bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Different Lassa Virus Strains by Alpha and Gamma Interferons and Comparison with a Less Pathogenic Arenavirus
Authors: Asper Marcel , Sternsdorf Thomas , Hass Meike , Drosten Christian , Rhode Antje , Schmitz Herbert , Günther Stephan
Published: February 2004

The high pathogenicity of Lassa virus is assumed to involve resistance to the effects of interferon (IFN). We have analyzed the effects of alpha IFN (IFN-α), IFN-γ, and tumor necrosis factor alpha (TNF-α) on replication of Lassa virus compared to the related, but less pathogenic, lymphocytic choriomeningitis virus (LCMV). Three low-passage Lassa virus strains (AV, NL, and CSF), isolated from humans with mild to fulminant Lassa fever, were tested. Lassa virus replication was inhibited by IFN-α and IFN-γ, but not TNF-α, in Huh7 and Vero cells. The degree of IFN sensitivity of a Lassa virus isolate did not correlate with disease severity in human patients. Furthermore, cytokine effects observed for Lassa virus and LCMV (strains CH-5692, Armstrong, and WE) were similar. To address the mechanisms involved in the IFN effect, we used cell lines in which overexpression of IFN-stimulated proteins promyelocytic leukemia protein (PML) and Sp100 could be induced. Both proteins reside in PML bodies, a cellular target of the LCMV and Lassa virus Z proteins. Overexpression of PML or Sp100 did not affect replication of either virus. This, together with the previous finding that PML knockout facilitates LCMV replication in vitro and in vivo (M. Djavani, J. Rodas, I. S. Lukashevich, D. Horejsh, P. P. Pandolfi, K. L. Borden, and M. S. Salvato, J. Virol. 75:6204-6208, 2001; W. V. Bonilla, D. D. Pinschewer, P. Klenerman, V. Rousson, M. Gaboli, P. P. Pandolfi, R. M. Zinkernagel, M. S. Salvato, and H. Hengartner, J. Virol. 76:3810-3818, 2002), describes PML as a mediator within the antiviral pathway rather than as a direct effector protein. In conclusion, the high pathogenicity of Lassa virus compared to LCMV is probably not due to increased resistance to the effects of IFN-α or IFN-γ. Both cytokines inhibit replication which is relevant for the design of antiviral strategies against Lassa fever with the aim of enhancing the IFN response.
A Mutation in the Latency-Related Gene of Bovine Herpesvirus 1 Inhibits Protein Expression from Open Reading Frame 2 and an Adjacent Reading Frame during Productive Infection
Authors: Jiang Yunquan , Inman Melissa , Zhang Yange , Posadas Nuria Alemañ , Jones Clinton
Published: February 2004

The latency-related (LR) gene of bovine herpesvirus 1 (BHV-1) is abundantly expressed during latency. A mutant BHV-1 strain that contains three stop codons at the 5′ terminus of the LR gene (LR mutant) does not reactivate from latency. This study demonstrates that the LR mutant does not express open reading frame 2 or an adjacent reading frame that lacks an initiating ATG (reading frame C). Since the LR mutant and wild-type BHV-1 express similar levels of LR RNA, we conclude that LR protein expression plays an important role in regulating the latency reactivation cycle in cattle.
Human Cytomegalovirus Stimulates Cellular IKK2 Activity and Requires the Enzyme for Productive Replication
Authors: Caposio Patrizia , Dreano Michel , Garotta Gianni , Gribaudo Giorgio , Landolfo Santo
Published: February 2004

Human cytomegalovirus (HCMV) exploits the host transcription factor NF-κB to enhance its own replication, dissemination, and reactivation from latency. Here we report that HCMV infection activates the upstream IκB kinase (IKK) complex and that its catalytic IKK2 subunit is required for HCMV-induced NF-κB activation, as well as the replication of different HCMV strains. These results indicate that IKK2 is essential for HCMV replication and emphasize the feasibility of blocking NF-κB activation as a way of inhibiting infection.
GENERALIZATION OF FEATURES IN THE ASSEMBLY NEURAL NETWORKS
Authors: GOLTSEV ALEXANDER , WUNSCH DONALD C.
Published: February 2004

The purpose of the paper is an experimental study of the formation of class descriptions, taking place during learning, in assembly neural networks. The assembly neural network is artificially partitioned into several sub-networks according to the number of classes that the network has to recognize. The features extracted from input data are represented in neural column structures of the sub-networks. Hebbian neural assemblies are formed in the column structure of the sub-networks by weight adaptation. A specific class description is formed in each sub-network of the assembly neural network due to intersections between the neural assemblies. The process of formation of class descriptions in the sub-networks is interpreted as feature generalization. A set of special experiments is performed to study this process, on a task of character recognition using the MNIST database.
MULTI-LAYERED GREEDY NETWORK-GROWING ALGORITHM: EXTENSION OF GREEDY NETWORK-GROWING ALGORITHM TO MULTI-LAYERED NETWORKS
Authors: KAMIMURA RYOTARO
Published: February 2004

In this paper, we extend our greedy network-growing algorithm to multi-layered networks. With multi-layered networks, we can solve many complex problems that single-layered networks fail to solve. In addition, the network-growing algorithm is used in conjunction with teacher-directed learning that produces appropriate outputs without computing errors between targets and outputs. Thus, the present algorithm is a very efficient network-growing algorithm. The new algorithm was applied to three problems: the famous vertical-horizontal lines detection problem, a medical data problem and a road classification problem. In all these cases, experimental results confirmed that the method could solve problems that single-layered networks failed to. In addition, information maximization makes it possible to extract salient features in input patterns.
ROUGH SETS AND GENETIC ALGORITHMS IN LEARNING CELLULAR NEURAL NETWORKS CLONING TEMPLATE FOR DECISION MAKING SYSTEM
Authors: RADWAN ELSAYED , TAZAKI EIICHIRO
Published: February 2004

We purpose to find a new beneficial method for accelerating the Decision-Making and classifier support applied on imprecise data. This acceleration can be done by integration between Rough Sets theory, which gives us the minimal set of decision rules, and the Cellular Neural Networks. Our method depends on Genetic Algorithms for designing the cloning template for more accuracy. Some illustrative examples are given to demonstrate the effectiveness of the proposed method, whose advantages and limitations are also discussed.
A SELF-STABILIZING LEARNING RULE FOR MINOR COMPONENT ANALYSIS
Authors: MÖLLER RALF
Published: February 2004

The paper reviews single-neuron learning rules for minor component analysis and suggests a novel minor component learning rule. In this rule, the weight vector length is self-stabilizing, i.e., moving towards unit length in each learning step. In simulations with low- and medium-dimensional data, the performance of the novel learning rule is compared with previously suggested rules.
AUTOMATIC KERNEL REGRESSION MODELLING USING COMBINED LEAVE-ONE-OUT TEST SCORE AND REGULARISED ORTHOGONAL LEAST SQUARES
Authors: HONG X. , CHEN S. , SHARKEY P. M.
Published: February 2004

This paper introduces an automatic robust nonlinear identification algorithm using the leave-one-out test score also known as the PRESS (Predicted REsidual Sums of Squares) statistic and regularised orthogonal least squares. The proposed algorithm aims to achieve maximised model robustness via two effective and complementary approaches, parameter regularisation via ridge regression and model optimal generalisation structure selection. The major contributions are to derive the PRESS error in a regularised orthogonal weight model, develop an efficient recursive computation formula for PRESS errors in the regularised orthogonal least squares forward regression framework and hence construct a model with a good generalisation property. Based on the properties of the PRESS statistic the proposed algorithm can achieve a fully automated model construction procedure without resort to any other validation data set for model evaluation.
NONSINGULAR COSMOLOGIES FROM BRANES
Authors: BISWAS ANINDYA , MUKHERJI SUDIPTA , PAL SHESANSU SEKHAR
Published: February 2004

We analyze possible cosmological scenarios on a brane where the brane acts as a dynamical boundary of various black holes with anti-de Sitter or de Sitter asymptotic. In many cases, the brane is found to describe the completely nonsingular universe. In some cases, quantum gravity era of the brane-universe can also be avoided by properly tuning bulk parameters. We further discuss the creation of a brane-universe by studying its wave function. This is done by employing Wheeler–De Witt equation in the mini superspace formalism.
ANOMALIES IN NONCOMMUTATIVE GAUGE THEORIES, SEIBERG–WITTEN TRANSFORMATION AND RAMOND–RAMOND COUPLINGS
Authors: BANERJEE RABIN
Published: February 2004

We propose an exact expression for the unintegrated form of the star gauge-invariant axial anomaly in an arbitrary even dimensional noncommutative gauge theory. The proposal is based on our earlier work,7 as well as on the inverse Seiberg–Witten map and identities related to it, obtained previously15,18 by comparing Ramond–Ramond couplings in different descriptions. The integrated anomalies, found from the unintegrated ones, are expressed in terms of a simplified version of the Elliott formula involving the noncommutative Chern character. These anomalies, under the Seiberg–Witten transformation, reduce to the ordinary (integrated) axial anomalies. Compatibility with existing results of anomalies in noncommutative theories is established.
SUPERPOTENTIAL OF THE M-THEORY CONIFOLD AND TYPE IIA STRING THEORY
Authors: CURIO GOTTFRIED
Published: February 2004

The membrane instanton superpotential for M-theory on the G2 holonomy manifold given by the cone on S3×S3 is given by the dilogarithm and has Heisenberg monodromy group in the quantum moduli space. We compare this to a Heisenberg group action on the type IIA hypermultiplet moduli space for the universal hypermultiplet, to metric corrections from membrane instantons related to a twisted dilogarithm for the deformed conifold and to a flat bundle related to a conifold period, the Heisenberg group and the dilogarithm appearing in five-dimensional Seiberg/Witten theory.
CONSISTENCY CONDITIONS FOR AdS/CFT EMBEDDINGS
Authors: FRAMPTON PAUL H. , KEPHART THOMAS W.
Published: February 2004

The group embeddings used in orbifolding the AdS/CFT correspondence to arrive at quiver gauge field theories are studied for both supersymmetric and nonsupersymmetric cases. For an orbifold AdS 5×S5/Γ the conditions for embeddings of the finite group Γ in the SU (4)~ O (6) isotropy of S5 are stated in the form of consistency rules, both for Abelian and non-Abelian Γ.
Simultaneous measurements of X-ray diffraction (XRD) and differential scanning calorimetry (DSC) data under controlled humidity condition: Instrumentation and application to studies on hydration, dehydration, and rehydration processes of pharmaceutical compounds
Authors: Kishi A. , Toraya H.
Published: March 2004

An instrument for the simultaneous measurement of X-ray powder diffraction (XRD) data and differential scanning calorimetry (DSC) data under a controlled humidity condition has been developed in order to achieve a design concept of reliable and simple in operation. Examples of the application to studies on hydration, dehydration, and rehydration processes of pharmaceutical compounds under various humidity conditions are presented. The usefulness of the present XRD-DSC system will be demonstrated.
Mathematics and Time
Authors:   Fraser
Published: February 2004

The structure of mathematics, as revealed by the exploration of axiomatic systems, bears striking similarities to the structure of nature, as revealed by the hierarchical theory of time. It is assumed that this isomorphism is not accidental but reflects the evolutionary development of the human capacity of handling numbers. This assumption permits a conjecture. Namely, if mathematics is found to possess certain systematic uncertainties, than nature must also possess corresponding qualities which may be identified. The paper proposes that the theme of the conference, "time and uncertainty," be understood in this broad context. I would like to demonstrate the existence of certain striking similarities between the structure and properties of mathematics on the one hand and, on the other hand, the structures and processes of nature at large, as revealed by the hierarchical theory of time. Then, using these correspondences, I propose a framework that promises to provide a unified perspective for the rich program we have ahead.
A Time to Regender: The Transformation of Roman Time
Authors: Dowling Melissa Barden
Published: February 2004

At the end of the first century A.D., at the height of the Roman empire, a new abstract deity of eternal time, Aeternitas, appeared. This first discrete personification of abstract time was initially a female image represented on official coins and monuments, but in A.D. 121, a new male personification of eternal time appeared in imperial, state sponsored art. Both male and female depictions of eternal time were accompanied by a rich array of attributes that connected eternity, immortality, and earthly prosperity. This change in the image of time occurred simultaneously with tremendous changes in Roman culture: the creation of universal time keeping, the creation of elaborate beliefs in the afterlife, and transformations in Romans' expectations of life, lead to the embodiment of an ideal of eternity in the personification Aeternitas, and explain the radical transformations in her/his iconography. It is through a study of the representation of time that we identify a profound reenvisioning of the nature of time in Western thought, when human temporal and metaphysical experiences of time were expanded, laying the foundation for the successful spread of the Christian conceptions of eternal blissful time after the apocalypse.
Darwinian Uncertainty
Authors: Greenspan Ralph
Published: February 2004

Reductionistic explanations in biology generally assume that biological mechanisms are highly deterministic. A contrasting view has emerged recently that takes into account the degeneracy of biological processes- the ability to arrive at a given endpoint by a variety of available paths- and pays particular attention to the role of history and contingency in biology.
An introduction to European Union health law
Authors: Dommers
Published: March 2004

No Abstract
Embryo Research and Human Rights An Overview of Developments in Europe
Authors: Kriari-Catranis
Published: March 2004

This article discusses some of the human rights issues related to embryo research and overviews European legislation in this field.
The Persistent Vegetative State: A Duty (Not) To Treat and Conscientious Objection
Authors: Grubb
Published: March 2004

No Abstract
Learning Biology through Research Papers: A Stimulus for Question-Asking by High-School Students
Authors: Brill Gilat , Yarden Anat
Published: February 2004

Question-asking is a basic skill, required for the development of scientific thinking. However, the way in which science lessons are conducted does not usually stimulate question-asking by students. To make students more familiar with the scientific inquiry process, we developed a curriculum in developmental biology based on research papers suitable for high-school students. Since a scientific paper poses a research question, demonstrates the events that led to the answer, and poses new questions, we attempted to examine the effect of studying through research papers on students' ability to pose questions. Students were asked before, during, and after instruction what they found interesting to know about embryonic development. In addition, we monitored students' questions, which were asked orally during the lessons. Questions were scored according to three categories: properties, comparisons, and causal relationships. We found that before learning through research papers, students tend to ask only questions of the properties category. In contrast, students tend to pose questions that reveal a higher level of thinking and uniqueness during or following instruction with research papers. This change was not observed during or following instruction with a textbook. We suggest that learning through research papers may be one way to provide a stimulus for question-asking by high-school students and results in higher thinking levels and uniqueness.
Evaluation of Two CD-ROMs from a Series on Cell Biology
Authors: Sander Uwe , Kerlen Gertraude , Steinke Mattias , Huk Thomas , Floto Christian
Published: February 2004

Two CD-ROMs from a series dealing with various major aspects of cell biology are evaluated in this paper using quantitative and qualitative approaches. The findings delimit similarities and differences of the two CD-ROMs and shed light on how the programs could be used in the learning process and how they should not be. The overall impression, as well as the graphical and technical features, received a predominantly good rating. The defined target groups were reached (e.g., students in secondary schools), different learning approaches were supported (e.g., discovery and autonomous learning), the CD-ROMs' usability was assessed as being easy and intuitive, and the majority of the evaluators were satisfied with the level of interactivity. Navigational problems encountered in CD-ROM 1 were overcome by a successful implementation of new navigational functions in CD-ROM 2. Most students found the CD-ROM to be a suitable complement to, or an extension of, their lessons. We conclude that many, but not all of the requirements for the various stages of the learning process could be satisfied with the existing CD-ROMs. The requirements not met are discussed to obtain insights that could help to improve the production of multimedia learning material. The use of quantitative and qualitative approaches in the evaluation of learning modules is discussed, as the study began by collecting and analyzing anecdotal reviews and was then extended to include a qualitative evaluation.
Investigations of Protein Structure and Function Using the Scientific Literature: An Assignment for an Undergraduate Cell Physiology Course
Authors: Mulnix Amy B.
Published: February 2004

Undergraduate biology curricula are being modified to model and teach the activities of scientists better. The assignment described here, one that investigates protein structure and function, was designed for use in a sophomore-level cell physiology course at Earlham College. Students work in small groups to read and present in poster format on the content of a single research article reporting on the structure and/or function of a protein. Goals of the assignment include highlighting the interdependence of protein structure and function; asking students to review, integrate, and apply previously acquired knowledge; and helping students see protein structure/function in a context larger than cell physiology. The assignment also is designed to build skills in reading scientific literature, oral and written communication, and collaboration among peers. Assessment of student perceptions of the assignment in two separate offerings indicates that the project successfully achieves these goals. Data specifically show that students relied heavily on their peers to understand their article. The assignment was also shown to require students to read articles more carefully than previously. In addition, the data suggest that the assignment could be modified and used successfully in other courses and at other institutions.
Apoptosis: A Four-Week Laboratory Investigation for Advanced Molecular and Cellular Biology Students
Authors: DiBartolomeis Susan M. , Moné James P.
Published: February 2004

Over the past decade, apoptosis has emerged as an important field of study central to ongoing research in many diverse fields, from developmental biology to cancer research. Apoptosis proceeds by a highly coordinated series of events that includes enzyme activation, DNA fragmentation, and alterations in plasma membrane permeability. The detection of each of these phenotypic changes is accessible to advanced undergraduate cell and molecular biology students. We describe a 4-week laboratory sequence that integrates cell culture, fluorescence microscopy, DNA isolation and analysis, and western blotting (immunoblotting) to follow apoptosis in cultured human cells. Students working in teams chemically induce apoptosis, and harvest, process, and analyze cells, using their data to determine the order of events during apoptosis. We, as instructors, expose the students to an environment closely simulating what they would encounter in an active cell or molecular biology research laboratory by having students coordinate and perform multiple tasks simultaneously and by having them experience experimental design using current literature, data interpretation, and analysis to answer a single question. Students are assessed by examination of laboratory notebooks for completeness of experimental protocols and analysis of results and for completion of an assignment that includes questions pertaining to data interpretation and apoptosis.
Sphingosine 1-phosphate and its type 1 G protein-coupled receptor: trophic support and functional regulation of T Lymphocytes
Authors: Goetzl Edward J , Gräler Markus H
Published: March 2004

The lysophospholipid (LPL) growth factors sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are generated by macrophages, dendritic cells, mast cells, and platelets, which leads to lymph and plasma concentrations of 0.1–1 μM. Distinctive profiles of G protein-coupled receptors (GPCRs) for S1P and LPA are expressed by each type of immune cell and are regulated by cellular activation. At 1–100 nM, S1P signals T cells through their principal S1P1 GPCRs with consequent protection from apoptosis, enhancement of chemotaxis, and facilitation of optimal regulatory activity of CD4+25+ T cells. At 0.3–3 μM, S1P inhibits T cell chemotaxis and to a lesser extent other functions. These S1P–S1P1 GPCR signals suppress homing of blood and spleen T cells to secondary lymphoid tissues. S1P1 GPCR antagonists evoke lymphopenia by permitting blood T cells to enter lymph nodes and blocking S1P1 GPCR-dependent T cell efflux from lymph nodes. Inversely, there is a decrease in lymphoid tissue traffic of T cells in transgenic mice, which overexpress lymphocyte S1P1 GPCRs. The immunotherapeutic activity of S1P1 GPCR antagonists, which limits T cell access to organ grafts and autoimmune antigens, does not reduce other functional capabilities of T cells. LPLs and their GPCRs thus constitute an immunoregulatory system of sufficient prominence for pharmacological targeting in transplantation, autoimmunity, and immunodeficiency.
Culture-bound syndromes: the story ofdhatsyndrome
Authors: Sumathipala A. , Siribaddana S. H. , Bhugra Dinesh
Published: February 2004

Background

Culture-bound syndrome is a term used to describe the uniqueness of some syndromes in specific cultures.Dhat(semen-loss anxiety) has been considered to be an exotic ‘neurosis of the Orient’.

Aims

To ascertain the presence of similar symptoms and syndromes in different cultures and historical settings.

Method

Electronic and manual literature searches were used to gather information on the existence and description of semen-loss anxiety in different cultures and settings.

Results

Most of the empirical studies ondhatsyndrome have emerged from Asia, whereas its concepts have been described historically in other cultures, including Britain, the USA and Australia. The different sources indicate the universality of symptoms and global prevalence of this condition, despite its image as a ‘neurosis of the Orient’.

Conclusions

It appears thatdhat(semen-loss anxiety) is not as culture-bound as previously thought. We propose that the concept of culture-bound syndromes should be modified in line with DSM–IV recommendations.
Association between childhood feeding problems and maternal eating disorder: role of the family environment
Authors: Cooper Peter J. , Whelan Elizabeth , Woolgar Matthew , Morrell Julian , Murray Lynne
Published: February 2004

Background

There is a strong relationship between feeding problems in childhood and eating disorder in the mother. The mechanisms responsible for this relationship are not understood.

Aims

To elucidate family-environmental factors that could mediate this association.

Method

A general population sample of children with feeding problems (n=35), other problems (shyness, fears or behavioural problems; n=58), or no problems (n=23) was identified. The mental state of their mothers was evaluated, including an assessment of current and past eating disorder. Video recordings were made in the families' homes of a mealtime and of the mothers and children participating in a standardised exploratory task.

Results

Two family-environmental variables significantly distinguished the children with feeding problems from the other two groups: ‘mealtime disorganisation’ and ‘maternal strong control and disharmony’. Path analysis revealed the importance of these two environmental variables in mediating the association between child and maternal disturbance.

Conclusions

The degree of mealtime disorganisation and the level of maternal strong control and disharmony mediate the association between maternal eating disorder and child feeding disturbance.
Neural response to emotional prosody in schizophrenia and in bipolar affective disorder
Authors: Mitchell Rachel L. C. , Elliott Rebecca , Barry Martin , Cruttenden Alan , Woodruff Peter W.R.
Published: February 2004

Background

Evidence suggests a reversal of the normal left-lateralised response to speech in schizophrenia.

Aims

To test the brain's response to emotional prosody in schizophrenia and bipolar disorder.

Method

BOLD contrast functional magnetic resonance imaging of subjects while they passively listened or attended to sentences that differed in emotional prosody.

Results

Patients with schizophrenia exhibited normal right-lateralisation of the passive response to ‘pure’ emotional prosody and relative left-lateralisation of the response to unfiltered emotional prosody. When attending to emotional prosody, patients with schizophrenia activated the left insula more than healthy controls. When listening passively, patients with bipolar disorder demonstrated less activation of the bilateral superior temporal gyri in response to pure emotional prosody, and greater activation of the left superior temporal gyrus in response to unfiltered emotional prosody. In both passive experiments, the patient groups activated different lateral temporal lobe regions.

Conclusions

Patients with schizophrenia and bipolar disorder may display some left-lateralisation of the normal right-lateralised temporal lobe response to emotional prosody.
Cognitive–behavioural therapy in first-episode and early schizophrenia
Authors: Tarrier Nicholas , Lewis Shôn , Haddock Gillian , Bentall Richard , Drake Richard , Kinderman Peter , Kingdon David , Siddle Ronald , Everitt Julie , Leadley Karen , Benn Andy , Grazebrook Katy , Haley Cliff , Akhtar Shahid , Avies Lindad , Palmer Steve , Dunn Graham
Published: February 2004

Background

The initial phase of a trial of cognitive–behavioural therapy (CBT) for acutely ill patients with schizophrenia of recent onset showed that it speeded recovery.

Aims

To test the hypothesis that CBT in addition to treatment as usual (TAU) during the first or second acute episode of schizophrenia will confer clinical benefit over a follow-up period.

Method

This was an 18-month follow-up of a multicentre prospective trial of CBT or supportive counselling administered as an adjunct to TAU, compared with TAU alone, for patients hospitalised for an acute episode of schizophrenia of recent onset. Primary outcomes were total and positive symptom scales, time to relapse and re-hospitalisation.

Results

There were significant advantages for CBT and supportive counselling over TAU alone on symptom measures at 18 months but no group difference was seen for relapse or re-hospitalisation. There was a significant centre–treatment interaction, reflecting centre differences in the effect of introducing either treatment, but not in the comparison of CBT and supportive counselling. Medication dosage and compliance did not explain group differences.

Conclusions

Adjunctive psychological treatments can have a beneficial longterm effect on symptom reduction.
Post-traumatic stress and disability
Authors: Neal Leigh A. , Green Gillian , Turner Mark A.
Published: February 2004

Background

Post-traumatic stress is thought to account for significant disability. It is also known to be highly comorbid with other psychiatric conditions such as depression and alcohol dependence.

Aims

To determine the relationship between post-traumatic stress, depression, alcohol dependence and disability.

Method

Seventy armed services personnel were assessed for DSM–IV diagnoses of post-traumatic stress disorder, major depressive disorder and alcohol dependence, and with continuous measures of symptoms of post-traumatic stress, depression and alcohol dependence following a traumatic event. These variables, as predictors of disability (using the Sheehan Disability Scale), were analysed using multivariate analysis of variance, analysis of covariance and multiple regression backward elimination models.

Results

No significant interaction was found for the diagnostic variables even after controlling for the continuous symptom measures. In the regression models, symptoms of depression were a significant predictor of total disability (R2=0.39). Symptoms of alcohol dependence and post-traumatic stress did not significantly predict disability.

Conclusions

Since post-traumatic stress was not found to be associated with disability, its clinical importance may be questionable.
Suicide by prisoners
Authors: Shaw Jenny , Baker Denise , Hunt Isabelle M. , Moloney Anne , Appleby Louis
Published: February 2004

Background

The number of suicides in prison has increased over recent years. This is the first study to describe the clinical care of a national sample of prison suicides.

Aims

To describe the clinical and social circumstances of self-inflicted deaths among prisoners.

Method

A national clinical survey based on a 2-year sample of self-inflicted deaths in prisoners. Detailed clinical and social information was collected from prison governors and prison health care staff.

Results

There were 172 self-inflicted deaths: 85 (49%; 95% CI 42–57) were of prisoners on remand; 55 (32%; 95% CI 25–39) occurred within 7 days of reception into prison. The commonest method was hanging or self-strangulation (92%; 95% CI 88–96). A total of 110 (72%; 95% CI 65–79) had a history of mental disorder. The commonest primary diagnosis was drug dependence (39, 27%; 95% CI 20–35). Eighty-nine (57%; 95% CI 49–64) had symptoms suggestive of mental disorder at reception into prison.

Conclusions

Suicide prevention measures should be concentrated in the period immediately following reception into prison. Because hanging is the commonest method of suicide, removal of potential ligature points from cells should be a priority.
Ten books
Authors: Bloch Sidney
Published: February 2004

When I received the invitation to contribute to the ‘Ten Books' series, I resonated more with the phrase ‘sources of inspiration’ than with the guideline to select books that have had ‘a significant impact on my professional life’. It so happens that this rather unusual challenge is the second to have come my way in recent times. We initiated a similar project for medical students at the University of Melbourne in which faculty members select a text that ‘matters' to them, ostensibly in a professional way, although the request is left intentionally vague. Then, as now, I surmised that the books that have influenced us professionally are not dissimilar to those that occupy a central place in our lives generally.
Does protected time improve psychotherapy training in psychiatry?
Authors: Janmohamed Anis , Ward Anne , Smith Catherine , Davison Susan
Published: February 2004

Aims and Method

We surveyed all our senior house officers (SHOs) in 1998 to ascertain the nature and quality of their psychotherapy training. Following the introduction of a structured psychotherapy training programme, we wished to see what difference this had made to their training experience. The same questionnaire was used to survey all SHOs currently training in our trust, and compared their responses with those of the earlier cohort.

Results

There was a statistically significant increase in the number of trainees seeing patients, in the number of psychotherapy patients being seen, and in the expectations of trainees of being able to fulfil College requirements.

Clinical Implications

Our results demonstrate the value of a formal psychotherapy training programme for the quality of psychotherapy training at SHO level. In particular, the introduction of protected time may have been crucial in allowing the SHOs to gain the necessary experience.
Root cause analysis applied to the investigation of serious untoward incidents in mental health services
Authors: Neal L. A. , Watson D. , Hicks T. , Porter M. , Hill D.
Published: February 2004

The Department of Health publication Building a Safer NHS for Patients sets out the Government's plans for promoting patient safety (Department of Health, 2001). This follows growing international recognition that health services around the world have underestimated the scale of unintended harm or injury experienced by patients as a result of medical error and adverse events occurring in health care settings. These plans include a commitment to replace the procedures set out in the Department of Health circular HSG(94)27. This guidance details the methods for investigating every homicide (and some suicides) by patients in current or recent contact with specialist mental health services. Part of the process to modernise HSG(94)27 includes a plan to build expertise within the National Health Service (NHS) in the technique of root cause analysis. This investigative process was developed in industry to identify causal or systems factors in serious adverse events.
Should old age psychiatry develop memory clinics? A comparison with domiciliary work
Authors: Simpson S. , Beavis D. , Dyer J. , Ball S.
Published: February 2004

Aims and Method

Memory clinics have become very popular in old age psychiatry and there is some pressure for them to be developed in old age services. However, there is little evidence to suggest that they are more advantageous over the traditional domiciliary visits or who should be seen in clinic. This was a naturalistic comparison of 76 consecutive new referrals to a memory clinic, with 74 consecutive new domiciliary requests within the same service over the same period of time. A retrospective case note review collected the clinical features and an 18-month prospective follow-up examined the subsequent clinical management.

Clinical Implications

The two groups were characterised more by their similarities than their differences. However, the domiciliary group had greater behavioural and psychological complications. The memory clinic patients were less likely to receive psychotropic medication and here more likely to be followed up.

Results

We conclude that memory clinics might be less suitable for patients with prominent psychiatric complications. Memory clinics could complement the domiciliary model by providing early psychosocial/neuropsychiatric approaches, although this is likely to lead to an increased clinical case-load.
Who's happy with supervision?
Authors: Ho Hilda , McConville Pauline
Published: February 2004

Aims and Method

All psychiatry trainees and supervisors on the Southeast Scotland scheme were invited to complete a questionnaire about the regularity, responsibility, structure, content and value of supervision.

Results

Significantly more supervisors (87%) than trainees (69%) reported regular supervision. Some trainees still find it difficult to obtain regular supervision. Although it is seen as a joint responsibility, there is uncertainty about the role and responsibility of each trainee and supervisor. Most trainees and supervisors feel that supervision is useful, but supervisors are likely to rate their quality of supervision better than their trainees. Guidelines for the structure, content and boundaries of supervision might be useful. Supervision is viewed as useful for discussing clinical management, including the trainee's own case-load.

Clinical Implications

Training in the use of supervision should be available to all trainees and supervisors. Regular supervision should be a priority, and it is a joint responsibility to ensure that it happens. There should be greater accountability to the College and Trusts. Discussion of the trainee's clinical case-load during supervision is a necessary part of training and the supervision process.
Consent quiz: how well would you do?
Authors: Potter Rob
Published: February 2004

The law relating to consent to treatment in children can be confusing. It is made up of a patchwork of statutory and case law that reflects an ambivalence between respecting the rights and autonomy of the child and the pervading paternalism within the courts and society more generally. This has lead to an ebb and flow of these competing pressures over the years.
Caring for Sikh patients wearing akirpan(traditional small sword): cultural sensitivity and safety issues
Authors: Singh Swaran P.
Published: February 2004

Devout Sikh men wear thekirpan(a traditional small sword) as part of their religious faith. Thekirpanis one of five symbols of Sikhism (the fiveKs described below). Many traditional Sikhs undergo theamritceremony, akin to baptism, following which they are meant to wear the fiveKs at all times. Several legal controversies have emerged in the West, especially in the USA (Lal, 1999) and Canada (Wayland, 1997), over safety issues related to thekirpan, such as students wearing it to school or passengers wearing it during flights (for an overview of the recent cases, seewww.sikhs.ca/kirpan).
Hu and Voltage-Gated Calcium Channel (VGCC) Antibodies Related to the Prognosis of Small-Cell Lung Cancer
Authors: Monstad S.E. , Drivsholm L. , Storstein A. , Aarseth J.H. , Haugen M. , Lang B. , Vincent A. , Vedeler C.A.
Published: February 2004

Purpose

Hu antibodies previously have been associated with longer survival of patients with small-cell lung cancer (SCLC). Voltage-gated calcium channel (VGCC) antibodies play a pathogenic role in Lambert Eaton myasthenic syndrome, which is also associated with SCLC. These antibodies may reduce tumor growth in patients with the neurologic disease, but it is not clear whether they provide prognostic information in those without neurologic symptoms.

Patients and Methods

Two hundred patients with SCLC (age 39 to 79 years; mean, 62.3 years; 129 males and 71 females) receiving chemotherapy were studied for the presence of Hu and VGCC antibodies. Sera were examined for Hu antibodies by an in vitro transcription-translation–based immunoprecipitation technique and by immunohistochemistry/dot blot. VGCC (P/Q subtype) antibodies were detected by radioimmunoassay. Survival analysis was used to analyze the data.

Results

Hu antibodies were detected in 51 of 200 patients (25.5%) by in vitro transcription-translation–based immunoprecipitation and in 37 of 200 patients (18.5%) by immunohistochemistry or dot blot, whereas VGCC antibodies were detected in only 10 of 200 patients (5%). The presence of Hu antibodies did not correlate with VGCC antibodies, and there was no association between Hu or VGCC antibodies and the extent of disease or survival.

Conclusion

Hu and VGCC antibodies are found in a proportion of SCLC patients, irrespective of neurologic symptoms, but their presence does not correlate with the prognosis of the SCLC.
Pharmacokinetics and Pharmacodynamics of Imatinib in a Phase I Trial With Chronic Myeloid Leukemia Patients
Authors: Peng Bin , Hayes Michael , Resta Debra , Racine-Poon Amy , Druker Brian J. , Talpaz Moshe , Sawyers Charles L. , Rosamilia Marianne , Ford John , Lloyd Peter , Capdeville Renaud
Published: February 2004

Purpose

To evaluate the basic pharmacokinetic (PK) characteristics of imatinib mesylate and assess the relationship between the PK and pharmacodynamic (PD) properties of the drug.

Patients and Methods

The PK and PD properties of imatinib were investigated during a phase I trial that included 64 adult patients with Philadelphia chromosome–positive leukemias. Patients received imatinib orally once or twice daily. PK parameters of imatinib, derived from the plasma concentration–time curves, were determined. PD response, defined as the WBC after 1 month of treatment with imatinib, was used to develop an efficacy model. A maximum inhibition–effect model was used to describe the relationship between reduction in WBC and drug exposure parameters.

Results

Imatinib exposure was dose proportional after oral administration for the dose range of 25 to 1,000 mg. There was a 1.5- to three-fold drug accumulation after repeated once-daily dosing. Mean plasma trough concentration was 0.57 μg/mL (approximately 1 μmol/L) 24 hours after administration of 350 mg of imatinib at steady-state, which exceeds the 50% inhibitory concentration required to inhibit proliferation of Bcr-Abl–positive leukemic cells. Analysis of PK/PD relationships indicates that the initial hematologic response depends on the administered dose for patients with chronic myeloid leukemia.

Conclusion

Drug exposure (area under the concentration-time curve) is dose proportional for the dose range of 25 to 1,000 mg, and there is a 1.5- to three-fold drug accumulation at steady-state after once-daily dosing. Analysis of the relationship between PD (WBC reduction) and PK parameters at steady-state indicates that a dose of 400 mg or greater is required for maximal PD effect.
Prognostic Model of Pulmonary Adenocarcinoma by Expression Profiling of Eight Genes As Determined by Quantitative Real-Time Reverse Transcriptase Polymerase Chain Reaction
Authors: Endoh Hideki , Tomida Shuta , Yatabe Yasushi , Konishi Hiroyuki , Osada Hirotaka , Tajima Kohei , Kuwano Hiroyuki , Takahashi Takashi , Mitsudomi Tetsuya
Published: February 2004

Purpose

Recently, several expression-profiling experiments have shown that adenocarcinoma can be classified into subgroups that also reflect patient survival. In this study, we examined the expression patterns of 44 genes selected by these studies to test whether their expression patterns were relevant to prognosis in our cohort as well, and to create a prognostic model applicable to clinical practice.

Patients and Methods

Expression levels were determined in 85 adenocarcinoma patients by quantitative reverse transcriptase polymerase chain reaction. Cluster analysis was performed, and a prognostic model was created by the proportional hazards model using a stepwise method.

Results

Hierarchical clustering divided the cases into three major groups, and group B, comprising 21 cases, had significantly poor survival (P = .0297). Next, we tried to identify a smaller number of genes of particular predictive value, and eight genes (PTK7, CIT, SCNN1A, PGES, ERO1L, ZWINT, and two ESTs) were selected. We then calculated a risk index that was defined as a linear combination of gene expression values weighted by their estimated regression coefficients. The risk index was a significant independent prognostic factor (P = .0021) by multivariate analysis. Furthermore, the robustness of this model was confirmed using an independent set of 21 patients (P = .0085).

Conclusion

By analyzing a reasonably small number of genes, patients with adenocarcinoma could be stratified according to their prognosis. The prognostic model could be applicable to future decisions concerning treatment.
HER-2 Testing and Trastuzumab Therapy for Metastatic Breast Cancer: A Cost-Effectiveness Analysis
Authors: Elkin Elena B. , Weinstein Milton C. , Winer Eric P. , Kuntz Karen M. , Schnitt Stuart J. , Weeks Jane C.
Published: February 2004

Purpose

Trastuzumab therapy has been shown to benefit metastatic breast cancer patients whose tumors exhibit HER-2 protein overexpression or gene amplification. Several tests of varying accuracy and cost are available to identify candidates for trastuzumab. We estimated the cost-effectiveness of alternative HER-2 testing and trastuzumab treatment strategies.

Patients and Methods

We performed a decision analysis using a state-transition model to simulate clinical practice in a hypothetical cohort of 65-year-old metastatic breast cancer patients. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). Interventions included testing with the HercepTest (DAKO, Carpinteria, CA) immunohistochemical assay alone, fluorescence in situ hybridization (FISH) alone, and both tests, followed by trastuzumab and chemotherapy for patients with positive test results and chemotherapy alone for patients with negative test results.

Results

In the base case, initial HercepTest with FISH confirmation of all positive results had an ICER of $125,000 per QALY gained. The incremental cost-effectiveness of initial FISH was $145,000 per QALY gained. Other strategies yielded the same or poorer effectiveness at a higher cost, or lower effectiveness at a lower cost, but with a less favorable ICER. These findings persisted under a range of assumptions, and only changes in test characteristics substantially altered results.

Conclusion

It is more cost-effective to use FISH alone or as confirmation of all positive HercepTest results, rather than using FISH to confirm only weakly positive results or using HercepTest alone. When multiple tests are available to identify treatment candidates, test characteristics may have a substantial impact on the aggregate costs and effectiveness of treatment.
Lamivudine for the Prevention of Hepatitis B Virus Reactivation in Hepatitis B s-Antigen Seropositive Cancer Patients Undergoing Cytotoxic Chemotherapy
Authors: Yeo Winnie , Chan Paul K.S. , Ho Wing M. , Zee Benny , Lam Kwok C. , Lei Kenny I.K. , Chan Anthony T.C. , Mok Tony S.K. , Lee Jam J. , Leung Thomas W.T. , Zhong Sheng , Johnson Philip J.
Published: February 2004

Purpose

For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy.

Patients and Methods

Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared.

Results

In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P < .001), fewer incidences of hepatitis (17.5% v 44.6%; P < .0001) that were less severe (4.8% v 18.7%; P = .0005), and less disruption of chemotherapy (15.4% v 34.6%; P = .0029). The reduction in overall mortality was not statistically different.

Conclusion

Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.