalist founders 73
c. No actual intent 75
d. Amendments of the Treaties and accession to the EU 78
B. The Context of European Integration 79
1. The Nexus of the Activist and Integrationist Criticism 80
2. Fields of Activism and Integrationist Case Law 83
C. Why Context Matters in a Debate on Legal Interpretation 88
1. Scholarship on the ECJ’s Legal Interpretation and Context 88
2. ‘Veil of Integration’ 91
D. Conclusions 95
PART II: 97
THE PRESENT – CONFLICTS CONCERNING THE FOUNDATIONS OF THE EU AND THEIR IMPLICATIONS FOR THE DEBATE ON THE ECJ 97
III. LITIGATING THE FOUNDATIONS OF THE EU 98
A. Approach 99
B. Cases before the ECJ 101
1. The Horizontal Dimension: Mutual Trust 103
a. Overview 106
b. The ECJ’s approach 108
c. Analysis of changing context 116
2. The Vertical Dimension: Infring. Proced. and Jud. Independ. 120
a. Overview 122
b. Main arguments and the ECJ’s reasoning 127
(1) Arguments by the Commission and the Member States 127
(2) The ECJ’s decisions and reasoning 131
c. Analysis of changing context 138
3. The Financial Dimension: Conditionality 145
a. Overview 146
b. Main arguments and the ECJ’s approach 149
c. Analysis of changing context 158
C. Conceptualising the New Context 162
1. Conceptualising the EU and Contextual Changes 162
2. Contextual Changes 166
D. Conclusions 172
IV. THE END OF A PARADIGM: BLURRING ACTIVIST AND INTEGRATIONIST LINES 176
A. Towards a New Paradigm for the Debate on the ECJ’s Legal Reasoning 177
1. Limitations of the Activist Lens 177
2. Integrationist No More 188
a. Perspective of Poland and Hungary 189
b. Perspective from other Member States 191
c. The End of a Paradigm and the Renewal of the Debate 200
B. The Place of Legal Reasoning in the Debate on the ECJ 204
1. Scholarly Engagements with Rule of law Questions 206
d. ‘Reverse Solange’ 207
e. ‘Horizontal Solange’ 209
f. Operationalising Article 2 TEU (through other norms) 215
g. Relation of Article 7 TEU and other procedures 224
h. Const. implications of the conditionality mechanism 230
2. Contribution to the Debate 235
C. Conclusion 238
PART III: 241
THE FUTURE – REDEFINING THE ECJ’S ROLE IN A CONTEXT OF FUNDAMENTAL CONFLICTS 241
V. FOUNDATIONS OF A NEW APPROACH: IDENTIFYING COMMON GROUND 242
A. Requirements for a New Approach 244
1. Responding to Criticism: The Problem of Legitimacy 244
2. Responding to the New Context: Solving Conflicts Pertaining to the EU’s Foundations 252
3. Finding a Common Denominator: Towards a Shared Theory of Justification 256
B. Building on a Shared Understanding of the European Legal Order 258
1. Overarching Understandings of the Legal Order and Legal Interpretation – Constructive Legal Interpretation 260
2. Developing a Shared Understanding of the EU in a Context of Fundamental Disagreements 267
C. A Contractarian Understanding of the Treaties 269
1. Introduction to a Contractarian Understanding 270
2. Intergovernmentalism vs. Contractarianism 278
3. Situating a Contractarian Understanding in the Context of Conflicts on the Rule of Law 286
4. Responding to Objections to a Constructive Approach 291
D. Conclusions 295
VI. A CONTRACTARIAN APPROACH TO INTERPRETING THE TREATIES 298
A. Contractarian Reasoning: Developing Responses to Conflicts about the Foundations of the EU 299
1. From a Contractarian Understanding of the Treaties to Contractarian Reasoning 299
2. Revisiting the ECJ’s reasoning in Rule of Law decisions 302
a. Elements of contractarian reasoning 303
b. Non-contractarian reasoning 309
3. Added Value and Limitations of Contractarian Reasoning 312
a. Contractarian vs. originalist and textualist reasoning 312
b. Limitations and added value 316
B. Defending the Foundations of the EU: The ECJ as a Legitimate and Central actor in the New Context 319
1. Enforcing Contractual Obligations: The ECJ as a Legitimate Player in the New Context 319
2. The ECJ as a Central Actor in the New Context 326
a. The ECJ as an unbiased arbiter on disputes pertaining to the EU’s foundations 327
b. Preserving the EU’s foundational values in an uncertain future 330
c. Situating the ECJ in the context of other institutions 334
C. Conclusions 343
CONCLUSIONS 34
Calix[4]arene with a stiff upper rim bridge: spontaneous macrocyclization, structure, and dynamic behaviour
No full textMacrocyclisation of the upper-rim distal disubstituted bromomethylene calix[4]arene derivative proceeds spontaneously on a silica gel due to the spatial proximity of two reaction centers, affording the formation of a bridged calixarene derivative. Due to the short span of the bridge, the product represents an extreme example of calix[4]arenes fixed in the pinched cone conformation with two aromatic rings steeply inclined into the center of the calixarene cavity. Dynamic NMR spectroscopy was used to investigate the temperature-dependent rocking motion of the bridgehead and thermochemical parameters of this motion were determined experimentally, as well as estimated using computational methods. Mass spectrometry was employed to study the upper rim macrocyclization reaction in the gas phase
Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer
No full textRaloxifene, a selective oestrogen receptor modulator (SERM), has demonstrated efficacy in the prevention and therapy of oestrogen receptor-positive (ER+) breast cancer, with some degree of effectiveness against triple-negative forms. This suggests the presence of oestrogen receptor-independent pathways in raloxifene-mediated anticancer activity. To enhance the potential of raloxifene against the most aggressive breast cancer cells, hybrid molecules combining the drug with a metal chelator moiety have been developed. In this study, we synthetically modified the structure of raloxifene by incorporating a 2,2′-bipyridine (2,2′-bipy) moiety, resulting in [6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]-[4-(2,2′-bipyridin-4′-yl-methoxy)phenyl]methanone (bipyraloxifene). We investigated the cytotoxic activity of both raloxifene and bipyraloxifene against ER+ breast adenocarcinomas, glioblastomas, and a triple-negative breast cancer (TNBC) cell line, elucidating their mode of action against TNBC. Bipyraloxifene maintained a mechanism based on caspase-mediated apoptosis but exhibited significantly higher activity and selectivity compared to the original drug, particularly evident in triple-negative stem-like MDA-MB-231 cells
Elevated serum levels of anti-collagen type I antibodies in patients with spontaneous cervical artery dissection and ischemic stroke: a prospective multicenter study
No full textIntroduction: Spontaneous cervical artery dissection (sCAD) is a rare vasculopathy whose trigger is still unknown. We hypothesized that autoimmunity against components of the vascular wall might play a critical role in sCAD and examined anti-collagen type I antibodies in patients with sCAD, acute ischemic stroke, patients with thromboendarterectomy, and controls.
Methods: Fifty-seven patients with sCAD (age 45.7 ± 10.2 years, female 18 (31.6%)) were prospectively enrolled in four German stroke centers. Blood samples were collected at baseline, at day 10 ± 3, and after 6 ± 1 months. Patients with ischemic stroke not related to CAD (n=54, age 56.7 ± 13.7 years, female 15 (27.8%)), healthy probands (n=80, age 57.4 ± 12.9 years, female 56 (70%)), and patients undergoing thromboendarterectomy of the carotid artery (n=9, age 70.7 ± 9.3 years, female 2 (22.2%)) served as controls. Anti-collagen type I antibodies were determined by enzyme-linked immunosorbent assays (ELISAs).
Results: Patients with acute sCAD had higher serum levels of anti-collagen type I antibodies (33.9 ± 24.6 µg/ml) than probands (18.5 ± 11.0 µg/ml; p <0.001) but lower levels than patients with ischemic stroke not related to sCAD (47.8 ± 28.4 µg/ml; p=0.003). In patients with sCAD, serum levels of anti-collagen type I antibodies were similar in the acute, subacute, and chronic phase. Levels of anti-collagen type I antibodies significantly correlated with circulating collagen type I (rho=0.207, p=0.003).
Conclusion: Anti-collagen type I antibodies seem not to represent a trigger for acute sCAD or ischemic stroke but may rather be linked to the metabolism and turnover of collagen type I
Prevalence of nonconvulsive seizures and nonconvulsive status epilepticus in dogs and cats with a history of cluster seizures: A retrospective study
No full textBackground: Nonconvulsive seizures (NCS) and nonconvulsive status epilepticus
(NCSE) are frequently observed in human patients. Diagnosis of NCS and NCSE only
can be achieved by the use of electroencephalography (EEG). Electroencephalo-
graphic monitoring is rare in veterinary medicine and consequently there is limited
data on frequency of NCS and NCSE.
Objectives: Determine the prevalence of NCS and NCSE in dogs and cats with a his-
tory of cluster seizures.
Animals: Twenty-six dogs and 12 cats.
Methods: Retrospective study. Medical records of dogs and cats with cluster seizures
were reviewed. Electroencephalography was performed in order to identify electro-
graphic seizure activity after the apparent cessation of convulsive seizure activity.
Results: Nonconvulsive seizures were detected in 9 dogs and 2 cats out of the
38 patients (29%). Nonconvulsive status epilepticus was detected in 4 dogs and 2 cats
(16%). Five patients had both NCS and NCSE. A decreased level of consciousness
was evident in 6/11 patients with NCS, 3/6 also had NCSE. Mortality rate for
patients with NCS (73%) and NCSE (67%) was much higher than that for patients
with no seizure activity on EEG (27%).
Conclusion and Clinical Importance: Prevalence of NCS and NCSE is high in dogs
and cats with a history of cluster seizures. Nonconvulsive seizures and NCSE are dif-
ficult to detect clinically and are associated with higher in hospital mortality rates.
Results indicate that prompt EEG monitoring should be performed in dogs and cats
with cluster seizures