A Better Approach to Resolving Variable Selection Uncertainty in Meta Analysis for Benefits Transfer

Because original high-quality non-market valuation studies can be expensive, perhaps prohibitively so, benefits transfer (BT) approaches are often used for valuing, e.g., the outputs of multifunctional agriculture. Here we focus on the use of BT functions, a preferred method, and address an under-appreciated problem – variable selection uncertainty – and demonstrate a conceptually superior method of resolving it. We show that the standard method of value-function BT, using the full estimated model, may generate BT values that are too sensitive to insignificant variables, whereas models reduced by backward elimination of insignificant variables pay no attention to insignificant variables that may in fact have some influence on values. Rather than searching for the best single model for BT, Bayesian model averaging (BMA) is attentive to all of the variables that are a priori relevant, but uses posterior model probabilities to give systematically lower weight to less significant variables. We estimate a full value model for wetlands in the US, and then calculate BT values from the full model, a reduced model, and by BMA. Variable selection uncertainty is exemplified by regional variables for wetland location. Predicted values from the full model are quite sensitive to region; reduced models pay no attention to regional variables; and the BMA predictions are attentive to region but give it relatively low weight. However, the suite of insignificant RHS variables, taken together, have non-trivial influence on BT values. BMA predicted values, like values from reduced models, have much narrower confidence intervals than values calculated from the full model.Research Methods/ Statistical Methods,

Flexible combination of multiple diagnostic biomarkers to improve diagnostic accuracy

In medical research, it is common to collect information of multiple continuous biomarkers to improve the accuracy of diagnostic tests. Combining the measurements of these biomarkers into one single score is a popular practice to integrate the collected information, where the accuracy of the resultant diagnostic test is usually improved. To measure the accuracy of a diagnostic test, the Youden index has been widely used in literature. Various parametric and nonparametric methods have been proposed to linearly combine biomarkers so that the corresponding Youden index can be optimized. Yet there seems to be little justification of enforcing such a linear combination. This paper proposes a flexible approach that allows both linear and nonlinear combinations of biomarkers. The proposed approach formulates the problem in a large margin classification framework, where the combination function is embedded in a flexible reproducing kernel Hilbert space. Advantages of the proposed approach are demonstrated in a variety of simulated experiments as well as a real application to a liver disorder study

Meta Analysis for Benefits Transfer – Toward Value Estimates for Some Outputs of Multifunctional Agriculture

As a contribution to valuing the outputs of multifunctional agriculture, we report three new meta analyses estimating value functions for agricultural conservation program impacts on water quality, wetlands, and upland habitat and open space. As is often the case in valuation, where methods have yet to be standardized, the data sets are relatively small and noisy. With a clear objective of benefits transfer, we seek robust parameter estimates for key RHS variables, even at the cost of some loss of goodness of fit. We present our estimated full equations, and benefits transfer values calculated from equations estimated after backward elimination of insignificant variables, and offer a rationale for this approach to benefits transfer.meta analysis, benefits transfer, multifunctional agriculture, Resource /Energy Economics and Policy,

ENVIRONMENTAL LABELING OF ELECTRICITY: EFFECTS ON CONSUMER UNCERTAINTY ABOUT PRODUCT ATTRIBUTES AND LIKELIHOOD TO BUY DECISIONS

Using data collected by the U.S. Department of Energy we test how price and environmental marketing and labeling affects respondents' uncertainty about product attributes and about their purchase intentions.Consumer/Household Economics,

END-TO-END ENCRYPTION AND DECRYPTION WITHIN A HIERARCHICAL SD-WAN WITH AN IPV6 TRANSPORT

Techniques are presented herein that address a singular pain point in a hierarchical software-defined wide area network (SD-WAN) deployment comprising an Internet Protocol (IP) version 6 (IPv6) transport – end-to-end encryption and decryption. Aspects of the presented techniques leverage the IPv6 address schema to support a new concept that may be referred to herein as a micro-Transport Locator (TLOC) or uTLOC. Under the presented techniques, when an Overlay Management Protocol (OMP) virtual private network (VPN) route is published a next hop may be set to the combination of all of the uTLOCs along a path. Within such a context, each router (along the path) may program a customized action (such as, for example, the shifting of a destination, an insertion into a source, etc.) into a routing table for a uTLOC prefix and then forward a packet to a destination edge without the need for decryption and re-encryption operations in an intermediate border router

MAVS Is essential for primary CD4 + T cell immunity but not for recall T cell responses following an attenuated West Nile virus infection

ABSTRACT The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral signaling protein (MAVS), the adaptor protein for RIG-I-like receptor in regulating host immunity against the NS4B-P38G vaccine. We found that Mavs −/− mice were more susceptible to NS4B-P38G priming than WT mice. Mavs −/− mice had a transiently reduced production of antiviral cytokines and an impaired CD4 + T cell response in peripheral organs. However, antibody and CD8 + T cell responses were minimally affected. NS4B-P38G induced lower type I interferon (IFN), IFN-stimulating gene, and proinflammatory cytokine responses in Mavs −/− dendritic cells and subsequently compromised the antigen-presenting capacity for CD4 + T cells. Interestingly, Mavs −/− mice surviving NS4B-P38G priming were all protected from a lethal WT WNV challenge. NS4B-P38G-primed Mavs −/− mice exhibited equivalent levels of protective CD4 + T cell recall response, a modestly reduced WNV-specific IgM production, but more robust CD8 + T cell recall response. Taken together, our results suggest that MAVS is essential for boosting optimal primary CD4 + T cell responses upon NS4B-P38G vaccination and yet is dispensable for host protection and recall T cell responses during secondary WT WNV infection. IMPORTANCE The production of innate cytokines induced by the recognition of pathogen recognition receptors (PRRs) via their cognate ligands are critical for enhancing antigen-presenting cell functions and influencing T cell responses during microbial infection. The use of PRR agonists and the underlying molecular mechanisms have been the major focus in individual vaccine development. Here, we determined the role of mitochondrial antiviral-signaling protein (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the live attenuated West Nile virus (WNV) vaccine strain, the nonstructural (NS) 4B-P38G mutant. We found that MAVS is important for boosting optimal primary CD4 + T cell response during NS4B-P38G vaccination. However, MAVS is dispensable for memory T cell development and host protection during secondary wild-type WNV infection. Overall, these results may be utilized as a paradigm to aid in the rational development of other efficacious live attenuated flavivirus vaccines

Diet analysis of Atlantic salmon (Salmo salar) post-smolts after the ecological regime shift in the Northeast Atlantic

Transition from freshwater to saltwater presents multiple challenges for anadromous Atlantic salmon, and survival during this critical life-stage is thought to influence adult population abundance. Despite this, the role of feeding, which influences growth and therefore survival, is poorly studied. Here, we analyzed the diet of 580 post-smolts captured in four Norwegian fjords in 2018 and 2019. Post-smolt diet mainly consisted of fish larvae (Teleostei), krill (Euphasiidae), planktonic amphipods, and insects. However, diet varied among fjords and years. For example, post-smolts in Altafjord in northern Norway displayed a higher frequency of fish larvae in their diet compared to post-smolts from fjords in western Norway, although this effect was less clear in 2019 than in 2018. Post-smolts consuming fish larvae and/or krill displayed substantially higher feeding ratios, and these fish were on average 0.52 cm longer. This observation underpins results from earlier studies suggesting that consumption of fish larvae is important for marine growth and ultimately survival. The dietary observations reported here may therefore have implications for spatial and temporal patterns in Atlantic salmon marine survival rates in this region. Furthermore, we did not detect any clear differences in diet between post-smolts analyzed here in comparison with post-smolts collected in the same region approximately 20 years earlier. As there has been a well-documented ecological regime shift in the Northeast Atlantic between the present and earlier studies, we conclude that it has not had a large impact on post-smolt feeding conditions within Norwegian fjords. Diet Fish larvae Coastal ecosystem Migration EstuarypublishedVersio

Cancer Associated Fibroblasts Promote Tumor Growth and Metastasis by Modulating the Tumor Immune Microenvironment in a 4T1 Murine Breast Cancer Model

BACKGROUND:Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS:We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+) T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression. CONCLUSIONS/SIGNIFICANCE:Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer