bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling a Variable Displacement Axial Piston Pump in a Multibody Simulation Environment
Authors: Roccatello Alessandro , Mancò Salvatore , Nervegna Nicola
Published: June 2007

Analysis of a variable displacement axial piston pump, as in other complex fluid power and mechanical systems, requires appropriate insight into three multidisciplinary domains, i.e., hydraulics, mechanics and tribology. In recent years, at FPRL, modelling of axial piston pumps has evolved in AMESim (one-dimensional code) where a three-dimensional mechanical approach has required generation of proprietary libraries leading to the evaluation of internal forces/reactions in all pump subsystems. Tribologic aspects in axial piston pumps modelling are also being investigated but AMESim, in this respect, does not appear as the appropriate computational environment. Consequently, a new approach has been initiated grounded on MSC.ADAMS. In this perspective, the paper details how the model has been developed through proprietary macros that automatically originate all pump subsystems parametrically and further apply required constraints and forces (springs, contacts and pressure forces). The ADAMS environment has also been selected due to co-simulation capabilities with AMESim. Accordingly, the paper elucidates how the entire modelling has been construed where hydraulics is managed in AMESim while ADAMS takes care of mechanics. A comparison between simulated and experimental steady-state characteristics of the axial pump is also presented. As such this paper indicates an innovative methodology for the analysis of complex fluid power systems in the hope that, eventually, tribology will also fit into the scene.
A Procedure for the Development of Control-Oriented Linear Models for Horizontal-Axis Large Wind Turbines
Authors: Suryanarayanan Shashikanth , Dixit Amit
Published: June 2007

In this work we describe a methodology to construct control-oriented, multi-input, multi-output linear models representing the dynamics of variable-speed, pitch-controlled horizontal-axis wind turbines (HAWT). The turbine is treated as an interconnection of mechanical elements with distributed mass, damping, and stiffness characteristics. The behavior of the structural components of the turbine is approximated as that of their dominant modes and the wind-blade aerodynamic interaction is modeled using the Blade Element Momentum (BEM) theory. The modeling procedure explicitly exploits the horizontal-axis configuration and constraints imposed thereof. The models developed using the outlined procedure are parametrized based on a handful of parameters that are often used to specify mass/stiffness distributions and geometry. The predictions of the linear models so constructed are validated against that of an established nonlinear model. The use of the modeling procedure in addressing problems of immediate interest to the wind turbine industry is presented.
Efficient Algorithm for the Generation of QFT Bounds for Plants With Affinely Dependent Uncertainties
Authors: Yang Shih-Feng
Published: June 2007

This paper presents an efficient algorithm for the generation of quantitative feedback theory (QFT) bounds for plants with affinely dependent uncertainties. For a plant with m affinely dependent uncertainties, it is shown that whether a point in the complex plane lies in the QFT bound for a frequency-domain specification at a given frequency can be tested by checking if m2m−1 one-variable quadratic equations corresponding to the edges of the domain box are all non-negative on the interval [0,1]. This test procedure is then utilized along with a pivoting procedure to trace out the boundary of the QFT bound with a prescribed accuracy or resolution. The developed algorithm can avoid the unfavorable trade-off between the computational burden and the accuracy of QFT bounds. Moreover, it is efficient in the sense that no root-finding and iterative procedures are required. Numerical examples are given to illustrate the proposed algorithm and its computational superiority.
A Dissipative Control Design for Jupiter Icy Moons Orbiter
Authors: Shi Jianjun , Kelkar Atul G.
Published: June 2007

This technical brief presents a nonlinear dynamic model of Jupiter Icy Moons Orbiter (JIMO), a concept design of a spacecraft intended to orbit the three icy moons of Jupiter, namely, Europa, Ganymede, and Callisto. The work presented in this paper represents a part of a feasibility study conducted to assess control requirements of the JIMO mission. A nonlinear dynamic model of JIMO is derived that includes rigid body as well as flexible body dynamics. A nonlinear dissipative control law with guaranteed stability is used to perform a representative in-orbit maneuver. The results presented are part of an exhaustive study conducted to evaluate various controller designs.
Minding the gap between logic and intuition: an interpretative approach to ethical analysis
Authors: Kirklin D
Published: June 2007

In an attempt to be rational and objective, and, possibly, to avoid the charge of moral relativism, ethicists seek to categorise and characterise ethical dilemmas. This approach is intended to minimise the effect of the confusing individuality of the context within which ethically challenging problems exist. Despite and I argue partly as a result of this attempt to be rational and objective, even when the logic of the argument is accepted—for example, by healthcare professionals—those same professionals might well respond by stating that the conclusions are unacceptable to them. In this paper, I argue that an interpretative approach to ethical analysis, involving an examination of the ways in which ethical arguments are constructed and shared, can help ethicists to understand the origins of this gap between logic and intuition. I suggest that an argument will be persuasive either if the values underpinning the proposed argument accord with the reader’s values and worldview, or if the argument succeeds in persuading the reader to alter these. A failure either to appreciate or to acknowledge those things that give meaning to the lives of all the interested parties will make this objective far harder, if not impossible, to achieve. If, as a consequence, the narratives ethicists use to make their arguments seem to be about people living in different circumstances, and faced with different choices and challenges, from those the readers or listeners consider important or have to face in their own lives, then the argument is unlikely to seem either relevant or applicable to those people. The conclusion offered by the ethicist will be, for that individual, counterintuitive. Abortion, euthanasia and cadaveric organ donation are used as examples to support my argument.
Ethics in studies on children and environmental health: Table 1
Authors: Merlo D F , Knudsen L E , Matusiewicz K , Niebrój L , Vähäkangas K H
Published: June 2007

Children, because of age-related reasons, are a vulnerable population, and protecting their health is a social, scientific and emotional priority. The increased susceptibility of children and fetuses to environmental (including genotoxic) agents has been widely discussed by the scientific community. Children may experience different levels of chemical exposure than adults, and their sensitivity to chemical toxicities may be increased or decreased in comparison with adults. Such considerations also apply to unborn (fetal exposure) and newborn (neonatal exposure) children. Therefore, research on children is necessary in both clinical and environmental fields, to provide age-specific relevant data regarding the efficacy and safety of medical treatments, and regarding the assessment of risk from unintended environmental exposure. In this context, the stakeholders are many, including children and their parents, physicians and public health researchers, and the society as a whole, with its ethical, regulatory, administrative and political components. The important ethical issues are information of participants and consent to participate. Follow-up and protection of data (samples and information derived from samples) should be discussed in the context of biobanks, where children obtain individual rights when they become adults. It is important to realise that there are highly variable practices within European countries, which may have, in the past, led to differences in practical aspects of research in children. A number of recommendations are provided for research with children and environmental health. Environmental research with children should be scientifically justified, with sound research questions and valid study protocols of sufficient statistical power, ensuring the autonomy of the child and his/her family at the time of the study and later in life, if data and samples are used for follow-up studies. When children are enrolled, we recommend a consent dyad, including (1) parental (or legal guardian) informed consent and (2) the child’s assent and/or informed consent from older minors. For evaluation of the studies including children, a paediatrician should always be involved in the research ethics committee.
Perceptions of authorship criteria: effects of student instruction and scientific experience
Authors: Hren Darko , Sambunjak Dario , Ivaniš Ana , Marušić Matko , Marušić Ana
Published: June 2007

Objective:To analyse medical students’, graduate students’ and doctors’ and medical teachers’ perceptions of research contributions as criteria for authorship in relation to the authorship criteria defined by the International Committee of Medical Journal Editors (ICMJE).

Design:Medical students with (n = 152) or without (n = 85) prior instruction on ICMJE criteria, graduate students/doctors (n = 125) and medical teachers (n = 112) rated the importance of 11 contributions as authorship qualifications. They also reported single contributions eligible for authorship, as well as acceptable combinations of two or three qualifying contributions.

Results:Conception and design, Analysis and interpretation and Drafting of article formed the most important cluster in all four groups. Students without prior instruction rated Critical revision and Final approval lower than the other three groups. “Final approval” was a part of the least important cluster in all groups except among students with instruction.

Conclusions:Conception and design, Analysis and interpretation and Drafting of article were recognised as the most important of the ICMJE criteria by all participants. They can be considered independent of previous instruction or experience. Final approval and Critical revision should be actively taught as important authorship criteria to future scientists.
Clinical research with economically disadvantaged populations
Authors: Denny Colleen C , Grady Christine
Published: June 2007

Concerns about exploiting the poor or economically disadvantaged in clinical research are widespread in the bioethics community. For some, any research that involves economically disadvantaged individuals isde factoethically problematic. The economically disadvantaged are thought of as “venerable” to exploitation, impaired decision making, or both, thus requiring either special protections or complete exclusion from research. A closer examination of the worries about vulnerabilities among the economically disadvantaged reveals that some of these worries are empirically or logically untenable, while others can be better resolved by improved study designs than by blanket exclusion of poorer individuals from research participation. The scientific objective to generate generalisable results and the ethical objective to fairly distribute both the risks and benefits of research oblige researchers not to unnecessarily bar economically disadvantaged subjects from clinical research participation.
Can evidence-based medicine implicitly rely on current concepts of disease or does it have to develop its own definition?
Authors: Gerber Andreas , Hentzelt Frieder , Lauterbach Karl W
Published: June 2007

Decisions in healthcare are made against the background of cultural and philosophical definitions of disease, sickness and illness. These concepts or definitions affect both health policy (macro level) and research (meso level), as well as individual encounters between patients and physicians (micro level). It is therefore necessary for evidence-based medicine to consider whether any of the definitions underlying research prior to the hierarchisation of knowledge are indeed compatible with its own epistemological principles.
Attitudes toward physician-assisted suicide among physicians in Vermont
Authors: Craig Alexa , Cronin Beth , Eward William , Metz James , Murray Logan , Rose Gail , Suess Eric , Vergara Maria E
Published: June 2007

Background:Legislation on physician-assisted suicide (PAS) is being considered in a number of states since the passage of the Oregon Death With Dignity Act in 1994. Opinion assessment surveys have historically assessed particular subsets of physicians.

Objective:To determine variables predictive of physicians’ opinions on PAS in a rural state, Vermont, USA.

Design:Cross-sectional mailing survey.

Participants:1052 (48% response rate) physicians licensed by the state of Vermont.

Results:Of the respondents, 38.2% believed PAS should be legalised, 16.0% believed it should be prohibited and 26.0% believed it should not be legislated. 15.7% were undecided. Males were more likely than females to favour legalisation (42% vs 34%). Physicians who did not care for patients through the end of life were significantly more likely to favour legalisation of PAS than physicians who do care for patients with terminal illness (48% vs 33%). 30% of the respondents had experienced a request for assistance with suicide.

Conclusions:Vermont physicians’ opinions on the legalisation of PAS is sharply polarised. Patient autonomy was a factor strongly associated with opinions in favour of legalisation, whereas the sanctity of the doctor–patient relationship was strongly associated with opinions in favour of not legislating PAS. Those in favour of making PAS illegal overwhelmingly cited moral and ethical beliefs as factors in their opinion. Although opinions on legalisation appear to be based on firmly held beliefs, approximately half of Vermont physicians who responded to the survey agree that there is a need for more education in palliative care and pain management.
ON A CLASS OF PROJECTIVELY FLAT FINSLER METRICS WITH CONSTANT FLAG CURVATURE
Authors: LI BENLING , SHEN ZHONGMIN
Published: June 2007

In this paper, we study a class of Finsler metrics defined by a Riemannian metric and a 1-form. We classify those projectively flat with constant flag curvature.
THE GROMOV–WITTEN AND DONALDSON–THOMAS CORRESPONDENCE FOR TRIVIAL ELLIPTIC FIBRATIONS
Authors: EDIDIN DAN , QIN ZHENBO
Published: June 2007

We study the Gromov–Witten and Donaldson–Thomas correspondence conjectured in [16, 17] for trivial elliptic fibrations. In particular, we verify the Gromov–Witten and Donaldson–Thomas correspondence for primary fields when the threefold is E × S where E is a smooth elliptic curve and S is a smooth surface with numerically trivial canonical class.
NEW PHYSICS UPPER BOUND ON THE BRANCHING RATIO OF Bs → l+l-γ
Authors: ALOK ASHUTOSH KUMAR , SANKAR S. UMA
Published: June 2007

We consider the effect of new physics on the branching ratio of Bs → l+l-γ where l = e, μ. If the new physics is of the form scalar/pseudoscalar, then it makes no contribution to Bs → l+l-γ, unlike in the case of Bs → l+l-, where it can potentially make a very large contribution. If the new physics is in the form of vector/axial-vector operators, then the present data on B → (K, K*) l+l- does not allow a large enhancement for B(Bs → l+l- γ). If the new physics is in the form of tensor/pseudotensor operators, then the data on B → (K, K*) l+l- gives no useful constraint but the data on B → K* γ does. Here again, a large enhancement of B(Bs → l+l-γ), much beyond the Standard Model expectation, is not possible. Hence, we conclude that the present data on b → s transitions allow a large boost in B(Bs → l+l-) but not in B(Bs → l+l-γ).
GREEN FUNCTION METHOD FOR NONLINEAR SYSTEMS
Authors: FRASCA MARCO
Published: June 2007

We show that a Green function solution can be given for a class of nonhomogeneous nonlinear systems having relevance in quantum field theory. This in turn means that a quantum field theory in the strong coupling limit can be formulated and the spectrum obtained.
IMPULSIVE CONTROL STRATEGIES FOR PEST MANAGEMENT
Authors: ZHANG HONG , CHEN LANSUN , GEORGESCU PAUL
Published: June 2007

In this paper, we propose two impulsive differential systems concerning biological and, respectively, integrated pest management strategies. In each case, it is observed that there exists a globally asymptotically stable susceptible pest-eradication periodic solution on condition that the amount of infective pests released periodically is larger than a certain critical value. When the amount of infective pests released is less than this critical value, the system is shown to be permanent, which implies that the trivial susceptible pest-eradication solution loses its stability. Further, the existence of a non-trivial periodic solution is also studied by means of numerical simulations. In the case in which a single control is used, one can only use the amount of infective pests which are periodically released in order to control pests at desirable low levels, while in the case in which integrated management is used, one can use the proportion of pests removed by means of spraying chemical pesticides together with the amount of infective pests which are periodically released to control pests at desirable low levels.
THE DYNAMICS OF THE CONSTANT AND PULSE BIRTH IN AN SIR EPIDEMIC MODEL WITH CONSTANT RECRUITMENT
Authors: CAO WENJUN , JIN ZHEN
Published: June 2007

In this paper, an SIR epidemic model with constant recruitment is considered. The dynamic behavior of this disease model with constant and pulse birth are analyzed. With constant birth, the infection-free equilibrium is locally and globally stable when the basic reproductive number R0< 1. However, with pulse birth the system converges to a stable period solution with the number of infectious individuals equal to zero. Furthermore, the local and global stability of the periodic infection-free solution is obtained if the basic reproductive number [Formula: see text]. Numerical simulation shows that the periodic infection-free solution is unstable and the disease will persist when [Formula: see text]. The effectiveness of the constant and pulse birth to eliminating the disease are compared.
CYCLES AND CHAOTIC BEHAVIOR IN AN AIDS-RELATED CANCER DYNAMIC MODELIN VIVO
Authors: LOU JIE , RUGGERI TOMMASO , MA ZHIEN
Published: June 2007

Cancer remains a significant burden in HIV-infected individuals. We present an HIV-1 dynamical model which incorporates the AIDS-related cancer cells in vivo. The model consists of four components: cancer cells, healthy CD4+ T-lymphocytes, infected CD4+ T-lymphocytes and free HIV-1 virus. We discuss the existence, the stability properties and the biological meanings of the model's steady states, in particular the positive cancer-HIV steady state. We find that Hopf bifurcation of the positive steady state can exist, which lead to periodic solutions, sequences of period doubling bifurcations and the appearance of chaos. We also prove theoretically that HIV-1 is of help in the growth of cancer. The result fits very well with the clinical observations that several different types of cancer are observed at an increased frequency in HIV-1 infection individuals.
NEGATIVE FEEDBACK DYNAMICS AND OSCILLATORY ACTIVITIES IN REGULATORY BIOLOGICAL NETWORKS
Authors: YAN SHIWEI
Published: June 2007

The recent experiments on the dynamics of a common biological network motif, p53 and Mdm2 feedback loop, have shown the oscillatory behaviors for the activities of p53 and Mdm2 proteins in response to DNA damage. Exploiting the nonlinear dynamics in the negative feedback loop, we propose a statistical signal-response model with an aim to describe the p53-Mdm2 interaction under certain radiation environment. We discuss the existence of Hopf bifurcation, the stability of the solutions of model equations and their sensitivity to the changes of the parameters incorporated in the model. The proposed mathematical method may have the significance in the problems where the negative and/or positive feedback dynamics, as well as the time delay have the characteristic physical and biological background.
AN EXTENDED BRANCH AND BOUND ALGORITHM FOR BILEVEL MULTI-FOLLOWER DECISION MAKING IN A REFERENTIAL-UNCOOPERATIVE SITUATION
Authors: LU JIE , SHI CHENGGEN , ZHANG GUANGQUAN , RUAN DA
Published: June 2007

Within the framework of any bilevel decision problem, a leader's decision at the upper level is influenced by the reaction of their follower at the lower level. When multiple followers are involved in a bilevel decision problem, the leader's decision will not only be affected by the reactions of those followers, but also by the relationships among those followers. One of the popular situations within this framework is where these followers are uncooperatively making decisions while having cross reference of decision information, called a referential-uncooperative situation in this paper. The well-known branch and bound algorithm has been successfully applied to a one-leader-and-one-follower linear bilevel decision problem. This paper extends this algorithm to deal with the above-mentioned linear bilevel multi-follower decision problem by means of a linear referential-uncooperative bilevel multi-follower decision model. It then proposes an extended branch and bound algorithm to solve this problem with a set of illustrative examples in a referential-uncooperative situation.
Education for Sustainability: Creating Skills in Human Capital Analysis
Authors: Royal Carol , O'Donnell Loretta
Published: June 2007

This paper presents the role of an innovative university masters' degree programme as a basis for skills development in human capital analysis for finance and business students in their core degree programmes. The programme uses general systems theory to provide a framework for describing two components of the sustainable organisation: firstly, the inter-relationships of organisations to their context; and secondly, to describe the configuration of internal management systems. In the subject, the students take the role of human capital analysts in order to focus on defining, assessing and measuring the human elements of corporate sustainability. This postgraduate business subject has been developed within the framework of the UNSW guidelines on teaching and learning, designed to encourage innovation in both content and process. The authors conclude that the role of education is instrumental in creating a community of practice which uses sustainability principles as a basis for investment decision making amongst business students, who will be the next generation of executives and financial analysts.
AN EMPIRICAL ANALYSIS: VENTURE CAPITAL CLUSTERS AND FIRM MIGRATION
Authors: PLANT ROBERT
Published: June 2007

Regions and states utilize venture capital forums to raise the profiles of youthful, potentially high-growth firms located within their boundaries. They aim to help organizations raise capital, to widen professional networks and to stimulate regional development. As a contribution toward determining the success of the forum concept, the Florida venture forum was studied. This paper follows those companies who received funding subsequent to participating in the forum during the period 1997–2003; data is drawn from the forum and public records. Funding profiles are built up for successful participants and the funding entities. A secondary profile, post-funding, is developed that examines the role the funding agent plays in determining whether the funded company remains or migrates from its original location. The finding of this paper is that a significant number of funded entities are located within venture capital cores or clusters. The paper shows that funded companies are younger than non-funded companies, more likely to be acquired and move from their original location. The paper also shows that the participant companies that were acquired achieve an exit strategy by migrating out of the state of Florida.
FACTORS CONTRIBUTORY TO SUCCESS: A STUDY OF PAKISTAN'S SMALL BUSINESS OWNERS
Authors: COY STEVEN P. , SHIPLEY MARGARET F. , OMER KHURSHEED , KHAN RAO NISAR A.
Published: June 2007

Small business and entrepreneurship have been at the heart of Pakistan's economy for almost 60 years, yet little (if any) research has been conducted that identifies factors crucial for small business success in Pakistan. In the past, studies identifying factors crucial for small business success have focused primarily on the United States and Western Europe. This paper presents survey results from 265 small business owners located in and around Karachi, the largest city and hub of economic activity in Pakistan. The survey was designed to identify the internal and external factors that Pakistani small businesspersons believe are critical for success.
THE NATURE OF ENTREPRENEURSHIP IN THE INFORMAL SECTOR: EVIDENCE FROM ENGLAND
Authors: WILLIAMS COLIN C.
Published: June 2007

Mirroring the representation of informal workers in a third world context as displaying entrepreneurial qualities, recent years have witnessed the emergence of a similar view of the informal sector in western nations as a hidden enterprise culture. Until now, however, few attempts have been made to analyze the nature and motives of informal entrepreneurs in western economies. Instead, it has been widely assumed that those engaged in entrepreneurship in the informal sector are those marginalized from the formal economy and driven out of necessity into this endeavor as a last resort. The aim of this paper is to evaluate critically this "marginalization thesis". Reporting the findings of face-to-face structured interviews with 130 informal entrepreneurs in England, the conventional representation of these entrepreneurs as necessity-driven, as well as an emergent depiction of them as opportunity-driven, is transcended. Instead, a richer and more textured understanding of informal entrepreneurship is developed that replaces such either/or thinking by a both/and approach that depicts how the majority are concurrently both necessity- and opportunity-driven. The paper then concludes by exploring the public policy implications of this rereading of the nature of informal entrepreneurship in western economies.
CONDITIONED SELF-AVOIDING WALK (CSAW): STOCHASTIC APPROACH TO PROTEIN FOLDING
Authors: HUANG KERSON
Published: June 2007

Conditioned self-avoiding walk (CSAW) is a model of protein folding that combines the features of self-avoiding walk (SAW) and the MonteCarlo method. It simulates the Brownian motion of a chain-molecule in the presence of interactions. The model is designed so that one can add desired features step by step. It can be used as guide to structure prediction, as well as theoretical laboratory.
ORGANIC-SILICON INTERFACE
Authors: CHILCOTT TERRY C. , COSTER HANS G. L. , BÖCKING TILL
Published: June 2007

A review of the performances of existing field-effect-transistor (FET) based biosensing devices and reports of fundamental studies of FET structures in a planar geometry identify substantial amplification improvements in eliminating metal intermediaries between the biorecognitive surfaces and the silicon channels, reducing thicknesses of insulating gates and selecting channel apertures that are comparable with achievable thicknesses of depletion layers. Exemplary improvements have been achieved in FET-based silicon nano-wires in which biorecognitive surfaces were attached to the oxidized surfaces that functioned as insulating gates. Fundamental studies in which the silicon dioxide gate was replaced with an organic layer using Si – C chemistry demonstrate the retention of the field-effect characteristics and promise improved performance potential to present FET-based devices. These studies also report electrical field compression of the organic layer and electrical polarisation of the electrolyte that have operational implications for biorecognition. Development of practical robust devices that can exhibit unambiguous recognitive capabilities in diverse biological aquatic environments is dependent on further extensive fundamental studies of organic-silicon interfaces and bio-recognitive processes.
Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria
Authors: Gooijert Karin E. R. , Havinga Rick , Oosterloo-Duinkerken Alida R. , Venekamp-Hoolsema Enge E. A. , Kuipers Folkert , Verkade Henkjan J.
Published: June 2007

Erythropoietic protoporphyria (EPP) is characterized by toxic accumulation of the hydrophobic compound protoporphyrin (PP). Ferrochelatase-deficient ( fch/ fch) mice are an animal model for human EPP. Recently, we have demonstrated that the accumulation of another hydrophobic compound, unconjugated bilirubin, could effectively be treated by stimulation of fecal fat excretion. We investigated whether stimulation of fecal fat excretion enhanced the disposal of PP in fch/ fch mice. Fch/ fch mice were fed for 8 wk with a high-fat diet (16 wt% fat; control) or with the high-fat diet mixed with either a nonabsorbable fat (sucrose polyester) or the intestinal lipase inhibitor orlistat. The effects of the treatments on fecal excretion of fat and PP and on hepatic PP concentrations were compared with control diets. Fecal fat excretion in fch/ fch mice on a high-fat diet was higher than in mice on a low-fat diet (+149%, P < 0.05). Sucrose polyesters and orlistat increased fecal fat excretion even more, up to sixfold of control values. However, none of the different treatments affected fecal PP excretion or hepatic PP concentration. Treatment of fch/ fch mice with a high-fat diet, a nonabsorbable fat diet, or with orlistat increased the fecal excretion of fat but did not increase fecal PP excretion or decrease hepatic PP concentration. The present data indicate that accumulation of PP is not amenable to stimulation of fecal fat excretion.
The role of the cyclooxygenase products in evoking sympathetic activation in exercise
Authors: Cui Jian , McQuillan Patrick , Momen Afsana , Blaha Cheryl , Moradkhan Raman , Mascarenhas Vernon , Hogeman Cynthia , Krishnan Anandi , Sinoway Lawrence I.
Published: June 2007

Animal studies suggest that prostaglandins in skeletal muscles stimulate afferents and contribute to the exercise pressor reflex. However, human data regarding a role for prostaglandins in this reflex are varied, in part because of systemic effects of pharmacological agents used to block prostaglandin synthesis. We hypothesized that local blockade of prostaglandin synthesis in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing exercise. Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 12 young healthy subjects during static handgrip and postexercise muscle ischemia (PEMI) before and after local infusion of 6 mg of ketorolac tromethamine in saline via Bier block (regional intravenous anesthesia). In the second experiment ( n = 10), the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased the prostaglandins synthesis to ∼33% of the baseline. After ketorolac Bier block, the increases in MSNA from the baseline during the fatiguing handgrip was significantly lower than that before the Bier block (before ketorolac: Δ502 ± 111; post ketorolac: Δ348 ± 62%, P = 0.016). Moreover, the increase in total MSNA during PEMI after ketorolac was significantly lower than that before the Bier block ( P = 0.014). Saline Bier block had no similar effect. The observations indicate that blockade of prostaglandin synthesis attenuates MSNA responses seen during fatiguing handgrip and suggest that prostaglandins contribute to the exercise pressor reflex.
Cholinergic mechanisms of cutaneous active vasodilation during heat stress in cystic fibrosis
Authors: Kellogg D. L. , Hodges G. J. , Orozco C. R. , Phillips T. M. , Zhao J. L. , Johnson J. M.
Published: June 2007

To test the hypothesis that cutaneous active vasodilation in heat stress is mediated by a redundant cholinergic cotransmitter system, we examined the effects of atropine on skin blood flow (SkBF) increases during heat stress in persons with (CF) and without cystic fibrosis (non-CF). Vasoactive intestinal peptide (VIP) has been implicated as a mediator of cutaneous vasodilation in heat stress. VIP-containing cutaneous neurons are sparse in CF, yet SkBF increases during heat stress are normal. In CF, augmented ACh release or muscarinic receptor sensitivity could compensate for decreased VIP; if so, active vasodilation would be attenuated by atropine in CF relative to non-CF. Atropine was administered into skin by iontophoresis in seven CF and seven matched non-CF subjects. SkBF was monitored by laser-Doppler flowmetry (LDF) at atropine treated and untreated sites. Blood pressure [mean arterial pressure (MAP)] was monitored (Finapres), and cutaneous vascular conductance was calculated (CVC = LDF/MAP). The protocol began with a normothermic period followed by a 3-min cold stress and 30–45 min of heat stress. Finally, LDF sites were warmed to 42°C to effect maximal vasodilation. CVC was normalized to its site-specific maximum. During heat stress, CVC increased in both CF and non-CF ( P < 0.01). CVC increases were attenuated by atropine in both groups ( P < 0.01); however, the responses did not differ between groups ( P = 0.99). We conclude that in CF there is not greater dependence on redundant cholinergic mechanisms for cutaneous active vasodilation than in non-CF.
Is the Bipolar Spectrum the Psychopathological Substrate of Suicidality in Heroin Addicts?
Authors: Maremmani Icro , Pani Pier Paolo , Canoniero Stefania , Pacini Matteo , Perugi Giulio , Rihmer Zoltán , Akiskal Hagop S.
Published: June 2007

Background: To describe the prevalence and the risk factors of suicidal ideation in a cohort of Italian opioid addicts presenting for treatment. Method: Systematic cross-sectional clinical data on suicidal ideation, socio-demographic variables, psychiatric status, social adjustment, status and history of addiction in 616 patients were gathered. Results: Suicidal thoughts during the past week were reported by 29.1%. Suicidal thoughts were more frequent in patients with bipolar spectrum diagnoses (OR = 1.42) and in patients with depressive and aggressive symptoms (multiple R = 0.47). The odds of having suicidal thoughts were also higher for subjects receiving public welfare benefits (OR = 1.69), unemployed patients (OR = 1.37), those with early onset of heroin dependence (OR = 1.36), living alone (OR = 1.33), and experiencing problems in organizing social contacts and leisure time (OR = 1.28). Conclusion: Current suicidal ideation was a common feature of patients with opioid addiction. Depression and hostility as part of the bipolar spectrum – in the context of early-onset drug dependence, work and social/leisure problems – appear independently associated with suicidal ideation. Given the elevated rates of completed suicide in heroin addiction, these data have implications for preventing suicide in patients with this type of addiction. Prospective data are needed to further address this important clinical and public health agenda.
Dimensions of Delusional Experiences and Their Value as Predictors of Long-Term Outcome
Authors: Opjordsmoen Stein , Retterstøl Nils
Published: June 2007

Background: Delusions are categorized as present or not in classificatory systems, but can fluctuate in intensity over time. They are sometimes difficult to describe, and might be better conceptualized as continuous on a number of dimensions. The predictive value of dimensional ratings of delusions was studied. Material and Methods: Out of 180 first-episode psychotic patients who had been personally followed up after 30 years, a subsample of 41 was randomly drawn, 21 of the 180, 10 of those with GAS scores of 70 or more, and 10 of those with GAS scores of 30 or less at follow-up. They represented three different groups – a good outcome (n = 17), an intermediate outcome (n = 12), and a poor outcome (n = 12) group. Based on case histories at first presentation, scores on the Dimensions of Delusional Experience Scale were recorded. Results: Poor compared to good outcome patients had delusions at index admission characterized by more conviction, extension, disorganization, bizarreness and pressure. Intermediate outcome patients had scores in between, but closer to the poor outcome group. Conclusions: Dimensional rating scales for assessing delusions might have predictive power, and consequently they should be used in future research, and if replicated these findings might have clinical implications.
Thoracic Endometriosis Syndrome
Authors: Augoulea Areti , Lambrinoudaki Irene , Christodoulakos George
Published: June 2007

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity and is usually confined to the pelvis. Thoracic endometriosis syndrome (TES) is a rare disorder characterized by the presence of functioning endometrial tissue in the pleura, the lung parenchyma and the airways. TES may present with hemoptysis, due to the shedding of endometrial tissue in the bronchial tree, or spontaneous pneumothorax or hemothorax if the endometrial tissue is localized peripherally. Patients are of reproductive age, often nulliparous, with long-standing symptoms. The crucial issue for establishing the diagnosis is the cyclicity of the symptoms which occur along with the menstrual cycle. TES is virtually a diagnosis of exclusion, established on clinical grounds, since neither CT nor endoscopy are specific for TES. Treatment consists of gonadotropin-releasing hormone analogues, aiming to suppress the hypophyseal-gonadal axis, so as to ensure a regression of the endometrial implants. If medical treatment fails, surgical resection of the endometriomas is suggested, although relapse rate may be high.
Enhanced Levels of Oxidized Low-Density Lipoprotein Prime Monocytes to Cytokine Overproduction via Upregulation of CD14 and Toll-Like Receptor 4 in Unstable Angina
Authors: Pasini A. Fratta , Anselmi M. , Garbin U. , Franchi E. , Stranieri C. , Nava M.C. , Boccioletti V. , Vassanelli C. , Cominacini L.
Published: June 2007

Objectives—

The purpose of this study was to establish whether oxidized low-density lipoprotein (oxLDL) contributes to cytokine overproduction via upregulation of CD14 and toll-like receptor-4 (TLR-4) expression on circulating monocytes of unstable angina (UA) patients.

Methods and Results—

Expression of CD14 and TLR-4 on circulating monocytes, and the concentration of plasma oxLDL, (interleukin [IL])-6, IL-1 beta, IL-8, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 (MCP-1) were measured in 27 control (C) subjects, 29 patients with stable angina (SA), and 27 with UA. CD14 and TLR-4 expression on monocytes and circulating IL-6, IL-1 beta, and oxLDL were higher in UA than in SA and C subjects (
P
<0.001). In in vitro experiments, oxLDL increased CD14 and TLR-4 expression (
P
<0.001) in control monocytes as well as IL-6, IL-1 beta, and at a lower extent TNF-α and MCP-1 levels in the supernatant (
P
from <0.05 to <0.001). The preincubation of sera derived from UA patients but with control monocytes also induced a significant increase of CD14 and TLR-4 expression (
P
<0.001) and of IL-6 and IL-1 beta production (
P
<0.001) in the supernatant.

Conclusions—

In UA patients oxLDL may contribute to monocyte overproduction of some cytokines by upregulating CD14 and TLR-4 expression.
Murine Models of Vascular Thrombosis
Authors: Westrick Randal J. , Winn Mary E. , Eitzman Daniel T.
Published: June 2007

Thrombotic complications of vascular disease are the leading cause of morbidity and mortality in most industrialized countries. Despite this, safe and effective drugs targeting these complications are limited, especially in the chronic setting. This is because of the complexity of thrombosis in both arteries and veins, which is becoming increasingly evident as numerous factors are now known to affect the fate of a forming thrombus. To fully characterize thrombus formation in these settings, in vivo models are necessary to study the various components and intricate interactions that are involved. Genetic manipulations in mice are greatly facilitating the dissection of relevant pro- and antithrombotic influences. Standardized models for the study of thrombosis in mice as well as evolving techniques that allow imaging of molecular events during thrombus formation are now available. This review will highlight some of the recent developments in the field of thrombosis using mouse models and how these studies are expanding our knowledge of thrombotic disease.
CRP
Gene Haplotypes, Serum CRP, and Cerebral Small-Vessel Disease
Authors: Reitz Christiane , Berger Klaus , de Maat Moniek P.M. , Stoll Monika , Friedrichs Frauke , Kardys Isabella , Witteman Jacqueline C.M. , Breteler Monique M.B.
Published: June 2007

Background and Purpose—

It remains unclear whether C-reactive protein (CRP) is a serum marker for atherothrombotic disease or a causal factor in the pathogenesis of atherosclerosis. We explored the association between
CRP
gene variations and cerebral small-vessel disease (SVD) in the Rotterdam Scan Study (N=1035) and the MEMO Study (N=268).

Methods—

Common haplotypes within the
CRP
gene were determined by genotype-tagging single-nucleotide polymorphisms. Then their relation with periventricular and subcortical white matter lesions and the prevalence of lacunar brain infarcts was explored by regression analyses.

Results—

There was no association between
CRP
haplotypes and measures of cerebral SVD in either study. There was no effect modification of the association between serum CRP levels and measures of SVD by
CRP
haplotypes.

Conclusions—

Our observations suggest that CRP is not causally involved in the pathogenesis of SVD.
Correlation Between Carotid Intraplaque Hemorrhage and Clinical Symptoms
Authors: Gao Peng , Chen Zuo-quan , Bao Yu-hai , Jiao Li-qun , Ling Feng
Published: June 2007

Background and Purpose—

We sought to investigate the association between carotid intraplaque hemorrhage (IPH) and ipsilateral symptoms of cerebral ischemia.

Methods—

A search was performed for clinical observational studies comparing the incidence of IPH between symptomatic and asymptomatic patients. Odds ratios (ORs) for IPH as a factor in the pathogenesis of neurologic events were calculated and combined by a meta-analysis. Interstudy heterogeneity, estimated effects, and methodologic quality of the studies were assessed.

Results—

Thirty-one studies were included for analysis. The reported ORs varied widely. Overall, the incidence of IPH in the symptomatic groups was significantly higher than in the asymptomatic group. However, there was an apparent trend for heterogeneity (
P
<0.00001) between studies. The random-effects summary estimator of ORs was 2.25 (95% CI, 1.57 to 3.22;
P
<0.00001). To identify potential sources of heterogeneity, subgroup analyses were performed. The pooled ORs varied greatly by stratification. Major heterogeneity was found among studies with low quality, microscopic methods of examination, significant effects, small sizes, early publication, and unequal severity of carotid stenosis in both groups. Large, recent, macroscopic, or high-quality studies, as well as studies with equal degrees of stenosis, tended to yield insignificant associations. The methods in defining and evaluating hemorrhage were very heterogeneous. Characterizations of the age, size, number, and location of hemorrhages were poorly reported and highly variable. In addition, a lack of control of confounders and selection bias were frequently identified among studies.

Conclusions—

Statistical inferences have suggested a plausible role in the production of cerebral ischemia; however, reliable interpretation was strongly undermined by poor methodologic quality, substantial heterogeneity, and suspicious publication bias. To preciously estimate the underlying correlation, a well-designed study with uniformity in definition and evaluation for IPH might be warranted.
Neuroprotective Effects of Leptin Against Ischemic Injury Induced by Oxygen-Glucose Deprivation and Transient Cerebral Ischemia
Authors: Zhang Feng , Wang Suping , Signore Armando P. , Chen Jun
Published: June 2007

Background and Purpose—

Leptin is the major adipose hormone that regulates body weight and energy expenditure by activating leptin receptors in the hypothalamus. Leptin receptors are also present in other cell types, and a potent antiapoptotic effect for leptin has recently been reported. We investigated whether leptin was neuroprotective against ischemic brain injury.

Methods—

In vitro ischemic injury was induced in rat primary neuronal culture by oxygen-glucose deprivation for 90 minutes. In vivo ischemic brain injury was induced by middle cerebral artery occlusion in mice for 60 minutes.

Results—

Leptin receptors were detected in cultured rat cortical neurons, as well as in the mouse cortex, striatum, and hippocampus. In vitro results showed that leptin, 50 to 100 μg/mL, protected primary cortical neurons against death induced by oxygen-glucose deprivation in a concentration-dependent manner. In vivo studies in the mouse brain demonstrated that the intraperitoneal administration of leptin, 2 to 8 mg/kg, dose-dependently reduced infarct volume induced by middle cerebral artery occlusion. Leptin was effective when injected 5 minutes before or 30 to 90 minutes after reperfusion, but not 2 hours after reperfusion. Leptin improved animal body weight recovery and behavioral parameters after cerebral ischemia. Leptin enhanced the phosphorylation of extracellular signal-related kinase 1/2. Both extracellular signal-related kinase 1/2 activation and neuroprotection were abolished by the administration of PD98059 in vitro and in vivo.

Conclusions—

Leptin is neuroprotective against ischemic neuronal injury. Our findings suggest that leptin is a legitimate candidate for the treatment of ischemic stroke.