Structure of international cooperation in trade, investment and environment

This dissertation analyzes the obstacles against further cooperation in international economic relations. The first essay explains the gradual nature of trade liberalization. I show that existence of asymmetric information between governments provides a sufficient reason for gradualism to exist. Governments prefer starting small to reduce the cost of partner’s betrayal when there is sufficient degree of information asymmetry regarding the partner’s type. Learning about partner’s incentive structure enhances expectations, encouraging governments to increase their current level of cooperation. Specifically, the uninformed government’s subjective belief for the trading partner being good is improved as the partner acts cooperatively. This updated belief, in turn, lowers the subjective probability of future betrayal, enabling further progress in cooperation. The second essay analyzes the relationship between two countries facing two policy dilemmas in an environment with two way goods and capital flows. When issues are independent and countries are symmetric, signing separate agreements for tariffs (Free Trade Agreements-FTA) and for taxes (Tax Treaties-TT) provides the identical level of enforcement as signing a linked agreement. However, linkage can still improve the joint welfare by transferring the slack enforcement power in a case of asymmetric issues or countries. I report non-results in two cases where the policy issues are interconnected due to technological spillover effect of FDI. Moreover, I show that linking the agreements actually reduces enforcement when agreements are linked under a limited punishment rule and policy variables are strategic substitutes. The third essay investigates the welfare/enforcement consequences of linking trade and environmental agreements. In the standard literature, linking the agreements generate non-trivial results only when there is structural relation between the issues. I focus on institutional design of the linkage and show that even if environmental aspects of international trade are negligible linking the agreements might still have some interesting welfare implications under current GATT Rules. Specifically, when traded goods are substitutes in consumption, linking the environmental agreement with trade agreement under the Withdrawal of Equivalent Concession Rule (Article XXVIII) will reduce the enforcement. However, enforcement in environmental issue increases when the same rule is implemented in the absence of linkage.

Essays on international lending and increasing returns to scale

Standard economic theory suggests that capital should flow from rich countries to poor countries. However, capital has predominantly flowed to rich countries. The three essays in this dissertation attempt to explain this phenomenon. The first two essays suggest theoretical explanations for why capital has not flowed to the poor countries. The third essay empirically tests the theoretical explanations.^ The first essay examines the effects of increasing returns to scale on international lending and borrowing with moral hazard. Introducing increasing returns in a two-country general equilibrium model yields possible multiple equilibria and helps explain the possibility of capital flows from a poor to a rich country. I find that a borrowing country may need to borrow sufficient amounts internationally to reach a minimum investment threshold in order to invest domestically.^ The second essay examines how a poor country may invest in sectors with low productivity because of sovereign risk, and how collateral differences across sectors may exacerbate the problem. I model sovereign borrowing with a two-sector economy: one sector with increasing returns to scale (IRS) and one sector with diminishing returns to scale (DRS). Countries with incomes below a threshold will only invest in the DRS sector, and countries with incomes above a threshold will invest mostly in the IRS sector. The results help explain the existence of a bimodal world income distribution.^ The third essay empirically tests the explanations for why capital has not flowed from the rich to the poor countries, with a focus on institutions and initial capital. I find that institutional variables are a very important factor, but in contrast to other studies, I show that institutions do not account for the Lucas Paradox. Evidence of increasing returns still exists, even when controlling for institutions and other variables. In addition, I find that the determinants of capital flows may depend on whether a country is rich or poor.^

A comprehensive study of bankruptcy prediction: Accounting ratios, market variables, and microstructure

Bankruptcy prediction has been a fruitful area of research. Univariate analysis and discriminant analysis were the first methodologies used. While they perform relatively well at correctly classifying bankrupt and nonbankrupt firms, their predictive ability has come into question over time. Univariate analysis lacks the big picture that financial distress entails. Multivariate discriminant analysis requires stringent assumptions that are violated when dealing with accounting ratios and market variables. This has led to the use of more complex models such as neural networks. While the accuracy of the predictions has improved with the use of more technical models, there is still an important point missing. Accounting ratios are the usual discriminating variables used in bankruptcy prediction. However, accounting ratios are backward-looking variables. At best, they are a current snapshot of the firm. Market variables are forward-looking variables. They are determined by discounting future outcomes. Microstructure variables, such as the bid-ask spread, also contain important information. Insiders are privy to more information that the retail investor, so if any financial distress is looming, the insiders should know before the general public. Therefore, any model in bankruptcy prediction should include market and microstructure variables. That is the focus of this dissertation. The traditional models and the newer, more technical models were tested and compared to the previous literature by employing accounting ratios, market variables, and microstructure variables. Our findings suggest that the more technical models are preferable, and that a mix of accounting and market variables are best at correctly classifying and predicting bankrupt firms. Multi-layer perceptron appears to be the most accurate model following the results. The set of best discriminating variables includes price, standard deviation of price, the bid-ask spread, net income to sale, working capital to total assets, and current liabilities to total assets.

Understanding Annual Reports of Hospitality Firms

In her discussion - Understanding Annual Reports of Hospitality Firms - by Elisa S. Moncarz, Associate Professor, School of Hospitality Management, Florida International University, Associate Professor Moncarz initially offers: “Management bears full responsibility for the reporting function of annual reports prepared by publicly-held companies designed to provide interested parties with information that is useful in making business and economic decisions. In Part I the author reviews the content of annual reports of firms in the hospitality industry, while looking at recent developments affecting annual reports. Part 11, in a subsequent issue, will comprise an in-depth examination of the annual report of an actual firm in the hospitality industry, focusing on suggested guidelines and recommendations for how to use annual reports as an aid to the decision-making process in the hospitality industry.” This article is to be considered a primer on reading and understanding annual reports, as well as a glimpse into the dynamics that affect them. In defining what an annual report is, Associate Professor Moncarz informs you with citation, “Annual reports are required by the Securities Exchange Commission (SEC) ¹ for all companies with securities sold to the general public. These reports, which must be issued within 90 days after the close of the calendar (or fiscal) year, comprise a primary source of information about these companies,” she further reports. “Indeed, the official version of the company's history is summed up yearly in its annual report by providing full information of the company's operations over the period as well as what the company is gearing up to accomplish in the next year,” Professor Moncarz closes the definition. Why should thus happen over and above SEC requirements? The financial component is an important one; the author offers her informed view: “The major objective of financial statement reporting is to provide information that is useful to present and potential investors, creditors, and other financial statement users in making rational investment, credit, and similar decisions. Thus, financial statements represent the primary (and most reliable) source of knowledge about a particular firm in the hospitality industry.” The above two paragraphs crystallize the requirement and the objective of annual reports. “A typical annual report of a hospitality firm contains a number of standard features which may be broken down into the following three sections…” General, financial data, and supplementary data are variously bounded and circumscribed for you. As a marketing device and feel-good initiative, the annual report is a useful tool for a hospitality corporation that is in-the-black, and focused on the future, says the author. She cites the Marriott Corporation’s 1985 annual report as an example. Of course, an annual report can also be a harbinger of bad news for shareholders as well. Notes/footnotes and disclosure are key elements to the credibility of any annual report; Professor Moncarz discusses these concepts at length. “Given the likelihood that the hospitality industry will continue to face an uncertain economic environment for some time, financial statement users should become more demanding in their need for information that will help assure the firm's survival and evaluate its ability to generate earnings, increase the firm's investment value, and provide for its future growth,” Professor Moncarz says. “Accordingly, understanding annual reports in the hospitality industry should become even more critical.”

Controllers' Perceptions of the Importance of Accounting Skills to Lodging Managers

Are managerial accounting skills important to all managers? Which of the common managerial accounting skills are the most important to the non- accounting manager? The authors report on their descriptive research gathered from controllers in the hospitality industry which provides guide- lines for managers in these areas.

Historical analysis of two contemporary issues at the International Community School of Abidjan, Cote d'Ivoire: Local -hired and overseas -hired teacher relationships. Community perceptions of the U.S. Embassy at ICSA

This study was a qualitative investigation to ascertain and describe two of the current issues at the International Community School of Abidjan, examine their historical bases, and analyze their impact on the school environment.^ Two issues emerged during the inquiry phase of this study: (1) the relationship between local-hired and overseas-hired teachers in light of the January 1994 devaluation which polarized the staff by negating a four-year salary scale that established equity, (2) the school community's wide variance in the perceived power that the U.S. Embassy has on school operations based on its role as ICSA's founding sponsor.^ A multiple studies approach was used in gathering data. An extensive examination of the school's archives was used to reconstruct an historical overview of ICSA. An initial questionnaire was distributed to teachers and administrators at an educational conference to determine the scope of the 1994 devaluation of the West and Central African CFA and its impact on school personnel in West African American-sponsored overseas schools (ASOS). Personal interviews were conducted with the school staff, administration, school board members, and relevant historical participants to determine the principal issues at ICSA at that time. The researcher, an overseas-hired teacher, also used participant observations to collect data. Findings based on these sources were used to analyze the two issues from an historical perspective and to form conclusions.^ Findings in this study pertaining to the events induced by the French and African governments' decision to implement a currency devaluation in January 1994 were presented in ex post-facto chronological narrative form to describe the events which transpired, describe the perception of school personnel involved in these events, examine the final resolution and interpret these events within a historical framework for analysis.^ The topic of the U.S. Embassy and its role at ICSA emerged inductively from open-ended personal interviews conducted over the course of a year. Contradictory perspectives were examined and researched for accuracy and cause. The results of this inquiry presented the U.S. Embassy role at ICSA from a two-sided perspective, examined the historical role of the Embassy, and presented means by which the role and responsibility of the U.S. Embassy could best be communicated to the school community.^ The final chapter provides specific actions for mediation of problems stemming from these issues, implications for administrators and teachers currently involved in overseas schools or considering the possibility, and suggestions for future inquiries.^ Examination of a two-tier salary scale for local-hired and overseas-hired teachers generated the following recommendations: movement towards a single salary scale when feasible, clearly stated personnel policies and full disclosure of benefits, a uniform certification standard, professional development programs and awareness of the impact of this issue on staff morale.^ Divergent perceptions and attitudes toward the role of the U.S. Embassy produced these recommendations: a view towards limiting the number of Americans on ASOS school boards, open school board meetings, selection of Embassy Administrative Officers who can educate school communities on the exact role of the Embassy, educating parents through the outreach activities that communicate American educational philosophy and involve all segments of the international community, and a firm effort on the part of the ASOS to establish the school's autonomy from special interests. ^

Spatially explicit estimates of stock size, structure and biomass of North Atlantic albacore tuna (Thunnus alalunga) in the North Atlantic for the period 1956-2010, compiled from the International Commission for the Conservation of Atlantic Tunas

The development of the ecosystem approach and models for the management of ocean marine resources requires easy access to standard validated datasets of historical catch data for the main exploited species. They are used to measure the impact of biomass removal by fisheries and to evaluate the models skills, while the use of standard dataset facilitates models inter-comparison. North Atlantic albacore tuna is exploited all year round by longline and in summer and autumn by surface fisheries and fishery statistics compiled by the International Commission for the Conservation of Atlantic Tunas (ICCAT). Catch and effort with geographical coordinates at monthly spatial resolution of 1° or 5° squares were extracted for this species with a careful definition of fisheries and data screening. In total, thirteen fisheries were defined for the period 1956-2010, with fishing gears longline, troll, mid-water trawl and bait fishing. However, the spatialized catch effort data available in ICCAT database represent a fraction of the entire total catch. Length frequencies of catch were also extracted according to the definition of fisheries above for the period 1956-2010 with a quarterly temporal resolution and spatial resolutions varying from 1°x 1° to 10°x 20°. The resolution used to measure the fish also varies with size-bins of 1, 2 or 5 cm (Fork Length). The screening of data allowed detecting inconsistencies with a relatively large number of samples larger than 150 cm while all studies on the growth of albacore suggest that fish rarely grow up over 130 cm. Therefore, a threshold value of 130 cm has been arbitrarily fixed and all length frequency data above this value removed from the original data set.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Seawater carbonate chemistry, calcification and dissolution response, and skeletal mineralogy of benthic orhanisms during experiments, 2011

Increasing atmospheric pCO2 reduces the saturation state of seawater with respect to the aragonite, high-Mg calcite (Mg/Ca > 0.04), and low-Mg calcite (Mg/Ca < 0.04) minerals from which marine calcifiers build their shells and skeletons. Notably, these polymorphs of CaCO3 have different solubilities in seawater: aragonite is more soluble than pure calcite, and the solubility of calcite increases with its Mg-content. Although much recent progress has been made investigating the effects of CO2-induced ocean acidification on rates of biological calcification, considerable uncertainties remain regarding impacts on shell/skeletal polymorph mineralogy. To investigate this subject, eighteen species of marine calcifiers were reared for 60-days in seawater bubbled with air-CO2 mixtures of 409 ± 6, 606 ± 7, 903 ± 12, and 2856 ± 54 ppm pCO2, yielding aragonite saturation states of 2.5 ± 0.4, 2.0 ± 0.4, 1.5 ± 0.3, and 0.7 ± 0.2. Calcite/aragonite ratios within bimineralic calcifiers increased with increasing pCO2, but were invariant within monomineralic calcifiers. Calcite Mg/Ca ratios (Mg/CaC) also varied with atmospheric pCO2 for two of the five high-Mg-calcite-producing organisms, but not for the low-Mg-calcite-producing organisms. These results suggest that shell/skeletal mineralogy within some-but not all-marine calcifiers will change as atmospheric pCO2 continues rising as a result of fossil fuel combustion and deforestation. Paleoceanographic reconstructions of seawater Mg/Ca, temperature, and salinity from the Mg/CaC of well-preserved calcitic marine fossils may also be improved by accounting for the effects of paleo-atmospheric pCO2 on skeletal Mg-fractionation.

International Capital Flows and Monetary Policy Spillovers

This dissertation examines the drivers and implications of international capital flows. The overarching motivation is the observation that countries not at the centre of global financial markets are subject to considerable spillovers from centre countries, notably from their monetary policy. I present new empirical evidence on the determinants of the observed patterns of international capital flows and monetary policy spillovers, and study their effect on both financial markets and the real economy. In Chapter 2 I provide evidence on the determinants of a puzzling negative correlation observed between productivity growth and net capital inflows to developing and emerging market economies (EMEs) since 1980. By disaggregating net capital inflows into their gross components, I show that this negative correlation is explained by capital outflows related to purchases of very liquid assets from the fastest growing countries. My results suggest a desire for international portfolio diversification in liquid assets by fast growing countries is driving much of the original puzzle. In the reminder of my dissertation I pivot to study the foreign characteristics that drive international capital flows and monetary policy spillovers, with a particular focus on the role of unconventional monetary policy in the United States (U.S.). In Chapter 3 I show that a significant portion of the heterogeneity in EMEs' asset price adjustment following the quantitative easing operations by the Federal Reserve (the Fed) during 2008-2014 can be explained by the degree of bilateral capital market frictions between these countries and the U.S. This is true even after accounting for capital controls, exchange rate regimes, and domestic monetary policies. Chapter 4, co-authored with Michal Ksawery Popiel, studies unconventional monetary policy in a small open economy, looking specifically at the case of Canada since the global financial crisis. We quantify the effect Canadian unconventional monetary policy shocks had on the real economy, while carefully controlling for and quantifying spillovers from U.S. unconventional monetary policy. Our results indicate that the Bank of Canada's unconventional monetary policy increased Canadian output significantly from 2009-2010, but that spillovers from the Fed's policy were even more important for increasing Canadian output after 2008.

Transplanting diglossia: attitudes towards Standard and Cypriot Greek among London’s Greek Cypriot community

The linguistic situation in Greek-speaking Cyprus has been traditionally described as a textbook case of diglossia à la Ferguson (1959) with Standard Modern Greek (SModGr) being labelled as the High variety and Cypriot Greek (CypGr), the regional ModGr variety of Cyprus, being labelled the Low variety (Arvaniti, 2011; Moschonas, 1996). More recently, however, it has been proposed that the linguistic repertoire available to speakers features an array of forms of CypGr, which is best described as a continuum ranging from basilectal to acrolectal varieties (Katsoyannou et al., 2006; Tsiplakou et al., 2006). The basilectal end encompasses low prestige varieties predominantly spoken in rural areas. The acrolectal end is occupied by the version of SModGr used in the public domain in Cyprus (Arvaniti, 2006/2010). SModGr is known to carry high prestige in Cyprus. Speakers of CypGr describe speakers of the standard as more attractive, more intelligent, more interesting and more educated than speakers of the Cypriot dialect (Papapavlou, 1998). In this paper, I explore the relation between SModGr and CypGr in a diasporic setting, namely, the Greek Cypriot community of London. The United Kingdom is home to a sizeable Greek Cypriot community, whose population is presently estimated to fall between 200,000 and 300,000 individuals (Christodoulou-Pipis, 1991; National Federation of Cypriots in the UK). Similarly to the Cyprus homeland, the members of the Greek Cypriot parikia (‘community’) share a rich linguistic repertoire, which, in addition to varieties of Greek, crucially includes English. As is often the case with diasporas, the parikia does not form a homogeneous speech community in that not all of its members have an equally good command of Greek or even English. Rather, different types of monolingual and bilingual speakers are found including a large number of heritage speakers in the sense of Benmamoun et al. (2013), Montrul (2008, 2015) and Polinsky & Kagan (2007). Twenty British-born heritage speakers of CypGr were interviewed on their attitudes towards the different varieties of Greek. Results indicate that the prestige relation between SModGr and CypGr that holds in Cyprus has been transplanted to the parikia. SModGr is widely perceived as the prestigious variety and is described in positive terms (‘correct’, ‘proper’). The use of CypGr, on the other hand, enjoys covert prestige: it is perceived as an index of solidarity and in-group membership but at the same time is also viewed by heritage speakers as reminiscent of the hardship and lack of education of the generation that brought CypGr to the UK. In certain cases, the use of CypGr by heritage speakers is actively discouraged by the first generation not only in the public domain but also in private domains such as the home. Active discouragement targets both lexical and grammatical variants that are traditionally associated with basilectal varieties of CypGr, and heritage language features, especially the adoption of morphologically adapted loanwords from English. References Arvaniti, Amalia. 2006/2010. Linguistic practices in Cyprus and the emergence of Cypriot Standard Greek. Mediterranean Language Review 17, 15–45. Benmamoun, Elabbas, Silvina Montrul & Maria Polinsky. 2013. Heritage languages and their speakers: opportunities and challenges for linguists. Theoretical Linguistics 39(3/4), 129–181. Christodoulou-Pipis, Irina. 1991. Greek Outside Greece: Language Use by Greek-Cypriots in Britain. Nicosia: Diaspora Books. Ferguson, Charles A. 1959. Diglossia. Word 15(2), 325–340. Katsoyannou, Marianna, Andreas Papapavlou, Pavlos Pavlou & Stavroula Tsiplakou. 2006. Didialektikes koinotites kai glossiko syneches: i periptosi tis kypriakis [Bidialectal communities and linguistic continuum: the case of Cypriot Greek]. In Mark Janse, Brian D. Joseph & Angela Ralli (eds.), Proceedings of the 2nd International Conference of Modern Greek Dialects and Linguistic Theory, Mytilene, Greece, 30 September – 3 October 2004, 156–171. Patras: University of Patras. Montrul, Silvina A. 2008. Incomplete Acquisition in Bilingualism: Re-examining the Age Factor. Amsterdam/Philadelphia: John Benjamins. Montrul, Silvina. 2015. The Acquisition of Heritage Languages. Cambridge: Cambridge University Press. Moschonas, Spiros. 1996. I glossiki dimorfia stin Kypro [Diglossia in Cyprus]. In “Ischyres” – “Astheneis” Glosses stin Evropaiki Enosi: Opseis tou glossikou igemonismou [“Strong” – “Weak” Languages in the European Union: Aspects of Linguistic Imperialism], 121–128. Thessaloniki: Kentro Ellinikis Glossas. Polinsky, Maria & Olga Kagan. 2007. Heritage languages: in the ‘wild’ and in the classroom. Languages and Linguistics Compass 1(5), 368–395. Tsiplakou, Stavroula, Andreas Papapavlou, Pavlos Pavlou & Marianna Katsoyannou. 2006. Levelling, koineization and their implications for bidialectism. In Frans L. Hinskens (Eds.), Language Variation – European Perspectives: Selected Papers from the Third International Conference on Language Variation in Europe (ICLaVE 3), Amsterdam, June 2005, 265–279. Amsterdam/Philadelphia: John Benjamins.

Late-career international migration and reproductive work. A comparison between Peruvian and Ukrainian women in the Southern Europe

Research on the relationship between reproductive work and women´s life trajectories including the experience of labour migration has mainly focused on the case of relatively young mothers who leave behind, or later re-join, their children. While it is true that most women migrate at a younger age, there are a significant number of cases of men and women who move abroad for labour purposes at a more advanced stage, undertaking a late-career migration. This is still an under-estimated and under-researched sub-field that uncovers a varied range of issues, including the global organization of reproductive work and the employment of migrant women as domestic workers late in their lives. By pooling the findings of two qualitative studies, this article focuses on Peruvian and Ukrainian women who seek employment in Spain and Italy when they are well into their forties, or older. A commonality the two groups of women share is that, independently of their level of education and professional experience, more often than not they end up as domestic and care workers. The article initially discusses the reasons for late-career female migration, taking into consideration the structural and personal determinants that have affected Peruvian and Ukrainian women’s careers in their countries of origin and settlement. After this, the focus is set on the characteristics of domestic employment at later life, on the impact on their current lives, including the transnational family organization, and on future labour and retirement prospects. Apart from an evaluation of objective working and living conditions, we discuss women’s personal impressions of being domestic workers in the context of their occupational experiences and family commitments. In this regard, women report varying levels of personal and professional satisfaction, as well as different patterns of continuity-discontinuity in their work and family lives, and of optimism towards the future. Divergences could be, to some extent, explained by the effect of migrants´ transnational social practices and policies of states.

Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial

BACKGROUND: In the previously reported ALSYMPCA trial in patients with castration-resistant prostate cancer and symptomatic bone metastases, overall survival was significantly longer in patients treated with radium-223 dichloride (radium-223) than in patients treated with placebo. In this study, we investigated safety and overall survival in radium-223 treated patients in an early access programme done after the ALSYMPCA study and before regulatory approval of radium-223.

METHODS: We did an international, prospective, interventional, open-label, single-arm, phase 3b study. Enrolled patients were aged 18 years or older with histologically or cytologically confirmed progressive bone-predominant metastatic castration-resistant prostate cancer with two or more skeletal metastases on imaging (with no restriction as to whether they were symptomatic or asymptomatic; without visceral disease but lymph node metastases were allowed). Patients received intravenous injections of radium-223, 50 kBq/kg (current recommendation 55 kBq/kg after implementation of National Institute of Standards and Technology update on April 18, 2016) every 4 weeks for up to six injections. Other concomitant anticancer therapies were allowed. Primary endpoints were safety and overall survival. The safety and efficacy analyses were done on all patients who received at least one dose of the study drug. The study has been completed, and we report the final analysis here. This study is registered with ClinicalTrials.gov, number NCT01618370, and the European Union Clinical Trials Register, EudraCT number 2012-000075-16.

FINDINGS: Between July 22, 2012, and Dec 19, 2013, 839 patients were enrolled from 113 sites in 14 countries. 696 patients received one or more doses of radium-223; 403 (58%) of these patients had all six planned injections. Any-grade treatment-emergent adverse events occurred in 523 (75%) of 696 patients; any-grade treatment-emergent adverse events deemed to be related to treatment were reported in 281 (40%) patients. The most common grade 3 or worse treatment-related treatment-emergent adverse events were anaemia in 32 (5%) patients, thrombocytopenia in 15 (2%) patients, neutropenia in ten (1%) patients, and leucopenia in nine (1%) patients. Any grade of serious adverse events were reported in 243 (35%) patients. Median follow-up was 7·5 months (IQR 5-11) and 210 deaths were reported; median overall survival was 16 months (95% CI 13-not available [NA]). In an exploratory analysis of overall survival with predefined factors, median overall survival was longer for: patients with baseline alkaline phosphatase concentration less than the upper limit of normal (ULN; median NA, 95% CI 16 months-NA) than for patients with an alkaline phosphatase concentration equal to or greater than the ULN (median 12 months, 11-15); patients with baseline haemoglobin levels 10 g/dL or greater (median 17 months, 14-NA) than for patients with haemoglobin levels less than 10 g/dL (median 10 months, 8-14); patients with a baseline Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (median NA, 17 months-NA) than for patients with an ECOG PS of 1 (median 13 months, 11-NA) or an ECOG PS of 2 or more (median 7 months, 5-11); and for patients with no reported baseline pain (median NA, 16 months-NA) than for those with mild pain (median 14 months, 13-NA) or moderate-severe pain (median 11 months, 9-13). Median overall survival was also longer in patients who received radium-223 plus abiraterone, enzalutamide, or both (median NA, 95% CI 16 months-NA) than in those who did not receive these agents (median 13 months, 12-16), and in patients who received radium-223 plus denosumab (median NA, 15 months-NA) than in patients who received radium-223 without denosumab (median 13 months, 12-NA).

INTERPRETATION: Our findings show that radium-223 can be safely combined with abiraterone or enzalutamide, which are now both part of the standard of care for patients with metastatic castration-resistant prostate cancer. Furthermore, our findings extend to patients who were asymptomatic at baseline, unlike those enrolled in the pivotal ALSYMPCA study. The findings of prolonged survival in patients treated with concomitant abiraterone, enzalutamide, or denosumab require confirmation in prospective randomised trials.

FUNDING: Pharmaceutical Division of Bayer.

Vocational Rehabilitation in Early Psychosis: Cluster Randomised Trial

Background Individual placement and support (IPS) is effective in helping patients return to work but is poorly implemented because of clinical ambivalence and fears of relapse. Aims To assess whether a motivational intervention (motivational interviewing) directed at clinical staff to address ambivalence about employment improved patients’ occupational outcomes. Method Two of four early intervention teams that already provided IPS were randomised to receive motivational interviewing training for clinicians, focused on attitudinal barriers to employment. The trial was registered with the International Standard Randomised Controlled Trial Register (ISRCTN71943786). Results Of 300 eligible participants, 159 consented to the research. Occupational outcomes were obtained for 134 patients (85%) at 12-month follow-up. More patients in the intervention teams than in the IPS-only teams achieved employment by 12 months (29/68 v. 12/66). A random effects logistic regression accounting for clustering by care coordinator, and adjusted for participants’ gender, ethnicity, educational and employment history and clinical status scores, confirmed superiority of the intervention (odds ratio = 4.3, 95% CI 1.5-16.6). Conclusions Employment outcomes were enhanced by addressing clinicians’ ambivalence about their patients returning to work.

Standard Essential Patent in Telecommunication Standard: United States and China Comparison

Thesis (Ph.D.)--University of Washington, 2016-08