Analysis of time-to-event for observational studies: Guidance to the use of intensity models

This paper provides guidance for researchers with some mathematical background on the conduct of time-to-event analysis in observational studies based on intensity (hazard) models. Discussions of basic concepts like time axis, event definition and censoring are given. Hazard models are introduced, with special emphasis on the Cox proportional hazards regression model. We provide check lists that may be useful both when fitting the model and assessing its goodness of fit and when interpreting the results. Special attention is paid to how to avoid problems with immortal time bias by introducing time-dependent covariates. We discuss prediction based on hazard models and difficulties when attempting to draw proper causal conclusions from such models. Finally, we present a series of examples where the methods and check lists are exemplified. Computational details and implementation using the freely available R software are documented in Supplementary Material. The paper was prepared as part of the STRATOS initiative.Comment: 28 pages, 12 figures. For associated Supplementary material, see http://publicifsv.sund.ku.dk/~pka/STRATOSTG8

Hungarian International Development Cooperation: Context, Stakeholders and Performance

This paper explores the domestic and international context of Hungary's emerging international development policy. Specifically, it looks at three factors that may influence how this policy operates: membership in the European Union (EU) and potential ‘Europeanization’, Hungary's wider foreign policy strategy, and the influence of domestic stakeholders. In order to uncover how these factors affect the country's international development policy, semi-structured interviews were carried out with the main stakeholders. The main conclusions are: (1) While accession to the EU did play a crucial role in restarting Hungary's international development policy, the integration has had little effect since then; (2) international development policy seems to serve mainly Hungary's regional strategic foreign policy and economic interests, and not its global development goals; and (3) although all the domestic development stakeholders are rather weak, the Ministry of Foreign Affairs (MFA) still seems to play a dominating role. Convergence with European requirements and best practices is, therefore, clearly hindered by foreign policy interests and also by the weakness of non- governmental stakeholders

Inverse probability of treatment weighting with generalized linear outcome models for doubly robust estimation

There are now many options for doubly robust estimation; however, there is a concerning trend in the applied literature to believe that the combination of a propensity score and an adjusted outcome model automatically results in a doubly robust estimator and/or to misuse more complex established doubly robust estimators. A simple alternative, canonical link generalized linear models (GLM) fit via inverse probability of treatment (propensity score) weighted maximum likelihood estimation followed by standardization (the g-formula) for the average causal effect, is a doubly robust estimation method. Our aim is for the reader not just to be able to use this method, which we refer to as IPTW GLM, for doubly robust estimation, but to fully understand why it has the doubly robust property. For this reason, we define clearly, and in multiple ways, all concepts needed to understand the method and why it is doubly robust. In addition, we want to make very clear that the mere combination of propensity score weighting and an adjusted outcome model does not generally result in a doubly robust estimator. Finally, we hope to dispel the misconception that one can adjust for residual confounding remaining after propensity score weighting by adjusting in the outcome model for what remains `unbalanced' even when using doubly robust estimators. We provide R code for our simulations and real open-source data examples that can be followed step-by-step to use and hopefully understand the IPTW GLM method. We also compare to a much better-known but still simple doubly robust estimator

Lifetime measurement of the metastable 3d 2D5/2 state in the 40Ca+ ion using the shelving technique on a few-ion string

We present a measurement of the lifetime of the metastable 3d 2D5/2 state in the 40Ca+ ion, using the so-called shelving technique on a string of five Doppler laser-cooled ions in a linear Paul trap. A detailed account of the data analysis is given, and systematic effects due to unwanted excitation processes and collisions with background gas atoms are discussed and estimated. From a total of 6805 shelving events, we obtain a lifetime tau=1149+/-14(stat.)+/-4(sys.)ms, a result which is in agreement with the most recent measurements.Comment: 10 pages, 7 figures. Submitted for publicatio

Changes in the Frontotemporal Cortex and Cognitive Correlates in First-Episode Psychosis

Background: Loss of cortical volume in frontotemporal regions has been reported in patients with schizophrenia and their relatives. Cortical area and thickness are determined by different genetic processes, and measuring these parameters separately may clarify disturbances in corticogenesis relevant to schizophrenia. Our study also explored clinical and cognitive correlates of these parameters.Methods: Thirty-seven patients with first-episode psychosis (34 schizophrenia, 3 schizoaffective disorder) and 38 healthy control subjects matched for age and sex took part in the study. Imaging was performed on an magnetic resonance imaging 1.5-T scanner. Area and thickness of the frontotemporal cortex were measured using a surface-based morphometry method (Freesurfer). All subjects underwent neuropsychologic testing that included measures of premorbid and current IQ, working and verbal memory, and executive function.Results: Reductions in cortical area, more marked in the temporal cortex, were present in patients. Overall frontotemporal cortical thickness did not differ between groups, although regional thinning of the right superior temporal region was observed in patients. There was a significant association of both premorbid IQ and IQ at disease onset with area, but not thickness, of the frontotemporal cortex, and working memory span was associated with area of the frontal cortex. These associations remained significant when only patients with schizophrenia were considered.Conclusions: Our results suggest an early disruption of corticogenesis in schizophrenia, although the effect of subsequent environmental factors cannot be excluded. In addition, cortical abnormalities are subject to regional variations and differ from those present in neurodegenerative diseases

Longitudinal Examination of Everyday Executive Functioning in Children With ASD: Relations With Social, Emotional, and Behavioral Functioning Over Time

Executive functioning (EF) deficits are well-documented in Autism Spectrum Disorder (ASD), yet little is known about the longitudinal trajectory of “everyday” EF and links to social, emotional and behavioral outcomes in ASD. This study examined the profile of everyday EF utilizing parent-reported measures over 2 years, and explored whether prior estimates of EF were related to later co-morbid psychopathology and social functioning in 39 children with ASD and 34 typically developing (TD) children (ages 7–14 years). According to parent reports, children with ASD had impaired scores of EF in all domains at both time points, and showed no significant improvement across 2 years, compared to controls. Regression analyses showed that prior estimates of behavior regulation difficulties at time 1 uniquely predicted later emotional (i.e., symptoms of anxiety/depression) and behavioral (i.e., oppositionality/aggressiveness) problems in children with ASD 2 years later. Furthermore, an improvement of metacognitive skills predicted a reduction of social difficulties over 2 years in ASD. These results imply that EF may be a potential target of intervention for preventing and reducing co-morbid psychopathology and promoting social competence in youth with ASD. Furthermore, the findings that EF related to behavior is more critical for later emotional and behavioral functioning, whereas EF related to cognition is more critical for social functioning, indicates that it may be beneficial to tailor treatment. Future studies investigating the effectiveness of EF-based interventions in improving the cognitive, psychological and social outcomes in ASD are of high priority

Attentional WM is not necessarily specifically related with fluid intelligence: the case of smart children with ADHD symptoms.

Executive functions and, in particular, Attentional (active) Working Memory (WM) have been associated with fluid intelligence. The association contrasts with the hypothesis that children with ADHD exhibit problems with WM tasks requiring controlled attention and may have a good fluid intelligence. This paper examines whether children who are intelligent but present ADHD symptoms fail in attentional WM tasks. The latter result would be problematic for theories assuming the generality of a strict relationship between intelligence and WM. To study these issues, a battery of tests was administered to a group of 58 children who all displayed symptoms of ADHD. All children were between the age of 8 and 11 years, and were described by their teachers as smart. Children were compared to a control group matched for age, schooling, and gender. The battery included a test of fluid intelligence (Raven's Coloured Matrices), and a series of visuospatial WM tasks. Results showed that children with ADHD were high in intelligence but significantly lower than the controls in WM tasks requiring high attentional control, whereas there was no difference in WM tasks requiring low attentional control. Furthermore, only high attentional control WM tasks were significantly related to Raven's performance in the control group, whereas all WM tasks were similarly related in the ADHD group. It is concluded that performance in high attentional control WM tasks may be related to fluid intelligence, but also to a specific control component that is independent of intelligence and is poor in children with ADHD

Boundless plains

Scholarships & Prizes Office. University of Sydne