bluuebunny/crossref_metadata_2025 huggingface dataset:
Wall scanning probe for high-field side plasma measurements on Alcator C-Mod
Authors: Smick Noah , LaBombard Brian
Published: February 2009

A new, high-field side scanning probe has been added to Alcator C-Mod’s complement of edge diagnostics. The wall scanning probe is designed to provide all the benefits of a linear plunge, multielectrode scanning probe while working from the confined space of the inner tokamak wall. The drive mechanism is an embedded coil which produces a torque with the ambient toroidal magnetic field when energized, thus allowing the probe to plunge to different preprogramed depths at different times during a plasma discharge. The probe tip is designed for easy replacement and is presently configured to operate as a modified, high heat-flux “Gundestrup-type” probe with four tungsten electrodes. The probe has demonstrated the ability to obtain cross-field profiles for electron temperature, density, floating potential, and plasma flow information (parallel and perpendicular to B) up to a depth of a few millimiters inside the last-closed flux surface in standard C-Mod discharges. The tungsten-tipped probe has proved very robust and shows little or no damage though it routinely handles surface heat fluxes on the order of 100 MW/m2 at peak insertion.
Electronic structure of [121]tetramantane-6-thiol on gold and silver surfaces
Authors: Zhang Wenhua , Gao Bin , Yang Jinlong , Wu Ziyu , Carravetta Vincenzo , Luo Yi
Published: February 2009

The mechanism for electron photoemission of [121]tetramantane and its functionalized compound [121]tetramantane-6-thiol adsorbed on different noble metal surfaces has been investigated by density functional theory calculations. It is found that good chemical bonding between molecules and metal surfaces is a helpful but not a necessary condition for electron photoemission. A lower work function and weaker hybridization between the molecule and the metal could lead to much more efficient electron photoemission. It is observed that, neglecting final state effect, a simple ground state picture cannot result in negative electron affinity for the systems under investigation. Calculations have shown that by exciting an electron in the lowest unoccupied molecular orbital, the highest singly occupied molecular orbital of the molecule can be shifted above the vacuum level, resulting in negative electron affinity and emission of the accumulated electrons.
Modal and nonmodal growths of inviscid planar perturbations in shear flows with a free surface
Authors: Bakas Nikolaos A. , Ioannou Petros J.
Published: February 2009

Shear flows with a free surface possess diverse branches of modal instabilities. By approximating the mean flow with a piecewise linear profile, an understanding and classification of the instabilities can be achieved by studying the interaction of the edge waves that arise at the density discontinuity at the surface and the vorticity waves that are supported at the mean vorticity gradient discontinuities in the interior. The various branches of instability are identified and their physical origin is clarified. The edge waves giving rise to the modal instabilities can also lead to a modest transient growth that extends into the regions of neutrality of the flow. However, when the continuous spectrum is excited substantial transient growth can arise and the optimal perturbations attain greater energy when compared with the energy of the fastest modal growing perturbation. These optimal perturbations utilize the continuous spectrum to excite at large amplitude the neutral or amplifying modes of the system.
Photonic band structure evolution of a honeycomb lattice in the presence of an external magnetic field
Authors: Duque C. A. , Porras-Montenegro N. , Cavalcanti S. B. , Oliveira L. E.
Published: February 2009

A standard plane-wave expansion technique is used to investigate the evolution of the photonic band structure of a two-dimensional honeycomb lattice composed by cylindrical shell rods with dielectric permittivities ε1 and ε2, and embedded in a background with permittivity ε3. We have considered the effect of dispersive dielectric responses as well as the influence of an externally applied magnetic field aiming to obtain efficient tunable bandgaps. Present results suggest that a combination of a doped semiconductor constituent with an anisotropic geometry, which breaks symmetry and unfolds degeneracies, provides an efficient realization of photonic systems with tunable bandgaps.
Preliminary group classification of a class of fourth-order evolution equations
Authors: Huang Qing , Lahno V. , Qu C. Z. , Zhdanov R.
Published: February 2009

We perform preliminary group classification of a class of fourth-order evolution equations in one spatial variable. Following the approach developed by Basarab-Horwath et al. [Acta Appl. Math. 69, 43 (2001)], we construct all inequivalent partial differential equations belonging to the class in question which admit semisimple Lie groups. In addition, we describe all fourth-order evolution equations from the class under consideration which are invariant under solvable Lie groups of dimension n<=4. We have constructed all Galilei-invariant equations belonging to the class of evolution differential equations under study. The list of so obtained invariant equations contains both the well-known fourth-order evolution equations and a variety of new ones possessing rich symmetry and as such may be used to model nonlinear processes in physics, chemistry, and biology.
The influence of size distribution on the luminescence decay from excited states of InAs/GaAs self-assembled quantum dots
Authors: Harbord Edmund , Spencer Peter , Clarke Edmund , Murray Ray
Published: February 2009

We compare the time integrated and time resolved spectra of two samples having coincident ground state emission peaks: one consisting of highly uniform quantum dots, the other grown under conditions which produce a broad distribution of quantum dot sizes. The photoluminescence decay of the ground states in both samples is monoexponential from which we deduce a lifetime of ∼1100 ps independent of excitation power. The excited state decays for the two samples are biexponential with fast and slow components of ∼300 and ∼1100 ps, respectively. These are also independent of excitation power but their contribution to the decay curve changes with power. The data allow us to unequivocally associate the fast component with the excited state decay of larger dots and the slow component with the ground state decay of smaller dots which emit at the same energy. Furthermore, taking into account the degeneracy of the ground state and the optical selection rules for exciton recombination in a confined system we show that the lifetime of the excited state is consistent with the ground state as predicted from Fermi’s golden rule.
Short-range structure of Pb1−xBaxZr0.65Ti0.35O3 ceramic compounds probed by XAS and Raman scattering techniques
Authors: Mastelaro V. R. , Mesquita A. , Neves P. P. , Michalowicz A. , Bounif M. , Pizani P S. , Joya M. R. , Eiras J. A.
Published: February 2009

Ti K-edge x-ray absorption near-edge spectroscopy (XANES) and Raman scattering were used to study the solid solution effects on the structural and vibrational properties of Pb1−xBaxZr0.65Ti0.35O3 with 0.0<x<0.40. Compared with x-ray diffraction techniques, which indicates that the average crystal symmetry changes with the substitution of Pb by Ba ions or with temperature variations for samples with x=0.00, 0.10, and 0.20, local structural probes such as XANES and Raman scattering results demonstrate that at local level, the symmetry changes are much less prominent. Theoretical XANES spectra calculation corroborate with the interpretation of the XANES experimental data.
The secondary electron emission yield of muscovite mica: Charging kinetics and current density effects
Authors: Blaise G. , Pesty F. , Garoche P.
Published: February 2009

Using a dedicated scanning electron microscope, operating in the spot mode, the charging properties of muscovite mica have been studied in the energy range of 100–8000 eV. The intrinsic yield curve σ0(E), representing the variation of the yield of the uncharged material with the energy E, has been established: the maximum value of the yield is 3.92 at E=300 eV and the two crossovers corresponding to σ0(E)=1 are, respectively, at energies EI<100 eV and EII=4850 eV. At a given energy and under a low current density J≤100 nA/cm2, the yield varies with the electron fluence from its intrinsic value σ0 up to the value corresponding to the self-regulated regime for which σ=1. This variation is independent of J. The fluence dependence of the yield σ(D) is due to the internal field produced by the accumulation of charges that blocks the emission when the charging is positive and enhances it when it is negative. At room temperature, the relaxation time of stored charges is estimated to be of the order of 250 s for holes and 150 s for electrons. Three current density effects have been observed when J≥400 nA/cm2. (i) The variation of σ(D) with the fluence D depends on J. (ii) Negative charging is obtained at high current density in the energy range (EI, EII) where the material is normally positively charged at low current density. (iii) Electron exoemission (bursts of electrons) is produced at low energy when the net stored charge is positive. The interpretation of the current density effect on σ(D) is based on the high rate of charging, the effect relative to negative charging is due to the expansion of the electron distribution, while the exoemission effect is due to the collective relaxation process of electrons.
Determination of composition in stoichiometric Co–N ultrathin films by nitrogen plasma sputtering
Authors: Su C. W. , Huang M. S. , Chang Y. C. , Tsai T. H. , Lee Y. H. , Lee J. C.
Published: February 2009

This work utilizes low-energy sputtering to incorporate the generated nitrogen plasma into an epitaxial 1.4nm Co film on the surface of a ZnO(002) substrate. In this method, ultrathin Co–N amorphous films were formed. Interestingly, Co is key to the formation of Co–N films. Without the deposition of Co on the ZnO(002), nitride films cannot be formed. Observations of the surface composition of the Co–N films after the firing of a N+ ion beam onto it demonstrated that the surface concentration of Co reduced at the same rate as the reduction in the concentration of N upon successive sputtering. Theoretical calculations based on the Auger peak-to-peak amplitudes established that the composition of the amorphous Co–N thin films may be Co3N2.
Performance of an optimized substrate-free focal plane array for optical readout uncooled infrared detector
Authors: Cheng Teng , Zhang Qingchuan , Chen Dapeng , Shi Haitao , Gao Jie , Wu Xiaoping
Published: February 2009

This note presents an optimized substrate-free focal plane array (FPA), which is implemented in an optical readout uncooled infrared (IR) detector. The supporting frame of such FPA is a temperature-variable one due to the large decreases in both the heat capacity and the thermal conductance. This brings a unique thermal characteristic: the supporting frame functions as a “thermal isolation” frame which reduces the thermal conductance and therefore increases the temperature change and also functions as a “thermal diffusion” frame which certainly results in the temperature prechange in the ones not absorbing IR radiation. This characterization could significantly increase the temperature change of microcantilevers and therefore improve the performance of the substrate-free FPA. In the proposed IR detector, the fabricated 160×160 FPA has an average noise equivalent temperature difference (NETD) and a response time of 330 mK and 16 ms, respectively. The performance of the IR detector theoretically increases by about 5.5 times compared with the one using a substrate FPA. Here, the geometry of the substrate FPA is just the same as the fabricated FPA, but the supporting frame is assumed to be a temperature-constant one. If the optical readout sensitivity can be increased enough using an enhanced IR absorber, the fabricated FPA thus has the potential to achieve a NETD value of 70 mK.
High external emission efficiency in intentionally ordered GaInP/GaAs structures
Authors: Song J. S. , Seo S. H. , Choi Y. C. , Song H. S. , Chang Y. H. , Oh M. H. , Oh D. C. , Yao T. , Chang J. H. , Han C. S. , Koo K. W.
Published: February 2009

The authors report on an additional effect of the intentionally ordered GaInP layers obtained by using the double tilt GaAs substrates, i.e., the misoriented (001) GaAs substrates toward the two directions of [110] and [−110]. In photoluminescence (PL) spectra at 7 K, it is found that the emission intensity is enhanced with the increase in the substrate misorientation angle toward [−110] direction, along with the redshift of the bandedge. However, the redshift of the bandedge means that the GaInP layers suffer from the ordering of group III atoms. The authors note that the surface morphology in the ordered GaInP layers becomes rapidly rough by the substrate misorientation, even though the linewidths of their PL spectra and x-ray rocking curves are almost similar, irrespective of the misorientation angle. As a result, the light extraction mechanism in the roughened surface structure and the surface roughening mechanism in the intentionally ordered GaInP layers are suggested.
Influence of in-plane biaxial stress on the structural properties, ferroelectric response, and piezoelectricity of tetragonal PbTiO3
Authors: Duan Yifeng , Qin Lixia , Tang Gang , Chen Changqing
Published: February 2009

Tetragonal PbTiO3 under in-plane biaxial stress is investigated from first principles. We show that before the biaxial tensile stress applied in the plane perpendicular to the c axis reaches its ideal tensile strength of 28.95 GPa, PbTiO3 tend to show the paraelectric tetragonal symmetry. We also find that the biaxial tensile stress can enhance the piezoelectric stress coefficients, whereas the biaxial compressive stress can enhance the piezoelectric strain coefficients. The underlying mechanisms for the predicted piezoelectric responses are also discussed.
Optical modeling of chalcopyrite-based tandems considering realistic layer properties
Authors: Schmid M. , Krč J. , Klenk R. , Topič M. , Lux-Steiner M. Ch.
Published: February 2009

Previous models of chalcopyrite-based tandem solar cells have not taken into account the limited optical transmission of the top cell observed. We use a quantitative model derived from measured optical properties of the different layers of the top cell to re-evaluate the benefits and limitations of the tandems. Guidelines are provided for minimizing optical losses in the structure. Optimization of the bottom absorber band gap and top absorber thickness is carried out. In combination with straightforward assumptions concerning the electronic cell properties, we calculate tandem maximum efficiencies in the range of 26%–28% depending on the degree of nonideal optical absorption.
Balancing interlayer dipolar interactions in multilevel patterned media with out-of-plane magnetic anisotropy
Authors: Baltz V. , Rodmacq B. , Bollero A. , Ferré J. , Landis S. , Dieny B.
Published: February 2009

Nanostructures consisting of a stack of two magnetic multilayers with out-of-plane anisotropy and distinct coercivities hold great promises in spintronics devices. Yet their miniaturization leads to interlayer dipolar coupling, which results in detrimental asymmetrical behaviors of magnetization reversal or even in the loss of intermediate antiparallel configuration. In this letter, we take advantage of Ruderman–Kittel–Kasuya–Yosida interactions in order to compensate for this coupling and restore symmetry. The study has been performed on an array of square dots of 200 nm lateral size, each dot consisting of two [Co/Pt] multilayers antiferromagnetically coupled through a thin Ru spacer.
Determining the scale of the Bicoid morphogen gradient
Authors: Hecht Inbal , Rappel Wouter-Jan , Levine Herbert
Published: February 2009

Bicoid is a morphogen that sets up the anterior-posterior axis in early Drosophila embryos. Although the form of the Bicoid profile is consistent with a simple diffusion/degradation model, the observed length scale is much larger than should be expected based on the measured diffusion rate. Here, we study two possible mechanisms that could, in principle, affect this gradient and, hence, address this disagreement. First, we show that including trapping and release of Bicoid by the nuclei during cleavage cycles does not alter the morphogen length scale. More crucially, the inclusion of advective transport due to cytoplasmic streaming can have a large effect. Specifically, we build a simple model based on the (limited) experimental data and show that such a flow can lead to a Bicoid profile that is consistent with various experimental features. Specifically, the observed length scale is obtained, a steady profile is established, and improved scaling between embryos of different lengths is demonstrated.
Tri-split tRNA is a transfer RNA made from 3 transcripts that provides insight into the evolution of fragmented tRNAs in archaea
Authors: Fujishima Kosuke , Sugahara Junichi , Kikuta Kaoru , Hirano Reiko , Sato Asako , Tomita Masaru , Kanai Akio
Published: February 2009

Transfer RNA (tRNA) is essential for decoding the genome sequence into proteins. In Archaea, previous studies have revealed unique multiple intron-containing tRNAs and tRNAs that are encoded on 2 separate genes, so-called split tRNAs. Here, we discovered 10 fragmented tRNA genes in the complete genome of the hyperthermoacidophilic ArchaeonCaldivirga maquilingensisthat are individually transcribed and furthertrans-spliced to generate all of the missing tRNAs encoding glycine, alanine, and glutamate. Notably, the 3 mature tRNAGly's with synonymous codons are created from 1 constitutive 3′ half transcript and 4 alternatively switching transcripts, representing tRNA made from a total of 3 transcripts named a “tri-split tRNA.” Expression and nucleotide sequences of 10 split tRNA genes and their joined tRNA products were experimentally verified. The intervening sequences of split tRNA have high identity to tRNA intron sequences located at the same positions in intron-containing tRNAs in related Thermoproteales species. This suggests that an evolutionary relationship between intron-containing and split tRNAs exists. Our findings demonstrate the first example of split tRNA genes in a free-living organism and a unique tri-split tRNA gene that provides further insight into the evolution of fragmented tRNAs.
Differential NF-κB pathways induction by
Lactobacillus plantarum
in the duodenum of healthy humans correlating with immune tolerance
Authors: van Baarlen Peter , Troost Freddy J. , van Hemert Saskia , van der Meer Cindy , de Vos Willem M. , de Groot Philip J. , Hooiveld Guido J. E. J. , Brummer Robert-Jan M. , Kleerebezem Michiel
Published: February 2009

How do we acquire immune tolerance against food microorganisms and commensal bacteria that constitute the intestinal microbiota? We investigated this by stimulating the immune system of adults with commensal
Lactobacillus plantarum
bacteria. We studied the in vivo human responses to
L. plantarum
in a randomized double-blind placebo-controlled cross-over study. Healthy adults ingested preparations of living and heat-killed
L. plantarum
bacteria. Biopsies were taken from the intestinal duodenal mucosa and altered expression profiles were analyzed using whole-genome microarrays and by biological pathway reconstructions. Expression profiles of human mucosa displayed striking differences in modulation of NF-κB-dependent pathways, notably after consumption of living
L. plantarum
bacteria in different growth phases. Our in vivo study identified mucosal gene expression patterns and cellular pathways that correlated with the establishment of immune tolerance in healthy adults.
Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation
Authors: Marion Vincent , Stoetzel Corinne , Schlicht Dominique , Messaddeq Nadia , Koch Michael , Flori Elisabeth , Danse Jean Marc , Mandel Jean-Louis , Dollfus Hélène
Published: February 2009

Bardet-Biedl syndrome (BBS) is an inherited ciliopathy generally associated with severe obesity, but the underlying mechanism remains hypothetical and is generally proposed to be of neuroendocrine origin. In this study, we show that while the proliferating preadipocytes or mature adipocytes are nonciliated in culture, a typical primary cilium is present in differentiating preadipocytes. This transient cilium carries receptors for Wnt and Hedgehog pathways, linking this organelle to previously described regulatory pathways of adipogenesis. We also show that the BBS10 and BBS12 proteins are located within the basal body of this primary cilium and inhibition of their expression impairs ciliogenesis, activates the glycogen synthase kinase 3 pathway, and induces peroxisome proliferator-activated receptor nuclear accumulation, hence favoring adipogenesis. Moreover, adipocytes derived from BBS-patients' dermal fibroblasts in culture exhibit higher propensity for fat accumulation when compared to controls. This strongly suggests that a peripheral primary dysfunction of adipogenesis participates to the pathogenesis of obesity in BBS.
Improvement of survival in sex cord stromal tumors – an observational study with more than 25 years follow‐up
Authors: HÖLSCHER GABRIELE , ANTHUBER CHRISTOPH , BASTERT GUNTHER , BURGES ALEXANDER , MAYR DORIS , OBERLECHNER ERNST , SCHUBERT‐FRITSCHLE GABRIELE , SINZ SONJA , SOMMER HARALD , SCHMALFELDT BARBARA , ENGEL JUTTA ,   FOR THE PROJECT GROUP ‘MALIGNANT OVARIAN TUMORS’ OF THE MUNICH CANCER CENTER (MCC)
Published: February 2009

Objective. To highlight aspects of malignant ovarian sex cord stromal tumors, effects of treatment, and developments over the past 28 years. Design. Population‐based cohort study. Setting. Gynecological departments within the catchment‐area of the Munich Cancer Registry and associated with the project group ‘Malignant Ovarian Tumors’ of the Munich Cancer Center. Sample. One hundred and forty‐five women with an invasive single sex cord stromal tumor diagnosed between 1978 and 2005. Methods. Overall survival was estimated with the Kaplan–Meier method, relative survival was computed by the ratio of observed to expected survival rate. The impact of age, International Federation of Gynecology and Obstetrics (FIGO)‐stage, residual tumor, and chemotherapy was examined by multivariate analysis (Cox regression model). Main outcome measures. Overall and relative survival and multivariate adjusted overall survival. Results. Survival data showed a five‐/10‐year overall survival of 55.8%/42.8% (relative survival 58.6%/49.2%) for women diagnosed before 1988 and 89.1%/78.3% (relative survival 92.7%/85.2%) for women diagnosed after 1988. After adjustment for age and FIGO‐stage, the following hazard ratios and 95% confidence intervals (95% CI) for treatment methods resulted: 3.3 (95% CI 1.5–7.0) for women with compared to women without residual tumor and 2.2 (95% CI 1.2–4.2) for women with chemotherapy compared to women where no chemotherapy was given. Conclusions. Improvements in survival may be attributed to a stage‐shift toward more favorable stages at diagnosis and to advances in treatment such as improved surgery without residual tumor. There is no evidence for any benefit of adjuvant chemotherapy. Surgery remains the cornerstone of treatment, yet the benefit of postoperative therapy is still under debate.
Perinatal risk factors in young adult‐onset type 1 and type 2 diabetes – a population‐based case‐control study
Authors: LAMMI NIINA , BLOMSTEDT PAUL A. , MOLTCHANOVA ELENA , ERIKSSON JOHAN G. , TUOMILEHTO JAAKKO , KARVONEN MARJATTA
Published: February 2009

Objective. To examine the effects of the size of the mother and the newborn, including placental weight and gestational age at delivery, on the risk for young adult‐onset type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Design. Case‐control study. Setting. Finland. Population. Subjects with T1DM and T2DM aged 15–39 at diagnosis between the years 1992 and 1996. The number of case‐control pairs was 858 for T1DM and 355 for T2DM. Methods. Diabetic subjects were identified from the Finnish national healthcare registers and reports from diabetes nurses. Control subjects were obtained from the population register. Data on perinatal factors were obtained from the original healthcare records. The odds ratios (ORs) for both types of diabetes were estimated using conditional logistic regression. Results. The risk for early‐onset T2DM decreased with increasing birthweight until 4.2 kg (OR 0.49 (95% confidence interval 0.37–0.66) per 1 kg), but with birthweight above 4.2 kg the risk increased (OR 4.8 (1.3–17.6) per 1 kg). The risk for T2DM decreased also with increasing birth length (OR 0.88 (0.81–0.95) per 1 cm), body mass index at birth (OR 0.81 (0.73–0.90) per 1 kg/m2), and placental weight (OR 0.77 (0.61–0.98) per 100 g). The latter was not significant when adjusted for birthweight. The examined perinatal factors did not affect the risk for T1DM in young adults. Conclusions. Birth size significantly affects the risk for T2DM diagnosed in young adulthood but no evidence was found of an association between late‐onset T1DM and perinatal factors.
Preventing Healthcare Workers From Acquiring Influenza
Authors: Ng Tak Ching , Lee Nelson , Hui Shu-Cheong David , Lai Raymond , Ip Margaret
Published: February 2009

Our survey of 133 on-duty medical ward nurses showed that, during peak influenza season, 30 (23%) developed an influenza-like illness, despite wearing a mask at work. Suboptimal adherence to standard precautions, such as the use of a face shield (odds ratio, 3.56) during high-risk procedures, and failure to receive influenza vaccination (odds ratio, 4.82) were independent risk factors, adjusted for household contacts.
Successful Containment of a Norovirus Outreak in an Acute Adult Psychiatric Area
Authors: Gilbride Susan J. , Lee Bonita E. , Taylor Geoffrey D. , Forgie Sarah E.
Published: February 2009

We describe a norovirus outbreak in an acute adult psychiatric area in a tertiary care hospital. Containment of the outbreak was challenging because of the patients' psychiatric conditions and the area's configuration. On the basis of this experience, recommendations were made to help prevent a similar scenario in the future.
Systems biology metabolic modeling assistant: an ontology-based tool for the integration of metabolic data in kinetic modeling
Authors: Reyes-Palomares Armando , Montañez Raul , Real-Chicharro Alejando , Chniber Othmane , Kerzazi Amine , Navas-Delgado Ismael , Medina Miguel Ángel , Aldana-Montes José F. , Sánchez-Jiménez Francisca
Published: February 2009

Summary: We present Systems Biology Metabolic Modeling Assistant (SBMM Assistant), a tool built using an ontology-based mediator, and designed to facilitate metabolic modeling through the integration of data from repositories that contain valuable metabolic information. This software can be used for the visualization, design and management of metabolic networks; selection, integration and storage of metabolic information; and as an assistant for kinetic modeling.

Availability: SBMM Assistant for academic use is freely available at http://www.sbmm.uma.es.

Contact:  kika@uma.es
Prognostic value of plasma midregional pro‐adrenomedullin and C‐terminal‐pro‐endothelin‐1 in chronic heart failure outpatients
Authors: Adlbrecht Christopher , Hülsmann Martin , Strunk Guido , Berger Rudolf , Mörtl Deddo , Struck Joachim , Morgenthaler Nils G. , Bergmann Andreas , Jakowitsch Johannes , Maurer Gerald , Lang Irene M. , Pacher Richard
Published: February 2009

Aims

The identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or non‐ischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional‐pro‐adrenomedullin (MR‐proADM) and C‐terminal‐pro‐endothelin‐1 (CT‐proET‐1) in outpatients with CHF.

Methods and results

We measured plasma MR‐proADM and CT‐proET‐1 levels in 786 consecutive CHF outpatients and compared them with B‐type natriuretic peptide (BNP) levels. At 24‐month follow‐up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA > II, left ventricular ejection fraction (LVEF), MR‐proADM, CT‐proET‐1, and BNP as possible predictors revealed that MR‐proADM levels [hazard ratio (HR) = 1.77, P < 0.001] in addition to age (HR = 1.02, P = 0.004), ejection fraction (HR = 0.98, P = 0.004), and NYHA > II (HR = 1.86, P < 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA‐stage, MR‐proADM (HR = 2.12, P < 0.001) and LVEF (HR = 0.96, P = 0.006) were significant markers, but only in patients with mild/moderate CHF.

Conclusion

Our data suggest that MR‐proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non‐ischaemic CHF patients.
Pathophysiological and clinical relevance of simplified monitoring of nocturnal breathing disorders in heart failure patients
Authors: Pinna Gian Domenico , Maestri Roberto , Mortara Andrea , Johnson Paul , Andrews David , Ponikowski Piotr , Witkowski Tomasz , Robbi Elena , La Rovere Maria Teresa , Sleight Peter
Published: February 2009

Aims

Nocturnal breathing disorders in the form of periodic breathing (PB) are very common in heart failure (HF) patients. There is an increasing interest in simple and affordable tools to screen patients and monitor these disorders at home on a long‐term basis. We aimed to assess the pathophysiological and clinical relevance of a simplified method for monitoring of PB suitable to be self‐managed by the patient at home.

Methods and results

A night‐time respiratory recording was performed in 397 optimally treated HF patients (age 60 ± 11 years, NYHA class 2.4 ± 0.6, left ventricular ejection fraction 29 ± 7%) and the duration of PB (PBDur) automatically computed. Patients were followed‐up for 1 year and the prognostic value of PBDur evaluated. In 45 patients, we assessed the association between PBDur and severity of oxygen desaturations (number of desaturations >3%). Twenty six of the 397 patients died of cardiac causes. A PBDur ≥2 h was significantly associated with an increased risk of cardiac death after adjustment for major clinical predictors [hazard ratio (95% CI): 3.5 (1.6–7.9), P = 0.002]. The correlation between PBDur and severity of desaturations was 0.94 (P < 0.0001).

Conclusion

Relevant pathophysiological and clinical information can be obtained from simplified monitoring of breathing disorders managed by the patient. These results provide new perspectives in the investigation of the clinical impact of abnormal breathing in HF patients.
Effect of Enzymatic Tempering of Wheat Kernels on Milling and Baking Performance
Authors: Yoo J. , Lamsal B. P. , Haque E. , Faubion J. M.
Published: February 2009

This study examined the effect of cell‐wall‐degrading enzymes added to temper water on wheat milling performance and flour quality. An enzyme cocktail consisting of cellulase, xylanase, and pectinase and five independent variables (enzyme concentration, incubation time, incubation temperature, tempered wheat moisture content, and tempering water pH) were manipulated in a response surface methodology (RSM) central composite design. A single pure cultivar of hard red winter wheat was tempered under defined conditions and milled on a Ross experimental laboratory mill. Some treatment combinations affected flour yield from the break rolls more than that from the reduction rolls. However, a maximum for flour yield was not found in the range of parameters studied. Though treatments did not affect the optimum water absorption for breadmaking, enzyme‐treated flours produced dough exhibiting shorter mixing times and slack and sticky textures compared with the control. Regardless of differences in mixing times, specific loaf volumes were not significantly different among treatments. Crumb firmness of bread baked with flour milled from enzyme‐treated wheat was comparable to the control after 1 day but became firmer during storage up to 5 days.
Pilot study on photodynamic therapy for acne using indocyanine green and diode laser
Authors: KIM Beom Joon , LEE Ho Gyun , WOO Seung Man , YOUN Jai Il , SUH Dae Hun
Published: February 2009

To demonstrate the efficacy of photodynamic therapy using indocyanine green (ICG) dye with a diode laser for acne treatment of Asian subjects, an analysis was performed of 16 randomly chosen Korean patients with acne vulgaris treated by photodynamic therapy for a mean follow up of 2 months. Volunteers were divided into two groups, a single‐ and multiple‐treatment group, in which photodynamic therapy was repeated three times with 1‐week intervals. Photodynamic therapy using ICG dye with a diode laser was effective for acne treatment of Korean subjects. However, multiple treatments were not superior to single treatments in controlling acne lesions. Photodynamic therapy combined with ICG dye and diode laser might be an alternative treatment modality for acne in Asian subjects.
Cutaneous complications among i.v. buprenorphine users
Authors: HO Roger C. M. , HO Emily C. L. , MAK Anselm
Published: February 2009

i.v. buprenorphine hydrochloride (Subutex) misuse has been creating a number of medical complications, and cutaneous manifestations such as soft tissue infection are one of the commonest consequences. Between January 2004 and December 2006, amongst 130 i.v. buprenorphine abusers who presented to the National University Hospital, Singapore, cutaneous complications were identified in 45 patients (prevalence, 31%) with cellulitis and skin abscess being the commonest complications. Tissue and blood culture were positive in 19 (42%) patients and Methicillin‐sensitive Staphylococcus aureuswas the commonest microbiological isolate (20%). Univariate linear regression revealed significant relationships between body temperature (P = 0.03), heart rate (P = 0.02), respiratory rate (P < 0.001), total peripheral white cell count (P = 0.011), absolute neutrophil count (P < 0.001) and serum C‐reactive protein (CRP) level (P < 0.001) on admission and through the duration of hospitalization. In multivariate analysis, respiratory rate on admission remained significantly associated with longer duration of hospitalization (P = 0.01). i.v. cloxacillin, i.v. crystallized penicillin and oral cloxacillin were the most commonly prescribed antibiotics while 11 (24%) patients required surgical treatment. The mean duration of hospitalization was 8 ± 11 days and repeated cutaneous complications occurred in eight (18%) patients. In conclusion, cutaneous complications are common among i.v. buprenorphine users. Respiratory rates on admission predict duration of hospital stay. A high index of suspicion coupled with a correct choice of antibiotics based on local bacteriological surveillance is necessary in an attempt to reduce cutaneous complications and length of hospitalization.
Evaluation of the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) scoring system in elderly patients with pressure sores undergoing fasciocutaneous flap‐reconstruction
Authors: MIZUMOTO Kazuo , MORITA Eishin
Published: February 2009

The aim of the present study was to predict operative morbidity in elderly patients with deep pressure sores by using the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) scoring system. Fifteen patients over 70 years old were retrospectively reviewed who had undergone gluteus maximus fasciocutaneous flap‐reconstruction for pressure sores of the sacral region from 1 April 2005 to 31 March 2007. Complications were seen in six cases (40%) after operation. Four were wound infection, one was chest infection and another was septicemia. The subjects were divided into two groups by the presence (complicated group) or absence (non‐complicated group) of postoperative complications. Each item of physiological scores, physiological score (PS), operative severity score (OS) and predicted morbidity rate (R) were calculated and compared between two groups. As a result, hemoglobin (P = 0.0276), PS (P = 0.0023) and R (P = 0.0078) differed significantly between the two groups. It is noteworthy that the PS were over 25 in all of the complicated group, but in only one of nine in the non‐complicated group (P = 0.0014). Our study suggests that, for pressure sores in the sacral region in elderly patients, gluteus maximus fasciocutaneous flap‐reconstruction can be employed in patients whose PS are under 24 in the POSSUM scoring system.
Neuroendocrine stimulatory tests of hypothalamus–pituitary–adrenal axis in psoriasis and correlative implications with psychopathological and immune parameters
Authors: KARANIKAS Evangelos , HARSOULIS Faidon , GIOUZEPAS Ioannis , GRIVEAS Ioannis , CHRISOMALLIS Fotios
Published: February 2009

Psoriasis constitutes one of the most representative examples of psychosomatic disorders. The published work investigating the psychological parameters and the way they interact during the course of the disease is extensive, whereas only a few studies have focused on the neuroendocrine framework of psoriasis. In the present study, the objective was to investigate the neuroendocrine parameters of psoriasis and the way they interact with psychopathological and immune variables. Patients with psoriasis (n = 24) and the same number of matched healthy controls underwent psychiatric evaluation with interviews and psychometric questionnaires. Both of the groups underwent the corticotropin‐releasing hormone (CRH) test and the dexamethasone suppression test (DST) to investigate functional parameters of the hypothalamus–pituitary–adrenal (HPA) axis. The evaluation of immune variables included the estimation of the distribution of T‐cell and natural killer lymphocytes. Levels of depressive and anxiety features were increased within subjects with psoriasis and they were significantly correlated with stressful life events and the extent of the disease. The adrenocorticotrophic hormone and cortisol levels increased after CRH infusion without significant differences between the two groups and the psoriatic subjects’ cortisol suppression after DST was within normal range, though relatively blunted. No significant correlations were identified among neuroendocrine, psychopathological and immune parameters. No particular neuroendocrine profile has been identified among psoriatic patients and the hypothesized interaction with psychopathological and immune parameters was not replicated. Nevertheless, it is still premature to exclude the possibility that a subtle latent alteration of the HPA axis function might exist, in psoriasis, either stemming from the psychopathology or from the disease per se.
Effects ofSchisandra sphenantheraextract on the pharmacokinetics of midazolam in healthy volunteers
Authors: Xin Hua‐Wen , Wu Xiao‐Chun , Li Qing , Yu Ai‐Rong , Xiong Lei
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Schisandra sphenantheraextract (SchE) and tacrolimus are often co‐administered in treating renal and liver transplant recipients in China.

• Our previous study has demonstrated that SchE can increase the oral bioavailability of tacrolimus.

WHAT THIS STUDY ADDS

• The results of this study show that SchE can markedly increase the blood concentration and oral bioavailability of midazolam in healthy volunteers.

• This finding suggests that SchE may be an inhibitor of CYP3A and is likely to alter the disposition of drugs that are metabolized by CYP3A.

AIMSTo assess the effect ofSchisandra sphenantheraextract (SchE) on the pharmacokinetics of midazolam, a probe drug of CYP3A, and its metabolite 1′‐hydroxy midazolam in healthy volunteers.

METHODSTwelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 7 days. Pharmacokinetic investigations of oral midazolam administration at 15 mg were performed both before and at the end of the SchE treatment period. The plasma midazolam and 1′‐hydroxy midazolam concentrations were determined by high‐performance liquid chromatography–tandem mass spectrometry. Estimated pharmacokinetic parameters before and with SchE were calculated with noncompartmental techniques.

RESULTSFollowing administration of SchE, the average increases (%) of individual increases in AUC, AUMC andCmaxof midazolam were 119.4% [95% confidence interval (CI) 83.9, 155.0], 183.4% (95% CI 120.5, 246.2) and 85.6% (95% CI 14.4, 156.9), respectively (P< 0.01 or 0.05). On average, there was a 133.3% (95% CI 8.9, 257.7) increase in midazolamtmax(P< 0.01). The average decrease (%) in CL/Fwas 52.1% (95% CI 44.9, 59.4) (P< 0.01). No significant changes were seen in midazolam half‐life. After co‐administration of SchE, the average increase (%) intmaxof 1′‐hydroxy midazolam was 150.0% (95% CI 22.2, 277.8) (P< 0.05). No significant differences were observed in the other pharmacokinetic parameters of 1′‐hydroxy midazolam.

CONCLUSIONSSchE can markedly increase the oral bioavailability of midazolam in healthy volunteers. SchE is an inhibitor of CYP3A and has a high susceptibility to alter the disposition of drugs metabolized by CYP3A.
In vitroandin vivoglucuronidation of midazolam in humans
Authors: Hyland Ruth , Osborne Toby , Payne Anthony , Kempshall Sarah , Logan Y. Raj , Ezzeddine Khaled , Jones Barry
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Midazolam is extensively metabolized and is eliminated in urine predominantly as conjugates of 1′‐hydroxymidazolam.

• Midazolam is known to undergo N‐glucuronidationin vitroby UGT1A4.

• In vitro1′‐hydroxymidazolam is O‐glucuronidated by UGT2B4 and UGT2B7, and N‐glucuronidated by UGT1A4.

WHAT THIS STUDY ADDS

• N‐glucuronide of midazolam has been quantified in human urine, indicating for the first time that this route of metabolism occursin vivo.

• Metabolism of 4‐hydroxymidazolam has been compared with that of 1′‐hydroxymidazolamin vitro.

• This study provides further evidence,in vitroandin vivo, of the importance of N‐glucuronidation in the metabolism of midazolam and its metabolites.

AIMSMidazolam (MDZ) is a benzodiazepine used as a CYP3A4 probe in clinical andin vitrostudies. A glucuronide metabolite of MDZ has been identifiedin vitroin human liver microsome (HLM) incubations. The primary aim of this study was to understand thein vivorelevance of this pathway.

METHODSAn authentic standard of N‐glucuronide was generated from microsomal incubations and isolated using solid‐phase extraction. The structure was confirmed using proton nuclear magnetic resonance (NMR) and1H‐13C long range correlation experiments. The metabolite was quantifiedin vivoin human urine samples. Enzyme kinetic behaviour of the pathway was investigated in HLM and recombinant UGT (rUGT) enzymes. Additionally, preliminary experiments were performed with 1′‐OH midazolam (1′‐OH MDZ) and 4‐OH‐midazolam (4‐OH MDZ) to investigate N‐glucuronidation.

RESULTSNMR data confirmed conjugation of midazolam N‐glucuronide (MDZG) standard to be on the α‐nitrogen of the imidazole ring.In vivo, MDZG in the urine accounted for 1–2% of the administered dose.In vitroincubations confirmed UGT1A4 as the enzyme of interest. The pathway exhibited atypical kinetics and a substrate inhibitory cooperative binding model was applied to determineKm(46 µM, 64 µM),Vmax(445 pmol min−1 mg−1, 427 pmol min−1 mg−1) andKi(58 µM, 79 µM) in HLM and rUGT1A4, respectively. From incubations with HLM and rUGT enzymes, N‐glucuronidation of 1′‐OH MDZ and 4‐OH MDZ is also inferred.

CONCLUSIONSA more complete picture of MDZ metabolism and the enzymes involved has been elucidated. Direct N‐glucuronidation of MDZ occursin vivo. Pharmacokinetic modelling using Simcyp™ illustrates an increased role for UGT1A4 under CYP3A inhibited conditions.
Patterns of recruitment into acute myeloid leukaemia (AML) 15 and outcome for young patients with AML at a single referral centre
Authors: Stevens Jane M. , MacDougall Finlay , Jenner Michael , Oakervee Heather , Cavenagh Jamie , Lister Andrew T.
Published: February 2009

This study assessed the recruitment to an acute myeloid leukaemia (AML) trial (AML15) in a single centre, evaluated whether outcome was influenced by trial entry and whether the trial population could be considered representative of all AML patients by retrospective comparison of patient characteristics, trial entry and outcome for 81 consecutive patients (<60 years). All patients were considered for trial entry, however the trial was not offered to 12 (15%) patients. These patients had a worse outcome than the 69 (85%) patients that were invited to participate (P = 0·04). Sixteen patients (23%) invited to participate in the trial declined and were treated on equivalent protocols. These patients had a similar outcome to those who accepted entry into the trial (P = 0·2). These results suggested that physicians exert a selection bias when evaluating patients for trial entry. Thus the overall survival estimates generated from large phase III trials may indicate that the outcome for patients with AML is better than the outcome experienced in the ‘real’ world. Furthermore, patients who are considered appropriate for randomization into a trial, but decline entry, experience a similar outcome to those treated on trial when treated in an equivalent manner.
Pathogenesis and management of bleeding and thrombosis in plasma cell dyscrasias
Authors: Eby Charles
Published: February 2009

Unexpectedly high rates of venous thromboembolic events (VTE) concurrent with the introduction of highly effective immune modulating drugs thalidomide and lenolidomide for treatment of multiple myeloma have focused attention on the incidence and underlying pathophysiology of VTE in patients with plasma cell dyscrasias, and on thromboprophylaxis approaches. While bleeding complications are relatively uncommon in patients with lymphoproliferative disorders, acquired von Willebrand syndrome, typically occurring in patients with monoclonal gammopathy of unknown significance, and acquired coagulopathies associated with primary amyloidosis can present with haemorrhagic complications and both are challenging to manage. This review highlights these important haemostasis‐related complications of plasma cell dyscrasias and provides an overview of other uncommon bleeding and thrombotic events that can affect diagnostic and therapeutic management of clonal plasma cell disorders. Due to the infrequency of most of these haemostasis complications, available information is typically based on retrospective cases or series.