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the copyright), a 12-item patient-reported outcome questionnaire designed to quantify ocular disability due to dry eye disease. Methods: Study data were collected within the Restasis Review of Efficacy and Safety vs Tears in the Relief of Dry Eye (RESTORE), an observational registry. A clinician global impression (CGI) and a subject global assessment (SGA) served as anchors to estimate the MCID for the overall OSDI score (range, 0-100). The overall OSDI score defined the ocular surface as normal (0-12 points) or as having mild (13-22 points), moderate (23-32 points), or severe (33-100 points) disease. RESTORE patients were included if they completed the OSDI at the baseline visit and at a follow-up visit and had a global change rating (SGA or CGI). Results: Three hundred ten patients were included (82.3% white and 81.6% female [mean age, 57.8 years]). The CGI and SGA correlated with the OSDI score change for all OSDI categories except the normal category. The MCID ranged from 7.0 to 9.9 for all OSDI categories. The MCID ranged from 4.5 to 7.3 for mild or moderate disease and from 7.3 to 13.4 for severe disease. Conclusions: Using observational data, we estimated the MCIDs for different baseline OSDI categories of dry eye disease. These results will assist clinicians and researchers when interpreting OSDI score changes.

In this expository article we survey some properties of completely monotonic functions and give various examples, including some famous special functions.Such function are useful, for example, in probability theory. It is known, [3], p.450, for example, that a function w is the Laplace transform of an infinitely divisible probability distribution on (0, ∞), if and only if w = e −h where the derivative of h is completely monotonic and h(0+) = 0.

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Background: Immune thrombocytopenic purpura (ITP), a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL).

Inhibition of phosphodiesterase 10A (PDE10A) promotes cyclic nucleotide signaling, increases striatal activation, and decreases behavioral activity. Enhanced cyclic nucleotide signaling is a well established route to producing changes in gene expression. We hypothesized that chronic suppression of PDE10A activity would have significant effects on gene expression in the striatum. A comparison of the expression profile of PDE10A knockout (KO) mice and wild-type mice after chronic PDE10A inhibition revealed altered expression of 19 overlapping genes with few significant changes outside the striatum or after administration of a PDE10A inhibitor to KO animals. Chronic inhibition of PDE10A produced up-regulation of mRNAs encoding genes that included prodynorphin, synaptotagmin10, phosphodiesterase 1C, glutamate decarboxylase 1, and diacylglycerol Oacyltransferase and a down-regulation of mRNAs encoding choline acetyltransferase and Kv1.6, suggesting long-term suppression of the PDE10A enzyme is consistent with altered striatal excitability and potential utility as a antipsychotic therapy. In addition, upregulation of mRNAs encoding histone 3 (H3) and down-regulation of histone deacetylase 4, follistatin, and claspin mRNAs suggests activation of molecular cascades capable of neuroprotection. We used lentiviral delivery of cAMP response element (CRE)-luciferase reporter constructs into the striatum and live animal imaging of 2-{4-[-pyridin-4-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline succinic acid (TP-10)-induced luciferase activity to further demonstrate PDE10 inhibition results in CRE-mediated transcription. Consistent with potential neuroprotective cascades, we also demonstrate phosphorylation of mitogen-and stress-activated kinase 1 and H3 in vivo after TP-10 treatment. The observed changes in signaling and gene expression are predicted to provide neuroprotective effects in models of Huntington's disease.

It is well known that pebble diameter systematically decreases downstream in rivers. The contribution of abrasion is uncertain, in part because (1) diameter is insufficient to characterize pebble mass loss due to abrasion and (2) abrasion rates measured in laboratory experiments cannot be easily extrapolated to the field. A recent geometric theory describes abrasion as a curvature-dependent process that produces a two-phase evolution: in Phase I, initially blocky pebbles round to smooth, convex shapes with little reduction in axis dimensions; then, in Phase II, smooth, convex pebbles slowly reduce their axis dimensions. Here we provide strong evidence that two-phase abrasion occurs in a natural setting, by examining downstream evolution of shape and size of thousands of pebbles over 10 km in a tropical montane stream. The geometric theory is verified in this river system using a variety of manual and image-based shape parameters, providing a generalizable method for quantifying the significance of abrasion. Phase I occurs over~1 km, in upstream bedrock reaches where abrasion is dominant and sediment storage is limited. In downstream alluvial reaches, where Phase II occurs, we observe the expected exponential decline in pebble diameter. Using a discretized abrasion model (the so-called "box equations") with deposition, we deduce that abrasion removes more than one third of the mass of a pebble but that size-selective sorting dominates downstream changes in pebble diameter. Overall, abrasion is the dominant process in the downstream diminution of pebble mass (but not diameter) in the studied river, with important implications for pebble mobility and the production of fine sediments.

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