Regional Disparities in Diabetes Care for Pediatric Patients with Type 1 Diabetes. A Cross-sectional DPV Multicenter Analysis of 24,928 German Children and Adolescents.

BACKGROUND: Data on regional differences in the quality of medical care in Germany are scarce. This study aimed to compare outcome quality and medical treatment of pediatric patients with type 1 diabetes between the federal states of Germany. METHODS: 24,928 patients (< 18 years of age) with type 1 diabetes and German residence were selected from the Diabetes-Patienten-Verlaufsdokumentation database. Indicators of outcome quality were HbA1C, overweight prevalence, and rate of severe hypoglycemia. To reflect medical treatment, use of insulin pumps and use of rapid-acting or long-acting insulin analogues were analyzed. Logistic regression models were created for binary variables with federal state as independent predictor. Linear regression was applied for HbA1C and Poisson regression for rate of severe hypoglycemia. Confounders: Sex, age, diabetes duration, migratory background. RESULTS: Disparity was observed for indicators of outcome quality between the 16 federal states of Germany (all p<0.05). After adjustment, HbA1C varied between 55.8 mmol/mol and 67.3 mmol/mol, overweight prevalence between 10.0 and 15.3%, severe hypoglycemia ranged from 0.06 events/PY to 0.21 events/PY. Overall, the best outcome quality appeared to be present in Saxony. Medical treatment also differed. The percentage of pediatrics on insulin pumps varied between 26.3 and 51.8%. The use of rapid-acting analogues ranged from 56.6 to 96.2% and the use of long-acting analogues varied between 41.9 and 96.9% (all p<0.0001). CONCLUSIONS: Medical treatment and outcome quality in pediatrics with type 1 diabetes differed within Germany. Disparities in individual socioeconomic status, regional deprivation, or differences in medical reimbursement decisions might have contributed to the patterns observed.

Controlling the growth mode of para-sexiphenyl (6P) on ZnO by partial fluorination.

We report on the impact of partial fluorination of para-sexiphenyl (6P) on the growth mode when deposited on the non-polar ZnO(101̄0) surface. The evolution of the thin film structure and morphology is monitored by in situ atomic force microscopy and in situ real-time X-ray scattering. Both 6P and its symmetrical, terminally fluorinated derivative (6P-F4) grow in a highly crystalline mode, however, with a distinctly different morphology. While 6P films are characterised by the formation of two different phases with three-dimensional nanocrystallites and consequently a rather rough surface morphology, layer-by-layer growth and phase purity in case of 6P-F4 prevails leading to smooth terraced thin films. We relate the different growth behaviour to specifics of the thin film structure.

Frequency and cost of diabetic ketoacidosis in Germany--study in 12,001 paediatric patients.

AIMS: Recently, medical expenditures were found to be 2-fold increased in paediatric patients with diabetic ketoacidotic events (DKA) in the U.S., in particular due to hospitalization. Aim of our study was to analyse DKAs and associated costs in Germany, where structured diabetes care including education is available for all patients. METHODS: For all 12,001 diabetic patients 0-19 years of age (52.6% male, mean age (SD) 12.6 (3.9) years) documented in a German-wide database, all DKAs were assessed, as well as costs for diabetes-related treatment. Associations between costs and DKA were estimated using log-linear models. RESULTS: 457 (3.8%) patients had at least 1 DKA during 2007. Total annual costs for patients without, with 1, or ≥ 2 DKAs were € 3,330 (95%-CI 3,292-3,368), € 6,935 (CI 6,627-7,244), and € 10,728 (CI 9,813-11,644), respectively, with largest differences for hospitalization costs (€ 693, € 4,145, € 8,092). Age-sex-diabetes duration-adjusted cost ratios for patients with 1, or ≥ 2 DKAs compared to patients without DKA were 2.2 (CI 2.1-2.3) and 3.6 (CI 3.1-4.1), respectively. CONCLUSIONS: In Germany, paediatric diabetic patients with DKA had up to 3.6-fold higher diabetes-related costs compared to those without DKA. This cost excess was higher compared to a U.S. study, however, the proportion of patients with DKA was much lower (3.8% versus 14.9%). The lower frequency of DKA in Germany may be due to a higher access to and utilization of diabetes education. Interventions should reduce DKA and resulting hospital admission in pediatric patients in order to reduce costs and improve quality of life.

Costs of paediatric diabetes care in Germany: current situation and comparison with the year 2000.

AIMS: To estimate direct costs of paediatric Type 1 diabetes care and associated factors in Germany for the year 2007 and to compare results with the costs for the year 2000. METHODS: Our study includes clinical data and charges for any diabetes-related health care service of 14,185 continually treated subjects with paediatric diabetes aged < 20 years [52.5% male, mean age (SD) 12.1 (4.2) years], derived from a nationwide prospective patient documentation system (DPV). Health-care utilization was valued in monetary terms by using inpatient and outpatient medical fees and retail prices (perspective of the statutory health insurance). Associations between average total diabetes-related costs or various single cost categories per patient and age, sex, migration background, diabetes duration, and metabolic control were analysed by multiple regression procedures and by a two-part model for hospitalization costs. Total direct costs in the whole paediatric diabetes population in Germany were estimated. Mean costs per patient as well as total costs in the German paediatric diabetes population in 2007 were compared to 2000 costs (inflated to the year 2007). RESULTS: Mean direct diabetes-associated costs per subject were €3524 (inter-quartile range: 1831-4743). Main cost categories were hospitalization (32%), glucose self-monitoring (29%), insulin pump therapy (18%), and insulin (15%). Based on the present estimation, the total costs of paediatric diabetes care in Germany exceeded €110 million in 2007. Compared with estimates of the year 2000, average costs per patient had increased by 20% and total costs for German paediatric diabetes care by 47%. CONCLUSIONS: Direct costs for paediatric Type 1 diabetes care increased between 2000 and 2007, probably partly because of new therapeutic strategies and an increase in diabetes prevalence.

Inpatient and outpatient health care utilization of children and adolescents with type 1 diabetes before and after introduction of DRGs.

OBJECTIVE: To analyze the frequency and length of hospital stays as well as the frequency of diabetes-associated outpatient visits of children and adolescents with type 1 diabetes before and after the introduction of DRGs (diagnosis-related groups) in German hospitals. METHODS: For this prospective cohort study, data from 2000 (before introduction of DRGs) to 2008 (after introduction) was extracted from the German diabetes documentation software DPV. Incidence rates of hospitalizations, length of hospital stays as well as the incidence rates of outpatient visits of 21,502 children and adolescents were estimated. The associations between the target parameters and DRG introduction, age, sex, diabetes duration, calendar year and migration background were estimated using generalized linear mixed models. RESULTS: Incidence of hospitalization was 0.45 (95% CI 0.44-0.45) per person-year (PY), mean number of hospital days 2.77/PY (95% CI: 2.76-2.79). Children had 5.3 (95% CI: 5.3-5.3) outpatient visits per PY on average. The number of hospital stays, inpatient days, and outpatient visits decreased significantly between 2000 and 2008. Time of introduction of DRGs was related to a significant rise in the number of hospital stays and outpatient visits (p<0.05). There was no significant relation to the number of hospital days. Compared with children younger than eleven years of age, 11- to 14-year-old children had significantly more, adolescents older than 14 years significantly less hospital stays (RR 1.2, 95% CI: 1.14-1.23 and 0.92, 95%, CI: 0.87-0.97, respectively). Migration background was significantly associated with worse results for all analyzed target variables (RR 1.21 for hospital stays, 1.26 for hospital days, 1.07 number of outpatient visits). CONCLUSIONS: The introduction of DRGs in the care of patients with pediatric diabetes mellitus resulted in a leveling of the reduction of the number of outpatient visits and hospital stays. Especially adolescents at the age of puberty and patients from families with migration background seem to require particular attention in health care.

Expression pattern conferred by a glutamic acid-rich protein gene promoter in field-grown transgenic cassava (Manihot esculenta Crantz).

A major constraint for incorporating new traits into cassava using biotechnology is the limited list of known/tested promoters that encourage the expression of transgenes in the cassava's starchy roots. Based on a previous report on the glutamic-acid-rich protein Pt2L4, indicating a preferential expression in roots, we cloned the corresponding gene including promoter sequence. A promoter fragment (CP2; 731 bp) was evaluated for its potential to regulate the expression of the reporter gene GUSPlus in transgenic cassava plants grown in the field. Intense GUS staining was observed in storage roots and vascular stem tissues; less intense staining in leaves; and none in the pith. Consistent with determined mRNA levels of the GUSPlus gene, fluorometric analyses revealed equal activities in root pulp and stems, but 3.5 times less in leaves. In a second approach, the activity of a longer promoter fragment (CP1) including an intrinsic intron was evaluated in carrot plants. CP1 exhibited a pronounced tissue preference, conferring high expression in the secondary phloem and vascular cambium of roots, but six times lower expression levels in leaf vascular tissues. Thus, CP1 and CP2 may be useful tools to improve nutritional and agronomical traits of cassava by genetic engineering. To date, this is the first study presenting field data on the specificity and potential of promoters for transgenic cassava.

Nonlinear dynamics of magnetic islands imbedded in small-scale turbulence.

The nonlinear dynamics of magnetic tearing islands imbedded in a pressure gradient driven turbulence is investigated numerically in a reduced magnetohydrodynamic model. The study reveals regimes where the linear and nonlinear phases of the tearing instability are controlled by the properties of the pressure gradient. In these regimes, the interplay between the pressure and the magnetic flux determines the dynamics of the saturated state. A secondary instability can occur and strongly modify the magnetic island dynamics by triggering a poloidal rotation. It is shown that the complex nonlinear interaction between the islands and turbulence is nonlocal and involves small scales.

Control of transport-barrier relaxations by resonant magnetic perturbations.

Transport-barrier relaxation oscillations in the presence of resonant magnetic perturbations are investigated using three-dimensional global fluid turbulence simulations from first principles at the edge of a tokamak. It is shown that resonant magnetic perturbations have a stabilizing effect on these relaxation oscillations and that this effect is due mainly to a modification of the pressure profile linked to the presence of both residual magnetic island chains and a stochastic layer.

Evidence from numerical simulations of transport-barrier relaxations in tokamak edge plasmas in the presence of electromagnetic fluctuations.

The dynamics of transport barriers in fusion plasmas is studied in the presence of electromagnetic fluctuations. The work is based on numerical simulations using a new three-dimensional electromagnetic fluid turbulence code (EMEDGE3D). In these simulations, the transport-barrier exhibits intermittent relaxation cycles. It is found that magnetic fluctuations have a negligible influence on the relaxation process while the magnetic activity is enhanced during these relaxations, in agreement with experimental observations.

Nonlinear dynamics of transport barrier relaxations in tokamak edge plasmas.

A new mechanism for intermittent relaxations of transport barriers is found by using three dimensional fluid turbulence simulations. This mechanism is generic since it only requires a stationary E x B shear flow. It is found here that if the flow shear increases faster than linearly with heating power, the relaxation frequency decreases with power. An analytical study reveals that this nonlinear dynamics is governed by a time delay for effective velocity shear stabilization.

Pheochromocytoma in childhood: implication for further diagnostic procedures.

UNLABELLED: We report on our experience with two patients with pheochromocytoma. One patient underwent surgery of pheochromocytoma at the age of 30 y; 18 y later, medullary thyroid carcinoma (MTC) was detected in his son. Subsequently, multiple endocrine neoplasia (MEN) type 2A was diagnosed by genetic examination in both father and son. Further diagnostic procedures also revealed an MTC in the father. The other patient suffered from bifocal pheochromocytoma of the left suprarenal gland. Diagnostic work-up revealed papillary thyroid carcinoma, which was also detected in the mother 8 mo later. Whereas a point mutation in SDHB gene was found in the son, no genetic abnormality was detected in the mother. CONCLUSION: Every pheochromocytoma in childhood warrants further diagnostic work-up, including genetic examination. In addition, clinical data of patients suffering from pheochromocytoma and papillary thyroid carcinoma should be collected by an international registry, and a joint effort should be undertaken in order to define possible underlying mutated genes in these patients.

Transport reduction by rotation shear in tokamak-edge turbulence.

Effects of externally imposed and self-generated poloidal flows on turbulent transport in the edge region of a tokamak are investigated using 3D nonlinear global simulations of resistive pressure-gradient-driven turbulence. Transport reduction is found to be due to synergetic changes in the fluctuation amplitude and in the dephasing of the fluctuations. A scaling of the fluctuation level and turbulent diffusivity with E x B flow shear strength is deduced from these simulations. These scalings agree with recent experimental observations on edge biasing as well as with analytical models.

Use of the robot system Da Vinci for laparoscopic repair of gastro-oesophageal reflux in children.

In adult patients, laparoscopic surgery, using a robot system (Da Vinci, Intuitive Surgical, Mountain View, California), has been recently introduced into surgical practice. To investigate the feasibility of the system in paediatric surgery, laparoscopic fundoplications as well as cholecystectomies have been performed. In July 2000 we used the robot system for the first time on an 11-year-old girl with gastro-oesophageal reflux, and since that time on 7 other children. Altogether 5 Thal and 3 Nissen procedures have been carried out. The average age was 12 years, with a range of 7 to 16 years. All operations were performed without complications and without conversion to open surgery. The medium operating time was 146 min with a range of 105 to 180 minutes. Compared to conventional laparoscopy, the 3-dimensional high-quality vision, the advanced instrument movements and the ergonomic position of the surgeon seems to enhance surgical precision. In our opinion, the use of the robot system is feasible and safe in paediatric surgery. The technique is limited due to the fact that instruments adapted to the size of small children are not yet available.

A novel phytyltransferase from Synechocystis sp. PCC 6803 involved in tocopherol biosynthesis.

The deduced polypeptide sequence of open reading frame slr1736 reveals homology to chlorophyll synthase and 1,4-dihydroxy-2-naphthoic acid phytyltransferase in Synechocystis sp. strain PCC 6803. In tocopherol and plastoquinone biosynthesis, a condensation reaction mechanistically similar to that of these two enzymes is performed. To analyze the function of this novel prenyltransferase, a deletion mutant of slr1736 was generated by homologous recombination. The mutant showed a markedly decreased tocopherol content, while plastoquinone levels remained unchanged. Since the aromatic precursor homogentisic acid accumulated in the mutant, the function of the enzyme was proven to be a novel tocopherol phytyltransferase.

Biosynthesis of beta-carotene (provitamin A) in rice endosperm achieved by genetic engineering.

To obtain a functioning provitamin A (beta-carotene) biosynthetic pathway in rice endosperm, we introduced in a single, combined transformation effort the cDNAs coding for (1) phytoene synthase (psy) and (2) lycopene beta-cyclase (beta-lcy; both from Narcissus pseudonarcissus and both under control of the endosperm-specific glutelin promoter), with (3) a bacterial phytoene desaturase (crtI, from Erwinia uredovora under constitutive 35S promoter control). This combination covers the requirements for beta-carotene synthesis, and yellow, beta-carotene-bearing rice endosperm was obtained in the T0 generation. However, further experiments revealed that the presence of beta-lcy was not necessary, since psy and crtI alone were able to drive beta-carotene synthesis as well as the formation of further downstream xanthophylls. This finding could be explained if these downstream enzymes are either constitutively expressed in rice endosperm or are induced by the transformation, e.g. by products derived therefrom. Based on results in N. pseudonarcissus as a model system, a likely hypothesis can be developed that trans lycopene or a trans lycopene derivative acts as an inductor in a kind of feedback mechanism stimulating endogenous carotenogenic genes.

Advection of passive particles in the Kolmogorov flow.

A statistical analysis of the advection of passive particles in a flow governed by driven two-dimensional Navier-Stokes equations (Kolmogorov flow) is presented. Different regimes are studied, all corresponding to a chaotic behavior of the flow. The diffusion is found to be strongly asymmetric with a very weak transport perpendicular to the forcing direction. The trajectories of the particles are characterized by the presence of traps and flights. The trapping time distributions show algebraic decrease, and strong anomalous diffusion is observed in transient phases. Different regimes lead to different types of diffusion, i.e., no universal behavior of diffusion is observed, and both time and space properties are needed to define anomalous transport. (c) 2001 American Institute of Physics.

Nondiffusive transport in tokamaks: three-dimensional structure of bursts and the role of zonal flows

Large scale transport events are studied in simulations of resistive ballooning turbulence in a tokamak plasma. The spatial structure of the turbulent flux is analyzed, indicating radially elongated structures (streamers) at the low field side which are distorted by magnetic shear at different toroidal positions. The interplay between self-generated zonal flows and transport events is investigated, resulting in significant modifications of the frequency and the amplitude of bursts. The propagation of bursts is studied in the presence of a transport barrier generated by a strong shear flow.

Identification of a novel gene coding for neoxanthin synthase from Solanum tuberosum.

The polymerase chain reaction analysis of potato plants, transformed with capsanthin capsorubin synthase ccs, revealed the presence of a highly related gene. The cloned cDNA showed at the protein level 89.6% identity to CCS. This suggested that the novel enzyme catalyzes a mechanistically similar reaction. Such a reaction is represented by neoxanthin synthase (NXS), forming the xanthophyll neoxanthin, a direct substrate for abscisic acid formation. The function of the novel enzyme could be proven by transient expression in plant protoplasts and high performance liquid chromatography analysis. The cloned NXS was imported in vitro into plastids, the compartment of carotenoid biosynthesis.

Proper orthogonal decomposition and galerkin projection for a three-dimensional plasma dynamical system

A general method by which to investigate nonlinear dynamical systems close to a stability threshold is presented. This method combines a proper orthogonal decomposition and a subsequent Galerkin projection. This technique is applied to three-dimensional resistive ballooning plasma fluctuations in a tokamak. The corresponding dynamical system belongs to a large family of convective fluid systems including Rayleigh-Benard convection. A proper orthogonal decomposition of the fluctuating signal obtained by numerical simulation shows that the relevant modes are close to the linear (global) modes. The Galerkin projection provides a low-dimensional system that allows the study of shear flow generation, its subsequent fluctuation reduction, and the evolution to oscillating states.