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

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

Dressed States Approach to Quantum Systems

Using the non-perturbative method of {\it dressed} states previously introduced in JPhysA, we study effects of the environment on a quantum mechanical system, in the case the environment is modeled by an ensemble of non interacting harmonic oscillators. This method allows to separate the whole system into the {\it dressed} mechanical system and the {\it dressed} environment, in terms of which an exact, non-perturbative approach is possible. When applied to the Brownian motion, we give explicit non-perturbative formulas for the classical path of the particle in the weak and strong coupling regimes. When applied to study atomic behaviours in cavities, the method accounts very precisely for experimentally observed inhibition of atomic decay in small cavities PhysLA, physics0111042

Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention or after acute coronary syndrome

To prevent recurrent ischaemic events, dual antiplatelet therapy (DAPT) is the standard of care after percutaneous coronary intervention and in the treatment of acute coronary syndrome. Recent evidence supports an adjusted DAPT duration in selected patients. The current paper aims to encourage cardiologists to actively search for patients benefiting from either shorter or prolonged duration DAPT and proposes an algorithm to identify patients who are likely to benefit from such an alternative strategy. Individualised DAPT duration should be considered in high-risk anatomic and/or clinical subgroups or in patients at increased haemorrhagic risk with low ischaemic risk. Both thrombotic and haemorrhagic risk should be assessed in all patients. In patients undergoing percutaneous coronary intervention, the interventional cardiologist could advise on the minimal duration of DAPT. However, in contrast to the minimum duration of DAPT for stent thrombosis prevention, longer duration DAPT is aimed at prevention of spontaneous myocardial infarction, and not at stent thrombos