bluuebunny/crossref_metadata_2025 huggingface dataset:
Apparent Motion of the Human Body
Authors: Shiffrar Maggie , Freyd Jennifer J.
Published: April 2006

Observers viewed pairs of alternating photographs of a human body in different positions. Shortest-path motion solutions were pitted against anatomically possible movements. With short stimulus onset asynchronies (SOAs), observers tended to report the shortest path despite violations of anatomical constraints. However, with longer SOAs observers became increasingly likely to report the anatomically possible, but longer, paths. This finding, in conjunction with those from a second study, challenges the accepted wisdom that apparent motion paths are independent of the object. Instead, our findings suggest that when given enough time and appropriate stimuli, the visual system prefers at least some object-appropriate apparent motion paths.
The Genetics of Schizophrenia: A Review
Authors: Holzman Philip S. , Matthysse Steven
Published: April 2006

Family, twin, and adoption studies have produced strong evidence that genes play a major role in schizophrenic conditions. These conventional approaches, however, are not able to reveal anything about the way in which genes influence that disease except that the family prevalence of schizophrenia is too low to fit a classical Mendelian transmission mode. New molecular biological techniques offer bright possibilities for identifying the chromosomal loci of genetic diseases, but these techniques rely for their effectiveness on a Mendelian distribution of the trait under investigation. We show how psychological methods can play a decisive role in making these new biological techniques available for the study of schizophrenia by expanding the phenotype (schizophrenia) to include associated behaviors that fit a model of transmission by major loci.
Glucose Effects on Memory and Other Neuropsychological Tests in Elderly Humans
Authors: Manning C.A. , Hall J.L. , Gold P.E.
Published: April 2006

Recent experiments indicate that peripheral glucose administration enhances memory in rodents and humans. This study examined the effects of glucose on memory and nonmemory measures of neuropsychological functioning in elderly humans. Healthy older adults were given a series of neuropsychological tests after drinking glucose- or saccharin-flavored lemonade. A repeated measures design using counter-balanced beverages and tests was used. Glucose enhanced performance on declarative memory tests but not on short-term or nonmemory neuropsychological measures. Glucose tolerance predicted performance on declarative memory tasks but not on other measures.
Stereotypes as Judgmental Heuristics: Evidence of Circadian Variations in Discrimination
Authors: Bodenhausen Galen V.
Published: April 2006

The question of when people rely on stereotypic preconceptions in judging others was investigated in two studies. As a person's motivation or ability to process information systematically is diminished, the person may rely to an increasing extent on stereotypes, when available, as a way of simplifying the task of generating a response. It was hypothesized that circadian variations in arousal levels would be related to social perceivers' propensity to stereotype others by virtue of their effects on motivation and processing capacity. In support of this hypothesis, subjects exhibited stereotypic biases in their judgments to a much greater extent when the judgments were rendered at a nonoptimal time of day (i.e., in the morning for “night people” and in the evening for “morning people”). In Study One, this pattern was found in probability judgments concerning personal characteristics; in Study Two, the pattern was obtained in perceptions of guilt in allegations of student misbehavior. Results generalized over a range of different types of social stereotypes and suggest that biological processes should be considered in attempts to conceptualize the determinants of stereotyping.
The Electronic Archive: Scientific Publishing for the 1990s
Authors: Gardner William
Published: April 2006

I offer a description and rationale for an electronic journal publishing program for psychologists, called the electonic archive. Three principles are critical. First, electronic publishing must retain the readability of a traditional printed journal. Second, it must be both accessible and attractive to all members of the discipline, whether they use computers or not. Most importantly, it must provide improved facilities for retrieving information, while continuing to serve as a permanent archive of the Society. I argue that the primary advantage of electronic publishing is not the inexpensive delivery of text, but the use of a centralized archive to concentrate resources for discovering and utilizing information. The archive would provide a platform for programs embodying knowledge about the field and the intellectual goals of individual users to facilitate the intelligent retrieval of text. By using the dynamic branching and graphical display capacities of the computer, the archive can present texts in ways that cannot be rendered in print. These facilities can give scholars personalized access to information with increased scope and depth.
Teaching the Use of Cost-Benefit Reasoning in Everyday Life
Authors: Larrick Richard P. , Morgan James N. , Nisbett Richard E.
Published: April 2006

Our research shows that people can apply the cost-benefit rules of microeconomic theory to their everyday decisions. Two populations were examined: (a) people who had previously received extensive formal training in the rules and (b) naive subjects who were randomly assigned to receive brief training in the rules. Training affected reasoning and reported behavior in both populations. The results indicate that extremely general rules govern choices across a wide range of domains and that use of the cost-benefit rules can be improved through training.
Differential Use of Reproductive Strategies by Human Groups?
Authors: Mealey Linda
Published: April 2006

J.P. Rushton has presented a series of articles proposing that different racial groups, having evolved under different environmental conditions, have been differentially selected, resulting in genetic differences in their reproductive behavior, intelligence, and “social rule-following.” Rushton's model is discussed with respect to two controversial points: criticisms of the nature of the data and analyses, and alternative explanations of the data. I concur with Rushton in the belief that different human groups utilize different strategies, but find the differential use of species-wide, environmentally contingent tactics a more parsimonious explanation than genetic differences.
Training for Priesthood in the Modern World: A Zarathushtrian Perspective
Authors: Bagli Jehan
Published: April 2006

Abstract.  This essay traces the development of the Zarathushtrian (Zoroastrian) priesthood from the time of the prophet Zarathushtra, through the Median priestly tribe as Magi, and the Macedonian and Arab invasions. This sets the stage for the separation of the Zarathushti priesthood between Iran and India and the generation of independent training methods. Centuries later dialogue between the two groups revealed some remarkable differences due to diverse cultural influences. From the eighteenth to the twentieth century there is a loss of respect for the priestly class and organization by the community of learning institutions to revamp the priestly training. The last portion of the paper discusses factors that affect the training of priests in North America. Some recommendations are put forward to adapt the training of the priesthood in the changing world society, and how these ideas can be brought to reality.
Catholicity and Context: The Cenotaphs of Orthodox Theological Education
Authors: Marangos Frank
Published: April 2006

Abstract.  For more than twenty‐five years, field education programs have been the primary pedagogical strategy by which contextual (practical) theological training has occurred at most Orthodox theological schools in America. These programs are based on a developmental approach, with students progressing from observation to participation to actual leadership. A synthetic model of contextualism will prepare students more effectively for ministry in the third millennium by providing attention to the contemporary context throughout the entire curriculum. This article will: (a) discuss the current practice of Orthodox theological education in America, (b) examine six classifications of contextual theology, and (c) suggest nine core values and goals that support a synthetic model for the contextualization of Orthodox theological education in America.
Models and Methods of Continuing Education for Christian Ministry in the Religiously Plural Context
Authors: Mosher Lucinda Allen
Published: April 2006

Abstract.  This paper asserts that Continuing Education aimed at equipping Christian leaders (lay and ordained) to carry out their ministries in the midst of America's increasing religious diversity in a way that views this diversity positively must be two‐pronged: (1) it must provide accurate information about the beliefs and practices of the neighbors, and (2) it must provide theological resources rooted in Christian scripture and tradition. As this paper explores a variety of models, it reflects on the difficulty of holding these two goals together and the problems inherent in attempting to measure what such Continuing Education programs and events accomplish. In considering ways forward, it offers a Christian theology of religious difference informed by notions of neighbor‐love.
A Long and Winding Road: Soto Zen Training in America
Authors: Senauke Hozan Alan
Published: April 2006

Abstract.  This paper seeks to outline the broad parameters of Soto Zen Buddhist training in the North American context. Using his personal experience of training as a case study, the author argues that Zen in America is strongly oriented towards meditation and everyday practice in the world by dedicated lay people, a situation relatively rare in the history of Buddhism. The training of today's Zen teachers calls for unique skills conditioned by modern life in the developed world: pastoral counseling, psychological acuity, communication training, political awareness, and an ability to translate traditional teachings into terms that are relevant. Teacher training still observes traditional Soto Zen ordinations and pathways. But though the ritual forms endure, their meaning continues to evolve and shift according to the different needs and expressions of American Zen.
Sikh Leadership: Established Ideals and Diasporic Reality
Authors: Singh Harinder , Singh Simran
Published: April 2006

Abstract.  As established in the Sikh scriptural canon, ideal leaders internalize qualities of self‐sovereignty, intentional servitude, integrative creativity, authentic compassion, and perhaps most significant of all, Divine inspiration. Models of communal decision‐making can also be derived from the lives of the Gurū‐Prophets (1469–1708 C.E.) and the institutions they established. Though the faith recognizes no clergy class, graduates of historical seminaries often emerge as significant leaders for the Sikh nation. The community outside of the homeland, however, has experienced a lesser effort in the cultivation of leadership. With a primary focus on education, religious centers, youth camps, and retreats have played a critical role in imparting Sikh culture to the masses. While ideals are clearly articulated within the Sikh tradition, it is the application of the ideals that is necessary – Sikh leadership continually works towards these ends, and will ever seek to progress as individuals as well as a community.
On the Bias of the Multiple-Imputation Variance Estimator in Survey Sampling
Authors: Kim Jae Kwang , Michael Brick J. , Fuller Wayne A. , Kalton Graham
Published: April 2006

Multiple imputation is a method of estimating the variances of estimators that are constructed with some imputed data. We give an expression for the bias of the multiple-imputation variance estimator for data that are collected with a complex sample design. The bias may be sizable for certain estimators, such as domain means, when a large fraction of the values are imputed. A bias-adjusted variance estimator is suggested.
Testing for Order-Restricted Hypotheses in Longitudinal Data
Authors: Pilla Ramani S. , Qu Annie , Loader Catherine
Published: April 2006

In many biomedical studies, we are interested in comparing treatment effects with an inherent ordering. We propose a quadratic score test (QST) based on a quadratic inference function for detecting an order in treatment effects for correlated data. The quadratic inference function is similar to the negative of a log-likelihood, and it provides test statistics in the spirit of a χ2-test for testing nested hypotheses as well as for assessing the goodness of fit of model assumptions. Under the null hypothesis of no order restriction, it is shown that the QST statistic has a Wald-type asymptotic representation and that the asymptotic distribution of the QST statistic is a weighted χ2-distribution. Furthermore, an asymptotic distribution of the QST statistic under an arbitrary convex cone alternative is provided. The performance of the QST is investigated through Monte Carlo simulation experiments. Analysis of the polyposis data demonstrates that the QST outperforms the Wald test when data are highly correlated with a small sample size and there is a significant amount of missing data with a small number of clusters. The proposed test statistic accommodates both time-dependent and time-independent covariates in a model.
A New Approach to Cluster Analysis: the Clustering-Function-Based Method
Authors: Li Baibing
Published: April 2006

The purpose of the paper is to present a new statistical approach to hierarchical cluster analysis with n objects measured on p variables. Motivated by the model of multivariate analysis of variance and the method of maximum likelihood, a clustering problem is formulated as a least squares optimization problem, simultaneously solving for both an n-vector of unknown group membership of objects and a linear clustering function. This formulation is shown to be linked to linear regression analysis and Fisher linear discriminant analysis and includes principal component regression for tackling multicollinearity or rank deficiency, polynomial or B-splines regression for handling non-linearity and various variable selection methods to eliminate irrelevant variables from data analysis. Algorithmic issues are investigated by using sign eigenanalysis.
Regularized Semiparametric Model Identification with Application to Nuclear Magnetic Resonance Signal Quantification with Unknown Macromolecular Base-Line
Authors: Sima Diana M. , Van Huffel Sabine
Published: April 2006

We formulate and solve a semiparametric fitting problem with regularization constraints. The model that we focus on is composed of a parametric non-linear part and a nonparametric part that can be reconstructed via splines. Regularization is employed to impose a certain degree of smoothness on the nonparametric part. Semiparametric regression is presented as a generalization of non-linear regression, and all important differences that arise from the statistical and computational points of view are highlighted. We motivate the problem formulation with a biomedical signal processing application.
‘Voice’ and ‘exit’ in Japanese firms during the Second World War:Sanporevisited*
Authors: OKAZAKI TETSUJI
Published: April 2006

During the Second World War, the Japanese government and private sector searched for and implemented new mechanisms for coordination and motivation. One of these wassangyo hokokukai(sanpo). TheSanpounit was basically an organization of the employer and employees of each firm, which held meetings to moderate labour relations. As a result of government policy to promotesanpounits, around 70 per cent of the total workers in Japan were organized intosanpounits in the early 1940s. As the members of trades unions and the workers of the companies that had factory committees were only 7 per cent and 5 per cent of the total workers in 1936 respectively,sanpowas the first large‐scale mechanism for Japanese employees to have a voice. This article examines the role ofsanpo, using prefecture‐level and firm‐level data, based on a framework integrating the ‘voice view’ of unionism and transaction cost economics. It was found thatsanporeduced the participation rate in labour disputes, and enhanced labour productivity at least for some of the time.
English and Scottish overseas trade, 1300–16001
Authors: RORKE MARTIN
Published: April 2006

This article compares English and Scottish exports, from 1300–1600, using existing statistical data from England and a new data set of Scottish exports. It shows that the significant English and Scottish wool trades collapsed at almost identical rates. However, while England shifted towards exporting woollen cloth, a similar move in Scotland was weak—because of the poor quality of cloth and the urban form of the industry. In the second half of the sixteenth century, as English exports stagnated, Scottish trade began to grow, especially new and less‐established commodities. This ‘recovery’ was based on the heavy depreciation of the Scottish currency.
Sense of coherence: definition and explanation
Authors: Olsson Martin , Hansson Kjell , Lundblad Ann‐Marie , Cederblad Marianne
Published: April 2006

The present study is one of a few that have used ‘sense of coherence’ (SOC) as a dependent variable in an explanatory model. After studying three different samples – 680 students, 180 parents and 315 couples – we conclude that family relational and psychopathological variables contribute significantly to the explanation of SOC (explained variance between 10–27 and 26–50 per cent). In total, we obtained an explained variance of between 42 and 64 per cent. This leads us to the conclusion that in all three samples, SOC is multifaceted and thereby is more than simply an opposite state to depression. Context may play an important part in the explanation of SOC.
Fracture sealing and fluid overpressures in limestones of the Jabal Akhdar dome, Oman mountains
Authors: HILGERS C. , KIRSCHNER D. L. , BRETON J.‐P. , URAI J. L.
Published: April 2006

Fractures are important conduits for fluid flow in the Earth's crust. To better understand the spatial and temporal relations among fracturing, fracture sealing, and fluid flow, we have studied fractures, faults, and veins in a large dome (Jabal Akhdar) in the Oman mountains. Our work combines the results of meso‐ and microstructural analyses and stable isotope analyses. Seven generations of fractures and veins have been identified in the carbonate‐dominated dome. The earliest generations of veins developed during extension and subsidence of the Mesozoic basin. These veins formed in the inclined segments of bedding‐parallel stylolites and in extensional fractures that are perpendicular to bedding (#1 and #2, respectively). These extension‐related veins are truncated by bedding‐parallel veins (#4) that formed during top‐to‐north bedding‐parallel shear of both the northern and southern limbs of the dome. These veins are consistent with a change in stress regime and may be related to an earlier generation of strongly deformed pinch‐and‐swell veins (#3) that are exposed locally on the southern limb of the dome. Normal faults contain a set of en‐echelon tension gashes (#5) and veins emplaced in dilational jogs along the fault planes (#6). In the northern part of the dome, veins (#7) associated with thrusts post‐date the normal faults. Samples of veins and their host rocks were analyzed to provide information on fluid‐rock interaction in the dome and the scale(s) of fluid movement. Oxygen isotope values range from +16.2 to +29.3‰; carbon isotope values range from 0 to +3.6‰. The results of the structural and isotopic analyses are consistent with the early veins (#2–#5) having precipitated from overpressured fluid in a isotopically rock‐buffered system. During normal faulting (#5 and #6), a more open system allowed external fluid to infiltrate the dome at drained conditions and precipitate the youngest sets of veins (#6 and #7).
Development of a multibottle gas‐tight fluid sampler WHATS II for Japanese submersibles/ROVs
Authors: SAEGUSA S. , TSUNOGAI U. , NAKAGAWA F. , KANEKO S.
Published: April 2006

This paper summarizes the design and performance of our recently developed gas‐tight fluid sampler WHATS II, especially designed to collect seafloor venting gas‐rich fluid from submersibles/remotely operated vehicles (ROVs). It consists of four 150‐cm3 stainless steel sample cylinders, eight ball valves, a motor‐driven arm, a rail, a peristaltic pump, a control unit, and a flexible Teflon tube connected to a titanium inlet tube. All the parts have been designed to be used at undersea as deep as 4000 m. The motor‐driven arm on the rail can open and close each of the four cylinders. By pumping out distilled water that has filled an open cylinder and the dead spaces of the sampler, we can fill the cylinder with sample fluid. WHATS II can take a maximum of four different gas‐tight samples in a series. The whole operation can be arranged from the cabin, etc., of a submersible/ROV. Use of only one motor to operate eight valves makes the sampler small, light (21 kg in sea water), and easy to handle. In addition, the sampler is able to collect an almost uncontaminated gas‐tight sample from the seafloor. To date, the sampler has been used in more than 90 dive surveys by Japanese submersibles/ROVs, including Shinkai 2000, Shinkai 6500, and Hyper Dolphin, with a success rate of >90%.
JUSTIFIED COMMITMENTS? CONSIDERING RESOURCE ALLOCATION AND FAIRNESS IN MÉDECINS SANS FRONTIÈRES‐HOLLAND
Authors: FULLER LISA
Published: April 2006

Non‐governmental aid programs are an important source of health care for many people in the developing world. Despite the central role non‐governmental organizations (NGOs) play in the delivery of these vital services, for the most part they either lack formal systems of accountability to their recipients altogether, or have only very weak requirements in this regard. This is because most NGOs are both self‐mandating and self‐regulating. What is needed in terms of accountability is some means by which all the relevant stakeholders can have their interests represented and considered. An ideally accountable decision‐making process for NGOs should identify acceptable justifications and rule out unacceptable ones. Thus, the point of this paper is to evaluate three prominent types of justification given for decisions taken at the Dutch headquarters of Médecins sans Frontières. They are: population health justifications, mandate‐based justifications and advocacy‐based justifications. The central question at issue is whether these justifications are sufficiently robust to answer the concerns and objections that various stakeholders may have. I am particularly concerned with the legitimacy these justifications have in the eyes of project beneficiaries. I argue that special responsibilities to certain communities can arise out of long‐term engagement with them, but that this type of priority needs to be constrained such that it does not exclude other potential beneficiaries to an undesirable extent. Finally, I suggest several new institutional mechanisms that would enhance the overall equity of decisions and so would ultimately contribute to the legitimacy of the organization as a whole.
ETHICAL CONSIDERATIONS FOR CLINICAL PHOTOGRAPHY IN THE GLOBAL SOUTH
Authors: MACINTOSH TRACY
Published: April 2006

Clinical photography is an important tool for teaching practitioners and field workers about the clinical manifestations of famine and undernutrition, particularly with respect to the Global South. Current international guidelines for clinical photography are not consistently applied or enforced, which has led to violations of privacy and rights, particularly for patients and victims of disaster in the Global South. Combining existing clinical photography guidelines from the North with ongoing clinical ethics debates in the South, this paper explores approaches to establishing photography guidelines throughout the world that will be sensitive to the privacy and dignities of all patients and victims of emergencies.
DESCRIPTIVE ETHICS: A QUALITATIVE STUDY OF LOCAL RESEARCH ETHICS COMMITTEES IN MEXICO
Authors: VALDEZ‐MARTINEZ EDITH , TURNBULL BERNARDO , GARDUÑO‐ESPINOSA JUAN , PORTER JOHN D.H.
Published: April 2006

Objective:  To describe how local research ethics committees (LRECs) consider and apply research ethics in the evaluation of biomedical research proposals.

Design:  A qualitative study was conducted using purposeful sampling, focus groups and a grounded theory approach to generate data and to analyse the work of the LRECs.

Setting and participants:  11 LRECs of the Mexican Institute of Social Security (IMSS).

Results:  LRECs considered ethics to be implicit in all types of research, but that ethics reviews were only necessary for projects that included the direct participation of human beings. The LRECs appeared to understand the importance of consent, as in the completion of a consent form, but did not emphasise the importance of the process of acquiring ‘informed’ consent. The committees considered their main roles or functions to be: (a) to improve the methodological quality of research and to verify – if applicable – the ethical aspects; (b) to encourage personnel to undergo research training; (c) to follow‐up research to oversee the adherence to norms and compliance with a specified research timetable.

Conclusions:  This study provides a valuable insight into how these LRECs understand the ethical review process. The emphasis of the committees was on rules, regulations, improving research methodology and research training, rather than a focus on efforts to protect the rights and well being of research subjects. The results encourage further normative and descriptive lines of investigation concerning education and the development of LRECs.
STRENGTHENING MEDICAL ETHICS BY STRATEGIC PLANNING IN THE ISLAMIC REPUBLIC OF IRAN
Authors: LARIJANI BAGHER , MALEK‐AFZALI HOSSEIN , ZAHEDI FARZANEH , MOTEVASELI ELAHEH
Published: April 2006

To bring attention to medical ethics and to enhance the quality of health care in Iran, the Ministry of Health and Medical Education has introduced a strategic plan for medical ethics at a national level. This plan was developed through the organization and running of workshops in which experts addressed important areas related to medical ethics. They analysed strengths and weaknesses, opportunities and threats, and outlined a vision, a mission and specific goals and essential activities surrounding medical ethics. The current strategic plan has six main goals that will be reviewed in this paper. Some major activities that were carried out in recent years, and some future plans, will be also reviewed.
Altered growth characteristics of skin fibroblasts from wild‐derived mice, and genetic loci regulating fibroblast clone size
Authors: Yuan Rong , Flurkey Kevin , Van Aelst‐Bouma Renee , Zhang Weidong , King Benjamin , Austad Steve , Miller Richard A. , Harrison David E.
Published: April 2006

Mouse fibroblast senescence in vitro is an important model for the study of aging at cellular level. However, common laboratory mouse strains may have lost some important allele variations related to aging processes. In this study, growth in vitro of tail skin fibroblasts (TSFs) derived from a wild‐derived stock, Pohnpei (Pohn) mice, differed from growth of control C57BL/6 J (B6) TSFs. Pohn TSFs exhibited higher proliferative ability, fewer apoptotic cells, decreased expression of Cip1, smaller surface areas, fewer cells positive for senescence associated‐β‐galactosidase (SA‐β‐gal) and greater resistance to H2O2‐induced SA‐β‐gal staining and Cip1 expression. These data suggest that TSFs from Pohn mice resist cellular senescence‐like changes. Using large clone ratio (LCR) as the phenotype, a quantitative trait locus (QTL) analysis in a Pohn/B6 backcross population found four QTLs for LCR: Fcs1 on Chr 3 at 55 cm; Fcs2 on Chr X at 50 cm; Fcs3 on Chr 4 at 51 cm and Fcs4 on Chr 10 at 25 cm. Together, these four QTLs explain 26.1% of the variations in LCRs in the N2 population. These are the first QTLs reported that regulate fibroblast growth. Glutathione S transferase mu (GST‐mu) genes are overrepresented in the 95% confidence interval of Fcs1, and Pohn TSFs have higher H2O2‐induced GST‐mu 4, 5 and 7 mRNA levels than B6 TSFs. These enzymes may protect Pohn TSFs from oxidation.
Progressive Sclerodermatous Skin Changes in a Child with Phenylketonuria
Authors: Al‐Mayouf Sulaiman M. , Al‐Owain Mohammed A.
Published: April 2006

Abstract:  We report a child with phenylketonuria and unusually severe sclerodermatous skin changes. It is likely that prompt and aggressive therapy for these skin changes and phenylketonuria may have modified the clinical course.
Hemorrhagic Bullous Lesions in a Child with Henoch‐Schönlein Purpura
Authors: Leung Alexander K. C. , Robson Wm Lane M.
Published: April 2006

Abstract: An 8‐year‐old boy with Henoch–Schönlein purpura who developed hemorrhagic bullae is described. The occurrence of hemorrhagic bullae in children with Henoch–Schönlein purpura is rare. A perusal of the literature revealed but seven occurrences to which we add another one.
Simultaneous Multiple Pilomatrixomas
Authors: Avci Gülden , Akan M. , Akoz T.
Published: April 2006

Abstract:  We report a 10‐year‐old girl with synchronous multiple pilomatrixomas. Pilomatrixomas are generally solitary tumors; synchronous multiple tumors are very rare. Multiple or recurring tumors may be found in association with various syndromes, and multiple tumors may be familial. Concurrent disorders were not identified in our patient and the etiology of her pilomatrixomas was not understood. Thorough examination of the patient and long‐term follow‐up are necessary with these tumors.
Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABAA‐Receptor Channels
Authors: Quilichini Pascale P. , Chiron Catherine , Ben‐Ari Yehezkel , Gozlan Henri
Published: April 2006

Summary: Purpose:Stiripentol (STP) is currently an efficient drug for add‐on therapy in infantile epilepsies because it improves the efficacy of antiepileptic drugs (AEDs) through its potent inhibition of liver cytochromes P450. In addition, STP directly reduces seizures in several animal models of epilepsy, suggesting that it might also have anticonvulsive effects of its own. However, its underlying mechanisms of action are unknown.

Methods:We examined the interactions of STP with γ‐aminobutyric acid (GABA) transmission by using patch‐clamp methods in CA3 pyramidal neurons in the neonatal rat.

Results:STP markedly increased miniature inhibitory postsynaptic current (mIPSC) decay‐time constant in a concentration‐dependent manner. The prolongation of mIPSC duration does not result from an interaction with GABA transporters because it persisted in the presence of GAT‐1 inhibitors (SKF‐89976A and NO‐711). An interaction with benzodiazepine or neurosteroid binding sites also was excluded because STP‐mediated increase of decay time was still observed when these sites were initially saturated (by clobazam, zolpidem, or pregnanolone) or blocked (by flumazenil or dehydroepiandrosterone sulfate), respectively. In contrast, saturating barbiturate sites with pentobarbital clearly occluded this effect of STP, suggesting that STP and barbiturates interact at the same locus. This was directly confirmed by using outside‐out patches, because STP increased the duration and not the frequency of opening of GABAAchannels.

Conclusions:At clinically relevant concentrations, STP enhances central GABA transmission through a barbiturate‐like effect, suggesting that STP should possess an antiepileptic effect by itself.
The Opening Effect of Pregabalin on ATP‐Sensitive Potassium Channels in Differentiated Hippocampal Neuron–derived H19‐7 Cells
Authors: Huang Chin‐Wei , Huang Chao‐Ching , Wu Sheng‐Nan
Published: April 2006

Summary: Purpose:Adenosine triphosphate (ATP)‐sensitive K+(KATP) channels can couple an intracellular metabolic state to an electrical activity, which is important in the control of neuronal excitability and seizure propagation. We investigated whether the newer antiepileptic drug, pregabalin (PGB), could exert effects on KATPchannels in differentiated hippocampal neuron–derived H19‐7 cells.

Methods:The inside‐out configuration of the patch‐clamp technique was used to investigate KATPchannel activities in H19‐7 cells in the presence of PGB. Effects of various compounds known to alter KATPchannel activities were compared.

Results:The activity of KATPchannels in these cells was characterized. The single‐channel conductance from a linear current–voltage relation was 78 ± 2 pS (n = 8) with a reversal potential of 63 ± 2 mV (n = 8), similar to that of KATPchannels reported in pancreatic β cells. 2,4‐Dinitrophenol activated channel activity, but the further addition of glucose (20 mM) or glibenclamide (30 μM) could offset these increments. PGB significantly opened these KATPchannel activities in a concentration‐dependent fashion with a median effective concentration (EC50) value of 18 μM. A significant increase was noted in the mean open lifetime of KATPchannels in the presence of PGB (1.71 ± 0.04 to 5.62 ± 0.04 ms).

Conclusions:This study suggests that in differentiated hippocampal neuron–derived H19‐7 cells, the opening effect on KATPchannels could be one of the underlying mechanisms of PGB in the reduction of neuronal excitability.
Effects of Potassium Concentration on Firing Patterns of Low‐Calcium Epileptiform Activity in Anesthetized Rat Hippocampus: Inducing of Persistent Spike Activity
Authors: Feng Zhouyan , Durand Dominique M.
Published: April 2006

Summary:  Purpose: It has been shown that a low‐calcium high‐potassium solution can generate ictal‐like epileptiform activity in vitro and in vivo. Moreover, during status epileptiform activity, the concentration of [K+]o increases, and the concentration of [Ca2+]o decreases in brain tissue. Therefore we tested the hypothesis that long‐lasting persistent spike activity, similar to one of the patterns of status epilepticus, could be generated by a high‐potassium, low‐calcium solution in the hippocampus in vivo.

Methods: Artificial cerebrospinal fluid was perfused over the surface of the exposed left dorsal hippocampus of anesthetized rats. A stimulating electrode and a recording probe were placed in the CA1 region.

Results: By elevating K+ concentration from 6 to 12 mM in the perfusate solution, the typical firing pattern of low‐calcium ictal bursts was transformed into persistent spike activity in the CA1 region with synaptic transmission being suppressed by calcium chelator EGTA. The activity was characterized by double spikes repeated at a frequency ∼4 Hz that could last for >1 h. The analysis of multiple unit activity showed that both elevating [K+]o and lowering [Ca2+]o decreased the inhibition period after the response of paired‐pulse stimulation, indicating a suppression of the after‐hyperpolarization (AHP) activity.

Conclusions: These results suggest that persistent status epilepticus–like spike activity can be induced by nonsynaptic mechanisms when synaptic transmission is blocked. The unique double‐spike pattern of this activity is presumably caused by higher K+ concentration augmenting the frequency of typical low‐calcium nonsynaptic burst activity.
Differential Actions of NPY on Seizure Modulation via Y1 and Y2 Receptors: Evidence from Receptor Knockout Mice
Authors: Deborah Lin En‐Ju , Young Deborah , Baer Kristin , Herzog Herbert , During Matthew J.
Published: April 2006

Summary:  Purpose: Neuropeptide Y (NPY) has been shown to modulate seizure activities. To provide further understanding of the involvement of two of the most abundantly expressed NPY receptors, Y1 and Y2, we assessed the effect of Y1 and Y2 gene deletion on systemic kainic acid–induced seizures. We also examined the effect of rAAV‐mediated hippocampal NPY overexpression on seizure susceptibility in these receptor knockout mice.

Methods: Recombinant adeno‐associated viral vector overexpressing NPY (rAAV‐NPY) or an empty vector control (rAAV‐Empty) was injected into the hippocampus of adult C57BL/6–129/SvJ wild‐type male mice and mice deficient of Y1 or Y2 receptors on the same background. Four weeks after vector injection, mice were subjected to systemic kainic acid–induced seizures, and the seizure behaviors were scored.

Results: The rAAV‐mediated hippocampal overexpression of NPY led to a twofold reduction in seizures induced by systemic kainic acid in wild‐type mice and Y1 receptor knockout mice but not in mice deficient of Y2 receptors. A differential action by the receptors was observed in the seizure‐induced mortality rate, with increased fatality in Y2−/− mice. In addition, although NPY overexpression did not significantly affect the mortality rate in Y2−/− and wild‐type mice, it abolished KA‐induced mortality in Y1−/−mice.

Conclusions: This study shows for the first time an altered susceptibility to chemically induced seizures in Y1 and Y2 knockout mice and demonstrates a differential seizure modulation mediated by these receptors via a genetic approach.
Retinal Nerve Fiber Layer and Macular Thickness in Adolescents with Epilepsy Treated with Valproate and Carbamazepine
Authors: Lobefalo Lucio , Rapinese Marcello , Altobelli Emma , Di Mascio Raffaella , Lattanzi Daniela , Gallenga Pier Enrico , Chiarelli Francesco , Verrotti Alberto
Published: April 2006

Summary:  Purpose: To evaluate retinal nerve retinal nerve fiber layer (RNFL) and macular thickness by using optical coherence tomography (OCT) in epileptic adolescents before and during monotherapy with valproic acid (VPA) and carbamazepine (CBZ).

Methods: We examined prospectively 45 epilepsy patients with partial and generalized epilepsy. The patients were evaluated before the beginning of therapy and after 1 year of VPA or CBZ monotherapy. Forty‐five untreated healthy controls were evaluated at baseline and after 1 year.

Results: At the beginning of the study, the two groups of patients showed RNFL and macular thickness measurements similar to control values. At the end of the follow‐up, the data of the three groups were similar to baseline, showing no significant differences in the evaluated parameters.

Conclusions: The present study demonstrates that no modification of RNFL and macular thickness parameters is found after 1 year of treatment with VPA and CBZ monotherapy.
Distinct Cognitive Neurophysiologic Profiles for Lamotrigine and Topiramate
Authors: Smith Michael E. , Gevins Alan , McEvoy Linda K. , Meador Kimford J. , Ray Patricia G. , Gilliam Frank
Published: April 2006

Summary:  Purpose: To contrast the effects of lamotrigine (LTG) and topiramate (TPM) on cognitive task‐related and resting‐state EEG and evoked potential (EP) measures.

Methods: We used a double‐blind, randomized, crossover design. Healthy adults (N = 29) had two 8‐week periods of dose escalation, 4 weeks of drug maintenance (300 mg daily), and 4 weeks of washout. EEG was recorded during working memory (WM) tasks and resting conditions at baseline, at the end of each maintenance phase, and after final washout.

Results. LTG did not affect overt performance on the tasks, although it reduced EEG power in both resting and WM task conditions, most prominently in the 6‐ to 12‐Hz frequency range, and attenuated P300 evoked‐potential amplitude equally in both WM task loads. TPM slowed responses and increased errors. It also increased EEG power below 6 Hz in all conditions, and reduced the amplitude of a slow wave observed in a difficult version of the WM task.

Conclusions: The drugs produced both task‐independent and task‐related alterations in neurophysiologic measures. The EEG and EP changes produced by TPM are consistent with an impairment of WM, as evidenced by overt performance deficits on the behavioral tasks. By contrast, the reduction in synchronous cortical activity produced by LTG was not accompanied by cognitive impairment. It is unknown whether such effects would also be observed at lower doses, such as those that often are used in monotherapy for newly diagnosed patients.
The Ictal Bradycardia Syndrome: Localization and Lateralization
Authors: Britton Jeffrey W. , Ghearing Gena R. , Benarroch Eduardo E. , Cascino Gregory D.
Published: April 2006

Summary: Purpose:Previous studies have established the importance of the insular cortex and temporal lobe in cardiovascular autonomic modulation. Some investigators, based on the results of cortical stimulation response, functional imaging, EEG recordings of seizures, and lesional studies, have suggested that cardiac sympathetic and parasympathetic function may be lateralized, with sympathetic representation lateralized to the right insula, and parasympathetic, to the left. These studies have suggested that ictal bradycardia is most commonly a manifestation of activation of the left temporal and insular cortex. However, the evidence for this is inconsistent. We sought to assess critically the predictable value of ictal bradycardia for seizure localization and lateralization.

Methods:In this study, we reviewed the localization of seizure activity in 13 consecutive patients with ictal bradycardia diagnosed during prolonged video‐EEG monitoring at Mayo Clinic Rochester. The localization of electrographic seizure activity at seizure onset and bradycardia onset was identified in all patients. In addition, we performed a comprehensive review of the ictal bradycardia literature focusing on localization of seizure activity in ictal bradycardia cases.

Results:All occurrences of ictal bradycardia in the 13 identified patients were associated with temporal lobe–onset seizures. However, no consistent lateralization of seizure activity was found at onset of seizure activity or at onset of bradycardia in this population. Seizure activity was bilateral at bradycardia onset in nine of 13 patients. The results from the literature review also showed that a predominance of patients had bilateral activity at bradycardia onset; however, more of the ictal bradycardia cases from the literature had left hemispheric localization of seizure onset.

Conclusions:Ictal bradycardia most often occurs in association with bilateral hemispheric seizure activity and is not a consistent lateralizing sign in localizing seizure onset. Our data do not support the existence of a strictly unilateral parasympathetic cardiomotor representation in the left hemisphere, as has been suggested.
EEG Dipole Characteristics in Panayiotopoulos Syndrome
Authors: Yoshinaga Harumi , Koutroumanidis Michael , Kobayashi Katsuhiro , Shirasawa Atsushi , Kikumoto Kenichi , Inoue Takushi , Oka Makio , Ohtsuka Yoko
Published: April 2006

Summary: Purpose:Panayiotopoulos syndrome (PS) is a type of benign childhood partial epilepsy that is frequently associated with abundant multifocal spikes other than main occipital spikes on the EEG. In this study, we investigated the characteristic features of dipoles in PS.

Methods:We performed dipole analysis of the interictal occipital spike discharges seen in 10 children with PS (group A) and in 10 children with other types of symptomatic localization‐related epilepsy (group B). We analyzed the dipoles of the averaged spike in each patient.

Results:In group A, the averaged occipital spikes in each patient showed dense dipole locations in the mesial occipital area; in group B, widely scattered dipole locations were observed. In Group A, the geometric centers of the dipoles at each time point (such as at the main negative peak and before or after the main peak) were estimated in the neighboring locations. In contrast, they tended to be scattered in group B.

Conclusions:Our study reveals that PS has high dipole stability, similar to that of rolandic epilepsy. From the electroencephalographic view, this seems to indicate a close link between these two syndromes.
MRI Volumetry and Proton MR Spectroscopy of the Brain in Lafora Disease
Authors: Villanueva Vicente , Alvarez‐Linera Juan , Gómez‐Garre Pilar , Gutiérrez Jorge , Serratosa José M.
Published: April 2006

Summary:  Purpose: To determine brain involvement in Lafora disease by means of 3‐T MRI volumetry and 1H magnetic resonance (MR) spectroscopy.

Methods: Ten patients with Lafora disease and 10 healthy controls were included in the study. The diagnosis of Lafora disease was proven genetically by the presence of mutations in the EPM2A gene in all patients, and their evolution was staged in three groups according to their functional state. MRI volumetry was performed by means of AX3DT1 images with assessment of the cerebellum and the brainstem, by using the program Stereonauta, and all the brain structures, by using voxel‐based morphometry. [1H]MR spectroscopy was performed by using an Eclipse PRESS sequence probe system with 8‐cc voxels positioned in the occipital and frontal cortexes, basal ganglia, pons, and cerebellar hemispheres. Spectral peak areas corresponding to NAA (N‐acetylaspartate), creatine, and choline were obtained.

Results: MRI volumetry showed no statistically significant differences in patients compared with healthy controls in any of the analyzed structures. Analysis of [1H]MR spectroscopy data showed a statistically significant reduction in the NAA/creatine ratio in patients compared with controls in the frontal (p = 0.001) and occipital cortex (p = 0.043), basal ganglia (p = 0.002), and cerebellar hemispheres (p = 0.007). The NAA/choline and choline/creatine ratios were statistically significantly different in the frontal cortex (p = 0.005). No correlation was observed between the disease‐evolution stage and MRI‐measured volumes (range, –0.92 to 0.44) or [1H]MR spectroscopy values (range, –0.29 to 0.50).

Conclusions: In our series of Lafora disease patients, [1H]MR spectroscopy was more sensitive than structural MRI to detect brain involvement. The brain cortex, especially frontal cortex, cerebellum, and basal ganglia, showed the greatest metabolic changes.
Transient Athetosis Induced by Tiagabine
Authors: Tombini Mario , Pacifici Loredana , Passarelli Francesco , Rossini Paolo M.
Published: April 2006

Summary:  Movement disorders have been reported with use of different antiepileptic drugs (AEDs). We report a 32‐year‐old woman, affected by a symptomatic focal drug‐resistant epilepsy and a mild hemiparesis, with acute athetoid movements, transiently linked to increasing tiagabine (TGB) therapy. To our knowledge, no other cases of acute athetosis related to TGB have been reported to date. However, we cannot rule out the possibility that involuntary movements were induced by an interaction between TGB and concomitant AEDs, in particular phenobarbital (PB), possibly by increasing GABAergic transmission.

We hypothesize that the presence of a static encephalopathy may have influenced the kind of extrapyramidal side effect induced by TGB in our patient, leading to athetosis.