bluuebunny/crossref_metadata_2025 huggingface dataset:
7. Challenging decisions: appeals, administrative and judicial review
Authors: Clayton Gina , Firth Georgina , Sawyer Caroline , Moffatt Rowena , Wray Helena
Published: August 2018

Course-focused and comprehensive, the Textbook on series provides an accessible overview of the key areas on the law curriculum. This chapter discusses the structure of the appeals bodies—the Appeal Tribunal and the Special Immigration Appeals Commission—and their procedure and jurisdiction. It sets out the limited rights of appeal following implementation of the Immigration Act 2014. It has a section on administrative review. It concludes with a section on immigrants and asylum seekers’ access to legal representation.
10. Visitors: entry for temporary purposes
Authors: Clayton Gina , Firth Georgina , Sawyer Caroline , Moffatt Rowena , Wray Helena
Published: August 2018

Course-focused and comprehensive, the Textbook on series provides an accessible overview of the key areas on the law curriculum. This chapter discusses the law relating to individuals coming to the UK as visitors for short-term or finite purposes such as tourism, business visits, sporting and entertainment engagements, or for private medical treatment. There is a discussion of the withdrawal, reinstatement, and restriction of rights of appeal for those visiting family members in the UK, and the application of Article 8 ECHR to these situations. The revised visitor rules in Appendix V are described in detail. The chapter also discusses the special cases of marriage visitors, carers and transit visitors, and general conditions such as prohibited activities and the need for maintenance and accommodation.
13. Exclusion from asylum
Authors: Clayton Gina , Firth Georgina , Sawyer Caroline , Moffatt Rowena , Wray Helena
Published: August 2018

Course-focused and comprehensive, the Textbook on series provides an accessible overview of the key areas on the law curriculum. This chapter considers the provisions whereby an individual can be excluded from refugee status because of their conduct. These are as laid down in the Refugee Convention and the EC Qualification Directive. The chapter discusses up-to-date case law on exclusion from refugee status based on crimes against humanity, serious non-political crimes, and acts against the purpose and principles of the United Nations. It deals with the issue of complicity and the relationship with the UK’s anti-terrorism legislation. It also deals with the situations in which refugees can be removed from the host country.
16. Removal
Authors: Clayton Gina , Firth Georgina , Sawyer Caroline , Moffatt Rowena , Wray Helena
Published: August 2018

Course-focused and comprehensive, the Textbook on series provides an accessible overview of the key areas on the law curriculum. This chapter describes the development of the grounds in law for exercising the power to remove a person from the UK, from the Immigration Act 1971to Immigration Act 2014. These include people who have overstayed the limit of their leave, or have breached conditions of leave or obtained leave to remain by deception, and the families of such people. The chapter also examines the practical obstacles to removal. These are often as important to the individual as the legal ones.
5. Supremacy of EU law
Authors: Foster Nigel
Published: August 2018

This chapter focuses on the supremacy of European Union (EU) law over the law of the member states and the relationship with international law. It suggests that the reasons and logic for the supremacy of the EU law have been developed through the decisions and interpretation of the European Court of Justice (CoJ) and provides relevant cases to illustrate the views of the CoJ on the superiority of EU law. This chapter also describes the reception and implementation of EU law in several member states, including the UK, but now in the light of Brexit, Germany, Italy, France, the Czech Republic, Denmark, and Spain.
6. The preliminary ruling (Article 267 TFEU)
Authors: Foster Nigel
Published: August 2018

This chapter examines the procedural law of the European Union (EU), focusing on Article 267 of the Treaty on the Functioning of the European Union (TFEU). It explains that Article 267 is the reference procedure by which courts in member states can endorse questions concerning EU law to the European Court of Justice (CoJ). Under this Article, the Court of Justice of the European Union (CJEU) has the jurisdiction to provide preliminary rulings on the validity and interpretation of acts of the institutions, bodies, offices, or agencies of the Union and on the interpretation of the Treaties.
9. Direct actions before the Court of Justice
Authors: Foster Nigel
Published: August 2018

This chapter analyses direct actions filed before the Court of Justice of the European Union (CJEU) against European Union (EU) institutions. These include actions for damages for loss caused by an act of the Institutions under Articles 268 and 340 of the Treaty on the Functioning of the European Union (TFEU), action for failure of the institutions to act under Article 263 TFEU, and judicial review of EU acts under Article 263 TFEU. This chapter explains that the cases involving Article 263 TFEU and Article 340 TFEU received the most attention for their admissibility and merits.
11. Free movement of goods II: non-tariff barriers
Authors: Foster Nigel
Published: August 2018

This chapter examines European Union (EU) law concerning non-tariff barriers to free movement of goods. It describes member states’ attempts to influence imports and the way the European Commission and the European Court of Justice (CoJ) handled these issues. This chapter explains the provisions of the relevant legislation for non-tariff barriers, which include Articles 34, 36, and 35 of the Treaty on the Functioning of the European Union (TFEU). It also analyses example cases including ‘Dassonville’, ‘Cassis de Dijon’, and ‘Keck’.
13. An introduction to EU competition policy and law
Authors: Foster Nigel
Published: August 2018

This chapter provides an introduction to Competition Policy and law in the European Union (EU). It covers the principal rules of EU competition law, namely Articles 101 and 102 TFEU and also considers the enforcement of the competition law regime and merger policy and regulation in the EU.
3. The institutions of the Union
Authors: Horspool Margot , Humphreys Matthew , Wells-Greco Michael
Published: August 2018

This chapter discusses the institutions of the EU and associated bodies. These include the European Council, the Council, the Commission, the European Parliament, the Court of Justice of the European Union and the General Court, the Court of Auditors, the European Economic and Social Committee (EESC), the Committee of the Regions (COR), the European Investment Bank, and the European Central Bank.
5. The Union legal system
Authors: Horspool Margot , Humphreys Matthew , Wells-Greco Michael
Published: August 2018

This chapter discusses the EU legal system covering primary legislation; public international law in EU courts; secondary Union legislation; legislative procedures; decision-making procedure of the Commission; and legislative powers.
7. Doctrines of European Union law: direct effect, supremacy, state liability for breach of Union law and other remedies
Authors: Horspool Margot , Humphreys Matthew , Wells-Greco Michael
Published: August 2018

This chapter reviews the main doctrines or principles of EU law. It is divided into three sections: direct effect and indirect effect; supremacy or primacy; state liability for breach of Union law and other remedies.
8. Public enforcement of Union law (Articles 258–260 TFEU); review of legality and damages (Articles 263, 265, 268, 277 and 340(2) TFEU)
Authors: Horspool Margot , Humphreys Matthew , Wells-Greco Michael
Published: August 2018

This chapter focuses on direct actions before the Court of Justice. It is divided into two sections. Section I deals with direct actions relating to public enforcement of EU law between the Commission and Member States (Article 258 of the TFEU) and between Member States (Article 259 TFEU). The financial consequences of failure to remedy infringements are also covered (Article 260 TFEU). Section II deals with actions challenging the legality of binding institutional acts (action for annulment, Article 263 TFEU); action for failure to act (Article 265 TFEU); and the plea of illegality (Article 277 TFEU). It briefly examines the action for damages against EU institutions (Articles 268 and 340(2) TFEU), a Treaty-based action from which parallels can be drawn to the evolution of state liability, through the Court’s case law.
7. The purchase deed and mortgage
Authors: Abbey Robert M. , Richards Mark B.
Published: August 2018

The principal purpose of the purchase deed is to transfer the legal estate in the property from the seller to the buyer. The transfer of a legal estate is void unless it is made by deed. This chapter discusses types of purchase deed; joint representation of borrower and lender; commercial mortgages; the mortgage deed; and post-completion steps; and mortgage fraud.
11. New properties
Authors: Abbey Robert M. , Richards Mark B.
Published: August 2018

This chapter deals with the special areas of concern for practitioners who are required to deal with the sale or purchase of new residential properties, either recently constructed or in the course of construction. It looks at the roles of the practitioners acting for the developer and prospective buyer respectively. It also considers the arrangements for roads and sewers on a new estate and the importance of insurance against structural defects in new properties.
13. Business Tenancies and the Landlord and Tenant Act 1954, Part II
Authors: Abbey Robert M. , Richards Mark B.
Published: August 2018

This chapter considers the provisions of the Landlord and Tenant Act 1954, Part II, which regulates the ways in which business tenancies may be terminated and gives statutory protection to business tenants. Topics discussed include agreements to which the 1954 Act applies; requirement for ‘tenancy’ tenancies excluded from statutory protection; requirement for ‘occupation’ methods of termination under the 1954 Act; Section 40 notices; rules for service of notices; interim rent applications; landlord’s statutory grounds of opposition; tenant’s right to compensation for failure to obtain a new tenancy; and court order for new tenancy.
Principles of Banking Law
Authors: Cranston Sir Ross , Avgouleas Emilios , van Zwieten Kristin , Hare Christopher , van Sante Theodor
Published: August 2018

Principles of Banking Law provides an authoritative take on banking and services law, with coverage of global banking regulation, payment systems, capital markets, and trade finance. The text takes an international perspective, helping locate domestic banking law and financial law in its wider context. It takes a themed, policy-oriented approach to the subject. The text is composed of four parts. The first part looks at banks and bank regulation. Part II considers banks and customers. Part III examines payment and payment systems. The final part looks at banks and finance.
1. Banks in the Financial System
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

This chapter explains the economic functions and organizational structure of contemporary banking. It first discusses the role of banks in the economy, offering a brief account of the role of the financial system in capital allocation and risk management as well as key bank functions in this respect. It then details the rise and fall of the multifunctional bank in the era of globalization, and the different aspects of the too-big-to-fail bank problem and its possible causes. It explains the international nature of bank regulation and the standard-setting and regulatory coordination provided by key transnational regulatory networks such as the Basel committee on Bank Supervision and the Financial Stability Board; discusses the legal definition of the term ‘bank’ in the US and of ‘credit institution’ under EU legislation; advances a new understanding of what the term ‘bank’ means in the post-2008 era.
2. Prudential Regulation I: Capital and Liquidity Controls
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

This chapter begins with a discussion of the reasons for bank regulation. Traditionally the focus of bank regulation has been the protection of individual institutions' stability from a depositors' run, and of depositors and deposit guarantee schemes from incurring losses in the event of bank failures. Another fundamental goal was the protection of taxpayers from a public bailout and from the kind of moral hazard that arises when public bank rescues are likely. However, in recent years, and especially since the global financial crisis the focus of bank regulation has broadened to include eliminating too-big-to-fail institutions; increasing capital cushions and introducing liquidity requirements; and enhancing the resilience of the financial system to withstand system-wide shocks. The remainder of the chapter covers prudential regulation, capital regulation, the different phases of the Basel capital framework, and the total loss absorbing capacity standard.
3. Prudential Regulation II: Structural Reform, Deposit Insurance, Corporate Governance
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

This chapter discusses bank structural reform. Most structural reform initiatives that have been undertaken since 2008 were aimed at reversing the effects of the repeal of the Glass–Steagall Act in the late 1990s and of the EU legislation that promoted universal banking. The chapter first considers the financial stability concerns and the mechanics of contemporary structural reform legislation in the USA, the UK, and the EU, and the actual legal framework underpinning these reforms. It then covers the regulation of bank involvement in derivatives markets. Today, derivatives regulation is a clear part of macroprudential regulation to the extent that centralized clearing and settlement and increased transparency battle opacity and interconnectedness and limit systemic risk. The remainder of the chapter covers deposit insurance, bank corporate governance, risk control, and executive remuneration.
4. Fundamental Principles of Bank Supervision and the Lender of Last Resort—A Reconceptualization
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

This chapter examines the architecture and functions of bank supervision. Bank supervision is the process through which compliance with discussed prudential, conduct, and systemic regulations is safeguarded and enforced. It is normally exercised by public agencies that have the competence to approve the establishment and operation of credit institutions and monitor continuous compliance with the requisite regulatory framework. The same public bodies are also vested with remedial (early intervention) and enforcement powers in the event of a breach of any of the above. The chapter covers the fundamental principles of financial supervision; bank supervisors' accountability and judicial review; bankers' conduct, money laundering, and terrorist financing; and the central bank as the lender of last resort to the banking system.
6. Bank Insolvency and Resolution
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

Banks can become distressed for a range of reasons, just like other firms. These reasons may be internal to the distressed bank (e.g. risky lending practices) or external to it (both at industry level and at the macroeconomic level), or both. Distressed banks, however, are not always subject to the same regulatory regime that governs the treatment of distress in other kinds of firms. Banks have special characteristics and this has led to the special treatment, which is explored in this chapter. The discussions cover the justification for special treatment, special resolution regimes, bank resolution regimes at domestic level, and cross-border complexities.
13. Domestic Payment Systems
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

Payment involves the transfer of monetary value from payer to payee. This chapter deals with ‘payment systems’, which are the instruments, procedures, and institutions that enable persons to effect payment. Traditionally, payment systems have been classified in different ways. One distinction is between credit and debit transfers. Other distinctions include whether the payment system is paper-based, electronic, or both; whether the payment system is limited to small-value or large-value transfers or; or whether the payment system is operated by an emanation of the state or some private commercial entity. The consideration of payment systems will be illustrative, rather than exhaustive, and the discussion will focus on UK-based and domestic payment systems, covering money, cheques, payment cards, and electronic funds transfers in that order.
14. Lending
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

This chapter considers lending in liberalized markets, where banks enjoy greater autonomy in their choice of borrower, the terms on which they lend, and the exercise of remedies on a borrower's default. It focuses on commercial lending by banks, and thus does not consider the additional issues that arise in relation to consumer lending. Commercial lending by banks can take various forms. Bankers often use the generic term ‘facility’ to describe them all. The most basic is the term loan, where a specified maturity date sets the time for ultimate repayment. The chapter discusses the negotiation of the agreement for commercial loan facilities; the facility and its repayment; conditions precedent, representations and warranties, covenants; the negative pledge and pari passu clauses; and default.
16. Loan Sales and Securitization
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

This chapter examines one context in which contracts and debts are transferred — as banks and bank subsidiaries ‘sell’ their own assets, i.e. their loans, mortgages, credit card receivables, and so on. Commercially speaking, this divides into loan sales and securitization. Among the various motivations for these transactions are to reduce risk, to meet capital requirements, to allow for new lending, and to take advantage of financial and commercial opportunities. Securitization was abused, with many risky loans repackaged and sold as highly rated securities. Its contribution to the global financial crisis in 2008 made it unpopular. However, it remains significant as a financing technique. Before examining loan sales and securitization, the chapter lays out the different legal techniques for transferring debts and contractual rights.
18. Security
Authors: Cranston Ross , Avgouleas Emilios , van Zweiten Kristin , van Sante Theodor , Hare Christoper
Published: August 2018

This chapter discusses security in lending. Lending is in some cases unsecured, where the standing of the borrower is such that the banks cannot demand it or, because of the creditworthiness of the borrower, do not regard it as necessary. However, much international lending is now oriented towards particular projects, and security is taken. Security is often required so that the bank can recoup itself out of the collateral in the event of default. In relation to project financings, the security required by the banks will often be of a comprehensive nature; for example a fixed and floating charge, a charge over shares, a legal assignment of material contracts, and so on. With syndicated lending, the security might be granted in favour of a security trustee to hold to the benefit of the members of the lending syndicate. Within a corporate group, each member may contribute to the security, and there will be cross-guarantees.
The Bicanonical Map of Fake Projective Planes with an Automorphism
Authors: Catanese Fabrizio , Keum JongHae
Published: August 2018

We show, for several fake projective planes with a nontrivial group of automorphisms, that the bicanonical map is an embedding.
Competition policy and economics
Authors: Whish Richard , Bailey David
Published: August 2018

This chapter provides an overview of competition law and its economic context. Section 2 describes the practices that competition laws attempt to control in order to protect the competition process. Section 3 examines the theory of competition and gives an introductory account of why the effective enforcement of competition law is thought to be beneficial for consumer welfare. Section 4 considers the expected functions of a system of competition law. Section 5 then introduces two key economic concepts, market definition and market power, that are important to a better understanding of competition policy. The chapter concludes with a table of market share figures that are significant in the application of EU and UK competition law.
Article 102
Authors: Whish Richard , Bailey David
Published: August 2018

This chapter discusses the main features of Article 102 of the Treaty on the Functioning of the European Union (TFEU), which is concerned with the abusive conduct of dominant firms. It begins by introducing the European Commission’s Guidance on the Commission’s enforcement priorities in applying Article [102 TFEU] to abusive exclusionary conduct by dominant undertakings. It then discusses the concept of undertaking, the requirement of an effect on trade between Member States, the concept of a dominant position and the requirement that any dominant position must be held in a substantial part of the internal market. The chapter also considers the meaning of abuse of a dominant position, which is a complex and controversial issue. A discussion of the defences to allegations of abuse is followed by a brief look at the consequences of infringing Article 102.
Articles 101 and 102: public enforcement by the European Commission and national competition authorities under Regulation 1/2003
Authors: Whish Richard , Bailey David
Published: August 2018

This chapter explains the public enforcement of Articles 101 and 102 by the European Commission and the national competition authorities (‘the NCAs’) under Regulation 1/2003. It begins by describing the Commission’s powers of investigation and enforcement, including its power to accept commitments, its leniency programme, the cartel settlement procedure and its power to impose financial penalties. It then discusses the operation of Regulation 1/2003 in practice, with particular reference to the European Competition Network (‘the ECN’) that brings together the Commission and the NCAs. The chapter concludes by providing a brief account of judicial review of the Commission’s decisions.
Horizontal agreements (2): oligopoly, tacit collusion and collective dominance
Authors: Whish Richard , Bailey David
Published: August 2018

This chapter describes how competition law addresses oligopoly, tacit collusion and collective dominance. This chapter is concerned with the related topics of oligopoly, tacit collusion and collective dominance. Oligopoly exists where a few firms between them supply all or most of the goods or services on a market without any of them having a clear ascendancy over the others. This chapter begins with discussion of the theory of oligopolistic interdependence and of the possible ways of dealing with the ‘oligopoly problem’. It then considers the extent to which Articles 101 and 102 can be used to address that problem. The chapter also discusses UK law and, in particular, the possible use of market investigations to address market failure that may arise in oligopolies.
Vertical agreements
Authors: Whish Richard , Bailey David
Published: August 2018

This chapter examines the application of Article 101 TFEU and the Chapter I prohibition in the UK Competition Act 1998 to vertical agreements. The chapter begins by briefly describing the distribution chain, followed by sections on how the law applies to vertical integration and agency agreements. It discusses the competition policy considerations raised by vertical agreements, including the challenges presented by the emergence of online commerce. It explains the application of Article 101 to various vertical agreements while considering the case law of the EU Courts and the position of the Commission in its Guidelines on Vertical Restraints. The chapter goes on to discuss the provisions of Regulation 330/2010, the block exemption for vertical agreements; and the application of Article 101(3) to vertical agreements. The chapter then contains sections on Regulation 461/2010 on motor vehicle distribution and on sub-contracting agreements. Finally, it looks at the position in UK law.
Abuse of dominance (2): pricing practices
Authors: Whish Richard , Bailey David
Published: August 2018

This chapter considers abusive pricing practices under Article 102 TFEU and the Chapter II prohibition in the Competition Act 1998. It discusses cost concepts used in determining whether a price is abusive and deals with excessive pricing; conditional rebates; bundling; predatory pricing; margin squeeze; price discrimination; and practices harmful to the single market. Price discrimination may be both exploitative and exclusionary and an excessively high price may be a way of preventing parallel imports or excluding a competitor from the market; but the division may provide helpful insights into the way in which the law is applied in practice. In each section the application of Article 102 by the European Commission and the EU Courts is considered, followed by cases in the UK. Where appropriate, reference is made to the Commission’s Guidance on the Commission’s Enforcement Priorities in Applying Article [102 TFEU] to Abusive Exclusionary Conduct by Dominant Undertakings.
Collaborative Simulation Training: Strategies Used to Teach Root Cause Analysis Leadership Competencies
Authors: Junious DeMonica Latrice
Published: August 2018

Considered the norm in multiple academic settings, simulation provided a low-risk, transformational clinical learning environment across programs at a college of nursing. Undergraduate nursing students received feedback from practicing nurses, whereas graduate nursing students honed skills in evaluative feedback and communication. This intraprofessional learning opportunity cultivated a rich learning environment. Feedback revealed that the learning milieu was permeated with opportunities needed for skills, competencies, and leadership development. Focusing on the concept of root cause analysis, this experience provided nurse administration students with hands-on exposure that would ultimately lead to developing competencies needed for roles in nursing leadership.
Alcohol and Drug Overdose and the Influence of Pain Conditions in an Addiction Treatment Sample
Authors: Fernandez Anne C. , Bush Christopher , Bonar Erin E. , Blow Frederic C. , Walton Maureen A. , Bohnert Amy S.B.
Published: August 2018

Purpose:

Overdose from alcohol and/or drugs kills tens of thousands of Americans annually, with a large number of deaths attributed to opioid pain medications. Addiction treatment patients are known to be at high risk for overdose; however, the relationship between pain and overdose history within this group is understudied, especially in relation to alcohol overdoses. In the present study, we evaluated whether nonfatal overdose history was more likely among addiction treatment patients with pain, and examined the characteristics of overdoses among those with and without pain.

Methods:

We analyzed cross-sectional data from 739 patients at a large residential addiction treatment center (median age 37, 25.7% female). We used 2-stepped binary regression models to evaluate whether demographics, pain type (chronic, acute, or both), depression symptoms, and opioid misuse were associated with lifetime history of nonfatal (1) alcohol and (2) drug overdose (lifetime yes/no), and conducted follow-up analyses examining overdose characteristics.

Results:

In adjusted analyses, history of chronic pain (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.59, 4.27) and illicit drug use (OR 1.99, 95% CI 1.07, 3.68) were associated with an increased likelihood of nonfatal alcohol overdose. Opioid misuse (OR 3.11, 95% CI 2.51, 3.86), depression symptoms (OR 1.33, 95% CI 1.14, 1.55), and younger age (OR 0.96, 95% CI 0.94, 0.97) were associated with increased likelihood of drug overdose. Those with pain reported a higher number of lifetime alcohol overdoses and were more likely to combine numerous drugs with alcohol before overdose.

Conclusions:

Pain conditions may play an under-recognized role in the overdose epidemic, particularly alcohol-related overdose. Addiction treatment and overdose prevention interventions should incorporate appropriate assessment and treatment of pain including education about the risks of polysubstance use, particularly combining alcohol with sedatives and prescription pain relievers.
Clinicopathologic features correlated with paradoxical outcomes in stage IIC versus IIIA melanoma patients
Authors: Tan Sally Y. , Najita Julie , Li Xiaoxue , Strazzulla Lauren C. , Dunbar Haili , Lee Mee-young , Seery Virginia J. , Buchbinder Elizabeth I. , Tawa Nicholas E. , McDermott David F. , Lee Sandra J. , Atkins Michael B. , Kim Caroline C.
Published: August 2018

Under current AJCC staging criteria, stage IIC patients paradoxically have worse outcomes than IIIA patients despite the lack of nodal metastatic disease. This study sought to identify additional clinicopathologic characteristics correlated with worse patient outcomes. Retrospective chart review of stage IIC and IIIA melanoma patients were evaluated between 1995 and 2011 with clinical follow-up through 2015. Records were reviewed for demographics, clinical characteristics, and tumor pathology. Fisher’s exact test and Wilcoxon’s rank-sum test were used to assess group differences. Clinicopathologic features were evaluated relative to overall survival (OS), time to distant metastases, and local/regional recurrence. Overall, 128 patients were included (45 stage IIC and 83 stage IIIA) with a median follow-up time of 5.7 years. Compared with stage IIIA patients, stage IIC patients were older, and their melanomas were more likely to be nodular, amelanotic, thicker, have higher mitotic rate, tumor lymphocytic infiltrate, no radial growth phase, and less likely to have associated precursor lesions. Stage IIC patients had shorter OS and time to distant metastases; multivariate regression revealed that older age (>55 years) and mitotic rate (>5 mitoses/mm2) were independent predictors of OS. Melanomas in stage IIC disease may be biologically distinct from those that are seen in stage IIIA. While sentinel node biopsies remain the standard-of-care, these results suggest that clinicians may want to assess the clinicopathologic characteristics described above to aggressively counsel, screen for distant disease, and consider adjuvant therapy, in particular for older patients and higher mitotic rates in thicker primary tumors, regardless of nodal status.
Incomplete Vogt–Koyanagi–Harada disease following treatment with encorafenib and binimetinib for metastatic melanoma
Authors: Diamantopoulos Panagiotis T. , Stoungioti Sofia , Anastasopoulou Amalia , Papaxoinis George , Gogas Helen
Published: August 2018

Ophthalmological complications constitute a class effect of treatment with BRAF inhibitors. Encorafenib is a new BRAF inhibitor currently being tested in phase 3 clinical trials for advanced or metastatic melanoma as monotherapy or in combination with the MEK-inhibitor binimetinib. In this study, we present a case of severe bilateral panuveitis and neurosensory hearing loss in an elderly patient treated with encorafenib and binimetinib for metastatic BRAF-mutant melanoma. This constellation of findings is compatible with incomplete Vogt–Koyanagi–Harada (VKH) disease. VKH disease is a rare multisystem disease characterized by granulomatous panuveitis, serous retinal detachments, and neurologic and dermatologic manifestations. In patients with melanoma, its emergence has been correlated to a favorable prognosis of the underlying melanoma by several authors. The patient reported here had a severe panuveitis and bilateral retinal detachments causing permanent visual impairment. She was treated with a long course of systemic corticosteroids, but at the same time, she achieved complete remission of the melanoma lasting for 26 months after permanent encorafenib and binimetinib discontinuation, without further antineoplastic treatment. VKH disease is a rare entity and the need for interdisciplinary cooperation for its diagnosis in patients with melanoma and uveitis is emphasized.
Complementary Medicine & Spirituality
Authors: Joseph Rachel , Fernandes Samantha , Derstine Sarah , McSpadden Micaela
Published: August 2018

Over 3 million India-born immigrants live in the United States, yet their health-seeking behaviors are little understood. Information on health and access to care was collected from 20 adult Indian immigrants living in the United States. Participants preferred complementary and alternative medicine home remedies to address their health needs, although they accessed health services more quickly for their children. They also reported barriers in using insurance and accessing healthcare.
Inhibition of experimental visceral pain in rodents by cebranopadol
Authors: Schiene Klaus , Schröder Wolfgang , Linz Klaus , Frosch Stefanie , Tzschentke Thomas M. , Christoph Thomas , Xie Jennifer Y. , Porreca Frank
Published: August 2018

The aim of this study was to investigate the efficacy of cebranopadol in two rodent models of visceral pain. Cebranopadol is a first-in-class analgesic with agonist activity at the nociceptin/orphanin FQ opioid peptide receptor and classical µ-, δ- and κ-opioid peptide receptors. Colitis was induced in Naval Medical Research Institute mice by intra-rectal infusion of mustard oil. The effects of intravenous cebranopadol pretreatment on spontaneous pain behaviours and referred allodynia and hyperalgesia were assessed. Pancreatitis was induced in Sprague-Dawley rats by intravenous administration of dibutyltin dichloride. After 6 days, the effects of intravenous cebranopadol on withdrawal reactions to mechanical abdominal stimulation with von Frey filaments were assessed. In mice with experimental colitis, cebranopadol dose-dependently inhibited spontaneous pain behaviours and allodynic and hyperalgesic withdrawal reactions, with half-maximal effective dose values of 4.6 µg/kg [95% confidence interval (CI): 2.9–7.9] for inhibition of spontaneous pain behaviours, 2.2 µg/kg (95% CI: 1.3–3.4) for inhibition of referred allodynia and 2.4 µg/kg (95% CI: 1.4–3.6) for inhibition of referred hyperalgesia in mice with colitis. In rats with experimental pancreatitis, cebranopadol dose-dependently inhibited abdominal tactile allodynia (half-maximal effective dose, 0.13 µg/kg; 95% CI: 0.03–0.49). Behavioural manifestations of visceral pain were almost completely abolished at the highest doses tested in mice (17.2 µg/kg, intravenous) and rats (2.4 µg/kg, intravenous). We conclude that cebranopadol is a potent and effective antiallodynic and antihyperalgesic agent in rodent models of visceral pain.
A Population Pharmacokinetic–Pharmacogenetic Model of Lamotrigine in Chinese Children With Epilepsy
Authors: Chen Yanan , Xu Shansen , Wang Zhanyou , Zhao Mingming , Wang Huanxin , Lu Tong , Zhao Limei
Published: August 2018

Background:

The pharmacokinetics of lamotrigine (LTG) is complex and varies significantly among individuals, especially among children. Therefore, this study aimed to establish a population pharmacokinetic (PPK) model of LTG in Chinese children with epilepsy and to comprehensively evaluate the effects of genetic variations in drug-metabolizing enzymes, transporters, and a transcriptional regulator on LTG pharmacokinetics.

Methods:

Three hundred eighty-five steady-state plasma concentrations were obtained from 179 children (age 10.72 ± 3.05 years and body weight 46.23 ± 17.77 kg) with epilepsy during therapeutic drug monitoring. These patients were divided into the PPK-model group (n = 121) and the PPK-validation group (n = 58) and were genotyped for UGT1A4, UGT2B7, ABCB1, ABCG2, SLC22A1, and HNF4α. PPK analysis was performed by nonlinear mixed effects modeling.

Results:

In the final model, apparent clearance (CL/F) of LTG was estimated to be 1.48 L/h; 500 mg valproic acid, oxcarbazepine, and UGT2B7-161TT genotype changed the CL/F by −46.2, +31.1, and −21.8%, respectively. Body weight was also identified as a significant covariate affecting LTG CL/F.

Conclusions:

A PPK–pharmacogenetic model of LTG in Chinese children with epilepsy was successfully established with nonlinear mixed effects modeling. Genotyping for UGT2B7-161C>T may be useful in titrating the optimal LTG dose.
Antenatal treatment options for primary cytomegalovirus infections
Authors: Kagan Karl Oliver , Sonek Jiri , Hamprecht Klaus
Published: August 2018

Purpose of review

Cytomegalovirus (CMV) infection is by far the most common fetal viral infection. It carries a risk of long-term sequelae for the neonate; though the severity depends on the gestational age at the time of infection. Improvement in primary prevention of a CMV infection during pregnancy can be achieved by providing information regarding hygiene to the mother. Once a maternal infection occurs, treatment options include prevention of maternal-fetal transmission and, once transmission occurs, attempts to reduce the severity of its effect on the fetus.

Recent findings

Several recent studies have shown that providing detailed information regarding the effects of CMV on the fetus and providing common sense hygiene advice reduced new primary infections by more than 75%. In cases with a documented maternal primary CMV infection, treatment with intravenous immunoglobulins have been tried to reduce maternal fetal transmission with a variable degree of success. In the randomized controlled study of Revello et al., immunoglobulins did not reduce the transmission rate. In a recent study, immunoglobulins were given only to women with very recent first trimester infections. In this study, the transmission rate was 2.5%, which is significantly less than expected. Leruez-Ville et al. treated mothers with known transmission of CMV to the fetus with 8 g of valaciclovir daily. They observed a significant reduction in the number of neonatal symptoms in the treated cases.

Protocols are available to prevent primary CMV infections during pregnancy and, in cases where an infection does occur, steps can be taken to reduce its effect on the fetus thereby reducing the chance of long-term sequelae.
Cognitive Communication Impairments in Children With Traumatic Brain Injury: A Scoping Review
Authors: Cermak Carly A. , Scratch Shannon E. , Reed Nick P. , Bradley Kim , Quinn de Launay Keelia L. , Beal Deryk S.
Published: August 2018

Objective:

This scoping review synthesizes the scholarly literature on cognitive communication impairments in traumatic brain injury (TBI) sustained during childhood to identify gaps in research, and make recommendations that will further the field of cognitive communication in pediatric TBI.

Methods:

MEDLINE, PsycINFO, CINAHL, and EMBASE were searched to identify peer-reviewed studies that examined cognitive communication impairments in children who sustained a TBI between 3 months to 18 years of age.

Results:

Twenty-eight studies met inclusion criteria with 3 main categories identified in relation to cognitive communication: (1) impairments according to TBI severity, (2) impairments according to age at injury, and (3) trends in recovery according to TBI severity.

Conclusions:

The results of this scoping review suggest that (1) TBI severity is not the sole predictor of performance; other factors contribute to cognitive communication outcome and recovery; (2) developing skills at time of injury are most susceptible to impairment; and (3) standard, norm-referenced language assessments are not sensitive in detecting language impairments that are secondary to cognitive impairments found in TBI. Directions for future research and suggestions for clinical practice are proposed.
EFFICACY OF ADJUVANT TOPICAL DORZOLAMIDE–TIMOLOL IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION REFRACTORY TO ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Authors: Lee Ji Hwan , Lee Sung Chul , Byeon Suk Ho , Koh Hyoung Jun , Kim Sung Soo , Lee Christopher Seungkyu
Published: August 2018

Purpose:

To evaluate the efficacy of adjuvant topical dorzolamide–timolol in patients with neovascular age-related macular degeneration unresponsive to anti–vascular endothelial growth factor therapy.

Methods:

This retrospective, interventional study included 15 patients with neovascular age-related macular degeneration refractory to anti–vascular endothelial growth factor. Patients used topical dorzolamide–timolol twice daily in the neovascular age-related macular degeneration eye and received anti–vascular endothelial growth factor therapy at each visit, with the same fixed interval and agent as before the addition of dorzolamide–timolol. Central macular thickness, maximal subretinal fluid height, and maximal pigment epithelial detachment height were measured at baseline and every visit.

Results:

The mean follow-up period was 17.2 ± 5.5 weeks. The mean central macular thickness decreased from 383.5 μm at baseline to 298.3 μm at the final visit (P = 0.041). The mean maximal subretinal fluid height decreased from 105.0 μm at baseline to 58.3 μm at the final visit (P = 0.021). Complete resolution of subretinal fluid was observed in 3 of 11 subretinal fluid–type eyes. There was no significant change in the maximal pigment epithelial detachment height. The mean logarithm of the minimum angle of resolution visual acuity decreased from 0.61 (20/81 Snellen) at baseline to 0.66 (20/91 Snellen) at final visit, which was not significant (P = 0.314). The mean intraocular pressure decreased significantly from 14.9 mmHg at baseline to 12.3 mmHg at the final visit (P = 0.005).

Conclusion:

The use of adjuvant topical dorzolamide–timolol was effective in decreasing central macular thickness and subretinal fluid in patients with neovascular age-related macular degeneration refractory to continual fixed-interval intravitreal anti–vascular endothelial growth factor therapy, but did not result in functional improvement in this short-term study.
SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY TO DETERMINE THE RECOVERY OF RETINAL LAYERS AFTER INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR MACULAR HOLE
Authors: Morawski Krzysztof , Jędrychowska-Jamborska Justyna , Kubicka-Trząska Agnieszka , Romanowska-Dixon Bożena
Published: August 2018

Purpose:

To analyze the recovery of retinal lines using swept-source optical coherence tomography after inverted internal limiting membrane flap technique to treat full-thickness macular hole, and the relationship between best-corrected visual acuity and retinal line repair.

Methods:

Thirty-eight eyes were evaluated for recovery of the external limiting membrane, photoreceptor inner segment/outer segment junction line, and cone outer segment tips (COST) line. Correlation between the recovery of retinal lines and best-corrected visual acuity improvement was analyzed 6 months after surgery.

Results:

The closure rate of full-thickness macular hole was 97%. The best recovery rates were associated with external limiting membrane line recovery (25 eyes, 65.8%), followed by inner segment/outer segment line recovery (22 eyes, 57.9%), and less frequently, COST line recovery (9 eyes, 23.7%); moreover, recovery of the COST line was apparent only in eyes with recovered external limiting membrane and inner segment/outer segment lines. Mean postoperative visual acuity in the COST line recovery group (COST+) was 20/42 (0.48, 0.33 logarithm of the minimum angle of resolution), compared with 20/95 (0.21, 0.68 logarithm of the minimum angle of resolution) without COST line recovery (COST−). Final visual acuity was significantly better in the COST+ group compared with the COST− group (P = 0.002).

Conclusion:

Cone outer segment tips line recovery is correlated with best-corrected visual acuity improvement for eyes treated with inverted internal limiting membrane flap technique for full-thickness macular hole.
TWELVE-MONTH OUTCOMES OF INTRAVITREAL AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Veritti Daniele , Sarao Valentina , Missiroli Filippo , Ricci Federico , Lanzetta Paolo
Published: August 2018

Purpose:

To compare the clinical outcomes of aflibercept used with a fixed schedule with a pro-re-nata (PRN) retreatment regimen in patients affected by neovascular age-related macular degeneration.

Methods:

This is a prospective multicenter, noninferiority, propensity score–matched study evaluating the 12-month outcomes of aflibercept given either according to labeling or following a PRN regimen. Patients included in the latter group received one initial injection, followed by monthly visits and as-needed retreatment.

Results:

One-to-one matching resulted in fixed and PRN arms containing 92 eyes each. Visual acuity improved from baseline to 12 months in both the study groups. At Month 4, the fixed regimen was equivalent to the PRN regimen (mean difference: 1.75 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: −1.42 to +4.92). The pro-re-nata regimen failed to show noninferiority compared with the fixed regimen at both Month 8 (mean difference: 3.43 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: +0.25 to +6.22) and Month 12 (mean difference: 4.83 Early Treatment Diabetic Retinopathy Study letters, 95% confidence interval: +1.37 to +8.29). All patients in the fixed group received seven injections. Patients included in the PRN arm received a mean of 5.5 ± 1.6 treatments.

Conclusions:

Aflibercept given with a fixed treatment regimen produces better visual acuity outcomes than an individualized regimen.
Impact of Iontophoresis and PACK-CXL Corneal Concentrations of Antifungals in an In Vivo Model
Authors: Kalkanci Ayse , Yesilirmak Nilufer , Ozdemir Hüseyin Baran , Unal Elif Ayca , Erdoğan Merve , Seker Tamay , Tum Atakan Emre , Karakus Ahmet Kamil , Hizel Kenan , Bilgihan Kamil
Published: August 2018

Purpose:

To investigate voriconazole (VRZ) penetration and fungal load in the cornea after applying VRZ therapy with various treatment combinations in a fungal keratitis model.

Methods:

Fifty-four eyes of 27 young albino rabbits were provided for this experimental study. Twelve corneas were inoculated with Candida albicans, 12 corneas were inoculated with Fusarium solani, and 6 eyes were selected as controls. Infected corneas received various treatment combinations including VRZ 1% drop therapy alone, VRZ 1% plus amphotericin B 1% drop combination therapy, iontophoretic VRZ therapy, and VRZ 1% drop therapy after corneal cross-linking. Fungal load was measured by log reduction, and VRZ levels were quantified by liquid chromatography–tandem mass spectrometry.

Results:

Iontophoresis-assisted VRZ application showed the highest antifungal activity against F. solani keratitis (4-log reduction) and C. albicans keratitis (5-log reduction) compared with other treatment applications. VRZ levels were also found to be the highest in corneas that received iontophoretic VRZ treatment (3.6313 ± 0.0990 ppb for F.solani keratitis and 1.7001 ± 0.0065 ppb for C. albicans keratitis) compared with other treatment applications.

Conclusions:

Iontophoresis seems to provide the highest VRZ concentration and highest antifungal activity in the cornea compared with other treatment applications for C. albicans and F. solani keratitis.