bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE OBERBECK-BOUSSINESQ APPROXIMATION
Authors: RAJAGOPAL K.R. , RUZICKA M. , SRINIVASA A.R.
Published: October 2004

This paper deals with a derivation (using a perturbation technique) of an approximation, due to Oberbeck8,9 and Boussinesq,1 to describe the thermal response of linearly viscous fluids that are mechanically incompressible but thermally compressible. The present approach uses a nondimensionalization suggested by Chandrasekhar2 and utilizing the ratio of two characteristic velocities as a measure of smallness, systematically derives the Oberbeck-Boussinesq approximation as a third-order perturbation. In the present approach, the material is subjected to the constraint that the volume change is determined solely by the temperature change in the body and uses a novel approach in deriving the thermodynamical restrictions. Consequently, it is free from the additional assumptions usually added on in earlier works in order to obtain the correct equations.
PARALLEL DOMAIN DECOMPOSITION METHODS WITH THE OVERLAPPING OF SUBDOMAINS FOR PARABOLIC PROBLEMS
Authors: SHISHKIN GRIGORII I. , VABISHCHEVICH PETR N.
Published: October 2004

For a model of two-dimensional boundary value problem for a second-order parabolic equation, finite difference schemes on the base of a domain decomposition method, oriented on modern parallel computers, is constructed. In the used finite difference schemes iterations at time levels are not applied; some subdomains overlap. We study two classes of schemes characterized by synchronous and asynchronous implementations. It is shown that, under refining grids, the approximate solutions do converge to the exact one in the uniform grid norm.
DISCRETE KINETIC CELLULAR MODELS OF TUMORS IMMUNE SYSTEM INTERACTIONS
Authors: SCHIAVO M. LO
Published: October 2004

This paper deals with a kinetic modelling of the cellular dynamics of tumors interacting with an active immune defence system. The analysis starts from the model proposed in Refs. 4 and 5 where a kinetic (cellular) theory of the interactions and competition between tumor cells and immune system is developed in a framework similar to the one of nonlinear statistical mechanics. The class of models proposed in this paper replaces the system of integro-differential equations by a system of ordinary differential equations. This has several advantages. Firstly, it allows immediate interpretations of the control parameters and is characterized by a relatively lower computational complexity. Further, some interesting periodicity properties of the solutions are characterized.
KNOWLEDGE INTENSIVE ENTREPRENEURSHIP IN A SOCIAL CAPITAL PERSPECTIVE
Authors: NEERGAARD HELLE , MADSEN HENNING
Published: October 2004

In 1989 Mitton suggested that success for start-ups not only depends on who you are but also on whom you know. To study the importance of social capital and networks in relation to entrepreneurial activities, research in a Danish start-up context in two knowledge-intensive sectors has been carried out. The research methodology was based on a triangulation approach including a general questionnaire-based survey conducted through the Internet combined with a 85 in-depth interviews in purposefully sampled ventures. The analysis of the content and structure of social capital in relation to entrepreneurial networking activities in new technology-based small firms shows that teams are primarily composed of 'trusted alters', and that networking patterns and resource acquisition are highly influenced by entrepreneurs' attitude to and perception of networking.
ENTREPRENEURIAL CULTURES IN ASIA: BUSINESS POLICY OR CULTURAL IMPERATIVE
Authors: SWIERCZEK FREDRIC WILLIAM , QUANG TRUONG
Published: October 2004

The purpose of this paper is to examine the influence of national cultures and different business policy models on the degree of entrepreneurship and entrepreneurship orientations of managers in the Asia-Pacific: East Asia, Southeast Asia and South Asia. The results indicate that an economic policy, which is open and supportive of business development, stimulates greater entrepreneurship.
UNDERSTANDING THE GREY ENTREPRENEUR
Authors: WEBER PAULL , SCHAPER MICHAEL
Published: October 2004

Demographic trends in the developed world indicate that older entrepreneurs will play an increasingly important part of economic activity as populations age, yet this cohort has been largely ignored in entrepreneurship research. This paper provides an overview of current research about the so-called "grey entrepreneur" (also known as senior, older, third age or elderly entrepreneurs), drawing on research from a number of nations.

The extant literature indicates that a majority of older entrepreneurs are male, although the number of older female entrepreneurs is increasing; they are also less likely to possess formal educational qualifications than younger entrepreneurs. Some of the advantages that such entrepreneurs possess include greater levels of technical, industrial and management experience; superior personal networks; and a stronger financial asset base. Some of the disadvantages or potential barriers faced by older entrepreneurs can include lower levels of health, energy and productivity; ageism; and the value that his or her society places on active ("productive") ageing.

Numerous issues still remain to be investigated in this field of research. These include the differences between younger and older entrepreneurs; their motives and success criteria; the impact of financial, knowledge and other resources on venturing behaviour; the role of government policies in fostering or hampering individual enterprise; and the significance of cultural differences amongst older entrepreneurs. Research in this field is currently also hampered by a multiplicity of terms and definitions, a lack of age-related data about different entrepreneurial cohorts, and the problems inherent in operationalising the concept of the "grey entrepreneur."
CROSS-BORDER ENTREPRENEURS – A STUDY OF THE CHANGING STRATEGIES AND COMPETENCIES OF HONG KONG ENTREPRENEURS UPON EXPOSURE TO THE EMERGING MARKET OF CHINA
Authors: LAU THERESA , CHAN K. F. , HO RICKY
Published: October 2004

In a study of five entrepreneurs operating their business first in Hong Kong and later in the PRC, we examine the modes of entrepreneurship from the Kirznerian and Schumpeterian perspectives. The results showed that these entrepreneurs appeared basically Kirznerian in their strategy when their business focuses were in Hong Kong, and shifted toward a blend of the Kirznerian and Schumpterian modes when operating their businesses in the PRC. Such a shift can be explained by the adaptation of their competencies to the PRC context.
SEMIPRIME QUADRATIC ALGEBRAS OF GELFAND–KIRILLOV DIMENSION ONE
Authors: CEDÓ FERRAN , JESPERS ERIC , OKNIŃSKI JAN
Published: October 2004

We consider algebras over a field K with a presentation K, where R consists of [Formula: see text] square-free relations of the form xixj=xkxl with every monomial xixj, i≠j, appearing in one of the relations. The description of all four generated algebras of this type that satisfy a certain non-degeneracy condition is given. The structure of one of these algebras is described in detail. In particular, we prove that the Gelfand–Kirillov dimension is one while the algebra is noetherian PI and semiprime in case when the field K has characteristic zero. All minimal prime ideals of the algebra are described. It is also shown that the underlying monoid is a semilattice of cancellative semigroups and its structure is described. For any positive integer m, we construct non-degenerate algebras of the considered type on 4m generators that have Gelfand–Kirillov dimension one and are semiprime noetherian PI algebras.
ON m-FOLD STABLE IDEALS
Authors: CHEN HUANYIN , CHEN MIAOSEN
Published: October 2004

In this paper, we introduce m-fold stable ideals and show that m-fold stable range for ideals is invariant under matrix extension. Also we prove that every m-fold stable ideal is right and left symmetric.
CRYPTANALYSIS OF AN IMPLEMENTATION SCHEME OF THE TAMED TRANSFORMATION METHOD CRYPTOSYSTEM
Authors: DING JINTAI , HODGES TIMOTHY
Published: October 2004

A Tamed Transformation Method (TTM) cryptosystem was proposed by T. T. Moh in 1999. We describe how the first implementation scheme of the TTM system can be defeated. The computational complexity of our attack is 233 computations on the finite field with 28 elements.

The cipher of the TTM systems are degree 2 polynomial maps derived from composition of invertible maps of either total degree 2 or linear maps which can be easily calculated and can be easily inverted. To ensure the system to be of degree two, the key construction of the implementation schemes of the TTM systems is a multivariable polynomial Q8(x1,…,xn) and a set of linearly independent quadratic polynomials qi(x1,…,xm), i=1,…,n such that Q8(q1,…,qn) is again a degree 2 polynomials of x1,…,xm.

In this paper, we study the first implementation scheme of the TTM systems [6]. We discovered that in this implementation scheme the specific polynomial Q8 can be decomposed further into a factorization in terms of composition. By taking powers of the equality satisfied by the new composition factors, we can actually derive a set of equations, that can produce linear equations satisfied by the plaintext. These linear equations lead us to find a way to defeat this implementation scheme.
FINITE QUASI-FROBENIUS MODULES AND LINEAR CODES
Authors: GREFERATH MARCUS , NECHAEV ALEXANDR , WISBAUER ROBERT
Published: October 2004

The theory of linear codes over finite fields has been extended by A. Nechaev to codes over quasi-Frobenius modules over commutative rings, and by J. Wood to codes over (not necessarily commutative) finite Frobenius rings. In the present paper, we subsume these results by studying linear codes over quasi-Frobenius and Frobenius modules over any finite ring. Using the character module of the ring as alphabet, we show that fundamental results like MacWilliams' theorems on weight enumerators and code isometry can be obtained in this general setting.
TORSION-FREENESS FOR RINGS WITH ZERO-DIVISORS
Authors: DAUNS JOHN , FUCHS LASZLO
Published: October 2004

A right R-module MR over any ring R with 1 is called torsion-free if it satisfies the equality [Formula: see text] for every r∈R. An equivalent definition was used by Hattori [11]. We establish various properties of this concept, and investigate rings (called torsion-free rings) all of whose right ideals are torsion-free. In a torsion-free ring, the right annihilators of elements are always idempotent flat right ideals. The right p.p. rings are characterized as torsion-free rings in which the right annihilators of elements are finitely generated. An example shows that torsion-freeness ness is not a Morita invariant.

Several ring and module properties are proved, showing that, in several respects, torsion-freeness ness behaves like flatness. We exhibit examples to point out that the concept of torsion-freeness ness discussed here is different from other notions.
A CRASH COURSE ON STABLE RANGE, CANCELLATION, SUBSTITUTION AND EXCHANGE
Authors: LAM T. Y.
Published: October 2004

The themes of cancellation, internal cancellation, substitution and exchange have led to a lot of interesting research in the theory of modules over commutative and noncommutative rings. This article provides a quick and relatively self-contained introduction to the voluminous work in this area, using the notion of the stable range of rings as a unifying tool. With only a small number of exceptions, all theorems stated here are proved in full, modulo basic facts in the theory of modules and rings available in standard textbooks on ring theory.
Chemokine receptor CCR6 transduces signals that activate p130Cas and alter cAMP-stimulated ion transport in human intestinal epithelial cells
Authors: Yang Charles C. , Ogawa Hiroyuki , Dwinell Michael B. , McCole Declan F. , Eckmann Lars , Kagnoff Martin F.
Published: October 2004

Human colon epithelial cells express the G protein-coupled receptor CCR6, the sole receptor for the chemokine CCL20 (also termed MIP-3α). CCL20 produced by intestinal epithelial cells is upregulated in response to proinflammatory stimuli and microbial infection, and it chemoattracts leukocytes, including CCR6-expressing immature myeloid dendritic cells, into sites of inflammation. The aim of this study was to determine whether CCR6 expressed by intestinal epithelial cells acts as a functional receptor for CCL20 and whether stimulation with CCL20 alters intestinal epithelial cell functions. The human colon epithelial cell lines T84, Caco-2, HT-29, and HCA-7 were used to model colonic epithelium. Polarized intestinal epithelial cells constitutively expressed CCR6, predominantly on the apical side. Consistent with this, apical stimulation of polarized intestinal epithelial cells resulted in tyrosine phosphorylation of the p130 Crk-associated substrate (Cas), an adaptor/scaffolding protein that localizes in focal adhesions and has a role in regulating cytoskeletal elements important for cell attachment and migration. In addition, CCL20 stimulation inhibited agonist-stimulated production of the second messenger cAMP and cAMP-mediated chloride secretory responses by intestinal epithelial cells. Inhibition was abrogated by pertussis toxin, consistent with signaling through Gαi proteins that negatively regulate adenylyl cyclases and cAMP production. These data indicate that signaling events, occurring via the activation of the apically expressed chemokine receptor CCR6 on polarized intestinal epithelial cells, alter specialized intestinal epithelial cell functions, including electrogenic ion secretion and possibly epithelial cell adhesion and migration.
Static stretch promotes MEF2A nuclear translocation and expression of neonatal myosin heavy chain in C2C12 myocytes in a calcineurin- and p38-dependent manner
Authors: Rauch Cyril , Loughna Paul T.
Published: October 2004

Although the effects of mechanical stimuli have been studied extensively in fully differentiated skeletal muscle and have been shown to promote changes in phenotype, including altered myosin heavy chain isoform expression, the effects of a change in mechanical environment have been poorly studied at earlier stages of skeletal muscle differentiation. In particular, the early events elicited by mechanical stimuli upon differentiating myocytes have not been investigated. In the present study, the effect of static stretch on the activation of transcriptional factors MEF2A and NFATc1, which have been shown to be involved in the differentiation and phenotype regulation of skeletal muscle, have been examined. Furthermore, putative second messenger signaling pathways that could be involved in the dephosphorylation and hence activation of these factors were also examined. We have demonstrated that static stretch application produces a robust increase in p38 phosphorylation preceding MEF2A, but not NFATc1, nuclear translocation as well as deactivation of GSK-3β via its phosphorylation. Using SB-203580 and cyclosporine A drugs to inhibit both p38- or/and calcineurin-dependent signals, respectively, we have shown that MEF2A phosphorylation and subsequent nuclear translocation are regulated by p38 and calcineurin in a biphasic, time-dependent manner. Moreover, we also present evidence for another kinase that is involved in the stretch-related signal triggering MEF2A hyperphosphorylation, impairing its nuclear translocation, and that is related to p38. Finally, we have shown that static stretch application overnight promotes neonatal myosin heavy chain expression, which is inhibited by an inactivation of both p38 and calcineurin.
On the class of QS‐algebras
Authors: Kondo Michiro
Published: October 2004

We consider some fundamental properties of QS‐algebras and show that (1) the theory of QS‐algebras is logically equivalent to the theory of Abelian groups, that is, each theorem of QS‐algebras is provable in the theory of Abelian groups, and conversely, each theorem of Abelian groups is provable in the theory of QS‐algebras; and (2) a G‐part G(X) of a QS‐algebra X is a normal subgroup generated by the class of all elements of order 2 of X when it is considered as a group.
Construction of Nijenhuis operators and dendriform trialgebras
Authors: Leroux Philippe
Published: October 2004

We construct Nijenhuis operators from particular bialgebras called dendriform‐Nijenhuis bialgebras. It turns out that such Nijenhuis operators commute with TD‐operators, a kind of Baxter‐Rota operators, and are therefore closely related to dendriform trialgebras. This allows the construction of associative algebras, called dendriform‐Nijenhuis algebras, made out of nine operations and presenting an exotic combinatorial property. We also show that the augmented free dendriform‐Nijenhuis algebra and its commutative version have a structure of connected Hopf algebras. Examples are given.
Kontra- und Prozeption – Zur Kompetenz des Frauenarztes/der Frauenärztin bei der Lebensplanung der Frau
Authors: Hepp H. , Haller U. , Winter R.
Published: October 2004

Kontra- und Prozeption provozieren in unserem Lande und Kulturkreis andere Antworten als beim Blick auf die Weltbevölkerung und hier insbesondere auf jene der nicht industriell entwickelten Länder. Kontrazeption ist als Aufgabe der Präventivmedizin zu sehen. Dies gilt insbesondere im Hinblick auf die Vermeidung einer psychosozialen Notlage bei unerwünschter Schwangerschaft mit eventuell nachfolgendem Schwangerschaftsabbruch. In diesem Zusammenhang von besonderer Bedeutung ist die Kontrazeptionsberatung der Jugendlichen. Wirksame Antikonzeption verursacht nicht geänderte Moral, bestärkt und erleichtert jedoch die Lebensweise und bietet Sicherheit. Dieser Aspekt steht in enger Wechselwirkung zu den sozialen und familienpolitischen Rahmenbedingungen. Die Integration der Kontrazeption in die Lebensplanung der Frau ist entscheidend von diesen Bedingungen abhängig. Der Frauenarzt und die Frauenärztin sind Mitwirkende am Lebensplan von Frauen, die mit Bezug auf ihre berufliche Laufbahn zunächst Kontrazeption leben, später – und oft auch zu spät – mit maximaler Intension und Einsatz auch der assistierten Reproduktion ihr einziges Kind bekommen – wenn überhaupt. Aus einer zunächst gewollten wird nicht selten eine ungewollte Kinderlosigkeit. Es geht um eine in die Zukunft weisende Sozial- und Sexualpädagogik, in der die Aufteilung von Beruf oder Familie aufgehoben wird. Frauenärztinnen und -ärzte sind in der Beratung der Kontra- und Prozeption in der Wahrnehmung dieser pädagogischen Aufgabe Mitgestalter an der Lebensplanung der Frau wie auch am demographischen Wandel der Gesellschaft.
Hystérectomie vaginale leniens
Authors: Tapia Jorge E.
Published: October 2004

L’auteur présente une technique de l’hystérectomie vaginale intrafasciale, qui est une modification de l’hystérectomie extrafasciale de l’utérus à partir du fond utérin. L’incision selon Strassmann remplace la circoncision habituelle. Cela nous permet de garder le fascia pubovésicocervical postérieur. Ensuite bascule antérieure du corps utérin devant la vulve par l’ouverture du cul-de-sac, section de ligaments utéro-annexiels et dissection du tissu péri-cervical postérieur. Section et ligature intrafasciales des ligaments cardinaux sont nécessaires. Les techniques intrafasciales de l’hystérectomie présentent une morbidité plus faible que les opérations extrafasciales. Le risque de lésion de l’uretère serait aussi diminué. L’avantage décisif de cette technique est sa simplicité.
Naturheilmittel während Schwangerschaft und Stillzeit
Authors: Gut E. , Melzer J. , von Mandach U. , Saller R.
Published: October 2004

Bisher gibt es kaum systematisch erhobene Daten über den Gebrauch von Naturheilmitteln während Schwangerschaft und Stillzeit. Ziel dieser Pilotstudie an einem nicht repräsentativen Kollektiv von 139 Frauen, die von Mitte 1997 bis zum 2. Quartal 1998 zur Entbindung in drei geburtshilfliche Einrichtungen kamen, war es, Daten zu den Fragen nach der Häufigkeit und dem Spektrum der angewandten Naturheilmittel während Schwangerschaft und Stillzeit zu erheben. Während der Schwangerschaft nahmen mindestens 96% und in der Stillperiode 84% der Frauen mindestens 1 Naturheilmittel ein, wobei jeweils Phytotherapeutika am häufigsten benutzt wurden. Im Gegensatz zum weit verbreiteten Gebrauch von Naturheilmitteln bei Schwangeren und Stillenden in dieser Studie, und ihren Fragen dazu, existieren wenige nachvollziehbare Daten zur Wirksamkeit und zu einem eventuellen Risiko. Während der Schwangerschaft und Stillzeit benutzte Naturheilmittel sollten dahingehend gesichtet und beurteilt werden.
Platzbauch nach Misgav-Ladach-Sektio: Ein Fallbericht
Authors: Scholz H.S. , Petru E. , Tamussino K. , Winter R.
Published: October 2004

Einführung: Wir beschreiben den Fall einer Patientin, bei der eine Nahtinsuffizienz an der Rektusfaszie nach Misgav-Ladach-Sektio zur Manifestation eines Platzbauches führte. Fallbeschreibung: In der Schwangerschaftswoche 36 + 5 wurde bei einer 33-jährigen Nullipara eine primäre Schnittentbindung aus fetaler Indikation durchgeführt. Nach primär unauffälligem postoperativem Verlauf fand sich, als Folge einer Nahtinsuffizienz, am siebenten Tag das grosse Netz im mittleren Bereich der Laparotomie im Sinne eines Platzbauches prolabiert. Schlussfolgerung: Auch wenn aus einem Einzelfall keine generellen Empfehlungen abzuleiten sind, werden weitere Berichte über Komplikationen dieser Technik zeigen, ob sie so sicher ist wie bisher angenommen.
Chemotherapieassoziierte Enterokolitis – Eine seltene, aber potenziell letal verlaufende Nebenwirkung bei der adjuvanten Behandlung des Mammakarzinoms
Authors: Janni J.W. , Klanner E. , Rack B. , Sommer H. , Friese K.
Published: October 2004

Anamnese: Eine 60-jährige Patientin wurde wegen eines Mammakarzinoms im TNM-Stadium pT1a (m), pN2a (8/12), G2, pM0 brusterhaltend operiert. Im Anschluss erhielt sie 4 Zyklen Epirubicin/ Cyclophosphamid (90/600 mg/m2), gefolgt von 2 Zyklen Docetaxel (100 mg/m2). Vier Tage nach Erhalt des zweiten Zyklus Docetaxel stellte sich die Patientin mit Bauchschmerzen, Nausea, Emesis und Obstipation bestehend seit 3 Tagen vor. Befunde: Die körperliche Untersuchung zeigte ein geblähtes Abdomen, das Fehlen von Darmgeräuschen und eine Druckdolenz im linken Unterbauch. Im Labor fiel eine Granulozytopenie mit NCI Grad III und eine CRP-Erhöhung von 7,7 mg/dl auf. Diagnose: Als Hauptdiagnose wurde der Verdacht auf eine chemotherapieassoziierte Enterokolitis mit Zeichen eines paralytischen Ileus gestellt, der sich computertomographisch und per laparatomiam bestätigte. Therapie und Verlauf: Die Erstversorgung erfolgte mit einer Magensonde, Infusionstherapie, Breitbandantibiose und G-CSF. Im weiteren Verlauf wurde bei sich verschlechterndem Allgemeinzustand und Verdacht auf intraabdominelles Kompartmentsyndrom fünfmal eine Explorativlaparotomie mit abdomineller Lavage durchgeführt. Nach vorübergehender Besserung verstarb die Patientin 8 Wochen nach Aufnahme im protrahierten Multiorganversagen. Fazit: Bei der chemotherapieassoziierten Enterokolitis handelt es sich um eine seltene, aber potenziell letale Nebenwirkung einer zytostatischen Therapie. Gastrointestinalen Symptomen sollte deshalb eine grosse Aufmerksamkeit geschenkt werden, um durch eine rechtzeitige Therapieintervention das Mortalitätsrisiko zu minimieren.
Outcomes Research: An Overview
Authors: Stewart Michael G.
Published: October 2004

Outcomes research is increasingly important in contemporary medicine. Outcomes research differs from traditional clinical research in that outcomes are typically measured from the patient’s perspective, and expanded measures of outcome are used, such as quality of life and cost-effectiveness. In this introduction to the special journal edition, the author will discuss the background behind outcomes research and describe several of its important aspects. Outcomes research consists of the clinical study of expanded, patient-based outcomes, as well as the study of populations, databases, and the delivery of health care. Outcomes research also includes the development of validated instruments to assess patient-based outcomes, development of disease severity staging systems, identification of comorbid conditions, and meta-analysis.
Validation of Health Status Instruments
Authors: Chen Amy Y. , Whigham Amy S.
Published: October 2004

Health status instruments are questionnaires that are utilized to assess changes in health status of individuals. These surveys are increasingly of importance as health care providers are challenged to justify treatment approach and rationale. Objective criteria (e.g. CT scan of the sinuses) can be used to determine whether there is clinical evidence of disease. However, the impact of the disease on the individual’s life is not included in such a clinical assessment. The use of validated and reliable health instruments is directed at measuring this impact in a reproducible and valid fashion. In patient-centered research, ‘experimental’ conditions are constantly changing because we are dealing with human beings with values, feelings, and perspectives. It is especially important to use valid measurement tools when assessing these impacts. This article outlines the principles of the development and validation of health status instruments and offers examples of such instruments from the otolaryngology literature.
Development of Staging and Stratification Systems
Authors: Cho Lieu Judith E.
Published: October 2004

Physicians communicate with each other on a daily basis using staging and stratification systems, whether they recognize this or not. At a minimum, they help convey a wealth of information in communicating about patients and their disease; more sophisticated staging systems help physicians recommend therapy and prevention strategies for patients, or predict functional and survival prognoses in concordance with the current scientific evidence. The goal of this article is to discuss the purpose and rationale of staging or stratification systems, and to introduce the clinical and statistical development and evaluation of these systems. The practicing physician should be aware of basic methodologic principles in the development of staging systems that help ensure their quality and applicability, so that staging systems can help improve patient care.
The Impact of Comorbidity on Outcomes
Authors: Piccirillo Jay F. , Costas Irene
Published: October 2004

Patients often have other diseases, illnesses, or conditions in addition to the disease under study. These other medical conditions are referred to as comorbidity. Comorbidity can impact on diagnosis, prognosis, and selection of therapy. There are a variety of instruments available to measure the type and severity of comorbid ailments. Comorbidity information can be obtained from direct discussions with the patient, a review of the medical record, or from electronic databases that contain billing information. The method of comorbidity assessment can impact on the interpretation of results. Accurate comorbid information will improve the conduct of and generalizability of clinical trials, evaluation of outcomes from observational research, population-based epidemiological studies, and patient-physician communication.
Meta-Analysis
Authors: Rosenfeld Richard M.
Published: October 2004

Systematic reviews use explicit and reproducible criteria to assemble, appraise, and combine articles with a minimum of bias. Meta-analysis is a form of systematic review that uses statistical techniques to derive quantitative estimates of the magnitude of treatment effects and their associated precision. Valid meta-analyses address focused questions, use appropriate criteria to select articles, assess the quality and combinability of articles, provide graphic and numeric summaries, consider potential biases, and can be generalized to a meaningful target population. The rate difference, or absolute risk reduction, is the preferred measure of clinical effect size; the reciprocal tells the number needed to treat for one additional favorable outcome. The benefits of meta-analysis over individual trials include greater precision, increased statistical power, and the ability to identify and explore diversity among studies. Threats to validity include heterogeneity, citation bias, publication bias, language bias, and variations in study quality. Because meta-analysis defines rational treatment expectations at a population level, it is an adjunct to, not a substitute for, clinical judgment in the care of individual patients.
The Use of Population and Database Resources in Outcome-Based Research
Authors: Orvidas Laura J. , Jensen Leif E. , St. Sauver Jennifer L. , Weaver Amy L.
Published: October 2004

Many patient management decisions an otolaryngologist makes every day stem from good patient- and population-based evidence. This paper will explore the topic of population/database research and how these studies are useful. We also examine the current literature on this subject, explore the strengths and weaknesses of these studies and provide information on the practical aspects of performing this type of research. Overall, this paper should provide both an understanding of and an incentive for those with an interest in database use and the development of outcome-based projects.
Outcomes Research in Rhinology: Chronic Rhinosinusitis
Authors: Smith Timothy L.
Published: October 2004

Measuring ‘outcome’ in rhinology has been challenging investigators for decades. With the introduction of patient-based, quality of life outcomes, investigators have developed rhinologic-specific outcomes tools for allergic rhinitis, nasal obstruction, and chronic rhinosinusitis. Outcomes research in rhinology, however, is a nascent field. This article focuses on outcomes research in the management of chronic rhinosinusitis, especially as it relates to endoscopic sinus surgery. Quality of life outcomes are addressed not only as outcomes but as measures of disease and how they relate to other commonly used measures of disease such as CT and endoscopy.
Outcomes Research in Head and Neck Cancer
Authors: Fung Kevin , Terrell Jeffrey E.
Published: October 2004

Quality of life (QOL) considerations are uniquely important in head and neck oncology outcomes research due to the multidimensional impact of these tumors and their treatment. Patient variables, tumor variables and treatment variables must be considered comprehensively in order to maximize the validity of QOL outcome measures. There are a multitude of QOL instruments, which can be classified into: (1) general measures of health-related QOL, (2) general QOL instruments for patients with cancer, (3) disease-specific instruments for patients with head and neck cancer, (4) treatment-specific instruments and (5) symptom-specific instruments. This article will highlight commonly used validated QOL instruments in head and neck oncology.
Outcomes Research in Otology
Authors: Bhattacharyya Neil
Published: October 2004

Among the otolaryngologic subspecialties, otology has historically been at the forefront of outcomes research in our specialty. Many traditional outcomes reporting tools have been consistently employed in the study of otologic disease and treatment outcomes including standardized reporting schemes for Ménière’s disease and facial nerve dysfunction. However, recent interest has surfaced in disease-specific quality-of-life outcomes measures for many otologic diseases such as sensorineural hearing loss, conductive hearing loss and suppurative otitis media. Several reliable and validated outcomes tools are available for the assessment of the impact on quality of life and treatment outcomes for common otologic afflictions that carry with them significant quality-of-life burdens. Furthermore, similar outcomes tools have been developed that allow a scientific appraisal of disease status and quality of life for dizziness and tinnitus, which have been traditionally difficult to quantify. Increasing familiarity with these outcomes tools will allow investigators to accurately assess and compare treatments for these otologic diseases and justify treatment initiatives in the future.
Outcomes Research in Pediatric Otolaryngology
Authors: Johnson Romaine F. , Stewart Michael G.
Published: October 2004

There are several validated outcomes instruments available for use in the pediatric otolaryngology population. These include instruments for otitis media, rhinosinusitis, tonsil and adenoid disease; sleep-disordered breathing, voice disorders and tracheotomy. In addition, several prospective outcomes studies have been performed on common pediatric otolaryngology conditions. These studies have typically indicated that the quality of life impact of diseases such as otitis media and recurrent tonsillitis is quite high, and that surgical treatments (such as tympanostomy tube placement and adenotonsillectomy) result in significant improvements in quality of life and disease-specific health status. In addition, cost-effectiveness studies of cochlear implantation have indicated that implantation is a very cost-effective intervention when performed in children.
The Role of Ubiquitin-Protein Ligases in Neurodegenerative Disease
Authors: Ardley Helen C. , Robinson Philip A.
Published: October 2004

Alzheimer’s disease and Parkinson’s disease are the most common neurodegenerative conditions associated with the ageing process. The pathology of these and other neurodegenerative disorders, including polyglutamine diseases, is characterised by the presence of inclusion bodies in brain tissue of affected patients. In general, these inclusion bodies consist of insoluble, unfolded proteins that are commonly tagged with the small protein, ubiquitin. Covalent tagging of proteins with chains of ubiquitin generally targets them for degradation. Indeed, the ubiquitin/proteasome system (UPS) is the major route through which intracellular proteolysis is regulated. This strongly implicates the UPS in these disease-associated inclusions, either due to malfunction (of specific UPS components) or overload of the system (due to aggregation of unfolded/mutant proteins), resulting in subsequent cellular toxicity. Protein targeting for degradation is a highly regulated process. It relies on transfer of ubiquitin molecules to the target protein via an enzyme cascade and specific recognition of a substrate protein by ubiquitin-protein ligases (E3s). Recent advances in our knowledge gained from the Human Genome Mapping Project have revealed the presence of potentially hundreds of E3s within the human genome. The discovery that parkin, mutations in which are found in at least 50% of patients with autosomal recessive juvenile parkinsonism, is an E3 further highlights the importance of the UPS in neurological disease. To date, parkin is the only E3 confirmed to have a direct causal role in neurodegenerative disorders. However, a number of other (putative) E3s have now been identified that may cause disease directly or interact with neurological disease-associated proteins. Many of these are either lost or mutated in a given disease or fail to process disease-associated mutant proteins correctly. In this review, we will discuss the role(s) of E3s in neurodegenerative disorders.
Neurotrophic Factors and Amyotrophic Lateral Sclerosis
Authors: Ekestern Eva
Published: October 2004

The cause of motor neuron death in amyotrophic lateral sclerosis (ALS) remains a mystery. Initial implications of neurotrophic factor impairment involved in disease progression causing selective motor neuron death were brought forward in the late 1980s. These implications were based on several in vitro studies of motor neuron cultures in which a near to complete rescue of axotomized neonatal motor neurons in the presence of supplementary neurotrophic factors were revealed. These findings pawed the way for extensive investigations in experimental animal models of ALS. Neurotrophic factor administration in rodent ALS models demonstrated a remarkable effect on survival of degenerating motor neurons and rescue of axotomized motor neurons, both in vivo and in vitro. In the absence of efficient therapy for ALS, some of these promising neurotrophic factors have been administered to groups of ALS patients, as they appeared available for clinical trials. Up to date, none of tested factors has lived up to expectations, altering the outcome of the disease. This review summarizes current findings on neurotrophic factor expression in ALS tissue and these factors’ potential/debatable clinical relevance to ALS and the treatment of ALS. It also discusses possible interventions improving clinical trial design to obtain efficacy of neurotrophic factor treatment in patients suffering from ALS.
A Non-Viral Vector for Targeting Gene Therapy to Motoneurons in the CNS
Authors: Miana-Mena Francisco J. , Muñoz María J. , Roux Sylvie , Ciriza Jesús , Zaragoza Pilar , Brûlet Philippe , Osta Rosario
Published: October 2004

Gene therapy vectors that can be targeted to motoneuronal cells are required in the field of neurodegenerative diseases. We propose the use of the atoxic fragment C of tetanus toxin (TTC) as biological activity carrier to the motoneurons. Naked DNA encoding β-galactosidase-TTC hybrid protein was used to transfect muscle cells in vivo, resulting in a selective gene transfer of the enzymatic activity to the CNS. In the muscle, level expression of β-galactosidase was readily detectable 24 h after injection, reaching a maximum after 4 days and gradually decreasing thereafter. Labelling in the hypoglossal motoneurons and motor cortex was observed from 4 days after injection. In this paper, we show that TTC works as an enzymatic activity carrier to the CNS when muscle cells are transfected in vivo. We have also shown that the presence of TTC does not have any influence on the expression of the transfected gene. Both these results warrant further studies of TTC as a means of treating motoneuron diseases in the field of gene therapy.
Changes in Dopamine D2 Receptors and 6-[18F]Fluoro-L-3,4-Dihydroxyphenylalanine Uptake in the Brain of 6-Hydroxydopamine- Lesioned Rats
Authors: Ishida Yasushi , Kawai Keiichi , Magata Yasuhiro , Takeda Ryuichiro , Hashiguchi Hiroyuki , Abe Hiroshi , Mukai Takahiro , Saji Hideo
Published: October 2004

We studied tracer distributions in positron emission tomography of ligands for dopamine D1 receptors ([11C]SCH23390) and D2 receptors ([11C]raclopride) and the dopamine precursor analog 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA), as a measurement of presynaptic dopaminergic function, in the brain after 6-hydroxydopamine lesioning of the medial forebrain bundle in rats. The unilateral lesions were confirmed behaviorally by methamphetamine-induced rotation 2 weeks after lesioning, and the brains were analyzed by tissue dissection following an intravenous bolus of each tracer 3 weeks after lesioning. [11C]Raclopride, but not [11C]SCH23390, showed a higher accumulation in the striatum on the lesion side compared with that on the non-lesioned (intact) side. On the other hand, a lower accumulation of [18F]FDOPA was found in the striatum and cerebral cortex on the lesion side. Our studies demonstrate upregulation of dopamine D2 receptors in the striatum and a decrease in FDOPA uptake in both the striatum and cerebral cortex ipsilateral to the 6-hydroxydopamine lesions. Therefore, the combination of a D2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson’s disease.
Cell Proliferation Profile of Five Human Uveal Melanoma Cell Lines of Different Metastatic Potential
Authors: Marshall Jean-Claude , Caissie Amanda L. , Callejo Sonia A. , Antecka Emilia , Burnier Jr. Miguel N.
Published: October 2004

Objective: The aim of this study was to establish a proliferation profile of uveal melanoma cell lines, using different methods, and to compare it with their previously determined metastatic potential (MP). Methods: Four human uveal melanoma and one transformed human uveal melanocytic cell line were ranked according to proliferation profiles. The proliferation profiles of the cell lines were compared to their MPs, which were previously determined from an immunosuppressed rabbit model. Results: Ranking of the cell lines using pulse labeling with tritiated thymidine was similar to the MP of the cell lines. Conclusion: The correlation between the proliferative rate of the uveal melanoma cell lines and their previously determined MP resulted in the proposal of a new classification scheme: high proliferation/high MP, low proliferation/low MP, and high proliferation/no MP. High proliferative capacity of a cell line did not necessarily confer MP; therefore, further cellular functions/adaptations must be required for tumor cell dissemination, survival, and growth at a metastatic site.
Involvement of CD14 in Lipopolysaccharide- Induced Liver Injury in Mice Pretreated with Propionibacterium acnes
Authors: Uchida Tomohisa , Kataoka Masashi , Higuchi Yasunori , Matsuura Keiko , Hijiya Naoki , Yamamoto Shunsuke
Published: October 2004

Objective: The aim of this study was to elucidate the role of CD14 in the Propionibacterium acnes-lipopolysaccharide (LPS) system. Methods and Results: CD14 transgenic mice (M14M), which expressed heterotopic CD14 and showed decreased responses to LPS in vivo, were used. Seven days after priming, the size of granulomas induced by an intraperitoneal administration of P. acnes in the M14M mice was smaller than that in the nontransgenic mice. The number of CD14-positive cells in granulomas was also decreased in the M14M mice compared to the nontransgenic mice. An LPS challenge induced apoptotic and necrotic changes in hepatocytes in the nontransgenic mice but not in the M14M mice. Seven days after priming, tumor necrosis factor-α expression was found in monocytic cells in granulomas and Kupffer cells in the nontransgenic mice and was significantly upregulated after LPS injection, whereas the expression was very weak in these cells in the M14M mice. Conclusions: CD14 plays a role in the P. acnes-LPS system in both priming and induction phases.
Expression of Angiogenic Factors Is Upregulated in DMBA-Induced Rat Mammary Pathologies
Authors: Yan Mei , Schneider Joanne , Gear Robin , Lu Fengxian , LaDow Kathy , Warshawsky David , Heffelfinger Sue C.
Published: October 2004

Objective: In the 7,12-dimethylbenz[a]anthracene (DMBA) model of rat mammary carcinogenesis, microvascular density and angiogenic potential increase with progression from normal to invasive disease, but the mechanisms involved are unknown. Using RT-PCR, we determined the expression of angiogenic regulators in DMBA-induced intraductal hyperplasia (IDP), carcinoma in situ (CIS), invasive tumors (INV), as well as normal tissue. Methods: RT-PCR was performed on frozen tissue sections of each type of pathology for factors known to regulate angiogenesis in other systems. Results: MMP-2, MMP-9, uPA, PAI-1, IGF-2, BFGF, VEGF, ANG-1, IRS-1, and TSP-1 were significantly (p ≤ 0.05) upregulated in CIS and INV, whereas TIMP-1, ANG-2, MASPIN, IGF1-R and HBEGF were unchanged. IGF-1 was uniquely elevated in IDP. SPARC was downregulated in CIS. Inhibition of IGF-1R by the tyrphostin, AG1024, blocked endothelial tubulogenesis in vitro, confirming that IGF-1 functions as a regulator of angiogenesis. Conclusions: These data support the involvement of specific angiogenic mediators in mammary tumor formation. Angiogenesis at different stages of tumorigenesis may be regulated by unique factors.
Overexpression of 15-Lipoxygenase in the Vascular Endothelium Is Associated with Increased Thymic Apoptosis in LDL Receptor-Deficient Mice
Authors: Afek A. , Zurgil N. , Bar-Dayan Y. , Polak-Charcon S. , Goldberg I. , Deutsch M. , Kopolovich J. , Keren G. , Harats D. , George J.
Published: October 2004

Background: 15-Lipoxygenase (15-LO) is a nonheme iron-containing enzyme that catalyzes the peroxidation of fatty acids. Herein, we studied the effect of 15-LO overexpression in the vascular endothelium on thymocyte apoptosis by evaluating thymuses from low-density lipoprotein receptor-deficient (LDL-RD) mice and LDL-RD/15-LO mice. Thymuses were evaluated by immunhistochemistry and by TUNEL whereas in vitro studies were carried out by employing freshly isolated thymocytes from the respective mice and evaluation of apoptosis by propidium iodide and annexin V cytometry. Methods and Results: The apoptotic index in LDL-RD/15-LO mice was significantly higher than in the LDL-RD mice. In the thymic medulla the difference was smaller, although still significant. Freshly isolated thymus cells from LDL-RD/15-LO mice exhibited a higher rate of spontaneous cell death than controls. Incubation of thymus cells in the presence of the cell-permeable caspase-3 inhibitor DEVD-CMK resulted in a decrease in the frequency of apoptotic cells in LDL-RD/15-LO thymocytes, whereas no effect was evident in control thymocytes. The antioxidant N-acetylcysteine causes the increase in apoptosis in both groups. Conclusion: LDL-RD/15-LO mice exhibit increased thymocyte apoptosis both in vivo and in vitro. These findings may suggest a role for 15-LO in the natural selection of thymocytes.
Expression of Heart-Type Fatty Acid-Binding Protein in Human Gastric Carcinoma and Its Association with Tumor Aggressiveness, Metastasis and Poor Prognosis
Authors: Hashimoto Takeaki , Kusakabe Takashi , Sugino Takashi , Fukuda Takeaki , Watanabe Kazuo , Sato Yukio , Nashimoto Atsushi , Honma Keiichi , Kimura Hideki , Fujii Hiroshi , Suzuki Toshimitsu
Published: October 2004

Objective: Fatty acid-binding proteins (FABPs) are involved in lipid metabolism by intracellular transport of long-chain fatty acids. Heart-type (H-) FABP has been reported to inhibit cell growth and induce cell differentiation, but to our knowledge the significance of H-FABP expression in human gastric carcinoma has not been elucidated. The aim of the current study was to examine the expression of H-FABP and its relation to clinicopathologic parameters and fatty acid synthase (FAS) status of gastric carcinoma, since gastric cancer shows increased expression of FAS. Methods: Immunohistochemistry with anti-H-FABP antibody was performed in 669 gastric carcinomas and 60 tubular adenomas of the stomach. H-FABP-positive and H-FABP-negative carcinomas were analyzed for their clinicopathologic characteristics and FAS status. Results: None of the adenomas expressed H-FABP, whereas 127 of 669 carcinomas (19.0%) were positive for the protein. H-FABP positivity was associated with the depth of invasion (p < 0.0001), vascular invasion (p < 0.0001), lymph node metastasis (p < 0.0001), hepatic metastasis (p = 0.0011), stage of the carcinoma (p < 0.0001) and FAS status of the carcinoma (p = 0.0476). A higher survival rate was noted in H-FABP-negative cases compared with H-FABP-positive cases (p = 0.0004). Conclusions: A subset of human gastric carcinoma expresses H-FABP and its expression is associated with FAS status, disease progression, tumor aggressiveness and poor patient survival.