bluuebunny/crossref_metadata_2025 huggingface dataset:
Too much content, not enough thinking, and too little FUN!
Authors: DiCarlo Stephen E.
Published: November 2009

Teachers often overrate the importance of their content and underrate their influence. However, students forget much of the content that they memorize. Thus, attempts to teach students all that they will need to know is futile. Rather, it is important that students develop an interest and love for lifelong learning. Inspiring and motivating students is critical because unless students are inspired and motivated our efforts are pointless. Once students are inspired and motivated, there are countless resources available to learn more about a subject. Thus, teachers must abandon the mistaken notion that unless they “cover the content” students will be unprepared for the future and they will have failed as teachers. Teachers must not worry about “losing” or “wasting” valuable lecture time for in-class discussion, collaborative problem-solving, and inquiry-based activities that take time away from covering content. Rather than worrying about covering content, teachers must design activities to focus student learning on how to use scientific knowledge to solve important questions. This is important because learning is not committing a set of facts to memory but the ability to use resources to find, evaluate, and use information. In fact, memorizing anything discourages deep thinking. Deep thinking is essential because understanding is the residue of thinking! To encourage thinking we must create a joy, an excitement, and a love for learning. We must make learning fun; because if we are successful, our students will be impatient to run home, study, and contemplate-to really learn.
Ethical approval for research in physiology education
Authors: Kibble Jonathan D.
Published: November 2009

The goal of this article is to reflect on the contemporary ethical standards that should be applied to the publication of physiology education research. As teachers, we are all education researchers to some degree but our appreciation of when and how regulatory requirements apply to our work is variable. A significant number of articles in Advances in Physiology Education that might be classified as “research involving human participants” do not document ethical safeguards such as Institutional Review Board approval and informed consent, which are required according to journal policy. I elaborate my personal view that we should strive to maintain the present community standards for conducting and publishing education research. And, as always, I hope the road to hell is not paved with good intentions!
Living history: F. Eugene Yates
Authors: Urquhart John
Published: November 2009

In 2005, the American Physiological Society (APS) initiated the Living History of Physiology Archival Program to recognize senior members who have made significant contributions during their career to the advancement of the discipline and the profession of physiology. During 2008, the APS Cardiovascular Section selected Francis Eugene Yates to be profiled in Advances in Physiology Education.
Determinants of Resistive Index Shortly after Transplantation: Independent Relationship with Delayed Graft Function
Authors: Rodrigo E. , López-Rasines G. , Ruiz J.C. , Lastra P. , Gómez-Dermitt V. , Gómez-Alamillo C. , González-Cotorruelo J. , Calabia A. , Arias M.
Published: November 2009

Measurement of the vascular resistive index (RI) by Doppler ultrasonography has been proposed as a non-invasive method to evaluate renal allograft dysfunction, but there are conflicting reports about its clinical utility. The aim of our study was to analyse the donor and recipient characteristics related to RI measured at days 2 and 3 after renal transplantation and the relationship between RI and allograft outcome. RI was measured by Doppler ultrasonography in 333 patients at days 2 or 3 post-transplantation. Donor and recipient variables and allograft outcome were collected from a prospectively maintained institutional database. In patients with RI higher than 0.7, donor age, recipient age, duration of renal replacement therapy, incidence of diabetes, hypertension and atherosclerosis in the recipient, pulse pressure, initial creatinine and the incidence of delayed graft function (DGF) were higher. After multivariate analysis, the only variables that remained significant for an increased risk of higher RI were recipient age over 55 years, presence of diabetes in the recipient and DGF. Recipient age, previous diabetes mellitus and DGF are the most important determinants of transplant kidney RI in the first days after transplantation. So both the graft recipient and the graft itself, but not the donor, determine intra-renal Doppler indices.
Response of Secondary Hyperparathyroidism to Cinacalcet Depends on Parathyroid Size
Authors: Hirai Takayuki , Nakashima Ayumu , Takasugi Norihisa , Yorioka Noriaki
Published: November 2009

Background/Aims: Several reports have indicated that the measurement of parathyroid gland size assists the management of patients with secondary hyperparathyroidism. This study examined whether parathyroid gland enlargement influenced the response of secondary hyperparathyroidism to cinacalcet. Methods: Clinically stable hemodialysis patients with secondary hyperparathyroidism that was resistant to conventional treatment received cinacalcet for 6 months. Based on the parathyroid gland size measured by ultrasonography, the patients were divided into group S (gland <500 mm3) and group L (gland ≧500 mm3). Serum levels of intact parathyroid hormone (intact PTH), bone-specific alkaline phosphatase, osteocalcin, and cross-linked N-terminal telopeptide of type 1 collagen were measured over time. Results: Twenty-four patients completed the study. In group S, all markers of bone metabolism and intact PTH were significantly decreased after 3 months of cinacalcet treatment. In contrast, there were no significant changes of these parameters, except for intact PTH, after 3 months in group L. After 6 months of cinacalcet treatment, however, all of the markers of bone metabolism were significantly decreased in both groups. Conclusions: The response to cinacalcet differed between groups S and L. Thus, the presence of parathyroid enlargement (nodular hyperplasia) may delay the response of secondary hyperparathyroidism to cinacalcet.
Antibodies to Core Antigen of Hepatitis B Virus in Patients on Renal Replacement Therapy: Association with Demographic, Clinical and Laboratory Data
Authors: Grzegorzewska Alicja E. , Kurzawska-Firlej Danuta , Ratajewski Włodzimierz , Frankiewicz Dorota , Niepolski Leszek , Kaczmarek Andrzej
Published: November 2009

Background: Total antibodies to core antigen of hepatitis B virus (anti-HBc) are a marker for previous or current infection with hepatitis B virus (HBV). Our aim was to examine the prevalence and incidence of anti-HBc in relation to demographic, clinical and laboratory data of patients treated with intermittent hemodialysis (IHD). Methods: Predictors for anti-HBc positivity were evaluated in prevalence IHD patients with negative testing for surface antigen of HBV (HBsAg, n = 1,105) using the stepwise backward regression analysis. Patients starting IHD (n = 336) were introduced into the one-year prospective study evaluating seroconversion for anti-HBc. Results: Anti-HBc positivity (19.5% of all patients) was predicted by lack of vaccination against HBV with developed protective titer of antibodies to HBsAg (β = 0.592, p = 0.000), vintage of renal replacement therapy (RRT, β = 0.206, p = 0.000), history of hepatitis (β = 0.101, p = 0.000), and activity of alanine aminotransferase (β = 0.057, p = 0.037). In 85 prospective patients who finished first IHD year, seroconversion rate for anti-HBc was 1.23 episodes/100 patient-years. Conclusions: Lack of or not effective vaccination against HBV is the strongest predictor for prevalence of anti-HBc positivity in RRT patients. Periodical determination of anti-HBc, usually not required, may be helpful in evaluation of current epidemiological status and risk for further HBV infection in dialysis centers.
Vascular Access-Related Bloodstream Infections in First Nations, Community and Teaching Canadian Dialysis Units, and Other Centre-Level Predictors
Authors: Lafrance Jean-Philippe , Iqbal Sameena , Lelorier Jacques , Dasgupta Kaberi , Ritchie Judith , Ward Linda , Benaroya Samuel , Barré Paul , Cantarovich Marcelo , Ghannoum Marc , Proulx Normand , Vasilevsky Murray , Rahme Elham
Published: November 2009

Background/Aims: Vascular access-related bloodstream infection (BSI) is frequent among patients undergoing hemodialysis increasing their morbidity and mortality, but its occurrence across various dialysis centre types is not known. The aims of this study were to describe the incidence rates and assess the variability in BSI risk between dialysis centre types and other centre-level variables. Methods: We conducted a retrospective cohort study of 621 patients initiating hemodialysis in 7 Canadian dialysis centres. Cox regression models, where access type was continuously updated, were used to identify predictors of BSI occurrence. Results: During follow-up of the cohort (median age 68.1 years, 41.7% female, and 76.7% initiating with a central venous catheter, CVC), 73 patients had a BSI (rate: 0.21/1000 person-days). The BSI risk was not different in First Nation units (adjusted relative risk: 0.47, 95% confidence interval: 0.06–3.72) and teaching hospitals (1.33, 0.70–2.54) compared to community hospitals. No other centre-related variables were associated with the risk of BSI. Conclusion: We did not find differences in the BSI risk among dialysis unit types, or any other centre-related variables. The rates of BSI in our population were lower than those observed in other settings, but the high proportion of patients using CVCs is concerning.
Preattentive Phonotactic Processing as Indexed by the Mismatch Negativity
Authors: Steinberg Johanna , Truckenbrodt Hubert , Jacobsen Thomas
Published: November 2009

Processing of an obligatory phonotactic restriction outside the focus of the participants' attention was investigated by means of ERPs using (reversed) experimental oddball blocks. Dorsal fricative assimilation (DFA) is a phonotactic constraint in German grammar that is violated in *[ɛx] but not in [ɔx], [ɛ∫], and [ɔ∫]. These stimulus sequences engage the auditory deviance detection mechanism as reflected by the MMN component of the ERP. In Experiment 1 (n = 16), stimuli were contrasted pairwise such that they shared the initial vowel but differed with regard to the fricative. Phonotactically ill-formed deviants elicited stronger MMN responses than well-formed deviants that differed acoustically in the same way from the standard stimulation but did not contain a phonotactic violation. In Experiment 2 (n = 16), stimuli were contrasted such that they differed with regard to the vowel but shared the fricative. MMN was elicited by the vowel change. An additional, later MMN response was observed for the phonotactically ill-formed syllable only. This MMN cannot be attributed to any phonetic or segmental difference between standard and deviant. These findings suggest that implicit phonotactic knowledge is activated and applied in preattentive speech processing.
On the Approximation of Local and Linear Radiative Damping in the Middle Atmosphere
Authors: Hitchcock Peter , Shepherd Theodore G. , Yoden Shigeo
Published: November 2009

The validity of approximating radiative heating rates in the middle atmosphere by a local linear relaxation to a reference temperature state (i.e., “Newtonian cooling”) is investigated. Using radiative heating rate and temperature output from a chemistry–climate model with realistic spatiotemporal variability and realistic chemical and radiative parameterizations, it is found that a linear regression model can capture more than 80% of the variance in longwave heating rates throughout most of the stratosphere and mesosphere, provided that the damping rate is allowed to vary with height, latitude, and season. The linear model describes departures from the climatological mean, not from radiative equilibrium. Photochemical damping rates in the upper stratosphere are similarly diagnosed. Three important exceptions, however, are found. The approximation of linearity breaks down near the edges of the polar vortices in both hemispheres. This nonlinearity can be well captured by including a quadratic term. The use of a scale-independent damping rate is not well justified in the lower tropical stratosphere because of the presence of a broad spectrum of vertical scales. The local assumption fails entirely during the breakup of the Antarctic vortex, where large fluctuations in temperature near the top of the vortex influence longwave heating rates within the quiescent region below. These results are relevant for mechanistic modeling studies of the middle atmosphere, particularly those investigating the final Antarctic warming.
The Unit Symbol for the Logarithmic Scale of Radar Reflectivity Factors
Authors: Smith Paul L.
Published: November 2009

This note argues that the proper symbol for the logarithmic unit of radar reflectivity factor is dBz. The basis for this contention lies in both customary engineering practice and the international standard for unit symbols.
Acoustic Detection of Oceanic Double-Diffusive Convection: A Feasibility Study
Authors: Ross Tetjana , Lavery Andone
Published: November 2009

The feasibility of using high-frequency acoustic scattering techniques to map the extent and evolution of the diffusive regime of double-diffusive convection in the ocean is explored. A scattering model developed to describe acoustic scattering from double-diffusive interfaces in the laboratory, which accounted for much of the measured scattering in the frequency range from 200 to 600 kHz, is used in conjunction with published in situ observations of diffusive-convection interfaces to make predictions of acoustic scattering from oceanic double-diffusive interfaces. Detectable levels of acoustic scattering are predicted for a range of different locations in the world’s oceans. To corroborate these results, thin acoustic layers detected near the western Antarctic Peninsula using a multifrequency acoustic backscattering system are shown to be consistent with scattering from diffusive-convection interfaces.
An Improved Statistical Scheme for the Prediction of Tropical Cyclones Making Landfall in South China
Authors: Zung-Ching Goh Andy , Chan Johnny C. L.
Published: November 2009

This study describes an improved statistical scheme for predicting the annual number of tropical cyclones (TCs) making landfall along the coast of south China using data from 1965 to 2005. Based on the factors affecting TC behavior inside the South China Sea (SCS), those responsible for TCs making landfall are identified. Equations are then developed using the coefficients of empirical orthogonal functions of these factors to predict, in April, the number of these TCs in the early (May–August) and late (September–December) seasons, and in June, the number in the period between July to December. The new scheme achieves a forecast skill of 51% over climatology, or an improvement of about 11% compared to previous studies, when predicting landfalling TC for the whole season, and it seems to be able to capture the decrease in their number in the recent years. Analyses of the flow patterns suggest that the conditions inside the SCS are apparently the major factor affecting the number of landfalling TCs. In years in which this number is above normal, conditions inside the SCS are favorable for TC genesis, and vice versa. The strength of the 500-hPa subtropical high also seems to be a factor in determining whether TCs from the western North Pacific (WNP) could enter the SCS and make landfall.
Putting the ‘T’ into South African Human Rights: Transsexuality in the Post-Apartheid Order
Authors: Vincent Louise , Camminga Bianca
Published: November 2009

Informed by narratives provided by self-identified South African transsexuals, whose lives span different periods of South Africa’s political and social history, this article seeks to explore how South Africa’s medical, legal and military establishments have exerted power over the transsexual body. A variety of studies outline the extent to which the apartheid state was a highly gendered state characterized by inflexible patriarchal norms and the dominance of violent and authoritarian forms of masculine expression. Hyper masculinization and militarization were explicit goals of the apartheid state. Deviance from the state’s prescribed gender norms was not simply socially unacceptable, it was, in many cases, punishable. South Africa’s post-1994 democratic Constitution, in contrast, explicitly outlaws discrimination on the basis of sexual orientation. But the democratic legal framework, which provides significant protections for freedom of sexual expression and freedom from discrimination for homosexuals has arguably had less of an impact on the lives of South Africa’s transsexual community. The state, even the post-apartheid state, has been loathe to move beyond the idea of a necessary correlation between the physical make-up of the body and the gender identity of a person in the way in which it has treated the idea of transsexualism.
‘Just Take Viagra’: Erectile Insurance, Prophylactic Certainty and Deficit Correction in Gay Men’s Accounts of Sexuopharmaceutical Use
Authors: Holt Martin
Published: November 2009

Gay men’s recreational use of Viagra and similar drugs has received considerable attention in the public health literature, implicating Viagra as a risk factor for HIV transmission. Framed by work on the pharmaceuticalization of everyday life and critical Viagra studies, gay men’s accounts are analysed to assess the ways in which Viagra is understood, valued and experienced. Viagra was commonly described as a corrective remedy that guaranteed erectile performance, aided condom use and simplified decisions about safe sex. The mismatch between public health discourse and gay men’s understandings of Viagra, as well as the reliance on Viagra for safe sex, are discussed in relation to harm reduction and HIV prevention efforts, suggesting a need to encourage critical reflection on sexuopharmaceutical use among gay men.
Online consumer misbehaviour: an application of neutralization theory
Authors: Harris Lloyd C. , Dumas Alexia
Published: November 2009

Studies have argued that misbehaviour by customers is becoming increasingly prevalent in certain sectors. However, online consumer misbehaviour is comparatively under-researched. The focus of the current study is peer-to-peer activities, including copying music, movies, software or video games: a phenomenon which affects the entertainment sector as a whole and costs the industry billions of pounds each year. Neutralization theory provides a potentially fruitful perspective from which to explore consumer justifications and rationalizations for their online misbehaviour. The aim of this paper is to explore the extent to which peer-to-peer users employ techniques of neutralization to justify prior-to behaviour or rationalize their activities post behaviour. First, a review of online customer misbehaviour is provided, followed by an overview of existing research into the techniques of neutralization. Following a discussion of the research methods employed, findings regarding the peer-to-peer online misbehaviours and neutralization techniques are presented. Data analysis reveals that peer-to-peer file-sharers employ (often multiple) techniques of neutralization in order to pre-justify or post-event rationalize their activities, including: denial of victim; denial of injury; denial of responsibility; claim of normality; claim of relative acceptability; justification by comparison; and appeal to higher loyalties. The paper concludes with a series of implications for both theory and practice.
Freedom and constraint in the empowerment as jazz metaphor
Authors: Oakes Steve
Published: November 2009

This paper assesses the cultural diversity of improvisation. More specifically, it focuses upon the empowerment as jazz metaphor by highlighting a two-way process considering what marketers (including managers and empowered direct contact staff) and improvising jazz musicians can learn from each other. It examines the apparently polarized concepts of freedom and constraint by identifying how jazz guitarists differ on a hypothetical continuum in terms of the divergence of their performances, as demonstrated by the level of preconceived structuring and pre-composition evident in their work. The metaphorical link highlights the value of making scripted responses appear more customized and spontaneous in order to create the impression of a more personalized service encounter. It urges increased opportunities for employees to be creative and imaginative, but considers the extent to which the freedom to make real-time decisions may be a nebulous and partially illusory ideal for both the empowered service provider and the improvising jazz musician.
Effect of viscosity on microstructure characteristic in rheological behaviour of wrought aluminium alloys by compression and stirring process
Authors: Kim W. Y. , Kang C. G. , Lee S. M.
Published: November 2009

Compression and stirring tests were performed to investigate the rheological behaviour of wrought aluminium alloys with varying processing parameters, such as liquid fraction, strain rate, shear rate and materials. The present paper shows the results of an experimental investigation using Al2024, Al6061 and Al7075. Specimens of each aluminium alloy were characterised by their rheological behaviour during partial melting and holding in the semisolid state. The compression and stirring tests allow the apparent viscosity of the alloys to be determined as a function of the liquid fraction and shear rate. Moreover, the change of grain size and shape was examined by considering shear rate, stirring time and liquid fraction during stirring. These experimental results could be used in flow and solidification analyses and could be useful for manufacturing good rheological products by observing the microstructures according to changes in solid fraction and compression rates.
Preparation of Ti–Ni–Fe phase by levitation and its structural characterisation
Authors: Sypien A. , Przybylo W.
Published: November 2009

This paper presents results concerning the electromagnetic levitation of solid metal samples. It describes the levitation system and some coils designed to melt 10 g metal samples under controlled atmosphere, as well as melting the process. The main advantage of the method is the absence of any type of crucible and owing to this, the effect of side reaction can be avoided, resulting from the influence of the active metal on the walls of the ceramic crucible in the physicochemical investigations. In many cases, the side reaction makes the correct interpretation of the experimental results sometimes difficult and/or impossible. In order to describe the crystallisation process and the change in the microstructure of the samples obtained during electromagnetic melting at the intermetallic Fe–Ni–Ti phase, a scanning electron microscopy analysis and an X-ray diffraction analysis were used.
Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells
Authors: Gosens R. , Rieks D. , Meurs H. , Ninaber D. K. , Rabe K. F. , Nanninga J. , Kolahian S. , Halayko A. J. , Hiemstra P. S. , Zuyderduyn S.
Published: November 2009

Acetylcholine is the primary parasympathetic neurotransmitter in the airways and is known to cause bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine also regulates aspects of remodelling and inflammation through its action on muscarinic receptors.

In the present study, we aimed to determine the effects of muscarinic receptor stimulation on cytokine production by human airway smooth muscle cells (primary and immortalised cell lines). The muscarinic receptor agonists carbachol and methacholine both induced modest effects on basal interleukin (IL)-8 and -6 secretion, whereas the secretion of RANTES, eotaxin, vascular endothelial growth factor-A and monocyte chemoattractant protein-1 was not affected. Secretion of IL-8 and -6 was only observed in immortalised airway smooth muscle cells that express muscarinic M3 receptors. In these cells, methacholine also significantly augmented IL-8 secretion in combination with cigarette smoke extract in a synergistic manner, whereas synergistic effects on IL-6 secretion were not significant.

Muscarinic M3 receptors were the primary subtype involved in augmenting cigarette smoke extract-induced IL-8 secretion, as only tiotropium bromide and muscarinic M3 receptor subtype selective antagonists abrogated the effects of methacholine.

Collectively, these results indicate that muscarinic M3 receptor stimulation augments cigarette smoke extract-induced cytokine production by airway smooth muscle. This interaction could be of importance in patients with chronic obstructive pulmonary disease.
Tuberculosis screening in Portuguese healthcare workers using the tuberculin skin test and the interferon-γ release assay
Authors: Torres Costa J. , Sá R. , Cardoso M. J. , Silva R. , Ferreira J. , Ribeiro C. , Miranda M. , Plácido J. L. , Nienhaus A.
Published: November 2009

The prevalence of latent tuberculosis (TB) infection (LTBI) and the incidence of active tuberculosis in healthcare workers (HCWs) in a Portuguese hospital were examined.

This cross-sectional study comprises 4,735 hospital workers screened between May 2005 and September 2008. Tuberculin skin test (TST) and interferon-γ release assay (IGRA) were used simultaneously in 1,219 HCWs (25.7%). Radiographs were taken in symptomatic HCWs or in test-positive HCWs. The tests were repeated annually or bi-annually depending on risk assessment.

IGRA was positive in 32.6% and TST in 74.2% of the HCWs. Years spent in healthcare were a risk factor for a positive IGRA, but not for a positive TST. Repeated bacillus Calmette–Guérin vaccination increased the probability of TST+/IGRA- discordance (35.4%versus54.4%, respectively). In those tested three times with TST during the study period (n = 59), the mean diameter of TST increased from 5 to 7 to 10 mm. Within 3 yrs, 31 HCWs were diagnosed with active TB (annual incidence rate 191 out of 100,000 people). In eight HCWs with active TB, TST and IGRA were performed at the time of diagnosis and each test was positive.

TB burden in HCWs in Portugal is high. With IGRA, the number of radiographs needed to exclude active TB could have been reduced by about half without missing a case of active TB. Therefore IGRA should be introduced into TB screening programmes.
EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration
Authors: Field J. K. , Liloglou T. , Niaz A. , Bryan J. , Gosney J. R. , Giles T. , Brambilla C. , Brambilla E. , Vesin A. , Timsit J-F. , Hainaut P. , Martinet Y. , Vignaud J. M. , Thunnissen F. B. , Prinsen C. , Snijders P. J. , Smit E. F. , Sozzi G. , Roz L. , Risch A. , Becker H. D. , Elborn J. S. , Magee N. D. , Montuenga L. M. , Pajares M. J. , Lozano M. D. , O'Byrne K. J. , Harrison D. J. , Niklinski J. , Cassidy A. ,   the EUELC Collaborators
Published: November 2009

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens.

The molecular–pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARβ genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways.

The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes.
Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma
Authors: Aceto N. , Bertino P. , Barbone D. , Tassi G. , Manzo L. , Porta C. , Mutti L. , Gaudino G.
Published: November 2009

Malignant mesothelioma is an asbestos-related, aggressive tumour, resistant to most anticancer therapies. Akt is a key mediator of mesothelioma cell survival and chemoresistance. This study aimed to clarify the mechanism by which taurolidine (TN), a known synthetic compound with antimicrobial and antineoplastic properties, leads to mesothelioma cell death.

Apoptosis was studied by annexin V binding, cell cycle analysis, caspase-8 activation, poly(ADP-ribose) polymerase (PARP) cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL). Oxidative stress was measured by nitrite production and DNA oxidative damage. Protein expression and phosphorylation were evaluated by immunoprecipitation and immunoblotting.

TN induces cell death of mesothelioma cells, but not of non-neoplastic human mesothelial cells. After TN treatment of mesothelioma cells, Akt but not extracellular signal-regulated kinase (Erk) 1/2 activity is inhibited a in time- and dose-dependent manner. Protein phosphatase (PP)1α and PP2A are activated several hours after drug addition. Apoptosis induced by TN is driven by oxidative stress and cell exposure to sulfydryl donors, such as glutathione monoethylester andl-N-acetylcysteine, significantly reduced pro-apoptotic effects and Akt inhibition. Conversely, expression of constitutively activated Akt did not affect cytoxicity elicited by TN, which retained its ability to inhibit the kinase.

TN induces mesothelioma cell deathviaoxidative stress, accompanied by inhibition of Akt signalling. This provides a promising molecular rationale for TN as local treatment of malignant mesothelioma.
Effects of a leukotriene B4receptor antagonist on bleomycin-induced pulmonary fibrosis
Authors: Izumo T. , Kondo M. , Nagai A.
Published: November 2009

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Leukotrienes play an important role in IPF, and leukotriene (LT)B4is one of the key eicosanoids in IPF. In this study, we investigated whether ONO-4057, a LTB4receptor (BLTR) antagonist is capable of preventing bleomycin-induced pulmonary fibrosis.

On day 1, C57BL/6 male mice were given a single intratracheal injection of bleomycin (2.5 mg·kg−1), and ONO-4057 (1.0 mg·kg−1) or vehicle alone, administered by intraperitoneal injection on days 1–5 each week for 3 weeks after the bleomycin injection.

ONO-4057 reduced the total cell count in bronchoalveolar lavage fluid (BALF) on days 7, 14 and 21 and the Ashcroft score and the lung hydroxyproline content on days 14 and 21. The LTB4, interleukin (IL)-6, IL-13, transforming growth factor (TGF)-β levels in BALF and the TGF-β expression in lung tissue, assessed by immunohistochemistry were decreased on day 7, whereas interferon (IFN)-γ level in BALF was increased on day 14.

The results of this study indicated that the BLTR antagonist inhibited the development of bleomycin-induced pulmonary fibrosis in mice by decreasing inflammation and altering TGF-β, IL-6, IL-13 and IFN-γ.
Mechanisms controlling the volume of pleural fluid and extravascular lung water
Authors: Miserocchi G.
Published: November 2009

Pleural and interstitial lung fluid volumes are strictly controlled and maintained at the minimum thanks to the ability of lymphatics to match the increase in filtration rate. In the pleural cavity, fluid accumulation is easily accommodated by retraction of lung and chest wall (high compliance of the pleural space); the increase of lymph flow per unit increase in pleural fluid volume is high due to the great extension of the parietal lymphatic. However, for the lung interstitium, the increase in lymph flow to match increased filtration does not need to be so great. In fact, increased filtration only causes a minor increase in extravascular water volume (<10%) due to a marked increase in interstitial pulmonary pressure (low compliance of the extracellular matrix) which, in turn, buffers further filtration. Accordingly, a less extended lymphatic network is needed. The efficiency of lymphatic control is achieved through a high lymphatic conductance in the pleural fluid and through a low interstitial compliance for the lung interstitium. Fluid volume in both compartments is so strictly controlled that it is difficult to detect initial deviations from the physiological state; thus, a great physiological advantage turns to be a disadvantage on a clinical basis as it prevents an early diagnosis of developing disease.
Long-term outcome in pulmonary arterial hypertension: a plea for earlier parenteral prostacyclin therapy
Authors: Delcroix M. , Spaas K. , Quarck R.
Published: November 2009

The present review aims to examine the effect of specific drugs on long-term outcome of pulmonary arterial hypertension (PAH), to critically review the available data, and to derive useful information for daily patient care.

PAH is an intrinsic disease of the pulmonary circulation with a malignant evolution as a consequence of progressive right heart failure. Without specific therapy, median survival is only 2.8 yrs. The intravenous prostacyclin analogue epoprostenol is the only treatment with a demonstrated effect on survival, observed during a single 12-week randomised placebo-controlled trial. Three long-term observational studies have also shown that median survival is raised above 6 yrs with this therapy. Subcutaneous treprostinil appears to have similar beneficial effects on survival, as reported in two long-term observational studies. This is not the case for inhaled iloprost, as shown in one study in which a high proportion of patients needed the addition of, or the switch to, another therapy. Among the oral agents, long-term data have only been published for bosentan. The three studies including patients from expert centres also showed very good survival data, but again with a broad use of combination therapy. In less expert hands, with limited access to more complex therapies, reported survival seems much worse. In these studies, baseline New York Heart Association class and 6-min walk distance are repeatedly shown to be important predictors of survival. Finally, there is emerging data that prostanoid therapy results in a tendency to normalise C-reactive protein levels, a factor associated with improved long-term outcomes.
Epidemiology of COPD
Authors: Raherison C. , Girodet P-O
Published: November 2009

Chronic obstructive pulmonary disease (COPD) is responsible for early mortality, high death rates and significant cost to health systems. The projection for 2020 indicates that COPD will be the third leading cause of death worldwide (from sixth in 1990) and fifth leading cause of years lost through early mortality or handicap (disability-adjusted life years) (12th in 1990). Active smoking remains the main risk factor, but other factors are becoming better known, such as occupational factors, infections and the role of air pollution. Prevalence of COPD varies according to country, age and sex. This disease is also associated with significant comorbidities. COPD is a disorder that includes various phenotypes, the continuum of which remains under debate. The major challenge in the coming years will be to prevent onset of smoking along with early detection of the disease in the general population.
Pharmacological actions of statins: potential utility in COPD
Authors: Young R. P. , Hopkins R. , Eaton T. E.
Published: November 2009

Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD.
The endothelin system in pulmonary and renal vasculopathy: les liaisons dangereuses
Authors: Vachiéry J-L , Davenport A.
Published: November 2009

Endothelial cells regulate vascular tone largely by the actions of endothelin-1. Endothelin-1 is a potent vasoconstrictor, with effects that are dependent on the receptors to which it binds as well as their location. Endothelin-1 dysregulation is implicated in pathological conditions, including those of the pulmonary vasculature and the kidney. In this review, we describe the physiology and actions of endothelin-1 in lung and renal tissues and discuss therapies that disrupt these interactions in disease states. We provide an overview of the current clinical progress of these targeted agents and provide perspectives on the treatment of pulmonary and renal diseases with endothelin receptor antagonists.
Implementing the ESC/ERS pulmonary hypertension guidelines: real-life cases from a national referral centre
Authors: Montani D. , O'Callaghan D. S. , Jaïs X. , Savale L. , Natali D. , Redzepi A. , Hoette S. , Parent F. , Sitbon O. , Simonneau G. , Humbert M.
Published: November 2009

Pulmonary hypertension (PH) comprises a heterogeneous group of disorders characterised by increased pulmonary vascular resistance that results in progressive right ventricular failure. In order to translate current evidence into routine clinical practice, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) have recently jointly proposed evidence-based guidelines for the optimal management of different PH patient groups. This article describes a series of clinical cases of PH due to various aetiologies that were referred to a large national PH expert referral centre. In each case, the assessment and therapeutic approach undertaken is described in the context of the new ECS/ERS guidelines. The routine diagnostic work-up of suspected idiopathic pulmonary arterial hypertension (PAH) and recommended treatments for patients with functional class II, III and IV disease is emphasised. Familial screening and management of heritable PAH is discussed. Appropriate investigation and therapeutic strategies for patients with chronic thromboembolic disease and PH that is associated with congenital heart disease, pulmonary veno-occlusive disease and systemic sclerosis are also highlighted.
High genotypic diversity and a novel variant of human cytomegalovirus revealed by combined UL33/UL55 genotyping with broad-range PCR
Authors: Deckers Merlin , Hofmann Jörg , Kreuzer Karl-Anton , Reinhard Henrike , Edubio Abigail , Hengel Hartmut , Voigt Sebastian , Ehlers Bernhard
Published: November 2009

The known strains of human cytomegalovirus (HCMV) represent genotypic variants of a single species, and HCMV genotypic variability has been studied in order to reveal correlations between different disease patterns and the presence of certain HCMV genotypes, either as single or as multiple infections. The methods used for the detection of HCMV genotypes have not always been sophisticated enough to achieve complete comprehensiveness, mainly because only one genotype is usually detected in a certain specimen, due to primer specificity and genome copy number. To improve detection of variant HCMV genotypes in mixed infections, we developed PCR assays with degenerate primers targeting two variable HCMV genes, glycoprotein B (gB, UL55) and the G-protein-coupled receptor gene UL33. Primers were designed to bind conserved sites in the genomes of HCMV variants and great ape CMVs. To analyse if samples contained one or more HCMV genotypic variants, PCR assays were supplemented with oligonucleotides containing locked nucleic acids. This broad-range PCR methodology and subsequent sequence analysis detected all gB/UL55 and UL33 genotypic variants known to date in primary clinical specimens, but also revealed that many samples contained genotype mixtures. Importantly, a novel UL33 genotypic variant could be discovered in several specimens, and one HCMV isolate was plaque-purified containing the novel UL33 genotype and a so far undescribed variant of gB.
Editorial: Regulation of the regulator: sympathetic nervous system control of regulatory T cells
Authors: Grebe Kristie M
Published: November 2009

Discussion of data presented by Bhowmick et al. and the current knowledge of symptomatic nervous system interactions with immune function.
Late-life depression in Peru, Mexico and Venezuela: the 10/66 population-based study
Authors: Guerra Mariella , Ferri Cleusa P. , Sosa Ana Luisa , Salas Aquiles , Gaona Ciro , Gonzales Victor , de la Torre Gabriela Rojas , Prince Martin
Published: November 2009

Background

The proportion of the global population aged 60 and over is increasing, more so in Latin America than any other region. Depression is common among elderly people and an important cause of disability worldwide.

Aims

To estimate the prevalence and correlates of late-life depression, associated disability and access to treatment in five locations in Latin America.

Method

A one-phase cross-sectional survey of 5886 people aged 65 and over from urban and rural locations in Peru and Mexico and an urban site in Venezuela. Depression was identified according to DSM–IV and ICD–10 criteria, Geriatric Mental State–Automated Geriatric Examination for Computer Assisted Taxonomy (GMS–AGECAT) algorithm and EURO–D cut-off point. Poisson regression was used to estimate the independent associations of sociodemographic characteristics, economic circumstances and health status with ICD–10 depression.

Results

For DSM–IV major depression overall prevalence varied between 1.3% and 2.8% by site, for ICD–10 depressive episode between 4.5% and 5.1%, for GMS–AGECAT depression between 30.0% and 35.9% and for EURO–D depression between 26.1% and 31.2%; therefore, there was a considerable prevalence of clinically significant depression beyond that identified by ICD–10 and DSM–IV diagnostic criteria. Most older people with depression had never received treatment. Limiting physical impairments and a past history of depression were the two most consistent correlates of the ICD–10 depressive episode.

Conclusions

The treatment gap poses a significant challenge for Latin American health systems, with their relatively weak primary care services and reliance on private specialists; local treatment trials could establish the cost-effectiveness of mental health investment in the government sector.
Cannabis and suicide: longitudinal study
Authors: Price Ceri , Hemmingsson Tomas , Lewis Glyn , Zammit Stanley , Allebeck Peter
Published: November 2009

Background

Some studies suggest that cannabis use is associated with suicidal ideation, but no detailed longitudinal study has examined suicide as an outcome.

Aims

To examine the association between cannabis use and completed suicide.

Method

A longitudinal study investigated 50 087 men conscripted for Swedish military service, with cannabis use measured non-anonymously at conscription. Suicides during 33 years of follow-up were identified by linkage with the National Cause of Death Register.

Results

There were 600 (1.2% of cohort) suicides or deaths from undetermined causes. Cannabis use was associated with an increased risk of suicide (crude OR for ‘ever use’ 1.62, 95% CI 1.28–2.07), but this association was eliminated after adjustment for confounding (adjusted OR = 0.88, 95% CI 0.65–1.20).

Conclusions

Although there was a strong association between cannabis use and suicide, this was explained by markers of psychological and behavioural problems. These results suggest that cannabis use is unlikely to have a strong effect on risk of completed suicide, either directly or as a consequence of mental health problems secondary to its use.
Resetting Iran in US Policy
Authors: Pranger Robert J.
Published: November 2009

The Obama administration seems to have given considerable attention to the diplomatic idea of resetting various areas of US foreign policy. As Iran and Israel move toward possible war over regional hegemony with each other—a conflict that looms sooner rather than later—nuclear capability provides leverage for both powers. It is incumbent on the United States to intervene as a third-power mediator, rather than as leader of sanctions against Iran, in order to maintain a stable balance of power in the Middle East. This position would represent a genuine resetting of US foreign policy.
Middle East Vortex: An Unstable Iraq and Its Implications for the Region
Authors: Carpenter Ted Galen
Published: November 2009

The United States seems committed to withdrawing its forces from Iraq by the end of 2011. Experts worry that the relative calm since mid-2007 might not last once US troops depart. Indeed, there are serious questions about whether Iraq can be a viable state in the long run. If Iraq becomes a cockpit of instability, as it was during the first four years following the US invasion, the implications for the region are ominous. Unfortunately, the factors that cause turbulence, including Kurdish secessionist aspirations and simmering Sunni-Shiite tensions, are largely beyond the control of the United States.
America and the Russian-Georgian War
Authors: Blank Stephen
Published: November 2009

This article analyzes the consequences of the 2008 Russian-Georgian war and the unfocused US response to that war. It describes the negative tendencies in both Russian behavior and European security that were illuminated by the war, and concludes that the West, including the United States, suffered serious geopolitical defeats, with consequences that have not yet been remedied or overcome. Therefore, the West's security situation vis-à-vis Russia and Central Eurasia remains fraught with potential serious dangers.