bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing for Panel Cointegration with Multiple Structural Breaks*
Authors: Westerlund Joakim
Published: February 2006

This paper proposes a Lagrange multiplier (LM) test for the null hypothesis of cointegration that allows for the possibility of multiple structural breaks in both the level and trend of a cointegrated panel regression. The test is general enough to allow for endogenous regressors, serial correlation and an unknown number of breaks that may be located at different dates for different individuals. We derive the limiting distribution of the test and conduct a small Monte Carlo study to investigate its finite sample properties. In our empirical application to the solvency of the current account, we find evidence of cointegration between saving and investment once a level break is accommodated.
PRESENCE
Authors: RUNIA EELCO
Published: February 2006

“Erst wie eine fremde Gewalt [der Mensch] ergreift, ihm forttreibt, und … in ihm lebendig wird, kommt wirkliches und wahrhaftes Daseyn in sein Leben.”

—Fichte2

For more than thirty years now, thinking about the way we, humans, account for our past has taken place under the aegis of representationalism. In its first two decades, representationalism, inaugurated by Hayden White's Metahistory of 1973, has been remarkably successful, but by now it has lost much of its vigor and it lacks explanatory power when faced with recent phenomena such as memory, lieux de mémoire, remembrance, and trauma. It might be argued that many of the shortcomings of representationalism spring from the fact that it is exclusively geared to “transfer of meaning.” This essay posits that what may be called “presence” (“the unrepresented way the past is present in the present”) is at least as important as “meaning.”“Presence” can be dealt with by employing a “topical” view of history (in the manner of, for example, Vico) in which the whole of history is stored in “places” (that is, “institutions”) that can be “visited” on the plane of the present. Presence can be said to be stored in metonymy. Whereas metaphor is instrumental in the “transfer of meaning,” metonymy brings about a “transfer of presence.” A metonymy is a “presence in absence” not just in the sense that it presents something that isn't there, but also in the sense that in the absence (or at least the radical inconspicuousness) that is there, the thing that isn't there is still present. The presence of the past thus does not reside primarily in the intended story or the manifest metaphorical content of the text, but in what story and text contain in spite of the intentions of the historian. One might say that historical reality travels with historiography not as a paying passenger but as a stowaway. As a stowaway, as what is absently and unintentionally present on the plane of time, metonymy is a metaphor for discontinuity, or, rather, for the entwinement of continuity and discontinuity.
BEYOND COMPARISON: HISTOIRE CROISÉE AND THE CHALLENGE OF REFLEXIVITY1
Authors: WERNER MICHAEL , ZIMMERMANN BÉNÉDICTE
Published: February 2006

This article presents, in a programmatic way, the histoire croisée approach, its methodological implications and its empirical developments. Histoire croisée draws on the debates about comparative history, transfer studies, and connected or shared history that have been carried out in the social sciences in recent years. It invites us to reconsider the interactions between different societies or cultures, erudite disciplines or traditions (more generally, between social and cultural productions). Histoire croisée focuses on empirical intercrossings consubstantial with the object of study, as well as on the operations by which researchers themselves cross scales, categories, and viewpoints. The article first shows how this approach differs from purely comparative or transfer studies. It then develops the principles of pragmatic and reflexive induction as a major methodological principle of histoire croisée. While underlining the need and the methods of a historicization of both the objects and categories of analysis, it calls for a reconsideration of the way history can combine empirical and reflexive concerns into a dynamic and flexible approach.
CHARTING THE “TRANSITIONAL PERIOD”: THE EMERGENCE OF MODERN TIME IN THE NINETEENTH CENTURY
Authors: BLIX GÖRAN
Published: February 2006

This paper seeks to chart a concept of historical experience that French Romantic writers first developed to describe their own relationship to historical time: the notion of the “transitional period.” At first, the term related strictly to the evolving periodic conception of history, one that required breaks, spaces, or zones of indeterminacy to bracket off periods imagined as organic wholes. These transitions, necessary devices in the new grammar of history, also began to attract interest on their own, conceived either as chaotic but creative times of transformation, or, more often, as slack periods of decadence that possessed no proper style but exhibited hybrid traits. Their real interest, however, lies in their reflexive application to the nineteenth century itself, by writers and historians such as Alfred de Musset, Chateaubriand, Michelet, and Renan, who in their effort to define their own period envisioned the “transitional period” as a passage between more coherent and stable historical formations. This prospective self‐definition of the “age of history” from a future standpoint is very revealing; it shows not just the tension between its organic way of apprehending the past and its own self‐perception, but it also opens a window on a new and paradoxical experience of time, one in which change is ceaseless and an end in itself. The paper also presents a critique of the way the term “modernity” has functioned, from Baudelaire's initial use to the present, to occlude the experience of transition that the Romantics highlighted. By imposing on the nineteenth‐century sense of the transitory a heroic period designation, the term “modernity” denies precisely the reality it describes, and sublimates a widespread temporal malaise into its contrary. The paper concludes that the peculiarly “modern” mania for naming one's period is a function of transitional time, and that the concept coined by the Romantics still governs our contemporary experience.
MOMENTS OF TOTALITARIANISM
Authors: Rabinbach Anson
Published: February 2006

Hope And Memory: Lessons From The Twentieth Century. By Tzvetan Todorov. Translated by David Bellos

The Dictators: Hitler's Germany And Stalin's Russia. By Richard Overy

Stalinism And Nazism: History And Memory Compared. Edited by Henry Rousso. Translated by Lucy B. Golsan, Thomas C. Hilde, and Peter S. Rogers

Stalinism and Nazism: Dictatorships in Comparison. Edited by Ian Kershaw and Moshe Lewin

Did Somebody Say Totalitarianism? Five Interventions in the (Mis)Use of A Notion. By Slavoj Zizek
A GLOBAL AND MULTICULTURAL “DISCIPLINE” OF HISTORY?
Authors: Chakrabarty Dipesh
Published: February 2006

Western Historical Thinking: An Intercultural Debate. Edited by Jörn Rüsen
HISTORY, DISCOURSE, AND THE POSTSOCIAL PARADIGM: A REVOLUTION IN HISTORIOGRAPHY?1
Authors: Rigby S. H.
Published: February 2006

Postsocial Histroy: an Introduction. By Miguel A. Cabrera
SCIENTIFIC HISTORIOGRAPHY AND THE PHILOSOPHY OF SCIENCE
Authors: Kincaid Harold
Published: February 2006

Our Knowledge of The Past: A Philosophy of Historiography. By Aviezer Tucker
A HISTORY WITHOUT THE HISTORY
Authors: Allen Barry
Published: February 2006

In some remote corner of the universe, flickering in the light of the  countless solar systems into which it had been poured, there was  once a planet on which clever animals invented cognition. It was the  most arrogant and most mendacious minute in the “history of the  world”; but a minute was all it was. After nature had drawn just a  few more breaths the planet froze and the clever animals had to die.

—Friedrich Nietzsche

The History of Human Reason. By R. J. Robinson
The Influence of Anger‐arousal Level on Attribution of Hostile Intent and Problem Solving Capability in an Individual with a Mild Intellectual Disability and a History of Difficulties with Aggression
Authors: MacMahon Kenneth M. A. , Jahoda Andrew , Espie Colin A. , Broomfield Niall M.
Published: February 2006

Background  Recent studies have suggested that cognitive biases may play an important mediating role in aggressive outbursts from people with mild intellectual disabilities (IDs). Essentially, some individuals may frequently perceive other people as acting towards them in a hostile fashion. This biased perception may develop through repeated adverse experiences, and may make them more likely to respond, likewise, in an aggressive manner. These studies have led to the development of a cognitive behavioural model of aggression, incorporating factors both intrinsic and extrinsic to the individual. This study aimed to explore one facet of this model: a putative relationship between anger‐arousal level, problem‐solving ability and perception of hostile intent in others.

Method  Single‐case methodology was utilized, and a 44‐year‐old man with a mild ID and a history of difficulties with aggression participated. A series of vignettes, containing potentially provocative social interactions, were read to the participant. His perception of hostile intent, and suggestions of possible behavioural responses were recorded as dependent variables. Anger‐arousal was manipulated, through autobiographical recall, as a dependent variable.

Results  Although not conclusive, results indicate that anger‐arousal may act in an interactive fashion to increase perception of hostile intent. No effect of anger‐arousal was observed on problem‐solving ability; however, floor‐effects in the task used may provide an explanation for this.

Conclusions  A high level of anger‐arousal may exacerbate the probability of a frequently aggressive individual perceiving others as acting in a hostile manner. However, future research should take the limitations of this study into account, and continue development of a cognitive model of frequent aggression in those with a mild ID.
Interaction of Cognitive Distortions and Cognitive Deficits in the Formulation and Treatment of Obsessive–Compulsive Behaviours in a Woman with an Intellectual Disability
Authors: Willner Paul , Goodey Rebecca
Published: February 2006

Aims  This case study describes the formulation and cognitive–behavioural treatment (CBT) of obsessive–compulsive thoughts and behaviours in a woman with an intellectual disability. The report aimed to distinguish the cognitive deficits that reflect her disability from the cognitive distortions integral to her obsessive–compulsive disorder.

Case study  Hence, we present one account of the cognitive–behavioural interventions aimed at correcting the cognitive distortions, and a separate account of the modifications necessary to compensate for specific cognitive deficits, which include impairments not only of ‘cognitive therapy skills’, but also of aspects of memory and executive functioning skills.

Discussion  We suggest that this analysis may provide a rational approach to the problem of simplifying CBT to meet the needs of people with intellectually disabilities, by identifying more clearly the specific adaptations that are needed by a particular individual. We also discuss the assessment of cognitive deficits that might impact on CBT, and some implications of this approach for research and training.
Readiness for Cognitive Therapy in People with Intellectual Disabilities
Authors: Willner Paul
Published: February 2006

Aims  Cognitive therapies are increasingly being offered by clinical psychologists to people with intellectual disabilities. This paper reviews some of the factors that influence people's readiness to engage in cognitive therapy.

Literature review  Limited verbal ability, psychological‐mindedness (particularly in relation to the understanding of emotions and the mediating role of cognitions), and self‐efficacy, are all likely to present significant barriers. There may also be motivational barriers to treatment, including the functionality of some psychological presentations, maladaptive beliefs promoting resistance to change, the intellectually challenging nature of cognitive therapy, and external factors such as inappropriate settings. Engagement with therapy can be promoted by involving carers to support the therapy, but carers may themselves display a range of limitations of ability and motivation similar to those displayed by clients, which need to be recognized, and where possible addressed, in order for their involvement to be effective.

Recommendations  If barriers to treatment are recognized, significant steps can be taken to increase accessibility. In addition to simplifying the delivery of therapy, there is also scope to simplify the model; this point is illustrated by case examples, and some principles for formalizing modifications to standard procedures are suggested. As barriers to treatment can often be surmounted, a decision whether or not to offer cognitive therapy should be derived from a comprehensive formulation, and should never be based solely on a client's performance on tests of cognitive ability.
Adapting Individual Psychotherapy for Adults with Intellectual Disabilities: A Comparative Review of the Cognitive–Behavioural and Psychodynamic Literature
Authors: Whitehouse Richard M. , Tudway Jeremy A. , Look Roger , Kroese Biza Stenfert
Published: February 2006

Background  Historically, adults with intellectual disabilities have had little access to individual psychotherapy. Over the last 20 years an increasing body of literature has described psychotherapy with this client group and reported methods for adapting traditional psychotherapeutic techniques.

Method  The current review identified the frequency of adaptations suggested by Hurley et al. (1998) [Journal of Developmental and Physical Disabilities, vol. 10, pp. 365–386] within cognitive behavioural and psychodynamic studies with adults with intellectual disabilities. Twenty‐five studies were reviewed, 10 cognitive–behavioural and 15 psychodynamic.

Results  A total of 94 adaptations were identified. Within cognitive behavioural therapy (CBT) studies, flexibility in method was the most frequently considered adaptation whilst transference and countertransference issues were most frequently considered within psychodynamic studies. Across the two approaches, disability and rehabilitation issues were given the least consideration.

Conclusions  Implications for practitioners and services are highlighted along with recommendations for future research.
Cognitive–Behavioural Intervention for People with Intellectual Disability and Anxiety Disorders
Authors: Dagnan Dave , Jahoda Andrew
Published: February 2006

Background  Distinct cognitive models and treatments have been developed for people without intellectual disability with a wide range of anxiety disorders. However, these have not been reported as applied to people with intellectual disabilities. In fact, much of the cognitive therapy literature for people with intellectual disabilities does not distinguish between different presentations of anxiety.

Methods  We take the particular example of social phobia and describe the specific cognitive model and associated intervention developed for people without intellectual disabilities. We then consider research on the social context of people with intellectual disability and research on developmental factors predictive of anxiety and make suggestions for adaptation of treatment approaches.

Conclusion  We suggest that such an approach would be useful to apply to other anxiety presentations and to identify areas for further clinical and research development.
Do People with Intellectual Disabilities and Psychosis have the Cognitive Skills Required to Undertake Cognitive Behavioural Therapy?
Authors: Oathamshaw Stephen C. , Haddock Gillian
Published: February 2006

Background  Cognitive skills thought to be necessary to undertake cognitive–behavioural therapy (CBT) include the ability to recognize emotions, link events and emotions, and recognize cognitive mediation. These skills have been assessed in people with intellectual disabilities, but not in those who also have psychosis.

Materials and methods  Tasks assessing receptive language ability and cognitive skills including the ability to differentiate between behaviours, thoughts and feelings were administered to 50 participants who had intellectual disabilities and psychosis.

Results  The majority of participants were able to link events and emotions and differentiate behaviours and feelings. Participants found any task involving cognitions significantly more difficult. Performance on recognizing emotions, linking events and emotions and on some of the cognitive mediation and differentiation tasks was associated with receptive language ability.

Conclusions  People with intellectual disabilities and psychosis have some of the skills thought to be required to undertake cognitive behaviour therapy. Recognizing cognitions and cognitive mediation is particularly challenging. The differentiation task introduced in this study may usefully supplement existing assessments.
Assessment of the Component Skills for Cognitive Therapy in Adults with Intellectual Disability
Authors: Joyce Theresa , Globe Amanda , Moody Clare
Published: February 2006

Background  This study examines the extent to which a random sample of adults with intellectual disabilities possess the component skills necessary to undergo cognitive behaviour therapy (CBT).

Method  Seventy‐two individuals underwent a range of assessments, including measures of language ability, ability to identify and to label emotions, ability to link events and emotions and a cognitive mediation task. The method broadly replicated a previous study undertaken by Dagnan et al. [Cognitive Therapy and Research (2000) vol. 24, pp. 627–636].

Results  Results showed significant relationships between language ability and ability to recognize and label emotions, ability to link events and emotions and pass the cognitive mediation tasks. The majority of the participants were unable to pass the tasks linking emotions and events and the cognitive mediation tasks. They also demonstrated a limited emotional vocabulary. The findings were similar to those of Dagnan et al. (2000).

Conclusions  It is possible to assess some of the component skills necessary for undergoing CBT. People with intellectual disabilities will need support from therapists to teach the skills necessary to undertake cognitive interventions, and a ‘step‐wise’ approach to assessment will enable such support to be appropriately targeted to individual need.
Response Patterns on the Questionnaire on Attitudes Consistent with Sexual Offending in Groups of Sex Offenders with Intellectual Disabilities
Authors: Lindsay William R. , Michie Amanda M. , Whitefield Elaine , Martin Victoria , Grieve Alan , Carson Derek
Published: February 2006

Background  This report employs a recently developed assessment on attitudes consistent with sexual offending [Questionnaire on Attitudes Consistent with Sexual Offences (QACSO)] to compare different groups of sex offenders with intellectual disability.

Method  Two studies are reported each from a different region and each conducted by different individuals. Study 1 compared 12 sex offenders against adults with 12 offenders against children. The six‐scale version of the QACSO was administered including rape and attitudes to women, voyeurism, exhibitionism, dating abuse, homosexual assault and offences against children. Study 2 employed three groups of 10 participants each: offenders against adults, exhibitionists and offenders against children. The seven scale version of the QACSO (stalking added) was used. All questionnaires were administered individually.

Results  In both studies, the offenders against adults reported higher levels of attitudes consistent with sexual offending in the area of rape and attitudes to women with medium to large effect sizes and a significant difference in study 1. In both studies, offenders against children reported significantly higher levels of cognitive distortions (large effect sizes) in the area of offences against children. Both differences were in the predicted direction and there were no other significant differences on other sections. In general, all three groups reported higher levels of cognitive distortions than non‐offenders.

Conclusions  There would appear to be some specificity particularly for the rape and attitudes to women scale, and the offenders against children scale. The same specificity does not emerge from other scales of the QACSO. The study also lends support to the inclusion of techniques which explore and challenge attitudes consistent with offending both generally and in relation to specific offences.
On Some Recent Claims for the Efficacy of Cognitive Therapy for People with Intellectual Disabilities
Authors: Sturmey Peter
Published: February 2006

Background  Many authors have expressed concern regarding the efficacy of psychotherapy, including psychotherapy for people with intellectual disabilities.

Materials and Methods  Recently, many authors have made claims for the effectiveness of cognitive therapy for treating people with intellectual disabilities. During this debate, applied behaviour analysis has been misrepresented by incorrectly labelling behavioural as cognitive techniques, repeated misrepresentations of behaviourism and attributing the efficacy of treatment packages to cognitive components of undemonstrated efficacy when it is more parsimonious to attribute efficacy to behavioural elements of known efficacy.

Conclusions  This article documents and corrects these errors.
The Need for Credible Evidence: Comments on ‘On Some Recent Claims for the Efficacy of Cognitive Therapy for People with Intellectual Disabilities’
Authors: Emerson Eric
Published: February 2006

Sturmey (2005) argues that the evidence base underlying approaches to intervention based on applied behavioural analysis (ABA) are significantly stronger than that underlying approaches to intervention based on cognitive therapy. He concludes that ‘the ethical imperative of beneficence requires that people, including people with ID, receive known effective treatments. Those effective treatments are based on ABA’ (p. X). In this commentary, I argue that his selection of evidence to support the central argument (the superiority of ABA) involves some highly contestable assumptions and that evidence of the effectiveness of ABA falls far short of that required for evidence‐based policy and practice.
Effects of experience and object complexity on exploration in garden warblers (Sylvia borin)
Authors: Mettke‐Hofmann C. , Rowe K. C. , Hayden T. J. , Canoine V.
Published: February 2006

Animals are increasingly exposed to novel environmental conditions because of human activities. An organism's ability to cope with these challenges is critical to its survival. The decision of whether or not an animal should investigate environmental changes involves a trade‐off between the risk and the potential benefit of a novel resource. Novelty often elicits approach (exploratory) as well as avoidance behaviour in animals, and the extent of each of these behaviours may influence learning about the environment. We formulated and tested several hypotheses to determine how external factors (complexity of a novel stimulus) and internal factors (experience with objects) might influence exploration latencies to touch a novel object based on either cost or benefit considerations. Garden warblers were confronted with a simple and a complex novel object in their familiar cages, and latencies until first touch were measured. Additionally, corticosterone levels before and after the experiment were measured to assess whether differences in baseline levels might explain variations in latency to approach and whether presentation of novel objects is stressful. The complex object was touched significantly later than the simple object. Experienced birds investigated both types of objects later than inexperienced birds. Although birds showed marked approach–avoidance behaviour with the complex object, none of the objects elicited a corticosterone stress response. The results indicate that garden warblers consider both costs and benefits when exploring novel objects, and that the relative influence of costs and benefits varies with external and internal factors.
The Hyperinhibition Hypothesis in Epileptogenesis: An Assessment of the Evidence
Authors: Dudek F. Edward
Published: February 2006

Hippocampal Granule Cell Activity and c-fos Expression During Spontaneous Seizures in Awake, Chronically Epileptic, Pilocarpine-treated Rats: Implications for Hippocampal Epileptogenesis

Harvey BD, Sloviter RS

J Comp Neurol 2005;488(4):442–463

The process of postinjury hippocampal epileptogenesis may involve gradually developing dentate granule cell hyperexcitability caused by neuron loss and synaptic reorganization. We tested this hypothesis by repeatedly assessing granule cell excitability after pilocarpine-induced status epilepticus (SE) and monitoring granule cell behavior during 235 spontaneous seizures in awake, chronically implanted rats. During the first week post-SE, granule cells exhibited diminished paired-pulse suppression and decreased seizure discharge thresholds in response to afferent stimulation. Spontaneous seizures often began during the first week after SE, recruited granule cell discharges that followed behavioral seizure onsets, and evoked c-fos expression in all hippocampal neurons. Paired-pulse suppression and epileptiform discharge thresholds increased gradually after SE, eventually becoming abnormally elevated. In the chronic epileptic state, interictal granule cell hyperinhibition extended to the ictal state; granule cells did not discharge synchronously before any of 191 chronic seizures. Instead, granule cells generated only low-frequency voltage fluctuations (presumed “field excitatory postsynaptic potentials”) during 89% of chronic seizures. Granule cell epileptiform discharges were recruited during 11% of spontaneous seizures, but these occurred only at the end of each behavioral seizure. Hippocampal c-fos after chronic seizures was expressed primarily by inhibitory interneurons. Thus, granule cells became progressively less excitable, rather than hyperexcitable, as mossy fiber sprouting progressed and did not initiate the spontaneous behavioral seizures. These findings raise doubts about dentate granule cells as a source of spontaneous seizures in rats subjected to prolonged SE and suggest that dentate gyrus neuron loss and mossy fiber sprouting are not primary epileptogenic mechanisms in this animal model.
Dancing the Delta Shuffle: Neurosteroids Regulate GABAA Receptor Expression
Authors: Lagrange Andre
Published: February 2006

Ovarian Cycle-linked Changes in GABA(A) Receptors Mediating Tonic Inhibition Alter Seizure Susceptibility and Anxiety

Maguire JL, Stell BM, Rafizadeh M, Mody I

Nat Neurosci 2005;8(6):797–804

Disturbances of neuronal excitability changes during the ovarian cycle may elevate seizure frequency in women with catamenial epilepsy and enhance anxiety in premenstrual dysphoric disorder (PMDD). The mechanisms underlying these changes are unknown, but they could result from the effects of fluctuations in progesterone-derived neurosteroids on the brain. Neurosteroids and some anxiolytics share an important site of action: tonic inhibition mediated by δ subunit–containing GABAA receptors ( δGABAA Rs). Here we demonstrate periodic alterations in specific GABAA R subunits during the estrous cycle in mice, causing cyclic changes of tonic inhibition in hippocampal neurons. In late diestrus (high-progesterone phase), enhanced expression of δGABAA Rs increases tonic inhibition, and a reduced neuronal excitability is reflected by diminished seizure susceptibility and anxiety. Eliminating cycling of δGABAA Rs by antisense RNA treatment or gene knockout prevents the lowering of excitability during diestrus. Our findings are consistent with possible deficiencies in regulatory mechanisms controlling normal cycling of δGABAA Rs in individuals with catamenial epilepsy or PMDD.

Short-term Steroid Treatment Increases δ GABAA Receptor Subunit Expression in Rat CA1 Hippocampus: Pharmacological and Behavioral Effects

Shen H, Gong QH, Yuan M, Smith SS

Neuropharmacology 2005;49(5):573–586

In this study, 48-h administration of 3 α-OH-5 β-pregnan-20-one (3 α,5 β-THP) or 17 β-estradiol (E2)+progesterone (P) to female rats increased expression of the δ subunit of the GABAA receptor in CA1 hippocampus. Coexpression of α4 and δ subunits was suggested by an increased response of isolated pyramidal cells to the GABA agonist 4,5,6,7-tetrahydroisoxazolo[5,4- c]pyridin-3-ol (THIP), following 48-h steroid treatment, and nearly complete blockade by 300 μM lanthanum (La3+). Because α4 βδ GABAA receptors are extrasynaptic, we also recorded pharmacologically isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the slice. The La3+-sensitive THIP current, representative of current gated by α4 βδ GABAA receptor, was measurable only following 48-h steroid treatment. In contrast, the bicuculline-sensitive current was not altered by steroid treatment, assessed with or without 200 nM gabazine to block synaptic current. However, 48-h steroid treatment resulted in a tonic current insensitive to the benzodiazepine agonists lorazepam (10 μM) and zolpidem (100 nM). These results suggest that 48-h steroid treatment increases expression of α4 βδ GABAA receptors, which replace the ambient receptor population. Increased anxiolytic effects of THIP were also observed following 48-h steroid treatment. The findings from the present study may be relevant for alterations in mood and benzodiazepine sensitivity reported across the menstrual cycle.
Endocannabinoids: A Critical Regulator of Activity in the Developing Brain
Authors: Douglas A. Coulter
Published: February 2006

Altering Cannabinoid Signaling During Development Disrupts Neuronal Activity

Bernard C, Milh M, Morozov YM, Ben-Ari Y, Freund TF, Gozlan H

Proc Natl Acad Sci USA 2005;102(26):9388–9393

In adult cortical tissue, recruitment of GABAergic inhibition prevents the progression of synchronous population discharges to epileptic activity. However, at early developmental stages, GABA is excitatory and thus unable to fulfill this role. Here, we report that retrograde signaling involving endocannabinoids is responsible for the homeostatic control of synaptic transmission and the resulting network patterns in the immature hippocampus. Blockade of cannabinoid type 1 (CB1) receptor led to epileptic discharges, whereas overactivation of CB1 reduced network activity in vivo. Endocannabinoid signaling thus is able to keep population discharge patterns within a narrow physiological time window, balancing between epilepsy on one side and sparse activity on the other, which may result in impaired developmental plasticity. Disturbing this delicate balance during pregnancy in either direction, for example, with marijuana as a CB1 agonist or with an antagonist marketed as an antiobesity drug, can have profound consequences for brain maturation even in human embryos.
Posttraumatic Epilepsy: A Major Problem in Desperate Need of Major Advances
Authors: Garga Nina , Lowenstein Daniel H.
Published: February 2006

This brief review is meant to provide an update on the data from clinical and laboratory studies that have provided insight into the mechanisms underlying the development of epilepsy following traumatic brain injury (TBI). The link between severe brain trauma and epilepsy in humans is well recognized. However, we have yet to identify an effective intervention to prevent the development of epilepsy in patients who are at risk after TBI. Laboratory studies, which have relied primarily on the fluid-percussion model, have documented long-term hyperexcitability associated with TBI, and recent studies are shedding light on the structural and electrophysiological abnormalities that may underlie epileptogenesis in this setting. Nonetheless, given the extent of the clinical problem and our current state of knowledge, this area of epilepsy research deserves far more attention.
Is Breast Milk the Best for Babies of Mothers on Levetiracetam?
Authors: Pennell Page B.
Published: February 2006

Levetiracetam Concentrations in Serum and in Breast Milk at Birth and During Lactation

Johannessen SI, Helde G, Brodtkorb E

Epilepsia 2005;46(5):775–777

Purpose

To study the pharmacokinetics of levetiracetam (LEV) at birth, during lactation, and in the nursed infant.

Methods

Eight consecutive breast-feeding women with epilepsy treated with LEV twice daily and their infants were studied.

Results

The mean umbilical cord serum/maternal serum ratio was 1.14 (range, 0.97–1.45) ( n = 4). The mean milk-maternal serum concentration ratio was 1.00 (range, 0.761.33) at 3–5 days after delivery ( n = 7). At sampling 2 weeks to 10 months after delivery ( n = 5), it was similar (range, 0.85–1.38). At 3–5 days after delivery, the infants had very low LEV serum concentrations (<10–15 μM), a finding that persisted during continued breast-feeding. No malformations were detected, and in none of the infants did signs of adverse effects develop.

Conclusions

Our data indicate an extensive transfer of LEV from mother to fetus and into breast milk. However, breast-fed infants had very low LEV serum concentrations, suggesting a rapid elimination of LEV.
Impact of Epilepsy Surgery on Developing Minds: How do we Weigh the Consequences?
Authors: Garcia Paul A.
Published: February 2006

Cognitive Function in Preschool Children after Epilepsy Surgery: Rationale for Early Intervention

Freitag H, Tuxhorn I

Epilepsia 2005;46(4):561–567

Purpose

The detrimental effect of frequent early seizures on the cognitive potential of children is a significant clinical issue. Epilepsy surgery in childhood offers a good prognosis for seizure control and improved developmental outcome. We studied the postoperative outcome and the developmental velocity after surgery and analyzed risk factors for developmental delay in 50 consecutive preschool children treated surgically for severe epilepsy at ages 3 to 7 years.

Methods

Pre- and postoperative developmental quotients (DQs) were analyzed with analysis of variance; step-wise linear regressions were performed on preoperative DQs and on a difference score between post- and preoperative DQs to determine risk factors for preoperative development and factors influencing postoperative development.

Results

Of the 50 patients, 70% were retarded, with IQ <70; 16% were of average intelligence, with IQ ranging from 85 to 115. Age at seizure onset and extent of lesion were predictive variables for preoperative cognitive development. Six to 12 months after surgery (early postoperative phase), 66% were seizure free (Engel outcome class I), 26% had substantial to worthwhile seizure reduction (classes II and III), and 8% were unchanged (class IV). Forty-one (82%) children showed stable velocity of development; three children showed gains of 15 IQ points; three had developmental decline (loss of 10 IQ points), which was transient in two children; and three children moved from not assessable to assessable. At last follow-up (6 months to 10 years after surgery), 11 children showed IQ/DQ gains of 15 IQ points. Gains in IQ were observed only in seizure-free children and were stable over time. Shorter duration of epilepsy was significantly associated with a postoperative increase in DQ.

Conclusions

(a) Substantial global mental delay is common in young children treated for epilepsy with surgery; (b) in most patients, postoperative development proceeded at a stable velocity; (c) catch-up development may occur but only in seizure-free patients; (d) substantial cognitive losses were noted in only one child; and (e) early seizure control stabilized developmental velocity in this patient cohort.
In the End, New Antiepileptics May be Less Expensive than Older Antiepileptics for Geriatric Patients
Authors: Kanner Andres M.
Published: February 2006

New Onset Geriatric Epilepsy: A Randomized Study of Gabapentine, Lamotrigine, and Carbamazepine

Rowan AJ, Ramsay RE, Collins JF, Pryor F, Boardman KD, Uthman BM, Spitz M, Frederick T, Towne A, Carter GS, Marks W, Felicetta J, Tomyanovich ML; VA Cooperative Study 428 Group

Neurology 2005;64:1868–1873

Objective

To determine the relative tolerability and efficacy of two newer antiepileptic drugs, lamotrigine (LTG) and gabapentin (GBP), as compared with carbamazepine (CBZ) in older patients with epilepsy.

Methods

This was an 18-center, randomized, double-blind, double dummy, parallel study of 593 elderly subjects with newly diagnosed seizures. Patients were randomly assigned to one of three treatment groups: GBP 1,500 mg/day, LTG 150 mg/day, CBZ 600 mg/day. The primary outcome measure was retention in trial for 12 months.

Results

Mean age was 72 years. The most common etiology was cerebral infarction. Patients had multiple medical conditions and took an average of seven comedications. Mean plasma levels at 6 weeks were as follows: GBP 8.67 ± 4.83 μg/mL, LTG 2.87 ± 1.60 μg/mL, CBZ 6.79 ± 2.92 μg/mL. They remained stable throughout the trial. Early terminations: LTG 44.2%, GBP 51%, CBZ 64.5% ( p = 0.0002). Significant paired comparisons: LTG vs CBZ: p < 0.0001; GBP vs CBZ: p = 0.008. Terminations for adverse events: LTG 12.1%, GBP 21.6%, CBZ 31% ( p = 0.001). Significant paired comparisons: LTG vs CBZ: p < 0.0001; LTG vs GBP: p = 0.015. There were no significant differences in seizure-free rate at 12 months.

Conclusions

The main limiting factor in patient retention was adverse drug reactions. Patients taking LTG or GBP did better than those taking CBZ. Seizure control was similar among groups. LTG and GBP should be considered as initial therapy for older patients with newly diagnosed seizures.
What Does Flumazenil PET Add to an Evaluation for Temporal Lobectomy?
Authors: Theodore William H.
Published: February 2006

Periventricular White Matter Flumazenil Binding and Postoperative Outcome in Hippocampal Sclerosis

Hammers A, Koepp MJ, Brooks DJ, Duncan JS

Epilepsia 2005;46(6):944–948

Purpose

In patients with hippocampal sclerosis (HS), anterior temporal lobe resection offers the possibility of a long-lasting suppression of seizures in two-thirds of patients. White matter (WM) [11C]flumazenil volume of distribution (FMZ-Vd) reflects the number of neuronal cell bodies in WM. Our objective was to correlate WM FMZ-Vd in patients with unilateral HS and postsurgical outcome.

Methods

We performed [11C]flumazenil positron emission tomography ([11C]FMZ-PET) in 15 patients with refractory mesial temporal lobe epilepsy (mTLE) and a quantitative MRI diagnosis of unilateral HS subsequently histologically verified in all cases. Median follow-up was 7 years (range, 6–9 years). Metabolite-corrected arterial plasma input functions and spectral analysis were used to generate parametric images of [11C]FMZ-Vd. Statistical parametric mapping (SPM99) with explicit masking was used to investigate the entire brain volume including WM.

Results

Eight patients had Engel class IA outcome (completely seizure-free since surgery), and seven were not seizure-free. Comparison of seizure-free patients with those who continued to have seizures after surgery revealed areas of increased FMZ binding around the posterior horns of the ipsilateral (z = 3.7) and contralateral (z = 2.7) ventricles in those with suboptimal outcomes.

Conclusions

Preoperative [11C]FMZ-PET can detect periventricular increases of WMFMZ binding, implying heterotopic neurons in WM, in patients with mTLE. The presence of such increases correlates with a poorer outcome.
In‐Vitro Activity of Miltefosine and Voriconazole on Clinical Isolates of Free‐Living Amebas: Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri
Authors: SCHUSTER FREDERICK L. , GUGLIELMO B. JOSEPH , VISVESVARA GOVINDA S.
Published: February 2006

ABSTRACT. The anticancer agent miltefosine and the antifungal drug voriconazole were tested in vitro against Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri. All three amebas are etiologic agents of chronic (Balamuthia, Acanthamoeba) or fulminant (Naegleria) encephalitides in humans and animals and, in the case of Acanthamoeba, amebic keratitis. Balamuthia exposed to <40 μm concentrations of miltefosine survived, while concentrations of ≥40 μM were generally amebacidal, with variation in sensitivity between strains. At amebastatic drug concentrations, recovery from drug effects could take as long as 2 weeks. Acanthamoeba spp. recovered from exposure to 40 μM, but not 80 μM miltefosin. Attempts to define more narrowly the minimal inhibitory (MIC) and minimal amebacidal concentrations (MAC) for Balamuthia and Acanthamoeba were difficult due to persistence of non‐proliferating trophic amebas in the medium. For N. fowleri, 40 and 55 μM were the MIC and MAC, respectively, with no trophic amebas seen at the MAC. Voriconazole had little or no inhibitory effect on Balamuthia at concentrations up to 40 μg/ml, but had a strong inhibitory effect upon Acanthamoeba spp. and N. fowleri at all drug concentrations through 40 μg/ml. Following transfer to drug‐free medium, Acanthamoeba polyphaga recovered within a period of 2 weeks; N. fowleri amebas recovered from exposure to 1 μg/ml, but not from higher concentrations. All testing was done on trophic amebas; drug sensitivities of cysts were not examined. Miltefosine and voriconazole are potentially useful drugs for treatment of free‐living amebic infections, though sensitivities differ between genera, species, and strains.
Effect of Japanese Paramecium bursaria Extract on Photosynthetic Carbon Fixation of Symbiotic Algae
Authors: KAMAKO SHIN‐ICHIRO , IMAMURA NOBUTAKA
Published: February 2006

ABSTRACT. To investigate the relationship between the Japanese Paramecium bursaria host and its symbiont, we studied the effect of a host cell‐free extract on carbon fixation and photosynthate release of the symbiont. The host extract enhanced symbiotic algal carbon fixation about 3‐fold at an increased concentration; however, release of photosynthate hardly changed. Since the enhancing effect was not affected by elimination of carbon dioxide from the host extract, the existence of a host factor that stimulates algal carbon fixation was made clear. The host factor is a heat‐stable, low molecular weight substance. In relation to the pH dependence, the extract improved carbon fixation at acidic and neutral pH and showed almost no effect at pH 9.0. Therefore, the stimulation of carbon fixation by the host factor is unlikely to be caused by intracellular pH change. The extract also improved carbon fixation of several Chlorella species, symbiotic and free‐living, and apparently exhibited no species specificity. Therefore, the host seems to regulate the photosynthesis of the symbiont via a specific compound.
Pathogenesis of bone metastasis: a review
Authors: Raubenheimer E. J. , Noffke C. E. E.
Published: February 2006

Background: Metastasic deposits from malignancies frequently lodge in the skeleton, including the jawbones.

Method: A review of the literature was performed in order to provide a coherent overview on the pathogenesis of bone metastasis.

Results: Bone metastasis follows complex molecular interactions that enable tumor cells to detach from the primary site, invade the extracellular matrix, intravasate, extravasate, and proliferate within bone. They induce local bone changes that could manifest radiologically as either osteolytic or radiodense. In addition to the direct bone changes, malignancies can elaborate mediators that are released in circulation, leading to generalized osteopenia.

Conclusions: The spread of malignant neoplasms to bone is not a random process but rather a cascade of specific molecular events orchestrated through complex interactions between neoplastic cells and their environment.
Expression of Bcl‐2 but not Bax has a prognostic significance in tongue carcinoma
Authors: de Vicente Juan Carlos , Olay Sonsoles , Lequerica‐Fernandez Paloma , Sánchez‐Mayoral Jacobo , Junquera Luis Manuel , Fresno Manuel Florentino
Published: February 2006

Background:  Among the molecular mechanisms involved in carcinogenesis, defects in the regulation of programmed cell death (apoptosis) make important contributions to the pathogenesis and progression of cancer. Apoptosis regulatory genes include the antiapoptotic bcl‐2 gene and the proapoptotic bax gene. The aim of this study was to determine the spectrum of Bax and Bcl‐2 expression, and to correlate these findings with clinicopathologic variables and prognosis.

Methods:  In this study we have evaluated the immunohistochemical expression of Bcl‐2 and Bax proteins in a series of 35 squamous cell carcinomas of the tongue.

Results:  Immunoreactivity for Bax was detected in 37.1% and for Bcl‐2 in 8.6% of cells, and for both proteins the staining was cytoplasmic and granular. Bcl‐2 and Bax expression was mainly seen in peripheral cells of epithelial tumor islands with decreasing immunoreactivity toward the center of the neoplastic nests. Bax immunoexpression was significantly correlated with histologic grading (P = 0.05), but not with the remaining clinicopathologic variables. Bcl‐2 immunoreactivity was significantly correlated with N‐stage (P = 0.01) and survival. Patients with Bcl‐2‐negative tumors [mean survival: 73.97 months; 95% confidence interval (CI): 59–88] vs. Bcl‐2‐positive ones (mean survival: 17.67 months; 95% CI: 6–29) had a longer survival (P = 0.01; odds ratio = 6.9).

Conclusions:  Bcl‐2 is associated with aggressive disease, neck lymph node metastasis, and poor prognosis. Whereas Bax is related with histologic grade.
Glandular odontogenic cyst in China: report of 12 cases and immunohistochemical study
Authors: Shen Jing , Fan Mingwen , Chen Xinming , Wang Shuozhi , Wang Li , Li Yuan
Published: February 2006

Objective:  The purpose of this study was to present 12 additional cases of glandular odontogenic cyst (GOC) in the Department of Oral Pathology, School of Stomatology, Wuhan University, People's Republic of China, and to investigate their immunohistochemical cytokeratins (CKs) expression in the epithelial components.

Methods:  A total of 12 GOCs were reviewed clinically and radiographically, and immunohistologic CKs AE1, 7, 8/18, 10/13, 14, 16, 19 and 20 were performed by using a standard biotin‐streptavidin immunoperoxidase technique on paraffin sections.

Results:  The present series showed that eight occurred in males and four in females. The mean age was 37.6 years with a peak incidence occurring in the third decades (six of 12). Mandibles were more affected than maxillas (7:5), especially anterior mandible (four of seven). Radiographically, ratio multilocular to unilocular radiolucencies was 5:7 usually with well‐defined borders. Histologically, cystic spaces were lined by non‐keratinized stratified epithelia containing focal plaque‐like or whirlpool‐like thickenings; surface epithelial layer‐containing eosinophilic cuboidal cells; mucous cells; and mucin pools of microcystic areas in the epithelium. Immunohistochemistry showed that epithelium of GOCs stained for CKs AE1, 7, 8/18, 10/13, 14 and 19 with slight changes in their patterns, and no reaction to CKs 16 and 20.

Conclusions:  Most clinical and histologic features in this study were analogous to those reported west population, although with slight difference between them. Histologically, the morphology of the epithelium strongly suggested an odontogenic origin, and CKs expression of GOC was similar to that of odontogenic epithelium, suggesting histochemically that GOC might be derived from odontogenic epithelium.