bluuebunny/crossref_metadata_2025 huggingface dataset:
Media coverage of tobacco diversification: tradeoffs for community health
Authors: Austin W. David , Woodell Carol , Bailey Betty , Altman David G.
Published: September 2003

As part of a tobacco farmer diversification randomized intervention study in 14 eastern North Carolina counties, a media content analysis of 16 local newspapers was conducted. All available issues of each of the newspapers from the period 1 November 1996, through 31 December 1999, were reviewed, and all relevant articles were clipped, coded, and entered into a database. Media coverage intensity was compared, qualitatively, with data from interviews with local civic, health, and religious leaders. There was, on average, only one tobacco diversification article in every 100 newspaper issues. The hypothesis that coverage of tobacco diversification and tobacco control would become more favorable in the intervention counties over time was not supported. Interview data showed that organizational leaders placed a higher priority on tobacco diversification policy issues than evidenced by media coverage.
Falls in the elderly: challenges and opportunities in the rural settings: the Whyalla case. Preliminary report
Authors: Mwanri Lilian , Fuller Jeffrey
Published: September 2003

Describes the development of a management plan for prevention of falls and reduction of falls injuries for older and frail people in the community, nursing homes and acute care settings in Whyalla, South Australia. Falls among the elderly have been described as the most common causes of injury and hospital admissions for trauma in Australia. Prevention and control of injury is one of the five National Health Policy Priority Areas in Australia. As a response to the national initiative, and a felt need, the South Australian Centre for Rural and Remote Health was commissioned by the local health service to develop a plan that would address falls prevention in the older people in Whyalla. The plan was developed in consultation with the key stakeholders. An evidence‐based plan that uses messages from the scientific literature but modified to account for stakeholders’ feedback on what is feasible in practice, is considered a good example of best practice. Furthermore, the alignment of literature review alongside stakeholders’ consultation provides higher chances of the plan being adopted locally.
Revocable anonymous access to the Internet?
Authors: Claessens Joris , Díaz Claudia , Goemans Caroline , Dumortier Jos , Preneel Bart , Vandewalle Joos
Published: September 2003

With the worldwide growth of open telecommunication networks and in particular the Internet, the privacy and security concerns of people using these networks have increased. On the one hand, users are concerned about their privacy, and desire to anonymously access the network. On the other hand, some organizations are concerned about how this anonymous access might be abused. This paper intends to bridge these conflicting interests, and proposes a solution for revocable anonymous access to the Internet. Moreover, the paper presents some legal background and motivation for such a solution. However, the paper also indicates some difficulties and disadvantages of the proposed solution, and suggests the need for further debate on the issue of online anonymity.
Information seeking on the Web by women in IT professions
Authors: Wei Choo Chun , Marton Christine
Published: September 2003

The paper develops a behavioral model of Web information seeking that identifies four complementary modes of information seeking: undirected viewing, conditioned viewing, informal search, and formal search. In each mode of viewing or searching, users would adopt distinctive patterns of browser moves: starting, chaining, browsing, differentiating, monitoring, and extracting. The model is applied empirically to analyze the Web information seeking behavior of 24 women in IT professions over a two‐week period. Our results show that participants engaged in all four modes of information seeking on the Web, and that each mode may be characterized by certain browser actions. Overall, the study suggests that a behavioral approach that links information seeking modes (goals and reasons for browsing and searching) to moves (actions used to find and view information) may be helpful in understanding Web‐based information seeking.
Disconfirming user expectations of the online service experience: inferred versus direct disconfirmation modeling
Authors: O’Neill Martin , Wright Christine , Palmer Adrian
Published: September 2003

Heightened competition in the e‐commerce domain continues to force the need for a reliable and user‐friendly service quality measurement methodology. The challenge facing practitioners, however, is to identify and implement the most appropriate measurement tools for their operation. Disconfirmation measures have come to dominate the debate concerning this very issue, with both direct and inferred techniques presenting themselves as reliable and valid measures of online quality. This paper addresses this very debate in the context of an online library service setting. It presents findings that attest to the psychometric and diagnostic performance of both techniques and suggests that while much time is taken up discussing the former, the real power of such techniques for online operators rests with the latter, i.e. their ability to pinpoint service failures and direct continuous quality improvement efforts.
An exploratory study of advancing mobilization in the life insurance industry: the case of Taiwan’s Nan Shan Life Insurance Corporation
Authors: Luarn Pin , Lin Tom M.Y. , Lo Peter K.Y.
Published: September 2003

The practical application of enterprise mobilization is the use of a wireless network system and equipment to allow employees to update information on demand. This study employs a case study method, using in‐depth interviews of 29 corporate managers and experts to understand the current state of mobilization in the life insurance industry. The study suggests a conceptual framework for mobilization in the life insurance industry, and formulates possible research propositions incorporating a number of variables. The study also suggests a total of ten key success factors for the implementation of mobilization in the life insurance industry.
A case study of MMO2’s MADIC: a framework for creating mobile Internet systems
Authors: Olla Phillip , Patel Nayna , Atkinson Chris
Published: September 2003

Mobile Internet applications on ubiquitous mobile networks allows real‐time, anywhere, anytime connectivity to services. Owing to its scalability and potential cost savings, mobile communication is being increasingly applied in the business and consumer communities to create innovative data and voice application, which run over the Internet infrastructure. This paper reports on a case study at an organisation that created an innovative approach to developing mobile applications developed by third party independent developers. A conceptual wireless reference model is presented that was used to define the various system constituents required to create effective mobile applications.
Transition planning: how well does it work for young people with learning disabilities and their families?
Authors: Ward Linda , Mallett Robina , Heslop Pauline , Simons Ken
Published: September 2003

The legislation and guidance require that transition planning takes place for all children with a Statement of Special Educational Needs. The research reported here was undertaken by Linda Ward, Professor of Disability and Social Policy at the University of Bristol, where she is director of the Norah Fry Research Centre; Robina Mallett, Carer Support Officer at the Home Farm Trust; Pauline Heslop, Research Fellow at the Norah Fry Research Centre; and Ken Simons, Senior Research Fellow at the Norah Fry Research Centre until his untimely death in January 2003, to find out how well this legislation and guidance works in practice from the perspective of young people with learning disabilities and their families. Based on information from questionnaires completed by parents and separate in‐depth interviews with youngsters with learning disabilities and their parents, this article reveals that many young people in the study left school without any transition planning, as far as their parents were aware. Where transition planning had occurred, there was a stark mismatch between the topics families wanted to cover and those addressed by the professionals involved. Many of the youngsters who did receive transition planning had little if any involvement in the process; parental involvement was also significantly less than it should have been. In drawing conclusions from their research, the authors review the most positive aspects of the process from the perspective of the young people and their parents; parents' ideas for improving transition planning; and messages from the research for professionals, including those working in education.
Longevity and Life‐cycle Savings*
Authors: Bloom David E. , Canning David , Graham Bryan
Published: September 2003

We add health and longevity to a standard model of life‐cycle saving and show that, under plausible assumptions, increases in life expectancy lead to higher savings rates at every age, even when retirement is endogenous. In a stationary population these higher savings rates are offset by increased old age dependency, but during the disequilibrium phase, when longevity is rising, the effect on aggregate savings rates can be substantial. We find empirical support for this effect using a cross‐country panel of national savings rates.
Saving, Wealth and the Transition from Transfers to Individual Responsibility: The Cases of Taiwan and the United States*
Authors: Lee Ronald , Mason Andrew , Miller Timothy
Published: September 2003

Under the life‐cycle saving model, population aging leads to an increased demand for life‐cycle wealth. Changes in transfer systems create or destroy one component of life‐cycle wealth—transfer wealth. The decline in the familial transfer system in Taiwan and reform of the US Social Security system are two examples of ways that transfer wealth is reduced. The combined effects of aging and changes in transfer systems are analyzed using simulation analysis. Rapid aging and radical decline in transfer systems lead to a large but transitory surge in aggregate saving. Capital per worker increases rapidly and remains at a high level.
The Baby Boom and the Stock Market Boom*
Authors: Lim Kyung‐Mook , Weil David N.
Published: September 2003

This paper addresses two issues. The first is whether demographic change was plausibly responsible for the run‐up in stock prices over the last decade, and whether an attempt by the baby boom cohort to cash out of its investments in the period 2010–2030 might lead to an “asset meltdown”. The second issue is whether the rise in dependency that will accompany the retirement of the baby‐boom cohort calls for an increase in national saving. We analyze these issues using a forward‐looking macro‐demographic model, and show that they are related via the existence of installation costs for capital. If such costs are sufficiently large, then demographics do have the power to affect stock prices, but “saving for America's old age” is less optimal. However, conventional estimates of capital installation costs are not large enough to explain large stock price movements in response to actual demographic change.
Mortality and Early Growth in England, France and Sweden
Authors: Lagerlöf Nils‐Petter
Published: September 2003

We set up a stochastic open‐economy growth model with endogenous fertility and mortality. A three‐country version of the model is calibrated to pre‐industrial mortality data from England, France and Sweden. By fitting parameters to match observed rates of correlation in mortality rates, the model can also account for differences in both the volatility of mortality rates and the timing of the Industrial Revolution.
Communities in Nature : The Construction and Understanding of Forest Natures
Authors: Marsden Terry , Milbourne Paul , Kitchen Lawrence , Bishop Kevin
Published: September 2003

The paper outlines three different but interrelated theoretical strands associated with contemporary society‐nature debates; namely social constructionism, realism and ecological modernisation. By using empirical evidence from a case study of community and forestry interactions in a South Wales ex‐mining village, the paper argues for the need to incorporate into these theoretical debates a deeper analysis of community understandings and practices. It argues that variable aspects of nature are a critical element in understanding social community change, just as the latter is important in shaping the value and worth attributed to natural relations. The analysis begins to identify some of the conceptual and empirical gaps which exist in the theoretical interstices between the three approaches; suggesting a need to focus more effectively on aspects of community construction and practice, evolving governance and local embeddedness. These factors become important conceptual bridges in the larger social science quest to relate human materialities much more effectively to natural materialities (and vice versa).
The Complexities of Hunting in Rural England and Wales
Authors: Milbourne Paul
Published: September 2003

The recent ‘Liberty and Livelihood’ March in London highlights how the issue of hunting with dogs, which directly involves only a small minority of people in the British countryside and, opinion polls indicate, is opposed by the majority of the British population, can still dominate national political and media agendas. A key tactic of the March organisers, the Countryside Alliance, was to present hunting as an embedded part of rural life, emphasising important connections between natural discourses of rurality, hunting and broader rural social issues.It is these claimed embedded natures of hunting in rural areas that form the focus of this paper. Drawing on recent research in four case‐study hunting areas in the English and Welsh countryside, the paper positions hunting within a broader rural socio‐cultural context. It explores community understandings of and interactions with hunting, and considers the broader sociocultural role of hunting in these rural spaces. The case‐studies indicate that while hunting may be described as a socially and culturally embedded practice in these areas, its place within the rural community is bound up with a great deal of social and spatial complexity.
A Wolf at the Gate: The Anti‐Carnivore Alliance and the Symbolic Construction of Community
Authors: Skogen Ketil , Krange Olve
Published: September 2003

Controversies over the return of large carnivores (e.g. wolves) are often interpreted as clashes between rural traditionalism and urban modernity. Rural communities, however, have never been culturally monolithic, and modernization increases their diversity. However, the popular image is one of rural communities united against vermin and urban romantics. An important reason for this is probably the successful construction of the anti‐carnivore front as a last line of defence against destructive forces threatening rural life. Drawing on examples from a study in Østerdalen, Norway, the struggle against wolf protection is discussed as an instance of symbolic construction of community. Images of a threatened community are vital to the self‐understanding of the wolf adversaries, but cleavages run through the alliance. Three principal groups may be identified: sheep farmers, landowners who lease hunting, and people with strong ties to traditional land use practices (primarily hunting) and a rural working‐class culture. These groups have not always been allies, and conflicts of interest run through the ‘resistance front’. The task here is to identify the social forces that now bring them together, and to explain why the carnivore issue is well suited as a significant component in their symbolic construction of community.
Do Networks Matter for Innovation? The usefulness of the economic network approach in analysing innovation
Authors: Oerlemans Leon A.G. , Meeus Marius T.H. , Boekema Frans W.M.
Published: September 2003

Economic network theory emphasises the importance of external resource mobilisation. In this paper, the relations between the mobilisation and use of internal and external resources in innovation processes, and the innovative performance of firms, are explored empirically, using an adapted version of Håkansson's (1987) economic network model. The main research question was: to what extent do network variables contribute to the innovative performance of firms? To answer this question, we assessed the explanatory power of economic network theory within the empirical study of innovation. Firms were found to engage in various configurations of internal and external resource bases, enabling them to innovate with better results. The relations in the estimated models are strongly influenced by moderating variables such as sector, and type and level of innovations produced. Our main conclusion is that models that include both internal and external resources explain the innovative performance better than models in which only internal resources are used.
Synchronised Business Cycles in East Asia and Fluctuations in the Yen/Dollar Exchange Rate
Authors: McKinnon Ronald , Schnabl Gunther
Published: September 2003

Because many authors have proposed stimulating the ailing Japanese economy by monetary expansion and yen depreciation, we explore the repercussions of depreciating the yen against the dollar on the other East Asian economies – which largely peg to the dollar. Since 1980, economic integration among Japan's neighbours – China, Hong Kong, Indonesia, Korea, Malaysia, Philippines, Singapore and Thailand – has intensified and (except for China and Singapore) their business cycles have been highly synchronised. These cycles have been closely linked to fluctuations in the yen/dollar exchange rate – through changes in the export competitiveness, inflows of foreign direct investment and intra‐Asian income effects. We show that a major yen devaluation would have a negative impact on incomes in other East Asian economies and that it is not a sensible policy option for Japan.
Globalisation and Policy Effects in Africa
Authors: Bigsten Arne , Durevall Dick
Published: September 2003

Globalisation or market integration in Sub‐Saharan Africa is closely linked to the structural adjustment programmes. In this paper we focus on their dependence on the politics and institutional characteristics of the countries concerned. In particular, we argue that one important explanation for the dismal performance of many African countries, in spite of all the measures taken towards market liberalisation, is the combination of, first, a magnification of the effects of policy and, second, a lack of willingness or ability on the part of politicians to respect the restrictions imposed on their behaviour and policy choices by the liberalised markets. We look at how the increased exposure to international prices and returns on assets make the economic equilibrium relations – the law of one price and uncovered interest parity – relevant guidelines for economic policy. The argument is illustrated by the case of Zimbabwe, where lack of respect for the restrictions imposed by international markets has led to an economic crisis with negative growth rates and a departure from globalisation.
India's Informal Trade with Bangladesh: A Qualitative Assessment
Authors: Pohit Sanjib , Taneja Nisha
Published: September 2003

The large and vibrant informal trade between India, and Bangladesh continues to thrive despite unilateral/regional/multilateral trade liberalisation in these two countries. This calls for an in‐depth analysis of India's informal trade with Bangladesh. Using insights from the New Institutional Economics informal and formal institutions engaged in cross‐border trade are contrasted to examine whether informal trading arrangements provide better institutional solutions. The analysis, carried out on the basis of an extensive survey conducted in India and Bangladesh reveals that informal traders in India and Bangladesh have developed efficient mechanisms for contract enforcement, information flows, risk sharing and risk mitigation. Further, informal traders prefer to trade through the informal channel because the transaction costs of trading in the informal channel are significantly lower than the formal channel implying that informal trade takes place due to the inefficient institutional set up in the formal channel. The principal policy implication from the study is that unless the transacting environment of formal traders improves, informal trade will continue to coexist with formal trade, even if free trade is established in the SAARC region.
Honesty As Good Policy: Evaluating Maryland's Medicaid Managed Care Program
Authors: CHANG DEBBIE I. , BURTON ALICE , O'BRIEN JOHN , HURLEY ROBERT E.
Published: September 2003

Throughout the 1990s, the states launched many large‐scale innovations in health care financing and delivery. The demands associated with designing, implementing, and managing such initiatives compete for those resources needed to evaluate the impact of the innovations. But without a good faith effort to launch a credible evaluation, innovative and controversial programs may not be able to be sustained. Striking a balance between advocating for change and honestly determining how well the desired changes have been achieved is a delicate and daunting task, and state policymakers often do not spend much time evaluating their efforts, even though this may be critical to the success of their programs.

This article describes one state's assessment of a statewide, prepaid, Medicaid managed care program. We look at the evaluation as both an exercise in policy analysis and an indication of the response to various constituencies' concerns. Three of us either worked for the state or contracted with the state to help evaluate the program.
The Labor Market Consequences of Race Differences in Health
Authors: BOUND JOHN , WAIDMANN TIMOTHY , SCHOENBAUM MICHAEL , BINGENHEIMER JEFFREY B.
Published: September 2003

Differences in health status across different race and ethnic groups in the United States, particularly between black and white Americans, have been the subject of considerable medical and social science research. For instance, numerous studies using a variety of health measures have shown the health of black men and women to be worse than that of whites (e.g., Manton, Patrick, and Johnson 1987). The health disadvantage of Native Americans, relative to that of whites, has also been documented extensively. Patterns for other major ethnic groups (e.g., Hispanics and Asians) have been somewhat more variable, depending on the measure, the age of the study sample, and other factors such as place of birth and acculturation (Hayward and Heron 1999; Shalala et al. 1999).

Systematic health disparities are likely to have profound—and self‐reinforcing—consequences for the relative well‐being of different population groups. In this article, we focus on one dimension of such consequences: the association between race differences in health status and race differences in labor market outcomes.
Reciprocal Obligations: Managing Policy Responses to Prenatal Substance Exposure
Authors: JACOBSON PETER D. , ZELLMAN GAIL L. , FAIR C. CHRISTINE
Published: September 2003

Substance use during pregnancy poses substantial risks to the developing fetus and continues to generate considerable policy debate. Public policy responses to prenatal substance exposure (PSE) have varied depending in part on whether the substances in question are licit (e.g., tobacco and alcohol) or illicit (e.g., cocaine and heroin). The policy responses also have ranged from warning labels on the dangers to the developing fetus of using alcohol, to treating a pregnant woman's illicit substance use as child abuse. The most controversial case was Cornelia Whitner's criminal conviction in South Carolina for PSE after her newborn baby tested positive for cocaine metabolites. Although the conviction was upheld by the South Carolina Supreme Court, it is, to date, an isolated example (Whitner v. State of South Carolina, 492 S.E.2d 777 [S.C. 1997], cert denied, 523 U.S. 1145 [1998], but see Ferguson v. City of Charleston, 532 U.S. 67 [2001], and Ferguson v. City of Charleston, 308 F.3d 380 [4th Cir. 2002], ruling that PSE detection policies require the woman's informed consent).
The Quality of Analysts’ Earnings Forecasts During the Asian Crisis: Evidence from Singapore
Authors: Loh Roger K. , Mian Mujtaba
Published: September 2003

We bring together three disparate strands of literature to develop a comprehensive empirical framework to examine the efficiency of security analysts' earnings forecasts in Singapore. We focus specifically on how the increased uncertainty and the negative market sentiment during the period of the Asian crisis affected the quality of earnings forecasts. While we find no evidence of inefficiencies in the pre‐crisis period, our results suggest that after the onset of the crisis, analysts (1) issued forecasts that were systematically upward biased; (2) did not fully incorporate the (negative) earnings‐related news; and (3) predicted earnings changes which proved too extreme.
A Comparison of PIM Estimates with Direct Stock Information for Dwellings
Authors: Dalgaard Esben , Thomsen Annette
Published: September 2003

One of the major sources of uncertainty in capital stock estimates stems from the use of the perpetual inventory method (PIM) in all the cases where direct stock information is not available. In the Danish capital stock estimates, it has been possible to dispense with the PIM as far as buildings are concerned. Instead, an administrative register of buildings is used together with a property register and the business register to produce an exhaustive enumeration of practically all buildings in the economy broken down by industry and sector. For the most important type of buildings, namely dwellings, the paper compares direct stock estimates derived by multiplying physical quantities (square meters) by the replacement prices per square meter with those that would result from applying the PIM to historical investment series. Dwellings are by far the most important non‐financial assets in most developed economies.
Reconciling Household Surveys and National Accounts Data Using a Cross Entropy Estimation Method
Authors: Robilliard Anne‐Sophie , Robinson Sherman
Published: September 2003

This paper presents an approach to reconciling household surveys and national accounts data. The problem is how to use the information provided by the national accounts data to re‐estimate the household weights used in the survey so that the survey results are consistent with the aggregate data. The estimation approach uses an estimation criterion based on an entropy measure of information. The survey household weights are treated as a prior. New weights are estimated that are close to the prior and that are also consistent with the additional information. This approach is implemented to reconcile household survey data and macro data for Madagascar. The results indicate that the approach is powerful and flexible, supporting the efficient use of information from a variety of sources to reconcile data at different levels of aggregation in a consistent framework.
Bounds of the Gini Index Using Sparse Information on Mean Incomes
Authors: Ogwang Tomson
Published: September 2003

In this paper, bounds of the Gini index, based on grouped data, are proposed assuming sparse information on mean incomes in the sense that data on either the overall mean income or some of the group mean incomes are not reported. It turns out that the proposed bounds are identical to those proposed by other authors that have more stringent information requirements with respect to mean incomes.
Correcting NDP for SO2 and NOx Emissions: Implementation of a Theoretical Model in Practice
Authors: Ahlroth Sofia
Published: September 2003

The theoretical and the practical studies in the field of environmental accounting are often two separate lines of work. In this study, we develop an optimal control theory model for adjusting NDP for the effects of SO2 and NOx emissions, and subsequently insert empirically estimated values. The model includes correction entries for the effects on welfare, real capital, health and the quality and quantity of renewable natural resources. In the empirical valuation study, production losses were estimated with dose‐response functions. Recreational and other welfare values were estimated by the contingent valuation (CV) method. Effects on capital depreciation are also included. For comparison, abatement costs and environmental protection expenditures for reducing sulfur and nitrogen emissions were estimated. The theoretical model was then utilized to calculate the adjustment to NDP in a consistent manner. The estimated damage value of sulfur is close to the Swedish sulfur tax.
What Can Africa Learn from Asian Development Successes and Failures?
Authors: Klasen Stephan
Published: September 2003

Book reviewed in this article:

Peter Lawrence and Colin Thirtle (eds.), Africa and Asia in Comparative Economic Perspective
The Changing Role of the State in the Electricity Industry in Brazil, China, and India
Authors: Rufín Carlos , Rangan U. Srinivasa , Kumar Rajesh
Published: September 2003

ABSTRACT.Technological breakthroughs, macroeconomic pressures, and advances in economic thought have led to a redefinition of the role of the state from producer to arbiter among private interests. Still, the details of such a redefinition vary among countries. We aim to understand the reasons for such differences and draw their policy implications through a case study of the electricity industry in Brazil, China, and India. Over the past decade, these countries have sought to restructure their state‐owned electric utilities. The restructuring effort has led to different outcomes in the three countries. We argue that ideology, institutional arrangements, and the behavior of interest groups lie at the heart of such differences.
The Entrepreneurial Personality in the Context of Resources, Environment, and the Startup Process—A Configurational Approach
Authors: Korunka Christian , Frank Hermann , Lueger Manfred , Mugler Josef
Published: September 2003

The goal of this interdisciplinary study is to analyze the entrepreneurial personality in the context of resources, environment, and the startup process based on a configurational approach. The study focuses on the startup process. A questionnaire was developed to measure the configuration areas of personality, personal resources, environment, and organizing activities. A representative sample of 1,169 nascent entrepreneurs and new business owner–managers was examined. Three startup configurations were found which reveal different patterns of personality characteristics. These patterns are interpreted in the context of aspects of the environment, the resources, and the startup process.
Professional Employer Organizations and Their Role in Small and Medium Enterprises: The Impact of HR Outsourcing
Authors: Klaas Brian S.
Published: September 2003

While effective HR services and programs can help firms gain competitive advantage, small and medium enterprises (SMEs) often lack the internal resources required to develop and deliver these services and programs. As a result, SMEs increasingly are outsourcing HR activities to professional employer organizations (PEOs). Questions remain, however, about the conditions under which SMEs will benefit from outsourcing HR to a PEO, as well as about the type of benefits that are potentially available. The very nature of many HR activities raises questions about the risks associated with market governance and a PEO's ability to ensure service quality for SMEs. In order for these questions to be addressed, it is necessary to understand the process by which PEO utilization affects SME outcomes. In this article, we use transaction cost economics, social exchange theory, and the strategic HR literature to develop a framework for understanding the factors and conditions likely to affect whether and how an SME will benefit from using a PEO.
Anne Evans: Assessment of a Biotechnology Market Opportunity
Authors: Evans Anne G. , Varaiya Nikhil P.
Published: September 2003

This case describes Anne Evans’ search for a market opportunity in the biotechnology industry, and examines the feasibility of establishing a new venture to exploit this opportunity. The drug development process in the biopharmaceutical industry spans three critical phases: pharmaceutical discovery, pharmaceutical development, and product marketing. The drug development process is a very capital–intensive process with expenditures averaging $800 million per drug and with very high failure rates—only one out of 5,000 compounds that emerge from discovery and preclinical testing will make it into the market. The drug development process therefore contributes to very high cash burn rates and corporate failures in the biotechnology industry.
Isolation of the Arterial Supply to the Carotid and Central Chemoreceptors in the Sheep
Authors: Haouzi Philippe , Chenuel Bruno , Chalon Bernard , Braun Marc , Bedez Yvonne , Tousseul Bernard , Claudon Michel , Gille Jean‐Pierre
Published: September 2003

The aim of our study was to develop and validate a simple surgical model in the sheep which allows control of the gas composition of the blood supplying the carotid and central chemosensitive area independently of the rest of the body. This approach was made possible due to the specific features of the cranial circulation in the sheep. An extracorporeal circuit, consisting of a pump and a gas exchanger, was placed at the level of the two common carotid arteries to create a pressure gradient between the carotid and the systemic systems and to reverse blood flow in the vertebral vessels via the occipital arteries. When a pressure gradient of about 40 Torr was created between the systemic and carotid circulation, we found that no blood could reach the carotid bodies and the medulla without passing though the extracorporeal circulation. This was established (1) by measuring vertebral blood flow; and (2) by injecting either a coloured suspension or particles labelled with 99m*Tc into the systemic or the carotid circulation. The slope of the relationship between minute ventilation (V̇E) and systemic arterial PCO2 (Pa,CO2) during high CO2 inhalation in seven hyperoxic vagotomised and anaesthetised sheep was dramatically reduced, but remained above zero, when Pa,CO2 was maintained constant in the cephalic circuit (0.11 ± 0.15 vs. 0.70 ± 0.35 l min−1 Torr−1 for the control tests). This residual V̇E response to CO2 inhalation remains to be explained since it could not be accounted for by any of the chemical or circulatory changes occurring in the cephalic circulation. Nevertheless, this preparation provides an easy method of maintaining chemical and circulatory homeostasis at the chemoreceptor level.
Bumetanide, the Specific Inhibitor of Na+‐K+‐2Cl− Cotransport, Inhibits 1α,25‐Dihydroxyvitamin D3‐Induced Osteoclastogenesis in a Mouse co‐culture System
Authors: Lee Hyun‐A , Jeong Hyunjoo , Kim Eun‐Young , Nam Mi Young , Yoo Yun‐Jung , Seo Jeong‐Taeg , Shin Dong Min , Ohk Seung‐Ho , Lee Syng‐Ill
Published: September 2003

The Na+‐K+‐2Cl− cotransporter (NKCC1) is responsible for ion transport across the secretory and absorptive epithelia, the regulation of cell volume, and possibly the modulation of cell growth and development. It has been reported that a variety of cells, including osteoblasts, contain this cotransporter. In this study, the physiological role of NKCC1 in osteoclastogenesis was exploited in a co‐culture system. Bumetanide, a specific inhibitor of NKCC1, reduced the number of tartrate‐resistant acid phosphatase (TRAP)‐positive multinucleated cells. In order to investigate the mechanism by which bumetanide inhibits osteoclastogenesis, the mRNA expressions of the receptor activator of nuclear factor (NF)‐κB ligand (RANKL) and osteoprotegerin (OPG) were analysed by RT‐PCR. Exposure of osteoblastic cells to a medium containing 1 µM bumetanide reduced RANKL mRNA expression induced by 10 nM 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3, in a dose‐dependent manner. In addition, RANKL expression was also analysed with enzyme‐linked immunosorbant assay (ELISA) using anti‐RANKL antibody. The expression of RANKL was decreased with the increase of bumetanide concentration. In contrast, the expression of OPG mRNA, a novel tumour necrosis factor (TNF) receptor family member was increased in the presence of bumetanide. These results imply that bumetanide inhibits osteoclast differentiation by reducing the RANKL/OPG ratio in osteoblastic cells. However, no significant difference in M‐CSF mRNA expression was observed when bumetanide was added. Also, we found that the phosphorylation of c‐Jun NH2‐terminal kinase (JNK), which regulates the activity of various transcriptional factors, was reduced by bumetanide treatment. Conclusively, these findings suggest that NKCC1 in osteoblasts has a pivotal role in 1α,25(OH)2D3‐induced osteoclastogenesis partly via the phosphorylation of JNK.
Variability in End‐Tidal PCO2 and Blood Gas Values in Humans
Authors: Crosby Alexi , Robbins Peter A.
Published: September 2003

The aims of this study were: (1) to determine the within‐subject, between‐day variability in end‐tidal PCO2 (PET,CO2); (2) to determine whether the within‐subject, between‐day variability in PET,CO2 was caused by variations in metabolic acid‐base status; and (3) to determine whether between‐subject variations in blood gas variables arose predominantly through variations in respiratory or renal pH control mechanisms. Fourteen healthy males were studied, of whom 12 provided adequate data for further analysis. Each subject was studied on at least six different occasions, with each visit separated by at least 1 week. On each occasion, PET,CO2 was determined over a 4‐10 min period using a fine nasal catheter taped just inside the nose, and an arterialised capillary blood sample was obtained from each ear and analysed for blood gases. The following results were obtained. (1) PET,CO2 showed a standard deviation (S.D.) for the within‐subject, between‐day variation of 1.06 mmHg. (2) Less than 5 % (P = NS) of the variability in PET,CO2 could be explained by underlying variations in metabolic acid‐base status. (3) The variation in blood gas values between individuals did not fit a pattern associated with either a predominantly respiratory or a predominantly renal origin. Furthermore, the pattern of variation in the blood gas data suggested that variations in the renal controller for pH and the respiratory controller for pH were not independent. The precise origins of variability in blood gas regulation remain obscure.
Does Pulsatile and Sustained Neck Pressure or Neck Suction Produce Differential Cardiovascular and Sympathetic Responses in Humans?
Authors: Ogoh Shigehiko , Fadel Paul J. , Hardisty Janelle M. , Wasmund Wendy L. , Keller David M. , Raven Peter B. , Smith Michael L.
Published: September 2003

Although square‐wave sustained and R wave‐triggered pulsatile stimuli have been used to assess carotid baroreflex (CBR) function in humans, it remains unclear whether these different stimulus protocols elicit comparable responses and whether CBR responses adapt during prolonged stimulation. Thus, we measured muscle sympathetic nerve activity (MSNA), heart rate (HR) and mean arterial pressure (MAP) in response to +30 Torr neck pressure (NP) and ‐30 Torr neck suction (NS) delivered for 20 s either as a sustained or pulsatile stimulus. CBR‐mediated changes in MSNA, HR and MAP were similar with sustained and pulsatile stimuli. The time course of MSNA and HR responses identified that significant changes occurred during the initial 5 s and were better maintained over 20 s with NP than with NS. Changes in MAP exhibited a slower onset with the peak increase during NP occurring at 10 s (sustained, 7 ± 1 mmHg; pulsatile, 7 ± 1 mmHg; P > 0.05) and the nadir during NS occurring at 20 s (sustained, ‐7 ± 1 mmHg; pulsatile, ‐9 ± 2 mmHg; P > 0.05). These data demonstrate that sustained and pulsatile NP and NS produce comparable CBR‐mediated responses. Furthermore, despite MSNA and HR returning towards baseline during NS, CBR‐mediated changes in MAP are well maintained over 20 s of NS and NP.
Effects of Intravenous Perfusion of Glucagon on Renal Blood Flow in Conscious Sheep
Authors: Denis Nancy , Tebot Islamey , Bonnet Jeanne‐Marie , Cirio Alberto , Boivin Robert
Published: September 2003

The effect of glucagon on renal haemodynamics in sheep is controversial. In this study we have examined the effects of perfused glucagon on renal blood flow (RBF) in six conscious sheep bilaterally implanted with transit‐time ultrasonic flow metering probes around the renal arteries. Glucagon was perfused intravenously over 90 min at doses of 3.12, 6.25, 12.5, 25, 50 and 100 ng kg−1 min−1. Mean RBF was calculated over 10 min periods. Blood samples were taken to monitor the time course of the changes in glycaemia and glucagonaemia. The perfusions of glucagon induced rapid and progressive dose‐dependent increases in RBF (9‐19.2 %, P < 0.05) and glycaemia (29‐155 %, P < 0.05) for doses of 25‐100 ng kg−1 min−1. High positive correlations were found between the increases in RBF and glucagonaemia (R2= 0.95) and between the increases in RBF and glycaemia (R2= 0.96). At the lowest doses of glucagon (3.12‐12.5 ng kg−1 min−1), the increase in RBF was highly significant; however, the rise in glucose level was not. At the highest doses (25‐100 ng kg−1 min−1) the time course of the changes in RBF was parallel to that of glucagonaemia throughout the perfusion time. However, between minutes 45 and 90 of the glucagon perfusion, the increase in RBF was the inverse of the change in glycaemia, which decreased. One hour after the end of the 50 and 100 ng kg−1 min−1 perfusions, the glucose levels were still significantly higher than the baseline, while the RBF values were not. These results are consistent with the idea that the enhanced RBF cannot be attributed to a rise in blood glucose level. They also show that the haemodynamic response to glucagon perfusion was more sensitive than the metabolic response. It is concluded that the intravenous perfusion of physiological doses of glucagon induced a highly sensitive dose‐dependent increase in RBF in sheep.
Diabetes Increases Facilitative Glucose Uptake and GLUT2 Expression at the Rat Proximal Tubule Brush Border Membrane
Authors: Marks Joanne , Carvou Nicolas J. C. , Debnam Edward S. , Srai Surjit K. , Unwin Robert J.
Published: September 2003

The mechanism of renal glucose transport involves the reabsorption of filtered glucose from the proximal tubule lumen across the brush border membrane (BBM) via a sodium‐dependent transporter, SGLT, and exit across the basolateral membrane via facilitative, GLUT‐mediated, transport. The aim of the present study was to determine the effect of streptozotocin‐induced diabetes on BBM glucose transport. We found that diabetes increased facilitative glucose transport at the BBM by 67.5 % (P < 0.05) – an effect that was abolished by overnight fasting. Western blotting and immunohistochemistry demonstrated GLUT2 expression at the BBM during diabetes, but the protein was undetectable at the BBM of control animals or diabetic animals that had been fasted overnight. Our findings indicate that streptozotocin‐induced diabetes causes the insertion of GLUT2 into the BBM and this may provide a low affinity/high capacity route of entry into proximal tubule cells during hyperglycaemia.
Both dorsal horn and lamina VIII interneurones contribute to crossed reflexes from feline group II muscle afferents
Authors: Edgley S. A. , Jankowska E. , Krutki P. , Hammar I.
Published: September 2003

Previous studies have demonstrated that group II muscle afferents exert powerful actions on contralateral motoneurones and that these actions are mediated primarily via lamina VIII commissural interneurones. We examined whether dorsal horn interneurones also contribute to these actions, as they have been shown to contribute to the actions of group II afferents on ipsilateral motoneurones. We tested the susceptibility of IPSPs and EPSPs evoked from group II afferents in contralateral motoneurones to presynaptic inhibition as an indicator of the relative contribution of dorsal horn interneurones to these PSPs, since the monosynaptic activation of dorsal horn interneurones is more weakly and more briefly depressed by presynaptic inhibition than is the monosynaptic activation of lamina VIII and other intermediate zone and ventral horn interneurones. While the earliest components of IPSPs and EPSPs evoked by group II afferents were abolished by conditioning stimulation of group II afferents, consistent with them being evoked disynaptically by commissural interneurones, trisynaptic components of these PSPs were only partly reduced and are therefore attributed to dorsal horn interneurones. The same conditioning stimuli depressed the disynaptic excitation of lamina VIII commissural interneurones by group II afferents much less effectively than they depressed monosynaptic excitation, indicating that dorsal horn interneurones contribute to this disynaptic excitation. On the basis of these observations we conclude that that dorsal horn interneurones contribute to the late actions of group II muscle afferents on contralateral motoneurones through their disynaptic actions on commissural interneurones.
Effect of transcranial magnetic stimulation on single‐unit activity in the cat primary visual cortex
Authors: Moliadze Vera , Zhao Yongqiang , Eysel Ulf , Funke Klaus
Published: September 2003

Transcranial magnetic stimulation (TMS) has become a well established procedure for testing and modulating the neuronal excitability of human brain areas, but relatively little is known about the cellular processes induced by this rather coarse stimulus. In a first attempt, we performed extracellular single‐unit recordings in the primary visual cortex (area 17) of the anaesthetised and paralysed cat, with the stimulating magnetic field centred at the recording site (2 × 70 mm figure‐of‐eight coil). The effect of single biphasic TMS pulses, which induce a lateral‐to‐medial electric current within the occipital pole of the right hemisphere, was tested for spontaneous as well as visually evoked activity. For cat visual cortex we found that a single TMS pulse elicited distinct episodes of enhanced and suppressed activity: in general, a facilitation of activity was found during the first 500 ms, followed thereafter by a suppression of activity lasting up to a few seconds. Strong stimuli exceeding 50 % of maximal stimulator output could also lead to an early suppression of activity during the first 100–200 ms, followed by stronger (rebound) facilitation. Early suppression and facilitation of activity may be related to a more or less direct stimulation of inhibitory and excitatory interneurons, probably with different thresholds. The late, long‐lasting suppression is more likely to be related to metabotropic or metabolic processes, or even vascular responses. The time course of facilitation/inhibition may provide clues regarding the action of repetitive TMS application.