Robust heavy-traffic approximations for service systems facing overdispersed demand.

Arrival processes to service systems often display fluctuations that are larger than anticipated under the Poisson assumption, a phenomenon that is referred to as overdispersion. Motivated by this, we analyze a class of discrete-time stochastic models for which we derive heavy-traffic approximations that are scalable in the system size. Subsequently, we show how this leads to novel capacity sizing rules that acknowledge the presence of overdispersion. This, in turn, leads to robust approximations for performance characteristics of systems that are of moderate size and/or may not operate in heavy traffic.

Design and Processing of Invertible Orientation Scores of 3D Images.

The enhancement and detection of elongated structures in noisy image data are relevant for many biomedical imaging applications. To handle complex crossing structures in 2D images, 2D orientation scores U : R 2 × S 1 → C were introduced, which already showed their use in a variety of applications. Here we extend this work to 3D orientation scores U : R 3 × S 2 → C . First, we construct the orientation score from a given dataset, which is achieved by an invertible coherent state type of transform. For this transformation we introduce 3D versions of the 2D cake wavelets, which are complex wavelets that can simultaneously detect oriented structures and oriented edges. Here we introduce two types of cake wavelets: the first uses a discrete Fourier transform, and the second is designed in the 3D generalized Zernike basis, allowing us to calculate analytical expressions for the spatial filters. Second, we propose a nonlinear diffusion flow on the 3D roto-translation group: crossing-preserving coherence-enhancing diffusion via orientation scores (CEDOS). Finally, we show two applications of the orientation score transformation. In the first application we apply our CEDOS algorithm to real medical image data. In the second one we develop a new tubularity measure using 3D orientation scores and apply the tubularity measure to both artificial and real medical data.

Local clustering in scale-free networks with hidden variables.

We investigate the presence of triangles in a class of correlated random graphs in which hidden variables determine the pairwise connections between vertices. The class rules out self-loops and multiple edges. We focus on the regime where the hidden variables follow a power law with exponent τ∈(2,3), so that the degrees have infinite variance. The natural cutoff h_{c} characterizes the largest degrees in the hidden variable models, and a structural cutoff h_{s} introduces negative degree correlations (disassortative mixing) due to the infinite-variance degrees. We show that local clustering decreases with the hidden variable (or degree). We also determine how the average clustering coefficient C scales with the network size N, as a function of h_{s} and h_{c}. For scale-free networks with exponent 2<τ<3 and the default choices h_{s}∼N^{1/2} and h_{c}∼N^{1/(τ-1)} this gives C∼N^{2-τ}lnN for the universality class at hand. We characterize the extremely slow decay of C when τ≈2 and show that for τ=2.1, say, clustering starts to vanish only for networks as large as N=10^{9}.

Clustering spectrum of scale-free networks.

Real-world networks often have power-law degrees and scale-free properties, such as ultrasmall distances and ultrafast information spreading. In this paper, we study a third universal property: three-point correlations that suppress the creation of triangles and signal the presence of hierarchy. We quantify this property in terms of c[over ¯](k), the probability that two neighbors of a degree-k node are neighbors themselves. We investigate how the clustering spectrum k↦c[over ¯](k) scales with k in the hidden-variable model and show that c[over ¯](k) follows a universal curve that consists of three k ranges where c[over ¯](k) remains flat, starts declining, and eventually settles on a power-law c[over ¯](k)∼k^{-α} with α depending on the power law of the degree distribution. We test these results against ten contemporary real-world networks and explain analytically why the universal curve properties only reveal themselves in large networks.

Zernike expansion of derivatives and Laplacians of the Zernike circle polynomials.

The partial derivatives and Laplacians of the Zernike circle polynomials occur in various places in the literature on computational optics. In a number of cases, the expansion of these derivatives and Laplacians in the circle polynomials are required. For the first-order partial derivatives, analytic results are scattered in the literature. Results start as early as 1942 in Nijboer's thesis and continue until present day, with some emphasis on recursive computation schemes. A brief historic account of these results is given in the present paper. By choosing the unnormalized version of the circle polynomials, with exponential rather than trigonometric azimuthal dependence, and by a proper combination of the two partial derivatives, a concise form of the expressions emerges. This form is appropriate for the formulation and solution of a model wavefront sensing problem of reconstructing a wavefront on the level of its expansion coefficients from (measurements of the expansion coefficients of) the partial derivatives. It turns out that the least-squares estimation problem arising here decouples per azimuthal order m, and per m the generalized inverse solution assumes a concise analytic form so that singular value decompositions are avoided. The preferred version of the circle polynomials, with proper combination of the partial derivatives, also leads to a concise analytic result for the Zernike expansion of the Laplacian of the circle polynomials. From these expansions, the properties of the Laplacian as a mapping from the space of circle polynomials of maximal degree N, as required in the study of the Neumann problem associated with the transport-of-intensity equation, can be read off within a single glance. Furthermore, the inverse of the Laplacian on this space is shown to have a concise analytic form.

Closed-form solution of the convolution integral in the magnetic resonance dispersion model for quantitative assessment of angiogenesis.

Prostate cancer (PCa) diagnosis and treatment is still limited due to the lack of reliable imaging methods for cancer localization. Based on the fundamental role played by angiogenesis in cancer growth and development, several dynamic contrast enhanced (DCE) imaging methods have been developed to probe tumor angiogenic vasculature. In DCE magnetic resonance imaging (MRI), pharmacokinetic modeling allows estimating quantitative parameters related to the physiology underlying tumor angiogenesis. In particular, novel magnetic resonance dispersion imaging (MRDI) enables quantitative assessment of the microvascular architecture and leakage, by describing the intravascular dispersion kinetics of an extravascular contrast agent with a dispersion model. According to this model, the tissue contrast concentration at each voxel is given by the convolution between the intravascular concentration, described as a Brownian motion process according to the convective-dispersion equation, with the interstitium impulse response, represented by a mono-exponential decay, and describing the contrast leakage in the extravascular space. In this work, an improved formulation of the MRDI method is obtained by providing an analytical solution for the convolution integral present in the dispersion model. The performance of the proposed method was evaluated by means of dedicated simulations in terms of estimation accuracy, precision, and computation time. Moreover, a preliminary clinical validation was carried out in five patients with proven PCa. The proposed method allows for a reduction by about 40% of computation time without any significant change in estimation accuracy and precision, and in the clinical performance.

Do guidelines on euthanasia and physician-assisted suicide in Dutch hospitals and nursing homes reflect the law? A content analysis.

To describe the content of practice guidelines on euthanasia and assisted suicide (EAS) and to compare differences between settings and guidelines developed before or after enactment of the euthanasia law in 2002 by means of a content analysis. Most guidelines stated that the attending physician is responsible for the decision to grant or refuse an EAS request. Due care criteria were described in the majority of guidelines, but aspects relevant for assessing these criteria were not always described. Half of the guidelines described the role of the nurse in the performance of euthanasia. Compared with hospital guidelines, nursing home guidelines were more often stricter than the law in excluding patients with dementia (30% vs 4%) and incompetent patients (25% vs 4%). As from 2002, the guidelines were less strict in categorically excluding patients groups (32% vs 64%) and in particular incompetent patients (10% vs 29%). Healthcare institutions should accurately state the boundaries of the law, also when they prefer to set stricter boundaries for their own institution. Only then can guidelines provide adequate support for physicians and nurses in the difficult EAS decision-making process.

Follow-up of children born after ICSI with epididymal spermatozoa.

BACKGROUND: To evaluate the safety of ICSI with epididymal sperm, this study compared children born after ICSI treatment with epididymal sperm and children conceived after IVF and ICSI with ejaculated sperm. Additionally, the results of a multidisciplinary, multicentre follow-up of the children conceived with epididymal sperm at 2 years of age are described. METHODS: This follow-up study included 378 children conceived after ICSI with epididymal sperm (percutaneous epididymal sperm aspiration: PESA group) and a control group of 1192 IVF and 1126 ICSI (with ejaculated sperm) children, all with a gestational age of 20 weeks or more. Questionnaires were sent at birth, 1 year and 4 years of age, collecting data on parental, pregnancy and child factors. A total of 148 PESA children were assessed at 2 years of age for motor performance, mental- and language development and compared with the Dutch norms. RESULTS: PESA children showed no increased risks for stillbirths, total deaths and malformations. They also did not differ from IVF and ICSI children in gender rate, birthweight and gestational age. The mental Bayley score was higher (P < 0.05) for PESA singletons and parents reported fewer (P < 0.05) behavioural problems in the PESA group than the Dutch reference group. The scores for syntactic and lexical development for the PESA singletons were better (P < 0.05) than the Dutch standards. CONCLUSIONS: ICSI with epididymal sperm does not lead to more stillbirths or congenital malformations in comparison to IVF and ICSI with ejaculated sperm and does not lead to poor development in comparison with the Dutch reference group.

Time-frequency distribution of interferograms from a frequency comb in dispersive media.

We investigate general properties of the interferograms from a frequency comb laser in a non-linear dispersive medium. The focus is on interferograms at large delay distances and in particular on their broadening, the fringe formation and shape. It is observed that at large delay distances the interferograms spread linearly and that its shape is determined by the source spectral profile. It is also shown that each intensity point of the interferogram is formed by the contribution of one dominant stationary frequency. This stationary frequency is seen to vary as a function of the path length difference even within the interferogram. We also show that the contributing stationary frequency remains constant if the evolution of a particular fringe is followed in the successive interferograms found periodically at different path length differences. This can be used to measure very large distances in dispersive media.

Reactions between methanethiol and biologically produced sulfur particles.

Recently, new biotechnological processes have been developed to enable the sustainable removal of organic and inorganic sulfur compounds from liquid and gaseous hydrocarbon streams. In comparison to existing technologies (e.g., caustic scrubbing or iron based redox technologies) far less chemicals are consumed, while reusable elemental sulfur is formed as the main end-product. This research shows that in these processes a number of consecutive reactions occur between methanethiol (MT) from the hydrocarbon stream and the formed biosulfur particles, leading to the formation of (dimethyl) polysulfides. This is an important feature of this family of new bioprocesses as it improves the MT removal efficiency. The reaction kinetics depend on the MT and biosulfur concentration, temperature, and the nature of the biosulfur particles. The first reaction step involves a S8 ring-opening by nucleophilic attack of MT molecules to form CH3S9(-). This work shows that CH3S9(-) reacts to polysulfides (S3(2-), S4(2-), S5(2-)), dimethyl polysulfides [(CH3)2S2, (CH3)2S3], and dissociated H2S, while also some longer-chain dimethyl polysulfides [(CH3)2S4-7] are formed at µM levels. Control experiments using orthorhombic sulfur flower (S8) did not reveal these reactions.

Vectorial aerial-image computations of three-dimensional objects based on the extended Nijboer-Zernike theory.

We present details of a novel imaging algorithm based on the extended Nijboer-Zernike (ENZ) theory of diffraction. We derive integral expressions relating the electric field distribution in the entrance pupil of an optical system to the electric field in its focal region. The evaluation of these integrals is made possible by means of a highly accurate and efficient series expansion similar to those occurring in standard ENZ theory. Based on these results an ENZ imaging scheme is constructed and evaluated in detail with attention to the convergence properties and computational complexity of the new method.

Influence of behaviour and risk factors on motor performance in preterm infants at age 2 to 3 years.

The aim of this cross-sectional study was to determine the influence of test-taking behaviour and risk factors for delayed motor performance in 437 preterm infants (244 males, 193 females; < or = 32 weeks of gestation) at the corrected age of 2 to 3 years (mean 29mo [SD 3.3]). Other mean (SD) sample demographics were: postmenstrual age 29(+5) weeks (1(+5)), range 25(+0)-32(+0); birthweight 1213.7g (331.7), range 468-2350; and days in the neonatal intensive care unit 21.1 (21.3), range 1-165. Children (n=23) with a severe disability were excluded. We assessed motor performance and behaviour during testing with the Motor Scale and the Behaviour Rating Scale (BRS) of the Bayley Scales of Infant Development, 2nd edition (BSID-II). Risk factors were tested against delayed motor performance as the dependent variable in binary logistic regression analysis. Median score on the Motor Scale in terms of the BSID-II Psychomotor Developmental Index (PDI) was 86. 'Delayed' motor performance was observed in 46.5% of the children tested, and behaviour was 'not-optimal' in 31.4%. The Motor Scale and BRS scores were significantly correlated (r(s)=0.62, p<0.01). Risk factors for delayed motor performance were: neonatal convulsions (odds ratio [OR] 4.5; 95% confidence interval [CI] 1.6-12.9), low maternal educational level (OR 3.3; 95% CI 1.7-6.5), male sex (OR 2.8; 95% CI 1.8-4.3), and chronic lung disease (OR 2.1; 95% CI 1.1- 4.1). We conclude that preterm infants are at high risk of delayed motor performance and non-optimal test-taking behaviour.

Microbiological analysis of the population of extremely haloalkaliphilic sulfur-oxidizing bacteria dominating in lab-scale sulfide-removing bioreactors.

Thiopaq biotechnology for partial sulfide oxidation to elemental sulfur is an efficient way to remove H(2)S from biogases. However, its application for high-pressure natural gas desulfurization needs upgrading. Particularly, an increase in alkalinity of the scrubbing liquid is required. Therefore, the feasibility of sulfide oxidation into elemental sulfur under oxygen limitation was tested at extremely haloalkaline conditions in lab-scale bioreactors using mix sediments from hypersaline soda lakes as inoculum. The microbiological analysis, both culture dependent and independent, of the successfully operating bioreactors revealed a domination of obligately chemolithoautotrophic and extremely haloalkaliphilic sulfur-oxidizing bacteria belonging to the genus Thioalkalivibrio. Two subgroups were recognized among the isolates. The subgroup enriched from the reactors operating at pH 10 clustered with Thioalkalivibrio jannaschii-Thioalkalivibrio versutus core group of the genus Thioalkalivibrio. Another subgroup, obtained mostly with sulfide as substrate and at lower pH, belonged to the cluster of facultatively alkaliphilic Thioalkalivibrio halophilus. Overall, the results clearly indicate a large potential of the genus Thiolalkalivibrio to efficiently oxidize sulfide at extremely haloalkaline conditions, which makes it suitable for application in the natural gas desulfurization.

A novel mitochondrial ATP8 gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy.

PURPOSE: To identify the biochemical and molecular genetic defect in a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder. METHODS: Measurement of the mitochondrial energy-generating system (MEGS) capacity in muscle and enzyme analysis in muscle and fibroblasts were performed. Relevant parts of the mitochondrial DNA were analysed by sequencing. Transmitochondrial cybrids were obtained by fusion of 143B206 TK(-) rho zero cells with patient-derived enucleated fibroblasts. Immunoblotting techniques were applied to study the complex V assembly. RESULTS: A homoplasmic nonsense mutation m.8529G-->A (p.Trp55X) was found in the mitochondrial ATP8 gene in the patient's fibroblasts and muscle tissue. Reduced complex V activity was measured in the patient's fibroblasts and muscle tissue, and was confirmed in cybrid clones containing patient-derived mitochondrial DNA. Immunoblotting after blue native polyacrylamide gel electrophoresis showed a lack of holocomplex V and increased amounts of mitochondrial ATP synthase subcomplexes. An in-gel activity assay of ATP hydrolysis showed activity of free F(1)-ATPase in the patient's muscle tissue and in the cybrid clones. CONCLUSION: We describe the first pathogenic mutation in the mitochondrial ATP8 gene, resulting in an improper assembly and reduced activity of the complex V holoenzyme.

Modelling of an oil refinery wastewater treatment plant.

The Activated Sludge Model No. 3 (ASM3) and Dutch calibration guidelines (STOWA) were evaluated in the modelling of an activated sludge system treating effluents from a large oil refinery. The plant was designed to remove suspended solids, organic matter and nitrogen from wastewater at an average water temperature of 34 degrees C. The plant consists of three tanks in series; the first two tanks operate in on-off aeration mode with pure oxygen for N-removal, whilst extra methanol is added for the denitrification, and the third tank is maintained as constantly aerobic. Calibration was performed based on a simplified influent characterisation and extra batch experiments (nitrification and denitrification). With the adjustment of only four parameters the model proved capable of describing the performance of the plant concerning both the liquid phase and the biomass. The model was further used to analyse possible modifications in the plant layout and optimize operational conditions in order to reduce operating costs. Modelling results indicated reduction in methanol dosage by implementing an idle time between aerobic and anoxic phases. In this way, surplus methanol was prevented from entering during the aerobic period. Moreover, simulations showed that the most cost-effective option regarding the denitrification process was a combined pre-post-denitrification scheme, without the need for enlarging existing basins. It can be concluded that although ASM3 and STOWA guidelines were originally developed for domestic wastewater application at a temperature range of 10 to 20 degrees C, they proved well capable of describing the performance of an oil refinery wastewater treatment plant operating at 34 degrees C. Moreover, the plant model proved useful for optimization of the plant performance regarding operational costs.

Degradation of methanethiol by methylotrophic methanogenic archaea in a lab-scale upflow anaerobic sludge blanket reactor.

In a lab-scale upflow anaerobic sludge blanket reactor inoculated with granular sludge from a full-scale wastewater treatment plant treating paper mill wastewater, methanethiol (MT) was degraded at 30 degrees C to H2S, CO2, and CH4. At a hydraulic retention time of 9 h, a maximum influent concentration of 6 mM MT was applied, corresponding to a volumetric loading rate of 16.5 mmol liter-1 day-1. The archaeal community within the reactor was characterized by anaerobic culturing and denaturing gradient gel electrophoresis analysis, cloning, and sequencing of 16S rRNA genes and quantitative PCR. Initially, MT-fermenting methanogenic archaea related to members of the genus Methanolobus were enriched in the reactor. Later, they were outcompeted by Methanomethylovorans hollandica, which was detected in aggregates but not inside the granules that originated from the inoculum, the microbial composition of which remained fairly unchanged. Possibly other species within the Methanosarcinacaea also contributed to the fermentation of MT, but they were not enriched by serial dilution in liquid media. The archaeal community within the granules, which was dominated by Methanobacterium beijingense, did not change substantially during the reactor operation. Some of the species related to Methanomethylovorans hollandica were enriched by serial dilutions, but their growth rates were very low. Interestingly, the enrichments could be sustained only in the presence of MT and did not utilize any of the other typical substrates for methylotrophic methanogens, such as methanol, methyl amine, or dimethylsulfide.

Informing patients about small risks: A comparative approach.

This article relates to the question to what extent patients should be informed about risks in the context of obtaining consent in case of treatment. To explore this issue, a comparative study has been carried out. The legal position taken with regard to informing about treatment risks in the Netherlands has been compared to that in the UK and Germany.

Metabolic capacity of the diaphragm in patients with COPD.

Chronic obstructive pulmonary disease (COPD) is associated with an increased load on the diaphragm. Chronic loading on skeletal muscles results in metabolic changes and fiber-type shifts. Therefore, we investigated whether the load on the human diaphragm imposed by COPD altered oxidative enzyme activity, glycogenolytic enzyme activity and mitochondrial energy generating capacity and efficiency. Biopsies of the diaphragm from COPD patients and control subjects were obtained and activities of L(+)3-hydroxyacylCoA-dehydrogenase (HADH, marker for beta-oxidation capacity) and phosphorylase (marker for glycogenolytic capacity) were measured spectrophotometrically. Mitochondrial energy generating capacity was measured by spectrophotometrical and radiochemical methods. Fiber-type distribution was determined electrophoretically. We found that HADH activity was increased with increasing severity of COPD (P=0.05). No change in glycogenolytic enzyme activity was observed. The activity of the mitochondrial respiratory chain complexes III and IV and oxidation of pyruvate was increased with increasing airflow obstruction. These results suggest that in COPD the diaphragm adapts to a higher workload by increasing the oxidative capacity and mitochondrial function.

Application of the fractional Fourier transformation to digital holography recorded by an elliptical, astigmatic Gaussian beam.

The authors have studied the diffraction pattern produced by a particle field illuminated by an elliptic and astigmatic Gaussian beam. They demonstrate that the bidimensional fractional Fourier transformation is a mathematically suitable tool to analyse the diffraction pattern generated not only by a collimated plane wave [J. Opt. Soc. Am A 19, 1537 (2002)], but also by an elliptic and astigmatic Gaussian beam when two different fractional orders are considered. Simulations and experimental results are presented.