The Display and Manipulation of Temporal Information

Because medical data have complex temporal features, special techniques are required for storing, retrieving, and displaying clinical data from electronic databases. One significant problem caused by the temporal nature of medical data has been called the temporal granularity problem. The temporal granularity problem is said to occur when the set of facts relevant to a specific problem changes as the time scale changes. We argue that what is needed to deal with changes in the relevant time scale are temporal granularity heuristics. One heuristic that we have explored is that, for any level of problem abstraction, and for each type of data item in the record, there exists an optimal level of temporal abstraction. We describe an implemented database kernel and a graphical user interface that have features designed specially to support this temporal granularity heuristic. The basis for our solution is the use of temporal abstraction and temporal granularity. This heuristic encodes the relevant behavior of each type of event at different levels of temporal granularity. In doing so, we can define a specific behavior for each type of data as the level of abstraction changes

Model-Based Interpretation of Time-Varying Medical Data

Temporal concepts are critical is medical therapy-planning. If given early enough, specific therapeutic choices may abort or suppress evolving undesired changes in a patient’s clinical status. Effective medical decision making demands recognition and interpretation of complex temporal changes that permeate the medical record. This paper presents a methodology for representing and using medical knowledge about temporal relationships to infer the presence of clinically relevant events, and describes a program, called TOPAZ, that uses this methodology to generate a narrative summary of such events. A unique feature of TOPAZ is the use of numeric and symbolic modeling techniques to perform temporal reasoning tasks that would be difficult to encode and perform using only one modeling methodology

How selective are real wage cuts? : a micro-analysis using linked employer-employee data

Using linked employer–employee panel data for Germany, this paper investigates whether firms implement real wage reductions in a selective manner. In line with insider–outsider and several strands of efficiency wage theory, we find strong evidence for selective wage cuts with high-productivity workers being spared even when controlling for permanent differences in firms’ wage policies. In contrast to some recent contributions stressing fairness considerations, we also find that wage cuts increase wage dispersion among peers rather than narrowing it. Notably, the same selectivity pattern shows up when restricting our analysis to firms covered by collective agreements or having a works council

Self-trapping transition for nonlinear impurities embedded in a Cayley tree

The self-trapping transition due to a single and a dimer nonlinear impurity embedded in a Cayley tree is studied. In particular, the effect of a perfectly nonlinear Cayley tree is considered. A sharp self-trapping transition is observed in each case. It is also observed that the transition is much sharper compared to the case of one-dimensional lattices. For each system, the critical values of $\chi$ for the self-trapping transitions are found to obey a power-law behavior as a function of the connectivity $K$ of the Cayley tree.Comment: 6 pages, 7 fig

Meta-analysis of epigenetic aging in schizophrenia reveals multifaceted relationships with age, sex, illness duration, and polygenic risk

Background: The study of biological age acceleration may help identify at-risk individuals and reduce the rising global burden of age-related diseases. Using DNA methylation (DNAm) clocks, we investigated biological aging in schizophrenia (SCZ), a mental illness that is associated with an increased prevalence of age-related disabilities and morbidities. In a whole blood DNAm sample of 1090 SCZ cases and 1206 controls across four European cohorts, we performed a meta-analysis of differential aging using three DNAm clocks (i.e., Hannum, Horvath, and Levine). To dissect how DNAm aging contributes to SCZ, we integrated information on duration of illness and SCZ polygenic risk, as well as stratified our analyses by chronological age and biological sex. Results: We found that blood-based DNAm aging is significantly altered in SCZ independent from duration of the illness since onset. We observed sex-specific and nonlinear age effects that differed between clocks and point to possible distinct age windows of altered aging in SCZ. Most notably, intrinsic cellular age (Horvath clock) is decelerated in SCZ cases in young adulthood, while phenotypic age (Levine clock) is accelerated in later adulthood compared to controls. Accelerated phenotypic aging was most pronounced in women with SCZ carrying a high polygenic burden with an age acceleration of + 3.82 years (CI 2.02–5.61, P = 1.1E−03). Phenotypic aging and SCZ polygenic risk contributed additively to the illness and together explained up to 14.38% of the variance in disease status. Conclusions: Our study contributes to the growing body of evidence of altered DNAm aging in SCZ and points to intrinsic age deceleration in younger adulthood and phenotypic age acceleration in later adulthood in SCZ. Since increased phenotypic age is associated with increased risk of all-cause mortality, our findings indicate that specific and identifiable patient groups are at increased mortality risk as measured by the Levine clock. Our study did not find that DNAm aging could be explained by the duration of illness of patients, but we did observe age- and sex-specific effects that warrant further investigation. Finally, our results show that combining genetic and epigenetic predictors can improve predictions of disease outcomes and may help with disease management in schizophrenia.</p

Meta-analysis of epigenetic aging in schizophrenia reveals multifaceted relationships with age, sex, illness duration, and polygenic risk

Background: The study of biological age acceleration may help identify at-risk individuals and reduce the rising global burden of age-related diseases. Using DNA methylation (DNAm) clocks, we investigated biological aging in schizophrenia (SCZ), a mental illness that is associated with an increased prevalence of age-related disabilities and morbidities. In a whole blood DNAm sample of 1090 SCZ cases and 1206 controls across four European cohorts, we performed a meta-analysis of differential aging using three DNAm clocks (i.e., Hannum, Horvath, and Levine). To dissect how DNAm aging contributes to SCZ, we integrated information on duration of illness and SCZ polygenic risk, as well as stratified our analyses by chronological age and biological sex. Results: We found that blood-based DNAm aging is significantly altered in SCZ independent from duration of the illness since onset. We observed sex-specific and nonlinear age effects that differed between clocks and point to possible distinct age windows of altered aging in SCZ. Most notably, intrinsic cellular age (Horvath clock) is decelerated in SCZ cases in young adulthood, while phenotypic age (Levine clock) is accelerated in later adulthood compared to controls. Accelerated phenotypic aging was most pronounced in women with SCZ carrying a high polygenic burden with an age acceleration of + 3.82 years (CI 2.02–5.61, P = 1.1E−03). Phenotypic aging and SCZ polygenic risk contributed additively to the illness and together explained up to 14.38% of the variance in disease status. Conclusions: Our study contributes to the growing body of evidence of altered DNAm aging in SCZ and points to intrinsic age deceleration in younger adulthood and phenotypic age acceleration in later adulthood in SCZ. Since increased phenotypic age is associated with increased risk of all-cause mortality, our findings indicate that specific and identifiable patient groups are at increased mortality risk as measured by the Levine clock. Our study did not find that DNAm aging could be explained by the duration of illness of patients, but we did observe age- and sex-specific effects that warrant further investigation. Finally, our results show that combining genetic and epigenetic predictors can improve predictions of disease outcomes and may help with disease management in schizophrenia.</p

Wind clumping and the wind-wind collision zone in the Wolf-Rayet binary gamma Velorum

We present XMM-Newton observations of gamma^2 Velorum (WR 11, WC8+O7.5III, P = 78.53 d), a nearby Wolf-Ray binary system, at its X-ray high and low states. At high state, emission from a hot collisional plasma dominates from about 1 to 8 keV. At low state, photons between 1 and 4 keV are absorbed. The hot plasma is identified with the shock zone between the winds of the primary Wolf-Rayet star and the secondary O giant. The absorption at low state is interpreted as photoelectric absorption in the Wolf-Rayet wind. This absorption allows us to measure the absorbing column density and to derive a mass loss rate 8x10^{-6} M_sun/yr for the WC8 star. This mass loss rate, in conjunction with a previous Wolf-Rayet wind model, provides evidence for a clumped WR wind. A clumping factor of 16 is required. The X-ray spectra below 1 keV (12 Ang) show no absorption and are essentially similar in both states. There is a rather clear separation in that emission from a plasma hotter than 5 MK is heavily absorbed in low state while the cooler plasma is not. This cool plasma must come from a much more extended region than the hot material. The Neon abundance in the X-ray emitting material is 2.5 times the solar value. The unexpected detection of CV (25.3 Ang) and CVI (31.6 Ang) radiative recombination continua at both phases indicates the presence of a cool (~40,000 K) recombination region located far out in the binary system.Comment: 16 page

Time evolution of models described by one-dimensional discrete nonlinear Schr\"odinger equation

The dynamics of models described by a one-dimensional discrete nonlinear Schr\"odinger equation is studied. The nonlinearity in these models appears due to the coupling of the electronic motion to optical oscillators which are treated in adiabatic approximation. First, various sizes of nonlinear cluster embedded in an infinite linear chain are considered. The initial excitation is applied either at the end-site or at the middle-site of the cluster. In both the cases we obtain two kinds of transition: (i) a cluster-trapping transition and (ii) a self-trapping transition. The dynamics of the quasiparticle with the end-site initial excitation are found to exhibit, (i) a sharp self-trapping transition, (ii) an amplitude-transition in the site-probabilities and (iii) propagating soliton-like waves in large clusters. Ballistic propagation is observed in random nonlinear systems. The effect of nonlinear impurities on the superdiffusive behavior of random-dimer model is also studied.Comment: 16 pages, REVTEX, 9 figures available upon request, To appear in Physical Review

Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

OBJECTIVE: To investigate the mechanism of the lipid depletion by zinc-a(2)-glycoprotein (ZAG). DESIGN: Studies were conducted in the ob/ob mouse, or on isolated adipocytes from these animals or their lean counterparts. RESULTS: Treatment of these animals for 15 days with ZAG (100? µg, intravenously, daily) resulted in a reduction of body weight of 6.55? g compared with phosphate-buffered saline-treated controls, without a change in food or water intake, but with a 0.4?°C rise in rectal temperature. ZAG-treated mice had a 30% reduction in carcass fat mass and a twofold increase in weight of brown adipose tissue. Epididymal adipocytes from ZAG-treated mice showed an increased expression of ZAG and hormone-sensitive lipase (HSL), and this was maintained for a further 3 days in the absence of ZAG. There was an increased lipolytic response to isoproterenol, which was retained for 3 days in vitro in the absence of ZAG. Expression of HSL was also increased in subcutaneous and visceral adipose tissue, as was also adipose triglyceride lipase (ATGL). There was a rapid loss of labelled lipid from epididymal adipose tissue of ZAG-treated mice, but not from the other depots, reflecting the difference in sensitivity to lipolytic stimuli. The increased expression of HSL and ATGL may involve the extracellular signal-regulated kinase (ERK) pathway, as the active (phospho) form was upregulated in all adipose depots after ZAG administration, whereas in vitro studies showed induction of HSL and ATGL by ZAG to be attenuated by PD98059, an inhibitor of the ERK pathway. CONCLUSION: These results suggest that ZAG not only induces direct lipolysis, but also sensitizes adipose tissue to other lipolytic stimuli