Reconciling views of project success : a multiple stakeholder model

This paper presents a new model encompassing all the important critical attributes to measure project success across different stakeholder groups. The study investigates the possibility that project failure is a result of the interpretations of the criteria and factors used for success by multiple stakeholder groups. Unique projects must have their outcome parameters monitored and controlled to minimize the chances of failure and the likely major financial and managerial ramifications for the organization. Early testing of the model supports its use to increase the shared, multiple stakeholder perception of project success leading to more informed decision making and motivation of employees

One-Dimensional Fermi liquids

I attempt to give a pedagogical overview of the progress which has occurred during the past decade in the description of one-dimensional correlated fermions. Fermi liquid theory based on a quasi-particle picture, breaks down in one dimension because of the Peierls divergence and because of charge-spin separation. It is replaced by a Luttinger liquid whose elementary excitations are collective charge and spin modes, based on the exactly solvable Luttinger model. I review this model and various solutions with emphasis on bosonization (and its equivalence to conformal field theory), and its physical properties. The notion of a Luttinger liquid implies that all gapless 1D systems share these properties at low energies. Chapters 1 and 2 of the article contain an introduction and a discussion of the breakdown of Fermi liquid theory. Chapter 3 describes in detail the solution of the Luttinger model both by bosonization and by Green's functions methods and summarizes the properties of the model, expressed thorugh correlation functions. The relation to conformal field theory is discussed. Chapter 4 of the article introduces the notion of a Luttinger liquid. It describes in much detail the various mappings applied to realistic models of 1D correlated fermions, onto the Luttinger model, as well as important corrections to the Luttinger model properties discussed in Ch.3. Chapter 5 describes situations where the Luttinger liquid is not a stable fixed point, and where spin or charge gaps open in at least one channel. Chapter 6 discusses multi-band and multichain problems, in particular the stability of a Luttinger liquid with respect to interchain hopping. Ch. 7 gives a brief summary of experimental efforts to uncover Luttinger liquid correlations in quasi-1D materials.Comment: uuencoded Latex files and postscript figures, one Readme-file approx 160 pages + 13 figures; to be published by Reports on Progress in Physic

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