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In Transforming the Nation, leading Canadian politicians and scholars reflect on the major policy debates of the period and offer new and surprising interpretations of Brian Mulroney. Mulroney had a tremendous impact on Canada, charting a new direction for the country through his decisions on a variety of public-policy issues - free trade with the United States, social-security reform, foreign policy, and Canada's North. The Mulroney government represented a dramatic break with Canada's past.

\"'A masterful examination of Newfoundland-Canada relations from 18691949'-Corey Slumkowski, author of Inventing Atlantic Canada: Regionalism and the Maritime Reaction to Newfoundland's Entry into Canadian Confederation. Coming on the 70th anniversary of Newfoundland joining Confederation, as well as the 150th anniversary of its first rejection of Canada, Where Once They Stood challenges popular notions that those who voted against Confederation in 1869 and for union with Canada in 1948 were uninformed, incompetent, ignorant, and gullible. Raymond B. Blake and Melvin Baker demonstrate that, in fact, voters fully understood the issues at stake in both cases, and in 1948 women too became instrumental in determining the final outcome, voting for Canada, believing it provided the best opportunities for their children. 'Blake and Baker make a persuasive case, turn[ing] the conspiracy on its head and demonstrat[ing] how Newfoundlanders knew what they were doing and expressly acted in their own self-interest when they chose Canada. . . . It is hard to imagine any two other authors who would know more about the subject.' -David MacKenzie, author of Inside the Atlantic Triangle.\"-- Provided by publisher.

By beginning with the 1949 Confederation rather than the activities leading up to it, and by thoroughly documenting areas of agreement, contention, and neglect, Blake writes a solid, contemporary history of Newfoundland's integration into Canada.

\"Holidays are a key to helping us understand the transformation of national, regional, community and ethnic identities. In Celebrating Canada, Matthew Hayday and Raymond Blake situate Canada in an international context as they examine the history and evolution of our national and provincial holidays and annual celebrations. The contributors to this volume examine such holidays as Dominion Day, Victoria Day, Quebec's Fête Nationale and Canadian Thanksgiving, among many others. They also examine how Canadians celebrate the national days of other countries (like the Fourth of July) and how Dominion Day was observed in the United Kingdom. Drawing heavily on primary source research, and theories of nationalism, identities and invented traditions, the essays in this collection deepen our understanding of how these holidays have influenced the evolution of Canadian identities.\"-- Provided by publisher.

History provides some interesting case studies of what happens when trade barriers come down. Among them is the story told in this book of Newfoundland's integration into Canada in the aftermath of the province's 1948 referendum. Raymond B. Blake takes a refreshing approach to this episode in Canadian history, avoiding the old shibboleths of conspiracy and local nationalism, and instead making a down-to-earth study of economic and political events. Canadians at Last explores the efforts of the many Canadians and Newfoundlanders who tried to make Confederation work. Blake argues that Canada wanted union, to remove any uncertainty in its dealings with Newfoundland over civil aviation, defence, and trade. Newfoundland opted for union largely because Canada's burgeoning social welfare system promised a more secure existence. Investigating the complex problems they encountered, Blake details changes in trade, fishing, and manufacturing and in the political process in Newfoundland. He also looks at the introduction and impact of social programs, and the terms of the US military presence there. Finally, he demonstrates that by 1957 Newfoundland's integration into Canada was essentially complete; it was being treated the same as the other provinces, subject to the terms of union. By beginning with the 1949 Confederation rather than the activities leading up to it, and by thoroughly documenting areas of agreement, contention, and neglect, Blake writes a solid, contemporary history of Newfoundland's integration into Canada. Virtually the only complete academic treatment of this subject, Canadians at Last offers much basic information that so far has not been made available.

\"Driven by its strong narrative, Conflict and Compromise presents Canadian history chronologically, allowing a better understanding of the interrelationships between events. Its main objective is to demonstrate that although Canadian history has been marked by cleavages and conflicts, there has been a continual process of negotiation and a need for compromise which has enabled Canada to develop into arguably one of the most successful and pluralistic countries in the world. The authors have drawn from all genres characterizing the present state of Canadian historiography, including social, military, cultural, political, and economic approaches. In doing so their aim is to challenge readers to engage with debates and interpretations about the past rather than simply to study for an exam.\"-- From publisher's website.

This dissertation examines how Newfoundland was made a province after it voted to join Canada in July 1948. It is concerned primarily with the role of the federal government in the immediate post-confederation period, and the way Ottawa dealt with the problems associated with Confederation. It aims to demonstrate that Newfoundland was rapidly integrated into Canada and that by 1957 it was being treated the same as the other provinces. This study focuses on a number of issues that were important to this process. The re-establishment of political parties in Newfoundland after the hiatus of the Commission of Government and their subsequent integration with Canadian ones is examined. The introduction of Canadian social programs is traced. The effects of union on Newfoundland's manufacturing sector and the implications of a reduction in the tariff structure are explored as is Canada's struggle to renegotiate the 1941 Leased Bases Agreement which gave wide-ranging jurisdiction to the Americans. Finally, the dissertation examines Ottawa's involvement in the Newfoundland fishery from 1949 to 1957. This study seeks to fulfill several aims. It argues that Canada wanted union to remove the uncertainty in its dealings with Newfoundland over civil aviation, defence, and trade. It shows that by 1949 the primary reason for joining the Confederation had changed somewhat. The Maritime partners to the original union had hoped to create an industrial centre on the Atlantic Coast. Newfoundlanders, on the other hand, opted for union largely because Canada's burgeoning social welfare system promised them a more secure existence than facing the future as an independent nation. Concomitantly, it argues that Newfoundland made enormous gains in social welfare as a result of union. On another level, it examines the restraints on Canadian policy-makers and argues that fear of offending the other provinces limited Ottawa in what it could do economically for Newfoundland, most notably, in the fisheries. It also demonstrates that when American and Canadian interests collided, as they did over the Leased Bases in Newfoundland, the Americans demonstrated little concern for Canadian interests. Finally, this dissertation demonstrates that by 1957 Newfoundland had been largely integrated into Canada.

Background Databases of suspected adverse drug reactions (ADRs) are a cornerstone of pharmacovigilance. With increasing numbers of reports, additional statistical approaches are needed to better use the data. Aim The present study was aimed at elucidating the European Medicines Agency’s (EMA) use of a novel ‘paediatric’ query to analyse the data in its ADR database ‘EudraVigilance’. Methods The proportional reporting ratio (PRR) is a measure of disproportionality for which the underlying principle is that a drug–event pair of interest is reported more often than expected relative to an independence model. The EMA’s paediatric query, based on PRRs, was applied to the data in EudraVigilance to investigate the extent to which the known association between enalapril and renal toxicity was reflected in reported ADRs comparing children with adults and with adjustment for the effect of multiplicity. Results The comparison of PRRs for children (14.91, 95 % confidence interval [CI] 13.05–17.04) versus adults (2.66, 95 % CI 2.52–2.82) confirmed a higher risk of renal ADRs with enalapril when used in children compared with all other medicines and compared with adults. Conclusions The EMA’s paediatric query can be used to highlight an imbalance for a drug–event pair among ADRs for a medicine when used in children and as compared with adults. Applying the query in practice can help the EMA to decide on whether stand-alone paediatric medicine development is warranted, and which, if any, further studies are necessary. Ongoing evaluation of the query is contributing to the development of new methods and guidance.

Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading to poor outcome. Interleukin-1 (IL-1) is an important regulator of post-stroke inflammation, and blocking its actions is beneficial in pre-clinical stroke models and safe in the clinical setting. However, the distinct roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1β, and the specific role of IL-1α in ischemic stroke remain largely unknown. Here we show that IL-1α and IL-1β have different spatio-temporal expression profiles in the brain after experimental stroke, with early microglial IL-1α expression (4 h) and delayed IL-1β expression in infiltrated neutrophils and a small microglial subset (24-72 h). We examined for the first time the specific role of microglial-derived IL-1α in experimental permanent and transient ischemic stroke through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial IL-1α deletion did not influence acute brain damage, cerebral blood flow, IL-1β expression, neutrophil infiltration, microglial nor endothelial activation after ischemic stroke. However, microglial IL-1α knock out (KO) mice showed reduced peri-infarct vessel density and reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies for the first time a critical role for microglial IL-1α on neurorepair and functional recovery after stroke, highlighting the importance of targeting specific IL-1 mechanisms in brain injury to develop more effective therapies.