bluuebunny/crossref_metadata_2025 huggingface dataset:
On the enhanced convergence of standard lattice methods for option pricing
Authors: Widdicks Martin , Andricopoulos Ari D. , Newton David P. , Duck Peter W.
Published: October 2004

For derivative securities that must be valued by numerical techniques, the trade‐off between accuracy
and computation time can be a severe limitation. For standard lattice methods, improvements are achievable by
modifying the underlying structure of these lattices; however, convergence usually remains
non‐monotonic. In an alternative approach of general application, it is shown how to use standard
methods, such as Cox, Ross, and Rubinstein (CRR), trinomial trees, or finite differences, to produce
uniformly converging numerical results suitable for straightforward extrapolation. The concept of Λ, a
normalized distance between the strike price and the node above, is introduced, which has wide ranging
significance. Accuracy is improved enormously with computation times reduced, often by orders of magnitude.
© 2002 Wiley Periodicals, Inc. Jrl Fut Mark 22:315–338, 2002
Investor Sentiment and Return Predictability in Agricultural Futures Markets
Authors: Wang Changyun
Published: October 2004

This study examines the usefulness of trader‐position‐based sentiment index for forecasting
future prices in six major agricultural futures markets. It has been found that large speculator sentiment
forecasts price continuations. In contrast, large hedger sentiment predicts price reversals. Small trader
sentiment hardly forecasts future market movements. An investigation was performed into various
sentiment‐based timing strategies, and it was found that the combination of extreme large trader
sentiments provides the strongest timing signal. These results are generally consistent with the
hedging‐pressure theory, suggesting that hedgers pay risk premiums to transfer nonmarketable risks in
futures markets. Moreover, it does not appear that large speculators in the futures markets possess any superior
forecasting ability. © 2001 John Wiley & Sons, Inc. Jrl Fut Mark 21:929–952, 2001
Chromosomal alterations during metastasis formation of head and neck squamous cell carcinoma
Authors: Bockmühl Ulrike , Schlüns Karsten , Schmidt Sven , Matthias Sabine , Petersen Iver
Published: October 2004

Comparative genomic hybridization (CGH) was used to detect chromosomal changes during metastasis formation of head and neck squamous cell carcinomas (HNSCCs). In total, 92 tumors of 54 patients were investigated. In 34 of these, the metastases were compared to the corresponding primary tumors. The group of metastatic tumors was also compared with 20 nonmetastatic tumors. Gain of 3q was the earliest genetic marker for invasion and metastasis and also correlated with poor prognosis. Additional metastasis‐associated lesions were gains on 11q13, 7q11.2, 1q21‐q22, and losses on 8p, 11p14, 11q14‐qter, 10p12, 10q, and 14q. The incidence of the chromosomal changes was used to evaluate their significance and temporal order of appearance during tumor dissemination, thus leading to an extended progression model of HNSCC. In the clonality analysis, three different methods revealed a mean concordance of 64 and 68% between pairs of primaries and metastases, respectively. Using different similarity scores, the correct metastasis was identified from the pool of all metastatic lesions in 19–26 of the 34 cases. The study supplements previous genetic results on HNSCC pathogenesis and provides criteria for multiple tumor analysis.
Tree‐based recursive partitioning methods for subdividing sibpairs into relatively more homogeneous subgroups
Authors: Shannon William D. , Province Michael A. , Rao D.C.
Published: October 2004

We propose a new splitting rule for recursively partitioning sibpair data into relatively more homogeneous subgroups. This strategy is designed to identify subgroups of sibpairs such that within‐subgroup analyses result in increased power to detect linkage using Haseman‐Elston regression. We assume that the subgroups can be defined by patterns of non‐genetic binary covariates measured on each sibpair. The data we consider consists of the squared difference of a quantitative trait measurement on each sibpair, estimates of identity‐by‐descent (IBD) values at each genetic marker, and binary covariate data describing characteristics of the sibpair (e.g., race, sex, family history of disease). To test the efficacy of this method in linkage analysis, we performed two simulation experiments. In the first, we simulated a mixture consisting of 66.6% of the sibpairs with no linkage and 33.3% of the sibpairs with genetic linkage to one marker. The two groups were distinguished by the value of a single binary covariate. We also simulated one unlinked marker and one random covariate to include as noise in the data. In the second experiment, we simulated a mixture consisting of 55% of the sibpairs with no genetic linkage, 22.5% of the sibpairs with genetic linkage to one marker, and 22.5% of the sibpairs with linkage to a different marker. Each subgroup was defined by a distinct pattern of two binary covariates. We also simulated one unlinked marker and two random covariates to include as noise in the data. Our simulation studies found that we can significantly increase the overall power to detect linkage by fitting Haseman‐Elston regression models to homogeneous subgroups with only a small increase in the false‐positive rate. Second, the splitting rule can correctly identify important covariates and linked markers. Third, recursive partitioning of sibpair data using this splitting rule can correctly identify sibpair subgroups. These results indicate that partitioning sibpairs into homogeneous subgroups is feasible and significantly increases the power to detect linkage, thus demonstrating the practical utility and potential this new methodology holds. Genet. Epidemiol. 20:293–306, 2001. © 2001 Wiley‐Liss, Inc.
Estimation of allele frequencies with data on sibships
Authors: Broman Karl W.
Published: October 2004

Allele frequencies are generally estimated with data on a set of unrelated individuals. In genetic studies of late‐onset diseases, the founding individuals in pedigrees are often not available, and so one is confronted with the problem of estimating allele frequencies with data on related individuals. We focus on sibpairs and sibships, and compare the efficiency of four methods for estimating allele frequencies in this situation: (1) use the data for one individual from each sibship; (2) use the data for all individuals, ignoring their relationships; (3) use the data for all individuals, taking proper account of their relationships, considering a single marker at a time; and (4) use the data for all individuals, taking proper account of their relationships, considering a set of linked markers simultaneously. We derived the variance of estimator 2, and showed that the estimator is unbiased and provides substantial improvement over method 1. We used computer simulation to study the performance of methods 3 and 4, and showed that method 3 provides some improvement over method 2, while method 4 improves little on method 3. Genet. Epidemiol. 20:307–315, 2001. © 2001 Wiley‐Liss, Inc.
Swallowing and speech ability after treatment for head and neck cancer with targeted intraarterial versus intravenous chemoradiation
Authors: Newman Lisa A. , Thomas Robbins K. , Logemann Jeri A. , Rademaker Alfred W. , Lazarus Cathy L. , Hamner Annette , Tusant Stephanie , Huang Cheng Fang
Published: October 2004

Objective

RADPLAT (concurrent selective supradose intraarterial cisplatin and external‐beam irradiation) delivers extraordinarily high cisplatin concentration to head and neck structures. This study was designed to quantify and compare RADPLAT and systemic chemoradiation treatment effects on swallowing and speech.

Methods

Videofluorographic swallowing studies and articulation testing of 14 head and neck cancer patients treated with RADPLAT were compared with 16 treated with systemic chemoradiation 1 month after treatment.

Results

RADPLAT and systemic chemoradiation patients did not differ significantly on most swallow outcome measures, and there was significantly less aspiration on 1 and 3 mL liquid for RADPLAT individuals. Speech function was comparable except for RADPLAT's significantly worse /s, z/ productions.

Conclusions

Increased concentration of cisplatin to the head and neck did not result in generally reduced swallowing or articulatory function. © 2002 John Wiley & Sons, Inc. Head Neck 24: 68–77, 2002.
Management issues in massive pediatric facial plexiform neurofibroma with neurofibromatosis type 1
Authors: Wise Jeffrey B. , Patel Snehal G. , Shah Jatin P.
Published: October 2004

Background

Plexiform neurofibroma is a relatively common but potentially devastating manifestation of neurofibromatosis type 1 (NF1). Surgical management is the mainstay of therapy, but within the head and neck region it is limited by the infiltrating nature of these tumors, inherent operative morbidity, and high rate of regrowth.

Method

We describe a case of a 7‐year‐old girl with neurofibromatosis type 1 and a massive facial plexiform neurofibroma with the aim of emphasizing the treatment and timing issues involved in the management of this difficult problem. A MEDLINE search (1966 through December 2000) was carried out, and pertinent literature on the subject was reviewed.

Result

The patient described in this case report was carefully observed for a period of 6 years from diagnosis before surgical excision of the tumor was undertaken with an uneventful recovery.

Conclusion

Surgical management remains the mainstay of treatment for these locally invasive tumors, but functional disturbances are almost inevitable in resecting substantial tumors involving the head and neck region. The indication and timing of surgery in pediatric patients therefore needs to be carefully weighed against the physical and psychologic consequences of treatment. © 2002 John Wiley & Sons, Inc.
Radial clearance in resection of hypopharyngeal cancer: An independent prognostic factor
Authors: Ho Chiu M. , Ng Wing F. , Lam Kam H. , Wei William I. , Yuen Anthony P. W.
Published: October 2004

Background

The depth of infiltration of tumor is of particular relevance in hypopharyngeal cancers, because most of them are seen late, and extensive infiltration into the muscle wall and the cartilage are not uncommon.

Methods

The resected specimens of hypopharyngeal cancers were studied with whole‐organ step‐serial sectioning. The extent of infiltration into the thickness of the wall and the radial clearance were carefully documented. These parameters were correlated with the tumor recurrence and survival rates.

Results

Most patients with hypopharyngeal cancer had a minimal radial margin; the radial clearance was <1 mm in 56% of the patients. Despite such a minimal margin, the local recurrence rate was only 19% and occurred mainly in the upper and lower resection margins. Radial clearance was an independent prognostic factor for overall survival, disease‐free survival, and nodal recurrence‐free survival on multivariate analysis.

Conclusion

Radial clearance is an important independent prognostic factor, and it is recommended to be included in the routine pathologic reporting of the resected specimen in hypopharyngeal cancer. © 2002 John Wiley & Sons, Inc.
Hypercalcemia associated with parathyroid hormone–related protein at the terminal stage of uncomplicated squamous cell carcinoma in the head and neck region
Authors: Fujikawa Megumi , Takata Yutaka , Okamura Ken , Nakagawa Mizuho , Tateishi Akira , Kurokawa Hideo , Sato Kaori , Fukuda Jinichi , Kajiyama Minoru , Fujishima Masatoshi
Published: October 2004

Background

Parathyroid hormone–related protein (PTHrP) is mainly responsible for hypercalcemia in squamous cell carcinomas (SCCs).

Methods

We retrospectively checked the appearance of hypercalcemia among 33 patients who died with head and neck SCC. Serum concentrations of C‐terminal region of PTHrP (C‐PTHrP) were measured in 15 of them. The intracellular PTHrP expression was immunohistochemically stained in 42 SCC sections obtained from the 33 before the appearance of hypercalcemia.

Results

Hypercalcemia appeared in 24 of the 33, and increased serum C‐PTHrP levels were confirmed in 11 of 12 hypercalcemic patients. PTHrP was identified in all SCC sections, and a stronger intensity than in normal squamous epithelia was observed in 50% of those obtained within 1 year before the onset of hypercalcemia.

Conclusion

A high incidence of PTHrP‐induced hypercalcemia was shown among patients dying with head and neck SCCs. The intracellular increase in PTHrP might be observed preceding hypercalcemia. © 2002 John Wiley & Sons, Inc. Head Neck 24: 56–62, 2002.
FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma
Authors: Brun Eva , Kjellén Elisabeth , Tennvall Jan , Ohlsson Tomas , Sandell Anders , Perfekt Roland , Perfekt Roland , Wennerberg Johan , Strand Sven Erik
Published: October 2004

Background

Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2‐[18 F] fluoro‐2‐deoxy‐D‐glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC.

Methods

Between 1993 and 1999 47 patients underwent PET before (PET1) and after (PET2) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow‐up time was 3.3 years.

Results

Low and high MR FDG at PET2, with median value as cutoff, was associated with complete remission in 96% and 62% (p = .007), with 5‐year overall survival in 72% and 35% (p = .0042) and with local control in 96% and 55% (p = .002), respectively.

Conclusions

FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. © 2002 John Wiley & Sons, Inc.
Chromosomal integration of Epstein ‐ Barr virus genomes in nasopharyngeal carcinoma cells
Authors: Chang Yao , Cheng Sou‐De , Tsai Ching‐Hwa
Published: October 2004

Background

Little has been known about whether Epstein‐Barr virus (EBV) could persist in nasopharyngeal carcinoma (NPC) cells by chromosomal integration, and no NPC cell line harboring integrated EBV has been reported. In this study, we explored this issue through isolating EBV‐infected NPC cell clones generated from an in vitro infection system and examining the configuration of EBV DNA in these cells.

Methods and Results

EBV genomes were demonstrated in NPC cell clones using polymerase chain reaction and Southern hybridization. Viral nuclear antigens were also detected by use of an anticomplement immunofluorescence assay and an immunoblotting assay. Gardella gel analysis showed that two of the EBV‐positive cell clones, H2B4 and H2B17‐7, harbored no extrachromosomal form of the viral genome. Restriction analysis of EBV genomic termini indicated that EBV DNA in these two cell clones was not circularized, and the viral genomes were integrated into chromosomes as demonstrated by fluorescence in situ hybridization.

Conclusions

This is the first in vitro model of EBV persistence in NPC cells by genomic integration, which represents a unique state of virus‐cell interaction. Using this model, investigation into the association between EBV integration and chromosomal abnormality in tumor cells will help to reveal the underlying biologic significance. © 2002 John Wiley & Sons, Inc.
Relapsing paraganglioma of the inferior laryngeal paraganglion: Case report and review of the literature
Authors: Hinojar Adolfo G. , Prieto Juan Ramón , Muñoz Elia , Hinojar Adolfo A.
Published: October 2004

Background

Laryngeal paragangliomas are very rare neoplasms derived from the superior or inferior laryngeal paraganglia. The paragangliomas of the inferior laryngeal paraganglion, depending on their anatomic variability, can give rise to two different clinical expressions of the same process, namely the so‐called thyroid paragangliomas and the inferior laryngeal or subglottic paragangliomas.

Methods

We present a case for which we have not found any previous descriptions of a cervical and subglottictracheal relapse of a thyroid paraganglioma removed 3 years earlier. We review the literature.

Results

We have found a total of 22 paragangliomas of the inferior laryngeal paraganglia, 23 including our case.

Conclusions

Thyroid paragangliomas and inferior laryngeal or subglottic paragangliomas should be included under the term “paragangliomas” of the inferior laryngeal paraganglion. These tumors are slow growing, benign, hypervascular, and much more common in middle‐aged women. Immunohistochemistry is essential for its diagnosis. Open, conservative surgery is the treatment of choice. © 2002 John Wiley & Sons, Inc. Head Neck 24: 95–102, 2002.
Targeting the “species gene ensemble”
Authors: Routtenberg Aryeh
Published: October 2004

The members of a given species display a normal distribution of gene expression which is here termed the species gene ensemble. This more specific designation of the ‘genetic background’ leads to a consideration of why gene targeting outcomes are regulated by the species gene ensemble. One consequence is the utility of the heterozygous knockout which buffers the drastic compensatory reactions of the homozygous knockout thereby revealing subtle but yet consistent alterations in hippocampally‐dependent behaviors. Hippocampus 2002;12:105–108. © 2002 Wiley‐Liss, Inc.
Long‐term monitoring of hippocampus‐dependent behavior in naturalistic settings: Mutant mice lacking neurotrophin receptor TrkB in the forebrain show spatial learning but impaired behavioral flexibility
Authors: Vyssotski Alexei L. , Dell'Omo Giacomo , Poletaeva Inga I. , Vyssotski Dmitri L. , Minichiello Liliana , Klein Rüdiger , Wolfer David P. , Lipp Hans‐Peter
Published: October 2004

P revious behavioral studies (Minichiello et al., Neuron 1999;24:401–414) showed that mice deficient for the TrkB receptor in the forebrain were unable to learn a swimming navigation task with an invisible platform and were severely impaired in finding a visible platform in the same setup. Likewise, additional behavioral deficits suggested a malfunction of the hippocampus and proximally connected forebrain structures. In order to discriminate whether the behavioral impairment was caused either by deficits in spatial memory and learning, or alternatively by loss of behavioral flexibility, 8 trkB mutant, 13 wild‐type, and 22 heterozygous mice were implanted with transponders and released for 21 days into a large outdoor pen (10 × 10 m). The enclosure contained 2 shelters and 8 computer‐controlled feeder boxes, delivering food portions for every mouse only during their first visit. Every third day, mice received food ad libitum inside the shelters. All mice learned to patrol the boxes correctly within a few days. However, significant differences emerged during those days with free food available. Wild‐type mice remained inside the shelters, while all homozygous mutants continued to patrol the boxes in their habitual way, the heterozygous mutants showing intermediate scores. These and previous data suggest that one of the natural functions of the mouse hippocampus is to comediate behavioral flexibility, and that TrkB receptors might play an essential role in maintaining the neuronal short‐term plasticity necessary for this capacity. Hippocampus 2002;12:27–38. © 2002 Wiley‐Liss, Inc.
Age‐dependent differential regulation of genes encoding APP and α‐synuclein in hippocampal synaptic plasticity
Authors: Stéphan A. , Davis S. , Salin H. , Dumas S. , Mallet J. , Laroche S.
Published: October 2004

We investigated the modulation of the messenger RNA (mRNA) encoding the amyloid precursor protein (APP) and α‐synuclein following induction of long‐term potentiation (LTP) in the dentate gyrus of young and aged rats. Three hours after tetanic stimulation, LTP induced in the young rats was maintained; the aged rats, however, fell into two subgroups: those in which LTP was maintained, and those in which LTP had declined to basal levels. In young rats, the global expression of mRNAs of all isoforms of APP and in particular that of the isoform lacking the KPI domain were significantly upregulated. In aged rats, the global expression of mRNAs of all isoforms of APP was not modified, regardless of whether LTP was maintained or not. The level of mRNA encoding the Kunitz protease‐inhibitory (KPI)‐minus isoform of APP, however, was increased in aged rats in which LTP was maintained, suggesting that the gene of this isoform may be more specifically regulated by synaptic plasticity. In contrast, we found that the gene encoding α‐synuclein showed a trend towards being downregulated at the mRNA level in young rats following LTP, and significantly so in aged rats in which LTP was maintained, whereas it was not downregulated in aged rats with decremental LTP. These data suggest that the regulated expression of APP isoforms is part of the transcriptional response associated with the enduring forms of synaptic plasticity and is altered with age. Whereas the level of α‐synuclein mRNA is not apparently modified in normal LTP, it may reflect a mechanism of apoptotic cell death in aging that is in part responsible for decremental synaptic plasticity. Hippocampus 2002;12:55–62. © 2002 Wiley‐Liss, Inc.
Force transducer‐based movement detection in fear conditioning in mice: A comparative analysis
Authors: Fitch Thomas , Adams Benjamin , Chaney Stephen , Gerlai Robert
Published: October 2004

Fear conditioning (FC) allows the dissociation of hippocampal and nonhippocampal behavioral function in rodents, and has become a diagnostic tool in transgenic mouse research employed to investigate mutation‐induced changes in brain function. Although the procedural details of the paradigm have been established, quantification of the behavioral output, freezing, remains problematic in mice. Observation‐based techniques are time‐consuming and may be subject to bias, while movement detection with photocells is imprecise. Here we describe an alternative method for movement detection, based on an electronic force transducer system that allows the quantification of acceleration forces generated by a moving subject. We compare the behavior of two inbred strains of mice (C57BL/6 and DBA/2) whose performance is known to differ in hippocampal tasks, including FC. The comparison is made using multiple techniques: the force transducer approach, and three observation‐based methods, a computer‐aided event‐recording approach, a traditional time‐sampling paper/pencil method, and a subjective impression‐based scoring system. In addition, we investigate the correlation structures of behavioral elements quantified by event recording, using principal component analyses; we conclude that fear may manifest in multiple forms and in a stimulus‐ and genotype‐dependent manner. We suggest that the force transducer system provides precise quantification of movements in an automated manner and will allow high‐throughput screening for mutation and drug effects in mice. However, we also argue that fear responses can be complex, and freezing behavior may not be the only measure of fear or fear‐associated memory. Hippocampus 2002;12:4–17. © 2002 Wiley‐Liss, Inc.
Comparing Line and HR Executives' Perceptions of HR Effectiveness: Services, Roles, and Contributions
Authors: Wright Patrick M. , McMahan Gary C. , Snell Scott A. , Gerhart Barry
Published: October 2004

This study compares HR and line executives' evaluations of the effectiveness of the HR function in terms of its service delivery, roles, and contributions to the firm. Survey responses from 44 HR and 59 line executives from 14 companies indicated that (a) HR executives consistently rated the functions' effectiveness higher than did line executives, and (b) the greatest differences were observed on the more important and/or strategic aspects of HR. Implications for improving HR effectiveness are discussed. © 2001 John Wiley & Sons, Inc.
Outsourcing HR: The Impact of Organizational Characteristics
Authors: Klaas Brian S. , McClendon John A. , Gainey Thomas W.
Published: October 2004

This study investigates the relationship between a number of organizational characteristics and the decision to outsource HR. Determinants of the outsourcing of four categories of HR are examined: HR generalists activities (e.g., performance appraisal), transactional activities (e.g., payroll), human capital activities (e.g., training), and recruiting and selection. HR executives in 432 organizations provided data on outsourcing levels and organizational characteristics. Reliance on HR outsourcing was associated with idiosyncratic HR practices, strategic HR involvement, positive HR outcomes, promotional opportunities, demand uncertainty, and pay level. As predicted, however, the impact of organizational characteristics varied among the different types of HR activities outsourced. © 2001 John Wiley & Sons, Inc.
Who's in Charge? An Empirical Study of Executive Staffing Practices in Foreign Subsidiaries
Authors: Harzing Anne‐Wil
Published: October 2004

This study investigates executive staffing practices in foreign subsidiaries of multinational corporations. Grounded in a literature review of the reasons for employing either parent country nationals or host country nationals in top management positions in foreign subsidiaries, a number of factors influencing the choice between these alternatives are identified. Using a combination of an archival and mail survey research method, the influence of each of these factors is empirically tested with a sample of nearly 3000 observations. © 2001 John Wiley & Sons, Inc.
Incentive Alignment, CEO Pay Level, and Firm Performance: A Case of “Heads I Win, Tails You Lose”?
Authors: Sanders Wm. Gerard
Published: October 2004

In recent years, rewarding CEOs with long‐term forms of compensation (e.g., stock options, performance plans, restricted stock) has become more popular than using year‐end pay adjustments. Surprisingly, there is little empirical evidence to support the benefits of this trend. This study found that the benefits of long‐term compensation flowed primarily to CEOs as they received significantly greater levels of total compensation than CEOs in firms that emphasized year‐end pay adjustments. Paradoxically, however, firms that emphasized year‐end pay adjustments performed significantly better than firms that were heavy users of long‐term forms of contingent compensation. © 2001 John Wiley & Sons, Inc.
Employees' Nonwork Obligations and Organizational Commitments: A New Way to Look at the Relationships
Authors: Mellor Steven , Mathieu John E. , Barnes‐Farrell Janet L. , Rogelberg Steven G.
Published: October 2004

The authors1 adopted a family resource view of nonwork obligations and examined these obligations' relationships to dimensions of employees' organizational commitment. Complex interactions were found between employees' marital status, number of children, and having relatives nearby as related to the continuance dimension, but not the affective dimension, of commitment. In particular, results were strongest when the focus was on employees' perceptions of whether they would experience a high personal sacrifice if they were to leave their organizations. These findings are discussed in the context of developing family‐friendly human resource programs that may help employees feel less “trapped” in organizations. © 2001 John Wiley & Sons, Inc.
One Prudential Exchange—The Insurance Giant's Business Literacy and Alignment Platform
Authors: McKnight Richard , Doele Jody , Christine Kim
Published: October 2004

This article describes how Prudential—in a dramatically changed marketplace—engaged its 55,000
employees as partners in transforming the company's many disparate businesses into one integrated company.
Using a combination of large‐and small‐scale meetings, follow‐up actions at the work unit
level, and sophisticated performance enhancement processes, OPX (One Prudential Exchange) is helping
transform Prudential from a staid insurance company to a modern financial services powerhouse. OPX has introduced
the One Prudential vision to the company's 55,000 employees in nearly 300 large‐scale meetings in 12
cities, and has institutionalized problem resolution and breakthrough dialogue processes in over 3,500
follow‐up work unit meetings. © 2001 John Wiley & Sons, Inc.
Control of pore structure and size in freeze‐dried collagen sponges
Authors: Schoof Heike , Apel Jörn , Heschel Ingo , Rau Günter
Published: October 2004

Because of many suitable properties, collagen sponges are used as an acellular implant or a biomaterial in the field of tissue engineering. Generally, the inner three‐dimensional structure of the sponges influences the behavior of cells. To investigate this influence, it is necessary to develop a process to produce sponges with a defined, adjustable, and homogeneous pore structure. Collagen sponges can be produced by freeze‐drying of collagen suspensions. The pore structure of the freeze‐dried sponges mirrors the ice‐crystal morphology after freezing. In industrial production, the collagen suspensions are solidified under time‐ and space‐dependent freezing conditions, resulting in an inhomogeneous pore structure. In this investigation, unidirectional solidification was applied during the freezing process to produce collagen sponges with a homogeneous pore structure. Using this technique the entire sample can be solidified under thermally constant freezing conditions. The ice‐crystal morphology and size can be adjusted by varying the solute concentration in the collagen suspension. Collagen sponges with a very uniform and defined pore structure can be produced. Furthermore, the pore size can be adjusted between 20–40 μm. The thickness of the sponges prepared during this research was 10 mm. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 352–357, 2001
Animal study on surface‐modified defibrillator systems: Indications for enhanced infection resistance
Authors: van Wachem Pauline B. , Brouwer Linda A. , Kors Geert , Dijk Freark , Bel Klaas , Elstrodt Jan , van Wijk Frank , Cahalan Patrick T. , Hendriks Marc , van Luyn Marja J. A.
Published: October 2004

One of the most important problems with ICD systems is infection. The aim of this study was an in vivo evaluation of the efficacy of defibrillator systems in terms of infection resistance. The polyurethane leads were coupled with heparin and loaded with the antibiotic gentamicin, while the PGs were modified to release gentamicin. Group I was comprised of 10 pigs implanted with either a standard or a modified system for 2 weeks; group II was implanted during 4 weeks. The lead was inserted into the heart wall via the jugular vein. The other end was subcutaneously tunneled to the armpit where the PG was positioned. A cocktail of Staphylococcus aureus and epidermidis was injected at the site of the PG. Evaluation was performed macroscopically, by taking bacterial swabs during explantation and by microscopic processing. The results showed that 3 out of 5 modified defibrillator‐systems in group I and 1–2 out of 5 in group II were judged as noninfected, whereas all standard systems were infected. Infection rates of the remaining modified defibrillators showed variances, as found with the standards, from slight to moderate to high, to even high/severe in group II (1× standard and 1× modified). With the modified systems, this may be related to production of humoral factors by an intensified early tissue reaction, as indicated by a swelling at day 6 at the site of the PG. When infected, whether or not modified, usually only Staphylococcus aureus was present. Spreading of infection seemed to occur by inoculation via blood, for example, based on the observation that group II in general showed an increase in infected fibrotic overgrowth in the heart, while infectious problems were low in the jugular vein. It is concluded that the modification at short term shows enhanced infection resistance. An increased infection rate already at 4 weeks, however, indicates that the modification may not hold in the long run. Special attention is needed concerning the more intense early tissue reaction. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 384–392, 2001
New pulsatile bioreactor for fabrication of tissue‐engineered patches
Authors: Sodian Ralf , Lemke Thees , Loebe Matthias , Hoerstrup Simon P. , Potapov Evgenij V. , Hausmann Harald , Meyer Rudolf , Hetzer Roland
Published: October 2004

To date, one approach to tissue engineering has been to develop in vitro conditions to ultimately fabricate functional cardiovascular structures prior to final implantation. In our current experiment, we developed a new pulsatile flow system that provides biochemical and biomechanical signals to regulate autologous patch‐tissue development in vitro. The newly developed patch bioreactor is made of Plexiglas and is completely transparent (Mediport Kardiotechnik, Berlin). The bioreactor is connected to an air‐driven respirator pump, and the cell culture medium continuously circulates through a closed‐loop system. We thus developed a closed‐loop, perfused bioreactor for long‐term patch‐tissue conditioning, which combines continuous, pulsatile perfusion and mechanical stimulation by periodically stretching the tissue‐engineered patch constructs. By adjusting the stroke volume, the stroke rate, and the inspiration/expiration time of the ventilator, it allows various pulsatile flows and different levels of pressure. The whole system is a highly isolated cell culture setting, which provides a high level of sterility, gas supply, and fits into a standard humidified incubator. The bioreactor can be sterilized by ethylene oxide and assembled with a standard screwdriver. Our newly developed bioreactor provides optimal biomechanical and biodynamical stimuli for controlled tissue development and in vitro conditioning of an autologous tissue‐engineered patch.© 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 401–405, 2001
Quantitative characterization of polyethylene debris isolated from periprosthetic tissue in early failure knee implants and early and late failure Charnley hip implants
Authors: Howling Graeme I. , Barnett Petra I. , Tipper Joanne L. , Stone Martin H. , Fisher John , Ingham Eileen
Published: October 2004

This study isolated and characterized UHMWPE particles from 3 explant groups: early Charnley hip failures (ECE; < 10 years), late Charnley hip failures (LCE; > 10 years) and early knee failures (EKE; < 10 years). Debris isolated from the 3 groups had percentage particle number and percentage volumetric concentration distributions that were not significantly different. The greatest number of particles were found in the 0.1–0.5 μm size range and 19–20.6% of the volumetric concentration was below 1 μm in size in all groups. However, there were significant differences in the total volumetric concentration of debris isolated per g of tissue. LCE had significantly higher volumes of debris than ECE and EKE, there was no significant difference in the volume of debris from the EKE and ECE. The mean aspect ratio and mean irregularity ratio of the LCE group were also significantly higher than the ECE and EKE, suggesting that different wear mechanisms were occurring in the late Charnley group compared to the early Charnley and knee groups. These results also suggest that early knees, with normal surface wear, may have similar wear mechanisms to early Charnley hips and indicate that similar volumes of biologically active micrometer and sub‐micrometer UHMWPE particles were produced. This may have important implications in the longer‐term outcome of total knee arthroplasties, because it indicates a similar potential for osteolysis induced by wear debris. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 415–420, 2001
Air‐flow resistances of silicone rubber voice prostheses after formation of bacterial and fungal biofilms
Authors: Elving G. J. , van der Mei H. C. , Busscher H. J. , van Weissenbruch R. , Albers F. W. J.
Published: October 2004

Laryngectomized patients use silicone rubber voice prostheses to rehabilitate their voice. However, biofilm formation limits the lifetime of voice prostheses by causing leakage or an increased air‐flow resistance and the prosthesis has to be replaced. To determine which bacterial or yeast strains, isolated from explanted voice prostheses, contribute most to increases in air‐flow resistance of silicone rubber voice prostheses, biofilms consisting of either a bacterial or a yeast strain were grown on voice prostheses in the artificial throat model. The effects of these biofilms on air‐flow resistances were determined by calculating the difference in air‐flow resistance of the individual voice prosthesis as covered with a 7‐day‐old biofilm with the situation prior to biofilm formation. Conspicuously, voice prosthetic biofilms formed by the bacterial strains Staphylococcus aureus GB 2/1 and Rothia dentocariosa GBJ 41/25B and their excreted organic matter showed larger increases in air‐flow resistance (more then 30 cm H2O.s/L) than biofilms formed by Candida species. This is contrary to the literature, where there seems to be agreement that Candida species are mainly responsible for clinical failure of silicone rubber voice prostheses. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 421–426, 2001
Physicochemical, mechanical, and biological properties of commercial membranes for GTR
Authors: Milella E. , Ramires P.A. , Brescia E. , La Sala G. , Di Paola L. , Bruno V.
Published: October 2004

Barrier membranes for guided tissue regeneration (GTR) to treat bone defects have to satisfy criteria of biocompatibility, cell‐occlusiveness, spacemaking, tissue integration, and clinical manageability. In this study, the morphological and mechanical properties of two commercial biodegradable membranes (Resolut® LT and Biofix®) as a function of the incubation time have been compared. Moreover, their permeability to both fluids and epithelial cells as well as the bacteria adhesion have been evaluated. The membranes are asymmetric and composed of a dense polymeric layer coupled with nonwoven (Resolut® LT) or woven (Biofix®) fibers. Both of the membranes, when incubated in complete culture medium, completely lose the structural and mechanical properties within 30 days. Moreover the results of solute permeability show that Resolut® LT and Biofix® membranes cannot be considered selective membranes to the solute crossing. On the contrary, they act as a barrier to the passage of the gingivial cells and to S. mutans bacteria. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 427–435, 2001
Biodegradable poly(D,L‐lactide) coating of implants for continuous release of growth factors
Authors: Schmidmaier G. , Wildemann B. , Stemberger A. , Haas N. P. , Raschke M.
Published: October 2004

Local application of growth factors like insulin like growth factor‐I (IGF‐I) and transforming growth factor‐beta 1 (TGF‐β1) from a biodegradable thin layer of poly(D,L‐lactide) (PDLLA) coated implants could stimulate fracture healing. A new “cold coating technique” for metallic implants was established to produce a biodegradable coating with a high mechanical stability that provides a continuous release of incorporated growth factors. The properties of this bioactive coating were investigated in vitro and in vivo. Scanning electron microscope analysis revealed a coating thickness of in average 14.8 μm on titanium and 10.7 μm on steel wires. Intramedullary implantation and extraction experiments depicted a loss of PDLLA coating from titanium and steel implants of less than 5%. After explantation of the implants, the coating displayed a complete and regular layer without any defects of PDLLA uncovering the metallic surface. Smear tests demonstrate that the coating can be performed under sterile conditions. The PDLLA depicted a reduction of about 8% within 6 weeks in vitro and in vivo. The growth factors were incorporated in a stable form and demonstrated a loss of stability of less than 3% within 42 days and less than 5% within one year. In an elution experiment, 54% IGF‐I and 48% TGF‐β1 were released within the first 48 h. After 42 days, 76% of IGF‐I and 71% of TGF‐β1 were detected in the elution fluid by ELISA. Comparable results were obtained in the in vivo experiments after 42 days. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 449–455, 2001
Development of PMMA‐precoating metal prostheses via injection molding: Residual stresses
Authors: Zhao Wenping , Barsun Stephan , Ramani Karthik , Johnson Todd , King Richard , Lin Steve
Published: October 2004

Injection molding polymethylmethacrylate (PMMA) was developed as a potential metal prosthesis precoating method for surgical implantation. However, residual stresses generated in the injection‐molded PMMA affect the mechanical performance of the coating polymer. This study used plane polariscope testing to demonstrate the residual stress distribution in the injection‐molded polymer. Slitting and strain gages were combined with finite element analysis to give a quantitative measure of the residual stresses. The residual stress testing indicated that the highest circumferential residual stress in the injection‐molded PMMA was ≈5 MPa in tension. Two methods, water soaking and slitting, were developed for reducing residual stresses. A series of four surgical implantation simulation processes were designed. The two methods for reducing residual stress were used in the simulations. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 456–462, 2001
A tissue sealant based on reactive multifunctional polyethylene glycol
Authors: Wallace D. G. , Cruise G. M. , Rhee W. M. , Schroeder J. A. , Prior J. J. , Ju J. , Maroney M. , Duronio J. , Ngo M. H. , Estridge T. , Coker G. C.
Published: October 2004

A rapidly gelling synthetic tissue sealant was developed from tetra‐succinimidyl and tetra‐thiol‐derivatized polyethylene glycol (PEG). The two reagents were dissolved in aqueous buffers at 20% (w/v) solids and sprayed on the tissue site, with the use of a sprayer/mixer device. Good adhesion to collagen membranes, PTFE grafts, and carotid artery was observed in vitro. In a burst test on collagen membranes with a 2‐mm orifice defect, the gel sustained fluid pressures of 125 ± 36 mm Hg (n = 18), fivefold greater than capillary blood pressure and one‐half that observed in hypertension. On 0.4‐mm‐diameter puncture defects in PTFE grafts, pressures of 390–490 mm Hg were sustained, and on 0.6–0.9‐mm puncture defects in carotid arteries, pressures of 490 to 840 mm Hg were sustained. In vitro data corresponded to results in vivo, where bleeding in rabbit arteries was stopped immediately in five out of six trials. A significant reduction in time to hemostasis and blood loss, compared to controls, was observed. Carotid artery and subcutaneous implant data in rabbits showed that the formula was compatible with biological tissue. Rapid gelling and effective sealing were dependent on the presence of active succinimidyl ester and thiol groups on PEG. HPLC and chemical substitution methods were useful in predicting whether batches of derivatized PEG would perform satisfactorily. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 545–555, 2001
A composite polymer/tricalcium phosphate membrane for guided bone regeneration in maxillofacial surgery
Authors: Ignatius Anita A. , Ohnmacht Michael , Claes Lutz E. , Kreidler Joachim , Palm Frank
Published: October 2004

The aim of the study was the development of a resorbable membrane for guided bone regeneration (GBR) with improved biocompatibility, which should be stiff enough to avoid membrane collapse during bone healing. Combining a bioactive ceramic with a resorbable polymer may improve the biocompatibility and osteoconductivity of resorbable devices. The present article describes the preparation, the mechanical properties, and the in vitro degradation characteristic of a composite membrane made of poly(L, DL‐lactide) and α‐tricalcium phosphate in comparison to a membrane made of pure poly(L, DL‐lactide). The tensile strength and the elastic modulus as well as the molecular weight of the membranes were measured after in vitro degradation in buffer at 37 °C up to 28 weeks. The initial tensile strength of the composite and the polymer membrane was 37.3 ± 2.4 MPa and 27.7 ± 2.3 MPa and the elastic modulus 3106 ± 108 MPa and 3101 ± 104 MPa, respectively. The mechanical properties remained constant up to 8 weeks and then decreased slowly until week 28. The molecular weight of both membranes decreased steadily from 170,000 D to 30,000 D. It was concluded that the mechanical requirements for a membrane for GBR were fulfilled by the composite membrane. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 564–569, 2001
Time‐dependent mechanical properties of HA/TCP particles in relation to morsellized bone grafts for use in impaction grafting
Authors: Verdonschot N. , van Hal C. T. H. , Schreurs B. W. , Buma P. , Huiskes R. , Slooff T. J. J. H.
Published: October 2004

In reconstructive surgery human bone defects are sometimes filled with the use of the impaction bone grafting technique. Currently different types of biomaterial particles are being developed as bone‐substitute materials. Before these biomaterials can be applied their mechanical and biological behavior should be characterized. In this study the time‐dependent mechanical behavior of biomaterial particles with different tri‐calcium‐phosphate/hydroxy‐apatite (TCP:HA) ratios, particle sizes, and porosities is determined and compared to the behavior of human bone grafts, the latter being the standard material currently used to augment bone defects. The mechanical properties were assessed with the use of dynamic confined compression creep tests with a loading and unloading phase. Different graft material groups were tested, consisting of 100% human bone grafts, 100% biomaterial particles, and 50:50 weight mixtures of human grafts and biomaterial particles. No damage to the particles was observed by the impaction in the test chamber or by the dynamic load. Relative to the human graft material, the biomaterial particles hardly deformed under loading, were much stiffer, and showed almost no viscoelastic behavior. The mixtures showed intermediate results. Particle size and porosity influenced the behavior of the biomaterial particles. TCP:HA ratio did not have a great effect. The conclusion is that the application of these particles should be done with great care, as their mechanical behavior is drastically different than that of the human graft material. Mixing it with human bone grafts gave the material some biphasic, viscoelastic behavior that may be important for its biological response. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 599–604, 2001