bluuebunny/crossref_metadata_2025 huggingface dataset:
Construct and Criterion‐Related Validation of a Measure of Emotional Reasoning Skills: A two‐study investigation
Authors: Blickle Gerhard , Momm Tassilo S. , Kramer Jochen , Mierke Jan , Liu Yongmei , Ferris Gerald R.
Published: February 2009

In a two‐study investigation, the construct and criterion‐related validities of the Test of Emotional Intelligence, an ability‐based measure of emotional reasoning skills, were examined. In Study 1, as hypothesized, emotional reasoning skills were related to emotion recognition ability (i.e., as measured by Diagnostic Analysis of Nonverbal Accuracy), emotional empathy, and three measures of successful social functioning (i.e., social astuteness, interpersonal influence, and apparent sincerity) assessed by peers, after controlling for personality and occupational environment characteristics. In Study 2, results from a predictive validation study demonstrated that Emotional Intelligence explained additional variance in overall job performance ratings beyond general mental ability and personality traits. Contributions and implications of this research investigation, limitations, and directions for future research are discussed.
Controlled and dependent: experiences of living on social assistance in Sweden
Authors: Marttila Anneli , Whitehead Margaret , Canvin Krysia , Burström Bo
Published: February 2009

Marttila A, Whitehead M, Canvin K, Burström B. Controlled and dependent: experiences of living on social assistance in Sweden Int J Soc Welfare 2010: 19: 142–151 © 2009 The Author(s), Journal compilation © 2009 Blackwell Publishing Ltd and the International Journal of Social Welfare.

This study explored experiences of people receiving social assistance in 21st‐century Sweden, based on 33 in‐depth interviews conducted in 2005 and 2006. Two overarching themes emerged from the accounts, encompassing both a material and a psychosocial dimension of living on social assistance. Recipients reported that social assistance was generally sufficient for their basic material needs but allowed for no extras. It was possible to live on social assistance for a short time, but became difficult in the longer term. Perceptions of powerlessness, hopelessness and dependency were common and had the most damaging consequences for the recipients' perceived wellbeing. Some recipients believed that society at large had negative perceptions of people living on social assistance; it was something to be ashamed of but, at the same time, it was the recipients' only possible source of income. Findings of this study are partly similar to previous studies conducted in Sweden, suggesting that improvement in services should take into account the experiences of social assistance recipients.
The impact of the use of the social welfare services or social security benefits on attitudes to social welfare policies
Authors: Muuri Anu
Published: February 2009

Muuri A. The impact of the use of the social welfare services or social security benefits on attitudes to social welfare policies Int J Soc Welfare 2010: 19: 182–193 © 2009 The Author(s), Journal compilation © 2009 Blackwell Publishing Ltd and the International Journal of Social Welfare.

This article investigates the attitudes of citizens and clients to social welfare services and social security benefits. The data come from a Finnish national survey conducted at the end of 2006. First, the article overviews the previous welfare‐state studies relating especially to the theoretical perspectives of self‐interest and legitimacy. The empirical analysis indicates (i) that a different operation of self‐interest can only weakly explain the differences in attitudes between services and benefits; (ii) that there is general support for Finnish social welfare services and social security benefits, which, however, is mixed with growing criticism among women and pensioners who are supposed to benefit most from the welfare policies; and (iii) that such determinants of attitude as gender, use and, to some extent, lifecycle have become as important as class‐related factors such as income and education.
Chronic Daily Headache with Medication Overuse: A Randomized Follow-Up by Neurologist or PCP
Authors: Bøe MG , Salvesen R , Mygland Å
Published: February 2009

Several studies have shown the benefit of withdrawal therapy when medication overuse headache (MOH) is suspected. Our aim was to compare the effect of withdrawal therapy in patients followed by a neurologist (group A, n = 42) and a primary care physician (PCP) (group B, n = 38). Patients were randomized to A or B, and follow-up was at 3, 6 and 12 months. Calculated mean headache (MH at 6 months + MH at 12 months)/2 (primary end-point) was similar; A 1.04 (0.87, 1.21) and B 1.02 (0.82, 1.21) ( P = 0.87). The number of patients with 50% improvement of headache days was also similar; 14/42 in group A vs. 12/34 in B ( P = 0.86) at 3 months, 15/42 vs. 11/33 ( P = 0.83) at 6 months and 15/42 vs. 14/38 ( P = 0.92) at 12 months. Days without headache during the last 9 months of follow-up were 123 (96, 150) in group A and 137 (112, 161) in B ( P = 0.62). After 3 months one-third were classified as MOH. Patients with MOH improved similarly in group A and B, and so did patients without MOH. Within 1 year 7/42 in A and 9/38 in B had recurrent medication overuse ( P = 0.43). In summary, there were no significant differences in follow-up results between the two groups.
Effect of guard dogs on the behavior and reproduction of gazelles in cattle enclosures on the Golan Heights
Authors: Gingold G. , Yom‐Tov Y. , Kronfeld‐Schor N. , Geffen E.
Published: February 2009

Cattle on the Golan Heights are kept in enclosures and some of these enclosures have guard dogs. We studied the effect of such dogs on the behavior and breeding success of mountain gazelles Gazella gazella living within enclosures. We found that guard dogs have both direct and indirect effects on gazelles. Gazelles living in enclosures with dogs spent more time in vigilance behavior and running, and less time resting and walking, in comparison with gazelles in dog‐free enclosures. In the absence of dogs, gazelle female herds in enclosures tended to stay closer to the cattle, but shunned away from them in the presence of the dogs, which, in turn, remained near the cattle. The percentage of fawns per female was higher in enclosures without dogs in comparison with those with dogs, but the difference was not significant. However, the largest of the enclosures with dogs, which had the largest number of gazelles, had only an average number of dogs in it. Hence, the gazelles in this enclosure were better able to avoid the dogs in comparison with those in smaller enclosures. Removing this enclosure from the overall calculation revealed that guard dogs have a significant negative effect on gazelle reproductive success. In two of the four enclosures with dogs no fawn still survived 6 months after birth, while in each of the four enclosures without dogs some fawns did survive to that age and beyond, suggesting that the dogs themselves may predate the fawns.
Water sources and controls on water‐loss rates of epigeous ectomycorrhizal fungal sporocarps during summer drought
Authors: Lilleskov Erik A. , Bruns Thomas D. , Dawson Todd E. , Camacho Francisco J.
Published: February 2009

DOI: 10.1111/j.1469-8137.2009.02815.xCommentary p 290
Inter‐ and intra‐observer agreement of intrapartum ST analysis of the fetal electrocardiogram in women monitored by STAN
Authors: Westerhuis MEMH , van Horen E , Kwee A , van der Tweel I , Visser GHA , Moons KGM
Published: February 2009

Objective  The objective of this study was to quantify inter‐ and intra‐observer agreement on classification of the intrapartum cardiotocogram (CTG) and decision to intervene following STAN guidelines.

Design  A prospective, observational study.

Setting  Obstetrics Department of a tertiary referral hospital.

Population  STAN recordings of 73 women after 36 weeks of gestation with a high‐risk pregnancy, induced or oxytocin‐augmented labour, meconium‐stained amniotic fluid or epidural analgesia.

Methods  Six observers classified 73 STAN recordings and decided if and when they would suggest an intervention. Proportions of specific agreement (Ps) and kappa values (K) were calculated.

Main outcome measures  Agreement upon classification of the intrapartum CTG and decision to perform an intervention.

Results  Agreement for classification of a normal and a (pre)terminal CTG was good (Ps range 0.50–0.84), but poor for the intermediary and abnormal CTG (Ps range 0.34–0.56). Agreement on the decision to intervene was higher, especially on the decision to perform ‘no intervention’ (Ps range 0.76–0.94). Overall inter‐observer agreement on the decision to intervene was considered moderate in five of six observer combinations according to the kappa (K range 0.42–0.73). Intra‐observer agreement for CTG classification and decision to intervene was moderate (K range 0.52–0.67 and 0.61–0.75).

Conclusions  Inter‐observer agreement on classification of the intrapartum CTG is poor, but addition of information regarding fetal electrocardiogram, especially in case of intermediary or abnormal CTG traces, results in a more standardised decision to intervene.
Why women do not accept randomisation for place of birth: feasibility of a RCT in the Netherlands
Authors: Hendrix M , Van Horck M , Moreta D , Nieman F , Nieuwenhuijze M , Severens J , Nijhuis J
Published: February 2009

Objective  The purpose of this study was to investigate why low‐risk nulliparae were not willing to participate in a randomised controlled trial (RCT) of place of birth.

Design  Prospective study.

Setting  The Netherlands.

Population  All low‐risk nulliparous women starting their pregnancy under midwife.

Methods  A questionnaire for 107 nulliparae who were willing to participate in a cohort study on place of birth, but at an earlier stage in their pregnancy declined to participate in a RCT of place of birth. This questionnaire included 12 items on a 4‐point Likert scale but was not subjected to formal validation.

Main outcome measure  Reasons why nulliparae did not accept randomisation of place of birth.

Results  The most important reason why women refused participation in the trial was that they had already chosen their place of birth before they were asked to participate at 12 weeks of pregnancy. From their answers, it became clear that pregnant women strongly value their autonomy of choice. The decision not to participate in the trial was not influenced by the information given by the midwife and the additional written information.

Conclusions  Factors that prevent randomisation for place of birth are difficult to influence. There is a need to explore why there is such certainty of view among women having their first child. Until we have an understanding of why women select information to make these choices and why women are reluctant to participate in trials that challenge choice, it may well be impossible to mount a trial of place of birth.
Bibliometrics of global malaria vaccine research
Authors: Garg Kailash C. , Kumar Suresh , Madhavi Yennapu , Bahl Mala
Published: February 2009

Objectives:  This study evaluates malaria vaccine research carried out in different parts of the world during 1972–2004 using different bibliometric indicators.

Method:  Data have been downloaded from PubMed for the period 1972–2004 using the keywords (malaria* or plasmodium or falciparum) and (vaccine*) in the title and abstract fields. The study examined the pattern of growth of the output, its geographical distribution, profile of different countries in different subfields and pattern of citations using GOOGLE Scholar.

Results:  Malaria vaccine research output is gradually increasing. The USA, followed by the UK and Australia contributed the highest number of papers. Publication activity has decreased in Switzerland and Sweden, but has increased in Brazil and China. The majority of the countries have focused on the development of asexual blood stage malaria. Citations per paper and incidence of high‐quality papers for the USA, the UK, Papua New Guinea and Denmark are more than the average. The majority of the prolific institutions are located in the USA, the UK, France and Australia.

Conclusion:  The last two decades have witnessed considerable growth in research output in this field, while a successful malaria vaccine still remains elusive. Interestingly, the countries like the USA, the UK and Australia that lead in the quantity, quality and citation of this output are often not those directly affected by malaria.
Regulation and function of neuronal GTP‐Ras in facial motor nerve regeneration
Authors: Makwana Milan , Serchov Tsvetan , Hristova Mariya , Bohatschek Marion , Gschwendtner Andreas , Kalla Roger , Liu ZhiQiang , Heumann Rolf , Raivich Genndij
Published: February 2009

Activation of Ras into the GTP‐binding, ‘ON’ state is a key switch in the neurotrophin‐mediated neuronal survival and neurite outgrowth, in vitro as well as in vivo. In the current study we explored changes in GTP‐Ras levels following facial nerve injury and the ensuing regeneration and the effects of perturbing these changes in vivo using synapsin‐promoter mediated neuronal expression of constitutively active Val12H‐Ras (synRas). Quantification of GTP‐Ras and total Ras revealed a precipitous drop in the relative GTP‐Ras levels in the axotomized facial motor nucleus, to 40% of normal levels at 2 days after cut, followed by a partial recovery to 50–65% at 4–28 days. On western blots, control and axotomized nuclei from synRas mutants showed a 2.2‐ and 2.5‐fold elevation in GTP‐Ras, respectively, compared with their wild type littermate controls (p < 5%, anova, TUKEY post‐hoc), with the levels in the axotomized synRas nucleus slightly but not significantly above that in the uninjured littermate control (p = 9.9%). Similar increase was also observed in the pERK but not pAKT targets of the Ras cascade. This moderate elevation of GTP‐Ras strongly curtailed post‐traumatic neuronal cell death (−65%), the influx of T‐cells (−48%) as well as other parameters of neuroinflammatory response. Although synRas did not affect the speed of axonal regeneration or functional recovery it caused a very pronounced increase in central axonal sprouting. These current data emphasize the role of reduced active Ras, and by extension, the reduced overall level of retrograde neurotrophin signalling after axotomy, in mediating post‐traumatic cell death and inflammation and in restricting the sprouting response. Moreover, the neuroprotective and central sprouting‐enhancing effects of neuronal Val12H‐Ras could help promote recovery in CNS injury.
Characterization of cell‐surface prion protein relative to its recombinant analogue: insights from molecular dynamics simulations of diglycosylated, membrane‐bound human prion protein
Authors: DeMarco Mari L. , Daggett Valerie
Published: February 2009

The prion protein (PrP) is responsible for several fatal neurodegenerative diseases via conversion from its normal to disease‐related isoform. The recombinant form of the protein is typically studied to investigate the conversion process. This constructs lacks the co‐ and post‐translational modifications present in vivo, there the protein has two N‐linked glycans and is bound to the outer leaflet of the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. The inherent flexibility and heterogeneity of the glycans, the plasticity of the GPI anchor, and the localization of the protein in a membrane make experimental structural characterization of biological constructs of cellular prion protein (PrPC) challenging. Yet this characterization is central in determining not only the suitability of recombinant (rec)‐PrPC as a model for biological forms of the protein but also the potential role of co‐ and post‐translational modifications on the disease process. Here, we present molecular dynamics simulations of three human prion protein constructs: (i) a protein‐only construct modeling the recombinant form, (ii) a diglycosylated and soluble construct, and (iii) a diglycosylated and GPI‐anchored construct bound to a lipid bilayer. We found that glycosylation and membrane anchoring do not significantly alter the structure or dynamics of PrPC, but they do appreciably modify the accessibility of the polypeptide surface PrPC. In addition, the simulations of membrane‐bound PrPC revealed likely recognition domains for the disease‐initiating PrPC:PrPSc (infectious and/or misfolded form of the prion protein) binding event and a potential mechanism for the observed inefficiency of conversion associated with differentially glycosylated PrP species.
On the relationship between the two branches of the kynurenine pathway in the rat brainin vivo
Authors: Amori Laura , Guidetti Paolo , Pellicciari Roberto , Kajii Yasushi , Schwarcz Robert
Published: February 2009

In the mammalian brain, kynurenine aminotransferase II (KAT II) and kynurenine 3‐monooxygenase (KMO), key enzymes of the kynurenine pathway (KP) of tryptophan degradation, form the neuroactive metabolites kynurenic acid (KYNA) and 3‐hydroxykynurenine (3‐HK), respectively. Although physically segregated, both enzymes use the pivotal KP metabolitel‐kynurenine as a substrate. We studied the functional consequences of this cellular compartmentalizationin vivousing two specific tools, the KAT II inhibitor BFF 122 and the KMO inhibitor UPF 648. The acute effects of selective KAT II or KMO inhibition were studied using a radiotracing method in which thede novosynthesis of KYNA, and of 3‐HK and its downstream metabolite quinolinic acid (QUIN), is monitored following an intrastriatal injection of3H‐kynurenine. In naïve rats, intrastriatal BFF 122 decreased newly formed KYNA by 66%, without influencing 3‐HK or QUIN production. Conversely, UPF 648 reduced 3‐HK synthesis (by 64%) without affecting KYNA formation. Similar, selective effects of KAT II and KMO inhibition were observed when the inhibitors were applied acutely together with the excitotoxin QUIN, which impairs local KP metabolism. Somewhat different effects of KMO (but not KAT II) inhibition were obtained in rats that had received an intrastriatal QUIN injection 7 days earlier. In these neuron‐depleted striata, UPF 648 not only decreased both 3‐HK and QUIN production (by 77% and 66%, respectively) but also moderately raised KYNA synthesis (by 27%). These results indicate a remarkable functional segregation of the two pathway branches in the brain, boding well for the development of selective KAT II or KMO inhibitors for cognitive enhancement and neuroprotection, respectively.
Is satisfaction with doctors’ care related to health‐related quality of life, anxiety and depression among patients with carcinoid tumours? A longitudinal report
Authors: Fröjd Camilla , Lampic Claudia , Larsson Gunnel , Essen Louise von
Published: February 2009

The aim of this study was to investigate (i) whether specific aspects of the initial consultation (IC) and/or patients’ satisfaction with doctors’ care are related to health‐related quality of life (HRQoL), anxiety and depression among patients with carcinoid tumours and (ii) whether patients’ satisfaction with doctors’ care changes over time. The study has a longitudinal design. The HRQoL and psychosocial function among patients who met the doctors showing good ability to identify patients’ worry and wish for information were compared with those patients who met doctors showing less good ability. Patients’ HRQoL, anxiety, depression and satisfaction with doctors’ care were assessed longitudinally, shortly after each of the first four admissions to specialist care. Patients who met doctors showing good ability to identify their wish for information at the IC reported higher levels of cognitive function. Higher satisfaction with doctors’ care was related to higher emotional and cognitive function, to higher global QoL, and to lower levels of problems with diarrhoea, financial difficulties, constipation, anxiety and depression shortly after each of the first three admissions, although not after the fourth admission to the specialist care. Although most patients with carcinoid tumours report high satisfaction with care, it is important to be aware of the fact that some patients may be less satisfied. Doctors should provide patients with information which matches the individual patients’ needs and preferences as patients’ satisfaction with doctors’ provision of information is related to patients’ HRQoL, anxiety and depression.
Factors that influence collaboration between psychiatric care and CSSs: experiences of working together in the interest of persons with long‐term mental illness living in the community
Authors: Magnusson Annabella , Lützén Kim
Published: February 2009

Background:  Since de‐institutionalization of psychiatric care (PC) took place in Sweden during the second half of the 20th century, the intended collaboration between the two organizations, PC and community social service (CSS) has been evaluated as inadequate in providing care for persons with long‐term mental illness living in the community.

Aim:  The aim of this explorative study was to examine factors that influence interdisciplinary teamwork between PC and CSSs based on the experience of nursing staff within two separate organizations.

Method:  Five focus groups were selected as an appropriate method to collect data. Two of these groups were recruited from the PC and three from the CSSs. The focus groups consisted of psychiatric nurses and mental healthcare workers. A qualitative content analysis was used to identify major themes in the data.

Findings:  Two main themes were found, external organizational factors and interpersonal factors that deter or enhance collaboration between PC and CSS. Separate care plans, unclear times for meetings were found to be a plausible reason for communication failure. The focus groups representing each of the two organizations viewed themselves as ‘us and them’. Different ideologies and goals for caring and service and how to use each other’s competence seemed to be explanations as well as consequences of not finding ways to work together.

Conclusion:  The results of this study points to the need for the two organizations to find ways to work more effectively together to realize a joint responsibility for the patient/client.
Investigating idebenone and idebenone linoleate metabolism: in vitro pig ear and mouse melanocyte studies
Authors: Wempe Michael F , Lightner Janet W , Zoeller Elizabeth L , Rice Peter J
Published: February 2009

Objective  The aim of this study was to investigate inherent in vitro permeability, metabolism, and cytotoxicity of idebenone – an active used to protect skin as an anti‐aging agent – and compare it to idebenone linoleate.

Methods  Idebenone and idebenone linoleate were investigated in pig ear skin and melanoma (B16: F10 mouse) cells. Diffusion experiments were conducted at 37 °C (bath temperature) using Franz diffusion cells. Authentic metabolite samples were synthetically prepared. Samples were analyzed using liquid chromatography‐mass spectrometry/mass spectrometry. Cell viability was determined via the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide (MTT) assay.

Results  Idebenone was shown to permeate across viable porcine ear tissue; there was no evidence that idebenone linoleate permeated across porcine ear tissue after 4 h. Idebenone was metabolized to idebenone acid in both pig ear and mouse melanocytes; only minor idebenone linoleate metabolism was observed. Idebenone displayed delayed in vitro toxicity (via MTT assay) in melanocytes, while idebenone linoleate displayed no such in vitro toxicity.

Conclusions  The in vitro metabolism and cytotoxicity results suggest that metabolic activation of idebenone is the likely culprit that activates the skin irritation mechanism via idebenone in vivo usage. An idebenone ester (e.g. idebenone linoleate) appears to provide a superior in vitro safety profile over idebenone.
Relationships between bird morphology and prey selection in two sympatric Great Cormorant Phalacrocorax carbo subspecies during winter
Authors: FONTENEAU FREDERIC , PAILLISSON JEAN‐MARC , MARION LOÏC
Published: February 2009

Variation in bird morphology (notably sex size dimorphism) has been suggested to contribute to differences in food use between individuals. We explore the hypothesis of food partitioning (diet overlap and prey size selection) in two sympatric subspecies of the Great Cormorant Phalacrocorax carbo with respect to bird morphology (subspecies and sex) in inland French waters. These areas represent a recent and increasing contact zone used as a common non‐territorial winter feeding area by the continental P. c. sinensis and the marine P. c. carbo subspecies. A high dietary overlap between subspecies and sexes was found at the major sites studied. Prey size selection was found to be site‐specific and generally related to a gradient of structural size and body mass (male P. c. carbo > male P. c. sinensis > female P. c. carbo > female P. c. sinensis). With respect to bird morphology, differences in prey size consumed by Great Cormorants were more pronounced between sexes in freshwater habitats than between subspecies. This was reinforced by the fact that P. c. carbo birds entering inland areas were smaller than birds on the coast. These results also suggest that bird morphology is an important determinant of dietary differences. Our study demonstrated that P. c. carbo is an efficient generalist forager in continental areas, and food partitioning in type and size of prey between the two subspecies is low.
Bounds on the largest singular value of a matrix and the convergence of simultaneous and block‐iterative algorithms for sparse linear systems
Authors: Byrne Charles
Published: February 2009

We obtain the following upper bounds for the eigenvalues of the matrix A†A. For any a in the interval [0, 2] let
image

image

and ca and ra the maxima of the caj and rai, respectively. Then no eigenvalue of the matrix A†A exceeds the maximum of
image

over all i, nor the maximum of
image

over all j. Therefore, no eigenvalue of A†A exceeds cara.

Using these bounds, it follows that, for the matrix G with entries
image

no eigenvalue of G†G exceeds one, provided that, for some a in the interval [0, 2], we have
image

and
image

Using this result, we obtain convergence theorems for several iterative algorithms for solving the problem Ax=b, including the CAV, BICAV, CARP1, SART, SIRT, and the block‐iterative DROP and SART methods.
Inhibition of human recombinant T‐type calcium channels by the endocannabinoid N‐arachidonoyl dopamine
Authors: Ross Hamish R , Gilmore Andrew J , Connor Mark
Published: February 2009

Background and purpose:  N‐arachidonoyl dopamine (NADA) has complex effects on nociception mediated via cannabinoid CB1 receptors and the transient receptor potential vanilloid receptor 1 (TRPV1). Anandamide, the prototypic CB1/TRPV1 agonist, also inhibits T‐type voltage‐gated calcium channel currents (ICa). These channels are expressed by many excitable cells, including neurons involved in pain detection and processing. We sought to determine whether NADA and the prototypic arachidonoyl amino acid, N‐arachidonoyl glycine (NAGly) modulate T‐type ICa

Experimental approach:  Human recombinant T‐type ICa (CaV3 channels) expressed in HEK 293 cells and native mouse T‐type ICa were examined using standard whole‐cell voltage clamp electrophysiology techniques.

Key results:  N‐arachidonoyl dopamine completely inhibited CaV3 channels with a rank order of potency (pEC50) of CaV3.3 (6.45) ≥ CaV3.1 (6.29) > CaV3.2 (5.95). NAGly (10 µmol·L−1) inhibited CaV3 ICa by approximately 50% or less. The effects of NADA and NAGly were voltage‐ but not use‐dependent, and both compounds produced significant hyperpolarizing shifts in CaV3 channel steady‐state inactivation relationships. By contrast with anandamide, NADA and NAGly had modest effects on CaV3 channel kinetics. Both NAGly and NADA inhibited native T‐type ICa in mouse sensory neurons.

Conclusions and implications:  N‐arachidonoyl dopamine and NAGly increase the steady‐state inactivation of CaV3 channels, reducing the number of channels available to open during depolarization. These effects occur at NADA concentrations at or below to those affecting CB1 and TRPV1 receptors. Together with anandamide, the arachidonoyl neurotransmitter amides, NADA and NAGly, represent a new family of endogenous T‐type ICa modulators.
Characterization of histamine H3 receptors in Alzheimer's Disease brain and amyloid over‐expressing TASTPM mice
Authors: Medhurst AD , Roberts JC , Lee J , Chen CPL‐H , Brown SH , Roman S , Lai MKP
Published: February 2009

Background and purpose:  Histamine H3 receptor antagonists are currently being evaluated for their potential use in a number of central nervous system disorders including Alzheimer's Disease (AD). To date, little is known about the state of H3 receptors in AD.

Experimental approach:  In the present study we used the radiolabelled H3 receptor antagonist [3H]GSK189254 to investigate H3 receptor binding in the amyloid over‐expressing double mutant APPswe × PSI.MI46V (TASTPM) transgenic mouse model of AD and in post‐mortem human AD brain samples.

Key results:  No significant differences in specific H3 receptor binding were observed between wild type and TASTPM mice in the cortex, hippocampus or hypothalamus. Specific [3H]GSK189254 binding was detected in sections of human medial frontal cortex from AD brains of varying disease severity (Braak stages I–VI). With more quantitative analysis in a larger cohort, we observed that H3 receptor densities were not significantly different between AD and age‐matched control brains in both frontal and temporal cortical regions. However, within the AD group, [3H]GSK189254 binding density in frontal cortex was higher in individuals with more severe dementia prior to death.

Conclusions and implications:  The maintenance of H3 receptor integrity observed in the various stages of AD in this study is important, given the potential use of H3 antagonists as a novel therapeutic approach for the symptomatic treatment of AD.
Pharmacokinetics of oltipraz in diabetic rats with liver cirrhosis
Authors: Ahn CY , Bae SK , Bae SH , Kim T , Jung YS , Kim YC , Lee MG , Shin WG
Published: February 2009

Background and purpose:  The incidence of diabetes mellitus is increased in patients with liver cirrhosis. Oltipraz is currently in trials to treat patients with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus on pharmacokinetics of oltipraz and on expression of hepatic, CYP1A, 2B1/2, 2C11, 2D and 3A in rats with experimental liver cirrhosis.

Experimental approach:  Oltipraz was given intravenously (10 mg·kg−1) or orally (30 mg·kg−1) to rats with liver cirrhosis induced by N‐dimethylnitrosamine (LC rats) or with diabetes, induced by streptozotocin (DM rats) or to rats with both liver cirrhosis and diabetes (LCD rats) and to control rats, and pharmacokinetic variables measured. Protein expression of hepatic CYP1A, 2B1/2, 2C11, 2D and 3A was measured using Western blot analysis.

Key results:  After i.v. or p.o. administration of oltipraz to LC and DM rats, the AUC was significantly greater and smaller, respectively, than that in control rats. In LCD rats, the AUC was that of LC and DM rats (partially restored towards control rats). Compared with control rats, the protein expression of hepatic CYP1A increased, that of CYP2C11 and 3A decreased, but that of CYP2B1/2 and 2D was not altered in LCD rats.

Conclusions and implications:  In rats with diabetes and liver cirrhosis, the AUC of oltipraz was partially restored towards that of control rats.
Investigation of the effects of the novel anticonvulsant compound carisbamate (RWJ‐333369) on rat piriform cortical neuronesin vitro
Authors: Whalley BJ , Stephens GJ , Constanti A
Published: February 2009

Background and purpose: Carisbamate is being developed for adjuvant treatment of partial onset epilepsy. Carisbamate produces anticonvulsant effects in primary generalized, complex partial and absence‐type seizure models, and exhibits neuroprotective and antiepileptogenic properties in rodent epilepsy models. Phase IIb clinical trials of carisbamate demonstrated efficacy against partial onset seizures; however, its mechanisms of action remain unknown. Here, we report the effects of carisbamate on membrane properties, evoked and spontaneous synaptic transmission and induced epileptiform discharges in layer II‐III neurones in piriform cortical brain slices.

Experimental approach: Effects of carisbamate were investigated in rat piriform cortical neurones by using intracellular electrophysiological recordings.

Key results: Carisbamate (50–400 µmol·L−1) reversibly decreased amplitude, duration and rise‐time of evoked action potentials and inhibited repetitive firing, consistent with use‐dependent Na+channel block; 150–400 µmol·L−1carisbamate reduced neuronal input resistance, without altering membrane potential. After microelectrode intracellular Cl‐loading, carisbamate depolarized cells, an effect reversed by picrotoxin. Carisbamate (100–400 µmol·L−1) also selectively depressed lateral olfactory tract‐afferent evoked excitatory synaptic transmission (opposed by picrotoxin), consistent with activation of a presynaptic Cl‐conductance. Lidocaine (40–320 µmol·L−1) mimicked carisbamate, implying similar modes of action. Carisbamate (300–600 µmol·L−1) had no effect on spontaneous GABAAminiature inhibitory postsynaptic currents and at lower concentrations (50–200 µmol·L−1) inhibited Mg2+‐free or 4‐aminopyridine‐induced seizure‐like discharges.

Conclusions and implications: Carisbamate blocked evoked action potentials use‐dependently, consistent with a primary action on Na+channels and increased Cl‐conductances presynaptically and, under certain conditions, postsynaptically to selectively depress excitatory neurotransmission in piriform cortical layer Ia‐afferent terminals.
Self‐augmentation of the lengthening of repolarization is related to the shape of the cardiac action potential: implications for reverse rate dependency
Authors: Virág László , Acsai Károly , Hála Ottó , Zaza Antonio , Bitay Miklós , Bogáts Gábor , Papp Julius Gy , Varró András
Published: February 2009

Background and purpose: The aims of the present work were to study the mechanism of the reverse rate dependency of different interventions prolonging cardiac action potential duration (APD).

Experimental approach: The reverse rate‐dependent lengthening effect of APD‐prolonging interventions and the possible involvement ofIKr(rapid component of the delayed rectifier potassium current) andIK1(inward rectifier potassium current) were studied by using the standard microelectrode and the whole‐cell patch‐clamp techniques in dog multicellular ventricular preparations and in myocytes isolated from undiseased human and dog hearts.

Key results: All applied drugs – dofetilide (1 µmol·L−1), BaCl2(10 µmol·L−1), BAY‐K‐8644 (1 µmol·L−1), veratrine (1 µg·mL−1) – lengthened APD in a reverse rate‐dependent manner regardless of their mode of action, suggesting that reverse rate dependency may not represent a specific mechanism of APD prolongation. The E‐4031‐sensitive current (IKr) and the Ba2+‐sensitive current (IK1) were recorded during repolarizing voltage ramps having various steepness and also during action potential waveforms with progressively prolonged APD. Gradually delaying repolarization results in smaller magnitude ofIKrandIK1currents at an isochronal phase of the pulses. This represents a positive feedback mechanism, which appears to contribute to the reverse rate‐dependent prolongation of action potentials.

Conclusions and implications: Action potential configuration may influence the reverse rate‐dependent APD prolongation due to the intrinsic properties ofIKrandIK1currents. Drugs lengthening repolarization by decreasing repolarizing outward, or increasing depolarizing inward, currents are expected to cause reverse rate‐dependent APD lengthening with high probability, regardless of which current they modify.
The Wearable Artificial Kidney, Why and How: From Holy Grail to Reality
Authors: Gura Victor , Ronco Claudio , Davenport Andrew
Published: February 2009

Once hemodialysis had become established as a treatment for chronic kidney disease, the early pioneers realized the limitations of the treatment, particularly in terms of the impact intermittent thrice weekly hemodialysis had on a patient’s quality of life—not only time spent on dialysis and time traveling to and from treatment, but also dietary and fluid restrictions. This led to the search for the holy grail—a wearable hemodialysis device (WAK), that would allow patients to receive continuous treatment, while going on with the normal activities of daily life. Such a device would not only provide adequate solute clearances and control both electrolyte and acid–base status, but also improve blood pressure control—all while allowing a liberal diet. Despite many attempts, to develop such a wearable artificial kidney, it is only recently, with the advent of microtechnologies, that it has been possible to construct a truly wearable device, which can accurately regulate ultrafiltration and achieve adequate solute clearances. One such device has recently completed successful human pilot studies, designed to test device reliability, safety, and efficacy.
Impact of Training in Interventional Nephrology on Hemodialysis Vascular Access Types
Authors: Haq Naveed U. , Sayeed Sabinah , Ali Sayed A.
Published: February 2009

Vascular access has been a major problem in the management of end stage renal disease (ESRD) patients on chronic hemodialysis (HD). Native arteriovenous fistulas (AVFs) are the preferred vascular access for ESRD patients on HD. Multiple factors have been evaluated as causes for poor AVF rates. The purpose of this retrospective analysis was to assess the impact of training of nephrologist in interventional nephrology (IN) on vascular access outcomes. We studied the rates of different types of vascular access amongst patients on chronic HD under the care of two nephrology groups over 25 months in a community dialysis unit. In group A, all vascular access were managed directly by an interventional nephrologist, while in group B they were managed by general nephrologist with no exposure to IN during their training. A total of 129 patients received dialysis for at least 4 months at the unit during those 25 months. The rate of AVFs in group A was 56.6%, while in group B the rate of AVFs was 40.8% (p = 0.059). The rate of AVGs in group A was 22.9% and in group B it was 27.6% (p = 0.647). The tunneled HD catheter rate in group A was 20.4% and in group B it was 31.6% (p = 0.098). The results of this study demonstrate that training of nephrologists in IN leads to increased use of AVF as HD vascular access. We suggest that training programs in nephrology should consider incorporating IN into their programs to increase the prevalence of AVFs.
Reviews: Clinical Implications of Disordered Magnesium Homeostasis in Chronic Renal Failure and Dialysis
Authors: Navarro‐González Juan F. , Mora‐Fernández Carmen , García‐Pérez Javier
Published: February 2009

Magnesium (Mg) is the fourth most abundant cation in the body, mainly located within bone and skeletal muscle. The normal total plasma Mg concentration varies in a narrow range, with approximately 60% present as free Mg ions, the biologically active form. The kidney plays a principal role in Mg balance. Approximately 70–80% of plasma Mg is ultrafilterable, and under normal circumstances, 95% of the filtered load of Mg is reabsorbed. As chronic renal failure (CRF) progresses, urinary Mg excretion may be insufficient to balance intestinal Mg absorption and dietary Mg intake becomes a major determinant of serum and total body Mg levels. Until severe reductions in glomerular filtration rate (<30 ml/min), serum Mg levels are usually normal; with lower rates of renal function, serum Mg is increased. Concerning dialysis patients, dialysate Mg plays a critical role in maintaining Mg homeostasis, with serum Mg being largely dependent on the concentration of the ion in the dialysis solution. Magnesium has been implicated in diverse consequences, both beneficial and deleterious, in patients with CRF and dialysis. Potential harmful effects of elevated Mg include altered nerve conduction velocity, increased pruritus, and alterations to osseous metabolism and parathyroid gland function (mineralization defects, contribution to osteomalacic renal osteodystrophy, and adynamic bone disease). Hypermagnesemia also may retard vascular calcification. Low Mg levels have been associated with impairment of myocardial contractility, intradialytic hemodynamic instability, and hypotension. In addition, low Mg has been also linked to carotid intima‐media thickness, a marker of atherosclerotic vascular disease and a predictor of vascular events.
The Role of Hepcidin in Iron Homeostasis and Anemia in Hemodialysis Patients
Authors: Eleftheriadis Theodoros , Liakopoulos Vassilios , Antoniadi Georgia , Kartsios Charalambos , Stefanidis Ioannis
Published: February 2009

Anemia is a common complication in hemodialysis (HD) patients. Despite the great success of recombinant human erythropoietin in clinical practice, resistance to this therapy is common. Additionally, nephrologists frequently witness a rapid and significant drop in their patients’ hematocrit during the course of various acute events that regularly take place in this sensitive population. Hepcidin, a recently identified peptide, may mediate this development in many instances. Hepcidin production is regulated by hypoxia/anemia, iron status, and importantly, inflammation. This peptide can block iron absorption by the duodenum, iron release from both the liver (the main iron storage pool) and, more significantly, the macrophages interrupting iron recycling between senescent red cells and the reticuloendothelial system. The decreased availability of iron for erythropoiesis leads to the anemia of chronic disease or, in HD patients, aggravate an already existing anemia HD is now widely considered an inflammatory state probably accounting for the increased serum hepcidin levels that have been associated with it. The physiology of hepcidin and its possible contribution to the pathogenesis of anemia in HD patients are the subject of this review.
A Positive Theory of Moral Management, Social Pressure, and Corporate Social Performance
Authors: Baron David P.
Published: February 2009

This paper provides a theory of firm behavior motivated by moral duty, self‐interest, and social pressure. A morally managed and a self‐interested firm compete in a market in which their corporate social performance (CSP) provides product differentiation. Some citizens have altruistic or warm glow preferences for products with associated CSP, personal giving to social causes, holding shares in firms providing CSP, and contributing to social pressure to increase CSP. Social pressure is delivered by an activist NGO funded by voluntary contributions by citizens. The model characterizes an equilibrium in the product market, the capital market, and the market for social pressure. The equilibrium establishes a price for CSP and for activist‐induced social pressure. The theory provides predictions of the market values of firms, the prices of products, firm profits, target selection, contributions to the activist, and the amount of CSP supplied. For example, if citizens do not distinguish between morally motivated CSP and CSP induced by social pressure, the activist is more likely to target the softer, morally motivated firm. Higher quality activists are better funded, target self‐interested firms, and obtain greater corporate social performance. Lower quality activists target morally managed firms.
Private Environmental Activism and the Selection and Response of Firm Targets
Authors: Lenox Michael J. , Eesley Charles E.
Published: February 2009

Environmental activists are increasingly resorting to private strategies such as boycotts and protests focused on changing individual firms' behavior. In this paper, we examine activists' use of such “private politics” to engender firm compliance with activist objectives. We begin by developing a simple theoretical model of an activist campaign from which we develop a set of empirical hypotheses based on a set of observable features of firms. We test our hypotheses using a unique dataset of environmental activist campaigns against firms in the United States from 1988 to 2003. This paper fills an important need in the literature as one of the first empirical attempts to examine the private political strategies of activists and has important implications for the burgeoning literatures on industry self‐regulation and the nonmarket strategies of firms.
Public, Private and Nonprofit Regulation for Environmental Quality
Authors: Bottega Lucie , De Freitas Jenny
Published: February 2009

This paper studies the welfare implications of different institutions certifying environmental quality supplied by a monopoly. The monopolist can voluntarily certify the quality of the product through an eco‐label provided either by an NGO or a for‐profit private certifier (PC). The NGO and the PC may use advertisement to promote the label. We compare the NGO and PC regimes with the regime where the regulator imposes a minimum quality standard. The presence of a private certifier in the market decreases the scope for public intervention. The availability of green advertisement reinforces the above result.
Greening the Supply Chain: When Is Customer Pressure Effective?
Authors: Delmas Magali , Montiel Ivan
Published: February 2009

Suppliers face increasing pressure from their customers to improve their environmental performance. When firms downstream in the supply chain seek to achieve such improvements themselves, they frequently request that their suppliers adopt greener practices. This paper investigates the rationale for suppliers to comply with or resist the mandate of their customers to adopt the international environmental management standard ISO 14001 in the North American automotive industry. We argue that the effectiveness of such a mandate will vary according to the characteristics of the relationship between suppliers and customers. We contrast and test hypotheses based on both transaction cost and information theories to suggest that suppliers, whether in a dependent or distant relationship with their customers, have incentives to comply with the requests of their customers but through different mechanisms. Our study analyzed the characteristics of 3,152 automotive suppliers located in the United States, Canada, and Mexico over the 2000–2003 period. Findings indicate that suppliers with highly specialized assets, as well as younger suppliers, suppliers headquartered in Japan, and those reporting to the Toxic Release Inventory, are more likely to respond to their customers' pressures to adopt the certified management standard ISO 14001.
Households' Willingness to Pay for “Green” Goods: Evidence from Patagonia's Introduction of Organic Cotton Sportswear
Authors: Casadesus‐Masanell Ramon , Crooke Michael , Reinhardt Forest , Vasishth Vishal
Published: February 2009

To shed light on individuals' willingness to pay for “green” goods (i.e., goods that are supposed to have lower adverse environmental impacts either in production or in use), we study data from the introduction by Patagonia, Inc., of organic cotton sportswear in the mid‐1990s. Patagonia, a maker of high‐end outdoor wear, substituted organic cotton for conventionally grown cotton in all of its sportswear (i.e., casual clothing for travel and leisure) in 1996. We find that customers were willing to pay significant premiums for organic cotton garments although the organic cotton provided no demonstrable private incremental benefits to the customer.