Blockchain Papers

Miyoko Okamoto, Sithan Nhea, Hidechika Akashi, Leo Kawaguchi · 7 authors

The implementation of decentralization policies in the health sector of many developing countries has been a major issue in international health. The objectives were to focus on health sector reform, health financing system, and human resource development. However, less attention has been paid to the institutional capacity development of health systems. In this paper, institutional capacity refers to the abilities of organizations to make effective management in order to build local capacity and to achieve goals with local ownership. The aims of this paper were to explore the developmental process of districts institutional capacity by assistance of an NGO in Cambodia, and to identify the key factors influencing this development. We chose five operational districts (ODs) and two of them were contracted to NGO for management assistance. We conducted semi-structured in-depth interview to 17 managers and 16 key informant interviews. For analysis, we used qualitative analysis based on a grounded theory approach to clarify a conceptual framework for understanding management practices at district health institutions. There is a 4-stage capacity developmental process at the district-level institution. Supportive supervision and widening of decision-making authority were identified as key factors for sustainable institutional capacity development. They have complementary function each other. External agencies such as NGOs can use these key factors to develop local management capacities, and also this capacity development can be done internally within institutions such as OD health offices and by upper authorities such as the PHD.

Mark Zachary Taylor

Recent research has shown how federalism affects health care finance, health care reform, and health policy innovation. The purpose of this article is to extend this research program to study the linkages between federalism and technological change. It does so using comparative case studies spanning five countries to examine innovation and diffusion of two blood technologies-enzyme-linked immunosorbent assays (ELISA blood tests) and heat treatment-in response to the threat to the blood supply posed by HIV during the 1980s. Prior research has produced three contradictory models of the federalism-innovation relationship. This article attempts to resolve these contradictions, posits new hypotheses, and highlights sources of omitted variable bias that have important implications for understanding technological change. The case studies show that overall decentralization, rather than federalism alone, aids technological progress by allowing its supporters to "venue shop" around political resistance. Decentralization also makes the state less vulnerable to capture by status-quo interest groups. Moreover, political decentralization may have a positive effect on technological diffusion, but a far weaker effect on innovation. Thus, prior research that conflates these two effects should be revisited.

John W.P. Veugelers

Reviewed by: Max Weber’s ‘Objectivity’ Reconsidered John Veugelers (bio) Laurence H. McFalls. Max Weber’s ‘Objectivity’ Reconsidered. University of Toronto Press. viii, 390. $75.00 ‘All the analysis of infinite reality which the finite human mind can conduct rests on the tacit assumption that only a finite portion of this reality constitutes the object of scientific investigation, and that only it is “important” in the sense of being “worthy of being known.” But what are the criteria by which this segment is selected?’ These words come from ‘The “Objectivity” of Knowledge in Social Science and Social Policy’ by the great sociologist Max Weber. Like his better-known The Protestant Ethic and the Spirit of Capitalism, this essay was published in 1904, when Weber became the co-editor of the Archiv für Sozialwissenschaft und Sozialpolitik. His practical task was to lay out the [End Page 327] standards by which the journal’s editors would judge submissions. In doing so he entered the Methodenstreit, the debate among German historians and political economists over the goals and methods of the human sciences. The advocates of a scientistic and law-seeking approach (the followers of the Manchester school) argued against those for whom the uniqueness of historical individuals and events meant that knowledge could only be particular (and certainly not valid ‘across cases’). Weber disagreed with both sides. To stake out an alternative, his essay promotes the concept of the ideal type, analyzes the relationship between knower and known, defines the realm in which values belong in social science, and elaborates upon the kind of knowledge toward which social science might legitimately aspire. In my opinion, Weber took an overly restrictive view of the possibility of arriving at non-trivial generalizations that hold under specific social and historical conditions. With its mix of discernment, depth, and passion, his essay remains riveting nonetheless, and even today we can gain much from reading it. The hundredth anniversary of the essay’s publication provided the occasion for the conference that gave birth to this edited volume. Questions its fourteen chapters address include: What does objectivity mean for Weber? How do his ideas relate to those of others (Durkheim, Mannheim, Gramsci, Parsons, Wittgenstein, Winch, Kuhn)? In his substantive research, did Weber follow his own prescriptions on method? What are the advantages or disadvantages of applying a Weberian approach to the study of European as well as non-European societies? In general the answers this volume gives to the first two questions are insightful. The opening chapter by John Drysdale argues convincingly that Weber’s essay says more about what objectivity is not than what it is. Yet Weber does cast doubt on the assumption that the knower (subject) can know anything without also holding presuppositions about the known (object). Further, we can learn what Weber means by objectivity (as well as ideal types, historical individuals, and cultural significance) when he puts these concepts to work in The Protestant Ethic and the Spirit of Capitalism. John B. Gunnell’s chapter draws on Kuhn to show that Weber’s argument that social science can provide valid knowledge rests on the implicit notion that the categories used by social scientists and those they study are different. Oddly, Gunnell does not really develop the Kuhnian insight that Weber’s portrait of how science works (in the selection of problems, methods, evidence, and rules of proof) is fixed on the practices of the individual researcher and thus quite unsociological. Just as strange in Weber’s essay is the neglect of power. Typically his sociology gives much attention to social conflict. In the essay on [End Page 328] objectivity, however, Weber argues that knowledge arrived at impartially can help policy makers to make responsible decisions. Drawing on Mannheim and Gramsci, Peter Breiner’s chapter points out practical limits to the implementation of ‘impartial knowledge’: the barriers put up by incommensurate ideologies and antagonistic political forces. Among other outstanding chapters, that by Catherine Colliot-Thélène provides an adept comparison of Weber and Durkheim (though contemporaries working to institutionalize sociology in their respective countries, apparently they never read each other’s work). And the chapter by Jeffrey Kopstein poses a riddle. Elsewhere...

Elena Del Rey, Miguel-Ángel López-García

In OLG economies with life-cycle saving and exogenous growth, competitive equilibria in general fail to achieve optimality because individuals accumulate amounts of physical capital that differ from the one that maximizes welfare along a balanced growth path (the Golden Rule). With human capital, a second potential source of departure from optimality arises, related to education decisions. We propose to recover the Golden Rule of physical and also human capital accumu- lation. We characterize the optimal policy to decentralize the Golden Rule balanced growth path when there are no constraints for individuals to finance their education investments, and show that it involves education taxes. Also, when the government subsidizes the repayment of education loans, optimal pensions are positive

Eric Ayeh

Zero-knowledge proofs protocols are effective interactive methods to prove a node's identity without disclosing any additional information other than the veracity of the proof. They are implementable in several ways. In this thesis, I investigate the graph isomorphism based zero-knowledge proofs protocol. My experiments and analyses suggest that graph isomorphism can easily be solved for many types of graphs and hence is not an ideal solution for implementing ZKP.

Regina Birner, Kristin Davis, John Pender, Ephraim Nkonya · 11 authors

The article provides a conceptual framework and discusses research methods for analyzing pluralistic agricultural advisory services. The framework can also assist policy-makers in identifying reform options. It addresses the following question: Which forms of providing and financing agricultural advisory services work best in which situation? The framework ‘disentangles’ agricultural advisory services by distinguishing between (1) governance structures, (2) capacity, (3) management, and (4) advisory methods. The framework suggests an impact chain approach to analyze the performance and impact of agricultural advisory services and discusses theoretical and empirical research methods that can be used when applying the framework. The framework shows that reforms of agricultural advisory services can combine different reform elements—such as decentralization, contracting out, using new advisory methods, and changing the management style—in different ways so as to best fit local circumstances. Using a New Institutional Economics approach (transaction costs approach), the article shows that the following sets of contextual factors need to be considered in this regard: the policy environment; the capacity of potential service providers; the type of production systems and market access of farm households; and the characteristics of local communities. The framework can be used to develop assessment tools for agricultural advisory services, to inform processes of reforming of agricultural advisory services and to guide inter-disciplinary research. The framework is unique in combining the insights from different disciplines, which have, so far, been treated separately in the literature. The framework can help policy-makers and analysts to move from ‘ideological’ discussions on reform models to an evidence-based ‘best fit’ approach.

Val Burris

No abstract is available for this record.

Chang‐Hwan Lee, Byong‐Duk Rhee

No abstract is available for this record.

Frank C. Day, David L. Schriger

Discussion Points1Cruz et al1Cruz C.O. Meshberg E.G. Shofer F.S. et al.Interrater reliability and accuracy of clinicians and trained research assistants performing prospective data collection in emergency department patients with potential acute coronary syndrome.Ann Emerg Med. 2009; 54: 1-7Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar contains 2 parts, a comparison of the values gathered by trained research assistants and physicians about historical information in chest pain patients and the comparison of these participants' recordings with a “correct” value for each item.A. For each part, indicate whether the authors are studying reliability or validity and explain the difference between these concepts.B. What did the authors use as their criterion standard for the validity analysis?C. What are potential problems with their method of defining the criterion (gold) standard? Can you think of alternative approaches?D. The authors report crude agreement and interquartile range for their validity analysis. What part of a distribution is described by the interquartile range? List other statistics used to describe the validity of a measure and why they might be preferable to reporting crude agreement.2Tabled 1MD Recorded “Yes”MD Recorded “No”TotalRA recorded yes1176123RA recorded no18220Total1358143MD, Medical doctor; RA, research assistant. Open table in a new tab A. Calculate the crude percentage agreement for this table. What is the range of possible values for percentage agreement?B. Calculate Cohen's κ for this table. What is the formula for κ for raters making a binary assessment (eg, yes/no or true/false)? Discuss the purpose of Cohen's κ, its range, and the interpretations of key values such as –1, 0, and 1.C. What other measures can be used to measure reliability for binary, categorical, and continuous data? 3Cruz et al quote the oft-cited Landis and Koch2Landis J.R. Koch G.C. The measurement of observer agreement for categorical data.Biometrics. 1977; 33: 159-174Crossref PubMed Scopus (49675) Google Scholar article stating that a κ of “less than 0.2 represents poor agreement; 0.21 to 0.40, fair agreement; 0.41 to 0.60, moderate agreement; 0.61 to 0.80, good agreement; and 0.81 to 1.00, excellent agreement.” Consider studies of the agreement of airline pilots deciding whether it is safe to land and psychologists deciding whether interviewees have type A or type B personalities. the studies the κ the by Landis and Koch be 2 are in of a and to such as is a a or by a in the for and in the for are and the are to a for each that they percentage agreement is and κ is of are and are that the is the for a the the this the percentage agreement and κ for the the of the are and of the are by the of the are and of the are by the the are and of the are by the and of the are and of the are by the Discuss the of percentage agreement and κ in these Consider the 2 and percentage agreement and κ for is κ the What this that the table the described and that that to 2 in the raters are that are and the raters are that be with with or in with each of κ the in these 2 the of κ, that such that and or are for the and percentage agreement and κ for these is the measure for Consider the of the raters in the in this be reliability is might this be the percentage agreement κ for the in of et The are to indicate the in the and 2 Open table in a new tab A. in the table are with the the pain it to the it to the it to the for these Can you explain why these have percentage agreement you is the the Can you the between the of the in the table and the to κ percentage the problems with percentage agreement and κ in these you think it be the in the of each table of reporting the percentage agreement or et al contains 2 parts, a comparison of the values gathered by trained research assistants and physicians historical information in chest pain and the comparison of these participants' recordings with a “correct” value for each For each part, indicate whether the authors are studying reliability or validity and explain the difference between these part is assessment of and the is assessment of The between reliability and validity is the that the in a that a a The reliability of a to the agreement the the or assessment of validity a observer a or the criterion standard is to be validity studies report the of the observer statistics such as and or reliability such as percentage agreement or What did the authors use as their criterion standard for the validity the and the research it is that their is they a research the of the 2 is What are potential problems with their method of defining the standard? Can you think of alternative a standard for this is For can be 2 the and is For a you have pain in the might that is a for in the is a might that is its the with is the criterion standard for this the the have or the the information The of is that have to the emergency have the of reporting part of a to their and the the a be or the other of the physicians the in a that to the or or in the a the the or are or whether they are to the and the patients be in or to the authors have to the in the research and each and the of to a in accuracy with The authors report crude agreement and interquartile range for their validity analysis. What part of a distribution is described by the interquartile range? List other statistics used to describe the validity of a measure and why they might be preferable to reporting crude interquartile range to the of a of is a that represents the the to the this is the and the the can be by the to the that a distribution the is used to these The is the the the and the the The is the difference between the and is a by than the range of a and it is data are in the of a the and are to and and the the or you the to the and you the or a to in the research and did the authors report the percentage agreement with the “correct” by the criterion agreement is a for a reliability is the to describe this validity assessment of a observer with a criterion that are to a validity report statistics such as and or reliability such as percentage agreement or percentage agreement is a to report Consider the table for the the of the chest pain or 1MD Recorded “Yes”MD Recorded “No”TotalRA recorded recorded Open table in a new tab Calculate the crude percentage agreement for this table. What is the range of possible values for percentage 2 and 2 crude percentage agreement for this table is agreement can range between and Calculate Cohen's κ for this table. What is the formula for κ for raters making a binary assessment (eg, yes/no or true/false)? 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Koch G.C. 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The of a with data that the are as in the to as agreement and κ a percentage that the in κ the in of the et al article have to with the of the than of the of in the of the are to have of the reliability of the the problems with percentage agreement and κ in these you think it be the in the of each of reporting the percentage agreement or that this of the and that can a table data is to a reliability such as of reporting the reliability data than percentage agreement or information in it is to in the Discussion Points1Cruz et al1Cruz C.O. Meshberg E.G. Shofer F.S. et al.Interrater reliability and accuracy of clinicians and trained research assistants performing prospective data collection in emergency department patients with potential acute coronary syndrome.Ann Emerg Med. 2009; 54: 1-7Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar contains 2 parts, a comparison of the values gathered by trained research assistants and physicians about historical information in chest pain patients and the comparison of these participants' recordings with a “correct” value for each item.A. For each part, indicate whether the authors are studying reliability or validity and explain the difference between these concepts.B. What did the authors use as their criterion standard for the validity analysis?C. What are potential problems with their method of defining the criterion (gold) standard? Can you think of alternative approaches?D. The authors report crude agreement and interquartile range for their validity analysis. What part of a distribution is described by the interquartile range? List other statistics used to describe the validity of a measure and why they might be preferable to reporting crude agreement.2Tabled 1MD Recorded “Yes”MD Recorded “No”TotalRA recorded yes1176123RA recorded no18220Total1358143MD, Medical doctor; RA, research assistant. Open table in a new tab A. Calculate the crude percentage agreement for this table. What is the range of possible values for percentage agreement?B. Calculate Cohen's κ for this table. What is the formula for κ for raters making a binary assessment (eg, yes/no or true/false)? Discuss the purpose of Cohen's κ, its range, and the interpretations of key values such as –1, 0, and 1.C. What other measures can be used to measure reliability for binary, categorical, and continuous data? 3Cruz et al quote the oft-cited Landis and Koch2Landis J.R. Koch G.C. The measurement of observer agreement for categorical data.Biometrics. 1977; 33: 159-174Crossref PubMed Scopus (49675) Google Scholar article stating that a κ of “less than 0.2 represents poor agreement; 0.21 to 0.40, fair agreement; 0.41 to 0.60, moderate agreement; 0.61 to 0.80, good agreement; and 0.81 to 1.00, excellent agreement.” Consider studies of the agreement of airline pilots deciding whether it is safe to land and psychologists deciding whether interviewees have type A or type B personalities. the studies the κ the by Landis and Koch be 2 are in of a and to such as is a a or by a in the for and in the for are and the are to a for each that they percentage agreement is and κ is of are and are that the is the for a the the this the percentage agreement and κ for the the of the are and of the are by the of the are and of the are by the the are and of the are by the and of the are and of the are by the Discuss the of percentage agreement and κ in these Consider the 2 and percentage agreement and κ for is κ the What this that the table the described and that that to 2 in the raters are that are and the raters are that be with with or in with each of κ the in these 2 the of κ, that such that and or are for the and percentage agreement and κ for these is the measure for Consider the of the raters in the in this be reliability is might this be the percentage agreement κ for the in of et The are to indicate the in the and 2 Open table in a new tab A. in the table are with the the pain it to the it to the it to the for these Can you explain why these have percentage agreement you is the the Can you the between the of the in the table and the to κ percentage the problems with percentage agreement and κ in these you think it be the in the of each table of reporting the percentage agreement or et al1Cruz C.O. Meshberg E.G. Shofer F.S. et al.Interrater reliability and accuracy of clinicians and trained research assistants performing prospective data collection in emergency department patients with potential acute coronary syndrome.Ann Emerg Med. 2009; 54: 1-7Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar contains 2 parts, a comparison of the values gathered by trained research assistants and physicians about historical information in chest pain patients and the comparison of these participants' recordings with a “correct” value for each item.A. For each part, indicate whether the authors are studying reliability or validity and explain the difference between these concepts.B. What did the authors use as their criterion standard for the validity analysis?C. What are potential problems with their method of defining the criterion (gold) standard? Can you think of alternative approaches?D. The authors report crude agreement and interquartile range for their validity analysis. What part of a distribution is described by the interquartile range? List other statistics used to describe the validity of a measure and why they might be preferable to reporting crude agreement.2Tabled 1MD Recorded “Yes”MD Recorded “No”TotalRA recorded yes1176123RA recorded no18220Total1358143MD, Medical doctor; RA, research assistant. Open table in a new tab A. Calculate the crude percentage agreement for this table. What is the range of possible values for percentage agreement?B. Calculate Cohen's κ for this table. What is the formula for κ for raters making a binary assessment (eg, yes/no or true/false)? Discuss the purpose of Cohen's κ, its range, and the interpretations of key values such as –1, 0, and 1.C. What other measures can be used to measure reliability for binary, categorical, and continuous data? 3Cruz et al quote the oft-cited Landis and Koch2Landis J.R. Koch G.C. The measurement of observer agreement for categorical data.Biometrics. 1977; 33: 159-174Crossref PubMed Scopus (49675) Google Scholar article stating that a κ of “less than 0.2 represents poor agreement; 0.21 to 0.40, fair agreement; 0.41 to 0.60, moderate agreement; 0.61 to 0.80, good agreement; and 0.81 to 1.00, excellent agreement.” Consider studies of the agreement of airline pilots deciding whether it is safe to land and psychologists deciding whether interviewees have type A or type B personalities. the studies the κ the by Landis and Koch be 2 are in of a and to such as is a a or by a in the for and in the for are and the are to a for each that they percentage agreement is and κ is of are and are that the is the for a the the this the percentage agreement and κ for the the of the are and of the are by the of the are and of the are by the the are and of the are by the and of the are and of the are by the Discuss the of percentage agreement and κ in these Consider the 2 and percentage agreement and κ for is κ the What this that the table the described and that that to 2 in the raters are that are and the raters are that be with with or in with each of κ the in these 2 the of κ, that such that and or are for the and Calculate percentage agreement and κ for these is the measure for Consider the of the raters in the in this be reliability is might this be the percentage agreement κ for the in of et The are to indicate the in the and 2 Open table in a new tab A. in the table are with the the pain it to the it to the it to the for these Can you explain why these have percentage agreement you is the the Can you the between the of the in the table and the to κ percentage the problems with percentage agreement and κ in these you think it be the in the of each table of reporting the percentage agreement or et al contains 2 parts, a comparison of the values gathered by trained research assistants and physicians historical information in chest pain and the comparison of these participants' recordings with a “correct” value for each For each part, indicate whether the authors are studying reliability or validity and explain the difference between these part is assessment of and the is assessment of The between reliability and validity is the that the in a that a a The reliability of a to the agreement the the or assessment of validity a observer a or the criterion standard is to be validity studies report the of the observer statistics such as and or reliability such as percentage agreement or What did the authors use as their criterion standard for the validity the and the research it is that their is they a research the of the 2 is What are potential problems with their method of defining the standard? Can you think of alternative a standard for this is For can be 2 the and is For a you have pain in the might that is a for in the is a might that is its the with is the criterion standard for this the the have or the the information The of is that have to the emergency have the of reporting part of a to their and the the a be or the other of the physicians the in a that to the or or in the a the the or are or whether they are to the and the patients be in or to the authors have to the in the research and each and the of to a in accuracy with The authors report crude agreement and interquartile range for their validity analysis. What part of a distribution is described by the interquartile range? List other statistics used to describe the validity of a measure and why they might be preferable to reporting crude interquartile range to the of a of is a that represents the the to the this is the and the the can be by the to the that a distribution the is used to these The is the the the and the the The is the difference between the and is a by than the range of a and it is data are in the of a the and are to and and the the or you the to the and you the or a to in the research and did the authors report the percentage agreement with the “correct” by the criterion agreement is a for a reliability is the to describe this validity assessment of a observer with a criterion that are to a validity report statistics such as and or reliability such as percentage agreement or et al contains 2 parts, a comparison of the values gathered by trained research assistants and physicians historical information in chest pain and the comparison of these participants' recordings with a “correct” value for each For each part, indicate whether the authors are studying reliability or validity and explain the difference between these The part is assessment of and the is assessment of The between reliability and validity is the that the in a that a a The reliability of a to the agreement the the or assessment of validity a observer a or the criterion standard is to be validity studies report the of the observer statistics such as and or reliability such as percentage agreement or What did the authors use as their criterion standard for the validity the and the research it is that their is they a research the of the 2 is What are potential problems with their method of defining the standard? Can you think of alternative a standard for this is For can be 2 the and is For a you have pain in the might that is a for in the is a might that is its the with What is the criterion standard for this the the have or the the information The of is that have to the emergency have the of reporting part of a to their and the the a be or the other of the physicians the in a that to the or or in the a the the or are or whether they are to the and the patients be in or to A the authors have to the in the research and each and the of to a

VICTOR STANGO, JONATHAN ZINMAN

ABSTRACT Exponential growth bias is the pervasive tendency to linearize exponential functions when assessing them intuitively. We show that exponential growth bias can explain two stylized facts in household finance: the tendency to underestimate an interest rate given other loan terms, and the tendency to underestimate a future value given other investment terms. Bias matters empirically: More‐biased households borrow more, save less, favor shorter maturities, and use and benefit more from financial advice, conditional on a rich set of household characteristics. There is little evidence that our measure of exponential growth bias merely proxies for broader financial sophistication.

Tim Leiner, Walter Kucharczyk

“Bad times have a scientific value. These are occasions a good learner would not miss” Ralph Waldo Emerson (1803–1882) MRI contrast agents have been routinely used to enhance various structures, organs and lesions in the body for over 20 years now. There is strong evidence that these agents are highly efficacious, and routine clinical practice seems unthinkable without them. Almost all MR contrast agents are based on chelated heavy metals from the lanthanide group of elements, mainly gadolinium (Gd3+). Gadolinium is a rare earth metal that is known to be highly toxic in the free, unchelated form. However, when caged in a chelating molecule (from the Greek “χηλαι”, meaning “lobster claw”), gadolinium chelates can be safely administered by means of intravenous injection because the kidneys rapidly excrete them. Since the late 1980s, many toxicological and pharmacokinetics studies have been conducted by the major contrast vendors with various gadolinium-based contrast agents (GBCA). In all of these studies an extremely favorable safety profile was found. Therefore, the recent discovery of the association between administration of GBCA and nephrogenic systemic fibrosis (NSF) came as a surprise to almost everyone involved, although in retrospect maybe we should not have been so surprised. Perhaps after giving GBCA to over 200 million patients and rarely experiencing any adverse effects of any kind, we thought we could administer these drugs with impunity. On the other hand, would we not expect some adverse effects eventually to surface? We were injecting a heavy metal (albeit as a chelate), in ever larger doses, often multiple times, and often in patients with severely compromised renal excretion, knowing that these agents were primarily excreted by the kidneys. NSF is a rare, idiopathic systemic fibrosing disorder and is characterized clinically by pain, dermopathy, and joint contractures. NSF affects the skin, skeletal muscle, esophagus, lungs, heart, and kidneys. The first suggestion of the link between GBCA and NSF by Grobner et al. 3 years ago (1), sparked intense interest in this subject, illustrating just how important MR contrast media are today. It is now clear that NSF is a condition that almost exclusively affects patients with severely limited renal function. However, despite the deluge of publications on this subject—as of October 9, 2009, there were over 438 publications available on PubMed—surprisingly little is known about the exact pathogenesis of the disease, and who exactly is at risk for developing the disease. The discovery of NSF has been unfortunate for patients, and particularly patients with acute or chronic kidney disease (CKD) with severely impaired renal function. Worldwide, regulatory agencies have issued warnings on the use of GBCA in patients with severe CKD, which has led to a virtual cessation of use of contrast-enhanced MRI in this vulnerable patient group. Patients with CKD are a difficult population for the imaging community. MRI has always been and remains of high value in this patient group, because it is well known that administration of iodinated contrast agents is contraindicated, especially in the presence of residual renal function. Because of all the attention NSF has attracted, many clinicians are now ordering CT examinations instead of MRI. Many radiologists have experienced situations in their own practices where contrast-enhanced MRI examinations on their patients have been substituted with contrast-enhanced CT because of fear of NSF with GBCA-MRI only to have these patients go on to develop renal failure due to contrast induced nephropathy (CIN). While the desire to avoid NSF is understandable, care should be taken that contrast-enhanced MRI is not withheld in more patients than absolutely necessary. Paradoxically, the current FDA advice to only give GBCA to patients with estimated glomerular filtration rates (eGFR) greater than 60 mL/min/1.73 m2 may do more harm than good as there is no evidence of NSF occurring in patients with eGFR >30 mL/min/1.73 m2. The FDA guidelines can lead to patients in the eGFR 30–60 mL/min group being exposed to the high risk for negative effects from the administration of iodinated contrast agents, even though they have a negligible risk for development of NSF. Furthermore, whereas the FDA regards all GBCA as having an equal risk for inducing NSF, the FDA guidelines take no account of the chemical structure of the compound, and especially of the kinetic stability, which seems to be an important factor to consider. To date, no unequivocal NSF cases have been reported in patients who exclusively received macrocyclic agents with high kinetic stability, although some reports have suggested this possibility (2) . It is indeed highly likely that there is a relation between GBCA and NSF. The incidence of biopsy-confirmed NSF cases has dropped to nearly zero after the FDA warning and the institution of similar measures by the European Medicines Agency and similar regulatory bodies in other parts of the world. There have been no cases of NSF with onset after August 2008 reported by any of the GBCA vendors. Convincing proof is lacking that NSF can develop without administration of GBCA. NSF only occurs in patients with severe renal impairment (eGFR < 30). The few cases of NSF in cases with eGFR > 30 have been in situations of acute renal failure where the GFR was decreasing rapidly and did not accurately reflect renal excretory function (4, 5). Accumulating evidence suggests that GBCA with low kinetic stability confers a higher risk for NSF (4, 5). No unequivocal NSF cases have been reported after sole administration of GBCA with high kinetic stability. Higher cumulative doses of low kinetic stability GBCA confer a higher risk for NSF in patients with severely impaired renal function (6-8). Risk is relative, not absolute. Not only is the risk of NSF with GBCA-MRI small compared with the risk of CIN with iodinated CT, but also with risk of severe allergic reactions with iodine and allergic reactions with GBCA. The concern about NSF has masked our concerns for GBCA's other potential adverse effects. A survey of major American centers published in 1999 by Murphy et al indicated an incidence of severe allergic reactions to GBCA of approximately 20 cases per million doses administered (9). This is approximately 10-fold greater than the incidence of NSF. And what of the risk of making an incorrect diagnosis because the most appropriate imaging study was not done? Why do some patients with severely impaired renal function get NSF, whereas others, with similar degrees of impairment, do not? In fact, the vast majority of patients with severely impaired renal function do not get NSF, even when administered a high dose of low kinetic stability GBCA. This remains one of the most puzzling questions in the NSF saga. Which patients need to be screened for renal disease, and what is the safest and most cost-effective way to do this? Is a questionnaire sufficient? Or does every patient need to have their creatinine measured before a contrast-enhanced MRI examination can be performed? Or should laboratory screening only apply to certain subgroups of patients? Is the class of macrocyclic GBCA inert regardless of renal function, and can they be administered safely in patients with stage 4 and 5 CKD without causing NSF? At what level of renal function do the risks for NSF outweigh the risk for complications associated with administration of iodinated contrast agents? In other words: Is the newest generation of iodinated contrast agents safe or unsafe in patients with CKD? Can these agents be administered safely? In this special issue of the Journal of Magnetic Resonance Imaging, we present a series of review articles with the aim of summarizing the current knowledge about NSF in relation to administration of GBCA, and to answer some of the questions posed above. The issue begins with a summary of Dr. Jeff Weinreb's excellent keynote lecture as given at the 17th annual meeting of the ISMRM in May of this year (10). Subsequent articles cover a wide variety of related topics, ranging from a basic primer on gadolinium chemistry (11), the role of thermodynamic and kinetic parameters in gadolinium chelate stability (12), the biodistribution of GBCA, including gadolinium deposition (13), and biological effector mechanisms (14-16), to the clinical spectrum of NSF (17), to practical insights on measurement of renal function (18) as well as a review on how to remove gadolinium by dialysis (19). We present current guidelines for injection of GBCA as used in the United States, Canada, Europe (20) and Japan (21). Furthermore, risk factors for NSF are reviewed (22), and NSF is discussed in the context of renovascular (23) and liver disease (24). The issue of relative risk of NSF versus CIN is addressed in the excellent review by Martin and other experts on this topic (25). Finally, retrospective reviews of data from China (26) and the United States (27) confirm the safety of low-dose contrast-enhanced MRI, even in patients with renal impairment. It is our sincere hope that the material selected for this special issue will help with the further understanding of the relationship between the administration of GBCA and the development of NSF, and that the material in this issue will form the basis for further research and subsequent rational choices in patient management that ultimately lead to better clinical care for patients. We hope that by bringing together the most recent insights regarding the pathogenesis and strategies on how to avoid NSF in patients at high risk, contrast-enhanced MRI will again be used whenever indicated, except in that very small number of patients that are truly and significantly at risk. As Emerson eloquently stated: “Bad times have a scientific value. These are occasions a good learner would not miss”. We extend our gratitude to Dr. Leon Partain, Editor-in-Chief, for his support for this project and his insightful suggestions, and to the dedicated and skilled editorial office staff Martha Tanner, Barbara Sammons, and Kerry King. Finally, we would like to thank the contributors, all of whom are highly regarded experts in the field, for their time and effort to create this special issue of the Journal.

John Grundy

BACKGROUND: In recent years there have been innovations in immunization financing and new technologies, and the scaling up of investment by the Global Alliance for Vaccines and Immunization (GAVI) in the Asia region. The main mechanism for coordination of this global health initiative (GHI) investment is country-level 'Inter-Agency Coordination Committees' (ICCs). AIM: The aim of the evaluation was to determine the utility and future perspectives of stakeholders regarding the role of ICCs in improving immunization services in the Asian Region. METHODS: A literature review, documentary analysis and semi-structured interviews (n = 65) were undertaken in five countries (India, Bangladesh, Nepal, Sri Lanka and Indonesia), with senior level members of Ministries of Health and the GAVI partnership. RESULTS: The evaluation has identified that there have been significant changes recently in the strategic environment for immunization, including developments in new vaccines, increasing GAVI investment, trends towards health system integration and decentralization, and institutional development of the non-government sector. This evaluation found that ICCs are functioning well in relation to information sharing and GAVI application processes. However, they are performing less well in the areas of evaluation, strategic gap analysis and coordination of immunization technical co-operation. CONCLUSIONS: There are high levels of institutional and contextual complexity at country level that require a more focused global response by GAVI to the governance challenges of institutions and partners implementing GHIs at the country level. ICCs should be maintained and strengthened in the more pluralistic context of an 'immunization coordination system' that is represented by the wider health sector, regulatory authorities, and civil society and private sector interests. Managing through systems, rather than being over-reliant on committees, will broaden participation in implementation and, in doing so, expand the reach of immunization and maternal and child health care services in developing countries.

Francesc Sebé, Josep M. Miret, Jordi Pujolàs, Jordi Puiggalı́

No abstract is available for this record.

I AJ Semali, Marcel Tanner, Don de Savigny

This paper analyses health reforms in Tanzania since 1924 to 1993 to determine how each paradigm influenced the next by using the recent World Health Organization (WHO) framework of health system. Published and gray documents were reviewed and analyzed for the four discrete attempts at reforming the health sector, focusing on the district health system decentralization. The findings revealed that for each wave, there was a review of the health system, making information from preceding efforts to be available to the subsequent reforms. After independence the political party in power played a major role in ensuring availability of information and its utilization. Predominant information in each wave showed that the health system was underfinanced, there was poor performance of PHC strategies, non-integration of DMO and poor health workers income. Health reforms should focus on health system finance, integrated district health system, health workers welfare and community participation.

Sugeng Hadi Utomo, Hadi Sumarsono

Decentralization theory states that the higher degree of centralization will increase local economic growth, because local government will create public sector efficiently, so it will increase more local economic growth than central government. The implementation of Decentralization Law No. 23 & 33, 2004, and the balance of finance between the central and local government as the manifestation of the theory is expected to increase affectivity and efficiency of local government performance through the delegation process from the central government to the local government. This research was conducted to evaluate 5 years of fiscal decentralization of 29 districts and 9 cities in East Java with fixed effect model (fern) analysis. The result of this research are: (a) decentralization of expenditure has significant positive impact on economic growth, (b) decentralization of expenditure has significant positive impact on inefficiency of public expenditure, and (c) inefficiency of public expenditure has significant negative impact on economic growth. Keywords: decentralization of expenditure, inefficiency of public expenditure, economic growth

Norman G. Anderson

My 90 years have witnessed a basic transformation in the understanding of disease in terms of molecules, largely through the application of new instruments and technologies. The ultimate distillation of what really works at this level—the quantitative measurements that generate clinical insight from specimens like blood—is clinical chemistry. This field has fascinated me for a long time, partly because of my interest in inventing or improving analytical instruments, and partly as an anchor to real-world biology that is frequently missing in academic research. A second thread of interest to me is how successful research gets done, and how to know when a solitary inventor is needed and when it takes an army. Here I recount some personal experiences relevant to these interests, ranging across several fields and in organizations of widely varying scale, all ultimately linked to clinical chemistry and the human proteome. Interdisciplinary R&D has always fascinated me, and my introduction to it occurred in unusual times, during World War II. I was on active duty in the US Navy before Pearl Harbor as a Photographer’s Mate 2nd Class, and was discharged at the war’s end as a Lieutenant (jg) line officer, with zero instruction in between on how to be a naval officer. Despite (or because of) this fortuitous absence of formal tuition, I found that much of the fun and adventure in life lies in the cracks between disciplines, and that these cracks can be wider in large organizations (like a Navy in wartime) than smaller ones. Flying in blimps off the Carolina coast during the height of antisubmarine warfare, it occurred to me that maybe, lacking a bombsight, we couldn’t actually sink a German submarine if we found it. After developing proper instrumentation, I found experimentally this was largely true, and a proper bombsight was developed. This was the start of a series of projects that put together all sorts of technologies, raised interesting questions, and whose results were usually translated into immediate action. Transferred to the Pacific and the submarine service, I worked as a movie photographer on a project to be called “The Silent Service.” This was authorized by a personal letter from Franklin Delano Roosevelt, which proved to be a magical passport to getting things done far from home. As I was shooting background footage of 2 submarines I had arranged to do the required postrefit maneuvers, a radioman came topside to say that Truman had announced use of the atomic bomb. This ended the war and with it my introduction to interdisciplinary work with effectively unlimited resources. Suddenly I found myself at Duke University immersed in the culture of Little Science. I was taught (by a future president of the National Academy of Sciences) that proteins and nucleic acids were too complex to ever be sequenced, that chromatography, while interesting, could never be quantitative, and that no one knew for certain where and how genetic information was stored. The general attitude was very different from the “win at all costs” approach adopted in war—it was painstaking and slow, but it was biology. I began to realize I had been contaminated by the notion of Big Science, but felt I should learn to be comfortable at both ends of the Big Science–Little Science spectrum (1). This pendulum has swung back and forth for me several times, and is an invigorating oscillation. Returning to the Big end, I obtained an Atomic Energy Commission (AEC)1 postdoctoral fellowship in the Biology Division of the Oak Ridge National Laboratory (ORNL). My PhD thesis had concerned subcellular components isolated using very simple centrifuges, and my hope at Oak Ridge was to extend this work to proteins in different subcellular particles using some new type of centrifuges, yet to be conceived. ORNL’s unprecedented facilities, with staffs running into the tens of thousands, included almost all disciplines of science and engineering. Almost anything one could reasonably imagine was either available or could be designed and built quickly, even if it happened to involve nonstandard laboratory supplies like large titanium forgings. The saying, “Why use lead when gold will do?” reflects a little of the flavor. Separation, either physical (as in the case of uranium isotopes) or chemical (as was the case for plutonium), and accurate analysis were the key technologies at most of the Manhattan Project facilities. My initial laboratories were in the same valley that housed more than a thousand giant Calutrons (preparative mass spectrometers) used to enrich kilograms of U-235. After World War II, this facility was used to go straight through the atomic table, isolating and characterizing all the stable isotopes. I wondered if the same sort of effort and philosophy could be adapted to the comfortable field of biology? Could one ever separate the components of living cells into a “parts list” for man? If so, it should provide a powerful way to study and ultimately understand disease. As it happened, the major nuclear weapons laboratories needed new missions after the success of the Manhattan Project. I suggested one in the winter of 1959–60 entitled “The Cell Fractionation Project,” an effort to separate and characterize all the molecules in cells, which much later became the Molecular Anatomy Program. It appealed to nearly everyone at ORNL except my fellow biologists, who did not like big projects (unless it was mouse genetics). We had thought about sequencing DNA but were assured by biochemists that, while RNA could in theory be sequenced, DNA simply could not be for purely chemical reasons (this was before the discovery of restriction enzymes or dideoxy sequencing). So the thinking focused on proteins. Protein fractionation had been advancing on multiple fronts during the preceding decades. In the 1930s and ’40s, Svedberg had developed the analytical ultracentrifuge which showed, unexpectedly, that proteins had well-defined masses, and Tiselius, who once described to me how he had inadvertently left his gardening shoes on when he went to hand out Nobel Prizes, had developed electrophoresis by which plasma proteins could be classified into 4 discrete groups (albumin and the famous α, β, and γ globulins). By the mid-1950s, Sober and Peterson had begun to fractionate proteins on cellulose columns, and Waldo Cohn, who had pioneered separating fission products on ion-exchange columns at Oak Ridge, began to work on nucleic acids, convincing Moore and Stein to use ion exchange in place of starch columns for amino acid analysis. Precipitation was explored in parallel by Gerhard Schwick at the Behring Institute in Germany. He isolated dozens of human plasma proteins, made antibodies to them, and distributed these worldwide. This approach with distributable reagents allowed specific protein assays to be performed on clinical samples, thus starting immunodiagnostics on the present road to broad coverage of the human proteome. While largely forgotten in the field of proteomics, this effort has survived through multiple commercial marriages with Hoechst, then Dade Behring, and finally Siemens Diagnostics. My own work really began with the invention of the zonal centrifuge (2) to fractionate subcellular particles. In this device, the volume limitation inherent in swinging bucket gradient separations was surmounted by using large, hollow, bowl-shaped (zonal) rotors. In these, gradients and samples were caused to flow through rotating seals into a rotor spinning at low speed and then accelerated to maximum speed to effect a separation based on either sedimentation rate or isopycnic banding density (or, in later designs, both). This was followed by deceleration to a low speed and recovery of the gradient as isolated fractions by displacement from either the center or the edge. I had designed and built a slow and crude proof-of-principle zonal rotor and then had arranged to have one built commercially, which was unfortunately unstable at high speed. Instability of a large rotor at 40 000 rpm, especially if it leads to catastrophic self-disassembly (a phrase we adopted from Los Alamos, which knew about such things) is undesirable. We needed real engineering expertise in rotating systems, an unusual discipline but one that was by chance very popular at Oak Ridge. Gas centrifugation for uranium enrichment had been tried and abandoned in 1943 because of its high cost. Subsequently it was discovered that a captured German Luftwaffe engineer named Guernot Zippe had designed for the Russians a remarkably simple centrifuge that used very little power and was surprisingly efficient. The need to catch up with this development accounted for the presence of an engineering staff working at top speed (in all meanings of the phrase) in Oak Ridge. The resulting urgency, money, and minimal administration helped as usual to eliminate the curse of delayed gratification, chief destroyer of creativity. We built (and sometimes blew up) a lot of centrifuges, and they became progressively better at separating biological materials. In the early ’60s, Robert Huebner of the National Institute for Allergy and Infectious Diseases and others found that many animal cancers were caused by viruses, especially if the viruses were given to newborns. Numerous groups were set up across the US to attempt to isolate cancer viruses, grow them in culture, test them in primates, and see if a cancer vaccine was possible. When these efforts failed to find culturable human cancer viruses, I suggested to Huebner that we try to isolate them by physical means, using density gradient centrifugation, instead of relying on growth in culture. If this were successful, then similar physical methods could be used for large-scale purification of virus for a vaccine. The US Food and Drug Administration (FDA) was insistent that any killed virus vaccine should contain no (or at least very little) cancer cell DNA to be sure that the vaccine itself did not cause cancer. To make a pure virus vaccine for large-scale human use by physical means would require a liquid centrifuge of a size never before built. Testing these systems required large quantities of virus, and neither Sabin nor Salk, who were very cooperative, had poliovirus in the quantities we needed (milligrams rather than infectious doses). Initially we settled on seawater obtained from the Woods Hole laboratory and discovered to our surprise that the ocean has about the same viral load as a viremic human’s blood (3). For more realistic development, though, we obtained a batch of human viral vaccine that did not meet FDA standards and thus could not be sold. To avoid risk of viral contamination to ORNL’s enormous mouse genetics facility, we relocated the centrifuge development program to the most distant site available on the Oak Ridge reservation, which was, fortunately, right next to the giant Oak Ridge Gaseous Diffusion Plant, locus of the gas centrifuge project. Our “lab” was a mothballed power plant, whose Manhattan Project pedigree was visible on the wall as a framed single-page purchase order for “One coal-fired steam-driven electrical generating plant, 237 megawatt.” It had railroad tracks coming in one end of the 100-yard long main floor and a 30-ton overhead crane for moving large equipment, among other conveniences. We needed a general theory on which to base our search for viruses in tissue homogenates. To see the possibilities of such a separation, I plotted the sedimentation coefficient S against the banding density ρ for viruses and for the major subcellular particles and discovered that viruses generally are found in the middle of this plot in an otherwise thinly populated area away from nuclei, mitochondria, proteins, etc. (4). This plot was key to the whole project, and it suggested that we combine sequentially rate and banding techniques into one 2-dimensional (2D) S–ρ separation. This theoretical plot was converted into a real one in which bacteriophage were recovered from rat liver and other tissue homogenates (5), perhaps the first integrated high-resolution 2D separation in biology. As it became clear that no cancer viruses were being found around which to design a vaccine purification system, I decided that we should work on an existing vaccine that required better purification. We would thus be ready if a human cancer virus was actually found. At that time, egg-grown influenza vaccines contained appreciable amounts of egg proteins, resulting in many deaths from anaphylactic shock each year and the requirement that they be given under close medical supervision. We approached Eli Lilly about designing a centrifugal system specifically to purify influenza vaccine. Their batch size was 100 L, and the purification run had to be completed in an 8-h day. Knowing these parameters and both the sedimentation coefficient and banding density of influenza, it was possible to design a rotor system that used continuous flow to band the virus from 100-L batches in a narrow gradient that could be recovered at the end of a run. The result was the K-II continuous-sample-flow-with-banding ultracentrifuge (6). Use of this centrifuge essentially eliminated vaccination deaths from anaphylactic shock and allowed vaccination in supermarkets under minimal supervision. Almost 40 years later, it is still in use around the world with minimal modifications for vaccine manufacture, and we have recently proposed its use to isolate the viral load from 100-L batches of pooled diagnostic serum discarded in clinical reference laboratories each week (7). The viral DNA and RNA, concentrated and free of host nucleic acids, could then be shotgun-sequenced to screen for new viruses, while providing a running index of the known viruses “going around.” separations of cell components many To specific across these we used from clinical chemistry. I once to had most of the that be some other way to clinical chemistry. He that this was not possible. I thought about this a It was my introduction to clinical and clinical chemistry. The was to a system for between samples and reagents in parallel rather than It out that centrifugal is an way to and liquid while at the of a rotor spinning a provide measurements that very accurate The rate was in that we needed to a like the to it. these in the early was given ORNL’s but we that a a caused no The resulting was named the Energy centrifugal It was a commercial success for and and in many it did to the and it still be the system for very accurate The the rotor of an early centrifugal system At right is a of the system used to and measurements from at the of the spinning in during one of the Despite the success of zonal and the centrifugal the National that human cancer was to viral with interest in me to to the University of I was to be in by my who had completed a PhD at the University of under Nobel and done a with had famous on 2D electrophoresis and had the we set up a laboratory and a research to the most we ever had worked out a which was, of a In a system and the major plasma proteins by with the whole of Behring The of plasma proteins, called was many and Protein on were clear We found the 2D of plasma proteins to be and to an but it was more to a than a clinical 2D plasma and serum from the same The and the and on with This was in of plasma proteins, The plasma and genetic 2nd It became clear that to 2D we needed once the of a National and this with an to the biology at For several we worked in during the week and at on designing together what we called the system for and running large of 2D in parallel Our initial analysis system was an designed to 2 by between them, a used by to the This was by an and large for these we explored the protein called of human as as rat liver and many other We were to host the first 2 major on 2D first at and the second at the both as of (in and The results at these 2D are in some surprisingly similar to the of with the of protein using mass perhaps was before DNA we felt that of all the human proteins by cell fractionation and 2D electrophoresis was the way to in biology the effect that the had in chemistry. This was as the Protein at providing a for and ultimately what is systems biology. an effort would require large and so, with several we suggested of a Protein the general we had in Oak Ridge, to and this who was the of the US at the time, was in research with on and on in his in the on these a Protein was and in a was out the and size of a on the human and a new of much to and more to the the National Laboratory it that study of proteins was to a in the that time, the in biology to the Big Science approach of the National We left in and set up Biology to 2D and protein index and the the years a with in protein and finally a successful initial in the year an 2D electrophoresis system running 100 we explored in rat the of and to the of human a approach we had developed at Oak Ridge we the first columns that the plasma proteins used as the of the system columns with fractionation the of 2D from the most plasma proteins to more than The of mass for protein allowed finally to all the or we had in of and analysis quantitative of in specific protein this I to a in centrifugal systems, developing a large-scale centrifugal for and a centrifuge for viruses from clinical samples, banding them or them in to a plasma This has to and concentrated viruses from serum in about 2 in quantities that the of thus the way and sequencing of human viral it is a little for my own the broad of a approach to understanding the human and it for has recently begun to To start the of a human has the means to the proteins, and perhaps most that are really about of them rather than the 100 000 we were once to the and to on a protein of each this like a to at a or several large-scale are with an effort to the of all the proteins. because is really this is being done at Big Science like the at (in a large The resulting should provide a for understanding and thus the of cell and In and are of a project antibodies to each human and then to see where these proteins are in and success in this a broad for major clinical in will be the to be protein real with clinical to be into A new of mass for is that can ultimately in terms of and while and this it possible to specific assays for proteins starting from a and project to quantitative, and specific assays for all human proteins a of assays in the present protein and even into the clinical laboratory mass is for better of and It to me that this of project, up basic clinical research and clinical chemistry at the same time, is even more than the human and for a of Big Science thinking in the protein If all this to it will a in clinical it at the of biological and at the of clinical would be Atomic Energy Oak Ridge National US Food and Drug Energy Protein Biology initial and they have to the of this and have the to the and of or analysis and of or the for and of the of of any of of The organizations no in the design of of and of or or of I in to the of I have not and I my many and for at Oak Ridge, and through the especially of which extend through his

Joan Costa‐Font, Joan Gil

The regional organization of the Spanish national health system offers a ‘unique field’ for exploring the sources of health inequalities as well as for testing the effects of political decentralization on health and healthcare inequalities. Drawing from the results of an empirical analysis where inequalities in three dimensions of health (outcome), healthcare (access) and healthcare payments (financing) are estimated, this article first explores the association between three such inequality dimensions alongside other system and socio-economic controls. Second, we examine whether the first wave of asymmetric healthcare devolution which took place in Spain between (1980—2001) — whereby health policy responsibilities were transferred to a few region states (autonomous communities [ACs]) — correlates with higher inequalities in health, healthcare and health financing. Our findings suggest that inequalities in health and healthcare appear to be driven by income inequalities and inequalities in use but not by inequalities in financing and health expenditure. Region states politically responsible for the organization of healthcare did not exhibit significant differences in health and healthcare inequalities and tend to exhibit a better equity performance.

Federico Picinali

With its fundamental decision In re Winship (1970) the United States Supreme Court set the constitutional basis of the standard of persuasion in criminal trials. The long standing standard of “proof beyond a reasonable doubt" was selected by the Court as the bedrock that protects the values at stake in a criminal case.Soon after this decision a dispute started between scholars and Courts on whether the “reasonable doubt standard" ought to be defined by jury instructions or could be considered a matter of the jurors' “original understanding," that is a “self-evident" concept. Depending on the solution of the dispute, failing to define the standard through suitable instruction could amount to a reversible constitutional error (i.e. a constitutional error that imposes reversal).In 2006 the highly discussed law n.46 introduced the standard of “proof beyond a reasonable doubt" ( prova “al di là di ogni ragionevole dubbio") in the Italian Criminal Procedure Code. The law does not define the standard but just states it.Even prior to this, in Italy, the standard at issue had been applied in important decisions by the Corte di Cassazione and some scholars had strongly argued the need of its introduction in the Italian criminal system. Both the Italian courts and Italian scholars had impliedly or explicitly referred to the U.S. legal experience for guidance.The U.S. and Italian criminal systems are notably different. Apart from the differences in substantial criminal law, those in criminal procedure are pronounced. According to these differences it is possible to argue that the same standard of persuasion might be given a different regime of application in the two systems. The present paper doesn't deal with this last issue, but is based on the premise that the concept itself of “proof beyond a reasonable doubt" has the same significance in the two systems.The aim of this paper is to show that “proof beyond a reasonable doubt," far from being a self-evident concept, needs accurate explanation.In order to do that, the paper studies the Italian and the U.S. legal cultures on the subject; that is, using Lawrence M. Friedman's words, “the ideas, values, expectations and attitudes – towards the standard - which some public or some part of the public holds."First, it focuses on the so called “external legal culture" remembering that this kind of legal culture has, through the institution of the jury, a peculiar weight in the application of the law in the U.S. criminal system. At this stage, the study also takes into account the “ideas of the standard" that emerge from movies, literature and newspapers.Afterwards the paper quickly focuses on the so called “internal legal culture," studying relevant decisions and doctrinal contributions to the subject.The consideration of the Italian and U.S. legal cultures leads to the conclusion that there is widespread confusion on the concept of “proof beyond a reasonable doubt" even within the community of lawyers and judges. For a correct understanding of the standard there is the need for a definition and, especially, for the specification of its rationales and its contents.Thus, the last goal of the paper is to point out the fundamental traits of the reasonable doubt standard with the help of the legal cultures previously assessed. A hint is also offered by some linguistic and further sociological consideration.The hope is to contribute, even slightly, to the understanding and therefore the application of such an important rule.

Wayne Richenbacher

I am both humbled and honored to have been given the opportunity to serve the American Society for Artificial Internal Organs (ASAIO) as president for this past year. As some of you know, I am a cardiac surgeon and as such, I am keenly aware that governance of a society, like open heart surgery, is best accomplished by a dedicated, experienced group of individuals. Favorable outcomes in cardiac surgery and management of a society are dependent on a successful team effort. This past year I was quite fortunate to have been surrounded by a very dedicated and actively engaged group of individuals. As many of ASAIO's presidents have done in the past, I would like to thank Karen Burke, Executive Director for her commitment to ASAIO. Karen is truly the heart and soul of our society. I would also like to thank the ASAIO Board and, in particular, the members of the executive committee: Bill Holman, David Humes, Bill Wagner, and Kurt Dasse. Their collective wisdom and vision for the society made the management task far simpler than I would have imagined and assures me that our society is in very good hands for the future. In choosing a topic for the presidential address, I felt that conflict of interest considerations are not only timely but also of particular interest to the diverse membership of our society. Given that our membership roster has representatives from clinical medicine, engineering, basic science, the federal government, and industry, I believe we are in a unique position to acknowledge the potential for conflict of interest and influence the process by which such conflicts are managed. A conflict of interest has been defined as “a set of conditions in which professional judgment concerning a primary interest (such as a patient's welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain).”1 Although financial gain is the most easily recognized and readily quantified, it is only one of a number of possible secondary interests. Physician-scientists are driven to participate in clinical research out of a desire to advance knowledge thereby providing better therapeutic modalities for their patients. Academic medical centers exist to foster an environment in which such advances are made possible. A successful investigative effort oftentimes results in ongoing grant support and academic recognition.2 Academic medical centers derive nonfinancial gains from research conducted by their faculty. There is great prestige associated with recognition as a leading research institute. Personal career advancement and institutional recognition are powerful secondary interests. The common perception is that any relationship between an investigator or academic institution and industry creates doubt about the validity of an investigative effort and may jeopardize the quality of care provided to a research subject. However, the presence of a conflict of interest should not be considered evidence of misconduct on behalf of the investigator, academic institution, or industrial partner. Rather, conflicts of interest are inherent in the investigative process. The goal is to manage the conflicts of interest in an ethical manner thereby ensuring that a study is conducted with unquestionable scientific validity and that the patient's care is uncompromised. It is important to understand how human subjects research evolved to the point where conflicts of interest can occur. Public Law 96-517 known as the Bayh-Dole Act, was cosponsored by Birch Bayh of Indiana and Robert Dole of Kansas.3 This legislation was enacted on December 12, 1980, became effective in July 1981, and created a patent policy that permitted universities, for the first time, to elect title to inventions made under federal sponsorship. Universities were expected to file patents and subsequently commercialize these inventions. This piece of legislation is generally credited as the originator of academic technology transfer whereby university research, inventions, and intellectual property are transferred to private industry for purposes of commercialization. By doing so, public welfare is enhanced and industrial growth made possible, as university generated technology is developed into real world products. Currently, around 5,000 licenses and options are executed annually by universities with private industry, growth of more than 500% since 1991.4 Such tech transfer translates into $1.39 billion in annual licensing income to universities, a nearly $1 billion increase since 1995. The enhanced relationship between academic institutions and industry has led to a multitude of medical advances and the creation of biotechnology markets. However, an unintended consequence of the relationship is an academic institution's increased reliance on industrial funding to support further research. Between 1980 and 2000, industry's share of the total investment in biomedical research and development increased from 32% to 62%.5,6 Support from the federal government fell during the same period. The complex financial relationship among investigators, academic institutions, and industrial partners is well documented. Of 2,052 life science faculty at 50 US universities receiving research funding from the National Institutes of Health, surveyed in a report published in 1996, 28% received research support from industry.7 In 1984, 46% of life science companies supported academic research, whereas in 1994, 57% of firms provided such support, a number that achieves statistical significance (p = 0.05).8 In 1999, the Association of University Technology Managers reported that 124 of 183 members (68%) in the United States and Canada held equity ownership in businesses that sponsored research at the same institutions.6 Patent royalties and, to a greater extent, equity holdings by investigators and academic institutions create an entirely new dynamic in their relationship with the industrial partner.6 The creation of a new revenue model for research scientists and universities has blurred the lines between academic and commercial values. The rise in institutional entrepreneurialism carries with it a responsibility for business stewardship. Such a shift in mind set can easily portend a shift in academic mission. The potential for research bias ensues. The promise of financial rewards raises justifiable concern about the conduct, interpretation, and reporting of funded research.2 There is a well documented disparity in outcomes between industry-sponsored and nonindustry sponsored research. In one review of 332 randomized controlled trials, industry funded studies were 1.9 times more likely to report positive results, a statistically significant proindustry finding.9 Bekelman et al.6 summarized eight articles that compared the outcomes of industry-sponsored versus nonindustry sponsored research studies. These eight articles collectively evaluated 1,140 original studies. The summary odds ratio from these studies was 3.60, with the conclusion favoring industry regardless of whether the study was a randomized controlled trial or other study design. Although perhaps an overstatement, industry-sponsored research is, in general, designed to affirm a hypothesis that is anticipated to be affirmed.10 Industry studies are intended, in part, to mature a concept or product along a linear fashion, whereas government-funded studies may be designed to ask broader, more conceptual questions.10 More worrisome are potential impediments to the investigator's access to data and freedom to publish the results of industry-sponsored research studies. There are reported instances where publication of the results of research that were unfavorable to an industrial product were delayed or blocked altogether by the companies that had provided financial support for the study.11–13 In one survey of academic investigators, 19.8% of 410 respondents reported publication of their research results had been delayed for more than 6 months to slow the dissemination of undesired results and to resolve disputes over ownership of intellectual property, among other reasons.13 So, why the seeming sudden interest in recognition and management of conflicts of interest? The Joint Commission defines a sentinel event as “an unexpected occurrence involving death or serious physical or psychological injury … Such events are called ‘sentinel’ because they signal the need for immediate investigation and response.”14 The event that accelerated efforts to address the influence of conflicts of interest on the safety of research subjects occurred in 1999.15,16 Jesse Gelsinger was an 18-year-old man who suffered from a mild disorder of nitrogen metabolism known as ornithine transcarbamylase deficiency.16 On September 13, 1999, as part of a gene therapy clinical trial, he received an intrahepatic injection of adenovirus vector particles containing a gene to correct the genetic defect. He died 4 days later of what was presumed to be an immune reaction to the virus vector. This death was the first in a gene therapy trial. In the firestorm that ensued, it was alleged that investigators at the University of Pennsylvania where the death occurred held patents covering several aspects of the technology employed. In a wrongful death lawsuit, it was further alleged that James Wilson, the Director of the Institute for Human Gene Therapy at the University of Pennsylvania, and the University itself were reported to have equity holdings in Genovo, the private sector biotechnology company collaborating on the project.15,16 These conflicts of interest were allegedly never disclosed to the trial participant. The fallout from the tragedy in Philadelphia and elsewhere called into question physician–industry relationships and the impact of those relationships on the clinical investigative process. Kim et al.17 from the Psychiatry Department at the University of Rochester looked specifically at potential research participants' views of researcher and institutional financial conflicts of interest. In their article published in 2004, the authors presented seven different scenarios of financial conflicts of interest to 5,478 individuals. The majority of individuals surveyed responded that knowing conflict of interest information was “extremely” or “very” important. Sixty-four to 87% of respondents (depending on conflict of interest scenario) felt that financial conflicts of interest should be disclosed as part of the informed consent process. Although the majority of those individuals surveyed would chose to participate in a study in the face of a known financial conflict of interest, the effect of such a conflict of interest resulted in a sizeable minority to be less inclined (range, 3%–44%) to participate or would chose not to participate (range, 2%–32%). The erosion of trust was further reflected in the fact that pharmaceutical and medical technology companies paid more than $2.5 billion in healthcare fraud settlements in 2001 and 2002.10 Public trust had to be regained, and potential research participants needed assurance that clinical investigation could be conducted free of bias. The question to be answered was where to begin. On May 23, 2000, in direct response to the death of the patient in the gene therapy clinical trial, former Secretary of the Department of Health and Human Services, Donna Shalala, announced five new initiatives that were specifically designed to ensure patient safety and increase public confidence in clinical trials.18,19 Two of the five new initiatives specifically addressed conflicts of interest. The purpose of these initiatives was to “clarify and enhance the informed consent process” and specific mention was made “that any researchers' financial interest in a clinical trial be disclosed to potential participants.” A conference that specifically addressed financial conflicts of interest was held in Bethesda, MD, on August 15–16, 2000. Subsequent to that conference, a draft interim guidance document was prepared and made available for public comment on January 10, 2001. A second draft guidance document appeared in 2003, whereas the Final Guidance document entitled “Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subjects Protection” was made available in 2004.20 In part, these guidelines suggested that institutions establish a Conflict of Interest Committee to identify and address potential individual or institutional conflicts of interest. The Conflict of Interest Committee was to function in concert with the Institutional Review Board (IRB). The mandate of the latter committee is to protect the rights and welfare of human research subjects. As the Department of Health and Human Services was in the process of developing guidelines to address financial conflicts of interest in human subjects research, the Association of American Medical Colleges (AAMC) announced their own intent to examine the same process. In October 2000, the president of the AAMC, Jordan Cohen, announced the formation of a task force whose assignment was to revise and extend the AAMCs existing conflict of interest guidelines based on contemporary events and increased concern about the impact of financial conflicts of interest on public trust in the objectivity of human subjects research.21 Jordan charged this task force to address three issues: 1) To recommend upper limits of allowable financial interests that would motivate investigators to pursue the clinical research with due diligence but not raise concern that remuneration for research serve as a financial windfall for those providing oversight for the scientific process. 2) To consider inaugurating a voluntary, institution-based certification process for research faculty. The certification process would function much like board certification and would ensure that those involved with funded research were cognizant of the rules and regulations governing such research. 3) To consider additional safeguards that might be necessary to “address the potential downside of financial conflicts at the institutional level,” recognizing that institutions, as opposed to individual scientists, might also have a financial stake in the outcomes of clinical trials conducted onsite. The task force ultimately published two documents: one dealing with individual22 and the second with institutional23 financial conflicts of interest in research involving human subjects. Recommendations in these two reports also include the creation of a Conflict of Interest Committee or, in lieu of a committee, a conflict of interest official. The Conflict of Interest Committee is responsible for identifying, quantifying, and potentially reducing the financial conflict of interest of any individual conducting human subjects research. Findings from the Conflict of Interest Committee are to be made known to the IRB. Institutions were tasked with developing written policies detailing substantive prohibitions and restrictions, reporting, implementation, disclosure, monitoring, and review of financial conflicts of interest. The AAMC task force recommendations specific to managing institutional conflicts of interest make particular reference to the makeup of the Conflict of Interest Committee. The membership roster is to include only individuals who are independent of the direct line of authority for clinical research oversight within the institution. The task force further recommended the inclusion of at least one or more individuals with to the institution The institutional of Technology is to report to the Conflict of Interest Committee any licensing into by the institution that equity interest, and the reporting guidelines are recommended for institutional In potential financial conflicts of interest should be disclosed by the individual conducting the research. The should be into the patient consent and the financial interest in question should be and not to additional to the welfare of the research participants or to the of the industrial representatives also to their own of dealing with investigators and academic The Research and of developed a on with This effect on July and was in January Of greater interest to the membership of this society is the of on with Health by the Medical Technology Association is a of medical technology and the of was on January The of the into effect on July This and document such important as company conducted product and with healthcare and research and to the of the include guidelines that address with healthcare and the of companies that their of the for public review on The of have also done their part to for and the scientific of human subjects research. The two leading in the of surgery, the of and and the of that authors report any financial conflicts of interest a is for The of those have the of such conflicts on the title of the article at the of However, the of only one of a conflict of interest. To ensure that authors of research data and the freedom to publish the results of clinical research, the Committee of Medical the for to and for to of potential conflicts of interest, this document that authors potential conflicts to study participants and that they have done within the of the The document further that in reference to conflicts of interest to support should not into an that with their access to the data and their to and to and publish To ensure that investigators are for their own research, authors of a study funded by a with a or financial interest in the may also be to a to the effect that had access to the data in this study and I responsibility for the of the data and the of the data The of the of and and the of have new to their for that a policy in which a a study in which “an other than the investigator had of the data or had over might be on that Such policies serve two to research scientists in their with industrial in developing and to ensure of the have information to make an informed judgment about potential bias in the research In the since the death in the gene therapy clinical trial, significant has been made in the and management of of conflicts of interest. However, this is a process in The majority of management policies are in the of recommendations or There has been a response from institution to institution with to developing and on policies and that are a number of in which potential conflicts of interest can be and In clinical trials, investigators be involved in aspects of trial the of and In funded research, investigators of data and data The research scientists be the freedom of publication of a conflict of interest on behalf of the investigator or the institution at which funded research is should be should be in the consent document that a potential research to the presence and of a possible conflict of interest. By doing so, the potential research is made aware of the conflict and is the opportunity to an as to the impact of such a conflict on the investigative process. such written should include financial the of It has also been suggested by one that informed consent should include a of the quality of medical evidence on which recommendations are should an opportunity for between the investigator and the potential research the latter is that safety is and the study is conducted bias. of conflicts of interest is the responsibility of not only the investigator but also the institution. In to the informed consent of conflicts of interest and Institutional Conflict of Interest should be developed with a mandate to review potential conflicts of interest and ensure that such conflicts are disclosed and Conflict of Interest Committee membership should include research scientists who have conflicts with the institution, the investigators, or the clinical trial in which the faculty of the academic institution is To one or more members of the Conflict of Interest Committee should be from the institution. The Conflict of Interest Committee should be charged with developing policies for management of potential conflicts and should with the to ensure that such policies are It has been suggested that a for to AAMC guidelines might be better accomplished by the guidelines into the companies should to of should be in and an need for the and that such was for should be with and not based on the or of the business academic medical the Conflict of Interest Committee should oversight for faculty members who into The and potential research participants should be made aware of and be that such in influence the or of clinical research. A financial be it an investigator or institution should not serve as investigator or data in a clinical trial. The of a financial on industrial support or on an investigator's or institution's equity interest in an industrial have to be In for patient care should be first and in the of involved in human subjects research. To the of the scientific such investigation be conducted free of or advances in medical in general, and in particular, a relationship among academic medical and industrial In the would that may be an increased reliance on industry for financial support in the future. The of our society since has been to advance medical technology for the of our patients. To this ASAIO is with a membership that an and of to the task at The of our society is our to a clinical a to address that the new and, in and clinical trials our the complex process and more understand the process by which new technology is to the To ensure that we to be to new to the board and technology to the clinical we be open and in our management of conflicts of interest, the of our clinical research are and our to participate in the process

Dermot Maher

The global financial crisis poses a threat to global health, and may exacerbate diseases of poverty, e.g. HIV, malaria and tuberculosis. Exploring the implications of the global financial crisis for the health sector response to tuberculosis is useful to illustrate the practical problems and propose possible solutions. The response to tuberculosis is considered in the context of health sector development. Problems and solutions are considered in five key areas: financing, prioritization, government regulation, integration and decentralization. Securing health gains in global tuberculosis control depends on protecting expenditure by governments of countries badly affected by tuberculosis and by donors, taking measures to increase efficiencies, prioritizing health expenditures and strengthening government regulation. Lessons learned will be valuable for stakeholders involved in the health sector response to tuberculosis and other diseases of poverty.

Joel P. Trachtman

At a time when the Obama administration, the rest of the G20, and other governments, are emphasizing multilateral action to address global problems, such as global warming, terrorism, financial regulation, monetary policy, failed states, and public health, much is at stake in theoretical and empirical arguments about the possibility for effective collective action among groups of states. In The Perils of Global Legalism, Eric Posner argues that these efforts are largely futile. Can it be true that international law offers little or no assistance in response to global collective action problems? Posner grimly asserts that ‘if a world government is not possible, then solving global collective action problems is also not possible’1 (at 8). If he is right, and given that the kind of world government he has in mind is indeed implausible, then the efforts of policy-makers and diplomats should immediately be diverted from efforts to craft international legal responses to global collective action problems, and reallocated to more productive pursuits. The implication of Posner's book: call home the diplomats and be content with the inefficiency implicit in unilateral action to address global collective action problems. From one perspective, this book might be viewed as a welcome dissenting voice amid general calls for more international law, and it rightly rejects what are by now caricatures of the American and European idealists who believe that the world could be perfected if only we wrote and complied with the right laws. Indeed, international law is not a nirvana solution to all our global problems, but merely part of the toolbox of practical political efforts to improve our situation. Posner has applied his considerable analytical talent to the question of when and how international law may be useful. He has no doubt provided a provocative and interesting book. The problem is that Posner is not content merely to show the flaws in the idealistic general argument for more international law. He goes on to make a general argument against more international law. I do not believe that it is possible to make a general argument either for or against more international law. More refined and context-specific analysis will be necessary to know whether more international law is or is not useful in particular contexts. But there is little doubt that international law has been, and will be, useful to solve some global collective action problems. This utility is just as clear as the utility of contracts to solve some inter-firm collective action problems and the utility of social institutions to solve some village-level collective action problems, as shown by the 2009 Nobel economics laureates, Oliver Williamson and Elinor Ostrom, respectively. Posner defines ‘legalism’ as ‘the view that law and legal institutions can keep order and solve policy disputes’ (at 21), while ‘global legalism’ is ‘an excessive faith in the efficacy of international law’ (at xii). Posner describes American-style global legalists as overestimating the social value of international law, and therefore overestimating the reciprocal, retaliatory, or systemic costs of violation, with the effect that they overestimate the effectiveness of international law. How does Posner know that the legalists have generally overestimated the value of international law? Neither he nor they has the necessary context-specific data. Instead of presenting context-specific data, Posner makes a general theoretical argument that multilateral international law has little value to solve collective action problems (as contrasted with coordination problems, where there is by definition no reason to cheat), because it is generally ineffective to do so. For Posner, European-style global legalists simply make unwarranted natural law-based presumptions requiring unmitigated compliance with international law, even where, all things considered, compliance is not beneficial to the acting state. Posner ascribes a progressive vision to these global legalists, stating that the central tenet of global legalism is ‘faith that if international law advances then eventually true international law-enforcing (and eventually law-making) institutions will follow in its wake, and then people will transfer their loyalty’ (at 91, emphasis in original). More international law leads to more international institutions, which together lead to a transfer of loyalty and thus global government. Posner rightly rejects this millennial dialectic. But this is a straw man and in my experience very few, if any, European international lawyers or ‘liberal’ American international lawyers believe in this dialectic. And while we will not soon have global government of the kind Posner envisions, we need to know whether international law offers possible mechanisms to deal with practical, on the ground, global collective action problems. For Posner, a certain scale of institutional infrastructure, and a transfer of loyalty to a world government, would be necessary before international law can be effective. In this way, Posner's views are aligned with the most romantic, pie-in-the-sky, idealists—the only difference is in Posner's pessimism that this romantic vision can be achieved. He sees the transfer of loyalty as necessary to the establishment of a world state, and he sees a world state as essential to the effectiveness of international law. Posner fixates on the state as the exclusive repository of authority and loyalty, and thus argues that it is necessary that there be a world state in order for international law to have strength (at 128). Unlike most international lawyers, his evaluation of existing international law and institutions, and his view of the future, do not identify or anticipate possible centres of authority, and the possibility of law or government, outside even if not in place of, the state. For Posner, international law is generally epiphenomenal in connection with multi-state cooperation problems.2 As part of this fixation on the state, Posner argues that the biggest problem with global legalism is that it espouses law without government. For Posner, in order to have law, you need government in the form of the traditional institutions of the state, including fully empowered legislatures, judiciaries and executives, as well as a monopoly on the use of force. He posits that ‘if it is true that national governments are needed to solve national collective action problems, then it seems that it would follow that a world government would be needed to solve global collective action problems’ (at 8). Consider this syllogism. The premise is debatable, and its extension to the international setting is dependent on a highly questionable, and unsupported, assimilation of the international setting to the domestic setting. That is, even if we accept that a certain type of institution is needed within the state to solve intra-state collective action problems, it cannot simply be assumed that precisely the same institutions are needed or appropriate to solve international collective action problems. A parallel, and equally faulty, syllogism would state that ‘if it is true that humans need oxygen tanks to remain under water, then it follows that oxygen tanks would be needed by fish to remain under water’. In order for this syllogism to be true, a fish would have to be the same as a human with respect to the relevant characteristic. But Posner offers no evidence that the international setting is the same as the state in the relevant characteristic that concerns him. Based on this faulty syllogism, Posner does not allow that collective action problems might be solved by a variety of institutional mechanisms short of a kind of global government modelled on a strong national government. He neglects the possibility of a Coasian choice between the firm and the market – between integration and contract – to solve collective action problems, but insists on integration as the only basis for resolution. He seems to entertain no possibility for nuance or for distinct institutions that may be appropriate for distinctly international collective action problems, or for the distinct international context. In fact, he seems to see no difference between the role of law in the international context as compared to the domestic context. But while for Posner the dynamics of the international and domestic contexts are the same, there is for him a critical difference. The difference is that the domestic setting contains institutions that solve cooperation problems, while the international setting simply does not and will never do so. Posner thus purports to draw ‘a crisp analytic distinction between intrastate cooperation, which is capable of solving major nation-level collective action problems, and interstate cooperation, which is itself subject to collective action problems and thus cannot solve them, except in a very rudimentary fashion’ (at 7). He argues that ‘global collective action problems cannot be solved – or not very well’ (at 7–8). Note his evaluation: what exists or what can be is only ‘rudimentary’ or ‘not very good’. How can he know that what exists is not precisely what states wish to exist? A fundamental point in Posner's argument is that we ‘cannot solve global collective action problems by creating institutions that themselves depend on global collective action’ (at 34). This glib assertion is patently false: consider as an example the formation of any constitution – constitutions themselves depend on collective action, and they are used to address collective action problems. In domestic society, and in all other social contexts, the creation of institutions always depends on collective action, and always is intended to solve collective action problems. Similarly, Posner later emphasizes that ‘it is the conceit of global legalism that people – ordinary people, government officials, bureaucrats – will obey law even though they would not obey or consent to the international versions of government institutions that we all agree are necessary to make law workable at the domestic level’ (at 128). Here, Posner makes the additional error of extrapolating from the domestic context to the international context without recognizing contextual and teleological differences. The result is the breathtaking assertion that international law, to be effective, requires the same supporting institutions that domestic law has. Furthermore, when Posner specifies that the type of institutions for enforcement of law found in the state are the only adequate ones, he assumes a very idealized and narrow set of institutions available in the state for enforcement of law. A quick survey of comparative politics and comparative constitutionalism would confirm that state institutions are actually quite varied and malleable, and nuanced, even within the narrow category of advanced liberal states. And the literature of social norms, led by Robert Ellickson, shows how in domestic society rules can arise and be stable and effective without formal organizational support.3 Institutional economists distinguish between institutions, which may be formal or informal, and organizations, which are formal. Posner seems to consider that only organizations, of the type found in the state, are sufficient to support international law. An institutional economist surveying the existing field of international law would find a rich variety of institutions, including organizations. The rich literature of international regime theory, pioneered by Robert Keohane, recognizes the critical role of informal institutions in international society. So, while it is true that law requires institutions, or more accurately that certain types of law will be more efficiently made and enforced with certain types of institutions, we cannot move from there to the proposition that the government organizational features found in the state – indeed in Posner's idealized state – exhaust the category of institutions that may be effective to support international law. A social scientist examining international problems of cooperation would not take the top-down approach of asking whether there is a need for a global state that simply replicates the organizational features of the strong national state. Rather, a social scientist would take a bottom-up approach, examining each type of cooperation problem separately, in order to determine which institutional solutions would resolve strategic or transaction cost problems endemic to that problem. Only after examining the range of international problems, and their individual solutions, would a social scientist go on to examine the need for institutional or organizational responses and the potential synergies among the solutions. In this way, we might say that the state, with its wide range of internal subsidiarity, as well as its capacity to enter into international legal arrangements, is only a first approximation of the level at which collective action problems might be addressed. Posner says that the organizational features that are missing at the international level are legislatures, enforcers and adjudicators. And a cursory examination of the broad international legal system will confirm that there is little that looks like the organizational features of a strong state. At the multilateral level, there is no real parliament and no sheriff, and there are few courts of mandatory jurisdiction. And yet, the social scientific question is not whether there are institutions with these labels, or these formal functions, or that look like an idealized set of domestic institutions. State-type institutions are not the exclusive means to resolve collective action problems, even within the state. The social scientific question is whether there is a sufficient institutional structure to have the desired level of behavioural effect. And the appropriate reference is not the idealists’ desired level of behavioural effect, but the level of behavioural effect sought and agreed upon by the states parties. While Posner is obviously right that there is no world government modelled on strong national governments, it is not necessarily so that there is no world government at all. Much depends on what we mean by ‘government’. If we mean a formal set of institutions (including, but not limited to, organizations) that have some degree of legislative, adjudicative, and enforcement power – sufficient to affect behaviour – we already have that in international society. States follow agreed rules regarding legislation through treaty and custom, they adjudicate international law, and they enforce international law. As to mechanisms for legislation, while at the international level most of these require unanimity, all sorts of devices, including package deals, log-rolling, payoffs, and other mechanisms, are available to induce states to agree to rules that may not otherwise be in their narrower interests. While there is indeed generally no sheriff to engage in enforcement activities, there may be and other enforcement While there are few courts of mandatory there are and in some there are other of more or How does Posner know that this set of mechanisms, with existing international law, has no behavioural how does Posner know that this set of mechanisms is not precisely what states to to global collective action problems, given state one can say whether the existing international law institutions are responses to government but nor can that they are without the transaction costs or strategic problems that to remain or that they in to the of states. If Posner has a for a of a particular level of institutional or power to affect it is not in this book. If he has a to know that the level of that exists is to the that states to it is not in this book. So, it is simply to that the institutional structure for international law have the and power of a strong national state in order to be effective. that Posner's question is whether international law can address international cooperation the question is not whether this system looks like a domestic but whether it has the to address international cooperation by and to Posner's are distinct from cooperation How are they as Posner international cooperation compared with domestic cooperation will generally of individual of and and social This is implicit in the of we to do at the state level what is at the state level, and we to do at the international level what is at the international The of actually that cooperation at the international level be from cooperation at the domestic In international cooperation problems that can be by international law the behaviour of governments, and not the behaviour of so it would indeed be if domestic appropriate for use in the behaviour of the same needed to the behaviour of states. the structure of international cooperation and the structure of international society, that we would see institutions for cooperation at the international is no need for a world state to in order to have international law with real social effect. is no reason to that international formal institutions for legislation, and would look like domestic that international government would look like a world state. Posner has no reason to know that the types of institutions in in the international legal system are to address the collective action problems that states wish to He has no reason to know that if states their and to address collective action problems, they would be to do so. He has no reason to know that if states that it would be to additional institutions in order to have more effective law, they would be to do so. At the of this book is Posner's argument that international law is generally ineffective to address international collective action problems. He states (at that that cooperation to solve global collective action problems will be Neither this nor his does much to this theory, and analysis shows that no such For Posner, while world government is it as the of states in the world and the of states in the world seems to be Posner posits that there will be for cooperation as the of states because these states would necessarily be and therefore to public at the level when the level is their may also be social and more international law may for Posner the is that as the of states cooperation is does an of states mean that effective international law is this is central to Posner's it is not and in fact, while it is to be true in some particular it cannot be generally Posner (at that there is no basis for his stating that he that compliance with the of states, this is central to his Indeed, as and have shown in in response to by Posner and compliance with international law could either or with the of states on other For in the of public where the from the public with the of states that cooperation will more as the of states So, there will never be the Posner that compliance with international law generally with the of states. In fact, there may be reason to the effect. Posner posits that for cooperation will arise from a of states. This value of cooperation would make cooperation more not Furthermore, even if we accept Posner's assertion that cooperation generally more with more states, he has no of which effect is the value of cooperation or the of So, even if we to accept Posner's that cooperation generally more as the of states this effect makes it to draw the by that cooperation if Posner right in theory, cooperation with the of states, we have no of the of the or where we are on the might be that the effect he of is very at states, and only at states. this type of there simply is no of In fact, if we follow Posner's approach, is it that the for human cooperation not at the of Elinor the Nobel for 2009 for that they How we to the state with of How is it that the States and formal cooperation among its it Posner argues that there is a to the in the for cooperation to the of cooperation as the of states (at But he also that there is a to the right of the to the for cooperation by the same of states. He has no of the or of these So, even Posner's it is as that the level of cooperation would remain the same, or as it is that it would is no theoretical or empirical basis for Posner's pessimism regarding the social of international law. diplomats just Posner's is that international law has with collective action problems because it what he views as the needed institutions. He no evidence that the global has failed to solve the collective action problems it has desired to in he with a to his the of the European from to The European is an example of states to strong international institutions, and solving a wide variety of collective action problems. Indeed, the European has collective action problems to institutions in order to collective action problems. As the of not all at or to a but to time to for law and institutions. the of the Posner with a has in a strong legal but for him integration the effectiveness of international law in the international system (at is not this point European integration has the capacity for international would be given Posner's view that by the of the does where it of its cooperation in the international system more possible, not way, behaviour in the international system about the utility of the European experience as a to Posner's The critical to which Posner does not is that has precisely what he says cannot be in the international of has of states, and of and exists in the this is all a of and Posner offers no of these would distinguish the European the of these would be a useful to our of the potential of international law and institutions. But Posner simply an between the European experience and the multilateral setting. Furthermore, it may well be that or international law will be the more for cooperation global or multilateral international it depends on a of to each particular is only natural that a of more states, such as the European would see in cooperation, and so would But is it that a of states would not see some in cooperation, and is it that this possibility is to Posner offers no theoretical or empirical evidence that it is as he The general international law with its rules of treaty law, of state is the institutional setting for international law. But where cooperation can be with or with by organizational or other institutional states to do so. This is the of the European of the and indeed of all international to for that as in the European to legislation to address collective action problems, and in with the European it to be that would be useful in the global regime to make more or to against excessive and in with the of the it broad institutional features to on the as its approach to the establishment of institutions. The problem with Posner's is that it rejects on the basis of a and it that legal and institutional solutions to our multilateral cooperation problems are the of human society, with its of our for cooperation the broad of is or or has to determine to at of we have found to do so. it is true, as Posner that international cooperation is not necessarily or to and it is useful to have his response to any idealists who see international law as a for the problems. the argument in this to that international cooperation is or at (at because we simply do not and can never the appropriate institutions. as world there may well be in which states would from international The of The Perils of Global is that its pessimism about the possibility for cooperation, if it could our of and we cannot to the between and

Johann Wackerbauer

The German water sector is still an exception area in terms of competition law. In contrast to other network industries like electricity or telecommunication almost no competition takes place in the German water supply, which is to a high degree organized in decentralized, small scaled, regional monopolies. Water management competence in Germany is clearly located at the municipal level, which admittedly restricts international competitiveness. Compared to other countries, the German water sector is very fragmented and small-scaled. In the 1990ies there was a controversial debate on liberalization and privatization of German water supply. During the period 1997 – 2005 significant structural changes took place with respect to the organizational forms of water management. Public utilities that were organized as municipal departments in former times were transferred into more independent organizations: Now in the water supply sector the municipal enterprise and public-private partnership (PPP) models dominate and within the wastewater sector semi-autonomous municipal agencies and inter-municipal agencies/water management associations are prevailing. However, even if the legal form of companies was changed from public law to private law, the municipalities remained the owners of the new firms under private law by holding a majority. In Germany, privatisation of the water supply is neither linked with direct competition between municipal institutions for the market nor with an obligatory yardstick competition. However, the water supply companies are in a “quasi competition” as three out of four companies raise public charges in accordance with the Municipal Charges Law. Here, attention is to be paid to the principles of cost-covering and equivalence. The remaining quarter of the providers raises payments under private law and is subordinate to the anti-trust control of abusive practices. The anti-trust price control is oriented to the comparative market concepts and accepts price differences between providers on the strength of clearly defined criteria only. An important advantage of the structures in the German water supply is that the strong communal anchoring of the German providers ensures a high degree of political involvement. This system enjoys strong acceptance amongst the population because of the high quality of drinking water and the moderate prices for water and wastewater services.

Xiaohan Sun

The similarity of E-cash and E-lottery was taken into account to have designed a secure E-cash-lottery scheme by using zero-knowledge proof and blind signature on the basis of applications of the traditional lottery. This E-cash-lottery is characterized with anonymity, double stake resisting, forgery resisting, traceableness and off-line. For lottery players, banks, and lottery delivery to infer the identity of the winners by E-lottery is as difficult as for them to solve discrete logarithm. For lottery players to forge the E-cash or the E-cash-lottery is as difficult as for them to attack the RSA public key signature system. If there exists any repeated spending by using this E-cash- lottery, the bank can certainly determine the identity of the spender. Compared with the traditional lottery, the anonymity and privacy of the E-cash-lottery were preferable.

Panayiotis G. Curtis, Theodore

Regional form of Organization of the health care that are called today DyPE, have as a main&#13;\ngoal to promote more rational resource allocation through decentralization in the decision&#13;\nmaking process. The concern for more effective and efficient use of resources devoted into&#13;\nthe health care sector renders hospitals a critical vehicle of the quest for superior economic&#13;\nperformance, especially if we take into our consideration their mounting over time deficits.&#13;\nEconomic performance is primarily traced through a set of specific financial ratios, which&#13;\nembrace important elements that constitute the substance of the financial well-being of&#13;\nhospitals as economic units. An array of financial ratios is critically reviewed and a&#13;\ncombination of them is proposed as a means of effective financial management. The later is&#13;\nnecessary to ameliorate the funding strain imposed on the health care system and especially&#13;\non hospitals. The financial performance is determined by the return on capital (profitability)&#13;\nin connection with the risk involved. Both factors determine the value created, which in turn&#13;\naffects the amount of financing attracted in the sector. The financial information available&#13;\nto the supervising regional bodies (DyPE), don’t considered sufficient for their management&#13;\nto assess financial management of hospitals effectively. The lack of the appropriate economic&#13;\ndata is due to the fact that double entry accounting has not yet fully adopted by the economic&#13;\nunits that report to the corresponding DyPE. So, double entry accounting is prerequisite for&#13;\nreporting and monitoring acceptable financial performance. The later is vital in securing&#13;\nthat the financial needs of the health sector that are growing at an ever accelerating pace,&#13;\nare met.