Search

De kwaliteit van droge, oude bossen in Drentse Natura 2000-gebieden (habitattypen 9120 Beuken-eikenbossen en 9190 Oude eikenbossen) is onderzocht met nadruk op bodemkenmerken, vegetatie en stamhout van eik. De bossen worden beoordeeld ten aanzien van effecten van natuurlijke verzuring door bodemontwikkeling en kunstmatige verzuring door intensief historisch bosgebruik en atmosferische depositie. Kenmerken van de in zeer oude bossen voorkomende dikke humusprofielen krijgen expliciet aandacht. Voor locaties met gedegradeerde bodems worden herstelmaatregelen voorgesteld in de vorm van experimentele bemesting.

Introduction In the PURE-01 study, a proportion of patients (pts) with muscle-invasive bladder cancer (MIBC; T2-4N0M0) had residual invasive disease (ypT2-4) at radical cystectomy (RC) after neoadjuvant pembrolizumab (pembro). The pembro-induced alterations in immunotherapy-resistant tumors remain largely unstudied. We aimed to investigate the biological characteristics of pembro-resistant tumors in comparison to neoadjuvant chemotherapy (NAC)-resistant tumors. Methods Gene expression profiling was performed on 26 RC samples from pts with ypT2-4 disease post-pembro, of which 22 had matched pre-pembro transurethral resection of the bladder tumor (TURBT) samples. Matched cases were analyzed by differential gene expression, hallmark signatures, and molecular subtyping (Decipher Bladder, TCGA, Consensus and Lund classifiers). Unsupervised consensus clustering (CC) was used to compare the 26 post-pembro samples with 133 post-NAC samples and to 21 samples collected from the former tumor bed of NAC-treated patients (scar tissue), all derived from RC specimens. Results Molecular subtyping of the pre- and post-pembro samples revealed significant ‘subtype switching’ with only 41% of samples having concordant subtypes using the Decipher Bladder classifier. The post-pembro samples did not cluster with scar tissues on clustering but were highly associated with immune-infiltrated cases from the post-NAC cohort. Two major groups of post-pembro tumors were identified, the first defined by markedly higher immune, stromal, angiogenesis and epithelial-to-mesenchymal signature scores and the second by higher tumor purity, KRAS and reactive oxygen species signature scores. Checkpoint inhibitor genes (CD274, PDCD1LG2) were consistently expressed in both groups. Conclusions This study expands our knowledge of pembro-resistant tumors finding the molecular characteristics of these tumors is strikingly different from NAC-resistant tumors. Two distinct clusters of tumors were identified post-pembro, neither of which were characterized as having a scar-like character. A larger cohort will be required to further understand the clinical implications of these findings.

Background In PURE01 study (NCT02736266), neoadjuvant pembro resulted in 42% pT0 in patients (pts) with MIBC. pT0 pts had features suggesting pre-existing immunity or higher tumor mutational burden (TMB) may promote response. In this study, we investigated potential mechanisms for resistance to pembro, including FGFR3 genomic alterations (GA). Methods Pts enrolled in the PURE-01, which is still recruiting pts in its amended design, had predominant urothelial carcinoma histology and stage cT ≤ 4N0 MIBC. Biomarker analyses in the expanded cohort of 96 pts included PD-L1 combined positive score and comprehensive genomic profiling (FoundationCDx assay). In addition, TCGA MIBC (n = 405) and a prospective commercial cohort (PCC) of 415 MIBC pts from the clinical use of the Decipher Bladder TURB test from the GRID registry (NCT02609269) were analyzed. A single-sample genomic classifier (GC) was trained to identify FGFR3-active tumors (FGFR3+). Results In PURE01 cohort, despite a linear association of TMB with ypT0 in multivariable models (p = 0.017), there was no association between FGFR3 GA and pathological response nor with PD-L1 expression. FGFR3 GA were found in 17.6% ypT0 vs 20.7% in ypT3-4 disease (corrected p = 0.82). Applying the GC to the TCGA MIBC cohort, we found 45% of FGFR3+ cases had FGFR3 mutations vs 9% for the rest of the cohort. Applying the GC to the PCC, we found that the FGFR3+ tumors were Luminal (n = 14), Luminal Infiltrated (n = 10) or Luminal Papillary (n = 30). FGFR3+ pts showed significantly lower PD-L1 (-0.03 vs. 0.109, p Conclusions In our combined cohorts, FGFR3 GA did not correlate with response to pembro. FGFR3 GA are enriched in FGFR3+ tumors, which in turn tend to have lower immune activity, PD-L1 and PD-L2, suggesting FGFR3 activity may provide a potential tool for further discriminating the mechanisms underlying response and resistance to neoadjuvant pembro in MIBC. Clinical trial identification NCT02736266 (PURE01) NCT02609269 (GRID Registry). Legal entity responsible for the study The authors. Funding Decipher Bioscience. Disclosure A. Necchi: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (institution), Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Advisory / Consultancy: Clovis; Advisory / Consultancy: Janssen. R. Madison: Full / Part-time employment: Foundation Medicine. J. Chung: Full / Part-time employment: Foundation Medicine. Y. Liu: Full / Part-time employment: Decipher Bioscience. J. Chung: Full / Part-time employment: Foundation Medicine. J.S. Ross: Full / Part-time employment: Foundation Medicine. S.M. Ali: Full / Part-time employment: Foundation Medicine. E. Davicioni: Full / Part-time employment: Decipher Bioscience. E.A. Gibb: Full / Part-time employment: Decipher Bioscience. All other authors have declared no conflicts of interest.

Schizophrenia research has identified deficits in neurocognition, social cognition, and sensory processing. Because a cohesive model of “disturbed cognitive machinery” is currently lacking, we built a conceptual model to integrate neurocognition, social cognition, and sensory processing.In a cross-sectional study, the cognitive performance of participants was measured. In accordance with the Schedules for Clinical Assessment in Neuropsychiatry, the participants were assigned to either the schizophrenia group or the non-schizophrenic psychosis group. Exclusion criteria included substance abuse, serious somatic/neurological illness, and perceptual handicap. The male/female ratio, educational level, and handedness did not differ significantly between the groups.The data were analyzed using structural equation modeling. Based upon the results of all possible pairwise models correlating neurocognition, social cognition, and sensory processing, three omnibus models were analyzed. A statistical analysis of a pairwise model-fit (χ2, CFI, and RMSEA statistics) revealed poor interrelatedness between sensory processing and neurocognition in schizophrenia patients compared with healthy control participants. The omnibus model that predicted disintegration between sensory processing and neurocognition was statistically confirmed as superior for the schizophrenia group (χ2(53) of 56.62, p = 0.341, RMSEA = 0.04, CFI = 0.95). In healthy participants, the model predicting maximal interrelatedness between sensory processing/neurocognition and neurocognition/social cognition gave the best fit (χ2(52) of 53.74, p = 0.408, RMSEA = 0.03, CFI = 0.97). The performance of the patients with non-schizophrenic psychosis fell between the schizophrenia patients and control participants.These findings suggest increasing separation between sensory processing and neurocognition along the continuum from mental health to schizophrenia. Our results support a conceptual model that posits disintegration between sensory processing of social stimuli and neurocognitive processing.Keywords: Schizophreni, Psychosis, Cognition, Sensory processing, Disintegration, Structural equation modeling

Summary In this paper, we present a method to estimate the additional costs made by nature reserve managers to mitigate the effects of atmospheric deposition. Theoretically, these extra costs may be saved when deposition levels drop. The costs were calculated per Nature Target Type (NTT) and management intensity for both the current (high) and reduced deposition levels. The resulting ecological quality was estimated in both cases. We calculated the difference in costs based on the management intensities required to maintain ecological quality at the current and reduced nitrogen deposition levels. For the NTTs within the clusters grassland, reed and rough land, and heathland we used dynamic simulation models. For forests and moorland pools we used expert knowledge to estimate the reduction in management costs due to a decrease in deposition. The total amount of money that may be saved because of the reduction of deposition rates is estimated at 42 million euro per year for the period from 2000 to 2020 for the assessed NTTs. The highest savings can be made in grasslands; 28 million euro. On average the savings were 80 €/ha/yr, which ranged from 5 €/ha/yr for forest to 299 €/ha/yr for reed and rough land.

Since the late nineteenth century when high-cost equipment was introduced into forestry there has been a need to calculate the cost of this equipment in more detail with respect to, for example, cost of ownership, cost per hour of production, and cost per production unit. Machine cost calculations have been made using various standard economic methods, where costs have been subdivided into capital costs and operational costs. Because of differences between methods and between national regulations, mainly regarding tax rules and subsidies, international comparisons of machine costs are difficult. To address this, one of the goals of the European Cooperation in Science and Technology (COST) Action FP0902 was to establish a simple format for transparent cost calculations for machines in the forest biomass procurement chain. A working group constructed a Microsoft Excel–based spreadsheet model which is easy to understand and use. Input parameters are easy to obtain or possible to estimate by provided rules of thumb. The model gives users a simultaneous view of the input parameters and the resulting cost outputs. This technical note presents the model, explains how the calculations are made, and provides future users with a guide on how to use the model. Prospective users can view the model in the Supplementary Material linked to this article online.

In this paper we review the topic of sensitivity analysis in linear programming. We describe the problems that may occur when using standard software and advocate a framework for performing complete sensitivity analysis. Three approaches can be incorporated within it: one using bases, an approach using the optimal partition and one using optimal values. We elucidate problems and solutions with an academic example and give results from an implementation of these approaches to a large practical linear programming model of an oil refinery. This shows that the approaches are viable and useful in practice.

Contains fulltext : 89004.pdf (Publisher’s version ) (Closed access) BACKGROUND: Deficits in emotion perception are a well-established phenomenon in schizophrenic patients and studies have typically used unimodal emotion tasks, presenting either emotional faces or emotional vocalizations. We introduced bimodal emotion conditions in two previous studies in order to study the process of multisensory integration of visible and audible emotion cues. We now build on our earlier work and address the regulatory effects of selective attention mechanisms on the ability to integrate emotion cues stemming from multisensory channels. METHODS: We added a neutral secondary distractor condition to the original bimodal paradigm in order to investigate modality-specific selective attention mechanisms. We compared schizophrenic patients (n=50) to non-schizophrenic psychotic patients (n=46), as well as to healthy controls (n=50). A trained psychiatrist used the Schedules of Clinical Assessment in Neuropsychiatry (SCAN 2.1) to diagnose the patients. RESULTS: As expected, in healthy controls, and to a lesser extent in non-schizophrenic psychotic patients, modality-specific attention attenuated multisensory integration of emotional faces and vocalizations. Conversely, in schizophrenic patients, auditory and visual distractor conditions yielded unaffected and even exaggerated multisensory integration. CONCLUSIONS: These results suggest that schizophrenics, as compared to healthy controls and non-schizophrenic psychotic patients, have modality-specific attention deficits when attempting to integrate information regarding emotions that stem from multichannel sources. Various explanations for our findings, as well as their possible consequences, are discussed. 01 september 2010

Contains fulltext : 77421.pdf (Publisher’s version ) (Closed access) Since Kraepelin called dementia praecox what we nowadays call schizophrenia, cognitive dysfunction has been regarded as central to its psychopathological profile. Disturbed experience and integration of emotions are, both intuitively and experimentally, likely to be intermediates between basic, non-social cognitive disturbances and functional outcome in schizophrenia. While a number of studies have consistently proven that, as part of social cognition, recognition of emotional faces and voices is disturbed in schizophrenics, studies on multisensory integration of facial and vocal affect are rare. We investigated audiovisual integration of emotional faces and voices in three groups: schizophrenic patients, non-schizophrenic psychosis patients and mentally healthy controls, all diagnosed by means of the Schedules of Clinical Assessment in Neuropsychiatry (SCAN 2.1). We found diminished crossmodal influence of emotional faces on emotional voice categorization in schizophrenics, but not in non-schizophrenia psychosis patients. Results are discussed in the perspective of recent theories on multisensory integration.

Effects of atmospheric deposition on natural areas can be mitigated by management. For example, the effects of excessive nitrogen deposition can partly be overcome by intensifying measures like mowing or sod cutting. The costs of this extra management may, in the future, no longer be required when deposition rates decrease. We developed a method to calculate the costs of the intensified nature management that is required at increased deposition rates. We used a set of models that simulate the biomass development under different management regimes necessary to maintain a certain level of biodiversity. The costs were calculated for several vegetation types based on, among others, the biomass and litter that was removed. Preliminary results show that the models can be applied with some success to assess these costs. Model outcomes show a clear effect of management intensity on biomass growth in heathland and grassland although no differences were found in forest. The biodiversity in heathlands clearly increased when management was intensified. As an example, the extra costs in heathlands that are made to counteract the effects of atmospheric deposition were calculated for The Netherlands. The costs of maintaining heathlands with sods being removed from heathlands every 20 years (presently the usual rate) exceed those in a situation of sod cutting every 60 years (the expected rate without atmospheric deposition) by 1.4 in Euro per year. (c) 2004 Elsevier B.V. All rights reserved.

Two series of novel diarylethenes, the first containing one and the second two acetyl protected thiol groups, were synthesised in two and three steps from an easily available known intermediate. Newly synthesised compounds present ideal examples of model substrates for photochromic studies on metal surfaces.

The design of a new HBsAg screening assay, the Hepanostika HBsAg Ultra is based on the use of monoclonal antibodies raised against native wild-type HBsAg and reactive with HBsAg in which the common ‘a’-determinant is modified by site-directed mutagenesis of four of the cysteine moieties. The design was checked using the same cysteine variants and samples from patients known to be infected with HBsAg variants. The results found were compared with other state-of-the-art commercial screening assays. The design of the Hepanostika HBsAg Ultra enabled detection of all variant HBsAg-positive samples in contrast to the other commercial assays. An additional 980 samples were tested to assess the specificity and sensitivity of the Hepanostika HBsAg Ultra. Screening of presumed negative serum and plasma samples resulted in a specificity of 100%. This makes the Hepanostika HBsAg Ultra the first screening assay with a design able to detect HBsAg variants with high sensitivity and specificity.

Describes a system for learning models of polyhedral objects. The system does not require exact knowledge about poses, instead only some course requirements are needed. The system obtains a 3D wireframe model of the object together with the statistical data. This is illustrated with an example. >

Item does not contain fulltext ABSTRACT Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is considered a rare inherited mitochondrial fatty acid oxidation disorder. Less than 10 patients have been reported, diagnosed on the basis of ethylmalonic aciduria and low SCAD activity in cultured fibroblast. However, mild ethylmalonic aciduria, a biochemical marker of functional SCAD deficiency in vivo, is a common finding in patients suspected of having metabolic disorders. Based on previous observations, we have proposed that ethylmalonic aciduria in a small proportion of cases is caused by pathogenic SCAD gene mutations, and SCAD deficiency can be demonstrated in fibroblasts. Another - much more frequent - group of patients with mild ethylmalonic aciduria has functional SCAD deficiency due to the presence of susceptibility SCAD gene variations, i.e. 625G>A and 511C>T, in whom a variable or moderately reduced SCAD activity in fibroblasts may still be clinically relevant. To substantiate this notion we performed sequence analysis of the SCAD gene in 10 patients with ethylmalonic aciduria and diagnosed with SCAD deficiency in fibroblasts. Surprisingly, only one of the 10 patients carried pathogenic mutations in both alleles, while five were double heterozygotes for a pathogenic mutation in one allele and the 625G>A susceptibility variation in the other. The remaining four patients carried only either the 511C>T or the 625G>A variations in each allele. Our findings document that patients carrying these SCAD gene variations may develop clinically relevant SCAD deficiency, and that patients with even mild ethylmalonic aciduria should be tested for these variations.

(1998). Cultural diversity and cultural policy in The Netherlands. International Journal of Cultural Policy: Vol. 4, Cultural analysis and cultural policy, pp. 357-387.

Item does not contain fulltext 3 p.

Two additional patients with alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency are described. An 11-month-old girl with nonconsanguineous parents had generalized seizures and no angiokeratoma. Biochemical investigation showed persistent slight oligosacchariduria; enzymatic analysis of plasma, leukocytes, and fibroblasts revealed profound alpha-NAGA deficiency. Heterozygote enzyme levels were found in both parents. The mother has epilepsy, and epilepsy is present in the father's family. A younger, clinically healthy brother also had the enzyme deficiency. Electron microscopy of lymphocytes from the index patient showed no vacuolization. Incubation of cultured fibroblasts with Helix pomatia lectin showed the presence of intracellular N-acetylgalactosamine-containing storage material, not present in a series of 12 normal fibroblast lines. Our cases cannot be classified definitely as infantile cases. Biochemically the diagnosis could easily have been missed. Urinary oligosaccharide pattern after resorcinol staining was identical to those previously described, but excretion was significantly lower than in the reported infantile cases and the bands disappeared after the urine was desalted. The enzyme defect in leukocytes would have been missed with one of the commercial substrates used. For this mild variant of alpha-NAGA deficiency, the clinical pattern is not yet clear; a longer follow-up period is needed.

Sir: [3-mannosidosis is a lysosomal storage disorder caused by deficiency of the enzyme ~-mannosidase. We would like to report a girl (parents were first cousins), who besides a [3-mannosidase deficiency had an ethanolaminuria. She was born at term. Birth length and weight are unknown. Her development during the 1st year was unremarkable. She walked at 15 months. In that period the parents became worried about speech development. Because of recurrent upper respiratory tract infections the adenoids were removed and tympanotubes inserted. Otological examination revealed a hearing-loss of 45 DB. She was admitted to our clinic because of absent speech development and anorexia. Physical examination at the age of 5 years 10 months showed a slightly built girl: height and weight below 3rd percentile, head circumference 10th percentile. Motor and mental development were seriously retarded. There were no joint contractures, but she stood with slightly flexed hips and knees. No hepatosplenomegaly was present. Electroencephalography demonstrated a non-specific abnormality without c~production. A CT-scan of the brain was normal. Oligosaccharides in urine, analysed according to Blom et al. [1] and Dorland et al. [3], showed a strong band which could be identified as the 13-mannosidosis disaccharide mannosyl-13(1-4)-N-acetylglucosamine. ~-Mannosidase activity was measured with minor modifications of the method described by Panday et al. [4]. The activity of 13-mannosidase in leucocytes was 4.7nmol/h per milligram protein (normal: 160-360). In plasma and cultured fibroblasts the activity of 13-mannosidase was not detectable (normal respectively: 160-300 nmol/h per milliliter, 115-455nmol/h per milligram protein). Heparan sulphamidase was normal. Furthermore we found an ethanolaminuria: 607-1010gmol/mmol creatinine (normal 35-130). The ethanolamine concentration in the serum was also elevated ranging from 38-70 gmol/1 (normal: traces). All hitherto described patients with [3-mannosidosis had mental retardation. Most of them had hearing loss with delayed development of expressive language. Striking is their susceptibility to respiratory and dermal infections. There is no uniform facial or skeletal dysmorphism. The significance or ethanolaminuria in our patient is not known. Wenger et al. [6] described a combined deficiency of 13-mannosidase and heparan sulphamidase. Vietor et al. [5] reported two sibs with ethanolaminuria and generalized storage disease, cardiomegaly, cerebral dysfunction and early death. It was argued that a marked increase in ethanolamine excretion could result from a deficiency of kinase enzyme involved in the synthesis of membrane phospholipid phosphatidylethanolamine. As suggested by Cole et al. [2] ethanolamine may result from accelerated breakdown of ethanolamine phospholipids (e.g. from myelin) without compensatory re-utilization in the synthesis of new lipids. However, there were no clinical signs of myelin disease in our patient. References

Pressure wave propagation in liquids inside containers of arbitrary three-dimensional shape can be solved by the computer code BEWAVE based on the Boundary Element Retarded Potential Method. This code may be applied to acoustic wave propagation in homogenous, inviscid but compressible fluids. BEWAVE computes, using a semi-implicit time-stepping technique, the transient solution of the velocity potential, velocity components tangential or normal to the boudary and pressure at the whole boundary. The dynamic loading is due to a pressure source representing an explosion or a dynamic boundary condition as defined by the user. Several new developments will be discussed. The implementation of a fast linear solver optimises the use of available core and disc space of the computer system. Furthermore, a cost-efffective procedure is discussed for checking on possible intersection of the line-of-sight between any pair of nodal points with the structures to see whether the influence between these points has to be excluded. The boundary conditions currently allow for rigid walls, given pressure, rupture discs, non-reflecting openings and prescribed flow. Pre- and post-processing has been optimised through a coupling with the interactive colour graphics package PATRAN.TM The boundary of the fluid domain, which may consist of both flat and curve parts, must be divided in quadratic quadrilateral or triangular elements. Recently the coupling of BEWAVE to a finite-difference program for the computation of one-dimensional pressure waves in complex piping systems has been investigated. The coupling method will be discussed and an industrial example for a nuclear steam generator in which a violent reaction is assumed to occur and which is coupled to a piping system will be given. The occurence and importance of the three-dimensional effects in this example will be discussed.

A new technique is pesented for measuring soil water tension, using the relation between the dielectric behaviour and the water tension of an absorbent placed in the soil. A practical realisation of the dielectric tensiometer is described, consisting of a porous metal cylinder as an outer conductor, containing an inner conductor, and filled with glass beads which serve as an absorbent. Together they form a coaxial condenser system. The electrical capacitance between the two electrodes is a measure for the soil water tension. The dielectric tensiometer is usable from zero to over 10 bar, without suffering from most of the common disadvantages of tensiometer pressure transducer systems. The dielectric tensiometer is ideally suited for use in conjunction with a capacitive soil water content meter for determining the water-retention characteristics of soil material. Patent is pending for the dielectric tensiometer.

In this survey paper an attempt is made to describe present thinking on the technical, economic and human aspects of computer control. At the same time it is tried to assess the interaction between those three topics.

Publisher Summary This chapter discusses the number of characteristics in the fields of automation and control engineering which are slowly being rectified. Consideration of the new concepts and evaluation of human factors in industry still tended to come too late in the planning process. There was insufficient dialog and inadequate cooperation between control engineers and social scientists about human affairs in general, and about the needs and potential contributions of employees of all kinds. The significance of inadequate skill level in operative jobs to provide for those who wished it a degree of challenge and of the job satisfaction associated with this. A first consideration in the humanization of work was the provision of the opportunity to earn and work for this purpose.

The boundary element program BEWAVE has been developed for the computation of pressure waves in liquids propagating inside complex three-dimensional structures. BEWAVE computes the transient pressures and velocities arising from explosions or other highly-dynamic flow conditions. Since a variety of boundary conditions has been implemented, it is also possible to compute dynamic, three-dimensional flow of slightly compressible, inviscid fluids.