bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel human leucocyte antigen‐DRB1 genotyping method based on multiplex primer extension reactions
Authors: Jaakkola E. , Herzberg I. , Crane A.M. , Pointon J.J. , Laiho K. , Kauppi M. , Kaarela K. , Wordsworth B.P. , Tuomilehto J. , Brown M.A.
Published: June 2004

Abstract We have developed and validated a semi‐automated fluorescent method of genotyping human leucocyte antigen (HLA)‐DRB1 alleles, HLA‐DRB1*01–16, by multiplex primer extension reactions. This method is based on the extension of a primer that anneals immediately adjacent to the single‐nucleotide polymorphism with fluorescent dideoxynucleotide triphosphates (minisequencing), followed by analysis on an ABI Prism 3700 capillary electrophoresis instrument. The validity of the method was confirmed by genotyping 261 individuals using both this method and polymerase chain reaction with sequence‐specific primer (PCR‐SSP) or sequencing and by demonstrating Mendelian inheritance of HLA‐DRB1 alleles in families. Our method provides a rapid means of performing high‐throughput HLA‐DRB1 genotyping using only two PCR reactions followed by four multiplex primer extension reactions and PCR‐SSP for some allele groups. In this article, we describe the method and discuss its advantages and limitations.
A novel major histocompatibility complex class I‐related chain allele
Authors: Quiroga I. , Sweeney D. , Sutton P.M. , Chapple S.D.J. , Souto‐Grando J.P. , Barnardo M.C.N.M. , Fuggle S.V.
Published: June 2004

Abstract:  We report the identification of a novel major histocompatibility complex class I‐related chain (MICB) allele, provisionally designated as MICB‐0114 pending the WHO Nomenclature Classification for the MICB locus. This new allele is identical to MICB‐0103101v except for a single mutation of G to A in exon 4 that translates into an amino acid substitution from glutamic acid to lysine.
Involvement of the Major Histocompatibility Complex region in the genetic regulation of circulating CD8+ T‐cell numbers in humans
Authors: Cruz E. , Vieira J. , Gonçalves R. , Alves H. , Almeida S. , Rodrigues P. , Lacerda R. , Porto G.
Published: June 2004

Abstract Variability in T‐lymphocyte numbers is partially explained by a genetic regulation. From studies in animal models, it is known that the Major Histocompatibility Complex (MHC) is involved in this regulation. In humans, this has not been shown yet. The objective of the present study was to test the hypothesis that genes in the MHC region influence the regulation of T‐lymphocyte numbers. Two approaches were used. Association studies between T‐cell counts (CD4+ and CD8+) or total lymphocyte counts and HLA class I alleles (A and B) or mutations in the HFE (C282Y and H63D), the hemochromatosis gene, in an unrelated population (n = 264). A second approach was a sibpair correlation analysis of the same T‐cell counts in relation to HLA‐HFE haplotypes in subjects belonging to 48 hemochromatosis families (n = 456 sibpairs). In the normal population, results showed a strong statistically significant association of the HLA‐A*01 with high numbers of CD8+ T cells and a less powerful association with the HLA‐A*24 with low numbers of CD8+ T cells. Sibpair correlations revealed the most significant correlation for CD8+ T‐cell numbers for sibpairs with HLA‐HFE‐identical haplotypes. This was not observed for CD4+ T cells. These results show that the MHC region is involved in the genetic regulation of CD8+ T‐cell numbers in humans. Identification of genes responsible for this control may have important biological and clinical implications.
Chagas' disease susceptibility/resistance: linkage disequilibrium analysis suggests epistasis between major histocompatibility complex and interleukin‐10
Authors: Moreno M. , Silva E.L. , Ramírez L.E. , Palacio L.G. , Rivera D. , Arcos‐Burgos M.
Published: June 2004

Abstract Association between the major histocompatibility complex (MHC) and the susceptibility/resistance to acquire Chagas' disease has been largely demonstrated. To study the role of candidate genes in this susceptibility/resistance to Chagas, we designed a population‐genetic‐based case‐control approach (chagasic n = 104 and controls n = 60) and tested the presence of genotype and linkage disequilibrium on microsatellite loci establishing specific landmarks for the MHC, interleukin (IL)‐2, IL‐2Rβ chain, IL‐4, IL‐10, and natural resistance‐associated mactophage protein 1 (NRAMP1). After demonstrating no genetic stratification among cases and controls (Fst were not different from 0), we found significant allelic differences among chagasic patients and controls at microsatellite locus D6S291 (MHC) and at the microsatellite pointing out the IL‐10. At the MHC, we found significant differences between patients and controls in Hardy–Weinberg equilibrium‐expected genotype proportions. Additionally, MHC II‐locus‐inferred haplotypes in chagasic patients exhibited strong significant departures from the expected proportions predicted by the second Mendelian law. The linkage disequilibrium pattern at MHC involves a region of approximately 10 cM. These results replicate previous analyses and suggest that presence of epistasis between MHC with humoral systems, such as IL‐10, could be underlying the susceptibility/resistance to Chagas' disease.
On the closed form of the covariance matrix and its inverse of the causal ARMA process
Authors: Haddad John N.
Published: June 2004

Abstract.  Derivation of the theoretical autocovariance function of a causal autoregressive moving‐average process of order (p, q), ARMA(p, q), when q ≥ 1 is considered. A recursive relationship is established between the covariance matrices of an ARMA(p, q) process and its associated ARMA(p, q−1) process. The obtained recursion is shown to produce the inverse of the covariance matrix and its determinant. Moreover, the introduced method can be easily implemented in any programming environment.
Bootstrap predictive inference for ARIMA processes
Authors: Pascual Lorenzo , Romo Juan , Ruiz Esther
Published: June 2004

Abstract.  In this study, we propose a new bootstrap strategy to obtain prediction intervals for autoregressive integrated moving‐average processes. Its main advantage over other bootstrap methods previously proposed for autoregressive integrated processes is that variability due to parameter estimation can be incorporated into prediction intervals without requiring the backward representation of the process. Consequently, the procedure is very flexible and can be extended to processes even if their backward representation is not available. Furthermore, its implementation is very simple. The asymptotic properties of the bootstrap prediction densities are obtained. Extensive finite‐sample Monte Carlo experiments are carried out to compare the performance of the proposed strategy vs. alternative procedures. The behaviour of our proposal equals or outperforms the alternatives in most of the cases. Furthermore, our bootstrap strategy is also applied for the first time to obtain the prediction density of processes with moving‐average components.
Estimation and testing for the parameters of ARCH(q) under ordered restriction
Authors: Wang Dehui , Song Lixin , Shi Ningzhong
Published: June 2004

Abstract.  In this paper, we study a stationary ARCH(q) model with parameters α0,α1,α2,…,αq. It is known that the model requires all parameters αi to be non‐negative, but sometimes the usual algorithm based on Newton–Raphson's method leads us to obtain some negative solutions. So this study proposes a method of computing the maximum likelihood estimator (MLE) of parameters under the non‐negative restriction. A similar method is also proposed for the case where the parameters are restricted by a simple order: α1≥α2≥⋯≥αp. The strong consistency of the above two estimators is discussed. Furthermore, we consider the problem of testing homogeneity of parameters against the simple order restriction. We give the likelihood ratio (LR) test statistic for the testing problem and derive its asymptotic null distribution.
On testing for separable correlations of multivariate time series
Authors: Matsuda Yasumasa , Yajima Yoshihiro
Published: June 2004

Abstract.  We propose a test for separability of the correlation structure of a multivariate time series. We construct test statistics based on a spectral density matrix estimated in a nonparametric way and derive their asymptotic properties. We use simulation to check the performance in finite samples.
Analysis of the correlation structure of square time series
Authors: Palma Wilfredo , Zevallos Mauricio
Published: June 2004

Abstract. This paper analyses the asymptotic behaviour of the autocorrelation structure exhibited by squares of time series with a Wold expansion where the input error is a sequence of random variables with mean zero and finite kurtosis. Two important cases are discussed: (i) when the errors are independent and, (ii) when the errors are uncorrelated but their squares are correlated. Both situations are addressed when the process exhibits short or long memory. Consequences of these results on certain models widely used in many disciplines are also discussed.
Kernel deconvolution of stochastic volatility models
Authors: Comte Fabienne
Published: June 2004

Abstract. In this paper, we study the problem of the nonparametric estimation of the functionmin a stochastic volatility modelht =  exp(Xt/2λ)ξt,Xt = m(Xt−1) + ηt, whereξtis a Gaussian white noise. We show that the model can be written as an autoregression with errors‐in‐variables. Then an adaptation of the deconvolution kernel estimator proposed by Fan and Truong [Annals of Statistics, 21, (1993) 1900] estimates the functionmwith the optimal rate, which depends on the distribution of the measurement error. The rates vary from powers ofnto powers of  ln(n) depending on the rate of decay near infinity of the characteristic function of this noise. The performance of the method are studied by some simulation experiments and some real data are also examined.
Asymptotic mean‐squared forecast error when an autoregression with linear trend is fitted to data generated by an I(0) or I(1) process
Authors: Kim Tae‐Hwan , Leybourne Stephen J. , Newbold Paul
Published: June 2004

Abstract.  Assume that a time series is generated by an autoregression which has atmost one unit root. A correctly specified model, including linear time trend, is estimated by ordinary least squares, but no allowance is made for any unit root in the generating process. We investigate the impact of estimation error on the mean‐squared error of forecasts calculated from the fitted model.
Resistance Is Not Futile: Liberating Captain Janeway from the Masculine‐Feminine Dualism of Leadership
Authors: Bowring Michèle A.
Published: June 2004

. . . the boundary between science‐fiction and social reality is an optical illusion’ (Haraway, 1990, p. 191)

My underlying purpose in this article is to uncover the way in which research on leadership has been constrained by a reliance on the categories male‐female and/or masculine‐feminine for theorizing and for empirical work. I argue that both gender and leadership are caught within what Judith Butler calls the heterosexual matrix and that this has significant repercussions on leaders and leadership discourse. I use the character of Captain Kathryn Janeway from Star Trek: Voyager as a case study. I begin by analysing her leadership on the television series. I then perform a similar analysis of Janeway as she is represented in a text that subverts her gender by queering her character. I compare the two Janeways and the effect that the construction of each one's gender has on her leadership. In the conclusion I discuss ways in which we can use this analysis to move towards fluidity in the theorizing and practice of both gender and leadership.
Between Representations and Subjectivity: Gender Binaries and the Politics of Organizational Transformation
Authors: Knights David , Kerfoot Deborah
Published: June 2004

The distinction between male and female and masculinity and femininity continues to polarize relations between the sexes in ways that generally subordinate, marginalize, or undermine women with respect to men. The gender literature has recently challenged the singular and unitary conception of gender identity, arguing that there are a multiplicity of masculinities and femininities that are often fragile, fragmented and fluid. Despite this, the binary relationship between men and women continues to obstruct the development of sexual equality. This article is concerned with focusing critically on this binary and, in particular, its association with hierarchy, where men dominate women and masculinity assigns to femininity a marginal or ‘Other’ inferior status. It suggests that hierarchy is a condition and consequence of the reification of the binary that is difficult to challenge from within a representational epistemology that continues to dominate even studies of gender, let alone social science more generally. Deconstructing the gender binary is simply to challenge the reification of the terms wherein the divisions between male and female, masculine and feminine or men and women are treated as absolute and unchanging. The article examines conceptions of masculinity and the debate between Foucauldian and anti‐Foucauldian feminists as a basis for developing its argument. It then concludes that gender analysis can only deconstruct the hierarchical content of the gender binary by disrupting masculine hegemony at work. One way of facilitating this is temporarily to occupy a space between representations of gender and the conditions of subjectivity and language that make them possible.
General Economy and Productive Dualisms
Authors: Borgerson Janet , Rehn Alf
Published: June 2004

Through an investigation of the organizing potential of productive dualisms and ontological hierarchies that move toward epistemic and ontological closures, this essay theorizes the bounded potential of fluidity, and points to the possibility of waste, excess and sacrifice within a general economy of gender. We emphasize the apparently paradoxical role that dualisms — especially dualisms understood semiotically — have played in the foundational work to which many theorists look for clues about how to proceed in confounding limits and boundaries. Moreover, closures around the interrelated subordination of femininity and blackness emerge as a crucial reminder of the interlocking projects of gender and race theory. Drawing upon gender and critical race theory, philosophical phenomenology, and the work of Georges Bataille, we suggest that a general economy of gender can be explored by perceiving the closures, and other limits, enacted by dualism in organizational settings.
The information needs and information seeking behaviour of family doctors
Authors: Bryant Sue Lacey
Published: June 2004

Aims:  To explore the information needs and information seeking behaviour of family doctors, identifying any differences in attitudes and behaviours deriving from membership of a training practice and investigating the impact of a practice librarian.

Methods:  A case study of general practitioners (GPs) in Aylesbury Vale incorporated a quantitative study of use of the medical library, and two qualitative techniques, in‐depth interviews and group discussions.

Results:  A total of 58 GPs, almost three quarters of those in the Vale, participated; 19 via individual interviews and a further 39 via two group discussions. Family doctors are prompted to seek information by needs arising from a combination of professional responsibilities and personal characteristics. A need for problem‐orientated information, related to the care of individual patients, was the predominant factor that prompted these GPs to seek information. Personal collections remain the preferred information resource; electronic sources rank second. The study demonstrated low use of the medical library. However, both vocational training and the employment of a practice librarian impacted on library use.

Conclusions:  The study illuminates the information needs and preferences of GPs and illustrates the contribution that librarians may make at practice level, indicating the importance of outreach work.
Semantics and the medical web: a review of barriers and breakthroughs in effective healthcare query
Authors: Lorence Daniel P. , Spink Amanda
Published: June 2004

This paper provides an overview of the research into current medical vocabularies and their impact on searching the Web for health information. The Web provides growing opportunities for laypersons to gain knowledge about specific health conditions, though research to date has been incomplete. Many studies have examined aspects of controlled medical vocabularies. Other studies have examined aspects of medical Web searching vocabularies. In this context, there is a growing need to examine more closely laypersons’ Web queries using controlled medical vocabularies that were designed to serve the needs of medical professionals. It may be the case that the average consumer of Web health services is not able to use correct medical terminology, and may not be able to choose analogous or synonymous terms from a search result list. Our review suggests a growing need for studies to examine the current applicability of controlled medical vocabularies as well as alternatives to semantic query by Web search engine users.
Information overload within the health care system: a literature review
Authors: Hall Amanda , Walton Graham
Published: June 2004

There is a widespread view held by health clinicians that their work effectiveness is impaired by ‘information overload.’ Building upon a previous work by Wilson, a review of the literature was undertaken to look for the evidence of this. It was found that the literature, particularly in the context of the clinical environment, was limited. This review explores the diverse overarching theories of information overload, effects of the phenomenon that are perceived to occur and proposed solutions to this problem. Many of the papers noted an information explosion but only three authors explicitly attempted to measure both the quantity and the complexity of this information. It was also found that the typology of the information studied was severely limited with most studies exploring information such as guidelines, access to journals, research findings and other knowledge intensive areas. Solutions proposed seem to concentrate on technological means rather than exploring the use of humans either in management of information or as a step in the filtering process.
A Dual Role for
Hox
Genes in Limb Anterior-Posterior Asymmetry
Authors: Zákány József , Kmita Marie , Duboule Denis
Published: June 2004

Anterior-to-posterior patterning, the process whereby our digits are differently shaped, is a key aspect of limb development. It depends on the localized expression in posterior limb bud of
Sonic hedgehog
(
Shh
) and the morphogenetic potential of its diffusing product. By using an inversion of and a large deficiency in the mouse
HoxD
cluster, we found that a perturbation in the early collinear expression of
Hoxd11, Hoxd12
, and
Hoxd13
in limb buds led to a loss of asymmetry. Ectopic
Hox
gene expression triggered abnormal
Shh
transcription, which in turn induced symmetrical expression of
Hox
genes in digits, thereby generating double posterior limbs. We conclude that early posterior restriction of
Hox
gene products sets up an anterior-posterior prepattern, which determines the localized activation of
Shh
. This signal is subsequently translated into digit morphological asymmetry by promoting the late expression of
Hoxd
genes, two collinear processes relying on opposite genomic topographies, upstream and downstream
Shh
signaling.
Phospholipid Metabolism Regulated by a Transcription Factor Sensing Phosphatidic Acid
Authors: Loewen C. J. R. , Gaspar M. L. , Jesch S. A. , Delon C. , Ktistakis N. T. , Henry S. A. , Levine T. P.
Published: June 2004

Cells regulate the biophysical properties of their membranes by coordinated synthesis of different classes of lipids. Here, we identified a highly dynamic feedback mechanism by which the budding yeast
Saccharomyces cerevisiae
can regulate phospholipid biosynthesis. Phosphatidic acid on the endoplasmic reticulum directly bound to the soluble transcriptional repressor Opi1p to maintain it as inactive outside the nucleus. After the addition of the lipid precursor inositol, this phosphatidic acid was rapidly consumed, releasing Opi1p from the endoplasmic reticulum and allowing its nuclear translocation and repression of target genes. Thus, phosphatidic acid appears to be both an essential ubiquitous metabolic intermediate and a signaling lipid.
Femtotesla Magnetic Field Measurement with Magnetoresistive Sensors
Authors: Pannetier Myriam , Fermon Claude , Le Goff Gerald , Simola Juha , Kerr Emma
Published: June 2004

The measurement of magnetic fields in the femtotesla (fT, 10
–15
tesla) range is important for applications such as magnetometry, quantum computing, solid-state nuclear magnetic resonance, and magnetoencephalography. The only sensors capable of detecting these very small fields have been based on low-temperature superconducting quantum interference devices operating at 4.2 kelvin. We present a magnetic field sensor that combines a superconducting flux-to-field transformer with a low-noise giant magnetoresistive sensor. The sensor can be operated up to 77 kelvin. Our small-size prototype provides the capability of measuring 32 fT.
Picturing Nature, Producing Science
Authors: Werrett Simon
Published: June 2004

The Body of the Artisan
Art and Experience in the Scientific Revolution. by Pamela H. Smith. University of Chicago Press, Chicago, 2004. 377 pp. $35, £24.50. ISBN 0-226-76399-4.

Smith explores the synergy among art, craft, and science in the 16th and early 17th centuries to build an argument that in its early stages modern science owed much to the skills and knowledge of artisans and artists.
Msx1 Cooperates with Histone H1b for Inhibition of Transcription and Myogenesis
Authors: Lee Hansol , Habas Raymond , Abate-Shen Cory
Published: June 2004

During embryogenesis, differentiation of skeletal muscle is regulated by transcription factors that include members of the Msx homeoprotein family. By investigating Msx1 function in repression of myogenic gene expression, we identified a physical interaction between Msx1 and H1b, a specific isoform of mouse histone H1. We found that Msx1 and H1b bind to a key regulatory element of
MyoD
, a central regulator of skeletal muscle differentiation, where they induce repressed chromatin. Moreover, Msx1 and H1b cooperate to inhibit muscle differentiation in cell culture and in
Xenopus
animal caps. Our findings define a previously unknown function for “linker” histones in gene-specific transcriptional regulation.
Ferroelectricity in Ultrathin Perovskite Films
Authors: Fong Dillon D. , Stephenson G. Brian , Streiffer Stephen K. , Eastman Jeffrey A. , Auciello Orlando , Fuoss Paul H. , Thompson Carol
Published: June 2004

Understanding the suppression of ferroelectricity in perovskite thin films is a fundamental issue that has remained unresolved for decades. We report a synchrotron x-ray study of lead titanate as a function of temperature and film thickness for films as thin as a single unit cell. At room temperature, the ferroelectric phase is stable for thicknesses down to 3 unit cells (1.2 nanometers). Our results imply that no thickness limit is imposed on practical devices by an intrinsic ferroelectric size effect.
Dispelling Rumors of a Gene Shortage
Authors: Barrett H. Clark
Published: June 2004

The Birth of the MindHow a Tiny Number of Genes Creates the Complexities of Human Thought. by Gary Marcus. Basic Books, New York, 2004. 288 pp. $26, C$36.95, £19.99. ISBN 0-465-04405-0.

Marcus argues that a small number of genes underlie the emergence of the complex brain structure and mental capabilities of humans.
Phosphoryl Transfer and Calcium Ion Occlusion in the Calcium Pump
Authors: Sørensen Thomas Lykke-Møller , Møller Jesper Vuust , Nissen Poul
Published: June 2004

A tight coupling between adenosine triphosphate (ATP) hydrolysis and vectorial ion transport has to be maintained by ATP-consuming ion pumps. We report two crystal structures of Ca
2+
-bound sarco(endo)plasmic reticulum Ca
2+
–adenosine triphosphatase (SERCA) at 2.6 and 2.9 angstrom resolution in complex with (i) a nonhydrolyzable ATP analog [adenosine (β–γ methylene)–triphosphate] and (ii) adenosine diphosphate plus aluminum fluoride. SERCA reacts with ATP by an associative mechanism mediated by two Mg
2+
ions to form an aspartyl-phosphorylated intermediate state (Ca
2
-E1∼P). The conformational changes that accompany the reaction with ATP pull the transmembrane helices 1 and 2 and close a cytosolic entrance for Ca
2+
, thereby preventing backflow before Ca
2+
is released on the other side of the membrane.
Soils, Agriculture, and Society in Precontact Hawai`i
Authors: Vitousek P. M. , Ladefoged T. N. , Kirch P. V. , Hartshorn A. S. , Graves M. W. , Hotchkiss S. C. , Tuljapurkar S. , Chadwick O. A.
Published: June 2004

Before European contact, Hawai`i supported large human populations in complex societies that were based on multiple pathways of intensive agriculture. We show that soils within a long-abandoned 60-square-kilometer dryland agricultural complex are substantially richer in bases and phosphorus than are those just outside it, and that this enrichment predated the establishment of intensive agriculture. Climate and soil fertility combined to constrain large dryland agricultural systems and the societies they supported to well-defined portions of just the younger islands within the Hawaiian archipelago; societies on the older islands were based on irrigated wetland agriculture. Similar processes may have influenced the dynamics of agricultural intensification across the tropics.
Talking around embodiment: the views of GPs following participation in medical anthropology courses
Authors: Jaye C
Published: June 2004

Objectives:To explore the ways in which general practitioners talk around the concept of “embodiment” after participating in introductory courses in medical anthropology, and to contribute to the debate about what persons and bodies mean for biomedicine.

Design:This study used a qualitative interview methodology.

Participants:Participants were general practitioners who had all completed at least one introductory course in medical anthropology.

Results:In talking around embodiment, respondents articulated several interconnected dimensions of meaning. These included a Cartesian derived perspective of personhood involving complex relationships between intertwined components of soul, body, and mind; phenomenological perspectives on experience; the social meanings of the body; the ways in which individual bodies are acted upon by regulatory social and political bodies, and an implicit articulation of embodiment as relational, fluid, and processual. A theme of integrity or wholeness was discernible as a common thread linking all these understandings.

Conclusions:Critical interpretive medical anthropology crosses social science and humanities boundaries with its explicit orientation around the paradigm of embodiment as a means of understanding lived experience, social and personal meanings of the body, and the political economy of the body. Perhaps its major contribution to postgraduate medical education is its power to encourage or facilitate reflection that is grounded in practice. This study shows that it is possible for medical practitioners to problematise the Cartesianism of biomedicine and its effects on both patients and doctors, and to conceptualise the integrative framework encapsulated in the notion of embodiment as lived medicine.
Mental illness and cultural issues in West African films: implications for orthodox psychiatric practice
Authors: Aina O F
Published: June 2004

The portrayal of psychiatry and of the activities of supernatural forces in indigenous films produced in West Africa was critically examined in this study. Most often the content of these films is centred on African culture, African mythical stories, or real life events. Over a three year period, 163 such films were studied. Twenty five (15.3%) of them contained scenes of psychiatric illness. In 24 of these, there were “cases of psychoses”; and the remaining one was that of “deliberate self harm” via overdose with hypno-sedative drug. The causative factors of these “illnesses” were largely attributed to supernatural or preternatural forces. The effective treatment or “healing” of the illnesses was portrayed as arising mostly through magical means or traditional forms of care. In addition, sudden death from “spiritual attack” by these agents was shown in 35 (21.5%) of the films. Scenes of witches and occultists wreaking other forms of havoc on victims at night were shown in eight (4.9%) of the films. The implications of these films’ portrayals of psychiatry and supernatural forces for the public (particularly viewers with mental illness) and for orthodox psychiatric practice in the region were highlighted.
Can Mary Shelley’sFrankensteinbe read as an early research ethics text?: Table 1
Authors: Davies H
Published: June 2004

The current, popular view of the novelFrankensteinis that it describes the horrors consequent upon scientific experimentation; the pursuit of science leading inevitably to tragedy. In reality the importance of the book is far from this. Although the evil and tragedy resulting from one medical experiment are its theme, a critical and fair reading finds a more balanced view that includes science’s potential to improve the human condition and reasons why such an experiment went awry. The author argues thatFrankensteinis an early and balanced text on the ethics of research upon human subjects and that it provides insights that are as valid today as when the novel was written. As a narrative it provides a gripping story that merits careful analysis by those involved in medical research and its ethical review, and it is more enjoyable than many current textbooks! To support this thesis, the author will place the book in historical, scientific context, analyse it for lessons relevant to those involved in research ethics today, and then draw conclusions.
An introductory course in philosophy of medicine
Authors: Rudnick A
Published: June 2004

Philosophy of medicine, narrowly defined as ontology and epistemology of medicine, is a well developed research field, yet education in this field is less well developed. The aim of this paper is to present an educational development in philosophy of medicine—an introductory course in philosophy of medicine. Central features of the course are described. Participants (medical undergraduate students) scored high on average. The conclusion is that further such educational ventures in philosophy of medicine should be developed and implemented.
My self as an other: on autoimmunity and “other” paradoxes
Authors: Cohen E
Published: June 2004

The rubric autoimmunity currently encompasses sixty to seventy diverse illnesses which affect many of the tissues of the human body. Western medical practice asserts that the crisis known as autoimmune disease arises when a biological organism compromises its own integrity by misrecognising parts of itself as other than itself and then seeks to eliminate these unrecognised and hence antagonistic aspects of itself. That is, autoimmune illnesses seem to manifest the contradictory and sometimes deadly proposition that the “identity”: body/self both is and is not “itself”. Based on the assumption that under normal circumstances “the self” ought to coincide naturally with “the body”—or at the very least the self ought to inhabit the living location of the body more or less unproblematically—this scientific paradigm depicts autoimmune illness as a vital paradox. Yet for those of us who have lived through the experience of an autoimmune crisis, the living paradox that we embody may also lead us to question the basis upon which these medical assumptions rest. This essay raises some of these questions.
Rocking bed and prolonged independence from nocturnal non-invasive ventilation in neurogenic respiratory failure associated with limb weakness
Authors: Cormican L J , Higgins S , Davidson A C , Howard R , Williams A J
Published: June 2004

A 40 year old mother of three with autosomal dominant scapuloperoneal muscular dystrophy presented with severe neurogenic respiratory failure requiring nocturnal non-invasive ventilation (NIV). Because of the development of profound proximal muscular weakness as a consequence of the progressive nature of her neurological disease, she eventually was unable to apply and remove the facial interface to set up her NIV circuit. She therefore became dependent on her children and carers to start and stop NIV during the night. A rocking bed was successfully employed as an alternative to nocturnal NIV. Ventilation was facilitated by the passive movement of the diaphragm as a consequence of the movement of the abdominal contents under the effect of gravity. Benefit was demonstrated objectively by pulse oximetry and subjectively by the improvement in the patient’s symptomatology and continued independence at night. The ease of use of a rocking bed should be borne in mind when the necessity for nocturnal ventilatory support in neuromuscular disease results in the potential loss of independence for a patient.
Clinical presentation of acute chest syndrome in sickle cell disease
Authors: Taylor C , Carter F , Poulose J , Rolle S , Babu S , Crichlow S
Published: June 2004

In this study the records of 45 patients with sickle cell disease involved in 63 presentations of acute chest syndrome at the Princess Margaret Hospital in Nassau, the Bahamas, between 1997 and 2001 were examined. Patients were divided into three groups on the basis of age (<13 years, 13–18 years, ⩾19 years) with a view to assessing clinical presentation. The incidence of symptoms, physical signs, and laboratory findings were enumerated and significant differences between age groups determined. The data were analysed using analysis of variance, t test, and χ2 test and compared with existing knowledge on the subject.

This study proposed to evaluate the clinical presentation of acute chest syndrome with emphasis on historical and physical findings, and to encourage the physician to maintain a high index of suspicion for the condition in susceptible patients. It was found that presentation varied significantly with age groups, children presenting most classically with fever and cough and adults, with chest pain. The 13–18 age group emerged as the group which presented most frequently with the typical symptoms of chest infection, thus potentially making diagnosis easier. Of note, the most frequent finding was a normal examination, while the second commonest physical finding was crepitations on auscultation of the chest.
Implications of Harold Shipman for general practice
Authors: Baker R
Published: June 2004

Harold Shipman was an English general practitioner who murdered at least 215 of his patients between 1974 and 1998. A public inquiry is underway, but general practitioners and all doctors also need to consider the implications for their profession. The aim of this paper is to stimulate debate. Issues identified as important to consider include: trust between doctors; attitudes towards failing systems such as cremation certification; acceptance of the duty of accountability; ensuring patients can have reasonable confidence in their doctors; commitment to preventing such a case occurring again; and relationships with patients. It is argued that restricting debate to methods to detect doctors who murder would limit the opportunity to improve medical practice and would constitute a failure to fulfil the duty owed by doctors to Shipman’s victims and their families.
Dramatic levodopa responsiveness of dystonia in a sporadic case of spinocerebellar ataxia type 3
Authors: Nandagopal R , Moorthy S G K
Published: June 2004

A genetically confirmed case of spinocerebellar ataxia type 3 (SCA 3), presenting with disabling foot dystonia, peripheral neuropathy, and minimal cerebellar signs is reported. The dystonia improved dramatically with levodopa treatment in the absence of additional parkinsonian feature. A trial of levodopa for dystonia in SCA 3 may be of therapeutic benefit, at least in the initial stage of the disease.
Activity analysis of telemedicine in the UK
Authors: Debnath D
Published: June 2004

Background

Telemedicine is a new way of delivering health care to people, particularly in remote areas. The UK has experienced a surge of telematic projects in recent years. However, there is little information available in the literature regarding the past and present of telemedicine in the UK.

Objectives

To evaluate the state of telemedicine in the UK.

Methods

All the projects that took place in UK since 1991 were considered for the study and evaluated according to the population and area served.

Results

A total of 216 projects were identified. The number of projects was highest in England (172). Emergency medicine, medical specialties, and educational projects received most consideration (9.7% each). With the exception of Wales, the number of projects increased steadily with time. The projects, when correlated in accordance with the area (per 10 000 sq km) and population (per million), were found to be highest in England (49.5%) and Northern Ireland (36.2%) respectively. No dedicated educational project took place in Scotland, Northern Ireland, and Wales.

Conclusions

The UK embraced telemedicine in the early 1990s and the overall growth had been steady. Scotland, in spite of being the most likely beneficiary in UK, has lagged behind in telemedicine schemes and merits more projects. The issue of tele-education needs urgent review. Multisite trials and a combined approach involving the government, health professionals, technologists, and patients’ representatives would facilitate such developments and help widen the application of telemedicine.
Large-area plasma excitation in densely arrayed radial line slot antennas using TE11 rotating mode
Authors: Yamamoto T , Ishii N
Published: June 2004

A novel feeding structure using a TE11 (transverse electric) rotating mode in a radial line slot antenna for plasma production is proposed. Moreover, novel slot patterns with different coupling slot distributions are fabricated and tested. Extremely uniform plasma over a large diameter is observed and the possibility of control of the plasma distribution in the radial direction by changing to different coupling slot distributions is verified. PACS No.: 52.40.Fd
In vivo muscle amino acid transport involves two distinct processes
Authors: Miller Sharon , Chinkes David , MacLean David A. , Gore Dennis , Wolfe Robert R.
Published: June 2004

We have tested the hypothesis that transit through the interstitial fluid, rather than across cell membranes, is rate limiting for amino acid uptake from blood into muscle in human subjects. To quantify muscle transmembrane transport of naturally occurring amino acids, we developed a novel 4-pool model that distinguishes between the interstitial and intracellular fluid compartments. Transport kinetics of phenylalanine, leucine, lysine, and alanine were quantified using tracers labeled with stable isotopes. The results indicate that interstitial fluid is a functional compartment insofar as amino acid kinetics are concerned. In the case of leucine and alanine, transit between blood and interstitial fluid was potentially rate limiting for muscle amino acid uptake and release in the postabsorptive state. For example, in the case of leucine, the rate of transport between blood and interstitial fluid compared with the corresponding rate between interstitial fluid and muscle was 247 ± 36 vs. 610 ± 95 nmol·min−1·100 ml leg−1, respectively ( P < 0.05). Our results are consistent with the process of diffusion governing transit from blood to interstitial fluid without selectivity, and of specific amino acid transport systems with varying degrees of efficiency governing transit from interstitial fluid to muscle. These results imply that changes in factors that affect the transit of amino acids from blood through interstitial fluid, such as muscle blood flow or edema, could play a major role in controlling the rate of muscle amino acid uptake.
Chronic C75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass
Authors: Thupari Jagan N. , Kim Eun-Kyoung , Moran Timothy H. , Ronnett Gabriele V. , Kuhajda Francis P.
Published: June 2004

Obesity and its attendant disorders, such as type 2 diabetes, are global health problems. We previously reported that C75, an inhibitor of fatty acid synthase (FAS) and stimulator of carnitine palmitoyltransferase I (CPT I), caused anorexia and profound weight loss in lean and genetically obese mice. To approximate human obesity, we utilized a chronic C75 treatment model for diet-induced obese (DIO) mice. Chronic C75 treatment decreased food consumption and increased energy expenditure due to increased fatty acid oxidation in both DIO and lean mice. There was a substantial loss of adipose tissue and resolution of hepatic steatosis in C75-treated DIO mice. Analysis of changes in the expression of hypothalamic neuropeptides demonstrated that the reduced food consumption in C75-treated DIO mice was accompanied by an increase in cocaine and amphetamine-related transcript expression but not by changes in neuropeptide Y such as seen with acute C75 treatment of lean mice. Inhibition of FAS and stimulation of CPT I provide a means to achieve stable, sustained weight loss in DIO mice.
Reduced leptin concentrations are permissive for display of torpor in Siberian hamsters
Authors: Freeman David A. , Lewis Daniel A. , Kauffman Alexander S. , Blum Robert M. , Dark John
Published: June 2004

A photoperiod with a short photophase induces a winterlike phenotype in Siberian hamsters that includes a progressive decrease in food intake and body mass and reproductive organ regression, as well as reversible hypothermia in the form of short-duration torpor. Torpor substantially reduces energy utilization and is not initiated until body mass, fat stores, and serum leptin concentrations are at their nadir. Because photoperiod-dependent torpor is delayed until fat reserves are lowest, leptin concentrations may be a permissive factor for torpor onset. This conjecture was tested by implanting osmotic minipumps into Siberian hamsters manifesting spontaneous torpor; the animals received a constant release of leptin or vehicle for 14 days. Exogenous leptin treatment eliminated torpor in a significant proportion of treated hamsters, whereas treatment with the vehicle did not. Similarly, endogenous serum leptin concentrations were markedly reduced in all animals undergoing daily torpor. Although simply reducing leptin concentrations below a threshold value is not sufficient for torpor initiation, reduced leptin concentrations nevertheless appear necessary for its occurrence. It is proposed that drastically reduced leptin concentrations provide a “starvation signal” to an as yet unidentified central mechanism mediating torpor initiation.
Caveolae and Caveolins in the Cardiovascular System
Authors: Gratton Jean-Philippe , Bernatchez Pascal , Sessa William C.
Published: June 2004

Caveolae and the caveolae coat proteins, caveolins, are putatively implicated in many cellular processes, including transcytosis of macromolecules, cholesterol transport, and signal transduction. Recent insights into the physiological and pathophysiological roles of these organelles and the caveolins from genetically modified mice suggest that they may be profoundly important for postnatal cardiovascular function, including endothelial barrier function, regulation of nitric oxide synthesis, cholesterol metabolism, and cardiac function.
Blockage of VEGF-Induced Angiogenesis by Preventing VEGF Secretion
Authors: Björndahl Meit , Cao Renhai , Eriksson Anna , Cao Yihai
Published: June 2004

Vascular endothelial growth factor (VEGF)/vascular permeability factor is one of the most frequently expressed angiogenic factors in several pathological tissues. Development of VEGF antagonists has become an important approach in the treatment of angiogenesis-dependent diseases. Here we describe a novel anti-VEGF strategy by preventing the secretion of VEGF. We utilize the fact that placenta growth factor (PlGF)-1, a member of the VEGF family lacking detectable angiogenic activity, preferentially forms intracellular heterodimers with VEGF in cells coexpressing both factors. We constructed a retroviral vector containing human PlGF-1 or VEGF with a C-terminal KDEL sequence, which is a mammalian retention signal for the endoplasmic reticulum. Transduction of murine Lewis lung carcinoma cells with the retro-hPlGF-1-KDEL construct almost completely abrogated tumor growth. Consistent with the dramatic antitumor effect, most mouse VEGF molecules remained as intracellular mVEGF/hPlGF-1 heterodimers, and only a negligible amount of mVEGF homodimers were secreted. As a result, in hPlGF-1-KDEL–expressing tumors, blood vessels remained at very low numbers and lacked branching and capillary networks. Gene transfer of a hVEGF-KDEL construct into tumor cells likewise produced a dramatic antitumor effect. Thus, our study provides a novel antiangiogenic approach by preventing the secretion of VEGF.
Vernon Lidtke: A Tribute
Authors: Stark Gary D. , Stokes Lawrence D.
Published: June 2004

On9 October 2001 Vernon Lidtke delivered his valedictory lecture at The Johns Hopkins University on the topic of “Die Abstrakten,” a left-wing group of artists in Germany during the Weimar Republic. With this address before an appreciative audience comprising students, colleagues, and friends, Vernon concluded almost forty years of a distinguished scholarly career in the field of modern European and German history. In his scholarship Vernon is most widely identified with the study of the German labor movement in general and especially the Social Democratic Party, on which subjects he has thus far published two major books along with numerous journal articles and chapters. His formal retirement from academic life was also marked a few months earlier by a testimonial dinner held in Baltimore and attended by a large proportion of the twenty-five doctoral graduates whose dissertations he had supervised over more than three decades at Johns Hopkins. On both occasions he was fondly remembered as an accomplished historian, an inspiring teacher, and a generous mentor. In this and the four essays that follow, some of his former students wish also to commemorate Vernon's scholarly and teaching career.
Formalizing the Rule of Law in Prussia: The Supreme Administrative Law Court, 1876–1914
Authors: Ledford Kenneth F.
Published: June 2004

Inthe epilogue to his authoritative 1957 intellectual history,The German Idea of Freedom, Leonard Krieger concluded his exploration of German political thought from the Reformation to the Second Empire by excoriating the German liberal middle class, and especially the National Liberal Party, for its compromise with the authoritarian state and the landed aristocracy. He singled out for particular scorn theRechtsstaattheory of Rudolf Gneist: Rudolf Gneist's doctrine of the Rechtsstaat, from which all oppositional elements had now been removed, set the tone for the adaptation of the old liberal political ideal to cover the legal reality of the new national state … The concept ofRechtsstaat, that barometer of 19th-century liberalism, was no longer defined in terms of a state which permitted to the individual rights apart from the state. It became now simply the kind of state whose power was articulated in legal modes of action — that is, in measures which conformed to general rules.