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Local ethics committees/IRBs DOMESTICO. This file contains a list of the 44 (out of 53) local ethics committees from which approval for DOMESTICO is obtained. (DOCX 17 kb)

Objective: To evaluate the diagnostic value of computed tomography (CT) in detecting otosclerosis in patients with conductive hearing loss and a clinical suspicion of otosclerosis. Data Sources: PubMed, Embase, and the Cochrane Library. Study Selection: A systematic search was conducted. Studies reporting original study data were included. Data Extraction: Relevance and risk of bias of the selected articles were assessed. Studies with low relevance, high risk of bias, or both were excluded. Prevalences, sensitivities, specificities, and post-Test probabilities were extracted from the included articles. Data Synthesis: Seven studies characterized by a moderate to high relevance and moderate to low risk of bias were included for data extraction. The prevalence of otosclerosis was high (up to 100%) in the majority of the included studies. In those studies with a high prevalence of disease, both positive and negative post-Test probabilities were (relatively) high: 99% and between 51% and 67% respectively. In one study with a low prevalence of disease (9%), both positive and negative post-Test probabilities were low (23% and 3% respectively). Overall, reported sensitivities ranged between 60% and 95%. Conclusion: Preoperative CT has little to add in establishing otosclerosis and may not be necessary to confirm the diagnosis. We would recommend reserving CT for those patients with suspected additional abnormalities, for specific preoperative planning, or out of legal necessity. .

In dit hoofdstuk staat hoofdpijn zonder specifieke oorzaak, ook wel spanningshoofdpijn genoemd, centraal. Het onderscheid met andere vormen van hoofdpijn komt eveneens aan bod, zowel in de diagnostiek als in het beleid. Ook wordt het beleid bij medicatieovergebruikshoofdpijn beschreven, omdat spanningshoofdpijn in 50 % de aanleiding is voor medicatieovergebruikshoofdpijn. Medicatieovergebruikshoofdpijn kent een duidelijke verklaring en is daarmee geen SOLK in engere zin.

Medicatieafhankelijke hoofdpijn komt frequent voor en veroorzaakt een hoge ziektelast. Men moet er alert op zijn bij hoofdpijn op meer dan vijftien dagen per maand. Vaak speelt het zich buiten gezichtsveld van de huisarts af. Paracetamol, NSAID’s en triptanen veroorzaken het vaakst medicatieafhankelijke hoofdpijn. Preventie door beperking van medicatiegebruik bij hoofdpijn is belangrijk; maandelijks pijnstillergebruik tot op maximaal vijftien dagen en triptanen tot tien dagen. Bij medicatieafhankelijke hoofdpijn is er maar een interventie; stoppen met alle veroorzakende medicatie. Dat stoppen is vaak niet gemakkelijk, door rebound en doordat het vaak twee tot drie maanden duurt voordat de hoofdpijn in ernst afneemt.

There is a growing recognition of the important role of scale-dependent feedback for biogeomorphological landscape formation, where organisms locally improve survival and growth but at the same time negatively affect organisms at larger distance. However, little is known on how scale-dependent bio-geomorphic feedback is influenced by organism traits in combination with abiotic forcing. This was studied by measuring in a flume, the flow patterns around patches of three contrasting marsh species (Spartina anglica, Puccinellia maritima and Salicornia procumbens), using the flow acceleration around vegetation patches and deceleration within vegetation patches as quantitative proxy for the negative and positive feedback to the vegetation performance. The importance of external forcing was assessed by comparing three realistic current velocities: 0.1, 0.2 and 0.3 m s− 1. Our results showed that the dense clonal growth of stiff Spartina anglica shoots caused strongest flow deviations, irrespective of the applied current velocity. In contrast, the more sparsely growing, shorter stiff shoots of Salicornia procumbens induced much less flow deviation, allowing more water to pass through and over the vegetation canopy. The dense but highly flexible shoots of Puccinellia maritima caused strong flow deviations at low velocities, which diminished at higher velocities due to bending of the vegetation. Overall, these hydrodynamic results demonstrate that plant species traits interact with environmental conditions in creating scale-dependent feedbacks explaining why the effects of vegetation on landscape formation in saltmarshes are species specific.

Background Sex differences in the incidence, onset and course of schizophrenia have led to the hypothesis that estrogens play a protective role in the pathophysiology of this disorder. Several trials have assessed the potential of estrogens in reducing schizophrenia symptoms, showing inconsistent results. This quantitative review summarizes available evidence on the efficacy of estrogens in the treatment of schizophrenia. Methods Only double-blind, placebo-controlled, randomized studies were included. Primary outcome measure was total symptom severity, secondary outcome measures were subscores for positive and negative symptoms. Effect sizes were calculated for individual studies and, if possible, pooled in meta-analyses to obtain combined, weighted effect sizes (Hedges’s g). Results Superior efficacy was found for estrogen treatment in female patients (four RCTs, 214 patients) on total symptom severity (Hedges’s g = 0.66), although heterogeneity was moderate to high. Estrogens were also superior in reducing positive (Hedges’s g = 0.54) and negative symptoms (Hedges’s g = 0.34), with low heterogeneity. As the included studies applied different forms of estrogens, a separate analysis was conducted on the trials applying estradiol (three RCTs, 170 patients). Even larger effect sizes were found for total symptom severity (Hedges’s g = 0.79), positive (Hedges’s g = 0.57) and negative symptoms (Hedges’s g = 0.45), with reduced heterogeneity. Estrogen treatment in male patients (one study, 53 patients) was not superior to placebo. Conclusions Our results suggest that estrogens, especially estradiol, could be an effective augmentation strategy in the treatment of women with schizophrenia. However, future larger trials are needed before recommendations on clinical applications can be made.

For weeks, the air strikes that NATO executed in defence of the ‘safe area’ of Sarajevo were ‘hot news’. The fact that NATO would, eventually, execute these strikes had seemed inevitable for some time. The well-informed observer had sufficient indications to this effect via television and the newspapers. However, the media, and all of the debates in national parliaments, have never, or have scarcely, addressed the legal basis for these strikes. At first sight, this appeared to be a relatively simple question, since NATO repeatedly stressed that it was acting on a mandate from the UN Security Council. At a second glance, however, the legal basis of the NATO actions gives rise to a number of questions for which the answers are less easy to ascertain.

Traditionally, protection of the coastal area from flooding is approached from an engineering perspective. This approach has often resulted in negative or unforeseen impacts on local ecology and is even known to impact surrounding ecosystems on larger scales. In this paper, the utilization of ecosystem engineering species for achieving civil-engineering objectives or the facilitation of multiple use of limited space in coastal protection is focused upon, either by using ecosystem engineering species that trap sediment and damp waves (oyster beds, mussel beds, willow floodplains and marram grass), or by adjusting hard substrates to enhance ecological functioning. Translating desired coastal protection functionality into designs that make use of the capability of appropriate ecosystem engineering species is, however, hampered by lack of a generic framework to decide which ecosystem engineering species or what type of hard-substrate adaptations may be used where and when. In this paper we review successful implementation of ecosystem engineering species in coastal protection for a sandy shore and propose a framework to select the appropriate measures based on the spatial and temporal scale of coastal protection, resulting in a dynamic interaction between engineering and ecology. Modeling and monitoring the bio-physical interactions is needed, as it allows to upscale successful implementations and predict otherwise unforeseen impacts.

Feedback between vegetation growth, water flow, and landform is important for the biogeomorphic evolution of many landscapes, such as tidal marshes, alluvial rivers, and hillslopes. While experimental studies often focus on flow reduction within static homogeneous vegetation, we concentrate on flow acceleration around and between dynamically growing vegetation patches that colonize an initially bare landscape, with specific application to Spartina anglica, a pioneer of intertidal flats. Spartina patches were placed in a large-scale flow facility of 16 × 26 m, simulating the growth of two vegetation patches by increasing the patch diameter (D = 1–3 m) and decreasing the interpatch distance (d = 2.3–0 m). We quantified that the amount of flow acceleration next to vegetation patches, and the distance from the patch where maximum flow acceleration occurs, increases with increasing patch size. In between the patches, the accelerated flow pattern started to interact as soon as D/d ≥ 0.43–0.67. As the patches grew further, the flow acceleration increased until D/d ≥ 6.67–10, from which the flow acceleration between the patches was suppressed, and the two patches started to act as one. These findings are in accordance with theory on flow around and between nonpermeable structures; however, the threshold D/d values found here for permeable vegetation patches are higher than those for nonpermeable structures. The reported flow interactions with dynamic vegetation patches will be essential to further understanding of the larger-scale biogeomorphic evolution of landscapes formed by flowing water, such as tidal flats, floodplain rivers, and hillslopes.

Necessity plays a significant role in any legal system as unpredictable or extraordinary situations can require the adoption of measures departing from the normally applicable law in order to protect basic values and fundamental interests. International law is not an exception. The admissibility of the adoption of measures on grounds of necessity has been accepted by international courts and tribunals, in state practice, including international conventions, as well as in doctrine.

Bioengineering is a novel way to reduce the application or dimensions of hard constructions. In the Dutch Noordwaard polder a vegetation field is proposed in front of a planned dike to damp waves such that the desired dike height can be reduced. To investigate the impact of vegetation on waves, the description for wave attenuation as derived by Mendez and Losada (2004) was implemented in the wave model SWAN. The SWAN-VEG model was tested by performing a sensitivity analysis and by calibration and validation on experimental flume data. The model showed expected behavior and calibrated values for the drag coefficient gave reasonable correlations between predicted and measured wave attenuation, except for a plant with flexible floating leaves. Application of the model to the Noordwaard polder showed that a field of willows is able to reduce wave heights by 70% under extreme conditions. This allows a lower dike that fits better into the landscape while maintaining the required safety standard.

A large number of Al 5154-0 tensile test specimens were irradiated in a core position facility of the High Flux Reactor in Petten, the Netherlands. They were withdrawn from the irradiation rig in seven batches with successively higher accumulated neutron fluences. The highest fluences achieved were 5.7 x 10 2 6 n/m 2 (E 0.1 MeV), which leads to a mean thermal-to-fast flux ratio of 0.95. Tne irradiation temperature was 360 K ′ 10 K. After each withdrawal the material's tensile properties were determined at 293 K, 323 K and 373 K with a calculated strain rate e 1.65 x 10 - 4 /s. At the higher fluences the ductility figures appear to drop with increasing test temperature. Irradiation to a fluence level of 6 x 10 2 6 n/m 2 causes the 0.2% flow stress to increase from ∼ 100 MPa to ∼ 520 MPa and the uniform elongation to drop from more than 20% to less than 1% at the 323 K test temperature. The results of transmission electron microscopy (TEM), scanning electron microscopy (SEM) and light microscopy (LM) confirm that the behaviour of A1 5154-0 conforms to the general model for Al-Mg solid solution alloys obtained from the ORNL experiences with A1 5052-0. The objective of the irradiation program was to monitor the state of embrittlement that was expected to develop in the HFR core box material. The experimental results are representative for the PSF wall of the core box only. Because of the much higher thermal-to-fast neutron flux ratios prevailing in the other three walls, the test data are not directly applicable to these walls. By working out the implications of the basic model, however, it can be shown qualitatively that the ductility in the other walls will not be significantly better than in the PSF wall.

We are grateful to our Leiden colleagues Blokker and Muller for their comments on our contribution in the Nederlands Juristen Blad; just as their response in Transaktie to the elaborated version of our opinion, it is in many ways a well thought-out addition to what we maintained there. Insofar as the purpose of their contribution was to refute our positions, it has (again) failed to convince us.

The proliferation of international organizations of states and of norm-setting organs within these organizations has resulted in a large variety of types of decisions on the international level of administration.1 International organizations have shown a need for varying types of decisions to be able to respond to the need of establishing integration in different areas in a balanced manner (sometimes compelling, other times more directing). Reasons can be found in the necessity to find a balance between the process of integration and the degree of freedom of member states to continue setting their own policies, and the fact that citizens are often directly affected by decisions of these organizations. Each organization knows its own specific decision-types, but some well-known decision-types of the European Union can also be discovered in other international organizations.2

Foundations.- The Completeness of International Law and Hamlet's Dilemma: Non liquet, the Nuclear Weapons case, and Legal Theory*.- The Genuine Link Concept: Time for a Post Mortem?.- Sources.- On International Customary Law in the Netherlands.- The Role of State Practice in The Formation of Customary International Humanitarian Law.- From Dyestuffs to Kosovo Wine: from Avoidance to Acceptance by the European Community Courts of Customary International Law as Limit to Community Action.- Some Remarks on the Effect of the Termination of a Treaty under Article 70 of the 1969 Vienna Convention on the Law of Treaties.- Some Observations on The Consequences of The Termination of Treaties and The Reach of Article 70 of The Vienna Convention on The Law of Treaties.- Epilogue.- Herman Meijers 1923-2000.

Preface. Introduction by the Editors. I. Border Conflicts between Iraq and Iran. Comments. II. `Ius ad Bellum': Legal Implications of the Iran-Iraq War. Comments. III. Prohibitions or Restrictions on the Use of Methods and Means of Warfare. Comments. IV. Combatants and Non-Combatants. Comments. V. Targeting Theory in the Law of Armed Conflict at Sea: The Merchant Vessel as Military Objective in the Tanker War. Comments. VI. Neutrality at Sea. Comments. VII. The Law of Neutrality: Third States' Commercial Rights and Duties. Comments. VIII. Criminal Responsibilities and the Gulf War of 1980-1988: The Crime of Aggression. Comments. IX. The Gulf War of 1980-1988 and the Islamic Conception of International Law.

Objective. Cell death was evaluated in oral erythema multiforme to test the hypothesis that apoptosis may be a mechanism by which keratinocytes die in this condition. Study design. Ten erythema multiforme and five control oral mucosa biopsy specimens were evaluated in immunohistochemically stained sections for apoptosis-regulating proteins Bcl-2, Bcl-x, Bax, p53, Fas, and Fas-ligand. Apoptotic keratinocytes, determined by a detection method for DNA fragmentation (TUNEL) and by conventional morphologic criteria were counted per high power field. Results. Keratinocyte staining for Bcl-2 protein was comparable in erythema multiforme and controls. Bcl-x expression was reduced in five erythema multiforme cases. Staining for Bax protein differed in six erythema multiforme cases and showed variable intensity in layers under the parakeratin. Only slight differences in staining patterns of Fas and Fas-ligand proteins were noted between erythema multiforme and controls. The number of apoptotic keratinocytes evaluated by morphologic examination was significantly higher in erythema multiforme (mean per high power field, 0.90 ± 0.2; controls, 0.06 ± 0.04; p < 0.05, Mann-Whitney test) and was limited in significance by the TUNEL method (erythema multiforme, 0.43 ± 0.1; controls, 0.02 ± 0.02). Overexpression of p53 protein was seen in basal keratinocytes in five erythema multiforme specimens (mean, 17.5 ± 4.03 per high power field; controls 1.2 ± 0.3). Conclusions. There is evidence that cell death in erythema multiforme is at least in part due to apoptosis. The apoptotic mechanism may be related to an altered expression of apoptosis-regulating proteins. Although measurable alterations in the phenotypic expression of Fas and Fas-ligand proteins were not apparent, activation of Fas/Fas-ligand system could still be involved in the induction of apoptosis in erythema multiforme.

We have developed a novel system to study transcription by yeast RNA polymerase I (Pol I) of mutated rDNA units within the chromosomal context. For this, complete rDNA units carrying specific oligonucleotide tags in both the 17S and 26S rRNA genes were integrated into the chromosomal rDNA locus. Using this novel system, we analysed the action of the rDNA enhancer in stimulating transcription within the chromosomal context. We found that the enhancer acts as a stimulatory element in both directions, mainly on its two most proximal rRNA operons. Deletion of the sequences between the enhancer and the Pol I promoter in the tagged, integrated unit indicated that this part of the intergenic spacer contains no other transcriptional regulatory elements for Pol I. We also applied the system to study the function of the rDNA binding protein RBP1/REB1. For this purpose, we analysed tagged units in which either one or both of the binding sites for this protein have been inactivated. We found that mutations of both binding sites strongly diminish the transcription of the adjacent operon. The protein is hypothesized to play a crucial role in keeping the chromosomal rDNA units in an optimal spatial configuration by anchoring consecutive enhancers and promoters to the nucle(ol)ar matrix.

Over the years several types of remote sensing surveys have been acquired of the Eastern Papuan Fold Belt, in the Gulf Province of Papua New Guinea. These include aerial photographs, Landsat Multispectral Scanner (MSS), and Synthetic Aperture Radar (SAR). Each has been used by Petro-Canada Inc. for interpreting the geologic structure and stratigraphy of onshore hydrocarbon prospects. Analysis of available remotely sensed imagery reveals greater structural complexity than is shown on published geologic maps. Foremost among the images is SAR because of its low, artificial sun angle. Hence, a comprehensive view of the area has been acquired revealing many structural elements previously not appreciated. A distinct difference in structural style is found between the northern and southern segment of the Eastern Papuan fold belt in the study area. The northern segment shows discontinuous, open folds with widely separated anticlines set in featureless valleys. The southern segment is tightly folded, possessing few anticlines and synclines clearly recognizable on the imagery. However, structural components can be traced easily for tens of miles. Recent field work supports an SAR structural interpretation suggesting most, if not all, anticlines in the northern segment are overturned. The combination of remote sensing and field work proved invaluablemore » in understanding the fold belt tectonics and has aided considerably in the selection of drilling locations.« less

This contribution focuses on the accountability of international governmental organisations as a conceptual problem. To that end it gives a quite extensive summary of the Final Report of the International Law Association on the subject and examines whether accountability can be conceptualise as an actual or potential part of the existing legal system of international organisations. Mainly because of the underlying traditional approach to international (institutional) law, it is asserted that the ILA does not really succeed in this objective. Inspired by a more realistic view of the plurality of modern legal systems – as developed by the institutional legal theory – an alternative legal concept of accountability of international organisations is presented. Based on the fundamental value that legal power entails legal accountability, the legal concept covers all situations of alleged non-compliance by international organisations with a legally valid – but not necessarily also legally binding – rule of international law. For the time being such a concept will be heavily contested in theory and practice. However, for that very reason it can help to stimulate the development of international institutional law as long as the international legal community actually believes in the fundamental value and the divergent views only concern the content of the rules and practices involved in the accountability of international organisations.

Preface. Introduction by the Editors. I. Border Conflicts between Iraq and Iran. Comments. II. `Ius ad Bellum': Legal Implications of the Iran-Iraq War. Comments. III. Prohibitions or Restrictions on the Use of Methods and Means of Warfare. Comments. IV. Combatants and Non-Combatants. Comments. V. Targeting Theory in the Law of Armed Conflict at Sea: The Merchant Vessel as Military Objective in the Tanker War. Comments. VI. Neutrality at Sea. Comments. VII. The Law of Neutrality: Third States' Commercial Rights and Duties. Comments. VIII. Criminal Responsibilities and the Gulf War of 1980-1988: The Crime of Aggression. Comments. IX. The Gulf War of 1980-1988 and the Islamic Conception of International Law.

Deletion analysis of artificial rRNA minigenes transformed into Saccharomyces cerevisiae revealed that a 110 bp long fragment corresponding to positions -36 to +74 relative to the 3'-end of the 26S rRNA gene, is both necessary and sufficient for obtaining transcripts whose 3'-termini are identical to those of 26S and 37S (pre-)rRNA. These termini are produced via processing of longer transcripts because in an rna 82.1 mutant the majority of the minigene transcripts extend further downstream. Since the rna 82.1 mutation inactivates an endonuclease involved in the 3'-processing of 5S pre-rRNA it is concluded that the maturation of 37S- and that of 5S pre-rRNA requires a common factor. Comparison of the spacer sequences between Saccharomyces carlsbergensis, Saccharomyces rosei and Hansenula wingei revealed several conserved sequence blocks within the region between +10 and +55. These conserved sequence tracts, which are part of a longer region showing dyad symmetry, are supposed to be involved in the interaction with the processing component(s). Deletion of the sequences required for the formation of the 3'-ends of 26S rRNA and 37S pre-rRNA revealed a putative terminator for transcription by RNA polymerase I situated at position +210. This site maps within a DNA fragment that also contains the enhancing element for rDNA transcription by RNA polymerase I.

Deletions in the promoter region of the 37S pre-rRNA operon in yeast were constructed and analysed in vivo using an artificial ribosomal minigene present on an extrachromosomal yeast vector. Sequences required for correct transcription initiation were found to be located between positions -192 and +15 relative to the start; a 5'-deletion down to position -133 reduces the transcription yield of the minigene at least five-fold. To allow detection of transcription of the minigene in isolated nuclei of yeast transformed with a minigene-bearing plasmid we attempted to increase the minigene copy number. The transcription yield in vivo appeared not to be proportional to the copy number but was found to be greatly enhanced when two or three minigenes are present in tandem. alpha-Amanitin sensitivity of transcription of these minigenes in isolated nuclei proved that RNA polymerase I is responsible for their transcription.

The nucleotide sequences of the flanking regions of the genes coding for Spirodela oligorhiza chloroplast ribosomal RNA's have been determined. We have compared these sequences to the corresponding ones in chloroplast DNA of other plants and of E. coli and find a striking sequential or structural homology. The region 5'-proximal to the gene coding for 16S rRNA contains a gene coding for tRNAval, which is transcribed from the same strand. In this area three prokaryotic promoter motifs are found: one located in front of the tRNAval gene and two in the intergenic space between this gene and the 16S rRNA gene. The middle one is used for the start of the transcription of the large ribosomal RNA precursor.

The base sequence of Spirodela oligorhiza chloroplast DNA coding for 4.5S and 5S ribosomal RNA, the flanking regions and the spacer between these two genes has been determined. We have compared these sequences with the corresponding ones in other higher plants. Besides a high degree of homology, some interesting differences are found.

To define the RNA polymerase I promoter in the rDNA of Saccharomyces cerevisiae more precisely, we have constructed a series of 5'- and 3'-deletion mutants in a novel, plasmid-borne rDNA minigene, that also contains the transcriptional enhancer. Our data show that the Pol I promoter, in this context, extends from position -155 to +27, with 5'-deletions up to -134 and 3'-deletions up to -2 removing essential sequence information. To investigate the internal organization of the yeast Pol I promoter, linker scanning mutants were constructed, that traverse the Pol I promoter region and comprise between 5 and 12 clustered point mutations. Analysis of minigene transcription in yeast cells transformed with these plasmids demonstrates that the pol I promoter consists of three domains. Mutations in Domain I (from position -28 to +8) and Domain II (-70 to -51) drastically reduce promoter activity, whereas clustered point mutations in Domain III (starts at position -146 and presumably extends to position -76) appear to have less effect. Furthermore, the insertion of 4 nt between Domains I and II diminishes minigene transcription, indicating that the relative positions of these domains is essential.

The genes for the two large ribosomal RNAs (16S and 23S) and for the 4.5S rRNA in Spirodela oligorhiza chloroplast DNA are transcribed as one large, 7,000 nucleotides long precursor rRNA. Using S1-nuclease mapping, we have determined that the transcript ends 135 nucleotides 3′ distal of the 4.5S rRNA gene. 5S rRNA therefore, is most likely transcribed separately. Northern blotting of chloroplast RNA with distinct probes derived from the rDNA region reveals RNAs, which can be described as intermediates in the processing of the large precursor. With these findings a pathway for the maturation of this precursor is proposed.

The authors consider that ultrasonic examination is a simple, safe and highly informative method of examination having no contraindications. Due to its high informative value the USE is of decisive significance in diagnosis of cholelithiasis. The obtaining of more exact diagnosis of "acalculous cholecystitis" requires strict interpretation of all the findings of ultrasonic examination. The ultrasonic symptomatology of noninflammatory diseases of the bile duct requires more exact details.

The base sequence of Spirodela oligorhiza chloroplast DNA coding for 4.5S and 5S ribosomal RNA, the flanking regions and the spacer between these two genes has been determined. We have compared these sequences with the corresponding ones in other higher plants. Besides a high degree of homology, some interesting differences are found.

The enzymatic hydrolysis of plant carbohydrate polymers is discussed with particular emphasis on lignocellulose. The polysaccharides include starch, inulin, cellulose and the hemicelluloses, i.e., the heteroxylans and glucomannans. Commercial operations exist for the enzymatic hydrolysis of starch and its fermentation into chemicals such as ethanol. Enzymatic hydrolysis of lignocellulose is more complex and the enzymes are rather expensive to produce, which currently precludes the commercial processing of lignocellulosic materials. The bioconversion of lignocellulose consists of 4 process steps: pretreatment, enzyme production, enzymatic saccharification and fermentation. Except for the last step, each of these process steps is discussed. The discussion is highlighted with examples of lignocellulosic waste materials (e.g., sugar cane and a hardwood and softwood sawdust) which are of potential use in a bioconversion process for providing sugar hydrolysates that can serve as fermentation substrates.