Interferon-ε is a tumour suppressor and restricts ovarian cancer.

High-grade serous ovarian cancers have low survival rates because of their late presentation with extensive peritoneal metastases and frequent chemoresistance1, and require new treatments guided by novel insights into pathogenesis. Here we describe the intrinsic tumour-suppressive activities of interferon-ε (IFNε). IFNε is constitutively expressed in epithelial cells of the fallopian tube, the cell of origin of high-grade serous ovarian cancers, and is then lost during development of these tumours. We characterize its anti-tumour activity in several preclinical models: ovarian cancer patient-derived xenografts, orthotopic and disseminated syngeneic models, and tumour cell lines with or without mutations in Trp53 and Brca genes. We use manipulation of the IFNε receptor IFNAR1 in different cell compartments, differential exposure status to IFNε and global measures of IFN signalling to show that the mechanism of the anti-tumour activity of IFNε involves direct action on tumour cells and, crucially, activation of anti-tumour immunity. IFNε activated anti-tumour T and natural killer cells and prevented the accumulation and activation of myeloid-derived suppressor cells and regulatory T cells. Thus, we demonstrate that IFNε is an intrinsic tumour suppressor in the female reproductive tract whose activities in models of established and advanced ovarian cancer, distinct from other type I IFNs, are compelling indications of potential new therapeutic approaches for ovarian cancer.

A dynamic model of nonviolent resistance strategy.

Why have some nonviolent revolutions succeeded even with modest participation numbers, while others have failed despite massive mobilization? We develop an agent-based model that predicts the outcomes of three well-known activism strategies. The first rapidly recruits a wide number of activists, which overwhelms the opponent's support network and encourages large-scale defections. In the second, activists who have already mobilized remain committed to success and inspire other civilians to protest even when they are unable to protest themselves. In the third strategy, campaigns focus their energy and influence directly on the regime's pillars of support. We find that this third strategy outperforms the others in generating defections, even when the size of the campaign is small. When activists have information about pillars' levels of loyalty to the regime, they can target persuasion on the pillars most likely to defect. Importantly, for small or medium-sized movements, the strategy of focusing on pillars-especially the least loyal pillars-is more likely to yield success than relying on rapid mobilization and numerical advantage alone.

Patient satisfaction with the Nigerian National Health Insurance Scheme two decades since establishment: A systematic review and recommendations for improvement.

BACKGROUND: To improve healthcare access and mitigate healthcare costs for its population, Nigeria established a National Health Insurance Scheme (NHIS) in 1999. The NHIS remains Nigeria's leading vehicle for achieving universal health coverage; nonetheless, questions remain regarding its quality and effectiveness. Studies on patient satisfaction have served as a useful strategy to further understand the patient experience and the efficacy of health systems. AIM: To synthesise current knowledge on patient satisfaction with the NHIS. METHODS: The authors performed a systematic review of primary literature from 1999 to 2020 reporting on NHIS patient satisfaction in eight databases (including PubMed, Embase, and Africa-wide Information). RESULTS: This search returned 764 unique records of which 21 met criteria for full data extraction. The 21 qualifying studies representing 11 of the 36 Nigerian states, were published from 2011 to 2020, and found moderate overall satisfaction with the NHIS (64%). Further, when disaggregated into specific domains, NHIS enrolees were most satisfied with provider attitudes (77%) and healthcare environments (70%), but less satisfied with laboratories (62%), billings (62%), pharmaceutical services (56%), wait times (55%), and referrals (51%). Importantly, time trends indicate satisfaction with the NHIS is increasing - although to differing degrees depending on the domain. CONCLUSION: The beneficiaries of the NHIS are moderately satisfied with the scheme. They consider it an improvement from being uninsured, but believe that the scheme can be considerably improved. The authors present two main recommendations: (1) shorter wait times may increase patient satisfaction and can be a central focus in improving the overall scheme, and (2) more research is needed across all 36 states to comprehensively understand patient satisfaction towards NHIS in anticipation of potential scheme expansion.

Patient satisfaction with the Nigerian National Health Insurance Scheme two decades since establishment: A systematic review and recommendations for improvement

Background: To improve healthcare access and mitigate healthcare costs for its population, Nigeria established a National Health Insurance Scheme (NHIS) in 1999. The NHIS remains Nigeria's leading vehicle for achieving universal health coverage; nonetheless, questions remain regarding its quality and effectiveness. Studies on patient satisfaction have served as a useful strategy to further understand the patient experience and the efficacy of health systems. Aim: To synthesise current knowledge on patient satisfaction with the NHIS. Methods: The authors performed a systematic review of primary literature from 1999 to 2020 reporting on NHIS patient satisfaction in eight databases (including PubMed, Embase, and Africa-wide Information). Results: This search returned 764 unique records of which 21 met criteria for full data extraction. The 21 qualifying studies representing 11 of the 36 Nigerian states, were published from 2011 to 2020, and found moderate overall satisfaction with the NHIS (64%). Further, when disaggregated into specific domains, NHIS enrolees were most satisfied with provider attitudes (77%) and healthcare environments (70%), but less satisfied with laboratories (62%), billings (62%), pharmaceutical services (56%), wait times (55%), and referrals (51%). Importantly, time trends indicate satisfaction with the NHIS is increasing ­ although to differing degrees depending on the domain. Conclusion: The beneficiaries of the NHIS are moderately satisfied with the scheme. They consider it an improvement from being uninsured, but believe that the scheme can be considerably improved. The authors present two main recommendations: (1) shorter wait times may increase patient satisfaction and can be a central focus in improving the overall scheme, and (2) more research is needed across all 36 states to comprehensively understand patient satisfaction towards NHIS in anticipation of potential scheme expansion

PROPERTIES AND FUNCTIONS OF THE NOVEL TYPE I INTERFERON EPSILON.

Interferon epsilon (IFNε) is a type I IFN with unusual patterns of expression and therefore, function. It is constitutively expressed by reproductive tract epithelium and regulated by hormones during estrus cycle, reproduction, and menopause and by exogenous hormones. The IFNe protein is encoded by a gene in the type I IFN locus, binds to IFNAR1 and 2 which are required for signaling via the JAK STAT pathway. Its affinity for binding receptors and transducing signals is less potent than IFNα or ß subtypes in vitro. Nevertheless, in vivo experiments indicate its efficacy in regulating mucosal immune responses and protecting from bacterial and viral infections. These studies demonstrate a different mechanism of action to type I IFNs. In this organ system with dynamic fluxes in cellularity, requirement to tolerate an implanted fetus, and be protected from disease, there is co-option of a special IFN from a family of effective immunoregulators, with unique controls and modified potency to make it a safe and effective constitutive reproductive tract cytokine.