bluuebunny/crossref_metadata_2025 huggingface dataset:
The quality and qualities of population statistics, and the place of the census
Authors: Cook Len
Published: June 2004

Population counts are a key anchor for much of the official statistical system and the benchmark for many commercial and research surveys and analysis. Statistical offices around the world face a wide range of challenges in counting their population, most particularly in the years between censuses, as population flows become much freer and family structures continue to evolve. This paper considers these issues, reviewing how population counts have evolved over time in the UK and other countries. The paper also looks to the future, considering ways in which population count methodology might develop.
Neighbourhoods and area statistics in the post 2001 census era
Authors: Martin David
Published: June 2004

This paper examines the current interest in neighbourhood‐based policy in England and considers the extent to which the output geography developed for the 2001 census helps to meet the need for neighbourhood‐based data. The characteristics of the new census output geography are presented, and the difficulties of creating meaningful neighbourhood geographies from statistical reporting units reviewed. The new geography will provide a much improved basis for the consolidation of data from official administrative sources, but additional challenges are also discussed in relation to the future of census data collection and publication.
Simulating trends in poverty and income inequality on the basis of 1991 and 2001 census data: a tale of two cities
Authors: Ballas Dimitris
Published: June 2004

How much does the 2001 census tell us about the changes in people's life in British cities and regions since 1991? This paper attempts to answer this question by telling the stories of two British northern cities: Leeds and Sheffield. In particular, the paper investigates and compares socio‐economic change in these cities on the basis of actual 1991 and 2001 census data as well as estimated non‐census data. A static spatial microsimulation model is used to combine the outputs of the 1991 and 2001 censuses of UK population with data from the British Household Panel Survey (BHPS) data. In particular, selected Small Area Statistics (SAS) tables from the 1991 and 2001 censuses are used as constraints in the spatial microsimulation modelling exercise, which aims to reweight BHPS household records so that they satisfy these constraints. The paper briefly discusses the change in these census variables across different localities of the two cities. It is then shown how the changes in these variables affect the simulation of non‐census variables. Further, the microsimulation model is used to estimate the trends in income inequalities and child poverty between and within the two cities. Finally, the paper discusses the implication of the research findings for policy formulation.
The role of population change in widening the mortality gap in Scotland
Authors: Boyle Paul , Exeter Daniel , Flowerdew Robin
Published: June 2004

The social gradient in health and mortality has been acknowledged for some time and, more recently, there is some evidence that the gap between the richer and poorer is widening in Britain. Other studies have also shown that health and mortality outcomes are worse in places that are experiencing population decline and better in places that are growing. This analysis examines, first, whether there is a mortality gap between the least and most deprived people in Scotland, second, whether this gap has widened since the 1980s and, third, whether the gap can be explained by patterns of population change. Our results demonstrate that the widening mortality gap in Scotland cannot be explained simply as an artefact of population change, even though it is widening most in those places that are experiencing population decline. This type of research is made possible by the reliable denominator population information provided in the 1981 and 2001 censuses.
Finding work in 2001: urban–rural contrasts across England in employment rates and local job availability
Authors: Coombes Mike , Raybould Simon
Published: June 2004

Early results from the 2001 census of England allow a preliminary analysis of joblessness. People in the prime working ages (25–49) are more likely to be in work than those in their 50s, but the differences are quite subtle: in particular, men without qualifications are not much more likely to be in work when they are younger, despite the suggestions that too many men cease working in their 50s. The evidence supports the view that there is a national shortfall of demand for labour, that the low‐skilled are the least able to compete for scarce jobs, and older people are the most likely to be unqualified. Moreover there is a strong spatial clustering of areas where job availability has declined or grown least, undermining the government's claim that there were often available jobs near to concentrations of people without work.
The Appreciative System of Urban ICT Policies: An Analysis of Perceptions of Urban Policy Makers
Authors: COHEN‐BLANKSHTAIN GALIT , NIJKAMP PETER
Published: June 2004

ABSTRACT  Information and Communication Technology (ICT) has become an important tool to promote a variety of public goals and policies. In the past years much attention has been given to the expected social benefits from deploying ICTs in different urban fields (transportation, education, public participation in planning, etc.) and to its potential to mitigate various current or emerging urban problems. The growing importance of ICTs in daily life, business activities, and governance prompts the need to consider ICTs more explicitly in urban policies. Alongside the expectation that the private sector will play a major role in the ICT field, the expected benefits from ICTs also encourage urban authorities to formulate proper public ICT policies.

Against this background, various intriguing research questions arise. What are the urban policy‐makers’ expectations about ICTs? And how do they assess the future implications of ICTs for their city? A thorough analysis of these questions will provide a better understanding of the extent to which urban authorities are willing to invest in and to adopt a dedicated ICT policy.

This study is focusing on the way urban decision‐makers perceive the opportunities of ICT policy. After a sketch of recent development and policy issues, a conceptual model is developed to map out the driving forces of urban ICT policies in cities in Europe. Next, by highlighting the importance of understanding the decision‐maker's “black box,” three crucial variables are identified within this box. In the remaining part of the paper these three variables will be operationalized by using a large survey comprising more than 200 European cities. By means of statistical multivariate methods (i.e., factor and cluster analysis), the decision‐makers were able to be characterized according to the way they perceive their city (the concept of “imaginable city”), their opinion about ICT, and the way they assess the relevance of ICT policies to their city. Next, a solid explanatory framework will be offered by using a log‐linear logit analysis to test the relationships between these three aspects.
Chinese Assimilation Across America: Spatial and Cohort Variations
Authors: NEWBOLD K. BRUCE
Published: June 2004

ABSTRACT  Portes and Borocz's (1989) segmented assimilation framework argued that the assimilation of immigrants into American society does not necessarily or automatically lead to similarity and equality with the mainstream culture. Instead, endowed human capital, the nature of immigration, and reception contextualize the process and potentially lead to differential outcomes. Recognizing that spatial differences in assimilation may also exist, the segmented assimilation framework is extended within this paper to include a more explicit recognition of geography's role in shaping the assimilation trajectory. The empirical analysis draws upon the 1980 and 1990 PUMS data files, and compares the assimilation trajectory of Chinese immigrants (excluding Hong Kong and Taiwanese origins) across the New York, San Francisco, and Los Angeles metropolitan areas. Based upon period of arrival and age in 1980 and 1990, measures of assimilation are compared across these three metropolitan areas, along with the role of internal migration in maintaining or decreasing assimilation differences. The analysis indicates that the progress of assimilation varies significantly over space, with spatial differences in measures of assimilation persisting over time, despite the role of internal migration. Reasons as to why this occurs are presented in the conclusion.
Controlling business? Agency and constraint in call centre working
Authors: Beirne Martin , Riach Kathleen , Wilson Fiona
Published: June 2004

Studies of call centre working have focused almost exclusively on the sophistication of technological and bureaucratic systems of labour control. The commercial context in which firms operate remains relatively under‐researched, despite exerting a significant influence on job structures and the working out of labour relations.
Teams investing their knowledge shares in the stock market of virtuality: a gain or a loss?
Authors: Papacharalambous Lefki , McCalman James
Published: June 2004

Best knowledge‐sharing practices in team‐based work are a ‘must’ for success in flexible and adaptable organisation forms. This research study provides actionable insights on how managers can enhance the knowledge worker's willingness to collaborate in a specific type of virtual teaming, the learning team, and build better communication and collaboration practices in and between these teams.
How Useful Is Quantitative Risk Assessment?
Authors: Apostolakis George E.
Published: June 2004

This article discusses the use of quantitative risk assessment (QRA) in decision making regarding the safety of complex technological systems. The insights gained by QRA are compared with those from traditional safety methods and it is argued that the two approaches complement each other. It is argued that peer review is an essential part of the QRA process. The importance of risk‐informed rather than risk‐based decision making is emphasized. Engineering insights derived from QRAs are always used in combination with traditional safety requirements and it is in this context that they should be reviewed and critiqued. Examples from applications in nuclear power, space systems, and an incinerator of chemical agents are given to demonstrate the practical benefits of QRA. Finally, several common criticisms raised against QRA are addressed.
Ramifications of Risk Measures in Implementing Quantitative Performance Assessment for the Proposed Radioactive Waste Repository at Yucca Mountain, Nevada, USA
Authors: Mohanty Sitakanta , Codell Richard B.
Published: June 2004

As part of its preparation to review a potential license application from the U.S. Department of Energy (DOE), the U.S. Nuclear Regulatory Commission (NRC) is examining the performance of the proposed Yucca Mountain nuclear waste repository. In this regard, we evaluated postclosure repository performance using Monte Carlo analyses with an NRC‐developed system model that has 950 input parameters, of which 330 are sampled to represent system uncertainties. The quantitative compliance criterion for dose was established by NRC to protect inhabitants who might be exposed to any releases from the repository. The NRC criterion limits the peak‐of‐the‐mean dose, which in our analysis is estimated by averaging the potential exposure at any instant in time for all Monte Carlo realizations, and then determining the maximum value of the mean curve within 10,000 years, the compliance period. This procedure contrasts in important ways with a more common measure of risk based on the mean of the ensemble of peaks from each Monte Carlo realization. The NRC chose the former (peak‐of‐the‐mean) because it more correctly represents the risk to an exposed individual. Procedures for calculating risk in the expected case of slow repository degradation differ from those for low‐probability cases of disruption by external forces such as volcanism. We also explored the possibility of risk dilution (i.e., lower calculated risk) that could result from arbitrarily defining wide probability distributions for certain parameters. Finally, our sensitivity analyses to identify influential parameters used two approaches: (1) the ensemble of doses from each Monte Carlo realization at the time of the peak risk (i.e., peak‐of‐the‐mean) and (2) the ensemble of peak doses calculated from each realization within 10,000 years. The latter measure appears to have more discriminatory power than the former for many parameters (based on the greater magnitude of the sensitivity coefficient), but can yield different rankings, especially for parameters that influence the timing of releases.
Mesothelioma Among Brake Mechanics: An Expanded Analysis of a Case‐Control Study
Authors: Hessel Patrick A. , Teta M. Jane , Goodman Michael , Lau Edmund
Published: June 2004

The U.S. Environmental Protection Agency has begun discussions to consider its assessment of asbestos toxicity related to mineral form and fiber size. Brake workers are typically exposed to short chrysotile fibers. To explore the mesothelioma risk among brake workers, considering other occupational exposures to asbestos, data from a study that was published previously were obtained and the analysis was extended. The National Cancer Institute provided data from a case‐control study of mesothelioma. Because many participants with a history of brake work also had employment in other asbestos‐related occupations, mesothelioma cases and controls were compared for a history of brake work, controlling for employment in eight occupations with potential asbestos exposure. A stratified analysis was also performed excluding those with any of the eight occupations. Possible interactions between brake work and other occupational exposures related to risk of mesothelioma were also examined. The odds ratio (OR) for employment in brake installation or repair was 0.71 (95% CI: 0.30–1.60) when controlled for insulation or shipbuilding. When a history of employment in any of the eight occupations with potential asbestos exposure was controlled, the OR was 0.82 (95% CI: 0.36–1.80). ORs did not increase with increasing duration of brake work. Exclusion of those with any of the eight exposures resulted in an OR of 0.62 (95% CI: 0.01–4.71) for occupational brake work. There was no evidence of an interaction between brake work and other occupational exposures. These latter analyses were based on small numbers of exposed cases. The results are consistent with the existing literature indicating that brake work does not increase the risk of mesothelioma and adds to the evidence that fiber type and size are important determinants of mesothelioma risk.
Quantification of Variability and Uncertainty Using Mixture Distributions: Evaluation of Sample Size, Mixing Weights, and Separation Between Components
Authors: Zheng Junyu , Frey H. Christopher
Published: June 2004

Variability is the heterogeneity of values within a population. Uncertainty refers to lack of knowledge regarding the true value of a quantity. Mixture distributions have the potential to improve the goodness of fit to data sets not adequately described by a single parametric distribution. Uncertainty due to random sampling error in statistics of interests can be estimated based upon bootstrap simulation. In order to evaluate the robustness of using mixture distribution as a basis for estimating both variability and uncertainty, 108 synthetic data sets generated from selected population mixture log‐normal distributions were investigated, and properties of variability and uncertainty estimates were evaluated with respect to variation in sample size, mixing weight, and separation between components of mixtures. Furthermore, mixture distributions were compared with single‐component distributions. Findings include: (1) mixing weight influences the stability of variability and uncertainty estimates; (2) bootstrap simulation results tend to be more stable for larger sample sizes; (3) when two components are well separated, the stability of bootstrap simulation is improved; however, a larger degree of uncertainty arises regarding the percentiles coinciding with the separated region; (4) when two components are not well separated, a single distribution may often be a better choice because it has fewer parameters and better numerical stability; and (5) dependencies exist in sampling distributions of parameters of mixtures and are influenced by the amount of separation between the components. An emission factor case study based upon NOxemissions from coal‐fired tangential boilers is used to illustrate the application of the approach.
The Risk of MTBE Relative to Other VOCs in Public Drinking Water in California
Authors: Williams Pamela R. D. , Benton Laurie , Sheehan Patrick J.
Published: June 2004

Ongoing publicity about methyl tertiary butyl ether (MTBE) suggests that this chemical is of greater concern than other contaminants commonly found in drinking water. The purpose of this article is to evaluate the available MTBE data in context with other volatile organic compounds (VOCs) that are detected in public drinking water sources in California. We find that of the 28 VOCs with a primary maximum contaminant level (MCL) in California, 21 were found in 50 or more drinking water sources from 1985 to 2002. Over the last 10 years, the most frequently detected VOCs were chloroform, tetrachloroethylene (PCE), and trichloroethylene (TCE), which were found in about 9–15% of all sampled drinking water sources. These same chemicals were found to have the highest mean detected concentrations over the last 5 years, ranging from 13 to 15 μg/L. Many VOCs were also found to routinely exceed state and federal drinking water standards, including benzene and carbon tetrachloride. By comparison, MTBE was found in approximately 1% of sampled drinking water sources for most years, and of those drinking water sources found to contain MTBE from 1998 to 2002, over 90% had detected concentrations below California's primary MCL of 13 μg/L. Relative to the other VOCs evaluated, MTBE has the lowest estimated California cancer potency value, and was found to pose one of the least cancer risks from household exposures to contaminated drinking water. These findings suggest that MTBE poses an insignificant threat to public drinking water supplies and public health in California, particularly when compared to other common drinking water contaminants.
Value of Information Analysis in Environmental Health Risk Management Decisions: Past, Present, and Future
Authors: Yokota Fumie , Thompson Kimberly M.
Published: June 2004

Experts agree that value of information (VOI) analyses provide useful insights in risk management decisions. However, applications in environmental health risk management (EHRM) remain largely demonstrative thus far because of the complexity in modeling and solving VOI problems. Based on this comprehensive review of all VOI applications published in the peer‐reviewed literature of such applications, the complexity of solving VOI problems with continuous probability distributions as inputs in models emerges as the main barrier to greater use of VOI although simulation allows analysts to solve more complex and realistic problems. Several analytical challenges that inhibit greater use of VOI techniques include issues related to modeling decisions, valuing outcomes, and characterizing uncertain and variable model inputs appropriately. This comprehensive review of methods for modeling and solving VOI problems for applications related to EHRM provides the first synthesis of important methodological advances in the field. The insights provide risk analysts and decision scientists with some guidance on how to structure and solve VOI problems focused on evaluating opportunities to collect better information to improve EHRM decisions. They further suggest the need for some efforts to standardize approaches and develop some prescriptive guidance for VOI analysts similar to existing guidelines for conducting cost‐effectiveness analyses.
Agreement Between Scales in the Measurement of Breast Cancer Risk Perceptions
Authors: Schapira Marilyn M. , Davids Susan L. , McAuliffe Timothy L. , Nattinger Ann B.
Published: June 2004

The objective of this article is to compare the accuracy and numeric responses of breast cancer risk perception as measured by a frequency scale and percentage scale. A cross‐sectional survey was conducted. Perceptions of five‐year and lifetime breast cancer risk were measured using a frequency and a percentage scale. Estimation error was calculated as the absolute difference between actual breast cancer risk as determined by the Gail model and perceived risk. Agreement between scales was determined by calculating the mean and standard deviation of the difference between numeric responses. The study was conducted among women enrolled in two primary care clinics associated with an academic medical center. Two‐hundred‐fifty‐four participants were recruited from one of the two participating internal medicine clinics. Inclusion criteria included female gender and age 40–84 years. Exclusion criteria included a history of breast cancer, dementia, or a life expectancy of less than two years. The frequency scale was more accurate than the percentage scale in estimating lifetime risk (p= 0.05), but less accurate in estimating five‐year risk (p < 0.02). Only 79 participants (31%) were considered consistent scale users, providing identical responses when using the frequency and percentage scale for a given risk estimate. Although the mean difference (percentage‐frequency scale) for estimates of breast cancer lifetime risk was only 2.4, the empirically determined 90% limits of agreement between the frequency and percentage scale for lifetime risk were wide, from –30 to 40. Higher numeracy was associated with consistent use of scales (OR 1.61, 95% CI; 1.09–2.37). We report disagreement in breast cancer risk perceptions when measured by a frequency and a percentage scale. The accuracy and direction of bias associated with each scale varies according to the time frame of risk being assessed.
Local Acceptance of a High‐Level Nuclear Waste Repository
Authors: Sjöberg Lennart
Published: June 2004

The siting of nuclear waste facilities has been very difficult in all countries. Recent experience in Sweden indicates, however, that it may be possible, under certain circumstances, to gain local support for the siting of a high‐level nuclear waste (HLNW) repository. The article reports on a study of attitudes and risk perceptions of people living in four municipalities in Sweden where HLNW siting was being intensely discussed at the political level, in media, and among the public. Data showed a relatively high level of consensus on acceptability of at least further investigation of the issue; in two cases local councils have since voted in favor of a go‐ahead, and in one case only a very small majority defeated the issue. Models of policy attitudes showed that these were related to attitude to nuclear power, attributes of the perceived HLNW risk, and trust. Factors responsible for acceptance are discussed at several levels. One is the attitude to nuclear power, which is becoming more positive, probably because no viable alternatives are in sight. Other factors have to do with the extensive information programs conducted in these municipalities, and with the logical nature of the conclusion that they would be good candidates for hosting the national HLNW repository.
Macroeconomic Adjustment and the Poor: Analytical Issues and Cross‐Country Evidence
Authors: Agénor Pierre‐Richard
Published: June 2004

Abstract. This paper studies the links between macroeconomic adjustment and poverty. The first part summarizes some of the recent evidence on poverty in the developing world. The second reviews the various channels through which macroeconomic policies affect the poor, whereas the third is devoted to the specific role of the labor market. It presents an analytical framework that captures some of the main features of the urban labor market in developing countries and studies the effects of fiscal adjustment on wages, employment, and poverty. The fourth part presents cross‐country regressions linking various macroeconomic and structural variables to poverty. Higher levels and growth rates of per capita income, higher rates of real exchange rate depreciation, better health conditions, and a greater degree of commercial openness lower poverty, whereas inflation, greater income inequality, and macroeconomic volatility tend to increase it. Moreover, the impact of growth on poverty appears to be asymmetric; it seems to result from a significant relationship between episodes of increasing poverty and negative growth rates.
The Asymmetric Effects of Monetary Policy
Authors: Florio Anna
Published: June 2004

Abstract.  The paper deals with the asymmetric effects on output of tight and easy monetary policy: the output reduction following a negative monetary policy shock appears bigger than the expansion induced by similar sized positive shock. The paper first reviews historical evidence of asymmetry, focusing on the United States, Japan and Italy. This is followed by a review of the econometric literature on monetary policy asymmetry and consideration of the theoretical reasons that can explain this asymmetry.
Structural characteristics of repair tissue of cricoid cartilage defects treated with recombinant human bone morphogenetic protein‐2
Authors: Tcacencu Ion , Carlsöö Bengt , Stierna Pontus
Published: June 2004

We examined the structural characteristics of repair tissue induced by recombinant human bone morphogenetic protein‐2 in a rabbit model of laryngotracheal reconstruction. Twenty‐four New Zealand White rabbits were randomly divided into four groups of six rabbits. Two groups were treated with recombinant human bone morphogenetic protein‐2 delivered on an absorbable collagen sponge, while two groups were used as controls. Rabbits were euthanized at 1 and 4 weeks after surgery. The larynx was removed, fixed, and sectioned. The sections were stained with hematoxylin‐eosin, safranine O/fast green, and immunostained with an antibody for tissue inhibitor of metalloproteinases‐1. In rabbits treated with bone morphogenetic protein‐2, the defects were filled with new cartilage and bone at 4 weeks after surgery. There were no discontinuities or gaps at the margins of the cartilage defects. Proteoglycans were synthesized in new cartilage in rabbits treated with bone morphogenetic protein‐2, and were present 4 weeks after surgery. The general aspects of the vascular pattern and the pattern of tissue inhibitor of metalloproteinases‐1 expression were similar in control and treated rabbits, both 1 week and 4 weeks after surgery. The repair tissue induced by recombinant human bone morphogenetic protein‐2 consisted of new cartilage and bone perfectly integrated with host tissue at the site of the cricoid cartilage defects. This new cartilage was able to mature and produce proteoglycans.
Mast cells promote fibroblast populated collagen lattice contraction through gap junction intercellular communication
Authors: Moyer Kurtis E. , Saggers Gregory C. , Ehrlich H. Paul
Published: June 2004

The release of mast cell granules is commonly associated with inflammation and fibrosis. However, does direct communication between mast cells and fibroblasts through gap junction intercellular communication (GJIC) occur? Fibroblast populated collagen lattice (FPCL) cast with mast cells show enhanced lattice contraction. Do released granules or GJIC between mast cells and fibroblasts promote enhanced lattice contraction? Mast cells preloaded with a fluorescent dye that readily passes through gap junctions were cast in FPCL. Dye passed from mast cells into fibroblasts within these cocultured mast cell‐FPCLs. Fatty acid amide hydrolase inhibitor blocks the breakdown of oleamide, which is a potent endogenous inhibitor of GJIC. GJIC was blocked for 3 days when mast cells were pulsed for 3 hours with fatty acid amide hydrolase inhibitor. Mast cells pretreated with fatty acid amide hydrolase inhibitor cast in cocultured mast cell‐FPCLs failed to enhance cocultured lattice contraction. Mast cell‐FPCLs made with mouse fibroblasts unable to generate GJIC failed to show enhanced lattice contraction. Degranulated mast cells were equal to intact mast cells at enhancing cocultured mast cell‐FPCL contraction. The supernatant from degranulated mast cells had no effect upon FPCL contraction. Therefore, enhanced mast cell‐FPCL contraction appears to be independent of mast cell granules, but dependent upon GJIC between fibroblasts and mast cells. We speculate that mast cell–fibroblast GJIC may play a role in fibrosis.
Use of peracetic acid to sterilize human donor skin for production of acellular dermal matrices for clinical use
Authors: Huang Qizhi , Dawson Rebecca A. , Pegg David E. , Kearney John N. , Macneil Sheila
Published: June 2004

We previously reported methods for sterilizng human skin for clinical use. In a comparison of γ‐irradiation, glycerol, and ethylene oxide, sterilization with ethylene oxide after treatment with glycerol provided the most satisfactory dermis in terms of structure and its ability to produce reconstructed skin with many of the characteristics of normal skin. However, the use of ethylene oxide is becoming less common in the United Kingdom due to concerns about its possible genotoxicity. The aim of this study was to evaluate peracetic acid as an alternative sterilizing agent. Skin sterilized with peracetic acid was compared with skin sterilized using glycerol alone or glycerol with ethylene oxide. The effect of subsequently storing peracetic acid sterilized skin in glycerol or propylene glycol was also examined. Acellular dermal matrices were produced after removal of the epidermis and cells in the dermis, processed for histological and ultrastructural analysis, and the biological function was evaluated by reconstitution with keratinocytes and fibroblasts. Results showed that sterilized acellular matrices retained the integrity of dermal structure and major components of the basement membrane. There were no overall significant differences in the ability of these matrices to form reconstructed skin, but peracetic acid alone gave a lower histologic score than when combined with glycerol or propylene glycol. We conclude that peracetic acid sterilization followed by preservation in glycerol or propylene glycol offers a convenient alternative protocol for processing of human skin. It is suggested that this sterile acellular dermis may be suitable for clinical use.
Migration inhibitory factor‐related protein (MRP)8 and MRP14 are differentially expressed in free‐electron laser and scalpel incisions
Authors: Wu Nanjun , Davidson Jeffrey M.
Published: June 2004

Incisions made in mouse skin by scalpel or the free‐electron laser heal at different rates. To identify genes that are differentially expressed in free‐electron laser or scalpel wounds, we isolated total RNA from free‐electron laser‐ or scalpel‐produced incisions and normal skin at day 7 postwounding. cDNA microarray analysis identified 89 of 15,000 genes in a mouse microarray as having significantly different expression levels. Migration inhibitory factor‐related protein (MRP) 14 was almost 30 times more highly expressed in scalpel wounds than in free‐electron laser wounds. This result was confirmed by Northern blot analysis, which also showed that scalpel wounds expressed higher levels of MRP8, a related S100 protein that can heterodimerize with MRP14, at days 2, 7, and 14 postwounding. Free‐electron laser wounds also showed elevated expression of MRP8 and MRP14 relative to normal skin. In situ hybridization showed that the patterns of MRP14 and MRP8 expression in free‐electron laser and scalpel wound tissues were similar. MRP14 and MRP8 were expressed in the dermal wound margin, while a very low level of MRP14 and MRP8 expression was seen in the migrating epidermis. Dual immunofluorescence staining for MRP14 or MRP8 and macrophage (F4/80) showed that most of the wound macrophages simultaneously expressed MRP14 and MRP8. Some expression was also found in neutrophils, while neither antigen accumulated to a significant degree in the epidermis. Relatively lower MRP8 and 14 expression in free‐electron laser wounds was correlated with a higher level of matrix metalloproteinase‐13 expression and a reduced rate of wound healing. While the regulation of MRP8 expression in mouse may be different from human skin, we suggest that elevated expression of MRP8 and MRP14 may have a relevant therapeutic effect against inflammation in wound healing.
Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase‐2 and ‐9 and tissue inhibitor of metalloproteinase‐1 during human dermal wound healing
Authors: Gillard Judith A. , Reed Malcolm W. R. , Buttle David , Cross Simon S. , Brown Nicola J.
Published: June 2004

Proteolytic activity is required for the turnover of the extracellular matrix during wound healing. Matrix metalloproteinases can collectively cleave all components of the extracellular matrix, with the endogenous tissue inhibitor of metalloproteinase‐1 regulating their activity. Breast tissue taken at varying postoperative times (n= 92) or during surgery (controls, n= 17), was used to investigate the temporal and spatial activity of matrix metalloproteinase‐2 and ‐9 and tissue inhibitor of metalloproteinase‐1 during human wound healing. Matrix metalloproteinase activity, determined using a quenched fluorescence substrate assay, increased during early healing (3–8 weeks) compared to controls, and then decreased between 24 and 36 weeks after surgery (p < 0.05 until 24 weeks, Mann‐Whitney U‐test). Immunohistochemistry scores for matrix metalloproteinase‐9 expression were significantly elevated compared to controls in scar endothelial cells and fibroblasts from 2 until 12 and 20 weeks, respectively. Matrix metalloproteinase‐2 staining was observed exclusively in fibroblasts, reaching maximum levels 8–12 weeks after surgery, decreasing by 1.5 years but remaining significantly increased. Tissue inhibitor of metalloproteinase‐1 staining was relatively sparse but was significantly increased until 8 weeks after surgery. These results show that matrix metalloproteinases are present at elevated levels during early wound healing, when angiogenesis occurs, and suggest that matrix metalloproteinase‐9 may play a significant role. The later expression of matrix metalloproteinase‐2 and ‐9 in fibroblasts suggests a role in extracellular matrix remodeling.
Stimulation of fibroblast proliferation by lactate‐mediated oxidants
Authors: Wagner Silvia , Hussain M. Zamirul , Hunt Thomas K. , Bacic Biljana , Becker Horst D.
Published: June 2004

Lactate accumulation is a characteristic of wounds in which glycolysis, occurring both aerobically and anaerobically, contributes to its production. Cell proliferation is a critical component of healing wounds. Recently it has been shown that lactate can chelate iron and thus promotes production of hydroxyl radicals. We report here that exogenous lactate increases intracellular oxidants and that the oxidants promote cell growth in cultured dermal fibroblasts in a dose‐dependent manner. The production of lactate‐mediated oxidant requires iron and hydrogen peroxide and with increasing iron concentration oxidant production is raised as well. However, we found cell proliferation is retarded by 15 mM lactate in the presence of a high iron concentration (7.25 µM). The antioxidants catalase and mannitol abolish the inhibitory effect of high lactate. We conclude from these results that increased proliferation of cultured human fibroblasts by exogenous lactate is mediated by oxidant production.
Prediction of recurrence of nonfunctioning pituitary tumours by loss of heterozygosity analysis
Authors: Buch H. N. , Raskauskiene D. , Bahar A. , Bicknell E. J. , Farrell W. E. , Clayton R. N.
Published: June 2004

background  Postsurgical regrowth or recurrence of nonfunctioning pituitary adenomas (NFAs) is not uncommon and often requires further surgery or radiotherapy (DXT). Routine postoperative DXT increases the incidence of hypopituitarism, which is associated with increased morbidity and mortality. Identification of genetic abnormalities in the tumour tissue, which can predict recurrence, may allow targeting DXT to the most appropriate patients.

design and methods  We have performed loss of heterozygosity (LOH) analysis on 96 NFAs of which 43 (45%) were recurrent and 53 (55%) were nonrecurrent tumours. Analysis of all tumours was performed on the surgical specimen obtained at the time of first surgery. All tumours underwent allelotyping across nine highly informative microsatellite markers selected on the basis of high LOH frequency in an earlier study involving genome‐wide allelotyping. LOH frequency across all microsatellite markers as well as across individual markers was compared between the two cohorts of tumours.

results  LOH frequency in tumours that subsequently recurred was significantly higher across all microsatellite markers as compared to tumours that did not recur (P < 0·05). Allelic loss across one or more microsatellite marker was significantly higher in recurrent tumours (30/43) as compared to their nonrecurrent counterparts (17/53) (P < 0·01). On Poisson regression analysis, the higher LOH frequency in recurrent tumours was independent of the invasiveness of tumours determined radiologically. In addition, LOH at the microsatellite markers D1S215 and D1S459 was significantly higher in tumours that recurred as compared to tumours that did not (32%vs. 3% and 27%vs. 2%, respectively; P < 0·01 for both). No significant difference in LOH frequency between the two tumour groups was evident at the other markers. No association could be demonstrated between the frequency and pattern of LOH and the time to manifest recurrence.

conclusions  We have shown that it may be possible to predict recurrence of NFAs by LOH analysis of the initial tumour specimen at predefined microsatellite markers, especially on chromosome 1q. This merits further prospective study.
The sodium‐iodide symporter protein is always present at a low expression and confined to the cell membrane in nonfunctioning nonadenomatous nodules of toxic nodular goitre
Authors: Tonacchera Massimo , Viacava Paolo , Fanelli Giovanni , Agretti Patrizia , De Marco Giuseppina , De Servi Melissa , Di Cosmo Catia , Chiovato Luca , Pinchera Aldo , Vitti Paolo
Published: June 2004

objective  The sodium‐iodide (Na+/I−) symporter (NIS) is known to be overexpressed in toxic adenomas and in about half of benign solitary nonfunctioning adenomas of the thyroid. In nonfunctioning adenomas, however, the protein is localized mainly in the cytoplasm and fails to reach the basolateral membrane of the follicular cell where it is found in normal thyroid tissue and in hyperfunctioning adenomas. Our aim was to study both the level of expression and the cell localization of NIS in nonfunctioning nonadenomatous nodules of toxic nodular goitre.

design and patients  Tissue specimens from nine patients who were submitted to surgery for toxic or functionally autonomous goitre were studied. Tissues from 12 patients who underwent lobectomy for a toxic thyroid adenoma were used as controls.

measurements  Tissue sections embedded in paraffin were stained with haematoxylin–eosin for histological evaluation and for immunohistochemistry using a monoclonal antibody that recognized human (h) NIS.

results  Functioning and nonfunctioning nodules scattered in multinodular goitres consisted of unencapsulated micro/macrofollicular aggregates. All toxic adenomas were characterized by a micro/macrofollicular pattern of growth and histological examination showed that they were surrounded by a capsule. Like the 12 toxic adenomas, all the 14 functioning hyperplastic nodules and two adenomas of toxic multinodular goitre showed a high level of hNIS protein expression with respect to the normal collateral parenchyma and, in all cases, the protein was confined to the cell membrane.

conclusions  Contrary to what was observed for solitary nonfunctioning thyroid adenomas, all the 19 nonfunctioning hyperplastic nodules showed a very low hNIS and this was always confined to the cell membrane. These data suggest that the mechanisms leading to loss of iodide uptake in nonfunctioning hyperplastic nodules of toxic multinodular goitre are different from those that act on solitary nonfunctioning follicular adenomas.
Prepubertal gynaecomastia: aetiology, course and outcome
Authors: Einav‐Bachar R. , Phillip M. , Aurbach‐Klipper Y. , Lazar L.
Published: June 2004

background  Palpable and measurable glandular breast tissue is a rare finding in prepubertal boys and warrants thorough evaluation to rule out an underlying pathology.

objective  To characterize the course and outcome of prepubertal gynaecomastia, examine its effect on puberty, and try to identify its underlying cause.

patients and methods  Twenty‐nine out of 581 (5%) boys referred to our clinic for evaluation of gynaecomastia between 1980 and 2000 were prepubertal at diagnosis. Data on age at appearance of gynaecomastia, general and endocrine evaluation, course of growth and puberty, and treatment were collected from the medical files.

results  Prepubertal gynaecomastia was diagnosed at mean age of 8·9 ± 2·2 years. In 27 of the 29 boys (93·2%) no underlying cause was identified. The remaining two boys (6·8%) had hyperaromatase syndrome. Nine boys (31%) were obese. Spontaneous resolution was recorded in six boys (20·5%), no change in 15 (52%), and further breast enlargement in eight (including the two with hyperaromatase syndrome) (27·5%). Accelerated growth and bone maturation rates were noted only in the two boys with hyperaromatase syndrome. Pubertal onset was documented in 13 boys at 11·8 ± 1·1 years.

conclusions  According to our large single tertiary care centre experience, 5% of boys referred for evaluation of gynaecomastia were prepubertal. The develop‐ment of gynaecomastia was the only abnormality and was not associated with other pubertal signs or accelerated growth rate. In most cases, the gynaecomastia was idiopathic. Further prospective studies are needed to evaluate the pathophysiological mechanisms respon‐sible for this phenomenon.
Diagnostic value of serum thyroglobulin measurements in the follow‐up of differentiated thyroid carcinoma, a structured meta‐analysis
Authors: Eustatia‐Rutten C. F. A. , Smit J. W. A. , Romijn J. A. , Van Der Kleij‐Corssmit E. P. M. , Pereira A. M. , Stokkel M. P. , Kievit J.
Published: June 2004

objective  To investigate to what extent thyroid remnant ablation and withdrawal from thyroxine are required to achieve sufficient accuracy of serum thyroglobulin (Tg) measurements as an indicator of tumour recurrence in the follow‐up of patients with differentiated thyroid carcinoma.

design and methods  We conducted a meta‐analysis of the literature from 1975 to 2003 on serum Tg measurements in the follow‐up of differentiated thyroid carcinoma. In a computer‐based search, we initially found 915 articles that were finally narrowed down to 120. These 120 papers were subjected to strict in/and exclusion criteria, leaving 46 articles (totalling 9094 patients). Data from these articles were extracted in a structured fashion and were grouped according to initial therapy, TSH status, Tg assay method and definition of a ‘gold standard’. Original 2 × 2 tables were pooled by summary receiver operating characteristic curve analysis (sROCa), best estimates of sensitivity and specificity being obtained by the combination of sROCa and Mantel–Haenszel odds ratios.

results  Despite considerable differences between series in laboratory and clinical methodology, we consistently found higher specificity for Tg measurements after thyroid remnant ablation than after surgery alone. Highest pooled sensitivity 0·961 ± 0·013 (SE) was found for immunometric assay (IMA) after thyroid remnant ablation and thyroid hormone withdrawal, at a specificity of 0·947 ± 0·007. Pooled sensitivity decreased significantly if ablated patients were tested while on thyroid hormone (0·778 ± 0·023, at a specificity of 0·977 ± 0·005). Significantly decreased pooled specificity was found in patients who did not undergo remnant ablation (sensitivity 0·972 ± 0·023, at a specificity of 0·759 ± 0·028). If recombinant human TSH (rhTSH) stimulation was used as a substitute for thyroxine withdrawal, sensitivity remained high (0·925 ± 0·018) while specificity decreased to 0·880 ± 0·013. In all analyses, specificity of Tg would decrease when unspecified activity in the thyroid region at scintigraphy was considered benign, whereas sensitivity decreased when such activity was considered malignant.

conclusion  This study confirms that the best accuracy of Tg‐guided follow‐up in patients treated for differentiated thyroid carcinoma is obtained if treatment includes remnant ablation, and Tg testing is performed while off thyroxine.
Saliva and bloodspot cortisol: novel sampling methods to assess hydrocortisone replacement therapy in hypoadrenal patients
Authors: Wong Vincent , Yan Tony , Donald Andrew , McLean Mark
Published: June 2004

background  In patients with hypoadrenalism, it is often difficult to assess the optimal dose of glucocorticoid replacement. Serial serum cortisol measurements for a cortisol day curve are sometimes used, but this has low acceptability for patients. In this study, we evaluate the reliability of saliva and capillary bloodspot cortisol as alternative methods in assessing cortisol profiles in hypoadrenal patients on hydrocortisone replacement.

methods  We first examined the correlations between serum cortisol, saliva and bloodspot cortisol in in‐hospital patients not on glucocorticoid therapy. We then studied 18 hypoadrenal patients on hydrocortisone therapy and measured their serum, saliva and bloodspot cortisol concurrently at seven different time points in a single day.

results  For in‐hospital patients, a significant correlation exists between saliva and serum cortisol (R = 0·7121, P < 0·0001), but there is a stronger correlation between bloodspot and serum cortisol (R = 0·9494, P < 0·0001). The correlations were weaker in hypoadrenal patients on hydrocortisone (saliva and serum cortisol: R = 0·6262, P < 0·001; bloodspot and serum cortisol: R = 0·7871, P < 0·001). When we evaluated each measurement with respect to an arbitrary target range, there was a greater degree of agreement between serum and capillary bloodspot cortisol (85% agreement) than between serum and saliva cortisol (65% agreement) (P < 0·001).

conclusion  Bloodspot samplings provide a simple and convenient way for ambulant hypoadrenal patients on hydrocortisone replacement therapy to assess cortisol levels at multiple times in a single day. This may be useful in determining the optimal glucocorticoid dose for hypoadrenal patients.