bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor size as a prognostic factor in resected small hepatocellular carcinoma: A controversy revisited
Authors: Chen Yao‐Li , Ko Chih‐Jan , Chien Su‐Yu , Chen Li‐Sheng , Chen Mei‐Ling , Chi Chin‐Wen , Lai Hung‐Wen
Published: December 2010

Background and Aim:  The widespread use of screening programs has resulted in an increase in detection of small hepatocellular carcinoma (HCC). Surgical resection generally leads to favorable outcomes in this group of patients; however, the prognostic significance of tumor size and the optimal cutoff point in resected specimens of small HCC have not been well defined. The aim of current study is to evaluate the prognostic significance of tumor size in small resected HCC.

Methods:  Patients who underwent surgical resection for small HCC at the Changhua Christian Hospital during January 2001 to June 2007 were enrolled. Small HCC was defined as a single HCC nodule with maximum diameter ≤ 5 cm. Cox regression hazard ratios for cancer‐specific death were calculated to survey the prognostic significance of tumor size. We then determined the optimal cut‐point for tumor size that could be used to stratify patients into 5‐year disease‐free survival (DFS) and cancer‐specific survival (CSS) groups.

Results:  A total of 140 patients who underwent resection of small HCC were enrolled. The mean tumor size was 2.9 cm (range 0.9–5.0) and the mean follow‐up period was 43.4 months. The 5‐year DFS and CSS rates were 46.6% and 81.6%, respectively. Cox regression analysis revealed that tumor size (hazard ratio = 2.973, 95% confidence interval: 1.073–8.239, P = 0.036) was an independent prognostic factor. Our analysis showed that a tumor size of 3 cm was the cut‐point that could dichotomize patients into statistically different 5‐year DFS and CSS risk groups.

Conclusions:  Tumor size is an independent prognostic factor in resected small HCC and the prognostic significance of tumor size may vary according to different cut‐off points.
Prophylaxis of hepatic encephalopathy in acute variceal bleed: A randomized controlled trial of lactulose versus no lactulose
Authors: Sharma Praveen , Agrawal Amit , Sharma Barjesh C , Sarin Shiv K
Published: December 2010

Background and Aims:  Acute variceal bleed (AVB) is an important precipitating factor for development of hepatic encephalopathy (HE). However, there is paucity of data on the role of lactulose for prevention of HE after AVB. We evaluated the role of lactulose for prophylaxis of HE after AVB.

Methods:  Consecutive patients of cirrhosis with AVB enrolled. Patients included if >18 years old and had no HE at the time of presentation. Patients were randomized to receive lactulose (Group‐L) or no lactulose (Group‐P) along with standard treatment of AVB as per Baveno 4 guidelines. Primary endpoint was development of overt HE as per West Haven criteria within 120 h of randomization.

Results:  Seventy patients were randomized into group‐L (Gp‐L, n = 35) and group‐P (Gp‐P, n = 35). There was no significant difference in baseline characteristics between the two groups. Characteristics of variceal bleed were also similar (Gp‐L vs Gp‐P [mean arterial pressure 81.0 ± 10.5 vs 79.5 ± 9.9 mmHg], Hb [8.4 ± 1.5 vs 9.3 ± 2.3 g/dL], blood transfusion requirement [1.6 ± 1.1 vs 1.3 ± 0.9 units], time to endoscopy [6.3 ± 2.8 vs 7.0 ± 3.1 h], and esophageal source of bleed [92% vs 88%]). Nineteen (27%) patients developed HE; five patients (14%) in Gp‐L and 14 patients (40%) in Gp‐P, P = 0.03. The median grade of HE was 2 (range 2–4) and median time interval of development of HE after randomization was 2 days (range 1–4). Nine patients (13%) died; three (8.5%) patients in Gp‐L and six (17%) patients in Gp‐P, P = 0.23. Patients who developed HE had significantly higher baseline Child‐Turcotte‐Pugh score score (10.2 ± 1.2 vs 9.4 ± 1.4 P = 0.04), model for end stage liver disease score (18.2 ± 3.9 vs 15.4 ± 4.5 P = 0.02), arterial ammonia level (112.2 ± 22.7 vs 94.8 ± 17.6 umol/L, P = 0.001), baseline total leukocyte count (10 505.2 ± 8911.9 vs 5784.3 ± 3387.0 P = 0.002), total bilirubin (3.4 ± 1.3 vs 2.1 ± 1.8 mg%, P = 0.008) as compared to patients who did not develop HE. On multivariate analysis only baseline arterial ammonia, blood requirement during hospital stay and lactulose therapy were predictors of development of HE.

Conclusions:  Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed.
Evidence for a specific cross‐modal association deficit in dyslexia: an electrophysiological study of letter–speech sound processing
Authors: Froyen Dries , Willems Gonny , Blomert Leo
Published: December 2010

The phonological deficit theory of dyslexia assumes that degraded speech sound representations might hamper the acquisition of stable letter–speech sound associations necessary for learning to read. However, there is only scarce and mainly indirect evidence for this assumed letter–speech sound association problem. The present study aimed at clarifying the nature and the role of letter–speech sound association problems in dyslexia by analysing event‐related potentials (ERP) of 11‐year‐old dyslexic children to speech sounds in isolation or combined with letters, which were presented either simultaneously with or 200 ms before the speech sounds. Recent studies with normal readers revealed that letters systematically modulated speech sound processing in an early (mismatch negativity or MMN) and late (Late Discriminatory Negativity or LDN) time‐window. The amplitude of the MMN and LDN to speech sounds was enhanced when speech sounds were presented with letters. The dyslexic readers in the present study, however, did not exhibit any early influences of letters on speech sounds even after 4 years of reading instruction, indicating no automatic integration of letters and speech sounds. Interestingly, they revealed a systematic late effect of letters on speech sound processing, probably reflecting the mere association of letters and speech sounds. This pattern is strongly divergent from that observed in age‐matched normal readers, who showed both early and late effects, but reminiscent of that observed in beginner normal readers in a previous study (Froyen, Bonte, van Atteveldt & Blomert, 2009). The finding that the quality of letter–speech sound processing is directly related to reading fluency urges further research into the role of audiovisual integration in the development of reading failure in dyslexia.
Effects of joint attention on long‐term memory in 9‐month‐old infants: an event‐related potentials study
Authors: Kopp Franziska , Lindenberger Ulman
Published: December 2010

Joint attention develops during the first year of life but little is known about its effects on long‐term memory. We investigated whether joint attention modulates long‐term memory in 9‐month‐old infants. Infants were familiarized with visually presented objects in either of two conditions that differed in the degree of joint attention (high versus low). EEG indicators in response to old and novel objects were probed directly after the familiarization phase (immediate recognition), and following a 1‐week delay (delayed recognition). In immediate recognition, the amplitude of positive slow‐wave activity was modulated by joint attention. In the delayed recognition, the amplitude of the Pb component differentiated between high and low joint attention. In addition, the positive slow‐wave amplitude during immediate and delayed recognition correlated with the frequency of infants’ looks to the experimenter during familiarization. Under both high‐ and low‐joint‐attention conditions, the processing of unfamiliar objects was associated with an enhanced Nc component. Our results show that the degree of joint attention modulates EEG during immediate and delayed recognition. We conclude that joint attention affects long‐term memory processing in 9‐month‐old infants by enhancing the relevance of attended items.
Only self‐generated actions create sensori‐motor systems in the developing brain
Authors: James Karin Harman , Swain Shelley N.
Published: December 2010

Previous research shows that sensory and motor systems interact during perception, but how these connections among systems are created during development is unknown. The current work exposes young children to novel ‘verbs’ and objects through either (a) actively exploring the objects or (b) by seeing an experimenter interact with the objects. Results demonstrate that the motor system is recruited during auditory perception only after learning involved self‐generated interactions with objects. Action observation itself led to above‐baseline activation in one motor region during visual perception, but was still significantly less active than after self‐generated action. Therefore, in the developing brain, associations are built upon real‐world interactions of body and environment, leading to sensori‐motor representations of both objects and words.
The development of a phonological illusion: a cross‐linguistic study with Japanese and French infants
Authors: Mazuka Reiko , Cao Yvonne , Dupoux Emmanuel , Christophe Anne
Published: December 2010

In adults, native language phonology has strong perceptual effects. Previous work has shown that Japanese speakers, unlike French speakers, break up illegal sequences of consonants with illusory vowels: they report hearing abna as abuna. To study the development of phonological grammar, we compared Japanese and French infants in a discrimination task. In Experiment 1, we observed that 14‐month‐old Japanese infants, in contrast to French infants, failed to discriminate phonetically varied sets of abna‐type and abuna‐type stimuli. In Experiment 2, 8‐month‐old French and Japanese did not differ significantly from each other. In Experiment 3, we found that, like adults, Japanese infants can discriminate abna from abuna when phonetic variability is reduced (single item). These results show that the phonologically induced /u/ illusion is already experienced by Japanese infants at the age of 14 months. Hence, before having acquired many words of their language, they have grasped enough of their native phonological grammar to constrain their perception of speech sound sequences.
Developmental differences in prefrontal activation during working memory maintenance and manipulation for different memory loads
Authors: Jolles Dietsje D. , Kleibeuker Sietske W. , Rombouts Serge A.R.B. , Crone Eveline A.
Published: December 2010

The ability to keep information active in working memory is one of the cornerstones of cognitive development. Prior studies have demonstrated that regions which are important for working memory performance in adults, such as dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and superior parietal cortex, become increasingly engaged across school‐aged development. The primary goal of the present functional MRI study was to investigate the involvement of these regions in the development of working memory manipulation relative to maintenance functions under different loads. We measured activation in DLPFC, VLPFC, and superior parietal cortex during the delay period of a verbal working memory task in 11–13‐year‐old children and young adults. We found evidence for age‐related behavioral improvements in working memory and functional changes within DLPFC and VLPFC activation patterns. Although activation profiles of DLPFC and VLPFC were similar, group differences were most pronounced for right DLPFC. Consistent with prior studies, right DLPFC showed an interaction between age and condition (i.e. manipulation versus maintenance), specifically at the lower loads. This interaction was characterized by increased activation for manipulation relative to maintenance trials in adults compared to children. In contrast, we did not observe a significant age‐dependent load sensitivity. These results suggest that age‐related differences in the right DLPFC are specific to working memory manipulation and are not related to task difficulty and/or differences in short‐term memory capacity.
Building Complementarities in Africa between Different Development Cooperation Modalities of Traditional Development Partners and China
Authors: Schiere Richard
Published: December 2010

Abstract:  China's relationship with Africa has grown exponentially over the last decade with US$95 billion in bilateral trade in 2008 and US$5.4 billion of Chinese investment in Africa for the same year. The growth of Sino‐African relations also has an impact on the role of traditional development partners in Africa in particular in the aftermath of the 2008 financial crisis, which has already led some traditional development partners to reduce their aid budgets and subsequently their Official Development Assistance (ODA) flows to Africa. The objective of this paper is to analyse different development cooperation modalities in Africa of traditional development partners and China. This requires identifying trends in aid, debt relief, general budget support, trade, preferential trade access, and investment flows of both traditional development partners and China. The paper advocates that complementarities can be built between these development modalities on a national, regional and global level. This would enhance development effectiveness, increase efficiency and create win‐win situations which would be beneficial to African countries, China and traditional development partners.
Poverty Alleviation in the People's Republic of China: The Implications for Sino–African Cooperation in Poverty Reduction
Authors: Wu Zhong , Cheng Enjiang
Published: December 2010

Abstract:  In the last thirty years, remarkable achievements have been made in China's poverty reduction course. The dramatic fall in China's poor can be attributed mainly to a high rate of economic growth, government poverty reduction policies and targeted programmes and pro‐poor macroeconomic and industrial policies. This paper focuses on China's poverty reduction policies and programmes and their impact on the poor regions and poor households. Lessons are drawn for poverty reduction and economic development in African countries. The paper also explores the potential for collaboration in poverty reduction between China and African countries and recommendations are made for the governments and donor agencies.
Back to the Future: Wells, Sociology, Utopia and Method
Authors: Levitas Ruth
Published: December 2010

This article explores the involvement of H.G. Wells in the early institutional development of sociology in Britain. It addresses Wells's aspiration to a Chair of Sociology as the context for his claim that that ‘the creation of utopias – and their exhaustive criticism – is the proper and distinctive method of sociology’, and the implications of a hundred years of suppression of utopianism and normativity within the discipline. It argues that Wells was substantially right, and that if sociology embraced the more utopian method of the Imaginary Reconstitution of Society, it would inform a greater range of social alternatives for confronting ecological and economic crises.
(How) is Childminding Family Like? Family Day Care, Food and the Reproduction of Identity at the Public/Private Interface
Authors: O'Connell Rebecca
Published: December 2010

This article is about family day care and the reproduction of identity at the intersection of public and private domains. It uses mealtimes as a lens to elucidate the social relations which popular fictive kinship ideologies at once suggest and obscure. Drawing on ethnographic fieldwork with childminders in an inner London borough, the paper explores some of the ways in which boundaries – principally of class and ethnicity – are dissolved and reproduced in everyday food practices within and between families. The paper suggests that food is an important medium for symbolic and material boundary work in home based childcare. Describing a continuum from incorporation to segregation, the paper suggests that the ‘objective’ description of home based childcare (as asymmetrical) and the subjective representation (as family like) are not mutually exclusive, but mutually constitutive, constructions.
Consenting to Domination? Theorising Power, Agency and Embodiment with Reference to Caste
Authors: Rafanell Irene , Gorringe Hugo
Published: December 2010

Conventional analyses of domination ultimately conceive of individuals internalizing aspects of their contextual social environments (desires or norms) which determine their future behaviour in a pre-conscious fashion. We suggest that this conception of domination is mistaken and stems from a commitment to theoretical models which view individuals' actions as the result rather than a cause, of durable social structures. We offer a critical analysis of Lukes and Bourdieu as paradigmatic theorists of power who hold such a view, and contrast their work to that of Barnes and Foucault. Drawing on the latter we develop an intrinsic model of power which views interaction as central to social phenomena and understands social processes as arising from the continuous interaction of heterogeneous and calculative but mutually susceptible individuals.

This approach re-conceptualises three central dichotomies in studies of power: consensus versus conflict, agency versus compliance and mind versus embodiment. We argue, contrary to extrinsic views of power, that calculative agency is essential to both compliance and consensus and view both domination and resistance as integral to power dynamics. Contrary to theories of false consciousness we understand bodies, rather than minds, as central to the routinization of power dynamics. Whilst the paper primarily develops theoretical debates on power we briefly illustrate our position by reference to empirical data on untouchables in India.
Faith, Science and the Political Imagination: Moderate Republicans and the Politics of Embryonic Stem Cell Research
Authors: Smith Alexander Thomas T.
Published: December 2010

The rise of the Christian Right and the pro-life movement over the last fifty years has transformed US politics in general, and the Republican Party in particular. Its seemingly all-pervasive influence on contemporary US politics has commanded much social scientific attention. However, policy debates over embryonic stem cell research during the Presidency of George W. Bush exposed deep, moral fissures amongst American conservatives. As one of the most recent ‘hot button’ issues in America's culture wars, embryonic stem cell research appeared to energize the under-studied moderate wing of the ‘Grand Old Party’ (GOP), which belatedly emerged to challenge what often seems like a homogeneous and monolithic Christian Right. This paper argues that during the 109th United States Congress, moderate Republicans identified in embryonic stem cells a powerful entity around which to mobilise themselves as a set of otherwise diverse interests. This enabled them to imagine a political future for themselves in which they could successfully challenge the hegemony of the Christian Right in grassroots Republican Party politics. In states like Missouri, however, which fought a referendum on embryonic stem cell research in the 2006 midterm elections, it could be argued that emboldened GOP moderates overplayed their hand. Furthermore, a fully-formed GOP moderate counter-movement to the Christian Right failed to materialize as centrists and moderates were amongst the first to lose their seats when the Democrats reclaimed Congress at the 2006 midterms.
Social Fluidity and Social Displacement
Authors: Smith Dennis
Published: December 2010

The recent prominence of analyses emphasising social fluidity within the social sciences has obscured the continuing relevance of the dynamics of social displacement. This paper contrasts the two approaches, traces their different trajectories as they have permeated sociology and adjacent disciplines, and, finally, proposes a research agenda investigating social displacement processes in the context of globalization.
BETTER THAN DYNAMIC MEAN‐VARIANCE: TIME INCONSISTENCY AND FREE CASH FLOW STREAM
Authors: Cui Xiangyu , Li Duan , Wang Shouyang , Zhu Shushang
Published: December 2010

As the dynamic mean‐variance portfolio selection formulation does not satisfy the principle of optimality of dynamic programming, phenomena of time inconsistency occur, i.e., investors may have incentives to deviate from the precommitted optimal mean‐variance portfolio policy during the investment process under certain circumstances. By introducing the concept of time inconsistency in efficiency and defining the induced trade‐off, we further demonstrate in this paper that investors behave irrationally under the precommitted optimal mean‐variance portfolio policy when their wealth is above certain threshold during the investment process. By relaxing the self‐financing restriction to allow withdrawal of money out of the market, we develop a revised mean‐variance policy which dominates the precommitted optimal mean‐variance portfolio policy in the sense that, while the two achieve the same mean‐variance pair of the terminal wealth, the revised policy enables the investor to receive a free cash flow stream (FCFS) during the investment process. The analytical expressions of the probability of receiving FCFS and the expected value of FCFS are derived.
RISK HORIZON AND REBALANCING HORIZON IN PORTFOLIO RISK MEASUREMENT
Authors: Glasserman Paul
Published: December 2010

This paper analyzes portfolio risk and volatility in the presence of constraints on portfolio rebalancing frequency. This investigation is motivated by the incremental risk charge (IRC) introduced by the Basel Committee on Banking Supervision. In contrast to the standard market risk measure based on a 10‐day value‐at‐risk calculated at 99% confidence, the IRC considers more extreme losses and is measured over a 1‐year horizon. More importantly, whereas 10‐day VaR is ordinarily calculated with a portfolio’s holdings held fixed, the IRC assumes a portfolio is managed dynamically to a target level of risk, with constraints on rebalancing frequency. The IRC uses discrete rebalancing intervals (e.g., monthly or quarterly) as a rough measure of potential illiquidity in underlying assets. We analyze the effect of these rebalancing intervals on the portfolio’s profit and loss distribution over a risk‐measurement horizon. We derive limiting results, as the rebalancing frequency increases, for the difference between discretely and continuously rebalanced portfolios; we use these to approximate the loss distribution for the discretely rebalanced portfolio relative to the continuously rebalanced portfolio. Our analysis leads to explicit measures of the impact of discrete rebalancing under a simple model of asset dynamics.
VALUATION OF CONTINUOUSLY MONITORED DOUBLE BARRIER OPTIONS AND RELATED SECURITIES
Authors: Boyarchenko Mitya , Levendorskiĭ Sergei
Published: December 2010

In this paper, we apply Carr's randomization approximation and the operator form of the Wiener‐Hopf method to double barrier options in continuous time. Each step in the resulting backward induction algorithm is solved using a simple iterative procedure that reduces the problem of pricing options with two barriers to pricing a sequence of certain perpetual contingent claims with first‐touch single barrier features. This procedure admits a clear financial interpretation that can be formulated in the language of embedded options. Our approach results in a fast and accurate pricing method that can be used in a rather wide class of Lévy‐driven models including Variance Gamma processes, Normal Inverse Gaussian processes, KoBoL processes, CGMY model, and Kuznetsov's β‐class. Our method can be applied to double barrier options with arbitrary bounded terminal payoff functions, which, in particular, allows us to price knock‐out double barrier put/call options as well as double‐no‐touch options.
ON THE EXISTENCE OF THE ENDOGENOUS MORTGAGE RATE PROCESS
Authors: Goncharov Yevgeny
Published: December 2010

The mortgage rate is a major factor in the refinancing decision. The refinancing behavior influences cash flow and, therefore, mortgage price. The prices of mortgage instruments drives the mortgage rates. We consider a problem of the existence of a dynamic mortgage rate process which resolves this circular dependence. The existence is proved by constructing a solution using a newly proposed level set method.
HAZARD PROCESSES AND MARTINGALE HAZARD PROCESSES
Authors: Coculescu Delia , Nikeghbali Ashkan
Published: December 2010

In this paper, we build a bridge between different reduced‐form approaches to pricing defaultable claims. In particular, we show how the well‐known formulas by Duffie, Schroder, and Skiadas and by Elliott, Jeanblanc, and Yor are related. Moreover, in the spirit of Collin Dufresne, Hugonnier, and Goldstein, we propose a simple pricing formula under an equivalent change of measure.

Two processes will play a central role: the hazard process and the martingale hazard process attached to a default time. The crucial step is to understand the difference between them, which has been an open question in the literature so far. We show that pseudo‐stopping times appear as the most general class of random times for which these two processes are equal. We also show that these two processes always differ when τ is an honest time, providing an explicit expression for the difference. Eventually we provide a solution to another open problem: we show that if τ is an arbitrary random (default) time such that its Azéma's supermartingale is continuous, then τ avoids stopping times.
ASYMPTOTICS OF IMPLIED VOLATILITY IN LOCAL VOLATILITY MODELS
Authors: Gatheral Jim , Hsu Elton P. , Laurence Peter , Ouyang Cheng , Wang Tai‐Ho
Published: December 2010

Using an expansion of the transition density function of a one‐dimensional time inhomogeneous diffusion, we obtain the first‐ and second‐order terms in the short time asymptotics of European call option prices. The method described can be generalized to any order. We then use these option prices approximations to calculate the first‐ and second‐order deviation of the implied volatility from its leading value and obtain approximations which we numerically demonstrate to be highly accurate.
‘My heart is always where he is’. Perspectives of mothers of young people with severe intellectual disabilities and challenging behaviour living at home
Authors: Hubert Jane
Published: December 2010

Accessible summary

The researcher visited twenty families over 2 years. In all of the families, there was a son or daughter (from 15 to 22 years old) who had severe or profound intellectual disabilities. This meant that the mothers had to do most things for them. They bathed and dressed them and helped them to eat. Many spent time in the night with them as well. Most of the young people could not speak at all. Many of them had epilepsy. They were very difficult to look after because they tried to hurt themselves or other people, or break up the furniture.

The researcher wanted to find out how the mothers coped with all they had to do and how they felt about their son or daughter. In spite of all they had to do the mothers felt very close to them and were determined not to let them go into long‐term care away. The mothers thought that if they lived somewhere else they would not be cared for and loved as they were now. They also thought that bad things might happen to them, and because they could not talk no one would know. The mothers felt that people who lived in long‐stay homes were not at all like their children. Many of them hoped that they would live longer than their son or daughter, so that they could stay at home and be looked after by their mothers all their lives.

Most of the families only saw their own sisters and brothers and other relatives now and again. They felt that other people did not really like having anything to do with them. This meant that they needed help and support from the social and health services, but they felt they had been let down by them as well.

Little research has focussed on the perspectives of families caring for someone with severe or profound intellectual disabilities and challenging behaviour. The main aim of this research was to gain understanding of the experiences and perspectives of families, especially mothers, of young people with these complex needs, including attitudes to long‐term residential care. Ethnographic methods were used, consisting of intensive interviews over 2 years, mainly with mothers, and participant observation. The analysis used grounded theory. The mothers’ main focus was on their son or daughter with intellectual disabilities. Most were socially isolated, even from close kin. Their negative attitudes to institutions and fears for the safety and well‐being of their sons and daughters led to determination not to put them into long‐term care. Mothers struggled to care for the young people at home, in spite of difficulties, family tensions and social isolation. Lack of effective services, especially around transition to adulthood, increased parents’ protectiveness.
Promoting service user inclusion in risk assessment and management: a pilot project developing a human rights‐based approach
Authors: Greenhill Beth , Whitehead Richard
Published: December 2010

Accessible summary

When people are risk assessed, they are sometimes denied their human rights.

In this paper, we say that if we balance the human rights of service users,1 their carers and people in their community we can manage risk much better.

This means that people who use services are involved in their own risk assessments.

It also means people’s human rights are looked at in the way they are supported.

Recent reports highlight the extent to which many people with learning disabilities are not afforded access to their basic human rights. In addition, traditional approaches to risk management often focus on professional assessments of risks and challenging behaviour and exclude service user perspectives. In this paper, we outline what we believe to be the key principles of a human rights‐based approach (HRBA) to risk assessment and management. We argue that if we balance the human rights of service users, their carers and members of their communities, we can, in effect, manage risk within a much more positive paradigm. A HRBA to risk emphasises service user inclusion, recognises the impact of diverse identities on risk behaviours and makes the human rights in risk management decisions explicit. We believe a human rights approach offer a coherent unifying framework for much current best practice; prompting all involved to design proactive, proportional risk management strategies which balance the rights involved in the person’s risky behaviours with the rights involved in the management strategy. The tools we have developed within our service, structuring a HRBA to risk assessment and management, are briefly presented. Case examples are included to illustrate key points.
Large vertebrate responses to forest cover and hunting pressure in communal landholdings and protected areas of the Yucatan Peninsula, Mexico
Authors: Urquiza‐Haas T. , Peres C. A. , Dolman P. M.
Published: December 2010

Although tropical forest vertebrate populations are often heavily impacted by both habitat loss and subsistence hunting, in many human‐dominated landscapes their fate depends on the wider habitat matrix outside protected areas. This study used line‐transect surveys to examine patterns of vertebrate species richness and encounter rates (ER) throughout Mexico's Yucatan Peninsula across a broad spectrum of anthropogenic forest disturbances. Censuses were carried out at eight forest sites, including two localities within the Sian Ka'an Biosphere Reserve, a communally managed protected area, a private forest reserve and three communal‐tenure landholding units. Species richness increased with increasing forest cover in the surrounding landscape, but was not affected by the degree of hunting pressure. Responses to different forms of disturbance varied markedly across species and functional groups. Aggregate ER of old‐growth specialists were positively correlated with forest cover, but unrelated to hunting pressure. Hunting pressure was strongly related to aggregate ER of game species, particularly of preferred prey, and a meta‐analysis of species‐specific correlations showed a significant effect of hunting pressure on the ER across individual game species. Sampling within old‐growth forest of Sian Ka'an yielded relatively high ER for almost all species. In comparison, low ER were obtained for several species at Sian Ka'an sites consisting of a higher proportion of open habitat. Landholding units showed low relative abundances, but species ER varied depending on disturbance type. The communally managed reserve exhibited high ER for both game and non‐game species. Synthesis of these results with comparable data from 19 additional Mesoamerican sites shows that species‐specific ER found across the Yucatan Peninsula are within the ranges observed elsewhere, with a consistent pattern of lower abundances in hunted sites. It is critical that private, communal and public‐sector reserves are integrated into a coordinated management approach across the wider landscape in this biodiversity hotspot and throughout the Mesoamerican Biological Corridor.
Chronic nicotine treatment differentially modifies acute nicotine and alcohol actions on GABAAand glutamate receptors in hippocampal brain slices
Authors: Proctor William R , Dobelis Peter , Moritz Anna T , Wu Peter H
Published: December 2010

BACKGROUND AND PURPOSETobacco and alcohol are often co‐abused producing interactive effects in the brain. Although nicotine enhances memory while ethanol impairs it, variable cognitive changes have been reported from concomitant use. This study was designed to determine how nicotine and alcohol interact at synaptic sites to modulate neuronal processes.

EXPERIMENTAL APPROACHAcute effects of nicotine, ethanol, and both drugs on synaptic excitatory glutamatergic and inhibitory GABAergic transmission were measured using whole‐cell recording in hippocampal CA1 pyramidal neurons from brain slices of mice on control or nicotine‐containing diets.

KEY RESULTSAcute nicotine (50 nM) enhanced both GABAergic and glutamatergic synaptic transmission; potentiated GABAAreceptor currents via activation of α7* and α4β2* nAChRs, and increasedN‐methyl‐d‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptor currents through α7* receptors. While ethanol (80 mM) also increased GABAAcurrents, it inhibited NMDA currents. Although ethanol had no effect on AMPA currents, it blocked nicotine‐induced increases in NMDA and AMPA currents. Following chronic nicotine treatment, acute nicotine or ethanol did not affect NMDA currents, while the effects of GABAergic responses were not altered.

CONCLUSIONS AND IMPLICATIONSAcute ethanol ingestion selectively attenuated nicotine enhancement of excitatory glutamatergic NMDA and AMPA receptor function, suggesting an overall reduction in excitatory output from the hippocampus. It also indicated that ethanol could decrease the beneficial effects of nicotine on memory performance. In addition, chronic nicotine treatment produced tolerance to the effects of nicotine and cross‐tolerance to the effects of ethanol on glutamatergic activity, leading to a potential increase in the use of these drugs.
Retrochalcone derivatives are positive allosteric modulators at synaptic and extrasynaptic GABAA receptors in vitro
Authors: Jiang Ruotian , Miyamoto Akiko , Martz Adeline , Specht Alexandre , Ishibashi Hitoshi , Kueny‐Stotz Marie , Chassaing Stefan , Brouillard Raymond , de Carvalho Lia Prado , Goeldner Maurice , Nabekura Junichi , Nielsen Mogens , Grutter Thomas
Published: December 2010

BACKGROUND AND PURPOSE Flavonoids, important plant pigments, have been shown to allosterically modulate brain GABAA receptors (GABAARs). We previously reported that trans‐6,4′‐dimethoxyretrochalcone (Rc‐OMe), a hydrolytic derivative of the corresponding flavylium salt, displayed nanomolar affinity for the benzodiazepine binding site of GABAARs. Here, we evaluate the functional modulations of Rc‐OMe, along with two other synthetic derivatives trans‐6‐bromo‐4′‐methoxyretrochalcone (Rc‐Br) and 4,3′‐dimethoxychalcone (Ch‐OMe) on GABAARs.

EXPERIMENTAL APPROACH Whole‐cell patch‐clamp recordings were made to determine the effects of these derivatives on GABAARs expressed in HEK‐293 cells and in hippocampal CA1 pyramidal and thalamic neurones from rat brain.

KEY RESULTS Rc‐OMe strongly potentiated GABA‐evoked currents at recombinant α1–4β2γ2s and α4β3δ receptors but much less at α1β2 and α4β3. Rc‐Br and Ch‐OMe potentiated GABA‐evoked currents at α1β2γ2s. The potentiation by Rc‐OMe was only reduced at α1H101Rβ2γ2s and α1β2N265Sγ2s, mutations known to abolish the potentiation by diazepam and loreclezole respectively. The modulation of Rc‐OMe and pentobarbital as well as by Rc‐OMe and the neurosteroid 3α,21‐dihydroxy‐5α‐pregnan‐20‐one was supra‐additive. Rc‐OMe modulation exhibited no apparent voltage‐dependence, but was markedly dependent on GABA concentration. In neurones, Rc‐Br slowed the decay of spontaneous inhibitory postsynaptic currents and both Rc‐OMe and Rc‐Br positively modulated synaptic and extrasynaptic diazepam‐insensitive GABAARs.

CONCLUSIONS AND IMPLICATIONS The trans‐retrochalcones are powerful positive allosteric modulators of synaptic and extrasynaptic GABAARs. These novel modulators act through an original mode, thus making them putative drug candidates in the treatment of GABAA‐related disorders in vivo.
Protein kinase C regulates the internalization and function of the human organic anion transporting polypeptide 1A2
Authors: Zhou Fanfan , Lee Andy C , Krafczyk Katja , Zhu Ling , Murray Michael
Published: December 2010

BACKGROUND AND PURPOSEThe human organic anion transporting polypeptide 1A2 (OATP1A2) is expressed in cells from several regions of the human body, including the kidney, cholangiocytes and the blood‐brain barrier, and mediates the cellular flux of various anionic substances, including drugs in clinical use. Several related mammalian transporters have been shown to be subject to post‐translational regulation, including kinase‐induced internalization. In the present study the role of protein kinase C (PKC) in the regulation of OATP1A2 was investigated in anin vitrocell model.

EXPERIMENTAL APPROACHCOS‐7 cells in which OATP1A2 was overexpressed were treated with the PKC‐specific activator (phorbol 12‐myristate 13‐acetate; PMA) and the PKC‐specific inhibitor (Go6976). The impact of these treatments on the function and regulation of OATP1A2 was determined.

KEY RESULTSPKC activation decreased the transport function of OATP1A2 in a time‐ and concentration‐dependent manner. PMA (0.1 µM) decreased theVmaxof oestrone‐3‐sulphate uptake and decreased the cell surface expression of OATP1A2 immunoreactive protein; these effects of PMA were prevented by the PKC specific inhibitor Go6976. In further studies, PMA treatment accelerated the internalization of OATP1A2 but did not affect its recycling. The disruption of clathrine‐dependent endocytosis attenuated both the constitutive and PKC‐modulated internalization of OATP1A2. In contrast, blocking the caveolin‐dependent pathway was without effect.

CONCLUSIONS AND IMPLICATIONSPKC regulates the transport function of OATP1A2 by modulating protein internalization; this effect of PKC is mediated in part by clathrine‐dependent pathways.
EDHF: spreading the influence of the endothelium
Authors: Garland Christopher J , Hiley C Robin , Dora Kim A
Published: December 2010

Our view of the endothelium was transformed around 30 years ago, from one of an inert barrier to that of a key endocrine organ central to cardiovascular function. This dramatic change followed the discoveries that endothelial cells (ECs) elaborate the vasodilators prostacyclin and nitric oxide. The key to these discoveries was the use of the quintessentially pharmacological technique of bioassay. Bioassay also revealed endothelium‐derived hyperpolarizing factor (EDHF), particularly important in small arteries and influencing blood pressure and flow distribution. The basic idea of EDHF as a diffusible factor causing smooth muscle hyperpolarization (and thus vasodilatation) has evolved into one of a complex pathway activated by endothelial Ca2+opening two Ca2+‐sensitive K+‐channels, KCa2.3 and KCa3.1. Combined application of apamin and charybdotoxin blocked EDHF responses, revealing the critical role of these channels as iberiotoxin was unable to substitute for charybdotoxin. We showed these channels are arranged in endothelial microdomains, particularly within projections towards the adjacent smooth muscle, and close to interendothelial gap junctions. Activation of KCachannels hyperpolarizes ECs, and K+efflux through them can act as a diffusible ‘EDHF’ stimulating Na+/K+‐ATPase and inwardly rectifying K‐channels. In parallel, hyperpolarizing current can spread from the endothelium to the smooth muscle through myoendothelial gap junctions upon endothelial projections. The resulting radial hyperpolarization mobilized by EDHF is complemented by spread of hyperpolarization along arteries and arterioles, effecting distant dilatation dependent on the endothelium. So the complexity of the endothelium still continues to amaze and, as knowledge evolves, provides considerable potential for novel approaches to modulate blood pressure.

LINKED ARTICLESThis article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visithttp://dx.doi.org/10.1111/bph.2011.164.issue‐3
Limited Influence? The Role of the Party of European Socialists in Shaping Social Democracy in Central and Eastern Europe
Authors: Holmes Michael , Lightfoot Simon
Published: December 2010

This article looks at the role of the Party of European Socialists (PES) in its attempts to shape social democratic parties in Central and Eastern Europe (CEE) towards a West European norm. It discusses how existing views in the academic literature on the role of transnational parties are inadequate. We argue that the PES did not play a key role in encouraging the establishment and development of parties in the CEE states from the 2004 enlargement in the early stages of accession. We contend that the overall influence of party federations has been limited, and that these limitations were as much in evidence before enlargement took place as they were afterwards.
Democracy by Delegation? Who Represents Whom and How in European Governance
Authors: Bellamy Richard , Castiglione Dario
Published: December 2010

The democratic legitimacy of European governance is often said to rest on its ‘output’. However, such arguments also make the implicit ‘input’ claim that the community method and new modes of governance offer a more participatory and deliberative style of democratic politics to standard democratic processes, which is best suited to represent the European interest. We test such claims by analysing them from three different perspectives: functional, societal and delegatory. We conclude that they are grounded on a substantive conception of representation in which the agents of European governance ‘stand’ or ‘act’ for the European public. However, such claims are empty without formal democratic processes of authorization and accountability that ensure European governance effectively promotes the democratic values of political equality and responsiveness.
Frequent manual repositioning and incidence of pressure ulcers among bed‐bound elderly hip fracture patients
Authors: Rich Shayna E. , Margolis David , Shardell Michelle , Hawkes William G. , Miller Ram R. , Amr Sania , Baumgarten Mona
Published: December 2010

Frequent manual repositioning is an established part of pressure ulcer prevention, but there is little evidence for its effectiveness. This study examined the association between repositioning and pressure ulcer incidence among bed‐bound elderly hip fracture patients, using data from a 2004–2007 cohort study in nine Maryland and Pennsylvania hospitals. Eligible patients (n=269) were age ≥65 years, underwent hip fracture surgery, and were bed‐bound at index study visits (during the first 5 days of hospitalization). Information about repositioning on the days of index visits was collected from patient charts; study nurses assessed presence of stage 2+ pressure ulcers 2 days later. The association between frequent manual repositioning and pressure ulcer incidence was estimated, adjusting for pressure ulcer risk factors using generalized estimating equations and weighted estimating equations. Patients were frequently repositioned (at least every 2 hours) on only 53% (187/354) of index visit days. New pressure ulcers developed at 12% of visits following frequent repositioning vs. 10% following less frequent repositioning; the incidence rate of pressure ulcers per person‐day did not differ between the two groups (incidence rate ratio 1.1, 95% confidence interval 0.5–2.4). No association was found between frequent repositioning of bed‐bound patients and lower pressure ulcer incidence, calling into question the allocation of resources for repositioning.
Development and validation of a pressure ulcer risk assessment tool for acute hospital patients
Authors: Page Karen Nicola , Barker Anna Lucia , Kamar Jeannette
Published: December 2010

The purpose of this study was to develop and validate a pressure ulcer risk assessment for acute hospitals. This tool was developed in a cohort of 342 patients with a mean age 63 years (SD 19.82) and validated in a second cohort of 165 patients with a mean age 68 years (SD 18.40). Risk factors for inclusion on The Northern Hospital Pressure Ulcer Prevention Plan (TNH‐PUPP) were identified from the literature then examined and weighted using logistic regression. Risk factors included on the TNH‐PUPP were requires assistance to move in bed (odds ratio [OR] 5.15; 95% confidence interval [CI]: 2.49–10.65), admission to intensive care during current admission (OR 2.98; 95% CI: 1.33–6.67), aged ≥65 years (OR 2.81; 95% CI: 1.24–6.36), reduced sensation (OR 2.29; 95% CI: 1.19–4.42), and cognitive impairment (OR 2.26; 95% CI: 1.09–4.67). The TNH‐PUPP was validated in a prospective sample. The new tool had high diagnostic validity (area under the receiver operating curve=0.86), consistent in the validation sample (area under the receiver operating curve=0.90). The TNH‐PUPP has a moderate positive predictive value (development=0.50; validation=0.13), and a high negative predictive value (development=0.94; validation=0.99) enabling low‐risk patients to be screened out, as noncandidates for pressure ulcer prevention interventions. An accurate pressure ulcer risk assessment has been developed and validated, which identifies a high‐risk group to whom limited pressure ulcer prevention resources should be directed. The TNH‐PUPP facilitates effective resource allocation and is likely to reduce unnecessary patient harm and costs from pressure ulcers in acute hospitals.