bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Sensitivity Analysis Methods Based on Applications to a Food Safety Risk Assessment Model
Authors: Patil Sumeet R. , Frey H. Christopher
Published: June 2004

Sensitivity analysis (SA) methods are a valuable tool for identifying critical control points (CCPs), which is one of the important steps in the hazard analysis and CCP approach that is used to ensure safe food. There are many SA methods used across various disciplines. Furthermore, food safety process risk models pose challenges because they often are highly nonlinear, contain thresholds, and have discrete inputs. Therefore, it is useful to compare and evaluate SA methods based upon applications to an example food safety risk model. Ten SA methods were applied to a draft Vibrio parahaemolyticus (Vp) risk assessment model developed by the Food and Drug Administration. The model was modified so that all inputs were independent. Rankings of key inputs from different methods were compared. Inputs such as water temperature, number of oysters per meal, and the distributional assumption for the unrefrigerated time were the most important inputs, whereas time on water, fraction of pathogenic Vp, and the distributional assumption for the weight of oysters were the least important inputs. Most of the methods gave a similar ranking of key inputs even though the methods differed in terms of being graphical, mathematical, or statistical, accounting for individual effects or joint effect of inputs, and being model dependent or model independent. A key recommendation is that methods be further compared by application on different and more complex food safety models. Model independent methods, such as ANOVA, mutual information index, and scatter plots, are expected to be more robust than others evaluated.
A Risk Assessment for Occupational Acrylonitrile Exposure Using Epidemiology Data
Authors: Starr Thomas B. , Gause Christine , Youk Ada O. , Stone Roslyn , Marsh Gary M. , Collins James J.
Published: June 2004

The extensive data from the Blairet al.(1)epidemiology study of occupational acrylonitrile exposure among 25,460 workers in eight plants in the United States provide an excellent opportunity to update quantitative risk assessments for this widely used commodity chemical. We employ the semiparametric Cox relative risk (RR) regression model with a cumulative exposure metric to model cause‐specific mortality from lung cancer and all other causes. The separately estimated cause‐specific cumulative hazards are then combined to provide an overall estimate of age‐specific mortality risk. Age‐specific estimates of the additional risk of lung cancer mortality associated with several plausible occupational exposure scenarios are obtained. For age 70, these estimates are all markedly lower than those generated with the cancer potency estimate provided in the USEPA acrylonitrile risk assessment.(2)This result is consistent with the failure of recent occupational studies to confirm elevated lung cancer mortality among acrylonitrile‐exposed workers as was originally reported by O'Berg,(3)and it calls attention to the importance of using high‐quality epidemiology data in the risk assessment process.
Dead Reckoning: Demographic Determinants of the Accuracy of Mortality Risk Perceptions
Authors: Hakes Jahn Karl , Viscusi W. Kip
Published: June 2004

General patterns of bias in risk beliefs are well established in the literature, but much less is known about how these biases vary across the population. Using a sample of almost 500 people, the regression analysis in this article yields results consistent with the well‐established pattern that small risks are overassessed and large risks are underassessed. The accuracy of these risk beliefs varies across demographic factors, as does the switch point at which people go from underassessment to overassessment, which we found to be 1,500 deaths annually for the full sample. Better educated people have more accurate risk beliefs, and there are important differences in the risk perception by race and gender that also may be of policy interest.
Applying the Partitioned Multiobjective Risk Method (PMRM) to Portfolio Selection
Authors: Reyes Santos Joost , Haimes Yacov Y.
Published: June 2004

The analysis of risk‐return tradeoffs and their practical applications to portfolio analysis paved the way for Modern Portfolio Theory (MPT), which won Harry Markowitz a 1992 Nobel Prize in Economics. A typical approach in measuring a portfolio's expected return is based on the historical returns of the assets included in a portfolio. On the other hand, portfolio risk is usually measured using volatility, which is derived from the historical variance‐covariance relationships among the portfolio assets. This article focuses on assessing portfolio risk, with emphasis on extreme risks. To date, volatility is a major measure of risk owing to its simplicity and validity for relatively small asset price fluctuations. Volatility is a justified measure for stable market performance, but it is weak in addressing portfolio risk under aberrant market fluctuations. Extreme market crashes such as that on October 19, 1987 (“Black Monday”) and catastrophic events such as the terrorist attack of September 11, 2001 that led to a four‐day suspension of trading on the New York Stock Exchange (NYSE) are a few examples where measuring risk via volatility can lead to inaccurate predictions. Thus, there is a need for a more robust metric of risk. By invoking the principles of the extreme‐risk‐analysis method through the partitioned multiobjective risk method (PMRM), this article contributes to the modeling of extreme risks in portfolio performance. A measure of an extreme portfolio risk, denoted by f4, is defined as the conditional expectation for a lower‐tail region of the distribution of the possible portfolio returns. This article presents a multiobjective problem formulation consisting of optimizing expected return and f4, whose solution is determined using Evolver—a software that implements a genetic algorithm. Under business‐as‐usual market scenarios, the results of the proposed PMRM portfolio selection model are found to be compatible with those of the volatility‐based model. However, under extremely unfavorable market conditions, results indicate that f4 can be a more valid measure of risk than volatility.
Computational Modeling of Serum‐Binding Proteins and Clearance in Extrapolations Across Life Stages and Species for Endocrine Active Compounds
Authors: Teeguarden Justin G. , Barton Hugh A.
Published: June 2004

One measure of the potency of compounds that lead to the effects through ligand‐dependent gene transcription is the relative affinity for the critical receptor. Endocrine active compounds that are presumed to act principally through binding to the estrogen receptor (e.g., estradiol, genistein, bisphenol A, and octylphenol) comprise one class of such compounds. For making simple comparisons, receptor‐binding affinity has been equated to in vivo potency, which consequently defines the dose‐response characteristics for the compound. Direct extrapolation of in vitro estimated affinities to the corresponding in vivo system and to specific species or life stages (e.g., neonatal, pregnancy) can be misleading. Accurate comparison of the potency of endocrine active compounds requires characterization of biochemical and pharmacokinetic factors that affect their free concentration. Quantitative in vitro and in vivo models were developed for integrating pharmacokinetics factors (e.g., serum protein and receptor‐binding affinities, clearance) that affect potency. Data for parameterizing these models for several estrogenic compounds were evaluated and the models exercised. While simulations of adult human or rat sera were generally successful, difficulties in describing early life stages were identified. Exogenous compounds were predicted to be largely ineffective at competing estradiol off serum‐binding proteins, suggesting this was unlikely to be physiologically significant. Discrepancies were identified between relative potencies based upon modeling in vitro receptor‐binding activity versus in vivo activity in the presence of clearance and serum‐binding proteins. The examples illustrate the utility of this approach for integrating available experimental data from in vitro and in vivo studies to estimate the relative potency of these compounds.
Engineered Containment and Control Systems: Nurturing Nature
Authors: Clarke James H. , MacDonell Margaret M. , Smith Ellen D. , Dunn R. Jeffrey , Waugh W. Jody
Published: June 2004

The development of engineered containment and control systems for contaminated sites must consider the environmental setting of each site. The behaviors of both contaminated materials and engineered systems are affected by environmental conditions that will continue to evolve over time as a result of such natural processes as climate change, ecological succession, pedogenesis, and landform changes. Understanding these processes is crucial to designing, implementing, and maintaining effective systems for sustained health and environmental protection. Traditional engineered systems such as landfill liners and caps are designed to resist natural processes rather than working with them. These systems cannot be expected to provide long‐term isolation without continued maintenance. In some cases, full‐scale replacement and remediation may be required within 50 years, at an effort and cost much higher than for the original cleanup. Approaches are being developed to define smarter containment and control systems for stewardship sites, considering lessons learned from implementing prescriptive waste disposal regulations enacted since the 1970s. These approaches more effectively involve integrating natural and engineered systems; enhancing sensors and predictive tools for evaluating performance; and incorporating information on failure events, including precursors and consequences, into system design and maintenance. An important feature is using natural analogs to predict environmental conditions and system responses over the long term, to accommodate environmental change in the design process, and, as possible, to engineer containment systems that mimic favorable natural systems. The key emphasis is harmony with the environment, so systems will work with and rely on natural processes rather than resisting them. Implementing these new integrated systems will reduce current requirements for active management, which are resource‐intensive and expensive.
Differential impairment of working memory performance in first-degree relatives of individuals with schizophrenia
Authors: Kent Aaron R. , Fox Allison M. , Michie Patricia T. , Jablensky Assen V.
Published: June 2004

Background:

Numerous studies have reported neuropsychological impairment in schizophrenia and increasing evidence suggests that individuals with schizophrenia or schizophrenia spectrum disorders and their unaffected first-degree family members exhibit similar deficits in some neuropsychological domains. Substantial modifications to the Wechsler Memory Scale (WMS) have resulted in more sensitive and reliable indicators of various aspects of memory functioning in the WMS-III, which enables generation of auditory, visual and working memory indices.

Objective:

The aim of the present study was to examine the memory profile of individuals with schizophrenia or schizophrenia spectrum disorder (n = 19), their unaffected first-degree family members (n = 11), and healthy controls (n = 9).

Methods:

The study involved neuropsychological testing, including the immediate and working memory subtests of the WMS-III, utilizing both auditory and visual domains. Symptom assessment was performed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), version 2.0. Two multivariate analyses of covariance (mancova) were conducted: (i) comparing patients, relatives and controls; and (ii) comparing relatives and controls only.

Results:

The first analysis indicated that the patient group obtained significantly lower index scores than both relatives and controls on all three indices. The second analysis indicated that the performance of relatives was significantly lower than controls on the working memory index, although there were no significant differences on the auditory and visual immediate index scores.

Conclusions:

The differential impairment in working memory performance in clinically asymptomatic family members suggests that the WMS-III working memory index score may be a potential phenotypic marker of schizophrenia.
Abnormal speech perception in schizophrenia with auditory hallucinations
Authors: Lee Seung-Hwan , Chung Young-Cho , Yang Jong-Chul , Kim Yong-Ku , Suh Kwang-Yoon
Published: June 2004

Background:

The neurobiological mechanism of auditory hallucination (AH) in schizophrenia remains elusive, but AH can be caused by the abnormality in the speech perception system based on the speech perception neural network model.

Objectives:

The purpose of this study was to investigate whether schizophrenic patients with AH have the speech processing impairment as compared with schizophrenic patients without AH, and whether the speech perception ability could be improved after AH had subsided.

Methods:

Twenty-four schizophrenic patients with AH were compared with 25 schizophrenic patients without AH. Narrative speech perception was assessed using a masked speech tracking (MST) task with three levels of superimposed phonetic noise. Sentence repetition task (SRT) and auditory continuous performance task (CPT) were used to assess grammar-dependent verbal working memory and non-language attention, respectively. These tests were measured before and after treatment in both groups.

Results:

Before treatment, schizophrenic patients with AH showed significant impairments in MST compared with those without AH. There were no significant differences in SRT and CPT correct (CPT-C) rates between both groups, but CPT incorrect (CPT-I) rate showed a significant difference. The low-score CPI-I group showed a significant difference in MST performance between the two groups, while the high-score CPI-I group did not. After treatment (after AH subsided), the hallucinating schizophrenic patients still had significant impairment in MST performance compared with non-hallucinating schizophrenic patients.

Conclusions:

Our results support the claim that schizophrenic patients with AH are likely to have a disturbance of the speech perception system. Moreover, our data suggest that non-language attention might be a key factor influencing speech perception ability and that speech perception dysfunction might be a trait marker in schizophrenia with AH.
Temperament and Character Inventory (TCI) in adolescents with anorexia nervosa
Authors: Rybakowski Filip , Slopien Agnieszka , Zakrzewska Marzena , Hornowska Elzbieta , Rajewski Andrzej
Published: June 2004

Background:

Female patients with anorexia nervosa differ significantly from the control women in various dimensions of personality.

Objective:

To investigate the personality dimensions measured with the Temperament and Character Inventory (TCI) in adolescent patients with restrictive-type and bulimic/purging-type anorexia nervosa (ANR and ANB, respectively), and contrast them with the results of control females.

Methods:

Sixty-one patients with anorexia nervosa (36 ANR and 25 ANB) and 60 controls were tested with the TCI. A concomitant assessment of depression, body mass index and age was made to evaluate the possible correlation with personality dimensions.

Results:

Adolescent ANR patients scored higher in persistence, harm avoidance and cooperativeness, and lower in novelty seeking and self-transcendence than control women. ANB patients scored in the middle between ANR and control females, but differences did not reach the significance level with either group, except for the self-transcendence dimension where they scored significantly higher than those with ANR.

Conclusions:

The deviations in temperamental profile of adolescent ANR are similar to those reported in adult patients. The ANB adolescent patients with anorexia nervosa show less prominent deviations from the personality of control women. With regard to the character dimension of cooperativeness, adolescents with ANR scored higher than controls, in contrast to the observations in adult patients. This may reflect the effect of illness on the development of character.
Financial Markets, Development and Economic Growth: Tales of Informational Asymmetries
Authors: Capasso Salvatore
Published: June 2004

Abstract.  The development of financial systems is very often characterised by the development of innovative financial contracts which allow a more efficient allocation of resources and a higher level of capital productivity and economic growth. By exploiting the microeconomic theory of the optimal financial contract under asymmetric information, economists have recently managed to shed new light on the well studied issue of the relationship between financial market development and economic growth. This paper reviews the most recent progress of this literature which shows that the amount of information asymmetry in the credit market and the degree of heterogeneity between borrowers (typically firms) and lenders (typically workers or savers) determine the nature of the financial system. Differences in endowments and in the level of information distribution can give rise to very different financial contracts which affect, and in turn are affected, by capital accumulation and growth.
Monetary Policy and the Zero Bound to Interest Rates: A Review1
Authors: Yates Tony
Published: June 2004

Abstract.  This paper reviews the literature on what the zero bound to nominal interest rates implies for the conduct of monetary policy. The aim is to evaluate the risks of hitting the zero bound; and to evaluate policies that are said to be able to reduce that risk, or policies that are proposed as means of helping the economy escape if it is in a zero bound ‘trap’. I conclude that policies aimed at ‘cure’ are arguably more uncertain tools than those aimed at ‘prevention’, so prevention is a less risky strategy for policymakers. But since the risks of hitting the zero bound seem quite small anyway, and the risks of encountering a deflationary spiral smaller still, it is conceivable that inflation objectives that typify modern monetary regimes already have more than enough insurance built into them to deal with the zero bound problem.
Increasing prevalence of obesity in South Australian 4‐year‐olds: 1995−2002
Authors: Vaska VL , Volkmer R
Published: June 2004

Objective:  To determine prevalence of, and trends in, overweight and obesity in South Australian children aged 4 years during the period 1995−2002.

Methods:  Data from 114 669 children collected as part of Child and Youth Health ‘preschool health assessments’ of 4‐year‐olds throughout the state in the years 1995−2002 were analysed. Body mass index was calculated from height and weight data and prevalence of overweight and obesity for males and females determined using a standard world‐wide definition. Yearly prevalence rates were compared for changes over time.

Results:  Rates of overweight and obesity have increased over the period 1995−2002. In 1995, of females 12.8% were overweight or obese (obese 3.5%). Of males 10.2% were overweight or obese (obese 3.2%). The equivalent figures in 2002 were for females 21.4% (obese 5.8%) and males 17.3% (obese 4.1%). Rates of overweight and obesity were greater in females than males in all years (except obesity rate in 1995).

Conclusion:  Data from this large, consecutive yearly dataset of South Australian 4‐year‐old children show a significant increase in the rates of overweight and obesity. Much of this increase appears to have occurred in the mid‐to‐late 1990s. It is uncertain if these changes have plateaued at this time. These results reinforce rising obesity prevalence as a significant child health issue. They also indicate that obesity is seen as early as the preschool years; with implications for theories of causation and for prevention and treatment strategies.
Extracellular matrix signaling through growth factor receptors during wound healing
Authors: Tran Kien T. , Griffith Linda , Wells Alan
Published: June 2004

Recently, extracellular matrix components have been shown to contain domains that can interact with and activate receptors with intrinsic tyrosine kinase activity. These receptor tyrosine kinases are strong mediators of the cell responses of proliferation, migration, differentiation, and dedifferentiation. However, an interesting question is raised as to why cells would present growth factor receptor ligands in such a manner, as the majority of growth factors are small, soluble, or only transiently tethered ligands. With the exception of the discoidin domain receptors that bind collagen, the other described domains interact with a receptor that binds ubiquitous soluble peptide growth factors, the epidermal growth factor receptor. Unlike traditional growth factors, these individual “matrikine” domains within tenascin‐C, laminin, collagen, and decorin possess relatively low binding affinity (high nanomolar or micromolar) and are often presented in multiple valency. The presentation of ligands within the extracellular matrix in this fashion might allow for unique biochemical and physiological outcomes. This new class of “matrikine” ligand may be critical for wound healing, as the majority of known extracellular matrix components possessing matrikines play a strong role, or are presented uniquely, during skin repair. Tenascin‐C expression, for instance, is uniquely regulated spatially and has been proposed to present pro‐migratory tracks during skin repair through its epidermal growth factor‐like repeats. The epidermal growth factor‐like repeats of laminin‐5 act as cryptic ligands revealed upon matrix metalloproteinase‐2 degradation of the surrounding extracellular matrix. The deletion of the discoidin domain receptors 1 and 2 for collagen have negative consequences on the role of fibroblasts and epithelial cells for matrix metalloproteinase production, migration, proliferation, and extracellular matrix turnover. Finally, decorin can bind to, inhibit, and down‐regulate epidermal growth factor receptor levels and signaling, suggesting a tonic role of the epidermal growth factor binding domain of decorin in the resolution of wound healing. We provide a model framework for further studies into this emerging class of signals.
Diffusible factors released by fibroblasts support epidermal morphogenesis and deposition of basement membrane components
Authors: El Ghalbzouri Abdoelwaheb , Ponec Maria
Published: June 2004

Epithelial–mesenchymal interactions play an important role in controlling epidermal morphogenesis and homeostasis but little is known about the mechanisms of these interactions. To examine whether diffusible factors produced by fibroblasts and/or keratinocytes support epidermal morphogenesis and basement membrane formation, organotypic keratinocyte monocultures were established in media collected either from organotypic fibroblast or keratinocyte‐monocultures or from keratinocyte‐fibroblast cocultures, and the expression of keratin 10, 16, and 17 and basement membrane components (types IV and VII collagen, laminin 5, nidogen, BP 180, LAD‐1) were examined. We found that diffusible factors released by keratinocytes were not sufficient to support the establishment of normalized epidermal phenotype and deposition of basement membrane components in contrast to fibroblast‐ or keratinocyte/fibroblast‐derived factors. Keratinocytes appear to affect the spectrum of secreted soluble factors, as keratinocyte/fibroblast‐derived factors were more effective to accomplish continuous linear deposition of laminin 5 and of nidogen. The finding that released amounts of keratinocyte growth factor and granulocyte macrophage colony stimulating factor were not sufficient to fully support epidermal morphogenesis and deposition of basement membrane components is suggestive for the involvement of other released diffusible factors. Generation of organotypic keratinocyte monocultures in the presence of fibroblast‐ or keratinocyte/fibroblast‐derived soluble factors resulted in enhanced expression of keratins K16 and K17 and the absence of type IV collagen. This observation indicates that next to paracrine acting factors, epidermal homeostasis is controlled by mutual keratinocyte–fibroblast interaction.
Regeneration in MRL mice: further genetic loci controlling the ear hole closure trait using MRL and M.m. Castaneus mice
Authors: Heber‐Katz Ellen , Chen Pan , Dvm Lise Clark , Zhang Xiang‐Ming , Troutman Scott , Blankenhorn Elizabeth P.
Published: June 2004

The MRL mouse has been shown to display an epimorphic regenerative response after ear hole punching leading to complete closure within 30 days and cartilage regrowth. The regenerative capacity of the MRL has also been seen after a severe cryoinjury to the heart leads to complete healing without scarring and functional myocardium. The wound healing ear hole closure response that occurs in MRL mice has been shown to be genetically controlled. We have previously identified 11 quantitative trait loci (QTL) that govern healing in an intercross of (MRL × C57BL/6 J) mice. However, it is desirable to use another poorly healing mouse strain to elucidate the full range of genetic factors that affect this important process. In the current study, we have used an inbred subspecies of the mouse, M. castaneus, and have confirmed a number of loci identified previously. In addition, we report three new healing QTL. Furthermore, in this strain combination, we note a strong sexual dimorphism also observed in the MRL × C57BL/6 cross, both in the healing trait and in the QTL that control it.
Differential proliferative response of fetal and adult human skin fibroblasts to transforming growth factor‐β
Authors: Pratsinis Harris , Giannouli Christina C. , Zervolea Irene , Psarras Stelios , Stathakos Dimitri , Kletsas Dimitris
Published: June 2004

Since pronounced differences exist between the fetal and adult repair processes, we studied the proliferative response of skin fibroblasts from these two stages to transforming growth factor‐β (TGF‐β), a cytokine with a broad range of activities in tissue repair. Here, we present evidence that TGF‐β inhibits fetal human skin fibroblasts, while it is stimulatory for adult ones. This proliferative effect of TGF‐β was found to be concentration‐ dependent, but isoform‐independent. Furthermore, even a transient exposure of the cells to this growth factor was sufficient to exert its stimulatory or inhibitory action. Accordingly, we have studied the immediate responses provoked by TGF‐β in major signaling pathways, and we have found that it induces a rapid activation of the SMAD pathway, i.e., phosphorylation and nuclear translocation of SMAD2, followed by dephosphorylation, most probably due to degradation by the proteasome. However, similar intensity and kinetics of this activation have been observed in both fetal and adult fibroblasts. On the other hand, curcumin, a natural product with wound healing properties that inhibits several intracellular signaling pathways, was found to completely abrogate the inhibitory effect of TGF‐β1 on human fetal skin fibroblasts, without affecting the stimulatory action on fibroblasts from adult donors. In conclusion, there is a major radical in the proliferative response of fetal and adult human skin fibroblasts to TGF‐β, possibly reflecting the different repair strategies followed in these two stages of development.
Circulating immunoglobulins that inhibit the binding of follicle‐stimulating hormone to its receptor: a putative diagnostic role in resistant ovary syndrome?
Authors: Chiauzzi Violeta A. , Bussmann Leonardo , Calvo Juan Carlos , Sundblad Victoria , Charreau Eduardo H.
Published: June 2004

objective  To evaluate the presence of circulating immunoglobulins that inhibit FSH binding to its receptor (Ig‐FSHR) in patients with premature ovarian failure (POF).

design  Non‐randomized study. Blood sampling for determination of circulating immunoglobulins.

patients  Two hundred and forty‐seven patients with POF and 60 normally menstruating women (controls).

measurements  Circulating immunoglobulins that inhibit FSH binding to its receptor were assessed by FSH‐binding inhibition assay.

results  Twenty‐three out of 247 women with POF presented circulating immunoglobulins that inhibit FSH binding to its receptor. These patients had been previously diagnosed as ROS. Sixty control subjects proved negative.

conclusion  Determination of the presence of circulating immunoglobulins that inhibit FSH binding to its receptor could be instrumental in diagnosing the gonadotropin resistance ovary syndrome.
Preoperative identification of clearly separated double pituitary adenomas
Authors: Kim Kyongsong , Yamada Shozo , Usui Masaaki , Sano Toshiaki
Published: June 2004

objective  Double pituitary adenomas are extremely rare. They can be divided into contiguous and clearly separated types. Most contiguous tumours are surgically removed as one tumour and the co‐existence of different adenoma types can be confirmed by histological methods. In contrast, detailed preoperative neuroimaging studies can suggest the co‐existence of separated multiple adenomas. In patients with multiple adenomas, surgical failure may result when one adenoma is missed during surgery. Among 600 surgical cases we encountered four patients with clearly separated double pituitary adenomas; all were highly suspect on preoperative MRI studies.

patients and results  All four patients manifested acromegalic symptoms; one patient also exhibited hyperprolactinemia and two had familial pituitary adenomas unrelated to multiple endocrine neoplasia type I (MEN‐1). All underwent transsphenoidal surgery and histology confirmed the diagnosis of GH‐producing plus gonadotroph adenoma in two cases and of two GH‐producing adenomas each in the other two patients.

conclusion  Although the pathogenesis of our double adenomas remains unknown, genetic abnormalities may be involved because two patients had familial pituitary adenomas unrelated to MEN‐1. When preoperative MRI is suggestive of double adenomas, careful surgical exploration is necessary to avoid missing the other adenoma because the risk of surgical failure is high, especially in patients with functioning adenomas.
Serum adiponectin concentrations predict the developments of type 2 diabetes and the metabolic syndrome in elderly Koreans
Authors: Choi K. M. , Lee J. , Lee K. W. , Seo J. A. , Oh J. H. , Kim S. G. , Kim N. H. , Choi D. S. , Baik S. H.
Published: June 2004

objective  To determine whether low serum adiponectin concentrations are able to predict the future developments of type 2 diabetes and the metabolic syndrome using the National Cholesterol Education Programme (NCEP) criteria. We also investigated the stability of adiponectin levels and the relationships between baseline adiponectin levels and changes in the parameters related to the metabolic syndrome over a period of 3 years.

patients and measurements  This prospective cohort study included 372 elderly Koreans who participate in the SWS (South‐West Seoul) study, which was conducted in 1999 and 2002 in Seoul, Korea. Fasting and postchallenge 2‐h plasma glucose, body mass index (BMI), waist‐to‐hip ratio (WHR), blood pressure, lipid profiles and serum adiponectin data obtained in 1999 and 2002 were examined.

results  The within‐person variation between 1999 and 2002 of serum adiponectin was not significant (P = 0·61). Serum adiponectin was closely correlated with the risks factors of cardiovascular disease (CVD), that is negatively with BMI, WHR, blood pressure, triglyceride and blood glucose levels, and positively with high density lipoprotein (HDL)‐cholesterol levels. Subjects with the metabolic syndrome showed lower serum adiponectin concentrations than those without the metabolic syndrome (P < 0·0001). Baseline adiponectin levels were found to be correlated with subsequent changes in WHR, low density lipoprotein (LDL)‐cholesterol, fasting and postload 2‐h glucose over the 3‐year period, after adjusting for baseline values. Multiple logistic regression analysis showed that lower baseline serum adiponectin concentrations were significantly associated with the developments of type 2 diabetes and the metabolic syndrome after adjusting for age, sex, obesity, history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), hypertension and dyslipidaemia.

conclusions  Reduced concentrations of adiponectin were found to be independently associated with increased risk of both type 2 diabetes and the metabolic syndrome in elderly Koreans.
Assessment of disease activity in acromegaly by means of a single blood sample: comparison of the 120th minute postglucose value with spontaneous GH secretion and with the IGF system
Authors: Minuto Francesco , Resmini Eugenia , Boschetti Mara , Arvigo Marica , Sormani Maria Pia , Giusti Massimo , Ferone Diego , Barreca Antonina
Published: June 2004

objective  It has been suggested that the threshold of 1 µg/l of GH nadir after glucose load for definition of controlled acromegalic disease proposed in the 2000 consensus statement should be lowered to 0·30. We evaluated these two cut‐off values in comparison with IGF‐I, ALS and IGFBP‐3 in a group of acromegalic patients. With the aim of simplifying the follow‐up protocol in these patients we also tested if one single sample taken after glucose load could replace the nadir value.

design and measurements  GH secretion was evaluated by oral glucose tolerance test (OGTT), and by studying spontaneous secretion (GH day curve) with sampling at hourly intervals from 08·00 to 18·00 h; from the day curve, mean (MGHDC) and minimum (TRGH) values were considered. IGF‐I, ALS, and IGFBP‐3 were measured in the basal state at the first testing.

patients  Fifty acromegalic patients (26–83 years, 31 females, 19 males) in various phases of disease activity. Forty‐two patients had previously undergone pituitary surgery (10 also radiotherapy), 23 were treated with SMS analogues and three with dopamine agonist drugs.

results  The nadir GH value after glucose load correlated most significantly with the 120th‐minute sample (R = 0·95). Comparison of the postglucose 120th minute at the two cut‐off values with IGF‐I, IGFBP‐3 and ALS showed higher concordance of postglucose level at 0·3 with IGF‐I, while concordance was similar for the two cut‐off values with ALS and IGFBP‐3. When the 120th minute postglucose GH value is lower than 1 µg/l and IGF‐I is within 2SD for age nearly all other parameters are normal. IGF‐I correlated more with ALS (R = 0·78) than with IGFBP‐3 (R = 0·50) and the latter was less concordant with GH secretion parameters than the previous two.

conclusions  A sample taken at the 120th minute after glucose load, together with IGF‐I and/or ALS evaluation can give sufficient information for a routine assessment of disease activity, both in the diagnosis and in the follow‐up to treatment. If GH is lower than 1 µg/l and IGF‐I/ALS are normal, then the patient can be classified as ‘nonactive’ or ‘controlled’; a pathological IGF‐I and/or ALS value is a sign of disease activity irrespective of the GH values, while normal IGF‐I/ALS with an elevated GH requires further assessment.
Different effects of short‐ and long‐term recombinant hGH administration on ghrelin and adiponectin levels in GH‐deficient adults
Authors: Giavoli Claudia , Cappiello Vincenzo , Corbetta Sabrina , Ronchi Cristina L. , Morpurgo Paola S. , Ferrante Emanuele , Beck‐Peccoz Paolo , Spada Anna
Published: June 2004

objective  To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH‐deficient (GHD) adults before and after short‐ and long‐term recombinant human GH (rhGH) administration.

patients and methods  Twenty‐three patients were studied. Seventeen subjects (Group A, 12 men, five women) were evaluated at baseline and after 1 year rhGH therapy (dose mean ± SD: 0·3 ± 0·1 mg/day) with the assessment of serum IGF‐I, ghrelin, ApN, leptin, insulin and glucose levels, percentage of body fat (BF%), HOMA‐IR and QUICKI. Seventeen age‐, sex‐ and body mass index (BMI)‐matched healthy subjects were recruited for comparisons. Six patients (Group B, three men, three women) underwent IGF‐I generation test (rhGH 0·025 mg/kg/day for 7 days), blood sampled at baseline and on day 8 for determination of IGF‐I, ghrelin and ApN levels.

results  Group A: at baseline GHD patients showed low IGF‐I levels and BF% significantly higher than controls (31·4 ± 2·5 vs. 26·4 ± 1·3, P < 0·05). Glucose, insulin, leptin, tryglicerides, low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) cholesterol levels, as well as HOMA‐IR and QUICKI values were similar in the two series, while total cholesterol levels were higher in GHD. In GHD, ghrelin levels were significantly lower than in controls (193·9 ± 27·1 vs. 298·1 ± 32·5 pmol/l, respectively, P = 0·02), while ApN levels were similar (10·2 ± 1·1 and 9 ± 1 mg/l, respectively, P = ns). After 1 year of rhGH therapy, BF%, BMI, serum total and LDL cholesterol significantly decreased, serum leptin levels showed a trend to decrease, while HOMA‐IR and QUICKI did not change. Ghrelin and ApN levels significantly increased from 193·9 ± 27·1 to 232·4 ± 26·3 pmol/l (P < 0·01) and from 8·6 ± 0·8 to 10·3 ± 1·1 mg/l (P < 0·05), respectively. In group B, the expected increase in IGF‐I levels was associated with a significant decrease in ghrelin levels, while ApN did not change.

conclusion  GHD patients showed serum ghrelin lower than controls, probably due to the higher BF%. No difference in ApN was observed. Ghrelin and ApN increments induced by long‐term treatment may be related to the significant BMI and BF% reduction that is the predominant metabolic effect of rhGH therapy. Conversely, the decrease in ghrelin levels observed after short‐term rhGH administration may be consistent with an inhibitory feedback of GH and/or IGF‐I on ghrelin release.
Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins
Authors: Wallace A. M. , Banfield E. , Ingram M. , Fraser R. , Swan L. , Hillis W. S. , Connell J. M. C.
Published: June 2004

objective  The precise interactions between glucocorticoids and leptin are complex and poorly understood. The aim of the study was to investigate whether the glucocorticoid/leptin interaction is influenced by shared environmental or genetic factors.

design  We investigated the heritability of body mass index (BMI), circulating leptin and urinary glucocorticoid metabolites [tetrahydrocortisol (THF), alloTHF and tetrahydrocortisone (THE)] in 54 monozygotic (MZ) and 39 dizygotic (DZ) female twins. Analysis was performed using a structural equation modelling package Mx, developed by Neale.

results  Leptin and BMI showed substantial heritability (68·3% and 71·3%, respectively). Bivariate analysis indicated that the genetic determinants of BMI and leptin are partly shared. Total cortisol metabolites (THF + alloTHF + THE), the (THE + alloTHF)/THE ratio [a marker of 11β‐hydroxysteroid dehydrogenase (11HSD) activity] and the alloTHF/THF ratio (marker for 5α‐reductase activity) followed an environmental pattern. The heritability of leptin was significantly lowered to 63·8% (P = 0·012) when values were corrected for the influence of total cortisol metabolites but unaffected by markers of 11HSD and 5α‐reductase activity.

conclusions  We confirm that the genetic influence on both BMI and the circulating leptin concentration is substantial and show that these genetic determinants are highly correlated. These genetic factors, which are more likely to be dominant than additive, can be modestly but significantly modified by urinary total cortisol metabolites implying an adrenal influence.
Different states of clinical control are associated with changes in IGF‐I and IGFBPs in children with congenital adrenal hyperplasia due to 21‐hydroxylase deficiency
Authors: Cunha Heloisa Marcelina , Elias Lucila Leico Kagohara , Camacho‐Hübner Cecilia , Moreira Ayrton Custódio , Martinelli Carlos Eduardo
Published: June 2004

objective  Congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency (21‐OHD) is characterized by high androgen levels, ambiguous genitalia or premature pubarche, increased height velocity and skeletal maturation. Considering the possibility of changes in the IGF system components depending on the state of clinical control, the objective of the present study was to analyse serum IGF‐I, IGF‐II and IGFBP levels in children with 21‐OHD under two states of clinical control.

patients and design  We studied 12 prepubertal children with 21‐OHD CAH aged 4·0 ± 0·7 years. They were classified as good (GC) or poor control (PC) based on growth rate, signs of adrenal insufficiency or Cushing syndrome, progression of sexual characteristics and serum androgens levels. Blood samples were obtained from each patient in two different states of clinical control (GC and PC) for biochemical measurements.

measurements  IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 were determined by immunoassays. IGFBPs were also analysed by Western ligand blotting (WLB).

results  Levels of IGF‐I (P = 0·03) and IGFBP‐3 (P = 0·01) were higher in GC than in PC while IGFBP‐1 (P = 0·004) concentrations were lower in GC patients. A trend towards higher levels of IGF‐II (P = 0·08) and lower levels of IGFBP‐2 (P = 0·08) was observed in GC children. Increased IGFBP‐4 band intensity was observed in GC children (P = 0·03).

conclusion  Higher levels of IGF‐I, IGFBP‐3 and IGFBP‐4, but lower levels of IGFBP‐1, were associated with better control in children with 21‐OHD CAH. These findings are different from those observed in children with other causes of increasing androgens levels and are likely to be related to the insufficient glucocorticoid status.
A paradigmatic and methodological examination of information systems research from 1991 to 2001
Authors: Chen WenShin , Hirschheim Rudy
Published: June 2004

Abstract.  The field of information systems (IS) has evolved for more than three decades. Although many schools of thought have emerged and even become well established, few historical analyses of research paradigms and methodologies have been undertaken. One of the rare exceptions is Orlikowski & Baroudi (1991). Yet, the IS research community has evolved substantially since 1991 in many aspects. A variety of journal outlets have emerged and become well established. More attention has been paid to paradigmatic and methodological issues. Political and professional contexts have also changed noticeably. Therefore, it should be an opportune time for the field to ask: ‘What changes are manifested in journal publications?’‘Is the field making progress regarding pluralism in IS research?’‘How will the field's publications practices change in the future?’ The purpose of this paper is to investigate these questions and, in turn, reflect on the paradigmatic and methodological progress made since 1991. We examined 1893 articles published in eight major IS publication outlets between 1991 and 2001. Our findings suggest that the long‐term endeavours of interpretivist researchers might need to continue because the paradigmatic progress appears somewhat inconsequential; positivist research still dominates 81% of published empirical research. In particular, US journals, as opposed to European journals, tend to be more positivist, quantitative, cross‐sectional and survey oriented. With respect to research design, survey research is still the most widely used method (41%), although case studies have gained substantial recognition (36%). Further, the increase of qualitative research (30%), empirical studies (61%) and longitudinal cases (33%) at the expense of laboratory experiments (18%) might suggest that IS researchers have become more interested in obtaining scientific knowledge in real world settings. In summary, we suggest that the field has been dominated by the positivist paradigm, despite calls to the contrary. Indeed, if the field was to truly embrace pluralism, it would have to find ways to fundamentally change the publication practices of the journal system, including the current tenure and promotion system, which pose considerable obstacles for the acceptance of alternative paradigms.
Localization of Transforming Growth Factors, TGFβ1 and TGFβ3, in Hypothalamic Magnocellular Neurones and the Neurohypophysis
Authors: Fèvre‐Montange M. , Dumontel C. , Chevallier P. , Isnard A. K. , Guigard M.‐P. , Trouillas J.
Published: June 2004

The distribution of transforming growth factor beta (TGFβ) in the rat and human hypothalamus and neurohypophysis was investigated by immunocytochemical techniques using rabbit polyclonal antisera against TGFβ1 and TGFβ3. Colocalization of TGFβ1 or TGFβ3 and arginine vasopressin (AVP) in the rat hypothalamus was studied by double immunolabelling in light microscopy, while their subcellular localization in the rat neurohypophysis was investigated by immunoelectron microscopy. TGFβ1 and TGFβ3 immunoreactivity was demonstrated in the cell bodies and processes of neurones in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). The TGFβ‐immunoreactive cells were more numerous in the SON compared to the PVN. TGFβ/AVP double‐labelled cells were seen in both nuclei, but some neurones in the SON were labelled for TGFβ1 or TGFβ3, although not for AVP. In the rat and human neurohypophysis, TGFβ3 immunolabelling was more diffuse and stronger than TGFβ1 immunolabelling. TGFβ1 expression was seen in axonal vesicles and in neurosecretory granules of the axonal endings, while TGFβ3 was observed in axonal fibres. Colocalization of TGFβ3 or TGFβ1 and AVP was observed in some neurosecretory granules, but many were either single‐labelled for TGFβ or AVP or unlabelled. Our results demonstrate, for the first time, the colocalization of TGFβ and neurohypophysial hormones in magnocellular neurones. We suggest that TGFβ secreted by the neurohypophysis regulates the proliferation and secretion of certain anterior pituitary cells.
Cellular Localization of GABAA Receptor α Subunit Immunoreactivity in the Rat Hypothalamus: Relationship With Neurones Containing Orexigenic or Anorexigenic Peptides
Authors: Bäckberg M. , Ultenius C. , Fritschy J.‐M. , Meister B.
Published: June 2004

γ‐Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, acts via two different type of GABA receptors. GABAA receptors are composed of five subunits that belong to eight different classes. Depending on their subunit composition, distinct pharmacological and electrophysiological properties are obtained. GABA is produced in certain hypothalamic neurones known to be involved in control of feeding behaviour. We report the detailed immunohistochemical localization of four GABAAR α subunits in hypothalamic regions associated with the regulation of feeding behaviour. Immunoreactive structures for all studied GABAAR α subunits were observed in the hypothalamus, but with subunit‐specific staining patterns. GABAAR α1 immunoreactivity was most prominent in the dorsomedial hypothalamic nucleus and in the lateral hypothalamic area (LHA), whereas GABAAR α2, α3 and α5 subunits exhibited particularly strong immunoreactivity in the ventromedial hypothalamic nucleus. In comparison, GABAAR α subunit immunoreactivities were generally weak in the arcuate nucleus. In the ventromedial part of the arcuate nucleus, neuropeptide Y‐ and agouti‐related peptide‐containing cell bodies, which also are known to be GABAergic, were immunoreactive for only the GABAAR α3 subunit, whereas pro‐opiomelanocortin‐ and cocaine‐ and amphetamine‐regulated transcript‐ containing cell bodies located in the ventrolateral subdivision of the arcuate nucleus, showed GABAAR α1, α2 and α3 subunit immunoreactivity. In the LHA, GABAAR α3 subunit immunoreactivity was demonstrated in both melanin‐concentrating hormone (MCH) and orexin‐containing neurones. In addition, MCH neurones contained GABAAR α2 immunoreactivity. In neurones of the tuberomammillary nucleus, GABAAR α2 and α5 subunits were colocalized with histidine decarboxylase, a marker for histamine‐containing neurones.