Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation: Molecular mechanisms, clinical aspects and opening for treatment

Knaap, M.S. van der [Promotor]Scheper, G.C. [Copromotor

Montesquieu and Judicial Review of Proportionality in Administrative Law

The present era has seen an unprecedented fragmentation of the public sphere, a breakup of public imperium into separate pieces, not only left in the hands of supranational or subnational authorities, but also entrusted to private actors. With the abandonment of previously undisputed notions of strict legal verticality and the undivided general interest, the separation of powers doctrine as applied in most European systems of administrative law is in need of serious rethinking. Current debates on the judicial control of governmental discretion are still hampered by a discursive language and a legal grammar that tend to draw sharp lines between law and policy, awarding each of the three branches of government its own well-defined domain. Contrary to widespread belief, the trias politica as an ideology of disjointed powers and separate spheres cannot be traced back to Montesquieu's theory of law, but only from its philosophical rebuttal and inaccurate reception in subsequent times. Ironically, a proper analysis of Montesquieu's theory may indicate a viable way forward for a system of review of government actions that attunes to its modern social and institutional context

Dealing with Ambiguity: Johan Maurits, Black Pete and the Crisis of Dutch Identity

A dominant way in which the Dutch think of themselves entails the image of an enlightened nation, too small to be really significant in world politics but nevertheless important as an ethical guiding light for other nations. In a globalizing world, that self- congratulatory image has recently been severely challenged, with public debate being dominated by the opposing sides of those who one-sidedly debunk Dutch culture and politics as oppressive and violent and others who persist in the myth of innocent bystandership and enlightened progressivism. Many scholars and publicists have called for a more nuanced discussion, typically emphasizing the ‘grey middle ground’ in between black and white opposites. This paper starts out by providing short accounts of Johan Maurits’s governorship of Dutch Brazil (1637-1644) and the stereotyped persona of Black Pete (one of the central figures of an annual children’s festival) as two topics of recent heated debate. Subsequently, it proposes an alternative way out of the current Dutch identity crisis while drawing on what may come as a surprising source: ancient Greek tragedy

'Rechtmatig tegenover den een, onrechtmatig tegenover den ander'

De relativering van rechtsnormen in privaat- en bestuursrecht roept tal van theoretische vragen op die in de rechtsgeleerde literatuur tot nog toe sterk onderbelicht zijn gebleven. Vertegenwoordigen wettelijke normen en algemene juridische beginselen een zelfstandige, ten opzichte van het gewone maatschappelijk leven geabstraheerde waarde, of dienen zij steeds te worden bezien in het licht van de belangen en sociale verhoudingen waarop zij concreet betrekking hebben? Dient het bestuursrecht zich in ieder geval deels te blijven richten op de abstracte rechtshandhaving erga omnes, of zou het zich moeten omvormen tot een stelsel dat zich – niet anders dan het privaatrecht – in beginsel oriënteert op de vaststelling van rechtsposities inter partes? De introductie van de relativiteitseis in het bestuursrecht is een belangrijk moment in de verschuiving van ‘toepassings-’ naar ‘belangenjurisdictie’ die voor de ontwikkeling van het huidige bestuursrecht kenmerkend is. Waar het ‘klassieke’ bestuursrecht zich in de eerste plaats richt op objectieve rechtshandhaving, concentreert het ‘moderne’ bestuursrecht zich veeleer op de vaststelling van de onderlinge rechtsposities van concrete partijen. Het privaatrecht maakte die ontwikkeling al eerder door; de opkomst van de privaatrechtelijke relativiteitsleer in het interbellum hangt er direct mee samen. De historische ontwikkeling van de privaatrechtelijke leer laat zien dat toepassing van de relativiteitseis draait om een precaire balans tussen ‘klassieke’ en ‘moderne’ uitgangspunten die geen van beide veronachtzaamd dienen te worden. Voor het bestuursrecht geldt dat evenzeer als voor het privaatrecht. Desalniettemin is een bestuursrechtelijke relativiteitsleer nodig die zich niet zomaar spiegelt aan zijn privaatrechtelijke pendant, maar recht doet aan de eigen aard van bestuursrechtelijke verhoudingen

Sophocles' Antigone and the Promise of Ethical Life

This article aims to demonstrate that works of art and literature can provide important insights in law and justice that are hard to grasp by one-sidedly rationalist methods of academic analysis. It takes Sophocles’ _Antigone_ – perhaps the most classical text of law and literature’s familiar catalogue – as a case in point, drawing attention to some important aspects of that play’s legal epistemic relevance that are still largely overlooked. Arguing that the widespread view on the confrontation between Antigone and Creon as a clash between ‘divine’ and ‘human’ law is mistaken, the article builds on Hegel’s view that the positions of both protagonists are likewise incomplete, denying elements of law and justice that are equally essential, the one being no less divine than the other. However, it departs from Hegel’s analysis in maintaining that the play does not entail the promise of ‘ethical life’ (_Sittlichkeit_) as some synthesis that recognizes the specific value of both Antigone’s and Creon’s stances on law and justice but takes away their incompatibility. Instead, it is argued that the play teaches us that such harmonization is unattainable – a no less valuable lesson indeed

De eeuwige stem van de verdachte

FdR – Publicaties zonder aanstelling Universiteit Leide

Cardiac impact of inhaled therapy in the largest randomised placebo-controlled trial in COPD history

SUMMIT supports the efficiency and cardiovascular safety of LABA and ICS in COPD patients at cardiovascular risk http://ow.ly/p6Is300ffoc

Intrinsic radiosensitivity of human pancreatic tumour cells and the radiosensitising potency of the nitric oxide donor sodium nitroprusside.

A panel of eight human pancreatic tumour cell lines displayed high intrinsic radioresistance, with mean inactivation doses between 2.4 and 6.5 Gy, similar to those reported for melanoma and glioblastoma. The radiosensitising potency of sodium nitroprusside, a bioreductive nitric oxide donor, was assessed in a model of metabolism-induced hypoxia in a cell micropellet. Sodium nitroprusside at 0.1 mM revealed a radiosensitising effect with an overall enhancement ratio of 1.9 compared with 2.5 for oxygen. Radiosensitising activity correlated with the enhancement of single-strand DNA breakage caused by radiation. In suspensions with cell densities of between 3% and 30% (v/v), the half-life of sodium nitroprusside decreased from 31 to 3.2 min, suggesting a value of around 1 min for micropellets. Despite this variation, the radiosensitising activity was similar in micropellets and in diluted cell suspensions. S-nitroso-L-glutathione was found to possess radiosensitising activity, consistent with a possible role of natural thiols in the storing of radiobiologically active nitric oxide adducts derived from sodium nitroprusside. As measured by a nitric oxide-specific microsensor, activation of sodium nitroprusside occurred by bioreduction, whereas S-nitroso-L-glutathione showed substantial spontaneous decomposition. Both agents appear to exert radiosensitising action through nitric oxide as its scavenging by carboxy phenyltetramethylimidazolineoxyl N-oxide (carboxy-PTI0) and oxyhaemoglobin resulted in attenuated radiosensitisation. Sodium nitroprusside was at least 10-fold more potent than etanidazole, a 2-nitroimidazole used as a reference. Our data suggest that sodium nitroprusside, a drug currently used for the treatment of hypertension, is a potential tumour radioresponse modifier

Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action