bluuebunny/crossref_metadata_2025 huggingface dataset:
Governing Innovation for Sustainable Development in the Danish Biogas Sector – a Historical Overview and Analysis of Innovation
Authors: Lybæk Rikke , Christensen Thomas Budde , Kjær Tyge
Published: October 2012

Drawing on innovation literature, this article contests the wisdom of the conventional linear innovation model (invention–demonstration–commercialization–diffusion) and argues that innovation in the case of biogas is, instead, characterized by numerous feedback loops between research, demonstration, commercialization and diffusion. Furthermore, these feedback loops are heavily influenced and shaped by public sector interventions in many aspects of the innovation activities. The article presents the history of Danish farm biogas plants and their present status and discusses the development and implementation of the technology in relation to innovation achievements. The article thus concludes that innovation can be better understood in terms of a dynamic model drawing on initiatives by private, public and academic actors. Copyright © 2012 John Wiley & Sons, Ltd and ERP Environment
Principal‐principal conflicts under weak institutions: A study of corporate takeovers in China
Authors: Li Jiatao , Qian Cuili
Published: October 2012

The principal‐principal perspective is tested and extended in the context of corporate takeovers of Chinese publicly listed firms from 1998 to 2007. The resistance of a target firm's controlling shareholder toward potential takeovers reflects the conflict between the principal and minority shareholders. It was found that this resistance weakens when target firms are located in regions with more institutional development, where the minority shareholders' interests are better protected. The resistance also decreases for target firms with CEOs who are politically connected, as these CEOs may be more interested in their own political careers than in representing the interests of the controlling shareholders.Copyright © 2012 John Wiley & Sons, Ltd.
Illuminating the 130 GeV gamma line with continuum photons
Authors: Cohen Timothy , Lisanti Mariangela , Slatyer Tracy R. , Wacker Jay G.
Published: October 2012

Abstract

There is evidence for a 130 GeV γ-ray line at the Galactic Center in the Fermi Large Area Telescope data. Dark matter candidates that explain this feature should also annihilate to Standard Model particles, resulting in a continuous spectrum of photons. To study this continuum, we analyze the Fermi data down to 5 GeV, restricted to the inner 3◦ of the Galaxy. We place a strong bound on the ratio of continuum photons to monochromatic line photons that is independent of uncertainties in the dark matter density profile. The derived constraints exclude neutralino dark matter as an explanation for the line.
Theoretical predictions for charm and bottom production at the LHC
Authors: Cacciari Matteo , Frixione Stefano , Houdeau Nicolas , Mangano Michelangelo L. , Nason Paolo , Ridolfi Giovanni
Published: October 2012

Abstract

We present predictions for a variety of single-inclusive observables that stem from the production of charm and bottom quark pairs at the 7 TeV LHC. They are obtained within the FONLL semi-analytical framework, and with two “Monte Carlo + NLO” approaches, MC@NLO and POWHEG. Results are given for final states and acceptance cuts that are as close as possible to those used by experimental collaborations and, where feasible, are compared to LHC data.
Continuous KAOS, ASM, and formal control system design across the continuous/discrete modeling interface: a simple train stopping application
Authors: Banach Richard , Zhu Huibiao , Su Wen , Huang Runlei
Published: October 2012

A very simple model for train stopping is used as a vehicle for investigating how the development of a control system, initially designed in the continuous domain and subsequently discretized, can be captured within a formal development process compatible with standard model based refinement methodologies. Starting with a formalized requirements analysis using KAOS, an abstract model of the continuous system is created in the ASM formalism. This requires extensions of the KAOS and ASM formalisms, capable of dealing with quantities evolving continuously over real time, which are developed. After considering how the continuous system, described as a continuous control system in the state space framework, can be discretized, a discrete control system is created in the state space framework. This is re-expressed in the ASM formalism. The rigorous results on the relationship between continuous and discrete control system models that are needed to establish provable properties of the discretization, then become the ingredients of a retrenchment between continuous and discrete ASM models, and are thus fully integrated into the formal development. The discrete ASM model can then be further refined towards implementation.
Scaling up: how do exogenous fluctuations in individual‐based resource competition models re‐emerge in aggregated stochastic population models?
Authors: Johst Karin , Lima Mauricio , Berryman Alan A.
Published: October 2012

In applied population dynamics the choice of stochastic per capita growth function has implications for population viability analyses, management recommendations, and pest control. This model choice is often based on statistical criteria, mathematical tractability or personal preferences, and general ecological guidelines are either too vague or entirely missing. To identify such guidelines, it is important to understand how exogenous and endogenous factors interact at the individual level and re‐emerge at the aggregated population level. We therefore study different types of resource competition (contest vs. scramble competition) and different types of exogenous fluctuations (food and weather fluctuations) at the individual level in a simple individual‐based simulation model. We statistically fit the resulting time series to find out (1) which functional form of the growth function (‘hyperbolic’ or ‘exponential’) better describes contest and scramble competition and (2) whether the pattern of population fluctuations resulting from the simulations can be assigned to vertical, lateral or nonlinear perturbations in the stochastic growth function (a classification scheme suggested by Royama 1992, Analytical Population Dynamics, Chapman and Hall, London). We found that the same type of competition can result in ‘hyperbolic’ or ‘exponential’ functional forms, depending on the type of exogenous fluctuations. So it is the interplay between exogenous variability and endogenous resource competition that affects model performance. In contrast to the widespread assumption of vertical (additive) perturbations, our findings highlight the importance of (non‐additive) lateral and nonlinear perturbations and their combinations with vertical perturbations. The choice of the stochastic growth function should therefore consider not only statistical criteria but also ecological guidelines. We derive such ecological guidelines from our analysis.
Determinant factors influencing the spatial distributions of subtropical lianas are correlated with components of functional trait spectra
Authors: Kusumoto Buntarou , Enoki Tsutomu , Kubota Yasuhiro
Published: October 2012

Lianas are important vegetation components that control structure and function, especially in tropical and subtropical forests. To explore the spatial assembly mechanisms of a subtropical liana community, we tested the following hypotheses: spatial distributions of subtropical lianas are determined by forest structures and topographic features, which are surrogates for host/light availability and edaphic/water conditions, respectively, and these effects are mediated through species functional traits. We examined the spatial distribution of lianas in two plots (areas 9 and 16 ha) representing landscapes in an intact forest and a secondary forest, and analyzed spatial distribution pattern at the species level using a simple, spatially explicit model. We also examined the correlations between determinant factors for species distribution and species functional traits, including climbing habits, leaf traits and wood density. The spatial distribution of lianas was controlled mainly by topographic gradient. Most species had preferences for concave topographies, i.e., valley habitats. Any covariates related to the host (or to light) had little influence on the distribution of most liana species. Distributional responses to topography were different among species, and associated significantly with leaf nitrogen content and climbing habit, but not with wood density. The correlation between variation in habitat preferences and leaf economic spectrum suggests that an environmental filter for physiological response to topography is the important mechanism shaping the spatial patterns of this subtropical liana community.
The Customer Engagement/Value Interface: An Exploratory Investigation
Authors: Hollebeek Linda D.
Published: October 2012

After generating significant interest among marketing practitioners, the customer engagement (CE) concept is rapidly gaining traction in the academic marketing literature. Although pioneering research has provided foundational insights in this emerging area, little is known regarding the ways in which CE may contribute to generating customer value (CV) and ensuing loyalty for utilitarian and hedonic brands. Addressing this research gap, this paper develops a conceptual model of the CE/CV interface for utilitarian and hedonic brands, which proposes: (i) The existence of a curvilinear relationship between CE/CV for utilitarian and hedonic brands; and (ii) Up to a focal brand-, category-, consumer-, and situation-specific optimum, growing CE generates greater CV increases for hedonic, than for utilitarian brands. By drawing on a sample of 14 consumers, depth-interviewing/focus group findings provided exploratory evidence for contentions (i) and (ii). The paper concludes with an overview of key research limitations and implications.
ncRNAs and thermoregulation: A view in prokaryotes and eukaryotes
Authors: de la Fuente Mercedes , Valera Santos , Martínez-Guitarte José Luis
Published: October 2012

During cellular stress response, a widespread inhibition of transcription and blockade of splicing and other post‐transcriptional processing is detected, while certain specific genes are induced. In particular, free‐living cells constantly monitor temperature. When the thermal condition changes, they activate a set of genes coding for proteins that participate in the response. Non‐coding RNAs, ncRNAs, and conformational changes in specific regions of mRNAs seem also to be crucial regulators that enable the cell to adjust its physiology to environmental changes. They exert their effects following the same principles in all organisms and may affect all steps of gene expression. These ncRNAs and structural elements as related to thermal stress response in bacteria are reviewed. The resemblances to eukaryotic ncRNAs are highlighted.
The Determinants of Quality Healthcare: Implications for Canadian Health Leaders
Authors: Mitchell Jonathan I. , Nicklin Wendy , MacDonald Bernadette
Published: October 2012

The Accreditation Canada program supports organizations in delivering quality healthcare using a quality framework that recognizes the complex interplay of multiple factors that define quality. This article highlights the Accreditation Canada quality framework and how these dimensions of quality together promote quality care. Using three dimensions of quality — population focus, safety, and worklife — we discuss how these quality dimensions can be utilized by healthcare leaders to improve quality in their organizations.
Creating an Organizational Culture for Evidence-Informed Decision Making
Authors: Ward Megan , Mowat David
Published: October 2012

A public health department in Ontario, Canada, seta 10-year strategic direction for evidence-informed decision making, defined as the systematic application of research evidence to program decisions. The multifaceted approach has identified eight key lessons for leadership, funding, infrastructure, staff development, partnerships, and change management. Results after 4 years include systematic and transparent application of research to >15 program decisions and, increasingly, evidence-informed decision making as a cultural norm.
Integrating a Population Health Approach into Healthcare Service Delivery and Decision Making
Authors: Neudorf Cordell
Published: October 2012

Most regional health authorities include “improving population health and health equity” in their mission, vision, or priority statements, yet few regional health authorities or hospitals have been shown to devote the sufficient time and resources to make significant progress toward this aim. Health system leaders want to act on this priority, but many barriers and challenges conspire to limit their effectiveness. Improving population health requires both population-based and individual-level initiatives aimed at preventing disease and improving health equity. Practical examples for integrating a population health approach into the health system are presented for healthcare leaders.
Antiresorptive drugs (bisphosphonates), atypical fractures and rebound effect: new evidence of similitude
Authors: Teixeira Marcus Zulian
Published: October 2012

Background:
Homeopathy is based on treatment by similitude (‘like cures like’) administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the secondary and paradoxical action of the organism as therapeutic response. This vital or homeostatic reaction of the organism can be scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after suspension of treatment. Bisphosphonates (BPs) reduce ‘typical’ fractures in patients with osteoporosis, but recent studies report ‘atypical’ fractures of the femur after stopping the BPs, a rebound effect may be the causal mechanism.

Method:
Review of the literature concerning the relationship between atypical femoral fractures and antiresorptive drugs (bisphosphonates), identifying the pathogenesis of this adverse event.

Results:
Several studies have described multiple cases of ‘atypical’ low-impact subtrochanteric stress fractures or complete fractures of the femur. These fractures are often bilateral, preceded by pain in the affected thigh, may have a typical X-ray appearance, and may delayed healing. Rebound of osteoclastic activity after suspension of antiresorptive drugs is a plausible mechanism to explain this phenomenon.

Conclusion:
As for other classes of drugs, the rebound effect of antiresorptive drugs supports Hahnemann's similitude principle (primary action of the drugs followed by secondary and opposite action of the organism), and clarifies this ‘unresolved’ issue. Unfortunately, the rebound effect is little discussed among health professionals, depriving them of important knowledge ensure safe management of drugs.
Tools for risk assessment in radiation therapy
Authors: Ortiz López P.
Published: October 2012

Radiotherapy has unquestionable benefits, but it is also associated with unique and specific safety issues. It is the only application of radiation in which humans are intentionally delivered very high doses. Safety in radiotherapy remains heavily dependent on human actions. A step-by-step approach is suggested for the prevention of accidental exposures in radiation therapy: (1) allocation of responsibilities to qualified professionals, and design of a quality and safety programme - no radiotherapy practice should be operated without these key elements; (2) use of the lessons from accidental exposures to test whether the quality and safety programme is sufficiently robust against these types of events –publications by the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency provide a collection of lessons to facilitate this step; and (3) find other latent risks by posing the questions ‘What else could go wrong?’ or ‘What other potential hazards might be present?’ in a systematic, anticipative manner - methods to do so are described briefly in ICRP Publication 112.
Neuropsychiatric Symptoms and the Use of Complementary and Alternative Medicine
Authors: Purohit Maulik P. , Wells Rebecca Erwin , Zafonte Ross D. , Davis Roger B. , Phillips Russell S.
Published: October 2012

Objectives

To assess the prevalence of complementary and alternative medicine (CAM) use by U.S. adults reporting neuropsychiatric symptoms and whether this prevalence changes based on the number of symptoms reported. Additional objectives include identifying patterns of CAM use, reasons for use, and disclosure of use with conventional providers in U.S. adults with neuropsychiatric symptoms.

Design

Secondary database analysis of a prospective survey.

Participants

A total of 23,393 U.S. adults from the 2007 National Health Interview Survey.

Methods

We compared CAM use between adults with and without neuropsychiatric symptoms. Symptoms included self‐reported anxiety, depression, insomnia, headaches, memory deficits, attention deficits, and excessive sleepiness. CAM use was defined as use of mind−body therapies (eg, meditation), biological therapies (eg, herbs), or manipulation therapies (eg, massage) or alternative medical systems (eg, Ayurveda). Statistical analysis included bivariable comparisons and multivariable logistical regression analyses.

Main Outcome Measures

The prevalence of CAM use among adults with neuropsychiatric symptoms within the previous 12 months and the comparison of CAM use between those with and without neuropsychiatric symptoms.

Results

Adults with neuropsychiatric symptoms had a greater prevalence of CAM use compared with adults who did not have neuropsychiatric symptoms (43.8% versus 29.7%, P < .001); this prevalence increased with an increasing number of symptoms (trend, P < .001). Differences in the likelihood of CAM use as determined by the number of symptoms persisted after we adjusted for covariates. Twenty percent of patients used CAM because standard treatments were either too expensive or ineffective, and 25% used CAM because it was recommended by a conventional provider. Adults with at least one neuropsychiatric symptom were more likely to disclose the use of CAM to a conventional provider (47.9% versus 39.0%, P < .001).

Conclusion

More than 40% of adults with neuropsychiatric symptoms commonly observed in many diagnoses use CAM; an increasing number of symptoms was associated with an increased likelihood of CAM use.
The reversal of agricultural reform in Uganda: Ownership and values
Authors: Kjær Anne Mette , Joughin James
Published: October 2012

This article explores the nature of ownership in a reform of the multi-donor-funded agricultural advisory service in Uganda. We argue that although there was a long process of programme formulation in which all stakeholders were heard, ownership was not as encompassing as it first appeared. In essence, the agricultural reform programme represented market-oriented values that were not echoed in large parts of the Ugandan polity. The eventual reversal of policy, back to government-provided extension, and to a large programme of heavily subsidised input supply, testifies to that. In addition, key stakeholders, notably local politicians and officials in the Ministry of Agriculture, Animal Industry, and Fisheries (MAAIF), were shut out from the original programme and this threatened its viability. If a genuine analysis of the economic and political context had been carried out, the donors might have anticipated this. Instead, they were revealed as ill-equipped to counteract the politicisation and re-claiming of ownership by the Ugandan government.
Saving a river: a joint management approach to the Mekong River Basin
Authors: Houba Harold , Pham Do Kim Hang , Zhu Xueqin
Published: October 2012

The Mekong River Basin (MRB) is a trans-boundary river shared by six countries. The governance by the Mekong River Commission (MRC) of the Lower Mekong Basin (LMB) is weak. This study investigates the welfare effects in the year 2030 arising from strengthening the MRC's governance versus joint management of the entire MRB. Without joint management, strengthening the MRC's governance has a huge potential to achieve welfare gains and it requires that the interests of all stakeholders be equally balanced. A bargaining approach shows that the LMB has no incentive to negotiate with China and is better off strengthening the MRC's governance instead. If such strengthening could be realized, further welfare gains of joint management by a wider and stronger MRC, including China, would be very small.
An unusual antithrombin-binding heparin octasaccharide with an additional 3-O-sulfated glucosamine in the active pentasaccharide sequence
Authors: Guerrini Marco , Elli Stefano , Mourier Pierre , Rudd Timothy R. , Gaudesi Davide , Casu Benito , Boudier Christian , Torri Giangiacomo , Viskov Christian
Published: October 2012

The 3-O-sulfation of N-sulfated glucosamine is the last event in the biosynthesis of heparin/heparan sulfate, giving rise to the antithrombin-binding pentasaccharide sequence AGA*IA, which is largely associated with the antithrombotic activity of these molecules. The aim of the present study was the structural and biochemical characterization of a previously unreported AGA*IA*-containing octasaccharide isolated from the very-low-molecular-mass heparin semuloparin, in which both glucosamine residues of the pentasaccharide moiety located at the non-reducing end bear 3-O-sulfate groups. Two-dimensional and STD (saturation transfer difference) NMR experiments clearly confirmed its structure and identified its ligand epitope binding to antithrombin. The molecular conformation of the octasaccharide–antithrombin complex has been determined by NMR experiments and docking/energy minimization. The presence of the second 3-O-sulfated glucosamine in the octasaccharide induced more than one order of magnitude increase in affinity to antithrombin compared to the pentasaccharide AGA*IA.
Genetic variation in fatty acid composition of subcutaneous fat in cattle
Authors: Kelly M. J. , Tume R. K. , Newman S. , Thompson J. M.
Published: October 2012

Genetic parameters were estimated for fatty acid composition of subcutaneous beef fat of 1573 animals which were the progeny of 157 sires across seven breeds grown out on pasture and then finished on either grain or grass in northern New South Wales or in central Queensland. There was genetic variation in individual fatty acids with estimates of heritability for the proportions of C14 : 0, C14 : 1c9, C16 : 0, C16 : 1c9, C18 : 0 and C18 : 1c9 fatty acids in subcutaneous beef fat of the order of 0.4 or above. Also substantial correlations between some fatty acids were observed. Genetic correlations between fatty acids and fat depth at the P8 site suggested that much of the genetic variation in fatty acid composition was related to changes in fatness. Selection for decreased fatness resulted in decreased proportions of C18 : 1c9 with concomitant increases in C18 : 0, C14 : 0 and C16 : 0. This suggested that selection for decreased fatness at a given weight will result in a decrease in the proportions of monounsaturated fatty acids in the subcutaneous fat in the carcass with a corresponding increase in the proportions of saturated fatty acids.
Role of prefrontal cortex and the midbrain dopamine system in working memory updating
Authors: D’Ardenne Kimberlee , Eshel Neir , Luka Joseph , Lenartowicz Agatha , Nystrom Leigh E. , Cohen Jonathan D.
Published: October 2012

Humans are adept at switching between goal-directed behaviors quickly and effectively. The prefrontal cortex (PFC) is thought to play a critical role by encoding, updating, and maintaining internal representations of task context in working memory. It has also been hypothesized that the encoding of context representations in PFC is regulated by phasic dopamine gating signals. Here we use multimodal methods to test these hypotheses. First we used functional MRI (fMRI) to identify regions of PFC associated with the representation of context in a working memory task. Next we used single-pulse transcranial magnetic stimulation (TMS), guided spatially by our fMRI findings and temporally by previous event-related EEG recordings, to disrupt context encoding while participants performed the same working memory task. We found that TMS pulses to the right dorsolateral PFC (DLPFC) immediately after context presentation, and well in advance of the response, adversely impacted context-dependent relative to context-independent responses. This finding causally implicates right DLPFC function in context encoding. Finally, using the same paradigm, we conducted high-resolution fMRI measurements in brainstem dopaminergic nuclei (ventral tegmental area and substantia nigra) and found phasic responses after presentation of context stimuli relative to other stimuli, consistent with the timing of a gating signal that regulates the encoding of representations in PFC. Furthermore, these responses were positively correlated with behavior, as well as with responses in the same region of right DLPFC targeted in the TMS experiment, lending support to the hypothesis that dopamine phasic signals regulate encoding, and thereby the updating, of context representations in PFC.
Negative blood oxygenation level dependent homunculus and somatotopic information in primary motor cortex and supplementary motor area
Authors: Zeharia Noa , Hertz Uri , Flash Tamar , Amedi Amir
Published: October 2012

A crucial attribute in movement encoding is an adequate balance between suppression of unwanted muscles and activation of required ones. We studied movement encoding across the primary motor cortex (M1) and supplementary motor area (SMA) by inspecting the positive and negative blood oxygenation level-dependent (BOLD) signals in these regions. Using periodic and event-related experiments incorporating the bilateral/axial movements of 20 body parts, we report detailed mototopic imaging maps in M1 and SMA. These maps were obtained using phase-locked analysis. In addition to the positive BOLD, significant negative BOLD was detected in M1 but not in the SMA. The negative BOLD spatial pattern was neither located at the ipsilateral somatotopic location nor randomly distributed. Rather, it was organized somatotopically across the entire homunculus and inversely to the positive BOLD, creating a negative BOLD homunculus. The neuronal source of negative BOLD is unclear. M1 provides a unique system to test whether the origin of negative BOLD is neuronal, because different arteries supply blood to different regions in the homunculus, ruling out blood-stealing explanations. Finally, multivoxel pattern analysis showed that positive BOLD in M1 and SMA and negative BOLD in M1 contain somatotopic information, enabling prediction of the moving body part from inside and outside its somatotopic location. We suggest that the neuronal processes underlying negative BOLD participate in somatotopic encoding in M1 but not in the SMA. This dissociation may emerge because of differences in the activity of these motor areas associated with movement suppression.
Identifying the Risk Factors for Hospital-Acquired Methicillin-Resistant Staphylococcus aureus (MRSA) Infection among Patients Colonized with MRSA on Admission
Authors: Fukuta Yuriko , Cunningham Candace A. , Harris Patricia L. , Wagener Marilyn M. , Muder Robert R.
Published: October 2012

Background.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospital-acquired infections. MRSA-colonized inpatients who may benefit from undergoing decolonization have not been identified.

Objective.

To identify risk factors for MRSA infection among patients who are colonized with MRSA at hospital admission.

Design.

A case-control study.

Setting.

A 146-bed Veterans Affairs hospital.

Participants.

Case patients were those patients admitted from January 2003 to August 2011 who were found to be colonized with MRSA on admission and then developed MRSA infection. Control subjects were those patients admitted during the same period who were found to be colonized with MRSA on admission but who did not develop MRSA infection.

Methods.

A retrospective review.

Results.

A total of 75 case patients and 150 control subjects were identified. A stay in the intensive care unit (ICU) was the significant risk factor in univariate analysis (P<.001). Prior history of MRSA (P = .03), transfer from a nursing home (P = .002), experiencing respiratory failure (P<.001), and receipt of transfusion (P = .001) remained significant variables in multivariate analysis. Prior history of MRSA colonization or infection (P = .02), difficulty swallowing (P = .04), presence of an open wound (P = .002), and placement of a central line (P = .02) were identified as risk factors for developing MRSA infection for patients in the ICU. Duration of hospitalization, readmission rate, and mortality rate were significantly higher in case patients than in control subjects (P< .001, .001, and <.001, respectively).

Conclusions.

MRSA-colonized patients admitted to the ICU or admitted from nursing homes have a high risk of developing MRSA infection. These patients may benefit from undergoing decolonization.
A thermo-chemical model of liquid iron oxidation during plasma arc or laser cutting
Authors: Nemchinsky Valerian
Published: October 2012

It is suggested that if liquid iron is in contact with an atmosphere of gaseous oxygen, the chemical reaction of oxidation inside the liquid metal is of a homogeneous type, as opposed to the heterogeneous reaction of oxidation which takes place in a solid metal. A system of equations describing the inter-related chemical and heat processes is formulated and solved numerically. The obtained solution demonstrated the existence of a relatively narrow reaction zone that moves inwards through the metal. It was shown that the temperature in the reaction zone could be rather high as a result of the following sequence of events: a chemical reaction heats the metal, which boosts the oxygen diffusion and the oxygen supply to the reaction zone, which in turn increases the rate of oxidation. Thermal conductivity and depletion of the reagents stop this explosive-like process. Calculations showed that after some initial period, the reaction zone motion follows the parabolic law.
RhoD regulates cytoskeletal dynamics via the actin nucleation–promoting factor WASp homologue associated with actin Golgi membranes and microtubules
Authors: Gad Annica K. B. , Nehru Vishal , Ruusala Aino , Aspenström Pontus
Published: October 2012

The Rho GTPases have mainly been studied in association with their roles in the regulation of actin filament organization. These studies have shown that the Rho GTPases are essential for basic cellular processes, such as cell migration, contraction, and division. In this paper, we report that RhoD has a role in the organization of actin dynamics that is distinct from the roles of the better-studied Rho members Cdc42, RhoA, and Rac1. We found that RhoD binds the actin nucleation–promoting factor WASp homologue associated with actin Golgi membranes and microtubules (WHAMM), as well as the related filamin A–binding protein FILIP1. Of these two RhoD-binding proteins, WHAMM was found to bind to the Arp2/3 complex, while FILIP1 bound filamin A. WHAMM was found to act downstream of RhoD in regulating cytoskeletal dynamics. In addition, cells treated with small interfering RNAs for RhoD and WHAMM showed increased cell attachment and decreased cell migration. These major effects on cytoskeletal dynamics indicate that RhoD and its effectors control vital cytoskeleton-driven cellular processes. In agreement with this notion, our data suggest that RhoD coordinates Arp2/3-dependent and FLNa-dependent mechanisms to control the actin filament system, cell adhesion, and cell migration.
Residual Neuromuscular Blockade Affects Postoperative Pulmonary Function
Authors: Kumar Gopalaiah Venkatesh , Nair Anita Pramod , Murthy Hanuman Srinivasa , Jalaja Koppa Ramegowda , Ramachandra Karnate , Parameshwara Gundappa
Published: October 2012

Background

Residual neuromuscular blockade (RNMB) is known to be associated with respiratory complications in the postoperative period after muscle relaxant usage. The authors hypothesized that RNMB causes reductions in pulmonary function test (PFT) parameters in the immediate postoperative period.

Methods

An open-label prospective randomized cohort study was conducted comparing reductions in PFT parameters due to RNMB among different neuromuscular blocking agents. One hundred and fifty patients were randomized to receive vecuronium, atracurium, or rocuronium. After reversal of neuromuscular blockade and extubation, train-of-four ratio was measured every 5 min until the train-of-four ratio of 0.9 or greater was attained. PFTs were performed preoperatively and postoperatively when the patients were willing and fit. The train-of-four ratio, measured at PFT, was used to classify patients into “RNMB absent” and “RNMB present.” RNMB was defined as a train-of-four ratio less than 0.9.

Results

Thirty-nine patients had RNMB at the time of performing PFT. There was no statistically significant difference in the postoperative reductions in PFT parameters in patients with RNMB among different neuromuscular blocking agents. Patients were regrouped as RNMB absent and RNMB present, irrespective of neuromuscular blocking agents. Postoperative PFT values for the RNMB-absent and RNMB-present groups were 62% and 49% of baseline forced vital capacity and 47% and 38% of baseline peak expiratory flow of the baseline, respectively. Postoperative forced vital capacity and peak expiratory flow values of RNMB-present patients were lower by 13% and 9% in absolute terms (P < 0.008) and 21% and 19% in relative terms, respectively, compared with RNMB-absent patients.

Conclusion

RNMB results in reductions in forced vital capacity and peak expiratory flow in the immediate postoperative period indicating impaired respiratory muscle function.
Relationship of Erythrocyte Transfusion with Short- and Long-term Mortality in a Population-based Surgical Cohort
Authors: Karkouti Keyvan , Stukel Thérèse A. , Beattie W. Scott , Elsaadany Susie , Li Ping , Berger Rachel , Wijeysundera Duminda N.
Published: October 2012

Background

When comparing transfused versus nontransfused patients, erythrocyte transfusion is consistently associated with increased mortality. Nonetheless, unmeasured confounding may unduly influence this comparison. This unmeasured risk may have less influence on comparisons of patients undergoing surgery at hospitals with differing transfusion rates.

Methods

Administrative databases were used to conduct a population-based cohort study of patients who underwent elective hip- or knee-replacement surgery from 1999 to 2008 in Ontario, Canada. The authors used Cox proportional-hazards models to determine the adjusted association of hospital-specific erythrocyte transfusion rates (i.e., comparing hospitals with differing transfusion rates) with postoperative mortality. For comparison, they also determined the adjusted association of patient receipt of transfusion (i.e., comparing transfused vs. nontransfused patients) with mortality.

Results

Of 162,190 patients, 23% (n=37,015) were transfused. Hospital-specific transfusion rates at the 66 included hospitals ranged from 10.3 to 57.9%. Compared with nontransfused patients, transfused patients experienced increased adjusted 30-day (hazard ratio 2.32; 95% CI, 1.91-2.83) and 1-yr mortality (hazard ratio 1.75; 95% CI, 1.60-1.91). However, when hospitals were categorized into quartiles based on hospital-specific transfusion rates, mortality rates were similar (highest transfusion quartile vs. lowest transfusion quartile: 30-day mortality, hazard ratio 1.11, 95% CI 0.82-1.50; 1-yr mortality, hazard ratio 1.02, 95% CI 0.82-1.26).

Conclusions

The association of transfusion with postoperative mortality differed significantly when comparing transfused versus nontransfused patients, as opposed to comparing hospitals with differing transfusion rates. This discrepancy raises questions about the true relationship between transfusion and mortality.
Differences in microRNA Changes of Healthy Rat Liver between Sevoflurane and Propofol Anesthesia
Authors: Ishikawa Masashi , Tanaka Shunsuke , Arai Masae , Genda Yuuki , Sakamoto Atsuhiro
Published: October 2012

Background

In previous studies, the authors showed that anesthetics affect the expression ratios of many genes in rat liver. microRNAs (miRNA) negatively regulate more than 30% of genes in cells, and control cell proliferation, inflammation, and metabolism. The authors hypothesized that anesthetics influence miRNA expression in the liver, and performed miRNA screening tests using TaqMan low-density arrays.

Methods

Rats were randomly assigned to the 2.4% sevoflurane group, the 600 µg·kg⁻¹·min⁻¹ propofol group, and the control group without anesthetics. Rats were allowed to breathe spontaneously under anesthesia for 6 h. The miRNA expression profile of the liver was analyzed, and 15 representative miRNAs were validated by quantitative real-time reverse transcriptase polymerase chain reaction.

Results

TaqMan low-density arrays analysis showed 46 miRNAs that were differentially expressed by anesthetics. After sevoflurane treatment, 16 miRNAs were significantly increased and 11 were significantly decreased compared with controls, whereas after propofol treatment, 31 miRNAs were increased and 8 were decreased. Twenty expressed miRNAs were common to both anesthetics, whereas three miRNAs were differentially expressed. Bland-Altman analysis was performed across the validations to compare the fold changes measured by both methods, and they were equivalent (mean difference=0.01, 95% CI=-0.26 to 0.27). This showed that the TaqMan low-density arrays results are accurate and can be confirmed using an independent experimental approach.

Conclusion

The results showed that anesthetics cause many miRNA expression changes, and the miRNA expression pattern was particular for each anesthetic. Further studies are needed to determine the functional consequence of miRNA modulation by anesthetics.
Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities
Authors: Pertwee Roger G.
Published: October 2012

Human tissues express cannabinoid CB
1
and CB
2
receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB
1
/CB
2
receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol;
Δ
9
-tetrahydrocannabinol (
Δ
9
-THC)) and Sativex (
Δ
9
-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB
2
receptors, and/or (v) adjunctive ‘multi-targeting’.
Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids
Authors: Puighermanal Emma , Busquets-Garcia Arnau , Maldonado Rafael , Ozaita Andrés
Published: October 2012

Exogenous cannabinoids, such as delta9-tetrahydrocannabinol (THC), as well as the modulation of endogenous cannabinoids, affect cognitive function through the activation of cannabinoid receptors. Indeed, these compounds modulate a number of signalling pathways critically implicated in the deleterious effect of cannabinoids on learning and memory. Thus, the involvement of the mammalian target of rapamycin pathway and extracellular signal-regulated kinases, together with their consequent regulation of cellular processes such as protein translation, play a critical role in the amnesic-like effects of cannabinoids. In this study, we summarize the cellular and molecular mechanisms reported in the modulation of cognitive function by the endocannabinoid system.
Endocannabinoids via CB1receptors act as neurogenic niche cues during cortical development
Authors: Díaz-Alonso Javier , Guzmán Manuel , Galve-Roperh Ismael
Published: October 2012

During brain development, neurogenesis is precisely regulated by the concerted action of intrinsic factors and extracellular signalling systems that provide the necessary niche information to proliferating and differentiating cells. A number of recent studies have revealed a previously unknown role for the endocannabinoid (ECB) system in the control of embryonic neuronal development and maturation. Thus, the CB1cannabinoid receptor in concert with locally produced ECBs regulates neural progenitor (NP) proliferation, pyramidal specification and axonal navigation. In addition, subcellularly restricted ECB production acts as an axonal growth cone signal to regulate interneuron morphogenesis. These findings provide the rationale for understanding better the consequences of prenatal cannabinoid exposure, and emphasize a novel role of ECBs as neurogenic instructive cues involved in cortical development. In this review the implications of altered CB1-receptor-mediated signalling in developmental disorders and particularly in epileptogenesis are briefly discussed.
Functional diversity on synaptic plasticity mediated by endocannabinoids
Authors: Cachope Roger
Published: October 2012

Endocannabinoids (eCBs) act as modulators of synaptic transmission through activation of a number of receptors, including, but not limited to, cannabinoid receptor 1 (CB1). eCBs share CB1 receptors as a common target with
Δ
9
-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana. Although THC has been used for recreational and medicinal purposes for thousands of years, little was known about its effects at the cellular level or on neuronal circuits. Identification of CB1 receptors and the subsequent development of its specific ligands has therefore enhanced our ability to study and bring together a substantial amount of knowledge regarding how marijuana and eCBs modify interneuronal communication. To date, the eCB system, composed of cannabinoid receptors, ligands and the relevant enzymes, is recognized as the best-described retrograde signalling system in the brain. Its impact on synaptic transmission is widespread and more diverse than initially thought. The aim of this review is to succinctly present the most common forms of eCB-mediated modulation of synaptic transmission, while also illustrating the multiplicity of effects resulting from specializations of this signalling system at the circuital level.
Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders
Authors: Campos Alline Cristina , Moreira Fabricio Araújo , Gomes Felipe Villela , Del Bel Elaine Aparecida , Guimarães Francisco Silveira
Published: October 2012

Cannabidiol (CBD) is a major phytocannabinoid present in the
Cannabis sativa
plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound
Δ
9
-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by
in vitro
studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent
in vivo
studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARγ receptors agonism, intracellular (Ca
2+
) increase, etc.), on CBD behavioural effects.
Mast cell–glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide
Authors: Skaper Stephen D. , Facci Laura
Published: October 2012

Communication between the immune and nervous systems depends a great deal on pro-inflammatory cytokines. Both astroglia and microglia, in particular, constitute an important source of inflammatory mediators and may have fundamental roles in central nervous system (CNS) disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Glial cells respond also to pro-inflammatory signals released from cells of immune origin. In this context, mast cells are of particular relevance. These immune-related cells, while resident in the CNS, are able to cross a compromised blood-spinal cord and blood-brain barrier in cases of CNS pathology. Emerging evidence suggests the possibility of mast cell–glia communication, and opens exciting new perspectives for designing therapies to target neuroinflammation by differentially modulating the activation of non-neuronal cells normally controlling neuronal sensitization—both peripherally and centrally. This review aims to provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of glia, neuro-immune interactions involving mast cells and the possibility that glia–mast cell interactions contribute to exacerbation of acute symptoms of chronic neurodegenerative disease and accelerated disease progression, as well as promotion of pain transmission pathways. Using this background as a starting point for discussion, we will consider the therapeutic potential of naturally occurring fatty acid ethanolamides, such as palmitoylethanolamide in treating systemic inflammation or blockade of signalling pathways from the periphery to the brain in such settings.