Cost drivers of locally advanced rectal cancer treatment-An analysis of a leading healthcare insurer.

To evaluate the economic burden of locally advanced rectal cancer (LARC) treatment from a society perspective through analysis of health insurance-derived data of commercially insured and Medicare Advantage (MA) patients. Retrospective cost analysis of patients undergoing rectal resection within a multimodal (neoadjuvant chemoradiation + adjuvant chemotherapy) treatment strategy between January 1, 2010 and October 31, 2018, using the claims OptumLabs Data Warehouse database. In total, 1738 (935 commercial and 803 MA) patients were included. Overall treatment costs totaled $230,881,746 (on average$183 653 ± 82 384 per commercially insured and $73 681 ± 32 917 per MA patient). Cost distribution according to category (commercially insured patients) was: 29.92% related to outpatient care (follow-up visits/diagnostics), radiotherapy: 21.83%, index resection: 20.62%, chemotherapy: 17.44%, surgical inpatient: 6.32%, medical inpatient: 3.28%, emergency room: 0.58%. Relative cost distribution of the index resection itself differed marginally between the three approaches and was 21.49% for open, 19.30% for laparoscopic, and 20.93% for robotic surgery. Relative cost distributions of neoadjuvant, adjuvant, and outpatient treatments remained unchanged, independently of the surgical approach. This representation was similar in MA patients. Index-surgery related costs were outweighed by costs related to oncological and outpatient workup/follow-up treatments independently of both surgical approach and insurance type

Demand for the quality conservation of Venice, Italy, according to different nationalities.

This paper focuses on visitor demand for the quality conservation of Venice according to different nationalities. The vast majority of visitors to Venice are foreigners (both tourists and day-visitors) who come from all over the world. In this research they are mainly categorized as non-Italian Europeans or non-Europeans. A specific theoretical model, in which quality conservation is provided publicly and also privately through donations, is presented for nationals and for foreigners. The data are obtained from a contingent valuation survey carried out in Venice, the aim of which was to estimate visitors' willingness to donate (WTD) to the Venice flood defence programme. Demand functions are estimated by applying a twostage regression model. The authors show that the majority of visitors are willing to donate. On average, Italians and non-Europeans would donate more than non-Italian Europeans. As expected, these visitor categories have different mean WTD and different behavioural functions which are affected by attitudinal and economic variables. Bequest value is the main donation motive. Those who identify this as a donation motive, on average, state the highest WTD and the highest degree of certainty to donate. This result seems to confirm empirically the validity of the sustainable development principle applied to the management of Venice as a cultural tourist site

ICZM and WTP of stakeholders for beach conservation: Policymaking suggestions from an Italian case study

In accordance with integrated coastal zone management (ICZM), private stakeholders could be asked to pay for the benefits from beach conservation projects. Since a private contribution is measured by the amount of other goods a person is willing to give up for beach quality, it can be solicited in monetary terms or, when possible, in other forms, such as specific works. In this paper, by analysing the results of two surveys in Italy concerning stakeholders' perceptions of ICZM and their willingness to pay for these benefits, suggestions for beach management are provided to policymakers. One survey focuses on beach visitors who are asked to pay in monetary terms, while the other focuses on sunbathing establishment managers, who are asked to pay not only in monetary terms but also through beach works. The results show that the majority of these stakeholders are fully or partially aware of what ICZM is, and are unwilling to pay. However, regression analysis of those willing to pay suggests that promoting an information and education campaign about ICZM may be important if stakeholders' probability of paying is to be increased

A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+T cell responses

Enterotoxigenic Escherichia coli (ETEC) are a common cause of diarrheal illness in young children and travelers. There is yet no licensed broadly protective vaccine against ETEC. One promising vaccine development strategy is to target strains expressing the heat-stable toxin (ST), particularly the human ST (STh), since infections with these strains are among the leading causes of diarrhea in children in low-and-middle income countries. A human challenge model based on an STh-only ETEC strain will be useful to evaluate the protective efficacy of new ST-based vaccine candidates. To develop this model, we experimentally infected 21 healthy adult volunteers with the epidemiologically relevant STh-only ETEC strain TW10722, identified a suitable dose, assessed safety, and characterized clinical outcomes and immune responses caused by the infection. Doses of 1x10(10) colony-forming units (CFU) of TW10722 gave a suitable attack risk of 67% for moderate or severe diarrhea and an overall diarrhea attack risk of 78%. Non-diarrheal symptoms were mostly mild or moderate, and there were no serious adverse events. During the first month after ingesting the challenge strain, we measured significant increases in both activated CD4+ T cells and levels of serum IgG and IgA antibodies targeting coli surface antigen 5 (CS5) and 6 (CS6), as well as the E. coli mucinase YghJ. The CS5-specific CD4+ T cell and antibody responses were still significantly elevated one year after experimental infection. In conclusion, we have developed a safe STh-only ETEC-based human challenge model which can be efficiently used in Phase 2B trials to evaluate the protective efficacy of new ST-based vaccine candidates

Performance benchmarks for a next generation numerical dynamo model

Numerical simulations of the geodynamo have successfully represented many observable characteristics of the geomagnetic field, yielding insight into the fundamental processes that generate magnetic fields in the Earth's core. Because of limited spatial resolution, however, the diffusivities in numerical dynamo models are much larger than those in the Earth's core, and consequently, questions remain about how realistic these models are. The typical strategy used to address this issue has been to continue to increase the resolution of these quasi-laminar models with increasing computational resources, thus pushing them toward more realistic parameter regimes. We assess which methods are most promising for the next generation of supercomputers, which will offer access to O(106) processor cores for large problems. Here we report performance and accuracy benchmarks from 15 dynamo codes that employ a range of numerical and parallelization methods. Computational performance is assessed on the basis of weak and strong scaling behavior up to 16,384 processor cores. Extrapolations of our weak-scaling results indicate that dynamo codes that employ two-dimensional or three-dimensional domain decompositions can perform efficiently on up to ∼106 processor cores, paving the way for more realistic simulations in the next model generation

Crowd computing as a cooperation problem: an evolutionary approach

Cooperation is one of the socio-economic issues that has received more attention from the physics community. The problem has been mostly considered by studying games such as the Prisoner's Dilemma or the Public Goods Game. Here, we take a step forward by studying cooperation in the context of crowd computing. We introduce a model loosely based on Principal-agent theory in which people (workers) contribute to the solution of a distributed problem by computing answers and reporting to the problem proposer (master). To go beyond classical approaches involving the concept of Nash equilibrium, we work on an evolutionary framework in which both the master and the workers update their behavior through reinforcement learning. Using a Markov chain approach, we show theoretically that under certain----not very restrictive-conditions, the master can ensure the reliability of the answer resulting of the process. Then, we study the model by numerical simulations, finding that convergence, meaning that the system reaches a point in which it always produces reliable answers, may in general be much faster than the upper bounds given by the theoretical calculation. We also discuss the effects of the master's level of tolerance to defectors, about which the theory does not provide information. The discussion shows that the system works even with very large tolerances. We conclude with a discussion of our results and possible directions to carry this research further.This work is supported by the Cyprus Research Promotion Foundation grant TE/HPO/0609(BE)/05, the National Science Foundation (CCF-0937829, CCF-1114930), Comunidad de Madrid grant S2009TIC-1692 and MODELICO-CM, Spanish MOSAICO, PRODIEVO and RESINEE grants and MICINN grant TEC2011-29688-C02-01, and National Natural Science Foundation of China grant 61020106002.Publicad

Age-dependent effects of protein restriction on dopamine release

FUNDING AND DISCLOSURE This work was supported by the Biotechnology and Biological Sciences Research Council [grant # BB/M007391/1 to J.E.M.], the European Commission [grant # GA 631404 to J.E.M.], The Leverhulme Trust [grant # RPG-2017-417 to J.E.M.] and the Tromsø Research Foundation [grant # 19-SG-JMcC to J. E. M.). The authors declare no conflict of interest. ACKNOWLEDGEMENTS The authors would like to acknowledge the help and support from the staff of the Division of Biomedical Services, Preclinical Research Facility, University of Leicester, for technical support and the care of experimental animals.Peer reviewedPublisher PD