Pathogenetic insights from the treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic autoimmune disease that causes progressive articular damage, functional loss, and comorbidity. The development of effective biologics and small-molecule kinase inhibitors in the past two decades has substantially improved clinical outcomes. Just as understanding of pathogenesis has led in large part to the development of drugs, so have mode-of-action studies of these specific immune-targeted agents revealed which immune pathways drive articular inflammation and related comorbidities. Cytokine inhibitors have definitively proven a critical role for tumour necrosis factor α and interleukin 6 in disease pathogenesis and possibly also for granulocyte-macrophage colony-stimulating factor. More recently, clinical trials with Janus kinase (JAK) inhibitors have shown that cytokine receptors that signal through the JAK/STAT signalling pathway are important for disease, informing the pathogenetic function of additional cytokines (such as the interferons). Finally, successful use of costimulatory blockade and B-cell depletion in the clinic has revealed that the adaptive immune response and the downstream events initiated by these cells participate directly in synovial inflammation. Taken together, it becomes apparent that understanding the effects of specific immune interventions can elucidate definitive molecular or cellular nodes that are essential to maintain complex inflammatory networks that subserve diseases like rheumatoid arthritis

Mixed dark matter with low-mass bosons

We calculate the linear power spectrum for a range of mixed dark matter (MDM) models assuming a massive (few eV) boson, $\phi$, instead of a neutrino as the hot component. We consider both the case where the hot dark matter (HDM) particle is a boson and the cold component is some other unknown particle, and the case where there is only one dark matter particle, a boson, with the cold dark matter (CDM) component in a Bose condensate. Models resembling the latter type could arise from neutrino decays - we discuss some variants of this idea. The power spectra for MDM models with massive bosons are almost identical to neutrino MDM models for a given mass fraction of HDM if the bosons are distinct from their antiparticles ($\phi\neq\bar\phi$) and have a temperature like that of neutrinos, whereas models with $\phi=\bar\phi$ tend to overproduce small-scale structure.Comment: 17 pages+4 postscript figures, to appear in Phys. Rev. D15 Marc

Biases in FX-Forecasts: Evidence from Panel Data

In this paper, we use the Wall Street Journal poll of FX forecasts to analyze how the group of forecasters form their expectations. One focus is whether forecasters build rational expectations. Furthermore, we analyze whether the group of forecasters can be regarded as homogeneous or heterogeneous. The results from our regressions strongly suggest that some forecasters combine different models of exchange rate forecasting, while others rely solely on one model. We also find evidence that some forecasters underly a bias, while others do not. Overall, our regression results indicate a high degree of heterogeneity. In conclusion, we show that the expectation formation process is not the same among all economists polled. Our findings carry importance for macroeconomic modelling: The assumption of rational agents forming homogeneous expectations is not supported by our results. --Foreign exchange market,forecast bias,random walk

The large core limit of spiral waves in excitable media: A numerical approach

We modify the freezing method introduced by Beyn & Thuemmler, 2004, for analyzing rigidly rotating spiral waves in excitable media. The proposed method is designed to stably determine the rotation frequency and the core radius of rotating spirals, as well as the approximate shape of spiral waves in unbounded domains. In particular, we introduce spiral wave boundary conditions based on geometric approximations of spiral wave solutions by Archimedean spirals and by involutes of circles. We further propose a simple implementation of boundary conditions for the case when the inhibitor is non-diffusive, a case which had previously caused spurious oscillations. We then utilize the method to numerically analyze the large core limit. The proposed method allows us to investigate the case close to criticality where spiral waves acquire infinite core radius and zero rotation frequency, before they begin to develop into retracting fingers. We confirm the linear scaling regime of a drift bifurcation for the rotation frequency and the core radius of spiral wave solutions close to criticality. This regime is unattainable with conventional numerical methods.Comment: 32 pages, 17 figures, as accepted by SIAM Journal on Applied Dynamical Systems on 20/03/1