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For offshore wind farms which are planned in sub-arctic regions like the Baltic Sea and Bohai Bay, support structure design has to account for load effects from dynamic ice-structure interaction. There is relatively high uncertainty related to dynamic ice loads as little to no load- and response data of offshore wind turbines exposed to drifting ice exists. In the present study the potential for the development of ice-induced vibrations for an offshore wind turbine on monopile foundation is experimentally investigated. The experiments aimed to reproduce at scale the interaction of an idling and operational 14 MW turbine with ice representative of 50-year return period Southern Baltic Sea conditions. A real-time hybrid test setup was used to allow the incorporation of the specific modal properties of an offshore wind turbine at the ice action point, as well as virtual wind loading. The experiments showed that all known regimes of ice-induced vibrations develop depending on the magnitude of the ice drift speed. At low speed this is intermittent crushing and at intermediate speeds is ‘frequency lock-in’ in the second global bending mode of the turbine. For high ice speeds continuous brittle crushing was found. A new finding is the development of an interaction regime with a strongly amplified non-harmonic first-mode response of the structure, combined with higher modes after moments of global ice failure. The regime develops between speeds where intermittent crushing and frequency lock-in in the second global bending mode develop. The development of this regime can be related to the specific modal properties of the wind turbine, for which the second and third global bending mode can be easily excited at the ice action point. Preliminary numerical simulations with a phenomenological ice model coupled to a full wind turbine model show that intermittent crushing and the new regime result in the largest bending moments for a large part of the support structure. Frequency lock-in and continuous brittle crushing result in significantly smaller bending moments throughout the structure.

Studies at 3T have shown that TTThe proposed method for morphometry delivered segmentation masks without statistically significant differences from those derived with the original pipeline at 3T and achieved accurate segmentation at 7T. The established normative atlas allowed characterizing tissue alterations in single-subject comparisons at 7T, and showed greater anatomical details compared with 3T results.A high-resolution quantitative atlas with an adapted pipeline was introduced and validated. Several case studies on different clinical conditions showed the feasibility, potential and limitations of high-resolution single-subject comparisons based on quantitative MRI atlases. This method in conjunction with 7T higher resolution broadens the range of potential applications of quantitative MRI in clinical practice.

With the recent surge in development of offshore wind in the Baltic Sea, Bohai Sea and other ice-prone regions, a need has arisen for new basin tests to qualify the interaction between offshore wind turbines and sea ice. To this end, a series of model tests was performed at the Aalto ice basin as part of the SHIVER project. The tests were aimed at modeling the dynamic interaction between flexible, vertically-sided structures and ice failing in crushing. A real-time hybrid test setup was used which combines numerical and physical components to model the structure. This novel test setup enabled the testing of a wide range of structure types, including existing full-scale structures for which ice-induced vibrations have been documented, and a series of single-degree-of-freedom oscillators to obtain a better understanding of the fundamental processes during dynamic ice-structure interaction. The tests were primarily focused on the dynamic behavior of support structures for offshore wind turbines under ice crushing loads. First results of the campaign show that the combination of the use of cold model ice and not scaling time and deflection of the structure can yield representative ice-structure interaction in the basin. This is demonstrated with experiments during which a scaled model of the Norströmsgrund lighthouse and Molikpaq caisson were used. The offshore wind turbine tests resulted in multi-modal interaction which can be shown to be relevant for the design of the support structure. The dataset has been made publicly available for further analysis.

Fixed offshore wind turbines continue to be developed for high latitude areas where not only wind and wave loads need to be considered but also moving sea ice. Current rules and regulations for the design of fixed offshore structures in ice-covered waters do not adequately consider the effects of ice loading and its stochastic nature on the fatigue life of the structure. Ice crushing on such structures results in ice-induced vibrations, which can be represented by loading the structure using a variable-amplitude loading (VAL) sequence. Typical offshore load spectra are developed for wave and wind loading. Thus, a combined VAL spectrum is developed for wind, wave, and ice action. To this goal, numerical models are used to simulate the dynamic ice-, wind-, and wave-structure interaction. The stress time-history at an exemplarily selected critical point in an offshore wind energy monopile support structure is extracted from the model and translated into a VAL sequence, which can then be used as a loading sequence for the fatigue assessment or fatigue testing of welded joints of offshore wind turbine support structures. This study presents the approach to determine combined load spectra and standardized time series for wind, wave, and ice action.

Fixed offshore wind turbines continue to be developed for high latitude areas where not only wind and wave loads need to be considered but also moving sea ice. Current rules and regulations for the design of fixed offshore structures in ice-covered waters do not adequately consider the effects of ice loading and its stochastic nature on the fatigue life of the structure. Ice crushing on such structures results in ice-induced vibrations, which can be represented by loading the structure using a variable-amplitude loading (VAL) sequence. Typical offshore load spectra are developed for wave and wind loading. Thus, a combined VAL spectrum is developed for wind, wave, and ice action. To this goal, numerical models are used to simulate the dynamic ice-, wind-, and wave-structure interaction. The stress time-history at an exemplarily selected critical point in an offshore wind energy monopile support structure is extracted from the model and translated into a VAL sequence, which can then be used as a loading sequence for the fatigue assessment or fatigue testing of welded joints of offshore wind turbine support structures. This study presents the approach to determine combined load spectra and standardized time series for wind, wave, and ice action. Fixed offshore wind turbines continue to be developed for high latitude areas where not only wind and wave loads need to be considered but also moving sea ice. Current rules and regulations for the design of fixed offshore structures in ice-covered waters do not adequately consider the effects of ice loading and its stochastic nature on the fatigue life of the structure. Ice crushing on such structures results in ice-induced vibrations, which can be represented by loading the structure using a variable-amplitude loading (VAL) sequence. Typical offshore load spectra are developed for wave and wind loading. Thus, a combined VAL spectrum is developed for wind, wave, and ice action. To this goal, numerical models are used to simulate the dynamic ice-, wind-, and wave-structure interaction. The stress time-history at an exemplarily selected critical point in an offshore wind energy monopile support structure is extracted from the model and translated into a VAL sequence, which can then be used as a loading sequence for the fatigue assessment or fatigue testing of welded joints of offshore wind turbine support structures. This study presents the approach to determine combined load spectra and standardized time series for wind, wave, and ice action. Fixed offshore wind turbines continue to be developed for high latitude areas where not only wind and wave loads need to be considered but also moving sea ice. Current rules and regulations for the design of fixed offshore structures in ice-covered waters do not adequately consider the effects of ice loading and its stochastic nature on the fatigue life of the structure. Ice crushing on such structures results in ice-induced vibrations, which can be represented by loading the structure using a variable-amplitude loading (VAL) sequence. Typical offshore load spectra are developed for wave and wind loading. Thus, a combined VAL spectrum is developed for wind, wave, and ice action. To this goal, numerical models are used to simulate the dynamic ice-, wind-, and wave-structure interaction. The stress time-history at an exemplarily selected critical point in an offshore wind energy monopile support structure is extracted from the model and translated into a VAL sequence, which can then be used as a loading sequence for the fatigue assessment or fatigue testing of welded joints of offshore wind turbine support structures. This study presents the approach to determine combined load spectra and standardized time series for wind, wave, and ice action.

It is well known that material properties undergo significant changes with temperature. In order to meet extreme environmental requirements for ships and offshore structures operating in Arctic regions, the effect of temperature on material behavior needs to be considered. In recent studies, significantly higher fatigue strength was observed for base materials and welded joints in comparison to room temperature. Fatigue strength increased even for temperatures far below the allowed service temperature based on fracture toughness results; however, sub-zero temperatures fatigue data are scarce and the effects of steel strength and welding type on fatigue strength changes are unknown. Material selection for ships and offshore structures is typically based on empirical Charpy and fracture toughness relations at the design temperature, minus a safety margin. Thus, this study presents material test results including fatigue tests of butt-welded joints, tensile test, and Charpy impact toughness tests at room and sub-zero temperatures of different structural steel types. Additionally, the effect of welding techniques and steel strength are discussed. The results can be used to extend design approaches for ships and offshore structures subject to sub-zero temperatures and to improve material selection for ships and offshore structures operating in Arctic regions.

The investigation of the physical traces of memories (engrams) has made significant progress in the last decade due to optogenetics and fluorescent cell tagging applied in rodents. Engram cells were identified. The ablation of engram cells led to the loss of the associated memory, silent memories were reactivated, and artificial memories were implanted in the brain. Human engram research lags behind engram research in rodents due to methodological and ethical constraints. However, advances in multivariate analysis techniques of functional magnetic resonance imaging (fMRI) data and machine learning algorithms allowed the identification of stable engram patterns in humans. In addition, MRI scanners with an ultrahigh field strength of 7 Tesla (T) have left their prototype state and became more common around the world to assist human engram research. Although most engram research in humans is still being performed with a field strength of 3T, fMRI at 7T will push engram research. Here, we summarize the current state and findings of human engram research and discuss the advantages and disadvantages of applying 7 versus 3T fMRI to image human memory traces.

Ships and offshore structures operating in Artic regions face specific challenges such as ice loads and seasonal low temperatures. In order to meet these extreme environmental requirements, the effect of temperature on material behaviour needs to be considered. It is well known that static material properties (yield strength, fracture toughness etc.) undergo significant changes with temperature. In recent studies, significantly higher fatigue strength was observed in welded joints in comparison to estimates based on international standards. Fatigue strength increased even for temperatures far below the allowed service temperature based on fracture toughness results; however, studies on fatigue strength of structural steel at sub-zero temperatures are scarce. Moreover, material selection for ships and offshore structures is usually based on empirical Charpy and fracture toughness relations at the design temperature, minus a safety margin. This study aims at introducing an S-N curve database for welded joints that can be used to verify the fatigue design approaches for ships and offshore structures subject to sub-zero temperatures. Therefore, the effect of temperature on the fatigue strength of butt-welded normal and high strength steel structures is analysed experimentally for sub-zero temperatures. For this purpose, fatigue test results of SAW and MAG welded joints for temperatures down to −50 °C are analysed and the potential for changes regarding material selection for ships and offshore structures are discussed.

In 2004 Flanders, the northern region of Belgium launched a range of large public–private partnership (PPP) projects for a total value of 6 billion euros. Ten years later, PPP has become a well-embedded procurement method for long-term public infrastructure projects. This article makes a critical ‘round-up’ of PPP experience in Belgium based on the perspectives of infrastructure professionals who were asked to provide their views on performance-related issues in PPP projects. Two workshops were held to further enrich the input and ideas. Based on this empirical material this article formulates 10 lessons to improve PPP performance, which is deliberately broadly defined. It argues that the dominant ‘value for money’ evaluations, following strictly financial or commercial logics (in both the private and public sectors), need to be broadened. Given the large impact and cost of large infrastructure projects on society, broader societal and spatial contributions of PPPs are needed.

Social interactions have a major impact on well-being. While many individuals actively seek social situations, others avoid them, at great cost to their private and professional life. The neural mechanisms underlying individual differences in social approach or avoidance tendencies are poorly understood. Here we estimated people’s subjective value of engaging in a social situation. In each trial, more or less socially anxious participants chose between an interaction with a human partner providing social feedback and a monetary amount. With increasing social anxiety, the subjective value of social engagement decreased; amygdala BOLD response during decision-making and when experiencing social feedback increased; ventral striatum BOLD response to positive social feedback decreased; and connectivity between these regions during decision-making increased. Amygdala response was negatively related to the subjective value of social engagement. These findings suggest a relation between trait social anxiety/social avoidance and activity in a subcortical network during social decision-making., eLife digest Your relationships with the people around you – friends, family, colleagues – have a strong influence on your overall life happiness. Even so, many people struggle to engage with the people around them. Social interactions can be stressful and many people choose to avoid them, even at a cost. Being able to measure these tendencies experimentally is a first useful step for assessing social avoidance without relying on people’s, often biased, recollections of their actions and behaviours. But how can a tendency to avoid social situations be quantified? And what can an experiment to measure this tendency reveal about the neural underpinnings of social avoidance? Schultz et al. asked volunteers to play a social game. If they played, the volunteers had the chance to win three euros, but they could choose not to play and receive a fixed amount of money, which varied across trials between zero and three euros. This approach allowed Schultz et al. to quantify how much the volunteers valued playing the game. The game involved playing with other virtual human partners, who gave either positive or negative social feedback depending on the outcome of the game in the form of videos of facial expressions. In a non-social control experiment, a computer gave abstract feedback in the form of symbols. Schultz et al. found that the value people placed on playing the social game varied with their level of social anxiety (established using a standard questionnaire). The more anxious people attributed less value to engaging in the game. Neuroimaging experiments revealed that the activity and connectivity between the amygdala and ventral striatum, two parts of the brain involved in processing emotions and reward-related stimuli, varied according to people’s levels of social anxiety. Social interactions have a major impact on the quality of life of both healthy people and those with mental disorders. Developing new ways to measure and understand the differences in the brain linked to social traits could help to characterise certain conditions and document therapy progress. Methods to quantify social anxiety and avoidance are also in line with efforts to explore the neuroscience behind the full range of human behaviour.

Foot-and-mouth disease virus (FMDV) is a highly variable RNA virus existing as seven different serotypes. The antigenic variability between and within serotypes can limit the cross-reactivity and therefore the in vivo cross-protection of vaccines. Selection of appropriate vaccine strains is crucial in the control of FMD. Determination of indirect relationships (r

Study design: This consisted of a translation and validation study. Background: Acute hamstring injury is a frequent muscle strain in sports that require high explosive strength, impulsion or running phases. Therefore, the Functional Assessment Scale for Hamstring Injury questionnaire was developed to assess pain, physical activity level and ability to perform various exercises in patients with hamstring injuries. The Functional Assessment Scale for Hamstring Injury questionnaire is currently available in English, German, and Greek. Objectives: The goal of this study was to provide a cross-culturally adapted French-translation of the FASH questionnaire and to assess its psychometric performance. Methods: The French-translation and cross-cultural adaptation process were based on international recommendations, following six rigorous steps: (a) two initial translations from English to French; (b) synthesis of the two translations; (c) back-translations; (d) comparisons between the back-translations and the original questionnaire by an expert committee; (e) pretest; and (f) approval of the final French version of the Functional Assessment Scale for Hamstring Injury questionnaire. To validate this French version, 116 subjects (17 pathological patients, 19 patients with other muscle injury, 40 athletes at risk, and 40 healthy control athletes) were recruited to complete the Functional Assessment Scale for Hamstring Injury questionnaire. The Short Form Health Survey (SF-36) was used as a comparative questionnaire. The psychometric properties of the questionnaire were evaluated by determining the test-retest reliability after a 48–60-h interval, internal consistency, construct validity, and floor/ceiling effects. Results: All of the items of the Functional Assessment Scale for Hamstring Injury questionnaire were translated without any major difficulties. The questionnaire showed excellent discriminative power by obtaining significantly different scores from the four groups (p = 0.01). Regarding psychometric performances, the test–retest reliability was excellent (IntraClass Coefficient Correlation of 0.997). Very high internal consistency was also observed (Cronbach's alpha of 0.969). Correlations with the physical health subscales of the SF-36 were significant and considered to be strong, indicating an excellent convergent validity. The other subscales of the SF-36 (mental health) were weakly correlated with the FASH, reflecting good divergent validity. No floor or ceiling effects were observed. Conclusion: The French-translation of the Functional Assessment Scale for Hamstring Injury questionnaire and its cross-cultural adaptation can be considered to be successful. Functional Assessment Scale for Hamstring Injury-French questionnaire is now a reliable and valid tool for patients suffering from acute hamstring injury, and its application in clinical practice is particularly relevant.Implications for rehabilitationThe FASH-F can be considered to be discriminant, reliable and valid for the evaluation of the severity of symptoms and sports ability in individuals with hamstring injuries.FASH-F is now a reliable and valid tool for French-speaking patients suffering from acute hamstring injury, and its application in clinical practice is particularly relevant.A limitation of our study could be that the distribution between the different study groups was not homogeneous implying that our findings may not be fully representative of the general population. The FASH-F can be considered to be discriminant, reliable and valid for the evaluation of the severity of symptoms and sports ability in individuals with hamstring injuries. FASH-F is now a reliable and valid tool for French-speaking patients suffering from acute hamstring injury, and its application in clinical practice is particularly relevant. A limitation of our study could be that the distribution between the different study groups was not homogeneous implying that our findings may not be fully representative of the general population.

Offshore wind turbines at locations where sea or lake ice is present need to be designed to withstand ice-induced loading. For vertical-sided support structures, such as monopiles, the effects of ice-induced vibrations need to be considered in the design. Current practice is either to use approaches provided in design standards, or for example to apply pre-generated ice load time series in the wind turbine aeroelastic model. These approaches have the drawback that the coupling between ice failure behavior and structural motion is not included. The effect of omitting this coupling on predictions for fatigue and ultimate limit states is currently not known. To enable fully coupled simulations in the design of offshore wind turbines, an existing simulation model for ice crushing has been recently coupled (“VANILLA”) to the in-house aeroelastic software package BHawC. In this paper this fully coupled model is applied to simulate ultimate limit state design load cases (DLCs) for a recent design of an offshore wind turbine on a monopile foundation. The project that is chosen for this case study is situated in the Southern Baltic Sea. The loads obtained for ice- and wind loading with the VANILLA model are compared to wind- and wave-induced loading. It is found that intermittent crushing is the governing ice interaction mode for offshore wind turbine support structures and rotor-nacelle-assembly components.

The current institutional set-up to fight EU fraud is considered unsatisfactory. With the creation of the EPPO, the definition of the offences it will investigate and prosecute, and the OLAF Regulation under revision, the EU has carved out a new institutional set-up. The objective, both from an administrative (OLAF) and criminal law perspective (EPPO), is to successfully investigate fraud and corruption affecting the EU’s financial interests. In addition to institutional and legal implementing steps, it is also important to consider what needs to be put in place in order to ensure the future quality of investigations, especially from the training perspective. This article presents some observations from the operational field with regard to what is arguably one of the major tools for enhancing the quality of PIF investigations: interviewing suspects.

This article analyses the (de)politicization dynamics in complex and technical matters like public–private partnerships, which is necessary given its social impact and budgetary consequences for the years and generations to come. The global financial crisis provides an excellent window of opportunity to present this argument, because PPP policy needs to reinvent itself. We argue that PPP policy needs to be (re)politicized at the broader societal and discursive levels, which means that their public nature is recognized and that policy alternatives are debated in the public forums. The ‘Private Finance Initiative’ reassessment process in the UK may serve as an example.

The effective control of foot-and-mouth disease (FMD) requires sensitive, specific and rapid diagnostic tools. However, the control and eradication of FMD in Africa is complicated by, among other factors, the existence of five of the seven FMD virus (FMDV) serotypes, including the SAT-serotypes 1, 2 and 3 that are genetically and antigenically the most variable FMDV serotypes. A key diagnostic assay to enable a country to re-gain its FMD-free status and for FMD surveillance, is the 3ABC or the non-structural protein (NSP) enzyme-linked immunosorbent assay (ELISA). Although many kits are available to detect 3ABC antibodies, none has been developed specifically for the variable SAT serotypes. This study designed a SAT-specific NSP ELISA and determined whether this assay could better detect NSP-specific antibodies from FMDV SAT-infected livestock. The assay's performance was compared to validated NSP assays (PrioCheck®-NSP and IZSLER-NSP), using panels of field and experimental sera, vaccinated and/or infected with FMDV SAT1, SAT2 or SAT3. The sensitivity () of the SAT-NSP was estimated as 76% (70%, 81%) whereas the specificity was 96% (95%, 98%) at a 95% confidence interval. The sensitivity and specificity were comparable to the commercial NSP assays, PrioCheck®-NSP (82% and 99%, respectively) and IZSLER-NSP (78% and 98%, respectively). Good correlations were observed for all three assays.

An antiviral containment strategy for foot-and-mouth disease (FMD) outbreaks could support or replace current contingency plans in case of an outbreak in Europe and could spare many healthy animals from being pre-emptively culled. Recently, substantial progress has been made towards the development of small molecule drugs that inhibit FMD virus (FMDV) replication in vitro. For the initial in vivo evaluation of antiviral lead molecules, a refined FMDV-infection model in guinea pigs (GP) is herewith described. This GP model was validated by demonstrating the antiviral effect of T-1105 (an influenza virus inhibitor with reported activity against FMDV). Sixteen animals were orally administered with T-1105 twice daily (400 mg/kg/day) for five consecutive days and inoculated intraplantarly with 100 GPID50 of the GP-adapted FMDV strain O1 Manisa 1 h after the first administration. The efficacy of T-1105 was compared with that of prophylactic vaccination with a highly potent double-oil emulsion-inactivated O1 Manisa vaccine. Ten animals received a single, full (2 ml) cattle vaccine dose and were inoculated 3 weeks later. Fourteen T-1105-treated and all vaccinated GP were completely protected from generalization of vesicular lesions. At 2 dpi, viral RNA was detected in serum of 9/16 T-1105-treated and of 6/10 vaccinated animals. At 4 dpi, viral RNA was detected in serum, organs and oral swabs of half of the T-1105-treated animals and only in the serum of 1/10 of the vaccinated animals. Mean viral RNA levels in serum and organs of T-1105-treated and vaccinated animals were reduced compared to untreated controls (P

This article questions the negative outlook on the democratic accountability in public–private partnerships (PPPs). It challenges this widely held perception in the literature with the empirical findings of a case study of Flemish school infrastructure (Belgium). A large design, build, finance, and maintenance (DBFM) programme is compared with the regular subsidizing system through the public agency AGIOn (Agency for School Infrastructure). This case study demonstrates that more accountability forums and actors can be active in the PPP, that they can behave more actively in the PPP, and that they get results in terms of accountability. It provides a critical example of having more accountability in the PPP variant of school infrastructure than in direct public provision, and there are reasons to argue that this also means improved accountability, because internal and latent processes of accountability become external and actual ones.

Summary Bluetongue virus serotype 8 (BTV-8) was responsible for a large outbreak among European ruminant populations in 2006–2009. In spring 2008, a massive vaccination campaign was undertaken, leading to the progressive disappearance of the virus. During surveillance programmes in Western Europe in 2010–2011, a low but significant number of animals were found weakly positive using BTV-specific real-time RT-PCR, raising questions about a possible low level of virus circulation. An interference of the BTV-8 inactivated vaccine on the result of the real-time RT-PCR was also hypothesized. Several studies specifically addressed the potential association between a recent vaccination and BTV-8 RNA detection in the blood of sheep. Results were contradictory and cattles were not investigated. To enlighten this point, a large study was performed to determine the risks of detection of bluetongue vaccine-associated RNA in the blood and spleen of cattle using real-time RT-PCR. Overall, the results presented clearly demonstrate that vaccine viral RNA can reach the blood circulation in sufficient amounts to be detected by real-time RT-PCR in cattle. This BTV-8 vaccine RNA carriage appears as short lasting.

In this article, we develop a theoretical argument that leads to a more optimistic outlook on the present state of accountability. By combining the different forums and functions of accountability in a multidimensional manner, the possibilities to hold power to account may be larger than often assumed. The main reason is that functions no longer depend on the well-functioning of a single forum and each forum serves multiple functions. In order to study accountability on a more systematic basis, we urgently need a solid conceptual framework. We aim to contribute to this much wanted coming to terms with accountability.

Background: Foot-and-mouth disease (FMD) vaccine potency testing involves hundreds of animals each year. Despite considerable efforts during the past decades, a challenge-free alternative vaccine potency test to replace the European protective dose 50% test (PD50) has not been implemented yet. The aim of the present study was to further characterize the properties of serological vaccine potency models. Methods: Logistic regression models were built for 5 serological assays from 3 different laboratories. The serum samples originated from 5 repeated PD50 vaccine potency trials with a highly potent A/IRN/11/96 vaccine. Receiver Operating Characteristic analysis was used to determine a serological pass mark for predicting in vivo protected animals. Subsequently, an estimated PD50 was calculated and the serotype dependency of the logistic models was investigated. Results: Although differences were observed between the laboratories and the serological assays used, the logistic models accurately predicted the in vivo protection status of the animals in 74-93% of the cases and the antibody pass levels corresponded to 84-97% of protection, depending on the serological assay used. For logistic models that combine different serotypes, the model fit can be increased by inclusion of a serotype factor in the logistic regression function. Conclusions: The in vitro estimated PD50 method may be at least as precise as the in vivo PD50 test and may accurately predict the PD50 content of a vaccine. However, the laboratory-effect and the serotype-dependency should be further investigated.

ResumePlusieurs auteurs font etat d’un abandon progressif des bureaucraties classiques au profit des accords de collaboration faisant intervenir des acteurs publics et prives. Dans le present article, nous etudions l’influence de cette evolution sur l’imputabilite. Notre analyse de cas de la politique de partenariat public prive (PPP) adoptee en Flandre (Belgique) nous amene a conclure a l’existence d’un paradoxe en matiere d’imputabilite. Nombreux sont les acteurs de premier plan dans la sphere politique qui font etat de serieuses defaillances dans le systeme d’imputabilite des PPP complexes. Avec l’introduction des PPP, cependant, le nombre de mecanismes d’imputabilite a effectivement augmente plutot que le contraire. Cette incoherence notable entre l’imputabilite en tant que moyen et resultat est le principal objet de notre article. Comment eviter que l’imputabilite se perde dans la diffusion des responsabilites publiques et privees ?Remarques a l’intention des praticiensLa plupart des recherches font observer que l’imputabilite dans les PPP pose probleme. Notre analyse empirique confirme cette interpretation negative d’une maniere generale. Les repondants se posent des questions sur la facon dont l’imputabilite fonctionne de nos jours dans la pratique. Nous affirmons des lors que : l’evolution vers les PPP fragilise la notion classique d’imputabilite ; elle comporte de nouveaux outils d’imputabilite, qui mettent l’accent sur le rendement ; ces outils ne font cependant pas contrepoids a la notion classique et fragilisee d’imputabilite. Ils font cependant aussi preuve d’un optimisme notable au sujet du potentiel des PPP en matiere d’imputabilite. En apportant les modifications necessaires (mineures ou majeures), il est possible de concilier les fonctions democratique, constitutionnelle et de rendement de l’imputabilite.

Cell-based assays are still used widely in foot-and-mouth disease (FMD) research, despite the existence of a wide variety of molecular techniques. The aim of this study was to validate an automated, quantitative spectrometric reading to replace the time-consuming and subjective microscopic (MIC) evaluation of the FMD virus-induced cytopathic effect (CPE). Therefore, the diagnostic performance of two commercial cell viability assays (CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS) and CellTiter-Blue® Cell Viability Assay (CTB), both from Promega, Leiden, The Netherlands) was evaluated. Following optimization of the assay protocols and using the MIC results as a reference standard, the absorbance-read MTS assay, the fluorescence-read CTB assay and the absorbance-read CTB (CTBabs) assay demonstrated similar high sensitivities (97%, 99% and 98%, respectively), specificities (100%, 98% and 99%, respectively), accuracy measures (0.99, 0.98 and 0.98, respectively), precision measures (1.00, 0.98 and 0.99, respectively) and Cohen kappa agreement indices (0.97, 0.97 and 0.96, respectively) for detecting CPE in cell cultures. Due to its performance, cost effectiveness and ease of use, the CTBabs assay was selected for further evaluation of its ability to detect virus neutralization and to screen antiviral compounds. The CTBabs assay had 99% sensitivity and 100% specificity for the detection of neutralizing antibodies in sera from cattle infected with FMDV and in sera from unvaccinated, uninfected cattle and resulted in a mean Z � -factor of 0.85 for antiviral compound test plates. The CTBabs assay is now used routinely in the Belgian FMD reference laboratory for serological testing and high-throughput antiviral compound screening. © 2011 Elsevier B.V. All rights reserved.

Solid dispersion formulations made up of d-alpha-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000) and polyvinyl pyrrolidone co-vinyl acetate 64 (PVPVA 64) or hydroxy propyl methyl cellulose 2910 (HPMC 2910) were developed in order to improve the dissolution of UC 781. UC 781 dissolution rate was markedly improved as compared to the physical mixtures and the pure drug, attaining maximum drug releases of up to 100% after only 5 min in the case of TPGS 1000-UC 781-PVPVA 64 solid dispersions and 30 min in TPGS 1000-UC 781-HPMC 2910. The increased UC 781 dissolution rate could be maintained when formulating UC 781 in PVPVA 64 tablets. The latter disintegrated in only 4 min, reaching drug releases of up to 90% (w/w). In addition, as opposed to the corresponding solid dispersions, no decrease in drug release occurred upon dissolution of PVPVA 64 tablets when the pH was increased to 6.8. Contrary to the PVPVA 64 tablet formulations, HPMC 2910 tablets showed a slow dissolution process due to the gelling nature of the polymer. The drug was slowly released as HPMC 2910 dissolved in the medium, however also in this case 90% (w/w) of the drug was dissolved after 4 h. Both polymers formed compatible blends in combination with the drug. Thermal analysis of the ternary mixtures revealed eutectic behavior exhibiting an extremely fine dispersion of the drug in the carrier. This was confirmed by the fact that no drug crystals could be detected using X-ray diffraction (XRD). As opposed to the physical mixtures, PVPVA 64 and HPMC 2910 solid dispersions did not contain any isolated polymer-rich phases, hence showed improved homogeneity. Amorphous TPGS 1000 clusters occurred in PVPVA 64 and HPMC 2910 formulations upon addition of at least 10% (w/w) UC 781, showing extremely low glass transition temperatures depending of the thermal history of the samples.

There is much scepticism about the accountability of regulatory agencies towards society. It is generally believed that their non-majoritarian nature and need for credible commitment, which motivate their formal independence, render the accountability of such agencies problematic (see Chapter 1 of this book). The need for upward accountability must be balanced with the strict principle of non-interference by politicians in the activities and decisions of such agencies. Agencification (or autonomization) of public sector organizations renders traditional forms of upward accountability towards political principals (ministers and parliaments) problematic, as autonomy and accountability have an uneasy relationship. Several authors point at alternative forms of accountability (see Chapter 1), including downward accountability towards stakeholders, peers and target groups, as ways to overcome deficiencies in upward accountability relations. However, it remains unclear to what extent such alternative accountability mechanisms are really effective (see, for instance, Schillemans 2008). In this chapter we look at the circumstances under which regulatory agencies have elaborated upward and downward accountability mechanisms, and to what extent their degree of formal independence, de facto managerial autonomy and political salience influence the use of such accountability mechanisms. Moreover, the chapter analyses to what extent and under what circumstances the use of upward and downward accountability mechanisms results in a high level of accountability towards society, as perceived by the senior management of regulatory agencies.

Satellite imagery, and specifically CORONA, is now of common use in archaeology. CORONA, as it produces two images of the same spot (afterward and forward), allows for stereoscopic view and is a perfect tool for the production of maps, especially in remote areas, where maps are not reliable of even absent. However, in all cases until now, often, it appears that only one of both images is used and that one considers this view as a geographical correct image. This is not correct. Using the test case of fieldwork and research in the Altai Mountains, we suggest that one should use both images of the same spot. Firstly, the two images give different information (shadow, lighting, different angles). Secondly, the use of both images, after georeferencing, makes it possible to produce orthophoto's and DSM's. For a correct georeferenced orthophoto, there is a need for a correct positioning of a certain amount of ground control points (GCP's). During the fieldwork in Altai, we tested several GPS devices. It appears that C&C C-Nav, a dual frequency, geodetic grade, GPS receiver, is a highly optimised equipment for the production of GCP's, and can be used for all types of satellite images. Common hand-held Garmin 12XL and Motorola Oncore VP hand-held GPS receivers are suitable for the localisation of archaeological sites and objects, on the condition of extensive post-processing using network solutions. These devices can also be used for CORONA as well as for other satellite images, with a resolution up to 2–4 m.

Satellite photographs, such as the CORONA series, are proving valuable instruments of archaeological reconnaissance, especially for landscapes that are relatively unknown or unprotected. Moreover, satellite imagery can be used for detailed mapping of remote areas, so that a topographic map or Digital Elevation Model can form the background for the archaeological information. However, images seen on the photographs may not be immediately recognisable as sites, and sites on the ground may escape detection from a satellite. In a current project in south Siberia the authors test the visibility of the one against the other.

Ciliary orientation (COR) is an important parameter of mucociliary clearance and ciliary disorientation has been reported in cases of acquired abnormalities [secondary ciliary dyskinesia (SCD)] and in a very few cases as the single abnormality in primary ciliary dyskinesia (PCD). The etiology, pathogenesis, consequences and relevance of ciliary (dis)orientation are still unclear.To elucidate the primary or secondary nature of ciliary (dis)orientation, COR was measured in 179 non-PCD and 59 PCD patients. COR was measured in biopsies and after ciliogenesis in culture and was correlated with a number of functional and ultrastructural parameters. COR was defined as the SD of the angles of lines through the central pair of microtubules using transmission electron microscopy. Internationally accepted normal values for COR areor = 20 degrees; COR values of 20-35 degrees indicate increased disorientation; and COR values35 degrees represent a random orientation.For non-PCD biopsies, COR increased with increasing SCD, from 15 +/- 7 degrees (n = 54) for normal (5%) SCD to 28 +/- 8 degrees (n = 16) for severe (25%) SCD. No correlation was found between COR and ciliary beat frequency. However, increased COR values (28 +/- 8 degrees) were found for immotility (n = 8), compared to (coordinated) ciliary activity (19 +/- 9 degrees) (n = 121). After ciliogenesis no ultrastructural abnormalities were found and COR was normal (13 +/- 5 degrees; n = 308). COR can therefore be considered to be secondary in non-PCD and correlates with SCD percentage and ciliary motility. In biopsies from PCD patients with dynein deficiency and with normal ultrastructure, COR was increased, to 28 +/- 11 degrees (n = 32) and 21 +/- 7 degrees (n = 15), respectively, and in cases with central pair abnormalities COR was random (38 +/- 11 degrees; n = 12). After ciliogenesis COR remained random in the PCD group with central pair abnormalities (38 +/- 9 degrees; n = 15), and was increased in the PCD groups with dynein deficiency (24 +/- 10 degrees; n = 35) and normal ultrastructure (25 +/- 8 degrees; n = 17). Ciliary disorientation was never found as the single abnormality.COR can be considered to be secondary in PCD. Both ciliary (im)motility and SCD percentage contribute to COR.

Atmospheric pressure loading is known to generate noise in GPS vertical time series. Even weekly solutions of GPS determined vertical coordinates are correlated with atmospheric loading in more than 70% of the stations investigated. When correcting the GPS coordinates resulting from the different GPS processing centres for atmospheric loading, different variance reductions or augmentations for the same station are found. However, stations in Central and Southern Asia show high variance reductions, whereas nearly all coastal stations and island stations sometimes show a small augmentation in the variance, possibly due to the small variances of the loading signal itself.

Purpose. The purpose of this study was to provide functional and molecular evidence to support the existence of large neutral amino acid transporters in human nasal epithelium using nasal primary cell culture model.

Public-private partnerships (PPPs) are used very widely but remarkably little empirical research has been published investigating the governance of PPPs. PPPs are complex infrastructure projects and present important governance challenges as the responsibilities of public and private partners are ambiguous and can be confused. This paper looks at the interactions between the elements of complexity and at the governance structure of PPPs, and their combined effect on performance. A case study in Flanders (the northern region of Belgium) is discussed.

The gold standard for the diagnosis of primary ciliary dyskinesia (PCD) is a dynein deficiency shown with transmission electron microscopy. However, there are many cases of PCD without dynein deficiency. When considering ciliary function, there are similar problems of sensitivity in diagnosis and there is also a major lack of specificity. Based on the normal ciliary function and ultrastructure and the absence of secondary abnormalities after ciliogenesis in sequential monolayer-suspension culture, the diagnostic value of ciliary function analysis after ciliogenesis was investigated in more than 70 PCD and 640 non-PCD cases. In biopsies, ciliary immotility was found in 66% of PCD cases but was also found in 8% of non-PCD cases. PCD was later confirmed in 61% of the biopsies with ciliary immotility. Normal ciliary beat frequency (CBF) was found in 20% of PCD biopsies. Coordinated ciliary activity was observed in 10% of PCD cases. After ciliogenesis in culture, ciliary immotility was present in 78% of the PCD cases but never in non-PCD cases. CBF was normal after ciliogenesis in 7% of the PCD cases and was always found in non-PCD cases. Absence of coordinated ciliary activity was found in 100% of PCD cases and 0% of non-PCD cases. In conclusion, while ciliary function analysis in a biopsy never proves, nor excludes the diagnosis of PCD, after ciliogenesis in culture CBF measurement can be diagnostic for PCD and reaches 100% specificity and sensitivity when considering coordinated ciliary activity, making it the single 100% diagnostic parameter for PCD.

Purpose. To test two in vitro human nasal epithelial cell culture systems for their ability to screen the effects of pharmaceutical compounds on ciliary beating.

Several authors have documented a shift from traditional bureaucracies to collaborative arrangements with joint public and private involvement. This article studies the impact of this shift on accountability. We conclude from our explorative case analysis of Public— Private Partnership (PPP) policy in Flanders (Belgium) that there is an accountability paradox. Many prominent players in the policy arena point to serious shortcomings in the accountability of complex PPPs. Yet, with the introduction of PPPs, the number of accountability mechanisms did increase rather than decrease. This remarkable inconsistency between accountability as a tool and as a result is the main focus of this article. How can we avoid that accountability gets lost in the diffusion of public and private responsibilities?Points for practitionersMost research concludes that there is something wrong with accountability in PPPs. Our empirical analysis confirms in general this negative interpretation. The respondents share important concerns about how accountability works nowadays in practice. We therefore state that: the shift towards PPPs erodes the traditional notion of accountability; it entails new tools of accountability with a strong emphasis on performance; these tools, however, do not counterbalance the eroded traditional notion of accountability. Yet, they also share a remarkable optimism about the accountability potential of PPPs. With the necessary modifications (minor or major) a balance between the democratic, constitutional and performance functions of accountability can be found.

The selection of matching strains for use in outbreaks of foot-and-mouth disease (FMD) virus can be assessed in vivo or by serological r-value determination. Sera from animals involved in vaccine potency and cross-protection trials performed using the "Protection against Podal Generalization" (PPG) test for two serotype A strains were collected and analyzed by the virus neutralization test (VNT) and liquid-phase ELISA (lpELISA) in three laboratories. The average VNT r-values for medium and high serum titer classes from the A(24) Cruzeiro vaccinated animals were in line with the A/Arg/01 heterologous PPG outcome for all testing laboratories, suggesting that the vaccine strain A(24) Cruzeiro is unlikely to protect against the field isolate A/Arg/01. The corresponding lpELISA r-values were slightly higher and indicate a closer relationship between both strains. Pooling of serum samples significantly reduced the inter-animal and inter-trial variation. The results suggest that a suitable reference serum for vaccine matching r-value experiments might be a pool or a medium to high VNT or lpELISA titer serum. Furthermore, the VNT seems to produce the most reproducible inter-laboratory results. More work is, however, needed in order to substantiate these claims.

Foot-and-mouth disease (FMD) vaccine potency testing has historically been performed by experimentally infecting vaccinated cattle. A few alternative approaches to the in vivo challenge test based on the correlation between serum titres of primo-vaccinated cattle and protection against infection have been proposed, but none have been accepted by the European Pharmacopoeia (Ph.Eur.) due to the lack of statistical power and the pooling of data over time. The present study addresses these issues and presents data of 150 cattle vaccinated according to Ph.Eur. standards. Four laboratories took part in the serological testing and different serological assays were used, including virus neutralisation assays and ELISA formats. Models correlating specific anti-FMD virus antibody titres to protection were built using logistic regression followed by Receiver Operating Characteristic (ROC) analysis. The best models accurately predicted the in vivo protection status in 80.0% of the cases. Although differences were observed between laboratories and assays used, the majority of antibody pass-levels, determined using ROC analysis, corresponded to at least 75.0% probability of protection. The indirect potency assessment procedure proposed is at least as precise (repeatability = 65.8%, reproducibility = 60.7%) as the in vivo test, can be standardised and results in a quantitative PD50 value. The validity of the procedure was also demonstrated. (c) 2008 Elsevier Ltd. All rights reserved

Background: A study was undertaken to assess the reliability of the nasal mucociliary transport test using 99mTc-albumin colloid as a screening test for primary ciliary dyskinesia (PCD) and to compare it with the gold standard nasal biopsy for study of ciliary motility and ultrastructure. Methods: During a 4 year period both tests were performed in 55 children referred with persistent or recurrent respiratory tract infections. Their median age was 4 years (range 1 month to 15 years). Results: The nasal biopsy results were as follows: PCD, n = 8; secondary ciliary dyskinesia (SCD), n = 19; normal, n = 28. The mucociliary transport test was abnormal in 29 patients (all 8 with PCD, 7/19 with SCD, and 14/28 with a normal biopsy). The sensitivity of the mucociliary transport test to diagnose PCD was therefore 100% (8/8) (95% exact confidence limits 63.06 to 100.00); the specificity was only 55% (26/47) (40.95 to 69.89). The negative predictive value was 100% (26/26) (86.77 to 100.00) and the positive predictive value was 28% (8/29) (12.37 to 47.24). Conclusion: Mucociliary transport is a non-invasive screening test that can be performed even in infants. The sensitivity of the test is high but its specificity is low. A normal test result excludes PCD.

The purpose of this study was to provide functional and molecular evidence to support the existence of large neutral amino acid transporters in human nasal epithelium using nasal primary cell culture model.L-Phenylalanine was used as a model substrate to characterize carrier-mediated permeation of amino acids across human nasal epithelium. The influence of temperature, concentration, other amino acids, metabolic/transport inhibitors, and polarity/stereo-selectivity on transport of the model compound was investigated. Reverse transcriptase polymerase chain reaction was used for molecular characterization of the existence of the transporters.The transport of L-phenylalanine across the human nasal epithelium was polarized (apical --basolateralbasolateral --apical), saturable (Km = 1.23 mM; Vmax = 805.1 nmol/mg protein/min) and stereo-selective (permeation of L-phenylalanineD-Phenylalanine). Its permeation was significantly (0.05) reduced by cationic, small and large neutral amino acids, oubain, amiloride, sodium-free medium, and temperature lowering. Reverse transcriptase polymerase chain reaction revealed the presence of the broad-scope cationic-dependent amino acid transporter gene (y+LAT-2) in the human nasal epithelium.Based on the results of this study, one may postulate that the human nasal epithelium expresses L-amino acid transporters. More studies are necessary for detailed characterization of the transporters.

The aim of this study was to investigate the suitability of a sequential monolayer-suspension culture system as a model to screen subacute effects of drug excipients on ciliary beat frequency (CBF). The CBF of the cultured cells was measured by computerized microscope photometry. Protease inhibitors (puromycin, bestatin, bacitracin, actinonin and thiomersal) were used as model compounds and the mechanisms of ciliary inhibition were investigated by probing the involvement of arachidonic acid metabolism, guanylate cyclase (cGMP), protein kinase C (PKC) and adenosinetriphosphate (ATP) inhibition. Bestatin concentration-dependently reduced CBF by inhibiting arachidonic acid metabolism, cGMP, PKC and endogenous ATP consumption. Thiomersal and DMSO used for dissolving actinonin reduced CBF (P0.05) via a non-specific mechanism. Bacitracin (8 mM) and puromycin (135 mM) had no effect on CBF after acute exposure (15-30 min) (P0.05), but significantly reduced the CBF by approximately 15.0% following daily 15-min exposure for 1 week. This study shows that (i) sequential monolayer-suspension culture system is a valid model to screen both acute and subacute effects of drug excipients on CBF; and (ii) bacitracin, puromycin and actinonin are more cilio-compatible than bestatin and thiomersal and as such are more potentially useful nasal absorption enhancer from ciliotoxicity perspective.

The aim of this study was to establish a collagen matrix-based nasal primary culture system for drug delivery studies. Nasal epithelial cells were cultured on derivatised (Cellagen membrane CD-24), polymerised (Vitrogen gel) and fibrillar (Vitrogen film) collagen substrata. Cell morphology was assessed by microscopy. The cells were further characterised by measurement of ciliary beat frequency (CBF), transepithelial resistance (TER), permeation of sodium fluorescein, mitochondrial dehydrogenase (MDH) activity and lactate dehydrogenase (LDH) release upon cell exposure to sodium tauro-24, 25 dihydrofusidate (STDHF). Among the three collagen substrata investigated, the best epithelial differentiated phenotype (monolayer with columnar/cuboidal morphology) occurred in cells grown on Cellagen membrane CD-24 between day 4 and day 11. Cell culture reproducibility was better with Cellagen membrane CD-24 (90%) in comparison with Vitrogen gel (70%) and Vitrogen film (< 10%). TER was higher in cells grown on Vitrogen gel than on Cellagen membrane CD-24 and Vitrogen film. The apparent permeability coefficient (Papp × 10−7 cm s−1) of sodium fluorescein in these conditions was 0.45 ± 0.08 (Vitrogen gel) and 1.91 ± 0.00 (Cellagen membrane CD-24). Except for LDH release, CBF and cell viability were comparable for all the substrata. Based on MDH activity, LDH release, CBF, TER and permeation studies, Cellagen membrane CD-24- and Vitrogen gel-based cells were concluded to be functionally suitable for in-vitro nasal drug studies. Vitrogen film-based cultures may be limited to metabolism and cilio-toxicity studies.