Measurements of 5,6 orthoquinone, surrogate for presumed active primaquine metabolite 5-hydroxyprimaquine, in the urine of Cambodian adults

2022 ◽  
Author(s):  
Pattaraporn Vanachayangkul ◽  
Darapiseth Sea ◽  
Mariusz Wojnarski ◽  
Somethy Sok ◽  
Chanikarn Kodchakorn ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Pharmacokinetic Studies ◽  
Radical Cure ◽  
Active Metabolites ◽  
Urine Creatinine ◽  
The Us ◽  
Median Plasma ◽  
The Relationship ◽  
Intermediate Metabolizer ◽  
Reduced Activity

The active metabolites of primaquine, in particular 5-hydroxyprimaquine, likely responsible for clearance of dormant hypnozoites, are produced through the hepatic CYP450 2D6 (CYP2D6) enzymatic pathway. With the inherent instability of 5-hydroxyprimaquine, a stable surrogate, 5,6 orthoquinone, can now be detected and measured in the urine as part of primaquine pharmacokinetic studies. This study performed CYP450 2D6 genotyping and primaquine pharmacokinetic testing, to include urine 5,6 orthoquinone, in 27 healthy adult Cambodians, as a preliminary step to prepare for future clinical studies assessing primaquine efficacy for Plasmodium vivax infections. The CYP2D6 *10 reduced activity allele was found in 57% of volunteers, and the CYP2D6 genotypes were dominated by *1/*10 (33%) and *10/*10 (30%). Predicted phenotypes were evenly split between Normal Metabolizer (NM) and Intermediate Metabolizer (IM) except one volunteer with a gene duplication and unclear phenotype, classifying as either IM or NM. Median plasma PQ area under the curve (AUC) was lower in the NM group (460 hr*ng/mL) compared to the IM group (561 hr*ng/mL), although not statistically significant. Similar to what has been found in the US study, no 5,6 orthoquinone was detected in the plasma. The urine creatinine-corrected 5,6 orthoquinone AUC in the NM group was almost three times higher than in the IM group, with peak measurements (T max ) at 4 hours. Although there is variation among individuals, future studies examining the relationship between the levels of urine 5,6 orthoquinone and primaquine radical cure efficacy could result in a metabolism biomarker predictive of radical cure.

The United States and the Iranian Nuclear Programme

2018 ◽  
Author(s):  
Steven Hurst
Keyword(s):  
United States ◽  
Decision Making ◽  
Domestic Politics ◽  
The United States ◽  
Nixon Administration ◽  
Comprehensive Plan ◽  
The Us ◽  
Nuclear Issue ◽  
The Relationship

The United States, Iran and the Bomb provides the first comprehensive analysis of the US-Iranian nuclear relationship from its origins through to the signing of the Joint Comprehensive Plan of Action (JCPOA) in 2015. Starting with the Nixon administration in the 1970s, it analyses the policies of successive US administrations toward the Iranian nuclear programme. Emphasizing the centrality of domestic politics to decision-making on both sides, it offers both an explanation of the evolution of the relationship and a critique of successive US administrations' efforts to halt the Iranian nuclear programme, with neither coercive measures nor inducements effectively applied. The book further argues that factional politics inside Iran played a crucial role in Iranian nuclear decision-making and that American policy tended to reinforce the position of Iranian hardliners and undermine that of those who were prepared to compromise on the nuclear issue. In the final chapter it demonstrates how President Obama's alterations to American strategy, accompanied by shifts in Iranian domestic politics, finally brought about the signing of the JCPOA in 2015.

From Competition to Cooperation: A History of Canada–US National Park Relations

2019 ◽  
Author(s):  
Terence Young ◽  
Alan MacEachern ◽  
Lary Dilsaver
Keyword(s):  
National Parks ◽  
National Park ◽  
The United States ◽  
The Us ◽  
Park Service ◽  
Settler Societies ◽  
History Of ◽  
Relationship Of ◽  
Flow Of Information ◽  
The Relationship

This essay explores the evolving international relationship of the two national park agencies that in 1968 began to offer joint training classes for protected-area managers from around the world. Within the British settler societies that dominated nineteenth century park-making, the United States’ National Park Service (NPS) and Canada’s National Parks Branch were the most closely linked and most frequently cooperative. Contrary to campfire myths and nationalist narratives, however, the relationship was not a one-way flow of information and motivation from the US to Canada. Indeed, the latter boasted a park bureaucracy before the NPS was established. The relationship of the two nations’ park leaders in the half century leading up to 1968 demonstrates the complexity of defining the influences on park management and its diffusion from one country to another.

THE EVOLUTION OF THE RELATIONSHIP BETWEEN THE US FINANCIAL ACCOUNTING STANDARDS BOARD AND THE INTERNATIONAL ACCOUNTING STANDARD SETTERS: 1973–2008

2012 ◽  
Vol 39 (1) ◽  
pp. 1-51 ◽  
Author(s):  
Robert J. Kirsch
Keyword(s):  
Accounting Standards ◽  
Financial Accounting ◽  
Working Relationships ◽  
International Accounting ◽  
International Accounting Standards ◽  
Financial Accounting Standards Board ◽  
Accounting Standard ◽  
Staff Members ◽  
The Us ◽  
The Relationship

ABSTRACT Utilizing archival materials as well as personal interviews and correspondence with personnel of the Financial Accounting Standards Board (FASB) and International Accounting Standards Committee/Board (IASC/B), including former Board chairmen and staff members, this paper examines the development of the working relationships between the FASB and the IASC/B from their earliest interactions in 1973 through the transformation of the IASC into the IASB and the Convergence Program rooted in the 2002 Norwalk Agreement up to 2008.

Conclusion

2017 ◽  
Author(s):  
Frédéric Grare
Keyword(s):  
United States ◽  
The United States ◽  
The Political ◽  
Slow Pace ◽  
Centre Of Gravity ◽  
The Us ◽  
The Future ◽  
Economic Interaction ◽  
The Asymmetry ◽  
The Relationship

India’s relationship with the United States remains crucial to its own objectives, but is also ambiguous. The asymmetry of power between the two countries is such that the relationship, if potentially useful, is not necessary for the United States while potentially risky for India. Moreover, the shift of the political centre of gravity of Asia — resulting from the growing rivalry between China and the US — is eroding the foundations of India’s policy in Asia, while prospects for greater economic interaction is limited by India’s slow pace of reforms. The future of India-US relations lies in their capacity to evolve a new quid pro quo in which the US will formulate its expectations in more realistic terms while India would assume a larger share of the burden of Asia’ security.

A University Education

2017 ◽  
Author(s):  
David Willetts
Keyword(s):  
Higher Education ◽  
Modern Society ◽  
University Education ◽  
Modern World ◽  
Controversial Issues ◽  
The Us ◽  
The Individual ◽  
The University ◽  
First Time ◽  
The Relationship

Universities have a crucial role in the modern world. In England, entrance to universities is by nation-wide competition which means English universities have an exceptional influence on schools--a striking theme of the book. This important book first investigates the university as an institution and then tracks the individual on their journey to and through university. In A University Education, David Willetts presents a compelling case for the ongoing importance of the university, both as one of the great institutions of modern society and as a transformational experience for the individual. The book also makes illuminating comparisons with higher education in other countries, especially the US and Germany. Drawing on his experience as UK Minister for Universities and Science from 2010 to 2014, the author offers a powerful account of the value of higher education and the case for more expansion. He covers controversial issues in which he was involved from access for disadvantaged students to the introduction of L9,000 fees. The final section addresses some of the big questions for the future, such as the the relationship between universities and business, especially in promoting innovation.. He argues that the two great contemporary trends of globalisation and technological innovation will both change the university significantly. This is an authoritative account of English universities setting them for the first time in their new legal and regulatory framework.

Archaeologists and the Dead

2016 ◽  
Keyword(s):  
Historical Context ◽  
Ethical Considerations ◽  
International Context ◽  
The Public ◽  
The Us ◽  
The Dead ◽  
The Many ◽  
The Uk ◽  
The Relationship ◽  
Experience Effect

This volume addresses the relationship between archaeologists and the dead, through the many dimensions of their relationships: in the field (through practical and legal issues), in the lab (through their analysis and interpretation), and in their written, visual and exhibitionary practice--disseminated to a variety of academic and public audiences. Written from a variety of perspectives, its authors address the experience, effect, ethical considerations, and cultural politics of working with mortuary archaeology. Whilst some papers reflect institutional or organizational approaches, others are more personal in their view: creating exciting and frank insights into contemporary issues that have hitherto often remained "unspoken" among the discipline. Reframing funerary archaeologists as "death-workers" of a kind, the contributors reflect on their own experience to provide both guidance and inspiration to future practitioners, arguing strongly that we have a central role to play in engaging the public with themes of mortality and commemoration, through the lens of the past. Spurred by the recent debates in the UK, papers from Scandinavia, Austria, Italy, the US, and the mid-Atlantic, frame these issues within a much wider international context that highlights the importance of cultural and historical context in which this work takes place.

The New Progressive Dilemma through the Lens of Comparative Welfare State and Party Research

2018 ◽  
Author(s):  
Dennis C. Spies
Keyword(s):  
Public Opinion ◽  
Political Parties ◽  
Welfare State ◽  
Voting Behavior ◽  
Attitudinal Change ◽  
Welfare Institutions ◽  
The Us ◽  
Social Expenditures ◽  
The Relationship ◽  
Cross National

The chapter summarizes the New Progressive Dilemma (NPD) debate, identifying three arguments from comparative welfare state and party research likely to be relevant to the relationship between immigration and welfare state retrenchment: public opinion, welfare institutions, and political parties. Alignment of anti-immigrant sentiments and welfare support varies considerably between countries, especially between the US and Europe, leading to different party incentives vis-à-vis welfare state retrenchment. The chapter introduces insights from comparative welfare state and party research to the debate, discussing inter alia, political parties in terms of welfare retrenchment, immigrants as a voter group, and cross-national variation of existing welfare institutions. It addresses the complex debates around attitudinal change caused by immigration, levels of welfare support, voting behavior, and social expenditures. Combining these strands of literature, a common theoretical framework is developed that is subsequently applied to both the US and Western European context.

The Historiography of Environmental History

2018 ◽  
Author(s):  
J. R. McNeill
Keyword(s):  
Climate Change ◽  
Environmental History ◽  
Industrial Pollution ◽  
Full Scale ◽  
Environmental Concerns ◽  
The Us ◽  
The World ◽  
History Of ◽  
The 1960S ◽  
The Relationship

This chapter discusses the emergence of environmental history, which developed in the context of the environmental concerns that began in the 1960s with worries about local industrial pollution, but which has since evolved into a full-scale global crisis of climate change. Environmental history is ‘the history of the relationship between human societies and the rest of nature’. It includes three chief areas of inquiry: the study of material environmental history, political and policy-related environmental history, and a form of environmental history which concerns what humans have thought, believed, written, and more rarely, painted, sculpted, sung, or danced that deals with the relationship between society and nature. Since 1980, environmental history has come to flourish in many corners of the world, and scholars everywhere have found models, approaches, and perspectives rather different from those developed for the US context.

Ascertaining an efficient eligibility cut-off for extended Medicare items for eating disorders

2021 ◽  
pp. 103985622110286
Author(s):  
Tracey Wade ◽  
Jamie-Lee Pennesi ◽  
Yuan Zhou
Keyword(s):  
Eating Disorders ◽  
Eating Disorder ◽  
False Positive Rate ◽  
Area Under The Curve ◽  
Rate Sensitivity ◽  
True Positive Rate ◽  
Eating Disorder Examination Questionnaire ◽  
Eating Disorder Examination ◽  
Positive Rate ◽  
The Relationship

Objective: Currently eligibility for expanded Medicare items for eating disorders (excluding anorexia nervosa) require a score ⩾ 3 on the 22-item Eating Disorder Examination-Questionnaire (EDE-Q). We compared these EDE-Q “cases” with continuous scores on a validated 7-item version of the EDE-Q (EDE-Q7) to identify an EDE-Q7 cut-off commensurate to 3 on the EDE-Q. Methods: We utilised EDE-Q scores of female university students ( N = 337) at risk of developing an eating disorder. We used a receiver operating characteristic (ROC) curve to assess the relationship between the true-positive rate (sensitivity) and the false-positive rate (1-specificity) of cases ⩾ 3. Results: The area under the curve showed outstanding discrimination of 0.94 (95% CI: .92–.97). We examined two specific cut-off points on the EDE-Q7, which included 100% and 87% of true cases, respectively. Conclusion: Given the EDE-Q cut-off for Medicare is used in conjunction with other criteria, we suggest using the more permissive EDE-Q7 cut-off (⩾2.5) to replace use of the EDE-Q cut-off (⩾3) in eligibility assessments.

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