B2B Channel Partner Programs: Disentangling Indebtedness from Gratitude

Many suppliers invest heavily in channel partner programs that incentivize selling and learning. The authors conduct a multi-wave field study to investigate the roles of indebtedness and gratitude in transforming these investments into returns. The results show that indebtedness has negative effects on commitment to the supplier, as well as the reseller's sales effort. Gratitude however attenuates the effects of indebtedness on sales effort and commitment, and thus offers a buffer against indebtedness' negative effects. Indebtedness and gratitude thus play key roles in channel partner programs. In addition, the results highlight the importance of perceived motives as they differentially predict these two states. Benevolent motives are found to increase gratitude, though ulterior motives do not detract from it. Ulterior motives do however increase indebtedness. Finally, the results also reveal how entitlement negatively impacts channel partner programs: It decreases the positive effect of perceived program value on partner gratitude while increasing the effect of ulterior motives on indebtedness. This study thus assesses the simultaneous yet contrasting role of gratitude and indebtedness, as well as the complexity associated with realizing the full benefits of channel partner programs. The findings have implications for suppliers, marketers, and further research

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved

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

A comparative case study of a DiE-inspired music and theatre project for linguistically and culturally diverse pupils in Hong Kong and London

This chapter reports a comparative case study – from practitioners’ perspectives – of the process of implementing a Cantonese-based music and theatre project for culturally and linguistically diverse pupils in Hong Kong and London. Both groups – the majority-language learners of South and Southeast Asian origins in Hong Kong, and heritage-language learners of Chinese descent in London – are linguistic minorities in these two world cities. They are learning Cantonese for different purposes (i.e., majority language versus heritage language) in the early years. This project primarily focuses on how this project manifested itself in relation to contextual factors situated in different language-learning settings. Findings on the potential of the DiE pedagogy as an overall humanistic approach adaptable across language-learning contexts will be discussed, with future avenues explored

A Review on All Terrain Vehicle Safety

All-terrain vehicles (ATVs) have become increasing popular in many countries around the world, both for occupational use, as well as recreational use. With an increase in popularity, and the supply of heavier and more powerful machines on the market, major traumas and deaths from ATV use are growing concerns for public health and injury prevention professionals. This review of the literature on ATVs will focus on the mechanism and patterns of ATV-related injuries, the challenges of injury prevention, and the effects of legislation and regulations regarding ATV usage. The increasing burden of injuries and the substantial economic cost from ATV-related traumas and deaths calls for intensification of injury prevention efforts. Modification of risk factors, institution of regulations and legislation, and enforcement of those rules are important steps for prevention of ATV-related harm