Estimating a population cumulative incidence under calendar time trends

Abstract Background The risk of a disease or psychiatric disorder is frequently measured by the age-specific cumulative incidence. Cumulative incidence estimates are often derived in cohort studies with individuals recruited over calendar time and with the end of follow-up governed by a specific date. It is common practice to apply the Kaplan\u2013Meier or Aalen\u2013Johansen estimator to the total sample and report either the estimated cumulative incidence curve or just a single point on the curve as a description of the disease risk. Methods We argue that, whenever the disease or disorder of interest is influenced by calendar time trends, the total sample Kaplan\u2013Meier and Aalen\u2013Johansen estimators do not provide useful estimates of the general risk in the target population. We present some alternatives to this type of analysis. Results We show how a proportional hazards model may be used to extrapolate disease risk estimates if proportionality is a reasonable assumption. If not reasonable, we instead advocate that a more useful description of the disease risk lies in the age-specific cumulative incidence curves across strata given by time of entry or perhaps just the end of follow-up estimates across all strata. Finally, we argue that a weighted average of these end of follow-up estimates may be a useful summary measure of the disease risk within the study period. Conclusions Time trends in a disease risk will render total sample estimators less useful in observational studies with staggered entry and administrative censoring. An analysis based on proportional hazards or a stratified analysis may be better alternatives

Effects of music on agitation in dementia: A meta-analysis

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Matching Tree-Level Matrix Elements with Interleaved Showers

We present an implementation of the so-called CKKW-L merging scheme for combining multi-jet tree-level matrix elements with parton showers. The implementation uses the transverse-momentum-ordered shower with interleaved multiple interactions as implemented in PYTHIA8. We validate our procedure using e+e--annihilation into jets and vector boson production in hadronic collisions, with special attention to details in the algorithm which are formally sub-leading in character, but may have visible effects in some observables. We find substantial merging scale dependencies induced by the enforced rapidity ordering in the default PYTHIA8 shower. If this rapidity ordering is removed the merging scale dependence is almost negligible. We then also find that the shower does a surprisingly good job of describing the hardness of multi-jet events, as long as the hardest couple of jets are given by the matrix elements. The effects of using interleaved multiple interactions as compared to more simplistic ways of adding underlying-event effects in vector boson production are shown to be negligible except in a few sensitive observables. To illustrate the generality of our implementation, we also give some example results from di-boson production and pure QCD jet production in hadronic collisions.Comment: 44 pages, 23 figures, as published in JHEP, including all changes recommended by the refere

Dynamics of the rotational degrees of freedom in a supercooled liquid of diatomic molecules

Using molecular dynamics computer simulations, we investigate the dynamics of the rotational degrees of freedom in a supercooled system composed of rigid, diatomic molecules. The interaction between the molecules is given by the sum of interaction-site potentials of the Lennard-Jones type. In agreement with mode-coupling theory (MCT), we find that the relaxation times of the orientational time correlation functions C_1^(s), C_2^(s) and C_1 show at low temperatures a power-law with the same critical temperature T_c, and which is also identical to the critical temperature for the translational degrees of freedom. In contrast to MCT we find, however, that for these correlators the time-temperature superposition principle does not hold well and that also the critical exponent gamma depends on the correlator. We also study the temperature dependence of the rotational diffusion constant D_r and demonstrate that at high temperatures D_r is proportional to the translational diffusion constant D and that when the system starts to become supercooled the former shows an Arrhenius behavior whereas the latter exhibits a power-law dependence. We discuss the origin for the difference in the temperature dependence of D (or the relaxation times of C_l^(s) and D_r. Finally we present results which show that at low temperatures 180 degree flips of the molecule are an important component of the relaxation dynamics for the orientational degrees of freedom.Comment: 17 pages of RevTex, 12 figure

Disease-Related Changes in the Cerebrospinal Fluid Metabolome in Amyotrophic Lateral Sclerosis Detected by GC/TOFMS

The changes in the cerebrospinal fluid (CSF) metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF.Using gas chromatography coupled to mass spectrometry (GC/TOFMS) and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls.The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS) have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS) without superoxide dismutase-1 gene (SOD1) mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar.Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

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