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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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}.

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.

Multiple deficiencies of mitochondrial DNA- and nuclear-encoded subunits of respiratory NADH dehydrogenase detected with peptide- and subunit-specific antibodies in mitochondrial myopathies.

Antibodies have been raised against synthetic peptides corresponding to several computer-predicted epitopes of three mtDNA-encoded subunits, ND4, ND5 and ND6, of the human respiratory chain NADH dehydrogenase (Complex I). Antibodies were characterized by a sensitive immunoblotting assay using proteins from human skeletal muscle mitochondria and by immunoprecipitation of radio-labeled HeLa cell mitochondrial translation products. Only antibodies against two of six selected peptides of the ND4 subunit, i.e., the C-terminal peptide and an internal peptide close to the C-terminus, reacted in both assays with the subunit. Antibodies raised against an internal peptide close to the N-terminus of the ND5 subunit and antibodies raised against an internal epitope of the ND6 subunit also reacted in both the immunoblotting and immunoprecipitation assays. The antibodies described above and other Complex I subunit- or holoenzyme-specific antibodies were used to investigate the subunit deficiencies of the respiratory NADH dehydrogenase in the skeletal muscle of patients affected by mitochondrial myopathies associated with Complex I defects. The reduction in enzyme activity correlated in an immunoblot assay with a decrease of four mtDNA-encoded subunits of the enzyme, as well as with a decrease of other subunits of Complex I encoded in the nDNA. The present work provides the first evidence of a decrease in NADH dehydrogenase subunits encoded in the mitochondrial genome in myopathy patients.

A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I.

The thiamine transporter gene SLC19A2 was recently found to be mutated in thiamine responsive megaloblastic anaemia with diabetes and deafness (TRMA, Rogers syndrome), an early onset autosomal recessive disorder. We now report a novel G1074A transition mutation in exon 4 of the SLC19A2 gene, predicting a Trp358 to ter change, in a girl with consanguineous parents. In addition to the typical triad of Rogers syndrome, the girl presented with short stature, hepatosplenomegaly, retinal degeneration, and a brain MRI lesion. Both muscle and skin biopsies were obtained before high dose thiamine supplementation. While no mitochondrial abnormalities were seen on morphological examination of muscle, biochemical analysis showed a severe deficiency of pyruvate dehydrogenase and complex I of the respiratory chain. In the patient's fibroblasts, the supplementation with high doses of thiamine resulted in restoration of complex I activity. In conclusion, we provide evidence that thiamine deficiency affects complex I activity. The clinical features of TRMA, resembling in part those found in typical mitochondrial disorders with complex I deficiency, may be caused by a secondary defect in mitochondrial energy production.

Lethal infantile mitochondrial disease with isolated complex I deficiency in fibroblasts but with combined complex I and IV deficiencies in muscle.

A 2-month-old boy died of a lethal infantile mitochondrial disease with severe lactic acidosis and involvement of the CNS. Histochemical analysis of skeletal muscle showed that cytochrome c oxidase staining was lacking in all muscle fibers but was present in arterioles. Ragged red fibers were not seen, but some fibers showed excessive staining for succinate dehydrogenase. Biochemical analysis revealed a combined complex I and IV deficiency in skeletal muscle but only a complex I deficiency in his fibroblasts. Two-dimensional native SDS electrophoresis confirmed these enzymatic findings at the protein level. Analysis of mitochondrial translation products in fibroblasts revealed no abnormalities, and analysis of mitochondrial DNA in muscle showed no depletion, large-scale deletions, or frequently occurring point mutations. We conclude that this disease must have been the result of either a nuclear DNA mutation in a gene controlling the expression or assembly of both complex I and the muscle-specific isoform of complex IV or, alternatively, a heteroplasmic point mutation in a mitochondrial tRNA, which codon is used more often by mtDNA encoded subunits of complex I than by mtDNA encoded subunits of complex IV. A different degree of heteroplasmy in skeletal muscle and fibroblasts would then explain the curious heterogeneous tissue expression of defects in this patient.

Short report: smoking habits and the acquisition of metronidazole resistance in patients with Helicobacter pylori-related gastritis.

Thirty-three dyspeptic patients with colonization of Helicobacter pylori in the gastric antrum were treated with tripotassium dicitrate bismuthate 120 mg q.d.s. for 28 days and metronidazole 250 mg q.d.s. for 10 days starting on day 19. Five weeks after cessation of this treatment regimen H. pylori was eradicated in 23 patients. In 8 of the remaining 10 patients, H. pylori had become resistant to metronidazole. In this study resistance was significantly associated with smoking habits, but not with age, bacterial load, gastritis score or alcohol consumption.

In vitro activity of loracarbef against common respiratory pathogens compared with amoxicillin-clavulanic acid: a multi-centre study in The Netherlands.

Loracarbef (LC) is the first clinically available carbacephem. In order to evaluate the antimicrobial activity of LC, a total of 593 clinical strains of H. influenzae, M. catarrhalis, S. pneumoniae and S. pyogenes were collected by seven participating study centres. Minimal inhibitory concentrations for loracarbef and amoxycillin-clavulanic acid combination (AC) were determined by a microdilution method. The MIC-90 of beta-lactamase-negative strains of H. influenzae was 2.0 (LC) and 0.5 (AC), and for beta-lactamase-positive strains 4.0 (LC) and 2.0 (AC) mg/l. For beta-lactamase-negative and beta-lactamase-positive strains of M. catarrhalis, the MIC-90 results were 0.5 and 2.0 (LC) and 0.13 and 0.5 (AC) mg/l. The MIC-90 for AC was