Early treatment with rasagiline at a dose of 1 mg per day provided benefits that were consistent with a possible disease-modifying effect, but early treatment with rasagiline at a dose of 2 mg per day did not. Because the two doses were associated with different outcomes, the study results must be interpreted with caution. (ClinicalTrials.gov number, NCT00256204.)
Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.
Simple yet practically efficient conditions for the ergodicity of a Markov chain on a general state space have recently been developed. We illustrate their application to non-linear time series models and, in particular, to random coefficient autoregressive models.As well as ensuring the existence of a unique stationary distribution, geometric rates of convergence to stationarity are ensured. Moreover, sufficient conditions for the existence and convergence of moments can be determined by a closely related method. The latter conditions, in particular, are new.
Today's call center managers face multiple operational decision-making tasks. One of the most common is determining the weekly staffing levels to ensure customer satisfaction and meeting their needs while minimizing service costs. An initial step for producing the weekly schedule is forecasting the future system loads which involves predicting both arrival counts and average service times. We introduce an arrival count model which is based on a mixed Poisson process approach. The model is applied to data from an Israeli Telecom company call center. In our model, we also consider the effect of events such as billing on the arrival process and we demonstrate how to incorporate them as exogenous variables in the model. After obtaining the forecasted system load, in large call centers, a manager can choose to apply the QED (Quality-Efficiency Driven) regime's "square-root staffing" rule in order to balance the offered-load per server with the quality of service. Implementing this staffing rule requires that the forecasted values of the arrival counts and average service times maintain certain levels of precision. We develop different goodness of fit criteria that help determine our model's practical performance under the QED regime. These show that during most hours of the day the model can reach desired precision levels.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS255 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org
By investigating a Markov chain whose limiting distribution corresponds to that of the Dirichlet process we are able directly to ascertain conditions for the existence of linear functionals of that process. Together with earlier analyses we are able to characterize those functionals which are a.s. finite in terms of the parameter measure of the process. We also show that the appropriate Markov chain in the space of measures is only weakly convergent and not Harris ergodic.
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