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Met het Wilders II-arrest heeft de Hoge Raad een verdere invulling gegeven aan het in het Felter-arrest geïntroduceerde onverdraagzaamheidscriterium. Helder is nu dat dit criterium geactiveerd wordt wanneer er sprake is van beledigende uitlatingen specifiek gericht tegen een minderheidsgroep. Dergelijke uitlatingen, in de specifieke wijze waarop deze gedaan werden in Wilders II, dienen binnen het toetsingskader van artikel 137c (en d) Sr als ‘onnodig grievend’ te worden beoordeeld. Een politicus verliest daarmee de bescherming die de disculperende context van het maatschappelijke debat hem of haar normaal gesproken kan bieden. In diezelfde beweging heeft de Hoge Raad de artikelen 137c en 137d Sr nu nog duidelijker in de sfeer van de weerbare democratie getrokken, dat wil zeggen: als bepalingen (mede) ter verdediging van de democratische rechtsstaat.

Naval vessels around the world are looking to reduce their fuel consumption to not only drive down their environmental impact, but also gain the additional benefit of improving their endurance and reducing their (strategic) dependency on their primary fuel sources. Therefore, based on the strategic value of fuel in the operational environment, multiple navies around the world are investigating alternative energy conversion devices and fuels. In recent years, solid oxide fuel cells (SOFCs) have gathered increasing attention for maritime applications as an alternative to the traditional diesel engines. SOFCs showcase high power generation efficiency, ultralow emissions and noise-free operation, which are ideal pre-requisites for power generation onboard naval and commercial ships. Capitalizing on these attributes of SOFCs, this paper aims to investigate the potential of a novel COmbined drive of Fuel cell And Internal Combustion Engine (COFAICE) for naval vessels that employs a SOFC-ICE integration concept for power generation. In this paper, the performance of SOFC-ICE integration is tested for three different case studies of naval ships, namely, an oceangoing patrol vessel, a landing platform dock and a high-speed surface combatant. We investigate the optimal load sharing between the two energy conversion devices for different operational profiles and operating modes of a notional naval vessel. Optimal load sharing strategies are generated to study the impact on power-generation efficiency and CO2 emissions while taking into account the space and weight considerations for the system and fuel bunkering. The performance of the natural gas-fuelled SOFC-ICE integration concept is compared against the conventional and existing power plants onboard comparable ships. Furthermore, based on the optimal power split, potential of two SOFC-ICE integration methods are investigated for part-load operations. We find that significant improvements in efficiency and CO2 emission reductions can be achieved for the integrated SOFC-ICE power plants with optimized space and weight considerations.

International audience; Nanoparticle organic photovoltaics, a subfield of organic photovoltaics (OPV), has attracted increasing interest in recent years due to the eco-friendly fabrication of solar modules afforded by colloidal ink technology. Importantly, using this approach it is now possible to engineer the microstructure of the light absorbing/charge generating layer of organic photovoltaics; decoupling film morphology from film deposition. In this study, single-component nanoparticles of poly(3-hexylthiophene) (P3HT) and phenyl-C61 butyric acid methyl ester (PC61BM) were synthesized and used to generate a two-phase microstructure with control over domain size prior to film deposition. Scanning transmission X-ray microscopy (STXM) and electron microscopy were used to characterize the thin film morphology. Uniquely, the measured microstructure was a direct input for a nanoscopic kinetic Monte Carlo (KMC) model allowing us to assess exciton transport properties that are experimentally inaccessible in these singlecomponent particles. Photoluminescence, UV−vis spectroscopy measurements, and KMC results of the nanoparticle thin films enabled the calculation of an experimental exciton dissociation efficiency (ηED) of 37% for the two-phase microstructure. The glass transition temperature (Tg) of the materials was characterized with dynamic mechanical thermal analysis (DMTA) and thermal nnealing led to an increase in ηED to 64% due to an increase in donor−acceptor interfaces in the thin film from both sintering of neighboring opposite-type particles in addition to the generation of a third mixed phase from diffusion of PC61BM into amorphous P3HT domains. As such, this study demonstrates the higher level of control over donor−acceptor film morphology enabled by customizing nanoparticulate colloidal inks, where the optimal three-phase film morphology for an OPV photoactive layer can be designed and engineered.

In this cross-sectional study among vaccine-eligible female sexually transmitted infection clinic visitors, high vaccine effectiveness of the bivalent vaccine against the vaccine types HPV-16/18 was demonstrated and significant cross-protection against the nonvaccine high-risk HPV types 45, 35, 31, and 52., Background Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. Methods We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. Results We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%–94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who were offered vaccination 5/6 years ago, we estimated similar VE against HPV-16/18 (92%) and all hrHPV types (35%) compared to women who were offered vaccination

BACKGROUND: Violence perpetrated by women has attracted more and more attention in the past few years. However, there is lack of background information about women admitted to forensic psychiatric hospitals and about risk factors for recidivism. AIM: To conduct a multicenter study which will give more insight into female psychiatric patients and which will probably have implications for psychodiagnostics, risk assessment and treatment in (forensic) psychiatric settings. METHOD: We coded the files of 297 women who, between 1984 and 2013, had been admitted to one of four Dutch forensic psychiatric facilities by reason of violent delinquent behaviour. We used an extensive coding list and several risk assessment tools including the recently developed Female Additional Manual (fam) for women. RESULTS: The general picture that emerged was one of severely traumatised women with complex pathology and a high level of comorbidity. Many of the women had experienced previous treatment failures and had caused many incidents during treatment. CONCLUSION: Female forensic psychiatric patients are a complex group that deserves more specific attention. Attention for traumas from the past, intensive supervision in relationships and training for staff in dealing with, for instance, manipulative behaviour are the most important implications from this study.

Hydrological ensemble prediction systems (HEPS) have in recent years been increasingly used for the operational forecasting of floods by European hydrometeorological agencies. The most obvious advantage of HEPS is that more of the uncertainty in the modelling system can be assessed. In addition, ensemble prediction systems generally have better skill than deterministic systems both in the terms of the mean forecast performance and the potential forecasting of extreme events. Research efforts have so far mostly been devoted to the improvement of the physical and technical aspects of the model systems, such as increased resolution in time and space and better description of physical processes. Developments like these are certainly needed; however, in this paper we argue that there are other areas of HEPS that need urgent attention. This was also the result from a group exercise and a survey conducted to operational forecasters within the European Flood Awareness System (EFAS) to identify the top priorities of improvement regarding their own system. They turned out to span a range of areas, the most popular being to include verification of an assessment of past forecast performance, a multi-model approach for hydrological modelling, to increase the forecast skill on the medium range (>3 days) and more focus on education and training on the interpretation of forecasts. In light of limited resources, we suggest a simple model to classify the identified priorities in terms of their cost and complexity to decide in which order to tackle them. This model is then used to create an action plan of short-, medium- and long-term research priorities with the ultimate goal of an optimal improvement of EFAS in particular and to spur the development of operational HEPS in general.

Hydrological ensemble prediction systems (HEPS) have in recent years been increasingly used for the operational forecasting of floods by European hydrometeorological agencies. The most obvious advantages of HEPS are that more of the uncertainty in the modelling system can be assessed; and that ensemble prediction systems generally have better skill than deterministic systems both in the terms of the mean forecast performance and the potential forecasting of extreme events. Research efforts have so far mostly been devoted to the improvement of the physical and technical aspects of the model systems, such as increased resolution in time and space and better description of physical processes. Developments like these are needed, however, in this paper we argue that there are other areas of HEPS that also need urgent attention; such as assessment of the full uncertainties in the forecast chain, a robust forecast skill assessment and focus on the interactions between model developing community, users of the system and the receiving end of the information. In this paper we identify research priorities within the users of the European Flood Awareness System (EFAS) and in light of limited resources we suggest a simple model to classify the identified priorities in terms of their cost and complexity to decide in which order to tackle them. This model is then used to create an action plan of short-, medium- and long-term research priorities with the ultimate goal of an optimal improvement of EFAS in particular and to spur on the development of operational HEPS in general., JRC.H.7-Climate Risk Management

Summary Background Thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. After alteplase-induced recanalisation, reocclusion occurs in 14–34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after alteplase could reduce the risk of reocclusion and improve outcome. We compared the effects of early addition of intravenous aspirin to alteplase with standard alteplase without aspirin. Methods In this multicentre, randomised, open-label trial with blind-endpoint assessment, patients with acute ischaemic stroke treated with alteplase were randomly assigned to 300 mg intravenous aspirin within 90 min after start of alteplase treatment or to no additional treatment. In both groups, oral antiplatelet therapy was started 24 h after alteplase treatment. The primary endpoint was favourable outcome, defined as a score of 0–2 on the modified Rankin scale at 3 months. This trial is registered with the Netherlands Trial Register (NTR822). Findings Between July 29, 2008, and April 20, 2011, 642 patients (322 patients aspirin, 320 patients standard treatment) of the targeted 800 patients were enrolled. At that time, the trial was terminated prematurely because of an excess of symptomatic intracranial haemorrhage (SICH) and no evidence of benefit in the aspirin group. At 3 months, 174 (54·0%) patients in the aspirin group versus 183 (57·2%) patients in the standard treatment group had a favourable outcome (absolute difference −3·2%, 95% CI −10·8 to 4·2; crude relative risk 0·94, 0·82 to 1·09, p=0·42). Adjusted odds ratio was 0·91 (95% CI 0·66–1·26, p=0·58). SICH occurred more often in the aspirin group (14 [4·3%] patients) than in the standard treatment group (five [1·6%]; absolute difference 2·8%, 95% CI 0·2–5·4; p=0·04). SICH was more often the cause of poor outcome in the aspirin group compared with the standard treatment group (11 vs 1, p=0·006). Interpretation Early administration of intravenous aspirin in patients with acute ischaemic stroke treated with alteplase does not improve outcome at 3 months and increases the risk of SICH. The results of this trial do not support a change of the current guidelines, which advise to start antiplatelet therapy 24 h after alteplase. Funding The Dutch Heart Foundation.

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A recent trial revealed a reduction in ischaemic infarcts after carotid endarterectomy in patients with asymptomatic carotid stenosis. However, the number needed to treat (NNT) was 22 to prevent 1 stroke in 10 years (including perioperative death as a primary outcome measurement). This is a modest effect in comparison to the trials with symptomatic patients with a 70-99% stenosis (NNT: 6). Furthermore, the number of surgical complications outweighs the benefits of surgery during the first 2 years after treatment. Finally, current medical treatment is significantly more effective than the medical treatment used in the control arm of this trial. Therefore, in our opinion, endarterectomy should not be performed routinely in asymptomatic patients

The number of second opinions (SO) and tertiary referrals (TR) in neurology is increasing. Previously, we showed that a day-care admission for neurological SO's and TR's often results in a new diagnosis and/or treatment advice and increases patient satisfaction. However, long-term satisfaction for these consultations has never been studied. The main purpose of this study was to investigate long-term satisfaction in these groups of patients. A 2-year follow-up study in 300 patients who had attended a day-care clinic for SO and TR. Long-term satisfaction was assessed with a questionnaire using four Visual Analogue Scale (VAS) satisfaction items (ranging 0-10). Patients were asked if they had sought further consultations for the same problem after they had consulted the day-care clinic. A model was constructed to assess predictors for seeking new consultations. Overall satisfaction decreased 2.4 (SD 2.4) points during follow-up to the same level as before the consultation. The decrease was similar in SO and TR patients. Twenty-eight per cent of the patients consulted other health-care workers. Greater satisfaction immediately after the consultation was the only predictor for not seeking additional consultations (OR 0.78, 95% CI 0.61-0.99 for every point increase on VAS). Despite a high rate of new diagnoses and advised treatments, long-term satisfaction decreased after 2 years to baseline levels. These results question the long-term efficacy of a day-care clinic to evaluate neurological second opinions and tertiary referrals

BACKGROUND: Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for

In the bronchoalveolar lavage of sarcoidosis patients the mononuclear cell infiltrate was enumerated on T helper and suppressor lymphocytes as well as macrophages by means of a triple-staining assay on cytospin slides. As was seen on the slides, lymphocytes were often adhered very closely to macrophages. This phenomenon, many times described but not understood, was studied in a group of 13 sarcoidosis patients, of whom 7 received prednisolone treatment. It could be shown that treatment with the corticosteroid was followed by an increase in the percentage of suppressor lymphocytes adhered to macrophages. Second, the number of such alveolar T suppressor lymphocyte-macrophage aggregates was dramatically increased in the prednisolone-treated patients.

Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alte plase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P = 0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P

The atmospheres of (exo) planets and moons, as well as reflection nebulae, contain in general independently scattering particles in random orientation and are often supposed to be plane-parallel. Relations are presented for the (bidirectional) reflection function and several related functions of such a medium in case the directions of incidence and reflection both tend to horizontal directions. The results are quite general. The medium may be semi-infinite or finite, with or without a reflecting surface underneath, and vertically homogeneous or inhomogeneous. Some approximative formulae for the reflection function of a plane-parallel medium with independently scattering particles in random orientation, including Lambert's law, may be very inaccurate if the directions of incidence and reflection are both nearly horizontal., Accepted for publication in Astron. Astrophys

In the European Cooperative Acute Stroke Study 3 (ECASS3), the efficacy of intravenous thrombolysis between 3 and 4.5 hours following onset of ischaemic stroke was investigated. Compared to the placebo group, patients treated with intravenous alteplase had a better functional outcome after 3 months (odds ratio 1.34, 95% confidence interval 1.02-1.76). The risk of symptomatic intracerebral haemorrhage was higher in the alteplase group (2.4% versus 0.3%). The time window for intravenous alteplase can be safely extended to 4.5 hours, but efforts should be made to start treatment as soon as possible, since the effectiveness ofalteplase decreases over time.

A recent trial revealed a reduction in ischaemic infarcts after carotid endarterectomy in patients with asymptomatic carotid stenosis. However, the number needed to treat (NNT) was 19 to prevent one stroke in 5 years, a modest effect in comparison to the trials with symptomatic patients (a NNT of only 6 in patients with a symptomatic stenosis of 70-99%). Furthermore, the number of surgical complications outweighs the benefits of surgery during the first two years after treatment. Finally, the benefits also included the prevention of contralateral strokes, whereas it is unlikely that these are prevented by endarterectomy. Therefore, endarterectomy should not be performed routinely in asymptomatic persons

The practice guideline for the treatment of ischemic stroke, issued by the Dutch College of General Practitioners, is a timely and most welcome update. It incorporates the new evidence and the important changes in stroke treatment of the past years, and is a good starting point for the collaboration between general practitioners and neurologists in the care of patients with a cerebrovascular accident. The guideline acknowledges the evidence for the benefit ofthrombolysis, but is somewhat vague concerning the magnitude of the effect because it compares the net effect of treatment (which incorporates the risk of bleeding) and the number of cerebral haemorrhages. Furthermore, the discussion of minor stroke could lead to the erroneous conclusion that such patients can be safely cared for at home. Apart from these reservations, the guideline fully agrees with the need to treat all patients with a cerebral infarct, in the absence of contraindications, with thrombolysis within three hours, and to offer specialised care in a dedicated stroke-unit

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The prognosis of cerebral venous sinus thrombosis (CVST) is variable, and outcome may range from complete recovery to death. Prognostic factors to predict outcome in the acute phase of CVST have not been analysed in a prospective study. Prognostic factors in patients enrolled in a clinical treatment trial were prospectively investigated. Poor outcome after 12 weeks, defined as death or dependency (Oxford handicap score > or =3), was used as the principle outcome measure. Univariate relations between possible prognostic factors and outcome at 12 weeks were analyzed with chi(2) tests. Treatment and all factors associated with prognosis (p

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Two patients with cerebral sinus thrombosis were successfully treated with neuroradiological intervention procedures, one with local thrombolysis and the other with mechanical thrombosuction using a hydrolyser catheter. The first patient, a 20-year-old woman, was treated with asparaginase for acute lymphatic leukaemia. She lapsed into coma with extensor posturing due to superior sagittal and right transverse sinus thrombosis. She recovered completely after local thrombolysis with 2,940,000 units urokinase, administered over a period of 40 hours. The second patient was a 29-year-old man who presented with clinical deterioration after seizures due to superior sagittal, left transverse and straight sinus thrombosis. A CT-scan demonstrated bilateral haemorrhagic cerebral infarctions. Since the risk of haemorrhage during thrombolysis with urokinase was considered to be high, mechanical thrombosuction with a hydrolyser catheter was performed. This procedure took only 4 hours. The patient recovered completely in two weeks. These cases add further evidence to the effectiveness of thrombolysis and thrombosuction in selected patients with severe cerebral sinus thrombosis

To investigate whether users of oral contraceptives and in [corrected] carriers of a hereditary prothrombotic condition (factor V Leiden mutation, protein C, S, or antithrombin deficiency) have an increased risk of cerebral sinus thrombosis. Comparison of a prospective series of cases of cerebral sinus thrombosis with population data. Neurological teaching hospitals from different regions in the Netherlands (cases) and a representative sample of the non-institutionalised Dutch population (controls). 40 women aged 18-54 years with cerebral sinus thrombosis (cases) and 2248 women aged 18-49 years (controls). Current use of oral contraceptives at the time of the thrombosis (cases) or at the time of the questionnaire (controls). Prevalences of a hereditary prothrombotic condition in patients and in the population with odds ratios. 34 of 40 (85%) women with cerebral sinus thrombosis used oral contraceptives, versus 1007 of 2248 (45%) of the control women; the age adjusted odds ratio was 13 (95% confidence interval 5 to 37). Seven of 36 patients (19%) had a prothrombotic deficiency, versus 7% expected in the population; this corresponds to a threefold to fourfold increase in risk. In women who used oral contraceptives and also carried a prothrombotic defect, the odds ratio for cerebral sinus thrombosis was about 30 relative to women who had neither risk factor. The use of oral contraceptives and being a carrier of a hereditary prothrombotic condition increase the risk of and interact in a multiplicative way in the development of cerebral sinus thrombosis

We compared the frequencies of signs of old intracerebral hemorrhages on brain magnetic resonance imaging scans in 66 patients with ischemic stroke, 69 with myocardial infarction, and 86 with peripheral arterial disease (a total of 221 patients). Magnetic resonance imaging scans were independently assessed by two investigators without knowledge of clinical or laboratory data. In 31 patients (14%) we found local cerebral hemosiderin deposits. In 24 patients they were clinically silent. Hemosiderin deposits were significantly more frequent in patients with ischemic stroke (26%) than in patients with myocardial infarction (4%) or peripheral arterial disease (13%). Hemosiderin deposits were associated with cerebral white matter lesions (odds ratio, 5.3; 95% confidence interval, 2.5-12.4). The odds ratios were higher in patients with severe cerebral white matter lesions. Our findings support the hypothesis that cerebral vessels of patients with ischemic stroke are more prone to rupture than those of patients with other manifestations of atherosclerotic disease, which may explain the higher incidence of intracerebral hemorrhages when these patients are treated with oral anticoagulants. The microhemorrhages were associated with cerebral white matter lesions, which suggests that they are another manifestation of cerebral small-vessel disease

Protein S is a vitamin K-dependent glycoprotein involved in the regulation of the anticoagulant activity of activated protein C (APC). Also, an anticoagulant role for protein S, independent of APC, has been described. Protein S has a unique C-terminal sex hormone binding globulin (SHBG)-like domain that represents about half of the molecule. To define the role of this domain in APC cofactor activity and in binding to C4b-binding protein (C4BP), we have constructed a recombinant protein S molecule of N-terminal residues 1-242 that lacks the SHBG domain (mini-protein S). A panel of monoclonal antibodies directed against the N-terminal region of protein S recognized plasma-derived protein S, wild-type recombinant protein S and mini-protein S with similar affinities, whereas a monoclonal antibody that recognizes an epitope in the SHBG domain did not detect mini-protein S. Mini-protein S did not bind to C4BP in a solid-phase binding assay, and the cofactor activity of mini-protein S was not inhibited by preincubation with C4BP. In a plasma coagulation assay, the cofactor activity of mini-protein S was lower than wild-type or plasma-derived preparations. In contrast, no difference in APC cofactor activities was observed when the preparations were tested in purified systems that monitor the APC-mediated degradation of factors Va or VIIIa. In conclusion, we constructed a protein S molecule that fails to bind C4BP and still displays cofactor activity for APC. This confirms the role of the C-terminal SHBG region in C4BP binding and demonstrates that N-terminal residues 1-242 are sufficient for the expression of APC cofactor activity in a system using purified components. In plasma, however, the C-terminal SHBG region plays a role in the expression of optimal APC cofactor activity

To examine the clinical relevance of isolated pontine hyperintense lesions (PHLs) on MRI in patients with atherosclerosis. Seventeen atherosclerotic patients with isolated PHL on MRI were compared with 17 patients without PHL and were matched for age, sex, and initial manifestation of atherosclerosis. Subjects and observer were blinded to the MRI findings. We assessed symptoms, impairment, and disability with a structured interview and neurologic examination as well as disability scales. On all items, patients with PHL scored worse than did their controls. We found the largest differences in frequencies of symptoms of disequilibrium, difficulties with speech or swallowing, the Timed Walking Test, and the body care and movement subscale of the Sickness Impact Profile. Except for disequilibrium (p = 0.04), these differences did not reach statistical significance. Abnormal tandem-walking tests were more frequent in patients than they were in controls. Pyramidal signs were equally distributed. We propose PHL as a cause of symptoms of disequilibrium in patients with atherosclerosis. Symptoms are probably elicited by dysfunction of the corticopontine fibers, the pontocerebellar fibers, or the pontine nuclei