bluuebunny/crossref_metadata_2025 huggingface dataset:
An Integrated Investment and Financial Planning Model
Authors: Güven S. , Kaynarca A.
Published: August 2006

In countries where investment incentives and tax exemptions are offered, directing investments into high priority sectors and areas, evaluation of investment alternatives and methods of financing them necessitates an integrated approach. This paper presents an integrated investment and financial planning model developed for a Turkish company where the objective is maximization of after tax cash flows. Experiments conducted with the model demonstrate that initial financial structure and financial ratio restrictions are determinant on the solution, and that decisions based on investment incentive and tax exemption schemes only may not be optimal. Another group of experiments demonstrate the use of the model as a strategic planning tool to investigate the sensitivity of decisions to parameter values and areas where further data analysis and marketing research would be helpful.
On the Comparison of Solutions in Stochastic Simulation—optimization Problems with Several Performance Measures
Authors: Mebarki N. , Dussauchoy A. , Pierreval H.
Published: August 2006

In a stochastic simulation context, iterative methods of optimization which perform at each step of their optimization procedure a comparison between two different values of the objective function, need the use of statistical tests in order to properly evaluate and compare the simulation results. However, when the objective function to optimize is a multi‐criteria function involving several performance measures, conflicting situations may arise. In particular, these situations are observed for models of manufacturing systems, where the performance criteria to evaluate may be contradictory. In this case, the statistical test may lead to the rejection of acceptable solutions. To avoid this, we propose a simple and effective procedure to evaluate a multi‐criteria function when it is computed as a weighted sum of different performance measures. This procedure allows retention of all solutions which present a significant improvement, while other solutions are rejected.
Coordination Between Production and Commercial Planning: Organisational and Modelling Issues
Authors: Soler L.G. , Tanguy H.
Published: August 2006

Coordination between commercial activities and production has long been identiffied as a cause of major difficulties within a company which is structured according to the main functions. Various analytical frameworks have tried to elucidate the organisational, information processing and incentive issues raised by this problem. Using the example of an agro‐food company seeking new organisational forms while its markets were becoming increasingly deregulated, the design of material planning systems as the main managerial driver for reforming the organisation is identied. The critical role of modelling in an intervention process focused on planning design is discussed and the question as to why innovative efficient organisational forms can be devised this way is explained.
Minimizing Empty Hauls in Multi‐day, Multi‐depot Trucking
Authors: Arcelus F.J. , Eiselt H.A. , Lin E.Y.H.
Published: August 2006

In this paper we approach an empty haul problem by Day and Ross, one of Eastern Canada's largest trucking companies. Based on past data, we optimize the company's backhaul. Sensitivity analyses then allow conclusions regarding whether or not it is worth taking on additional freight for specific origin—destination pairs.
Design of Interconnection of Local Area Networks
Authors: Filho V.J.M.F. , Galvão R.D.
Published: August 2006

This paper addresses the interconnection of local area networks (LANs) using bridges. The interconnection problem is difficult to solve and feasible solutions are usually obtained through heuristics. The description of a simplified approach to solve the problem of interconnecting LANs is followed by the formulation of the problem and the development of a Lagrangean relaxation. A Tabu search metaheuristic for designing minimum cost spanning tree topologies is also presented. Computational results are given for the interconnection of up to ten local area networks.
A Best‐first Branch‐and‐bound Algorithm for Orthogonal Rectangular Packing Problems
Authors: Hifi M. , Ouafi R.
Published: August 2006

In this paper we discuss the problem of packing a set of small rectangles (pieces) in an enclosing final rectangle. We present first a best‐first branch‐and‐bound exact algorithm and second a heuristic approach in order to solve exactly and approximately this problem. The performances of the proposed approaches are evaluated on several randomly generated problem instances. Computational results show that the proposed exact algorithm is able to solve small and medium problem instances within reasonable execution time. The derived heuristic performs very well in the sense that it produces high‐quality solutions within small computational time.
Stochastic Equilibrium Traffic Assignment with Value‐of‐time Distributed Among Users
Authors: Cantarella G.E. , Binetti M.
Published: August 2006

In this paper, existing fixed‐point models for stochastic equilibrium traffic assignment to transportation networks are extended to deal with the value of time distributed among users. This problem is relevant when transporation demand management measures affecting travelling monetary costs are to be evaluated. Analysis of existence and uniqueness of solutions is carried out, leading to mild assumptions about link cost‐flow functions, path choice model, and value‐of‐time distribution. Some quite simple solution algorithms are also specified and their convergence analysed. Results of some applications are also reported.
Application of fuzzy logic and neural networks for dynamic travel time estimation
Authors: Palacharla P.V. , Nelson P.C.
Published: August 2006

The effectiveness of loop detectors as a data source for advanced traveler information systems has been researched recently [V. P. Sisiopiku (1993 Travel Time Estimation from Loop Detector Data for Advanced Traveler Information System Applications, Ph.D. Thesis, University of Illinois at Chicago]. In urban traffic control schemes loop detectors provide on‐line information on traffic conditions consisting of volume counts and occupancy levels. The need to convert loop detector data into travel times is recognized mostly in data fusion applications [P. Nelson and P. Palacharla (1993) A neural network model for data fusion in ADVANCE, Pacific Rim Transportation Technology Conference Proceedings, Vol. I, pp. 237–243, Seattle, WA, 1993]. Literature review indicates limited knowledge on the actual relationship between travel times and loop detector data under interrupted traffic conditions [V. P. Sisiopiku and N. M. Rouphail (1994) Towards the Use of Detector Output for Arterial Link Travel Time Estimation: a Literature Review. Transportation Research Record Series, Washington, DC]. Currently available statistical regression models cannot capture the dynamics of traffic conditions under signalized control and suffer from limited calibration and empirical validation. This paper presents a fuzzy reasoning model to convert loop detector data into link travel times obtained from empirical studies. This model incorporates flexible reasoning and captures non‐linear relationship between link specific detector data and travel times.
Transient solutions of some multiserver queueing systems with finite spaces
Authors: Chaudhry M.L. , Zhao Y.Q.
Published: August 2006

The purpose of this paper is to provide explicit transient solutions for the multiserver queueing systemGeom(n)/Geom(n)/c/N+c. The method proposed here can also be used for obtaining transient solutions of Markov chains having the transition matrix of Hesselberg type. To support this, we also consider a more complex model such asGI/M/c/N+c. In our analysis, we use eigenvalues and generalized eigenvectors of transition probability matrices. Since we use the Jordan canonical form from linear algebra, the method is good even if the eigenvalues are repeated. Numerical procedures for computations involved in various examples are also provided.
A strategic investment model for phased implementation of flexible manufacturing systems
Authors: Lamar B.W. , Lee A.
Published: August 2006

This paper describes a set of strategic, tactical, and operational models that can be used to analyze the phased implementation of flexible technology in a manufacturing system. The strategic model represents capital investment decisions, the tactical model represents aggregate production decisions, and the operational model represents the functional form of the production costs. Learning effects and other nonlinearities (such as setup costs, economies of scale, and congestion effects) can be quantified in the models. An efficient solution procedure (using dynamic programming and minimum cost network flow optimization) is described. The efficiency of the solution method permits a host of ‘what‐if’ scenarios to be examined by the decision maker.
Scheduling of client‐server applications
Authors: Blażewicz J. , Dell'Olmo P. , Drozdowski M.
Published: August 2006

In this paper, we analyze the problem of deterministic scheduling of applications (programs) in a client‐server environment. We assume that the client reads data from the server, processes it, and stores the results on the server. This paradigm can also model a wider class of parallel applications. The goal is to find the shortest schedule. It is shown that the general problem is computationally hard. However, any list scheduling algorithm delivers solutions not worse than twice the optimum when tasks are preallocated, and three times the optimum when tasks are not preallocated. A polynomially solvable case is also presented.
Approximation algorithms for combinatorial multicriteria optimization problems
Authors: Ehrgott M.
Published: August 2006

The computational complexity of combinatorial multiple objective programming problems is investigated. NP‐completeness and #P‐completeness results are presented. Using two definitions of approximability, general results are presented, which outline limits for approximation algorithms. The performance of the well‐known tree and Christofides' heuristics for the traveling salesman problem is investigated in the multicriteria case with respect to the two definitions of approximability.
An AHP/DEA methodology for ranking decision making units
Authors: Sinuany‐Stern Z. , Mehrez A. , Hadad Y.
Published: August 2006

This paper presents a two‐stage model for fully ranking organizational units where each unit has multiple inputs and outputs. In the first stage, the Data Envelopment Analysis (DEA) is run for each pair of units separately. In the second stage, the pairwise evaluation matrix generated in the first stage is utilized to rank scale the units via the Analytical Hierarchical Process (AHP). The consistency of this AHP/DEA evaluation can be tested statistically. Its goodness of fit with the DEA classification (to efficient/inefficient) can also be tested using non‐parametric tests. Both DEA and AHP are commonly used in practice. Both have limitations. The hybrid model AHP/DEA takes the best of both models, by avoiding the pitfalls of each. The nonaxiomatic utility theory limitations of AHP are irrelevant here: since we are working with given inputs and outputs of units, no subjective assessment of a decision maker evaluation is involved. AHP/DEA ranking does not replace the DEA classification model, rather it furthers the analysis by providing full ranking in the DEA context for all units, efficient and inefficient.
Constrained two‐dimensional cutting stock problems a best‐first branch‐and‐bound algorithm
Authors: Cung V‐D. , Hifi M. , Le Cun B.
Published: August 2006

In this paper, we develop a new version of the algorithm proposed in Hifi (Computers and Operations Research 24/8 (1997) 727–736) for solving exactly some variants of (un)weighted constrained two‐dimensional cutting stock problems. Performance of branch‐and‐bound procedure depends highly on particular implementation of that algorithm. Programs of this kind are often accelerated drastically by employing sophisticated techniques. In the new version of the algorithm, we start by enhancing the initial lower bound to limit initially the space search. This initial lower bound has already been used in Fayard et al. 1998 (Journal of the Operational Research Society, 49, 1270–1277), as a heuristic for solving the constrained and unconstrained cutting stock problems. Also, we try to improve the upper bound at each internal node of the developed tree, by applying some simple and effcient combinations. Finally, we introduce some new symmetric‐strategies used for neglecting some unnecessary duplicate patterns. The performance of our algorithm is evaluated on some problem instances of the literature and other hard‐randomly generated problem instances.
A scenario‐based stochastic programming model for water supplies from the highland lakes
Authors: Watkins D.W. , McKinney D.C. , Lasdon L.S. , Nielsen S.S. , Martin Q.W.
Published: August 2006

A scenario‐based, multistage stochastic programming model is developed for the management of the Highland Lakes by the Lower Colorado River Authority (LCRA) in Central Texas. The model explicitly considers two objectives: (1) maximize the expected revenue from the sale of interruptible water while reliably maintaining firm water supply, and (2) maximize recreational benefits. Input data can be represented by a scenario tree, built empirically from a segment of the historical flow record. Thirty‐scenario instances of the model are solved using both a primal simplex method and Benders decomposition, and results show that the first‐stage (‘here and now’) decision of how much interruptible water to contract for the coming year is highly dependent on the initial (current) reservoir storage levels. Sensitivity analysis indicates that model results can be improved by using a scenario generation technique which better preserves the serial correlation of flows. Ultimately, it is hoped that use of the model will improve the LCRA's operational practices by helping to identify flexible policies that appropriately hedge against unfavorable inflow scenarios.
Tetanus: pathophysiology, clinical signs, diagnosis, and update on new treatment modalities
Authors: Linnenbrink Thomas , McMichael Maureen
Published: August 2006

Objective: To review the pathophysiology, clinical signs, diagnosis, and current treatment modalities used in treating tetanus in small animals and humans.

Etiology: Tetanus is caused by the activity of a toxin released from the bacterial organism, Clostridium tetani. The disease has an incubation period of 3 days to 3 weeks and usually follows a deep penetrating wound.

Diagnosis: The diagnosis of tetanus is usually based on history and clinical signs.

Therapy: Therapy of tetanus consists of direct and supportive care and includes toxin neutralization via human or equine derived immunoglobulin, antimicrobial therapy to eliminate C. tetani, and central and peripheral muscle relaxants to control hypertonicity. Adjunctive care may include positive pressure ventilation, anticonvulsant medication, drugs to treat autonomic dysfunction, and nutritional support.

Prognosis: Prognosis varies based on severity of clinical signs at the time of diagnosis and the availability of appropriate care.
Does Supplementary Prenatal Nursing and Home Visitation Support Improve Resource Use in a Universal Health Care System? A Randomized Controlled Trial in Canada
Authors: Tough Suzanne C. , Johnston David W. , Siever Jodi E. , Jorgenson Gayleen , Slocombe Linda , Lane Carolyn , Clarke Margaret
Published: August 2006

ABSTRACT:  Background:
The addition of supplementary prenatal support may improve the health and well‐being of high‐risk women and families. The objective of this randomized controlled trial was to examine the impact of supplementary prenatal care on resource use among a community‐based population of pregnant women.
Methods:
Pregnant women from three urban maternity clinics were randomized (a) to current standard of physician care, (b) to current standard of care plus consultation with a nurse, or (c) to (b) plus consultation with a home visitor. Participants were 1,352 women who received 3 telephone interviews. The primary outcome was resource use (e.g., attended prenatal classes, used nutritional counseling).
Results:
Overall, those in the nurse intervention group were more likely to attend an “Early Bird” prenatal class and parenting classes, and to use nutrition counseling and agencies that assist with child care. Women provided with extra nursing and home visitation supports were more likely to use a written resource guide, nutrition counseling, and agencies that assist with child care. Among women at higher risk (e.g., language barriers, young maternal age, low income), the nurse intervention significantly increased use of early prenatal classes, whereas the nurse and home visitor intervention significantly increased use of the written resource guide and nutrition counseling. The intervention substantially increased the amount of information received on numerous pregnancy‐related topics but had little impact on resource use for mental health and poverty‐related needs. Among those with added support, resource use among low‐risk women was generally greater than among high‐risk women.
Conclusions:
Additional support provided by nurses, or nurses and home visitors, can successfully address informational needs and increase the likelihood that women will use existing community‐based resources. This finding was true even for high‐risk women, although this intervention did not reduce the difference in resource use between high‐ and low‐risk women. (BIRTH 33:3 September 2006)
Systematic Review of Nulliparous Women’s Views of Planned Cesarean Birth: The Missing Component in the Debate about a Term Cephalic Trial
Authors: Kingdon Carol , Baker Lisa , Lavender Tina
Published: August 2006

Abstract:  Background:
The suggestion that planned cesarean birth is gaining acceptance among women has led some physicians to advocate the need for a trial of primary planned cesarean section versus planned vaginal birth in healthy women with singleton cephalic pregnancies at term. This paper reviews published studies of nulliparous women’s views of mode of birth collected in the antenatal period, examining why women may express a preference for cesarean birth and exploring implications for the debate about the need for a trial.
Methods:
A systematic literature review was undertaken of Cochrane, CINAHL, EMBASE, MEDLINE, and PsycINFO using the MeSH heading “cesarean section” and four free text spellings of “cesarean,” or “birth” or “delivery,” near truncated synonyms of 17 words meaning expressed preference. Studies of nulliparous women with a medical indication for cesarean birth, studies where a woman’s preference for mode of birth was reported in the postpartum period, surveys of midwives or obstetricians, and opinion and non‐English language papers were all excluded.
Results:
Nine papers were included in the review, which reported rates of women expressing a preference for cesarean birth that ranged from 0 to 100 percent at recruitment. However, the papers raised specific methodological, conceptual, and cultural issues that may have influenced women’s preferences for mode of birth in the populations studied. These issues included the timing and frequency of data collection, complexity of factors determining individual women’s decision making, and influence of societal norms.
Conclusions:
Little evidence is available that an increasing cultural acceptance of cesarean delivery will bring about support for a trial among pregnant nulliparous women. Further qualitative research investigating the influence of both obstetric and psychosocial factors on women’s views of vaginal and cesarean birth is required. (BIRTH 33:3 September 2006)
Is a novel I214M substitution in the NEFL gene a cause of Charcot‐Marie‐Tooth disease? Functional analysis using cell culture models
Authors: Kabzińska Dagmara , Perez‐Olle Raul , Goryunov Dmitry , Drac Hanna , Ryniewicz Barbara , Hausmanowa‐Petrusewicz Irena , Kochański Andrzej , Liem Ronald K.H
Published: August 2006

Abstract  Recent studies have shown that mutations in neurofilament light subunit gene (NEFL) cause Charcot‐Marie‐Tooth (CMT) disease. Since the first description of the Gln333Pro mutation in the NEFL gene, 10 pathogenic mutations in the NEFL gene have been reported in patients affected with CMT disease. We report a novel I214M amino acid substitution in the NEFL gene in two unrelated patients affected with CMT. Because the I214M amino acid substitution in the NEFL protein was not detected in a CMT affected brother of the proband, its pathogenic effect became unclear. In order to determine whether this amino acid substitution is a benign polymorphism or causative of the disease, we performed a functional analysis of the mutant I214M neurofilament protein (NFL). Transfections of the mutant protein in cultured cells revealed an increased tendency to form highly compacted filamentous structures but no other alterations of neurofilament assembly or transport were observed. Furthermore, the sibling of one of the patients was also affected with CMT but did not have the I214M substitution. These data suggest that this I214M substitution in the NEFL gene was not a direct cause of the disease but could be a polymorphism or possibly a modifier of the CMT phenotype.
Acquired lysosomal storage caused by frequent plasmapheresis procedures with hydroxyethyl starch
Authors: Auwerda Johannes J.A. , Leebeek Frank W.G. , Wilson J.H. Paul , Van Diggelen Otto P. , Lam King H. , Sonneveld Pieter
Published: August 2006

BACKGROUND: Hydroxyethyl starch (HES) solutions have largely replaced conventional plasma expanders such as human albumin and colloidal fluids. Only a few side effects have been reported and mainly concern pruritus or blood coagulation disorders. Excessive HES exposure can result in diffuse tissue storage and accumulation with foamy appearing macrophages which produce the enzyme chitotriosidase (CT). In case of massive tissue storage, this enzyme activity can reach levels comparable to those of Gaucher disease.

STUDY DESIGN AND METHODS: In this single‐center retrospective analysis of 11 consecutive patients receiving large amounts of HES for chronic plasmapheresis, plasma CT activity was investigated. Five patients receiving chronic intermittent plasmapheresis with conventional plasma expanders served as controls. Plasma CT activity was measured and plotted against creatinine clearance. Where available, marrow aspirate was analyzed with light microscopy to detect foamy macrophages. One patient developed a lysosomal storage disease and was examined extensively.

RESULTS: Conventional plasma expanders did not alter plasma CT activity. In patients with impaired renal function, frequent plasma replacement with HES resulted in an increase in plasma CT activity. In the patient with the acquired lysosomal storage disease, massive tissue infiltration with activated foamy macrophages was observed. The phagocytic capacity in this patient, however, did not seem to be altered.

CONCLUSION: Patients with impaired renal function receiving large amounts of HES exhibit an increase in plasma CT activity. Because excessive HES exposure can result in an acquired lysosomal storage disease, this should be avoided in chronic plasmapheresis procedures.
Evaluation of a prototype Trypanosoma cruzi antibody assay with recombinant antigens on a fully automated chemiluminescence analyzer for blood donor screening
Authors: Chang Chi‐Deu , Cheng Kevin Y. , Jiang Lily X. , Salbilla Vince A. , Haller Alla S. , Yem Alex W. , Bryant Jane D. , Kirchhoff Louis V. , Leiby David A. , Schochetman Gerald , Shah Dinesh O.
Published: August 2006

BACKGROUND: Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite that can be transmitted by transfusion. The diagnosis of chronic T. cruzi infection is generally made by detecting specific antibodies that bind to parasite antigens. The aim of this study was to assess the sensitivity and specificity of a new serologic assay for antibodies to T. cruzi on a fully automated analyzer (PRISM, Abbott Laboratories).

STUDY DESIGN AND METHODS: A prototype chemiluminescent immunoassay based on chimeric recombinant antigens and run on the automated PRISM system was developed for detecting antibodies to T. cruzi in human serum and plasma. Assay specificity was evaluated by testing samples from random blood donors and from a diverse group of specimens from persons with diseases or conditions often associated with false‐positive reactions in T. cruzi assays. Sensitivity was determined by testing 377 geographically diverse T. cruzi antibody–positive specimens.

RESULTS: Six of 7911 samples (0.08%) from random donors were repeatedly reactive in the prototype PRISM Chagas assay. One of these was reactive in three other tests, including the radioimmune precipitation assay and was presumed to be a true positive. Hence, the specificity was 99.94 percent (7905/7910) in the negative donor group studied. All 377 T. cruzi antibody–positive specimens were positive in the prototype assay and thus the sensitivity was 100 percent.

CONCLUSION: The results obtained to date, in terms of sensitivity as well as specificity, strongly suggest that the PRISM Chagas assay should function well as a tool for screening blood for serologic evidence of T. cruzi infection.
The American Welfare State Decoded: Uncovering the Neglected History of Public‐Private Partnerships
Authors: Oakley Deirdre
Published: August 2006

The American welfare system has always been characterized by extensive public‐private partnerships in the provision of social services. In addition, government financial support became important to private charitable agencies long before the emergence of nationally administered social welfare programs in the 1930s. Although recent research has acknowledged the expanded use of private organizations to deliver government‐sponsored services since the Reagan Era, and focused more fully on public‐private arrangements since the welfare reform initiatives of 1996, the larger historical context has received scant attention. This article presents a case study of the public‐private organizational and financial arrangements in the provision of relief service both before (up to 1934) and after (1935 and beyond) the emergence of nationally‐sponsored programs. The study addresses the following questions: (1) What was the public‐private organizational arrangement in the delivery of welfare services prior to the expanded government role initiated with the New Deal Legislation of the mid 1930s? (2) How has this arrangement changed since then? (3) How dependent have private charitable organizations (known today as nonprofits) become on government funding? Findings indicate that the inter‐organizational arrangement of government entities contracting services through community organizations remains in place despite the emergence of the welfare state. This study also reveals that government‐nonprofit partnerships extend beyond funding in the form of citywide coordinating coalitions. Lastly, although investigation of the distribution of nonprofit income sources in 1929 and 1999 reveals a shift away from private funds (the typical agency now receiving between 7 and 61.4 percent of total revenues from government resources), this has not negated the importance of other private income sources. Thus, even though nonprofit agencies have become more financially dependent on government resources, they have maintained a significant degree of independence.
Between Growth and Exclusion in Technopolis: Managing Inequalities in Toulouse, France
Authors: Nicholls Walter J.
Published: August 2006

As high technology development has created important resources and opportunities for some residents of cities, it has also introduced a new set of barriers and constraints for others. The new inequalities resulting from this pathway of economic development present local public officials with important challenges for managing their cities. This article argues that local strategies to confront inequalities in high technology cities are dependent on how individual states have undertaken restructuring reforms over the last 30 years. In France, the state has ceded some control over the allocation of economic resources to markets while retaining some control over the allocation of welfare resources. The rising importance of markets and the continued centrality of a redistributive state in French cities have resulted in the formation of distinct types of policy communities in the areas of economic development and welfare. The former community operates according to an entrepreneurial logic and the latter community continues to operate according to a political/statist logic. These local policy communities are like two ships passing in the night, embedded in and responding to distinct institutional constraints that lead them in very different directions.
A Method for Estimating Penetrance from Families Sampled for Linkage Analysis
Authors: Wang Yuanjia , Ottman Ruth , Rabinowitz Daniel
Published: August 2006

Summary When a gene variant is discovered to segregate with a disease, it may be of interest to estimate the risk (or the age‐specific risk) of the disease to carriers of the variant. The families that contributed to the discovery of the variant would typically contain multiple carriers, and so, especially if the variant is rare, might prove a valuable source of study subjects for estimation of the risk. These families, by virtue of having brought the gene in question to the attention of researchers, however, may not be representative of the relationship between carrier status and the risk of the disease in the population. Using these families for risk estimation could bias the observed association between the variant and the risk. The purpose here is to present an approach to adjusting for the potential bias while using the families from linkage analysis to estimate the risk.
Measurement Error in a Random Walk Model with Applications to Population Dynamics
Authors: Staudenmayer John , Buonaccorsi John P.
Published: August 2006

Summary Population abundances are rarely, if ever, known. Instead, they are estimated with some amount of uncertainty. The resulting measurement error has its consequences on subsequent analyses that model population dynamics and estimate probabilities about abundances at future points in time. This article addresses some outstanding questions on the consequences of measurement error in one such dynamic model, the random walk with drift model, and proposes some new ways to correct for measurement error. We present a broad and realistic class of measurement error models that allows both heteroskedasticity and possible correlation in the measurement errors, and we provide analytical results about the biases of estimators that ignore the measurement error. Our new estimators include both method of moments estimators and “pseudo”‐estimators that proceed from both observed estimates of population abundance and estimates of parameters in the measurement error model. We derive the asymptotic properties of our methods and existing methods, and we compare their finite‐sample performance with a simulation experiment. We also examine the practical implications of the methods by using them to analyze two existing population dynamics data sets.
Regression Modeling of Semicompeting Risks Data
Authors: Peng Limin , Fine Jason P.
Published: August 2006

Summary Semicompeting risks data are often encountered in clinical trials with intermediate endpoints subject to dependent censoring from informative dropout. Unlike with competing risks data, dropout may not be dependently censored by the intermediate event. There has recently been increased attention to these data, in particular inferences about the marginal distribution of the intermediate event without covariates. In this article, we incorporate covariates and formulate their effects on the survival function of the intermediate event via a functional regression model. To accommodate informative censoring, a time‐dependent copula model is proposed in the observable region of the data which is more flexible than standard parametric copula models for the dependence between the events. The model permits estimation of the marginal distribution under weaker assumptions than in previous work on competing risks data. New nonparametric estimators for the marginal and dependence models are derived from nonlinear estimating equations and are shown to be uniformly consistent and to converge weakly to Gaussian processes. Graphical model checking techniques are presented for the assumed models. Nonparametric tests are developed accordingly, as are inferences for parametric submodels for the time‐varying covariate effects and copula parameters. A novel time‐varying sensitivity analysis is developed using the estimation procedures. Simulations and an AIDS data analysis demonstrate the practical utility of the methodology.
A Unified Likelihood‐Based Approach for Estimating Population Size in Continuous‐Time Capture–Recapture Experiments with Frailty
Authors: Xi Liqun , Yip Paul S. F. , Watson Ray
Published: August 2006

Summary A unified likelihood‐based approach is proposed to estimate population size for a continuous‐time closed capture–recapture experiment with frailty. The frailty model allows the capture intensity to vary with individual heterogeneity, time, and behavioral response. The individual heterogeneity effect is modeled as being gamma distributed. The first‐capture and recapture intensities are assumed to be in constant proportion but may otherwise vary arbitrarily through time. The approach is also extended to capture–recapture experiments with possible random removals. Simulation studies are conducted to examine the performance of the proposed estimators. By asymptotic efficiency comparison and simulation studies, the proposed estimators have been shown to be superior to their discrete‐time model counterparts in genuine continuous‐time capture–recapture experiments.
Inferring the Location of Tumor Suppressor Genes by Modeling Frequency of Allelic Loss
Authors: Sterrett Andrew , Wright Fred A.
Published: August 2006

Summary Allelic loss is often part of a multistep process leading to tumorigenesis. Analysis of genomic markers highlights regions of elevated allelic loss, which in turn suggests a nearby tumor suppressor. Furthermore, pooling published analyses to combine evidence can increase the power to detect a tumor suppressor gene. If the pattern of loss for each tumor, or allelotype, is known, a stochastic model proposed by Newton et al. (1998, Statistics in Medicine17, 1425–1445) can be used to analyze the correlated binary data. Many studies report only incomplete allelotypes, augmented with frequencies of allelic loss (FAL) at each marker, in which the number of informative tumors showing allelic loss is provided along with the number of informative tumors. We describe an extension of the allelotype model to handle FAL data, using a hidden Markov model or a normal approximation to compute the likelihood. The FAL model is illustrated using data from a study of colorectal cancer.
C957T DRD2 polymorphism is associated with schizophrenia in Spanish patients
Authors: Hoenicka J. , Aragüés M. , Rodríguez‐Jiménez R. , Ponce G. , Martínez I. , Rubio G. , Jiménez‐Arriero M. A. , Palomo T. ,   Psychosis and Addictions Research Group (PARG)
Published: August 2006

Objective:  The objective was to confirm whether a homozygous genotype for the C957 allele of the C957T DRD2 gene single nucleotide polymorphism (SNP) is associated with schizophrenia in an independent study population.

Method:  We examined the genotypic distribution of this SNP in a set of clinically ascertained schizophrenic patients (n = 131) and age‐matched control subjects (n = 364). Individuals were genotyped using automated analysis of fluorescently labeled PCR products.

Results:  The distribution of grouped genotypes for the C957T DRD2 SNP (CC vs. CT, TT) showed that C homozygote genotype was over‐represented in our patient sample when compared with control subjects. This difference reaches the statistical significance (χ2 = 7.0; df = 1; P = 0.008; OR = 2.05; % CI 1.2–3.4).

Conclusion:  The findings of this study provide additional evidence that genetic variation at the DRD2 gene plays an important role in the vulnerability to schizophrenia.
Pegfilgrastim compared with filgrastim after high‐dose melphalan and autologous hematopoietic peripheral blood stem cell transplantation in multiple myeloma patients
Authors: Martino Massimo , Praticò Giulia , Messina Giuseppe , Irrera Giuseppe , Massara Elisabetta , Messina Giuseppe , Console Giuseppe , Iacopino Pasquale
Published: August 2006

Abstract:  We undertook a comparative study of Pegfilgrastim vs. Filgrastim after high‐dose melphalan and autologous peripheral blood stem cell transplantation (APBSCT) in multiple myeloma (MM) patients. Thirty‐seven consecutive patients were randomly assigned to receive a single 6 mg dose of Pegfilgrastim on day 1 post‐transplant (n = 18 patients) vs. daily subcutaneous injections of Filgrastim 5 μg/kg (n = 19 patients) starting on day 5 post‐transplant. The median duration of grade 4 neutropenia in the Pegfilgrastim and Filgrastim groups was 5 and 6 d, respectively (P = ns). The results for the two groups were also not significantly different for time to neutrophil and platelet recovery, but incidence of febrile neutropenia (61.1% vs. 100%, P = 0.003) and duration of febrile neutropenia (1.5 d vs. 4 d, P = 0.005), were lower in the Pegfilgrastim arm. After initial haematopoietic reconstitution, we observed significantly higher value of leukocytes × 109 L on day 15 (6.0 vs. 2.7, P = 0.004), in the Pegfilgrastim group compared with the Filgrastim group. This study shows that a single injection Pegfilgrastim can be used with safety and efficacy similar to those provided by daily injections of Filgrastim and it is associated with a decrease incidence of infectious events after APBSCT in MM patients.
Effect of granulocyte colony‐stimulating factor on IL‐12 p40 production during chemotherapy for B‐cell lineage non‐Hodgkin's lymphoma patients
Authors: Toubai Tomomi , Tanaka Junji , Ota Shuichi , Fukuhara Takashi , Hashino Satoshi , Kondo Takeshi , Shono Yusuke , Morioka Masanobu , Kawamura Tsugumichi , Masauzi Nobuo , Kakinoki Yasutaka , Kobayashi Hajime , Kunieda Yasuyuki , Kasai Masaharu , Kurosawa Mitsutoshi , Asaka Masahiro , Imamura Masahiro
Published: August 2006

Abstract:  Interleukin (IL)‐12 is a 70‐kDa cytokine comprised of two disulfide‐linked proteins (p35 and p40) and is essential for the initiation of effective immune response. Granulocyte‐colony stimulating factor (G‐CSF) affects the balance in the production of anti‐inflammatory cytokines. We investigated the serum IL‐12 p40 and IL‐12 Mix (p40 and p70) production in 28 patients with B‐cell lineage non‐Hodgkin's lymphoma (NHL) treated with chemotherapy (e.g., CHOP regimen) with or without G‐CSF administration and eight healthy volunteers. We found that serum levels of IL‐12 p40 (191.2 ± 150.0 pg/mL) and IL‐12 Mix (277.4 ± 274.5 pg/mL) in the patients before chemotherapy were higher than those in the healthy volunteers (IL‐12 p40: 76.4 ± 25.3 pg/mL, IL‐12 Mix: 48.5 ± 33.4 pg/mL) (P = 0.04 and 0.02, respectively). Next, we examined the serum IL‐12 p40 and IL‐12 Mix levels in nine patients receiving chemotherapy with administration of G‐CSF (CG group, n = 9) and without G‐CSF (C group, n = 9). Serum IL‐12 p40 and IL‐12 Mix levels were decreased on 10 d after chemotherapy in both groups, and those in CG groups were significantly lower than those in C group. These results indicated that administration of G‐CSF decreased serum IL‐12 p40 and IL‐12 Mix levels. Overall survival (OS) at 24 months was not significantly different in the two groups (58.3% in group C vs. 80.0% in group CG, P = 0.67). However, the survival rate of patients at clinical stages III and IV in CG group (n = 6, 66.0%) was significantly better than that of patients in C group (n = 4, 25.0%) (P = 0.02). Long‐term administration of G‐CSF appears to influence the survival rate by reducing immunosuppressive IL‐12 p40 production.
Salivary matrix metalloproteinase‐8 in patients with and without coronary heart disease may indicate an increased susceptibility to periodontal disease
Authors: Furuholm J. , Sorsa T. , Qvarnström M. , Janket S.‐J. , Tervahartiala T. , Nuutinen P. , Meurman J. H.
Published: August 2006

Background and Objective:  Tissue destruction caused by periodontitis may increase the number of cytokines implicated in the pathogenesis of cardiovascular diseases. We measured the concentration of the leukocyte‐derived proteolytic enzyme, salivary neutrophil collagenase‐2 [matrix metalloproteinase‐8 (MMP‐8)], as a marker of periodontal disease and assessed its relationship to coronary heart disease (CHD). Our aim was to study whether salivary MMP‐8 levels were different among patients with and without CHD. The hypothesis was that patients with heart disease might present higher salivary MMP‐8 levels than cardiologically healthy controls.

Material and Methods:  Saliva samples were taken from 256 patients with CHD and from 250 matched controls with known oral and general health status. The MMP‐8 levels in saliva were analyzed by immunofluorometric assay, salivary albumin was assessed by enzyme‐linked immunosorbent assay (ELISA) and total protein was determined using the colorimetric method. We further investigated the molecular forms and isoform distribution of salivary MMP‐8 by western immunoblotting. The MMP‐8 results were adjusted for the number of teeth and salivary protein concentrations.

Results:  The adjusted logarithmic MMP‐8 values were 0.145 ± 0.245 µg/l in patients with CHD and 0.088 ± 0.115 µg/l in controls (p < 0.01). The respective MMP‐8 : total protein and MMP‐8 : albumin ratios were also significantly higher in CHD patients than in non‐CHD subjects.

Conclusion:  Elevated salivary MMP‐8 levels seemed to associate with CHD, suggesting more tissue breakdown as a result of periodontitis among the patients with heart disease.
The potential of melatonin in reducing morbidity–mortality after craniocerebral trauma
Authors: Maldonado M.D. , Murillo‐Cabezas F. , Terron M. P. , Flores L. J. , Tan D. X. , Manchester L. C. , Reiter R. J.
Published: August 2006

Abstract:  Craniocerebral trauma (CCT) is the most frequent cause of morbidity–mortality as a result of an accident. The probable origins and etiologies are multifactorial and include free radical formation and oxidative stress, the suppression of nonspecific resistance, lymphocytopenia (disorder in the adhesion and activation of cells), opportunistic infections, regional macro and microcirculatory alterations, disruptive sleep–wake cycles and toxicity caused by therapeutic agents. These pathogenic factors contribute to the unfavorable development of clinical symptoms as the disease progresses. Melatonin (N‐acetyl‐5‐methoxytryptamine) is an indoleamine endogenously produced in the pineal gland and in other organs and it is protective agent against damage following CCT. Some of the actions of melatonin that support its pharmacological use after CCT include its role as a scavenger of both oxygen and nitrogen‐based reactants, stimulation of the activities of a variety of antioxidative enzymes (e.g. superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase), inhibition of pro‐inflammatory cytokines and activation–adhesion molecules which consequently reduces lymphocytopenia and infections by opportunistic organisms. The chronobiotic capacity of melatonin may also reset the natural circadian rhythm of sleep and wakefulness. Melatonin reduces the toxicity of the drugs used in the treatment of CCT and increases their efficacy. Finally, melatonin crosses the blood–brain barrier and reduces contusion volume and stabilizes cellular membranes preventing vasospasm and apoptosis of endothelial cells that occurs as a result of CCT.
Effect of the catechol‐O‐methyltransferase val158met genotype on children’s early phases of facial stimuli processing
Authors: Battaglia M. , Zanoni A. , Giorda R. , Pozzoli U. , Citterio A. , Beri S. , Ogliari A. , Nobile M. , Marino C. , Molteni M.
Published: August 2006

The ability to process and identify human faces matures early in life, is universal and is mediated by a distributed neural system. The temporal dynamics of this cognitive–emotional task can be studied by cerebral visual event‐related potentials (ERPs) that are stable from midchildhood onwards. We hypothesized that part of individual variability in the parameters of the N170, a waveform that specifically marks the early, precategorical phases of human face processing, could be associated with genetic variation at the functional polymorphism of the catechol‐O‐methyltransferase (val158met) gene, which influences information processing, cognitive control tasks and patterns of brain activation during passive processing of human facial stimuli. Forty‐nine third and fourth graders underwent a task of implicit processing of other children’s facial expressions of emotions while ERPs were recorded. The N170 parameters (latency and amplitude) were insensitive to the type of expression, stimulus repetition, gender or school grade. Although limited by the absence of met‐ homozygotes among boys, data showed shorter N170 latency associated with the presence of 1‐2 met158 alleles, and family‐based association tests (as implemented in the pbat version 2.6 software package) confirmed the association. These data were independent of the serotonin transporter promoter polymorphism and the N400 waveform investigated in the same group of children in a previous study. Some electrophysiological features of face processing may be stable from midchildhood onwards. Different waveforms generated by face processing may have at least partially independent genetic architectures and yield different implications toward the understanding of individual differences in cognition and emotions.
Intralesional therapy of metastatic spreading melanoma with beta‐interferon
Authors: Rapprich Harriet , Hagedorn Manfred
Published: August 2006

A 74‐year‐old female patient developed multiple local metastases after excision of a nodular melanoma of the left cheek. There was no regression after treatment with dacarbazine (DTIC®) and radiotherapy. After treatment with intralesional interferon‐β, the metastases regressed completely. The dosage was 5 million IU interferon‐β (Fiblaferon®) three times weekly with courses of two and four weeks, separated by a month. Except for local swelling and inflammation, no side effects occurred. Five years after completing therapy, the patient is still tumor‐free.