Nemaline myopathy: pathophysiology and therapeutic targets

Stienen, G.J.M. [Promotor]Ottenheijm, C.A.C. [Copromotor

Neonatal morbidities and developmental delay in moderately preterm-born children

BACKGROUND AND OBJECTIVE: Children born moderately preterm (32-35(6/7) weeks' gestation) are at increased risk of both neonatal morbidities and developmental delays in early childhood. It is unknown whether neonatal morbidities contribute to the increased risk of developmental delay. The objective of this study was to determine the effect of neonatal morbidities after moderately preterm birth on development at preschool age. METHODS: In a community-based, stratified cohort, parents of 832 moderately preterm children born in 2002 or 2003 completed the Ages and Stage Questionnaire when their child was 43 to 49 months old. Data on Apgar scores, asphyxia, tertiary NICU admission, hospital transfer, circulatory insufficiency, hypoglycemia, septicemia, mechanical ventilation, continuous positive airway pressure, apneas, caffeine treatment, and hyperbilirubinemia were obtained from medical records. We assessed associations of neonatal characteristics with developmental delay, adjusted for gender, small-for-gestational-age status, gestational age, and maternal education. RESULTS: Hypoglycemia and asphyxia were associated with developmental delay; odds ratios (ORs) were 2.42 (95% confidence interval [CI]: 1.23-4.77) and 3.18 (95% CI: 1.01-10.0), respectively. Tertiary NICU admission and hyperbilirubinemia had positive but statistically borderline nonsignificant associations with developmental delay: ORs were 1.74 (95% CI: 0.96-3.15) and 1.52 (95% CI: 0.94-2.46), respectively. No other neonatal morbidities were associated with developmental delay. In multivariate analyses, only hypoglycemia was associated with developmental delay (OR: 2.19; 95% CI: 1.08-4.46). CONCLUSIONS: In moderately preterm-born children, only hypoglycemia increased the risk of developmental delay at preschool age. A concerted effort to prevent hypoglycemia might enhance developmental outcome in this group

Effects and side-effects of integrating care: the case of mental health care in the Netherlands

Contains fulltext : 56200.pdf ( ) (Open Access)Purpose: Description and analysis of the effects and side-effects of integrated mental health care in the Netherlands. Context of case: Due to a number of large-scale mergers, Dutch mental health care has become an illustration of integration and coherence of care services. This process of integration, however, has not only brought a better organisation of care but apparently has also resulted in a number of serious side-effects. This has raised the question whether integration is still the best way of reorganising mental health care. Data sources: Literature, data books, patients and professionals, the advice of the Dutch Commission for Mental Health Care, and policy papers. Case description: Despite its organisational and patient-centred integration, the problems in the Dutch mental health care system have not diminished: long waiting lists, insufficient fine tuning of care, public order problems with chronic psychiatric patients, etc. These problems are related to a sharp rise in the number of mental health care registrations in contrast with a decrease of registered patients in first-level services. This indicates that care for people with mental health problems has become solely a task for the mental health care services (monopolisation). At the same time, integrated institutions have developed in the direction of specialised medical care (homogenisation). Monopolisation and homogenisation together have put the integrated institutions into an impossible divided position. Conclusions and discussion: Integration of care within the institutions in the Netherlands has resulted in withdrawal of other care providers. These side-effects lead to a new discussion on the real nature and benefits of an integrated mental health care system. Integration requires also a broadly shared vision on good care for the various target groups. This would require a radicalisation of the distinction between care providers as well as a recognition of the different goals of mental health care.11 p

Nowcasting GDP Growth: statistical models versus professional analysts

This thesis contains four chapters that cast new light on the ability of professional analysts and statistical models to assess economic growth in the current quarter (nowcast) and its development in the near future. This is not a trivial issue. An accurate assessment of the current state of the economy is important as starting point for medium-term forecasts, especially during times of heightened volatility, such as the recent financial crisis. Nowadays, practitioners have a wealth of statistical model to choose from; but which one should they use? Can statistical models be modified to improve their forecasting accuracy? What are the gains from combining the forecasts of different statistical models? Did the financial crisis change the forecasting performance of statistical models relative to professional analysts? Can practitioners use the near-term outlook of professional analysts to improve the forecasting accuracy of statistical models? This thesis gives answers to these questions, providing new insights of interest to both academics and practitioners. Central to this research is the construction of a new dataset, comprised of the near-term economic growth forecast of professional analysts, and the monthly indicators available when analysts made their forecasts

Proving refinement transformations using extended denotational semantics

TAMPR is a fully automatic transformation system based on syntactic rewrites. Our approach in a correctness proof is to map the transformation into an axiomatized mathematical domain where formal (and automated) reasoning can be performed. This mapping is accomplished via an extended denotational semantic paradigm. In this approach, the abstract notion of a program state is distributed between an environment function and a store function. Such a distribution introduces properties that go beyond the abstract state that is being modeled. The reasoning framework needs to be aware of these properties in order to successfully complete a correctness proof. This paper discusses some of our experiences in proving the correctness of TAMPR transformations

Performance of a direct steam generation solar thermal power plant for electricity production as a function of the solar multiple

This paper describes the influence of the solar multiple on the annual performance of parabolic trough solar thermal power plants with direct steam generation (DSG). The reference system selected is a 50 M We DSG power plant, with thermal storage and auxiliary natural gas-fired boiler. It is considered that both systems are necessary for an optimum coupling to the electricity grid. Although thermal storage is an opening issue for DSG technology, it gives an additional degree of freedom for plant performance optimization. Fossil hybridization is also a key element if a reliable electricity production must be guaranteed for a defined time span. Once the yearly parameters of the solar power plant are calculated, the economic analysis is performed, assessing the effect of the solar multiple in the levelized cost of electricity, as well as in the annual natural gas consumption

Systematic Cu-63 NQR studies of the stripe phase in La(1.6-x)Nd(0.4)Sr(x)CuO(4) for 0.07 <= x <= 0.25

We demonstrate that the integrated intensity of Cu-63 nuclear quadrupole resonance (NQR) in La(1.6-x)Nd(0.4)Sr(x)CuO(4) decreases dramatically below the charge-stripe ordering temperature T(charge). Comparison with neutron and X-ray scattering indicates that the wipeout fraction F(T) (i.e. the missing fraction of the integrated intensity of the NQR signal) represents the charge-stripe order parameter. The systematic study reveals bulk charge-stripe order throughout the superconducting region 0.07 <= x <= 0.25. As a function of the reduced temperature t = T/T(charge), the temperature dependence of F(t) is sharpest for the hole concentration x=1/8, indicating that x=1/8 is the optimum concentration for stripe formation.Comment: 10 pages of text and captions, 11 figures in postscript. Final version, with new data in Fig.

Correction factors for oxygen and flow-rate effects on neonatal Fleisch and Lilly pneumotachometers

Objective: To assess the effects of different oxygen concentrations and flow rates on the measurement errors of neonatal pneumotachometers in heated and unheated situations and to develop correction factors to correct for these effects. Design: Prospective laboratory study. Setting: Outpatient clinic with equipment in a standardized setting. Subjects: Neonatal pneumotachometers. Interventions: In standardized conditions, the tested pneumotachometer was calibrated at a flow rate of 3 L/min with 60% oxygen and was set in series with a closed spirometer system being used as a reference. Different air-flow levels (1-9 L/min) and oxygen concentrations (21-100%) were infused into the closed system with the pneumotachometer and spirometer. Measurements and Main Results: The pneumotachometers were significantly affected by changing oxygen concentrations (p < .01) and increasing flow rates (p < .01), increasing the actually measured flow rate. Correction factors, developed by multiple regression analysis, significantly reduced the overall maximum errors of the pneumotachometers from -1.1 to 0.6 L/min to -0.5 to 0.4 L/min. Conclusions: The effects of changes in oxygen concentrations and flow rates on neonatal pneumotachometers could be considerably decreased by the use of correction factors such as were calculated in this study. This will preclude frequent calibration procedures with actual flow and oxygen levels during changes in experimental settings. Copyrigh