bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring long‐distance dispersal and topographic barriers during post‐glacial colonization from the genetic structure of red maple (Acer rubrum L.) in New England
Authors: Gugger Paul F. , McLachlan Jason S. , Manos Paul S. , Clark James S.
Published: July 2008

Aim  This study aims to assess the role of long‐distance seed dispersal and topographic barriers in the post‐glacial colonization of red maple (Acer rubrum L.) using chloroplast DNA (cpDNA) variation, and to understand whether this explains the relatively higher northern diversity found in eastern North American tree species compared with that in Europe.

Location  North‐eastern United States.

Methods  The distribution of intraspecific cpDNA variation in temperate tree populations has been used to identify aspects of post‐glacial population spread, including topographic barriers to population expansion and spread by long‐distance seed dispersal. We sequenced c. 370 cpDNA base pairs from 221 individuals in 100 populations throughout the north‐eastern United States, and analysed spatial patterns of diversity and differentiation.

Results  Red maple has high genetic diversity near its northern range limit, but this diversity is not partitioned by topographic barriers, suggesting that the northern Appalachian Mountains were not a barrier to the colonization of red maple. We also found no evidence of the patchy genetic structure that has been associated with spread by rare long‐distance seed dispersal in previous studies.

Main conclusions  Constraints on post‐glacial colonization in eastern North America seem to have been less stringent than those in northern Europe, where bottlenecks arising from long‐distance colonization and topographic barriers appear to have strongly reduced genetic diversity. In eastern North America, high northern genetic diversity may have been maintained by a combination of frequent long‐distance dispersal, minor topographic obstacles and diffuse northern refugia near the ice sheet.
Characterization of CetA and CetB, a bipartite energy taxis system in Campylobacter jejuni
Authors: Elliott Kathryn T. , DiRita Victor J.
Published: July 2008

The energy taxis receptor Aer, in Escherichia coli, senses changes in the redox state of the electron transport system via an flavin adenine dinucleotide cofactor bound to a PAS domain. The PAS domain (a sensory domain named after three proteins Per, ARNT and Sim, where it was first identified) is thought to interact directly with the Aer HAMP domain to transmit this signal to the highly conserved domain (HCD) found in chemotaxis receptors. An apparent energy taxis system in Campylobacter jejuni is composed of two proteins, CetA and CetB, that have the domains of Aer divided between them. CetB has a PAS domain, while CetA has a predicted transmembrane region, HAMP domain and the HCD. In this study, we examined the expression of cetA and cetB and the biochemical properties of the proteins they encode. cetA and cetB are co‐transcribed independently of the flagellar regulon. CetA has two transmembrane helices in a helical hairpin while CetB is a peripheral membrane protein tightly associated with the membrane. CetB levels are CetA dependent. Additionally, we demonstrated that both CetA and CetB participate in complexes, including a likely CetB dimer and a complex that may include both CetA and CetB. This study provides a foundation for further characterization of signal transduction mechanisms within CetA/CetB.
Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalacia
Authors: Lechpammer M. , Manning S. M. , Samonte F. , Nelligan J. , Sabo E. , Talos D. M. , Volpe J. J. , Jensen F. E.
Published: July 2008

Aims: Periventricular white matter injury in premature infants occurs following hypoxia/ischaemia and systemic infection, and results in hypomyelination, as well as neuromotor and cognitive deficits later in life. Inflammatory infiltrates are seen within human cerebral white matter from periventricular leucomalacia (PVL) cases. Methods: In this study, we examine the time course of CD‐68+ microglial cell responses relative to cell death within white matter following hypoxia/ischaemia in a rat model of PVL. We also tested the efficacy of the minocycline, an agent that suppresses microglial activation, in this model when administered as a post‐insult treatment. Results: We show that preoligodendrocyte injury in the post‐natal day 6 begins within 24 h and continues for 48–96 h after hypoxia/ischaemia, and that microglial responses occur primarily over the first 96 h following hypoxia/ischaemia. Minocycline treatment over this 96 h time window following the insult resulted in significant protection against white matter injury, and this effect was concomitant with a reduction in CD‐68+ microglial cell numbers. Conclusions: These results suggest that anti‐inflammatory treatments may represent a useful strategy in the treatment of PVL, where clinical conditions would favour a post‐insult treatment strategy.
Recombinant pig TFPI efficiently regulates human tissue factor pathways
Authors: Lee K. F. Eddy , Salvaris Evelyn J. , Roussel Jean‐Christian , Robson Simon C. , D’Apice Anthony J. F. , Cowan Peter J.
Published: July 2008

Abstract:  Rejected pig‐to‐primate organ xenografts almost invariably exhibit significant microvascular thrombosis, believed to be due in part to several molecular incompatibilities affecting the regulation of coagulation. In this study, we tested one such proposed incompatibility: whether there is, at least in part, a functional incompatibility in pig tissue factor pathway inhibitor (TFPI) that impedes binding of human factor Xa and regulation of human tissue factor‐initiated coagulation. TFPIα cDNA was cloned from pig aortic endothelial cells and found to encode a 279‐residue mature protein with 79% overall identity to human TFPIα, increasing to 88 to 90% in the functional Kunitz‐1 and Kunitz‐2 domains. Transfected primate cells expressing equivalent levels of GPI‐linked pig or human TFPIα were assayed for binding of human factor Xa and inhibition of the human factor VIIa/tissue factor complex. The activity of the expressed pig anticoagulant was equivalent to that of the human protein in both measures of TFPI function in these systems. These data indicate that there are no apparent incompatibilities between recombinant pig TFPI and the human tissue factor pathway. Other factors must account for the thromboregulatory failure of pig endothelium and aberrant tissue factor activity in xenograft rejection.
Successful treatment for chromoblastomycosis caused by Fonsecaea monophora: a report of three cases in Guangdong, China
Authors: Zhang Junmin , Xi Liyan , Lu Changming , Li Xiqing , Xie Ting , Zhang Hui , Xie Zhi , Sybren De Hoog
Published: July 2008

Fonsecaea pedrosoi is the most prevalent aetiological agent of chromoblastomycosis. Fonsecaea monophora is a new species segregated from Fonsecaea pedrosoi. Herein, we report on three cases of chromoblastomycosis caused by F. monophora that were successfully treated with terbinafine and/or itraconazole. Clinical characteristics and mycological parameters are described. Two of the three patients underwent combination therapy with itraconazole and terbinafine during early stages of treatment and were completely healed in a relatively short course of treatment.
Rural carers online: A feasibility study
Authors: Dow Briony , Moore Kirsten , Scott Peter , Ratnayeke Amodha , Wise Kate , Sims Jane , Hill Keith
Published: July 2008

Objective:  To test the feasibility (for a potential randomised controlled trial) of a computer intervention for improving social interaction and promoting the mental health of rural carers.

Design:  The study combined pre‐ and post‐intervention measures with interviews to determine the feasibility of the intervention and the acceptability of the study design to participants. The intervention consisted of providing 14 rural carers with computers and a 4‐week training program on basic computer skills, using email and the Internet.

Setting:  The study was conducted in a rural community setting.

Participants:  The carers were 12 women and two men, aged from 50 to 81 years, with an average of 65.5 years.

Main outcome measures:  Measures of social isolation (UCLA Loneliness Scale), depression (Geriatric Depression Scale), carer burden (Zarit Burden Interview) and computer confidence were taken at baseline and at a 3‐month follow‐up. Interviews were completed at follow‐up to discuss outcomes of the study. A focus group discussion was conducted with 11 participants to discuss the study and resolve computer issues.

Results:  Most carers reported increased confidence in email and Internet use. There was improvement for most participants in depressive symptoms and social isolation, but little change in carer burden. Participants identified many social benefits associated with the computer intervention, such as intergenerational connection, community building, skills and confidence and preparation for the future.

Conclusion:  The intervention was found to be practical and acceptable for a group of older carers. It was concluded that it would be feasible to conduct a large randomised controlled trial of the intervention.
Juvenile onset globoid cell leukodystrophy masquerading as XL‐adrenoleukodystrophy
Authors: Srinivasan Jayasri , Coleman Lee , Kornberg Andrew J.
Published: July 2008

Abstract:  Krabbe's disease, or globoid cell leukodystrophy (GLD), is an autosomal recessive condition where the commonest presentation is the rapid neurological deterioration typical of the early onset subtype. Later onset subtypes, with more protean presentations and outcomes, also exist. These must be distinguished from other types of leukodystrophies, such as Adrenoleukodystrophy, as the prognosis is extremely variable. We describe a patient with late onset GLD (LOGLD) with imaging findings consistent with a diagnosis of Adrenoleukodystrophy. The importance of interpreting imaging findings in conjunction with the clinical and biochemical information is highlighted.
The physiology and pharmacology of incretins in type 2 diabetes mellitus
Authors: Holst Jens J.
Published: July 2008

Two incretin hormones, glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide (GLP)‐1, help control blood glucose levels by affecting plasma insulin levels in response to oral glucose intake – this is known as the incretin effect. Incretins increase plasma insulin by a number of mechanisms, most of which are mediated through GIP and GLP‐1 receptors (GIPR and GLP‐1R respectively). Incretins act through the pancreas to stimulate insulin release and can also act at the cellular level by increasing insulin gene transcription and insulin biosynthesis. Incretins can also lower plasma glucose through non‐insulin routes including inhibition of gastric emptying and reduced food intake. In type 2 diabetes, the incretin effect is reduced; as a result, insulin secretion is reduced and plasma glucose levels rise. However, the incretin effect can be restored in such individuals by the administration of exogenous incretins. Intravenous GLP‐1 can stimulate insulin secretion, reduce glucagon secretion and normalize fasting plasma glucose in individuals with type 2 diabetes who were previously poorly controlled. The therapeutic potential of such agents is currently being explored.
Mixing Closures for Conservation Laws in Stratified Flows
Authors: Jacobson Tivon , Milewski Paul A. , Tabak Esteban G.
Published: July 2008

A closure for shocks involving the mixing of the fluids in two‐layer stratified flows is proposed. The closure maximizes the rate of mixing, treating the dynamical hydraulic equations and entropy conditions as constraints. This closure may also be viewed as yielding an upper bound on the mixing rate by internal shocks. It is shown that the maximal mixing rate is accomplished by a shock moving at the fastest allowable speed against the upstream flow. Depending on whether the active constraint limiting this speed is the Lax entropy condition or the positive dissipation of energy, we distinguish precisely between internal hydraulic jumps and bores. Maximizing entrainment is shown to be equivalent to maximizing a suitable entropy associated to mixing. By using the latter, one can describe the flow globally by an optimization procedure, without treating the shocks separately. A general mathematical framework is formulated that can be applied whenever an insufficient number of conservation laws is supplemented by a maximization principle.
Private Provision of a Discrete Public Good: Continuous‐Strategy Equilibria in the Private‐Information Subscription Game
Authors: BARBIERI STEFANO , MALUEG DAVID A.
Published: July 2008

We reconsider Laussel and Palfrey's analysis of private provision of discrete public goods via the subscription game. We show their semi‐regular equilibria do not exist, casting doubt on their efficiency analysis. Taking players' values for the public good as uniformly distributed on , we exhibit previously unrecognized continuous equilibria—those with contribution strategies strictly increasing up to their maximum values, not necessarily equal to the provision cost, c, at which point they become flat. We show piecewise‐linear equilibria are not incentive efficient; and if and , then all symmetric equilibria are interim incentive inefficient.
Standard Tax Competition and Increasing Returns
Authors: KROGSTRUP SIGNE
Published: July 2008

The “race to the bottom” result of the standard tax competition literature implies that capital taxes are competed downward as capital becomes more mobile. The new economic geography literature, in contrast, finds that increasing capital mobility can be associated with a rise in capital tax rates, or a “race to the top.” This paper derives the race to the top result from within the standard tax competition modeling framework augmented with agglomeration forces. When agglomeration forces are sufficiently strong, tax competition pressures are mitigated and capital taxes are instead driven by tax exporting incentives.
R×CEcological Inference: Bounds, Correlations, Flexibility and Transparency of Assumptions
Authors: James Greiner D. , Quinn Kevin M.
Published: July 2008

Despite its potential pitfalls, ecological inference is an unavoidable part of some quantitative settings, including US voting rights litigation. In such applications, the analyst will typically encounter two-way tables with more than two rows and columns. Although several ecological inference methods are currently available for 2×2 tables, there are fewer options for analysing general R×C tables, and virtually none that model counts as opposed to fractions. We propose a count R×C method that respects the bounds deterministically, that allows for complex relationships between internal cell quantities, that is easily extensible and that results from transparent assumptions. We study the method via simulation, and then apply it to an example that is drawn from the state of Texas relevant to recent redistricting litigation there.
Robust Monetary Policy with the Cost Channel
Authors: TILLMANN PETER
Published: July 2008

Recent research argues that model uncertainty leads the central bank to adjust interest rates stronger to exogenous disturbances than under certainty. This paper investigates whether the introduction of a cost channel of monetary transmission, whose presence is empirically supported, changes the impact of model uncertainty on interest rate setting. The model is simple enough to facilitate an analytical solution. I find that the presence of the cost channel dampens the effect of model uncertainty on interest rate setting and can offset the activist policy stance. A richer model that allows for persistent supply and demand shocks corroborates these findings.
The Change from Private to Public Governance of British Higher Education: Its Consequences for Higher Education Policy Making 1980–2006
Authors: Shattock Michael
Published: July 2008

This article argues that in moving from being self governed to being state governed the policy drivers for higher education are no longer those of the system itself but are derived from a set of policies designed for the reform and modernisation of the public sector of the economy. The formation of higher education policy therefore needs to be reinterpreted as an adjunct of public policy, rather than as something intrinsic to higher education. The impact of ‘new public management’ approaches and of political interventions are explored in illustrating the consequences of the centralisation of the management of the public services and of higher education becoming an issue in national politics.
Work, family and intentions to withdraw from the workplace
Authors: Forma Pauli
Published: July 2008

In this article, municipal workers’ experience of the relationship between family and work in Finland is analysed. The relationship between the reconciliation of family life and work, and intentions to change jobs or industry or to withdraw from work, are also investigated. Results show that the negative effect of work on family life is more common than the spillover effect of family life on work. Demanding jobs, job insecurity, working as a supervisor, having children, being a single parent, and having informal care responsibilities were found to be risk factors for the challenge of reconciling work and family. Difficulties in reconciling work and family were found to be connected to plans to change jobs or industry and intentions to withdraw from work. It can be concluded that the work−family relationship is an important determinant of the supply of labour.
Direct versus indirect effects of habitat reduction on the loss of avian species from tropical forest fragments
Authors: Feeley K. J. , Terborgh J. W.
Published: July 2008

Tropical forest fragments typically decrease in avian diversity at rates inversely related to area. However, the mechanisms by which area reduction drives avian species loss remain poorly understood. Changes in habitat area may directly lead to species loss through stochastic fluctuations of reduced populations. Alternatively, area‐dependent changes in top‐down and bottom‐up processes associated with fragmentation may indirectly lead to accelerated avian extinctions. For example, on land‐bridge islands in Lago Guri, Venezuela, fragmentation has resulted in complex changes in the biotic environments through altered abundances of nest predators and generalist herbivores. Using path analysis, we quantified the relative importance of these indirect versus direct effects of area reduction on the rates of avian species loss from 11 fragments during the period 1993–2003. Area reduction had a direct effect on species loss but this was relatively minor compared with indirect effects, especially those mediated through changes in herbivore abundances: species loss was slowed on islands occupied by hyperdense howler monkeys and accelerated on islands with leaf‐cutter ants but lacking howlers. The effects of herbivores on bird species loss are likely indirect and resulting from bottom‐up processes. The primacy of indirect effects at Lago Guri suggests that the loss of species from forest fragments may be driven by active biotic processes (i.e. changes in trophic structure) and is not only a passive response to reduction in habitat areaper se. These findings have important implications for the design and management of reserves aimed at protecting birds and other threatened species.
Changing land management of lowland wet grasslands of the UK: impacts on snipe abundance and habitat quality
Authors: Smart J. , Amar A. , O'Brien M. , Grice P. , Smith K.
Published: July 2008

Snipe Gallinago gallinago breeding on lowland wet grasslands in England have undergone widespread and dramatic declines in abundance and distribution since at least the 1970s. There are many potential drivers of the decline but reductions in habitat quality, driven by land management, are often proposed as a contributing factor in the historical declines of breeding waders. Breeding snipe are now restricted to a few key places such as nature reserves and environmentally sensitive areas where management for breeding waders is implemented. On average, populations have continued to decline, even in these key areas, though population trends vary from a decline of 98% to an increase of 61% between the early 1990s and 2006. We examined the relationship between regional variation in snipe population trends and soil conditions, other habitat features and land management. Snipe were more likely to persist in fields where the soil conditions were wet and soft. Fields are wetter and softer now than in the early 1990s and management influenced these conditions. Soil softness increased with decreasing grazing pressure and increasing surface flooding. Soil moisture increased with surface flooding and was higher in organic soils. Changes in field condition were consistent with decreases in grazing pressure and increases in surface flooding. In spite of habitat condition being altered in a way that should have been beneficial to snipe, the numbers have continued to decline. Thus, it is unlikely that the measures of habitat condition examined here have been the driver of the decline and other factors must be involved. Research efforts should now focus on alternative explanations of the decline, for example, changes in other key aspects of habitat quality such as prey abundance, or changes in snipe productivity or mortality.
Colonic and colorectal cancer stem cells: progress in the search for putative biomarkers
Authors: Willis Naomi D. , Przyborski Stefan A. , Hutchison Christopher J. , Wilson Robert G.
Published: July 2008

The maintenance of healthy colonic crypts is dependent on the integrity of the adult epithelial stem cells located within them. Perturbations in stem cell dynamics are generally believed to represent the first step towards colorectal tumorigenesis. Experimental manipulation of intestinal stem cells has greatly increased our understanding of them, but further progress has been slowed due to the absence of a reliable stem cell biomarker. In this review we discuss the candidate colonic stem cell biomarkers which have been proposed. Furthermore, we investigate the putative biomarkers for so‐called colorectal cancer stem cells, a highly aggressive subpopulation of cells considered to drive tumour development.
An in situ hybridization study of Runx2, Osterix, and Sox9 in the anlagen of mouse mandibular condylar cartilage in the early stages of embryogenesis
Authors: Shibata Shunichi , Yokohama‐Tamaki Tamaki
Published: July 2008

Mandibular condylar cartilage is the best‐studied mammalian secondary cartilage, differing from primary cartilage in that it originates from alkaline phosphatase‐positive progenitor cells. We previously demonstrated that three transcription factors related to bone and cartilage formation, namely Runx2, Osterix and Sox9, are simultaneously expressed in the anlage of mandibular condylar cartilage (condylar anlage) at embryonic day (E)14. In this study, expression of these transcription factors was investigated in the anlagen of mandibular bone (mandibular anlagen) from E11.0 to 14.0. Runx2 mRNA was first expressed in the mandibular anlage at E11.5. Osterix mRNA was first expressed at E12.0, and showed a different expression pattern from that of Runx2 from E12.5 to E14.0, confirming that Osterix acts downstream of Runx2. Sox9 mRNA was expressed in Meckel's cartilage and its anlagen throughout the experimental period, but not clearly in the mandibular anlagen until E13.0. At E13.5, the condylar anlage was morphologically identified at the posterior end of the mandibular anlage, and enhanced Sox9 mRNA expression was detected here. At this stage, Runx2 and Osterix mRNA were simultaneously detected in the condylar anlage. These results indicate that the Sox9 mRNA‐expressing condylar anlage is derived from Runx2/Osterix mRNA‐expressing mandibular anlage, and that upregulation of Sox9 in this region acts as a trigger for subsequent condylar cartilage formation.
Continental speciation in the tropics: contrasting biogeographic patterns of divergence in theUroplatusleaf‐tailed gecko radiation of Madagascar
Authors: Raxworthy C. J. , Pearson R. G. , Zimkus B. M. , Reddy S. , Deo A. J. , Nussbaum R. A. , Ingram C. M.
Published: July 2008

A fundamental expectation of vicariance biogeography is for contemporary cladogenesis to produce spatial congruence between speciating sympatric clades. TheUroplatusleaf‐tailed geckos represent one of most spectacular reptile radiations endemic to the continental island of Madagascar, and thus serve as an excellent group for examining patterns of continental speciation within this large and comparatively isolated tropical system. Here we present the first phylogeny that includes complete taxonomic sampling for the group, and is based on morphology and molecular (mitochondrial and nuclear DNA) data. This study includes all described species, and we also include data for eight new species. We find novel outgroup relationships forUroplatusand find strongest support forParoeduraas its sister taxon.Uroplatusis estimated to have initially diverged during the mid‐Tertiary in Madagascar, and includes two major speciose radiations exhibiting extensive spatial overlap and estimated contemporary periods of speciation. All sister species are either allopatric or parapatric. However, we found no evidence for biogeographic congruence between these sympatric clades, and dispersal events are prevalent in the dispersal–vicariance biogeographic analyses, which we estimate to date to the Miocene. One sister‐species pair exhibits isolated distributions that we interpret as biogeographic relicts, and two sister‐species pairs have parapatric distributions separated by elevation. Integrating ecological niche models with our phylogenetic results finds both conserved and divergent niches between sister species. We also found substantial intra‐specific genetic variation, and for the three most widespread species, poor intra‐specific predictive performance for ecological niche models across the latitudinal span of Madagascar. These latter results indicate the potential for intra‐specific niche specialization along environmental gradients, and more generally, this study suggests a complex speciation history for this group in Madagascar, which appears to include multiple speciation processes.
Inhibition of glutaminyl cyclase prevents pGlu‐Aβ formation after intracortical/hippocampal microinjection in vivo/in situ
Authors: Schilling Stephan , Appl Thomas , Hoffmann Torsten , Cynis Holger , Schulz Katrin , Jagla Wolfgang , Friedrich Daniel , Wermann Michael , Buchholz Mirko , Heiser Ulrich , Von Hörsten Stephan , Demuth Hans‐Ulrich
Published: July 2008

Modified amyloid β (Aβ) peptides represent major constituents of the amyloid deposits in Alzheimer’s disease and Down’s syndrome. In particular, N‐terminal pyroglutamate (pGlu) following truncation renders Aβ more stable, increases hydrophobicity and the aggregation velocity. Recent evidence based on in vitro studies suggests that the cyclization of glutamic acid, leading to pGlu‐Aβ, is catalyzed by the enzyme glutaminyl cyclase (QC) following limited proteolysis of Aβ at the N‐terminus. Here, we studied the pGlu‐formation by rat QC in vitro as well as after microinjection of Aβ(1–40) and Aβ(3–40) into the rat cortex in vivo/in situ with and without pharmacological QC inhibition. Significant pGlu‐Aβ formation was observed following injection of Aβ(3–40) after 24 h, indicating a catalyzed process. The generation of pGlu‐Aβ from Aβ(3–40) was significantly inhibited by intracortical microinjection of a QC inhibitor. The study provides first evidence that generation of pGlu‐Aβ is a QC‐catalyzed process in vivo. The approach per se offers a strategy for a rapid evaluation of compounds targeting a reduction of pGlu formation at the N‐terminus of amyloid peptides.
Role of cysteinyl leukotriene receptor antagonists in the management of allergic rhinitis
Authors: Shirasaki H. , Himi T.
Published: July 2008

The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic diseases. Pharmacological studies using CysLTs indicate that there exist two classes of receptors named CysLT1 and CysLT2. The former is sensitive to CysLT1 receptor antagonists currently used for the treatment of asthma and allergic rhinitis. Our previous immunohistochemical and autoradiographic studies showed that anti‐CysLT1 receptor antibody adhered to eosinophils, mast cells, macrophages, neutrophils, and vascular endothelial cells in human nasal mucosa, and that a novel radioactive CysLT1 receptor antagonist, [3H]‐pranlukast, bound specifically to CysLT1 receptors in human inferior turbinate and its binding sites were localized to vascular endothelium and interstitial cells. These data suggest that in allergic rhinitis, the major targets of CysLT1 receptor antagonists are the vascular bed and infiltrating leucocytes such as mast cells, eosinophils, and macrophages. Clinical trials have demonstrated that CysLT1 receptor antagonists are as effective as antihistamines, but are less effective than intranasal steroids for the treatment of allergic rhinitis. The use of CysLT1 receptor antagonists in combination with antihistamines has generally resulted in greater efficacy than when these agents were used alone.
Mechanism of action and resistance to glucocorticoid and selective glucocorticoid receptor modulator to overcome glucocorticoid‐related adverse effects
Authors: Nawata H. , Okabe T. , Yanase T. , Nomura M.
Published: July 2008

Glucocorticoids are lipid substances synthesized by the adrenal cortex that are essential for life and regulate myriad physiological processes ubiquitously in organs and tissues as mediated by intracellular glucocorticoid receptors (GRs). From the clinical standpoint, although glucocorticoids have potent anti‐inflammatory and immunosuppressive effects, their adverse effects profiles and so‐called glucocorticoid resistance are barriers to their widespread use. GRβ, a splice variant isoform of GRα, the predominant isoform of the receptor, and co‐activators and co‐repressors are believed to be important for GR‐mediated actions. The mechanism of action of GRα and its co‐activators and co‐repressors and the mechanism of resistance to glucocorticoid treatment were investigated by confocal microscopic imaging of GRα and GRβ and by assessing protein–protein interaction of GRα and nuclear factor‐κB and of GRα and activator protein‐1 (AP‐1). The possibility of new drug development of selective GR modulators, which reduce GR‐related adverse effects such as steroid‐induced osteoporosis, steroid‐induced diabetes mellitus, and infection yet confer beneficial anti‐inflammatory effects and immunosuppressive action is discussed.
Current status of intranasal glucocorticosteroids in the management of allergic rhinitis
Authors: Okano M.
Published: July 2008

Glucocorticosteroids are the most effective drugs for controlling inflammation of allergic rhinitis (AR). Because of their strong pharmacological action, which can be a so‐called ‘double‐edged sword’, glucocorticosteroids are usually taken intranasally so as to reduce their potential for eliciting adverse effects. Accumulating evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H1‐receptor antagonists, intranasal glucocorticosteroids can improve impaired performance such as daytime sleepiness associated with AR. In Japanese cedar pollinosis, treatment begun immediately after initiation of pollen release or onset of initial symptoms, known as prophylactic (initial) treatment, is recommended. The current version of the practical guideline for management of allergic rhinitis in Japan recommends the use of chemical mediator release inhibitors, second‐generation H1‐receptor antagonists, or leukotriene receptor antagonists for prophylactic treatment. However, recent evidence suggests that intranasal glucocorticosteroids might also be useful as first‐line drugs for prophylactic treatment. The molecular mechanism of anti‐inflammatory action of glucocorticosteroids supports this contention. Moreover, a meta‐analysis of studies of intranasal glucocorticosteroids given as monotherapy has revealed that these agents are superior to oral H1‐receptor antagonists and leukotriene antagonists for controlling major symptoms of AR. These findings suggest that glucocorticosteroids, especially intranasal glucocorticosteroids, might be positioned as first‐line drugs for the treatment of both perennial and seasonal AR.
Relationships between important soil variables in moderately acidic soils (pH ≥5.5) in the highlands of Papua New Guinea and management implications for subsistence farmers
Authors: Bailey J. S. , Ramakrishna A. , Kirchhof G.
Published: July 2008

The fertility of farmed soils in parts of the Papua New Guinea (PNG) highlands reputedly has been declining for some time owing to population pressure. To assess the extent of the problem, a survey of sweet potato gardens was conducted across four of the highlands provinces and information on soil variables was obtained for gardens on soils of volcanic and non‐volcanic origins. In the absence of fertilizer application, soil fertility in the humid tropics is largely a function of soil cation exchange capacity (CEC), and soils of low CEC had previously been reported in this region. In the present study, relationships between effective CEC (ECEC) and other soil properties in moderately acidic soils (pH 5.5–6.3) were investigated to see if there was scope for improving soil cation retention characteristics through management of key soil variables. For volcanic soils of varying allophane content, ECEC was, unexpectedly, negatively correlated with soil C and soil C/N, most probably because of the formation of humus–allophane complexes which had facilitated organic matter accumulation whilst dramatically reducing the free negative charges on the material. Given the latter outcome, the indigenous practice of heaping compost in the centre of soil mounds appeared to be one of the best strategies for circumventing the problem of low CEC, as nutrients in the compost are held in an environment virtually independent of the surrounding soil mineralogy. Although the positive correlation between soil pH and soil ECEC was weak for volcanic soils, it was concluded that liming might nevertheless be an effective means of enhancing the nutrient retention characteristics of these soils provided the practicalities and costs were not prohibitive.
Meeting the challenges of urban river habitat restoration: developing a methodology for the River Thames through central London
Authors: Francis Robert A , Hoggart Simon P G , Gurnell Angela M , Coode Chris
Published: July 2008

The River Thames is a heavily engineered urban system in recovery, though absence of habitat in the reaches through central London has restricted recovery in this area, making habitat creation or improvement a restoration priority. Here we discuss the pre‐disturbance Thames, its current ecological status, and then present a methodology for establishing habitat restoration potential through central London. Habitats primarily supporting ecological communities include inter‐tidal foreshore and artificial structures, and novel techniques for improving these habitats are under development. It is hoped that such approaches along the Thames will provide a template for habitat creation along other large urban rivers.
Explaining the salience of left–right ideology in postindustrial democracies: The role of structural economic change
Authors: HELLWIG TIMOTHY
Published: July 2008

Does left–right ideology structure electoral competition? While many studies show that ideology is a powerful determinant of party choice, a growing number of scholars claim that the salience of ‘left’ and ‘right’ has declined in recent decades. These contrasting views motivate a consideration of whether the salience of the left–right dimension varies across political parties and national contexts. Drawing on recent advances in the study of the welfare state, this article argues that just as policy appeals expressed in the language of left and right crystallised during a period of economic change, changes in the organisation of postindustrial economies should weaken the left–right bases of competition. Analyses of 87 parties in 16 parliamentary democracies show that occupational heterogeneity in postindustrial economies – indicated by employment in the private service sector and in industries exposed to international competition – reduces the salience of the left–right dimension for the vote. The implications of study findings for future work on policy responsiveness and electoral change in advanced capitalist democracies are discussed.
On the linkage between electoral volatility and party system instability in Central and Eastern Europe
Authors: TAVITS MARGIT
Published: July 2008

Abstract.  Electoral volatility is assumed to be a precursor to, or even an indicator of, party system instability. Such an assumption has strong implications for the underlying elite–mass electoral linkage and for the prospects of party system stabilisation in young democracies. This article demonstrates that electoral volatility follows from, rather than leads to, changes in the supply of parties. Thus, the choices of elites may be more responsible for instability in the early stages of party system development than the erratic behaviour of voters.
Review The Role of Medical Directors in Dialysis Facilities Series Editor: Robert A. Gutman: Medical Director Contracting
Authors: Pristave Robert J. , Velez Ruben L.
Published: July 2008

Those nephrologists who are entering into new, or re‐negotiating old, medical director contracts should take into consideration the large number of changes in the environment that have a bearing on the structure and wording of proposed contracts. This contribution offers specific guidance to assist with those efforts.
Hemodialysis Graft with Blind Loop Inflow Segment Treated with Stent Placement
Authors: Wusirika Raghav , Leavitt Matthew , Boyer Charles , Wilson Tamara J. , Gorrell Vickie L. , Segal Jonathan , Weitzel William F.
Published: July 2008

We report a case of occlusion of a graft related to residual thrombus collection at the inflow in a blind pouch formed by conversion of a previous brachial cephalic fistula to a graft. The thrombus was unable to be dislodged by conventional methods with the use of a Fogarty balloon and maceration of thrombus with angioplasty. A covered stent was placed at the inflow segment over this thrombus in order to restore the flow through the graft. Angiographic evidence for this case is also reported.
Alcohol Content Variation of Bar and Restaurant Drinks in Northern California
Authors: Kerr William C. , Patterson Deidre , Koenen Mary Albert , Greenfield Thomas K.
Published: July 2008

Objective:  To estimate the average of and sources of variation in the alcohol content of drinks served on premise in 10 Northern Californian counties.

Methods:  Focus groups of bartenders were conducted to evaluate potential sources of drink alcohol content variation. In the main study, 80 establishments were visited by a team of research personnel who purchased and measured the volume of particular beer, wine, and spirit drinks. Brand or analysis of a sample of the drink was used to determine the alcohol concentration by volume.

Results:  The average wine drink was found to contain 43% more alcohol than a standard drink, with no difference between red and white wine. The average draught beer was 22% greater than the standard. Spirit drinks differed by type with the average shot being equal to one standard drink while mixed drinks were 42% greater. Variation in alcohol content was particularly wide for wine and mixed spirit drinks. No significant differences in mean drink alcohol content were observed by county for beer or spirits but one county was lower than two others for wine.

Conclusions:  On premise drinks typically contained more alcohol than the standard drink with the exception of shots and bottled beers. Wine and mixed spirit drinks were the largest with nearly 1.5 times the alcohol of a standard drink on average. Consumers should be made aware of these substantial differences and key sources of variation in drink alcohol content, and research studies should utilize this information in the interpretation of reported numbers of drinks.
The American Red Cross donor hemovigilance program: complications of blood donation reported in 2006
Authors: Eder Anne F. , Dy Beth A. , Kennedy Jean M. , Notari IV Edward P. , Strupp Annie , Wissel Mary Ellen , Reddy Ramakrishna , Gibble Joan , Haimowitz Marcia D. , Newman Bruce H. , Chambers Linda A. , Hillyer Christopher D. , Benjamin Richard J.
Published: July 2008

BACKGROUND: The American Red Cross (ARC) initiated a comprehensive donor hemovigilance program in 2003. We provide an overview of reported complications after whole blood (WB), apheresis platelet (PLT), or automated red cell (R2) donation and analyze factors contributing to the variability in reported complication rates in our national program.

STUDY DESIGN AND METHODS: Complications recorded at the collection site or reported after allogeneic WB, apheresis PLT, and R2 donation procedures in 36 regional blood centers in 2006 were analyzed by univariate and multivariate logistic regression.

RESULTS: Complications after 6,014,472 WB, 449,594 PLT, and 228,183 R2 procedures totaled 209,815, 25,966, and 12,282 (348.9, 577.5, and 538.3 per 10,000 donations), respectively, the vast majority of which were minor presyncopal reactions and small hematomas. Regional center, donor age, sex, and donation status were independently associated with complication rates after WB, PLT, and R2 donation. Seasonal variability in complications rates after WB and R2 donation correlated with the proportion of donors under 20 years old. Excluding large hematomas, the overall rate of major complications was 7.4, 5.2, and 3.3 per 10,000 collections for WB, PLT, and R2 procedures, respectively. Outside medical care was recorded at similar rates for both WB and automated collections (3.2 vs. 2.9 per 10,000 donations, respectively).

CONCLUSION: The ARC data describe the current risks of blood donation in a model multicenter hemovigilance system using standardized definitions and reporting protocols. Reported reaction rates varied by regional center independently of donor demographics, limiting direct comparison of different regional blood centers.
The effects of additive solution pH and metabolic rejuvenation on anaerobic storage of red cells
Authors: Yoshida Tatsuro , AuBuchon James P. , Dumont Larry J. , Gorham James D. , Gifford Sean C. , Foster Kevin Y. , Bitensky Mark W.
Published: July 2008

BACKGROUND: Red cell (RBC) storage can be extended to 9 weeks under anaerobic or alkaline conditions. Simultaneous use of these approaches has not provided additive benefit. Our objective was to determine whether anaerobic storage with acidified additive solution (AS) coupled with metabolic rejuvenation might further improve the benefits of anaerobic storage.

STUDY DESIGN AND METHODS: RBC storage in AS with a pH value of 6.5, 7.4, or 8.3 in aerobic or anaerobic conditions was examined using a panel of in vitro biochemical and RBC markers. RBC rejuvenation during cold storage was also evaluated. A randomized crossover radiolabeled recovery study (eight subjects) evaluated anaerobic RBC storage using AS65 with cold rejuvenation for up to 16 weeks of storage.

RESULTS: Adenosine triphosphate (ATP) and diphosphoglycerate acid (DPG) were better maintained in anaerobic storage than in aerobic storage. Acidic or neutral AS preserved ATP concentration better, while a neutral or basic pH AS favored maintenance of DPG levels at higher levels for a longer period. AS pH had less of an effect on exposure of phosphatidylserine (PS), vesicle protein release, and hemolysis. Rejuvenation of RBCs during cold, anaerobic storage resulted in increases in ATP and DPG levels and a reversal of PS exposure. Anaerobic storage of RBCs in pH 6.5 AS rejuvenated at 7 weeks of storage yielded RBC 24‐hour recoveries of 77.3 ± 12.5 percent after 10 weeks' storage time. After a second rejuvenation at Week 11, six subjects' units demonstrated a recovery of 75.9 ± 7.3 percent at 12 weeks of storage.

CONCLUSION: Extended RBC storage may be achieved using anaerobic conditions combined with low‐pH AS and rejuvenation during storage.
Management of blood shortages in a tertiary care academic medical center: the Yale‐New Haven Hospital frozen blood reserve
Authors: Erickson Michelle L. , Champion Melanie H. , Klein Roger , Ross Rebecca L. , Neal Zena M. , Snyder Edward L.
Published: July 2008

Threats to national and local blood supplies in America mandate development of an effective blood management system for emergency preparedness and efficient blood inventory management. Seasonal or acute blood shortages could be compounded by the unavoidable distribution inefficiencies of the blood pipeline during an emergency. The Yale‐New Haven Hospital (YNHH) Blood Bank has developed a comprehensive emergency blood management plan, which includes maintenance of a tactical, limited frozen blood supply. A computer spreadsheet–based disaster prediction model has been designed to guide the use of the frozen reserve by testing various emergency scenarios. The frozen blood reserve can likely support normal hospital red blood cell (RBC) demands during typical (3‐4 days) seasonal shortages, provide a reduced supply for up to 10 days, or meet an unexpected transient increased RBC demand without requiring intensive support from the regional blood center. However, the frozen blood supply is not designed to meet the massive transfusion demand associated with extreme or sustained disasters. Rather, it serves as a short‐term bridge‐over supply until blood center support can be reestablished. We review the reasons for initiating a blood management plan and describe how YNHH has implemented and sustains a frozen blood reserve as part of a comprehensive disaster management plan. Despite the operational complexity, the benefits of self‐sufficiency, the ability to support routine hospital requirements, and the security of having a backup supply justify the expense and difficulty of maintaining a frozen blood reserve.
Detrimental Impact of Trans Fats on Human Health: Stearic Acid‐Rich Fats as Possible Substitutes
Authors: Crupkin Marcos , Zambelli Andres
Published: July 2008

ABSTRACT:  Strong evidence demonstrated the negative effect of trans fatty acid (TFA) intake on cardiovascular diseases (CVD), diabetes, systemic inflammation, and hemostasis. As a consequence, different regulatory actions have been developed around the world, aiming to reduce human consumption of TFA. Replacement for TFA functionality requires incorporation of plastic and stable saturated fats; the present options are palm or fully hydrogenated oils. Palm oil has been described as responsible for negative biological effects on serum cholesterol levels and CVD risk. Different epidemiological and clinical studies recommend reduction of saturated fatty acid (SFA) intake, mainly myristic and palmitic acids. Experimental evidence strongly suggests that stearic acid is a wholesome substitute for TFAs and other SFAs in food manufacturing. In this article, biological effects of stearic acid on human health are reviewed in comparison to TFAs, SFAs, and unsaturated fatty acids. Current revised understanding on dietary intake, digestion, and absorption is also covered.