Spillovers of Pharmaceutical Price Regulations: evidence from the AMNOG Reform in Germany

In years of growing pharmaceutical spending, the adoption of new health technologies faces several regulatory hurdles. Such policies are typically studied at the country level, even though there are explicit and implicit channels that link decisions made in different countries. This can be relevant in the EU, where external reference pricing is widely adopted. This work exploits the IMS pricing database of cancer drugs approved by the European Medicine Agency between 2007 and 2017 to assess the impact of a pharmaceutical pricing regulation change that occurred in Germany in 2011 (the AMNOG bill) on foreign pharmaceutical prices. We show that the impact on foreign prices depends on whether the foreign country adopts external reference pricing policies and whether it includes Germany in its basket of reference countries and, symmetrically, if it enters Germany’s reference set. In particular, our diff-in-diff approach shows that AMNOG led to a price reduction for products launched in countries that refer to Germany (indirect spillover effect), whereas products launched in countries referenced by Germany experienced a 5.48% price increase (strategic spillover effect)

A Bistable Model of Cell Polarity

Ultrasensitivity, as described by Goldbeter and Koshland, has been considered for a long time as a way to realize bistable switches in biological systems. It is not as well recognized that when ultrasensitivity and reinforcing feedback loops are present in a spatially distributed system such as the cell plasmamembrane, they may induce bistability and spatial separation of the system into distinct signaling phases. Here we suggest that bistability of ultrasensitive signaling pathways in a diffusive environment provides a basic mechanism to realize cell membrane polarity. Cell membrane polarization is a fundamental process implicated in several basic biological phenomena, such as differentiation, proliferation, migration and morphogenesis of unicellular and multicellular organisms. We describe a simple, solvable model of cell membrane polarization based on the coupling of membrane diffusion with bistable enzymatic dynamics. The model can reproduce a broad range of symmetry-breaking events, such as those observed in eukaryotic directional sensing, the apico-basal polarization of epithelium cells, the polarization of budding and mating yeast, and the formation of Ras nanoclusters in several cell types

Application of Traditional Cooking Methods in Chestnut Processing: Effects of Roasting and Boiling on Secondary Metabolites and Antioxidant Capacity in Castanea spp. Fruits

More information on the effects of traditional cooking methods (roasting or boiling) on the chestnut composition may be important if health-promoting aspects are considered. The main aims of this study were to investigate and describe the phenolic profile and antioxidant capacity of raw, boiled, and roasted chestnuts from several Castanea spp. genotypes, evaluating the influence of the application of different traditional cooking methods on the nut phytochemical composition by chromatographic and spectroscopic strategies. The amounts of phenolics were used as selected variables together with total polyphenol content and antioxidant capacity to perform a Principal Component Analysis (PCA). Catechins and tannins were the main molecules in the phenolic phytocomplex, reaching 30-40% of the total, followed by phenolic acids (5-20%) and flavonols (about 5%). Gallic and ellagic acids were the most important phenolic acids in raw and processed chestnuts (about 20-70 mg center dot 100 g(-1) dried weight-DW and 10-50 mg center dot 100 g(-1) DW, respectively). Both of the cooking processes significantly influenced the polyphenolic content and the relative antioxidant capacity. This research may support and confirm the potential use of chestnuts for human health, increasing the information on the phenolic pattern of differently processed Castanea spp. fruits from different genotypes to (i) assess the potential health-positive effects, (ii) help processing companies to select specific varieties to commercialise in the market, and (iii) increase the use of these fruits with the relative increase in income for the producers

Development of a preliminary extraction protocol for phenol compounds during table grape grafting formation

The development of rootstocks that are less sensitive to abiotic and biotic stresses can help mitigate the negative effects of climate change on crop productivity, soil health, and water use. Though, the phenomenon of graft incompatibility is a significant limitation to the spread of new rootstock genotypes. Numerous studies have focused on this issue, highlighting the role of certain phenolic molecules as predictive markers of incompatibility. Given the lack of specific research on table grape, , this study proposes a protocol for the extraction of polyphenols from its woody tissues, which is a fundamental prerequisite for further analysis on secondary metabolites involved in graft incompatibility. The proposed eco-friendly method coupled a traditional maceration using solvent with a green technique utilizing an ultrasound-assisted extractor. The following parameters were compared: (1) sample weight (0.1 g, 0.5 g, and 1 g), (2) time of ultrasound-assisted extraction (10 min, 20 min, and 30 min), and (3) solvent volume for maceration (10 mL, 15 mL, and 20 mL). Four phenol classes were considered based on previous works on Vitis spp.: cinnamic acids, flavonols, benzoic acids, and catechins. The characterization of polyphenolic biomarkers was carried out via HPLC. 1 g of plant material, 30 minutes of sonification, and 20 mL of organic solvent was the combination of factors that resulted in the most efficient fingerprint, both quantitatively (267.68 ± 3.91 mg/100 g fresh weight [FW]) and qualitatively, with the four classes analyzed significantly represented. This is the first work to come up with an extraction protocol for phenol compounds in table grape woody tissue based on both ecological and routine techniques

Single-cell states in the estrogen response of breast cancer cell lines

Estrogen responsive breast cancer cell lines have been extensively studied to characterize transcriptional patterns in hormone-responsive tumors. Nevertheless, due to current technological limitations, genome-wide studies have typically been limited to population averaged data. Here we obtain, for the first time, a characterization at the single-cell level of the states and expression signatures of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we employ a recently proposed model that allows for dissecting single-cell states from time-course microarray data. We show that within 32 hours following stimulation, MCF-7 cells traverse, most likely, six states, with a faster early response followed by a progressive deceleration. We also derive the genome-wide transcriptional profiles of such single-cell states and their functional characterization. Our results support a scenario where estrogen promotes cell cycle progression by controlling multiple, sequential regulatory steps, whose single-cell events are here identified. © 2014 Casale et al

IMPACT STUDY ON CYBER THREATS TO GNSS AND FMS SYSTEMS

Within this work, that was carried out following a call for tender by the European Aviation Safety Agency (EASA), the impact of cybersecurity threats especially on Global Navigation Satellite Systems (GNSS) and Flight Management Systems (FMS) was assessed. In order to do so, simulation studies were carried out. The German Aerospace Center (DLR) operates the research simulator AVES (Air Vehicle Simulator) which was used for the flight simulation exercises within this project. The AVES combines two facilities to simulate airplanes and helicopters to the highest technical level. The cockpit unit used was a complete replica of an Airbus A320. The corresponding simulation software (incl. flight dynamical models and system simulation) is entirely developed at DLR according to the official documentation providing full access and flexibility in the investigations. The motion platform provides a motion system with six degrees of freedom, whose motion cueing algorithms can be specifically tuned for a given task if needed. This unique infrastructure has been built during the last years with the aim of providing a highly-representative test platform for new cockpit functions and flight crew training research. To assess the impact of cyber-attacks on GNSS and FMS, different scenarios were developed and ranked by their likelihood of occurrence and their expected impact on safety and the continuation of the flight. Based on the identified threats, realistic scenarios according to airline operations were designed and implemented into the AVES research simulator. Synthetic error models reproducing the same effects on the aircraft systems as identified in the projects preceding GNSS and FMS threat assessment work were integrated into the AVES software architecture. In particular, the impact of GNSS jamming and spoofing attacks during satellite based approach procedures was investigated. In addition, attacks on the FMS through the open protocol of the Aircraft Communications Addressing and Reporting System (ACARS) were assessed. In this paper, we are going to present the results that were obtained during the simulations with airline pilots holding Air Transport Pilot Licenses (ATPL) with a special focus on the attacks on the FMS and its related systems. We are going to describe the simulation setup and the reaction of the pilots and we will give pilot training and cockpit systems design recommendations in order to mitigate risks that stem from the investigated threat scenarios

Visualization and analysis of cellular & Twitter data using qgis

The study is to understand individual presence and movement in Friuli Venezia Giulia region. It is important for tourism planning, hazard management, business marketing, implementing government lifetime policies and benefit. The aim of this study is achieved by advanced web 2.0 applications. We need real time and geo-located data to monitor the inflow of tourist and to come up with effective promoting and benefiting plans for tourism, the evacuation and mitigation strategies during hazards to protect social life and environment with less infrastructure damage, marketing plans for advertising or selling of products. Despite wide spread success in predicting specific aspects of human behavior by social media information, a little attention is given to twitter and cell phone data. Accessibility to detailed human movements with fine spatial and temporal granularity is challenging due to confidentiality and safety reasons. With rapid development of web2.0 applications people can post about events, share opinion and emotions online. Using twitter data, how short term travelers, such as tourists, can be recognized and how their travel pattern can be analyzed. Study of finding tourist dynamics such as arriving and outgoing of tourist, sum of trips, sum of days and night spent, number of unique visitors, country of residence, main destination, secondary destination, transits pass through, repeat visits are achieved using CDR (call detail records) and DDR (data detail records)