Modeling seasonality in new product diffusion

We propose a method to include seasonality in any diffusion model that has a closed-form solution. The resulting diffusion model captures seasonality in a way that naturally matches the original diffusion model's pattern. The method assumes that additional sales at seasonal peaks are drawn from previous or future periods. This implies that the seasonal pattern does not influence the underlying diffusion pattern. The model is compared with alternative approaches through simulations and empirical examples. As alternatives, we consider the standard Generalized Bass Model (GBM) and the basic Bass Model, which ignores seasonality. One of the main findings is that modeling seasonality in a GBM generates good predictions but gives biased estimates. In particular, the market potential parameter is underestimated. Ignoring seasonality in cases where data of the entire diffusion period are available gives unbiased parameter estimates in most relevant scenarios. However, ignoring seasonality leads to biased parameter estimates and predictions when only part of the diffusion period is available. We demonstrate that our model gives correct estimates and predictions even if the full diffusion process is not yet available

Modeling Seasonality in New Product Diffusion

Although high frequency diffusion data is nowadays available, common practice is still to only use yearly figures in order to get rid of seasonality. This paper proposes a diffusion model that captures seasonality in a way that naturally matches the overall S-shaped pattern. The model is based on the assumption that additional sales at seasonal peaks are drawn from previous or future periods. This implies that the seasonal pattern does not influence the underlying diffusion pattern. The model is compared with alternative approaches through simulations and empirical examples. As alternatives we consider the standard Generalized Bass Model and ignoring seasonality by using the basic Bass model. One of our main findings is that modeling seasonality in a Generalized Bass Model does generate good predictions, but gives biased estimates. In particular, the market potential parameter will be underestimated. Ignoring seasonality gives the true parameter estimates if the data is available of the entire diffusion period. However, when only part of the diffusion period is available estimates and predictions become biased. Our model gives correct estimates and predictions even if the full diffusion process is not yet available

The local power of the gradient test

The asymptotic expansion of the distribution of the gradient test statistic is derived for a composite hypothesis under a sequence of Pitman alternative hypotheses converging to the null hypothesis at rate $n^{-1/2}$, $n$ being the sample size. Comparisons of the local powers of the gradient, likelihood ratio, Wald and score tests reveal no uniform superiority property. The power performance of all four criteria in one-parameter exponential family is examined.Comment: To appear in the Annals of the Institute of Statistical Mathematics, this http://www.ism.ac.jp/editsec/aism-e.htm

Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration

Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from \u3b2-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on \u3b2-cell growth, differentiation and regeneration. Finally, we describe a peculiar vascular phenotype in tcf7l2 mutant larvae, characterized by significant reduction in the average number and diameter of pancreatic islet capillaries. Overall, the zebrafish Tcf7l2 mutant, characterized by hyperglycemia, pancreatic and vascular defects, and reduced regeneration proves to be a suitable model to study the mechanism of action and the pleiotropic effects of Tcf7l2, the most relevant T2D GWAS hit in human populations

Global Analysis of Aerosol Properties Above Clouds

The seasonal and spatial varability of Aerosol Above Cloud (AAC) properties are derived from passive satellite data for the year 2008. A significant amount of aerosols are transported above liquid water clouds on the global scale. For particles in the fine mode (i.e., radius smaller than 0.3 m), including both clear sky and AAC retrievals increases the global mean aerosol optical thickness by 25(+/- 6%). The two main regions with man-made AAC are the tropical Southeast Atlantic, for biomass burning aerosols, and the North Pacific, mainly for pollutants. Man-made AAC are also detected over the Arctic during the spring. Mineral dust particles are detected above clouds within the so-called dust belt region (5-40 N). AAC may cause a warming effect and bias the retrieval of the cloud properties. This study will then help to better quantify the impacts of aerosols on clouds and climate

Redox-Dependent Modulation of T-Type Ca2+ Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P

Aims: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. Results: SP acutely inhibited T-type voltage-gated Ca2+ channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS. This redox-mediated T-type Ca2+ channel inhibition operated through the modulation of CaV3.2 channel sensitivity to ambient zinc, as it can be prevented or reversed by zinc chelation and mimicked by exogenous zinc. Elimination of the zinc-binding site in CaV3.2 rendered the channel insensitive to SP-mediated inhibition. Importantly, peripherally applied SP significantly reduced bradykinin-induced nociception in rats in vivo; knock-down of CaV3.2 significantly reduced this anti-nociceptive effect. This atypical signaling cascade shared the initial steps with the SP-mediated augmentation of M-type K+ channels described earlier. Innovation: Our study established a mechanism underlying the peripheral anti-nociceptive effect of SP whereby this neuropeptide produces ROS-dependent inhibition of pro-algesic T-type Ca2+ current and concurrent enhancement of anti-algesic M-type K+ current. These findings will lead to a better understanding of mechanisms of endogenous analgesia. Conclusion: SP modulates T-type channel activity in nociceptors by a redox-dependent tuning of channel sensitivity to zinc; this novel modulatory pathway contributes to the peripheral anti-nociceptive effect of SP

Cost-effectiveness study of early versus late parenteral nutrition in critically ill children (PEPaNIC)

__Background:__ The multicentre randomised controlled PEPaNIC trial showed that withholding parenteral nutrition (PN) during the first week of critical illness in children was clinically superior to providing early PN. This study describes the cost-effectiveness of this new nutritional strategy. __Methods:__ Direct medical costs were calculated with use of a micro-costing approach. We compared the costs of late versus early initiation of PN (n = 673 versus n = 670 pa

Comparison of aerosol optical properties above clouds between POLDER and AeroCom models over the South East Atlantic Ocean during the fire season

Aerosol properties above clouds have been retrieved over the South East Atlantic Ocean during the fire season 2006 using satellite observations from POLDER (Polarization and Directionality of Earth Reflectances). From June to October, POLDER has observed a mean Above-Cloud Aerosol Optical Thickness (ACAOT) of 0.28 and a mean Above-Clouds Single Scattering Albedo (ACSSA) of 0.87 at 550 nm. These results have been used to evaluate the simulation of aerosols above clouds in 5 AeroCom (Aerosol Comparisons between Observations and Models) models (GOCART, HadGEM3, ECHAM5-HAM2, OsloCTM2 and SPRINTARS). Most models do not reproduce the observed large aerosol load episodes. The comparison highlights the importance of the injection height and the vertical transport parameterizations to simulate the large ACAOT observed by POLDER. Furthermore, POLDER ACSSA is best reproduced by models with a high imaginary part of black carbon refractive index, in accordance with recent recommendations

Multiple mechanisms mediating carbon monoxide inhibition of the voltage-gated K+ channel Kv1.5

The voltage-gated K+ channel plays key roles in the vasculature and in atrial excitability, and contributes to apoptosis in various tissues. In this study, we have explored its regulation by carbon monoxide (CO), a product of the cytoprotective heme oxygenase enzymes, and a recognized toxin. CO inhibited recombinant Kv1.5 expressed in HEK293 cells in a concentration-dependent manner which involved multiple signalling pathways. CO inhibition was partially reversed by superoxide dismutase mimetics, and by suppression of mitochondrial reactive oxygen species. CO also elevated intracellular nitric oxide (NO) levels. Prevention of NO formation also partially reversed CO inhibition of Kv1.5, as did inhibition of soluble guanylyl cyclase. CO also elevated intracellular peroxynitrite levels, and a peroxynitrite scavenger markedly attenuated the ability of CO to inhibit Kv1.5. CO caused nitrosylation of Kv1.5, an effect which was also observed in C331A and C346A mutant forms of the channel, which had previously been suggested as nitrosylation sites within Kv1.5. Augmentation of Kv1.5 via exposure to hydrogen peroxide was fully reversed by CO. Native Kv1.5 recorded in HL-1 murine atrial cells was also inhibited by CO. Action potentials recorded in HL-1 cells were increased in amplitude and duration by CO, an effect mimicked and occluded by pharmacological inhibition of Kv1.5. Our data indicate that Kv1.5 is a target for modulation by CO via multiple mechanisms. This regulation has important implications for diverse cellular functions, including excitability, contractility and apoptosis

‘Wrongful’ Inheritance: Race, Disability and Sexuality in Cramblett v. Midwest Sperm Bank

In 2014 Jennifer Cramblett, a white lesbian, filed a Complaint forWrongful Birth alleging that the Midwest Sperm Bank mistakenly provided sperm from an African–American donor. In this article, we trace the complex and over-lapping lines of legal and social inheritance that have conditioned not only the possibility of such a lawsuit, but also the legal language and arguments within theComplaint itself. First, we trace the racial politics of homonormativity, which set the conditions of possibility for an out, white lesbian to bring this case forward. Second, we trace the inheritance of wrongful birth tort law, reviewing its prior race and disability-related uses, and its basis in feminist reproductive rights. Third, we trace how disability, race and sexuality interlock within the eugenic inheritance of both ‘wrongful birth’ and reproductive technologies. Finally, we follow traces of racial inheritance, namely, the loss of white property and proximity to whiteness