Accommodating Complex Substitution Patterns in a Random Utility Model of Recreational Fishing

We employed a cross-nested logit (CNL) model that permits a rich pattern of substitution among alternatives within a closed form choice model. The specification we employed is ideal for applications with many choice alternatives, such as the 431 fishing sites in this application. The CNL model provided a significant improvement over multinomial and nested logit model specifications at explaining observed recreational fishing site choices by residents of northern Ontario, Canada. Results from two scenarios illustrated the implications of using the CNL model on spatial substitution patterns and welfare measures associated with attribute change scenarios. The CNL model forecasts demonstrated that the relative change in fishing site use was lower at the most affected sites and higher at sites near the affected sites than was predicted by the multinomial logit model. No consistent pattern was found in mean or variance of welfare estimates associated with hypothetical attribute changes.Compensating variation, cross-nested logit, fishing site choice, random utility model, spatial substitution, Demand and Price Analysis, Institutional and Behavioral Economics, Q26,

Representation of western disturbances in CMIP5 models

Western disturbances (WDs) are synoptic extratropical disturbances embedded in the subtropical westerly jet stream. They are an integral part of the South Asian winter climate, both for the agriculture-supporting precipitation they bring to the region and for the associated isolated extreme events that can induce devastating flash flooding. Here, WD behaviour and impacts are characterised in 23 CMIP5 historical simulations and compared with reanalysis and observations. It is found that WD frequency has a strong relationship with model resolution: higher resolution models produce significantly more WDs, and a disproportionately high fraction of extreme events. Exploring metrics of jet strength and shape, we find that the most probable cause of this relationship is that the jet is wider in models with coarser resolution, and therefore the northern edge in which WDs are spun up sits too far north of India. The frequency of WDs in both winter and summer is found to be overestimated by most models, and thus the winter frequency of WDs estimated from the multi-model mean (30 winter−1) is above the reanalysis mean (26 winter−1). In this case, the error cannot be adequately explained by local jet position and strength. Instead, we show that it is linked with a positive bias in upstream mid-tropospheric baroclinicity. Despite a positive winter precipitation bias in CMIP5 models over most of India and Pakistan and a dry bias in the western Himalaya, the fraction of winter precipitation for which WDs are responsible is accurately represented. Using partial correlation, it is shown that the overestimation in WD frequency is the largest contributor to this bias, with a secondary, spatially heterogeneous contribution coming from the overestimation of WD intensity

Extreme daily rainfall in Pakistan and north India: scale-interactions, mechanisms, and precursors

While much of India is used to heavy precipitation and frequent low-pressure systems during the summer monsoon, towards the northwest and into Pakistan, such events are uncommon. Here, as much as a third of the annual rainfall is delivered sporadically during the winter monsoon by western disturbances. Such events of sparse but heavy precipitation in this region of typically mountainous valleys in the north and desert in the south can be catastrophic, as in the case of the Pakistan floods of July 2010. In this study, we identify extreme precipitation events (EPEs) in a box approximately covering this region (65◦ -78◦W, 25◦ -38◦N) using the APHRODITE gauge-based precipitation product. The role of the large-scale circulation in causing EPEs is investigated: it is found that, during winter, they often coexist with an upper-tropospheric Rossby wave train that has prominent anomalous southerlies over the region of interest. These winter EPEs are also found to be strongly colocated with incident western disturbances whereas those occurring during the summer are found to have a less direct relationship. Conversely, summer EPEs are found to have a strong relationship with tropical lows. A detailed Lagrangian method is used to explore possible sources of moisture for such events, and suggests that in winter, the moisture is mostly drawn from the Arabian Sea, whereas during the summer, it comes from along the African coast and the Indian monsoon trough region

Increased Gut Permeability and Microbiota Change Associate with Mesenteric Fat Inflammation and Metabolic Dysfunction in Diet-Induced Obese Mice

We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD). Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80+) was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P = 0.020) and serum levels of serum amyloid A3 (131%; P = 0.008) but reduced circulating adiponectin (64%; P = 0.011). In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P = 0.025) respectively and TNF-α mRNA level was 6.6-fold higher (P = 0.037). HFD reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P = 0.004) in fecal microbiota. Correlations were found between abundances of Lactobacillus (r = 0.52; P = 0.013) and Oscillibacter (r = −0.55; P = 0.007) with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P = 0.020), TNF-α (2.5-fold, P<0.001) and IL-6 mRNA levels (2.5-fold; P = 0.008) in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P = 0.006) but neither TNF-α nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity

The impacts of climate change on the winter water cycle of the western Himalaya

Some 180 million people depend on the Indus River as a key water resource, fed largely by precipitation falling over the western Himalaya. However, the projected response of western Himalayan precipitation to climate change is currently not well constrained: CMIP5 GCMs project a reduced frequency and vorticity of synoptic-scale systems impacting the area, but such systems would exist in a considerably moister atmosphere. In this study, a convection-permitting (4 km horizontal resolution) setup of the Weather Research and Forecasting (WRF) model is used to examine 40 cases of these synoptic-scale systems, known as western disturbances (WDs), as they interact with the western Himalaya. In addition to a present-day control run, three experiments are performed by perturbing the boundary and initial conditions to reflect pre-industrial, RCP4.5 and RCP8.5 background climates respectively. It is found that in spite of the weakening intensity of WDs, net precipitation associated with them in future climate scenarios increases significantly; conversely there is no net change in precipitation between the pre-industrial and control experiments despite a significant conversion of snowfall in the pre-industrial experiment to rainfall in the control experiment, consistent with the changes seen in historical observations. This shift from snowfall to rainfall has profound consequences on water resource management in the Indus Valley, where irrigation is dependent on spring meltwater. Flux decomposition shows that the increase in future precipitation follows directly from the projected moistening of the tropical atmosphere (which increases the moisture flux incident on the western Himalaya by 28%) overpowering the weakened dynamics (which decreases it by 20%). Changes to extreme rainfall events are also examined: it is found that such events may increase significantly in frequency in both future scenarios examined. Two-hour maxima rainfall events that currently occur in 1-in-8 WDs are projected to increase tenfold in frequency in the RCP8.5 scenario; more prolonged (one-week maxima) events are projected to increase fiftyfold

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival