bluuebunny/crossref_metadata_2025 huggingface dataset:
Lithostratigraphy and study of planktonic foraminifera of the Abderaz Formation at type section, Kopet-Dagh basin, IRAN
Authors: Shafiee Ardestani Meysam , allameh Mohsen , Kohansal Esmail
Published: November 2009

In order to study the fossil contents of the Abderaz Formation for biostratigraphical purposes the 300 meters thick section was sampled at type section. The sequence is mainly made up of grey shales and marls with two units of chalky limestone in upper part. The lower contact of the formation with Aitamir Formation is disconform while the upper contact with Abtalkh is continuous. There are huge amounts of inoceramids and ammonite. In the chalk limestone bonds of this formation which is belong to Santonian time planktonic, would exist some foraminifera with a less diversity because during the Santonian, the members of morphotype group three (M3) shows a regression in the above-mentioned section, with association of tegilla shapes decreases in the area and sea water. The study of the planktonic foraminifera in isolated form led to differentiate three morphotype groups. The first group is characterized by trochospiral tests usually indicate shallow waters, the second group contains forms with strong ornamentations and the primary keels representing mid waters and finally compact trochospiral tests with keels known as deep water indices are included in the third group. Studies on the morphotypes showed a regressive cycle for Abderaz Formation.
Exercise, Abdominal Obesity, Skeletal Muscle, and Metabolic Risk: Evidence for a Dose Response
Authors: Slentz Cris A. , Houmard Joseph A. , Kraus William E.
Published: November 2009

The obese are at increased risk for cardiovascular disease and type 2 diabetes. However, some who are obese have no metabolic abnormalities. So, it is not adipose tissue per se, but perhaps where it is located that is important for determining metabolic consequences. Regular exercise is known to reduce risk for metabolic disease through numerous mechanisms. The purpose of this report is to highlight some of the efficacy‐based data on the effects of exercise (and also a sedentary lifestyle) on abdominal obesity, visceral fat, and metabolic risk. We also discuss how impaired fatty acid oxidation (FAO) in skeletal muscle may be related to both insulin resistance and a contributor to weight gain. In summary, it is evident that exercise in sufficient amounts can lead to substantial decreases in body weight, total body fat, and visceral fat. Additionally, evidence now supports the conclusion that there is a dose‐response relationship between exercise amount and these changes, i.e., more exercise leads to additional benefits. Additionally, there are a number of important cardiometabolic risk factors that were most favorably effected by moderate‐intensity compared to vigorous‐intensity exercise. Unfortunately, it is also apparent that in sedentary middle‐aged men and women, short periods of physical inactivity lead to significant weight gain, substantial increases in visceral fat, and further metabolic deterioration. Finally, favorable modulation of mitochondrial oxidative capacity in skeletal muscle by exercise training may reduce a block for complete oxidation of fatty acids in muscle and thereby relieve a block to effective insulin signaling.
A compact interferometric sensor design using three waveguide coupling
Authors: Vernon K. C. , Gómez D. E. , Davis T. J.
Published: November 2009

The use of metal stripes for the guiding of plasmons is a well established technique for the infrared regime and has resulted in the development of a myriad of passive optical components and sensing devices. However, the plasmons suffer from large losses around sharp bends, making the compact design of nanoscale sensors and circuits problematic. A compact alternative would be to use evanescent coupling between two sufficiently close stripes, and thus we propose a compact interferometer design using evanescent coupling. The sensitivity of the design is compared with that achieved using a hand-held sensor based on the Kretschmann style surface plasmon resonance technique. Modeling of the new interferometric sensor is performed for various structural parameters using finite-difference time-domain and COMSOL Multiphysics. The physical mechanisms behind the coupling and propagation of plasmons in this structure are explained in terms of the allowed modes in each section of the device.
Unpinning of a spiral wave anchored around a circular obstacle by an external wave train: Common aspects of a chemical reaction and cardiomyocyte tissue
Authors: Tanaka Masanobu , Isomura Akihiro , Hörning Marcel , Kitahata Hiroyuki , Agladze Konstantin , Yoshikawa Kenichi
Published: November 2009

It is well known that spiral waves are often stabilized by anchoring to a local heterogeneity (“pinning”) and that such pinned waves are rather difficult to eliminate. In the present report, we show that pinned spiral waves can be eliminated through collision with a wave train arriving from the outer region, as confirmed in experiments on the Belousov–Zhabotinsky (BZ) reaction as well as in cardiomyocyte tissue culture. A numerical simulation using the Oregonator, a mathematical model for the BZ reaction, provides the parameter area for successful unpinning. The scenario of unpinning is discussed in terms of the dispersion relation of the wave train by taking into account the curvature effect of the excitation wave.
Spin-locking of half-integer quadrupolar nuclei in nuclear magnetic resonance of solids: Second-order quadrupolar and resonance offset effects
Authors: Ashbrook Sharon E. , Wimperis Stephen
Published: November 2009

Spin-locking of spin I=3/2 and I=5/2 nuclei in the presence of small resonance offset and second-order quadrupolar interactions has been investigated using both exact and approximate theoretical and experimental nuclear magnetic resonance (NMR) approaches. In the presence of second-order quadrupolar interactions, we show that the initial rapid dephasing that arises from the noncommutation of the state prepared by the first pulse and the spin-locking Hamiltonian gives rise to tensor components of the spin density matrix that are antisymmetric with respect to inversion, in addition to those symmetric with respect to inversion that are found when only a first-order quadrupolar interaction is considered. We also find that spin-locking of multiple-quantum coherence in a static solid is much more sensitive to resonance offset than that of single-quantum coherence and show that good spin-locking of multiple-quantum coherence can still be achieved if the resonance offset matches the second-order shift of the multiple-quantum coherence in the appropriate reference frame. Under magic angle spinning (MAS) conditions, and in the "adiabatic" limit, we demonstrate that rotor-driven interconversion of central-transition single- and three-quantum coherences for a spin I=3/2 nucleus can be best achieved by performing the spin-locking on resonance with the three-quantum coherence in the three-quantum frame. Finally, in the "sudden" MAS limit, we show that spin I=3/2 spin-locking behavior is generally similar to that found in static solids, except when the central-transition nutation rate matches a multiple of the MAS rate and a variety of rotary resonance phenomena are observed depending on the internal spin interactions present. This investigation should aid in the application of spin-locking techniques to multiple-quantum NMR of quadrupolar nuclei and of cross-polarization and homonuclear dipolar recoupling experiments to quadrupolar nuclei such as L7i, B11, O17, N23a, and A27l.
Autonomous microfluidic transport using electrowetting-based valves and integrated cells
Authors: Siribunbandal Papaorn , Yamaguchi Shigeki , Kojima Kenichi , Fukuda Junji , Suzuki Hiroaki
Published: November 2009

Autonomous control of the transport of solutions in microfabricated flow channels using electrowetting-based valves and integrated electrochemical cells is proposed. An electrowetting-based valve formed with a gold electrode was opened when an electrolyte solution reached a zinc electrode in a controlling flow channel and a potential was applied to the gold electrode, causing the transport of the solution in the flow channel. Independent composite electrodes consisting of gold and zinc could function in the same manner without requiring additional electrodes. Controlled autonomous transport of solutions in a network of flow channels could also be carried out using the integrated valves.
Mechanism of CPDB-Mediated RAFT Polymerization of Methyl Methacrylate: Influence of Pressure and RAFT Agent Concentration
Authors: Buback Michael , Meiser Wibke , Vana Philipp
Published: November 2009

Reversible addition–fragmentation chain transfer (RAFT) polymerizations of methyl methacrylate (MMA) in bulk at 60°C were performed at five pressures up to 200 MPa using 2-(2′-cyanopropyl)dithiobenzoate (CPDB) as RAFT agent at concentrations between 1.5 × 10–3 and 2.0 × 10–2 mol L–1. Applying high pressure during polymerization increases the rate of polymerization, but no effect on polydispersity was observed. Molecular weight distributions and average molecular weights of the final polymer indicated the successful control of MMA polymerization even at low CPDB concentrations. The slight retardation observed is adequately described by the dependence the termination rate coefficient, kt, on the chain-length.
MADIX Thermoresponsive Amphiphilic Block Copolymers as Stimulable Emulsion Stabilizers
Authors: Destarac Mathias , Papon Aurélie , Van Gramberen Eric , Karagianni Katerina
Published: November 2009

A series of Macromolecular Design by Interchange of Xanthates (MADIX)-derived amphiphilic block copolymers exhibiting lower critical solution temperature behaviour was synthesized and evaluated as silicone oil-in-water emulsion co-stabilizers. It was demonstrated that the cloud point of the block copolymer is mainly controlled by the chemical composition of the N-isopropylacrylamide-based hydrophilic block. The reversible stabilization and destabilization phenomena of the silicone emulsions occurred at a temperature equal to the cloud point of the block copolymer taken alone.
Searching for Stars: Selective Desulfurization and Fluorescence Spectroscopy as New Tools in the Search for Cross Termination Side-products in RAFT Polymerization
Authors: Brown Steven L. , Konkolewicz Dominik , Gray-Weale Angus , Motherwell William B. , Perrier Sébastien
Published: November 2009

We present a novel approach to the examination of the ‘controversial’ three-armed stars that are argued to exist in rate-retarded reversible addition–fragmentation chain transfer (RAFT) polymerizations by using a fluorescent carbazole-containing RAFT agent that exhibits classical signs of retardation, and provides a route to polymer-RAFT agent cross termination. We also pioneer the use of an existing desulfurization technique for the purification of polymers by removal of the coloured RAFT derived moiety, with the added benefit of potentially isolating and identifying the presence of cross termination side-products. Our findings suggest that the rate retardation is either due to the RAFT intermediate being sufficiently stable that it does not cross terminate, or that most of cross termination events occur between the intermediate and short radicals. Our findings are consistent with a model proposed earlier by this group for rate retardation in RAFT systems, which assumed a slow rate for long-chain cross termination, and a fast short chain cross termination rate.
A different mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by tepraloxydim
Authors: Xiang Song , Callaghan Matthew M. , Watson Keith G. , Tong Liang
Published: November 2009

Acetyl-CoA carboxylases (ACCs) are crucial metabolic enzymes and are attractive targets for drug discovery. Haloxyfop and tepraloxydim belong to two distinct classes of commercial herbicides and kill sensitive plants by inhibiting the carboxyltransferase (CT) activity of ACC. Our earlier structural studies showed that haloxyfop is bound near the active site of the CT domain, at the interface of its dimer, and a large conformational change in the dimer interface is required for haloxyfop binding. We report here the crystal structure at 2.3 Å resolution of the CT domain of yeast ACC in complex with tepraloxydim. The compound has a different mechanism of inhibiting the CT activity compared to haloxyfop, as well as the mammalian ACC inhibitor CP-640186. Tepraloxydim probes a different region of the dimer interface and requires only small but important conformational changes in the enzyme, in contrast to haloxyfop. The binding mode of tepraloxydim explains the structure-activity relationship of these inhibitors, and provides a molecular basis for their distinct sensitivity to some of the resistance mutations, as compared to haloxyfop. Despite the chemical diversity between haloxyfop and tepraloxydim, the compounds do share two binding interactions to the enzyme, which may be important anchoring points for the development of ACC inhibitors.
Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries
Authors: Goodman Morris , Sterner Kirstin N. , Islam Munirul , Uddin Monica , Sherwood Chet C. , Hof Patrick R. , Hou Zhuo-Cheng , Lipovich Leonard , Jia Hui , Grossman Lawrence I. , Wildman Derek E.
Published: November 2009

Specific sets of brain-expressed genes, such as aerobic energy metabolism genes, evolved adaptively in the ancestry of humans and may have evolved adaptively in the ancestry of other large-brained mammals. The recent addition of genomes from two afrotherians (elephant and tenrec) to the expanding set of publically available sequenced mammalian genomes provided an opportunity to test this hypothesis. Elephants resemble humans by having large brains and long life spans; tenrecs, in contrast, have small brains and short life spans. Thus, we investigated whether the phylogenomic patterns of adaptive evolution are more similar between elephant and human than between either elephant and tenrec lineages or human and mouse lineages, and whether aerobic energy metabolism genes are especially well represented in the elephant and human patterns. Our analyses encompassed ≈6,000 genes in each of these lineages with each gene yielding extensive coding sequence matches in interordinal comparisons. Each gene's nonsynonymous and synonymous nucleotide substitution rates and dN/dS ratios were determined. Then, from gene ontology information on genes with the higher dN/dS ratios, we identified the more prevalent sets of genes that belong to specific functional categories and that evolved adaptively. Elephant and human lineages showed much slower nucleotide substitution rates than tenrec and mouse lineages but more adaptively evolved genes. In correlation with absolute brain size and brain oxygen consumption being largest in elephants and next largest in humans, adaptively evolved aerobic energy metabolism genes were most evident in the elephant lineage and next most evident in the human lineage.
AQUA: automated quality improvement for multiple sequence alignments
Authors: Muller Jean , Creevey Christopher J. , Thompson Julie D. , Arendt Detlev , Bork Peer
Published: November 2009

Summary: Multiple sequence alignment (MSA) is a central tool in most modern biology studies. However, despite generations of valuable tools, human experts are still able to improve automatically generated MSAs. In an effort to automatically identify the most reliable MSA for a given protein family, we propose a very simple protocol, named AQUA for ‘Automated quality improvement for multiple sequence alignments’. Our current implementation relies on two alignment programs (MUSCLE and MAFFT), one refinement program (RASCAL) and one assessment program (NORMD), but other programs could be incorporated at any of the three steps.

Availability: AQUA is implemented in Tcl/Tk and runs in command line on all platforms. The source code is available under the GNU GPL license. Source code, README and Supplementary data are available at http://www.bork.embl.de/Docu/AQUA.

Contact:  muller@embl.de, bork@embl.de
Spring 2009 H1N1 Influenza Outbreak in King County, Washington
Authors: Kwan-Gett Tao Sheng , Baer Atar , Duchin Jeffrey S.
Published: November 2009

Background:In April 2009, King County, Washington, experienced a sustained outbreak of 2009 H1N1 influenza A. This report describes the epidemiology of that outbreak in King County, home to a diverse population of 1.9 million people.

Methods:The 2 primary sources of data are case investigations of reported laboratory-confirmed 2009 H1N1 influenza A and a population-based syndromic surveillance system that captures data from emergency departments (EDs). A syndromic category for influenza-like illness was defined based on chief complaint and diagnosis.

Results:ED visits for influenza-like illness peaked quickly in the first week of the outbreak and remained high for approximately 6 weeks, with school-age children accounting for the greater number of ED visits, followed by young adults. Children ages 0 to 4 years had the highest rate of hospitalization. Among reported cases, blacks, Asians, and Hispanics were more likely to be hospitalized. Predisposing factors associated with admission were immune compromise, chronic lung disease, chronic heart disease, pregnancy, diabetes, and asthma. Of people receiving antiviral treatment, 34% started their medication more than 2 calendar days after the onset of illness. Mean days between illness onset and antiviral treatment were greater for blacks, Hispanics, and foreign language speakers.

Conclusions:The spring 2009 influenza A H1N1 outbreak disproportionately affected children, young adults, and racial and ethnic minorities. Opportunities exist to improve the timeliness of antiviral treatment. Potential barriers to care for racial and ethnic minorities should be proactively addressed to ensure prompt evaluation and treatment. (Disaster Med Public Health Preparedness. 2009;3(Suppl 2):S109–S116)
Courtship learning in Drosophila melanogaster: Diverse plasticity of a reproductive behavior
Authors: Griffith Leslie C. , Ejima Aki
Published: November 2009

Mechanisms for identifying appropriate mating partners are critical for species propagation. In many species, the male uses multiple sensory modalities to search for females and to subsequently determine if they are fit and receptive. Males can also use the information they acquire in this process to change their courtship behavior and reduce courtship of classes of targets that are inappropriate or unreceptive. In Drosophila, courtship plasticity, in the form of both nonassociative and associative learning, has been documented—the type of learning depending on the nature of the trainer. The conditions in which the male is presented with the training target can profoundly alter the cues that he finds salient and the longevity of the memory that he forms. With the exception of habituation and sensitization, these types of plasticity have an operant component in that the male must be courting to respond to the behavior-altering cues. Courtship plasticity is therefore a complex and rich range of behaviors rather than a single entity. Our understanding of these plastic behaviors has been enhanced by recent advances in our understanding of the circuitry underlying courtship itself and the identification of chemical cues that drive and modify the behavior. Courtship learning is providing a window into how animals can use a variety of sensory inputs to modulate a decision making process at many levels.
TheGibberellic Acid Stimulated-LikeGene Family in Maize and Its Role in Lateral Root Development
Authors: Zimmermann Roman , Sakai Hajime , Hochholdinger Frank
Published: November 2009

In an approach to study lateral root development in monocots, genome-wide searches for homologs of the Gibberellic Acid Stimulated Transcript-like (GAST-like) gene family in rice (Oryza sativa) and maize (Zea mays) were carried out. Six novel GAST-like genes in rice and 10 members of the gene family in maize, which were designated ZmGSL (for Z. mays Gibberellic Acid Stimulated-Like), were identified. The ZmGSL family encodes small proteins of 75 to 128 amino acids, which are characterized by a conserved 59 to 64 amino acid C-terminal domain. Within this domain, 17 amino acids, including 12 cysteines, are perfectly conserved. The transcript of the ZmGSL1 gene is differentially spliced into the alternative variants ZmGSL1a and ZmGSL1b, the latter of which is translated into a premature protein that lacks the C-terminal domain. The presence of an additional N-terminal cleavable signal sequence in eight of the 10 ZmGSL proteins suggests that they are secreted into the extracellular matrix. In-depth root-specific gene expression analyses carried out in the wild type and the lateral root mutants lrt1 and rum1 suggest a role for ZmGSL genes in early lateral root development, which is likely regulated by gibberellic acid. Expression patterns of ZmGSL1a and ZmGSL1b propose antagonistic functions of these splice variants during early lateral root formation.
Ribavirin with either standard or pegylated interferon to treat recurrent hepatitis C after liver transplantation
Authors: CICINNATI V. R. , IACOB S. , KLEIN C. G. , BABA H. A. , SOTIROPOULOS G. C. , HILGARD P. , ERIM Y. , BROELSCH C. E. , GERKEN G. , BECKEBAUM S.
Published: November 2009

Aim  To investigate the efficacy of two anti‐viral protocols in hepatitis C virus‐reinfected liver transplant recipients.

Methods  In this prospective study, 26 liver transplant patients were treated with standard interferon‐α2b for 12 months or standard interferon‐α2b for 3 months followed by pegylated interferon‐α2b for 9 months. Interferon was combined with ribavirin in all patients. The histological course of the study population was compared with an untreated historic control group (n = 38) with similar baseline characteristics.

Results  The sustained virological response rates in the standard interferon group and in the pegylated interferon group were 27.3% and 26.7%, respectively. Only 29% of patients with sustained virological response had end of treatment histological response, whereas 47% of viral non‐responders showed end of treatment histological response. The percentage of patients with histological improvement was significantly higher in the study population when compared to the controls. Univariate analysis indicated that hepatitis C virus genotype non‐1, high baseline alanine aminotransferase, the time interval between liver transplant and interferon therapy and the body mass index predicted sustained virological response. In the multivariate model, baseline alanine aminotransferase and the body mass index remained a significant predictor of sustained virological response.

Conclusions  Both treatment regimens offer similar efficacy profiles. Failure to eradicate hepatitis C virus should not lead to treatment discontinuation if serial liver biopsies demonstrate histological response.
Adherence to thiopurine treatment in out‐patients with Crohn’s disease
Authors: BOKEMEYER B. , TEML A. , ROGGEL C. , HARTMANN P. , FISCHER C. , SCHAEFFELER E. , SCHWAB M.
Published: November 2009

Background  High frequency of incomplete or non‐response to azathioprine (AZA) and/or mercaptopurine (MP) limit their use in Crohn’s disease (CD). Non‐adherence is considered to be of relevance for ineffectiveness.

Aim To assess adherence to thiopurines in CD out‐patients treated in a single gastroenterology practice.

Methods Patients were eligible for inclusion if they received AZA/MP for at least 3 months. After follow‐up of 3 months, adherence to AZA/MP was assessed by quantitation of relevant thiopurine metabolite levels in red blood cells as well as by patients’ self‐report using standardized questionnaire.

Results Sixty‐five patients were prospectively included. Six patients (9.2%) had metabolite profiles indicative of non‐adherence. Self‐assessed questionnaire revealed non‐adherence in four of 56 patients (7.1%). Therapeutic drug monitoring (TDM) and self‐assessment as two independent methods had a concordance rate of 75%. Metabolite levels and self‐assessed adherence were not significantly different between patients in remission compared with those with active disease.

Conclusions Out‐patients with CD treated in a single gastroenterology practice had a satisfactory adherence (>90%) to thiopurine therapy. Different measures of adherence (TDM and self‐report) applied to the same patient suggest comparable levels. TDM appears to be a reliable tool to assess adherence to thiopurines in clinical practice.
Hospitalizations for gastrointestinal and cardiovascular events in the CADEUS cohort of traditional or Coxib NSAID users
Authors: Laharie David , Droz‐Perroteau Cécile , Bénichou Jacques , Amouretti Michel , Blin Patrick , Bégaud Bernard , Guiard Estelle , Dutoit Sylvie , Lamarque Stéphanie , Moride Yola , Depont Fanny , Fourrier‐Réglat Annie , Moore Nicholas
Published: November 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Traditional or COX‐2‐specific (coxib) nonsteroidal anti‐inflammatory drugs (NSAIDs) are widely used.

• Their use is associated with gastrointestinal toxicity and cardiovascular events.

WHAT THIS STUDY ADDS

• The low event rates observed for gastrointestinal bleeding and myocardial infarction in the real‐life conditions of NSAID use (traditional and coxib) in France preclude their exploration using realistic field studies.

• Large population healthcare databases are required to study such risks.

AIMS To assess hospital admission rates for gastrointestinal (GI) or cardiovascular (CV) events in real‐life use of nonsteroidal anti‐inflammatory drugs (NSAIDs).

METHODS CADEUS is a real‐life population‐based cohort study of 23 535 coxib (celecoxib or rofecoxib) and 22 919 traditional NSAID (tNSAID) users. Each hospitalization reported between index day (NSAID delivery) and questionnaire submission (median = 75 days) was explored using hospital discharge summaries. An expert committee validated blindly serious GI and CV events according to predefined criteria.

RESULTS Coxib users were older and had more GI history than tNSAID users. There were 21 hospitalizations for GI events, 12 in the coxib cohort and nine in the tNSAID cohort (respectively one and three upper GI haemorrhages and no ulcer perforations). Rates of GI events were 0.39 per 1000 patients [95% confidence interval (CI) 0.18, 0.75] for tNSAID users and 0.51 per 1000 patients (95% CI 0.26, 0.89) for coxib users. There were 21 hospitalizations for CV events, 13 in the coxib cohort and eight in the tNSAID cohort. None was fatal. Rates of CV events were, respectively, 0.59 (95% CI 0.24, 1.22), 0.51 (95% CI 0.19, 1.11) and 0.35 (95% CI 0.15, 0.69) per 1000 patients for celecoxib, rofecoxib and tNSAIDs. GI or CV event rates were not different between products even for patients >60 years old.

CONCLUSIONS Hospitalization rates for GI bleeding were 10–20 times lower than expected from published randomized clinical trials, probably because of differences in drug usage and concomitant gastroprotection. CV event rates conformed to those expected from general population data. These results emphasize the necessity of developing population healthcare databases to explore such low event rates.
Prolonged pharmacodynamic effects of S‐0139, an intravenously administered endothelin A (ETA) antagonist, in the human forearm blood flow model
Authors: Lunnon Martin W. , Wallace Sharon M. L. , Palmer Joanne E. , Francis‐Lang Andrew , Laurijssens Bart E. , Mistry Prafull , Albala Bruce , Nagafuji Toshiaki , Wilkinson Ian B. , Maltby Kay
Published: November 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Using the technique of venous occlusion plethysmography, endothelin (ET) antagonists have been shown to block the vasoconstrictive effects of intra‐brachial ET‐1 infusion on forearm blood flow.

• Effects have been reported only when significant plasma concentrations of the antagonists are present.

WHAT THIS STUDY ADDS

• S‐0139 is a selective ET antagonist given by intravenous administration.

• In this study it is shown to have a prolonged duration of pharmacodynamic activity beyond that expected from its pharmacokinetic profile.

AIMSTo estimate the pharmacologically active dose range of a new investigational compound S‐0139, a selective endothelin A (ETA) receptor antagonist, in man, and to examine the duration of its pharmacodynamic effect.

METHODSVenous occlusion plethysmography was performed to assess changes in forearm blood flow following intra‐brachial administration of endothelin‐1 (ET‐1). ETAantagonists have been shown to block ET‐1‐induced vasoconstriction in this model. The study was conducted in three parts: (1) a pilot study to explore dose–response (dose range 0.08–13.33 µg kg−1 min−1), (2) a randomized study to confirm dose–response (placebo, 2.5, 6.67 and 15 µg kg−1 min−1), and (3) a delayed administration study (15.7 µg kg−1 min−1) to explore the duration of the pharmacodynamic effect. In all studies a 3‐h infusion of S‐0139 was given and during the last 90 min of the infusion, ET‐1 was infused concurrently for 90 min. In study (3) a second ET‐1 infusion was given starting 3 h after completion of the first.

RESULTSIntravenously administered S‐0139 resulted in significant inhibition of ET‐1‐induced vasoconstriction in the forearm (plasma concentration 800–2000 ng ml−1). In the delayed administration study, the same extent of inhibition was still present when ET‐1 was administered 3 h after the end of infusion of S‐0139, even though the S‐0139 plasma concentrations (mean 17 ng ml−1) were well below pharmacologically active concentrations as determined in studies 1 and 2.

CONCLUSIONSS‐0139 dose‐dependently blocks ET‐1‐mediated vasoconstriction in the forearm and has a prolonged duration of effect beyond that expected from its pharmacokinetic profile.
Langerhans cell histiocytosis in lymph nodes – cytomorphological diagnosis and pitfalls
Authors: Ouwerkerk‐Noordam E. , Boon M. E. , Van Loon A. , Van Leeuwen A. W. F. M.
Published: November 2009

Background It is a well‐known fact that when an invasive cervical carcinoma is sampled, the smear may exclusively contain blood and no diagnostic cells. We analysed a series of 77 smears of 46 patients who developed squamous cell carcinoma to detect in this series unsatisfactory cervical smears rich in blood and to define their macroscopical features.

Materials and Methods All patients who developed squamous cell carcinoma in the Dordrecht region were retrieved and all preceding smears were evaluated light microscopically and with neural network technology to detect abnormal cells. The nine smears containing no diagnosable epithelial cells (neither normal or abnormal) were chosen for this study. The macroscopic features and light microscopic characteristics of the smear background (clean, inflammatory pattern, fresh blood, old blood, fibrin and necrosis) were classified.

Results All nine unsatisfactory cervical smears were bloody, often showing a characteristic curdled pattern. Fibrin and lysed blood were seen in the background of the nine smears and can be considered as hall marks of cancer growth.

Conclusion Light microscopically, both old and fresh blood were present in thick clumps explaining the curdled macroscopical pattern of the nine smears. The mean period between the unsatisfactory cervical smear rich in blood and the final diagnosis was less than 6 months. We conclude that women with such bloody smears should immediately be sent to the gynaecologist for a histological investigation.
Identification of CENP‐V as a novel microtubule‐associating molecule that activates Src family kinases through SH3 domain interaction
Authors: Honda Zen‐ichiro , Suzuki Takeshi , Honda Hiroaki
Published: November 2009

The activation mechanisms of Src family kinases (SFKs) involve the dissociation of the intramolecular interaction between the Src homology (SH) 3 and kinase domain. This process is mediated by the intermolecular attack of outer ligands to the SH3 domain. By using a yeast two‐hybrid screen, we isolated a relevant ligand involved in the activation mechanisms of SFKs. This molecule was found to be identical to a recently recognized kinetochore protein – designated as centromere protein (CENP)‐V – which is required for the progression of mitosis. We show here that human CENP‐V plays further roles in cell dynamics; the proline‐rich region of human CENP‐V associates with the SH3 domains of SFKs and potently activates SFKs, whereas another domain of CENP‐V that possesses a highly conserved cysteine array confers the ability to associate with stabilized microtubules (MTs). Human CENP‐V distributes to the cell protrusion and to the leading edge of migrating cells in response to external stimuli, and depletion of CENP‐V by RNA interference significantly attenuates closure of a scratch wound. These findings indicate that human CENP‐V is involved in directional cell motility as well as in the progression of mitosis, as a scaffolding molecule that links MTs and SFKs.
Anaphylaxis to patent blue V: a case series and proposed diagnostic protocol
Authors: Haque R. A. , Wagner A. , Whisken J. A. , Nasser S. M. , Ewan P. W.
Published: November 2009

To cite this article: Haque RA, Wagner A, Whisken JA, Nasser SM, Ewan PW. Anaphylaxis to patent blue V: a case series and proposed diagnostic protocol. Allergy 2010; 65: 396–400.

Patent blue V is widely used in the identification of sentinel lymph nodes in patients with breast cancer and other malignancies. Individual case reports of allergy to patent blue V have been described in the medical literature since the 1960s. However, there is little data on clinical features and little experience of which allergy tests are appropriate or useful.

We gathered all cases of patent blue V allergy that had been seen and diagnosed in the Department of Allergy, Addenbrooke's Hospital over a 3‐year period. We collected clinical details of each case including skin test results. For comparison we recruited 12 healthy control subjects who then underwent skin testing to patent blue V.

Six cases of patent blue V allergy were identified, all occurring during sentinel lymph node identification for breast carcinoma. All 6 had positive skin prick tests to neat patent blue V (25 mg/ml). Skin prick testing with a 1 : 10 dilution (2.5 mg/ml) produced positive results in 3 of 4 patients tested, and intradermal testing at a 1 : 100 dilution was (0.25 mg/ml) was positive in all patients tested. Of 12 control subjects, 11 had negative skin prick tests to both neat and 1 : 10 patent blue V with one subject showing a positive reaction to the higher concentration only.

On the basis of our experience of patent blue V allergy, we propose a diagnostic protocol that can be safely and reliably utilised in centres equipped for allergy testing.
Risk factors for portal vein complications in pediatric living donor liver transplantation
Authors: Shibasaki Susumu , Taniguchi Masahiko , Shimamura Tsuyoshi , Suzuki Tomomi , Yamashita Kenichiro , Wakayama Kenji , Hirokata Gentaro , Ohta Minoru , Kamiyama Toshiya , Matsushita Michiaki , Furukawa Hiroyuki , Todo Satoru
Published: November 2009

Shibasaki S, Taniguchi M, Shimamura T, Suzuki T, Yamashita K, Wakayama K, Hirokata G, Ohta M, Kamiyama T, Matsushita M, Furukawa H, Todo S. Risk factors for portal vein complications in pediatric living donor liver transplantation. Clin Transplant 2010: 24: 550–556. © 2009 John Wiley & Sons A/S.

Abstract:  Background:  Portal vein (PV) complications in pediatric living donor liver transplantation (LDLT) are often asymptomatic in the early stages after transplantation and can be serious enough to lead to graft failure. There have been few reports on risk factors for PV complications in LDLT. The aim of this study is to investigate the influence of hepatic inflow upon PV complications and to predict patients at risk for these complications.

Material/method:  From 1997 to 2008, 46 pediatric patients underwent LDLT at our center. Portal venous and hepatic arterial flows and PV diameter were analyzed.

Results:  PV complications were identified in seven patients (15.2%) and occurred at a younger age and lower weight. As a result of appropriate treatment, none of the patients suffered graft failure. Analysis of the 46 patients and 27 patients under two yr of age indentified smaller PV diameter in recipient and larger discrepancy of PV diameter as risk factors. Portal venous flow tended to be low, in contrast to hepatic arterial flow, which tended to be high.

Conclusion:  PV size strongly influences PV complications. Other factors such as younger age, low portal venous flow, and high hepatic arterial flow may be risk factors for PV complications.
Factors associated with population risk perceptions of continuing drought in Australia
Authors: Raphael Beverley , Taylor Melanie , Stevens Garry , Barr Margo , Gorringe Matthew , Agho Kingsley
Published: November 2009

Objective:  To determine factors associated with risk perception of continuing drought in Australia.

Design and setting:  Computer Assisted Telephone Interview survey. The sample was weighted to the New South Wales population.

Participants:  A total of 2004 adults aged 16 years and over.

Results:  Overall 55.9% of the respondents thought drought was extremely or very likely to continue, 60.1% were extremely or very concerned that they or their family would be affected, and 86.3% reported that they had made some level of change to the way that they lived their lives because of the perceived risk of continuing drought. After controlling for confounding factors, the odds of perceived drought being extremely or very likely to continue, concern for self or family and making changes to behaviour because of the possibility of continuing drought were significantly higher in women than men by 43%, 59% and 86%, respectively. Compared with those who lived in highly accessible geographical areas, respondents who lived in remote or very remote geographical areas were 3.22 (adjusted odds ratios = 3.22; 95% CI, 1.69–6.14) times more likely to think that drought would continue and were 3.72 (adjusted odds ratios = 3.72; 95% CI, 1.10–12.56) times more likely to have changed the way they lived their lives because of the possibility of continuing drought.

Conclusion:  Over half of the New South Wales population thought drought was very or extremely likely to continue. The baseline data collected in this survey will be useful for monitoring changes over time in the population's perceptions of continuing drought.
Laparoscopic splenectomy may be a superior supportive intervention for cirrhotic patients with hypersplenism
Authors: Tomikawa Morimasa , Akahoshi Tomohiko , Sugimachi Keishi , Ikeda Yasuharu , Yoshida Kisaku , Tanabe Yuichi , Kawanaka Hirofumi , Takenaka Kenji , Hashizume Makoto , Maehara Yoshihiko
Published: November 2009

Background and Aims:  To evaluate and compare laparoscopic splenectomy and partial splenic embolization as supportive intervention for cirrhotic patients with hypersplenism to overcome peripheral cytopenia before the initiation of and during interferon therapy or anticancer therapy for hepatocellular carcinoma.

Methods:  Between December 2000 and April 2008, 43 Japanese cirrhotic patients with hypersplenism underwent either laparoscopic splenectomy or partial splenic embolization as a supportive intervention to facilitate the initiation and completion of either interferon therapy or anticancer therapy for hepatocellular carcinoma. We reviewed the peri‐ and post‐intervention outcomes and details of the subsequent planned main therapies. For interferon therapy, the rate of completion, the rate of treatment cessation and virological responses were evaluated. Anti‐cancer therapies for hepatocellular carcinoma included liver resection, ablation therapy, intra‐arterial chemotherapy, and transarterial chemoembolization.

Results:  All patients tolerated the operations well with no significant complications. The platelet count was significantly higher in the laparoscopic splenectomy group than in the partial splenic embolization group at 1 and 2 weeks after the intervention. Interferon therapy was stopped in two patients in the partial splenic embolization group due to recurrent thrombocytopenia whereas all patients in the laparoscopic splenectomy group completed interferon therapy. The planned anticancer therapies were performed in all patients, and were completed in all patients without any problems or major complications.

Conclusion:  Laparoscopic splenectomy may be superior to partial splenic embolization as a supportive intervention for cirrhotic patients with hypersplenism. Future prospective, randomized controlled patient studies are required to confirm these findings.
Five cases of severe hyponatremia in the elderly successfully treated with low doses of hydrocortisone
Authors: Takei Masahiro , Suzuki Satoru , Sato Ai , Yamazaki Masanori , Shi Shun , Sato Yoshihiko , Hashizume Kiyoshi
Published: November 2009

Hyponatremia is commonly defined as a serum sodium concentration of 135 mEq/L or less, which is reported to occur in 0.97–2.48% of hospitalized patients. Especially, in elderly patients, severe hyponatremia is sporadically developed without any complaints. Although a variety of causes of hyponatremia are documented, diagnosis of functional adrenal insufficiency is difficult because of a lack of the diagnostic criteria. In this case report, we present five cases of hyponatremia in the elderly, who were presumed to have functional adrenal insufficiency, successfully treated with low doses of hydrocortisone.
Reasons and Causes: Children's Understanding of Conformity to Social Rules and Physical Laws
Authors: Kalish Charles
Published: November 2009

The notion of conformity to law is an explanatory principle that appears in commonsense theories of both intentional and natural phenomena. Yet, adults distinguish sharply between conformity mediated by intentions and conformity mediated by physical interactions. To what extent do young children also see these processes as different? Three‐ to 5‐year‐old children gave different justifications for why actors “can't” violate physical laws or social rules. Consequences and permission/obligation were said to produce conformity to social rules. Justifications for laws involved reference to physical limitations or explicit statements of impossibility. Two follow‐up studies assessed understanding of the role of mental states in producing conformity. Older preschool‐aged children (but not 3‐year‐olds) appreciated that conformity to social rules depended on the knowledge and intentions of actors, whereas conformity to physical laws was independent of mental state. These studies suggest that, by age 5, children recognize different sorts of constraint or modality expressed in laws.
BORDERS MAKE THE DIFFERENCE: MIGRANT TRANSNATIONALISM AS A BORDER EXPERIENCE
Authors: GIELIS RUBEN
Published: November 2009

This paper tries to accomplish cross‐fertilisation between border studies and transmigration studies, research fields which exist almost separated from each other. It claims that the concept of border can contribute to the theoretical growth to maturity of the relatively young field of transmigration studies, and especially to a deeper understanding of the in‐between lifeworlds of transmigrants (migrant transnationalism). In transmigration studies, borders are usually considered as boundaries, the physical lines on the ground, and therefore are seen as beginnings and endings of migrant transnationalism. In this paper, it is argued that borders can also have a constitutive role in migrant transnationalism. This constitutive function of borders has been thoroughly theorised in border studies in the last two decades. Contemporary border scholars regard borders not as passive lines, but as active and polymorphous social constructions which are the outcome of people's need to make differences. By bringing this broader notion of borders to the transmigration debate, it is argued that migrant transnationalism is about experiencing the border, or experiencing the difference. This broader sense of borders might help to bare the soul of migrant transnationalism, namely the condition of being continuously between here and there.
THE BEAUTIFUL AND THE SUBLIME IN NATURAL SCIENCE
Authors: Walhout Peter K.
Published: November 2009

The various aesthetic phenomena found repeatedly in the scientific enterprise stem from the role of God as artist. If the Creator is an artist, how and why natural scientists study the divine art work can be understood using theological aesthetics and the philosophy of art. The aesthetic phenomena considered here are as follows. First, science reveals beauty and the sublime in natural phenomena. Second, science discovers beauty and the sublime in the theories that are developed to explain natural phenomena. Third, the search for beauty often guides scientists in their work. Fourth, where beauty is perceived, feelings of the sublime often also follow upon further contemplation. This linkage of beauty in science with truth and the sublime runs counter to most aesthetic theory since Kant. Scholarship in theological aesthetics has recently argued that the modern and postmodern elevation of the sublime over beauty is merely a preference that reveals a bias against transcendence—against God. If doing and understanding science can show this sundering of the sublime from the beautiful to be in error, science also gives evidence of transcendence.
STUDENT THINKING WHEN STUDYING SCIENCE‐AND‐RELIGION
Authors: Stolberg Tonie L.
Published: November 2009

Thirteen theology/religious studies students were interviewed while studying science‐and‐religion courses at four different institutions of higher education in the United Kingdom. They held a range of views about science and religion, their respective ontological status, and their science‐and‐religion studies. The interviews reveal that it may be possible to assign individuals to one of four different religioscientific conceptual frameworks and, furthermore, to relate differences in their approach when studying science‐and‐religion to their conceptual framework. The implications for course designers are discussed, including how the frameworks may enable teachers to be more aware of the range of possible reactions students may have while being introduced to science‐and‐religion topics.
THREE THEORIES OF HUMAN NATURE
Authors: Stenmark Mikael
Published: November 2009

In The Blank Slate: The Modern Denial of Human Nature, Steven Pinker maintains that at present there are three competing views of human nature—a Christian theory, a “blank slate” theory (what I call a social constructivist theory), and a Darwinian theory—and that the last of these will triumph in the end. I argue that neither the outcome of such competition nor the particular content of these theories is as clear as Pinker believes. In this essay I take a critical as well as a constructive look at the challenge presented by a Darwinian theory of human nature—a challenge to the social sciences and the humanities and also to theology and more specifically to a Christian understanding of human nature.