Topambtenaren en de crisis

__Abstract__ Bezuinigingen op de centrale overheid zijn aan de orde van de dag. Hoe worden zij op organisatieniveau in verschillende Europese landen gerealiseerd? De crisis heeft vanzelfsprekend gevolgen voor publieke organisaties in Nederland. In eerdere jaren waren het vooral private bedrijven die door de crisis werden getroffen. De crisis werd in publieke organisaties aanvankelijk als kans aangegrepen om krapte op de arbeidsmarkt voor gekwalificeerd personeel te verhelpen. Waar de commissie-Van Rijn in 2001 nog waarschuwde voor grootschalige tekorten aan hoogopgeleid personeel in publieke organisaties, is de situatie vandaag bijna tegenovergesteld. De economische crisis, of liever de financiële druk als gevolg van de crisis, maakt ingrijpen in overheidsorganisaties noodzakelijk, waarbij ook het personeel niet ontzien wordt. Dit artikel gaat in op bezuinigingen in organisaties in de centrale overheid van twaalf Europese landen (Engeland, Duitsland, Frankrijk, Spanje, Portugal, Italië, Oostenrijk, Noorwegen, Hongarije, Litouwen en Estland). Welke bezuinigingsstrategieën worden in verschillende Europese landen gehanteerd, welke bezuinigingsmaatregelen zijn genomen en wat zijn de gevolgen ervan? De analyse is gebaseerd op de percepties van 3555 topambtenaren, waarvan 196 uit Nederland, op het niveau van secretaris-generaal, directeur-generaal, directeur of equivalenten in de centrale overheid. De vergelijking tussen Nederland en de overige Europese landen staat centraal

Poly(triazolyl methacrylate) glycopolymers as potential targeted unimolecular nanocarriers

© The Royal Society of Chemistry 2019.Synthetic glycopolymers are increasingly investigated as multivalent ligands for a range of biological and biomedical applications. This study indicates that glycopolymers with a fine-tuned balance between hydrophilic sugar pendant units and relatively hydrophobic polymer backbones can act as single-chain targeted nanocarriers for low molecular weight hydrophobic molecules. Non-covalent complexes formed from poly(triazolyl methacrylate) glycopolymers and low molecular weight hydrophobic guest molecules were characterised through a range of analytical techniques-DLS, SLS, TDA, fluorescence spectroscopy, surface tension analysis-and molecular dynamics (MD) modelling simulations provided further information on the macromolecular characteristics of these single chain complexes. Finally, we show that these nanocarriers can be utilised to deliver a hydrophobic guest molecule, Nile red, to both soluble and surface-immobilised concanavalin A (Con A) and peanut agglutinin (PNA) model lectins with high specificity, showing the potential of non-covalent complexation with specific glycopolymers in targeted guest-molecule delivery.Peer reviewedFinal Published versio

The Effect of Lattice Vibrations on Substitutional Alloy Thermodynamics

A longstanding limitation of first-principles calculations of substitutional alloy phase diagrams is the difficulty to account for lattice vibrations. A survey of the theoretical and experimental literature seeking to quantify the impact of lattice vibrations on phase stability indicates that this effect can be substantial. Typical vibrational entropy differences between phases are of the order of 0.1 to 0.2 k_B/atom, which is comparable to the typical values of configurational entropy differences in binary alloys (at most 0.693 k_B/atom). This paper describes the basic formalism underlying ab initio phase diagram calculations, along with the generalization required to account for lattice vibrations. We overview the various techniques allowing the theoretical calculation and the experimental determination of phonon dispersion curves and related thermodynamic quantities, such as vibrational entropy or free energy. A clear picture of the origin of vibrational entropy differences between phases in an alloy system is presented that goes beyond the traditional bond counting and volume change arguments. Vibrational entropy change can be attributed to the changes in chemical bond stiffness associated with the changes in bond length that take place during a phase transformation. This so-called ``bond stiffness vs. bond length'' interpretation both summarizes the key phenomenon driving vibrational entropy changes and provides a practical tool to model them.Comment: Submitted to Reviews of Modern Physics 44 pages, 6 figure

Measurement of the inelastic branch of the 14^{14}O(α,p)17^{17}F reaction: Implications for explosive burning in novae and x-ray bursters

A measurement of the inelastic component of the key astrophysical resonance in the 14O(α,p)17F reaction for burning and breakout from hot carbon-nitrogen-oxygen (CNO) cycles is reported. The inelastic component is found to be comparable to the ground-state branch and will enhance the 14O(α,p)17F reaction rate. The current results for the reaction rate confirm that the 14O(α,p)17F reaction is unlikely to contribute substantially to burning and breakout from the CNO cycles under novae conditions. The reaction can, however, contribute strongly to the breakout from the hot CNO cycles under the more extreme conditions found in x-ray bursters

X-ray reflectivity of an Sb delta-doping layer in silicon

X‐ray reflectivity measurements were made on Si(001) crystals containing a delta‐doping layer of Sb atoms a few nanometers below the surface. The measurements show the Sb doping profile to be abrupt towards the substrate side of the sample and to decay towards the surface with a characteristic decay length of 1.01 nm

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation

Abstract Purpose There is a need for alternative analgosedatives such as dexmedetomidine in neonates. Given the ethical and practical difficulties, protocol design for clinical trials in neonates should be carefully considered before implementation. Our objective was to identify a protocol design suitable for subsequent evaluation of the dosing requirements for dexmedetomidine in mechanically ventilated neonates. Methods A published paediatric pharmacokinetic model was used to derive the dosing regimen for dexmedetomidine in a firstin-neonate study. Optimality criteria were applied to optimise the blood sampling schedule. The impact of sampling schedule optimisation on model parameter estimation was assessed by simulation and re-estimation procedures for different simulation scenarios. The optimised schedule was then implemented in a neonatal pilot study. Results Parameter estimates were more precise and similarly accurate in the optimised scenarios, as compared to empirical sampling (normalised root mean square error: 1673.1% vs. 13,229.4% and relative error: 46.4% vs. 9.1%). Most importantly, protocol deviations from the optimal design still allowed reasonable parameter estimation. Data analysis from the pilot group (n = 6) confirmed the adequacy of the optimised trial protocol. Dexmedetomidine pharmacokinetics in term neonates was scaled using allometry and maturation, but results showed a 20% higher clearance in this population compared to initial estimates obtained by extrapolation from a slightly older paediatric population. Clearance for a typical neonate, with a post-menstrual age (PMA) of 40 weeks and weight 3.4 kg, was 2.92 L/h. Extension of the study with 11 additional subjects showed a further increased clearance in pre-term subjects with lower PMA. Conclusions The use of optimal design in conjunction with simulation scenarios improved the accuracy and precision of the estimates of the parameters of interest, taking into account protocol deviations, which are often unavoidable in this event-prone population

Evidence of a new state in 11^{11}Be observed in the 11^{11}Li β\beta-decay

Coincidences between charged particles emitted in the $\beta$-decay of $^{11}$Li were observed using highly segmented detectors. The breakup channels involving three particles were studied in full kinematics allowing for the reconstruction of the excitation energy of the $^{11}$Be states participating in the decay. In particular, the contribution of a previously unobserved state at 16.3 MeV in $^{11}$Be has been identified selecting the $\alpha$ + $^7$He$\to\alpha$ + $^6$He+n channel. The angular correlations between the $\alpha$ particle and the center of mass of the $^6$He+n system favors spin and parity assignment of 3/2$^-$ for this state as well as for the previously known state at 18 MeV.Comment: 13 pages, 6 figure

In vitro digestion and lactase treatment influence uptake of quercetin and quercetin glucoside by the Caco-2 cell monolayer

BACKGROUND: Quercetin and quercetin glycosides are widely consumed flavonoids found in many fruits and vegetables. These compounds have a wide range of potential health benefits, and understanding the bioavailability of flavonoids from foods is becoming increasingly important. METHODS: This study combined an in vitro digestion, a lactase treatment and the Caco-2 cell model to examine quercetin and quercetin glucoside uptake from shallot and apple homogenates. RESULTS: The in vitro digestion alone significantly decreased quercetin aglycone recovery from the shallot digestate (p < 0.05), but had no significant effect on quercetin-3-glucoside recovery (p > 0.05). Digestion increased the Caco-2 cell uptake of shallot quercetin-4'-glucoside by 2-fold when compared to the non-digested shallot. Despite the loss of quercetin from the digested shallot, the bioavailability of quercetin aglycone to the Caco-2 cells was the same in both the digested and non-digested shallot. Treatment with lactase increased quercetin recovery from the shallot digestate nearly 10-fold and decreased quercetin-4'-glucoside recovery by more than 100-fold (p < 0.05), but had no effect on quercetin recovery from apple digestates. Lactase treatment also increased shallot quercetin bioavailability to the Caco-2 cells approximately 14-fold, and decreased shallot quercetin-4'-glucoside bioavailability 23-fold (p < 0.05). These Caco-2 cells had lactase activity similar to that expressed by a lactose intolerant human. CONCLUSIONS: The increase in quercetin uptake following treatment with lactase suggests that dietary supplementation with lactase may increase quercetin bioavailability in lactose intolerant humans. Combining the digestion, the lactase treatment and the Caco-2 cell culture model may provide a reliable in vitro model for examining flavonoid glucoside bioavailability from foods