bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateralized reward‐related visual discrimination in the avian entopallium
Authors: Verhaal Josine , Kirsch Janina A. , Vlachos Ioannis , Manns Martina , Güntürkün Onur
Published: March 2012

In humans and many other animals, the two cerebral hemispheres are partly specialized for different functions. However, knowledge about the neuronal basis of lateralization is mostly lacking. The visual system of birds is an excellent model in which to investigate hemispheric asymmetries as birds show a pronounced left hemispheric advantage in the discrimination of various visual objects. In addition, visual input crosses at the optic chiasm and thus testing of each hemisphere is easily accomplished. We aimed to find a neuronal correlate for three hallmarks of visual lateralization in pigeons: first, the animals learn faster with the right eye–left hemisphere; second, they reach higher performance levels under this condition; third, visually guided behavior is mostly under left hemisphere control. To this end, we recorded from the left and right forebrain entopallium while the animals performed a colour discrimination task. We found that, even before learning, left entopallial neurons were more responsive to visual stimulation. Subsequent discrimination acquisition recruited more neuronal responses in the left entopallium and these cells showed a higher degree of differentiation between the rewarded and the unrewarded stimulus. Thus, differential left–right responses are already present, albeit to a modest degree, before learning. As soon as some cues are associated with reward, however, this asymmetry increases substantially and the higher discrimination ratio of the left hemispheric tectofugal pathway would not only contribute to a higher performance of this hemisphere but could thereby also result in a left hemispheric dominance over downstream motor structures via reward‐associated feedback systems.
Mechanisms and urodynamic effects of a potent and selective EP4 receptor antagonist, MF191, on cyclophosphamide and prostaglandin E2‐induced bladder overactivity in rats
Authors: Chuang Yao‐Chi , Tyagi Pradeep , Huang Chao‐Cheng , Chancellor Michael B. , Yoshimura Naoki
Published: March 2012

Study Type – Aetiology (case control)

Level of Evidence 3b

What's known on the subject? and What does the study add?

Recent evidence has suggested that up‐regulation of the prostaglandin E2 (PGE2) receptor subtype 4 (EP4) receptor in the bladder is involved in bladder overactivity.

The present study found that MF191, a selective EP4 receptor antagonist, may have effects on the bladder urothelium and inflammatory cells and suppress CYP‐ or PGE2‐induced bladder overactivity. Systemic or intravesical MF191 administration for the treatment of overactive bladder may merit clinical study.

OBJECTIVE

To investigate the mechanisms and urodynamic effects of a potent and selective prostaglandin E2 (PGE2) receptor subtype 4 (EP4) antagonist, MF191, on cyclophosphamide (CYP) or PGE2‐induced bladder overactivity in rats.

MATERIALS AND METHODS

Experimental and control rats were injected with CYP (200 mg/kg i.p.) or saline on day 1. Continuous cystometrogram (CMGs) were performed on day 3.

In group 1, MF191 (vehicle 0.1 and 1 mg/kg) was given i.v. The bladder was then harvested for histology and immunohistochemistry. Some bladders were harvested for analysis of EP4 expression by Western blotting without a CMG study.

In group 2, MF191 (vehicle 10 nM, and 100 nM) was continuously infused into the bladder.

In group 3, bladder overactivity was induced by intravesical instillation of PGE2 (200 uM) and vehicle or MF191 (1 mg/kg) was given i.v.

RESULTS

CYP induced bladder inflammation, overactivity and EP4 upregulation. The CYP effects were suppressed by MF191 (1 mg/kg i.v.; intercontraction interval [ICI]: 39.4% increase, and reduced inflammatory cells infiltration, and EP4 expression).

Intravesical instillation of MF191 (100 nM) suppressed CYP‐induced bladder overactivity (ICI: 71.8% increase).

PGE2‐induced bladder overactivity was suppressed by MF191 (ICI: 43.2% increase).

MF191 had no significant effects on other CMG variables or on control rats.

CONCLUSIONS

MF191 might affect the bladder urothelium and inflammatory cells and suppresses CYP‐ or PGE2‐induced bladder overactivity.

Systemic or intravesical MF191 administration for the treatment of overactive bladder merits clinical study.
The extent and nature of alcohol advertising on Australian television
Authors: PETTIGREW SIMONE , ROBERTS MICHELE , PESCUD MELANIE , CHAPMAN KATHY , QUESTER PASCALE , MILLER CAROLINE
Published: March 2012

Introduction and Aims. Current alcohol guidelines in Australia recommend minimising alcohol consumption, especially among minors. This study investigated (i) the extent to which children and the general population are exposed to television advertisements that endorse alcohol consumption and (ii) the themes used in these advertisements.

Design and Methods. A content analysis was conducted on alcohol advertisements aired over two months in major Australian cities. The advertisements were coded according to the products that were promoted, the themes that were employed, and the time of exposure. Advertising placement expenditure was also captured.

Results. In total, 2810 alcohol advertisements were aired, representing one in 10 beverage advertisements. Advertisement placement expenditure for alcohol products in the five cities over the two months was $15.8 million. Around half of all alcohol advertisements appeared during children's popular viewing times. The most common themes used were humour, friendship/mateship and value for money.

Discussion and Conclusions. Children and adults are regularly exposed to advertisements that depict alcohol consumption as fun, social and inexpensive. Such messages may reinforce existing alcohol‐related cultural norms that prevent many Australians from meeting current intake guidelines.[Pettigrew S, Roberts M, Pescud M, Chapman K, Quester P, Miller C. The extent and nature of alcohol advertising on Australian television. Drug Alcohol Rev 2012;31:797–802]
Optimal environmental policy design for mine rehabilitation and pollution with a risk of non‐compliance owing to firm insolvency*
Authors: White Ben , Doole Graeme J. , Pannell David J. , Florec Veronique
Published: March 2012

The modified Pigovian tax approach to regulating stock and flow pollutants from a non‐renewable resource firm (Farzin, 1996) provides incentives for the firm to abate optimally, but does not allow for the possibility that a firm may become insolvent. In contrast, the current environmental bond policy applied in most jurisdictions across Australia and New Zealand provides funds in the case of insolvency, but often does not provide optimal incentives for rehabilitation. This study analyses these alternative policy approaches through a theoretical model and an empirical case study. From the case study for a mineral sands firm, the policy recommendation is that, based on economic efficiency alone, a modified Pigovian tax (termed here a damaged land tax) is optimal for most combinations of parameters. However, both risk‐sharing and efficiency objectives can be simultaneously addressed by a mixed policy that includes a damaged land tax and an environmental bond.
Zuckerman‐Kuhlman‐Aluja Personality Questionnaire (ZKA‐PQ) and Cloninger’s Temperament and Character Inventory Revised (TCI‐R): A comparative study
Authors: GARCÍA ÓSCAR , ALUJA ANTON , GARCÍA LUIS F. , ESCORIAL SERGIO , BLANCH ANGEL
Published: March 2012

García, Ó., Aluja, A., García, L.F., Escorial, S. & Blanch, A. (2012). Zuckerman‐Kuhlman‐Aluja Personality Questionnaire (ZKA‐PQ) and Cloninger’s Temperament and Character Inventory Revised (TCI‐R): A comparative study. Scandinavian Journal of Psychology.

The aim of this study was to compare the psychometric properties (normal distribution values, reliabilities and factor structure) of the Zuckerman‐Kuhlman‐Aluja Personality Questionnaire (ZKA‐PQ) and the Temperament and Character Inventory revised (TCI‐R). The total sample consisted of 482 subjects (53.1% men and 46.9% women) from diverse age. Results showed somewhat better psychometric properties, like reliability and facet‐factor structure, for the ZKA‐PQ than the TCI‐R. The expected five‐factor facet structure of the ZKA‐PQ was clear found. However, the seven‐factor structure of TCI‐R was not clear and it did not show a clear distinction between Temperament and Character factors. When ZKA‐PQ and TCI‐R variables are analyzed together, the ZKA‐PQ factors are related to the Character as well as the Temperament factors. In some cases they represent the opposite poles of ZKA‐PQ factors; for example, Neuroticism versus Self‐Directiveness and Aggression versus Cooperativeness. Some are directly and highly related to ZKA‐PQ factors; for example, Sensation Seeking and Novelty Seeking, Extraversion and Reward Dependence, Neuroticism and Harm Avoidance, and Activity and Persistence.
A comparison of impulsivity and sensation seeking in pathological gamblers and skydivers
Authors: MYRSETH HELGA , TVERÅ RENATE , HAGATUN SUSANNE , LINDGREN CAMILLA
Published: March 2012

Myrseth, H., Tverå, R., Hagatun, S. & Lindgren, C. (2012). A comparison of impulsivity and sensation seeking in pathological gamblers and skydivers. Scandinavian Journal of Psychology 53, 340–346.

The aim of this study was to compare pathological gamblers and skydivers in relation to measures of impulsivity and sensation seeking. The Eysenck Impulsivity Scale – Narrow Impulsiveness Subscale and the Arnett Inventory of Sensation Seeking were administered to pathological gamblers (n = 29), skydivers (n = 93), and a control group (n = 43). A two‐way multivariate analysis of variance was conducted to explore differences in impulsivity and sensation seeking between the groups and possible group by gender and group by age interaction effects. The significant effects were further investigated using follow‐up univariate analysis of variance. The results showed significant main effects of Group, Gender and Age, and a significant Group by Gender interaction effect. The results showed no statistically significant differences in impulsivity between pathological gamblers and skydivers; however, both groups scored higher than the controls. The skydivers scored higher compared to the pathological gamblers and controls on both sensation seeking subscales. Pathological gamblers scored higher than the controls on the subscale Need for Stimulus Intensity, although lower than the controls on the subscale Need for Novelty. We conclude that skydivers and pathological gamblers do not seem to differ in terms of impulsivity, but that the two groups differ in terms of sensation seeking. Skydivers are hence characterized by more sensation seeking compared to pathological gamblers. Skydiving, as opposed to pathological gambling, is not considered a psychiatric disorder, and skydiving may represent a more non‐pathological way to fulfill the need for stimulus intensity.
Future‐oriented emotions in the prediction of binge‐drinking intention and expectation: the role of anticipated and anticipatory emotions
Authors: CARRERA PILAR , CABALLERO AMPARO , MUÑOZ DOLORES
Published: March 2012

Carrera, P., Caballero, A. & Muñoz, D. (2012). Future‐oriented emotions in the prediction of binge‐drinking intention and expectation: the role of anticipated and anticipatory emotions. Scandinavian Journal of Psychology 53, 273–279.

The Theory of Planned Behavior (TPB) offers a parsimonious explanation of purposive behavior, but in the study of healthy and risk behaviors its sufficiency may be questioned. Working with binge‐drinking, a very common risk behavior in Spanish undergraduate students, we used two strategies for improving predictions from TPB: using behavioral intention (BI) and behavioral expectation (BE) as proximal antecedents of behaviors and adding as new predictors two future‐oriented emotions (anticipated and anticipatory). Hierarchical regression analyses show that while anticipated emotions improved TPB explanations of BI, anticipatory emotions improved the explanations of BE. The present results show the influence of future emotions in the prediction of behavioral intention and behavioral expectation.
‘Between Authenticity and Pretension’: Parents', Pupils' and Young Professionals' Negotiations of Minority Ethnic Middle-Class Identity
Authors: Archer Louise
Published: March 2012

Despite an increasing sociological interest in the middle classes and their educational practices, research has largely concentrated on the white middle classes. This paper considers the case of the minority ethnic (ME) middle classes through empirical data from a small, exploratory study conducted in England with 36 minority ethnic, ‘middle-class’ individuals (parents, pupils and young professionals) from a range of ME backgrounds. It is argued that participants experienced ME middle-class identity as a profoundly conflictual and precarious space, negotiated through a matrix of relational classed and racialized positionings. ‘Authentic’ middle-classness remains the preserve of white society due to racial inequalities and the dominance of whiteness as the popularly legitimated marker of middle classness. Moreover, attempts to define an acceptable, legitimate and principled ME middle-class identity are compromised by the discursive threats of ‘inauthenticity’, ‘pretension’ and ‘misrecognition’.
Protecting Our Non-Citizens: Iraqi Women on Australian Temporary Spouse Visas
Authors: Shabbar Fatin
Published: March 2012

Migration is a complex experience that differs from one migrant group to the other. Migrants have often been mistakenly seen as one homogenous group with shared experience, overlooking the diversity that exists within their visa conditions, cultural backgrounds and gender category. The generalization of the migration experience among all migrant groups usually overlooks the very specific issues arising within different types of migration and within different migrant groups. Generally, research on migrant women often portrays a victim image of them and neglects their strength and resilience. This paper addresses some of the gaps in the literature concerned with generalization and concepts of resilience. Utilizing a qualitative feminist methodology, conversations were made with eight Iraqi sponsored women living in Adelaide who arrived in Australia holding a Temporary Spouse Visa (TSV), with no specified period of entry. Within the focus on Iraqi women, the paper explores two concepts: challenges of a TSV within marriage migration and patterns of resilience amongst Iraqi sponsored women. The core argument of this paper is that the Australian TSV category which facilitates marriage migration is politically discriminative against women and significantly contributes to women's vulnerability to abuse.
Money Management and Control in the Indian Joint Family across Generations
Authors: Singh Supriya , Bhandari Mala
Published: March 2012

Studies of money management and control will have more cross-cultural relevance if the family context of money across generations is taken into account. The study of money management and control in middle-income nuclear and joint family households in urban India illustrates the importance of examining money flows within the wider family context because there is a two-way flow of money beyond the married couple – between parents and adult children, siblings and other members of the extended family. In the three or four generational joint family, control and management at the household level is not necessarily duplicated for the constituent couples. We draw on open-ended interviews of 40 persons from 27 urban middle-income households in North India, between November 2007 and January 2008, to show that the male control of money is the dominant pattern. This pattern is linked to the ideology of male dominance that is found among the middle, lower middle and struggling households, particularly in non-metropolitan households. The upper-middle-class households predominantly in metropolitan households show a pattern of joint or independent control. The focus is on the couple's money decisions within the context of the wider family.
Difficult Friendships and Ontological Insecurity
Authors: Smart Carol , Davies Katherine , Heaphy Brian , Mason Jennifer
Published: March 2012

In this paper we explore some of the negative aspects of friendship. In so doing we do not seek to join the debate about whether or not friendships are more or less important than other relationships but rather to explore precisely how significant friendships can be. Based on written accounts submitted to the British Mass Observation Project, we analyse how friendship, when it goes wrong, can challenge one's sense of self and even produce ontological insecurity. Friendship, it is argued, is tied into the process of self-identification and so staying true to friends, even when the relationships becomes uneven or tiresome, can be a sign of ethical standing. Meeting ‘old’ friends can also become very challenging, especially if one does not wish to be reminded of the self one once was. The paper contributes to the growing interest in relationships beyond kin.
Optimal Extraction of a Polluting Nonrenewable Resource with R&D toward a Clean Backstop Technology
Authors: HENRIET FANNY
Published: March 2012

We study the optimal extraction of a polluting nonrenewable resource within the following framework: environmental regulation is imposed in the form of a ceiling on the stock of pollution and a clean unlimited backstop technology can be developed by research and development. More specifically, the time taken to develop a new technology depends on the amount spent on R&D. A surprising result is that the stringency of the ceiling and the size of the initial stock of the polluting nonrenewable resource have a bearing on whether environmental regulation speeds up the optimal arrival date of this new technology. Compared to a scenario with no environmental externalities, stringent environmental regulation drives up the optimal R&D investment and brings forward the optimal backstop arrival date only in the case of a large initial resource stock. Otherwise, if the initial resource stock is small, regulation reduces optimal R&D and postpones the optimal backstop arrival date. These results are explained by the two roles played by the backstop technology. First, the backstop serves to replace oil once it has been exhausted. As extraction is slowed down by regulation, the exhaustion of the nonrenewable resource is postponed and the long‐run gains of innovation are lowered. Second, environmental regulation raises the short‐run gains of innovation by increasing the cost of consuming just oil.
ClimatePolicy, Uncertainty,and theRole ofTechnologicalInnovation
Authors: FISCHER CAROLYN , STERNER THOMAS
Published: March 2012

We study how uncertainty about climate change severity affects the relative benefits of early abatement and a portfolio of research and development (R&D) in lowering future abatement costs. Optimal early abatement depends on the curvature of the marginal benefit and marginal abatement cost (MAC) functions and how the uncertain parameter affects marginal benefits. R&D in a particular technology depends on whether uncertainty increases early abatement; whether investment lowersmarginalcosts for that technology; whether R&D lowers theslopeof that technology's MAC function; and the shape of that technology's MAC function. We illustrate, focusing on the role of backstop technologies.
Economic Policy in the Face of Severe Tail Events
Authors: NORDHAUS WILLIAM D.
Published: March 2012

From time to time, something occurs which is outside the range of normal expectations. We will call these “tail events” in the sense that they are way out of the tail of a probability distribution. I consider the question of the implications of tail events for economic policy and climate‐change economics. This issue has been analyzed by Martin Weitzman who proposed a Dismal Theorem. The general idea is that, under limited conditions concerning the structure of uncertainty and risk aversion, society has an indefinitely large expected loss from high‐consequence, low‐probability events. Under such conditions, standard economic tools such as cost‐benefit analysis cannot be applied. The present study is intended to put the Dismal Theorem in context and examine the range of its relevance, with an application to catastrophic climate change. I conclude that tail events are sometimes of extreme importance, and we must be extremely careful to include them in situations of deep uncertainty. However, we conclude that no loaded gun of strong tail dominance has been uncovered to date.
ResourceUse underClimateStabilization: CanNuclearPowerProvideCleanEnergy?
Authors: CHAKRAVORTY UJJAYANT , MAGNE BERTRAND , MOREAUX MICHEL
Published: March 2012

The long‐term goal of the Intergovernmental Panel on Climate Change (IPCC) is the stabilization of carbon concentration in the atmosphere. In this paper, we impose a carbon target concentration on a partial equilibrium model of the global energy sector. Specifically, we ask whether nuclear power can provide carbon‐free energy as fossil fuel resources become costly due to scarcity and externality costs. We find that nuclear power can reduce the cost of generating clean energy significantly and relatively quickly. However, beyond a few decades the role of nuclear power may be considerably reduced as uranium becomes scarce and renewables become economical. The cost of carbon when nuclear power supplies a significant share of energy is much lower than that of other studies. A policy implication is that current political and regulatory impediments to the expansion of nuclear generation may prove to be costly if large volumes of clean energy need to be supplied over a relatively short period of time.
Expertise in Moral Reasoning? Order Effects on Moral Judgment in Professional Philosophers and Non‐Philosophers
Authors: SCHWITZGEBEL ERIC , CUSHMAN FIERY
Published: March 2012

We examined the effects of order of presentation on the moral judgments of professional philosophers and two comparison groups. All groups showed similar‐sized order effects on their judgments about hypothetical moral scenarios targeting the doctrine of the double effect, the action‐omission distinction, and the principle of moral luck. Philosophers' endorsements of related general moral principles were also substantially influenced by the order in which the hypothetical scenarios had previously been presented. Thus, philosophical expertise does not appear to enhance the stability of moral judgments against this presumably unwanted source of bias, even given familiar types of cases and principles.
A Causal Model of Intentionality Judgment
Authors: SLOMAN STEVEN A. , FERNBACH PHILIP M. , EWING SCOTT
Published: March 2012

We propose a causal model theory to explain asymmetries in judgments of the intentionality of a foreseen side‐effect that is either negative or positive (Knobe, 2003). The theory is implemented as a Bayesian network relating types of mental states, actions, and consequences that integrates previous hypotheses. It appeals to two inferential routes to judgment about the intentionality of someone else's action: bottom‐up from action to desire and top‐down from character and disposition. Support for the theory comes from three experiments that test the prediction that bottom‐up inference should occur only when the actor's primary objective is known. The model fits intentionality judgments reasonably well with no free parameters.
REALIZING PLEASANT GROVE: THE REAL PRESENCE OF THE ESCHATON IN THE LIFE OF STANLEY HAUERWAS
Authors: BOERSMA HANS
Published: March 2012

Taking my cue from Hannah's Child: A Theologian's Memoir, I discuss the struggles Stanley Hauerwas experiences in trying to identify a place he can call home. The memoir suggests that his academic endeavours have taken Hauerwas far from his hometown, Pleasant Grove, Texas. The book shows, however, that places such as Pleasant Grove function for Hauerwas as anticipations of the heavenly eschaton. To suggest that Christians have no home here on earth does not take into account sufficiently the “real presence” of the heavenly future in everyday realities, such as Stanley's love of Paula Gilbert and a person's appropriate affection of his country.
HANNAH'S CHILD: A LIFE GIVEN AND THEREFORE LIVED
Authors: RICHES AARON
Published: March 2012

In response to Hannah's Child, this essay begins from the reality of “unlikely friendships” and the idea of the “conservative radical”. The essay then moves into a discussion of three particular themes raised in Hauerwas's memoir and in his work generally: Christocentrism as sequela Christi; Christian politics as eschatology; and witness as the heart of Christian life. What draws the various themes of the essay together is the proposal that givenness is the unique and Christocentric key to the Christian unity of thought and practice.
Promises and practices: job evaluation and equal pay forty years on!
Authors: Gilbert Kay
Published: March 2012

This article examines the claim made by Barbara Castle when introducing the Equal Pay Act (EPA) in 1970 that there is nothing preventing unions pressing for job evaluation schemes to achieve equal pay. It does this by examining the research on potential hurdles to job evaluation and those that can be found in the UK law since the introduction of the EPA. The article concludes that the standards for selecting job evaluation and the obstacles of introducing job evaluation have significantly changed over the period, leaving little promise of an extension of its use to achieve equal pay.
Feasibility and reliability of measuring strength, sprint power, and aerobic capacity in athletes and non‐athletes with cerebral palsy
Authors: DE GROOT SONJA , JANSSEN THOMAS W J , EVERS MARIJN , VAN DER LUIJT PIETER , NIENHUYS KIRSTEN N G , DALLMEIJER ANNET J
Published: March 2012

Aim  The aim of this study was to analyse the feasibility and reliability of the tests used to determine muscle strength, sprint power, and aerobic capacity in athletes and non‐athletes with cerebral palsy (CP).

Methods  Twenty individuals with spastic CP (four females, 16 males; age range 18–49y; Gross Motor Function Classification System level I, n=15; II, n=5; unilateral CP, n=10; bilateral CP, n=10; athletes, n=12; non‐athletes, n=8) participated in the study. Isometric and isokinetic knee flexor and extensor strength, sprint power, and aerobic capacity were determined, using, respectively an isokinetic dynamometer, a Wingate cycling test, and a graded maximal bicycle exercise test, on three occasions. Intraclass correlation coefficients (ICC), standard error of measurements, and smallest detectable differences (SDD) were calculated.

Results  The feasibility of the isometric strength test, Wingate test, and graded exercise test was good; the isokinetic strength test was difficult to perform for five participants. The strength parameters showed moderate to good ICCs (isometric, 0.74–0.94; isokinetic, 0.88–0.93) but high SDDs (isometric, 25–45%; isokinetic, 30–45%). Sprint power (ICC 0.98; SDD 24%) and aerobic capacity (ICC 0.98–0.99; SDD 16–21%) showed good ICCs and moderate SDDs.

Interpretation  All tests, except for the isokinetic strength test, seemed to be feasible for almost all participants. All tests are suitable for evaluating changes in a group; however, only large improvements (16–45%) can be detected when monitoring individual changes.
Expanding the measures of physical capacity in cerebral palsy
Authors: THORPE DEBORAH
Published: March 2012

This commentary is on the original article by de Groot et al. on pages 647‐653 of this issue
Effects of poly‐γ‐glutamic acid on the physicochemical characteristics of skim milk yoghurt
Authors: LIM SU‐MIN , SHIM JAE‐YONG , OH SEJONG , RHEE MINSUK , SUNG MOON‐HEE , IMM JEE‐YOUNG
Published: March 2012

The physicochemical and sensory properties of skim milk yoghurts containing poly‐γ‐glutamic acid (PGA) at different levels (0.0025, 0.005 and 0.01%) were evaluated. Addition of PGA up to 0.01% to reconstituted skim milk (11%, w/v) did not affect the growth of lactic acid bacteria or the development of titratable acidity in yoghurt, whereas full‐fat control yoghurt had reduced acid production. No changes were found in viable cell counts of PGA yoghurts during storage (4 weeks at 4 °C). The addition of PGA (0.005%) significantly decreased syneresis in skim milk yoghurt and did not cause any undesirable effects in sensory acceptability.
Quality of life following liver transplantation in patients with liver metastases from colorectal carcinoma
Authors: Andersen Marit Helen , Dueland Svein , Hagness Morten , Vidnes Tone , Finstad Ellen Drolsum , Wahl Astrid Klopstad , Foss Aksel
Published: March 2012

Purpose: To study quality of life (QoL) in patients with liver metastases from colorectal carcinoma (CRC) following liver transplantation (Ltx).

Methods: Ten patients participated in a prospective explorative pilot study. Inclusion criteria were nonresectable liver‐only metastases determined by CT/MRI‐, PET/CT‐ scans and colonoscopy, and ECOG 0‐1. Primary outcome was QoL assessed by the EORTC‐C30 questionnaires at baseline, and at 3, 6 and 12 months after Ltx.

Results: The patients’ age ranged from 50 to 63 years. Nine of 10 patients were observed for 12 months. One patient did not return the form at 6 months and died shortly after because of recurrence of the malignant disease. Compared to baseline, Ltx resulted in sustained excellent global health status scale (score of 100) in one patient, improved scores in 4 and unchanged scores in 3 patients at 12 months. The majority of the patients also reported good functional scores at follow‐ups. Although two patients had marked symptoms both before and after Ltx, the patients in general reported low levels of pain and fatigue before and after surgery.

Conclusion: The present study indicates that CRC patients with liver‐only metastases who receive Ltx have good QoL and have mostly minor symptoms the first year after Ltx.
pH‐dependent inhibition of native GABAA receptors by HEPES
Authors: Hugel S , Kadiri N , Rodeau JL , Gaillard S , Schlichter R
Published: March 2012

BACKGROUND AND PURPOSE Artificial buffers such as HEPES are extensively used to control extracellular pH (pHe) to investigate the effect of H+ ions on GABAA receptor function.

EXPERIMENTAL APPROACH In neurones cultured from spinal cord dorsal horn (DH), dorsal root ganglia (DRG) and cerebellar granule cells (GC) of neonatal rats, we studied the effect of pHe on currents induced by GABAA receptor agonists, controlling pHe with HCO3‐ or different concentrations of HEPES.

KEY RESULTS Changing HEPES concentration from 1 to 20 mM at constant pHe strongly inhibited the currents induced by submaximal GABA applications, but not those induced by glycine or glutamate, on DH, DRG or GC neurones, increasing twofold the EC50 for GABA in DH neurones and GC. Submaximal GABAA receptor‐mediated currents were also inhibited by piperazine‐N,N′‐bis(2‐ethanesulfonic acid) (PIPES), 3‐(N‐morpholino)propanesulfonic acid, tris(hydroxymethyl)aminomethane or imidazole. PIPES and HEPES, both piperazine derivatives, similarly inhibited GABAA receptors, whereas the other buffers had weaker effects and 2‐(N‐morpholino)ethanesulfonic acid had no effect. HEPES‐induced inhibition of submaximal GABAA receptor‐mediated currents was unaffected by diethylpyrocarbonate, a histidine‐modifying reagent. HEPES‐induced inhibition of GABAA receptors was independent of membrane potential, HCO3‐ and intracellular Cl‐ concentration and was not modified by flumazenil, which blocks the benzodiazepine binding site. However, it strongly depended on pHe.

CONCLUSIONS AND IMPLICATIONS Inhibition of GABAA receptors by HEPES depended on pHe, leading to an apparent H+‐induced inhibition of DH GABAA receptors, unrelated to the pH sensitivity of these receptors in both low and physiological buffering conditions, suggesting that protonated HEPES caused this inhibition.
Role of H2O2 in hypertension, renin‐angiotensin system activation and renal medullary disfunction caused by angiotensin II
Authors: Sousa T , Oliveira S , Afonso J , Morato M , Patinha D , Fraga S , Carvalho F , Albino‐Teixeira A
Published: March 2012

BACKGROUND AND PURPOSE Activation of the intrarenal renin‐angiotensin system (RAS) and increased renal medullary hydrogen peroxide (H2O2) contribute to hypertension. We examined whether H2O2 mediated hypertension and intrarenal RAS activation induced by angiotensin II (Ang II).

EXPERIMENTAL APPROACH Ang II (200 ng·kg−1·min−1) or saline were infused in Sprague Dawley rats from day 0 to day 14. Polyethylene glycol (PEG)‐catalase (10 000 U·kg−1·day−1) was given to Ang II‐treated rats, from day 7 to day 14. Systolic blood pressure was measured throughout the study. H2O2, angiotensin AT1 receptor and Nox4 expression and nuclear factor‐κB (NF‐κB) activation were evaluated in the kidney. Plasma and urinary H2O2 and angiotensinogen were also measured.

KEY RESULTS Ang II increased H2O2, AT1 receptor and Nox4 expression and NF‐κB activation in the renal medulla, but not in the cortex. Ang II raised plasma and urinary H2O2 levels, increased urinary angiotensinogen but reduced plasma angiotensinogen. PEG‐catalase had a short‐term antihypertensive effect and transiently suppressed urinary angiotensinogen. PEG‐catalase decreased renal medullary expression of AT1 receptors and Nox4 in Ang II‐infused rats. Renal medullary NF‐κB activation was correlated with local H2O2 levels and urinary angiotensinogen excretion. Loss of antihypertensive efficacy was associated with an eightfold increase of plasma angiotensinogen.

CONCLUSIONS AND IMPLICATIONS The renal medulla is a major target for Ang II‐induced redox dysfunction. H2O2 appears to be the key mediator enhancing intrarenal RAS activation and decreasing systemic RAS activity. The specific control of renal medullary H2O2 levels may provide future grounds for the treatment of hypertension.
Mitochondrial F0F1‐ATP synthase is a molecular target of 3‐iodothyronamine, an endogenous metabolite of thyroid hormone
Authors: Cumero S , Fogolari F , Domenis R , Zucchi R , Mavelli I , Contessi S
Published: March 2012

BACKGROUND AND PURPOSE 3‐iodothyronamine (T1AM) is a metabolite of thyroid hormone acting as a signalling molecule via non‐genomic effectors and can reach intracellular targets. Because of the importance of mitochondrial F0F1‐ATP synthase as a drug target, here we evaluated interactions of T1AM with this enzyme.

EXPERIMENTAL APPROACH Kinetic analyses were performed on F0F1‐ATP synthase in sub‐mitochondrial particles and soluble F1‐ATPase. Activity assays and immunodetection of the inhibitor protein IF1 were used and combined with molecular docking analyses. Effects of T1AM on H9c2 cardiomyocytes were measured by in situ respirometric analysis.

KEY RESULTS T1AM was a non‐competitive inhibitor of F0F1‐ATP synthase whose binding was mutually exclusive with that of the inhibitors IF1 and aurovertin B. Both kinetic and docking analyses were consistent with two different binding sites for T1AM. At low nanomolar concentrations, T1AM bound to a high‐affinity region most likely located within the IF1 binding site, causing IF1 release. At higher concentrations, T1AM bound to a low affinity‐region probably located within the aurovertin binding cavity and inhibited enzyme activity. Low nanomolar concentrations of T1AM increased ADP‐stimulated mitochondrial respiration in cardiomyocytes, indicating activation of F0F1‐ATP synthase consistent with displacement of endogenous IF1,, reinforcing the in vitro results.

CONCLUSIONS AND IMPLICATIONS Effects of T1AM on F0F1‐ATP synthase were twofold: IF1 displacement and enzyme inhibition. By targeting F0F1‐ATP synthase within mitochondria, T1AM might affect cell bioenergetics with a positive effect on mitochondrial energy production at low, endogenous, concentrations. T1AM putative binding locations overlapping with IF1 and aurovertin binding sites are described.
Curcumin ameliorates hepatic fibrosis in type 2 diabetes mellitus – insights into its mechanisms of action
Authors: Stefanska B
Published: March 2012

A wide variety of beneficial effects have been attributed to curcumin, a major polyphenol from the golden spice Curcuma longa known as turmeric, including amelioration of severe complications of type 2 diabetes such as hepatic fibrosis, retinopathy, neuropathy and nephropathy. In the present issue of BJP, Lin and colleagues reveal new mechanisms by which curcumin inhibits the activation of hepatic stellate cells in vitro, a hallmark of non‐alcoholic steatohepatitis and hepatic fibrogenesis associated with type 2 diabetes mellitus. They demonstrated that curcumin suppresses the advanced glycation end‐products (AGEs)‐mediated induction of the receptor for AGEs (RAGE) gene expression by increasing PPARγ activity and stimulating de novo synthesis of glutathione. As a result, downstream elements of RAGE‐activated pathways are inhibited, which prevents oxidative stress, inflammation and hepatic stellate cell activation. This report suggests that curcumin may have potential as an anti‐fibrotic agent in type 2 diabetes and opens the door to the evaluation of curcumin therapeutic effects in liver conditions of different aetiology and in other disorders linked to the impairment of PPARγ activity, such as obesity and atherosclerosis.

LINKED ARTICLE This article is a commentary on Lin et al., pp. 2212–2227 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01910.x
Farmers’ Income and Production Responses to Rural Taxation Reform in Three Regions in China
Authors: Xu Cuiping , Holly Wang H. , Shi Qinghua
Published: March 2012

The relationship between agricultural taxation and production efficiency has been thoroughly explored for many countries. Recently, China has taken various measures including the rural taxation reform (RTR) to promote grain production and to increase farmer incomes. In this study, we investigate whether the Chinese policy of abolishing rural taxation has improved farm households’ incomes and affected their production decisions. Using household survey data obtained from three regions in China, we estimate the effect of the RTR on farmers’ income. Results show that the RTR has significantly improved farmers’ post‐tax net income by 9.2% in Shandong, 16.9% in Shanxi and 16.8% in Zhejiang. These increments, mostly from farm income rather than from off‐farm income, are much higher than the direct income increase from the tax savings. In addition, we examine the dynamic impact of farmers’ net income, and find that the RTR has a sustained positive income effect in Shandong and Shanxi, whereas its positive effect in Zhejiang appears temporary. We also examine farmers’ production responses to the RTR. Results show that farmers in the three regions respond in different ways: farmers in Shandong significantly increase their labour input, farmers in Zhejiang increase intermediate inputs, whereas Shanxi farmers augment their intermediate inputs and enlarge their crop acreage. It appears that the farmers’ responses to the taxation reform vary due to the agronomic and economic factors in these three regions, suggesting that diverse post‐RTR supplemental policies should be implemented in different regions.
Preexisting Venous Calcification Prior to Dialysis Vascular Access Surgery
Authors: Lee Timmy , Safdar Nida , Mistry Meenakshi J. , Wang Yang , Chauhan Vibha , Campos Begoña , Munda Rino , Cornea Virgilius , Roy‐Chaudhury Prabir
Published: March 2012

Vascular calcification is present in arterial vessels used for dialysis vascular access creation prior to surgical creation. Calcification in the veins used to create a new vascular access has not previously been documented. The objective of this study was to describe the prevalence of venous calcification in samples collected at the time of vascular access creation. Sixty‐seven vein samples were studied. A von Kossa stain was performed to quantify calcification. A semi‐quantitative scoring system from 0 to 4+ was used to quantify the percentage positive area for calcification as a fraction of total area (0: 0; 1+: 1–10%; 2+: 11–25%; 3+: 26–50%; 4+: >50% positive). Twenty‐two of 67 (33%) samples showed evidence of venous calcification. Histologic examination showed varying degrees of calcification within each cell layer. Among the subset of patients with calcification, 4/22 (18%), 19/22 (86%), 22/22 (100%), and 7/22 (32%) had calcification present within the endothelium, intima, media, and adventitia, respectively. The mean semi‐quantitative scores of the 22 samples with calcification were 0.18 ± 0.08, 1.2 ± 0.14, 1.6 ± 0.13, and 0.36 ± 0.12 for the endothelium, intima, media, and adventitia, respectively. Our results demonstrate that vascular calcification is present within veins used to create new dialysis vascular access, and located predominately within the neointimal and medial layers.
A standard blood bank donation alters the thermal and cardiovascular responses during subsequent exercise
Authors: Mora‐Rodriguez Ricardo , Aguado‐Jimenez Roberto , Del Coso Juan , Estevez Emma
Published: March 2012

BACKGROUND: The fear for adverse effects of blood donation on subsequent exercise may prevent physically active people from donating. We studied the impact of a standard blood bank donation (i.e., 450‐mL blood withdrawal) on the thermoregulatory and cardiovascular responses to prolonged exercise in the heat.

STUDY DESIGN AND METHODS: Eight moderately trained, heat‐acclimated males cycled for 1 hour at 60% in a hot environment (34.9 ± 0.6°C) on four occasions: 1) 2 days before blood donation (CON), 2) 2 hours after donation (DON), 3) 2 days after donation (2 DAYS), and 4) 7 days after donation (7 DAYS).

RESULTS: Two‐thirds of the blood volume withdrawn was endogenously restored before exercise in the DON trial (p < 0.05). DON started with increased preexercise rectal temperature (TRE; 0.42 ± 0.1°C above CON; p < 0.05), which resulted in high levels of hyperthermia (i.e., 39.0 ± 0.2°C) after 1 hour of exercise. Skin temperature (34.5 ± 0.1°C) and sweat rate (1.15 ± 0.1 L/h) were not affected by DON. However, DON lowered the skin blood flow : TRE relationship and elevated heart rate (HR) above CON (12 ± 4 beats/min; p < 0.05) maintaining cardiac output. After 2 DAYS, TRE and HR were restored to CON levels while cardiac output increased above CON (6%; p < 0.05) in association with reduced hemoglobin concentration (i.e., peak hemodilution).

CONCLUSION: A blood bank donation increases preexercise TRE. Subsequent exercise in a hot environment results in high levels of hyperthermia and HR. These thermoregulatory and cardiovascular perturbations observed during exercise disappear 2 days after donation.
Distinct roles of trauma and transfusion in induction of immune modulation after injury
Authors: Jackman Rachael P. , Utter Garth H. , Muench Marcus O. , Heitman John W. , Munz Matthew M. , Jackman Robert W. , Biswas Hope H. , Rivers Ryan M. , Tobler Leslie H. , Busch Michael P. , Norris Philip J.
Published: March 2012

BACKGROUND: Trauma and transfusion can both alter immunity, and while transfusions are common among traumatically injured patients, few studies have examined their combined effects on immunity.

STUDY DESIGN AND METHODS: We tracked the plasma levels of 41 immunomodulatory proteins in 56 trauma patients from time of injury up to 1 year later. In addition, a murine model was developed to distinguish between the effects of transfusion and underlying injury and blood loss.

RESULTS: Thirty‐one of the proteins had a significant change over time after traumatic injury, with a mixed early response that was predominantly anti‐inflammatory followed by a later increase in proteins involved in wound healing and homeostasis. Results from the murine model revealed similar cytokine responses to humans. In mice, trauma and hemorrhage caused early perturbations in a number of the pro‐ and anti‐inflammatory mediators measured, and transfusion blunted early elevations in interleukin (IL)‐6, IL‐10, matrix metalloproteinase‐9, and interferon‐γ. Transfusion caused or exacerbated changes in monocyte chemotactic protein‐1, IL‐1α, IL‐5, IL‐15, and soluble E‐selectin. Finally, trauma and hemorrhage alone increased CXCL1 and IL‐13.

CONCLUSIONS: This work provides a detailed characterization of the major shift in the immunologic environment in response to trauma and transfusion and clarifies which immune mediators are affected by trauma and hemorrhage and which by transfusion.
Efficacy and safety of peripheral blood stem cell mobilization and collection: a single‐center experience in 190 allogeneic donors
Authors: Rinaldi Cristina , Savignano Chiara , Pasca Samantha , Sperotto Alessandra , Patriarca Francesca , Isola Miriam , Fanin Renato , De Angelis Vincenzo
Published: March 2012

BACKGROUND: In the past two decades peripheral blood stem cells (PBSCs) have increasingly replaced marrow as stem cells source for allogeneic transplantation. The PBSC donation initially applied only to related donors; later, due to the safety of the procedure, it was extended to unrelated donors.

STUDY DESIGN AND METHODS: We have retrospectively collected data regarding mobilization, collection, and short‐ and long‐term follow‐up of 190 consecutive donors, 174 related and 16 unrelated. All donors followed a standard protocol for mobilization and underwent at least one PBSC collection. Follow‐up in related donors was performed every 4 months in the first year and then annually, with no time limits, while unrelated donors were monitored for 10 years.

RESULTS: All 190 donors completed the established mobilization protocol. The mobilizing capacity was significantly greater in males and in donors less than 60 years old. No case of major toxicity by granulocyte–colony‐stimulating factor was found, nor thromboembolic events. The total dose of CD34+/recipient (median 5.8 × 106/kg recipient/body weight) was statistically correlated with age, CD34+ before and after mobilization, and collection efficiency. Compliance to follow‐up was 66%, with a significant difference between related and unrelated (63% vs. 100%, p = 0.03). During follow‐up no significant abnormalities in hematologic variables or hematologic malignancies were reported.

CONCLUSION: Our study allowed us to define the PBSC donation as “a safe procedure for the donors,” with short‐ and long‐term effects limited to a small percentage of donors and “effective for the recipient,” due to the dose of collected CD34+, adequate for transplantation in almost all recipients.