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BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

This article examines the tortuous path from economic regulation, to deregulation and liberalization, to consolidation and collusion. It examines several elements of antitrust and competition law and policy, including mergers and acquisitions, coordination of pricing and service between competitors, and the failure of governmental institutions to advance a coherent transportation policy.

This article examines the tortuous path from economic regulation, to deregulation and liberalization, to consolidation and collusion. It examines several elements of antitrust and competition law and policy, including mergers and acquisitions, coordination of pricing and service between competitors, and the failure of governmental institutions to advance a coherent transportation policy.

This article examines several of the major issues Public International Air Law likely will confront during this century, including revisions of the Chicago Convention, aerospace transport, unmanned aerial systems, aviation security, competition, cabotage and foreign ownership, safety and environmental issues.

In recent years, the European Union (EU) has promulgated several ‘consumer protection’ regulations that address a variety of airline passenger issues, including flight delay, cancellation, and denied boarding. The new rules require airlines to grant financial compensation to passengers in the event of denied boarding or flight delay or cancellation, assist them in revising their travel plans by giving them the choice between a rescheduling of the ticket or a refund, and pay for their board and lodging. However, both the Warsaw and the Montreal Conventions for the Unification of Certain Rules for International Carriage by Air directly address the issue of air carrier compensation to passengers for damages suffered as a consequence of ‘delay’, and explicitly provide that the remedies specified therein are exclusive. As all Member States of the EU have ratified those Conventions, it would seem that the promulgation of conflicting EU Regulations raises serious legal questions regarding the relation with the international conventions. The overall conclusion the authors draw from the examination of the EU Regulations and the case law they produced is that EU law conflicts with the international conventions and the exclusivity of their application. The position of the European Court of Justice (ECJ) in interpreting the EU Regulations does not facilitate a uniform application of different rules. In case after case, the Court has stated that the jurisprudence surrounding the Warsaw and the Montreal Conventions, broadly speaking, is irrelevant when interpreting the Regulations. It is incomprehensible that these Regulations, and their interpretation by the ECJ, would be so fundamentally inconsistent with the explicit provisions of the Conventions. If the Court had taken a more consensual approach, the EU rules might have complemented, rather than conflicted with, the Conventions.

Before filing suit, plaintiffs’ attorneys engage in a Conflicts of Laws analysis to find the jurisdiction with the most sympathetic law, and most likely to result in the largest possible judgment for their clients. Juries in the United States are perceived to be the most generous in awarding judgments; hence, aviation suits often are filed in U.S. courts, even when they involve injuries and death of foreign citizens on an aircraft flown by a foreign air carrier and crew that crashed into foreign soil. The concept of forum non conveniens remains among the most useful tools for defendants seeking to remove the case to a less generous jurisdiction.

The article provides a comprehensive outline and comparative analysis of national space statutes that have been adopted by various space-faring States around the world. The article identifies several common components of national space law, such as provisions dealing with licensing, registration of space objects and third party liability insurance. It concludes by noting that national space laws are an important means not only to regulate space activities to ensure the protection of a State’s citizens from damage or injury, but also to limit the burden of exposure to risks so as to foster the development of private space activities.

This article examines the jurisprudence surrounding federal preemption of state regulation of airlines.

The European Union has banned numerous airlines from flying to or through its airspace. The United States has evaluated and downgraded States for aviation safety concerns. The International Civil Aviation Organization has audited States for compliance with Standards and Recommended Practices. This article examines each of these efforts, and concludes that the EU process is unlawful.

Improved technology allows enhanced data opportunities. Yet, the more useful the data collected may be – whether financial, demographic or personal – the more intrusive is the impact on personal liberty and individual privacy. Thus, there is a trade-off in terms of the costs and benefits of the Smart Card. The smarter the card, the more useful it is, yet the more intrusive it becomes.

This paper examines the jurisdictional reach of the Montreal Convention of 1999 to aircraft manufacturers.

Objectives. We tested the hypothesis that nitric oxide (NO) cyclic guanosine 5′-monophosphate (GMP) signaling is deficient in pressure overload hypertrophy due to ascending aortic stenosis, and that long-term l-arginine treatment will increase cardiac cyclic GMP production and modify left ventricular (LV) pressure overload hypertrophy and beta-adrenergic contractile response.Background. Nitric oxide cyclic GMP signaling is postulated to depress vascular growth, but its effects on cardiac hypertrophic growth are controversial.Methods. Forty control rats and 40 rats with aortic stenosis left ventricular hypertrophy ([LVH] group) were randomized to receive either l-arginine (0.40 g/kg/day) or no drug for 6 weeks.Results. The dose of l-arginine did not alter systemic blood pressure. Animals with LVH had similar LV constitutive nitric oxide synthase (cNOS) mRNA and protein levels, and LV cyclic GMP levels as compared with age-matched controls. In rats with LVH l-arginine treatment led to a 35% increase in cNOS protein levels (p = 0.09 vs untreated animals with LVH) and a 1.7-fold increase in LV cyclic GMP levels (p < 0.05 vs untreated animals with LVH). However, l-arginine treatment did not suppress LVH in the animals with aortic stenosis. In contrast, in vivo LV systolic pressure was depressed in l-arginine treated versus untreated rats with LVH (163 ± 16 vs 198 ± 10 mm Hg, p < 0.05). In addition, the contractile response to isoproterenol was blunted in both isolated intact hearts and isolated myocytes from l-arginine treated rats with LVH compared with untreated rats with LVH. This effect was mediated by a blunted increase in peak systolic intracellular calcium in response to beta-adrenergic stimulation.Conclusions. Left ventricular hypertrophy due to chronic mechanical systolic pressure overload is not characterized by a deficiency of LV cNOS and cyclic GMP levels. In rats with aortic stenosis, l-arginine treatment increased cardiac levels of cyclic GMP, but it did not modify cardiac mass in rats with aortic stenosis. However, long-term stimulation of NO-cyclic GMP signaling depressed in vivo LV systolic function in LVH rats and markedly blunted the contractile response to beta-adrenergic stimulation.

Several entities have developed, or are involved in the process of developing, safety regulations or guidelines that are appropriate for civil space activities both at the national and international levels. This section provides a brief overview of such entities and of their standardization activities with a view to assessing their (in)adequacy regarding regulatory protection and promotion of space safety.

This paper examines the liability of airline employees for acts taken against unruly passengers under the Tokyo Convention of 1961.

On 15 October 2002, a Russian Soyuz launcher exploded some twenty seconds after lift-off from the Russian Plesetsk cosmodrome. The launcher’s payload was an unmanned Foton M-1 research satellite containing 44 experiments belonging to the European Space Agency. One of the four Soyuz boosters malfunctioned after launch and lost power. It fell away from the vehicle as it is designed to do when thrust no longer holds it in place and upon impact with the ground its tanks ruptured causing a large fire that resulted in significant damage to the pad. The launcher then automatically shut down the three other boosters about twenty seconds into the launch and the entire rocket fell back, struck the ground, and exploded in a huge fireball at a location about 1 km away from the launch pad. Apparently, the supply of hydrogen peroxide to the propellant turbo pumps was blocked by a metallic object. The explosion killed a Russian soldier watching the launch from the first floor of the integration building. Fortunately, all forty engineers and scientists from various European countries involved in the preparation of the spacecraft who were also watching the launch from a location closer to the explosion but on lower ground were unharmed in the accident.

In this Chapter, several other factors and developments are examined to further assess the rationale for ICAO’s involvement in space. Also included are the modalities for implementing the ICAO for Space proposal.

The United States has been a major participant in space exploration and use. Its policies have helped shape the development of international law on the subject. Its domestic laws also provide a framework for the use of space by the private sector.

Publisher Summary The chapter deals with Chicago Convention without any restrictions on the International Civil Aviation Organization (ICAO)'s authority to control civil aircraft simply due to the traverse of the aircraft as it reaches upper layer of the reaches of Earth's atmosphere. According to the principle, civil aircraft engaged in international flight are subject to ICAO jurisdiction. The chapter also denotes that interpreting the definition of “aircraft” in the Chicago Convention—an instrument of international public law—to include SATVs which might possess consequences with regard to the interpretation and application of other public and private international air law instruments. The Conventions seek to attain, inhibit investment, and retard the development of commercial space transportation when the conflicts and inconsistencies are embedded in the respective legal regimens of Air Law and Space Law threatening to unravel the uniformity of law. The laws governing commercial space transportation required to be integrated with the prevailing rules of safety, navigation, security, and liability applicable under Air Law are revealed here. The public's safety is the foremost important among those dealt in the chapter.

The landscape of aviation is inherently international. It is therefore not at all surprising that nations would attempt to establish universal and uniform laws governing air transport. Aviation therefore has been the subject of a number of international legal conferences, which has resulted in multilateral agreements in both Public and Private International Law governing such issues as air safety and navigation, security, sovereignty, transit and commercial traffic rights, and liability.

The Chicago Convention on International Civil Aviation of 1944 accomplished two purposes. First, it established certain principles of substantive public international law. Second, it established an international organization - ICAO - and vested it with jurisdiction to accomplish certain objectives, and prescribed the procedures to govern the exercise of its jurisdiction.

With the enactment of the Intermodal Surface Transportation Efficiency Act in 1991, metropolitan planning organizations (MPOs) became more important institutions for planning and funding regional transportation systems. This study attempts to assess the success of MPOs in four fast-growing areas- Dallas/Ft. Worth, Denver, Phoenix, and Seattle-in meeting regional transportation needs. The research identifies the criteria that distinguish more successful from less successful MPOs-effective leadership, staff competence and credibility, quality public involvement, development of a regional ethos, streamlined and efficient processes, cooperative relationships with the state DOT, land-use coordination, and accountability to members-and offers suggestions for improving transportation planning. Copyright 2002, Oxford University Press.

This article examines international and intermodal transport regulation under the Interstate Commerce Act.

This article examines the regulation of foreign transportation under the Interstate Commerce Act.

Many, if not most, nations of the world community routinely comply with the vast majority of their international legal obligations in the commercial arena despite the absence of formal mandatory judicial-decisional and police-enforcement mechanisms for compelling compliance. They may be motivated by reciprocity or enlightened self-interest in preserving order, stability and predictability in their economic affairs in our increasingly interdependent global trading system. Even in the absence of an explicit threat, the mere possibility of reciprocal noncompliance or retaliation often has the significant prophylactic effect of encouraging nations to continue their good faith compliance with obligations imposed by a treaty from which they derive significant commercial benefits.

This article provides a comparative analysis of State inducements for foreign direct investment.