Increasingly, donors that subsidize socially-desirable products in the developing world are shifting from distributing through non-commercial to commercial channels, ceding control of the product price to for-profit intermediaries. This study advises a donor as to how the donor's loss of price control and the level of consumer awareness—defined as the fraction of the consumer population that is informed of the product's benefits—influence the donor's optimal subsidy and utility: First, in shifting to the commercial channel, the donor should increase (decrease) the subsidy when consumer awareness is low (high). Second, with the commercial channel, the donor should be prepared to increase the subsidy as awareness increases, which is contrary to her actions with a non-commercial channel. Third, contrary to the lesson obtained with non-commercial distribution, with commercial distribution the donor can be hurt by increased awareness. This occurs when awareness is moderate. The implication is that a donor that operates in such a setting should be wary in encouraging entities (e.g., governments, non-governmental organizations) to institute campaigns that increase the awareness of the product's benefits. The intermediary's decision of whether to target either only informed consumers or the broad market drives our results.
In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 186, S. 109753
This is the final version. Available on open access from Frontiers Media via the DOI in this record ; Data Availability Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. ; Ocean submesoscale dynamics are thought to play a key role in both the climate system and ocean productivity, however, subsurface observations at these scales remain rare. Seismic oceanography, an established acoustic imaging method, provides a unique tool for capturing oceanic structure throughout the water column with spatial resolutions of tens of meters. A drawback to the seismic method is that temperature and salinity are not measured directly, limiting the quantitative interpretation of imaged features. The Markov Chain Monte Carlo (MCMC) inversion approach has been used to invert for temperature and salinity from seismic data, with spatially quantified uncertainties. However, the requisite prior model used in previous studies relied upon highly continuous acoustic reflection horizons rarely present in real oceanic environments due to instabilities and turbulence. Here we adapt the MCMC inversion approach with an iteratively updated prior model based on hydrographic data, sidestepping the necessity of continuous reflection horizons. Furthermore, uncertainties introduced by the starting model thermohaline fields as well as those from the MCMC inversion itself are accounted for. The impact on uncertainties of varying the resolution of hydrographic data used to produce the inversion starting model is also investigated. The inversion is applied to a mid-depth Mediterranean water eddy (or meddy) captured with seismic imaging in the Gulf of Cadiz in 2007. The meddy boundary exhibits regions of disrupted seismic reflectivity and rapid horizontal changes of temperature and salinity. Inverted temperature and salinity values typically have uncertainties of 0.16°C and 0.055 psu, respectively, and agree well with direct measurements. Uncertainties of inverted results are found to be highly dependent on the resolution of the hydrographic data used to produce the prior model, particularly in regions where background temperature and salinity vary rapidly, such as at the edge of the meddy. This further advancement of inversion techniques to extract temperature and salinity from seismic data will help expand the use of ocean acoustics for understanding the mesoscale to finescale structure of the interior ocean. ; China Scholarship Council ; University of Exeter ; European Union ; Youth Innovation Promotion Association, CAS ; Rising Star Foundation, South China Sea Institute of Oceanology
In: Fox , BA , Schendel , D J , Butterfield , L H , Aamdal , S , Allison , J P , Ascierto , P A , Atkins , M B , Bartunkova , J , Bergmann , L , Berinstein , N , Bonorino , C C , Borden , E , Bramson , J L , Britten , C M , Cao , X , Carson , W E , Chang , A E , Characiejus , D , Choudhury , A R , Coukos , G , de Gruijl , T D , Dillman , R O , Dolstra , H , Dranoff , G , Durrant , L G , Finke , J H , Galon , J , Gollob , J A , Gouttefangeas , C , Grizzi , F , Guida , M , Hakansson , L , Hege , K , Herberman , R B , Hodi , F S , Hoos , A , Huber , C , Hwu , P , Imai , K , Jaffee , E M , Janetzki , S , June , C H , Kalinski , P , Kaufmann , H L , Kawakami , K , Kawakami , Y , Keilholtz , U , Khleif , S N , Kiessling , R , Kotlan , B , Kroemer , G , Lapointe , R , Levitsky , H I , Lotze , M T , Di Maio , M , Marschner , J P , Mastrangelo , M J , Masucci , G , Melero , I , Nelief , C , Murphy , W J , Nelson , B , Nicolini , A , Nishimura , M I , Odunsi , K , Ohashi , P S , O'Donnell-Tormey , J , Old , L J , Ottensmeier , C , Papamichail , M , Parmiani , G , Pawelec , G , Proietti , E , Qin , S , Rees , R , Ribas , A , Ridolfi , R , Ritter , G , Rivoltini , L , Romero , P J , Salem , M L , Scheper , R J , Seliger , B , Sharma , P , Shiku , H , Singh-Jasuja , H , Song , W , Straten , P T , Tahara , H , Tian , Z , van der Burg , S H , von Hoegen , P , Wang , E , Welters , M J , Winter , H , Withington , T , Wolchok , J D , Xiao , W , Zitvogel , L , Zwierzina , H , Marincola , F M , Gajewski , T F , Wigginton , J M & Disis , M L A 2011 , ' Defining the Critical Hurdles in Cancer Immunotherapy ' , Journal of Translational Medicine , vol. 9 , no. 1 , 214 . https://doi.org/10.1186/1479-5876-9-214
ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer.
Background: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. Methods: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. Results: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. Conclusion: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.