Scope Of Regulation Research Articles

Opposition in International Law – Alternativity and Revisibility as Elements of a Legitimacy Concept for Public International Law

AbstractAs international law is widening in regulatory scope and intensity, it arguably suffers from a legitimacy deficit. This article conceives of this deficit as a deficit in possibilities to politicize, criticize, and contest international law-making proposals in the way a loyal opposition does in a domestic constitutional context: through the representation of relevant societal interests, the voicing of critique, and the safeguarding of alternative proposals for the future. The author of this article tries to bring together the current debate in political theory on the value of legitimate disagreement and dissent in political institutions and the ongoing discussion on the legitimacy of international law. Therefore, a concept of an institutionalized opposition for international law-making processes is developed, referencing authors such as Hannah Arendt and Claude Lefort. Next, the author analyses whether one can already find instances of an institutionalized opposition in international law – in parliamentary assemblies and in international agreements which are designed to present a legal–political counterweight to specific legal concepts and institutions.

Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

BackgroundBorna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. MethodsThe acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. ResultsWe identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). ConclusionsUpon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites.

EU Sanitary Regulation on Livestock Disposal: Implications for the Diet of Wolves.

Sanitary and environmental regulations may have indirect effects on the wildlife and ecosystem services beyond their regulatory scope. To illustrate such effects, this paper examines how EU sanitary measures, in conjunction with additional regulations and socio-economic changes, have caused wolf diet to shift in Galicia, northwestern Spain. Prior to the bovine spongiform encephalopathy (BSE) crisis in Europe in 2000, livestock carcasses used to be left on the field and were eaten by scavengers and carnivores. As a result of the BSE crisis, sanitary regulations regarding the disposal of livestock carcasses were introduced. These regulations affected the populations of avian scavengers. We hypothesize that wolf ecology has also been affected by the aforementioned regulations. We analysed wolf diet for the period 2003-2006 and compared the results with those of a previously published study (1974-1978). We found a shift in wolf feeding habits following the implementation of these EU regulations. A decrease in carrion consumption was registered, and wolves increased their feeding on the rising population of wild ungulates, especially on roe deer, and on wild pony. Future regulations should assess their potential indirect effects in the early stages of drafting to allow for the design of proper mitigation measures.

Governance in public procurement: the reform of Turkey’s public procurement system

Regulation and control of public procurement constitute a crucial field for the application of governance ideals and practices. This study explores the public procurement reform process in Turkey with reference to the implementation of governance as part of an ongoing neoliberal discourse and practice. Turkey’s public procurement system was reformed in 2002 in line with governance principles of transparency, anti-corruption, securing competition and by establishing an independent regulatory institution. A decade after this reform, our analysis shows that political will, economic forces in the procurement market and problems in the institutional-organizational setting are factors that play a role in the relapses from governance ideals and practices. Points for practitioners Reforms aimed at achieving good governance in public procurements are hard to sustain. The specific institutional traditions of local contexts, interventions of political authorities and powerful economic interests play an important role in the success of reforms. Persistent ad hoc modifications of public procurement laws erode the regulatory scope, change the composition and political autonomy of board membership, and undermine the principles of transparency, accountability and competitiveness. There is a need to actively ensure sustainability of governance principles through strong defense mechanisms which should be institutionalized within local social dynamics.

The global network of biofuel sustainability standards-setters

The role of network structure in shaping the regulatory scope and content of sustainability standards for biofuels is examined. A critical review of the literature on hybrid governance networks suggests the need to bring in network theory. Through a specific network analysis of the standards-setters, it is shown that not only does the institutional hybridity of the standards boards influence the regulatory scope of the standards, but the network centrality and specific topology in which standards-setters are embedded are equally important structural features of hybrid governance. These findings foreground the relevance of incorporating in the current attributional conception of hybridity a network element, taking seriously the role of network structure in shaping regulatory fields. Social Network Analysis as an analytical tool holds great potential for further research into the structural features of hybrid governance.

Arabidopsis protein arginine methyltransferase 3 is required for ribosome biogenesis by affecting precursor ribosomal RNA processing.

Ribosome biogenesis is a fundamental and tightly regulated cellular process, including synthesis, processing, and assembly of rRNAs with ribosomal proteins. Protein arginine methyltransferases (PRMTs) have been implicated in many important biological processes, such as ribosome biogenesis. Two alternative precursor rRNA (pre-rRNA) processing pathways coexist in yeast and mammals; however, how PRMT affects ribosome biogenesis remains largely unknown. Here we show that Arabidopsis PRMT3 (AtPRMT3) is required for ribosome biogenesis by affecting pre-rRNA processing. Disruption of AtPRMT3 results in pleiotropic developmental defects, imbalanced polyribosome profiles, and aberrant pre-rRNA processing. We further identify an alternative pre-rRNA processing pathway in Arabidopsis and demonstrate that AtPRMT3 is required for the balance of these two pathways to promote normal growth and development. Our work uncovers a previously unidentified function of PRMT in posttranscriptional regulation of rRNA, revealing an extra layer of complexity in the regulation of ribosome biogenesis.

Reframing the anti-mercenary norm: Private military and security companies and mercenarism

Since the nineteenth century, the anti-mercenary norm has prohibited violent market actors from participating in combat. Today, however, private military and security companies (PMSCs) are widely perceived as legitimate. How did they achieve that legitimacy? This article argues that PMSCs initially resembled mercenaries. Previously, mercenaries were defined as fighters participating in combat for pay, be it offensive or defensive. PMSC advocates aimed to alter the combat component of the anti-mercenary norm. By arguing that PMSCs’ use of force was not combat, but rather individual self-defence, they created an alternative interpretation that established the practice as appropriate. As critical actors like the US, the United Kingdom, and the United Nations adopted their interpretation, the regulatory scope of the norm changed. In short, PMSCs are perceived to be legitimate because they are no longer implicated in the anti-mercenary norm.

Hanging together or hanging separately: is competition law in the process of eclipsing financial regulation?

This article examines the potential for the application of competition law in the banking sector to eclipse financial regulation. Financial regulation has changed in response to the global financial crisis. Competition law acts to promote the interests of consumers, whereas finance regulation at best only protects the interests of consumers. Successful use of leniency provisions means that competition law is achieving successes in punishing financial institutions that have engaged in cartel conduct. This success may lead to regulatory scope creep and the application of abuse of market power provisions in the financial sector unless financial regulation can be seen to be for the benefit of consumers, rather than the regulated.

Expanding the RpoS/σS-network by RNA sequencing and identification of σS-controlled small RNAs in Salmonella.

The RpoS/σS sigma subunit of RNA polymerase (RNAP) controls a global adaptive response that allows many Gram-negative bacteria to survive starvation and various stresses. σS also contributes to biofilm formation and virulence of the food-borne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). In this study, we used directional RNA-sequencing and complementary assays to explore the σS-dependent transcriptome of S. Typhimurium during late stationary phase in rich medium. This study confirms the large regulatory scope of σS and provides insights into the physiological functions of σS in Salmonella. Extensive regulation by σS of genes involved in metabolism and membrane composition, and down-regulation of the respiratory chain functions, were important features of the σS effects on gene transcription that might confer fitness advantages to bacterial cells and/or populations under starving conditions. As an example, we show that arginine catabolism confers a competitive fitness advantage in stationary phase. This study also provides a firm basis for future studies to address molecular mechanisms of indirect regulation of gene expression by σS. Importantly, the σS-controlled downstream network includes small RNAs that might endow σS with post-transcriptional regulatory functions. Of these, four (RyhB-1/RyhB-2, SdsR, SraL) were known to be controlled by σS and deletion of the sdsR locus had a competitive fitness cost in stationary phase. The σS-dependent control of seven additional sRNAs was confirmed in Northern experiments. These findings will inspire future studies to investigate molecular mechanisms and the physiological impact of post-transcriptional regulation by σS.

Phosphoproteomic Analysis of Protein Phosphorylation Networks in Tetrahymena thermophila, a Model Single-celled Organism

Tetrahymena thermophila is a widely used unicellular eukaryotic model organism in biological research and contains more than 1000 protein kinases and phosphatases with specificity for Ser/Thr/Tyr residues. However, only a few dozen phosphorylation sites in T. thermophila are known, presenting a major obstacle to further understanding of the regulatory roles of reversible phosphorylation in this organism. In this study, we used high-accuracy mass-spectrometry-based proteomics to conduct global and site-specific phosphoproteome profiling of T. thermophila. In total, 1384 phosphopeptides and 2238 phosphorylation sites from 1008 T. thermophila proteins were identified through the combined use of peptide prefractionation, TiO2 enrichment, and two-dimensional LC-MS/MS analysis. The identified phosphoproteins are implicated in the regulation of various biological processes such as transport, gene expression, and mRNA metabolic process. Moreover, integrated analysis of the T. thermophila phosphoproteome and gene network revealed the potential biological functions of many previously unannotated proteins and predicted some putative kinase-substrate pairs. Our data provide the first global survey of phosphorylation in T. thermophila using a phosphoproteomic approach and suggest a wide-ranging regulatory scope of this modification. The provided dataset is a valuable resource for the future understanding of signaling pathways in this important model organism.

Characteristics of the FDI legal regime in the EU law

Once the Lisbon Treaty entered into force on 1 January 2009, the regulatory competences over Foreign Direct Investments (FDI) were transferred from the Member States to the European Union. The change was instituted as a result of a new EU Common Commercial Policy (CCP) framework, which was extended by including the legal treatment of foreign direct investment into the CCP regulatory scope. The effect of this development has a dual paradigm: first, the above change affects the existing legal regime of foreign direct investment in the Member States, which is primarily based on the rules of Bilateral Investment Treaties (BITs) concluded by those States; second, the new CCP format calls for a precise regulation of some open questions and issues pertaining to its implementation in the post-Lisbon FDI regulation process by means of secondary legislation of the Union. The second paradigm is reflected in the effort to address the outstanding issues of the concrete implementation of the new CCP framework in the context of division of competences between the EU and the Member States. This effort resulted in issuing the Draft Regulation establishing transitional arrangements for bilateral investment agreements between Member States and third countries. The directions for future development of the FDI regime in the light of the extended CCP framework are also contained in the case law generated by EU judicial bodies.

The effect of internal control and risk management regulation on earnings quality: Evidence from Germany

We investigate the impact of mandatory internal control and risk management (ICRM) reform on earnings-based attributes of accounting quality in Germany. Although prior studies examine changes in accounting quality under SOX Sections 302 and 404, there is scant evidence of the accounting quality effects of ICRM reform in foreign jurisdictions. Such evidence is warranted given the ongoing global policy debate of ICRM reform in the post-SOX era. We extend existing research by examining changes in earnings quality following the 1998 German legislation on control and transparency (KTG). The KTG regime provides a unique setting in which the regulatory scope extends beyond internal control over financial reporting (ICFR) to include broad business and enterprise risk control. Using both a differences and difference-in-differences research design, we find that German firms experience an increase in timely loss recognition and a decrease in earnings smoothing after KTG. We also find some evidence of a decrease in loss avoidance behavior. Additional analyses show that the sensitivity of capital investment efficiency to earnings quality increases in the German market after KTG, suggesting that earnings quality effects of mandatory ICRM reform has positive consequences for capital resource allocation. Together, our results are consistent with the achievement of one of the intended outcomes of ICRM regulation—increased accounting quality through effective ICRM systems.

Significance of Postoperative Changes in Hemodynamics and Biochemical Indices in Pediatric Recipients of Live-Donor Liver Transplants

ObjectiveThe aim of this study was to evaluate the postoperative changes in hemodynamics and biochemical indices in pediatric recipients of live-donor liver transplants (LDLT). MethodsHemodynamics and biochemical indices (coagulation function, electrolytes, kidney function, liver function, and blood analysis) were monitored on the day before and the 1st, 3rd, 5th, and 7th days after the procedure in 20 children who underwent LDLT from June 2006 to January 2009. ResultsCompared with preoperative measurements, systolic and diastolic blood pressure and mean arterial pressure increased and prothrombin time was prolonged significantly during the first 7 days after LDLT (P < .05). Fibrinogen, platelet count, total protein, globulin, and blood magnesium decreased significantly (P < .05). Liver enzymes (aspartate transaminase [AST], alanine transaminase [ALT]) and blood sodium increased significantly; serum potassium and calcium declined on the first postoperative day (P < .05). On the 7th day, AST returned to nearly normal (P < .05) and ALT returned to the preoperative levels. Blood urea nitrogen fluctuated within the normal range (P < .05). Total and direct bilirubin decreased on the 1st day but returned to near normal levels on the 7th day (P <.001). ConclusionsOur data demonstrated postoperative changes in hemodynamics, electrolytes, and biochemical indices in pediatric LDLT recipients. The changes in clotting factors and platelet count did not result in severe coagulation function disorder; kidney function was normal. Changes in liver enzymes and bilirubin compared with the preoperation indices were within the regulatory scope of liver and did not result in severe complications. These preliminary postoperative trends suggest that further prospective evaluation is needed.

Global Phosphoproteomic Analysis Reveals Diverse Functions of Serine/Threonine/Tyrosine Phosphorylation in the Model Cyanobacterium Synechococcus sp. Strain PCC 7002

Increasing evidence shows that protein phosphorylation on serine (Ser), threonine (Thr), and tyrosine (Tyr) residues is one of the major post-translational modifications in the bacteria, involved in regulating a myriad of physiological processes. Cyanobacteria are one of the largest groups of bacteria and are the only prokaryotes capable of oxygenic photosynthesis. Many cyanobacteria strains contain unusually high numbers of protein kinases and phosphatases with specificity on Ser, Thr, and Tyr residues. However, only a few dozen phosphorylation sites in cyanobacteria are known, presenting a major obstacle for further understanding the regulatory roles of reversible phosphorylation in this group of bacteria. In this study, we carried out a global and site-specific phosphoproteomic analysis on the model cyanobacterium Synechococcus sp. PCC 7002. In total, 280 phosphopeptides and 410 phosphorylation sites from 245 Synechococcus sp. PCC 7002 proteins were identified through the combined use of protein/peptide prefractionation, TiO2 enrichment, and LC-MS/MS analysis. The identified phosphoproteins were functionally categorized into an interaction map and found to be involved in various biological processes such as two-component signaling pathway and photosynthesis. Our data provide the first global survey of phosphorylation in cyanobacteria by using a phosphoproteomic approach and suggest a wide-ranging regulatory scope of this modification. The provided data set may help reveal the physiological functions underlying Ser/Thr/Tyr phosphorylation and facilitate the elucidation of the entire signaling networks in cyanobacteria.

The Effect of Internal Control and Risk Management Regulation on Earnings Quality: Evidence from Germany

We investigate the impact of mandatory internal control and risk management (ICRM) reform on earnings-based attributes of accounting quality in Germany. Although prior studies examine changes in accounting quality under SOX Sections 302 and 404, there is scant evidence of the accounting quality effects of ICRM reform in foreign jurisdictions. Such evidence is warranted given the ongoing global policy debate of ICRM reform in the post-SOX era. We extend existing research by examining changes in earnings quality following the 1998 German legislation on control and transparency (KTG). The KTG regime provides a unique setting in which the regulatory scope extends beyond internal control over financial reporting (ICFR) to include broad business and enterprise risk control. Using both a differences and difference-in-differences research design, we find that German firms experience an increase in timely loss recognition and a decrease in earnings smoothing after KTG. We also find some evidence of a decrease in loss avoidance behavior. Additional analyses show that the sensitivity of capital investment efficiency to earnings quality increases in the German market after KTG, suggesting that earnings quality effects of mandatory ICRM reform has positive consequences for capital resource allocation. Together, our results are consistent with the achievement of one of the intended outcomes of ICRM regulation—increased accounting quality through effective ICRM systems.

Antitrust and the Future of Nursing: Federal Competiton Policy and the Scope of Practice

In 2011, the Institute of Medicine (IOM) released a major report on the nursing profession and its present and potential roles in U.S. health care: The Future of Nursing: Leading Change, Advancing Health. According to the IOM, nurses’ regulatory scope of practice often proves to be narrower than the ideal, socially desirable, or medically prudent scope of practice; and the space between the regulatory standard and the ideal is large enough that it is a substantial health policy problem. To ameliorate the problem the IOM suggests, among other things, that regulatory restrictions on the scope of practice receive attention from the federal antitrust agencies. This paper considers what such antitrust therapy might entail, chiefly by explaining some of what antitrust law and policy have had to say about licensure and scope of practice already. We focus, in particular, on a species of soft antitrust intervention employed by one of the nation’s two competition authorities, the Federal Trade Commission (FTC). Recent years have seen the issuance of a series of competition policy analyses addressing the IOM’s concern about over-strict limits on nurses’ scope of practice. In these, the staffs of the FTC’s Office of Policy Planning, Bureau of Economics, and Bureau of Competition have observed that (1) many geographic areas (or markets) are subject to primary care workforce or manpower shortages, (2) market forces may be slow to clear those shortages for reasons that include, among others, regulatory impediments to competition; (3) such shortages may impinge upon both price and non-price competition between health care service providers; (4) in some places, such shortages may impede patient access to primary care services and may, in the limit, drive the supply of certain services to nil; and (5) certain licensing or scope of practice restrictions on APRNs appear under-rationalized (at best), where they purport to rest upon patient protection concerns that are unsupported either by demonstrated patient harms or empirically grounded assessments of substantial patient risks. Because regulatory restrictions on APRNs’ licensure and scope of practice may come at a substantial competitive cost, FTC staff have recommended that such limits not be more stringent than patient protection requires. In broad strokes, they have asked that state policy makers account for competitive costs when considering scope of practice restrictions, and they have suggested that certain costs should not be imposed on the public absent an evidence-based promise of countervailing consumer protection benefits.The paper synthesizes these various advocacy comments, expands upon their bases in competition law and economics, and describes future research pertinent to the access issues of concern to both the IOM and the FTC.

Private Regulation, Freedom of Expression and Journalism: Towards a European Approach?

The increasing role of electronic media in news and, more generally, in content production is changing the scope and boundaries of the journalism profession and the instruments deployed to regulate the activity. Historically, journalism has primarily been self-regulated. The limits of public legislation, mainly driven by the constitutional constraints posed by the freedom of expression, have created different models of national private regulatory regimes across Europe. Media regulation is a multilevel architecture and national legal systems still play a primary role in designing rules concerning news production. Self-regulation reflects national approaches and varies according to legal and social regulatory cultures. Within the private sphere, different forms of regulation have been implemented reflecting the changing balance between the profession, the industries and the new players which have emerged after the Web revolution. The development of new media poses the following important challenges to that regulatory framework: the criteria to be used to define journalism; the distinction and the boundaries between professional and non-professional journalism; the distinction between commercial and social/not for profit content production. This essay will examine these challenges looking at practice and litigation in European countries, identifying the different conflicting interests generating this litigation and the (private) regulatory responses. It will explore the differences between professional and industry regulation both within and across media: looking at the national and European or transnational regulatory scope of these regimes.

Proteome-wide Analysis of Lysine Acetylation Suggests its Broad Regulatory Scope in Saccharomyces cerevisiae

Post-translational modification of proteins by lysine acetylation plays important regulatory roles in living cells. The budding yeast Saccharomyces cerevisiae is a widely used unicellular eukaryotic model organism in biomedical research. S. cerevisiae contains several evolutionary conserved lysine acetyltransferases and deacetylases. However, only a few dozen acetylation sites in S. cerevisiae are known, presenting a major obstacle for further understanding the regulatory roles of acetylation in this organism. Here we use high resolution mass spectrometry to identify about 4000 lysine acetylation sites in S. cerevisiae. Acetylated proteins are implicated in the regulation of diverse cytoplasmic and nuclear processes including chromatin organization, mitochondrial metabolism, and protein synthesis. Bioinformatic analysis of yeast acetylation sites shows that acetylated lysines are significantly more conserved compared with nonacetylated lysines. A large fraction of the conserved acetylation sites are present on proteins involved in cellular metabolism, protein synthesis, and protein folding. Furthermore, quantification of the Rpd3-regulated acetylation sites identified several previously known, as well as new putative substrates of this deacetylase. Rpd3 deficiency increased acetylation of the SAGA (Spt-Ada-Gcn5-Acetyltransferase) complex subunit Sgf73 on K33. This acetylation site is located within a critical regulatory domain in Sgf73 that interacts with Ubp8 and is involved in the activation of the Ubp8-containing histone H2B deubiquitylase complex. Our data provides the first global survey of acetylation in budding yeast, and suggests a wide-ranging regulatory scope of this modification. The provided dataset may serve as an important resource for the functional analysis of lysine acetylation in eukaryotes.

The Legal Problems of Regulatory Scope of the Specially Related Persons under the Commercial Act

The Legal Problems of Regulatory Scope of the Specially Related Persons under the Commercial Act

Linking Insurance Coverage for Innovative Invasive Procedures With Participation in Clinical Research

A RECENT RANDOMIZED CONTROLLED TRIAL (RCT) evaluating a self-expanding intravascular stent (the Wingspan stent system), a device intended to open stenotic intracranial arteries via angioplasty and thereby prevent thrombotic stroke, reported surprising results. Based on case series data, this type of stent system was expected to be better than usual care; however, patients who underwent the stent procedure were more than twice as likely to experience stroke or death within 30 days compared with patients treated with aggressive medical therapy (14.7% vs 5.8%). These “negative” test results were disappointing. A promising new approach to a serious medical problem turned out to be worse than current best practice. However, within this failure was an important lesson worthy of notice and support from patients, clinicians, and policy makers. Through cooperation between the US Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS), this trial represented the successful use of a policy mechanism that can balance the goal of rapid access to innovative medical procedures with the need to obtain rigorous evidence on the risks and benefits of these procedures before they become widespread in clinical practice. The key was to make initial coverage conditional on participation in clinical research. Expensive invasive procedures often become widely adopted in clinical practice without high-quality evidence of effectiveness. In part, this is because the FDA does not regulate invasive therapeutic procedures unless those procedures involve use of medical devices. Even novel interventions using FDA-approved devices often receive unconditional coverage from public and private insurers without rigorous evidence of effectiveness produced by RCTs, the standard required for new pharmaceutical products. These differences in regulatory scope and evidentiary standards contribute to the proliferation of expensive invasive procedures for which the clinical effectiveness, in comparison with other less expensive and often more extensively studied treatment options, is unknown. Early, unrestricted insurance coverage grants physicians and patients rapid access to “innovative” procedures, but with significant disadvantages— limited understanding of the actual risks and benefits of new procedures for different kinds of patients; barriers to recruiting clinicians and patients to perform subsequent RCTs; and creation of financial incentives that will often fuel overuse of new procedures, increase health care costs, and undermine attempts to gain better evidence of comparative clinical effectiveness to guide treatment decisions for future patients. However, the policy tools to address this problem are available. When novel and promising invasive procedures lack adequate evidence of effectiveness, insurers can decide to offer coverage conditional for patients participating in RCTs designed to develop the needed evidence. Medicare has implemented this approach under the label of “coverage with evidence development in selected cases, including lung volume reduction surgery and home use of oxygen.” The example of the stent for cerebral arterial disease demonstrates how this approach can achieve the difficult but critical balance between rapid access and better evidence on the safety and effectiveness of new procedures. The investigational stent was approved by the FDA under a humanitarian device exemption (HDE) in 2005. The HDE allows device manufacturers to market a device without going through the regular FDA approval process if several criteria are satisfied, including estimated use in fewer than 4000 patients per year in the United States and the existence of preliminary evidence suggesting a favorable riskbenefit ratio. The self-expanding stent system met these criteria, based on a small case series suggesting a low stroke rate compared with historical controls. However, even with the HDE, there was an important barrier to using this procedure in practice or to studying it in randomized trials—Medicare had a standing national coverage determination denying coverage for all intracranial stenting procedures. Once aware of the HDE approval, however, Medicare changed its national coverage determination to cover the device and procedure, but only in the context of an RCT. Unconditional coverage would have inflated the number of patients treated while simultaneously creating major barriers to any attempt to recruit physicians and patients for participation in an RCT. At more than $20 000