Faciliating More Efficient Negotiations for Innovative Therapies: A Value-Based Negotiation Framework

OBJECTIVES: An increasing number of innovative therapies (e.g., gene- and cell-based treatments) have been developed in the past 20 years. Despite the significant clinical potential of these therapies, access delays may arise because of differing perspectives of manufacturers and payers regarding issues such as the value of the product, clinical and financial uncertainties, and sustainability.Managed entry agreements (MEAs) can enable access to treatments that would not be reimbursed by conventional methods because of such concerns. However, although MEA typologies exist, there is currently no structured process to come to agreements on MEAs, which can be difficult to decide upon and implement.To facilitate more structured MEA negotiations, we propose a conceptual "value-based negotiation framework" with corresponding application tools. METHODS: The framework was developed based on an iterative process of scientific literature review and expert input. RESULTS: The framework aims to (i) systematically identify and prioritize manufacturer and payer concerns about a new treatment, and (ii) select a mutually acceptable combination of MEA terms that can best address priority concerns, with the lowest possible implementation burden. CONCLUSIONS: The proposed framework will be tested in practice, and is a step toward supporting payers and manufacturers to engage in more structured, transparent negotiations to balance the needs of both sides, and enabling quicker, more transparent MEA negotiations and patient access to innovative products

FIRBACK IV: Towards the nature of the 170microns source population

We present a detailed study of the brighter ($> 4\sigma$ detections) sources in the 170$\mu$m FIRBACK northern N1 ISO survey, with the help of complementary data in the optical, radio, and mid-IR domain. For 82% of them, an optical galaxy counterpart is identified, either as the unique source of the IR emission, or as part of a multiple identification. With less than 15% of AGNs, these sources are essentially local, moderate starbursters with a dominating cold dust component. and represent a population of cold galaxies rather neglected up to now. Their colours do not match those of the far-IR Cosmic IR Background (CIB), to which they contribute less than 5%. The bulk of the sources contributing to the CIB is thus to be searched for in more distant galaxies, possibly counterparts of the fainter FIRBACK sources still under study. These bright, local, galaxies however play an important role in the evolution of IR galaxies: they dominate the number counts at high 170 $\mu$m fluxes, and represent half of the contribution at 250 mJy. Although not particularly massive (typically M*), they form more stars than a typical spiral galaxy and many are bulge dominated, that could represent the remnant of a former merger. The fainter part of this population may represent the missing link with the higher-z sources found in sub-mm observations.Comment: 40 pages, 10 figures, accepted for publication in Astronomy & Astrophysic

Measurement report: The Palau Atmospheric Observatory and its ozonesonde record – continuous monitoring of tropospheric composition and dynamics in the tropical western Pacific

The tropical western Pacific is recognized as an important region for stratosphere–troposphere exchange but lies in a data-sparse location that had a measurement gap in the global ozone sounding network. The Palau Atmospheric Observatory (PAO, approx. 7.3∘ N, 134.5∘ E) was established to study the atmospheric composition above the remote tropical western Pacific with a comprehensive instrumental setup. Since 2016, two laboratory containers in Palau host a Fourier transform infrared spectrometer; a lidar (micro-lidar until 2016, cloud and aerosol lidar from 2018); a Pandora 2S photometer; and laboratory space for weather balloon soundings with ozone, water vapor, aerosol, and radiosondes. In this analysis, we focus on the continuous, fortnightly ozone sounding program with electrochemical concentration cell (ECC) ozonesondes. The aim of this study is to introduce the PAO and its research potential, present the first observation of the typical seasonal cycle of tropospheric ozone in the tropical western Pacific based on a multiannual record of in situ observations, and investigate major drivers of variability and seasonal variation from January 2016 until December 2021​​​​​​​ related to the large-scale atmospheric circulation. We present the PAO ozone (O3) volume mixing ratios (VMR) and relative humidity (RH) time series complemented by other observations. The site is exposed to year-round high convective activity reflected in dominating low O3 VMR and high RH. In 2016, the impact of the strong El Niño is evident as a particularly dry, ozone-rich episode. The main modulator of annual tropospheric O3 variability is identified as the movement of the Intertropical Convergence Zone (ITCZ), with the lowest O3 VMR in the free troposphere during the ITCZ position north of Palau. An analysis of the relation of O3 and RH for the PAO and selected sites from the Southern Hemispheric Additional Ozonesondes (SHADOZ) network reveals three different regimes. Palau's O3 / RH distribution resembles the one in Fiji, Java and American Samoa but is unique in its seasonality and its comparably narrow Gaussian distribution around low O3 VMR and the evenly distributed RH. A previously found bimodal distribution of O3 VMR and RH could not be seen for the full Palau record but only during specific seasons and years. Due to its unique remote location, Palau is an ideal atmospheric background site to detect changes in air dynamics imprinted on the chemical composition of the tropospheric column. The efforts to establish, run and maintain the PAO have succeeded to fill an observational gap in the remote tropical western Pacific and give good prospects for ongoing operations. The ECC sonde record will be integrated into the SHADOZ database in the near future.</p

Inter-annual decrease in pulse rate and peak frequency of Southeast Pacific blue whale song types

The decrease in the frequency of two southeast Pacific blue whale song types was examined over decades, usingacoustic data from several different sources ranging between the Equator and Chilean Patagonia. The pulse rate ofthe song units as well as their peak frequency were measured using two different methods (summed auto-correlationand Fourier transform). The sources of error associated with each measurement were assessed. There was a lineardecline in both parameters for the more common song type (southeast Pacific song type n ◦ 2). An abbreviated analysisalso showed a frequency decline in the scarcer southeast Pacific song type n ◦ 1 between 1970 to 2014, revealing thatboth song types are declining at similar rates. We discussed the use of measuring both pulse rate and peak frequencyto examine the frequency decline. Finally, a comparison of the rates of frequency decline with other song typesreported in the literature is presented.La décroissance en fréquence des deux chants de baleine bleue de l'océan pacifique sud est est examiné sur plusieurs décennies en utilisant comme source des données acoustiques de l'Equateur à la Patagonie chilienne. La fréquence de pulsation et la fréquence pic des signaux sont mesurés en utilisant deux méthodes distinctes (auto-corrélation sommée et transformée de Fourier rapide). Les sources d'erreur associées à chaque mesure sont estimées. Il y a un déclin linéaire de ces deux fréquences pour le chant le plus commun de cette zone (chant du Pacifique Sud Est n°2, SEP2). Un analyse plus rapide montre aussi une baisse linéaire, entre 1970 et 2014, de la fréquence du chant SEP1, plus rarement enregistré dans cette zone. Ces deux baisses ont des amplitudes similaires. L'intérêt de mesurer la fréquence de pulsation et la fréquence pic de façon concomitante est estimé. Enfin, une comparaison globale des déclins en fréquence de tous les types de chants de baleines bleues est fournie

A 50-year record of NOx and SO2 sources in precipitation in the Northern Rocky Mountains, USA

Ice-core samples from Upper Fremont Glacier (UFG), Wyoming, were used as proxy records for the chemical composition of atmospheric deposition. Results of analysis of the ice-core samples for stable isotopes of nitrogen (δ15N, ) and sulfur (δ34S, ), as well as and deposition rates from the late-1940s thru the early-1990s, were used to enhance and extend existing National Atmospheric Deposition Program/National Trends Network (NADP/NTN) data in western Wyoming. The most enriched δ34S value in the UFG ice-core samples coincided with snow deposited during the 1980 eruption of Mt. St. Helens, Washington. The remaining δ34S values were similar to the isotopic composition of coal from southern Wyoming. The δ15N values in ice-core samples representing a similar period of snow deposition were negative, ranging from -5.9 to -3.2 ‰ and all fall within the δ15N values expected from vehicle emissions. Ice-core nitrate and sulfate deposition data reflect the sharply increasing U.S. emissions data from 1950 to the mid-1970s

Semantic Knowledge Influences Prewired Hedonic Responses to Odors

Background Odor hedonic perception relies on decoding the physicochemical properties of odorant molecules and can be influenced in humans by semantic knowledge. The effect of semantic knowledge on such prewired hedonic processing over the life span has remained unclear. Methodology/Principal Findings The present study measured hedonic response to odors in different age groups (children, teenagers, young adults, and seniors) and found that children and seniors, two age groups characterized by either low level of (children) or weak access to (seniors) odor semantic knowledge, processed odor hedonics more on the basis of their physicochemical properties. In contrast, in teenagers and young adults, who show better levels of semantic odor representation, the role of physicochemical properties was less marked. Conclusions/Significance These findings demonstrate for the first time that the biological determinants that make an odor pleasant or unpleasant are more powerful at either end of the life span