Early prediction of median survival among a large AIDS surveillance cohort

<p>Abstract</p> <p>Background</p> <p>For individuals with AIDS, data exist relatively soon after diagnosis to allow estimation of "early" survival quantiles (<it>e.g.</it>, the 0.10, 0.15, 0.20 and 0.30 quantiles, etc.). Many years of additional observation must elapse before median survival, a summary measure of survival, can be estimated accurately. In this study, a new approach to predict AIDS median survival is presented and its accuracy tested using AIDS surveillance data.</p> <p>Methods</p> <p>The data consisted of 96,373 individuals who were reported to the HIV/AIDS Reporting System of the California Department of Health Services Office of AIDS as of December 31, 1996. We defined cohorts based on quarter year of diagnosis (<it>e.g.</it>, the "931" cohort consists of individuals diagnosed with AIDS in the first quarter of 1993). We used early quantiles (estimated using the Inverse Probability of Censoring Weighted estimator) of the survival distribution to estimate median survival by assuming a linear relationship between the earlier quantiles and median survival. From this model, median survival was predicted for cohorts for which a median could not be estimated empirically from the available data. This prediction was compared with the actual medians observed when using updated survival data reported at least five years later.</p> <p>Results</p> <p>Using the 0.15 quantile as the predictor and the data available as of December 31, 1996, we were able to predict the median survival of four cohorts (933, 934, 941, and 942) to be 34, 34, 31, and 29 months. Without this approach, there were insufficient data with which to make any estimate of median survival. The actual median survival of these four cohorts (using data as of December 31, 2001) was found to be 32, 40, 46, and 80 months, suggesting that the accuracy for this approach requires a minimum of three years to elapse from diagnosis to the time an accurate prediction can be made.</p> <p>Conclusion</p> <p>The results of this study suggest that early and accurate prediction of median survival time after AIDS diagnosis may be possible using early quantiles of the survival distribution. The methodology did not seem to work well during a period of significant change in survival as observed with highly active antiretroviral treatment, but results suggest that it may work well in a time of more gradual improvement in survival.</p

Moderation in management research: What, why, when and how.

Many theories in management, psychology, and other disciplines rely on moderating variables: those which affect the strength or nature of the relationship between two other variables. Despite the near-ubiquitous nature of such effects, the methods for testing and interpreting them are not always well understood. This article introduces the concept of moderation and describes how moderator effects are tested and interpreted for a series of model types, beginning with straightforward two-way interactions with Normal outcomes, moving to three-way and curvilinear interactions, and then to models with non-Normal outcomes including binary logistic regression and Poisson regression. In particular, methods of interpreting and probing these latter model types, such as simple slope analysis and slope difference tests, are described. It then gives answers to twelve frequently asked questions about testing and interpreting moderator effects

Evaluation of the ADOS Revised Algorithm: The Applicability in 558 Dutch Children and Adolescents

The revised ADOS algorithms, proposed by Gotham et al. (J Autism Dev Disord 37:613–627, 2007), were investigated in an independent sample of 558 Dutch children (modules 1, 2 and 3). The revised algorithms lead to better balanced sensitivity and specificity for modules 2 and 3, without losing efficiency of the classification. Including the restricted repetitive behaviour domain in the algorithm contributes to a clinical ASD classification in modules 2 and 3. For module 1, the results indicate less improvement, probably due to the low-functioning population. In most groups, the advantages of the revised algorithms are achieved without losing the strength of the original algorithm

Internalization Dissociates β2-Adrenergic Receptors

G protein-coupled receptors (GPCRs) self-associate as dimers or higher-order oligomers in living cells. The stability of associated GPCRs has not been extensively studied, but it is generally thought that these receptors move between the plasma membrane and intracellular compartments as intact dimers or oligomers. Here we show that β2-adrenergic receptors (β2ARs) that self-associate at the plasma membrane can dissociate during agonist-induced internalization. We use bioluminescence-resonance energy transfer (BRET) to monitor movement of β2ARs between subcellular compartments. BRET between β2ARs and plasma membrane markers decreases in response to agonist activation, while at the same time BRET between β2ARs and endosome markers increases. Energy transfer between β2ARs is decreased in a similar manner if either the donor- or acceptor-labeled receptor is mutated to impair agonist binding and internalization. These changes take place over the course of 30 minutes, persist after agonist is removed, and are sensitive to several inhibitors of arrestin- and clathrin-mediated endocytosis. The magnitude of the decrease in BRET between donor- and acceptor-labeled β2ARs suggests that at least half of the receptors that contribute to the BRET signal are physically segregated by internalization. These results are consistent with the possibility that β2ARs associate transiently with each other in the plasma membrane, or that β2AR dimers or oligomers are actively disrupted during internalization

The effect of disgust-related side-effects on symptoms of depression and anxiety in people treated for cancer: a moderated mediation model

As maladaptive disgust responses are linked to mental health problems, and cancer patients may experience heightened disgust as a result of treatments they receive, we explored the associations between disgust-related side-effects and symptoms of depression and anxiety in people treated for cancer. One hundred and thirty two (83 women, Mage = 57.48 years) participants answered questions about their treatments, side-effects, disgust responding, and mental health. Experiencing bowel and/or bladder problems, sickness and/or nausea (referred to here as “core” disgust-related side-effects) was significantly related to greater symptoms of depression and borderline increased anxiety. Further, these links were explained by a moderated mediation model, whereby the effects of core disgust side-effects on depression and anxiety were mediated by (physical and behavioural) self-directed disgust, and disgust propensity moderated the effect of core disgust side-effects on self-disgust. These findings stress the importance of emotional responses, like disgust, in psychological adaptation to the side-effects of cancer treatments

Contribution of Social Isolation, Restraint, and Hindlimb Unloading to Changes in Hemodynamic Parameters and Motion Activity in Rats

The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint), and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient

Reward devaluation disrupts latent inhibition in fear conditioning

Three experiments explored the link between reward shifts and latent inhibition (LI). Using consummatory procedures, rewards were either downshifted from 32% to 4% sucrose (Experiments 1–2), or upshifted from 4% to 32% sucrose (Experiment 3). In both cases, appropriate unshifted controls were also included. LI was implemented in terms of fear conditioning involving a single tone-shock pairing after extensive tone-only preexposure. Nonpreexposed controls were also included. Experiment 1 demonstrated a typical LI effect (i.e., disruption of fear conditioning after preexposure to the tone) in animals previously exposed only to 4% sucrose. However, the LI effect was eliminated by preexposure to a 32%-to-4% sucrose devaluation. Experiment 2 replicated this effect when the LI protocol was administered immediately after the reward devaluation event. However, LI was restored when preexposure was administered after a 60- min retention interval. Finally, Experiment 3 showed that a reward upshift did not affect LI. These results point to a significant role of negative emotion related to reward devaluation in the enhancement of stimulus processing despite extensive nonreinforced preexposure experience