bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging Humanitarianism: NGO Identity and the Iconography of Childhood
Authors: Manzo Kate
Published: September 2008

Abstract:  This paper asks how images of children are used by prominent signatories to NGO codes of conduct. The answer is that images of childhood and shared codes of conduct are both means through which development and relief NGOs produce themselves as rights‐based organisations. The iconography of childhood expresses institutional ideals and the key humanitarian values of humanity, neutrality and impartiality, and solidarity. Images of children are useful for NGOs in reinforcing the legitimacy of their ‘emergency’ interventions as well as the very idea of development itself. But the dominant iconography is also inherently paradoxical, as the child image can be read as both a colonial metaphor for the majority world and as a signifier of humanitarian identity. The question then for NGOs using this image in social justice campaigns is whether overtly political accompanying texts can nullify the contradictory subliminal messages that emanate from the iconography of childhood.
The Guests' Guests: Palestinian Refugees, Lebanese Civilians, and the War of 2006
Authors: Ramadan Adam
Published: September 2008

Abstract:  In the war between Israel and Hizbullah in 2006, 10,000 displaced Lebanese citizens were granted shelter and hospitality by Palestinian refugees in the camps of southern Lebanon. For the duration of the war, the Palestinian guests became hosts to their own hosts, and this temporary reversal of the usual relations of refuge set the scene for the rebuilding and renegotiation of relations between Palestinian refugees and their host country and its citizens. This paper addresses these events through a focus on the nature, politics and ethics of Palestinian hospitality and argues that hospitality was not simply a selfless act of giving, but also an instrumental act that had the potential to transform Palestinian–Lebanese relations in lasting ways.
The Provocations of Neoliberalism: Contesting the Nation and Liberation after Apartheid
Authors: Hart Gillian
Published: September 2008

Abstract:  This paper is part of an ongoing effort to make sense of the turbulent forces at play in South Africa in relation to other parts of the world. Engaging debates over neoliberalism from a South African vantage point, I show how currently influential theories cast in terms of class project, governmentality, and hegemony are at best partial. A more adequate understanding is not just a matter of combining these different dimensions into a more encompassing model of “neoliberalism in general”. The challenge, rather, is coming to grips with how identifiably neoliberal projects and practices operate on terrains that always exceed them. A crucially important dimension of what is going on in South Africa is that escalating struggles over the material conditions of life and livelihood are simultaneously struggles over the meaning of the nation and liberation, as well as expressions of profound betrayal. These processes underscore the analytical and political stakes in attending to interconnected historical geographies of specifically racialized forms of dispossession, and how they feature in the present. The paper concludes with a call for a properly post‐colonial frame of understanding that builds on the synergies and complementarities between a Gramscian reading of Fanon and relational conceptions of the production of space set forth by Lefebvre.
Exploring the cost effectiveness of land conservation auctions and payment policies*
Authors: Connor Jeffery D. , Ward John R. , Bryan Brett
Published: September 2008

This article evaluates the cost‐effectiveness of the Catchment Care Australian conservation auction. It provides evidence of auction cost effectiveness, and estimates cost savings from two discrete components: (i) the opportunity cost revelation incentive provided by the auction mechanism, and (ii) the improved environmental targeting capacity that results from development of a scientifically based environmental benefits assessment capacity. Results show that there are potentially very large returns associated with the latter component that have been overlooked in the literature.

Additionally, transaction costs involved with administering the case study conservation auction and the prior non‐auction payment policy are compared. We find that the administration costs for the auction were greater than or equal to those associated with the prior policy. Estimates of relative cost effectiveness across policies are shown to be sensitive to the methods of comparison. In this case study, there is inelastic supply of the last units of environmental benefit. This inelasticity results in large estimated auction comparative cost advantage when the benefit metric is the estimated cost required to achieve auction aggregate environmental benefit. Estimated benefit of the auction is much less when measured as environmental benefits attainable with alternative payment policies subject to the auction budget constraint.
China's agriculture, smallholders and trade: driven by the livestock revolution?*
Authors: Rae Allan
Published: September 2008

China's sustained rapid economic growth and development has contributed to the surge in consumption and production of livestock in that country  termed the livestock revolution. Consumption trends are first reviewed, and changes in food consumption patterns include a marked shift away from grains and towards meats and dairy products. A question is to what extent this rapid increase in demand for livestock products is reflected in China's agri‐food trade statistics? While her agri‐food imports have dramatically increased since China's accession to the WTO, livestock products have not made a noticeable contribution, although the import of certain animal feedstuffs has. This implies China's continuing self‐sufficiency in most livestock products. The paper next considers developments in China's livestock farming sector and policies that have been contributing to these supply‐side developments. The paper concludes with an examination of issues that may be important to the future development of China's, and the world's, livestock situation;  this includes future demand developments, and the question of whether future demand growth in China might be met with local production, imports of final product, and/or imports of feedstuffs.
Bringing competition to urban water supply*
Authors: Sibly Hugh , Tooth Richard
Published: September 2008

This paper proposes a market‐based reform that would introduce competition into the provision of urban water. This proposal calls for a decoupling of infrastructure control and ownership of water whereby the property rights to water would be transferred to private hands. The proposal involves periodically allocation (e.g. by auction) of existing water stock held in urban catchments to virtual suppliers who then compete in providing bulk water. This change when coupled with effective third party access and retail competition would lead to a competitive market for the provision of urban water. The approach aims to address concerns over inefficient pricing and infrastructure provision under the current arrangement.
Design efficiency for non‐market valuation with choice modelling: how to measure it, what to report and why*
Authors: Scarpa Riccardo , Rose John M.
Published: September 2008

We review the basic principles for the evaluation of design efficiency in discrete choice modelling with a focus on efficiency of WTP estimates from the multinomial logit model. The discussion is developed under the realistic assumption that researchers can plausibly define a prior belief on the range of values for the utility coefficients. D‐, A‐, B‐, S‐ and C‐errors are compared as measures of design performance in applied studies and their rationale is discussed. An empirical example based on the generation and comparison of fifteen separate designs from a common set of assumptions illustrates the relevant considerations to the context of non‐market valuation, with particular emphasis placed on C‐efficiency. Conclusions are drawn for the practice of reporting in non‐market valuation and for future work on design research.
Optimal management of annual ryegrass (Lolium rigidum Gaud.) in phase rotations in the Western Australian Wheatbelt*
Authors: Doole Graeme J.
Published: September 2008

Lucerne (Medicago sativa L.) helps to prevent soil salinisation in the Western Australian Wheatbelt by reducing recharge to saline water tables. There is broad consensus, though, that it is not sufficiently profitable to motivate producers to plant it at the intensity at which considerable off‐site benefits would be conferred. This paper employs a multiple‐phase optimal control model to explore the value of this perennial pasture for the management of herbicide‐resistant annual ryegrass (Lolium rigidum Gaud.) in a crop–pasture rotation, given the difficulty of observing this value in practice. The availability of selective herbicides for efficient weed control is found to determine whether or not it is profitable to adopt lucerne pasture under optimal management. Herbicide resistance requires producers to employ costly, non‐selective treatments for in‐crop weed control. Thus, it motivates the adoption of perennial pasture in which cost‐effective forms of control can be implemented. Moreover, this result is robust to feasible changes in the current economic environment.
Demand for fish in Asia: a cross‐country analysis*
Authors: Dey Madan Mohan , Garcia Yolanda T. , Praduman Kumar , Piumsombun Somying , Haque Muhammad Sirajul , Li Luping , Radam Alias , Senaratne Athula , Khiem Nguyen Tri , Koeshendrajana Sonny
Published: September 2008

Fish demand patterns in nine Asian countries were investigated using a multistage budgeting framework allowing a disaggregated approach to analysing fish consumption. This paper highlights the heterogeneity of fisheries products in terms of species, sources and cultural responses of consumers, factors that are important in fish demand under the Asian setting. Specifically, fish demand by income groups were compared to determine how the low‐ and high‐income households respond to price and income changes. Results showed that the estimated price and income elasticities of all fish types included in the study were relatively more elastic among the poorer households.
A Latent Gaussian Model for Compositional Data with Zeros
Authors: Butler Adam , Glasbey Chris
Published: September 2008

Compositional data record the relative proportions of different components within a mixture and arise frequently in many fields. Standard statistical techniques for the analysis of such data assume the absence of proportions which are genuinely zero. However, real data can contain a substantial number of zero values. We present a latent Gaussian model for the analysis of compositional data which contain zero values, which is based on assuming that the data arise from a (deterministic) Euclidean projection of a multivariate Gaussian random variable onto the unit simplex. We propose an iterative algorithm to simulate values from this model and apply the model to data on the proportions of fat, protein and carbohydrate in different groups of food products. Finally, evaluation of the likelihood involves the calculation of difficult integrals if the number of components is more than 3, so we present a hybrid Gibbs rejection sampling scheme that can be used to draw inferences about the parameters of the model when the number of components is arbitrarily large.
Design and Analysis of Clustered, Unmatched Resource Selection Studies
Authors: Clark Robert G. , Strevens Tanya C.
Published: September 2008

Studies which measure animals’ positions over time are a vital tool in understanding the process of resource selection by animals. By comparing a sample of locations that are used by animals with a sample of available points, the types of locations that are preferred by animals can be analysed by using logistic regression. Random-effects logistic regression has been proposed to deal with the repeated measurements that are observed for each animal, but we find that this is not feasible in studies where the sample of available points cannot readily be matched to specific animals. Instead, we investigate the use of marginal logistic models with robust variance estimators, by using a study of Australian bush rats as a case-study. Simulation is used to check the properties of the approach and to explore alternative designs.
Analysis of Interval-Censored Data from Clustered Multistate Processes: Application to Joint Damage in Psoriatic Arthritis
Authors: Sutradhar Rinku , Cook Richard J.
Published: September 2008

A conditionally Markov multiplicative intensity model is described for the analysis of clustered progressive multistate processes under intermittent observation. The model is motivated by a long-term prospective study of patients with psoriatic arthritis with the aim of characterizing progression of joint damage via an irreversible four-state model. The model accommodates heterogeneity in transition rates between different individuals and correlation in transition rates within patients. To do this we introduce subject-specific multivariate random effects in which each component acts multiplicatively on a specific transition intensity. Through the association between the components of the random effect, correlations in transition intensities are accommodated. A Monte Carlo EM algorithm is developed for estimation, which features closed form expressions for estimators at each M-step.
Dual Response Surface Optimization with Hard-to-Control Variables for Sustainable Gasifier Performance
Authors: Coetzer R. L. J. , Rossouw R. F. , Lin D. K. J.
Published: September 2008

Dual response surface optimization of the Sasol–Lurgi fixed bed dry bottom gasification process was carried out by performing response surface modelling and robustness studies on the process variables of interest from a specially equipped full-scale test gasifier. Coal particle size distribution and coal composition are considered as hard-to-control variables during normal operation. The paper discusses the application of statistical robustness studies as a method for determining the optimal settings of process variables that might be hard to control during normal operation. Several dual response surface strategies are evaluated for determining the optimal process variable conditions. It is shown that a narrower particle size distribution is optimal for maximizing gasification performance which is robust against the variability in coal composition.
Identifying and Diagnosing Population Declines: A Bayesian Assessment of Lapwings in the UK
Authors: King Ruth , Brooks Stephen P. , Mazzetta Chiara , Freeman Stephen N. , Morgan Byron J. T.
Published: September 2008

We combine data from separate ring recovery and survey studies to provide indices of estimated abundance for the UK lapwing Vanellus vanellus population. Using a descriptive state space model, we demonstrate the observed decline in population size in relation to directly interpretable parameters describing the demographic characteristics of the population. The Bayesian approach readily provides information that is directly relevant to the conservation of this important bird species. The method proposed extends previous work in this area in several ways. Restrictive normality assumptions that have traditionally been imposed are removed, in addition to the assumption of constant measurement error by using information relating to the index variability across time to account fully for this source of uncertainty within the model. We also provide model-averaged inference to help to inform management policy and uses.
Social capital and business and management: Setting a research agenda
Authors: Lee Robert
Published: September 2008

This paper adopts the template of systematic reviewing and provides an up‐to‐date synthesis of the literature on social capital and business and management. The review demonstrates that social capital research is concentrated into three core dimensions: structural, relational and cognitive. First, structural social capital includes social interaction and the frequency of contact and connectivity levels among and between actors’ network relations. Secondly, relational social capital refers to the underlying normative conditions of trust, obligation, expectation and identity that guide actors’ network relations. Thirdly, cognitive social capital refers to the meaningful contexts of communication among and between actors, and includes the shared language, codes and narratives used to create understanding. However, the rich linkages between structural, relational and cognitive social capital across equivalent/hierarchical social space and geographical boundaries are neglected. A further research focus identified is that the role of face‐to‐face and the increasingly routine tool of electronic mediated communication may produce different characteristics and levels of social capital. The paper also discusses the ways in which critical realism and mixed methodology may enhance understanding of the process‐based linkages between structural, relational and cognitive social capital.
Heat transport at boiling, near‐critical conditions
Authors: COUMOU D. , DRIESNER T. , HEINRICH C. A.
Published: September 2008

Two‐phase flow and near‐critical phenomena are likely to enhance energy transport in high‐temperature hydrothermal systems. We present a series of two‐dimensional simulations of two‐phase flow of pure water at near‐critical conditions. The results show that at near‐critical conditions, two‐phase convection can be more efficient in transporting energy than single‐phase convection. The highest heat fluxes are attained when two‐phase heat‐pipes form near the bottom boundary, recharging the root of the upflow zone and thereby enabling the formation of broad upflow regions. When the system becomes more vapor‐dominated, it loses this ability, upflow zones become narrower and the energy efficiency drops to more moderate values.
Psychiatric and behavioural symptoms and the use of psychotropic medication in Special Care Units and Regular Units in Norwegian nursing homes
Authors: Selbæk Geir , Kirkevold Øyvind , Engedal Knut
Published: September 2008

Background:  In a number of countries Special Care Units (SCUs) have been established to meet the particular needs of patients with dementia. The criteria for SCUs are poorly defined and often not met.

Aim:  To assess the frequency distributions of dementia, psychiatric and behavioural symptoms and the use of psychotropic medication in SCUs and Regular Units (RUs) across different regions.

Methods and material:  By means of a structured interview, comprising the Neuropsychiatric Inventory, the Clinical Dementia Rating Scale and Lawton’s Physical Self‐maintenance scale, a representative sample of 1163 nonselected nursing home patients was assessed. In addition, information was collected from the patients’ records.

Results:  Overall SCU patients were significantly more likely to be younger, to have higher level of functioning, to have dementia, to exhibit clinically significant psychiatric and behavioural symptoms and to receive psychotropic medication. There were significant differences across regions in terms of psychiatric and behavioural symptoms and the use of psychotropic medication. The ratio of accommodation in SCUs to that in RUs varied across the regions.

Conclusion:  Patients in SCUs and patients in RUs are distinct nursing home populations. Regional differences, which might be due to diverse ratios of SCUs, are evident.
Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice
Authors: Strong Randy  , Miller Richard A.  , Astle Clinton M.  , Floyd Robert A.  , Flurkey Kevin  , Hensley Kenneth L.  , Javors Martin A.  , Leeuwenburgh Christiaan  , Nelson James F.  , Ongini Ennio  , Nadon Nancy L.  , Warner Huber R.  , Harrison David E. 
Published: September 2008

The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age‐related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4‐OH‐α‐phenyl‐N‐tert‐butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex, with 80% power, using data from two of the three sites. Pooling data from all three sites, a log‐rank test showed that both NDGA (p = 0.0006) and aspirin (p = 0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan; neither NDGA (p = 0.12) nor aspirin (p = 0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age‐related outcomes reproducibly in mice.
Phase equilibria modelling of kyanite‐bearing anatectic paragneisses from the central Grenville Province
Authors: INDARES A. , WHITE R. W. , POWELL R.
Published: September 2008

Kyanite‐bearing paragneisses from the Manicouagan Imbricate Zone and its footwall (high‐P belt of the central Grenville Province) preserve evidence of partial melting with development of metamorphic textures involving biotite–garnet ± kyanite ± plagioclase ± K‐feldspar–quartz. Garnet in these rocks displays a variety of zoning patterns with respect to Ca. Pseudosection modelling in the Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–O (NCKFMASHTO) system using measured bulk rock compositions accounts for the textural evolution of two aluminous and two sub‐aluminous samples from the presumed thermal peak to conditions at which retained melt solidified. The prograde features are best explained by pseudosections calculated with compositions to account for melt loss. The intersection of isopleths of grossular content and Fe/(Fe + Mg) relating to large porphyroblasts of garnet provide constraints on the P–T conditions of the metamorphic peak. These P–T estimates are considered to be minima because of the potential for diffusional modification of the composition of garnet at high‐T and during the early stages of cooling. However, they are consistent with textural observations and pseudosection topology, with peak assemblages best preserved in rocks for which the calculated pseudosections predict only small changes in mineral proportions in the P–T interval, in which retrograde reactions are inferred to have occurred between the thermal peak and the solidus. Maximum P–T conditions (14.5–15.5 kbar and 840–890 °C) and steep retrograde P–T paths inferred for rocks from the Manicouagan Imbricate Zone are comparable with those determined for mafic rocks from the same area. In contrast, maximum P–T conditions of 12.5–13 kbar and 815–830 °C and flatter P–T paths are inferred for the rocks of the footwall to the Manicouagan Imbricate Zone. The general consistency between textures, mineral compositions and the topologies of the calculated pseudosections suggests that the pseudosection approach is an appropriate tool for inferring the P–T evolution of high‐P anatectic quartzo‐feldspathic rocks.
Effect of sleep stage on interictal high‐frequency oscillations recorded from depth macroelectrodes in patients with focal epilepsy
Authors: Bagshaw Andrew P. , Jacobs Julia , LeVan Pierre , Dubeau François , Gotman Jean
Published: September 2008

Purpose:  To investigate the effect of sleep stage on the properties of high‐frequency oscillations (HFOs) recorded from depth macroelectrodes in patients with focal epilepsy.

Methods:  Ten‐minute epochs of wakefulness (W), stage 1–2 non‐REM (N1‐N2), stage 3 non‐REM (N3) and REM sleep (R) were identified from stereo‐electroencephalography (SEEG) data recorded at 2 kHz in nine patients. Rates of spikes, ripples (>80 Hz), and fast ripples (>250 Hz) were calculated, as were HFO durations, degree of spike–HFO overlap, HFO rates inside and outside of spikes, and inside and outside of the seizure‐onset zone (SOZ).

Results:  Ripples were observed in nine patients and fast ripples in eight. Spike rate was highest in N1‐N2 in 5 of 9 patients, and in N3 in 4 of 9 patients, whereas ripple rate was highest in N1‐N2 in 4 of 9 patients, in N3 in 4 of 9 patients, and in W in 1 of 9 patients. Fast ripple rate was highest in N1‐N2 in 4 of 8 patients, and in N3 in 4 of 8 patients. HFO properties changed significantly with sleep stage, although the absolute effects were small. The difference in HFO rates inside and outside of the SOZ was highly significant (p < 0.000001) in all stages except for R and, for fast ripples, only marginally significant (p = 0.018) in W.

Conclusions:  Rates of HFOs recorded from depth macroelectrodes are highest in non‐REM sleep. HFO properties were similar in stages N1‐N2 and N3, suggesting that accurate sleep staging is not necessary. The spatial specificity of HFO, particularly fast ripples, was affected by sleep stage, suggesting that recordings excluding REM sleep and wakefulness provide a more reliable indicator of the SOZ.
Infantile spasms in tuberous sclerosis complex: Prognostic utility of EEG
Authors: Muzykewicz David A. , Costello Daniel J. , Halpern Elkan F. , Thiele Elizabeth A.
Published: September 2008

Purpose:  To assess cognitive and epilepsy outcomes in tuberous sclerosis complex (TSC) patients with a history of infantile spasms (IS), in relation to spasm history, electroencephalography (EEG) characteristics, genetic mutation, and treatment history.

Methods:  The authors conducted a retrospective review of 45 children and adults with TSC and a history of IS. EEG reports from the time of spasms were evaluated for all patients, and EEG tracings were accessible and evaluated for 20 patients.

Results:  Clinical outcome was unfavorable for the majority of patients. However, 33% had experienced at least one year of seizure freedom at follow‐up, and 24% of those tested had IQs above 70. Hypsarrhythmia severity scores varied widely, with some EEGs severely hypsarrhythmic and others essentially normal. Lower IQ was significantly associated with higher hypsarrhythmia severity scores on EEG report, the presence of background disorganization on EEG report, the absence of normal sleep patterns on EEG, and a lower degree of treatment success on vigabatrin. A relationship between poor cognitive outcome and poor epilepsy outcome was confirmed. The correlation between poor epilepsy outcome and a greater degree of background disorganization on EEG approached significance, as did the association between subsequent intractable epilepsy and an older age at IS cessation. A greater than expected ratio of TSC2 to TSC1 patients was observed across this IS population.

Discussion:  Early detection and successful treatment portend a more favorable outcome in TSC patients with IS. Although EEG findings in these patients vary, specific characteristics may serve as clinically useful prognostic markers.
Gene Therapy Reduces Ethanol Intake in an Animal Model of Alcohol Dependence
Authors: Ocaranza Paula , Quintanilla María Elena , Tampier Lutske , Karahanian Eduardo , Sapag Amalia , Israel Yedy
Published: September 2008

Background: Some gene polymorphisms strongly protect against the development of alcoholism. A large proportion of East Asians carry a protective inactivating mutation in aldehyde dehydrogenase (ALDH2*2). These subjects display high levels of blood acetaldehyde when consuming alcohol, a condition that exerts a 66 to 99% protection against alcohol abuse and alcoholism. Present knowledge allows the incorporation of therapeutic genes that can modify the expression of disease predisposing genes, an effect that can last from months to years. In line with the above, we have tested if inhibiting the expression of the aldehyde dehydrogenase gene (ALDH2) by an anti‐Aldh2antisense gene can curtail the drive of alcohol‐dependent animals to consume alcohol.

Methods: Wistar‐derived rats bred as high alcohol drinkers (UChB; Universidad de Chile Bibulous) were rendered alcohol dependent by a 2‐month period of voluntary ethanol (10%) intake, subjected to a 3‐day withdrawal period and further allowed access to 10% ethanol for only 1 hour each day. This condition results in a high ethanol intake (1.2 g/kg/60 min) which is 10 times higher than that of naïve UChB rats.

Results: The single intravenous administration of an anti‐Aldh2antisense gene carried by an adenoviral vector reduced liver ALDH2 activity by 85% (p < 0.002) and inhibited voluntary ethanol intake by 50% (ANOVAp < 0.005) for 34 days.

Conclusions: This proof‐of‐principle study indicates that gene therapy approaches can be employed to achieve a long‐term reduction of alcohol intake in alcohol‐dependent animals and suggests that gene vectors may be developed as long‐lasting therapeutic adjuncts for the treatment of alcoholism.
Naltrexone Is Associated With Reduced Drinking by Alcohol Dependent Patients Receiving Antidepressants for Mood and Anxiety Symptoms: Results From VA Cooperative Study No. 425, “Naltrexone in the Treatment of Alcoholism”
Authors: Krystal John H. , Gueorguieva Ralitza , Cramer Joyce , Collins Joseph , Rosenheck Robert ,   The VA CSP No. 425 Study Team
Published: September 2008

Background:  It is not clear whether naltrexone is effective in reducing alcohol consumption among patients with clinically significant mood symptoms and whether naltrexone favorably interacts with antidepressant medications when they are co‐prescribed.

Methods:  This study reflects a secondary analysis of the first 13 weeks of VA CSP #425, a study that evaluated the efficacy of naltrexone 50 mg/d in 627 alcohol dependent military veterans receiving Twelve Step Facilitation therapy at 20 VA Medical Centers. This study included patients with comorbid mood and anxiety disorders, providing they did not need treatment for these comorbid conditions at the time of study entry. Sixty patients developed sufficiently severe mood symptoms while on study medication that they required antidepressant treatment. This analysis evaluated whether the efficacy of naltrexone and placebo was influenced by the prescription of antidepressant medications to some study patients for their mood and anxiety symptoms.

Results:  In patients randomized to placebo (n = 209), prescription of antidepressants was associated with a significantly higher percentage of drinking days (lsmean = 24.4, se = 4.85 vs. lsmean = 12.9, se = 1.69, p = 0.02). Although the group of patients receiving naltrexone (n = 418) was larger than the group assigned to placebo, there were no significant differences in drinking‐related outcomes in the groups who did or did not receive antidepressants (lsmean = 11.5, se = 1.18 vs. lsmean = 12.9, se = 1.69, p = 0.47). Among the group of patients receiving antidepressants, naltrexone prescription was associated with a reduction in the percent drinking days compared to placebo [lsmean = 10.1, se = 3.47 vs. lsmean = 24.4, se = 4.85, F(1,556) = 5.84, p = 0.02].

Conclusions:  Further investigation will be needed to determine whether naltrexone is efficacious among depressed alcohol dependent patients and whether naltrexone and antidepressant medications show interactive efficacy for treating alcohol dependence.
Time Trends in Heavy Drinking Among Middle‐Aged and Older Adults in Denmark
Authors: Bjørk Christina , Thygesen Lau Caspar , Vinther‐Larsen Mathilde , Grønbæk Morten N.
Published: September 2008

Background:  Studies have indicated an increasing proportion of heavy drinking among middle‐aged and older Danes. Trends in consumption are often extremely sensitive to influence from various components of the time trends but only few have explored the age, period and cohort‐related influences on late life alcohol consumption. By using age, period, and cohort modeling this study explores the time trends in heavy drinking.

Methods:  Data derive from five National Health and Morbidity Surveys conducted by the Danish National Institute of Public Health in 1987, 1994, 2000, 2003, and 2005. A total of 15,144 randomly selected Danes between the age of 50 and 74 were interviewed about their alcohol intake on the last weekday and their alcohol intake in the last week. By applying the age‐period‐cohort model the probability of heavy alcohol drinking is estimated to separate the influence of age, period (calendar time) and cohort (year of birth).

Results:  The unadjusted probability of heavy drinking declines by age and increases by calendar year and year of birth for both men and women. However, the negative effect of age is attenuated for women when adjusted for birth cohort, indicating that the proportion of heavy drinking women increases in younger birth cohorts. This trend is not observed for men as their drinking pattern mainly increase slightly by calendar year.

Conclusions:  Our Danish observations for older aged individuals correspond to the social and cultural changes in the 1960s and 1970s that possibly have affected the drinking behavior of the cohorts. Time trend analyses, such as this may serve as an excellent opportunity to extrapolate and forecast alcohol mortality and morbidity.
The Effects of Ethanol Consumption on Vasculogenesis Potential in Nonhuman Primates
Authors: Williams J. Koudy , Baptista Pedro M. , Daunais James B. , Szeliga Kendall T. , Friedman David P. , Soker Shay
Published: September 2008

Background:  Vasculogenesis is essential to the preservation and repair of damaged or diseased vessels. Alcohol is the most commonly abused drug among young adults, but its effects on vessel growth and repair are unknown. The basis of vascular repair is endothelial progenitor cell (EPC) recruitment to assist in the formation of new vascular network (vasculogenesis). Therefore, the objective of this study was to measure the effects of ethanol consumption on the production, mobilization and vasculogenesis potential EPCs in nonhuman primates.

Methods:  Four to five year‐old (young adult) male rhesus monkeys consumed monkey chow and water (Control, n = 7), or chow and water + ethanol (Alcohol, 2.45 g/d, n = 7) for 12 months. Peripheral blood (PB) and bone marrow (BM) samples were collected for fluorescence‐activated cell‐sorting analysis of cell surface antigens (CD45, CD31, CD44, CD133, VEGF‐R2 – or KDR); and for capillary formation on Matrigel‐coated plates.

Results:  There were greater numbers of nonhematopoeitic stromal cells (CD45−) and putative mesenchymal progenitor cells (CD45−/CD44+) in the PB and BM of Alcohol versus Control monkeys (p < 0.05). Additionally, there were greater numbers of EPCs (CD45−/CD133+/KDR+) in the BM and PB of Alcohol versus Control monkeys (p < 0.05). However, the EPCs of Alcohol monkeys were less likely to form capillaries on matrigel‐coated plates than Control monkeys (p < 0.05).

Conclusions:  Ethanol consumption in monkeys markedly increased the production and mobilization of EPCs, but decreased their ability to form capillaries. The pathophysiologic consequences of such effects are unclear, but may represent an ethanol‐induced chronic stress on the BM, resulting in EPC.
Normal Acute Behavioral Responses to Moderate/High Dose Ethanol in GABAAReceptor α4 Subunit Knockout Mice
Authors: Chandra Dev , Werner David F. , Liang Jing , Suryanarayanan Asha , Harrison Neil L. , Spigelman Igor , Olsen Richard W. , Homanics Gregg E.
Published: September 2008

Background: γ‐Aminobutyric acid type A receptors (GABAA‐Rs) have been implicated in mediating some of the behavioral effects of ethanol (EtOH), but the contribution of specific GABAA‐R subunits is not yet fully understood. The GABAA‐R α4 subunit often partners with β2/3 and δ subunits to form extrasynaptic GABAA‐Rs that mediate tonic inhibition. Several in vitro studies have suggested that these extrasynaptic GABAA‐Rs may be particularly relevant to the intoxicating effects of low doses of EtOH. In α4 subunit knockout mice, tonic inhibition was greatly reduced, as were the potentiating effects of EtOH. We therefore hypothesized that those behavioral responses to EtOH that are mediated by α4‐containing GABAA‐Rs would be diminished in α4 knockout mice.

Methods: We investigated behavioral responses to acute administration of moderate/high dose EtOH or pentylenetetrazol in α4 subunit knockout mice. We compared behavioral responses to EtOH in α4 knockout and wild‐type littermates in the elevated plus maze (0.0, 1.0 g/kg EtOH), screen test (1.5, 2.0 g/kg), hypothermia (1.5, 2.0 g/kg), fixed speed rotarod (1.5, 2.0, 2.5 g/kg), open field (0.0, 1.0, 2.0 g/kg), radiant tail flick (2.0 g/kg), loss of righting reflex (3.5 g/kg), and EtOH metabolism and clearance assays. Sensitivity to pentylenetetrazol‐induced seizures was also analyzed.

Results: No differences were observed between α4 knockout mice and wild‐type controls in terms of the baseline behavior in the absence of EtOH treatment or in the behavioral effects of EtOH in the assays tested. In contrast, α4 knockout mice were significantly more sensitive to pentylenetetrazol‐induced seizures.

Conclusions: We conclude that GABAA‐Rs containing the α4 subunit are not absolutely required for the acute behavioral responses to moderate/high dose EtOH that were assessed with the elevated plus maze, screen test, hypothermia, fixed speed rotarod, open field, radiant tail flick, and loss of right reflex assays. We further suggest that these findings are complicated by the demonstrated compensatory alterations in synaptic GABAA‐R EtOH sensitivity and function in α4 knockout mice.
Lesions of the Extended Amygdala in C57BL/6J Mice Do Not Block the Intermittent Ethanol Vapor‐Induced Increase in Ethanol Consumption
Authors: Dhaher Ronnie , Finn Deborah , Snelling Christopher , Hitzemann Robert
Published: September 2008

Background:  The central extended amygdala (cEA) which includes the central nucleus of the amygdala (CeA) and the lateral posterior bed nucleus of the stria terminalis (BNSTLP), has been proposed to play a key role in excessive ethanol consumption in humans (Koob and Le Moal, 2005 Nat Neurosci 8:1442). To examine this relationship, we used a murine model of ethanol dependence (Becker and Lopez, 2004 Alcohol Clin Exp Res 28:1829; Lopez and Becker, 2005 Psychopharmacology (Berl) 181:688) and compared animals with sham lesions and electrolytic lesions of the CeA and BNSTLP.

Methods:  Male C57BL/6J (B6) mice were first acclimated to a limited‐access 2‐bottle‐choice preference procedure. The access period began 3 hours into the dark phase of the light‐dark cycle and continued for 2 hours. Once acclimated (1 week), mice underwent chronic exposure to and intermittent withdrawal from ethanol vapor. The animals were then retested in the limited‐access 2‐bottle‐choice preference procedure. In some experiments, electrolytic and sham lesions of the CeA or BNSTLP were performed prior to initiating the 2‐bottle choice procedure.

Results:  In a series of 5 preliminary experiments, mice were randomly assigned either to the standard intermittent ethanol vapor procedure or to the standard procedure but with air in the vapor chamber (control). The air‐control procedure produced no change in ethanol intake when compared to baseline consumption. In contrast, intermittent ethanol vapor exposure increased ethanol consumption by almost 50%. The increase in consumption was associated with an increase in total fluid volume consumed and no change in ethanol preference. Lesions of both the BNSTLP and CeA significantly decreased baseline ethanol consumption, the former by decreasing fluid consumption and the latter by decreasing ethanol preference. Intermittent ethanol vapor exposure significantly increased consumption in both the BNSTLP‐ and CeA‐lesioned animals, largely by increasing the total volume of fluid consumed.

Conclusions:  The results obtained clearly demonstrate that the cEA has a role in the regulation of ethanol consumption in the limited‐access procedure. However, neither lesions of the CeA nor BNSTLP prevented the intermittent ethanol vapor‐induced increase in consumption. These data do not preclude some role of the cEA in the increased ethanol consumption following intermittent ethanol vapor exposure, but would suggest that other brain regions also must have a significant influence.
Effects of Ethanol on Cytokine Production After Surgery in a Murine Model of Gram‐Negative Pneumonia
Authors: Spies Claudia D. , Lanzke Nadine , Schlichting Uwe , Muehlbauer Steffen , Pipolo Carlotta , Von Mettenheim Moritz , Lehmann Anett , Morawietz Lars , Nattermann Herbert , Sander Michael
Published: September 2008

Background:  Both alcohol abuse and surgery have been shown to impair immune function. The frequency of postoperative infectious complications is 2‐ to 5‐fold increased in long‐term alcoholic patients, leading to prolonged hospital stay. Following surgery, an increase in interleukin (IL)‐6 has been shown to be associated with increased tissue injury and interleukin 1‐(IL‐10) is known to represent an anti‐inflammatory signal. The purpose of this study was to test the hypothesis that several days of excess alcohol consumption results in more pronounced immunosuppression. We assume that alcoholic animals show increased levels of IL‐10 in response to infection and increased IL‐6 due to a more pronounced lung pathology.

Methods:  Thirty‐two female Balb/c mice were pretreated with ethanol (EtOH) at a dose of (3.8 mg/g body weight) or saline (NaCl) for 8 days. At day 8 of the experiment all mice underwent a median laparotomy. Two days postsurgery mice were either applicated 104 CFU Klebsiella pneumoniae or received sham‐infection with saline. A total number of 4 groups (EtOH/K. pneumoniae; NaCl/K. pneumoniae; EtOH/Sham‐infection, NaCl/Sham‐infection) was investigated and a clinical score evaluated. Twenty‐four hours later mice were killed; lung, spleen, and liver were excised for protein isolation and histological assessment. IL‐6 and IL‐10 levels were detected by ELISA.

Results:  Alcohol‐exposed mice exhibited a worsened clinical appearance. The histological assessment demonstrated a distinct deterioration of the pulmonary structure in alcohol‐treated animals. In the lung, IL‐6 and IL‐10 was significantly increased in alcohol‐exposed infected mice compared to saline‐treated infected mice. The clinical score correlated significantly with IL‐6 (r = 0.71; p < 0.01) and IL‐10 levels (r = 0.64; p < 0.01) in the lung.

Conclusions:  Ethanol treatment in this surgical model led to a more severe pulmonary infection with K. pneumoniae which was associated with more tissue destruction and increased levels of IL‐6 and IL‐10 and a worsened clinical score.
Regulation of Motivation to Self‐Administer Ethanol by mGluR5 in Alcohol‐Preferring (P) Rats
Authors: Besheer Joyce , Faccidomo Sara , Grondin Julie J. M. , Hodge Clyde W.
Published: September 2008

Background:  Emerging evidence indicates that Group I metabotropic glutamate receptors (mGluR1 and mGluR5) differentially regulates ethanol self‐administration in several rodent behavioral models. The purpose of this work was to further characterize involvement of Group I mGluRs in the reinforcing effects of ethanol using a progressive ratio schedule of reinforcement.

Methods:  Alcohol‐preferring (P) rats were trained to self‐administer ethanol (15% v/v) versus water on a concurrent schedule of reinforcement, and the effects of the Group I mGluR antagonists were evaluated on progressive ratio performance. The rats were then trained to self‐administer sucrose (0.4% w/v) versus water, and the effects of the antagonists were tested on progressive ratio performance.

Results:  The mGluR1 antagonist, 3,4‐dihydro‐2H‐pyrano[2,3]b quinolin‐7‐yl (cis‐4‐methoxycyclohexyl) methanone (JNJ 16259685; 0 to 1 mg/kg) and the mGluR5 antagonist, 6‐methyl‐2‐(phenylethynyl) pyridine (MPEP; 0 to 10 mg/kg) dose‐dependently reduced ethanol break point. In separate locomotor activity assessments, the lowest effective dose of JNJ 16259685 (0.3 mg/kg) produced a motor impairment, whereas the lowest effective dose of MPEP (3 mg/kg) did not. Thus, the reduction in ethanol break point by mGluR1 antagonism was probably a result of a motor impairment. JNJ 16259685 (0.3 mg/kg) and MPEP (10 mg/kg) reduced sucrose break point and produced motor impairments. Thus, the reductions in sucrose break point produced by both Group I antagonists were probably because of nonspecific effects on motor activity.

Conclusions:  Together, these results suggest that glutamate activity at mGluR5 regulates motivation to self‐administer ethanol.
A Comparison of Results From an Alcohol Survey of a Prerecruited Internet Panel and the National Epidemiologic Survey on Alcohol and Related Conditions
Authors: Heeren Timothy , Edwards Erika M. , Dennis J. Michael , Rodkin Sergei , Hingson Ralph W. , Rosenbloom David L.
Published: September 2008

Background:  Given today’s telecommunications environment, random digit dial (RDD) telephone surveys face declining response rates and coverage, and increasing costs. As an alternative to RDD, we surveyed participants in a randomly recruited standing Internet panel supplemented with a randomly sampled telephone survey of nonpanel members for a study of associations between onset of alcohol use and later alcohol‐related problems. The purpose of this paper was to compare results from our survey with results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a face‐to‐face probability sample survey of 43,093 adults, with a focus on associations between demographics, age of drinking onset, and alcohol dependence.

Methods:  Demographic and drinking characteristics from our survey of 4,021 ever‐drinkers between the ages of 18 and 39 years were compared with the characteristics of 11,549 similarly aged ever‐drinkers from the NESARC. Weighted analyses accounting for sampling design compared these 2 samples on drinking characteristics over the past year and during a respondent’s heaviest period of drinking, and in multivariate models examining associations between demographics, age of drinking onset, and lifetime alcohol dependence.

Results:  Participants in the supplemented Internet panel were similar to the national population of 18‐ to 39‐year‐old ever drinkers on gender, education, and race/ethnicity, while adults who were aged 18 to 25 years were under‐represented in the Internet panel. The supplemented Internet panel reported higher rates of moderate risk drinking over the past 12 months, lifetime high‐risk drinking, and lifetime (ever) alcohol dependence. Estimates of the associations between alcohol dependence and age of drinking onset, risky drinking, and family history of alcohol problems did not significantly differ between the supplemented Internet sample and the NESARC survey.

Conclusions:  Randomly recruited Internet‐based panels may provide an alternative to random digit dial telephone surveys and in‐person surveys for some studies of factors associated with alcohol‐related problems.