Responsibility and Well-Being: Resource Integration Under Responsibilization in Expert Services

Responsibilization, or the shift of functions and risks from providers and producers to consumers, has become an increasingly common policy in service systems and marketplaces (e.g., financial, health, governmental). As responsibilization is often considered synonymous with consumer agency and well-being, the authors take a transformative service research perspective and draw on resource integration literature to investigate whether responsibilization is truly associated with well-being. The authors focus on expert services, for which responsibilization concerns are particularly salient, and question whether this expanding policy is in the public interest. In the process, they develop a conceptualization of resource integration under responsibilization that includes three levels of actors (consumer, provider, and service system), the identification of structural tensions to resource integration, and three categories of resource integration practices (access, appropriation, and management) necessary to negotiate responsibilization. The findings have important implications for health care providers, public and institutional policy makers, and other service systems, all of which must pay more active attention to the challenges consumers face in negotiating responsibilization and the resulting well-being outcomes.

Responsibility and Well-being: Resource Integration under Responsibilization in Expert Services

Responsibilization, or the shift in functions and risks from providers and producers to the consumer, has become an increasingly common policy in service systems and marketplaces (e.g., financial, health, governmental). Responsibilization is often presented as synonymous with consumer agency and well-being. We take a transformative service research perspective and utilize the resource integration framework to investigate whether responsibilization is truly associated with well-being. We focus on expert services, where responsibilization concerns are particularly salient, and question whether this expanding policy is in the public interest. In the process, we develop a conceptualization of resource integration under responsibilization that includes three levels of actors (consumer, provider and service system), the identification of structural tensions to resource integration and three categories of resource integration practices (access, appropriation and management) necessary to negotiate responsibilization. Our findings have important implications for health care providers, public policy makers, and other service systems, all of which must pay more active attention to the challenges consumers face in negotiating responsibilization and the resulting well-being outcomes.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents.

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G₁ -S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1Amutant OCCC. Mol Cancer Ther; 15(7); 1472-84. Ó2016 AACR.