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Modelling is key to adapting agriculture to climate change (CC), facilitating evaluation of the impacts and efficacy of adaptation measures, and the design of optimal strategies. Although there are many challenges to modelling agricultural CC adaptation, it is unclear whether these are novel or, whether adaptation merely adds new motivations to old challenges. Here, qualitative analysis of modellers' views revealed three categories of challenge: Content, Use, and Capacity. Triangulation of findings with reviews of agricultural modelling and Climate Change Risk Assessment was then used to highlight challenges specific to modelling adaptation. These were refined through literature review, focussing attention on how the progressive nature of CC affects the role and impact of modelling. Specific challenges identified were: Scope of adaptations modelled, Information on future adaptation, Collaboration to tackle novel challenges, Optimisation under progressive change with thresholds, and Responsibility given the sensitivity of future outcomes to initial choices under progressive change., (© 2019 The Authors.)

The hypothesis to be tested is that reduced cell-cell interactions between T cells and monocytes are one of the reasons for the observed depression of the "in vitro" activation of human lymphocytes in microgravity. Locomotion is essential for cell-cell contacts. Lymphocytes in suspension are highly motile in microgravity, whereas no data are available so far on the motility of adherent monocytes. It can be argued that an impaired locomotion of monocytes and cytoskeletal changes, both linked to cell contacts, could be responsible for their reduced interaction with T lymphocytes. This study is aimed at revealing how locomotion as well as cytoskeletal structures of adherent monocytes are modified under modeled microgravity conditions using the Random Positioning Machine (RPM, Dutch-Space) as earth based model of spaceflight.

Several experiments demonstrated the influence of microgravity on mitogenic activation of T cells at molecular level. To discriminate between effects of microgravity and cosmic radiations, in this work we studied the effects of high cosmic radiations on the genetic expression in human T cells boarded in a stratospheric balloon (BIRBA-1 mission, 22 hours of flight). The genetic expression was analyzed by the cDNA microarray hybridization technology, which allows the comparative and simultaneous estimate of hundreds of mRNAs Activated cells react to the ionizing stress by activating genes involved in cell cycle check-point, oxidative stress response, heat shock proteins production or by repressing genes involved in antigen recognition.

The aim was to compare the efficacy of ondansetron and a combination of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis over three consecutive courses of chemotherapy. Cancer patients scheduled to receive for the first time cisplatin (>50 mg/m(2)) in combination with other cytotoxic agents, were recruited in a multicentre, randomised, double-blind study and treated with ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. Twenty-four hours after the start of chemotherapy, patients were randomised to treatment either with oral ondansetron 8 mg bd plus placebo on days 2-5 (group A) or with oral ondansetron 8 mg bd plus oral dexamethasone 8 mg bd on days 2-3, and 4 mg bd on days 4 and 5 (group B). Two hundred and thirty-six cancer patients were recruited into the study. Complete protection from delayed vomiting/nausea in group A and group B was Obtained in 50/39% and in 63/42% of patients, respectively in the first course; in 55/34% and in 64/40% in the second and in 49/31% and 60/37% in the third. Logistic regression analysis reveals a statistically significant difference in incidence of emesis between the combination of ondansetron plus dexamethasone and ondansetron alone (P<0.05). The same model, however, shows no difference in incidence of nausea between the two treatment regimens. Ondansetron plus dexamethasone reduces the risk of delayed emesis following cisplatin chemotherapy as compared to ondansetron alone.

We monitored the expression of MHC class I antigens in a clonal isolate (M1) of B16-F10 murine melanoma cells, under various condition of growth in vitro. We found that, compared to exponentially growing cultures, cells from confluent M1 cultures expressed higher levels of H-2D(b) and H-2K(b) surface antigens. Expression of MHC class I antigens could be enhanced further by incubation of M1 cells in serum-free medium for 24-48 hours. Northern blot analyses indicated that the up-regulation of MHC class I antigen expression was associated with increased levels of H-2K(b) and H-2D(b) mRNAs, without a concomitant decrease in c-myc expression. Analyses of the cell cycle distribution of M1 cells stained for MHC class I antigens failed to show any differential segregation of H-2D(b)- or H-2K(b)-positive cells in any phase of the cell cycle. Enhanced MHC class I antigen expression appeared not to be due to the release into the medium of known cytokines like IFN-alpha, -beta, -gamma, TNF-alpha, IL-6 (IFN-beta(2)), and IL-1 by the M1 cells either at confluence, or after growth in serum-free medium. Taken together, our experimental results indicate that expression of MHC class I genes by M1 cells can be greatly enhanced by manipulating culture conditions; these observations are particularly important for the re-expression of the H-2K(b) gene, which was assumed to be phenotypically silent in B16 cells. These data also suggest that re-expression of H-2K(b) antigen in M1 cells at confluence may be related to cell-cell contact, consistent with the concept that H-2K(b) molecules can play a nonimmune role in cellular communication and growth control.

The colon cancer cell line HCT fails to express HLA class I antigens on the cell surface as a consequence of two independent mutations occurring in both copies of the beta2-microglobulin (beta2-mu) gene. Restoration of HLA class I antigen expression in HCT cells transfected with the wild-type human beta2-mu gene is accompanied by the expression of beta2-mu-free HLA class I heavy chains on the cell surface. HCT cells expressing a transfected H-2L(d) gene (HCT-L(d) transfectants) exhibited high levels of H-2L(d) heavy chains on the cell surface, following treatment with human interferon a (IFN-alpha). IFN-treated HCT-L(d) transfectants also expressed high levels of endogenous beta2-g-free HLA class I heavy chains on the cell surface. Incubation of HCT-L(d) transfectants at 26-degrees-C for 24 hours is associated with a striking increase in the surface expression of H-2L(d) heavy chains (comparable to that observed at 37-degrees-C in the presence of IFN), without a concomitant increase in the surface expression of beta2-mu-free HLA class I heavy chains, suggesting that IFN and low temperature act by different mechanisms. These results also indicate that human IFN and H-2L(d) heavy chain can act synergistically in inducing the surface expression of endogenous beta2-mu-free HLA class I heavy chains by HCT cells. The combination of 26-degrees-C incubation and IFN treatment results in the surface expression of beta2-mu-free HLA class I heavy chains in HCT-neo transfectants, suggesting that IFN plays a crucial role in allowing the surface expression of endogenous HLA class I heavy chains in beta2-mu-negative HCT cells.