bluuebunny/crossref_metadata_2025 huggingface dataset:
A polymorphism in lipoprotein lipase affects the severity of Alzheimer's disease pathophysiology
Authors: Blain Jean‐François , Aumont Nicole , Théroux Louise , Dea Doris , Poirier Judes
Published: September 2006

Emerging evidences indicate a role for lipoprotein lipase (LPL) in degenerative states. Genetic variations in the LPL gene were previously associated to lipid imbalance and coronary artery disease (CAD) risk and severity, a condition that shares pathological features with common Alzheimer's disease (AD). To evaluate whether these genetic variations associate with the risk and pathophysiology of common AD, autopsy‐confirmed patients (242 controls, 153 AD) were genotyped for a PvuII single nucleotide polymorphism (SNP; rs285; referred to as the P+ allele) of LPL. Brain LPL mRNA levels, cholesterol levels, amyloid concentration, senile plaques and neurofibrillary tangles density counts were measured and contrasted with specific LPL genotypes. When adjusted for age and sex, homozygosity for the P+ allele resulted in an odds ratio of 2.3 for the risk of developing AD. More importantly, we report that the presence of the P+ allele of LPL significantly affects its mRNA expression level (n = 51; P = 0.026), brain tissue cholesterol levels (n = 55; P = 0.0013), neurofibrillary tangles (n = 52; P = 0.025) and senile plaque (n = 52; P = 0.022) densities. These results indicate that a common polymorphism in the lipoprotein lipase gene modulates the risk level for sporadic AD in the eastern Canadian population but more importantly, indirectly modulates the pathophysiology of the brain in autopsy‐confirmed cases.
Irreversible blockade of monoamine oxidases reveals the critical role of 5‐HT transmission in locomotor response induced by nicotine in mice
Authors: Villégier Anne‐Sophie , Salomon Lucas , Blanc Gérard , Godeheu Gérard , Glowinski Jacques , Tassin Jean‐Pol
Published: September 2006

Although nicotine is generally considered as the main compound responsible for addictive properties of tobacco, some experimental data indicate that nicotine does not exhibit all the characteristics of other substances of misuse such as psychostimulants and opiates. For example, nicotine generally fails to induce locomotor response in mice and self‐administration of nicotine is difficult to obtain in rats. We have shown recently that a pretreatment with mixed irreversible monoamine oxidase inhibitors (MAOIs), such as tranylcypromine, triggers a locomotor response to nicotine in mice and induces a robust self‐administration of nicotine in rats. We show here that when mice were pretreated with enhancers of extracellular levels of noradrenaline, dopamine or serotonin (d‐amphetamine, GBR12783 or para‐chloro‐amphetamine, respectively) and injected with nicotine (1 mg/kg), only those animals pretreated with para‐chloro‐amphetamine exhibited a specific locomotor response to nicotine. These data indicate a critical role of serotonin in nicotine‐induced locomotor activity in mice. This was further confirmed in microdialysis experiments showing that nicotine induces an increase in extracellular serotonin levels in the ventral striatum in mice pretreated with tranylcypromine. This effect of nicotine on extracellular serotonin levels was absent in mice lacking the β2‐subunit of the nicotinic acetylcholine receptor. Our data suggest that mixed irreversible MAOIs contained in tobacco facilitate the effects of nicotine on serotonin release, thus allowing the locomotor and rewarding effects of nicotine.
Diet‐induced obesity and diabetes reduce coronary responses to nitric oxide due to reduced bioavailability in isolated mouse hearts
Authors: Bender S. B. , Herrick E. K. , Lott N. D. , Klabunde R. E.
Published: September 2006

Aim:  The aim of the present study was to examine nitric oxide (NO)‐mediated coronary vascular responses in a mouse model of obesity and diabetes induced by a high‐fat, high‐carbohydrate diet. We hypothesized that endogenous NO bioavailability would be reduced in obese/diabetic mouse hearts due to enhanced superoxide anion production, and that coronary smooth muscle responses to exogenous NO would be reduced.

Methods:  Age‐matched, male C57BL/6J mice were fed either a control diet or a high‐fat, high‐carbohydrate diet. After 15 weeks, the mice were anesthetized and their hearts were removed and perfused by the Langendorff method under constant flow conditions with an oxygenated buffer solution, and changes in coronary vascular resistance were quantified.

Results:  Mice fed the high‐fat, high‐carbohydrate diet became obese, hyperglycaemic and hyperinsulinaemic. Coronary vasoconstrictor responses to NO synthase inhibition by Nω‐nitro‐L‐arginine methyl ester were reduced in obese/diabetic mice; normal responses were restored by pretreatment with the superoxide dismutase mimetic 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (Tempol). Coronary endothelium‐independent vasodilation to the NO donor (±)‐S‐nitroso‐N‐acetylpenicillamine (SNAP) was reduced; however, 8‐bromo‐cyclic guanosine monophosphate (cGMP)‐induced vasodilation was unchanged in obese/diabetic hearts.

Conclusions:  These findings suggest that in a diet‐induced mouse model of obesity and diabetes, NO bioavailability is reduced by increased superoxide NO scavenging leading to impaired NO‐mediated vasodilation. Furthermore, the attenuation of SNAP‐induced vasodilation may be due to increased reactive oxygen species scavenging of exogenous NO because normal vascular smooth muscle NO signalling is maintained as indicated by similar 8‐bromo‐cGMP responses in control and obese/diabetic hearts.
Premixed insulin treatment for type 2 diabetes: analogue or human?
Authors: Garber Alan J. , Ligthelm Robert , Christiansen Jens S. , Liebl Andreas
Published: September 2006

The progressive nature of type 2 diabetes makes insulin initiation a necessary therapeutic step for many patients. Premixed insulin formulations containing both basal and prandial insulin (so called biphasic insulin) are often prescribed because they are superior to long‐ or intermediate‐acting insulin in obtaining good metabolic control. In addition, they are considered as an attractive alternative to classical basal‐bolus therapy as fewer daily injections are required. Premixed insulin formulations include conventional (e.g. biphasic human insulin 70/30, or 30/70 in European countries, BHI 30) and newer premixed human analogues (e.g. biphasic insulin aspart 70/30, or 30/70 in Europe, BIAsp 30; insulin lispro mix 75/25–Mix 75/25, or Mix 25/75 in Europe). Like conventional premixed human insulin, premixed insulin analogues contain a fixed proportion of soluble, rapid‐acting insulin analogue, with protaminated analogue comprising the remainder. Unlike conventional premixes, analogue premixes have more physiological pharmacokinetic and therapeutically more desirable pharmacodynamic profiles than premixed human insulin. Consequently, postprandial glycaemic control is better with premixed insulin analogues than with premixed human insulin. In nontreat‐to‐target registration trials, the lowering of haemoglobin A1c with premixed insulin analogues was not inferior to that seen with premixed human insulin. Minor hypoglycaemia was similar for premixed analogue and premixed human insulins, while major hypoglycaemia appears to be rare with either formulation. The occurrence of adverse events, other than hypoglycaemia, was also similar between various premix insulins. The premixed insulin analogues, BIAsp 30 and Mix 75/25, like the fast‐acting analogues from which they are derived, also allow flexible injection timing, relative to meal timing, thus improving adherence, compliance and quality of life compared with premixed human insulin. Overall, the evidence suggests that premixed insulin analogues are cost effective and have useful advantages over premixed human insulin for the treatment of type 2 diabetes.
The Pathological Export Boom and the Bazaar Effect: How to Solve the German Puzzle
Authors: Sinn Hans‐Werner
Published: September 2006

Germany is the laggard of Europe, yet the country is world champion in merchandise exports. The paper tries to solve this theoretical and empirical puzzle by diagnosing a ‘pathological export boom’ and a ‘bazaar effect’. Excessively high wages defended by unions and the welfare state against the forces of international low‐wage competition destroy too big a fraction of the labour‐intensive sectors and drive too much capital and labour into the capital‐intensive export sectors, causing both unemployment and excessive value added in exports. Moreover, excessive wages induce too much outsourcing of upstream production activities, which implies that export quantities grow too much in relation to value added contained in exports. Finally, excessive wages cause capital flight resulting in a too large current account surplus.
A NORMATIVE THEORY OF REPARATIONS IN TRANSITIONAL DEMOCRACIES
Authors: VERDEJA ERNESTO
Published: September 2006

Abstract:This essay outlines a normative theory of reparations for transitional democracies. The article situates the theory within current critical‐theory debates on recognition and redistribution, and it argues that any model of reparations should aim to achieve what Nancy Fraser calls “status parity.” Such a model should be conceptualized according to a typology of acknowledgment along one axis (symbolic and material) and a typology of recipients (individual and collective) along the other. I conclude by identifying several key contributions that reparations can make to transitional societies.
GENOCIDE AND THE MORAL AGENCY OF ETHNIC GROUPS
Authors: KOVACH KAREN
Published: September 2006

Abstract:Genocide is the deliberate destruction, in whole or in part, of a people. Typically, it is a crime that is committedbya people. In this essay, I propose an analysis of the concept of anethnic identity group, which is, I argue, the concept of ethnicity at issue in many important discussions of group rights, group acts, and the moral responsibility of group members for the acts of the groups to which they belong. I develop the account of collective agency presupposed by this analysis and explore its implications for assessments of individual moral responsibility for genocide. I argue, further, that among other advantages over culturalist approaches to questions about group rights, the approach that follows from the concept of an ethnic identity group sheds light on the specific moral wrong of genocide. I reply to individualist objections to the idea that ethnic group membership may be morally significant and argue that morally adequate responses to genocide presuppose acknowledgment of the fact that groups act and are acted upon in morally significant ways.
ACKNOWLEDGING AND RECTIFYING THE GENOCIDE OF AMERICAN INDIANS: “WHY IS IT THAT THEY CARRY THEIR LIVES ON THEIR FINGERNAILS?”
Authors: BRADFORD WILLIAM C.
Published: September 2006

Abstract:Although genocide—a coordinated plan of different actions aiming at the destruction of essential foundations of the life of national groups, with the aim of annihilating the groups themselves—remains a sickeningly frequent phenomenon in the twenty‐first century, it is not an immutable aspect of the human condition. Genocide is a choice, and the civilized world must choose its demise. The unique experience of American Indians—a group subjected to genocide in the process of the creation and expansion of the United States—presents a logical heuristic through which to assess more broadly the requirements of redress for historical episodes of genocide and, even more important, the means to prevent its recurrence.
RETHINKING THE LEGITIMACY OF TRUTH COMMISSIONS: “I AM THE ENEMY YOU KILLED, MY FRIEND”
Authors: EISIKOVITS NIR
Published: September 2006

Abstract: The most contentious aspect of South Africa's Truth and Reconciliation Commission (TRC) concerned its amnesty‐granting powers. In return for perpetrators providing full disclosure about their crimes, the TRC was authorized to release them from both criminal responsibility and civil liability. This essay takes up the thorny question of how such a commission might be morally justified. Part 1 discusses the political circumstances that led to the creation of the TRC. Part 2 provides a critical survey of some previous attempts to justify the commission's work. Part 3 offers a new justification, grounded in Adam Smith's notion of sympathy; after outlining some of the benefits of sympathy for political reconciliation, I argue that the work of a South African–style truth commission can promote sympathy between former enemies.
THE COUNTERFACTUAL CONCEPTION OF COMPENSATION
Authors: ROBERTS RODNEY C.
Published: September 2006

Abstract: My aim in this essay is to remove some of the rubbish that lies in the way of an appropriate understanding of rectificatory compensation, by arguing for the rejection of the counterfactual conception of compensation. Although there is a significant extent to which contemporary theorists have relied upon this idea, the counterfactual conception of compensation (CCC) is merely a popular assumption, having no positive argument in support of it. Moreover, it can make rendering compensation impossible, and absurd notions of compensation can result from its use, results that may themselves constitute injustices. This latter difficulty is most troubling when the CCC is employed in large compensatory cases like the case of rectificatory compensation for the descendants of American slaves. I want to suggest that, taken together, the difficulties with the CCC yield sufficient reason for rejecting it as an acceptable rectificatory notion.
The challenges of poverty and social welfare in the Caribbean
Authors: Bowen Glenn A.
Published: September 2006

Poverty and related social problems have presented a long‐standing challenge to policy makers and development planners throughout the Caribbean. This article is a social primer on anti‐poverty strategies and welfare programmes established in Caribbean countries. It presents a comprehensive overview of poverty and attendant problems, discusses the social welfare approach and poverty reduction strategies, and outlines practical proposals for pursuing social development.
What determines exit from social assistance in Spain?
Authors: Ayala Luis , Rodríguez Magdalena
Published: September 2006

The aim of this article is two‐fold. Firstly, we try to identify the main socioeconomic characteristics that explain the dynamics of social assistance in Spain. Secondly, we carry out a number of tests to assess to what extent individual characteristics accounting for duration differ in the different types of exit from social assistance. Analysis of periods on social assistance shows that belonging to an ethnic minority and employability are the two main determining factors leading to prolonged spells of social assistance. The results also show a striking similarity between the profiles of exits from the programmes due to ‘successful reasons’ and due to fraud. Exits from the programmes for other reasons occur in a clearly different way.
Assessment processes in social work with children at risk in Sweden and Croatia
Authors: Brunnberg Elinor , Pećnik Ninoslava
Published: September 2006

The aim of this article is to compare Swedish and Croatian social workers’ assessments and protection of a 4‐year‐old child exposed to risk in its own family. The data were collected from 87 Croatian and 72 Swedish social workers by means of a questionnaire, which incorporated a vertical vignette. Effects of the participant's country of residence were investigated with respect to: (i) risk assessments; (ii) perception of the main problems; (iii) tolerance of corporal punishment; (iv) judgements about appropriateness of interventions. The results suggest that Croatian social workers have a more child‐protective approach than their Swedish colleagues. Swedish social workers have a more supportive approach than Croatian social workers. Despite fundamental similarities in assessments between the countries, significant differences were found in preferred interventions. The Swedish social workers were more in favour of keeping the child at home with the support of social services. The Croatian social workers were more in favour of removing the child from home by means of a care order. This might primarily be attributed to the differences in availability of family support services and to different discourses in Sweden and Croatia.
Continuing Medical Education, Continuing Professional Development, and Knowledge Translation: Improving Care of Older Patients by Practicing Physicians
Authors: Thomas David C. , Johnston Bree , Dunn Kathel , Sullivan Gail M. , Brett Belle , Matzko Marilyn , Levine Sharon A.
Published: September 2006

Many community‐based internists and family physicians lack familiarity with geriatrics knowledge and best practices, but they face overwhelming fiscal and time barriers to expanding their skills and improving their behavior in the care of older people. Traditional lecture‐and‐slide‐show continuing medical education (CME) programs have been shown to be relatively ineffective in changing this target group's practice. The challenge for geriatrics educators, then, is to devise CME programs that are highly accessible to practicing physicians, that will have an immediate and significant effect on practitioners' behavior, and that are financially viable. Studies of CME have shown that the most effective programs for knowledge translation in these circumstances involve what is known as active‐mode learning, which relies on interactive, targeted, and multifaceted techniques. A systematic literature review, supplemented by structured interviews, was performed to inventory active‐mode learning techniques for geriatrics knowledge and skills in the United States. Thirteen published articles met the criteria, and leaders of 28 active‐mode CME programs were interviewed. This systematic review indicates that there is a substantial experience in geriatrics training for community‐based physicians, much of which is unpublished and incompletely evaluated. It appears that the most effective methods to change behaviors involved multiple educational efforts such as written materials or toolkits combined with feedback and strong communication channels between instructors and learners.
Age‐Related Macular Degeneration: Self‐Management and Reduction of Depressive Symptoms in a Randomized, Controlled Study
Authors: Brody Barbara L. , Roch‐Levecq Anne‐Catherine , Kaplan Robert M. , Moutier Christine Y. , Brown Stuart I.
Published: September 2006

OBJECTIVES: To assess the effectiveness of a self‐management program for age‐related macular degeneration (AMD) in reducing depressive symptoms.

DESIGN: Analysis of 6‐month follow‐up for a subset of participants in a randomized, controlled trial who were clinically depressed at baseline.

SETTING: University ophthalmology clinic.

PARTICIPANTS: Thirty‐two depressed older adult volunteers (mean age 81.5) with advanced AMD who had been randomized to a self‐management program (n=12) or one of two control conditions (n=20). Subjects were included if at baseline they met criteria from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Axis, I, Fourth Edition, Research Version, for major or minor depressive disorder with significant depressive symptoms (≥5 points) on the 15‐item Geriatric Depression Scale (GDS‐15).

INTERVENTION: AMD self‐management program consisting of cognitive and behavioral elements including health education and enhancement of problem‐solving skills.

MEASUREMENTS: Primary outcome measure was GDS‐15. Secondary outcome measures included National Eye Institute Visual Function Questionnaire (NEI‐VFQ) and AMD Self‐Efficacy Questionnaire.

RESULTS: At 6‐month follow‐up, the self‐management group had a significantly greater reduction in depressive symptoms on the GDS‐15 than the controls (P=.03). The mean reduction of 2.92 points in the self‐management group was more than the 2‐point change threshold considered to be clinically meaningful. Change on the NEI‐VFQ was nonsignificant. Reduction in depressive symptoms was associated with greater self‐efficacy in the self‐management group.

CONCLUSION: These findings may support the effectiveness of an AMD self‐management program for depressed older adults with advanced vision loss from AMD.
Behavior and biology of the tomato psyllid, Bactericerca cockerelli, in response to the Mi‐1.2 gene
Authors: Casteel Clare L. , Walling Linda L. , Paine Timothy D.
Published: September 2006

The Mi‐1.2 gene, identified from wild varieties of tomato, Solanum peruvianum (Mill) (Solanaceae), has been incorporated into near‐isogenic commercial varieties of tomato and has been shown to confer resistance to three different species of phloem feeders: aphids, whiteflies, and nematodes. The results presented here show that plants bearing Mi‐1.2 were also resistant to the tomato psyllid, Bactericerca [Paratrioza] cockerelli (Sulc) (Homoptera: Psyllidae), a serious pest of tomato, Solanum lycopersicon (Mill), in the western half of North America. In choice studies, tomato psyllids preferred to settle on plants that did not contain the gene [Moneymaker (mi‐1.2)] compared to near‐isogenic plants with the gene [Motelle (Mi‐1.2)]. As a result, total oviposition was higher on the susceptible variety, although no‐choice studies indicated that there were no differences in numbers of eggs laid by individual females on either variety. Survival from egg to adult was higher on plants lacking the gene compared to plants containing the gene. However, there were no differences in total development time of individuals reared from either variety. The results suggest that mechanisms of resistance to the tomato psyllid observed in plants bearing the Mi‐1.2 gene are distinct from the mechanisms of resistance to the three phloem feeders examined in other studies.
Parsing the clinical phenotype of depression: the need to integrate brief depressive episodes
Authors: Angst J. , Gamma A. , Pezawas L. , Ajdacic‐Gross V. , Eich D. , Rössler W. , Altamura C.
Published: September 2006

Objective:  To expand the concept of recurrent brief depression (RBD) to brief depression (BD) and to test its clinical relevance.

Method:  Subjects (N = 591) were studied prospectively six times from ages 20/21 to 40/41 years. RBD was defined according to DSM‐IV as episodes under 2 weeks with about monthly recurrence and work impairment. BD embraces RBD and brief depressive episodes with a frequency of 1–11 per year.

Results:  Pure BD and pure major depressive episodes (MDE) did not differ in treatment rates, family history of mood and anxiety disorders or comorbidity with bipolar spectrum and anxiety disorders but they differed in work impairment, suicide attempt rates and distress self‐ratings.

The combination of BD + MDE identified a very severe group of MDE, comparable with combined depression (MDE + RBD) and double depression (MDE + dysthymia).

Conclusion:  Our data argue for the use of BD as a diagnostic specifier for severe MDE. RBD remains an important independent subgroup.
Deficits in acetylcholine homeostasis, receptors and behaviors in choline transporter heterozygous mice
Authors: Bazalakova M. H. , Wright J. , Schneble E. J. , McDonald M. P. , Heilman C. J. , Levey A. I. , Blakely R. D.
Published: September 2006

Cholinergic neurons elaborate a hemicholinium‐3 (HC‐3) sensitive choline transporter (CHT) that mediates presynaptic, high‐affinity choline uptake (HACU) in support of acetylcholine (ACh) synthesis and release. Homozygous deletion of CHT (−/−) is lethal shortly after birth (Fergusonet al.2004), consistent with CHT as an essential component of cholinergic signaling, but precluding functional analyses of CHT contributions in adult animals. In contrast, CHT+/− mice are viable, fertile and display normal levels of synaptosomal HACU, yet demonstrate reduced CHT protein and increased sensitivity to HC‐3, suggestive of underlying cholinergic hypofunction. We find that CHT+/− mice are equivalent to CHT+/+ siblings on measures of motor co‐ordination (rotarod), general activity (open field), anxiety (elevated plus maze, light/dark paradigms) and spatial learning and memory (Morris water maze). However, CHT+/− mice display impaired performance as a result of physical challenge in the treadmill paradigm, as well as reduced sensitivity to challenge with the muscarinic receptor antagonist scopolamine in the open field paradigm. These behavioral alterations are accompanied by significantly reduced brain ACh levels, elevated choline levels and brain region‐specific decreased expression of M1 and M2 muscarinic acetylcholine receptors. Our studies suggest that CHT hemizygosity results in adequate baseline ACh stores, sufficient to sustain many phenotypes, but normal sensitivities to physical and/or pharmacological challenge require full cholinergic signaling capacity.
Depressive symptoms in mid‐pregnancy, lifetime stressors and the 5‐HTTLPR genotype
Authors: Scheid J. M. , Holzman C. B. , Jones N. , Friderici K. H. , Nummy K. A. , Symonds L. L. , Sikorskii A. , Regier M. K. , Fisher R.
Published: September 2006

Few studies of gene–environment interactions for the serotonin transporter promoter polymorphism (5‐HTTLPR), life stressors and depression have considered women separately or examined specific types of stressful life events. None have looked at depression during pregnancy. In the Pregnancy Outcomes and Community Health (POUCH) Study, women were queried about history of stressful life events and depressive symptoms at the time of enrollment (15–27 weeks gestation). Stressful life events were grouped a priori into “subconstructs” (e.g. economic, legal, abuse, loss) and evaluated by subconstruct, total subconstruct score and total stressful life event score. The effect of genotype on the association between stressful life events and elevated depressive symptoms was assessed in 568 white non‐Hispanic participants. The relationship between exposure to abuse and elevated depressive symptoms was more pronounced in the s/s group (OR = 24.5) than in the s/l group (OR = 3.0) and the l/l group (OR = 7.7), but this significant interaction was detected only after excluding 73 (13%) women with recent use of psychotropic medications. There was no evidence of gene–environment interaction in analytic models with other stressful life events subconstructs, total subconstruct score or total stressful life events score. These data offer modest support to other reports of gene–environment interaction and highlight the importance of considering specific stressful life events.
Association of the glutamate receptor subunit gene GRIN2B with attention‐deficit/hyperactivity disorder
Authors: Dorval K. M. , Wigg K. G. , Crosbie J. , Tannock R. , Kennedy J. L. , Ickowicz A. , Pathare T. , Malone M. , Schachar R. , Barr C. L.
Published: September 2006

The glutamatergic signaling pathway represents an ideal candidate susceptibility system for attention‐deficit/hyperactivity disorder (ADHD). Disruption of specific N‐methyl‐D‐aspartate‐type glutamate receptor subunit genes (GRIN1, 2A‐D) in mice leads to significant alterations in cognitive and/or locomotor behavior including impairments in latent learning, spatial memory tasks and hyperactivity. Here, we tested for association of GRIN2B variants with ADHD, by genotyping nine single nucleotide polymorphisms (SNPs) in 205 nuclear families identified through probands with ADHD. Transmission of alleles from heterozygous parents to affected offspring was examined using the transmission/disequilibrium test. Quantitative trait analyses for the ADHD symptom dimensions [inattentive (IA) and hyperactive/impulsive (HI)] and cognitive measures of verbal working memory and verbal short‐term memory were performed using the fbat program. Three SNPs showed significantly biased transmission (P < 0.05), with the strongest evidence of association found for rs2284411 (χ2= 7.903, 1 degree of freedom, P= 0.005). Quantitative trait analyses showed associations of these markers with both the IA and the HI symptom dimensions of ADHD but not with the cognitive measures of verbal short‐term memory or verbal working memory. Our data suggest an association between variations in the GRIN2B subunit gene and ADHD as measured categorically or as a quantitatively distributed trait.
Evidence, Virulence, and the Disappearance of Nursing Knowledge: A Critique of the Evidence‐Based Dogma
Authors: Holmes Dave , Perron Amélie , O'Byrne Patrick
Published: September 2006

Context: Within the domain of health care, the new discourse of evidence‐based practice has appeared and gained momentum, giving rise to a plethora of correlates such as specialized scientific journals and best practice guidelines. Following the crowd, nursing has jumped onto this trend's bandwagon. Although some scholars and clinicians have tried to expand these notions, few have considered a deconstructive approach to do so.

Approach: Drawing on the works of continental postmodern thinkers such as Baudrillard, Deleuze & Guattari, and Foucault, this paper critically examines the rise of the evidence‐based nursing (EBN) movement in order to deconstruct the “taken‐for‐granted” assumption that EBN is in and of itself the favored path to the sound development of nursing knowledge.

Discussion: We argue against the hierarchical differentiation of varied research approaches so as to allow diverse methodologies to guide research and ultimately practice. The status quo is challenged, where research agendas are currently dominated by one paradigm of knowledge development; that of post‐positivism in which randomized control trials are portrayed as superior evidence. There is a hazard in excluding many other venues to build nursing knowledge and in oversimplifying the complexity of clinical nursing practice. Furthermore, we argue that this preferred path of knowledge development contradicts nursing academics' efforts to distance itself from the medical model of health care provision and research.
Line-of-sight velocity distributions of elliptical galaxies from collisionless mergers
Authors: González-García A. C. , Balcells M. , Olshevsky V. S.
Published: September 2006

We analyse the skewness of the line-of-sight velocity distributions in model elliptical galaxies built through collisionless galaxy mergers. We build the models using large N-body simulations of mergers between either two spiral or two elliptical galaxies. Our aim is to investigate whether the observed ranges of skewness coefficient (h3) and the rotational support (V/σ), as well as the anticorrelation between h3 and V, may be reproduced through collisionless mergers. Previous attempts using N-body simulations failed to reach V/σ≈ 1–2 and corresponding high h3 values, which suggested that gas dynamics and ensuing star formation might be needed in order explain the skewness properties of ellipticals through mergers. Here we show that high V/σ and high h3 are reproduced in collisionless spiral–spiral mergers whenever a central bulge allows the discs to retain some of their original angular momentum during the merger. We also show that elliptical–elliptical mergers, unless merging from a high-angular momentum orbit, reproduce the strong skewness observed in non-rotating, giant, boxy ellipticals. The behaviour of the h3 coefficient therefore associates rapidly-rotating discy ellipticals to disc-disc mergers, and associates boxy, slowly rotating giant ellipticals to elliptical–elliptical mergers, a framework generally consistent with the expectations of hierarchical galaxy formation.
The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?
Authors: Margolis Elyssa B. , Lock Hagar , Hjelmstad Gregory O. , Fields Howard L.
Published: September 2006

The ventral tegmental area (VTA) and in particular VTA dopamine (DA) neurons are postulated to play a central role in reward, motivation and drug addiction. However, most evidence implicating VTA DA neurons in these functions is based on indirect electrophysiological characterization, rather than cytochemical identification. These physiological criteria were first established in the substantia nigra pars compacta (SNc), but their validity in the VTA is uncertain. In the current study we found that while 88 ± 2% of SNc neurons labelled by the neuronal marker NeuN were co‐labelled for the catecholamine enzyme tyrosine hydroxylase (TH), a much smaller percentage (55 ± 2%) of VTA neurons co‐expressed TH. In addition, using in vitro whole‐cell recordings we found that widely accepted physiological criteria for VTA DA neurons, including the hyperpolarization‐activated inwardly rectifying non‐specific cation current (Ih), spike duration, and inhibition by DA D2 receptor agonists, do not reliably predict the DA content of VTA neurons. We could not distinguish DA neurons from other VTA neurons by size, shape, input resistance, Ih size, or spontaneous firing rate. Although the absence of an Ih reliably predicted that a VTA neuron was non‐dopaminergic, and Ih(−) neurons differ from Ih(+) neurons in firing rate, interspike interval (ISI) standard deviation, and ISI skew, no physiological property examined here is both sensitive and selective for DA neurons in the VTA. We conclude that reliable physiological criteria for VTA DA neuron identification have yet to be determined, and that the criteria currently being used are unreliable.
Structure of the 70
S
Ribosome Complexed with mRNA and tRNA
Authors: Selmer Maria , Dunham Christine M. , Murphy Frank V. , Weixlbaumer Albert , Petry Sabine , Kelley Ann C. , Weir John R. , Ramakrishnan V.
Published: September 2006

The crystal structure of the bacterial 70
S
ribosome refined to 2.8 angstrom resolution reveals atomic details of its interactions with messenger RNA (mRNA) and transfer RNA (tRNA). A metal ion stabilizes a kink in the mRNA that demarcates the boundary between A and P sites, which is potentially important to prevent slippage of mRNA. Metal ions also stabilize the intersubunit interface. The interactions of E-site tRNA with the 50
S
subunit have both similarities and differences compared to those in the archaeal ribosome. The structure also rationalizes much biochemical and genetic data on translation.
Unraveling the Mystery of Indian Monsoon Failure During El Niño
Authors: Kumar K. Krishna , Rajagopalan Balaji , Hoerling Martin , Bates Gary , Cane Mark
Published: September 2006

The 132-year historical rainfall record reveals that severe droughts in India have always been accompanied by El Niño events. Yet El Niño events have not always produced severe droughts. We show that El Niño events with the warmest sea surface temperature (SST) anomalies in the central equatorial Pacific are more effective in focusing drought-producing subsidence over India than events with the warmest SSTs in the eastern equatorial Pacific. The physical basis for such different impacts is established using atmospheric general circulation model experiments forced with idealized tropical Pacific warmings. These findings have important implications for Indian monsoon forecasting.
The Consensus Coding Sequences of Human Breast and Colorectal Cancers
Authors: Sjöblom Tobias , Jones Siân , Wood Laura D. , Parsons D. Williams , Lin Jimmy , Barber Thomas D. , Mandelker Diana , Leary Rebecca J. , Ptak Janine , Silliman Natalie , Szabo Steve , Buckhaults Phillip , Farrell Christopher , Meeh Paul , Markowitz Sanford D. , Willis Joseph , Dawson Dawn , Willson James K. V. , Gazdar Adi F. , Hartigan James , Wu Leo , Liu Changsheng , Parmigiani Giovanni , Park Ben Ho , Bachman Kurtis E. , Papadopoulos Nickolas , Vogelstein Bert , Kinzler Kenneth W. , Velculescu Victor E.
Published: September 2006

The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of ∼90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.
A 60-Kilodalton Protein Component of the Counting Factor Complex Regulates Group Size in
Dictyostelium discoideum
Authors: Brock Debra A. , van Egmond Wouter N. , Shamoo Yousif , Hatton R. Diane , Gomer Richard H.
Published: September 2006

Much remains to be understood about how a group of cells or a tissue senses and regulates its size.
Dictyostelium discoideum
cells sense and regulate the size of groups and fruiting bodies using a secreted 450-kDa complex of proteins called counting factor (CF). Low levels of CF result in large groups, and high levels of CF result in small groups. We previously found three components of CF (D. A. Brock and R. H. Gomer, Genes Dev.
13:
1960-1969, 1999; D. A. Brock, R. D. Hatton, D.-V. Giurgiutiu, B. Scott, R. Ammann, and R. H. Gomer, Development
129:
3657-3668, 2002; and D. A. Brock, R. D. Hatton, D.-V. Giurgiutiu, B. Scott, W. Jang, R. Ammann, and R. H. Gomer, Eukaryot. Cell
2:
788-797, 2003). We describe here a fourth component, CF60. CF60 has similarity to acid phosphatases, although it has very little, if any, acid phosphatase activity. CF60 is secreted by starving cells and is lost from the 450-kDa CF when a different CF component, CF50, is absent. Although we were unable to obtain cells lacking CF60, decreasing CF60 levels by antisense resulted in large groups, and overexpressing CF60 resulted in small groups. When added to wild-type cells, conditioned starvation medium from CF60 overexpressor cells as well as recombinant CF60 caused the formation of small groups. The ability of recombinant CF60 to decrease group size did not require the presence of the CF component CF45-1 or countin but did require the presence of CF50. Recombinant CF60 does not have acid phosphatase activity, indicating that the CF60 bioactivity is not due to a phosphatase activity. Together, the data suggest that CF60 is a component of CF, and thus this secreted signal has four different protein components.
COMPRESSION AND RECOGNITION OF SPATIO-TEMPORAL SEQUENCES FROM CONTEMPORARY BALLET
Authors: CHENEVIÈRE FREDERIC , BOUKIR SAMIA , VACHON BERTRAND
Published: September 2006

We aim at recognizing a set of dance gestures from contemporary ballet. Our input data are motion trajectories followed by the joints of a dancing body provided by a motion-capture system. It is obvious that direct use of the original signals is unreliable and expensive. Therefore, we propose a suitable tool for nonuniform sub-sampling of spatio-temporal signals. The key to our approach is the use of polygonal approximation to provide a compact and efficient representation of motion trajectories. Our dance gesture recognition method involves a set of Hidden Markov Models (HMMs), each of them being related to a motion trajectory followed by the joints. The recognition of such movements is then achieved by matching the resulting gesture models with the input data via HMMs. We have validated our recognition system on 12 fundamental movements from contemporary ballet performed by four dancers.
IMPROVING THE EFFICIENCY OF A LEAST MEDIAN OF SQUARES SCHEMA FOR THE ESTIMATION OF THE FUNDAMENTAL MATRIX
Authors: TRUJILLO MARIA , IZQUIERDO EBROUL
Published: September 2006

A robust and efficient approach to estimate the fundamental matrix is proposed. The main goal is to reduce the computational cost involved in the estimation when robust schemas are applied. The backbone of the proposed technique is the conventional Least Median of Squares (LMedS) technique. It is well known that the LMedS is one of the most robust regressors for highly contaminated data and unstable models. Unfortunately, its computational complexity renders it useless for practical applications. To overcome this problem, a small number of low-dimensionality least-square problems are solved using well-selected subsets from the input data. The results of this initial approach are fed into the LMedS schema, which is applied to recover the final estimation of the Fundamental matrix. The complexity is substantially reduced by applying a selection process based on an effective statistical analysis of the inherent correlation of the input data. This analysis is used to define a suitable clustering of the data and to drive the subset selection aiming at the reduction of the search space in the LMedS schema. It is shown that avoiding redundancies better estimates can be obtained while keeping the computational cost low. Selected results of computer experiments were conducted to assess the performance of the proposed technique.
DEVELOPMENT OF THERAPEUTIC BRAIN STIMULATION TECHNIQUES WITH METHODS FROM NONLINEAR DYNAMICS AND STATISTICAL PHYSICS
Authors: TASS PETER A. , HAUPTMANN CHRISTIAN , POPOVYCH OLEKSANDR V.
Published: September 2006

Synchronization processes may severely impair brain function, for instance, in Parkinson's disease, essential tremor or epilepsies. We present three different effectively desynchronizing stimulation techniques which have been developed with methods from nonlinear dynamics and statistical physics. These techniques exploit either stochastic phase resetting principles or complex delayed feedback mechanisms. We explain how these methods work and how they can be applied to therapeutic brain stimulation.
REACTION PATHS AND ELEMENTARY BIFURCATIONS TRACKS: THE DIABATIC 1B2-STATE OF OZONE
Authors: FARANTOS S. C. , QU ZHENG-WANG , ZHU H. , SCHINKE R.
Published: September 2006

Bifurcations of equilibrium points and periodic orbits are common in nonlinear dynamical systems when some parameters change. The vibrational motions of a molecule are nonlinear, and the bifurcation phenomena are seen in spectroscopy and chemical reactions. Bifurcations may lead to energy localization in specific bonds, and thus, they have important consequences for elementary chemical reactions, such as isomerization and dissociation/association. In this article we investigate how elementary bifurcations, such as saddle-node and pitchfork bifurcations, appear in small molecules and show their manifestations in the quantum mechanical frequencies and in the topology of wave functions. We present the results of classical and quantum mechanical calculations on a new (diabatic) potential energy surface of ozone for the 1 B 2 state.This excited electronic state of ozone is pertinent for the absorption of the harmful UV radiation from the sun. We demonstrate that regular localized overtone states, which extend from the bottom of the well up to the dissociation or isomerization barrier, are associated with families of periodic orbits emanated from elementary bifurcations.
ADAPTIVE ALGORITHMS FOR NEURAL NETWORK SUPERVISED LEARNING: A DETERMINISTIC OPTIMIZATION APPROACH
Authors: MAGOULAS GEORGE D. , VRAHATIS MICHAEL N.
Published: September 2006

Networks of neurons can perform computations that even modern computers find very difficult to simulate. Most of the existing artificial neurons and artificial neural networks are considered biologically unrealistic, nevertheless the practical success of the backpropagation algorithm and the powerful capabilities of feedforward neural networks have made neural computing very popular in several application areas. A challenging issue in this context is learning internal representations by adjusting the weights of the network connections. To this end, several first-order and second-order algorithms have been proposed in the literature. This paper provides an overview of approaches to backpropagation training, emphazing on first-order adaptive learning algorithms that build on the theory of nonlinear optimization, and proposes a framework for their analysis in the context of deterministic optimization.
DESYNCHRONIZATION AND DECOUPLING OF INTERACTING OSCILLATORS BY NONLINEAR DELAYED FEEDBACK
Authors: POPOVYCH OLEKSANDR V. , HAUPTMANN CHRISTIAN , TASS PETER A.
Published: September 2006

A novel control method for desynchronization of strongly synchronized populations of interacting oscillators is described. We show that an ensemble's mean field, nonlinearly processed and fed back into the ensemble, causes an effective desynchronization. The method is mild, demand controlled, and robust against system and stimulation parameter variations. The desynchronization and decoupling effects of the method are illustrated by examples of one and two interacting populations of limit-cycle oscillators. We suggest our method for mild and effective deep brain stimulation in neurological diseases characterized by pathological cerebral synchronization.
DELAYED FEEDBACK SUPPRESSION OF COLLECTIVE RHYTHMIC ACTIVITY IN A NEURONAL ENSEMBLE
Authors: ROSENBLUM MICHAEL , TUKHLINA NATALIA , PIKOVSKY ARKADY , CIMPONERIU LAURA
Published: September 2006

We analyze the delayed feedback approach to suppression of collective synchrony in a population of globally or randomly coupled neurons. In particular, we consider the main factors of imperfection of the control scheme and their influence on the suppression efficiency. Next, with the help of a realistic model of synaptically coupled population of inhibitory and excitatory neurons we demonstrate the potential of the suppression scheme for neurophysiological applications.
RED NOISE ESTIMATION
Authors: LEONTITSIS ALEXANDROS
Published: September 2006

This paper presents a method for the correct estimation of the red (linearly autocorrelated of order 1) noise from chaotic time series. The idea is to increase the time delay in order to have a reliable reconstruction. The results indicate that only on extremely correlated noise cases this increase helps, because otherwise the correlation integrals are not affected. The proposed method is successfully applied on time series of the Hénon map and is extended to weekly closes of the Nasdaq Cmp. index. The main advantage of the method presented here is that it can be used on time series with any kind of linearly correlated noise.
Drug Targeting to the Brain
Authors: de Boer A.G. , Gaillard P.J.
Published: September 2006

The central nervous system (CNS) is a sanctuary site and is protected by various barriers. These regulate brain homeostasis and the transport of endogenous and exogenous compounds by controlling their selective and specific uptake, efflux, and metabolism in the brain. Unfortunately, potential drugs for the treatment of most brain diseases are therefore often not able to cross these barriers. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. Here we discuss briefly the biology and physiology of the blood-brain barrier (BBB) and the blood-cerebro-spinal-fluid barrier (BCSFB), and, in more detail, the possibilities for delivering large-molecular-weight drugs by local and global delivery and by viral and receptor-mediated nonviral drug delivery to the (human) brain.