bluuebunny/crossref_metadata_2025 huggingface dataset:
New and Old Keynesians
Authors: Greenwald Bruce , Stiglitz Joseph
Published: August 2012

The purpose of this paper is to describe one strand of New Keynesian literature which explores how increased flexibility of wages and prices might exacerbate the economy's downturn, and to contrast it with other strands of New Keynesian literature. This strand of literature holds that even if wages and prices were perfectly flexible, output and employment would be highly volatile. It sees the economy as amplifying the shocks that it experiences and making their effects persist. It identifies incomplete contracts, and, in particular, imperfect indexing, as central market failures, and it attempts both to explain the causes and consequences of these market failures. The models described here contain three basic ingredients: risk-averse firms; a credit allocation mechanism in which credit-rationing, risk-averse banks play a central role; and new labor market theories, including efficiency wages and insider-outsider models. These building blocks should help to explain how price flexibility contributes to macroeconomic fluctuations and to unemployment. In particular, the first two building blocks will explain why small shocks to the economy can give rise to large changes in output, while the new labor market theories will explain why those changes in output (with their associated changes in the demand curve for labor) result in unemployment.
Price Flexibility and Output Stability: An Old Keynesian View
Authors: Tobin James
Published: August 2012

In this symposium I shall play the role in which I was cast, the unreconstructed old Keynesian. Considering the alternatives, I do not mind being billed as a Keynesian, an old Keynesian at that. But old Keynesians come in several varieties, and I speak for no one but myself. Nor do I defend the literal text of The General Theory. Several generations of economists have criticized, amended, and elaborated that seminal work. I shall argue for the validity of the major propositions that distinguish Keynesian macroeconomics from old or new classical macroeconomics.
Economics of Development and the Development of Economics
Authors: Bardhan Pranab
Published: August 2012

The purpose of this paper is to restore some historical perspective by highlighting the many contributions of development economics to the rest of economics. We will point out to the younger generations how some of the glittering ideas they currently play with originally came from that now-neglected field and how in some cases they have rediscovered, with great fanfare, insights that were well-known in the development literature, familiarity with which would have enriched their own work.
Policy Watch: Designing an Effective Investment Tax Credit
Authors: Meyer Laurence H , Prakken Joel L , Varvares Chris P
Published: August 2012

The investment tax credit (ITC) allows firms to reduce their tax liability by an amount related to their expenditures on equipment, and thus reduces the cost of acquiring capital. An investment tax credit can be introduced temporarily to stimulate investment as part of a countercyclical fiscal policy or permanently as part of a strategy to enhance capital formation, raise labor productivity, and so speed longer-term economic growth. The discussion in this paper will focus mainly on the permanent ITC, although it will include some comments on the temporary version. As this paper is being written, President-elect Bill Clinton is widely expected to propose an ITC (of some sort) to Congress soon after taking office. Since the federal deficit continues to constrain fiscal policy, attention has been focused on designing an ITC that delivers the greatest stimulus per dollar loss of revenue.
The Nation in Depression
Authors: Romer Christina D
Published: August 2012

This paper examines the American Great Depression and the ways in which the U.S. experience during the 1930s resembled that of other countries in some regards and fundamentally differed in other aspects. I also evaluate the evidence on the causes of the Great Depression in the United States and the sources of the eventual recovery. The picture painted of the American Great Depression is one that stresses the importance of national, rather than international, aggregate demand shocks. The experience of the United States during the 1930s differed in important ways from that of other countries because the American experience had many uniquely American roots.
Retrospectives: Ethics and the Invisible Hand
Authors: Evensky Jerry
Published: August 2012

As modern economists, we use Adam Smith's "invisible hand" metaphor confident that we all know what it means in our discourse: it reflects our admiration for the elegant and smooth functioning of the market system as a coordinator of autonomous individual choices in an interdependent world. But in Adam Smith's moral philosophy, the invisible hand has a much broader responsibility: if individuals are to enjoy the fruits of a classical liberal society, the invisible hand must not only coordinate individuals' choices, it must shape the individuals into constructive social beings—ethical beings. I begin by presenting the philosophical basis for Smith's invisible hand, describing the sense in which the hand is invisible and whose hand it is. I then describe the story Smith tells of the invisible hand creating and maintaining a constructive classical liberal society and show how Smith's story evolved as his faith in the ability of the invisible hand to shape an appropriate ethical foundation waned. I conclude with some thoughts on the legacy of Adam Smith and of our predecessors in economic inquiry more generally.
Distinguished Lecture on Economics in Government: Accounting for Saving and Capital Formation in the United States, 1947–1991
Authors: Ruggles Richard
Published: August 2012

This paper is concerned with accounting for the saving and capital formation taking place in different sectors of the U.S. economy. In brief, where does saving arise and where is it used? Do some sectors save more than they spend for capital formation and thus are net lenders? Do other sectors save less than is required for their capital formation and thus are net borrowers? The U.S. national income accounts contain the basic data relating to these questions. However, at several points, these data must be recast in order to yield analytically useful results. When such a reformulation is made, the conclusions that can be drawn differ strikingly from much of the currently received conventional wisdom.
Financial Factors in the Great Depression
Authors: Calomiris Charles W
Published: August 2012

Macroeconomists have long argued that financial markets were important sources and propagators of decline during the Great Depression. Turning points during the Depression often coincided with or were preceded by dramatic events in financial markets: stock market collapse, waves of bankruptcy and bank failure, and contractions in the money stock. But the mechanism through which financial factors contributed to the Depression has been a source of controversy, as has been the relative importance of financial factors in explaining the origins and persistence of the Depression. This essay reviews the literature on the role of financial factors in the Depression and draws some lessons that have more general relevance for the study of the Depression and for macroeconomics.
Transmission of the Great Depression
Authors: Temin Peter
Published: August 2012

To a first approximation, the question of how the Great Depression spread from country to country is short and straightforward: fixed exchange rates under the gold standard transmitted negative demand shocks. The first half of this paper will describe current thinking about the relationship between the gold standard and the Great Depression. The second half of the paper will look at a phenomenon not included in this first approximation: financial crises. Many have noted that banking panics and currency crises are bad for national economies, but few have tried to model their international spread.
The Economics of Treasury Securities Markets
Authors: Bikhchandani Sushil , Huang Chi-fu
Published: August 2012

The market for Treasury securities attracted considerable attention recently, after alleged infringements by Salomon Brothers. Several questions have been raised about the best way of selling U.S. government debt. One issue is whether altering the auction format would yield greater revenues for the Treasury. Another related question is how susceptible the existing mechanism for selling Treasury securities is to manipulation by buyers. In this paper, we describe what economists' analyses of auctions imply about the market for Treasury securities.
The Causes of Metropolitan Suburbanization
Authors: Mieszkowski Peter , Mills Edwin S
Published: August 2012

In this paper, we investigate the causes of metropolitan suburbanization. We consider two classes of theories of suburbanization, both of which are important: the first, favored by urban theorists and transportation experts, might be called a natural evolution theory; the second stresses the fiscal and social problems of central cities. We sketch the monocentric model of urban areas, discuss the gradient measure of suburbanization, and offer some cross-country comparisons of suburbanization. Finally we present conclusions and policy implications.
Land and Stock Prices in Japan
Authors: Stone Douglas , Ziemba William T
Published: August 2012

This paper discusses the rise of Japanese stock and land prices in the past four decades and their dramatic decline in the early 1990s. To what extent can fundamental factors explain both the price levels and the returns from land and stock in Japan? Are land prices driving stock prices, or the other way around, or are still other factors affecting both? How has government policy interacted with the price changes? In practice, it is very difficult to solve the problem of separating the explanation that a bubble occurred from the possibility that the underlying fundamental problem is misspecified. We believe that the bulk of the rise in Japanese asset prices from 1985–89 and the decline during 1990–92 was driven by interest rate and credit market conditions. However, in certain speculative land markets, there is some evidence in support of the bubble hypothesis.
Do Students Go to Class? Should They?
Authors: Romer David
Published: August 2012

Lectures and other class meetings are a primary means of instruction in almost all undergraduate courses. Yet almost everyone who has taught an undergraduate course has probably noticed that attendance at these meetings is far from perfect. There is surprisingly little systematic evidence, however, about attendance and its effects. There are three natural questions: What is the extent of absenteeism? How much, if at all, does absenteeism affect learning? Should anything be done about absenteeism? This article presents quantitative evidence on the first two of these questions and speculative comments on the third.
Retrospectives: The Law of Diminishing Returns
Authors: Brue Stanley L
Published: August 2012

From introductory economics to theoretical papers, the law of diminishing returns is a part of every economist's tool kit. But the evolution of this law in the history of economic analysis reveals more complexity than is perhaps generally understood. Even among those most responsible for its evolution, the law has been loosely defined, and many so-called “proofs” of the law have been weak and incomplete. Moreover, those who expounded the law and its economic implications rarely offered empirical evidence to support it. In fact, economists have offered alternative explanations for rising short-run marginal cost curves and other implications of the law of diminishing returns. This last point raises an interesting question: Have economists used the law of diminishing returns simply for convenience, or is the law fundamental to economic analysis?
Policy Watch: Income-Contingent College Loans
Authors: Krueger Alan B , Bowen William G
Published: August 2012

We consider the recently proposed “income-contingent loan” (ICL), in which Congress would establish a national trust fund from which students could borrow money to finance the cost of attending college; students would repay these loans by contributing a fixed proportion of their subsequent income for a specified number of years. One key issue is whether proposed income-contingent loan plans will be self-financing; that is, will the value of loan repayments cover the initial cost of providing the loan? What about adverse selection? And how should income be defined for purposes of an income-contingent loan plan? In essence the typical income-contingent loan proposal involves three parameters: the amount of the loan; the period over which income is “taxed”; and the rate at which income is taxed. At what level must the tax rate be set for an ICL plan to be self-financing? We present several illustrative calculations that might be useful to those who wish to evaluate various proposals and present some conclusions.
What Does Japanese Trade Structure Tell Us About Japanese Trade Policy?
Authors: Saxonhouse Gary R
Published: August 2012

Some argue foreign access to Japanese markets remains tightly controlled and that if Japan is to be a member in good standing of the international economic system, Japan must do more than just adhere to the formal rules of the GATT; Japan must show by the results of its international economic transactions that foreign access to its market is not tightly controlled. As this point of view is increasingly dominating American economic diplomacy with Japan, it is particularly important that its premise be examined. First I examine Japan's growth record and trade record. To the extent that Japan's trade performance is different, I explore whether the difference can legitimately be attributed to Japanese policies. This paper finds that neither the price behavior of Japanese firms nor the pattern and volume of what Japan imports or exports suggests that Japan's trade regime is different. Some of Japan's economic institutions may be distinctive but there is little evidence they produce outcomes which distort the international economic system. What remains to be explained is the conviction of so many that Japan is more a parasite than a pillar of the international economic system. The record of economic research directly and indirectly bearing on this issue does not support such a conclusion at all.
Japan's Different Trade Regime: An Analysis with Particular Reference to Keiretsu
Authors: Lawrence Robert Z
Published: August 2012

Many claim that although formal trade barriers have been removed at the border, Japanese markets remain unusually closed because of non-tariff barriers. After describing Japan's development strategy and the debate over the sources of Japanese growth, we consider current trade barriers. Recent research has made some headway investigating the impact of one of the alleged “invisible” barriers. In particular, efforts have been made to test if the behavior of Japanese corporate groups, known as keiretsu, creates a barrier to trade. Finally we consider whether private sector trade restrictions warrant a public response; what, if anything, should be done about keiretsu?
The Impact of Economic Development on Democracy
Authors: Huber Evelyne , Rueschemeyer Dietrich , Stephens John D
Published: August 2012

Any account of the social and economic conditions of democracy must come to terms with the central finding of the cross-national statistical research: a sturdy (though not perfect) association between economic development and democracy. To tackle these questions of causation, we adopted a strategy of analytic induction based on comparative historical research. Our program of comparative historical research confirmed the conclusion of the cross-national statistical analyses of the correlates of political democracy: the level of economic development is causally related to the development of political democracy. However, the underlying reason for the connection, in our view, is that capitalist development transforms the class structure, enlarging the working and middle classes and facilitating their self-organization, thus making it more difficult for elites to exclude them politically. Simultaneously, development weakens the landed upper class, democracy's most consistent opponent.
Was Schumpeter Right After All?
Authors: Heilbroner Robert
Published: August 2012

In Capitalism, Socialism, and Democracy (1947) Schumpeter asks “Can capitalism survive?” He answers: “No. I do not think it can.” In an essay I wrote in 1981 entitled “Was Schumpeter Right?” I began with the words: “No. I do not think he was.” Now, over a decade later, I wish to reconsider the question of whether Schumpeter was right, from a somewhat different point of view. To the question “Was Schumpeter Right?” I now give two answers. Was he right in his analysis of the prospects for capitalism? No, I still do not think he was. But was he right in his approach to the question of economic inquiry itself, an approach that recognized the presence of Vision as the precursor to Analysis? Yes, there I believe that he was not only right, but even more right than he himself realized
Managing Local Commons: Theoretical Issues in Incentive Design
Authors: Seabright Paul
Published: August 2012

Local commons encompass a wide range of resources whose shared feature is the need for some form of collective management. In what follows, we shall be concerned mainly with the problems of implementing a collective management plan. Whatever the mechanisms invoked, many recent contributions to the literature have stressed that relatively informal collective management of common property resources can in the right circumstances avoid the severe resource degradation predicted by “the tragedy of the commons.” Nevertheless, both empirical and theoretical arguments suggest that cooperative behavior may be only partial, and the incentives of short-term self-interest only partially held in check. Under what circumstances, then, can more formal implementation mechanisms make good the deficiency? And, given that formal incentives are typically stronger than informal ones, are there any reasons why informal incentives might nevertheless sometimes be preferred?
Supply-Side and Demand-Side Cost Sharing in Health Care
Authors: Ellis Randall P , McGuire Thomas G
Published: August 2012

In health markets, the price paid by insured consumers when health care services are demanded can be set separately from the price paid to providers when services are supplied. This fact suggests two alternate strategies for controlling the costs of health care: demand-side cost sharing, where patients must pay more in co-payments or deductibles, and supply-side cost sharing, which seeks to alter the incentives of health care workers to provide certain services. We review the rationale, limits, and comparative advantage of demand- and supply-side cost sharing in health care while primarily focusing on the short-run pursuit of consumer financial risk protection and efficiency. We then turn briefly to the long-run issue of technology adoption, as well as the how supply- and demand-side cost sharing may affect the fairness of the health system.
The Case of the Missing Currency
Authors: Sprenkle Case M
Published: August 2012

In late 1992, currency in the hands of the public was close to $300 billion, representing nearly 30 percent of M1. One would think that an economic variable of this magnitude would be well-analyzed and well-understood. Quite the contrary. The last serious surveys of currency holdings commissioned by the Federal Reserve were in 1984 and 1986. These surveys indicate that currency demand is not at all understood. Probably the most intriguing and newsworthy result of these surveys was that about 80 percent of currency holdings simply could not be explained. Despite the stir of general interest that followed those studies, economists have shown little lasting interest in considering the implications of these findings. This paper is written in hopes of stimulating more interest in currency behavior.
American and European Economics and Economists
Authors: Frey Bruno S , Eichenberger Reiner
Published: August 2012

America and Europe differ with regard to what economics is understood to be, how it is practiced, and how professional academic economists behave. Specifically, 1) American (U.S. and Canadian) economists contribute by far the largest share of journal publications and are cited much more often than European economists, while (West-) European economists consider other aspects of their professional activities more relevant, in particular participating in local and national affairs; 2) economic research by Americans tends to focus on abstract issues defined within the profession itself and involves fads, while the activities of European economists (though not necessarily their research) are more concerned with practical issues and follow a more steady course: and 3) American academics are geared to postgraduate teaching, while in Europe they are mostly engaged in undergraduate teaching. These differences can be explained by the different market conditions faced by American and European economists: in America, the academic market is much larger, and the degree of government intervention is typically much smaller. This paper explores how this leads to different focuses for European and American economists. In addition, it asks whether the ongoing economic unification in Europe may not alter these patterns.
Policy Watch: Alcohol and Cigarette Taxes
Authors: Grossman Michael , Sindelar Jody L , Mullahy John , Anderson Richard
Published: August 2012

Increased excise taxes on cigarettes and alcohol have been suggested as a means to finance (at least partially) the Clinton administration's proposed program of health care reform. We consider the revenue potential of cigarette and alcohol tax hikes and explore the effects on consumption and related outcomes. We present estimates of the social costs and implied optimal tax rates on cigarettes and alcohol. The bulk of the evidence presented here does support higher taxes on cigarettes and alcohol.
Symposium on Global Climate Change
Authors: Schmalensee Richard
Published: August 2012

Global climate change, and policies to slow it or adapt to it, may be among the primary forces shaping the world's economy throughout the next century and beyond. Nonetheless, popular treatments of this issue commonly ignore economics. This introductory essay sketches some of the uncertainties and research questions.
Coping with Asymmetries in the Commons: Self-Governing Irrigation Systems Can Work
Authors: Ostrom Elinor , Gardner Roy
Published: August 2012

Many analysts presume that the appropriators of a common-pool resource are trapped in a Hobbesian state of nature and cannot themselves create rules to counteract the perverse incentives they face in managing the resource. The logical consequence of this view is to recommend that an external authority—"the" government—take over the commons. But considerable empirical evidence from field and experimental settings holds that appropriators frequently do constitute and enforce their own rules, and that these rules work. Our research agenda is to develop a coherent understanding of the set of conditions that enhance or detract from self-organizing capabilities when individuals differ substantially from one another. For the sake of concreteness, this paper focuses on the asymmetry present in most irrigation systems between those who are physically near the source of water (the head-enders) and those who are physically distant from it (the tail-enders). This paper first explores the interaction between head-end and tail-end farmers, particularly their decisions about whether to devote resources to the upkeep of the irrigation system, and how bargaining between the parties can benefit all sides. Finally, we examine empirical evidence from a study of irrigation institutions in Nepal and discuss the broader practical significance of our findings.
Web-based survey Contraception and attitudes to sexual behaviour’ completed by women accessing a UK menopause website
Authors: Cumming Grant P , Cochrane Rosemary , Currie Heather D , Moncur Rik , Lee Amanda J
Published: August 2012

Background and methodology.

Sociodemographic trends mean increasing numbers of new relationships in later life. These trends may not only have health consequences for women and health services but also impact on the targeting of sexual health messages. This study aimed to examine attitudes and knowledge surrounding contraception, sexual health and unwanted pregnancy among those accessing the website www.menopausematters.co.uk . A voluntary online survey was completed.

Results.

Survey was completed by 550 respondents. Three hundred and sixty-six women, 94% of whom self-classified as pre- or perimenopausal, had been sexually active with a male partner in the previous four weeks. Commonest contraceptive methods used by perimenopausal and postmenopausal women were condoms, combined oral contraceptive pill (COCP) and male sterilization. Up to 42% of women surveyed were unhappy with their contraception. A total of 27% premenopausal, 32% perimenopausal women and 40% postmenopausal used no contraception. One-third of women were unhappy about this and 19 unplanned pregnancies had occurred. The majority of women were informed regarding COCP use over 35 years, hormone replacement therapy, emergency contraception and ceasing contraception. The majority of women were unaware that more terminations of pregnancy are performed in women over 40 than any other age group per total pregnancies.Almost a third of women were unaware that chlamydia incidence is increasing in older women. Most would use condoms in new relationship.

Discussion and conclusions.

Women accessing www.menopausematters.co.uk are well informed about contraception and sexual health. The majority of those accessing the site are sexually active, but many use no contraception, or are unhappy with their chosen method, leaving them vulnerable to unwanted pregnancy or sexually transmitted infection.
Recombinant human endostatin combined with definitive chemoradiotherapy as primary treatment for patients with unresectable but without systemic metastatic squamous cell carcinoma of the oesophagus
Authors: Zhong Z , Gu X , Zhang Z , Wang D , Qing Y , Li M , Dai N
Published: August 2012

Objective

The objective of this study was to review the outcomes of recombinant human endostatin combined with chemoradiotherapy (CRT) as primary treatment for patients with unresectable but without systemic metastatic squamous cell carcinoma (SCC) of the oesophagus.

Methods

A total of 38 patients with unresectable but without systemic metastatic SCC of the oesophagus (T4 or stage IVA) were retrospectively studied. 18 patients were treated with recombinant human endostatin combined with 5-fluorouracil (5-FU)/cisplatin (CDDP)-based CRT and 20 were treated with 5-FU/CDDP-based CRT alone. Short- and long-term effects including initial treatment response, survival and treatment-related complications were assessed with a median follow-up period of 36.1 months.

Results

CRT combined with endostatin resulted in a marked improvement in complete response rates (44.4% vs 30% in the CRT-alone group), and an increase in the 1-year and 3-year overall survival rates (72% vs 50.0% and 32% vs 22.0%, respectively), while the median time to progression was extended to 11.3 months in the combination group vs 8.1 months in the CRT-alone group. There were no treatment-related toxicities that could be attributed specifically to the endostatin, and the toxicities observed across the two groups are probably due to the CRT itself.

Conclusions

The short- and long-term effects of CRT combined with endostatin were an improvement over that of CRT alone in this retrospective cohort study. This combined treatment modality may be a promising treatment modality for the patients with unresectable but without systemic metastatic oesophageal cancer. Further prospective randomised control studies are needed to confirm this finding.
Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)
Authors: Thornton James E. , Chang Hao-Ming , Piskounova Elena , Gregory Richard I.
Published: August 2012

The pluripotency factor Lin28 recruits a 3′ terminal uridylyl transferase (TUTase) to selectively block let-7 microRNA biogenesis in undifferentiated cells. Zcchc11 (TUTase4/TUT4) was previously identified as an enzyme responsible for Lin28-mediated pre-let-7 uridylation and control of let-7 expression. Here we investigate the protein and RNA determinants for this interaction. Biochemical dissection and reconstitution assays reveal the TUTase domains necessary and sufficient for Lin28-enhanced pre-let-7 uridylation. A single C2H2-type zinc finger domain of Zcchc11 was found to be responsible for the functional interaction with Lin28. We identify Zcchc6 (TUTase7) as an alternative TUTase that functions with Lin28 in vitro, and accordingly, we find Zcchc11 and Zcchc6 redundantly control let-7 biogenesis in embryonic stem cells. Our study indicates that Lin28 uses two different TUTases to control let-7 expression and has important implications for stem cell biology as well as cancer.
Quantum Dot Immunocytochemical Localization of Somatostatin in Somatostatinoma by Widefield Epifluorescence, Super-resolution Light, and Immunoelectron Microscopy
Authors: Killingsworth Murray C. , Lai Ken , Wu Xiaojuan , Yong Jim L. C. , Lee C. Soon
Published: August 2012

Quantum dot nanocrystal probes (QDs) have been used for detection of somatostatin hormone in secretory granules of somatostatinoma tumor cells by immunofluorescence light microscopy, super-resolution light microscopy, and immunoelectron microscopy. Immunostaining for all modalities was done using sections taken from an epoxy resin-embedded tissue specimen and a similar labeling protocol. This approach allowed assessment of labeling at light microscopy level before examination at super-resolution and electron microscopy level and was a significant aid in interpretation. Etching of ultrathin sections with saturated sodium metaperiodate was a critical step presumably able to retrieve some tissue antigenicity masked by processing in epoxy resin. Immunofluorescence microscopy of QD-immunolabeled sections showed somatostatin hormone localization in cytoplasmic granules. Some variable staining of tumor gland-like structures appeared related to granule maturity and dispersal of granule contents within the tumor cell cytoplasm. Super-resolution light microscopy demonstrated localization of somatostatin within individual secretory granules to be heterogeneous, and this staining pattern was confirmed by immunoelectron microscopy.
Functional characterization of four novel PAX8 mutations causing congenital hypothyroidism: new evidence for haploinsufficiency as a disease mechanism
Authors: Narumi Satoshi , Araki Shunsuke , Hori Naoaki , Muroya Koji , Yamamoto Yukiyo , Asakura Yumi , Adachi Masanori , Hasegawa Tomonobu
Published: August 2012

Background

Individuals carrying a heterozygous inactivatingPAX8mutation are affected by congenital hypothyroidism (CH), although heterozygousPax8knockout mice are not. It has remained unclear whether CH inPAX8mutation carriers is caused by haploinsufficiency or a dominant negative mechanism.

Objective

To report clinical and molecular findings of four novelPAX8mutations, including one early-truncating frameshift mutation.

Subjects and methods

Four probands were CH patients. Two had family history of congenital or childhood hypothyroidism. Three probands were diagnosed in the frame of newborn screening for CH, while one had a negative result in screening but was diagnosed subsequently. Three had thyroid hypoplasia and one had a slightly small thyroid with low echogenicity. For these probands and their family members, we sequencedPAX8using a standard PCR-based method. Pathogenicity of identified mutations was verifiedin vitro.

Results

We found four novel heterozygousPAX8mutations in the four probands: L16P, F20S, D46SfsX24, and R133Q. Family studies showed four additional mutation carriers, who were confirmed to have high serum TSH levels. Expression experiments revealed that three mutations (L16P, F20S, and R133Q) had defects in target DNA binding, while D46fs had protein instability that was rescued by the proteasome inhibitor MG132. All four mutations had reduced transactivation on the thyroglobulin promoter, supporting that they were inactivating mutations.

Conclusion

D46fs is the firstPAX8mutation with confirmed protein instability. Our clinical andin vitrofindings together suggest that purePAX8haploinsufficiency can cause CH in humans.
MECHANISMS IN ENDOCRINOLOGY: Ghrelin: the differences between acyl- and des-acyl ghrelin
Authors: Delhanty Patric J D , Neggers Sebastian J , van der Lely Aart J
Published: August 2012

Des-acyl ghrelin (DAG) is one of the three preproghrelin gene-encoded peptides. Compared with ghrelin and obestatin, it has not received the attention it deserves. DAG has long been considered an inert degradation product of acyl ghrelin (AG). Recent evidence, however, indicates that DAG behaves like a separate hormone. DAG can act together with AG, can antagonize AG, and seems to have AG-independent effects. Therefore, it is believed that DAG must activate its own receptor and that it may also interact with AG at this receptor. Of potential clinical importance is that an increasing number of studies suggest that DAG might be a functional inhibitor of ghrelin and that DAG can suppress ghrelin levels in humans. Therefore, DAG or DAG analogs might be good candidates for future treatment of metabolic disorders or other conditions in which antagonism of AG actions could be beneficial, such as diabetes, obesity, and Prader–Willi syndrome.
Effects of retarders on the fluidity of pastes containing β-naphthalenesulfonic acid-based superplasticiser
Authors: Li Guoxin , He Tingshu , Hu Dawei , Huang Rujie , Shi Chen
Published: August 2012

The workability of a superplasticised cement paste can be improved by a higher fluidity and a lower flow loss. The effects of two retarders, sodium gluconate (SG) and citric acid (CA), on the workability of pastes containing 0·7 wt% β-naphthalenesulfonic acid-based superplasticiser (BNS) were determined. At the same BNS dosage, improved workability only occurred with the addition of 0·03–0·09 wt% SG, and not with 0·12–0·15 wt% SG or with 0·03–0·15 wt% CA. The reasons for this phenomenon were investigated by way of the adsorbed amount of BNS on C3S, C2S, C4AF-gypsum, and C3A-gypsum surfaces at different SG or CA dosages using ultraviolet spectrophotometry. SG and CA were found to reduce the adsorbed amounts of BNS on C3S, C2S, and C4AF-gypsum surfaces at 5 and 60 min because of the competitive adsorption between the retarders and BNS. CA also had a more remarkable reducing effect than SG. On the other hand, the adsorbed amount of BNS on C3A-gypsum was enhanced because the retarders accelerated the formation rate of ettringite. The adsorbed BNS amount was also higher in the presence of CA than that of SG, indicating that CA enhances the consumption of BNS in the structure of ettringite. Overall, 0·03–0·09 wt% SG distributes BNS better on different minerals and improves paste workability.
Effect of n-CaCO3 and metakaolin on hydrated Portland cement
Authors: Makar Jonathan M. , Beaudoin James J. , Trischuk Ken , Chan Gordon W. , Torres Faroan
Published: August 2012

The effect of calcium carbonate nanoparticles (nCaCO3) on the hydration of ordinary Portland cement (OPC) blended with metakaolin was studied through comparison with OPC, OPC plus metakaolin and OPC plus nCaCO3 control samples. Isothermal conduction calorimetry measurements showed that the hydration of the ternary OPC–metakaolin–nCaCO3 blend had pronounced early secondary phase hydration activity compared to the controls. X-ray diffraction and thermogravimetric analysis identified the phases as calcium aluminosulfates, with both ettringite and monosulfate forming more quickly in the ternary blend than in the other samples. The presence of the nCaCO3 also enhanced the formation of C3A·CaCO3·12H2O in both blends that contained it. The presence of the secondary phases or the nCaCO3 itself was associated with a significant reduction in strength in the ternary blend as compared to the OPC–metakaolin binary blend. The results suggest that caution is needed in the development of concrete with nanoparticle additions in order to avoid detrimental combinations of nanoparticles, OPC and supplementary cementing materials.
Dicalcium silicate doped with sulfur
Authors: Staněk Theodor , Sulovský Petr
Published: August 2012

Dicalcium silicate (Ca2SiO4 or C2S) containing foreign ions occurs as a component of Portland cement clinker and is called belite. Belite has a lower hydraulic activity than alite, which is the main component of Portland cement clinker. Belite can be prepared at lower expenditure and its hydraulic activation can have important impact on the economy and sustainability of the cement industry. This research focused on the activation of C2S by incorporation of SO3 into its crystal structure. This paper describes experiments with pure chemicals that characterise substitution of SiO2 by SO3 and its influence on the hydraulic activation of C2S. It was confirmed that sulfur stabilises the monoclinic modification β-C2S. The maximum content of SO3 in C2S under common laboratory burning conditions was approximately 4·4 wt%. The hydraulic activity of prepared β-C2S doped with SO3 was up to three times higher than in the reference non-activated β-C2S.
Effective medium approach to thermal conductivity: applying to core-shell nanocomposites
Authors: Poon S. J. , Petersen A. S.
Published: August 2012

The effective medium method is employed to study thermal conductivity of nanostructured phases consisting of embedded particles in a host. Beyond the average T-matrix single-particle approximation, the effect of higher-order inter-particle terms on heat transport is estimated to be small, which can be validated by using a re-formulated differential effective medium (DEM) approach. However, the effect of higher-order terms on heat transport is found to become significant when phonon scattering from embedded particles is considered. Applying the DEM approach to two-phase nanocomposites, particularly core-shell materials that mimic a three-dimensional superlattice, it results in a large reduction of thermal conductivity, and potentially high ZT.
Vertical drain consolidation with non-Darcian flow and void-ratio-dependent compressibility and permeability
Authors: WALKER R. , INDRARATNA B. , RUJIKIATKAMJORN C.
Published: August 2012

Vertical drains increase the rate of consolidation in soft soils by facilitating faster dissipation of excess pore water pressure through short, horizontal drainage paths. This paper presents an analytical solution for non-linear radial consolidation under equal-strain conditions incorporating smear but ignoring well resistance. Three aspects of non-linearity are considered: (a) non-Darcian flow, (b) a log-linear void-ratio–stress relationship; and (b) a log-linear void-ratio–permeability relationship. The analytical solution to non-linear radial consolidation can explicitly capture the behaviour of both overconsolidated and normally consolidated soils. For non-linear material properties, consolidation may be faster or slower when compared with the cases with constant material properties. The difference depends on the compressibility/permeability ratios (Cc/Ck and Cr/Ck), the preconsolidation pressure and the stress increase. If Cc/Ck < 1 or Cr/Ck < 1 then the coefficient of consolidation increases as excess pore pressures dissipate, and the corresponding rate of consolidation is greater.
Groundwater intrinsic vulnerability and risk mapping
Authors: Farjad Babak , Shafri Helmi Zulhaidi bin Mohd , Mohamed Thamer Ahmed , Pirasteh Saied , Wijesekara Nishad
Published: August 2012

Groundwater vulnerability mapping is an important key to improving planning and decision-making processes in order to prevent groundwater contamination. This study generates groundwater vulnerability maps for the Izeh Plain in Iran using a modified Drastic model, geographical information system and remote sensing data. Sensitivity analysis was used to assign weight by showing the importance of each parameter in the Drastic model. The highest weight (5) was assigned to the aquifer media factor of the model, which had the highest mean value (4·53), and the lowest weight was assigned to the topography factor. The resulting maps revealed that the groundwater is highly vulnerable in the southwest Izeh Plain.
System leakage by night flow analysis: a case study in Guyana
Authors: Peters Everson J. , Ben-Ephraim Yedidyah
Published: August 2012

In the Caribbean, water utility companies widely acknowledge the high levels of non-revenue water (NRW). In 2004, Guyana Water Incorporated (GWI) implemented a project as part of the company's strategy to reduce water leakage. This paper reports on the use of bottom-up real loss assessment to estimate customer night consumption and background leakage for the test No. 56 district metered area (DMA) based on minimum night flow (MNF) analyses. The results from the test site show that leakage may be more than 50% of the supply. However, there is evidence that interrupted supply may affect estimates of MNF. Therefore, the results should be used with caution as water collection and storage during the nights can lead to overestimation of recoverable losses. To improve the results of similar studies in Guyana, testing should be carried out during the rainy season when there is increased availability of supply and the DMAs should be smaller with a greater number of individual consumption monitors.
Recharge processes and groundwater evolution of multiple aquifers, Beijing, China
Authors: Wu Dong-jie , Wang Jin-sheng , Lin Xue-yu , Hu Qin-hong
Published: August 2012

A geological and hydrogeological survey was performed in the upper alluvial and proluvial fan and the northern mountain area of the Chaobai River in Beijing. Samples of local precipitation, surface water and groundwater (including spring discharges, groundwater from the fractured bedrock, and shallow and deep groundwater of the alluvium) were collected and analysed to assemble hydrochemical and isotopic data. Q-mode hierarchical cluster analysis (HCA) was used to classify the groundwater samples from multiple aquifers into objective groups. Two groups and six subgroups with distinct groundwater recharge sources, flowpath histories and geochemical evolution histories were identified. Inverse geochemical modelling was adopted to study the deep groundwater chemical evolution. Hydrochemical data and isotopic data on 2H, 3H and 18O were used to evaluate groundwater recharge, flowpath histories and geochemical evolution, and 87Sr was used to provide further insight into groundwater recharge sources and flow directions. It was found that particularly in areas of groundwater cones of depression, the deep alluvial groundwater may be partly derived from the groundwater of the underlying fractured bedrock. The phreatic, or unconfined, groundwater within the northern area of the alluvial and proluvial fan is sustained mainly by the lateral flow of groundwater from the piedmont regions and by recharge from surface water bodies such as the Miyun reservoir. The shallow alluvial groundwater within the central and southern areas of the alluvial and proluvial fan is recharged primarily by the local precipitation and agricultural irrigation. The deep alluvial groundwater within the central and southern areas of the fan is sustained chiefly by the flow of groundwater from the northern area of the fan or from the underlying fractured bedrock. Methodologies adopted in this work may be useful to future investigation of groundwater in multiple aquifer systems similar to this area.
Association of Dialysis Modality with Risk for Infection-Related Hospitalization
Authors: Lafrance Jean-Philippe , Rahme Elham , Iqbal Sameena , Elftouh Naoual , Vallée Michel , Laurin Louis-Philippe , Ouimet Denis
Published: August 2012

Background and objectives

Peritonitis is a well known complication of peritoneal dialysis (PD), whereas in hemodialysis (HD), bacteremia can be life threatening. Whether patients undergoing PD have higher risk than HD patients for infection-related hospitalizations (IRH) remains unknown.

Design, setting, participants, & measurements

A propensity score–matched retrospective cohort of patients undergoing long-term dialysis between January 2001 and December 2007 was assembled. Propensity scores were calculated using multivariable (demographic characteristics, smoking, body mass index, comorbid conditions, and laboratory data) logistic regression to estimate probability of receiving PD versus HD. A comparison of IRH risk by dialysis modality was estimated using a counting-process survival model.

Results

A total of 910 pairs of patients were matched by propensity scores. During a median follow-up of 2.1 years (interquartile range, 1.1–3.5 years), 341 patients were hospitalized once for an infection, 123 twice, and 106 at least three times. PD was associated with an increased risk for IRH compared with HD (propensity-matched hazard ratio [HR], 1.52). PD was associated with a reduced risk for septicemia (HR, 0.31) and pneumonia (HR, 0.58) but also an increased risk for dialysis-related infectious hospitalizations (HR, 3.44), defined as all cases of peritonitis and vascular access-related bacteremia, but not all septicemia cases.

Conclusions

PD patients are at higher risk for IRH than are HD patients. This risk is mostly explained by dialysis-related infections. However, further studies are needed to evaluate whether the severity of those hospitalizations is similar and whether this increased risk for IRH is associated with worse outcomes.
Clinical Analysis of Perioperative Complement Activity during Ischemia/Reperfusion Injury following Renal Transplantation
Authors: Błogowski Wojciech , Dołęgowska Barbara , Sałata Daria , Budkowska Marta , Domański Leszek , Starzyńska Teresa
Published: August 2012

Background and objectives

The complement cascade seems to be an important mediator modulating renal ischemia/reperfusion injury. This study analyzed whether significant changes occur in the levels of a terminal panel of complement molecules (C3a, C5a, and C5b-9/membrane attack complex) during the early phase of human kidney allograft reperfusion and evaluated the potential association of these changes with clinical post-transplant graft function in kidney transplant recipients.

Design, setting, participants, & measurements

Seventy-five renal transplant recipients undergoing transplantation between 2004 and 2006 were enrolled in the study and divided into early, slow, and delayed graft function groups. Blood samples were collected perioperatively during consecutive minutes of allograft reperfusion from the renal vein. Levels of complement molecules were measured using ELISA.

Results

Analysis revealed no significant changes in C3a and C5a levels throughout reperfusion. The main complement molecule that was significantly associated with post-transplant graft function was C5b-9/membrane attack complex; throughout the reperfusion period, perioperative levels of C5b-9/membrane attack complex were around two to three times higher in delayed graft function patients than early and slow graft function individuals (P<0.005). In addition, C5b-9/membrane attack complex levels had a relatively high clinical sensitivity and specificity (70%–87.5%) for the prediction of early and long-term (1 year) post-transplant allograft function.

Conclusions

This clinical study supports a role for the complement cascade in delayed graft function development. However, additional studies are needed to elucidate the exact mechanisms responsible for this phenomenon. In addition, perioperative measurements of C5b-9/membrane attack complex are highlighted as promising potential clinical markers of post-transplant renal allograft function.