bluuebunny/crossref_metadata_2025 huggingface dataset:
Missing Data, Sensitivity Analysis
Authors: Molenberghs Geert
Published: October 2004

With the growing amount of methodology to analyze incomplete data, the awareness has grown that the results of such an analysis may be very sensitive to the modeling assumptions made, many of which are not, strictly speaking, verifiable from the data. Therefore, a lot of the later work is devoted to the exploration of such sensitivities. For both categorical as well as continuous outcomes, we provide a broad definition for such sensitivity analyses, give an overview of methods, and provide some detail about a number of strategies that have become available.
Surrogate Markers
Authors: Molenberghs Geert
Published: October 2004

The validation of surrogate endpoints has been studied by Prentice. He presented a definition as well as a set of criteria that are equivalent if the surrogate and true endpoints are binary. Freedman and colleagues supplemented these criteria with the so‐calledproportion explained. Buyse and Molenberghs proposed to replace the proportion explained by two quantities:(i)therelative effectlinking the effect of treatment on both endpoints and(ii)theadjusted association, an individual‐level measure of agreement between both endpoints. Later, a number of proposals have been made to replace the single‐unit validation measures by multiunit (e.g., meta‐analytic) counterparts.
Generalized Variance
Authors: Sengupta Ashis
Published: October 2004

Generalized variance (GV), proposed by Wilks, is an one‐dimensional measure of multidimensional scatter. It plays an important role in both theoretical and applied research. GV has been extended to Standardized GV (SGV) to enable comparison of scatters in differing dimensions. Interesting results on the distribution, estimation, and testing of GVs and SGVs have been emerging. Also, these measures have been finding novel applications in a variety of applied problems, ranging from such age‐old areas as agriculture and sample surveys to the modern developments in signal processing and Bioinformatics.
Generalized Canonical Variables
Authors: Sengupta Ashis
Published: October 2004

Often the random vector variable, X, being encountered, for example, in atmospheric, biological, economic and environmental and other research, is of a large dimension but admits of meaningful grouping(s) into two or more mutually exclusive and exhaustive subvectors. Dimension reduction techniques are then sought to obtain “representative” new variables for each group to be formed by taking suitable compounds of the components within that group. This results in the substantially reduced dimensional vector variable Y to represent X. This greatly facilitates the associated computational and inferential statistical analyses. Hotelling's construction of canonical variables for the case of two groups of quantitative variables has been generalized in various directions to yield Generalized Canonical Variables that encompass more than two groups, both quantitative and qualitative components in X, order constraints imposed by the user on the compounding coefficients, and so on. The availability of packages makes the implementation of such techniques for real‐life problems quite feasible and attractive. On the inferential side, a variety of new types of hypotheses is posed: determination of optimal number of groups, best grouping for the same number of groups, and so on. While the corresponding distribution theory is quite involved, some interesting results are, nevertheless, emerging also. This topic is a fertile area and is in need of further theoretical and applied research, which should be very useful to a wide variety of practitioners.
Hospital response to chemical terrorism: Personal protective equipment, training, and operations planning
Authors: Georgopoulos Panos G. , Fedele Paul , Shade Pamela , Lioy Paul J. , Hodgson Michael , Longmire Atkinson , Sands Melody , Brown Mark A.
Published: October 2004

Background

Hospitals distant from the immediate site of an incident involving a hazardous materials (HAZMATs) release which could include chemical warfare agents, must develop emergency response plans (ERPs) to protect healthcare professionals if they receive potentially contaminated victims. The ERP must address OSHA, EPA, and JCAHO requirements.

Methods

The VHA convened groups to develop a hazard and exposure assessment, identify actions for compliance with existing regulatory standards, and review site and operational planning issues. Exposure modeling results were used to derive relationships between operational parameters (time and distance from sites/sources) and potential exposure for healthcare workers.

Results

According to exposure modeling, level C personal protective equipment is adequate to protect hospital staff distant from the chemical release site. Decontamination runoff and contaminated clothing should also be controlled to limit exposure.

Conclusions

Development and coordination of ERPs must include the local emergency planning committee, with clear assignment of tasks, locations, and training in order to prevent exposures to healthcare workers. Am. J. Ind. Med. 46:432–445, 2004. © 2004 Wiley‐Liss, Inc.
Polyisocyanates in occupational environments: A critical review of exposure limits and metrics
Authors: Bello Dhimiter , Woskie Susan R. , Streicher Robert P. , Liu Youcheng , Stowe Meredith H. , Eisen Ellen A. , Ellenbecker Michael J. , Sparer Judy , Youngs Fred , Cullen Mark R. , Redlich Carrie A.
Published: October 2004

Background

Determination of polyisocyanates is important because they are a major contributor of exposure to the isocyanate functional group in many workplace environments and are capable of inducing sensitization and asthma. However, with multiple different measurement metrics in use, comparison of isocyanate exposure data between studies and development of occupational exposure limits (OELs) for polyisocyanates is difficult.

Methods

An analysis of existing problems in the measurement and regulation of isocyanates is presented based on the published analytical, toxicological, and regulatory literature, and the authors' own analytical data and experience with isocyanates.

Results

This analysis supports a need for standardization of isocyanate measurement metrics and provides a framework for the development of an OEL for polyisocyanates.

Conclusions

The total isocyanate group (μg NCO/m3) is recommended as the most feasible and practical metric (unit) by which to express polyisocyanate exposures for research, control, and regulatory purposes. The establishment of a comprehensive isocyanate OEL that simplifies the current agent‐by‐agent approach and expands coverage to polyisocyanates is also recommended. Am. J. Ind. Med. 46:480–491, 2004. © 2004 Wiley‐Liss, Inc.
Elbow and wrist/hand symptoms among 6,943 computer operators: A 1‐year follow‐up study (the NUDATA study)
Authors: Lassen Christina Funch , Mikkelsen Sigurd , Kryger Ann Isabel , Brandt Lars P.A. , Overgaard Erik , Thomsen Jane Frølund , Vilstrup Imogen , Andersen Johan Hviid
Published: October 2004

Background

The aim of this study was to examine relations between computer work aspects and elbow and wrist/hand pain conditions and disorders.

Methods

In a 1‐year follow‐up study among 6,943 technical assistants and machine technicians self‐reported active mouse and keyboard time, ergonomic exposures and associations with elbow and wrist/hand pain were determined. Standardized clinical examinations were performed among symptomatic participants at baseline and at follow‐up.

Results

For continuous duration of mouse time adjusted linear effects were statistically significant for all investigated pain conditions. For continuous duration of keyboard time the corresponding effects were statistically significant for wrist/hand pain conditions except incident ‘severe’ wrist/hand pain. There were no threshold effects above 0 hr per week (hr/w) of mouse exposure in association with pain conditions, while keyboard exposure showed a threshold effect with 12‐month wrist/hand pain at follow‐up. Clinical diagnoses were not associated with exposure.

Conclusions

Detailed examination of self‐reported exposures showed that mouse and keyboard time predicted elbow and wrist/hand pain from low exposure levels without a threshold effect, but mouse and keyboard time were not predictors of clinical conditions. Am. J. Ind. Med. 46:521–533, 2004. © 2004 Wiley‐Liss, Inc.
The British approach to asbestos standard setting: 1898–2000
Authors: Greenberg Morris
Published: October 2004

Background

The asbestos industry started in the late 1870s, and the first accounts of severe respiratory disease in its workers were published in England (1898, 1906), France (1907), and Italy (1908). For a hundred years, a series of increasingly lower standards were set for asbestos in Britain: initially they purported to prevent asbestosis, and latterly to reduce asbestosis and malignancies to acceptable levels.

Methods

Published accounts of how British asbestos exposure standards came to be derived are reviewed in the light of archival materials originated by industry and government.

Results

The earliest standard, of necessity, was not evidence based and while subsequent standards purported to relate doses to effects, the indifferent quality of the measurement of dose, and the poor discrimination of effects, militated against arriving at a standard in which trust should be placed. Each successive standard that was accepted, conformed to what could be achieved in production processes, as far as it was reasonably practicable on technological and economic grounds.

Conclusions

For the better part of a hundred years, confidence was misplaced in the ability of process engineers and physicians to protect workers against asbestos. Finally, deciding that asbestos was neither technologically nor economically essential, and was unsafe in use, Europe issued a Directive, to which Britain will conform, that will virtually ban it use throughout the Community by 2006. Am. J. Ind. Med. 46:534–541, 2004. © 2004 Wiley‐Liss, Inc.
Respiratory findings in pharmaceutical workers
Authors: Zuskin Eugenija , Mustajbegovic Jadranka , Schachter E. Neil , Kern Josipa , Deckovic‐Vukres Vlasta , Pucarin‐Cvetkovic Jasna , Nola‐Premec Iskra A.
Published: October 2004

Background

Pharmaceutical workers may be at risk for the development of respiratory problems as a result of their work environment.

Methods

This study investigated 163 female and 35 male workers, employed in a pharmaceutical plant processing different types of medication, primarily antibiotics, in order to characterize the risk of this environment. Chronic respiratory symptoms were recorded by using the British Medical Research Council questionnaire. Acute symptoms, which developed during the work shift, were also recorded. Ventilatory capacity was measured by recording maximum expiratory flow‐volume (MEFV) curves on which FVC, FEV1, FEF50, and FEF25 were measured. Controls (113) were selected from a food packing facility.

Results

A significantly higher prevalence of chronic respiratory symptoms was recorded among workers (compared to controls), the highest being for sinusitis, nasal catarrh, and dyspnea. There was also a high prevalence of acute symptoms recorded during the workshift. Odds ratio showed that the most significant risk factors for these respiratory findings were smoking and length of time worked in the pharmaceutical industry, particularly in men. Pulmonary function testing demonstrated significantly decreased measured values in comparison to predicted European pulmonary function measurements (P < 0.01). This was particularly pronounced for FEF50 and FEF25, suggesting obstructive changes in smaller airways.

Conclusions

Our data suggest that workers employed in the pharmaceutical industry may develop respiratory symptoms accompanied by ventilatory impairment. Am. J. Ind. Med. 46:472–479, 2004. © 2004 Wiley‐Liss, Inc.
Emergency management program operational responses to weapons of mass destruction: Veterans Health Administration, 2001–2004
Authors: Hodgson Michael J. , Bierenbaum Arnold , Mather Susan , Brown Mark A. , Beatty John , Scott Margie , Brewster Peter
Published: October 2004

Background

Despite the recognition of chemical emergencies, terrorist events, and ongoing threats, little practical guidance exists for healthcare facilities.

Methods

An approach and materials developed by the Veterans Health Administration in a five‐element program over the last 2 years to enhance the existing emergency management program is outlined. Nine steps to the development of a comprehensive all‐hazards, emergency plan and program, with auditing and improvement tools are offered.

Results

Cognitive aids for clinical use are available on‐line and in hard copy. A hazard assessment modeled patients as emission sources documenting the operations strategies under which level C personal protective equipment will protect healthcare workers. The development of this response program appears to support a broader, long‐standing VHA approach to problem solving. This involves bringing together individual talented field staff, representing specific skills, geographic regions, and work styles; investing in face‐to‐face consensus development; and developing programs with extensive internal peer‐review (“field‐based,” “bottom‐up and top‐down,” and external reviews).

Conclusions

Comprehensive and effective programs can be constructed at low cost with reasonable speed within large systems with a public mandate, leading to responsible use of public funds internally, and as models for private sector programs. It is the long‐term operational cost implications, under budget constraints in health care, which often present the true challenge. Am. J. Ind. Med. 46:446–452, 2004. Published 2004 Wiley‐Liss, Inc.
Worker training for new threats: A proposed framework
Authors: Mitchell Clifford S. , Doyle Mary L. , Moran John B. , Lippy Bruce , Hughes Joseph T. , Lum Max , Agnew Jacqueline
Published: October 2004

Background

In an effort to identify health and safety training needs for various groups of workers related to weapons of mass destruction, including chemical, biological, radiological, and nuclear weapons and high yield explosives (CBRNE), a conference, “Worker Training in a New Era: Responding to New Threats,” was held at the Johns Hopkins Bloomberg School of Public Health in October 2002.

Methods

Two questions were addressed: Which general skills and knowledge are common to all workers who might be exposed to terrorist threats from CBRNE weapons? What are the particular skills and knowledge relevant to these threats that are specific to workers in different sectors?

Results

Thirteen core components for pre‐ and post‐event training were identified. Pre‐event training applies to all workers. Post‐event training applies to selected personnel including first responders, skilled support personnel, and other workers involved in these operations. Recommendations to improve worker safety training related to preparedness include: identify specific competencies for worker pre‐ and post‐event training; coordinate Federal policy on worker training for CBRNE hazards; adopt federal guidelines or standards on worker training for new CBRNE threats, based on the competencies and coordinated Federal policy; conduct an inventory of training programs and other resources that could be used or adapted for use for new threats; and develop new training content and methods for pre‐ and post‐event training to address specific competencies.

Conclusions

Given the possibility for the introduction of CBRNE threats into the workplace, all workers need some training in the potential hazards involved: the individual worker's specific role in an emergency; incident command; activation of the emergency notification system; use of personal protective equipment (PPE); and safe evacuation of the workplace. While some occupational sectors have developed effective training related to these new threats, there is a need to develop, implement, and evaluate training programs across many different sectors of the workforce. Am. J. Ind. Med. 46:423–431, 2004. © 2004 Wiley‐Liss, Inc.
Cancer mortality and incidence among a cohort of benzidine and dichlorobenzidine dye manufacturing workers
Authors: Rosenman Kenneth D. , Reilly Mary Jo
Published: October 2004

Background

Benzidine is classified as a definite human carcinogen and dichlorobenzidine as a probable human carcinogen.

Methods

A cohort study of 538 workers potentially exposed to benzidine and/or dichlorobenzidine from a single chemical manufacturing facility was conducted. Social Security records were used to identify all employees who worked at the facility from 1960 to 1977. Vital status was determined through 2001 and cancer incidence through 2002.

Results

A total of 22 bladder cancer cases were identified. For three individuals, bladder cancer was the underlying cause of death. Increased standardized mortality ratios (SMRs) were found for all cancer 1.54 (95% CI 1.04–2.19), bladder cancer 8.34 (95% CI 1.72–24.78), and lymphohematopoietic cancer 2.84 (95% CI 1.04–6.18). The standardized incidence ratio (SIR) for bladder cancer was 6.85 (95% CI 4.30–10.4). Only one case of bladder cancer was identified among the workers who were exposed to dichlorobenzidine only. However, an increased risk for lymphohematopoietic cancer was found among these dichlorobenzidine only workers (SMR 6.62 (95% CI 1.37–19.36)).

Conclusions

This study confirms the high risk of bladder cancer among benzidine exposed workers even years after exposure has ceased, and raises suggestive evidence of increased risk to lymphohematopoietic cancer from exposure to benzidine or dichlorobenzidine. Am. J. Ind. Med. 46:505–512, 2004. © 2004 Wiley‐Liss, Inc.
Treatment of multiple sclerosis with an anti–interleukin‐2 receptor monoclonal antibody
Authors: Rose John W. , Watt Hilary E. , White Andrea T. , Carlson Noel G.
Published: October 2004

We examined whether treatment with daclizumab, a humanized monoclonal antibody specific for the interleukin‐2 receptor α chain, was safe and efficacious in relapsing–remitting and secondary progressive multiple sclerosis patients. Nineteen ambulatory patients with clinically active disease were treated for 5 to 25 months. Seventeen patients were not responding to other immunotherapies. Daclizumab was generally well tolerated. Sustained clinical improvement (10 patients) or stabilization (9 patients) was observed. Daclizumab treatment produced significant reduction in magnetic resonance imaging activity. Ann Neurol 2004
Study on limiting nutrients and phytoplankton at long‐line‐culture areas in Laizhou Bay and Sanggou Bay, northeastern China
Authors: Liu Hui , Fang Jianguang , Zhu Jianxin , Dong Shuanglin , Wang Fang , Liang Xingming , Zhang Jihong , Lian Yan , Wang Lichao , Jiang Weiwei
Published: October 2004

Concentrations of major nutrients (NH4+‐N, NO3−‐N, NO2−‐N, HPO4−‐P, Si(OH)4‐Si) were measured, nutrient enrichment experiments (oxygen‐production bioassay) were conducted and phytoplankton were analysed at typical long‐line‐culture areas in Laizhou Bay and Sanggou Bay, northeastern China, from March 2001 to March 2002.

Generally, much variation of nutrient indices was detected among the sampling stations, between the two bays and in different seasons: the concentration of dissolved inorganic nitrogen (DIN) fluctuated more violently and ranged much more widely in Sanggou Bay. N‐limitation was usually found in both bays, and the ranking of limiting potentials of major nutrients was N>Fe>P=Si in Laizhou Bay and N>P>Fe>Si in Sanggou Bay. Diatoms dominated the phytoplankton community in Sanggou Bay, but only dominated in eight months (with flagellates dominant in four months) in Laizhou Bay.

Linear and nonparametric correlation analyses suggested that a large number of the nutrient and phytoplankton variables measured have intrinsic relationships within themselves. Much more complicated correlations between phytoplankton and nutrient indices were found in Laizhou Bay than in Sanggou Bay. This, together with the violent fluctuations of DIN concentrations, indicated a more fragile ecosystem stability in Sanggou Bay.

The relatively exposed locations and less crowded settings of the rafts in the long‐line‐culture areas in Laizhou Bay allowed for a better water exchange, and the effect of aquaculture activity on the environment was not significant. Because of the intensity of aquaculture activities in Sanggou Bay, the biological, chemical and physical characteristics in the bay are greatly affected; a reduced cultivation density based on more comprehensive studies of carrying capacity of the bay is suggested.

Copyright © 2004 John Wiley & Sons, Ltd.
Descriptive analysis of parent–child interactions in young children with or at risk for developmental delay
Authors: Passey Jennifer , Feldman Maurice
Published: October 2004

Children with developmental delay (DD) are at risk for behavior problems, but little is known about natural contingencies of reinforcement that these children experience. The present study used descriptive analysis (antecedent–behavior–consequence observations) to study parent–child interactions of fourty‐seven, 2–3 year‐old children with or at risk for DD. Child adaptive and inappropriate behavior as well as their antecedents and consequences were observed across four conditions (free play, parent‐directed play, mealtimes, parental distraction). When parents were engaged in another task (distraction), child appropriate behavior occurred less frequently than in the other conditions, and child inappropriate behavior occurred 63% of the time. A lack of parental attention and no activity were the most frequent antecedents for inappropriate behavior. Potential positive reinforcers appeared as consequences of inappropriate child behavior 77% of the time. These findings have implications for the development and prevention of serious behavior disorders. Copyright © 2004 John Wiley & Sons, Ltd.
Quantitative screening of embryonic stem cell differentiation: Endoderm formation as a model
Authors: Chang Karen H. , Zandstra Peter W.
Published: October 2004

Embryonic stem (ES) cells have attracted much attention as a possible source of functional cells for regenerative medicine. Therapeutic use of ES cells requires control over the types and frequencies of cells generated during their in vitro differentiation. Due to the complexity of factors that impact upon ES cell differentiation, novel approaches for the optimization of tissue‐specific development are required. This motivates our use of factorial and composite design methods to make empirical investigations more efficient, and to reveal unexpected interactions missed by conventional dose–response analysis. Factorial experiments would benefit from the high content evaluation of a large number of test conditions, necessitating the development of a quantitative screening technology (QST) capable of reporting the absolute number and frequency of target cells. We have developed and validated such a technology for ES cell differentiation analysis using automated fluorescence microscopy, employing endoderm differentiation as a model system. To test this platform, a two‐level factorial experiment was carried out to identify major and interactive effects of glucose, insulin, retinoic acid (RA), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on endoderm formation. RA was found to have inhibitory effects on endoderm formation, while low glucose proved beneficial. QST was demonstrated to be a powerful tool to study factors impacting endoderm‐specific ES cell differentiation, and should be applicable to the analysis of a range of ES cell–derived tissues. © 2004 Wiley Periodicals, Inc.
Cell population dynamics model for deconvolution of murine embryonic stem cell self‐renewal and differentiation responses to cytokines and extracellular matrix
Authors: Prudhomme Wendy A. , Duggar Keith H. , Lauffenburger Douglas A.
Published: October 2004

Stem cell self‐renewal versus differentiation fate decisions are difficult to characterize and analyze due to multiple competing rate processes occurring simultaneously among heterogeneous cell subpopulations. To address this challenge, we describe a mathematical model for cell population dynamics that allows flow cytometry measurement of population distributions of molecular markers to be deconvoluted in terms of subpopulation‐specific rate parameters distinguishing commitment to differentiation, proliferation of differentiated cells, and proliferation of undifferentiated cells (i.e., self‐renewal). We validate this model‐based parameter determination by means of dedicated, independent cell‐tracking studies. Our approach facilitates interpretation of relationships underlying effects of external cues on cell responses in differentiating cultures via intracellular signals. © 2004 Wiley Periodicals, Inc.
Empirical models of the proliferative response of cytokine‐dependent hematopoietic cell lines
Authors: Chaudhry Muhammad A.S. , Bowen Bruce D. , Eaves Connie J. , Piret James M.
Published: October 2004

There is an expanding need for predictive mathematical models to accelerate the optimization of cell therapy culture processes. Here we demonstrate the ability of simple mathematical models to describe quantitatively the cytokine growth‐rate dependence of two human hematopoietic cell lines, TF‐1 and MO7e. These cells are immortal but depend on either interleukin‐3 (IL‐3) or granulocyte‐macrophage colony stimulating factor (GM‐CSF) for their continued survival and maximal proliferation. They are also responsive to interleukin‐6 (IL‐6) and exhibit saturation kinetics when these cytokines are limiting. A Monod‐type relationship consistently failed to fit measured cytokine dose–proliferation response curves while a Hill‐type relationship showed a good fit. Cytokine interactions were first modeled by modifying the Hill‐function to include an interaction parameter, γ. This model did not indicate either synergistic or even additive effects between IL‐3 and GM‐CSF. Based on the reported competition between IL‐3 and GM‐CSF for their common receptor (βc) subunit, a competitive model was also developed. This model had no new parameters beyond those obtained from single cytokine cultures and provided improved prediction of the growth rates for both cell lines exposed to combinations of IL‐3 and GM‐CSF over a wide range of concentrations. As expected, the competitive model failed to fit the data for IL‐6 in combination with either IL‐3 or GM‐CSF, since IL‐6 signaling does not involve the βc chain of the IL‐3/GM‐CSF receptors. Interestingly, the cell‐specific rates of GM‐CSF uptake and cell proliferation were found to be uncoupled processes. Taken together, these results illustrate the utility of appropriately designed empirical models to describe the proliferative responses of hematopoietic cells to cytokine stimulation. © 2004 Wiley Periodicals, Inc.
Runx2/Cbfa1‐genetically engineered skeletal myoblasts mineralize collagen scaffolds in vitro
Authors: Gersbach Charles A. , Byers Benjamin A. , Pavlath Grace K. , Guldberg Robert E. , García Andrés J.
Published: October 2004

Genetic engineering of progenitor and stem cells is an attractive approach to address cell sourcing limitations associated with tissue engineering applications. Bone tissue engineering represents a promising strategy to repair large bone defects, but has been limited in part by the availability of a sustained, mineralizing cell source. This study examined the in vitro mineralization potential of primary skeletal myoblasts genetically engineered to overexpress Runx2/Cbfa1, an osteoblastic transcriptional regulator essential to bone formation. These cells were viable at the periphery of 3D fibrous collagen scaffolds for 6 weeks of static culture. Exogenous Runx2 expression induced osteogenic differentiation and repressed myogenesis in these constructs relative to controls. Runx2‐modified cells deposited significant amounts of mineralized matrix and hydroxyapatite, as determined by microcomputed tomography, histological analysis, and Fourier transform infrared spectroscopy, whereas scaffolds seeded with control cells exhibited no mineralized regions. Although mineralization by Runx2‐engineered cells was confined to the periphery of the construct, colocalizing with cell viability, it was sufficient to increase the compressive modulus of constructs 30‐fold relative to controls. This work demonstrates that Runx2 overexpression in skeletal myoblasts may address current obstacles of bone tissue engineering by providing a potent cell source for in vitro mineralization and construct maturation. Additionally, the use of genetic engineering methods to express downstream control factors and transcriptional regulators, in contrast to soluble signaling molecules, represents a robust strategy to enhance cellular activities for tissue engineering applications. © 2004 Wiley Periodicals, Inc.
Engineering cartilage‐like tissue using human mesenchymal stem cells and silk protein scaffolds
Authors: Meinel Lorenz , Hofmann Sandra , Karageorgiou Vassilis , Zichner Ludwig , Langer Robert , Kaplan David , Vunjak‐Novakovic Gordana
Published: October 2004

Human mesenchymal stem cells (hMSC) derived from bone marrow aspirates can form the basis for the in vitro cultivation of autologous tissue grafts and help alleviate the problems of immunorejection and disease transmission associated with the use of allografts. We explored the utility of hMSC cultured on protein scaffolds for tissue engineering of cartilage. hMSC were isolated, expanded in culture, characterized with respect to the expression of surface markers and ability for chondrogenic and osteogenic differentiation, and seeded on scaffolds. Four different scaffolds were tested, formed as a highly porous sponge made of: 1) collagen, 2) cross‐linked collagen, 3) silk, and 4) RGD‐coupled silk. Cell‐seeded scaffolds were cultured for up to 4 weeks in either control medium (DMEM supplemented with 10% fetal bovine serum) or chondrogenic medium (control medium supplemented with chondrogenic factors). hMSC attachment, proliferation, and metabolic activity were markedly better on slowly degrading silk than on fast‐degrading collagen scaffolds. In chondrogenic medium, hMSC formed cartilaginous tissues on all scaffolds, but the extent of chondrogenesis was substantially higher for hMSC cultured on silk as compared to collagen scaffolds. The deposition of glycosaminoglycan (GAG) and type II collagen and the expression of type II collagen mRNA were all higher for hMSC cultured on silk than on collagen scaffolds. Taken together, these results suggest that silk scaffolds are particularly suitable for tissue engineering of cartilage starting from hMSC, presumably due to their high porosity, slow biodegradation, and structural integrity. © 2004 Wiley Periodicals, Inc.
Quartz crystal microbalance‐based measurements of shear‐induced senescence in human embryonic kidney cells
Authors: Jenkins M. S. , Wong K. C. Y. , Chhit O. , Bertram J. F. , Young R. J. , Subaschandar N.
Published: October 2004

Fluid shear and other mechanical forces play an important role in the normal biophysical, biochemical, and gene regulatory responses of vertebrate tissue that are reflected in the expression of normal cell differentiation, growth, and function. Despite some promising work reported on the application of the quartz crystal microbalance (QCM) to both prokaryote and eukaryote cells over the last decade, QCM has yet to be successfully applied to cells in culture under conditions of flow‐induced shear. In this study, high sensitivity QCM in conjunction with fluid modelling was used to monitor the onset of senescence in immortalised human embryonic kidney cells under laminar shear stresses of between 0.04 and 335 dyne/cm2. The feasibility of this approach as a means of quantification and characterisation of cell physiological response and adhesion are explored and discussed. © 2004 Wiley Periodicals, Inc.
Movements at the low back during normal walking
Authors: Rice J. , Kaliszer M. , Walsh M. , Jenkinson A. , O'Brien T.
Published: October 2004

We present a technique for measuring the kinematics of the functional low back during normal gait. We have used a similar technique previously to measure low back movement simultaneously with hip, knee, and ankle movement during the toe‐touching manoeuvre. We noted that movements at the low back were biphasic. The greatest low back movements were found to occur in the transverse plane (mean = 23°), whereas a mean of 17° movement occurred in the coronal plane and only 5° movement in the sagittal plane. These findings confirm, using a non‐invasive technique, that there are significant ranges of movement at the low back during walking and lend some support to the theory that rotational movement at the low back is a major component of human locomotion. Clin. Anat. 17:662–666, 2004. © 2004 Wiley‐Liss, Inc.
Imaging microscopy of the middle and inner ear: Part I: CT microscopy
Authors: Lane John I. , Witte Robert J. , Driscoll Colin L.W. , Camp John J. , Robb Richard A.
Published: October 2004

Anatomic definition of the middle ear and bony labyrinth in the clinical setting remains limited despite significant technological advances in computed tomography (CT). Recent developments in ultra‐high resolution imaging for use in the research laboratory on small animals and pathologic specimens have given rise to the field of imaging microscopy. We have taken advantage of this technique to image a human temporal bone cadaver specimen to delineate middle ear and labyrinthine structures, only seen previously using standard light microscopy. This approach to the study of the inner ear avoids tissue destruction inherent in histological preparations. We present high‐resolution MicroCT images of the middle ear and bony labyrinth to highlight the utility of this technique in teaching radiologists and otolaryngologists clinically relevant temporal bone anatomy. This study is not meant to function as a complete anatomic atlas of the temporal bone. We have selected several structures that are routinely delineated on clinical scanners to highlight the utility of imaging microscopy in displaying critical anatomic relationships in three orthogonal planes. These anatomic relationships can be further enhanced using 3D volume rendering. Clin. Anat. 17:607–612, 2004. © 2004 Wiley‐Liss, Inc.
Notice of Retraction and Apology
Authors: Schuster Peter , Casti John L.
Published: October 2004

The original article to which this Retraction refers was published in Complexity 2001, 6, 11–14

No abstract.
Design and operational aspects of airlift bioreactors for petroleum biodesulfurization
Authors: Mehrnia Mohammad Reza , Bonakdarpour Babak , Towfighi Jafar , Akbarnejad Mohammad Mehdi
Published: October 2004

The effects of important design and operating parameters on the hydrodynamics and oxygen transfer characteristics of draft‐tube airlift bioreactors (DTABs) were investigated. A water‐in‐kerosene microemulsion system was used inside the DTAB to simulate the physicochemical properties of the fermentation broths used in petroleum biodesulfurization (BDS) processes. For this system, the churn‐turbulent regime occurred at higher air flow rates compared to those of water‐based systems. An increase in draft‐tube surface area was found to be a more effective means for enhancement of both mixing and oxygen transfer than an increase in top‐section surface area expansion. An increase in the draft‐tube height and liquid level had a similar effect on the performance of DTABs containing the microemulsion or water‐based media. Correlations were developed that predicted overall and local gas holdups, liquid velocity, mixing time, and overall volumetric oxygen transfer coefficient as a function of aeration rate, bioreactor geometry, and liquid level inside the DTAB containing water‐in‐oil microemulsion for all experimental conditions examined. © 2004 American Institute of Chemical Engineers Environ Prog, 23: 206–214, 2004
Waste minimization techniques and options for the wet and pretreatment sections of coil coating plants
Authors: Brown Nicola J. , Dempster Heather J.
Published: October 2004

Waste minimization has proven successful in recent years for many companies in reducing their raw material and utility consumption and costs as well as their waste‐treatment and disposal costs. Although waste minimization opportunities can be identified through observation of plant operation practices and through application of generalized heuristic principles, many opportunities are determined only through analysis of plant data. In this study, two preassessment techniques (scoping audit and true cost of waste assessment) and two techniques for a more detailed assessment (mass balances and monitoring and targeting) were evaluated to determine whether they identified similar waste minimization opportunities on two coil coating lines. All techniques identified similar waste minimization opportunities, although the true cost of waste assessment and the monitoring and targeting analysis were found to be the most accurate in prioritizing the waste minimization opportunities. The raw material “scope to save” percentage in the scoping audit requires modification for application to South African industry. General waste minimization options for the wet and pretreatment sections of the coil coating industry are also presented. © 2004 American Institute of Chemical Engineers Environ Prog, 23: 185–193, 2004
Discrete breakpoint mapping and shortest region of overlap of chromosome arm 1q gain and 1p loss in human hepatocellular carcinoma detected by semiquantitative microsatellite analysis
Authors: Nishimura Takafumi , Nishida Naoshi , Itoh Teruaki , Komeda Toshiki , Fukuda Yoshihiro , Ikai Iwao , Yamaoka Yoshio , Nakao Kazuwa
Published: October 2004

Recurrent chromosomal gain at 1q is one of the most common features of human hepatocellular carcinoma (HCC), but how the gain at 1q contributes to hepatocarcinogenesis is still unclear. To identify the target genes, precise determination of the shortest region of overlap (SRO) and of breakpoints is necessary. Similarly, the role of loss at 1p, which is also a major cytogenetic aberration in HCC, needs to be determined. Fifty HCCs were examined with the aid of 59 microsatellite markers distributed throughout both arms of chromosome 1. To detect allelic gain effectively, the cutoff value of the allelic imbalance index was set at 0.70. Alleles showing imbalance were subjected to multiplex PCR, using a retained allele as an internal control, to determine whether the imbalance was the result of chromosomal gain or loss. The SRO of the gains was defined as D1S2878–D1S2619 (1q23.–q25.3, 16.9 Mb), which involved 36 cases (72%). Gains in the number of copies of certain oncogenes within this region seemed to be critical for the pathogenesis of HCC. In contrast, the centromeric breakpoints of these gains varied, but they tended to occur mainly in the pericentromeric region (26 of 50 cases, 52%). Rearrangement of specific genes associated with the gains is unlikely. On the other hand, the SRO of deletion was defined as D1S2893–D1S450 (1p36.32–p36.22, 5.1 Mb). Four known putative tumor‐suppressor genes (TP73, RIZ1, NBL1/DAN, and CDKN2C) were outside the SRO, suggesting the presence of other candidate genes with critical roles in hepatocarcinogenesis. © 2004 Wiley‐Liss, Inc.
On a policy of transferring public patients to private practice
Authors: González Paula
Published: October 2004

We consider an economy where public hospitals are capacity‐constrained, and we analyse the willingness of health authorities to reach agreements with private hospitals to have some of their patients treated there. When physicians are dual suppliers, we show that a problem of cream‐skimming arises and reduces the incentives of the health authority to undertake such a policy. We argue that the more dispersed are the severities of the patients, the greater the reduction in the incentives will be. We also show that, despite the patient selection problem, when the policy is implemented it is often the case that health authorities decide a more intensive transfer of patients to private practice. Copyright © 2004 John Wiley & Sons, Ltd.
Effects of socio‐economic status on mortality: separating the nearby from the farther away
Authors: Smits Jeroen , Keij‐Deerenberg Ingeborg , Westert Gert
Published: October 2004

Socio‐economic status effects on total and cause‐specific mortality are studied using data on all 15.8 million inhabitants of the Netherlands in 1999. Two problems are addressed that often hamper this kind of research: the lack of reliable social status information at the individual level and the intermingling of individual and neighbourhood status effects. The first problem is dealt with by using socio‐economic status information of the very close environment of the detailed postcode areas (average 41 inhabitants) in which one is living and the second one by combining this information with such area information at the much larger level of neighbourhoods (1500 inhabitants) or boroughs (6600 inhabitants). Clear and independent effects of socio‐economic status at all three levels of aggregation are found on total mortality and for a majority of causes of death. In almost all cases, the effects are to the disadvantage of people living in the lowest status areas. The effects are generally strongest at the detailed postcode level and weakest at the borough level, suggesting greater importance of factors at the nearby or individual level than at the farther away level(s). Copyright © 2004 John Wiley & Sons, Ltd.
Outcome versus service based payments in health care: lessons from African traditional healers
Authors: Leonard Kenneth L. , Zivin Joshua Graff
Published: October 2004

We compare the more common physician compensation method of fee‐for‐service to the less common payment‐for‐outcomes method. This paper combines an investigation of the theoretical properties of both of these payment regimes with a unique data set from rural Cameroon in which patients can choose between outcome and service based payments. We show that consideration of the role of patient effort in the production of health leads to important differences in the performance of these contracts. Theory and empirical evidence show that when illnesses require (or are responsive to) large amounts of both patient and practitioner effort, outcome based payment schemes are superior to effort based schemes. The traditional healer – a practitioner who offers health services on an outcome‐contingent basis – is advanced as an important example of how patient effort can be better understood and tapped in health care. Copyright © 2004 John Wiley & Sons, Ltd.
Pivotal role of nuclear factor κB signaling in anti-CD40-induced liver injury in mice
Authors: Kimura Kiminori , Nagaki Masahito , Takai Shinji , Satake Shinichi , Moriwaki Hisataka
Published: October 2004

Nuclear factor κB (NF-κB) has a central role in coordinating the expression of a wide variety of genes that control immune responses and is also recognized as an antiapoptotic transcription factor. Here, we focused on the role of the NF-κB signaling pathway in the interaction between inflammatory cells and hepatocytes in liver inflammation. We found that pretreatment of mice with adenoviruses expressing a mutant form of the inhibitor κB superrepressor (Ad5IκB), a NF-κB inhibitor, reduced the migration of inflammatory cells and cytokine and chemokine expression in the liver 12 hours after a single intravenous injection of an anti-CD40 antibody (αCD40) compared with mice infected with control adenoviruses (Ad5LacZ). We also confirmed reductions in cytokine production by macrophages, T cells, and natural killer (NK) cells in the liver of Ad5IκB-treated mice by FACS analysis. However, αCD40 treatment in Ad5IκB-infected mice induced elevation of serum alanine aminotransferase at 24 hours, and the liver injury was associated with massive hepatocyte apoptosis. Furthermore, interferon gamma (IFN-γ) production by NK cells and T cells was increased and stimulated tumor necrosis factor alpha (TNF-α) production by macrophages in the Ad5IκB-infected liver. Moreover, the liver injury was completely suppressed by the administration of anti-IFN-γ and anti-TNF-α. These results suggest that inhibition of NF-κB activity suppressed αCD40-induced liver inflammation at an early phase, resulting in a reduction in cytokine and chemokine production, whereas it sensitized hepatocytes to TNF-α-induced apoptosis and exacerbated liver injury at the late phase. In conclusion, NF-κB exerts pivotal activities at inflammatory sites, and caution should be exercised in NF-κB-targeted therapy of liver disease. (Hepatology 2004;40:1180-1189.)
ACAT2 deficiency limits cholesterol absorption in the cholesterol-fed mouse: Impact on hepatic cholesterol homeostasis
Authors: Repa Joyce J. , Buhman Kimberly K. , Farese Robert V. , Dietschy John M. , Turley Stephen D.
Published: October 2004

Acyl CoA:cholesterol acyltransferase (ACAT) 2 is the major cholesterol-esterifying enzyme in mouse enterocytes and hepatocytes. Male ACAT2+/+ and ACAT2−/ − mice were fed chow containing added cholesterol (0%-0.500% w/w) for 24 days. Over this range, fractional cholesterol absorption in the ACAT2+/+ mice fell from 41.4% ± 6.6% to 21.0% ± 5.2%, and in their ACAT2−/− counterparts it fell from 35.1% ± 4.5% to 7.9% ± 0.8%. The mass of dietary cholesterol absorbed (mg/d per 100 g body weight) increased from 1.2 ± 0.2 to 14.7 ± 4.4 in the ACAT2+/+ mice and from 1.0 ± 0.2 to 5.5 ± 0.6 in those without ACAT2. In the ACAT2+/+ mice, hepatic cholesterol concentrations increased as a function of intake despite compensatory changes in cholesterol and bile acid synthesis and in the expression of adenosine triphosphate-binding cassette transporter G5 (ABCG5) and ABC transporter G8 (ABCG8). In contrast, in ACAT2−/− mice in which the amount of cholesterol absorbed at the highest intake was only 37% of that in the ACAT2+/+ mice, suppression of synthesis was a sufficient adaptive response; there was no change in bile acid synthesis, ABCG5/G8 expression, or hepatic cholesterol concentration. The expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) in the jejunum was markedly elevated in the ACAT2−/− mice, irrespective of dietary cholesterol level. In conclusion, although ACAT2 deficiency limits cholesterol absorption, the extent to which it impacts hepatic cholesterol homeostasis depends on cholesterol intake. Loss of ACAT2 activity may result in unesterified cholesterol being absorbed via an ABCA1-mediated basolateral efflux pathway. (Hepatology 2004;40:1088-1097.)
Concanavalin a injection activates intrahepatic innate immune cells to provoke an antitumor effect in murine liver
Authors: Miyagi Takuya , Takehara Tetsuo , Tatsumi Tomohide , Suzuki Takahiro , Jinushi Masahisa , Kanazawa Yoshiyuki , Hiramatsu Naoki , Kanto Tatsuya , Tsuji Shingo , Hori Masatsugu , Hayashi Norio
Published: October 2004

Concanavalin A (ConA), directly injected into mice, induces T cell-mediated liver injury. However, it remains unclear whether ConA injection can activate innate immune cells, including natural killer (NK) cells and natural killer T (NKT) cells, both of which exist abundantly in the liver. Here we report that ConA injection stimulated interferon (IFN)-γ production from liver NKT cells as early as 2 hours after injection and augmented YAC-1 cytotoxicity of liver NK cells. ConA-induced NK cell activation required other types of immune cells and critically depended on IFN-γ. Because a nonhepatotoxic low dose of ConA was capable of fully activating both NKT cells and NK cells, we next addressed the possibility of ConA injection displaying an antitumor effect in the liver without liver injury. A nonhepatotoxic low-dose ConA injection augmented the cytotoxicity of liver NK cells against Colon-26 colon cancer cells and suppressed hepatic metastasis of Colon-26 cells in a NK cell- and IFN-γ-dependent manner. In conclusion, a nonhepatotoxic low dose of ConA might serve as an immunomodulator that can preferentially activate the innate immune cells to induce an antitumor effect against metastatic liver tumor. (Hepatology 2004;40:1190-1196.)