bluuebunny/crossref_metadata_2025 huggingface dataset:
WiFi networks and malware epidemiology
Authors: Hu Hao , Myers Steven , Colizza Vittoria , Vespignani Alessandro
Published: January 2009

In densely populated urban areas WiFi routers form a tightly interconnected proximity network that can be exploited as a substrate for the spreading of malware able to launch massive fraudulent attacks. In this article, we consider several scenarios for the deployment of malware that spreads over the wireless channel of major urban areas in the US. We develop an epidemiological model that takes into consideration prevalent security flaws on these routers. The spread of such a contagion is simulated on real-world data for georeferenced wireless routers. We uncover a major weakness of WiFi networks in that most of the simulated scenarios show tens of thousands of routers infected in as little as 2 weeks, with the majority of the infections occurring in the first 24–48 h. We indicate possible containment and prevention measures and provide computational estimates for the rate of encrypted routers that would stop the spreading of the epidemics by placing the system below the percolation threshold.
Expression profiling during ocular development identifies 2
Nlz
genes with a critical role in optic fissure closure
Authors: Brown Jacob D. , Dutta Sunit , Bharti Kapil , Bonner Robert F. , Munson Peter J. , Dawid Igor B. , Akhtar Amana L. , Onojafe Ighovie F. , Alur Ramakrishna P. , Gross Jeffrey M. , Hejtmancik J. Fielding , Jiao Xiaodong , Chan Wai-Yee , Brooks Brian P.
Published: January 2009

The gene networks underlying closure of the optic fissure during vertebrate eye development are poorly understood. Here, we profile global gene expression during optic fissure closure using laser capture microdissected (LCM) tissue from the margins of the fissure. From these data, we identify a unique role for the C
2
H
2
zinc finger proteins Nlz1 and Nlz2 in normal fissure closure. Gene knockdown of
nlz1
and/or
nlz2
in zebrafish leads to a failure of the optic fissure to close, a phenotype which closely resembles that seen in human uveal coloboma. We also identify misregulation of
pax2
in the developing eye of morphant fish, suggesting that Nlz1 and Nlz2 act upstream of the
Pax2
pathway in directing proper closure of the optic fissure.
Nodal points and complexity of Notch-Ras signal integration
Authors: Hurlbut Gregory D. , Kankel Mark W. , Artavanis-Tsakonas Spyros
Published: January 2009

Metazoans use a handful of highly conserved signaling pathways to create a signaling backbone that governs development. How these few signals have such a versatile action likely depends upon the larger-scale network they form through integration, as exemplified by cross-talk between the Notch and receptor tyrosine kinase (RTK) pathways. We examined the transcriptional output of Notch–RTK cross-talk duringDrosophiladevelopment and present in vivo data supporting a role for selected mutually regulated genes in signal integration. Interestingly, Notch–RTK integration did not lead to general antagonism of either pathway, as is commonly believed. Instead, integration had a combinatorial effect on specific cross-regulated targets, which unexpectedly included numerous core components of the RTK and other major signaling pathways (TGF-β, Hh, Jak/Stat, nuclear receptor and Wnt). We find the majority of Ras-responsive genes are also Notch-responsive, suggesting Notch may function to specify the response to Ras activation.
Generalized ensemble methods for de novo structure prediction
Authors: Shmygelska Alena , Levitt Michael
Published: January 2009

Current methods for predicting protein structure depend on two interrelated components: (i) an energy function that should have a low value near the correct structure and (ii) a method for searching through different conformations of the polypeptide chain. Identification of the most efficient search methods is essential if we are to be able to apply such methods broadly and with confidence. In addition, efficient search methods provide a rigorous test of existing energy functions, which are generally knowledge-based and contain different terms added together with arbitrary weights. Here, we test different search methods with one of the most accurate and predictive energy functions, namely Rosetta the knowledge-based force-field from Baker's group [Simons K, Kooperberg C, Huang E, Baker D (1997)J Mol Biol268:209–225]. We use an implementation of a generalized ensemble search method to scale relevant parts of the energy function. This method, known as Hamiltonian Replica Exchange Monte Carlo, outperforms the original Monte Carlo Simulated Annealing used in the Rosetta package in terms of sampling low-energy states. It also outperforms another widely used generalized ensemble search method known as Temperature Replica Exchange Monte Carlo. Our results reveal clear deficiencies in the low-resolution Rosetta energy function in that the lowest energy structures are not necessarily the most native-like. By using a set of nonnative low-energy structures found by our extensive sampling, we discovered that the long-range and short-range backbone hydrogen-bonding energy terms of the Rosetta energy discriminate between the nonnative and native-like structures significantly better than the low-resolution score used in Rosetta.
Phase separation in hydrogen–helium mixtures at Mbar pressures
Authors: Morales Miguel A. , Schwegler Eric , Ceperley David , Pierleoni Carlo , Hamel Sebastien , Caspersen Kyle
Published: January 2009

The properties of hydrogen–helium mixtures at Mbar pressures and intermediate temperatures (4000 to 10000 K) are calculated with first-principles molecular dynamics simulations. We determine the equation of state as a function of density, temperature, and composition and, using thermodynamic integration, we estimate the Gibbs free energy of mixing, thereby determining the temperature, at a given pressure, when helium becomes insoluble in dense metallic hydrogen. These results are directly relevant to models of the interior structure and evolution of Jovian planets. We find that the temperatures for the demixing of helium and hydrogen are sufficiently high to cross the planetary adiabat of Saturn at pressures ≈5 Mbar; helium is partially miscible throughout a significant portion of the interior of Saturn, and to a lesser extent in Jupiter.
The default mode network and self-referential processes in depression
Authors: Sheline Yvette I. , Barch Deanna M. , Price Joseph L. , Rundle Melissa M. , Vaishnavi S. Neil , Snyder Abraham Z. , Mintun Mark A. , Wang Suzhi , Coalson Rebecca S. , Raichle Marcus E.
Published: January 2009

The recently discovered default mode network (DMN) is a group of areas in the human brain characterized, collectively, by functions of a self-referential nature. In normal individuals, activity in the DMN is reduced during nonself-referential goal-directed tasks, in keeping with the folk-psychological notion of losing one's self in one's work. Imaging and anatomical studies in major depression have found alterations in both the structure and function in some regions that belong to the DMN, thus, suggesting a basis for the disordered self-referential thought of depression. Here, we sought to examine DMN functionality as a network in patients with major depression, asking whether the ability to regulate its activity and, hence, its role in self-referential processing, was impaired. To do so, we asked patients and controls to examine negative pictures passively and also to reappraise them actively. In widely distributed elements of the DMN [ventromedial prefrontal cortex prefrontal cortex (BA 10), anterior cingulate (BA 24/32), lateral parietal cortex (BA 39), and lateral temporal cortex (BA 21)], depressed, but not control subjects, exhibited a failure to reduce activity while both looking at negative pictures and reappraising them. Furthermore, looking at negative pictures elicited a significantly greater increase in activity in other DMN regions (amygdala, parahippocampus, and hippocampus) in depressed than in control subjects. These data suggest depression is characterized by both stimulus-induced heightened activity and a failure to normally down-regulate activity broadly within the DMN. These findings provide a brain network framework within which to consider the pathophysiology of depression.
Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy
Authors: Crittenden Jill R. , Cantuti-Castelvetri Ippolita , Saka Esen , Keller-McGandy Christine E. , Hernandez Ledia F. , Kett Lauren R. , Young Anne B. , Standaert David G. , Graybiel Ann M.
Published: January 2009

Voluntary movement difficulties in Parkinson's disease are initially relieved by
l
-DOPA therapy, but with disease progression, the repeated
l
-DOPA treatments can produce debilitating motor abnormalities known as
l
-DOPA-induced dyskinesias. We show here that 2 striatum-enriched regulators of the Ras/Rap/ERK MAP kinase signal transduction cascade, matrix-enriched CalDAG-GEFI and striosome-enriched CalDAG-GEFII (also known as RasGRP), are strongly and inversely dysregulated in proportion to the severity of abnormal movements induced by
l
-DOPA in a rat model of parkinsonism. In the dopamine-depleted striatum, the
l
-DOPA treatments produce down-regulation of CalDAG-GEFI and up-regulation of CalDAG-GEFII mRNAs and proteins, and quantification of the mRNA levels shows that these changes are closely correlated with the severity of the dyskinesias. As these CalDAG-GEFs control ERK cascades, which are implicated in
l
-DOPA-induced dyskinesias, and have differential compartmental expression patterns in the striatum, we suggest that they may be key molecules involved in the expression of the dyskinesias. They thus represent promising new therapeutic targets for limiting the motor complications induced by
l
-DOPA therapy.
Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS
Authors: Wang Jiou , Farr George W. , Zeiss Caroline J. , Rodriguez-Gil Diego J. , Wilson Jean H. , Furtak Krystyna , Rutkowski D. Thomas , Kaufman Randal J. , Ruse Cristian I. , Yates John R. , Perrin Steve , Feany Mel B. , Horwich Arthur L.
Published: January 2009

Recent studies suggest that superoxide dismutase 1 (SOD1)-linked amyotrophic lateral sclerosis results from destabilization and misfolding of mutant forms of this abundant cytosolic enzyme. Here, we have tracked the expression and fate of a misfolding-prone human SOD1, G85R, fused to YFP, in a line of transgenic G85R SOD1-YFP mice. These mice, but not wild-type human SOD1-YFP transgenics, developed lethal paralyzing motor symptoms at 9 months. In situ RNA hybridization of spinal cords revealed predominant expression in motor neurons in spinal cord gray matter in all transgenic animals. Concordantly, G85R SOD-YFP was diffusely fluorescent in motor neurons of animals at 1 and 6 months of age, but at the time of symptoms, punctate aggregates were observed in cell bodies and processes. Biochemical analyses of spinal cord soluble extracts indicated that G85R SOD-YFP behaved as a misfolded monomer at all ages. It became progressively insoluble at 6 and 9 months of age, associated with presence of soluble oligomers observable by gel filtration. Immunoaffinity capture and mass spectrometry revealed association of G85R SOD-YFP, but not WT SOD-YFP, with the cytosolic chaperone Hsc70 at all ages. In addition, 3 Hsp110's, nucleotide exchange factors for Hsp70s, were captured at 6 and 9 months. Despite such chaperone interactions, G85R SOD-YFP formed insoluble inclusions at late times, containing predominantly intermediate filament proteins. We conclude that motor neurons, initially “compensated” to maintain the misfolded protein in a soluble state, become progressively unable to do so.
The influence of soccer‐specific activity on the kinematics of an agility sprint
Authors: Greig Matt
Published: January 2009

The aim of this study was to investigate the influence of soccer‐specific fatigue on the kinematics of an agility sprint. Ten male professional soccer players (age 24.7±4.4 years, body mass 77.1±8.3 kg) completed an intermittent treadmill protocol replicating the activity profile of match‐play, comprising two 45‐min halves separated by a 15‐min passive half‐time interval. Pre‐exercise and at 15‐min intervals each player completed an agility sprint that consisted of a 180° cutting manoeuvre. Knee joint kinematics in the frontal and sagittal planes were determined for both the support and turning leg using a nine‐camera automated motion analysis system operating at 200 Hz. During the penultimate foot contact, knee kinematics were characterized by joint flexion and increased varus alignment. Knee flexion at touchdown decreased significantly (P<0.05) as a function of exercise duration from 57.4±15.5° before exercise to 37.0±5.9° at the end of the second half. The range of joint movement during the knee flexion phase increased significantly during the first half (T 45=66.6±18.2°) and remained elevated during the second half (T 75=66.4±18.1°; T 90=65.7±20.4°; T 105=70.2±19.4°) relative to pre‐exercise values (51.8±18.8°). During the final foot contact, knee kinematics were also characterized by flexion and increased varus alignment. Knee flexion at touchdown decreased during each half, with the knee angle at the end of the first half (30.6±7.0°) significantly (P=0.02) straighter than before exercise (39.5±6.3°), and significantly straighter at the end of the second half (30.2±2.9°) than after the half‐time interval (37.7±7.8°) or before exercise. The range of knee flexion during ground contact increased significantly during each half. The range of knee varus during flexion changed from a varus displacement during the first 15 min to a valgus displacement thereafter. Peak valgus observed at the end of each half (T 45=4.7±7.9°; T 105=6.9±7.4°) was significantly (P<0.05) greater than before exercise. The range of valgus movement during knee extension was greatest following the passive half‐time interval (T 60=6.2±7.3°), and tended to increase throughout the second half. Prolonged exposure to soccer‐specific intermittent exercise therefore induced changes in knee kinematics that may have implications for injury incidence. The increased varus alignment and time‐dependent decrease in knee flexion at touchdown represent two potential mechanisms for increased injury risk.
An acute bout of whole‐body vibration on skeleton start and 30‐m sprint performance
Authors: Bullock Nicola , Martin David T. , Ross Angus , Rosemond Doug , Jordan Matthew J. , Marino Frank E.
Published: January 2009

Maximal 30‐m upright sprinting and bent over, skeleton push performance were examined in five female national team skeleton athletes before and 10 min after an acute bout of whole‐body vibration or no vibration. The whole‐body vibration was applied at a frequency of 45 Hz with 4‐mm displacement for 3×1‐min treatments separated by 1 min. All changes in 30‐m sprint and skeleton push times before and after whole‐body vibration were small or trivial and within the tests’ typical variation (∼3.7% for the skeleton push and ∼3.2% for the upright sprint). Athletes were able to achieve 75–79% of their 30‐m upright sprinting velocities when pushing a skeleton sled. These results question the effectiveness of whole‐body vibration as an ergogenic aid immediately before performing a maximal upright sprint or skeleton push following a comprehensive warm‐up.
The main and interactive effects of immediate and reflective attributions upon subsequent self‐efficacy
Authors: Coffee Pete , Rees Tim
Published: January 2009

In this study, we examined the effects of immediate and reflective attributions upon subsequent self‐efficacy. At Time 1 (Day 1), 117 participants (mean age 25.8 years, s=8. 5) completed a measure of attributions after performance (immediate attributions). At Time 2 (Day 4), the participants completed the same measure of attributions (reflective attributions). At Time 3 (Day 7, 8 or 9), they completed a measure of self‐efficacy relating to an up‐coming performance. Immediately after more successful performances, global attributions were associated with higher subsequent self‐efficacy; upon reflection, stable, global, and/or personal attributions were associated with higher subsequent self‐efficacy. Immediately after and upon reflection of less successful performances, controllable attributions were associated with higher subsequent self‐efficacy; an interaction for controllability and stability demonstrated that when causes are perceived as likely to recur, greater controllability is associated with higher subsequent self‐efficacy. Results suggest that following more successful performances, analysis of reflective assessments of attributions may help to further understanding of the relationships between attributions and outcomes such as self‐efficacy. This study serves as a stimulus for future research to examine relationships between attributions assessed across time and outcomes such as self‐efficacy, as well as to examine interactions among attribution dimensions.
Angular momentum and landing efficiency in the long jump
Authors: Bouchouras Georgios , Moscha Dimitra , Papaiakovou Georgios , Nikodelis Thomas , Kollias Iraklis
Published: January 2009

The purpose of this study was to compare the amount of angular momentum and the efficiency of landing for the hang and 2½ hitch kick long jump techniques. Twelve male long jumpers participated in this investigation and were divided into two groups based on their flight technique (hang group, n=6; hitch kick group, n=6). The participants performed three jumps with full run‐up, the best of which was selected for analysis. A two‐dimensional DLT analysis of the take‐off, flight, and landing was conducted for the two groups. Three cameras (JVC GR‐DVL 9800 GL, Victor Company, Japan) with a sampling frequency 50 Hz were used. Two of the cameras were placed perpendicular to the run‐up, on the right and left side of the take‐off board, to record the take‐off and the flight of the athletes (from both sides of the movement); the third was placed perpendicular to the pit, on the right side, to record the landing. The two groups differed in their angular momentum at the instant of take‐off (hang: −11.92 kg·m2·s−1; hitch kick: −22.69 kg·m2·s−1; P<0.001) in the front direction, and in linear and angular velocity, mainly of the arms, at the instant of take‐off. According to the results, the 2½ hitch kick group had greater angular and linear velocities (P<0.05). The 2½ hitch kick group had better landing efficiency than the hang style group (P<0.05), as the athletes in the former group managed to land their pelvis in front of their heels during landing. On the other hand, the hang style group landed their pelvis almost 5.81 cm behind the heels during landing and shortened their final distance. It seems that the 2½ hitch kick group had better landing efficiency because of their greater amount of angular momentum. The hang style group could have achieved better landing through an increase in angular momentum, which depends on an increase of the linear and angular velocities of the two arms during take‐off.
Relational property between head and eye regions is the primary determinant of the efficiency in search for a deviant gaze
Authors: Doi Hirokazu , Ueda Kazuhiro , Shinohara Kazuyuki
Published: January 2009

The human visual system is extremely sensitive to the directions of the gazes of others. However, the mechanism underlying gaze direction perception has yet to be clarified. The primary aim of the present study is to investigate whether the relational property between the local eye region and other facial regions serves as the primary visual system cue in detecting a direct gaze. Our results showed that search efficiency was determined primarily by the gaze direction indicated by the relational property regardless of the direction indicated by the local feature information of the eye region; this was true even when the gaze directions indicated by these two types of information were conflicting. These results bolster the hypothesis that the human visual system primarily accesses socially meaningful information in searching for a deviant gaze.
Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease
Authors: Wilson John , Cullup Hannah , Lourie Rohan , Sheng Yonghua , Palkova Anna , Radford Kristen J. , Dickinson Anne M. , Rice Alison M. , Hart Derek N.J. , Munster David J.
Published: January 2009

Allogeneic (allo) hematopoietic stem cell transplantation is an effective therapy for hematological malignancies but it is limited by acute graft-versus-host disease (GVHD). Dendritic cells (DC) play a major role in the allo T cell stimulation causing GVHD. Current immunosuppressive measures to control GVHD target T cells but compromise posttransplant immunity in the patient, particularly to cytomegalovirus (CMV) and residual malignant cells. We showed that treatment of allo mixed lymphocyte cultures with activated human DC-depleting CD83 antibody suppressed alloproliferation but preserved T cell numbers, including those specific for CMV. We also tested CD83 antibody in the human T cell–dependent peripheral blood mononuclear cell transplanted SCID (hu-SCID) mouse model of GVHD. We showed that this model requires human DC and that CD83 antibody treatment prevented GVHD but, unlike conventional immunosuppressants, did not prevent engraftment of human T cells, including cytotoxic T lymphocytes (CTL) responsive to viruses and malignant cells. Immunization of CD83 antibody-treated hu-SCID mice with irradiated human leukemic cell lines induced allo antileukemic CTL effectors in vivo that lysed 51Cr-labeled leukemic target cells in vitro without further stimulation. Antibodies that target activated DC are a promising new therapeutic approach to the control of GVHD.
Posttranslational regulation of the NKG2D ligand Mult1 in response to cell stress
Authors: Nice Timothy J. , Coscoy Laurent , Raulet David H.
Published: January 2009

NKG2D is a major stimulatory receptor expressed by natural killer (NK) cells and some T cells. The receptor recognizes major histocompatability complex class I–like cell surface ligands that are poorly expressed by normal tissues but are often induced in transformed and infected cells. The existence of several NKG2D ligands in each individual, some with strikingly divergent protein sequences, raises the possibility that different ligands are regulated by distinct disease-associated stresses. The transcripts for some ligands, including murine UL16-binding proteinlike transcript 1 (Mult1), are abundant in certain normal tissues where cell surface expression is absent, suggesting the existence of translational or posttranslational regulation. We report here that under normal conditions, Mult1 protein undergoes ubiquitination dependent on lysines in its cytoplasmic tail and lysosomal degradation. Mult1 degradation and ubiquitination is reduced in response to stress imparted by heat shock or ultraviolet irradiation, but not by other forms of genotoxicity, providing a novel mechanism for stress-mediated cellular control of NKG2D ligand expression.
Anaphylactic shock depends on endothelial Gq/G11
Authors: Korhonen Hanna , Fisslthaler Beate , Moers Alexandra , Wirth Angela , Habermehl Daniel , Wieland Thomas , Schütz Günther , Wettschureck Nina , Fleming Ingrid , Offermanns Stefan
Published: January 2009

Anaphylactic shock is a severe allergic reaction involving multiple organs including the bronchial and cardiovascular system. Most anaphylactic mediators, like platelet-activating factor (PAF), histamine, and others, act through G protein–coupled receptors, which are linked to the heterotrimeric G proteins Gq/G11, G12/G13, and Gi. The role of downstream signaling pathways activated by anaphylactic mediators in defined organs during anaphylactic reactions is largely unknown. Using genetic mouse models that allow for the conditional abrogation of Gq/G11- and G12/G13-mediated signaling pathways by inducible Cre/loxP-mediated mutagenesis in endothelial cells (ECs), we show that Gq/G11-mediated signaling in ECs is required for the opening of the endothelial barrier and the stimulation of nitric oxide formation by various inflammatory mediators as well as by local anaphylaxis. The systemic effects of anaphylactic mediators like histamine and PAF, but not of bacterial lipopolysaccharide (LPS), are blunted in mice with endothelial Gαq/Gα11 deficiency. Mice with endothelium-specific Gαq/Gα11 deficiency, but not with Gα12/Gα13 deficiency, are protected against the fatal consequences of passive and active systemic anaphylaxis. This identifies endothelial Gq/G11-mediated signaling as a critical mediator of fatal systemic anaphylaxis and, hence, as a potential new target to prevent or treat anaphylactic reactions.
Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain
Authors: Kuball Jürgen , Hauptrock Beate , Malina Victoria , Antunes Edite , Voss Ralf-Holger , Wolfl Matthias , Strong Roland , Theobald Matthias , Greenberg Philip D.
Published: January 2009

Adoptive transfer of T lymphocytes transduced with a T cell receptor (TCR) to impart tumor reactivity has been reported as a potential strategy to redirect immune responses to target cancer cells (Schumacher, T.N. 2002. Nat. Rev. Immunol. 2:512–519). However, the affinity of most TCRs specific for shared tumor antigens that can be isolated is usually low. Thus, strategies to increase the affinity of TCRs or the functional avidity of TCR-transduced T cells might be therapeutically beneficial. Because glycosylation affects the flexibility, movement, and interactions of surface molecules, we tested if selectively removing conserved N-glycoslyation sites in the constant regions of TCR α or β chains could increase the functional avidity of T cells transduced with such modified TCRs. We observed enhanced functional avidity and improved recognition of tumor cells by T cells harboring TCR chains with reduced N-glycosylation (ΔTCR) as compared with T cells with wild-type (WT) TCR chains. T cells transduced with WT or ΔTCR chains bound tetramer equivalently at 4°C, but tetramer binding was enhanced at 37°C, predominantly as a result of reduced tetramer dissociation. This suggested a temperature-dependent mechanism such as TCR movement in the cell surface or structural changes of the TCR allowing improved multimerization. This strategy was effective with mouse and human TCRs specific for different antigens and, thus, should be readily translated to TCRs with any specificity.
Variability in the Hawthorne Effect With Regard to Hand Hygiene Performance in High- and Low-Performing Inpatient Care Units
Authors: Kohli Erol , Ptak Judy , Smith Randall , Taylor Eileen , Talbot Elizabeth A. , Kirldand Kathryn B.
Published: January 2009

Objective.

To determine the impact of known observers on hand hygiene performance in inpatient care units with differing baseline levels of hand hygiene compliance.

Design.

Observational study.

Setting.

Three inpatient care units, selected on the basis of past hand hygiene performance, in a hospital where hand hygiene observation and feedback are routine.

Participants.

Three infection control practitioners (ICPs) and a student intern observed hospital staff.

Methods.

Beginning in late 2005, the 3 ICPs, who were well known to the hospital staff, performed frequent, regular observations of hand hygiene in all 3 inpatient care units of the hospital, as part of routine surveillance. During the study period (January-May 2007), a student intern who was unknown to the hospital staff also performed observations of hand hygiene in the 3 inpatient care units. The rates of hand hygiene compliance observed by the 3 ICPs were compared with those observed by the student intern.

Results.

The 3 ICPs observed 332 opportunities for hand hygiene during 15 observation periods, and the student intern observed 355 opportunities during 19 observation periods. The overall rate of hand hygiene compliance observed by the ICPs was 65% (ie, in 215 of the 332 opportunities, the performance of proper hand hygiene by hospital staff was observed), and the overall rate of hand hygiene compliance observed by the student intern was 58% (ie, in 207 of the 355 opportunities, the performance of proper hand hygiene by hospital staff was observed) (P = .1). Both the ICPs and the student intern were able to distinguish between inpatient care units with a high rate of hand hygiene compliance (hereafter referred to as high-performing units) and those with a low rate (hereafter referred to as low-performing units). However, in the 2 high-performing units, the ICPs observed significantly higher compliance rates than did the student intern, whereas in the low-performing unit, both the ICPs and the student intern measured similarly low rates of hand hygiene compliance.

Conclusions.

Recognized observers are associated with higher rates of hand hygiene compliance, even in a healthcare setting where such observations have become routine. This effect (ie, the Hawthorne effect) is more pronounced in high-performing units and insignificant in low-performing units. The use of unrecognized observers may be important for verifying high performance but is probably unnecessary for documenting poor performance. Moreover, the Hawthorne effect may be a useful tool for sustaining and improving hand hygiene compliance.
CPU0213, A NON‐SELECTIVE ETA/ETB RECEPTOR ANTAGONIST, IMPROVES PULMONARY ARTERIOLAR REMODELING OF MONOCROTALINE‐INDUCED PULMONARY HYPERTENSION IN RATS
Authors: Cui Bing , Cheng Yu‐Si , Dai De‐Zai , Li Na , Zhang Tian‐Tai , Dai Yin
Published: January 2009

The aim of the present study was to explore the effects of CPU0213, a dual endothelin ETA/ETB receptor antagonist, and nifedipine, a calcium antagonist, in relieving pulmonary hypertension (PH). Both endothelin receptor and calcium antagonists have been reported to be effective in alleviating the remodelling of pulmonary arteries induced by monocrotaline (MCT) in rats.

After an initial single dose of 60 mg/kg, s.c., MCT, CPU0213 was administered to rats at doses of 25, 50 or 100 mg/kg, p.o., for 28 days. In addition, nifedipine was administered to another group of rats at a dose of 10 mg/kg, p.o., for 28 days. The haemodynamics of the right ventricle, pulmonary vascular activity, remodelling of the pulmonary arterioles (< 150 µm) and biochemical changes were evaluated.

Right ventricular systolic pressure (RVSP), central venous pressure (CVP), the maximum rate of uprising pressure (dP/dTmax) and the weight index of the right ventricle were significantly elevated in MCT‐treated rats. In addition, increases in pulmonary endothelin‐1, malonyldialdehyde (MDA) and hydroxyproline content and a reduction in superoxide dismutase activity was found after MCT treatment. The thickness and area of the pulmonary arterial wall were significantly increased in MCT‐treated rats compared with control rats. At all three doses tested, CPU0213 ameliorated these changes in a dose‐dependent manner and the effects were associated with a greater reduction in the remodelling of pulmonary arterioles. However, nifedipine was only partially effective in amelerioating biochemical and haemodynamic changes induced by MCT, significantly reducing RVSP, CVP, +dp/dtmax, tissue MDA, inducible nitric oxide synthase and hydroxyproline content, increasing –dp/dtmin and having no effect on the other parameters investigated. In addition, nifedipine had no effect on remodelling of the arterial wall.

In conclusion, CPU0213 is more effective than nifedipine in suppressing the remodelling of pulmonary arterioles in PH induced by MCT treatment of rats. Furthermore, CPU0213 may have promise in treating PH secondary to connective tissue disease.
FLUID MECHANICS OF ARTIFICIAL HEART VALVES
Authors: Dasi Lakshmi P , Simon Helene A , Sucosky Philippe , Yoganathan Ajit P
Published: January 2009

Artificial heart valves have been in use for over five decades to replace diseased heart valves. Since the first heart valve replacement performed with a caged‐ball valve, more than 50 valve designs have been developed, differing principally in valve geometry, number of leaflets and material. To date, all artificial heart valves are plagued with complications associated with haemolysis, coagulation for mechanical heart valves and leaflet tearing for tissue‐based valve prosthesis. For mechanical heart valves, these complications are believed to be associated with non‐physiological blood flow patterns.

In the present review, we provide a bird's‐eye view of fluid mechanics for the major artificial heart valve types and highlight how the engineering approach has shaped this rapidly diversifying area of research.

Mechanical heart valve designs have evolved significantly, with the most recent designs providing relatively superior haemodynamics with very low aerodynamic resistance. However, high shearing of blood cells and platelets still pose significant design challenges and patients must undergo life‐long anticoagulation therapy. Bioprosthetic or tissue valves do not require anticoagulants due to their distinct similarity to the native valve geometry and haemodynamics, but many of these valves fail structurally within the first 10–15 years of implantation.

These shortcomings have directed present and future research in three main directions in attempts to design superior artificial valves: (i) engineering living tissue heart valves; (ii) development of advanced computational tools; and (iii) blood experiments to establish the link between flow and blood damage.
EFFECT OF ENDURANCE TRAINING ON HYPOTHALAMIC SEROTONIN CONCENTRATION AND PERFORMANCE
Authors: Caperuto EC , Dos Santos RVT , Mello MT , Costa Rosa LFBP
Published: January 2009

Serotonin is a neurotransmitter that modulates several functions, such as food intake, energy expenditure, motor activity, mood and sleep. Acute exhaustive endurance exercise increases the synthesis, concentration and metabolism of serotonin in the brain. This phenomenon could be responsible for central fatigue after prolonged and exhaustive exercise. However, the effect of chronic exhaustive training on serotonin is not known. The present study was conducted to examine the effect of exhaustive endurance training on performance and serotonin concentrations in the hypothalamus of trained rats.

Rats were divided into three groups: sedentary rats (SED), moderately trained rats (MOD) and exhaustively trained rats (EXT), with an increase of 200% in the load carried during the final week of training.

Hypothalamic serotonin concentrations were similar between the SED and MOD groups, but were higher in the EXT group (P < 0.05). Performance was lower in the EXT group compared with the MOD group (P < 0.05).

Thus, the present study demonstrates that exhaustive training increases serotonin concentrations in the hypothalamus, together with decreased endurance performance after inadequate recovery time. However, the mechanism underlying these changes remains unknown.
Bronchoscopy in Japan: A survey by the Japan Society for Respiratory Endoscopy in 2006
Authors: NIWA Hiroshi , TANAHASHI Masayuki , KONDO Takashi , OHSAKI Yoshinobu , OKADA Yoshinori , SATO Shigeki , SUZUKI Eiichi , SENBA Hiroshi , FUJINO Shozo , MIYAZAWA Teruomi , KOBAYASHI Koichi
Published: January 2009

Background and objective:  In order to obtain information on the clinical application of bronchoscopy in Japan, the Japan Society for Respiratory Endoscopy (JSRE) conducted a postal survey.

Methods:  A questionnaire was sent to 526 authorized institutes of the JSRE. The subject was bronchoscopy procedures performed during 2006.

Results:  The response rate was 71.3%. The total number of bronchoscopies performed was 74 770. Of these, 74 412 were flexible bronchoscopies and 358 were rigid bronchoscopies. At least one JSRE‐authorized specialist had worked with 97% of respondents. Eighty‐five per cent of respondents performed bronchoscopy under topical anaesthesia for almost all patients. Seventy‐five per cent of respondents routinely used the oral route. The reported numbers of diagnostic bronchoscopies was 12 509 for simple bronchoscopy, 25 971 for forceps biopsy, 26 289 for brush biopsy, 25 659 for bronchial washing, 1387 for transbronchial needle aspiration and 6716 for BAL. Three deaths were caused by forceps biopsy (0.012%). The morbidity rates for these diagnostic procedures ranged from 0.14% to 2.5%. The reported numbers of therapeutic bronchoscopies was 476 for tracheobronchial stent, 164 for neodymium (Nd): yttrium‐aluminium garnet (YAG) laser photoresection (LPR), 40 for photodynamic therapy, 81 for balloon dilatation, 145 for endobronchial electrocautery, 120 for argon plasma coagulation, 109 for microwave coagulation (MWC), 116 for ethanol injection, 110 for foreign body removal and 89 for bronchial occlusion. Deaths occurred only as a consequence of Nd : YAG LPR (0.61%). The morbidity rates for these therapeutic procedures ranged from 0% to 5%.

Conclusions:  The preparation for, and practice of, bronchoscopy varied greatly between respondents. Diagnostic bronchoscopy was well tolerated and safe. Therapeutic procedures did not appear to be practised widely or frequently.
T‐cell cytokine profiles are altered in childhood asthma exacerbation
Authors: CALDERON Czarina , RIVERA Luis , HUTCHINSON Paul , DAGHER Hayat , VILLANUEVA Elmer , GHILDYAL Reena , BARDIN Philip G. , FREEZER Nicholas J.
Published: January 2009

Background and objective:  Stable asthma is characterized by the production of Th2 cytokines, although Th1 cytokines may play a key role in aspects such as airway hyper‐responsiveness. This study explored cytokine profiles associated with asthma exacerbation.

Methods:  Intracellular T‐cell cytokine production was measured in 16 children with acute severe asthma (emergency department), after convalescence (6 weeks, n = 13), with stable disease (after 6 months, n = 7) and in 14 age‐matched hospital controls. Flow cytometry was used to identify CD4+ and CD8+ cells and to quantify intracellular T‐cell production of the cytokines interferon (IFN)‐γ, IL‐4 and IL‐13. Cytokine production was compared using analysis of variance and random‐effects generalized linear models and associations were examined using Pearson's correlation.

Results:  Cytokine production was evident in CD4+ and CD8+ cells, and compared with asthmatic children, non‐asthmatics had a higher percentage of IFN‐γ+CD4+ cells (P = 0.01). The percentage of CD8+IFN‐γ+ cells was increased in the convalescent phase compared with acute (P = 0.009) and stable asthma (P = 0.004). IL‐4+ cells were not significantly altered. IL‐13 levels were higher in acute disease than in stable asthma (P = 0.009 in CD4+ cells) and IFN‐γ/IL‐13 ratios indicated a Th2 profile during exacerbation (P = 0.005 in CD4+ cells).

Conclusions:  IL‐13, rather than IL‐4, may play a pro‐inflammatory role during acute severe asthma, whereas IFN‐γ responses were associated with recovery from acute severe asthma. These results suggest that altered T‐cell cytokine profiles may contribute to the pathogenesis of and recovery from asthma exacerbations.
The effectiveness of a bronchial drainage technique (ELTGOL) in COPD exacerbations
Authors: KODRIC Metka , GARUTI Giancarlo , COLOMBAN Mario , RUSSI Barbara , PORTA Rossana D. , LUSUARDI Mirco , CONFALONIERI Marco
Published: January 2009

Background and objective:  Exacerbations of COPD are often characterized by increased mucus production that is difficult to treat and worsens patients' outcome. This study evaluated the efficacy of a chest physiotherapy technique (expiration with the glottis open in the lateral posture, ELTGOL) during acute exacerbations of COPD using as outcome measures sputum volume, length of hospitalization, reduction in dyspnoea (Borg score), improvement in quality of life (assessed by the St George Respiratory Questionnaire) and incidence of COPD exacerbations during follow up.

Methods:  The study recruited 59 patients hospitalized for the treatment of acute exacerbation of COPD, who were randomly assigned to a control group and an intervention group. The control group was treated with standard medical therapy while the intervention group was treated with ELTGOL plus medical therapy. A subgroup of patients was followed for 6 months to verify the effects on COPD exacerbations and need for hospitalizations.

Results:  At the time of hospital discharge there was no significant difference between the two groups in the outcome measures, with the exception of the Borg score, which was significantly improved in the ELTGOL group (4.3 ± 1.5 in the control group vs 3.0 ± 1.8 in the ELTGOL group, P = 0.004). After 6 months there was no significant difference in the other measured parameters between a subset of the groups available for follow up. During follow up, the ELTGOL group had numerically fewer exacerbations and less need for hospitalization though differences were not statistically significant.

Conclusions:  Chest physiotherapy using the ELTGOL technique has a limited role in patients with mild exacerbation of moderate to severe COPD with a tendency towards fewer exacerbations and hospitalizations.
A case of hypereosinophilic syndrome presenting with chronic cough successfully treated with imatinib
Authors: KOBAYASHI Makoto , KUBOTA Tetsuya , UEMURA Yoshiki , TAGUCHI Hirokuni
Published: January 2009

Chronic cough is caused by a wide variety of disease conditions, including asthma, rhino‐sinusitis and gastro‐oesophageal reflux. We describe the case of a 42‐year‐old man with hypereosinophilic syndrome presenting with chronic dry cough. The cough did not respond to inhaled corticosteroid or leucotriene receptor antagonists. Hepatosplenomegaly was noted and the patient became anaemic and thrombocytopenic. He was refractory to treatment with hydroxyurea and interferon‐α. Administration of imatinib resulted in complete resolution of eosinophilia and cough, without the use of anti‐asthma drugs. Analysis of RNA from this patient demonstrated expression of the Fip1‐like 1/platelet‐derived growth factor receptor‐alpha (FIP1L1–PDGFRA) fusion gene. The myeloproliferative variant of hypereosinophilic syndrome may cause chronic intractable cough, and a trial of imatinib treatment may be warranted.
Pulmonary complications of immune reconstitution inflammatory syndromes in HIV‐infected patients
Authors: CROTHERS Kristina , HUANG Laurence
Published: January 2009

Immune reconstitution inflammatory syndrome (IRIS) describes a paradoxical worsening of clinical status related to recovery of the immune system, as can occur after the initiation of highly active antiretroviral therapy (HAART) in HIV‐infected patients. Most commonly, IRIS results from opportunistic infections that can unmask or develop paradoxical worsening following HAART. Cancers, autoimmune conditions and sarcoidosis have also been associated with IRIS. Pulmonary complications may be frequently encountered. This article reviews the types and clinical presentation of IRIS, with a focus on the pulmonary manifestations. Management and outcome of IRIS are considered.
Frequency of Foxp3+CD4+CD25+ T cells is associated with the phenotypes of allergic asthma
Authors: MATSUMOTO Koichiro , INOUE Hiromasa , FUKUYAMA Satoru , KAN‐O Keiko , EGUCHI‐TSUDA Miyuki , MATSUMOTO Takafumi , MORIWAKI Atsushi , NAKANO Takako , NAKANISHI Yoichi
Published: January 2009

Background and objective:  A forkhead/winged‐helix family transcriptional repressor, Foxp3, is highly expressed on CD4+CD25+ T regulatory cells. The role of Foxp3+CD4+CD25+ T regulatory cells in asthma remains to be elucidated. Using mouse models and peripheral blood mononuclear cells (PBMC) from subjects with allergic asthma, we aimed to explore whether Foxp3+CD4+CD25+ T regulatory cells associate with asthma phenotypes.

Methods:  Foxp3+CD4+CD25+ T cells were detected by FACS and the correlation between the frequency of Foxp3+CD4+CD25+ T cells and asthma phenotypes was assessed.

Results:  The frequency of Foxp3+CD4+CD25+ T cells among total CD4+CD25+ T cells in the lungs showed an inverse correlation with eosinophilic inflammation in BALB/c, A/J and C57BL/6 strains. In addition, the frequency of Foxp3+CD4+CD25+ T cells was inversely correlated with BHR and allergen‐specific IgE levels in the serum of A/J mice. In BALB/c mice, the frequency of Foxp3+CD4+CD25+ T cells correlated with the level of IL‐10 in BAL fluid. The inverse correlation between the frequency of Foxp3+CD4+CD25+ T cells and eosinophilic inflammation disappeared when mice were treated with anti‐IL‐10 receptor mAb during allergen challenge. Interestingly, intracellular cytokine staining of lung cells revealed that IL‐10 was predominantly produced by Foxp3‐CD4+CD25+ T cells. The frequency of Foxp3+CD4+CD25+ T cells among total CD4+CD25+ T cells in PBMC of asthmatics was significantly lower than that of healthy subjects, although there was no significant correlation between the frequency of Foxp3+CD4+CD25+ T cells and asthma severity.

Conclusions:  These results suggest a role for lung Foxp3+CD4+CD25+ T cells in the regulation of asthma phenotypes, presumably through an IL‐10‐mediated mechanism.
Langerhans' cell histiocytosis mimicking metastatic carcinoma of the lung
Authors: NIKSARLIOGLU Yelda O. , GUREL Bora , TEZEL Gaye G. , FIRAT Pinar , DOGAN Riza , KARS Ayse , COPLU Lutfi
Published: January 2009

Langerhans' cell histiocytosis (LCH), previously known as Histiocytosis X, is characterized by abnormal accumulations of large mononuclear cells forming granulomas in various organs, mainly bone, skin and lung. This case report describes a 50‐year‐old man with a history of left pneumonectomy due to squamous cell carcinoma (SCC). During routine follow up, a CXR showed new parenchymal nodules in the right lung 57 months post treatment. Chest CT scan confirmed the presence of multiple parenchymal nodules. Open lung biopsy from the right upper lobe was performed and LCH was diagnosed. Re‐analysis of the initial pneumonectomy specimen revealed no evidence of LCH in the surrounding lung tissue. On diagnosis, the patient stopped smoking and was treated with vinblastine and prednisolone for LCH. The nodules disappeared and have not returned in a further 18 months of follow up. In this patient LCH was diagnosed after SCC, which highlights that smoking‐related diseases can be seen concomitantly or sequentially in the same patient.
Posterior mediastinal paragangliomas: A report of three patients with peculiar tumours
Authors: AYADI‐KADDOUR Aïda , BRAHAM Emna , ISMAIL Olfa , SMATI Bellahssan , DJILANI Habiba , EL MEZNI Faouzi
Published: January 2009

Paragangliomas of the mediastinum are rare neoplasms, representing less than 0.3% of mediastinal tumours and less than 2% of all paragangliomas. To date, no definitive morphologic criteria exist that correlate with the clinical outcome of these tumours. This report describes three patients with peculiar primary paragangliomas of the posterior mediastinum: gangliocytic, dumbbell and functional paraganglioma. The clinicopathological characteristics of these patients are presented and the literature reviewed.