bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Parameterization of Surface Roughness at Regional Scales
Authors: Bou-Zeid Elie , Parlange Marc B. , Meneveau Charles
Published: January 2007

A parameterization for surface roughness and blending height at regional scales, under neutral atmospheric stability, is studied and tested. The analysis is based on a suite of large-eddy simulations (LES) over surfaces with varying roughness height and multiple variability scales. The LES are based on the scale-dependent Lagrangian dynamic subgrid-scale model, and the surface roughnesses at the ground are imposed using the rough-wall logarithmic law. Several patterns of roughness distribution are considered, including random tiling of patches with a wide distribution of length scales. An integral length scale, based on the one-dimensional structure function of the spatially variable roughness height, is used to define the characteristic surface variability scale, which is a critical input in many regional parameterization schemes. Properties of the simulated flow are discussed with special emphasis on the turbulence properties over patches of unequal roughness. The simulations are then used to assess a generalized form of the parameterization for the blending height and the equivalent surface roughness at regional scales that has been developed earlier for regular patterns of surface roughness (regular stripes). The results are also compared with other parameterizations proposed in the literature. Good agreement is found between the simulations and the regional-scale parameterization for the surface roughness and the blending height when this parameterization is combined with the characteristic surface variability scale proposed in this paper.
Intelligent instrumentation
Authors: Clarke D. W.
Published: January 2007

With the falling cost of microelectronics, intelligent instruments are increasingly used in process control. They are designed to integrate into data networks such as Fieldbus, so that remote users can access internal values and reconfigure their function. It is argued that such instruments should exploit models of the plant’s data generation to achieve optimal filtering, of their own internal behaviour as verified by self-testing, and of the user’s needs. A figure-of-merit for sensor signal processing is defined, and some fundamental results indicating the benefit of appropriate signal models are deduced. The value of validation, in which diagnosed faults affect the measurement status and its uncertainty, is emphasized. Examples of a self-validating thermocouple, a dissolved-oxygen sensor and a flow-control valve are described together with some guidelines about practical implementation.
Relay autotuning: a use of old ideas in a new setting
Authors: Atherton D. P.
Published: January 2007

The paper discusses the relatively new approach of relay autotuning and shows how a sound understanding of the approach requires knowledge of two approaches introduced early in the search for methods to study nonlinear control systems. The two approaches - the describing function method and procedures for evaluating limit cycles exactly in relay systems - are first reviewed. After a short section on techniques for choosing parameters of fixed controllers it is shown how relay autotuning can be used for PID controllers based on either plant critical point information or the estimation of a plant model. Finally some examples are given which illustrate the controller design techniques presented.
Genetic algorithms for scheduling: incorporation of user preferences
Authors: Shaw K. J. , Fleming P. J.
Published: January 2007

Genetic algorithms (GAs) are optimization tools that simulate evolutionary processes in order to develop solutions for a wide range of optimization problems. In recent years, they have increasingly gained acceptance in industry, as confidence improves in their abilities to solve complex problems that have previously appeared to be unsolvable. One example of an industrial application for GAs is scheduling, an area that can present many difficulties for the manufacturing industry. Much of the advantage of GAs lies in the flexibility with which they may be implemented. In this work, two practically motivated improvements are made to the basic GA used for schedule optimization, to allow the technique to include additional complexities that arose in an industrial application. The first improvement enables the GA to deal with uncertain information in the factory, and illustrates the ability of the GA to aid scheduling decision-making. The second improvement is the application of the GA to multiobjective optimization, in the form of a multiobjective genetic algorithm (MOGA). In this way, the GA can solve problems with several conflicting or incompatible objectives, and allow the user to interact with the process as it evolves solutions. These variations permit the inclusion of specific user preferences, extending the scheduling choices available, whilst still ensuring that global optimization performance is not diminished. Thus the schedule optimization system becomes more interactive, accurate and effective for manufacturing schedule optimization.
Nonlinear dynamic tools for characterizing abdominal electromyographic signals before and during labour
Authors: Sabry-Rizk M. , Zgallai W. , Carson E. R. , Hardiman P. , MacLean A. , Grattan K. T.V.
Published: January 2007

This paper presents evidence that electromyographic signals during healthy uterine contractions may have a fractal temporal structure. Healthy uterine contractions start from the 16th week of the human pregnancy. These contractions become more and more frequent and increase in strength up to the end of pregnancy. Here we investigate the possibility that time series generated by labour physiological control systems may be members of a special class of complex processes which are noise driven and may require more than one exponent to characterize their fractal scaling properties. We use a simplified version of the Hurst analysis algorithm to detect fractility in abdominal electromyographic signals (AEMG) and quadratic Volterra structures to estimate nonlinearity in them. We uncover a loss of chaoticity in very early segments of uterine contractions for typical cases of failure to progress in the first stage of labour and ending with surgical procedure (Caesarean section). Results are shown for representatives of the following groups: (1) healthy pregnancy, spontaneous labour and parturition, (2) full term at 40 weeks, prolonged labour (arbitrarily defined as lasting more than 12 h) and ending with Caesarean delivery, and (3) preterm spontaneous labour (less than 37 weeks).
Clinical implementation of advanced control in anaesthesia
Authors: Linkens D. A. , Abbod M. F. , Peacock J. E.
Published: January 2007

A multi-sensor fusion system for monitoring and control of depth of anaesthesia in the operating theatre is described. Two types of anaesthesia measures are considered, the first being based on auditory evoked responses, while the second measure is based on cardiovascular system signals. The first measure is based on analysis of the signal using wavelets and a neuro-fuzzy system, while the second measure is based on analysis of the measurements using a rule-based fuzzy logic system. The two measures are combined to give a final level of depth of anaesthesia using another rule-based fuzzy logic system. The depth of anaesthesia level is fed back to a target controlled infusion system (TCI) to control the infusion of the drug propofol for maintaining a constant level of depth of anaesthesia.
Control aspects of clinical support systems
Authors: Blom J. A. , Hoeksel S. A.A.P.
Published: January 2007

Standard control theory approaches alone are not sufficient for the design of clinical control systems. Additional medical expertise has to be incorporated in order to achieve high quality and robust performance. The main problem to be overcome is the fact that no real time identifiability of the patient’s characteristics can be guaranteed, due to the low signal-to-noise ratio of the feedback signals in combination with unknown and possibly rapid changes in patient characteristics. Solutions to this problem are suggested by the manual control methods of expert clinicians. One solution is to adjust the controller’s parameters through monitoring its control performance. Another solution, in multi-input-multi-output controllers, is to allow variation of only one drug at a time. In addition, sometimes other goals are more important than keeping feedback signals at setpoint values. These goals need to be part of the clinical support system as well. The success of adding clinician-derived heuristics to standard control systems is illustrated by a number of single and multiple drug controllers, whose goal it is to support the clinician in the stabilization of the systemic arterial and/or the pulmonary artery pressure during and after cardiac surgery.
Decentralized tracking for a class of interconnected nonlinear systems using fuzzy variable structure control with application to a drill and dry jet mixing machine
Authors: Cheng X. Y. , Leung T. P.
Published: January 2007

In this paper we have presented a novel decentralized fuzzy variable structure controller (DFVSC) for the tracking problem of a class of uncertain interconnected nonlinear systems. The decentralized variable structure control principle is utilized to deal with model uncertainties, nonlinear interactions between subsystems, control input gain uncertainties and external disturbances. A fuzzy logic function is applied to eliminate the chattering problem and improve the tracking performance. The proposed DFVSC is applied to a drill and dry jet mixing machine. The performances of the proposed DFVSC are compared with the conventional decentralized variable structure control (DVSC) and suboptimal PID control (SPIDC) by computer simulation. Simulation results show that the proposed DFVSC can achieve excellent transient performance, faster response, better precision and good robustness against system parameter uncertainties, various airflow conditions and uncertain time-varying external disturbance.
Design considerations for a Model Reference Fuzzy Adaptive Controller
Authors: Banerjee J. S. , Jones K. O. , Williams D.
Published: January 2007

A major difficulty with fuzzy logic control is the development of an adequate rule-base and its modification such that the desired performance is maintained with changing operating conditions. Rule elicitation is a lengthy process and specific to each application. To overcome this problem, the concepts of self-organizing fuzzy logic control and other self-learning approaches have been widely investigated. In this paper, a different type of learning fuzzy control algorithm has been discussed. The control method has been called Model Reference Fuzzy Adaptive Control (MRFAC) indicating the method of adaptation. A reference model is used to provide performance feedback for automatically synthesizing and modifying a fuzzy controller’s rule-base on-line, as new information on how to control the system is gathered. The method employs a simple iterative adaptation algorithm compared to other methods in the literature. The design issues involving the method have been thoroughly investigated. Extensive simulation tests have been executed on the MRFAC to examine the effectiveness of choice of its different parameters. The results provide an useful insight into the design considerations involving the MRFAC.
Laser inspection and modelling of shoe components in automatic stitching
Authors: Crispin A. J. , Pokric B. , Rankov M. , Reedman D. C. , Taylor G. E.
Published: January 2007

This paper describes work relating to the laser-based inspection of shoe uppers loaded into a pallet prior to the sewing operation. Shape modelling from scanned edge data is divided into two steps: significant point detection and curve fitting. Methods for identifying significant points such as knots and corner points are discussed, with examples given for a range of typical shoe component shapes. Techniques are proposed for stitch path generation from an edge model, the detection of badly loaded components and the detection of local defects along an edge.
Geomorphometry -diversity in quantitative surface analysis
Authors: Pike Richard J.
Published: January 2007

A widening variety of applications is diversifying geomorphometry ( digital terrain modelling), the quantitative study of topography. An amalgam of earth science, mathematics, engineering and computer science, the discipline has been revolutionized by the computer manipulation of gridded terrain heights, or digital elevation models (DEMs). Its rapid expansion continues. This article reviews the remarkable diversity of recent morphometric work in 15 selected topics and discusses their significance and prospects. The quantitative analysis of industrial microsurface topography is introduced to the earth science community. The 14 other topics are Internet access to geomorphometry; global DEMs; DEM modelling of channel networks; self-organized criticality; fractal and wavelet analysis; soil resources; landslide hazards; barchan dunes; harvesting wind energy; sea-ice surfaces; sea-floor abyssal hills; Japanese work in morphometry; and the emerging fields of landscape ecology and image understanding. Closing remarks note reasons for the diversity within geomorphometry, speculate on future trends and recommend creating a unified field of surface representation.
Hydrological modelling using artificial neural networks
Authors: Dawson C. W. , Wilby R. L.
Published: January 2007

This review considers the application of artificial neural networks (ANNs) to rainfall-runoff modelling and flood forecasting. This is an emerging field of research, characterized by a wide variety of techniques, a diversity of geographical contexts, a general absence of intermodel comparisons, and inconsistent reporting of model skill. This article begins by outlining the basic principles of ANN modelling, common network architectures and training algorithms. The discussion then addresses related themes of the division and preprocessing of data for model calibration/validation; data standardization techniques; and methods of evaluating ANN model performance. A literature survey underlines the need for clear guidance in current modelling practice, as well as the comparison of ANN methods with more conventional statistical models. Accordingly, a template is proposed in order to assist the construction of future ANN rainfall-runoff models. Finally, it is suggested that research might focus on the extraction of hydrological ‘rules’ from ANN weights, and on the development of standard performance measures that penalize unnecessary model complexity.
Remote sensing of animals
Authors: Gillespie Thomas W.
Published: January 2007

The improved accuracy and precision of animal tracking via satellites has made a significant impact on quantifying large-scale biogeographic patterns for a variety of taxa with important implications for conservation and natural resource management. This paper reviews research undertaken from 1995 to 1999 to provide an overview of advances in the remote sensing of animal movements in both terrestrial and marine environments and to identify promising trends for biogeographic research in the twenty-first century. Remote sensing of animals by satellite provides a new method to test a number of biogeographic hypotheses related to migration and can identify a number of environmental correlates associated with the distributions of species. Tracking of smaller species and increases in sample size are sure to occur as transmitter size and cost continue to decrease in the next decade. Geographers can significantly contribute to the understanding of species dispersal and distributional patterns by combining real-time and archived global and regional datasets with existing data from past studies and future research projects. Only four studies used GIS data or remote sensed imagery in this review, while the remaining studies cited used simple digital line graphs of countries, topography, land and sea boundaries.
Snowmelt runoff models
Authors: Ferguson R. I.
Published: January 2007

Models that predict meltwater runoff at a daily timescale are important in water resource management, flood hazard assessment and climate-change impact studies. This article identifies four basic components of such models: meteorological extrapolation, snowmelt estimation at a point, snow-cover depletion and runoff routing. Alternative ways of handling these are discussed, with emphasis on the contrasting treatments in two widely used models: HBV and SRM. Many of the issues in meltwater modelling reflect wider debates in hydrological and environmental modelling, including problems of complexity vs. simplicity, the appropriate level of spatial disaggregation, parameter identification and calibration, and internal validation. In reviewing current trends emphasis is placed on the potential and limitations of fully distributed models, problems in using energy-balance rather than temperature-index melt models at basin scale, ways to deal with spatial variability in snow cover, and the value and limitations of earth observation data.
The Role of Parents and Partners in the Pregnancy Behaviors of Young Latinas
Authors: Gilliam Melissa L.
Published: January 2007

Pregnancy among young Latinas demands attention. These teens have higher birthrates than other teen populations. Seven focus groups ( N = 40) were conducted with Latinas to explore how relationships between young Latinas and their mothers, fathers, and male partners contribute to teen pregnancy. ATLAS/ti (a qualitative data analysis software program) was used to assist in coding and analysis of data. Salient themes were identified. Mothers rely on cultural values regarding sexuality and pregnancy outside of marriage and fear about birth control to dissuade their daughters from pregnancy. Fathers echo these traditional messages. Open communication about sexuality and contraception rarely occurs. Male partners increase pregnancy susceptibility given the difficulty with negotiating condom use. It is important that research and prevention programs recognize the social context in which pregnancy prevention and susceptibility occur.
The Prevalence and Comorbidity Between Delinquency, Drug Abuse, Suicide Attempts, Physical and Sexual Abuse, and Self-Mutilation Among Delinquent Hispanic Females
Authors: Cuellar Jeanette , Curry Theodore R.
Published: January 2007

Representative data show that drug abuse, delinquency, and suicide attempts are major concerns among adolescent Hispanic females. Although comorbidity research indicates that such problems tend to be related to each other, this research largely neglects Hispanic females. Using data from presentence investigations on 141 Hispanic girls sentenced to probation, the present research assesses the prevalence of drug abuse, delinquency, suicide attempts, physical and sexual abuse, and self-mutilation as well as the extent of comorbidity among these problems. Results show very high levels of violent delinquency, marijuana abuse, suicide attempts, and self-mutilation. Comorbidity was also extensive between suicide attempts, self-mutilation, physical and sexual abuse, and between these variables and drug abuse and certain forms of delinquency. This study is among the first to describe the problems of adolescent Hispanic females and highlights the need for additional research to better understand and address the serious issues many of these young women face.
Toxnet: A computerized collection of toxicological and environmental health information
Authors: Fonger George Charles , Stroup Dorothy , Thomas Phillip L. , Wexler Philip
Published: January 2007

The Toxicology and Environmental Health Information Program, managed by the National Library of Medicine's Division of Specialized Information Services, provides access to a number of online bibliographic and factual computer files concerned with the toxicology, safety and handling, and environmental fate of chemicals, along with other files that cover genetic toxicology, developmental and reproductive toxicology, mutagenesis, carcinogenesis and toxic chemical releases.
The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro
Authors: Ostby Joseph , Kelce William R. , Lambright Christy , Wolf Cynthia J. , Mann Peter , Gray L. Earl
Published: January 2007

Procymidone is a dicarboximide fungicide structurally related to the well-characterized fungicide vinclozolin. Vinclozolin metabolites bind to mammalian androgen receptors (AR) and act as AR antagonists, inhibiting androgen-dependent gene expression in vivo and in vitro by inhibiting AR-binding to DNA. The current study was designed to determine if procymidone acted as an AR antagonist in vitro and to describe the dosage levels of procymidone that alter sexual differentiation in vivo. In vitro, procymidone inhibited androgen from binding the human AR (hAR) in COS (monkey kidney) cells transfected with hAR at 3.16 μM. In vitro, procymidone acted as an androgen antagonist, inhibiting dihydrotestosterone (DHT)-induced transcriptional activation at 0.2 μM in CV-1 cells (cotransfected with the hAR and a MMTV-luciferase reporter gene). In vivo, maternal procymidone exposure at 0, 25, 50, 100, or 200 mg kg−1 day−1 during gestation and early lactation (gestational day 14 to postnatal day 3) altered reproductive development of male offspring at all dosage levels tested. Male offspring exhibited shortened anogenital distance (at 25 mg kg−1 day−1 and above), permanent nipples, reduced weight of several androgen-dependent tissues (levator ani and bulbocavernosus muscles, prostate, seminal vesicles, Cowper's gland and glans penis), and malformations (hypospadias, cleft phallus, exposed os penis, vaginal pouch, hydronephrosis, occasional hydroureter, epididymal granulomas, and ectopic, undescended testes). In addition, perinatal procymidone treatment had a marked effect on the histology of the lateral and ventral prostatic and seminal vesicular tissues of the offspring (at 50 mg kg−1 day−1 and above). These effects consisted of fibrosis, cellular infiltration, and epithelial hyperplasia. This constellation of effects is similar to that produced by perinatal exposure to vinclozolin. However, procymidone appears to be slightly less potent in inducing malformations than vinclozolin by a factor of about two. In summary, the antiandrogenic activity of procymidone was demonstrated in vivo and in vitro in cell lines transfected with hAR. Since the role of androgens in mammalian sexual differentiation is highly conserved, it is likely that humans would be adversely affected by procymidone in a predictable manner if the human fetus was exposed to sufficient levels during critical stages of intrauterine and neonatal life.
Neural sensitization model for multiple chemical sensitivity: overview of theory and empirical evidence
Authors: Bell Iris R. , Baldwin Carol M. , Fernandez Mercedes , Schwartz Gary E.R.
Published: January 2007

This paper summarizes theory and evidence for a neural sensitization model of hyperresponsivity to low-level chemical exposures in multiple chemical sensitivity (M]CS). MCS is a chronic polysymptomatic condition in which patients report illness from low levels of many different, structurally unrelated environmental chemicals (chemical intolerance, CI). Neural sensitization is the progressive host amplification of a response over time from repeated, intermittent exposures to a stimulus. Drugs, chemicals, endogenous mediators, and exogenous stressors can all initiate sensitization and can exhibit cross-sensitization between different classes of stimuli. The properties of sensitization overlap much of the clinical phenomenology of MCS. Animal studies have demonstrated sensitization to toluene, formaldehyde, and certain pesticides, as well as cross-sensitization, e.g., formaldehyde and cocaine. Controlled human studies in persons with self-reported CI have shown heightened sensitizability in the laboratory to nonspecific experimental factors and to specific chemical exposures. Useful outcome measures include spectral electroencephalography, blood pressure, heart rate, and plasma beta-endorphin. Findings implicate, in part, dopaminergic mesolimbic pathways and limbic structures. A convergence of evidence suggests that persons with MCS or with low-level CI may share some characteristics with individuals genetically vulnerable to substance abuse: (a) elevated family histories of alcohol or drug problems; (b) heightened capacity for sensitization of autonomic variables in the laboratory; (c) increased amounts of electroencephalographic alpha activity at rest and under challenge conditions over time. Sensitization is compatible with other models for MCS as well. The neural sensitization model provides a direction for further systematic human and animal research on the physiological bases of MCS and CI.
Evolutionary game theory and multiple chemical sensitivity
Authors: Newlin David B.
Published: January 2007

Newlin's [Newlin D.B. Evolutionary game theory of tolerance and sensitization in substance abuse. Paper presented to the Research Society on Alcoholism, Hilton Head, SC, 1998] evolutionary game theory of addictive behavior specifies how evolutionarily stable strategies for survival and reproduction may lead to addiction. The game theory of multiple chemical sensitivity (MCS) assumes that: (1) the MCS patient responds to low-level toxicants as stressors or as direct threats to their survival and reproductive fitness, (2) this activates the cortico-mesolimbic dopamine system, (3) this system is a survival motivation center—not a `reward center', (4) the subject emits a counter-response that is in the same direction as the naive response to the chemicals, (5) previously neutral stimuli associated with chemicals also trigger conditioned responses that mimic those to the chemicals, (6) these counter-responses further activate the dopaminergic survival motivation system, and (7) this produces a positive feedback loop that leads to strong neural sensitization in these structures and in behavior controlled by this system, despite a small initial response. Psychologically, the MCS patient with a sensitized cortico-mesolimbic dopamine system is behaving as though his/her survival is directly threatened by these chemicals. Non-MCS subjects have counter-responses opposite in direction to those of the chemicals and show tolerance. An autoshaping/sign-tracking model of this game is discussed. This evolutionary game makes several specific, testable predictions about differences between MCS subjects, non-MCS controls, and substance abusers in laboratory experiments, and between sensitized and nonsensitized animals.
Mechanisms of allergy and chemical sensitivity
Authors: Meggs William J.
Published: January 2007

Allergy and chemical sensitivity are closely related disorders in which environmental exposures produce inflammatory reactions. For allergy, environmental proteins bind to IgE antibody on mast cells leading to the release of inflammatory mediators. In chemical sensitivity, low molecular weight chemicals bind to chemoreceptors on sensory nerve C-fibers leading to the release of inflammatory mediators. Clinical manifestations are similar in the two conditions. The overlap between the two conditions has a basis in mechanism, so the similarity of clinical manifestations and high percentage of individuals with both conditions may have a biological basis. Chronic exposures can lead to adaptation phenomena. Depression has been associated with both allergy and chemical sensitivity. Both the allergic and chemical irritant responses may be subjected to conditioning so that the response is triggered by other stimuli. Evidence for conditioning is strongest for allergy. Both allergy and chemical sensitivity can be acquired in association with irritant exposures.
Exacerbation of chemical sensitivity: a case study
Authors: Miller C. S. , Gammage R. B. , Jankovic J. T.
Published: January 2007

We report exacerbation of symptoms and chemical intolerances in three of four self-described chemically sensitive women following relocation to a newly constructed office building. Levels of total volatile organic compounds (TVOCs) in this building prior to occupancy were approximately 200 μg/m3 (toluene equivalent units) with a myriad of individual components present. By day 50 after occupancy, the concentration of TVOCs in the building dropped to approximately 50 μg/m3. Nevertheless, three women reported significant worsening of their symptoms with spreading of their sensitivities to previously tolerated chemical exposures. One woman relocated to another building, while the other two managed their symptoms by reducing time spent in the building or by using a room air cleaner. By day 600 following occupancy, although TVOCs had increased significantly (perhaps due to cleaning agents), there were fewer individual VOCs present in the air, and some of the women were able to tolerate the air in the building. We conclude that complex mixtures of VOCs at very low levels tolerated by the majority of building occupants may pose problems for persons who report pre-existing chemical sensitivities. TVOC measurements may not correlate with symptoms in these individuals. Reasonable accommodations by an employer can reduce problem exposures, making it possible for some affected individuals to continue productive employment.
Development of a brief questionnaire for screening for multiple chemical sensitivity syndrome
Authors: Hu Howard , Stern Amy , Rotnitzky Andrea , Schlesinger Lauren , Proctor Susan , Wolfe Jessica
Published: January 2007

The objective of this study was to identify a parsimonious set of questions that has high sensitivity and specificity for screening for individuals with multiple chemical sensitivity (MCS) syndrome. We performed a cross-sectional survey using a case-control design. Subjects were derived from patients seen at an academically based Occupational and Environmental Medicine Clinic. Cases consisted of patients who fulfilled the Cullen definition for MCS. Controls were patients who had diagnoses excluding MCS and asthma and who were matched to cases by age and sex. Cases and controls filled out a screening questionnaire that, among things, elicited responses as to whether and how subjects reacted to 122 different types of environmental exposures. Data from 44 pairs of cases and controls were available for analysis. The average age of cases was 50.2 years, and 91% was female. Among cases, the most common exposure that was purported to incite MCS was `indoor air quality contaminants (unspecified)' (59%), followed by solvents (27.3%). After randomly excluding five cases and controls, a stepwise selection procedure for two-group discriminant analysis revealed that the main contributors to the discrimination of the remaining cases and controls were self-reported reactions to copy machine emissions, marking pens, aftershave, window cleaner, nylon fabric, pine-scented products, and rayon material. When a positive response to these factors was used as the sole method for discriminating cases from controls, only one of 41 cases was misclassified as a control while none of the controls was misclassified as a case. When the same method was applied to the five excluded cases and five excluded controls, only one of the five cases was misclassified while none of the five controls was misclassified as a case. Among patients with MCS defined by the Cullen criteria in this clinical setting, having a reaction to these seven common potential exposures comprised a parsimonious set of factors that discriminated between MCS patients and age- and sex-matched normal controls. These questions may have utility in screening for individuals with MCS in general population survey studies.
Agency for Toxic Substances and Disease Registry's 1997 priority list of hazardous substances. Latent effects—carcinogenesis, neurotoxicology, and developmental deficits in humans and animals
Authors: Ostrowski Stephanie R. , Wilbur Sharon , Chou C.-H. Selene J. , Pohl Hana R. , Stevens Yee-Wan , Allred Phillip M. , Roney Nickolette , Fay Mike , Tylenda Carolyn A.
Published: January 2007

In support of Superfund re-authorization legislation, the Division of Toxicology of the Agency for Toxic Substances and Disease Registry (ATSDR) prepared a chemical-specific consultation document for Congress that identified those chemicals with carcinogenic, neurological, or developmental adverse effects having a latency period longer than 6 years. The review was limited to the top 50 substances listed on ATSDR's 1997 Priority List of Hazardous Substances (Priority List). Among the top 50 chemicals, a review of the technical literature indicated that 38 (76%) were classified as “reasonably anticipated,” “possibly,” or “probably” capable of causing cancer in humans, based either on human and animal data. Eight chemicals (16%) had well-established cancer latency periods in humans of 6 years or more following exposure. Three substances (6%)—arsenic, creosote, and benzidine—had data indicating latency periods longer than 6 years. The technical literature review likewise confirmed the potential for neurological and development effects with a latency of 6 years. Twenty-seven (54%) of the top 50 substances caused acute and/or chronic neurotoxic effects; a number of these also caused neurological effects that persisted beyond 6 years (or the equivalent in animal studies) such as: behavioral problems, neurological deficiencies, reduced psychomotor development, cognitive deficiencies, and reduced IQ. Twenty-eight substances (56%) caused adverse developmental effects in offspring of exposed individuals or animals including increased fetal and infant mortality, decreased birth weights and litter sizes, and growth delays. Latency periods for related chemicals are expected to be similar due to structural and toxicological similarities.
The impact of introducing pre-printed chemotherapy medication charts to a day chemotherapy unit
Authors: Tran May
Published: January 2007

Context. The cytotoxic regimens used in the contemporary day chemotherapy unit are often complicated and present numerous opportunities for error, inadvertent misadventure in prescription orders and variations in drug administration. The introduction of pre-printed chemotherapy charts for each protocol was introduced to minimise incorrect or incomplete prescribing by medical staff.

Objective. To assess the benefits of introducing pre-printed chemotherapy charts into a day chemotherapy unit.

Method. Commonly used protocols in the unit were assessed and assembled into pre-printed chemotherapy charts. The doses and administration details of each protocol were reviewed by chemotherapy nursing staff, medical staff and the oncology pharmacist before the charts were finalised. Clinical interventions performed by the oncology pharmacist were recorded for 1 month prior and 1 month following the introduction of the pre-printed charts. Nursing and medical staff were surveyed on their level of satisfaction with the pre-printed chemotherapy charts.

Results. Prior to the introduction of the pre-printed charts, 74% of chemotherapy charts were problematic requiring multiple pharmacy interventions per chart. After the introduction of the pre-printed charts, 43% of charts were problematic requiring an average of one pharmacy intervention per chart. Pharmacy interventions were significantly reduced, which has resulted in a significant reduction in workload for the oncology pharmacist. The medical and nursing staff strongly supported the introduction of the pre-printed charts. There has been a reduction in the variation of orders amongst medical officers, reduction in prescribing errors, decreased anxiety amongst staff and better work-flow in the Day Chemotherapy Unit.

Conclusion. Pre-printed chemotherapy medication charts have promoted a more methodical approach to the prescribing and administration of chemotherapy, which has resulted in a more efficient day chemotherapy unit.
A review of dolasetron as management of nausea and vomiting in cancer patients
Authors: Valley Amy W.
Published: January 2007

Objective. To systematically review the literature about the pharmacology, pharmacokinetics, efficacy, dosing, and adverse effects of dolasetron, and to define its role in the management of chemotherapy-and radiation-induced nausea and vomiting.

Data Synthesis. A MedLine search was conducted using 5-HT3-receptor antagonists, antiemetics, chemotherapy toxicity, dolasetron, emesis, nausea, and vomiting as search terms. Reference lists and bibliographies of pertinent articles were also identified and reviewed. Both preclinical and clinical literature were reviewed and analyzed.

Data Synthesis. Dolasetron is a serotonin type 3 (5-HT3)-receptor antagonist with potent antiemetic effects in the management of nausea and vomiting. Following administration, dolasetron is rapidly converted to hydrodolasetron, which is believed to be responsible for the drug's antiemetic activity. Results of multiple studies have demonstrated the efficacy of this agent in the prevention of chemotherapy-induced emesis, including that induced by cisplatin. As a single agent, dolasetron produces a complete response rate (RR) in 44% to 57% of patients treated with cisplatin (≥70 mg/m2) and in 59% to 80% of patients treated with moderately emetogenic chemotherapy, such as cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy. When combined with dexamethasone, the RRs are increased. Dolasetron is well tolerated, with headache (24%) and diarrhea (12%) the most commonly reported adverse effects. The efficacy and safety of dolasetron are comparable to those observed with other 5-HT3-receptor antagonists. According to four recently published clinical practice guidelines for use of antiemetics, dolasetron is an appropriate first-line option for the prevention of nausea and vomiting due to moderately to highly emetogenic chemotherapy. Further clinical trials will determine the optimal dose and the role of this highly effective antiemetic agent for other purposes, such as treatment of delayed emesis and emesis resulting from radiation therapy and high-dose chemotherapy followed by bone marrow transplantation.
Novel treatment for the management of ifosfamide neurotoxicity: Rationale for the use of methylene blue
Authors: Donegan Sarah
Published: January 2007

Objective. To provide an overview of the proposed pathophysiology of ifosfamide encephalopathy and the role of methylene blue for the treatment and prevention of this toxicity.

Data Source. A Medline search using the terms ‘‘ifosfamide encephalopathy’’ and ‘‘methylene blue’’ was conducted for the period of 1990-2001. The reference lists from retrieved articles were reviewed

Data Extraction. The author reviewed the retrieved material and included animal and pharmacokinetic data related to ifosfamide and the pathophysiology of ifosfamide neurotoxicity. Additionally, preclinical data and case reports describing the clinical use and rationale for methylene blue were included.

Data Synthesis. Encephalopathy is a unique toxicity described with ifosfamide, but not with cyclophosphamide. Ifosfamide undergoes a secondary ‘‘deactivation’’ metabolic pathway to yield dechloroethylated metabolites and chloroacetalde-hyde. Chloroacetaldehyde is a metabolite that contributes to both the nephrotoxicity and neurotoxicity described with ifosfamide. Chloroacetaldehyde (or a dechloroethylated metabolite) may exert neurotoxic effects by one or more of the following mechanisms: (a) direct neurotoxic damage, (b) depletion of central nervous system (CNS) glutathione level, or (c) inhibition of mitochondrial oxidative phosphorylation resulting in impaired fatty acid metabolism. The biochemical derangements described with this acute toxicity appear to mimic a neonatal mitochondrial disorder, for which methylene blue has been used. Methylene blue has been shown to restore and maintain mitochondrial respiration and therefore can be used to correct or prevent acute neurotoxic effects. Methylene blue has been used to treat moderate to severe cases of ifosfamide neurotoxicity and has also been used prophylactically to prevent encephalopathy in high-risk conditions with the use of oral and bolus iv ifosfamide regimens. Methylene blue may be useful in the treatment of grade III or IV neurotoxicity or in those patients with recurrent neurological symptoms associated with ifosfamide administration. The use of prophylactic or concurrent administration of methylene blue with ifosfamide requires further clinical evaluation.
Viability of microorganisms in bags of cytotoxic drugs
Authors: Favier Bertrand , Latour Jean François , Fuhrmann Christine
Published: January 2007

Objectives. The aim of this report was to study the viability of five microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, S epidermidis and Candida albicans) in chemotherapeutic solutions made up 1-2 days before administration.

Methods. The four preparations studied were 0.5 mg/mL cisplatin, 1.8 mg/mL doxorubicin, 5 mg/mL 5-fluorouracil, and 5 mg/mL cyclophosphamide. All four solutions were tested at a temperature of 258C, and doxorubicin and cyclophosphamide were also tested at 48C. The concentrations of the microorganisms in the preparations were determined 2, 24, 48, 72, and 96 hours after inoculation.

Results. No microbial growth was found; on the contrary, bacterial and fungal growth decreased rapidly and substantially with cisplatin and doxorubicin (by 2log after 24 hours), moderately with 5-fluorouracil, and weakly or not at all with cyclophosphamide. Refrigeration at 48C appeared to slow the decreased growth of the microorganisms when compared with storage at 258C.

Conclusion. As no bacterial or fungal growth was seen in the four solutions of cytotoxic agents tested, the practice of preparing such solutions under a hood with vertical laminar ventilation according to good practice in the preparation of sterile solutions 1 or 2 days before administration to patients is validated. J Oncol Pharm Practice (2001) 6, 167-171.
Pharmacologic study of Cremophor EL in cancer patients with impaired hepatic function receiving paclitaxel
Authors: Panday Vinodh R Nannan , Huizing Manon T , van Tellingen Olaf , Hakvoort Robert A , Willemse Pax H B , De Graeff Alexander , Vermorken Jan B , Beijnen Jos H
Published: January 2007

Aims. Cremophor EL (CrEL) (polyoxyethylene glycerol triricinoleate 35) is used as a pharmaceutical vehicle for the formulation of several drugs, including the anticancer agent paclitaxel (Taxolt). This excipient has been associated with hypersensitivity reactions and affects the pharmacokinetic properties of paclitaxel, especially in patients with hepatic dysfunction. In this study, we investigated the pharmacokinetics of CrEL in a specific population of patients.

Methods. Patients were stratified in five cohorts based on hepatic function, received paclitaxel for metastatic disease, and were monitored pharmacokinetically during course 1 and course 2. CrEL levels were measured and related to the extent of hepatic dysfunction.

Results. A total of 46 courses were measured from 27 patients. CrEL pharmacokinetic parameters in patients with mild hepatic dysfunction (cohorts I-III) were not significantly different from patients with normal hepatic function, whereas the patients with moderate to severe hepatic dysfunction (cohorts IV and V) displayed a different pharmacokinetic profile.

Conclusions. The results indicate a nonlinear pharmacokinetic behavior of CrEL. No differences were found for CrEL pharmacokinetics when course 1 was compared with course 2 per cohort. A possible influence of the specific characteristics of patients with severe hepatic dysfunction, such as altered physiologic and metabolic states, could play a role in the deposition of CrEL.
Risk of breast cancer associated with hormone replacement therapy
Authors: Dopp John M , Kolesar Jill M
Published: January 2007

Purpose. The primary objective of this paper is to provide a brief overview of the risk of breast cancer associated with hormone replacement therapy (HRT) in healthy postmenopausal women, in breast cancer survivors, and in women at increased risk for breast cancer.

Data Sources. The literature was reviewed through a MEDLINE search covering the years 1988 to 1999. Relevant articles cited in the literature obtained by MEDLINE searching were also considered. The following terms were searched: estrogen, progesterone, breast cancer, and HRT. The search was restricted to the English language.

Data Extraction. The current literature is reviewed with regard to the risk of breast cancer associated with HRT in healthy postmenopausal women, in breast cancer survivors, and in women at increased risk for breast cancer.

Data Synthesis. HRT is used commonly in post-menopausal women to alleviate both climacteric menopausal symptoms such as hot flashes and urogenital atrophy and to reduce the degree and frequency of osteoporosis. However, exposure to estrogen is one of the most important risk factors for breast cancer, and HRT is a relative contraindication in women with a personal history of breast cancer. The majority of epidemiological literature indicates that healthy women taking short-term HRT are not at increased risk of developing breast cancer. In breast cancer survivors, HRT does not appear to increase the risk of relapse. Some epidemiological studies show that women with a family history of breast cancer are at a substantially increased risk of developing breast cancer when receiving HRT. The decision to use HRT should be made individually by each woman and her health care provider by weighing the expected benefits and potential risks of therapy.