bluuebunny/crossref_metadata_2025 huggingface dataset:
Saturated absorption and reverse saturated absorption of Cu:SiO2 at λ = 532 nm
Authors: Ganeev R. A. , Ryasnyansky A. I. , Stepanov A. L. , Usmanov T.
Published: February 2004

Nonlinear absorption in copper‐doped silicate glasses was investigated by the Z‐scan technique using second harmonic radiation of a Nd:YAG laser (λ = 532 nm, τ = 55 ps). The simultaneous influence of saturated and reverse saturated nonlinear absorption processes was analyzed. The nonlinear absorption coefficient and the saturation intensity of copper‐doped glasses at laser intensity of 5.4 × 109 W cm−2 were measured to be 6 × 10−6 cm W−1 and 4.3 × 108 W cm−2, respectively. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Temperature dependence of the energy gap of MgxZnyCd1−x−ySe alloy
Authors: Maksimov O. , Muñoz Martin , Wang W. H. , Tamargo M. C. , Samarth N.
Published: February 2004

The temperature dependence of the energy gap of MgxZnyCd1−x−ySe (x ∼ 0.5) and Zn0.5Cd0.5Se alloys was determined from reflectivity measurements at temperatures between 4.2 and 300 K. The data were fitted to a Bose–Einstein type relationship and temperature dependence of band gaps was compared. A similar temperature dependence of band gap was observed indicating that quantum confinement in the MgxZnyCd1−x−ySe/Zn0.5Cd0.5Se quantum wells did not depend on temperature. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Second order nonlinear susceptibility coefficients of porous semiconducting compounds
Authors: Monecke J. , Bezrukova J. , Cordts W. , Richardson G.
Published: February 2004

It is proven that effective second order nonlinear susceptibility coefficients of porous semiconductors, responsible for second harmonic generation, are not bounded and can be enhanced compared to those of the bulk material. The proof is based on an effective medium theory for a special fractal structure, large electric fields between nearly touching pores resulting in an enhancement of higher order field fluctuations. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Intersubband absorption in n‐type GaAs/AlGaAs (001) quantum wells: A tight‐binding study
Authors: Shtinkov N. , Vlaev S. J.
Published: February 2004

We present theoretical calculations of the intersubband absorption in the conduction band of GaAs/AlGaAs (001) quantum wells (QWs), performed using the sp3d5s* empirical tight‐binding model and a Green’s functions approach. The absorption spectra for both in‐plane (TE) and perpendicular (TM) polarizations are calculated. The obtained TE/TM absorption ratio is in excellent agreement with recent experimental results. We find that the asymmetry of the QW potential has no significant effect on the TE/TM ratio. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Slow mode degradation mechanism of ZnSe based white LEDs
Authors: Adachi Masahiro , Ando Koshi , Abe Tomoki , Tsutsumi Shigeyuki , Inoue Noboru , Kasada Hirofumi , Katayama Koji , Nakamura Takao
Published: February 2004

The cover picture is a photograph showing a row of ZnSe based white LEDs. In this issue's ‘Editor's Choice’ [1], the point defect induced degradation in these high quality diodes is investigated by electroluminescence, deep level transient spectroscopy, and isothermal capacitance transient spectroscopy investigations.

The first author, Masahiro Adachi, is member of the Optoelectronics Laboratory at Tattori University, where he is working on microscopic defects in ZnSe based devices, defect induced degradation, and defect behaviour.

The paper is an invited presentation from the II–VI '03 Conference held in Niagara Falls, New York, USA, 22–26 September 2003.

The full Proceedings of the Eleventh International Conference on II–VI Compounds are published in physica status solidi (c) – conferences and critical reviews 1, No. 4 (March 2004) (ISBN 3‐527‐40510‐0).
Reversing the objective: Adding guinea pig pedagogies
Authors: Weinstein Matthew
Published: February 2004

This article explores objectification in science and science education, i.e., the way material is turned into an object of interest to scientists. Drawing on sociological and anthropological drama theory, it examines how objectification does and does not occur in classrooms and schools. To understand the role and relationship of the object to the scientist, I look at current literature from the social studies of science concerning human and nonhuman objects as well as my own ethnographic work on the activism of politicized human research subjects. The paper concludes by how and why a more self‐conscious focus on the object of science is important for those concerned with equity in science education, suggesting that such guinea pig pedagogies restore missing historical and ethical dimensions to science education. © 2004 Wiley Periodicals, Inc.Sci Ed88:248–262, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10107
Finding meaning in science: Lifeworld, identity, and self
Authors: Kozoll Richard H. , Osborne Margery D.
Published: February 2004

Despite the many hours students spend studying science, only a few relate to these subjects in such a manner that it becomes a part of their essential worldview and advances their education in a larger sense—one in which they make a connection to the subject matter so that it becomes a source of inspiration and occupies a formative position in their life. Using the hermeneutic/phenomenological sense of lifeworld as our “being in the world,” we explore questions of identity in the teaching and learning of science. We suggest that by taking the notion of identity in science to include students' identities in their collective, inclusive of an orientation toward both who the student is and who he wants to become, we can enable this broader educative process. Science's link to lifeworld, identity, and self as well as the literature surrounding each are treated separately in the context of empirical case studies drawn from interviews with young college‐aged migrant agricultural workers. This population of students is living within a distinct culture where ideological systems are spread across lines of ethnicity, class, and vocation that place this population of students at risk of dropping out of school. Given the nature of their circumstances and their desire to leave the life of migration behind, these students show how their perceptions of science are embedded within particular issues of lifeworld, identity, and self while illustrating their interrelationships. © 2004 Wiley Periodicals, Inc.Sci Ed88:157–181, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10108
Newton's laws beyond the classroom walls
Authors: Pugh Kevin J.
Published: February 2004

One of the most profound qualities of science is its potential to transform and enrich students' experiences with the world. In prior work, I have conceptualized this quality of science in the construct of transformative experience. In order to illustrate the difference between transformative and nontransformative experience, this article presents the contrasting experiences of two students learning Newton's Laws in a seventh‐grade general science class. One student exemplifies engagement in a transformative experience—the learning of Newton's Laws enriches his experience with events of motion in his everyday, out‐of‐school life. The other student exemplifies the “good” student who is engaged in the class and learns the content, but does not undergo a transformative experience. The experiences of these two students are analyzed and discussed. Recommendations include a need to focus on student experience outside the classroom and engagement with content (as opposed to engagement with peripheral things, such as humor or mere activity). © 2004 Wiley Periodicals, Inc. Sci Ed 88:182–196, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10109
Urban middle‐school students' attitudes toward a defined science
Authors: Zacharia Zacharias , Barton Angela Calabrese
Published: February 2004

Recent studies have shown that urban students and students of color have exceptionally negative attitudes toward school science and their futures in that field as compared with white students and nonurban students. In this paper we summarize research findings on students' attitudes toward science. We note that most of the studies of students' attitudes toward science that have been conducted so far have measured students' attitudes against the backdrop of a “generalized science.” Thus, we develop a detailed argument for why science needs to be more clearly defined in attitude instruments. We report on our development of this instrument as well as our initial findings. © 2004 Wiley Periodicals, Inc. Sci Ed 88:197–222, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10110
Science education as/for participation in the community
Authors: Roth Wolff‐Michael , Lee Stuart
Published: February 2004

In this paper, we take up and advance the project of rethinking “scientific literacy” by Eisenhart, Finkel, and Marion (American Educational Research Journal, 1996, 33, 261–295). As part of a project of rethinking science education, we advance three propositions. First, because society is built on division of labor, not everybody needs to know the same basic sets of concepts; it is more important to allow the emergence of scientific literacy as a collective property. Second, scientific knowledge ought not to be privileged in democratic collective decision making but ought to be one of many resources. Third, rethinking science education as and for participation in community life sets up the potential for lifelong participation in and learning of science‐related issues. To show the viability of these propositions, we provide a case study based on a 3‐year, multisite ethnographic research project as part of which we investigated science in the community. Framing our work in terms of activity theory, we provide descriptions of science in a local middle school, where students learn science while participating in a community effort to contribute to the knowledge base about a local creek. The children's activities are continuous with those of adults concerned about environmental health. In this way, rather than preparing for life after school, science education allows students to participate in legitimate ways in community life and therefore provides a starting point for uninterrupted lifelong learning across the presently existing boundary separating formal schooling from everyday life outside schools. © 2004 Wiley Periodicals, Inc.Sci Ed88:263–291, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10113
Multiple modes of meaning‐making in a science center
Authors: Rahm Jrene
Published: February 2004

In this paper, I address some of the unique challenges of studies of learning in museums through a microanalytic case study of meaning‐making among a group of youth and a curator. Through an examination of youths' forms of participation in one exhibit, I illustrate local meaning making achieved through multiple modalities—by doing, talking, and the manipulation of the exhibit. In turn, I show how multiple on‐going dialogues come to interact and constitute talk and action at the science exhibit underlining the idiosyncratic nature of meaning‐making. While the dialogue examined in this paper may be considered as a rather unremarkable event in terms of learning, it underlines that the study of meaning‐making entails a focus on more than mere conversations in situ in that verbal and nonverbal interactions need to be considered simultaneously. Furthermore, the analysis suggests that museums may be best seen as one among many resources for science literacy development whose impact can only be understood through an assessment of learning trajectories over time and across space. Suggestions are made for museum design and future studies of learning in consideration of the issues raised. © 2004 Wiley Periodicals Inc. Sci Ed 88: 223–247, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10117
Modelling HIV‐RNA viral load in vertically infected children
Authors: Gray Linsay , Cortina‐Borja Mario , Newell Marie‐Louise
Published: February 2004

Human immunodeficiency virus (HIV) ribo‐nucleic acid (RNA) viral load is a measure of actively replicating virus and is used as a marker of disease progression. For a thorough understanding of the dynamics of the evolution of the virus in the early life of HIV‐1 vertically infected children, it is important to elucidate the pattern of HIV‐RNA viral load over age.

An aspect of assay systems used in the quantification of RNA viral load is that they measure values above particular cut‐off values for detection, below which the assays used are not sufficiently sensitive. In this way, measurements are potentially left‐censored. Recent adult studies suggest that to adequately model RNA pattern over age, it is necessary to account for within‐subject correlation, due to repeated measures, and censoring.

The aim of this study, therefore, was to establish whether it is necessary to use complex methods to allow for repeated measures within individuals and censoring of the HIV‐RNA viral load in children enrolled in a cohort study.

The approach involved the identification of an appropriate model for the basic pattern of RNA viral load by age and subsequent assessment of various estimation procedures accounting for repeated measures and censoring in different ways. Methods developed by Hughes involving the expectation‐maximization (EM) algorithm and the Gibbs sampler were taken as the benchmark for comparison of simpler alternatives. Other approaches considered involve linear mixed‐effects and ordinary least squares in which censoring is dealt with informally by taking the cut‐off value as absolute or taking the mid‐point between cut‐off and zero.

Fractional polynomials provided a substantially superior approach for modelling the dynamics of viral load over age compared to conventional polynomials or change‐point models. Allowing for repeated measures was necessary to improve the power of the likelihood ratio tests required to establish the final model, but methods beyond taking the mid‐point for censored values did not further improve the fit. Although Hughes' methodology is the best approach, its implementation is not necessary for the identification of the optimal model. Copyright © 2004 John Wiley & Sons, Ltd.
A new measure of prognostic separation in survival data
Authors: Royston Patrick , Sauerbrei Willi
Published: February 2004

Multivariable prognostic models are widely used in cancer and other disease areas, and have a range of applications in clinical medicine, clinical trials and allocation of health services resources. A well‐founded and reliable measure of the prognostic ability of a model would be valuable to help define the separation between patients or prognostic groups that the model could provide, and to act as a benchmark of model performance in a validation setting. We propose such a measure for models of survival data. Its motivation derives originally from the idea of separation between Kaplan–Meier curves. We define the criteria for a successful measure and discuss them with respect to our approach. Adjustments for ‘optimism’, the tendency for a model to predict better on the data on which it was derived than on new data, are suggested. We study the properties of the measure by simulation and by example in three substantial data sets. We believe that our new measure will prove useful as a tool to evaluate the separation available‐with a prognostic model. Copyright © 2004 John Wiley & Sons, Ltd.
Uncertainty and the value of diagnostic information, with application to axillary lymph node dissection in breast cancer
Authors: Parmigiani Giovanni
Published: February 2004

In clinical decision making, it is common to ask whether, and how much, a diagnostic procedure is contributing to subsequent treatment decisions. Statistically, quantification of the value of the information provided by a diagnostic procedure can be carried out using decision trees with multiple decision points, representing both the diagnostic test and the subsequent treatments that may depend on the test's results. This article investigates probabilistic sensitivity analysis approaches for exploring and communicating parameter uncertainty in such decision trees. Complexities arise because uncertainty about a model's inputs determines uncertainty about optimal decisions at all decision nodes of a tree. We present the expected utility solution strategy for multistage decision problems in the presence of uncertainty on input parameters, propose a set of graphical displays and summarization tools for probabilistic sensitivity analysis in multistage decision trees, and provide an application to axillary lymph node dissection in breast cancer. Copyright © 2004 John Wiley & Sons, Ltd.
Electronic monitoring device event modelling on an individual‐subject basis using adaptive Poisson regression
Authors: Knafl George J. , Fennie Kristopher P. , Bova Carol , Dieckhaus Kevin , Williams Ann B.
Published: February 2004

An adaptive approach to Poisson regression modelling is presented for analysing event data from electronic devices monitoring medication‐taking. The emphasis is on applying this approach to data for individual subjects although it also applies to data for multiple subjects. This approach provides for visualization of adherence patterns as well as for objective comparison of actual device use with prescribed medication‐taking. Example analyses are presented using data on openings of electronic pill bottle caps monitoring adherence of subjects with HIV undergoing highly active antiretroviral therapies. The modelling approach consists of partitioning the observation period, computing grouped event counts/rates for intervals in this partition, and modelling these event counts/rates in terms of elapsed time after entry into the study using Poisson regression. These models are based on adaptively selected sets of power transforms of elapsed time determined by rule‐based heuristic search through arbitrary sets of parametric models, thereby effectively generating a smooth non‐parametric regression fit to the data. Models are compared using k‐fold likelihood cross‐validation. Copyright © 2004 John Wiley & Sons, Ltd.
Comparison of Bayesian, classical, and heuristic approaches in identifying acute disease events in lung transplant recipients
Authors: Troiani John S. , Carlin Bradley P.
Published: February 2004

This study compares a typical heuristic algorithm with classical and Bayesian regression models in ascertaining the presence of acute bronchopulmonary disease events in lung transplant recipients. These models attempt to predict whether an epoch will end in an event, based on the preceding two weeks of data. The data consist of 150 two‐week epochs of daily to biweekly spirometry and symptom covariates for 30 subjects over 60 subject‐years. Seventy‐five ‘event’ epochs end on a day when an acute bronchopulmonary disease event is documented in the medical record; 75 randomly selected ‘non‐event’ epochs end on a day when no event is documented. The data are partitioned by randomly assigning 15 subjects for training and the remaining 15 subjects for testing. For cross‐validation, a second random partition is generated from the same data set. The statistical models are trained and tested on both partitions. For the heuristic algorithm, its historical event classifications on the same test cases are used. Classification performance on both partitions of all models is compared using receiver operating characteristic curves, sensitivity and specificity, and a Shannon information score. Data partition did not appreciably affect statistical model performance. All statistical models, unlike the heuristic algorithm, performed significantly different than chance (family significance <0.05, Pearson independence chi‐square, Bonferroni multiple correction), and better than the heuristic algorithm. The best models were Bayesian changepoint models. Through a clinically oriented discussion, a case classified by all of these algorithms is presented, suggesting the clinical usefulness of the Bayesian approach compared with the classical and heuristic approaches. Copyright © 2004 John Wiley & Sons, Ltd.
Non‐linear survival analysis using neural networks
Authors: Ripley Ruth M. , Harris Adrian L. , Tarassenko Lionel
Published: February 2004

We describe models for survival analysis which are based on a multi‐layer perceptron, a type of neural network. These relax the assumptions of the traditional regression models, while including them as particular cases. They allow non‐linear predictors to be fitted implicitly and the effect of the covariates to vary over time. The flexibility is included in the model only when it is beneficial, as judged by cross‐validation.

Such models can be used to guide a search for extra regressors, by comparing their predictive accuracy with that of linear models. Most also allow the estimation of the hazard function, of which a great variety can be modelled.

In this paper we describe seven different neural network survival models and illustrate their use by comparing their performance in predicting the time to relapse for breast cancer patients. Copyright © 2004 John Wiley & Sons, Ltd.
Sensitivity analyses for unmeasured confounding assuming a marginal structural model for repeated measures
Authors: Brumback Babette A. , Hernán Miguel A. , Haneuse Sebastien J. P. A. , Robins James M.
Published: February 2004

Robins introduced marginal structural models (MSMs) and inverse probability of treatment weighted (IPTW) estimators for the causal effect of a time‐varying treatment on the mean of repeated measures. We investigate the sensitivity of IPTW estimators to unmeasured confounding. We examine a new framework for sensitivity analyses based on a nonidentifiable model that quantifies unmeasured confounding in terms of a sensitivity parameter and a user‐specified function. We present augmented IPTW estimators of MSM parameters and prove their consistency for the causal effect of an MSM, assuming a correct confounding bias function for unmeasured confounding. We apply the methods to assess sensitivity of the analysis of Hernánet al., who used an MSM to estimate the causal effect of zidovudine therapy on repeated CD4 counts among HIV‐infected men in the Multicenter AIDS Cohort Study. Under the assumption of no unmeasured confounders, a 95 per cent confidence interval for the treatment effect includes zero. We show that under the assumption of a moderate amount of unmeasured confounding, a 95 per cent confidence interval for the treatment effect no longer includes zero. Thus, the analysis of Hernánet al.is somewhat sensitive to unmeasured confounding. We hope that our research will encourage and facilitate analyses of sensitivity to unmeasured confounding in other applications. Copyright © 2004 John Wiley & Sons, Ltd.
Test for qualitative interaction in equivalence trials when the number of centres is large
Authors: Yan Xin
Published: February 2004

We propose a generalized testing procedure to test for qualitative interaction in equivalence trails when the number of centres is large. The proposed testing procedure allows for an adaptable definition of qualitative interaction that can take into account the total number of centres. A tuning parameter k (k 0) is introduced to quantify qualitative interaction. The testing procedure is proposed for equivalence trials with symmetric or asymmetric margins. In addition to the test procedure, we also provide explicit formulae for the power calculation. The proposed test is relatively easy to implement using any statistical software. Examples for detecting qualitative interaction are given to illustrate the method. Copyright © 2004 John Wiley & Sons, Ltd.
FGF‐2 enhances TGF‐β1‐induced periosteal chondrogenesis
Authors: Stevens Molly M. , Marini Robert P. , Martin Ivan , Langer Robert , Shastri V. Prasad
Published: February 2004

The use of periosteum as a cell source for the in vitro engineering of grafts for articular cartilage repair requires the development of methods to obtain high viable cell numbers in the early stages of culture. In this study, we demonstrate that the addition of a mitogen, fibroblast growth factor‐2 (FGF‐2), during the early stage of the in vitro culture of periosteum in the presence of transforming growth factor‐β1 (TGF‐β1), significantly enhances cell proliferation, which results in increased neo‐cartilage formation at later stages. Periosteal explants were cultured in vitro within alginate or agarose based gels in the presence of either FGF‐2 for the first week, TGF‐β1 for the first 2 weeks, FGF‐2 and TGF‐β1 for the first week and first 2 weeks respectively, or no added factors. Consistent with previous studies, periosteum derived neo‐chondrogenesis occurred only in the presence of TGF‐β1. The neo‐cartilage was found to contain cartilage specific proteoglycans and Type‐II collagen as determined by safranin‐O and immunohistochemical staining respectively. Further medium supplementation with FGF‐2 stimulated early cell proliferation (>3 fold higher total DNA content per explant at day 10). This resulted in a marked increase in the size of the cultured explants and in the total area of the explant staining positive for safranin‐O (from around 50% to 85%, (p < 0.05)) after 6 weeks culture. The ability to generate significant quantities of neo‐cartilage within a biocompatible and biodegradable matrix such as alginate, which lacks the immunogenicity of agarose, could open new pathways to utilizing such constructs in articular cartilage tissue engineering applications. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Experiments on the nature of the signal that induces spinal neuroplastic changes following a peripheral lesion
Authors: Hoheisel U. , Sárdy M. , Mense S.
Published: February 2004

This study aimed at identifying the signal(s) that elicit myositis‐induced neuroplastic changes in background activity and responsiveness of spinal neurones. It is based on previous data suggesting that in dorsal horn neurones, responsiveness to peripheral input on one hand and background activity on the other are probably controlled by different mechanisms. In anaesthetized rats, myositis was induced in the gastrocnemius‐soleus muscle and the activity of single dorsal horn neurones was recorded in segment L3. Impulse traffic and axoplasmatic transport in dorsal roots L4 and L5 were selectively blocked by lignocaine or vinblastine for various time periods relative to the induction of the myositis. The results show that the main triggering signal for the myositis‐induced changes in both responsiveness and background activity is the altered impulse activity in primary afferent fibres. In contrast, ‘no axonally transported chemical signal controlling the discharge behaviour of dorsal horn neurones was found’. However, the time course of the electrical signals that cause the myositis‐induced changes in background activity and responsiveness is different. For changes in responsiveness, a rather narrow time window of 2 h directly after induction of the myositis existed, during which the impulses from the inflamed muscle must reach the spinal cord. Accordingly, to prevent the increase in responsiveness, the electrical input had to be blocked during the first 2 h; a block of the same duration at another time had no effect. The change in background activity seems to be due to a continuous input from the inflamed muscle which adds up over the hours. Therefore, with regard to background activity, blocking the electrical signals is effective at any time, but only a block of long duration has a significant effect.
Referred pain is dependent on sensory input from the periphery: A psychophysical study
Authors: Laursen R.J. , Graven‐Nielsen T. , Jensen T.S. , Arendt‐Nielsen L.
Published: February 2004

Muscle pain can be characterized by local pain and pain referred to distant somatic structures with concomitant cutaneous and deep somatosensory changes. The mechanisms responsible for referred muscle pain are poorly understood. The aim of this study was to study the origin of experimentally‐induced referred muscle pain by anaesthetizing the skin overlying the referred pain area and to quantify deep somatosensory changes in the area.

Fourteen healthy subjects (mean age = 25.1 years, range 22–34 years) were included in a placebo controlled study consisting of two sessions separated by 1 week. Two stimulation needles were inserted into the right anterior tibial muscle. Electrical stimuli (1Q Hz) were delivered by a computer‐controlled constant current stimulator. The intensity required to generate referred pain was determined and the circumference of the referred pain area was marked. At the centre of the area, pressure pain threshold and pinprick perception threshold were determined. Either an anaesthetic cream (EMLA®, Astra AB, Sweden) or a placebo cream (Astra AB, Sweden) covered by an occlusive dressing was applied to the marked referred pain area for 90 min. Afterwards, a 600‐s stimulation at 150% of the referred pain threshold was induced while the VAS score of referred pain was recorded continuously. Pressure pain threshold and pinprick perception threshold were determined before, during and 5 min after the prolonged stimulation.

A significantly lower referred pain visual analogue scale (VAS) score was recorded during the interval from 50 to 150s (p=0.04). The area under the referred pain VAS score vs time curve tended to be lower (22.7%) with the application of skin anaesthetic (p=0.07). The mean referred pain threshold and the mean referred pain area did not differ significantly between the two sessions (p>0.6). No difference was found in pressure pain threshold between the two treatments or between the four recordings during each session (p>0.8). Pinprick perception threshold increased significantly after EML® application (p<0.04).

Decreased referred pain intensity with application of anaesthetic cream at the referred pain site indicates that referred muscle pain depends on input from the periphery (skin) in humans.
Greater disability with increased pain involvement, pain intensity and depressive preoccupation
Authors: Türp J.C. , Kowalski C.J. , Stohler C.S.
Published: February 2004

Persistent pain is often accompanied by functional disability. This study investigated the effect of pain extent and the involvement of specific pain sites on pain‐related disability, as determined by the Pain Disability Index (PDI). Complete data were available from 278 persistent facial pain (PFP) patients. Patients were divided into one of two groups based on drawings of their pain distribution. When the patient's pain drawing was limited to the region supplied by the trigeminal nerves (Nn. V1 V2, and/or V3), with or without the inclusion of any combination of the cervical dermatomes C2, C3 and C4, the patient was assigned to the local/regional pain group. If the pain extended beyond this area, the patient was allocated to the group exhibiting widespread pain. In addition to the PDI, patients fille'd out the Beck Depression Inventory (BDI) and the State‐Trait Anxiety Inventory (STAI). The local/regional pain group had significantly lower scores on the PDI, the BDI and STAI state than cases with widespread pain. Patients with widespread pain who indicated pain locations in any one or more of the extremities plus the lower back scored significantly higher on the PDI and the BDI than patients with no such combined involvement. Multiple regression analysis revealed that depressive preoccupation, pain extent and pain intensity were significant predictors of pain‐related disability, whereas the STAI was not. If controlled for pain extent and pain intensity, the presence of high as opposed to low depressive scores added almost 11 points to the PDI score. These results showed that pain distribution, pain intensity and depressive mood are significant predictors of pain‐related disability.
Multidisciplinary rehabilitation for chronic back pain in an outpatient setting: A controlled randomized trial
Authors: Keller S. , Ehrhardt‐Schmelzer S. , Herda C. , Schmid S. , Basler H.‐D.
Published: February 2004

Based on existing models for pain chronicity and effective treatment strategies for patients with chronic low back pain, a multidisciplinary rehabilitation programme for an outpatient group setting was developed. The main treatment components address the patient's physical functional capacity (functional restoring), cognitive and affective processes (pain management strategies), and behavioural and ergonomical aspects (back school elements).

Short‐term (immediately after intervention) and long‐term effects (at 6‐months follow‐up) of the intervention were assessed in a randomized controlled study. Dependent variables were pain measures, functional capacity, disability, muscular strength and endurance, pain and posture‐related self‐efficacy, attitudes, depression, well‐being, beiavioural habits and posture assessed by a standardized behavioural observation method.

Immediately after the intervention, patients in the treatment group (n= 36) showed significant improvement over patients in the control group (n= 29) in all variables except depression and muscular strength and endurance. At 6‐months follow‐up, compared to pretreatment scores, patients continued to show beneficial effects in pain intensity and frequency, posture, posture‐related self‐efficacy and well‐being. In contrast to post‐treatment results, there were also significant improvements in strength and endurance.

Overall results testify to the effectiveness of the intervention programme. Future studies (with larger sample sizes) should aim at a further improvement of functional capacity and disability perception, an analysis of differential treatment effects, and strategies for an improved long‐term maintenance of the changes induced by the programme.
Nociceptive and morphine antinociceptive sensitivity of 129 and C57BL/6 inbred mouse strains: Implications for transgenic knock‐out studies
Authors: Mogil J.S. , Wilson S.G.
Published: February 2004

Gene‐targeting studies of pain, using transgenic ‘knock‐out'; mice possessing null mutations of pain‐relevant genes, are becoming increasingly common. This approach is a potentially powerful tool for the molecular dissection of complex traits such as pain modulation, but is subject to several theoretical drawbacks. One problem arises from the fact that the genetic background of knock‐out mice is virtually always a mixture of alleles from two different strains; commonly 129 and C57BL/6. A more general caveat to knock‐out findings derives from the demonstration that null mutations interact with genetic background to produce phenotypic changes. ‘The present study investigated basal’ nociceptive sensitivity (on the 49°C tail‐immersion/withdrawal test) and sensitivity to morphine antinociception in 129 and C57BL/6 mice (129/J, 129/Sv—/p/Tyr‐c/Mgf‐SIJ, and C57BL/6J substrains). C57BL/6 mice displayed almost two‐fold greater initial sensitivity to thermal stimulation than 129 mice, and three‐fold reduced sensitivity to morphine inhibition of that noxious stimulus. These findings suggest that gene targeting studies of pain are particularly subject to the aforementioned concerns, and that C57BL/6 mice represent a suboptimal background strain for such efforts.
Adenosine for pain relief in a patient with intractable secondary erythromelalgia
Authors: Lindblom U. , Nordfors L.‐O. , Sollevi A. , Sydow O.
Published: February 2004

An unusual case is reported with severe erythromelalgia secondary to a sensorimotor polyneuropathy of immunological aetiology. The dominating symptoms were ongoing burning dysesthesia and pain in the legs, sustained thermal hyperalgesia and allodynia to pressure which produced intolerable pain on standing and walking. The primary pain‐producing pathophysiology was apparently peripheral neurogenic inflammation with sensitization and excitation of nociceptors. The variable and progressive course prompted reassessments and successively amended multitargeted analgesic regimens. The most intensive bout of widespread pain and allodynia indicating secondary central sensitization was only controlled by adenosine treatment.
Cerebral blood‐flow changes evoked by two levels of painful heat stimulation: A positron emission tomography study in humans
Authors: Svensson P. , Johannsen P. , Jensen T.S. , Arendt‐Nielsen L. , Nielsen J. , Stødkilde‐Jørgensen H. , Gee A.D. , Hansen S. Baarsgaard , Gjedde Albert
Published: February 2004

Positron emission tomography (PET) and accumulation of H2
15O as a marker of neuronal activity were used to create maps of cerebral blood‐flow changes evoked by painful heat stimulation in 10 subjects. Two levels of painful tonic and phasic heat stimuli were applied with use of a newly developed contact heat thermode on the volar surface of the dominant (right) arm. The subjects participated in two separate PET sessions. Maps reflecting low and high levels of painful tonic heat were obtained in the first session, and low and high levels of painful phasic heat in the second session. The subjects scored their peak pain intensity and unpleasantness on 10‐cm visual analogue scales. For each subject, PET images were aligned to nuclear magnetic resonance (NMR) images and remapped into the standardized co‐ordinate system of Talairach. After normalization of the PET volumes, subtraction images were formed voxel‐by‐voxel and converted to a t‐statistic volume. The perceived pain intensity and unpleasantness were identical with painful tonic and phasic heat stimulation. Directed searches revealed significant blood‐flow increases in the contralateral primary sensorimotor cortex (MI/SI), SII, insular cortex and cingulate cortex when the low tonic heat map was subtracted from the high. A similar, but not identical, pain‐processing network was observed for the maps representing the subtraction of low and high phasic heat. In this subtraction, the blood‐flow increases in MSI/SI did not reach statistical significance, and significant blood flow decreases were found in the contralateral middle temporal gyrus. Finally, the location of the activation site in the cingulate cortex was different from that observed during tonic heat pain. This study has provided more evidence for the existence of a common pain‐processing network engaged during the perception of different levels of toxic and phasic heat pain.
Pain management of arteriovenous fistula cannulation in haemodialysis children: Efficacy of EMLA anaesthetic cream
Authors: Benini F. , Gobber D. , Lago P. , Agosto C. , Carli G. , Zacchello F.
Published: February 2004

The aim of the present study was to evaluate the efficacy of EMLA cream (containing a eutectic mixture of local anaesthetics) in controlling pain due to arteriovenous fistula cannulation in teenagers undergoing chronic haemodialysis. The study was conducted in two phases, one prospective, the other a blind randomized trial, at the Paediatric Haemodialysis service of the Paediatrics Department of Padua University, Italy. It involved six teenagers, aged 12–18 years. Pain was measured using the visual analogue scale, indirect evaluation by nurses and a four‐category verbal rating scale.

Results showed that: (1) the visual analogue scale calls for an adequate training period; and (2) the EMLA cream might be effective in controlling cannulation‐related pain but emotional factors, such as uncontrolled fear and stress, can interfere with the global efficacy of the analgesic approach.
Morphine use and pharmacokinetics in patients with chest pain due to suspected or definite acute myocardial infarction
Authors: Everts B. , Karlson B.W. , Herlitz J. , Hedner T.
Published: February 2004

The characteristics of chest pain due to suspected acute myocardial infarction and morphine use during the first 3 hospital days are described in a population of 2988 consecutive patients admitted to hospital.

The duration of pain was usually less than 24h (mean 20.9±0.55h), and only 24.8% of patients experienced chest pain of longer duration. The majority of patients had only one attack of pain, but 34.4% experienced four or more attacks during hospitalization. A mean morphine dose of 6.7±0.2mg was administered over the 3 hospitalization days, but surprisingly 52.4% of all patients required no morphine analgesia at all. Independent predictors of an increased morphine consumption were initial degree of suspicion of acute myocardial infarction, ST changes on admission ECG, male sex, a history of angina pectoris and a history of congestive heart failure. In a separate pharmacokinetic/pharmacodynamic study in 10 patients, plasma concentrations of morphine and its major metabolites, morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide (M6G), were measured after intravenous administration of morphine. In this patient group, terminal half‐life of unchanged morphine ranged from 0.77 to 3.22h. M3G and M6G plasma concentrations increased gradually up to 60–90 min after the intravenous morphine injection.

Initial pain intensity by numerical rating scale was 6.6±0.6 (arbitrary units), and after morphine administration, there was a rapid and significant decrease in pain intensity. After 20 min, pain relief was 69±11% and remained at this level during the following 8 h observation period.

It is concluded that the need for morphine administration in patients with suspected or definite acute myocardial infarction, differs among subgroups of patients and, in particular, higher doses are needed in those with a strong suspicion of myocardial infarction at arrival. When intravenous morphine is given, it attains full effect 20 min after injection. Furthermore, the active morphine metabolites M3G and M6G appear rapidly in thecirculation, which could influence the analgesic response to morphine treatment.
Imipramine does not affect argon‐laser‐induced pin‐prick pain thresholds and laser‐evoked cerebral potentials
Authors: Sindrup S.H. , Nielsen J.C. , Bjerring P. , Arendt‐Nielsen L.
Published: February 2004

The tricyclic antidepressant imipramine has shown analgesic effect in human clinical and experimental pain studies. The aim of the present study was to test the effect of imipramine on a pure short‐term nociceptive stimulus with pin‐prick pain quality. In a randomized, placebo‐controlled, double‐blind, crossover study, the hypoalgesic effect of a single oral dose of 100 mg imipramine was investigated in 10 healthy volunteers. Test procedures performed before and 2, 4, 6, 8, 10, 12 and 14 h after medication included determination of warmth and pin‐prick pain thresholds to high‐energy argon laser light stimulation on the hand, as well as laser‐evoked cerebral potentials to suprathreshold stimulation. Both the warmth and the pin‐prick pain thresholds (p=0.49 and 0.85) and the root mean square of the laser‐evoked potentials (p=0.89) were unaltered by imipramine. It is concluded that a single oral dose of 100 mg imipramine has no effect on pin‐prick pain. This study demonstrates the important fact that a drug may show clear analgesic effect in some experimental pain models while it is without effect in other models; e.g. imipramine is known to affect pain tolerance and summation thresholds. Pre‐clinical tests of potentially analgesic drugs should therefore be based on different pain‐stimulation modalities.
Effects of staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome
Authors: Andersson M. , Bagby J.R. , Dyrehag L.‐E. , Gottfries C.‐G.
Published: February 2004

Positive results of pilot studies of the effect of staphylococcus toxoid vaccine in patients with fibromyalgia and chronic fatigue syndrome were the incitement to the present, placebo‐controlled study. It included 28 patients who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome. The effect of vaccination with a staphylococcus toxoid was compared with the effect of injections of sterile water. Psychometric assessment was made using 15 items from the comprehensive psychopathological rating scale (CPRS), Zung's self‐rating depression scale and clinical global impressions (CGI). The visual analogue scale (VAS) was used to measure pain levels, and a hand‐held electronic pressure algometer was used to measure pressure pain thresholds.

Significant improvement was seen in seven of the 15 CPRS items in the vaccine group when pretreatment values were compared to post‐treatment values. In CPRS ‘fatiguability';, there were significant intergroup differences, and in CPRS ‘pain'; intergroup differences bordered on significance. There was no significant improvement in CPRS items in the placebo group. Clinical global impressions showed significant improvement in the vaccine‐treated group, and VAS did so in both groups.

In a follow‐up study of 23 patients, the vaccine treatment was continued for 2–6 years. Fifty percent were rehabilitated successfully and resumed half‐time or full‐time work.

The results of this study support the authors' hypothesis that treatment with staphylococcus toxoid may be a fruitful strategy in patients with fibromyalgia and chronic fatigue syndrome.
Immunoisolating encapsulation of intrathecally implanted bovine chromaffin cells prolongs their survival and produces anti‐allodynic effect in spinally injured rats
Authors: Yu Wei , Haoa Jing‐Xia , Xu Xiao‐Jun , Saydoff Joel , Sherman Sandy , Eriksson Anders , Haegerstrand Anders , Wiesenfeld‐Hallin Zsuzsanna
Published: February 2004

We have previously reported that intrathecal (i.t.) implantation of bovine chromaffin cells has an anti‐allodynic effect in a rat model of mechanical and cold allodynia‐like neuropathic pain after spinal cord injury. The technique of encapsulation of the cells by a semipermeable membrane has been developed recently. The present study was undertaken to investigate the effects of encapsulated bovine chromaffin cells on the allodynia‐like pain in the same model. Capsules with bovine chromaffin cells or control capsules were implanted in the spinal subarachnoidal space in rats. Their response in behavioural tests were recorded for 2 months. At termination, the capsules were explanted and examined morphologically with tyrosine hydroxylase immunohistochemistry. The mechanical allodynia was totally abolished from week 2 after implantation of the cells and throughout the 8‐week test period. The abnormal cold response was also attenuated in about half of the animals. The threshold to acute nociceptive stimulation was not affected. Eight weeks after implantation, 60–80% of the encapsulated chromaffin cells were still tyrosine hydroxylase positive. No effects were observed with control capsules. The results indicate that spinal implantation of encapsulated xenogeneic chromaffin cells may be useful in treating some refractory painful states associated with spinal cord injury. Immunoisolation of chromaffin cells by a semipermeable membrane may inhibit immunorejection, prolong the survival of the cells and enhance their anti‐allodynic effect.