bluuebunny/crossref_metadata_2025 huggingface dataset:
IS GLOBAL ETHICS MORAL NEO‐COLONIALISM? AN INVESTIGATION OF THE ISSUE IN THE CONTEXT OF BIOETHICS
Authors: WIDDOWS HEATHER
Published: June 2007

This paper considers the possibility and desirability of global ethics in light of the claim that ‘global ethics’ in any form is not global, but simply the imposition of one form of local ethics – Western ethics – and, as such, a form of moral neo‐colonialism. The claim that any form of global ethics is moral neo‐colonialism is outlined using the work of a group of ‘developing world bioethicists’ who are sceptical of the possibility of global ethics. The work of virtue ethicists is then introduced and compared to the position of the developing world bioethicists in order to show that the divide between ‘Western’ and ‘non‐Western’ ethics is exaggerated. The final section of the paper turns to the practical arena and considers the question of global ethics in light of practical issues in bioethics. The paper concludes that practical necessity is driving the creation of global ethics and thus the pertinent question is no longer ‘Whether global ethics?’, but ‘Why global ethics?’.
A CRITIQUE OF THE INNOVATION ARGUMENT AGAINST A NATIONAL HEALTH PROGRAM
Authors: RAJCZI ALEX
Published: June 2007

President Bush and his Council of Economic Advisors have claimed that the US shouldn't adopt a national health program because doing so would slow innovation in health care. Some have attacked this argument by challenging its moral claim that innovativeness is a good ground for choosing between health care systems. This reply is misguided. If we want to refute the argument from innovation, we have to undercut the premise that seems least controversial – the premise that our current system produces more innovation than a national health program would. I argue that this premise is false. The argument requires clarifying the concept ‘national health program’ and examining various theories of human well‐being.
SOLIDARITY AND JUSTICE AS GUIDING PRINCIPLES IN GENOMIC RESEARCH
Authors: HOEDEMAEKERS ROGEER , GORDIJN BERT , PIJNENBURG MARTIEN
Published: June 2007

In genomic research the ideal standard of free, informed, prior and explicit consent is sometimes difficult to apply. This has raised concern that important genomic research will be restricted. Different consent procedures have therefore been proposed. This paper explicitly examines the question how, in genomic research, the principles of solidarity and justice can be used to justify forms of diminished individual control over personal data and bio‐samples. After a discussion of the notions of solidarity and justice and how they can be related to health care and genomic research, we examine how and in which situations these notions can form a strong moral basis for demanding certain financial sacrifices. Then we examine when these principles can justify consent procedures which diverge from the ideal standard. Because much genomic research is not expected to lead to immediate (clinical) benefits we also discuss the question of whether we can be obliged to make any sacrifices for future (not yet existing) patients. We conclude with the formulation of a number of conditions that have to be met before autonomy sacrifices can be reasonably demanded in genomic research.
In the Temple of the Passions: D. Z. Phillips and the Possibility of Philosophical Contemplation
Authors: Amesbury Richard
Published: June 2007

D. Z. Phillips’ work in philosophy was animated by his interest in the diversity and heterogeneity of moral and religious perspectives and his antipathy towards philosophical theories that afford this variety little or no conceptual space. In contrast to what he perceived as essentialist efforts to promote certain viewpoints and to disparage others, Phillips championed a “contemplative conception” of philosophy, according to which the philosopher's aim is neither to underwrite nor to undermine but to understand. This paper argues that philosophy, while disinterested in its aims, nevertheless derives its elucidatory force from the normative contexts within which it is practised and read.
D. Z. Phillips on Belief in God
Authors: Davies Brian
Published: June 2007

In this paper I try briefly to say why I think that what D.Z. Phillips had to say about belief in God can be defended against certain familiar criticisms, and why I think that his treatment could have been improved. I note passages in his writings which might be thought not to reflect what belief in God amounts to, but I argue that these passages can be read as reflecting belief in God as we find it in biblical authors and in writers like Thomas Aquinas. Having noted that Phillips rejects attempts to do natural theology on largely Humean grounds, I argue against these grounds as echoed by Phillips and draw attention to a tradition of natural theology not subject to Humean objections, a tradition to which Phillips might have paid more attention than he did.
Luck, Mystery and Supremacy: D. Z. Phillips Reads Nagel and Williams on Morality
Authors: Mulhall Stephen
Published: June 2007

This paper critically examines D. Z. Phillips’ critical examination of Nagel's and Williams's famous exchange about moral luck. It argues that Phillips fails properly to identify the fundamental issues at stake in the exchange – particularly with respect to the role of scepticism, of the picture of the will as an extensionless point, and of the putative supremacy of morality – and so fails to recognise a certain commonality of interest between himself and those he criticises.
D. Z. Phillips and Wittgenstein's On Certainty
Authors: Stock Guy
Published: June 2007

I start from Phillips' discussion of Rhees's dissatisfaction with the idea of a language‐game. Then, from a rereading of Moore, I go on to exemplify interconnected uses of the expressions “language‐game,”“recurrent procedure,”“world‐picture,”“formal procedure,”“agreement in judgment,”“genre picture” and “form of life.” The discussion is related to sense perception, our knowledge of time and space, and the picture‐theory. These topics connect with Wittgenstein's earlier treatment of the will – which changed markedly later. The subtext (in footnotes) confronts (i) the sceptical methods of Descartes and Hume with the grammatical methods of Leibniz, Kant and Wittgenstein, and (ii) the realism of Leibniz and the Tractatus with the transcendental idealism of Kant. My conclusion is that, although the method of Wittgenstein's later work remains in a sense grammatical, (i) in its new form it can free us from the conviction that the intellect can and must resolve one way or the other the conflicts that arise in the course of the latter confrontation, and that (ii), although release from such a conviction is to be seen as the aim of philosophical discourse in general, it allows philosophy to retain its overriding significance. A positive element in that lies in the respect the method demands for that in a human life which is transcendental to the activity of scientific theorising: respect, therefore, for the unique perspective of the individual historical agent.
Convergence of Heavy‐tailed Monte Carlo Markov Chain Algorithms
Authors: JARNER SØREN F. , ROBERTS GARETH O.
Published: June 2007

Abstract. In this paper, we use recent results of Jarner & Roberts (Ann. Appl. Probab.,12, 2002, 224) to show polynomial convergence rates of Monte Carlo Markov Chain algorithms with polynomial target distributions, in particular random‐walk Metropolis algorithms, Langevin algorithms and independence samplers. We also use similar methodology to consider polynomial convergence of the Gibbs sampler on a constrained state space. The main result for the random‐walk Metropolis algorithm is that heavy‐tailed proposal distributions lead to higher rates of convergence and thus to qualitatively better algorithms as measured, for instance, by the existence of central limit theorems for higher moments. Thus, the paper gives for the first time a theoretical justification for the common belief that heavy‐tailed proposal distributions improve convergence in the context of random‐walk Metropolis algorithms. Similar results are shown to hold for Langevin algorithms and the independence sampler, while results for the mixing of Gibbs samplers on uniform distributions on constrained spaces are rather different in character.
Problem Solving is Often a Matter of Cooking Up an Appropriate Markov Chain*
Authors: HÄGGSTRÖM OLLE
Published: June 2007

Abstract.  By means of a series of examples, from classic contributions to probability theory as well as the author's own, an attempt is made to convince the reader that problem solving is often a matter of cooking up an appropriate Markov chain. Topics touched upon along the way include coupling, correlation inequalities, and percolation.
Factors associated with thorough skin self‐examination for the early detection of melanoma
Authors: Martin RA , Weinstock MA , Risica PM , Smith K , Rakowski W
Published: June 2007

Background  Regular thorough skin self‐examination (TSSE) has potential for detecting melanoma early and reducing melanoma mortality.

Objectives  We sought to model factors associated with skin self‐examination (SSE) and test whether efficacy and attitudes about SSE mediated these relationships.

Patients/Methods  The Check‐It‐Out project is a randomized trial of an intervention to encourage TSSE; 2126 participants were recruited from the practices of primary care physicians. Correlates predicting baseline TSSE included demographic variables, skin cancer risk, physician advice to examine skin, and appropriate conditions for conducting SSE (availability of partner to assist with self‐examination, availability of a wall mirror, and use of contact lenses/glasses).

Results  Those who were given physician advice, had a wall mirror, and had a partner available were more likely to perform TSSE.

Limitations  We identified the factors associated with concurrent TSSE practices. Further research is needed to determine if these same factors predict future behaviour. Our findings may not be applicable in geographical areas other than our recruitment area.

Conclusions  Primary care providers can recommend SSE and provide materials to increase ability to recognize skin problems. Providing instructions and aids for conducting TSSE may increase self‐efficacy.
Perceptions of facial aesthetics in surgical patients with basal cell carcinoma
Authors: Essers B , Nieman F , Prins M , Smeets N , Neumann H
Published: June 2007

Background  Basal cell carcinoma (BCC) is a non‐melanoma form of skin cancer that is frequently localized within the cervicofacial area. So far, little research is available on how patients perceive their facial aesthetics after surgical treatment for BCC.

Objectives  To analyse (i) if there was a statistically significant improvement over time with regard to the perceived facial aesthetics of surgical patients; (ii) if there was a significant difference between primary and recurrent BCC patients; and (iii) between patients who had Mohs micrographic surgery (MMS) or surgical excision (SE). To assess (iv) which baseline perceptions and/or clinical parameters may predict the evaluation of facial aesthetics at 6 months after surgery.

Methods  Parallel to a clinical trial, a survey was carried out in which patients were asked, by means of a newly developed disease‐specific questionnaire, about perceptions with regard to their facial aesthetics before and after surgery.

Results  Aesthetic perceptions of all surgical patients improved over time. There was no statistically significant difference on facial aesthetics between the group with a primary or recurrent BCC and patients treated with MMS or SE. Results also showed that the evaluation of postsurgical facial aesthetics can be predicted by both visibility of the tumour and preoperative perceptions.

Conclusion  It is recommended to administer preoperatively a short questionnaire in which perceptions related to facial aesthetics are included. In doing so, physicians will become more familiar with the aesthetic problems patients might have regarding their afflicted facial site. Ultimately, it may help physicians in deciding whether patients will benefit from additional cosmetic procedures after surgery.
Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness
Authors: Gogtay Nitin , Ordonez Anna , Herman David H. , Hayashi Kiralee M. , Greenstein Deanna , Vaituzis Cathy , Lenane Marge , Clasen Liv , Sharp Wendy , Giedd Jay N. , Jung David , Nugent III Tom F. , Toga Arthur W. , Leibenluft Ellen , Thompson Paul M. , Rapoport Judith L.
Published: June 2007

Background:  There are, to date, no pre‐post onset longitudinal imaging studies of bipolar disorder at any age. We report the first prospective study of cortical brain development in pediatric bipolar illness for 9 male children, visualized before and after illness onset.

Method:  We contrast this pattern with that observed in a matched group of healthy children as well as in a matched group of 8 children with ‘atypical psychosis’ who had similar initial presentation marked by mood dysregulation and transient psychosis (labeled as ‘multi‐dimensionally impaired’ (MDI)) as in the bipolar group, but have not, to date, developed bipolar illness.

Results:  Dynamic maps, reconstructed by applying novel cortical pattern matching algorithms, for the children who became bipolar I showed subtle, regionally specific, bilaterally asymmetrical cortical changes. Cortical GM increased over the left temporal cortex and decreased bilaterally in the anterior (and sub genual) cingulate cortex. This was seen most strikingly after the illness onset, and showed a pattern distinct from that seen in childhood onset schizophrenia. The bipolar neurodevelopmental trajectory was generally shared by the children who remained with MDI diagnosis without converting to bipolar I, suggesting that this pattern of cortical development may reflect affective dysregulation (lability) in general.

Conclusions:  These dynamic trajectories of cortical development may explain age‐related disparate findings from cross‐sectional studies of bipolar illness, and suggest the importance of mood disordered non‐bipolar control group in future studies.
Overlap and specificity of genetic and environmental influences on mathematics and reading disability in 10‐year‐old twins
Authors: Kovas Y. , Haworth C.M.A. , Harlaar N. , Petrill S.A. , Dale P.S. , Plomin R.
Published: June 2007

Background:  To what extent do genetic and environmental influences on reading disability overlap with those on mathematics disability? Multivariate genetic research on the normal range of variation in unselected samples has led to a Generalist Genes Hypothesis which posits that the same genes largely affect individual differences in these abilities in the normal range. However, little is known about the etiology of co‐morbidity for the disability extremes of reading and mathematics.

Method:  From 2596 pairs of 10‐year‐old monozygotic and dizygotic twins assessed on a web‐based battery of reading and mathematics tests, we selected the lowest 15% on reading and on mathematics. We conducted bivariate DeFries–Fulker (DF) extremes analyses to assess overlap and specificity of genetic and environmental influences on reading and mathematics disability defined by a 15% cut‐off.

Results:  Both reading and mathematics disability are moderately heritable (47% and 43%, respectively) and show only modest shared environmental influence (16% and 20%). There is substantial phenotypic co‐morbidity between reading and mathematics disability. Bivariate DF extremes analyses yielded a genetic correlation of .67 between reading disability and mathematics disability, suggesting that they are affected largely by the same genetic factors. The shared environmental correlation is .96 and the non‐shared environmental correlation is .08.

Conclusions:  In line with the Generalist Genes Hypothesis, the same set of generalist genes largely affects mathematical and reading disabilities. The dissociation between the disabilities occurs largely due to independent non‐shared environmental influences.
Listen to the noise: noise is beneficial for cognitive performance in ADHD
Authors: Söderlund Göran , Sikström Sverker , Smart Andrew
Published: June 2007

Background: Noise is typically conceived of as being detrimental to cognitive performance. However, given the mechanism of stochastic resonance, a certain amount of noise can benefit performance. We investigate cognitive performance in noisy environments in relation to a neurocomputational model of attention deficit hyperactivity disorder (ADHD) and dopamine. The Moderate Brain Arousal model (MBA;Sikström & Söderlund, 2007) suggests that dopamine levels modulate how much noise is required for optimal cognitive performance. We experimentally examine how ADHD and control children respond to different encoding conditions, providing different levels of environmental stimulation.

Methods: Participants carried out self‐performed mini tasks (SPT), as a high memory performance task, and a verbal task (VT), as a low memory task. These tasks were performed in the presence, or absence, of auditory white noise.

Results: Noise exerted a positive effect on cognitive performance for the ADHD group and deteriorated performance for the control group, indicating that ADHD subjects need more noise than controls for optimal cognitive performance.

Conclusions: The positive effect of white noise is explained by the phenomenon of stochastic resonance (SR), i.e., the phenomenon thatmoderatenoise facilitates cognitive performance. The MBA model suggests that noise in the environment, introduces internal noise into the neural system through the perceptual system. This noise induces SR in the neurotransmitter systems and makes this noise beneficial for cognitive performance. In particular, the peak of the SR curve depends on the dopamine level, so that participants with low dopamine levels (ADHD) require more noise for optimal cognitive performance compared to controls.
Research Review: A neuroscience framework for pediatric anxiety disorders
Authors: Pine Daniel S.
Published: June 2007

Across a range of mammalian species, early developmental variations in fear‐related behaviors constrain patterns of anxious behavior throughout life. Individual differences in anxiety among rodents and non‐human primates have been shown to reflect early‐life influences of genes and the environment on brain circuitry. However, in humans, the manner in which genes and the environment developmentally shape individual differences in anxiety and associated brain circuitry remains poorly specified. The current review presents a conceptual framework that facilitates clinical research examining developmental influences on brain circuitry and anxiety. Research using threat‐exposure paradigms might most directly integrate basic and clinical perspectives on pediatric anxiety.
Specificity of facial expression labeling deficits in childhood psychopathology
Authors: Guyer Amanda E. , McClure Erin B. , Adler Abby D. , Brotman Melissa A. , Rich Brendan A. , Kimes Alane S. , Pine Daniel S. , Ernst Monique , Leibenluft Ellen
Published: June 2007

Background:  We examined whether face‐emotion labeling deficits are illness‐specific or an epiphenomenon of generalized impairment in pediatric psychiatric disorders involving mood and behavioral dysregulation.

Method:  Two hundred fifty‐two youths (7–18 years old) completed child and adult facial expression recognition subtests from the Diagnostic Analysis of Nonverbal Accuracy (DANVA) instrument. Forty‐two participants had bipolar disorder (BD), 39 had severe mood dysregulation (SMD; i.e., chronic irritability, hyperarousal without manic episodes), 44 had anxiety and/or major depressive disorders (ANX/MDD), 35 had attention‐deficit/hyperactivity and/or conduct disorder (ADHD/CD), and 92 were controls. Dependent measures were number of errors labeling happy, angry, sad, or fearful emotions.

Results:  BD and SMD patients made more errors than ANX/MDD, ADHD/CD, or controls when labeling adult or child emotional expressions. BD and SMD patients did not differ in their emotion‐labeling deficits.

Conclusions:  Face‐emotion labeling deficits differentiate BD and SMD patients from patients with ANX/MDD or ADHD/CD and controls. The extent to which such deficits cause vs. result from emotional dysregulation requires further study.
Effects of methylphenidate on working memory components: influence of measurement
Authors: Bedard Anne‐Claude , Jain Umesh , Johnson Sheilah Hogg , Tannock Rosemary
Published: June 2007

Background:  To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in attention‐deficit hyperactivity disorder (ADHD) and determine the responsiveness of WM measures to MPH.

Methods:  Participants were a clinical sample of 50 children and adolescents with ADHD, aged 6 to 16 years old, who participated in an acute randomized, double‐blind, placebo‐controlled, crossover trial with single challenges of three MPH doses. Four components of WM were investigated, which varied in processing demands (storage versus manipulation of information) and modality (auditory‐verbal; visual‐spatial), each of which was indexed by a minimum of two separate measures.

Results:  MPH improved the ability to store visual‐spatial information irrespective of instrument used, but had no effects on the storage of auditory‐verbal information. By contrast, MPH enhanced the ability to manipulate both auditory‐verbal and visual‐spatial information, although effects were instrument specific in both cases.

Conclusions:  MPH effects on WM are selective: they vary as a function of WM component and measurement.
RACE, SCIENCE AND A NOVEL: AN INTERDISCIPLINARY DIALOGUE
Authors: BURNS LAWRENCE , LANOIX MONIQUE , MELNYCHUK RYAN M. , PAULY BERNIE
Published: June 2007

In the novel Racists by Kunal Basu (2006), two competing scientists initiate an experiment that they believe will prove which race is superior. The research subjects, one white and one black infant, are sequestered on an isolated island in the care of a mute nurse. The contest must be waged in a ‘natural laboratory’ with no artificial interventions and with the prospect that one will die at the hands of the other. The politics of empire, the slave trade and the advent of a new scientific way of viewing life, Darwinism, set the stage for the fictional experiment, but the ramifications of such thinking extend into the present. Coming from the disciplines of nursing, philosophy and science, we discuss how a novel can illuminate the moral dimensions of science and healthcare.

The critical distance afforded by the novel provides a rich terrain for the examination of issues such as race, care and the purity of science. Despite the recent dominance of social explanations of race, science requires the examination of the differences between human beings at the biological level. The view that biology is destiny is a powerful one with dangerous consequences, especially since the belief that certain human beings' destinies are far worthier than others is a corollary of such a view. In this paper, we present the cross‐disciplinary conversation, which has been facilitated by this novel. We hope this will inform ethics educators of the rich potential of using fiction as a pedagogical tool.
SHOULD RAPID TESTS FOR HIV INFECTION NOW BE MANDATORY DURING PREGNANCY? GLOBAL DIFFERENCES IN SCARCITY AND A DILEMMA OF TECHNOLOGICAL ADVANCE
Authors: SMITH CHARLES B. , BATTIN MARGARET P. , FRANCIS LESLIE P. , JACOBSON JAY A.
Published: June 2007

Since testing for HIV infection became possible in 1985, testing of pregnant women has been conducted primarily on a voluntary, ‘opt‐in’ basis. Faden, Geller and Powers, Bayer, Wilfert, and McKenna, among others, have suggested that with the development of more reliable testing and more effective therapy to reduce maternal‐fetal transmission, testing should become either routine with ‘opt‐out’ provisions or mandatory. We ask, in the light of the new rapid tests for HIV, such as OraQuick, and the development of antiretroviral treatment that can reduce maternal‐fetal transmission rates to <2%, whether that time is now. Illustrating our argument with cases from the United States (US), Kenya, Peru, and an undocumented Mexican worker in the US, we show that when testing is accompanied by assured multi‐drug therapy for the mother, the argument for opt‐out or mandatory testing for HIV in pregnancy is strong, but that it is problematic where testing is accompanied by adverse events such as spousal abuse or by inadequate intrapartum or follow‐up treatment. The difference is not a ‘double standard’, but reflects the presence of conflicts between the health interests of the mother and the fetus – conflicts that would be abrogated by the assurance of adequate, continuing multi‐drug therapy. In light of these conflicts, where they still occur, careful processes of informed consent are appropriate, rather than opt‐out or mandatory testing.
LOCAL ATTITUDES, MORAL OBLIGATION, CUSTOMARY OBEDIENCE AND OTHER CULTURAL PRACTICES: THEIR INFLUENCE ON THE PROCESS OF GAINING INFORMED CONSENT FOR SURGERY IN A TERTIARY INSTITUTION IN A DEVELOPING COUNTRY
Authors: IRABOR DAVID O. , OMONZEJELE PETER
Published: June 2007

The process of obtaining informed consent in a teaching hospital in a developing country (e.g. Nigeria) is shaped by factors which, to the Western world, may be seen to be anti‐autonomomous: autonomy being one of the pillars of an ideal informed consent. However, the mix of cultural bioethics and local moral obligation in the face of communal tradition ensures a mutually acceptable informed consent process. Paternalism is indeed encouraged by the patients who prefer to see the doctor as all‐powerful and all‐knowing, and this is buttressed by the cultural practice of customary obedience to those ‘above you’: either in age or social rank. The local moral obligation reassures the patients that those in authority will always look after others placed in their care without recourse to lengthy discussions or signed documentation, while the communal traditions ensure that the designated head of a family unit has the honor and sole responsibility of assenting and consenting to an operation to be carried out on a younger, or female, member of the family. Indeed it is to only a few educated patients that the informed consent process is deemed a shield against litigation by the doctors. This paper later addresses the need for physicians to update their knowledge on the process of informed consent through the attendance of biomedical ethics courses, which should highlight socio‐cultural practices that may make this process different from the Western concept, but perfectly acceptable in this setting.
The Paradoxes of Indian Politics
Authors: Vanaik Achin
Published: June 2007

This article by one of India's foremost writers on contemporary politics surveys twelve paradoxes. These are the key themes which have shaped domestic political change in India in recent decades and particularly since the mid‐eighties. It outlines how social and economic changes have intersected with political possibilities and especially stresses the way in which India's continued social inequalities have been played out in a democratic setting. It is very useful for anybody wanting to understand the present day politics of India or who is interested in the consequences of colonial economies for postcolonial states.
New Statistical Method for Analyzing Time to First Seizure: Example Using Data Comparing Carbamazepine and Valproate Monotherapy
Authors: Cowling Benjamin J. , Shaw J. Ewart H. , Hutton Jane L. , Marson Anthony G.
Published: June 2007

Summary:  Introduction: Time to first seizure is a common outcome in antiepileptic drug (AED) studies. Previous studies have typically failed to find statistically significant differences between carbamazepine (CBZ) and valproate (VPS). We re‐analyzed a meta‐analysis comparing CBZ and VPS monotherapy with new powerful statistical methods that incorporate baseline seizure rate information.

Methods: Individual patient data were available on 1,265 patients from a meta‐analysis of five trials. The outcome measure was time to first seizure after randomization, adjusted for background variables and baseline seizure rate.

Results: We found strong evidence of an interaction between treatment and epilepsy type, and between treatment and age. For generalized onset seizures, VPS was statistically significantly better than CBZ: VPS delayed the first seizure after treatment 58%, 52%, 44%, and 36% longer than CBZ for individuals aged 10, 20, 30, or 40, respectively. For partial onset seizures in individuals older than 30, CBZ was significantly better then VPS; CBZ delayed the time to first seizure by 9%, 25%, 44%, and 66% longer than VPS for individuals aged 20, 30, 40, or 50, respectively.

Conclusion: The results show clear age‐varying differences between the effectiveness of CBZ and VPS for generalized onset and partial onset seizures, which have not been identified in previous studies using standard statistical methods. In future trials of AED monotherapy or add‐on where time to first or Nth seizure is an outcome, methodology that can incorporate baseline seizure rate information would allow more powerful comparisons between treatments or between treatment and placebo.
Brain Mapping of Epileptic Activity in a Case of Idiopathic Occipital Lobe Epilepsy (Panayiotopoulos Syndrome)
Authors: Leal Alberto J.R. , Nunes Sofia , Martins António , Secca Mário Forjaz , Jordão Constança
Published: June 2007

Summary:  The Panayiotopoulos type of occipital lobe epilepsy has generated great interest, but the particular brain areas involved in the peculiar seizure manifestations have not been established. We studied a patient with the syndrome, using high‐resolution EEG and simultaneous EEG and functional magnetic resonance imaging (fMRI). Resolution of the scalp EEG was improved using a realistic spline Laplacian algorithm, and produced a complex distribution of current sinks and sources over the occipital lobe. The spike‐related blood oxygen level dependent (BOLD) effect was multifocal, with clusters in lateral and inferior occipital lobe and lateral and anterior temporal lobe. We also performed regional dipole seeding in BOLD clusters to determine their relative contribution to generation of scalp spikes. The integrated model of the neurophysiologic and vascular data strongly suggests that the epileptic activity originates in the lateral occipital area, spreading to the occipital pole and lateral temporal lobe.
Effect of the Adenosine A2a Receptor Antagonist 3,7‐Dimethyl‐Propargylxanthine on Anxiety‐like and Depression‐like Behavior and Alcohol Consumption in Wistar Rats
Authors: Thorsell Annika , Johnson Justin , Heilig Markus
Published: June 2007

Background: It has been suggested that the reinforcing properties of ethanol are in part mediated via an A2 activation of cAMP/PKA signaling in the nucleus accumbens, predicting that administration of an A2a antagonist might reduce ethanol reward and consumption. We therefore examined the effect of the adenosine A2a receptor antagonist 3,7‐dimethylpropargylxanthine (DMPX, 3, and 10 mg/kg intraperitoneal) on alcohol reinforcement, anxiety‐related, depression, and rewarding behaviors in nonselected Wistar rats.

Methods: Operant ethanol self‐administration was used for examining alcohol intake, elevated plus‐maze and Vogel conflict test for anxiety‐related behavior, Porsolt swim test for depression‐like behavior, and conditioned place preference for examination of the rewarding properties of the drug.

Results: 3,7‐Dimethylpropargylxanthine decreased lever‐pressing for ethanol in a dose‐dependent manner. When analyzed as percentage of pretreatment baseline, maximum suppression was approximately 60% (39±7.5 vs 98±12%, mean±SEM, p=0.017). This effect was behaviorally specific, as no effect was found on the water lever. In agreement with previously published data, stimulation of locomotion was found (beam‐breaks: 3590±540 vs 2475±240, 10 mg/kg vs saline, p=0.048). No anxiety‐modulating effects were seen in either the elevated plus‐maze or the Vogel conflict test. 3,7‐Dimethylpropargylxanthine was not found to have intrinsic rewarding properties in the conditioned place preference model.

Conclusions: In summary, DMPX produced a robust and behaviorally selective reduction of ethanol reinforcement, while anxiety‐modulating effects were less consistent. These results bring further support to a role for adenosine in the regulation of ethanol consumption and possibly alcohol addiction/abuse, and the A2a receptor as a potential target for the treatment of alcoholism and alcohol abuse.
Component Cognitive and Motor Processes of the Digit Symbol Test: Differential Deficits in Alcoholism, HIV Infection, and Their Comorbidity
Authors: Sassoon Stephanie A. , Fama Rosemary , Rosenbloom Margaret J. , O'Reilly Anne , Pfefferbaum Adolf , Sullivan Edith V.
Published: June 2007

Background: Alcoholism (ALC) is highly prevalent in patients with human immunodeficiency virus (HIV) infection (HIV), and those with comorbidity (ALC+HIV) may suffer compounded deficits in cognitive and motor functions affected by both conditions. Given that each disease can adversely affect motor, visuospatial, and executive functions, we used an expanded version of the Digit Symbol (DS) test to assess the separate and combined effects of ALC and HIV infection on these cognitive and motor components.

Methods: Participants were 44 ALC, 43 HIV, 55 ALC+HIV, and 49 normal controls (NC). We modified DS test administration to assess sustained attention (grid completion speed), associative learning (number of boxes completed in 15‐second epochs), and incidental learning (total number–symbol pairs correctly recalled) and also used ancillary tests of fine motor, visuospatial, and executive functions to assess their relationship with the different components of DS performance. All scores were corrected for age and education based on NC performance.

Results: Neither single diagnosis group—ALC nor HIV—was impaired on DS score or grid completion speed compared with the NC group, but the dual‐diagnosis ALC+HIV group was impaired. Greater lifetime alcohol consumption was associated with longer grid completion time in both ALC and ALC+HIV. The HIV group demonstrated associative learning on DS but ALC+HIV and ALC did not. All groups performed similarly on incidental learning. Multiple regression analyses demonstrated that executive functions, assessed by Color Trails 2, predicted traditional DS performance in all groups. Fine Finger Movement additionally predicted traditional DS performance and grid completion speed in HIV. Visuospatial function, assessed by ability to copy the Rey‐Osterrieth complex figure, did not contribute independently to DS performance in either alcohol group.

Conclusions: Alcoholism combined with HIV infection resulted in deficits in visuospatial psychomotor function, as assessed by the DS test, although deficits were not observed in either disease condition alone. Neither alcohol group showed associative learning, and both had compromised sustained attention. Combined cognitive and motor adverse effects of alcoholism and HIV infection were manifest in psychomotor speed, sustained attention, and associative learning of visuospatial material and are testimony to the dangers of alcohol abuse even in relatively healthy patients with HIV infection.
Matching Law Choice Analyses of Ethanol and Sucrose Consumption in Alcohol‐Preferring (P), Nonpreferring (NP), and Sprague–Dawley (SD) Rats
Authors: Martinetti Margaret P. , Khan Zeeshan , Lewis Michael J.
Published: June 2007

Background: Quantitative models of choice, such as the matching law and behavioral economics, allow for the analysis of alcohol consumption within a choice context. Such models can provide further knowledge of phenotypic differences between selected lines of rats. The current study applied the generalized matching law to the ethanol (EtOH) and sucrose consumption of alcohol‐preferring (P), nonpreferring (NP), and Sprague–Dawley (SD) rats.

Methods: Male P, NP, and SD rats were trained to consume increasing concentrations of EtOH and water in a limited access, 2‐bottle choice procedure. The animals were then given concurrent access to pairs of differing EtOH solutions (2, 4, 6, and 10%, v/v) for 1 h/d. A subset of animals from each rat type was subsequently given access to 8% sucrose for 1 h/d for 5 days, and then concurrent access to pairs of differing sucrose solutions (3, 8, and 15%, w/v) for 1 h/d. The generalized matching law was used to assess the relationship between the relative EtOH and sucrose concentrations and the relative volumes of solutions consumed.

Results: The P rats consumed more EtOH and sucrose than the NP and SD rats overall. However, only the P rats consistently consumed disproportionately greater quantities of the higher EtOH concentration than the lower one, indicating overmatching. Additionally, all 3 types of rats displayed overmatching in the sucrose choice experiment.

Conclusions: These data provide further evidence of phenotypic differences between the P rats and other types of rats, and suggest that the generalized matching law can be a useful tool for describing rats' EtOH or sucrose consumption in a 2‐bottle choice, limited access paradigm.
Effect of the Medicaid Deficit Reduction Act on Older Adults
Authors: Koss Diana B.
Published: June 2007

The Deficit Reduction Act (DRA) was recently enacted and implemented significant changes to Medicaid. Some of these changes may affect enrollment eligibility for older adults who need long‐term care such as assisted living or nursing home care. The DRA changes regulations on maintaining personal assets, shortens the time allowed to make monetary donations without a penalty, and requires more legal documentation. These changes could delay enrollment or discourage people from applying for benefits. Physicians who see elderly patients will need to know the basic aspects of the Medicaid program and how the DRA affects eligibility. Physicians should also know where to refer their elderly patients for more information or guidance through the application process.
Exercise: A Potential Contributing Factor to the Relationship Between Folate and Dementia
Authors: Middleton Laura E. , Kirkland Susan A. , Maxwell Colleen J. , Hogan David B. , Rockwood Kenneth
Published: June 2007

OBJECTIVES:To investigate whether exercise confounds the relationship between folate and cerebrovascular events, all‐cause dementia, and Alzheimer's disease.

DESIGN:Prospective cohort study.

SETTING:Multiple centers in Canada.

PARTICIPANTS:In the Canadian Study of Health and Aging, 466 people reported exercise levels, had folate measurements, and were not demented at baseline. After 5 years, 194 had adverse cerebrovascular events, and 65 had dementia (Alzheimer's disease in 47).

MEASUREMENTS:Associations between folate and cerebrovascular outcomes were examined using logistic regression in the presence and absence of exercise and other confounders.

RESULTS:Folate was associated with greater risk of Alzheimer's disease (odds ratio (OR)=2.12, 95% confidence interval (CI)=1.01–4.54) and cerebrovascular outcomes (OR=2.05, 95% CI=1.11–3.78) in adjusted analyses before the inclusion of exercise and neared significance with all‐cause dementia (OR=1.80, 95% CI=0.94–3.45). After the inclusion of exercise, the association between folate and dementia and Alzheimer's disease was 29% and 25% lower, respectively, and neither association was any longer significant (Alzheimer's disease: OR=1.91, 95% CI=0.89–4.11; all‐cause dementia: OR=1.62, 95% CI=0.84–3.15). Exercise was a significant confounder in the relationship between folate and Alzheimer's disease (P=.03) and dementia (P=.003) but not cerebrovascular outcomes (P=.64). Unlike folate, exercise was significantly associated with Alzheimer's disease (OR=0.43, 95% CI=0.19–0.98) and dementia (OR=0.35, 95% CI=0.17–0.72) in adjusted analyses.

CONCLUSION:Exercise seems to account for much of the relationship between folate and incident dementia and Alzheimer's disease.
An Educational Intervention to Improve Antimicrobial Use in a Hospital‐Based Long‐Term Care Facility
Authors: Schwartz David N. , Abiad Homer , DeMarais Patricia L. , Armeanu Emilian , Trick William E. , Wang Yue , Weinstein Robert A.
Published: June 2007

OBJECTIVES: To improve antimicrobial use in patients receiving long‐term care (LTC).

DESIGN: Prospective, quasi‐experimental before–after assessment of the effects of physician education and guideline implementation.

SETTING: Public LTC and acute care hospital.

PARTICIPANTS: Twenty salaried internists who provided most of the medical care to LTC patients.

INTERVENTION: National guidelines, hospital resistance data, and physician feedback were incorporated into a series of four teaching sessions presented over 18 months and into booklets detailing institutional guidelines on the optimal management of common LTC infection syndromes.

MEASUREMENTS: One hundred randomly selected LTC patients treated with antimicrobials were reviewed before these interventions were implemented and 100 after, and measures of the quality of care were compared. The effect of the interventions on antimicrobial days and starts were also assessed using interrupted time series analysis.

RESULTS: Charted clinical abnormalities met guideline diagnostic criteria (62% vs 38%, P=.006), and initial therapy agreed with guideline recommendations (39% vs 11%, P<.001), more often in the post‐ than in the preintervention cohort. Mean census‐adjusted monthly LTC antimicrobial days fell 29.7%, and antimicrobial starts fell 25.9% during the intervention period; both decreases were sustained during the 2‐year postintervention period.

CONCLUSION: The teaching and guideline intervention improved the quality and reduced the quantity of antimicrobial use in LTC patients.
Are the Insider Trades of a Large Institutional Investor Informed?
Authors: Golec Joseph
Published: June 2007

We use a unique data set to consider whether a large institution's (Fidelity funds) insider trades are informed. Theoretical studies of large informed traders suggest that their information advantage could be greater for buy trades than sell trades, be short‐ or long‐lived, and be exploited by varying the pace of trade execution. Although there is evidence of each of these, Fidelity seems to be informed only for quickly executed buy trades. Other trades outperform a stock market index but not a four‐factor return model. This performance profile is consistent with Fidelity's fees, which depend on performance compared to an index.
Price Clustering on the Tokyo Stock Exchange
Authors: Aşçıoğlu Aslı , Comerton‐Forde Carole , McInish Thomas H.
Published: June 2007

This paper examines price clustering on the Tokyo Stock Exchange (TSE). Regardless of tick and lot size, prices ending in zero and five are the most popular. The TSE has no market makers or direct negotiation between traders; therefore, clustering is not explained by collusion or negotiation. Our evidence supports the attraction hypothesis. Clustering also extends to order book depth. There is evidence of strategic trading behavior as traders place orders one price tick better than zero and five to avoid queuing orders at prices ending in these digits. Strategic trading behavior declined and clustering increased when the market became anonymous.
RhoB‐Dependent Modulation of Postendocytic Traffic in Polarized Madin‐Darby Canine Kidney Cells
Authors: Rondanino Christine , Rojas Raul , Ruiz Wily G. , Wang Exing , Hughey Rebecca P. , Dunn Kenneth W. , Apodaca Gerard
Published: June 2007

The Rho family of GTPases is implicated in the control of endocytic and biosynthetic traffic of many cell types; however, the cellular distribution of RhoB remains controversial and its function is not well understood. Using confocal microscopy, we found that endogenous RhoB and green fluorescent protein‐tagged wild‐type RhoB were localized to early endosomes, and to a much lesser extent to recycling endosomes, late endosomes or Golgi complex of fixed or live polarized Madin‐Darby canine kidney cells. Consistent with RhoB localization to early endosomes, we observed that expression of dominant‐negative RhoBN19 or dominant‐active RhoBV14 altered postendocytic traffic of ligand‐receptor complexes that undergo recycling, degradation or transcytosis. In vitro assays established that RhoB modulated the basolateral‐to‐apical transcytotic pathway by regulating cargo exit from basolateral early endosomes. Our results indicate that RhoB is localized, in part, to early endosomes where it regulates receptor egress through the early endocytic system.
Differential Requirements for ts‐O45‐G and Procollagen Biosynthetic Transport
Authors: Starkuviene Vytaute , Pepperkok Rainer
Published: June 2007

Emerging experimental evidence favours the existence of cargo sorting occurring upon the endoplasmic reticulum (ER) exit. Recent studies revealed that, in contrast to the conventional secretory marker ts‐O45‐G, procollagen (PC I) exits the ER at sites not coated with coat protein II and is transported to the Golgi complex in carriers devoid of coat protein I. Here, we investigated whether PC I trafficking requires a different molecular machinery in comparison with the ts‐O45‐G. By combining colocalization of the cargoes with endogenous markers, downregulation of transport machinery by RNA interference and knock‐ins by complementary DNA over‐expression, we provide strong evidence that PC I and ts‐O45‐G have common but also different molecular requirements during pre‐ and post‐Golgi trafficking events.
Structure/Function Analysis of Four Core ESCRT‐III Proteins Reveals Common Regulatory Role for Extreme C‐Terminal Domain
Authors: Shim Soomin , Kimpler Lisa A. , Hanson Phyllis I.
Published: June 2007

Endosomal sorting complex required for transport‐III (ESCRT‐III) is a large complex built from related ESCRT‐III proteins involved in multivesicular body biogenesis. Little is known about the structure and function of this complex. Here, we compare four human ESCRT‐III proteins – hVps2‐1/CHMP2a, hVps24/CHMP3, hVps20/CHMP6, and hSnf7‐1/CHMP4a – to each other, studying the effects of deleting predicted α‐helical domains on their behavior in transfected cells. Surprisingly, removing ∼40 amino acids from the C‐terminus of each protein unmasks a common ability to associate with endosomal membranes and assemble into large polymeric complexes. Expressing these truncated ESCRT‐III proteins in cultured cells causes ubiquitinated cargo to accumulate on enlarged endosomes and inhibits viral budding, while expressing full‐length proteins does not. hVps2‐1/CHMP2a lacking its C‐terminal 42 amino acids further fails to bind to the AAA+ adenosine triphosphatase VPS4B/SKD1, indicating that C‐terminal sequences are important for interaction of ESCRT‐III proteins with VPS4. Overall, our study supports a model in which ESCRT‐III proteins cycle between a default ‘closed’ state and an activated ‘open’ state under control of sequences at their C‐terminus and associated factors.